Health Literacy Interventions and Outcomes: An Updated Systematic Review

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2 Evidence Report/Technology Assessment Number 199 Health Literacy Interventions and Outcomes: d Systematic Review An Update Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov -2007- 10056- Contract No. 290 I Prepared by: RTI International –University of North Carolina Evidence -based Practice Center Research Triangle Park, North Carolina Investigators: Nancy D. Berkman, Ph.D., M.L.I.R. Stacey L. Sheridan, M.D., M.P.H. Katrina E. Donahue, M.D., M.P.H. David J. Halpern, M.D., M.P.H. Anthony Viera, M.D., M.P.H. Karen Crotty, Ph.D., M.P.H. Audrey Holland, M.P.H . Michelle Brasure, Ph.D. Kathleen N. Lohr, Ph.D. Elizabeth Harden, M.P.H. Elizabeth Tant, B.A. Ina Wallace, Ph.D. Meera Viswanathan, Ph.D. AHRQ Publication No. 11- E006 March 2011

3 This document is in the public domain and may be used and reprinted wit hout special permission. Citation of the source is appreciated. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. Suggested citation: Berkman ND, Sheridan SL, Donahue KE, Halpern DJ, Viera A, Crotty K, Holland A, Brasure M, Lohr KN, Harden E, Tant E, Wallace I, Viswanathan M. Health Literacy d Systematic Review Interventions and Outcomes: An Update . Evidence Report/Technology Assesment No. 199. (Prepared by RTI Internationa - l–University of North Carolina Evidence -2007- 10056- based Practice Center under contract No. 290 I. AHRQ Publication Number 11- E006. Rockville, MD. Agency for Healthcar e Research and Quality. March 2011. This report is based on research conducted by the RTI International –University of North Carolina at Chapel Hill, North Carolina (RTI -UNC) Evidence -based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290- -10056- I). The finding s and conclusions in this document are those of the 2007 author(s), who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this article should be construed as an official pos ition of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decision- makers, patients and clinicians, health system leaders, and policymakers -informed decisions and thereby make well improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or impli ed. ii

4 Preface -based The Agency for Healthcare Research and Quality (AHRQ), through its Evidence Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public - an d private -sector organizations in their efforts to improve the quality of health care in the United States. The reports and assessments provide organizations -based information on common, costly medical conditions and new with comprehensive, science health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments. ts into the development of evidence reports and health To bring the broadest range of exper technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release. AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality. We welcome comments on this evidence rep ort. They may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, or by e -mail to [email protected] Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. Director, Centre for Outcomes and Evidence Director Agency for Healthcare Research and Q Agency for Healthcare Research and Quality uality Marian James, Ph.D., M.A. Stephanie Chang, M.D., M.P.H. EPC Program Task Order Officer Director, EPC Program Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality iii

5 Acknowledgments I from the Agency for Healthcare This study was supported by Contract 290- 2007- 10056- Research and Quality (AHRQ), Task No. 5. We acknowledge the continuing support of -based Practice Center (EPC) Stephanie Chang, M.D., M.P.H., Director of the AHRQ Evidence Program, and Marian D. James, Ph.D., M.A., the AHRQ Task Order Officer for this project. We extend our appreciation to our Technical Expert Panel (TEP). All provided thoughtful advice and input during our research process. The TEP was both a substantive resource and a “sounding board” throughout the study. It was also the body from which expertise was formally sought at several junctions. The investigators would like to particularly thank Cindy Brach for her assistance in querying intervention study researchers. TEP members are listed below: Michael Paasche - Orlow, M.D., M.A., , M.P.H. Marilyn Shapira, M.D. Medical College of Wisconsin M.P.H. Milwaukee, WI Internal Medicine, Boston University School of Medicine Boston, MA David Baker, M.D. Internal Medicine, Northwestern University Cindy Brach, M.P.P. Chicago, IL Agency for Healthcare Research and Quality Rockville, MD Rima Rudd, Sc.D. Darren DeWalt, M.D. Harvard School of Public Health Internal Medicine, University of North Boston, MA Carolina Chapel Hill, NC Joanne Schwartzberg, M.D. American Medical Association Sue Stableford, M.P.H., M.S.B. Health Literacy Institute, University of Chicago, IL New England Portland, ME The investigators deeply appreciate the considerable support, commitment, and contributions of the EPC team staff at RTI International and the University of North Carolina at Chapel Hill. We express our gratitude to Megan Van Noord, M.S.I.S., Christiane Voisin, M.S.L.S., and Lynn Whitener, M.S.L.S., Dr.P.H. our EPC Librarians; Loraine Monroe, our EPC publications specialist; Jennifer Drolet, M.A., our editor; and Linda Lux, M.P.A., the RTI -UNC Administrator. We wo uld also like to thank Shrikant Bangdiwala, Ph.D. for his helpful consultation on questions related to statistical methodology included in the literature. Finally, we would like to thank Michael Pignone and Darren Dewalt, who were our collaborators on the original review we performed in 2004; our discussions and work with them provided a critical foundation for the current review. iv

6 Health Literacy Interventions and Outcomes: d Systematic Review An Update Structured Abstract Objectives. ematic review of health care service use and health outcomes To update a 2004 syst related to differences in health literacy level and interventions designed to improve these outcomes for individuals with low health literacy. Disparities in health outcomes and effectiveness of interventions among different sociodemographic groups were also examined. ® We searched MEDLINE , Data sources. the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, PsychINFO, and the Educational Resources Information Center. For health literacy, we searched using a variety of terms, limited to English and studies published from 2003 to May 25, 2010. For numeracy, we searched from 1966 to May 25, 2010. We used standard Evidence Review methods. -based Practice Center methods of dual review of -text articles, abstractions, quality ratings, and strength of evidence grading . We abstracts, full resolved disagreements by consensus. We evaluated whether newer literature was available for answering key questions, so we broadened our definition of health literacy to include numeracy and oral (spoken) health literacy. We excluded intervention studies that did not measure health literacy directly and updated our approach to evaluate individual study risk of bias and to grade strength of evidence. Results. We included good- and fair -quality studies: 81 studies addressing health outcomes (reported in 95 articles including 86 measuring healt h literacy and 16 measuring numeracy, of which 7 measure both) and 42 studies (reported in 45 articles) addressing interventions. Differences in health literacy level were consistently associated with increased hospitalizations, greater emergency care use, lower use of mammography, lower receipt of influenza vaccine, poorer ability to demonstrate taking medications appropriately, poorer ability to interpret labels and health messages, and, among seniors, poorer overall health status and higher mortality. H ealth literacy level potentially mediates disparities between blacks and whites. The strength of evidence of numeracy studies was , limiting conclusions insufficient to low about the influence of numeracy on health care service use or health outcomes. Two studies suggested numeracy may mediate the effect of disparities on health outcomes. We found no evidence concerning oral health literacy and outcomes. Among intervention studies (27 randomized controlled trials [RCTs], 2 cluster RCTs, and 13 quasi -experi mental designs), the strength of evidence for specific design features was low or insufficient. However, several specific features seemed to improve comprehension in one or a entions on few studies. The strength of evidence was moderate for the effect of mixed interv health care service use; the effect of intensive self -management inventions on behavior; and the effect of disease- management interventions on disease prevalence/severity . The effects of other mixed interventions on other health outcomes, including knowledge, self -efficacy, adherence, and quality of life, and costs were mixed; thus, the strength of evidence was insufficient. Conclusions. The field of health literacy has advanced since the 2004 report. Future research priorities include justifyin g appropriate cutoffs for health literacy levels prior to conducting studies; developing tools that measure additional related skills, particularly oral (spoken) health v

7 literacy; and examining mediators and moderators of the effect of health literacy. Prio rities in advancing the design features of interventions include testing novel approaches to increase motivation, techniques for delivering information orally or numerically, “work around” interventions such as patient advocates; determining the effective components of already -tested interventions; determining the cost -effectiveness of programs; and determining the effect of policy and practice interventions. vi

8 Contents ...ES Executive Summary -1 Introduction ...1 Health Literacy ...1 Definition ...1 ...1 Burden of Low Literacy and Low Health Literacy ...3 Measuring Health Literacy Relationship B etween Health Literacy and Outcomes ...8 Effects of Interventions T o Reduce Burden of Low Health Literacy ...9 Need for Update of the Earlier Review ...9 Prod uction of This Report ...10 Organization ...10 ...10 Technical Expert Panel Use of This Updated Systematic Review ...11 ...12 Methods Key Questions and Analytic Framework ...15 Literature Search and Retrieval Process ...17 Database Search Terms ...17 Study Selection Process ...17 Inclusion and Exclusion Criteria ...17 Process for Considering Abstracts and Full Articles for Inclusion...20 Literature Synthesis ...21 Development of Evidence Tables and Data Abstraction Process ...21 Quality Rating of Individual Studies ...21 ...22 Data Synthesis ...22 Gradin g the Strength of Available Evidence ...23 Applicability of the Evidence ...23 Peer Review Process Results: Relationship of Health Literacy to Outcomes and Disparities ...24 Results of Literature Search ...26 Key Question 1. Relationship of Health Literacy to Vario us Outcomes and Disparities ...26 KQ 1a. Use of Health Care Services ...27 Summary of Outcomes on Use of Health Care Services ...30 KQ 1b. Health Outcomes ...30 Summary of Outcomes and Strength of Evidence on Health Outcomes ...39 KQ 1c. Costs of Health Care ...39 KQ 1d. Disparities in Health Outcomes or Health Care Service Use ...40 Key Question 1. Relationship of Numeracy to Various Outcomes and Disparities ...41 KQ 1a. Use of Health Care Services ...41 KQ 1b. Health Outcomes ...42 KQ 1c. Costs ...45 KQ 1d. Potential Mediator of Dispar ities ...45 The Effect of Interventions T o Mitigate the Effects of Low Health Literacy ...143 Introduction ...143 Search Results ...143 vii

9 Study Quality ...144 Characteristics of Included Studies ...144 Intervention Effects of Health Literacy Interventions Using Single Strategies, by Type ...144 ...144 Intervention: Alternative Document Design Intervention: Alternative Numerical Presentation ...145 ...146 Intervention: Additive and Alternative Pictorial Representation Intervention: Alternative Media ...148 Intervention: Alternative Readability and Document Design ...150 ...151 Intervention: Physician Notification of Patient Literacy Status Summary of Interventions Using Single Intervention Design Strategie s ...151 Effects of Mixed Strategy Interventions, by Analytic Framework ...152 KQ 2a. Effect of Mixed Interventions on Use of Health Care Services ...152 KQ 2b. Effect of Mixed Interventions on Health Outcomes ...153 KQ 2c. Effect of Mixed Interventions on Health Care Costs ...157 ...158 KQ 2d. Effect of Mixed Interventions on Disparities Summary of ...158 Interventions Using Mixed Intervention Strategies -Cutting Observations About Interventions Designed T Cross o Mitigate Low Health Literacy ...158 Discussion ...216 Overview ...216 ...216 Principal Findings KQ 1 . Health Literacy and Outcomes ...216 T o Improve Health Literacy ...218 KQ 2. Interventions What This Update Adds to the Literature Included in the 2004 Review ...220 Limitations ...221 Limitations of the Literature ...221 Limitations of Our Review ...222 Opportunities for Future Research ...223 Into the Future Research Relationship Between Health Literacy and Health Outcomes ...223 Into Interventions To Mitigate the Effects of Low Health Future Research ...224 Literacy Implications of This Report for Clinicians and Policymakers ...226 Conclusions ...227 ...232 References Figures A . Logic Model for A nalyzing S Figure Health Literacy ...ES -3 tudies of Figure 1. Analytic Framework for the Health Literacy S ystematic R eview ...14 Figure 2. Logic M ealth Literacy S ystematic R eview ...15 odel for the H Figure 3. PRISMA T ree: Flow D iagram D epicting R eview and D isposition of A rticles ...25 Tables Table 1. Measures of H ealth Literacy ...4 Table 2. Measures of N umeracy ...7 pdate ...20 Table 3. Inclusion/ Exclusion C riteria for S tudies C onsidered in T his U viii

10 Table 4. Strength of E vidence G Definitions ...23 rades and Health Literacy S ...46 Table 5. Overview of tudies riteria U sed T easure Health Literacy or L iteracy in Table 6. Measurement T ools and C o M ...63 rticles KQ 1 A tudies of the R elationship B etween H ealth Literacy and E mergency Table 7. Summary of S ates (KQ 1a) ...66 Department an d Hospitalization R Literacy S ealth trength of E vidence Grades by H ealth C are Table 8. KQ 1a H tudies: S ...69 utcomes Service O elationship B etween H ealth Table 9. Summary of S olon tudies of the R Literacy and C creening (KQ 1a) ...70 Cancer S tudies of the R elationship B etween H ealth Literacy and Pap T Table 10. Summary of S ests (KQ 1a) ...71 tudies of the R elationship B ealth Literacy and M ammography Table 11. Summary of S etween H ...72 (KQ 1a) Table 12. Summary of S etween H ealth Literacy and S exually tudies of the R elationship B esting (KQ 1a) ...73 Infections T Transmitted tudies of the R elationship B etween H ealth Literacy and Table 13. Summary of S Immunizations (KQ 1a) ...74 tudies of the R etween H ealth Literacy and A ccess t o C are Table 14. Summary of S elationship B ccess to Insurance (KQ 1a) and A ...75 Table 15. Summary of S elationship B etween H ealth tudies of the R dherence Literacy and A (KQ 1b) ...79 Table 16. KQ 1b H ealth Literacy S tudies: S trength of E vidence Grades by Health O utcomes ...84 Table 17. Summary of S tudies of the R etween H ealth Literacy and S elf -Efficacy elationship B ...86 (KQ 1b) elationship B etween H ealth Literacy and H ealth Table 18. Summary of S tudies of the R Behaviors (KQ 1b) ...88 Table 19. Summary of S tudies of the R elationship B etween H ealth Literacy and the ealth C are Related S kills (KQ 1b) Outcome of H ...93 Table 20. Summary of S elationship B etween H ealth Literacy and the O utcome of tudies of the R epression and O ental H M Prevalence of D ealth O utcomes (KQ 1b) ...98 ther tudies of the R elationship B etween H ealth Literacy and the Table 21. Summary of S Outcome of P reval ence of C hronic D iseases (KQ 1b) ...101 Table 22. Summary of S tudies of the R etween H ealth Literacy and HIV elationship B ymptoms (KQ 1b) Patient S ...105 tudies of the R elationship B etween H ealth Literacy and A sthma P atient Table 23. Summary of S s (KQ 1b) ...106 Symptom Table 24. Summary of S tudies of the R elationship B etween H ealth Literacy and Diabetes C ontrol (KQ 1b) ...107 Table 25. Summary of S elationship B etween H ealth Literacy and H ypertension tudies of the R Control (KQ 1b) ...111 Table 26. Summary of S tudies of the R elationship B etween H ealth Literacy and Prostate C ontrol (KQ1b) ...112 ancer C Table 27. Summary of S tudies of the R etween H ealth Literacy and H ealth elationship B ...112 Status (KQ 1b) ix

11 Table 28. Summary of S tudies on the R ealth Literacy and elationship B etween H Mortality (KQ 1b) ...120 Table 29. Summary of S ealth Literacy and C osts tudies of the R etween H elationship B (KQ 1c) ...122 trength of E vidence Grades by Costs of iteracy S ealth L Table 30. KQ 1c H tudies: S ...123 are Health C elationship B etween H ealth Literacy and Table 31. Summary of S tudies of the R Disparities (KQ 1d) ...124 Table 32. KQ 1d H tudies: S trength of E vidence Grades by Disparities ealth Literacy S utcomes ealth O Across H ...128 Numeracy S tudies ...129 Table 3 3. Overview of ervices etween N Level and U se of Health C are S elationship B Table 34. The R umeracy ...132 (KQ 1a) umeracy Studies: S trength of E vidence G rades by U se of Health C are Table 35. KQ 1 N ealth O Services and H utcomes ...132 etween N ccuracy of R isk P erception Level and A umeracy elationship B Table 36. The R ...133 (KQ 1b) umeracy Table 37. Relationship B nowledge (KQ 1b) ...135 etween N Level and K etween N um eracy and S elf -Efficacy (KQ 1b) ...136 Table 38. Relationship B etween N ume racy Level and B ehavior (KQ 1b) ...137 Table 39. Relationship B etween N Level and S kills (KQ 1b) ...138 umeracy Table 40. Relationship B etween N umeracy Level and D isease P revalence and Table 41. Relationship B (KQ 1b) ...141 Severity Table 42. Relationship B etween N umerac y Level and D isparities (KQ 1d) ...142 Table 43. Summary of Included Intervention S tudies ...160 Tabl e 44. Intervention S etail ...168 tudy D Intervention S trategi lternative D ocument D esign ...178 Table 45. Single es: A Interventions: S ype of vidence Grades by T pecific O utcome ...180 Table 46. KQ 2 S trength of E trategies: A lternative N umerical P resentation ...182 Table 47. Single Intervention S Intervention S trategies: A dditive and Table 48. Single ictorial Representation ...185 Alternative P Table 49. Single on S trategies: A lternative M edia ...192 Interventi Intervention S esign eadability and Document D Table 50. Single ...194 trategies: Alternative R Intervention S Table 51. Single hysician N otification of P atient Literacy Levels ...198 trategies: P Table 52. Effect of M ixed Interventions on U se of H ealth C are S ervices ...199 Table 53. KQ 2 Mixed Interventions: S Evidence G rades by T ype of O utcome ...201 trength of ixed nowledge ...202 Table 54. Effect of M Interventions on K ixed Interventions on S elf -Efficacy ...204 Table 55. Effect of M Table 56. Effect o f M Interventions on S kills ...206 ixed ixed Interventions on B ehavior ...207 Table 57. Effect of M Table 58. Effect of M ixed Interventions on A dherence ...208 Table 59. Effect of M ixed isease P revalence and S everity ...210 Interventions on D ixed Interventions on Q uality of L ife ...213 Table 60. Effect of M Table 61. Effect of M ixed Interventions on H ealth C are C osts ...215 Table 62. Health O utcome S tudy R esults (KQ 1): Summary and C omparison of 2004 ...228 and 2010 S ystematic R eviews x

12 Table 63. Numeracy O utcome S esults (KQ 1): S ummary of 2010 S ystematic tudy R ...230 Review Intervention S tudies with S ingle D esign S trategies (KQ 2): S ummary Table 64. Results of omparison of 2004 and 2010 S ystematic R eviews ...230 and C Interventions with M Table 65. Results of esign S trategies: S ummary and Comparison of ultiple D 2004 and 2010 S ystematic R eviews ...231 Appendixes . Author Queries Appendix A Appendix B . Search Strings . Inclusion/Exclusion Criteria and Study Internal Validity Quality Form Appendix C . Evidence Tables Appendix D Appendix E . Characteristics of Studies With Poor Internal Validity Appendix F . Strength of Evidence Appendix G . Peer Reviewers Appendix H . Excluded Studies Appendix I . Articles by Database Search Appendix J . Summary of KQ 1 Findings from Literacy and Health Outcomes Report xi

13 Executive Summary Introduction Health literacy is “the degree to which individuals can obtain, process, and understand the basic health information and services they need to make appropriate health decisions.” It represents a constellation of skills necessary for people to function effectively in the health care environment and act appropriately on health care information. These skills include the ability to interpret documents, read and write prose (print literacy), use quantitative information (numeracy), and speak and listen effectively (oral literacy). oximately 80 Low health literacy is a significant problem in the United States. In 2003, appr million adults in the United States (36 percent) had limited health literacy. Rates of limited health literacy in certain population subgroups were higher. For instance, rates were higher completed high school, adults who among the elderly, minorities, individuals who have not spoke a language other than English before starting school, and people living in poverty. Highlighting the health impact of low health literacy, a 2004 systematic evidence review found a teracy and poor health outcomes. Specifically, health literacy relationship between low health li -related knowledge and comprehension, (measured by reading skills) was associated with health hospitalization rates, global health measures, and some chronic diseases. Given the burden of low health literacy and the potential to reduce poor outcomes using novel interventions to address it, several national organizations have called for action. In 2010, the U.S. Department of Health and Human Services (HHS) released a National Action Plan to Impr ove Health Literacy. Additionally, in recent years, several national organizations and agencies, including the Institute of Medicine, American Medical Association, National Institutes of Health, and HHS (in Healthy People 2010), have promoted health litera cy as a research priority. Researchers responded to these calls with new and more sophisticated work. Thus, to synthesize the increasing volume of literature on health literacy, the Agency for Healthcare Research and Quality (AHRQ) commissioned the RTI In −University of North ternational Carolina Evidence -based Practice Center (EPC) to update its 2004 systematic review examining the effects of literacy on health outcomes and interventions to improve those outcomes. In this updated report, we focus on the sam e Key Questions as the original report: Key Question 1. Outcomes: Are health literacy skills related to (a) use of health care services, (b) health outcomes, (c) costs of health care, and (d) disparities in health outcomes or health care service use? Key Q uestion 2. Interventions: For individuals with low health literacy skills, what are effective interventions to (a) improve use of health care services, (b) improve health outcomes, (c) affect the costs of care, and (d) improve health care service use and/o r health outcomes among different racial, ethnic, cultural, or age groups? In contrast to our earlier report, we concentrate on “health literacy” rather than “literacy” for several reasons. First, we aimed to be consistent with recent conceptualizations of health literacy skills that separately examine print literacy, numeracy, and oral literacy. Second, an increasing -1 ES

14 number of newer measures are framed in specific health contexts and assess condition -related int literacy (including prose and document literacy), skills. Finally, measures of health literacy, pr and numeracy are highly correlated in national samples. Although we believe our focus on health literacy appropriately represents the directions of research and policy in this field, we acknowledge tha t the literature contributing to this field does not organize itself neatly within our health literacy framework. For instance, several measures of health literacy assess a combination of print literacy and numeracy skills, making distinctions between prin t literacy and numeracy difficult. Furthermore, the quantitative skills components of some measures have been extracted and used independently as measures of numeracy. To simplify this report, we separate health literacy (including any studies that presume to measure literacy or health literacy) from those that solely measure numeracy or oral literacy. Methods Changes From Our Prior Review Our overall goals in this update were to evaluate whether newer literature was appropriate for answering our Key Questions and to determine whether earlier conclusions changed. Following discussions with our Technical Expert Panel, we modified the original methods as follows: • We broadened our definition of health literacy to be consistent with the Ratzan and Parker ( 2000) definition used by Healthy People 2010 and the Institute of Medicine. Thus, our inclusion criteria included studies that measured numeracy and oral skills of participants. • We required that studies directly measured the health literacy of the study p opulation and did not assign health literacy level via self -report or similarity to other populations. • To evaluate individual study quality, we incorporated advances in the methods of conducting systematic reviews. We included studies conducted in developi ng countries as long as they used an objective • measure of literacy or health literacy in their participants. • We reviewed knowledge as an outcome only for numeracy and intervention studies because evidence in the earlier review clearly concluded that greate r literacy skills and higher health -related knowledge levels are positively related. • If articles about intervention studies were missing information about intervention content, we queried the investigators to allow richer interpretation about what interve ntions may be effective in mitigating the effects of low health literacy. Outcomes of Interest The logic model in Figure A details outcomes that we included in our review as well as other conceptually important variables. It draws on several models of heal th literacy proposed by researchers in the field and on an integrated model of behavioral theory called the Integrative Theory. We applied this model to determine whether studies considered for inclusion had relevant health outcomes and to guide our presentation of included articles. It is not, however, a definitive guide to the relationship among variables because researchers have not explicitly tested many of these relationships yet. Furthermore, it does not specify the directionality of a or some outcomes, increases represent the good outcome (e.g., adherence, most good outcome; f screening tests) and for others, decreases represent the good outcome (e.g., hospitalizations, -2 ES

15 mortality). We did not examine outcomes related to attitudes because of the belief that attitudes result from knowledge, which, as mentioned above, is not examined in the current report. Further, we did not examine outcomes related to social norms or patient -provider relationships (e.g., shared decisionmaking) because we thought that the se variables likely affected the direction or strength of the relationship between behavioral intent and health outcomes, rather than laying on the causal pathway. Clearly, however, empiric work is needed to test these assertions prior to future reviews. Figure A. Logic model for analyzing studies of health literacy Literature Search and Retrieval Process ® We searched MEDLINE , the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, PsycINFO, and the Educational Resources Information Center. For health literacy, we searched from 2003 to May 25, 2010. For numeracy, we searched from 1966 to May 25, 2010. We conducted keyword searches because no Medical Subject Headings terms -related articles. The terms health literacy, numeracy, and specifically identify health -literacy literacy, and terms or phrases related to instruments known to measure health literac y and numeracy, were the focus of the search. We excluded editorials, letters to the editor, case reports, English language studies. We also manually searched reference lists of pertinent review and non- articles and editorials for additional studies. le Review and Data Abstraction Artic We used standard EPC methods for dual review of abstracts and full text of articles to determine article inclusion. After determining article inclusion, one reviewer entered data about studies into evidence tables and a second, senior reviewer checked information for accuracy and completeness. Quality Review Two reviewers independently rated the quality of studies (good, fair, or poor) using criteria designed to detect selection bias, measurement bias, confounding, and inadequate power. Reviewers resolved all disagreements about quality ratings by consensus. We did not consider further any studies that we rated poor quality. -3 ES

16 Data Synthesis and Grading Strength of Evidence e did not have a sufficient number of We synthesized the data in our review qualitatively. W studies with similar outcomes or similar interventions to consider quantitative analysis (meta - analysis or statistical pooling) of data. Furthermore, we primarily discussed information from the current searches, providing only aggregate summaries of data from our 2004 review. As part of data synthesis, we paid particular attention to a few issues. First, we closely examined whether studies accounted for relevant confounding variables in their analyses. Because the goal of etiologic research focuses on understanding the relationship between exposures and outcomes of interest, it is important that confounders are controlled for to determine accurate estimates of effect. Second, we looked closely at studies that reported the relationship between both health literacy and numeracy and the same outcome. This allowed inferences about the relative strengths of the measures on outcomes. Third, for intervention studies, we looked at common features of successful interventions and a t the impact of interventions on multiple related outcomes. This allowed inference about the effective components and mechanisms of health literacy interventions. The investigative team jointly discussed and graded the overall body of literature and gener ated recommendations for future research. For grading strength of evidence, we used the AHRQ EPC program’s approach: assigning grades of high, moderate, low, or insufficient to the ness, and precision. We evidence after considering the domains of risk of bias, consistency, direct resolved disagreements by consensus discussion. Results Search Results and Included Studies Our searches of electronic databases and review articles produced 3,496 unduplicated records. Ultimately, for the two main questions, we included studies rated either good or fair quality: 81 studies (95 articles) addressed Key Question 1 and 42 studies (45 articles) addressed Key Question 2. Key Question 1 results are presented separately in relation to health literacy (86 articles) and nu meracy (16 articles). Of these, we identify the 7 articles that address both health literacy and numeracy. Key Question 1 . Relationship of health literacy to various outcomes and disparities Sixty -four articles pertaining to this part of Key Question 1 had cross -sectional designs; 22 were cohort studies. We categorized studies examining outcomes associated with differences in health literacy level into two main domains: use of health care services and health outcomes. Strength of evidence evaluations focuse d on the relationship between the lowest health literacy group and the highest. The evidence was sparse for evaluating differences between those with marginal health literacy (a middle category) and adequate health literacy (the highest category). Use of Health Care Services —Health Literacy Moderate evidence about health care service use showed that lower health literacy was associated with increased hospitalization (five studies), greater emergency care use (nine studies), lower use of mammography (four s tudies), and lower receipt of influenza vaccine (four studies). Evidence for all other analyses of health care service use was low or insufficient -4 ES

17 because of inconsistent findings or outcomes; this includes studies about colon screening, Papanicolau (Pap) tests tion, , testing for sexually transmitted infections, pneumococcal immuniza and access to care. —Health Literacy Health Outcomes Lower health literacy was associated with poorer outcomes in some of the health outcomes examined. A higher risk of mortality for seniors (two studies) was clearly associated with lower health literacy (high strength of evidence). Lower health literacy was associated with poorer ability to demonstrate taking medications appropriately (five studies), poorer ability to interpret labels and health messages (three studies), and poorer overall health status among seniors (five studies) (all of moderate strength of evidence). In these studies, the evidence consisted of all observational studies, generally with a medium risk of bias and results in a consistent direction. The strength of evidence for the many other outcomes we examined —adherence, self - efficacy, smoking, alcohol use, healthy lifestyle, review of prescription information, HIV risks valence, HIV severity and symptoms, asthma severity and sexual behaviors, chronic disease pre and control, diabetes control and related symptoms, hypertension control, prostate cancer control, quality of life, and costs —was either low or insufficient. The literature consisted of only a small numbe r of studies, poorly designed studies, and/or inconsistent results. Potential moderators and mediators of the relationship between health literacy and health outcomes were also identified during our review. Two studies concluded that social support and health care system characteristics modify the magnitude and/or direction of the relationship between health literacy and adherence and health literacy and blood pressure control. Four studies concluded that knowledge, patient self -efficacy, and stigma might act as mediators or intermediaries in the causal pathway between health literacy and health outcomes and explain at least some of the negative impact of low health literacy on these health outcomes. In addition, one study suggested that health literacy may mediate the effect of education, income, and urbanicity on health outcomes. Costs —Health Literacy Evidence was insufficient to evaluate the relationship between differences in health literacy ayment sources (Medicaid and levels and costs. The two relevant studies examined different p Medicare) and different populations, and found inconsistent results. —Health Literacy Disparities in Outcomes In relation to disparities, health literacy appeared to mediate the effect of race on several health outcomes. These included conditions that keep a person from working, long -term illness, self -reported health status, receipt of an influenza vaccine, physical and mental health- related quality of life, self -specific antigen levels, nonadherence t o HIV -reported health, prostate medications, and enrollment in health insurance. Health literacy also mediated differences by both race and gender in the misinterpretation of medication label instructions. Key Question 1 . Relationship of n umeracy to various outcomes and disparitie s In this update, we identified 16 studies examining the relationship between numeracy and health outcomes. Eleven were cross -sectional in design. Four studies were randomized controlled -5 ES

18 trials (RCTs) that analyzed their data in a cross -sectional manner fo r this analysis; one study used a prospective cohort design. In general, the evidence pertaining to this Key Question was either low or insufficient given the small number of studies; these studies often had high risk of bias or, collectively, gave us d results. mixe Use of Health Care Services —Numeracy Only one study addressed the relationship between numeracy and use of health care services -to-date screening for breast (low strength of evidence). It reported no effect of numeracy on up and colon cancer, but it appeared to be limited by inadequate power to detect a meaningful effect. Health Outcomes —Numeracy Relationships between numeracy level and accuracy of risk perception (five studies), knowledge (four studies), skills taking medication (six studies) , and disease prevalence and severity (three studies) were mixed. The evidence for the relationship between numeracy and other health outcomes, such as self -efficacy or behavior , was insufficient to draw conclusions. No study addressed the costs associated with differences in numeracy level. Disparities in Outcomes —Numeracy Two studies examined whether numeracy level mediates health disparities. Numeracy appeared to mediate the relationship between race and levels of hemoglobin A1c and between IV medication management capacity. gender and H Key Question 1 . Comparison of the relationship of health literacy and numeracy to the same outcomes Seven studies addressed the effects of both health literacy and numeracy on various outcomes. Of the seven, only four per formed adjusted analyses on the same outcomes, thereby allowing assessment of whether these exposures affect health outcomes differently. All suggest that numeracy is more highly correlated with outcomes than health literacy. However, all must be interpret ed with caution, because the proportion of individuals with low health literacy was small, raising the possibility of ceiling effects that could obscure effects in the literacy analyses. Key Question 2 . Interventions to improve low health literacy In this update, we included 42 studies of good or fair quality addressing the effect of interventions designed to mitigate the effects of low health literacy; of these, 27 were RCTs, 2 were cluster randomized trials, and 13 were quasi -experimental studies. We focused our analyses on 2 separate sets of studies: 21 that used one specific strategy (single design features) to lessen the effects of low health literacy and 21 that used a mixture of strategies combined into a single intervention. Interventions With Single Design Features Of intervention studies testing single design features, two focused on alternative document design, three on alternative numerical presentation, eight on additive or alternative pictorial representations, four on alternative media, and seven on a combination of alternative readability -6 ES

19 and document design. Additionally, one intervention focused on the effects of physician notification about patients’ literacy status on health outcomes. Effects were measured primaril y in terms of comprehension. Overall, the strength of evidence for specific design features in these interventions was low or insufficient. This is attributable, in large part, to differences in the types of interventions and, subsequently, in the mix of results. Looking closely within categories of design features, however, the following specific design features seemed to improve comprehension for low - health -literacy populations in one or a few studies: (1) presenting essential information by itself (i.e. , information on hospital death rates without other distracting information, such as information on consumer satisfaction); (2) presenting essential information first (i.e., information on hospital death rates before information about consumer satisfaction); (3) presenting health plan quality information such that the higher number (rather than the lower number) indicates better quality; (4) using the same denominators to present baseline risk and treatment benefit; (5) adding icon arrays to numerical prese ntations of treatment benefit; and (6) adding video to verbal narratives. Additionally, in reexamining data from our 2004 review within these categories, we identified further evidence of potential benefit from using reduced reading level and/or illustrate d narratives. In contrast, one study raised questions about whether certain design features, such as colored traffic symbols to denote death rates in hospitals of varying quality or symbols accompanying nonessential quality information, may actually worsen health choices among those with low health literacy. Interventions With a Combination of Features The strength of evidence for studies combining multiple strategies to mitigate the effects of low health literacy on either health care use or outcomes was more variable than it was for single -feature interventions. Use of Health Care Services Across all studies in this category, we found moderate strength of evidence that interventions included in the review changed health care service use. Specifically, in -management tensive self and adherence interventions appeared to be effective i n reducing emergency room visits and hospitalizations. Additionally, educational interventions and/or cues for screening increased (although we note that the health benefits of colorectal cancer and prostate cancer screening additional prostate cancer screening are not clear). Health Outcomes We found evidence of moderate strength that some interventions changed health outcomes. For instance, intensive disease -management programs appeared to be effective at reducing disease prevalence/severity. Furthermore, self -management interventions increased self - management behavior; however, in the only study that stratified a subgroup analysis by health literacy level, improvements were sometimes greater for those who had adequate health literacy and at other times greater for those with inadequate health literacy in adjusted analyses. The effects of other interventions on other health outcomes, including knowledge, self -efficacy, health -related skills, adherence, quality of life, and costs were mixed; thus, the strength of evidence was insufficient. Components of effective interventions were their high intensity, theory basis, pilot testing ng, and delivery of the intervention by a before full implementation, emphasis on skill buildi -7 ES

20 health professional. Interventions that changed distal outcomes (e.g., health care service use or health outcomes) appeared to work by affecting intermediate factors, such as increasing -efficacy, or by changing behavior. knowledge or self Too few studies addressed the effects of health literacy interventions on the outcomes of behavioral intent, and disparities to draw any meaningful conclusions; the strength of evidence is insufficient. Discussion Adds to the 2004 Review What This Update The results of this review expand our understanding of the relationship between health literacy and health outcomes in several ways. First, a majority of studies included in this review performed multivariate analysis, allowing us to make better estimates of the true effect of health literacy on health outcomes. Second, new studies have addressed the relationship between numeracy level and health outcomes. This allows a better understanding of what it means to be health literate. Third, we identified a limited body of research that begins to identify variables that may be on a causal pathway between health literacy and health outcomes. These variables include knowledge, self -efficacy, and social stigma. Finally, new studies suggest th at health literacy can be a mediator of racial disparities in health outcomes. We also learned many new things about interventions to mitigate the effect of low health literacy. First, we identified several design features of interventions that were effective in one or a few studies (enumerated above); they all warrant further study in broader populations. Second, interventions focused on a broader range of outcomes, allowing us to make inferences about effect across outcomes. Preliminary examination of th ese studies suggests that effective interventions to mitigate the effects of low health literacy may work by increasing knowledge and self -efficacy or by changing behavior. Additionally, certain factors appear to be key in making the interventions effectiv -management, e with respect to distal outcomes (e.g., self hospitalizations, mortality); these include high intensity, theory basis, pilot testing before full implementation, emphasis on skill building, and delivery of the intervention by a health nal (e.g., pharmacist, diabetes educator). professio Limitations of the Literature As with all systematic reviews, our results and conclusions depend on the quality of the published literature. Heterogeneity in outcomes, populations, study designs (or interventions) , and measured outcomes was a problem for both K ey Questions. This level of diversity in the knowledge base precluded us from pooling results statistically. The limitations of the literature for Key Question 1 studies included: • Lack of a priori specificati on and inconsistent approaches to creating health literacy and numeracy levels or thresholds in analyses, hampering comparisons between studies; • Inconsistent choices of potential confounding variables in multivariate analyses; • Small sample sizes, making it impossible for us to determine whether null findings represented a true lack of effect or simply limitations in statistical power; • Studies in just one clinic or in other narrowly defined patient populations, rendering the applicability of findings to othe r settings or populations unknowable; Use of health literacy tools that continue to focus primarily on reading ability; • -8 ES

21 • The limited number of studies examining potential mediators of health literacy, such as -efficacy, knowledge, or beliefs; self • Few stu dies examining the role of health literacy on health disparities; and • No studies examining differences in outcomes related to oral literacy skills. The limitations of the literature for Key Question 2 studies included: • Lack of an adequate control or comparator group in many studies, limiting the ability to determine the true effect(s) of the intervention; • Measurement of multiple outcomes with insufficient attention to ensure that each had been adequately powered to detect a difference; Testing interventions that combined various design features to mitigate the effect of low • health literacy but offering no way to determine the effectiveness of individual components; • Failure to perform adequately controlled subgroup anal yses that would elucidate differential effects of interventions in low - and high- health -literacy populations; and • Failure to report adequately the intervention design features that would allow future content analyses of effective interventions. Future Res earch The field of health literacy has clearly advanced since our 2004 review appeared. The progress has been both conceptual and empirical. Nonetheless, many opportunities remain for important future research. Such investigations will improve our understa nding of the impact of health literacy on the use and outcomes of health care and will expand the knowledge base about the impact of interventions intended to improve health literacy. Our recommendations for future research involve both better methods and specific clinical or operational topics. In examining the relationship between literacy and health outcomes, investigators should consider: • Specifying a priori their cutpoints for distinguishing levels of health literacy and noting the relevance of those levels to (a) the outcomes and population being studied and (b) the body of similar work in the field; • Using health literacy measurement tools that go beyond health -related literacy and numeracy to capture additional and potentially critical skills, part icularly oral health literacy; • Ensuring sufficient statistical power to detect differences among relevant health literacy levels; • Controlling for an adequate set of potential confounders; • Improving the applicability of results to broader populations and settings; and • Further examining potential mediators and moderators of the relationship between health literacy and health outcomes. In examining the impact of interventions to mitigate the effects of low health literacy, investigators should consider: • Te sting novel approaches to increase motivation; improved techniques for delivering written, oral, or numerical information; and “work -around” interventions such as patient advocates; -9 ES

22 • Determining the effective components of already -tested interventions that employ a combination of features intended to lessen the effects of low health literacy. Although a combination of intervention features has repeatedly been shown to ensure the success of interventions, paring away ineffective features could save delivery t ime and result in more cost -effective delivery; • Determining the cost- effectiveness of effective programs; and • Determining the effect of practice and policy interventions. We found almost no studies that addressed such interventions. port for Clinicians and Policymakers Implications of This Re We anticipate that this update will continue to raise awareness among clinicians and policymakers alike that low health literacy has a substantial impact on the use of health care services and health outcomes; it also h ints at the role of health literacy in disparities in utilization or outcomes among groups defined by various sociodemographic characteristics. However, little remains known about the direct effect of lower health literacy on the costs of health care. Addr essing the burden of low health literacy that we have identified warrants the attention of many stakeholders. We highlight effective interventions that could be implemented in clinical practice now. Intensive interventions related to medication adherence, self -management, and disease management delivered by clinical practitioners are of special interest. Additionally, for policymakers, we underscore the critical need for research funding to test practice and policy interventions, particularly those that, t o date, have gone largely untested. The recent HHS National Action Plan to Improve Health Literacy helps enumerate these and other critical actions for health care professionals and policymakers to take in addressing the multifaceted issues involving health literacy in this country. -10 ES

23 Introduction −University of North Carolina Evidence -based Practice Center In 2004, the RTI International (RTI −UNC EPC) published a systematic review examining the relationship between literacy and 1 This work, supported by the Agency for Healthcare Research and Quality health outcomes. (AHRQ), concluded: Low literacy is associated with several adverse health outcomes, including low health • knowledge, increased incidence of chronic illness, poorer intermediate disease markers, and less than optimal use of preventive health services. Interventions to mitigate the effects of low literacy have been studied, and some have shown promise for improving ient health and receipt of health care services. Future research, using more rigorous pat methods, is required to better define these relationships and to guide development of new interventions. Given a rapidly growing body of literature on literacy and health outcomes, AHRQ • commissioned an update to the 2004 review. The current report describes that update and focuses on health literacy as contrasted with literacy per se. Although the first report was we now consider numeracy limited to the print literacy component of health literacy, (ability to use numbers) and oral literacy (speaking and listening skills) as crucial components of health literacy. Health Literacy Definition 2 2,3 and adopted by Healthy People 2010 Health literacy, as defined by Ratzan and Parker and the Institute of Medicine (IOM) in their 2004 report Health Literacy: A Prescription to End 4 Confusion is “the degree to which individuals can obtain, process, and understand the basic health information and services they need to make appropriate hea lth decisions.” The concept of health literacy represents a constellation of skills necessary to function effectively in the health care environment and act appropriately on health care information. These skills include print literacy (the ability to read and understand text and locate and interpret information in documents), numeracy (the ability to use quantitative information), and oral literacy (the ability 5,6 Some authors include in this definition a working knowledge to speak and listen effectively). of disease processes, an ability to use technology, an ability to network and interact with others 7,8 -efficacy. socially, motivation for political action regarding health issues, and self Numeracy is an important component of health literacy and represents “the ability to 9 Numeracy has been independently associated with understand and use numbers in daily life.” 10 health outcomes. Additionally, some individuals may have adequate print literacy but lack the 11 These individuals numeracy skills needed to interact successfully wit h the health care system. cannot reliably carry out health -related tasks that rely on numeric information, such as interpreting food labels, measuring blood sugar, comparing risk information, or following dosing 9 instructions for medicat ions. Burden of Low Literacy and Low Health Literacy In 2003, the US Department of Education conducted a survey entitled “National Assessment of Adult Literacy” (NAAL). The most comprehensive examination of adult literacy to date, the 1

24 NAAL surveyed more t han 19,000 adults age 16 and older and included items intended to measure health literacy directly. More than one- third of respondents (36 percent) taking the NAAL scored in the lowest two (“basic” and “below basic”) out of four categories on health cy items, suggesting that approximately 80 million adults in the United States have limited litera 12 health literacy, including related prose, document, and quantitative skills. These adults may have difficulty with even simple tasks such as reading and understanding the instructions on a prescription bottle or filling out an insurance form. Although the NAAL did not independently report on prose, document, or quantitative health literacy, its predecessor, the National Adult Literacy Survey (NALS), reported simila r proportions of individuals scoring in the lowest ,13 11 proficiency levels across these domains. More recent (although not nationally representative) 14 data suggest that many adults may have higher print literacy than quantitative literacy. Although a significant proportion of the general population has low health literacy, certain groups have an even higher prevalence of the problem. Such groups include the elderly, minorities, individuals who have not completed high school, adults who spoke a language other 12 than English before starting school, and people living in poverty. For instance, the NAAL demonstrated a higher prevalence of poor health literacy among the elderly. Compared with the 36 percent of all adults who scored in the bottom two categories on the NAAL survey, 59 percent 12 This association below basic” and “basic” range. of adults age 65 and older scored in the “ between age and health literacy has proven consistent in other studies of literacy in health care settings. However, the majority of these studies are cross -sectional, making it difficult to determine whet her the higher prevalence of poor health literacy in the elderly population results from a cohort effect (e.g., fewer educational opportunities; higher prevalence of a native 15 unction. language other than English) or whether literacy declines with age or cognitive f Both factors likely play a contributing role. The NAAL also reported a strong relationship between health literacy and race or ethnicity. White respondents scored better on the survey than any of the other racial or ethnic groups 9 percent of white respondents scored in the lowest (“below basic”) category on evaluated. Only the NAAL survey, but 24 percent of black, 41 percent of Hispanic, 13 percent of Asian, and 25 12 sic” range. percent of American Indian and Native Alaskan respondents scored in the “below ba Differences in the quality of education received by disadvantaged members of nonwhite populations may, at least partially, explain this finding. Further, issues of language and acculturation likely play a significant role. The association between health literacy and race and ethnicity raises the question of whether health literacy serves as a mediator of racial and ethnic disparities in health. If literacy is related to health outcomes, disparate health literacy levels ould contribute to differential health outcomes. among different groups c In addition to age, race, and ethnicity, educational attainment plays a predictably strong role -quarters (76 percent) of respondents who in health literacy. In the NAAL study, more than three had not complet ed high school scored in the “below basic” or “basic” range of health literacy, 12 Although one’s year college degrees. compared with only 13 percent of individuals with 4- literacy level is related to one’s educational status, the correlation between years of education and literacy is imperfect. People often score reading grade levels that are several grades lower 16 In addition to the ability to read, the ability to than the last year of school they completed. complete 12 years of education may draw on sever al factors, including social support, community resources, motivation, and family expectations. Using statistical modeling and demographics, such as those above, the National Center for 17 -20 have provided estimates of local and regional literacy and Education Statistics and others 2

25 health literacy prevalence. As might be expected, these estimates suggest variation across states 18 ,20 and counties, which might affect health outcomes in important ways. To assist clinicians and lth literacy prevalence in their own environments, calculators policymakers in estimating the hea 19 based on such work are now available online. Measuring Health Literacy To date, instruments for measuring health literacy skill levels have focused primarily on the ability to read and, in s ome cases, to use numbers. A variety of measures focusing on these skills are available and have been applied in the health setting (see Tables 1 and 2). Currently, no instruments are widely available to measure oral health literacy or a comprehensive set of skills that have been conceptualized as the components of health literacy. Commonly used measures of health literacy. The instruments most commonly used in the health literature to measure health literacy are the Rapid Estimate of Adult Literacy in Medicine 21 22 (REALM) The REALM is a and the Test of Functional Health Literacy in Adults (TOFHLA). word recognition test that assesses whether a person can correctly pronounce a series of health- related words listed in order of increasing difficulty. The REALM has been validated as an instrument of reading ability and is highly correlated with traditional reading assessments in the 21 educational literature (correlation with the Wide Range Achievement Test [WRAT]: r = 0.88). The TOFHLA employs a different approach and assesses both reading skills and numeracy. It assesses reading skills using a modified cloze procedure. In this procedure, subjects read -related passages in which every fifth to seventh word has been deleted; they then fill in health 22 the blanks by selecting the correct word from four choices. The TOFHLA assesses numeracy by asking a subject to respond to health- related prompts, such as pill bottle instructions and appointment slips. While developing and validating the TOFHLA, the authors found tha t the reading comprehension subtest and quantitative or “numeracy” subtest were highly correlated (r = 0.79). The TOFHLA has also been noted to be highly correlated with the REALM (r = 0.84) 22 23 A short version (S -TOFHLA) ble and has also been widely is availa and the WRAT (r = 0.74). applied in the literature. The most common instruments used to measure numeracy in the health literature are the Schwartz and Woloshin Numeracy Test and the WRAT math subtest. Neither of these focuses h context. The Schwartz and Woloshin Numeracy Test consists of three specifically on the healt items that assess individuals’ understanding of probability and their ability to convert between 24 percentages and proportions. The WRAT math subtest assesses individuals’ ability to count, 25 read numerical symbols, and perform simple arithmetic operations. A growing number of newer tools (e.g., Diabetes Numeracy Test) measure numerical skills in the health context, but acy and health have not been widely employed to assess the relationship between numer outcomes. No gold- standard instrument is currently available to assess adequately the more global concept of health literacy, including the interactions of reading ability, numeracy, and oral , work to define and measure a wider set of literacy. However, as recommended by policymakers 26 skills that might more adequately reflect health literacy has begun. 3

26 Table 1. Measures of health literacy Health Method of Type of Score Description of Test Focus Assessment Validation Instrument Chew 1 - Categorical score: - reported report item self - Self Partial Yes Subjective validation assessment of inadequate Literacy confidence in filling out literacy/literacy 27 Screener hospital forms; 2 additional items were tested, but didn’t increase performance of measure Demographic Demographics 1. Continuous score Yes Yes A demographic Assessment of -91) (14 assessment of the used to predict Health Literacy lity likelihood of low health reading abi 28 (DAHL) 2. Categorical score: -TOFHLA literacy; S 0-53: inadequate scores predicted from 4 53-100: marginal/ demographic variables: age, gender, race, education Hebrew Health 12-item instrument, Partial Yes Reading 1. Continuous score 29 Literacy Test validation assessing reading comprehension (0-12) comprehension and method) (Cloze quantitative skills plus quantitative 2. Categorical score: -TOFHLA) (based on s skills test 0-2: low 3-10: marginal 12: high - 11 Literacy 1. Continuous score 60 - item word Word Yes Yes Assessment recognition test for recognition for Diabetes diabetes 2. Grade level (4th- 30 (LAD) 16th) Length ≤ 3 minutes Medical 42-item measure of Word 1.Continuous score Yes Partial Terminology health literacy; recognition and (range NR) validation Achievement designed with small pronunciation Reading Test print size and glossy test 2. Categorical score 31 (MART) cover to allow patients (grade level range an excuse for difficulties NR) in completing the task National Adult Reading No; ~200 questions 1. Continuous score Yes Literacy passages, measuring literacy however, (0-500) Survey documents, (prose, quantitative, health 11 (NALS) word problems questions and document literacy); 2. Grouped into 5 delivered by item - embedded levels (1-5, 5 best): in survey response theory; Level 1: <224 includes questions on Level 2: 225- 274 health literacy 324 Level 3: 275- 374 Level 4: 325- ≥375 Level 5: 4

27 Table 1. Measures of health literacy (continued) Method of Health Instrument Assessment Type of Score Description of Test Focus Validation National 1. Continuous score Reading Yes ~200 questions Yes, Assessment of (0-500) passages, measuring functional separate Adult Literacy health documents, health literacy (prose, 12 (NAAL) 2. Grouped into four quantitative, and literacy word problems categories: below document literacy), assessment basic, basic, - delivered by item intermediate and response theory; proficient literacy includes separate 28- level item subtest on health literacy Newest Vital 6 questions about an Partial Yes 1. Continuous score Document and 32 Sign quantitative ice cream nutrition label (0-6) validation literacy skill test Length: 3 minutes 2. Categorical score: < 2: low literacy 2-4: possible low literacy > 4: adequate literacy Nutritional Reading 28-item assessment of Yes Yes Continuous score Literacy Scale comprehension reading comprehension (0-28) 33 (NLS) (modified -cloze in the context of food method) content areas such as foods, fiber, calcium, and sugar Rapid Estimate item Yes Yes 1. Continuous score 66 - measure of Word of Adult (0-66) recognition and health literacy Literacy in pronunciation Medicine Length about 1 to 2 2. Grade level: 21 (REALM) 3rd grade 0-18: < minutes 19-44: 4-6th grade Also available in short 45-60: 7th- 8th grade 61-66: 9th grade > form as REALM -R and REALM -SF and for special populations as -30 and REALD 34- 37 REALM - Teen Short 1. Continuous score Word Yes 50 - item instrument that Yes Assessment of includes word (0-50) recognition and Health Literacy reading recognition and for Spanish 2. Categorical score: comprehension test to comprehension Adults 0-37: inadequate examine health literacy 38 (SAHLSA) 38-50: adequate for the Spanish- speaking population Single Item Partial Yes 1 - item assessment of Continuous score report - Self Literacy validation whether an individual (0-5) Screener needs help reading 39 (SILS) -off health-related materials Categorical/cut score: -5: positive SILS 2 SILS < 2: negative 5

28 Table 1. Measures of health literacy (continued) Method of Health Assessment Type of Score Description of Test Focus Validation Instrument Test of 1. Continuous - item measure of Reading 67 Yes Yes Functional health literacy, including weighted score comprehension Health Literacy (0-100) (Cloze method) reading comprehension in Adults and quantitative skills and quantitative 22 (TOFHLA) 2. Categorical score: skills test 0-59: inadequate Length about 20 to 25 60-74: marginal minutes. Available in 75-100: adequate Spanish and English Also available in short form (S-TOFHLA) and for special populations - as British version (UK TOFHLA) and dental 40 version (TOFHLiD); length about 5 to 10 minutes Wide Range Continuous score Yes 57 - item measure of Word No Achievement (0-57) literacy from recognition and Test, Reading pronunciation educational literature subtest 41 (WRAT) Length about 10 minutes Woodcock Yes No Test of literacy from Continuous score Reading Johnson, comprehension (0-43) educational literature Passage (cloze method) Comprehension Length 60 to 70 42 SubTest minutes 6

29 Table 2. Measures of numeracy Health Type of Score Description of Test Focus Validation Instrument Method of Assessment Diabetes Yes - Yes item scale assessing Addition, subtraction, 43 Percentage of Numeracy Test essential numeracy skills correct responses multiplication, division, fractions 43 (DNT) - for diabetes self and decimals, multistep Performance on management. Topic mathematics, time, numeration, the DNT areas include: nutrition, correlates with counting Includes word problems; exercise, blood glucose diabetes interpretation of tables, graphs, monitoring, oral - knowledge, self or figures; and selection of medications, insulin efficacy, necessary math functions to behaviors, and 30 minutes to administer solve diabetes -specific glycemic control problems Lipkus Percentage of Yes Converting percentages to No 8 or 11 questions Numeracy proportions, proportions to correct responses assessing numeracy 44 Test percentages, and using probability Schwartz and Yes 3 word problems No Percentage of 1. Probability Woloshin 2. Converting a percentage to a assessing numeracy correct responses Numeracy proportion 24 Test 3. Converting a proportion to a percentage Subjective report 8 Not reported item measure of - Yes No Self - Numeracy perceived ability to , 46 45 Scale (SNS) perform various mathematical tasks and preference for the use of numerical vs. prose information Test of Yes Continuous score Yes 17 - item scale assessing Assessed the ability to employ Functional 50) (weighted 0- ability to apply numbers numbers in health setting Health Literacy through interpretation of pill in health context in Adults bottles, appointment slips, etc. (TOFHLA), 22 numeracy Wide Range Counting, No 55 - item scale assessing Continuous score Yes Achievement ills (0-55) numeracy sk reading number symbols, Test solving simple arithmetic WRAT -3, Length about 15 minutes problems arithmetic 25 subtest Standard scores and percentiles compare individual performance with that of others of the same age Woodcock Yes No Continuous score 63 - item numeracy test Identify relevant information to Johnson, from educational solve problems, simple (0-63); converted applied arithmetic to literature problems demographically 47 subtest corrected z - scores with mean of 0 and standard deviation o f 1 7

30 Measuring Health Literacy vs. Literacy As we note in our original report (and reiterate above), several of the primary instruments used to measure health literacy are highly correlated with general measures of literacy applied in 21 the health care setting. This suggests that health literacy and literacy measures are strongly related. It has additionally raised questions about what terminology to apply to measures in the 48 field. In this review, in distinction to our earlier report, we focus on “health literacy” rather than “literacy.” We made this decision for several reasons. First, we were interested in expanding our -20 17 review to be consistent with the recent conceptions of health literacy skills that separately focus on print literacy, n umeracy, and oral literacy. To acknowledge this spectrum of skills, we felt it important to focus on health literacy. The traditional conception of literacy has focused 18 more narrowly on print literacy and numeracy skills. Second, an increasing number of newer measures (e.g., Newest Vital Sign, Diabetes Numeracy Test) are framed in specific health contexts and assess condition- related skills. Finally, measures of health literacy, print literacy (including prose and document literacy), and numeracy are highly correlated in national 18 samples. Although we believe our focus on “health literacy” appropriately represents the directions of research and policy in the field, we acknowledge that the literature contributing to this field does not organize itself neat ly within our health literacy framework. For instance, several measures of health literacy assess a combination of print literacy and numeracy skills (e.g., Newest Vital Sign, TOFHLA), making distinctions between print literacy and numeracy difficult. Furt hermore, the quantitative skills components of some measures (e.g., TOFHLA) have been extracted and used independently as measures of numeracy. To simplify this report, we separate “health literacy” (including any studies that presume to measure literacy o r health literacy) from “numeracy” and “oral literacy.” Relationship B etween Health Literacy and Outcomes -reaching In the past 15 years, researchers have demonstrated that low literacy can have far 49 ,50 matic review and related articles, consequences for an individual’s health. In our 2004 syste we identified 44 articles describing results that addressed the relationship between literacy and use of health care services, health outcomes, costs of health care, and disparities. The report found that low or inadequate literacy (compared to adequate literacy) was strongly associated 49 ,50 with poorer knowledge or comprehension of health care services and health outcomes. Limited literacy was also associated with higher probability of hospitalization, higher prevale nce and severity for some chronic diseases, poorer global measures of health, and lower utilization of ,50 49 In many cases, however, the evidence was mixed; both screening and preventive services. 49 ,50 Although literacy was often outcomes assessed and analytic methods differed across studi es. related to health outcomes in bivariate associations, the relationship sometimes weakened and became statistically nonsignificant after the investigators adjusted results for covariates such as age, education, socioecon omic status, health care access, or experience in the health care setting, calling into question whether low literacy was truly an independent problem or merely a marker of other social problems. Outcome differences were rare between a middle literacy grou p (marginal) and the adequate group. Only one study that was reviewed examined differences in costs and one study examined differences between race or ethnicity groups, resulting in insufficient data to reach conclusions concerning these issues. 8

31 Based on these findings, the 2004 review recommended that future research: (1) examine more closely and include in analytic models factors that may be confounding the relationship between literacy and health outcomes (e.g., age, income, or health insurance status); (2) consider other factors, referred to as mediators, that may be in the causal pathway between health literacy and health outcomes (e.g., self -care, trust, and satisfaction); (3) consider -efficacy, self prospective cohort studies to examine the relations hip between literacy, age, and changes in health outcomes such as health status; (4) stratify outcomes by numeracy level to gain a greater understanding of how these skills may uniquely affect health outcomes and under what conditions numeracy would be a useful indicator for targeting individuals for interventions; and -related disparities. (5) examine the effect of literacy on costs and on racial, ethnic, and age Effects of Interventions To Reduce Burden of Low Health Literacy ,51 49 In our prior review, we identified 29 articles describing interventions to mitigate the effects of low literacy on health outcomes. Of the 29 articles, 20 measured literacy in individual participants and were performed in developed countries. These 20 studies tested a wide ra nge of interventions for improving health outcomes in patients with poor literacy. Most of the interventions occurred in a single session and attempted to make health information more readily available to patients with limited literacy. Some studies compar ed standard handouts with materials that were written in simpler, easier -to-read prose. Others compared standard materials -ROMs specially designed for low with pictographs, booklets, videotapes, or CD -literacy audiences. A few interventions used multiple m ethods. In aggregate, these studies suggested that interventions may reduce the adverse health effects ,51 49 associated with low literacy. However, few studies examined each type of intervention; few examined the interventions’ effects in literacy subgroups ; a minority examined outcomes other than knowledge; and many had methodological flaws limiting conclusions. Based on observations from our 2004 review, we recommended that (1) additional studies of sure the interventions’ effects by interventions be pursued, (2) any new investigations mea literacy subgroup, and (3) investigations examine a broader range of outcomes. Need for Update of the Earlier Review Given the ongoing concern about an association between health literacy level and poor health outcomes an d the potential to reduce these outcomes with novel interventions, the US Department of Health and Human Services (HHS) has released a National Action Plan to 52 53 Additionally, several national organizations, including the IOM, the Improve Health Literacy. 5 American Medical Association (AMA), the National Institutes of Health (NIH), and HHS 3 Healthy People 2010 ), ( have promoted health literacy as a research priority. With such attention, the research community in this field has responded with considerable new work since 2004. Additionally, AHRQ has released a Health Literacy Universal Precautions Toolkit based 54 on evidence and best practices. To synthesize the increasing volume of literature on health literacy and further the larger goal in health literacy, AHRQ commissioned the RTI –UNC EPC to update its 2004 of improvements systematic review to examine the effects of health literacy on health outcomes and interventions as the to improve those outcomes. In this updated report, we focus on the same key questions — original report, but we expand our conception of literacy to health literacy and consider 9

32 separately and in combination —print literacy, numeracy, and oral health literacy skills. In the only studies that have been results chapters of this report (Chapters 3 and 4), we include published since our last review; we did not systematically reabstract studies from our earlier review or reassess their quality. We did, however, reorganize data about intervention studies tures of the interventions reviewed earlier and allow from our first review to highlight fea interpretation of these features in light of current evidence. Additionally, we compared all findings from the current review to findings from our 2004 review to allow for comprehensive conclusions. Fur ther, following our review of information available through publications and our review of the quality of the studies based on that information, we queried intervention authors from both the first review and this updated review about key features of the interventions that they had not reported in published articles. This additional information is included in Appendix A. Production of This Report Organization Health literacy is of particular concern to the AMA, which had originally nominated the topic in 2004, and whose continued interest in the topic is expressed through their representation on the Technical Expert Panel (TEP) for the update review. The earlier report was updated to incorporate an expanding literature and an ongoing interest in the topic are a. Our new systematic review consolidates and analyzes the body of literature that has been produced to date regarding the relationship between health literacy and health outcomes and the evidence about interventions intended to improve the health of peopl e with low health literacy. Chapter 2 describes our methodological approach, including the development of key questions (KQ s) and their analytic framework, our search strategies, and inclusion/exclusion criteria. In Chapter 3, we present the results of our literature search and synthesis of KQ 1 concerning the relationship between health literacy and numeracy levels and health outcomes and we evaluate the strength of the evidence concerning these outcomes. In Chapter 4, we present the results of our litera ture search and synthesis of KQ 2 concerning interventions to assist populations with low health literacy and evaluate the strength of the evidence concerning these interventions. Chapter 5 further discusses the findings and offers our recommendations for future research as well as for clinicians and policymakers. Chapter 5 is followed by the list of references. Appendixes are provided electronically at Appendixes and Evidence Tables for this report are provided electronically at http://www.ahrq.gov/clinic/ tp/lituptp.htm and provide a detailed description of our search strings (Appendix B), our Full -Text Inclusion/Exclusion Form and our quality review form used for evaluating the internal validity (including risk of bias) of tailed evidence tables (Appendix D), poor quality studies included studies (Appendix C), de (Appendix E), Strength of Evidence (SOE) tables (Appendix F), peer reviewers (Appendix G), excluded studies (Appendix H), full bibliography (Appendix I), and summary tables of KQ 1 findings from our original literacy and health outcomes report (Appendix J). Technical Expert Panel We identified technical experts in the field of health literacy to provide assistance throughout the project. The TEP was expected to contribute to AHRQ’s broader goals of ( 1) creating and maintaining science partnerships as well as public -private partnerships and (2) meeting the needs of an array of potential customers and users of its products. Thus, the TEP was both an additional 10

33 resource and a sounding board during the pr oject. The TEP included eight members: five technical/clinical experts; one member whose expertise and mission concerns the interests and perspectives of patients and consumers; one potential user of the final evidence report; and an AHRQ health literacy e xpert (see Acknowledgments, page iv). To ensure robust, scientifically relevant work, the TEP was called on to provide advice on substantive issues or possibly overlooked areas of research. TEP members participated in -mail to refine the scope of this update (including conference calls and discussions through e inclusion/exclusion criteria) and discuss our preliminary assessment of the literature. Because of their extensive knowledge of the literature on health literacy, including numerous articles authored by TEP members themselves, and their active involvement in professional societies and as practitioners in the field, we also asked some TEP members to participate in the external peer review of the draft report. Use of This Updated Systematic Review This u pdated report addresses the key questions outlined in Chapter 2 through a systematic review of published literature. We anticipate that the report will be of value to the AMA for its various efforts to inform and educate physicians. This report can also inform practitioners about the current state of evidence and provide an assessment of the quality of studies that aim to improve health for people with low health literacy. Researchers can obtain a concise analysis of the current state of knowledge in this f ield and will be poised to pursue further investigations that are needed to improve health for low -health -literacy populations. Health educators can also use this report to guide future interventions to improve health communication. Finally, policymakers can use this report to inform new strategies and the allocation of resources toward future research and initiatives that are likely to be successful. 11

34 Methods −University of In this chapter, we document the procedures used by the RTI International North Ca -based Practice Center (RTI −UNC EPC) to develop this comprehensive rolina Evidence evidence report Health Literacy Interventions and Outcomes , an update to our 2004 systematic review Literacy and Health Outcomes . The key questions (KQ s) for this update review are the literacy has been replaced by the same as those in the original review, with the exception that broader term health literacy . This decision, which is discussed in detail in Chapter 1, was se quantitative information) and oral primarily made to acknowledge numeracy (the ability to u literacy (the ability to listen and speak effectively) in addition to print literacy. Thus, in this review as in our original report, we include studies that purport to measure either participants’ health literacy or their general literacy in a health setting; we, however, refer to these measures in aggregate as measures of health literacy. We additionally separately review studies of numeracy and health outcomes to highlight the findings from this relatively new body of research. Although we attempted to review the relationship between oral health literacy skills and health outcomes, we found no studies that measured oral health literacy skills that met our other inclusion criteria. ng an updated review is discussed below. To provide a Our specific methodology in conducti framework for the review, we first present changes from our prior review. We then describe the KQ s and their underlying analytic framework, our inclusion and exclusion criteria, search and retrieval pr ocess, and methods of abstracting relevant information from the eligible articles to generate evidence tables. We also discuss our criteria for rating the quality of individual studies and for grading the strength of evidence as a whole. Our overall goals were to evaluate whether newer literature was appropriate for answering our key questions and to determine whether earlier conclusions changed. We modified the original methods as follows: h the Ratzan and • We broadened our definition of health literacy to be consistent wit Parker (2000) definition used by Healthy People 2010 and the Institute of Medicine. Thus, we now include studies that evaluated the numeracy skills of participants. Our (spoken) health inclusion criteria also encompassed studies that used measures of oral -based approaches to health literacy measurement, but we did literacy or other skills not find any such published studies. • We examined the outcome of knowledge only in relation to outcomes related to numeracy level and intervention studies because evidence in the earlier review clearly concluded that greater literacy skills and higher health- related knowledge levels are positively related. • We required that studies directly measured the health literacy of the study population and did not conc lude health literacy level via self -report or similarity to other populations. • We modified criteria for evaluating individual study quality to incorporate advances in the methodology of conducting systematic reviews, including not using a numeric summary of individual criteria in determining the overall quality rating. • We included studies conducted in developing countries as long as an objective assessment of literacy or health literacy was measured directly in participants. 12

35 • If information was missing from articles about intervention studies, we queried the investigators to allow richer interpretation about what interventions may be effective in mitigating the effects of low health literacy. Key Questions and Analytic Framework Based on the growing appreciation of the complexity of the relationship between health literacy and obtaining medical care and achieving good health outcomes, we pose two key questions in this report. Both have four parts. . Are health literacy skills related to KQ 1 Use of health care services? (a) Health outcomes? (b) (c) Costs of health care? (d) Disparities in health outcomes or health care service use according to race, ethnicity, culture, or age? KQ 2 . For individuals with low health literacy skills, what are effective interventions to (a) Improve use of health care services? (b) Improve health outcomes? (c) Affect the costs of health care? (d) Improve health outcomes and/or health care service use among different racial, ethnic, cultural, or age groups? 13

36 Figure 1. Analytic framework for the health literacy systematic review Figure 1 depicts the analytic framework for our KQ s. Solid lines show the relationship between health literacy skills and outcomes (KQ 1) and between interventions and outcomes (KQ 2); dotted lines show factors that might influence or be intermediaries in these relationships. Figure 2 outlines a more detailed logic model explicating outcomes that were included in our review. This model draws both on several models of health literacy proposed by researchers in 55,56 The Integrative Theory, proposed the field and on an integrated model of behavioral theory. by Fishbein in 2000, reflects a growing consensus that (1) a core set of variables (e.g., attitudes, social norms, and self ajor predictive theories of behavior change -efficacy) derived from the m (e.g., Health Belief Model, Theory of Reasoned Action, Social Cognitive Theory) are responsible for most of behavioral intention, and that (2) these variables, in combination with an 55 adequate skill set and remova l of environmental constraints, predict actual behavior change. 14

37 Figure 2. Logic model for the health literacy systematic review Our logic model was used to determine whether studies considered for inclusion have relevant health outcomes. It also g uided our presentation of included articles. It was not meant to be a definitive guide to the relationship between variables because many of these relationships have not been explicitly tested in the field of health literacy. Furthermore, it was not meant to provide a definitive statement about what constitutes a “good outcome.” For some outcomes in the logic model, increases represent the good outcome (e.g., adherence, most screening tests). For other outcomes, decreases represent the good outcome (e.g., hospitalizations, mortality). For KQ 1a and 2a, we consider any process of care as a health service; this includes clinic and hospital visits, hospitalizations, and use of preventive and screening services. For KQ 1b and 2b, we use the term “health outcome s” broadly to encompass both intermediate and distal outcomes, even though in many cases the intermediate outcomes will be only surrogates or proxies for health -related end results of care. Outcome categories include the following: 15

38 Knowledge : As described above, we consider knowledge as a final outcome only in relation to numeracy (KQ 1) and intervention studies (KQ 2). We do not include it in our consideration of the relationship between health literacy and health outcomes (KQ 1) because evidence in the earlier review clearly concluded that greater literacy skills and higher health -related knowledge levels are positively related. Self Self -efficacy: -efficacy, a person’s confidence in his or her ability to carry out a health diate outcome in many behavioral theoretical models. It is a behavior, is an important interme predictor of behavioral intent. Behavioral intent is a person’s stated likelihood of starting a behavior. It is Behavioral intent: y between health literacy level an important hypothesized intermediate step in the causal pathwa and health outcomes. Skills and behaviors: The relationship between health literacy and intermediate and ultimate outcomes depends on a person’s health skills and behaviors. Skills include a person’s ability to recognize emergency situations, seek additional health information, or access needed health care. Behaviors include actions such as taking medication, changing one’s lifestyle, or monitoring one’s health. Adherence is the ability to car ry out a health behavior over a Adherence to health behavior: meaningful period of time, such as regularly taking a medication “as prescribed” over the period of time for which it is prescribed. Adherence is an important predictor of health outcomes. Measures of disease incidence, prev alence, morbidity, and mortality: This category includes such outcomes as rates of physical and mental health conditions, stages of cancer presentation, severity of diseases, measures of disease control and complications, and death rates. These y be measured by biomarkers, validated survey instruments and questionnaires, outcomes ma -report, or, in the case of mortality, vital records or proxy reports. patient self This outcome includes generic (and condition- specific) measures of health status Health status: or health -related quality of life; the domains of interest are physical health and mental health functioning (e.g., cognitive abilities), pain or fatigue, and perhaps social functioning and social networks. They are usually assessed by self -report questionnaires that have been shown to predict health outcomes. Of particular note for KQ 1b is that we did not examine outcomes related to attitudes. This decision was based on the belief that attitudes result from knowledge, which, as described above, is not e xamined in the current report. Further, we did not examine outcomes related to social norms or patient -provider relationships (e.g., shared decisionmaking) because we thought that these variables likely affected the direction or strength of the relationshi p between behavioral intent and health outcomes rather than lying on the causal pathway. Clearly, however, empiric work is needed to test these assertions prior to future reviews. For KQ 1c on measuring the cost of health care, we included any study that measured the monetary cost of health care services, including both direct and indirect costs. For KQ 2c, we also included studies measuring the cost of the intervention. 16

39 Finally, to address KQ s 1d and 2d concerning disparities in health outcomes and use of health care services, we looked for studies that reported on health literacy level as a mediator of the relationship between age, race, ethnicity, or cultural background and health outcomes (or the moderators of the strength s that reported effectiveness of interventions) and also included studie of the relationship between health literacy and health outcomes. This distinction between mediating and moderating is important. A moderator affects the direction or strength of a relationship between an independe nt and dependent variable and is generally examined by looking for differential effects in subgroup analysis. A moderator effect is commonly observed in an analytic model through a statistically significant interaction of the exposure and the for that relationship, answering the question accounts moderator. A mediator, on the other hand, as to how or why things occur. There are multiple approaches to mediation analysis, including path analysis, structural equation modeling, and methods such as those propose d by Baron and 57 Kenny. All test the relationships between the exposure and mediator, mediator and outcome, and exposure and outcome before and after adjusting for the mediator. To determine mediation, ionship between the exposure and outcome they require a reduction in the magnitude of the relat when the mediator is added to the model. Literature Search and Retrieval Process Database Search Terms To identify the relevant literature for our review, we searched five electronic databases: ® MEDLINE, ative Index to Nursing and Allied Health Literature (CINAHL), the the Cumul Cochrane Library, PsychINFO, and the Educational Resources Information Center (ERIC). For health literacy, we searched using a variety of terms limited to English and studies conducted with human participants (no laboratory or animal studies) published from 2003 to May 25, 2010. For numeracy, we searched the same databases from 1966 to May 25, 2010. We conducted key -literacy -related articles. word searches because no MeSH headings specifically identify health The terms “health literacy,” “numeracy,” and “literacy,” and terms or phrases related to instruments known to measure health literacy and numeracy were the focus of the search. We limited the “health literacy” and “literacy [tw = ‘text wo rd’]” searches to 2003 forward (including up to 1 year overlap with our earlier review) to be confident that we did not miss studies between the first review and this update, and we compared new and earlier reference lists sarily overlap with the literature reviewed earlier. Editorials, to ensure that we did not unneces letters to the editor, and case reports were excluded. Across all databases searched, our initial searches yielded 2,855 citations (Appendix A). We reviewed our search strategy with the TEP and further supplemented our electronic searches by hand searching pertinent excluded articles, including other reviews. We imported all citations into an electronic database (EndNote X.3) for a final unduplicated yield of 3,496 articles. Study Selection P rocess Inclusion and Exclusion Criteria For each KQ , we developed detailed eligibility criteria with respect to population, 58 intervention, comparison, outcomes, time frames, and settings (the PICOTS framework). The final criteria include the following: 17

40 KQ 1 . Relationship of health literacy levels to utilization, outcomes, costs, and disparities Population: Individuals and caregivers of all races and ethnicities. Intervention: Not applicable. Comparison: Different levels of health literacy or numeracy skills. For studies of outcomes by levels of health literacy, relevant health or cost outcomes Outcomes: with the exception of knowledge; the relationship between literacy and health- related knowledge was considered well -established through the earlier review. For studies of outcomes by and knowledge. numeracy levels, relevant health or cost outcomes -sectional or longitudinal studies, with varying lengths of time for followup, and Cross Time: with no restrictions for when the studies or data collection activities were done. Setting: No exclusions by setting, so includes inpatient or outpatient settings in health care -based settings, or homes. systems and institutions, various community . Effective interventions to improve utilization or health outcomes or to KQ 2 affect costs or disparities among low literacy individuals Population: Populations including individuals and caregivers of all races and ethnicities with only low health literacy. Although the ideal populations to answer our question would include individuals with low health literacy, much of the research about interventions designed to mitigate the effects of low health literacy has been done in populations that include a combination of low and high health literacy individuals and failed to perfor m separate analyses in these subgroups. Instead of excluding a large portion of the intervention literature, we decided to permit inclusion of populations with a combination of low and high literacy individuals (but no subgroup analysis), knowing that they may provide only indirect information about the effect of interventions on an exclusively low literacy population. All interventions specifically designed to mitigate the effects of low health Intervention: -literacy or -health literacy by improving the use of health care services or health outcomes in low -numeracy individuals; this includes, but is not limited to, interventions designed to simplify low information presentation, circumvent poor reading skills (e.g. video), facilitate patient/provider -efficacy or health unication, circumvent barriers to health care, improve self comm -related skills. Comparison: Any comparator designated by the investigators. A comparator is not necessary for studies with pre/post -intervention measures. Outcomes: Any health -related health care utilization, outcome, or cost. Time : Studies (controlled and uncontrolled trials and observational studies) with varying lengths of time for followup and with no restrictions for when the studies or data collection activities were done. 18

41 Setting: No exclusions by settings. Based on the final KQ s specified above, we generated a list of inclusion and exclusion criteria (Table 3). We included prospective and cross -sectional observational studies of health oped for low -health -literacy populations, and trials of outcomes, trials of materials devel interventions that compared materials designed to be “easier to read or understand” with standard materials. We limited studies to those with outcomes related to health and use and costs of health ser vices. Because this is an update to our original report, we limited our searches to studies that would not have been considered during the earlier review (e.g., those more recently published or those for which numeracy was the exposure). As described in Ta ble 3, we excluded studies for several reasons, including lack of any outcome of interest or results limited to the readability of materials. We also excluded studies that focused on literacy or health literacy as an outcome rather than an exposure, as is seen, for instance, in studies of physician office -based programs designed to improve children’s literacy or studies of sociodemographic characteristics more likely to be associated with differences in health literacy level. We also excluded studies that u sed cognitive impairment or dementia as an outcome of interest because we would not be able to determine whether health literacy levels were causing or being affected by the condition. 19

42 Table 3. Inclusion/exclusion criteria for studies considered in this u pdate Criteria Category Study population All races, ethnicities, and cultural groups. Patients of all ages and caregivers whose primary language is the same as that of the health care provider or intervention material. Health literacy, numeracy, or oral health literacy levels of the population must be reported. Published from 2003 to May 25, 2010: Print literacy or health literacy studies meeting Time period other inclusion criteria and newly published since our earlier review. Published from 1980 to May 25, 2010: Numeracy and oral health literacy studies excluded from the earlier review and meeting other inclusion criteria. English only. Publication criteria Articles in print. nal, articles in Excluded were articles accepted for publication but not in print in the jour the so - called “gray literature,” and articles we could not obtain during the review period. Admissible evidence Original research studies that provided sufficient detail regarding methods and results to (study design and other enable use and adjustment of the data and results. Eligible study designs included criteria) and- after studies; before- controlled trials; and observational studies: prospective and retrospective cohort studies, case control studies and cross -sectional studies. Relevant outcomes must be able to be abstracted from data presented in the papers. Sample sizes must be appropriate for the study question addressed in the paper; single case reports or small case series (fewer than 10 subjects) were excluded. Other study exclusion criteria included studies of dyslexia and dementia. of normal reading development in children. with no health outcomes or no use of health care services. with an outcome limited to satisfaction or likeability of one intervention material to another, or attitudes, perceived social norms, or patient compared -physician interaction measures. solely about the readability of materials, but not about the relationship between health literacy and outcomes when readability is the focus of the intervention. in which health literacy, numeracy, or oral health literacy are not directly measured in the population by an objective measure or linked to outcomes at an individual level. in which the outcome is limited to dementia or cognitive impairment. in which heal th literacy is the exposure (KQ 1) and the only study outcome is knowledge. of the basic experimental science of reading ability (e.g., studies of brain function, including results from magnetic resonance imaging or electroencephalogram) or basic educational achievement. solely or chiefly for validation of an instrument. in which the intervention was not designed to address low health literacy or numeracy. Process for Considering Abstracts and Full Articles for Inclusion Once we had identified articles through the electronic database searches, review articles, and reference lists, we examined abstracts of articles to determine whether the studies met our criteria for inclusion. Each abstract was independently, dually reviewed for inclusion or exclusion. If one reviewer concluded that the article should be included in the review, we obtained the full text. If two reviewers independently determined that the abstract did not meet eligibility criteria, we excluded it. In the full article review, two team memb ers again read each article and decided whether it -Text Inclusion/Exclusion Form (Appendix C). Reviewers met our inclusion criteria, using a Full 20

43 discussed any disagreements, and, if they could not resolve them, the disposition of the article was decided b y discussion among the larger team. Excluded articles are listed in Appendix H. Literature Synthesis Development of Evidence Tables and Data Abstraction Process The senior staff members for the systematic review jointly developed the design of the evidence tables. Evidence tables were designed to provide sufficient information to enable readers to understand the study and to determine study quality. In our design, we gave particular emphasis to essential information to answer our KQ s and to determine study quality. The format of the tables, which was based on successful designs used for many prior systematic reviews from this EPC (not just the review of health literacy and outcomes), varied slightly by KQ; the tables for KQ 2 have additional columns that de scribe the control group, the intervention group, and specifics of the intervention. We trained abstractors by having them abstract several articles into evidence tables and then reconvened as a group to discuss the results, including the utility of the ta ble design. The abstractors repeated this process several times until everybody was capable of working with the tables, instructions, and other elements of the process. Abstractors entered data directly into evidence tables. The first abstractors entered all relevant information into the evidence table. Second reviewers subsequently checked each abstraction for accuracy and completeness against the original articles. Abstractors reconciled all e tables. disagreements concerning the information reported in the evidenc Abstractors, at the time of initial data abstraction, also performed a quality review (internal validity including risk of bias relevant to the study design) and rating of each study, using a separate quality review form for this process (Appendi x C). As with data abstraction, second reviewers independently conducted a quality review and rating of each article. When ratings conflicted, each pair of reviewers discussed the problem; issues they could not resolve were olution. brought to a third party for res The final evidence tables for KQ 1 (health literacy and numeracy separately) and KQ 2 are presented in their entirety in Appendix D. Entries for all evidence tables are listed alphabetically by the last name of the first author; multiple articles by the same team of authors are entered alphabetically by second or later authors. A list of abbreviations used in the evidence tables appears at the beginning of the appendix. Quality Rating of Individual Studies To assess the quality (internal validity including risk of bias) of studies, we used predefined criteria based on those developed for the earlier review. We adapted criteria from the US Preventive Services Task Force, the National Health Service Centre for Reviews and , and a Evi dence -based Practice Center Systematic Review Manual Dissemination, the AHRQ’s 59 We specifically report on the quality of observational studies developed by the RTI -UNC EPC. addressed methodological issues including selection bias, measurement bias, confounding, and power. Unlike our previous review, we rated the overall quality of studies qualitatively. In general terms, a “good” study has the least bias and results are considered to be valid. A “fair” study is ts results. A “poor” rating susceptible to some bias but probably not enough to invalidate i indicates significant bias (stemming, e.g., from serious errors in design or analysis) that may 21

44 invalidate the study’s results. Studies rated as “poor” were excluded from the analysis. A copy of the form used for quality rating a study is included in Appendix C. As described above, two independent reviewers with no conflict of interest assigned quality ratings to each study. Disagreements were resolved by discussion and consensus or by discussion with the larger study team. Studies that met all criteria were rated good quality. Studies received a quality rating of fair when they presumably fulfilled all quality criteria but did not report their methods to an extent that answered all our questions or did not adequately fulfill all quality criteria. Thus, the fair -quality category includes studies with quite different strengths and weaknesses. Studies that had a fatal flaw (defined as a methodological shortcoming that leads to s were rated poor quality and excluded a very high probability of bias) in one or more categorie from our analyses. Poor -quality studies and reasons for that rating are presented in Appendix E. In situations where we concluded different quality ratings for different outcomes within the same study, we provide the quality rating for each. Data Synthesis We synthesized the data in our review qualitatively. We did not have a sufficient number of studies with similar outcomes or similar interventions to consider quantitative analysis (meta - analysis or statistical pooling) of data. Furthermore, we primarily considered only information from the current searches. Given changes in our evidence tables and quality forms, we reviewed individual studies from the 2004 review in depth if new evidence would seem to change only ove rall conclusions. Because the structure of analysis for KQ 2 changed for this current review, we reorganized the 2004 review findings from KQ 2 to be consistent with our current organizational structure for results. As part of data synthesis, we paid parti cular attention to a few issues. First, we closely examined whether studies accounted for relevant confounders in their analyses. Because the goal of etiologic research focuses on understanding the relationship between exposures and outcomes t is important that confounders are controlled for to determine accurate estimates of of interest, i effect. Second, we looked closely at studies that reported the relationship between both health literacy and numeracy and the same outcome. This allowed inferences about the relative strengths of the relationships between the variables and the outcome. Third, for intervention studies, we looked at common features of successful interventions and at the impact of nce about the effective components interventions on multiple related outcomes. This allows infere and mechanisms of health literacy interventions. Grading the Strength of Available Evidence We evaluated the strength of evidence based on the AHRQ Methods Guide for Comparative 60 . Effectiveness Research To determine ove rall strength, we first examined several key features contributing to evidence strength: risk of bias, consistency, directness, precision, and the presence of other modifying factors. We then combined these factors to grade the overall strength of evidence . As described in Owens et al., the evaluation of risk of bias includes 60 quality studies We judged good- assessment of study design and aggregate quality of studies. with strong designs to yield evidence with low risk of bias. We graded evidence as consist ent when effect sizes across studies were in the same direction and of similar magnitude. For studies addressing KQ1, when the evidence linked differences in health literacy skill level or interventions directly to health outcomes, we graded the evidence a s being direct. For studies addressing KQ2, the evidence was graded as direct when at least one study for any given type of 22

45 intervention or outcome included low literacy specific analyses. We graded evidence as being precise when results were in the same d irection and had a narrow range. Consistent with EPC policy, we independently dually evaluated the overall strength of evidence for each outcome based on a qualitative assessment of strength of evidence for each of the key features listed above. We then re conciled all disagreements through discussion by senior members of the team. The levels of strength of evidence as specified by AHRQ are shown in Table 4. Full results of our strength of evidence reviews are presented in Appendix F. Table 4. Strength of ev idence grades and definitions Definition Grade High confidence that the evidence reflects the true effect. Further research is very unlikely High to change our confidence in the estimate of effect. Moderate confidence that the evidence reflects the true effect. Further research may Moderate change our confidence in the estimate of effect and may change the estimate. Low confidence that the evidence reflects the true effect. Further research is likely to Low change our confidence in the estimate of effect and is likely to change the estimate. Insufficient Evidence either is unavailable or does not permit estimation of an effect. Applicability of the Evidence We evaluated the applicability of the evidence based on a qualitative assessment of the population, intensity, or quality of treatment, outcomes, and timing of followup. Specifically, we considered whether enrolled populations differ from target populations, whether studied interventions are comparable with those in routine use, whether measured outcomes are known to reflect the most important clinical outcomes, and whether followup was sufficient. Peer Review Process Among the more important activities involved in producing a credible evidence report i s conducting an unbiased and broadly based review of the draft report. External reviewers are clinicians, researchers, representatives of professional societies, and potential users of the report, including TEP members (see Appendix G). Peer reviewers prov ided comments on the content, structure, and format of the evidence report and completed a peer review checklist. We revised the report, as appropriate, based on comments from peer reviewers. 23

46 Results: Relationship of Health Literacy to Outcomes arities and Disp This chapter presents the results of our literature search for the project, including results for key questions (KQ s) 1 and 2. It also reports our findings for KQ 1; we illustrated and discussed ly, KQ 1 asked whether health literacy skills this KQ in Chapter 2 and Figures 1 and 2. Specifical are related to (a) use of health care services, (b) health outcomes, (c) costs, and (d) disparities in outcomes or utilization according to race, ethnicity, culture, or age. We report our results in three Organization of KQ 1 Related Tables - main sections: specific details about the yields of the literature searches For ease of navigation, all tables in the chapter and the number of studies meeting related to the KQ 1 results are presented at the end, ria to answer KQ s our inclusion crite following the text. 1 and 2, the effects of health literacy on health outcomes, and the effects of Health literacy tables: numeracy on health outcomes. In Overview of included studies (Table 5) studies that measured health literacy, Studies grouped by health literacy measurement tool we compared the new results broadly and skill -lev el groupings used (Table 6) with those found during the earlier Aggregate strength of evidence grades (Tables 8, 16, Literac y and Health review ( 30, and 32) 1 , 2004 Outcomes ). All numeracy Summary information on each included study, sorted studies are discussed in this chapter by outcome (Tables 7, 9 29, and 31) -15, 17- are new; none had been included in the earlier review. We did not find Numeracy tables: any studies meeting our inclusion Overview of included studies (Table 33) criteria addressing outcomes or Aggregate strength of evidence grades (Table 35) interventions related to oral health Summary information on each included study, sorted literacy. 42) by outcome (Tables 34, 36- References for each study are provided in the summary and Detailed evidence tables appear in Appendix D. evidence tables. By convention, references are not given in tables Literacy Summary tables from the original report ( presenting the strength of evidence. 2004) that briefly describe each and Health Outcomes, Chapter 2 describes the methods for of the studies included to answer KQ 1 appear in arriving at strength of evidence Appendix J. x F gives the domain- grades; Appendi specific scores used in deriving the overall grades. Results of Literature Search Our literature search yielded 3,496 articles (Figure 3). We also conducted full text reviews of -searching articles and Web- based bibliographies and 73 articles identified by hand recommendations from our Technical Expert Panel (TEP). Of the 3,569 articles retrieved, we excluded 2,653 articles after reviewing the abstracts and pulled 916 articles for full text review. ppendix I. Ultimately, for the two main questions, we The full bibliography is included in A included studies rated either good or fair quality: 81 studies addressed KQ 1 and 42 studies 24

47 addressed KQ 2. KQ 1 results are presented separately in relation to health literacy (86 articles) and numera cy (16 articles). Of these, 7 articles address both health literacy and numeracy. Figure 3. PRISMA tree: Flow diagram depicting review and disposition of articles Titles and abstracts through electronic database Articles identified through hand searches: searches: n = 73 n = 3,496 Total articles retrieved: n = 3,569 Full text articles excluded: Citations n = 738 excluded: n = 2,653 321 Studies that do not measure literacy or health literacy Studies with no original data 206 172 Studies with no health outcomes (i.e., descriptive only or have outcomes like likability, satisfaction) 17 Studies answering KQ 1 where literacy (not numeracy) is measured and the only study outcome is Full-text articles knowledge. retrieved: 6 Studies examining normal reading development in n = 916 children Ecological data only 5 4 Studies in which the outcome is limited to dementia or cognitive impairment. Systematic Evidence Review only 3 Articles included 2 Studies about dyslexia in this review: 1 Studies published in abstract form only n = 178 Unable to obtain the article 1 Poor quality n = 40 Good and fair quality Includes by key question (KQ): KQ 1 Total = 95 articles (81 studies) KQ 1a health literacy = 24 (23 studies) KQ 1b health literacy = 72 (60 studies) KQ 1c health literacy = 2 (2 studies) KQ 1d health literacy = 9 (8 studies) KQ 1a-d Numeracy = 16 (16 studies) KQ 2 Total = 45 articles (42 studies) KQ 2a intervention = 13 (6 studies) KQ 2b intervention = 35 (21 studies) KQ 2c intervention = 3 (2 studies) KQ 2d intervention = 0 Some articles were included for more than one KQ 25

48 . Relationship of Health Literacy to Various Outcomes and Key Question 1 Disparities We identified 86 good- or fair- quality articles reporting on 72 unique studies for this topic. Some studies report on more than one key question. These studies report results about the ealth outcomes, and costs of relationship between health literacy and use of health care services, h health care and disparities between specific racial, ethnic, cultural, or age groups. Fourteen studies were of good quality and 72 of fair quality, according to the criteria described in 2. In addition, we identified 40 studies which were considered to be of poor quality and Chapter therefore not included in the analysis (poor -quality studies are listed in Appendix E; we do not discuss them further in this review.) In the text below, we identify only studies of good quality; all others for which quality is not specifically called out are fair quality. Most studies had a cross -sectional design (N = 64), but 22 were cohort designs (Table 5). Multiple studies reported results using the same data. For instance, eight articles reported results collected during the “Prudential study.” This study was conducted with 3,260 new members in a Prudential Medicare managed care plan of enrollees in Cleveland, Ohio, Houston, -68 61 Texas, and Tampa and south Florida. iple articles include four Other studies reported in mult articles reporting on a sample of patients at Chicago, Illinois, and Shreveport, Louisiana, HIV -72 69 73 ,74 and three articles two articles reporting on pharmacy patients in Atlanta, Georgia, clinics, reporting on patients in three primary care clinics in Chicago, Illinois; Shreveport, Louisiana; 75 -77 and Jackson, Michigan. Studies examined a variety of outcome measures including use of health care services (hospitalization and emergency department visits and screening and immunizations), access to -efficacy, health behaviors, health -care- care, and health outcomes (adherence, self related skills, disease prevalence and severity, health status, and mortality). Studies also examined differences in costs and disparities related to health literacy level (Table 5). Table 6 groups KQ 1 health literacy studies based on the health literacy measurement tool used in the analysis and, further, the skill -level groupings used to distinguish study participants. We found that health literacy was most ly measured with the Rapid Estimate of Adult Literacy in Medicine (REALM; 33 articles) or the Test of Functional Health Literacy in Adults (TOFHLA) -TOFHLA; 42 articles). Three articles or Short Test of Functional Health Literacy in Adults (S used the Natio nal Assessments of Adult Literacy (NAAL), and, unlike our earlier review, no article used the Wide Range Achievement Test (WRAT; a general literacy measure that was 1 ). Literacy and Health Outcomes commonly used in studies included in our earlier review Sev eral other literacy measures (in contrast to health literacy measures intended to be used in a health care environment) were included in one study apiece: the Cape Area Panel Study Literacy and Numeracy Evaluation, a reading comprehension instrument in Nepalese, an instrument for the diagnosis of reading, and the Woodcock Language Proficiency Battery. Although the validity 42 is well known, information about these other literacy and reliability of the Woodcock battery measures is quite limited. The health literacy levels used to compare study participants evaluated using the REALM, TOFHLA, or S -TOFHLA varied among studies, ranging from a continuous measure to two, three, or even more groups. In some studies, three groups were identified (i.e., inadequate, mar ginal, and adequate); in others, two of the three groups were combined in the statistical analysis. Studies varied concerning whether the two lower or the two higher groups were combined. Conceptually, an individual’s health literacy level could change ove r time. However, the instruments included in the reviewed studies capture only static measures of health literacy or numeracy. 26

49 In contrast to our earlier review, studies reviewed in the update by and large include multivariate analyses (rather than just u nadjusted bivariate analyses) (Table 5). However, the choice of variables controlled for in analyses varied greatly across studies. Potential confounders (related to health literacy and health outcomes) controlled for in many studies include education, age, race, gender, and income. KQ 1a. Use of Health Care Services We identified 24 articles reporting on 23 unique studies examining the relationship between health literacy skills and the use of health care services. Three studies were of good quality and 21 were of fair quality. Nine studies included cohort designs; the rest were cross -sectional. These studies focused on emergency department admissions or hospitalizations, general preventive screenings (mammogram, colon, Papanicolau [Pap], sexually transmitt ed infection testing, and influenza and pneumococcal vaccination), and access to office visits and insurance. Six studies —one good- quality prospective Hospitalization and emergency department rates. 68 78 ,79 cohort study (hereafter, the Prudential study), two fai r-quality prospective cohort study, one 80 81 ,82 —examined the risk of and two cross -sectional studies retrospective cohort study, hospitalization by health literacy level (Table 7). All but one study showed a statistically significant association of increased hospitalization and use of inpatient services with lower health ,81 79 ,80 68 literacy level. Populations included the elderly, patients with asthma, and patients with 78 The one study that did not find an association with hospitalizations congestive heart failure. included a cross -sectional subpopulation of HIV -positive adolescents, which may be a healthier 82 One of the larger cohort studies, the Prudential study, population compared to the other studies. examined the impact of low health literacy on medical care use among 3,260 Prudential 68 Medicare managed care enrollees. Patients with low health literacy had higher probabilities of using inpatient services than those with adequate health literacy (mean differences in probability of use, 0.05; 95% confidence interval [CI], 0.00- 0.09). Enrollees with marginal and adequate health literacy did not differ in use of inpatient services. The strength of evidence is moderate (Table 8 and Appendix F). These findings are consistent with previous findings in our 2004 1 systematic review. 62 ,68 -quality prospective analyses from the Prudential study, Nine studies, including two good 78,79,83 80 -sectional and three cross one retrospective cohort, three other prospective cohorts, 81 ,82 ,84 studies, examined emergency and u rgent care visits by literacy level (Table 7). All but two 82 ,84 studies showed an association of greater emergency department use and low health literacy. 62 The Prudential study examined the association of emergency department visits with health literacy level. After controlling for multiple confounders, both the inadequate health literacy and the marginal health literacy groups had a higher rate of two or more emergency department visits when compared with those with adequate health literacy (marginal lite racy relative risk [RR], 2.02; inadequate literacy RR, 1.34; 95% CI, 1.00- 1.79). 1.44; 95% CI, 1.01- The two studies that did not find an association with health literacy examined associations of 84 and the ith persistent asthma parent health literacy and child asthma care among children w 82 -positive adolescents described above. HIV The other study, a cross sectional study of 499 children with persistent asthma, examined parental health literacy and multiple aspects of asthma care (preventive medicine use, acu te care, unmet needs, parental worry, and parental quality of life). Parental health literacy was not associated with children’s use of any urgent care. This particular outcome was limited because the outcome of urgent care visits was measured by 27

50 parental self -report. The strength of evidence is moderate (Table 8 and Appendix F). No studies of emergency department use were reported in our earlier report. 85 81 ,86 -91 General screening. We found one good and seven fair studies examining the association of healt h literacy with general screening services. These services included colon screening (Table 9), Pap testing (Table 10), mammography (Table 11), and testing for sexually transmitted diseases (Table 12). -sectional studies found mix Five cross ed results for the probability of having Colon screening. ,86 -89 81 Of note, the two larger studies received colon screening by health literacy level (Table 9). 81 ,86 found a lower probability of colon screening in patients with lower health literacy. The 86 largest study found a decreased probability of colon cancer screening among those 65 years of -basic health literacy compared with those with proficient skills in a age and older with below ng multiple self - nationally representative US cross -sectional study of 18,100 individuals examini reported preventive services (data not reported [NR]; P < 0.05). The three studies not finding an association with health literacy were smaller in size (samples of 50 to 136) and limited to one -89 87 geographic area. e is low (Table 8 and Appendix F). No studies of The strength of evidenc 1 colon screening use were reported in the earlier 2004 report. -sectional studies found that women with lower health literacy had a lower Three cross Pap tests. 81 ,86 ,91 However, this result was present only probability of ever having had a Pap test (Tabl e 10). in certain age cohorts. In a nationally representative sample, researchers found that women less than 40 years of age with below -basic health literacy had a lower probability of having a Pap test than women in the same age group with proficient health literacy (NR; P < 0.05), but the 86 Results also probabilities did not differ by literacy level in women 40 to 64 years of age. ne study seemed to differ by degree of lower health literacy (inadequate vs. marginal). O 91 In examined Pap screening in 205 low -income Spanish- speaking Latinas in New York City. adjusted analyses, controlling for age, years in the United States, education, and having a source t women with inadequate health of care and health insurance, these investigators found tha literacy were less likely to have ever had a Pap test than women with adequate literacy (odds ratio [OR], 0.06; 95% CI, 0.01- 0.55). However, the marginal and adequate health literacy groups did not differ significantly (OR, 0.14; 95% CI, 0.01- 1.41). This discrepancy in findings between 92 1 in the 2004 report. Thus, inadequate and marginal groups is consistent with an earlier study the overall strength of evidence is low (Table 8 and Appendix F). Four cross -sectional studies examined use of mammography by health literacy Mammography. 81 ,85 ,86 ,90 All studies found a lower use of mammography in the lower health group (Table 11). literacy group compared with the adequate group. However, one study found a difference in 86 and another found differences between groups by receipt of mamm ograms among older women 90 frequency of mammograms. In the Prudential study, women ages 65 and older with low health literacy had a lower probability of having a mammogram than those with adequate health literacy (NR; < 0.05); health literacy was not associated with the probability of having mammography P 86 Another study evaluated mammography rates in 97 women in among women ages 40 to 64. three community health clinics in Philadelphia; inadequate health literacy was associated only with significantly lower odds of ever having a mammogram (OR, 0.88; 95% CI, 0.79 -0.98), but 90 not with having a mammogram in the past year, past 3 years, or as part of a check- up. The 28

51 strength of evidence is moderate (Table 8 and Appendix F). These results are consistent with the 2004 report. Researchers conducted a cross -sectional study (N = 372) Sexually transmitted infection testing. 93 of HIV test acceptors in an inner -city urgent care hospital (Table 12). Subjects with inadequa te health literacy had greater odds of accepting an HIV test result than those with adequate health 3.42). In the 2004 report, the one study about this type of literacy (OR, 2.02; 95% CI, 1.19- service showed a lower probability of having received a gonorrh ea test in the past year among 94 -literacy group. those in the low The strength of evidence is low (Table 8 and Appendix F). 63 85 ,86 ,95 One good cohort -sectional studies found inadequate and three cross Immunizations. health literacy associated with lower receipt of influenza vaccine (Table 13). In a Prudential study analysis, controlling for age, sex, race, ethnicity, education, income, site, morbidity, and eiving an influenza vaccine in the inadequate health smoking, researchers found lower odds of rec = 0.020), but no significant differences in literacy group than in the adequate group (OR, 0.76; P 63 the marginal health literacy group compared with the adequate health literacy group. These 86 findings ar e similar to those in our 2004 report. Age also appears to be a factor in a study that found a lower receipt of influenza vaccine by health literacy level among adults under 40 years eracy level in adults 40 to P < 0.05), but no differences by health lit of age and 65 or older (NR; 64 years of age (NR; P = nonsignificant [NS]). The strength of evidence is moderate (Table 8 and Appendix F). Pneumococcal vaccine did not follow a pattern similar to influenza vaccine (Table 13). In the 63 ,86 no significant association between two studies that examine d pneumococcal vaccine, pneumococcal vaccine and health literacy level was found. The strength of evidence is insufficient (Table 8 and Appendix F). 62 ,68 ,96 ,97 82 ,86 ,95 ,98- 100 -sectional stu dies Access to care. Four cohort and five cross examined various measures of access to office visits and general care; these types of services included pharmacy visits, dental visits, and vision checkups as well as hospital choice and transplant waitlists (Table analyses from the Prudential study did not find an association of 14). Two good cohort 62 68 or pharmacy services used. inadequate health literacy level with number of physician visits 101 described in the 2004 report. Similarly, on These results are consistent with the one study e prospective cohort of 68 individuals did not find differences in time to follow up after an 96 abnormal Pap test by health literacy level. However, results were mixed for dental and vision 86 Another large study (N =2,512) of Medicare recipients visits in one Prudential study analysis. 95 found less access to medical care by lower health literacy groups. One interesting retrospective cohort study involved 62 patients in five outpatient dialysis 97 units in San Francisco, California. After controlling for multiple confounders, the investigators found a significantly longer time from start of dialysis to referral to a transplant list in patients with inadequate health literacy (hazard ratio [HR], 4.54; 95% CI, 1.67- saw 12.5). However, they no subsequent differences in time from being on a transplant list to making the waitlist for transplant. The strength of evidence is insufficient given the variation among studies (Table 8 and Appendix F). 102 ative cross One nationally represent Access to insurance. -sectional study of 6,100 parents examined parental health literacy and their children’s access to health insurance. After controlling for multiple confounders, the odds of having at least one child without health 29

52 insurance in their household was higher among parents with below -basic literacy compared to -4.9). The strength of evidence is parents with proficient health literacy (OR, 2.4; 95% CI, 1.1 low because there is only one study and there are biases associated with using self -reported measures as the outcome (Table 8 and Appendix F). Summary of Outcomes on Use of Health Care Services Differences in health literacy level were associated with use of some health care services (Table 5). Specifically, lower literacy was associated with increas ed emergency department and hospital use, less screening for cervical cancer (through a Pap test) and breast cancer (mammography), lower influenza immunization, and less access to insurance. Evidence was fice visits. The strength of evidence to mixed for pneumococcal immunization and access to of support these findings was moderate for hospitalizations, emergency department visits, mammography, and influenza immunization. Evidence for other health care service use was low or insufficient because of inconsist ent findings and outcomes. KQ 1b. Health Outcomes We identified 72 articles reporting on 60 unique studies examining the relationship between literacy skills and health outcomes. Of these, 13 articles were of good quality and 59 were fair quality. Adherence. Eleven studies, reported in 15 articles, evaluated the relationship between health -74,81,82,103 -108 61,69 literacy level and adherence in adjusted analyses (Table 15). Five studies reported in 8 articles examined nonadherence in taking HIV medication and 69 -72 ,82 ,103 -105 found mixed evidence of a direct relationship. Studies found no relationship examining 100 percent adherence to medications over 3 days among patients with a history of 82 105 90 percent adherence over the past 3 day alcohol problems, and less s among adolescents, than 95 percent adherence over the past 3 months among a small sample (N = 87) of clinic 104 patients. In the last study, the relationship between health literacy level and nonadherence was examined, comparing the unadjusted relationship with an adjusted model, controlling only for the potential mediation of a patient’s norms about an acceptable level of adherence and no potential confounding variables. Norms were found to mediate the relationship. In contrast, in study using self -reported pill counts and controlling for education and other variables, researchers found a positive relationship between lower health literacy level (measured ) as a TOFHLA score of less than 90 percent correct rather than more commonly used categories 103 Similarly, based on findings 9.93). and probability of nonadherence (OR, 3.77; 95% CI, 1.46- from a study of 204 patients in clinics in Shreveport, Louisiana, and Chicago, Illinois, researchers found a positive relationship: nonadherence to HIV regimen was higher among those with low health literacy than those with adequate health literacy (OR, 2.12; 95% CI, 1.93 - ,72 69 However, this study found no difference between the marginal and adequate groups. In 2.32). subsequent analyses of this sample, the resea rchers conducted formal mediation analyses and found that the relationship between low health literacy and nonadherence to HIV medications was mediated by the combination of HIV treatment knowledge and medication self -efficacy in 71 69 and by stigma related to taking HIV medications in another. one analysis Medication -taking adherence, refill adherence, and adherence to procedural instructions were examined in various other patient populations with mixed results. Among 110 caregivers of infants in pediatric clinics, a combined group of those with low or marginal health literacy were 30

53 significantly likely to be adherent in providing vitamins to their infants than those with more 108 4.2). adequate health literacy (OR, 2.4; 95% CI, 1.37- However, no significant di fferences by health literacy level emerged in other patient populations for medication -taking, refill adherence, or adherence to procedural instructions. Studies included patients at an anticoagulation clinic 106 81 missing doses of warfarin, inics filling any medication prescriptions on time, seniors at two cl 61 seniors refilling medications for cardiovascular disease, preoperative clinic patients following 107 fasting and preoperative medication instructions, and adults reporting adherence at hospital 74 pharmacies in Atlanta, Georgia. However, in the Atlanta study, researchers found that the relationship between health literacy and adherence was moderated by social support; at the highest levels of social support, patients with adequate health literacy reporte d better adherence, and, at the lowest levels of social support, patients with lower health literacy reported better 74 adherence. Three studies examining the relationship between health literacy level and adherence and adequate -literacy assessed outcome differences between ind ividuals in the marginal- -health -72 ,105 ,69 61 groups but found no significant difference. Our research team found mixed evidence of a relationship between health literacy and health outcomes resulting in a strength of evidence grade of insufficient, which may be the result of differences in adherence measure, disease state, and adjustment for relevant confounders (Table 16 and Appendix F). Our earlier review also found mixed results across studies. One study reported a significant relat -reported adherence; ionship between lower literacy and poorer self 109 -112 three found no significant relationship. -efficacy. Five studies examined the relationship between participant health literacy level Self 70,82,87,113,114 (Table 17). One study found greater self - and self -efficacy for a variety of behaviors efficacy for taking HIV medications in the adequate- health - -literacy group than in the low -health 70 A second study literacy group, but no difference between the adequate and marginal groups. ater self -efficacy for colorectal cancer screening among individuals with higher health found gre 114 literacy levels (measured by the UK TOFHLA). In contrast, another study found no difference -efficacy for taking medications or kee ping appointments between groups in relation to self 82 Furthermore, self -efficacy for obtaining a fecal occult blood among adolescent HIV patients. test or colonoscopy was not related to limited health literacy level (low and marginal groups combined) compared with a group with adequate literacy in a small, potentially underpowered 87 d analysis of 99 patients at one clinic. adjuste Finally, although higher self -efficacy for taking hormone therapy among postmenopausal women was correlated with higher health literacy level, 113 this was in an unadjusted analysis. Based on the mixed results in these studies, our research team graded the strength of evidence as insufficient (Table 16 and Appendix F). Our earlier review included no self -efficacy studies. Health Behaviors. We identified studies reporting on a variety of health behaviors including smoking, alcohol and drug use, healthy lifestyle, review of prescription information, HIV risk behaviors, and sexual activity. Smoking. Two large studies evaluated the relationship between health literacy level and self - report of smoking in adjusted analyse s (Table 18); results were statistically different even though 64,115 A study examining current smoking status in a national odds ratios were fairly similar. sample of British adults (N = 719) found that higher health literacy, measured as a continuous 31

54 vari able, was associated with a small increased likelihood of not smoking (OR, 1.02; 95% CI, 115 1.003- 1.03). In contrast, among the Prudential sample of American seniors (N = 2,923), nts’ smoking status researchers found no relationship between health literacy level and participa 64 (never, former, or current). Due to these mixed results, the strength of evidence was graded as insufficient (Table 16 and Appendix F). We reported mixed results in our earlier review through one adjusted analysis of adolescents (boys and girls reported separately) and two unadjusted analyses examining outcomes of smoking in adults; therefore, these studies do not modify our 116 -118 evaluation of the strength of evidence. The Prudential study also examined the relationship between health Alcohol and drug use. 64 literacy level and current alcohol consumption; they found no relationship. Among adolescents 82 Neither study with HIV, higher health literacy was associated with greater substance use. adjusted for comorbid depression. With only one study concerning alcohol consumption and one concerning substance use, strength of evidence was graded as insufficient (Table 16 and Appendix F). In our earlier review, we included one study of alcohol consumption among 118 adolescents and no significant r elationship with health literacy was found. Healthy lifestyle. Eight studies addressed the relationship between health literacy level and various measures of healthy lifestyle, including level of physical activity, eating habits, seat belt 9,10,64,65,81,95,115,119 (Table 18). use, and wei ght Two studies, discussed above for smoking outcomes, measured level of physical activity. ,115 64 Neither study found significant differences by health literacy level. belt use were examined in one study each. Healthy eating, overall healthy lifestyle, and seat In a sample of British adults, higher health literacy level was associated with a small but significantly higher probability of eating five or more servings of fruits or vegetables per day 115 1.03). Among 489 seniors receiving care at two clinics in Chicago, (OR, 1.02; 95% CI, 1.003- health literacy level did not have a direct effect on a composite measure, the Health -Promoting 81 Lifestyle Profile, which assesses a combination of exercise, nutrition, and health responsibility. Only one unadjusted analysis examined the relationship between health literacy level and seat 64 belt use. The researchers found no significant differences. Among obese children, body mass index (BMI) was inversely related to the child’s health 119 Four literacy level, controlling for their parent’s health literacy level and other confounders. additional studies examined differences in rates of obesity or BMI by health literacy level in 9,10 ,65, 95 unadjusted analyses. Results were mixed. ch team judged the strength of evidence as insufficient (Table 16 and Appendix F) The resear for the relationship between health literacy and physical activity, eating habits, and seat belt use eight or obesity was as a group based on mixed findings. The strength of evidence concerning w also insufficient (Table 16 and Appendix F). Our earlier review included no studies with any healthy lifestyle outcomes. Review of prescription information. One adjusted analysis examined the relationship between health literacy and review of prescription information (Table 18). Clinic patients (N = 251) in Shreveport, Louisiana, were asked to report on whether they ever looked at the consumer 120 After controlling for potential confounders, information included with their prescriptions. including the number of prescriptions taken, those with low health literacy were less likely to 5.2). The look at the material than persons of adequate health literacy (OR, 2.5; 95% CI, 1.2- 32

55 marginal -health - and adequate -literacy groups did not differ. The strength of evidence was low (Table 16 and Appendix F). Two adjusted analyses examined the relationship HIV risk behaviors and sexual activity. between health literacy and sexual behaviors (Table 18). One study of female inmates did not find a relationship between health literacy level and HIV risk behaviors (sex without a condom 121 or sharing injecting equipment), controlling for age, race, and problem drinking. A large study a, found that higher of adolescents and young adults (N = 4,751) in Cape Town, South Afric literacy level (measured using the Cape Area Panel Study Literacy and Numeracy Evaluation) was associated with a lower probability of sexual debut but not first pregnancy, controlling for 122 socioeconomic variables. The research team j udged the strength of evidence to be insufficient based on mixed findings (Table 16 and Appendix F). Our earlier review included no studies with these outcomes. related skills. Eleven studies reported in 13 articles included outcomes concerning Health care- a variety of health care- related skills (Table 19). Among these were appropriate medication 47,123 9,75 - -127 interpreting prescription medication, nutritional labels, and health messages; use; 77,102,128 79 -care skills. and asthma self Taking medications appropriately . Three studies directly observed whether participants could take prescription medications appropriately; their results generally found a relationship with health literacy level. In one study we rated good quality, researchers required 152 corona ry heart disease patients to perform four tasks relating to their medication: identify the appropriate medication, open the container, select the correct dose, and report the appropriate timing of 123 literacy levels in patients’ scores The researchers found no difference across health doses. from completing all four tasks in an unadjusted analysis. However, after controlling for age, education, and cognitive functioning, low health literacy (but not marginal health literacy) was associated with poorer performance on one of the tasks —being less likely to identify all of one’s -56.08). Using a similar approach, a second team of medications (OR, 12.00; 95% CI, 2.57 researchers conducted a mock exercise concerning successful medication management 47 Patients with higher health (Medication Mana gement Test) among HIV -positive patients. literacy scored significantly higher in an adjusted analysis. Similarly, in a small sample of seniors in Texas (N = 57), researchers found that lower health literacy (measured continuously) was associated with poorer ability to open and take one’s own medications, in adjusted 124 analysis. Three additional adjusted analyses examined other measures of whether patients take medications properly, the first through self -report, the second through direct observation, and the third through biologic test results, and found limited evidence of a relationship with health 125 -127 One study examined whether health literacy level was associated with literacy level. parents’ use of nonstandardized dosi ng instruments (such as kitchen spoons) when providing medications to their children; they found no relationship in an analysis adjusting for all identified 125 However, after removing from the adjusted analysis only the potential confounding variables. var iables in the analysis that were confounded with health literacy level (caregiver’s education, country of origin, language, and socio- economic status), participants with marginal/inadequate health literacy (combined into one group) were more likely to use nonstandardized instruments than those with adequate health literacy (OR, 1.9; 95% CI, 1.0 -3.5). In a second study, researchers tested parents’ health literacy level using the Newest Vital Sign and evaluated 33

56 whether they made dosing errors using common dos ing instruments (i.e., dosing cups, droppers, 127 dosing spoons, and syringes). Parents with a high likelihood of limited health literacy and those with possible limited health literacy were significantly more likely to make a dosing error (greater than 20 percent deviation) than parents with adequate health literacy, in adjusted analyses; parents with a high likelihood of limited health literacy were significantly more likely to make a large dosing error (greater than 40 percent deviation). One study examined warfarin control measured by international normalized ratio (INR) variability. Results did not differ by health literacy level, controlling only for age, in a population of adults 50 years of age and 126 older. Interpreting labels and health messages. Tw o studies examined participants’ ability to interpret labels (prescription medications and nutrition); both found a positive relationship with health literacy level. One study among 395 adult patients in three primary care clinics in Shreveport, Louisiana, Jackson, Michigan, and Chicago, Illinois, examined interpretation of prescription 75 -77 medication labels. Participants demonstrated their ability to understand prescription label instructions by describing to physicians how they would take five medications in adjusted 4.28) as well as those analyses, those with inadequate health literacy (RR, 2.32; 95% CI, 1.26- with marginal health literacy (RR, 1.94; 95% CI, 1.14- 3.27) had a greater probability of 75 A with adequate health literacy. misunderstanding one or more label instructions than those further (unadjusted) examination of participants’ correct interpretation of each of the five primary labels found significant differences in interpretation of four of five primary medication labels. They also found diffe rences in whether participants attended to auxiliary labels in two of 76 five comparisons. Lastly, researchers found in an adjusted analysis that those with lower health 9 literacy (less than high school level) were less likely to understand nutrition labels. One study examined health literacy and the ability to give an organized oral health narrative. Among a community sample of mothers of young children in Nepal, higher literacy level was associated with greater ability to give an organized health narrativ e (a skill associated with 128 higher oral health literacy) in an adjusted analysis. One study examined self -care. Asthma self -care skills relating to asthma among hospitalized 79 In adjusted analysis, those with inadequate health literacy, compared with those with adults. adequate literacy, were less likely to have mastery of their dose inhaler (OR, 0.29; 95% CI, 0.08- 129 1.00). We had found a similar result in our earlier review. Health care -related skills strength of evidence. The research team separately d etermined that the strength of evidence concerning taking medications appropriately and interpreting labels and health messages was moderate and the strength of evidence concerning asthma self -care was low care- related skills study uded one health- (Table 16 and Appendix F). Our earlier review incl 129 concerning asthma self -care. Disease prevalence and severity. We found multiple studies examining the relationship between health literacy level and disease prevalence (specifically, mental health diagnoses and chronic conditions) or disease severity (specifically, HIV, asthma, diabetes, hypertension, and prostate cancer). Mental health outcomes. Eight of ten studies evaluating the relationship between depression and health literacy level found that patients with lower health literacy were more likely to have 34

57 symptoms of depression or to be considered depressed; however, the majority of studies 68,95,103,130 -135 controlled for a limited number or no potential confounders. One additional study 82 examined the relat (Table 20). ionship between health literacy level and psychological distress In the most rigorous study of depression (a prospective cohort conducted among 390 patients receiving inpatient detoxification from alcohol and substance abuse), depression tomatology did not differ between health literacy groups at baseline, but was higher among symp those with lower health literacy at 2 -year followup, controlling for a number of potential confounders including sociodemographic characteristics, primary substance of choice, and 130 mental state. Other analyses were conducted among subpopulations with limited adjustments -literacy -health for potential confounders. One reported that depression was greater in the lower 131 group among HIV -positive adults in five urban clini cs, controlling for Hispanic nationality. A second reported that depression was also greater among pregnant patients with lower (but not 132 marginal) health literacy, controlling for Mexican nativity and marijuana use. Finally, a third -health that depression scores were higher among recent Spanish - -speaking immigrants in the low 135 literacy groups, controlling for a scale measuring the demands of immigration. In unadjusted analyses, lower health literacy was also related to depression among rheumatology and diabetes 133,134 68,95 patients and among seniors in two community samples. However, no difference by 103 In relation to -positive patients in Atlanta. health literacy level was found among HIV psychological distress, differences were not found by health l iteracy level among HIV -positive 82 adolescents. The research team judged the strength of evidence to be low because, although studies generally found consistent results, only one rigorously controlled for potential confounders (Table 16 and Appendix F). Re sults of studies evaluating differences in depression across different levels of health literacy in our earlier review were mixed, including among the two -140 136 studies that controlled for potential confounders. ree studies examined differences in rates of . Th Chronic disease outcomes and prevalence -term illnesses) by health literacy level (Table chronic disease (defined in a group as any long 9,65,141 Four additional studies examined differences in rates of specific diseases by health 21). 68,95,142,143 66, literacy level. Using the large, nationally representative NALS (N = 23,889), researchers found that lower term illness (one lasting more health literacy was associated with higher odds of having a long- than 6 months) and greater odds of having a condition that would keep the individual from 141 In working after controlling for various sociodemographic characteristics including education. other studies with unadjusted analyses, the number of chronic conditions among seniors and the percentage with a chronic d isease among adults in a clinic population did not differ by health 9,65 literacy level. Three studies, discussed in four articles, examined differences in rates of specific diseases by health literacy level; one used a well -designed adjusted analysis and t he others used unadjusted 66,68,95,142 -quality analyses All analyses were limited to senior citizens. In adjusted good analyses. of the Prudential sample, inadequate compared with adequate health literacy was associated with significantly higher rates of di abetes and heart failure, but not with higher rates of hypertension, 66 In contrast, the investigators coronary heart disease, bronchitis, asthma, arthritis, or cancer. found no differences in rates of specific diseases between those with marginal and adequ ate health literacy. Potential limitations of this analysis are that respondents’ outcomes are self - reported shortly after joining the health plan and differences in prior access to care may have e state. Also, by testing multiple resulted in differences in knowledge concerning their diseas 35

58 outcomes, significant differences were more likely to be found in at least some of the comparisons. Two unadjusted analyses measured the probability of differences in prevalence of chronic disease across three health literacy levels; however, their design was insufficient to determine if differences existed between any two groups (inadequate compared with adequate or ,95 68 marginal compared with adequate). A third unadjusted analysis among seniors in Korea found that health literacy was associated with significantly higher rates of arthritis and 142 hypertension, but not sensory disease, diabetes, or pulmonary or heart disease. Among individuals with diabetes, heart failure rates were higher in the limited health literacy 143 up in one bivariate comparison. gro Overall, the body of evidence found mixed results and was limited by differences in outcomes across studies with the majority of studies not controlling for potential confounders. nce was graded insufficient (Table 16 and Appendix F). Given these issues, the strength of evide 144 Our earlier review found one study of children with migraines and no relationship was found. HIV infection severity and symptoms. Three adjusted and one unadjusted analyses of individuals with HIV did not find differences in severity of HIV (measured by viral load suppression, CD4 cell counts, and number of HIV symptoms) by health literacy level (Table 82,103,105,145 y In contrast, higher health literacy was associated with greater symptom intensit 22). 131 In this study, health literacy was in one study controlling only for Hispanic ethnicity. measured as a continuous variable among a population with relatively high health literacy (REALM mean score = 59.1). Even though four of five studies found no rel ationship, the research team evaluated the strength of evidence as low because these studies included limited control for confounding and had small sample sizes (Table 16 and Appendix F). Our earlier 138,146,147 review was limited to unadjusted analyses and found mixe d results. Asthma severity and control . The relationship between health literacy and asthma severity of children was examined in two studies reporting a mix of adjusted and unadjusted analyses (Table 80,84 ty by parent report. In one, an adjusted analysis Both studies measured asthma severi 23). concluded that lower -health -literacy parents of children with asthma were more likely to report that their children were in fair or poor health; however, in an unadjusted comparison, these same 84 In a orts of their children’s asthma control did not differ by health literacy level. parents’ rep different unadjusted analysis, parents with lower health literacy reported greater use of albuterol 80 (a bronchodilator) by their children, indicating poorer asthma contr ol. Overall, the strength of evidence was insufficient (Table 16 and Appendix F). Diabetes control, complications, and related outcomes. Five adjusted studies examined the relationship between glycosylated hemoglobin (HbA1c) level and health literacy level and found 134,148 -151 One good- quality study measuring the HbA1c levels in 1,002 mixed results (Table 24). diabetic adults in Vermont found no relationship with health literacy level after measuring health literacy as a continuous variable using the T OFHLA and controlling for demographic characteristics and several factors related to successful diabetes control, such as duration, 134 Similarly, a second good- quality study diabetes education, medication, and alcohol use. conducted with diabetic patients in the Midwest also found no relationship between HbA1c and health literacy levels after controlling for different factors related to successful diabetes control including patient trust, depression, diabetes knowledge, and performance of self -care activiti es. The lack of a finding of association between health literacy and the outcome may be due to over - adjustment given that researchers controlled for potentially mediating variables in this 36

59 151 analysis. In contrast, a very small study (N = 68) from one general internal medicine clinic found significant differences in HbA1c between the four health literacy levels; each increasingly 149 higher level of health literacy, however, was not associated with better control. In a good- quality study, using a path analy sis statistical technique and controlling for potential confounders, researchers found that higher health literacy was related to better glycemic control 150 and that health literacy mediated the direct relationship between education and HbA1c level. -literacy diabetic patients had better Also, in a study conducted in Hong Kong, higher -health 148 glycemic control. The large study of diabetic patients in Vermont, did not find health literacy level to be related to blood pressure, cholesterol level, or the proba bility of having other potential side effects of poor diabetes control (retinopathy, nephropathy, foot or leg problems, gastroparesis, 134 cerebrovascular disease, or coronary artery disease) after adjusting for confounders. g to diabetes outcomes from this review was insufficient The strength of evidence relatin 129,152,153 -related results were mixed. (Table 16 and Appendix F). In our earlier review, diabetes Hypertension control. Two studies examined blood pressure control among patients diagnosed 154,155 with hype The larger study (N rtension; results were mixed (Table 25). = 1,224), measuring health literacy using the REALM, did not find a significant main effect between systolic blood pressure and health literacy level (limited compared to adequate), controlling for education level, 154 diabetes status, medication adherence, smoking, exercise, and participatory decisionmaking. However, the interaction between health literacy and health care system was significant, indicating that the relationship between bloo d pressure and health literacy differed in the Veterans Administration vs. the private health care system. A second analysis (N = 330) measured health literacy using the S -TOFHLA subdivided into five categories and found that ere less likely than those in the highest category to have controlled those in the lowest category w blood pressure (less than 140 mmHg systolic and less than 90 mmHg diastolic [or less than 130 mm Hg systolic and less than 80 mm Hg diastolic among those with diabetes] RR, 2.68; 95% CI, 1.54- 4.70) after controlling for sociodemographic characteristics, education level, insurance 155 In this study, the status, number of comorbid conditions, and years treated for hypertension. percentage of patients with controlled blood pressure was not consistently larger with every category of increasingly higher health literacy, and only some comparisons between various -literacy -level groups were significantly different. Based on mixed results, the other health research team judged the strength of evidence to be insufficient (Table 16 and Appendix F). Our earlier review did not find a relationship in hypertensive patients between blood pressure control and health literacy level in an adjusted analysis from the one study reviewed with this ,1998 156 outcome. Prostate cancer patients with low health literacy (sixth grade or less) Prostate cancer control. were more likely than those with adequate health literacy (ninth grade or higher) to have an -quality study (OR, 2.5; 95% specific antigen (PSA) level in an adjusted good elevated prostate- 157 -health -literacy (seventh or eighth grade) In contrast, the marginal CI, 1.5- 4.2) (Table 26). group and the functional -health -literacy group did not differ. With only a single study, the strength of evidence was low (Table 1 6 and Appendix F). In our earlier review, stage of 158 presentation of prostate cancer did not differ by health literacy level, in an adjusted analysis. Global health status measures. Twelve studies reported in 14 articles examined health status differences by health literacy level among a variety of populations, including all adults, seniors, 37

60 63,65,66,81,85,95,100,131,142,159 -163 and adults with various specific disease states (Table 27). Health status was measured using an assortment of measures, including self -report of overall health status (excellent/very good/good/fair/poor) and physical and mental health subscales of the 12 - Item Short Form Health Survey (SF -12) and SF -36, among others. 159 Only one study measured self -reported health status among all adults (ages 18 to 85). Limited to one clinic population in Canada, this work indicated that self -reported health status was not related to health literacy level after adjustment for confounders. With only a single study, the strength of evidence was low (Table 16 and Appendix F). Our earlier review found 101,164 similar results in two adjusted analyses. In studies limited to senior citizens, five studies, reported in six articles, all found differences 63 ,81,85,95,142,160 -reported health status by health literacy level. in self Within a nationally representative sample (N = 2,668), one good- quality study reported that lower health literacy -reported health status, after level measured through the NAAL was related to poorer self 85 . adjusting for potential confounders Self -reported health status was also poorer in lower health literacy groups in three additional adjusted analyses: among Medicare patients in Chicago, 81,160 Illinois, - and adequate- in the Prudential study comparing differences between the low 63 ,65 -literacy groups), and among older Korean literacy groups (but not marginal - and adequate 142 The relationship was also found in one unadjusted analysis of 2,512 seniors in adults. 95 Pittsburgh, Pennsylvania, and Memphis, Tennessee. The research team judged the strength of evidence to be moderate (Table 16 and Appendix F). In our earlier review, one unadjusted analysis from the Prudential study also found poorer overall health status among those with 165 lower health literacy. rs reported additional health status measures and results Three of the studies limited to senio were mixed. In adjusted analyses, the Prudential study found lower health literacy to be -health -related quality of life and physical associated with poorer physical - and mental - and the marginal -literacy groups (SF he inadequate functioning in both t -36) compared with the ,65 ,66 63 In contrast, a sample of Medicare beneficiaries in Chicago, Illinois, was adequate group. 160 One of these two not found to differ in physical or mental functioning by health literacy level. studies, the Prudential study, also found that persons with inadequate health literacy had higher probabilities of having activity limitations, fewer accomplishments, and greater pain related to 66 alth literacy. Among Korean seniors, physical physical health than those with adequate he functioning (SF -12) did not differ by health literacy level in adjusted analyses, but significant 142 differences were found in limitations in activities and pain that interfered with normal work. Given mixed results, the research team judged the strength of evidence to be insufficient (Table 16 and Appendix F). Five studies examined differences in a variety of health status measures in adult populations 131 and patients with itive -pos with various diseases, including persons who were HIV 161 162 163 100 asthma, glaucoma, spinal cord injuries, and cancer. No more than one study examined each disease state, and results were mixed by disease state and outcome measure (e.g., general health, physical health, mental health , disease -specific quality of life). In HIV patients, better global physical health (using a scale developed by the researchers) was related to lower health 131 In glaucoma patients, those with lower health literacy had poorer physical, but not literacy. 161 -of-life scores. Among patients with spinal vision or mental, quality of life based on quality cord injuries, lower health literacy was associated with poorer physical morbidity, but not with 162 mental health morbidity, physical health, or mental health statu s (SF -12). In cancer patients of all types, Functional Assessment of Cancer Therapy scores (related to physical and emotional 38

61 -36 showed no difference by health functioning) and general health scores measured by the SF 163 literacy level. In asthma patien ts, lower health literacy was associated with poorer asthma quality of life (Asthma Quality of Life Quotient) and physical health status (SF -36), adjusting for 100 asthma severity and asthma self -sufficiency. However, the relationship with both outcomes was no longer significant after the investigators added age, education, depressive symptoms, and knowledge confounders to their analyses. Based on mixed results, the research team judged the strength of evidence as insufficient (Table 16 and Appendix F). In our earlier review of studies 139,166 of global health measures, two unadjusted studies found no significant relationship. Mortality. Differences in all -cause mortality rates of seniors were related to health literacy in 65,67,167 quality studies reported in three articles (Table 28). adjusted analyses in two good- The Prudential study reported higher mortality rates in the inadequate health literacy group than in 67 the adequate health literacy group—first in an analysis controlling for cognitive functioning and second in an analysis not controlling for cognitive functioning but instead controlling for 65 baseline measures of disease, physical functioning, and healthy lifestyle. Both analyses did not - and the adeq uate- health -literacy groups. In a find significant differences between the marginal population of seniors in Pittsburgh, Pennsylvania, and Memphis, Tennessee, those with limited 167 -cause mortality rate than those with adequate health literacy. health literacy had a higher all -related mortality The Prudential study also reported, in adjusted analyses, higher cardiovascular -literacy groups than in the adequate group, but no in the inadequate - and marginal -health 65 The research team graded -related mortality across health literacy levels. differences in cancer the strength of evidence as high (Table 16 and Appendix F). No studies examining the association between health literacy and mortality were included in our earlier review. Summary of Outcomes and Strength of Evidence on Health Outcomes The effect of heal th literacy on health outcomes was variable (Table 16). The risk of mortality for seniors was clearly higher with lower health literacy. The strength of evidence to support this finding was high. There was also moderate strength of evidence to support a relationship between lower health literacy and poorer ability to take medications properly, poorer ability to interpret labels and health messages, and poorer overall health status among seniors. In these studies, the evidence consists of all observational s tudies generally having a medium risk of bias and results generally in a consistent direction. The strength of evidence for all other outcomes was either low or insufficient because the literature consisted of a small number of studies, poorly designed studies, and/or inconsistent results. Strength of evidence evaluations focused on the relationship between the lowest health- literacy group and the highest. The evidence was sparse for evaluating differences between those with marginal (a middle category) health literacy and adequate (the highest category) health literacy. In unreplicated studies, evidence is beginning to emerge that the effect of health literacy on health outcomes may be moderated by social support or the characteristics of the health care sy stem and that it may be mediated by knowledge, patient self -efficacy, and stigma. In addition, health literacy may mediate the effect of education, income, and urbanicity. KQ 1c. Costs of Health Care KQ 1c concerns differences in health literacy level and costs of health care (Table 29). The -year period. Prudential study of new Medicare managed care enrollees examined costs over a 1 39

62 In adjusted analyses, inadequate - and marginal had higher emergency -health -literacy groups department costs; however, no other patterns of differences were uncovered in relation to overall, 68 inpatient, outpatient, or pharmacy costs. In contrast, total Medicaid costs were higher in the rade) among a small sample of beneficiaries in Arizona lower literacy group (less than third g 169 168 = 74). (N Our earlier review found no relationship between literacy and Medicaid costs. In summary, the strength of evidence concerning differences by health literacy level in costs of health car e (KQ 1c) was insufficient (Table 30 and Appendix F). The two relevant studies examined different payment sources (Medicaid and Medicare), found inconsistent results, and included different patient populations. No studies examined differences in costs among those with private health insurance coverage or no coverage. KQ 1d. Disparities in Health Outcomes or Health Care Service Use Eight studies examined whether health literacy mediates the relationship between alth care services, and one study examined race/ethnicity and health outcomes or use of he whether health literacy moderates the effect between race/ethnicity and health outcomes (Table 31). As described in more detail in Chapter 2, health literacy would be considered a mediator of health outcomes, if differences in health literacy level between racial groups racial differences in explain all or a portion of the outcome differences observed by race. Analytically, health literacy or ethnicity and an level is determined to be a mediator when health literacy is related to race outcome and when the coefficient for the race or ethnicity variable is smaller or becomes statistically insignificant after health literacy is added to the analytic model. Alternatively, the 170 Health literacy was found to mediate relationships can be observed through a path analysis. the effect of race on a variety of health outcomes in a variety of populations: on health conditions that keeps respondents from working and having a long -term illness in a nationally 141 on self -reported health status and representative sample of adults included in the NALS, receipt of an influenza vaccine among seniors included in the nationally representative NAAL 85 -health on physical and mental ng -related quality of life and self -reported health amo sample, 63 PSA levels among newly diagnosed prostate cancer seniors included in the Prudential study, 157 69 on nonadherence to HIV medications in a population of HIV patients, patients in Chicago, 102 e, on child health insurance among parents included in the NAAL sampl and misinterpretation 77 The relationship was not found in relation to of medication label instructions among adults. -the - receipt of a mammogram or a dental checkup or parents’ difficulty understanding over 85 ,102 counter medication labels in the NAAL study, rate of receipt of vaccines in the Prudential 171 63 or glycemic control in diabetic adults. study, Only the NAAL study examined whether health literacy mediated the effect of ethnicity 85 In contrast, only (Hispanic vs. white) on a health outcome, and this relationship w as not found. the study examining misinterpretation of medication label instructions in adults investigated whether health literacy was also a potential mediator of the relationship between gender and the 77 outcome, as well as race; the r elationship was found in this comparison as well. Health literacy is determined to be a moderator of the relationship between race/ethnicity and health outcomes when the relationship is different in magnitude or direction between the two race/ethnicity groups. Only one study examined moderation and found no differences in the relationship between mortality and health literacy level in blacks and whites or males and 167 females. The strength of evidence was low in relation to health literacy level explain ing racial differences in health outcomes based on findings of effect in some outcomes (Table 32 and 40

63 Appendix F). The strength of evidence was low in relation to health literacy level explaining differences in health outcomes between Hispanics and whites a nd between males and females (Table 32 and Appendix F). Data were not available to examine disparities related to cultural or age group differences. In our earlier review, only one study was available to examine this issue, and it did not find that health literacy was a mediator of differences between black and white 158 patients in late -stage prostate cancer diagnosis. In summary, our research team found that health literacy mediates or partially explains disparities in health outcomes between white and bla ck participants for a variety of outcomes; the strength of evidence for this conclusion is low because only one study examined each outcome (Table 32 and Appendix F). Health literacy was found to mediate outcome differences between blacks and whites in rel ation to the following outcomes: a health condition that keeps -reported health status, receipt of an -term illness, self respondents from working or having a long -reported health am ong influenza vaccine, physical and mental -health -related quality of life, self -specific antigen levels among newly diagnosed prostate cancer patients, seniors, prostate nonadherence to HIV medications, children’s lack of health insurance, and misinterpretation of medication labels. We cannot know whether health literacy level would also mediate racial disparities for other health outcomes that have not been tested. Only one study examined whether health literacy level mediated the relationship between race and health outcomes for persons of Hispanic ethnicity and whites, and one s tudy examined the relationship between males and females. The strength of evidence for these relationships was low. We found no studies that evaluated disparities related to differences in age, cultural group, or other sociodemographic characteristics. Key . Relationship of Numeracy to Various Outcomes and Question 1 Disparities We identified 16 unique studies of the relationship between numeracy and outcomes of interest (Table 33). Nearly all studies examining the relationship of numeracy to health outcomes -179 9,10,24,47,98,125,171 were cross Four studies were randomized controlled trials -sectional in design. 24,98,172,173 and one (RCTs) that analyzed their data in a cross -sectional manner for this analysis, 126 Fifteen studie used a prospective cohort design. s were of fair quality; only one was of good 171 quality. Studies employed a wide variety of numeracy measures. These included the WRAT -3, the Lipkus numeracy test, the Schwartz and Woloshin numeracy test (or adaptations thereof), the Diabetes Numeracy Test , the Black and Toteson numeracy test (or adaptations thereof), and the TOFHLA numeracy test. Using these measures, populations studied had a varying proportion of individuals with low numeracy (ranging from 5 percent to 74 percent). Studies also examined a wide variety of outcome measures. Among them were the accuracy -efficacy, actual of the use of health care services, accuracy of risk perception, knowledge, self behaviors, skills, disease prevalence and severity, and disparities. No studies measured inte nt for behavior, adherence, quality of life, or costs. 9,47,98,125,126,171 This allowed assessment of Six studies measured both literacy and numeracy. whether these exposures affect health outcomes differently. KQ 1a. Use of Health Care Services 178 examined the effect of numeracy on use of health care services One cross -sectional study 178 (Table 34). This study focused on the effects of numeracy on use of screening services. 41

64 Screening services. In adjusted analyses, researchers reported no effect of numerac y level on 178 to-date screening for either breast or colon cancer in women presenting for primary care. up- However, the sample for colon cancer screening was small (N = 152; 58 percent of the total sample due to age ineligibility for screening for colon, but not breast cancer), and the authors provided no power calculations for either analysis. In summary, only one study addressed the relationship between numeracy and use of Summary. wer. Based on this health care services and reported no effect, possibly due to inadequate po study, our research team judged the strength of the evidence for the relationship between numeracy and use of health care services to be low (Table 35 and Appendix F). KQ 1b. Health Outcomes Accuracy of risk perception. Five studies addr essed the effects of numeracy level on accuracy of risk perception (i.e., whether individuals correctly perceived their health risks and treatment 24,172,173 173,176 -sectional studies, benefits) (Table 36). Three were RCTs and two were cross lyzed their data in cross -sectional fashion to answer this question. Two examined although all ana 175,176 and four on the accuracy of the effects of numeracy on the accuracy of perceived risk 24,172,173,176 perceived treatment benefit. All used the Schwarz and Woloshin 3- item numeracy test to assess numeracy level. The two studies examining perceived risk found no effect of numeracy level on the accuracy 175,176 One study, of perceived risk of breast cancer or breast cancer survival over 5 years. however, reported that for every additional numeracy question answered incorrectly (scale range 175 0- 3), participants’ error in estimating lifetime risk increased by 18 percent (95% CI, 5 -30%). Four studies examined the effect of numeracy on the accuracy of perceived treatment benefit and found mixed results. Three studies reported lower accuracy of perceived treatment benefit at 24,172,173 Notably, the size lower levels of numeracy (0- 1 questions correct vs. 3 questions correct). of the effect was smaller in the one study that adjusted for covariates including age, income, education, and the framing of information about treatment benefit (e.g., relative risk reduction or 24 The fourth study, which also performed adjusted analysis, reported no absolute risk reduction). 176 significant differe nce between groups, but the authors dichotomized their numeracy exposure variable differently (0 -2 questions correct vs. 3 of 3 questions correct). Interestingly, results varied across studies by how the investigators assessed accuracy. The - and high- differences in accuracy of perceived treatment benefit were greater between low numeracy participants who were asked to calculate an exact treatment benefit than between those 172,173 who were asked merely to say which of two treatments provided more benefit. Considering all of these studies in aggregate, our research team judged the overall strength of evidence about the relationship between numeracy and accuracy of risk perception to be insufficient due to mixed results by task and study (Table 35 and Appendix F). Knowledge. We found four cross -sectional studies addressing the effect of numeracy level on 125,174,177,178 knowledge (Table 37). These focused on different types of knowledge as well as 177 174 general health and HIV, breast different health topics and conditions, including diabetes, 178 125 and colorectal cancer screening guidelines, and medication dosing. Results were mixed. 174,177,178 177,178 including two that adjusted for relevant covariates, Three studies, showed significantly lower knowledge about diabetes, HIV, and breast cancer screening with lower numeracy. These same studies, however, showed no effect of numeracy on general health 42

65 knowledge or colorectal cancer screening, although nearly half of the sa mple queried about colorectal cancer screening included individuals who were too young to be eligible for screening. A fourth study showed lower numeracy to be related to lower knowledge about medication 125 dosing in an analysis controlling for some confounde rs; however, results became nonsignificant after additional adjustment for education, acculturation, and socioeconomic status. Considering these studies in aggregate, our research team judged the overall strength of evidence regarding the relationship between numeracy and knowledge to be insufficient (Table 35 and Appendix F). -sectional study examined the effects of numeracy level on self -efficacy -efficacy. Self One cross 174 (Table 38). In an unadjusted analysis, this study found significant reductions i n self -efficacy (a 4- point reduction on the Perceived Diabetes Self -management scale ranging from 8 to 40) among those who scored in the lowest vs. the highest quartile of the Diabetes Numeracy Test. Based on this single unadjusted analysis, the overall st rength of evidence about the relationship between numeracy and self -efficacy was insufficient (Table 35 and Appendix F). Intent for behavior. We found no studies that examined the effect of numeracy on intent for behavior. One cross Behavior. -sectional study examined the effects of numeracy level on behavior (Table 174 39). In unadjusted analysis, this study found no significant differences in diabetes self - -Care Activities Scale, management behaviors in four of five domains of the Diabetes Self including general diet behavior, specific diet behavior, exercise behavior, or blood glucose -7; testing. However, there were small increases in foot care behavior (+2.25 on a scale of 0 P < 0.001) among those in the lowest vs. highest quartile of numeracy; these une xpected results (as well as the negative results for analyses of other self -care behaviors) may be the result of confounding. Based on this single unadjusted analysis, our research team judged the overall -efficacy to be insufficient strength of evidence about the relationship between numeracy and self (Table 35 and Appendix F). -related skills. Health -related skills Six studies examined the effects of numeracy level on health 126 79 9,47,125,1 four were cross -sectional studies, and one was an (Table 40). One was a cohort study, 98 -sectional fashion. RCT that analyzed data in cross The skills included taking medication, reading nutrition labels, and assessing health plan materials. The four studies that focused on skills in taking medication found mixed results. I n analyses adjusted for age, one found mixed effects of numeracy on two different but related variables denoting medication- taking skill: the proportion of INR tests within range (adjusted absolute 126 difference, NR; P = 0.35) and INR variability (adjusted absolute difference, NR; P = 0.03). Other studies measured medication -taking skill more directly and still found mixed effects. One study found a relationship between numeracy and HIV medication management capacity after adjusting for gender, education, health literacy, and time since HIV diagnosis (0.5 -point increase -16] for every 1- point increase in the Applied Problems in Medication Management skill [range 2 47 Another study reported that, after adjustment subtest of the Woodcock Johnson Test; P < 0.01). for some confounders, poor caregiver numeracy resulted in use of nonstandardized dosing 125 instruments for administering medications to children. Additional adjustment for education, acculturation, and socioeconomic status, however, led to nonsignificant differences between groups, based on TOFHLA numeracy scores split at the median. Finally, a third study found that 43

66 poor caregiver numeracy (second through eighth grade on the WRAT -math) was associated with -the lly harmful over -counter medication to be (1) an increased likelihood of thinking a potentia suitable (adjusted OR, 1.25; 95% CI, 0.99- 1.58), although results were not statistically significant, and (2) increased intent to use potentially harmful over -the -counter cold medicines in old (adjus ted OR for each a 13 in numeracy skill level, 1.19; 95% CI, 1.01- -month- decrease 16th 1.41). This study also reported that, paradoxically, for caregivers with higher numeracy (9th- grade), each increase in numeracy grade level made them more likely to intend to use ove r-the - increase in numeracy skill level, 1.78; 95% CI, counter cold medicines (adjusted OR for each 2.96). Investigators attributed this finding to heavier reliance on independent judgment. 1.07- Importantly, however, analyses were not adjusted for potential ly relevant confounders, such as prior physician prescriptions for these medications. Based on these studies, our research team judged the overall strength of evidence regarding the relationship between numeracy and skills in taking medication to be insuff icient (Table 35 and Appendix F). 9 —skill at reading nutrition labels The studies assessing other outcomes and at reviewing 98 —found lower comprehension of reviewed materials in participants with health plan materials However, only the nutrit ion label study adjusted for potential confounders. lower numeracy. Additionally, the health plan study found fewer participants choosing a higher quality hospital 98 among those with lower numeracy. Interestingly, this result was moderated by patient activation; subjects who were more motivated to process information were also more likely to make higher quality choices, regardless of their numeracy level. Based on these studies, our research team judged the overall strength of evidence regarding the relationship between numeracy and skill in interpreting health information as insufficient (Table 35 and Appendix F). Disease prevalence and severity. Three cross -sectional studies examined the effect of numeracy 9,10,174 These studies addressed the effects of level on disease prevalence and severity (Table 41). 9 174 9,10 and illness requiring dietary restriction. HbA1c, numeracy on BMI, -3 numeracy test) The two studies addressing the effect of numeracy (measured by the WRAT on BMI found mixed results in patients drawn from the same academic medicine practice. In one study, those scoring below the ninth- grade level on the WRAT -3 had higher mean BMIs 10 By contrast, the other study reported no effect of = 0.01). P (adjusted beta coefficient, 0.14; 9 -3 scores on obesity (BMI greater than 30) in unadjusted analysis. differential WRAT The differences in findings may be attributable to a combination of differences in recruiting e Huizinga study), handling of the outcome variable (continuous in the (physician referral in th Huizinga study, categorical in the Rothman study), and adjustment in analysis (adjusted in the Huizinga study, unadjusted in the Rothman study). lso mixed. One study reported modest effects of Findings on other health outcomes were a percentage- numeracy on HgbA1c (adjusted beta coefficient 0.09 for every 10- point decrease in 174 A second study, however, the proportion of correct responses on the Diabetes Numeracy Test). of numeracy on the proportion of individuals with illness requiring diet reported no effects 9 restriction in unadjusted analysis. Given the mixed nature of results, our research team judged the overall strength of evidence regarding the relationship between numeracy and dise ase prevalence to be insufficient (Table 35 and Appendix F). Summary. In summary, studies of the relationship between numeracy skill level and many health outcomes (including accuracy of risk perception, knowledge, skills taking medication, and 44

67 disease prevalence and severity) found mixed results. Based on these findings, we judged overall strength of evidence for its relationship to these outcomes to be insufficient. The relationship between numeracy skill level and other outcomes is also uncertain. One -reading skill. study suggests a possible relationship between numeracy skill level and label - Additionally, only one study each addressed the relationships between numeracy and self efficacy or behavior (both with unadjusted analyses), making conclusions impossible. KQ 1c. Costs We found no study that examined the effect of numeracy level on costs. KQ 1d. Potential Mediator of Disparities We found two studies that addressed the effects of numeracy as a potential mediator of 47,171 disparities in health outcomes. One examined numeracy as a potential mediator of the 171 relationship between race and HgbA1c. The other examined numeracy as a potential mediator 47 of the relationship between gender and HIV medication management capacity. Both used formal mediational a nalyses. In the study examining numeracy as a potential mediator of the relationship between race and HgbA1c, investigators used path analysis and structural equation models to examine the relationships between race, numeracy, and HgbA1c in a cross al sample of 383 diabetic -section patients who received care at primary care and diabetes specialty clinics at three medical centers. Investigators demonstrated significant negative relationships between both African -American P < 0.001) and numeracy and HgbA1c 0.46; race and numeracy (standardized path coefficient, - P 0.15; (standardized path coefficient, - < 0.01). They additionally demonstrated that the relationship between African -American race and HgbA1c (standardized path coefficient, 0.12; < 0.01) lessens and becomes nonsignificant with the addition of numeracy (standardized path P = NS), suggesting partial mediation of racial disparities by numeracy. coefficient, 0.10; P In the study examining numeracy as a potential mediator of the relationship between gender and HIV medication management capacity, investigators also used path analysis to examine the relationships between gender, numeracy, and HIV medication management capacity in a cross - sectional sample of 155 HIV -positive patients recruited from clinics or drug assistance programs in Miami, Florida. In this study, investigators demonstrated a significant negative relationship between female gender and numeracy (path coefficient, - 0.428; P < 0.01) and a significant positive relationship between numeracy and m edication management capacity (path coefficient, 0.644; P < 0.01). They additionally demonstrated that the correlation between female gender and medication management capacity (path coefficient = NR) lessened and became nonsignificant (path coefficient, 0.073; P = NS) with the addition of numeracy to the model. These findings suggest partial mediation of gender disparities in medication management capacity by numeracy. Our research team judged the overall strength of evidence to be low (Table 35 and Appendi x F). 45

68 Table 5. Overview of health literacy studies Source Design Covariates Included in Multivariate Analyses Population Quality Score Outcomes 77 Bailey et al., 2009 Analysis 1 Interpretation of a prescription label 373 patients at 3 outpatient family for amoxicillin Race Understanding of dosage -sectional Cross medicine clinics Age low -income measurement and frequency of use serving Sex populations in Education Fair Shreveport, LA; Analysis 2 Chicago, IL; and Race Jackson, MI Age Sex Education Health literacy 62 Baker et al., 2004 Age 3,260 new Prudential Any ED visits Medicare managed Gender Cohort 1 ED visit Good Race care enrollees in 2 or more ED visits Number of physician visits Physical and mental health Cleveland, OH; Houston, TX; and Chronic diseases Smoking Tampa and south Alcohol use Florida (including Ft. Lauderdale and Miami) BMI Study site Months enrolled 65 Age Baker et al., 2007 3,260 new Prudential All -cause mortality Prospective cohort Medicare managed Sex Cardiovascular mortality Good Cancer mortality care enrollees in Race/ethnicity Cleveland, OH; Noncardiovascular, noncancer Language Study site Houston, TX; and mortality Income Tampa and south Physical HRQoL (SF -12) -12) Mental HRQoL (SF Florida (including Ft. Social class Education IADL limitation Lauderdale and Miami) ADL limitation Number of chronic Number of chronic conditions conditions Physical health score (unadjusted) Mental health score BMI (unadjusted) IADL limitation ADL limitation = activities of daily living; AIDS =acquired immunodeficiency syndrome; ASI -Alc =Addiction Severity Index –Alcohol; ASI ADL - Drug =Addiction Severity Index – Drugs; BMI =body mass index; CD4= cluster of differentiation 4; CHF =congestive heart failure; COPD =Chronic Obs tructive Pulmonary Disease; CRC =colorectal cancer; C -SDSCA =Chinese version of the Summary of Diabetes Self -Care Activities measure; DBPdiastolic blood pressure; DRUGS =Drug Regimen Unassisted Grading Scale; =emergency department; ER -G=Functional Assessment of Cancer Therapy -General; FOBT =fecal ED =emergency room; FACT =federally qualified health center; HADS =hospital anxiety and depression scales; HAQ =health occult blood test; FQHC assessment questionnaire; HbA1c= =human immunodeficie ncy virus; HRQoL =health -related glycosylated hemoglobin; HIV quality of life; IADL =instrumental activities of daily living; INR =International Normalized Ratio; LDL =low density lipoproteins; LVEF =left ventricular ejection fraction; MMT =Medication Management Test; NYHA =New York Hospital Association; OTC -the -counter; Pap= Papanicolau test; SBP =systolic blood pressure; SES =socioeconomic status; Serum K =serum =over potassium; Serum Na =serum sodium; SF =short form; TOFHLA =Test of Functional Health Literacy in Adults; VA =Veteran’s Administration ; VRQoL =vision -related quality of life. 46

69 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Quality Score Multivariate Analyses Population Outcomes 67 Mortality Baker et al., 2008 Prudential Age 3,260 new Sex Medicare managed care enrollees in Race Prospective cohort Language Cleveland, OH; Houston, TX; and Income Good Tampa and south Education Florida (including Ft. SF -36 physical functioning Lauderdale and Miami) and mental health component scores Number of chronic diseases Number of impairments in ADLs Number of impairments in IADLs City of enrollment 93 HIV test acceptance Age Barragan et al., 2005 372 patients at an inner -city public -sectional Cross Education hospital urgent care Fair center in Atlanta, GA 132 Mexican nativity Elevated depressive Bennett et al., 2007 99 pregnant patients Recent marijuana use symptomatology receiving prenatal care -sectional Cross Fair in clinics in Philadelphia, PA 85 Age US adults 65 Mammography Bennett et al., 2009 2,668 Cross years and older in a Influenza vaccine Race -sectional Good Health status Gender nationally Income representative sample Nativity 107 Age Chew et al., 2004 332 patients at a Nonadherence to fasting Marital status Prospective cohort preoperative clinic of instructions Nonadherence to preoperative Fair Number of medications the VA Puget Sound medication instructions Cognitive functioning 47

70 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Outcomes Quality Score Multivariate Analyses Population 81 Race Cho et al., 2008 489 elderly outpatients ER visits at hospital and an Cross Ethnicity Hospitalizations -sectional FQHC in Chicago Preventive care Fair Gender Educational attainment FOBT Mammography -report) Health status (self Nonadherence Failed to fill prescriptions on time Health behavior measured through Health Promoting Lifestyle Profile Demands of immigration 99 participants from 2 Coffman and Norton, Depression 135 2010 Latino service agencies -sectional Cross Fair 75 ≥1 prescription Misunderstood Age 395 adults in primary Davis et al., 2006 care clinics in -sectional label instructions Sex Cross Correct demonstration of Race Fair Shreveport, LA; Education number of pills Jackson, MI; and Chicago, IL Number of medications currently taken daily Site 80 Child age 150 patients at a Child ED visits DeWalt et al., 2007 Retrospective cohort Household income general, asthma and Hospitalizations Parental race Albuterol use (unadjusted) Fair allergy, and pulmonary clinic at children’s Parental asthma knowledge Appropriate controller use hospital (unadjusted) Parental smoking Asthma severity classification Controller medication use Site of care 126 Estrada et al., 2004 Age 143 adults > 50 years Warfarin control measured Prospective cohort old on warfarin ≥ 1 through INR variability and INR month in 2 in the therapeutic range Fair anticoagulation management units 106 Adherence to medication as Age Fang et al., 2006 179 patients at an measured by self nic in -sectional anticoagulation cli -report of Sex Cross Fair Race/ethnicity San Francisco, CA missed doses over 3 time periods (last 3 days, last 2 Education weeks, > 3 months) Cognitive impairment No missed doses > past 3 Years on warfarin months 48

71 Table 5. Overview of health literacy studies (continued) Source Covariates Included in Design Quality Score Multivariate Analyses Outcomes Population 91 Garbers et al., 2004 205 women recruited Ever had a Pap test Having a source of care through their younger Pap test within past 3 years -sectional Cross Having any health insurance in 2 Fair Age female relatives Years in the US women's health Education centers in New York City 73 Gatti et al., 2009 Negative beliefs about reported medication - Self 275 participants adherence recruited from 3 medications -sectional Cross Age outpatient pharmacies -efficacy Low self at Grady Memorial -report of hyperlipidemia Self Fair Hospital, and from the DeKalb Grady Health Center pharmacy in Atlanta, GA 61 Nonadherence to cardiovascular Age Gazmararian et al., 2006 1,549 new Prudential Medicare managed Race Prospective cohort medication refill adherence (1- Fair Gender care enrollees in year peri od) Cleveland, OH; Education Regimen complexity Houston, TX; and Tampa and south Florida (including Ft. Lauderdale and Miami) 104 Individual’s norm 87 patients at an HIV for < 95% adherence to HIV Graham et al., 2007 clinic in Philadelphia, acceptable adherence medication regimen (self -report Retrospective cohort -conceptualized PA (investigator of pill counts over past 3 Fair as mediator) months) 97 Race 62 patients in 5 San Grubbs et al., 2009 Time from dialysis date to Francisco Bay transplant list referral date Retrospective cohort Gender outpatient dialysis units Fair Time from transplant Income list referral date to waitlist date Age at start of dialysis Support Hypertension Diabetes Peripheral vascular disease Coronary artery disease HIV Hepatitis C Congestive heart failure Depression Drug abuse 88 Guerra et al., 2005 FOBT 136 patients at 4 Ethnicity -sectional community clinics, 2 Cross Sigmoidoscopy or colonoscopy Medicaid Fair university practices in Education Pennsylvania Income 49

72 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Outcomes Multivariate Analyses Population Quality Score 90 Guerra et al., 2005 Mammography Age 97 patients at 3 community health -sectional Cross Education Fair Acculturation plans in Philadelphia, Insurance status PA 163 Age Hahn et al., 2007 being, emotional - 415 adult cancer Physical well patients in 5 Chicago Cross Gender -sectional well -being, and functional well - Good area cancer centers -G) Race/ethnicity being (FACT Physical functioning, role- Work status physical, bodily pain, vitality, Marital status mental health, fair/poor health Living arrangement -3 6) (SF Socioeconomic status Standard Gamble utility score Prior computer experience Cancer diagnosis Stage at diagnosis Months since diagnosis Current chemotherapy treatment status Performance 98 Hibbard et al., 2007 303 community Choosing a quality hospital Age participants Gender Cross -sectional Fair Education Comprehension Activation 108 110 caregivers of Hironaka et al., 2009 Days of adherence to giving Race/ethnicity Prospective cohort vitamins to their infants in prior Caregiver education infants who receive Fair care at 2 pediatric week Caregiver concerns regarding multivitamins and possible clinics side effects Randomized assignment to drops or sprinkle formulation 83 Hope et 61 control group RCT Race ED visits al., 2004 participants with CHF Prospective cohort NYHA classification in Indianapolis, IN Medications Fair Reading score 68 Howard, et al., 2005 3,260 new Prudential Use of inpatient, outpatient, ED, Age Prospective cohort Medicare managed or pharmacy services Sex Good enrollees in care Costs for 1 -year period: overall, Race/Ethnicity Cleveland, OH; inpatient, outpatient, pharmacy Income Houston, TX; and Depression (unadjusted) Education Tampa and south attack (unadjusted) Heart Tobacco Florida (including Ft. Angina (unadjusted) Alcohol Lauderdale and Miami) Stroke (unadjusted) Comorbidities COPD (unadjusted) 50

73 Table 5. Overview of health literacy studies (continued) Source Covariates Included in Design Multivariate Analyses Population Quality Score Outcomes 63 Age Howard, 2006 Physical HRQoL (SF 3,260 new Prudential - 12) -12) Gender Cohort Medicare managed Mental HRQoL (SF Race/ethnicity Fair IADL limitation care enrollees in Cleveland, OH; Education ADL limitation Income Houston, TX; and Physical HRQoL Tampa and south Mental HRQoL Site -reported health good or Morbidity Self Florida (including Ft. Smoker higher Lauderdale and Miami) Receipt of influenza vaccine Receipt of pneumococcal vaccine 10 Huizinga et al. 2008 None 160 patients at a BMI (unadjusted) primary care clinic at -sectional Cross Vanderbilt University Fair 162 Motor index Johnston et al., 2005 Physical morbidity 107 adult patients at spinal cord injury clinic Cross Education Mental health morbidity -sectional Fair - in New Jersey Physical Component score (SF 12) Mental Component score (SF - 12) Physical independence Mobility 74 Johnson et al., 2010 Age Adherence to medication 275 patients at 3 pharmacies at Grady Cross regimens -sectional Sex Fair Memorial Hospital in Atlanta, GA (intervention site) and a -based community satellite pharmacy in Decatur, GA (control site) 103 Kalichman et al., 2008 - positive adults Age Antiretroviral therapy pill 145 HIV Prospective cohort Education adherence (pill counts averaged in Atlanta, GA Fair Years since testing HIV over past 4 months) Depression (unadjusted) positive HIV symptoms (unadjusted) HIV symptoms Depression Internalized stigma Social support Alcohol use 142 Chronic disease Age - 103 community Kim, 2009 Education dwelling older adults at -sectional Cross Functional health status a community -based Income Fair Activity limitations senior welfare center in Daegu, Busan, and Kyungpook provinces in Korea 51

74 udies (continued) Table 5. Overview of health literacy st Source Covariates Included in Design Multivariate Analyses Outcomes Population Quality Score 123 Kripalani et al., 2006 152 patients with Age DRUGS: Requiring observed coronary heart disease Education Cross -sectional completion of 4 tasks: Identify appropriate medication Good Cognitive functioning at a clinic in Atlanta, GA Open container Select correct dose Report appropriate timing of doses 143 Heart failure None 998 adults with Laramee et al., 2007 diabetes in primary -sectional Cross Fair es in care practic Vermont, New Hampshire, and northern New York State 160 Age Lee, 2009 report) 489 seniors who are - General health (self -12) Gender -sectional Physical health (SF patients at 1 of 2 Cross Fair Mental health (SF Chicago, IL clinics -12) Race Education Marital status Income Social support level 128 LeVine et al., 2004 167 mothers of Comprehension of radio health Maternal schooling -sectional Cross kindergarten-age messages Childhood socioeconomic Fair children in urban and Comprehension of visual print status rural Nepal message health Age Ability to give an organized Current socioeconomic status health-related narrative Husband's schooling Urban/rural 130 Depressive symptomatology Lincoln et al., 2006 - 390 adults in an inner Time term inpatient short Prospective cohort -Alc - city ASI Sex detoxification unit Fair ASI -Drug Age Race Education Income Primary language Primary substance of choice Randomization group Mini -mental status exam Outcome variables at baseline 96 2006 Age Lindau et al., Patient followed up on time after 68 patients at clinics in Race Cohort a Chicago- abnormal Pap area Patient followed up within 1 year Fair HIV status academic medical center Cancer Unemployment Insurance 52

75 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Outcomes Quality Score Multivariate Analyses Population 151 HbA1c Patient trust 102 patients at 2 urban Mancuso, 2010 Depression Midwestern US primary care clinics -sectional Cross Diabetes knowledge -care Performance of self activities Good 100 , 99 Access to asthma care Mancuso et al., 2006 175 patients at a Age primary care practice in Cross -sectional Access to care due to other Race/ethnicity Fair New York City conditions Sex -related quality of life Asthma Comorbidity -related quality of ysical health Ph Language -36) life (SF Asthma duration Asthma severity Asthma control 122 Marteleto, 2008 4,751 individuals aged Grades completed in 2002 Sexual debut Prospective cohort 14-22 years old at time First pregnancy Enrolled in 2002 Fair of Wave 1 of study in Age Town, South Cape Age squared Africa Race Income Household shock Mother's education Father's education Living with mother Living with father 145 CD4 cell count: median Mayben et al., 2007 Gender 119 adults with HIV receiving care at 4 (interquartile range) -sectional Cross Reason for getting tested Fair publicly funded clinics Marijuana use in Houston, TX 89 Age 50 patients at a Miller et al., 2007 Last time received colon community - screening -sectional Cross university Fair based internal medicine clinic 134 Morris et al., 2006 1,002 adults with Age HbA1c level diabetes in primary Cross -sectional SBP Sex Good care practices in Race DBP LDL Vermont Marital status -cholesterol Retinopathy Insurance Income Nephropathy Duration of diabetes Foot/leg problems Diabetes education Gastroparesis Depression Cerebrovascular disease Coronary artery disease Alcohol use Medication use Depression (unadjusted) Depression, median Patient Physician practice Health Questionnaire Score (unadjusted) 53

76 Table 5. Overview of health literacy studies (continued) Source Covariates Included in Design Outcomes Quality Score Multivariate Analyses Population 161 Muir et al., 2008 110 glaucoma patients VRQoL Score (mean) Age Race -sectional Physical HRQoL at a Duke eye clinic in Cross Visual acuity -12) (SF Fair Durham, NC Mental HRQoL Visual field (SF - Education 12) 82 Medication adherence Murphy et al., 2010 186 patients at 5 US Age sites, primarily through Viral load Education level Cross -sectional -efficacy to adherence to Self the Adolescent Trials Network: medication regimens Fair Lauderdale, FL; Ft. Medical care received Philadelphia, PA; Baltimore, MD; and Los Angeles, CA; 1 nonnetwork site was located in Detroit, MI 78 192 patients at a Murray et al., 2009 ED use Age university -based public Cohort Hospitalizations Race clinic practice in Fair Insurance Indianapolis, IN NYHA class LVEF Hematocrit CHF score Serum Na, Income Serum K, Cardiomyopathy questionnaire Comparison refill adherence prescription label reading Depression 131 Depressive symptomatology Hispanic Nokes et al., 2007 489 HIV - positive adults over body changes receiving care in San Cross -sectional Distress Fair HIV symptom intensity Francisco, Fresno, Global physical health scale Richmond, NYC, (unadjusted) Corpus Christi 69 Osborn et al., 2007 Nonadherence to HIV 204 patients at 2 HIV Race -sectional clinics, 1 in Chicago, medications in past 4 days (self - Cross Gender Fair IL, and 1 in Shreveport, report) Age LA Income Number of medications in HIV regimen Non -HIV comorbid conditions Mental illness 54

77 Table 5. Overview of health literacy studies (continued) Source Covariates Included in Design Outcomes Multivariate Analyses Quality Score Population 171 Osborn et al., 2009 Analysis 1 383 patients from 2 HbA1c: most recent in medical primary care and 2 record Age Cross diabetes specialty -sectional Sex Years of education clinics located at 3 Good medical clinics Annual income Insulin use Diabetes type Years of diagnosed diabetes Race Analysis 2 and 3 Age Years of diagnosed diabetes Insulin use African American race 72 Age Osborn et al., 2010 204 patients at Adherence HIV knowledge and action Insurance coverage outpatient infectious Employment status disease clinics at Cross -sectional Northwestern Memorial Number of medications in HIV Hospital in Chicago, IL Fair regimen and Louisiana State Number of non-HIV University Health prescri ption meds currently Sciences Center in taken Shreveport, LA Presence of a comorbid chronic condition Treatment for a mental health condition in the past 6 months Treatment for alcohol or drug use in past 6 months - Paasche-Orlow et al., Mastery of metered dose inhaler inner 73 patients at 2 Age 79 city hospitals for severe 2005 technique Sex asthma Hospital visits (unadjusted) Prospective cohort Ethnicity Fair ED visits (unadjusted) Education Income History of near -fatal asthma Asthma Hospitalization in prior 12 months 121 Paasche-Orlow, 2 HIV risk behavior in past 3 005 Age 423 female inmates in -sectional Cross Race months (self -report of sex Rhode Island adult Fair Problem drinking without a condom or shared correctional institute injection drug equipment) 55

78 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Outcomes Multivariate Analyses Population Quality Score Orlow et al., 235 patients with HIV Gender - 100% adherence to HIV Paasche 105 and a history of alcohol 2006 -report Age medication regimen (self -day period) problems in Boston, Education for 3 Retrospective cohort Viral load suppressed MA Randomization group Fair Ethnicity Homeless status Drank to intoxication past 30 days Injected drugs past 6 months Complexity of regimen 155 Controlled blood pressure Pandit et al., 2009 330 adults with Age Race hypertension Cross -sectional receiving primary care Fair Gender from clinics in Grand Marital status Rapids, MI, Chicago, Employment status IL, and Shreveport, LA Insurance coverage location Site Number of comorbid conditions Years treated for hypertension Clinic site Education 87 Age -to -date colon screening Peterson et al., 2007 99 patients at a Up community health clinic Self -efficacy for FOBT Sex -sectional Cross in Nashville, TN Fair -efficacy for colonoscopy Self Race Insurance 149 Education 68 patients with Type 2 Powell et al., 2007 Diabetes Health Belief Model scale score Age diabetes treated in a -sectional Cross general medicine clinic Most recent HbA1c level Race Diabetes knowledge Fair Most recent HbA1c 56

79 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Population Multivariate Analyses Quality Score Outcomes 154 Powers et al., 2008 1,224 patients with Age SBP Cross hypertension receiving -sectional Race Fair primary care in the VA Marital status Education healthcare system and Adequacy of income Duke University Diabetic status Healthcare system in Medication adherence Durham, NC Smoking Exercise Participatory decision- making score 124 57 seniors in Amarillo, MedTake Test: ability to open Age Raehl et al., 2006 TX Number of OTC drugs and take own medications while -sectional Cross Fair Owned a car in last 10 years observed by pharmacist Received food assistance in last 10 years 9 200 adults in primary Understanding nutrition labels Age Rothman et al., 2006 care clinic Cross Obese (BMI > 30) (unadjusted) Gender -sectional Fair Race/ethnicity Number with chronic illness Income (unadjusted) Education Insurance status Presence of chronic disease Status of being on a specific diet Label reading frequency 150 395 diabetes patients Schillinger et al., 2006 HbA1c Age anguage other than Primary l (> 30 years old) treated -sectional Cross at 1 of 2 primary care Good English Insurance clinics at San Francisco General Education Hospital 141 Race Physical, mental, or other health Sentell and Halpin, 2006 23,889 adults in a condition that keeps respondent national sample -sectional Cross Education Fair Understand English from working Long-term illness (> 6 months) Born in US Unemployed Family income Income missing Sex Age Married Get food stamps Live in metropolitan statistical area Region 57

80 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Multivariate Analyses Population Quality Score Outcomes 119 Age 78 patients at a primary Z score - Sharif and Blank, 2010 BMI care pediatrics clinic in Parental BMI Cross -sectional eating self Fair Child an inner -efficacy -city academic -efficacy Parental eating self community health - TOFHLA center in the Bronx, NY Parental S 84 499 children in a New Ethnicity Shone et al., 2009 Any urgent care use Race -sectional Cross Child fair/poor health (adjusted) York school district, Fair Asthma not under good control where over 40% of Child health Insurance children live in poverty (unadjusted) Parent employment Age Smith and Haggerty, 229 adults in status Perceived general health 159 -affiliated university 2003 Smoking status Cross family practice center Maternal language -sectional in Montreal, Canada Fair 167 Sudore et al., 2006 Demographics: age, race, 2,512 well - functioning Mortality rate Prospective cohort, Medicare recipients gender, income, education Health status: self -rated retrospective analysis living in the community Good health, cardiac disease, in Memphis, TN and stroke, cancer, hypertension, Pittsburgh, PA diabetes, obesity Health-related behaviors: former or current smoker, drinking >1 alcoholic beverage per day Poor health care access: lack of a regular doc or clinic, no flu shot within past 12 months, no insurance for medications Psychosocial status: high depressive symptoms, poor personal mastery 95 2,512 well -functioning Sudore et al., 2006 Influenza shot Age Medicare recipients Cross -sectional Access measures: Race community living in the Fair No doctor/clinic Sex in Memphis, TN, and No insurance for medication Income Pittsburgh, PA Composite of access measures Study site Obesity (BMI >30) (unadjusted) Health status Depression (unadjusted) Cardiac disease Hypertension (unadjusted) Stroke Diabetes (unadjusted) Cancer Hypertension Diabetes Obesity Depressive symptoms 58

81 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Outcomes Quality Score Population Multivariate Analyses 148 Gender HbA1c level Tang et al., 2008 149 adults with Insurance Cross sectional survey and - diabetes in diabetes Duration of diabetes education management medical chart review center of a public Fair Patient awareness score C-SDSCA (management of hospital in Hong Kong diabetes) 113 Torres et al., 2009 106 women patients at None Self - efficacy for taking hormone therapy (unadjusted) a family health center -sectional Cross in New York City Fair 115 von Wagner, 2007 719 individuals in a Don’t smoke Age Cross -sectional national sample of Fruit and vegetable intake > Education Fair British adults 5/day Gender Any exercise in the last week Ethnicity Income 114 Self von Wagner et al., 2009 96 adults in London, efficacy for participating in Age - England between CRC screening -sectional Cross Ethnicity 50- Fair 69 years of age Employment Gender Number of computer links open Mean reading time CRC screening knowledge 71 Waite et al., 2008 204 patients at 2 HIV Stigma concerns related to Nonadherence to HIV Cross -sectional clinics, 1 in Chicago, IL medications in past 4 days (self - HIV medications (self -report) Fair and 1 in Shreveport, -conceptualized (Investigator report) LA as mediator) Age Gender Site Employment status Number of medications in HIV regimen Number of non-HIV prescription medications taken Comorbid chronic condition Treatment for mental health condition Treatment for substance abuse 59

82 Table 5. Overview of health literacy studies (continued) Source Covariates Included in Design Quality Score Population Outcomes Multivariate Analyses Waldrop - Gender Medication Management Test Valverde et al., 155 patients from an 47 2009 HIV clinic and (MMT) Education Time since HIV diagnosis participants in AIDS -sectional drug assistance Cross program in Miami, FL Fair 133 Walker et al., 2007 363 patients at 3 None Hospital Anxiety and Depression rheumatology clinics in Cross -sectional scales (HAQ and HAD) the United Kingdom Fair 168 Weiss et al. 2004 74 Medicaid Total Medicaid costs, 1-year Age period Retrospective cohort beneficiaries in Arizona Ethnic group Health status Fair 86 White et al., 2008 Age 18,100 participants in Colon cancer screening Gender Cross -sectional nationally Mammography Fair Race representative US flu shot Had Poverty level sample living in Vision checkup Insurance households Dental checkup Health status Prostate screening Osteoporosis screening Oral reading fluency 66 Age Wolf et al., 2005 3,260 new Prudential -36) Physical functioning (SF -sectional Cross Sex Medicare managed -36) Mental health functioning (SF Fair Race/ethnicity care enrollees in Hypertension Income Cleveland, OH; Asthma Education Houston, TX; and Bronchitis or emphysema Tobacco Tampa and south Heart failure Alcohol consumption Florida (including Ft. Coronary artery disease -reported comorbid Self Lauderdale and Miami) Diabetes conditions Arthritis Cancer IADL Activity limitations Limitations due to physical health Pain interfering with activities 76 Wolf et al., 2007 None Correctly interpreted primary in primary 395 adults -sectional care clinics in Cross prescription label (unadjusted) Correctly attended to auxiliary Shreveport LA; Fair label (unadjusted) Jackson MI; and Chicago, IL 60

83 Table 5. Overview of health literacy studies (continued) Source Design Covariates Included in Outcomes Multivariate Analyses Population Quality Score 157 Wolf et al., 2006 PSA level > 20 ng/mL Age 308 patients with newly -sectional diagnosed prostate Race Cross cancer in 4 outpatient Annual income Good Marital status oncology and urology clinics in Chicago area 120 Wolf et al., 2006 Age Read/looked at medication 251 adults at a primary guides and consumer information -sectional Gender Cross care clinic in Fair included with prescription Race Shreveport, LA medications Education Number of prescriptions taken 70 HIV treatment knowledge 204 patients at 2 HIV Wolf et al., 2007 Nonadherence to HIV -sectional clinics, 1 in Chicago, -conceptualized Cross medications in past 4 days (self - (investigator report) as mediator) IL, and 1 in Shreveport, Fair Perception of self LA -efficacy to -efficacy HIV medication self (investigator conceptualized take and manage HIV properly medications as mediator) Age Insurance coverage Employment status Number of medications in HIV regimen Number of -HIV non prescription medications currently taking Presence of comorbid chronic conditions Treatment for mental health condition past 6 months Treatment for alcohol or drug use past 6 months 64 Age 2,923 new Prudential Wolf, 2007 Smoking (never, former, or Medicare managed Gender -sectional Cross current) care enrollees in Race/ethnicity Fair Current alcohol use (none, light to moderate, or heavy) Language (English or Cleveland, OH; Spanish) Houston, TX; and Level of physical activity per week Tampa and south Site Florida (including Ft. use (unadjusted) Education Seat belt Lauderdale and Miami) Annual income Occupation (white or blue collar) 61

84 Table 5. Overview of health literacy studies (continued) Source Covariates Included in Design Outcomes Population Multivariate Analyses Quality Score 125 reported use of Self Yin et al., 2007 Experience of ever receiving 292 parents or - caregivers of children -sectional nonstandardized dosing Cross a dosing instrument in a care setting instrument health Fair at an ED in New York Child’s age City Child has regular health care provider Confounders with health literacy: caregiver’s education, country of origin, language, socioeconomic status 102 Yin et al., 2009 -report of children's Parent's self 6,100 parents from US Age households health insurance status and Gender Cross -sectional difficulty understanding OTC Number of children living in medication labels the home Fair Educational attainment Race/ethnicity Country of birth English proficiency Income Region Metropolitan statistical area 127 302 patients at a public Parent's age Dosing accuracy Yin et al., 2010 Relationship to child hospital (Bellevue) -sectional survey Cross Marital status pediatric clinic in New York, NY Language Fair Ethnicity US birth SES Presence of a child in the house < 8 years old Presence of a child in the house with a chronic medical condition 62

85 Table 6. Measurement tools and criteria used to measure health literacy or literacy in KQ 1 articles Measurement Tool Study Measurement Levels (Continuous or Cutpoints) 122 Continuous Marteleto, 2008 Cape Area Panel Study Literacy and Numeracy Evaluation 168 Weiss, 2004 < 3rd grade, > 3rd grade Instrument for the Diagnosis of English/Spanish) - Reading (IDR 83 Medication Skills Assessment 0 = no correct answers, 1 = correctly answered Hope, 2004 some questions, 2 = correctly answered all (Reading Score) questions 141 Continuous Sentell, 2006 National Adult Literacy Survey (NALS) literacy and numeracy 85 Bennett, 2009, National Assessment of Adult Below basic, basic, intermediate, proficient 102 86 Literacy (NAAL) , Yin, 2009 White, 2008 127 Yin, 2010 High likelihood of limited, possible limited, Newest Vital Sign adequate 128 Reading comprehension and No school, 1-4 years, 5-9 years, 10+ years Levine, 2004 ic language proficiency academ (noun definitions) in Nepalese 93 Low or < 6th grade, not low or > 6th grade Rapid Estimate of Adult Barragan, 2005 Literacy in Medicine (REALM) 104 Huizinga, < 9th grade (score: 0-60), > 9th grade (score: 61- Graham, 2007, Rapid Estimate of Adult 96 10 Lindau, 2006, Literacy in Medicine (REALM) 2008, 66) 87 Powers, Peterson, 2007, 80 154 DeWalt, 2007, 2008, 130 Muir, Lincoln, 2006, 84 161 Shone, 2009, 2008, 167 Miller, Sudore, 2006, 89 9 2007, Rothman, 2006, 133 , Gatti, Walker, 2007 74 73 Johnson, 2010 2008, 131 Raehl, Nokes, 2007, Rapid Estimate of Adult Continuous 124 159 Smith 2003 2006, Literacy in Medicine (REALM) 105 - Orlow, 2006, Rapid Estimate of Adult 44) - Low or < 6th grade (score: 0 Paasche 121 Marginal or 7th-8th grade (score: 45- Literacy in Medicine (REALM) 60) Paasche-Orlow, 2005, 75 Kripalani, Adequate or > 9th grade (score: 61-66) Davis, 2006, 157 123 Wolf, 2006, 2006, 69 Wolf, Osborn, 2007, 70 120 Wolf, 2007, 2006, 95 Sudore, 2006, Waite, 76 71 Wolf, 2007, 2008, 72 Osborn, 2010 149 Powell, 2009, Estrada, 8th grade, > 9th - Rapid Estimate of Adult 6th grade, 7th - < 3rd grade, 4th 126 2004 grade Literacy in Medicine (REALM) 62 Baker, 2004, Inadequate (0-55), Marginal (56-66), Adequate (67- Short Test of Functional Health Baker, 64 65 Wolf, 2007, 100) 2007, -TOFHLA) Literacy in Adults (S 67 Howard, Baker, 2008, 63 66 Wolf, 2005 2006, 63

86 Table 6. Measurement tools and criteria used to measure health literacy or literacy in KQ 1 articles (continued) Study Measurement Tool Measurement Levels (Continuous or Cutpoints) 107 Chew, 2004, Short Test of Functional Health - - Inadequate (0 - 16), Marginal (17 22), Adequate (23 78 36) -TOFHLA) Literacy in Adults (S Murray, 2009 113 Torres, 2009, 124 Raehl, 2006 61 Gazmararian, 2006, Short Test of Functional Health - 66), Adequate (67 - 53), Marginal (54 - Inadequate (0 68 TOFHLA) - 100) Howard, 2005 Literacy in Adults (S 97 Inadequate/Marginal (Limited) (0 - Grubbs, 2009, 22), Adequate Short Test of Functional Health 81 -36) (23 Cho, 2008, -TOFHLA) Literacy in Adults (S 88 Guerra, Guerra, 2005, 90 108 Hironaka, 2009, 2005, 143 Laramee, 2007 160 L ee, 2009 134 22), Adequate ( - 23 Morris, 2006 Short Test of Functional Health Inadequate (0 - 16), Marginal (17 - - 36) and continuous measurement Literacy in Adults (S TOFHLA) 79 Paasche-Orlow, 2005 Short Test of Functional Health Inadequate (0-16), Marginal/Adequate (17-36) - Literacy in Adults (S TOFHLA) 155 Short Test of Functional Health Pandit, 2009 Category I: 0 - 30, Category II: 31 - 50, Category III: Literacy in Adults (S - 51 - 70, Category IV: 71 - 90, Category V: 91 - 100 TOFHLA) 150 Short Test of Functional Health Schillinger, 2006, Continuous Raehl, 124 2006, Literacy in Adults (S -TOFHLA) von Wagner, 115 98 Hibbard, 2007, 2007, 119 Sharif, 2010 148 Ta ng, 2007 Short Test of Functional Health Continuous Literacy in Adults (S -TOFHLA) (Chinese) 106 Fang, 2006 - 22), Adequate (23 - Short Test of Functional Health Limited (inadequate/marginal, 0 -TOFHLA) 36) Literacy in Adults (S (English or Spanish) 132 - Short Test of Functional Health Bennett - 66), Adequate (67 , 2007 Inadequate (0 - 55), Marginal (56 Literacy in Adults (S 100) -TOFHLA) (Spanish) 47 - Valverde, 2009 Test of Functional Health Continuous Waldrop Literacy in Adults (TOFHLA) 162 Johnston, 2005, 74), Adequate - Inadequate/Marginal (combined; 0 Test of Functional Health 145 (75 Mayben, 2007, -100) Literacy in Adults (TOFHLA) 100 Mancuso, 2006, 99 Murphy, Mancuso, 2006 82 2010 103 Test of Functional Health High er literacy (90% correct or 45 of 50 questions Kalichman, 2008 Literacy in Adults (TOFHLA) correct), Lower literacy (<90% correct or < 45 correct) 125 Yin, 2007, Marginal (60 - Test of Functional Health - 74), Adequate (75 Inadequate (0 - 59), (English or 91 100) Literacy in Adults (TOFHLA) Spanish), Garbers, 2004 (Spanish), Mancuso, 151 2010 64

87 Table 6. Measurement tools and criteria used to measure health literacy or literacy in KQ 1 articles (continued) Measurement Tool Measurement Levels (Continuous or Cutpoints) Study 142 Functional Kim 2009 Higher, lower Korean Test of Health Literacy in Adults (TOFHLA) 114 United Kingdom Test of Continuous Von Wagner, 2009 Functional Health Literacy in Adults (TOFHLA) 163 Woodcock Language Hahn, 2007 < 7th grade, > 7th grade Proficiency Battery (passage comprehension subtest) 65

88 Table 7. Summary of studies of the relationship between health literacy and emergency department and hospitalization rates (KQ 1a) Authors, Year, Outcome Measure Study Design, Population and Variables Used in Literacy tool, Differences in Results Between Results By Health Setting, Health Multivariate Sample Size, Quality Analysis Literacy Skill Level Health Literacy Skill Levels Literacy Level Any ED visits Higher rate in inadequate or Age Baker et al., Enrollees in 62 Inadequate: Cleveland, 2004 30.4% marginal compared with adequate Gender Any ED visits Marginal: 27.6% Race Houston, Tampa, Marginal: NR; P = 0.01 Physical and Adequate: 21.8% and south Florida Cohort Inadequate: NR; P < 0.001 mental health S-TOFHLA Chronic diseases N = 3,260 1 ED visit Inadequate: 24.5% Higher rate in inadequate than Inadequate: 17.0% Smoking Marginal: 11.2% adequate; no difference for marginal Alcohol use Good Marginal: 15.3% Adequate: 64.2% 1 ED visit Adequate: 15.0% BMI Marginal: RR, 1.01; 95% CI, 0.76- Study site 1.33 Months enrolled 2 or more ED visits Inadequate: RR, 1.07; 95% CI, 0.86- Inadequate: 13.4% 1.33 Marginal: 12.3% Adequate: 6.8% Higher rate in inadequate or marginal compared with adequate 2 or more ED visits Marginal: RR, 1.44; 95% CI, 1.01- 2.02 Inadequate: RR, 1.34; 95% CI, 1.00- 1.79 Higher probability of Age Inpatient use New Medicare Howard, et al., inpatient and 68 Inadequate: 35% ED services in inadequate than Sex managed- 2005 care Marginal: 34% enrollees in adequate Race/ethnicity Income Cohort Adequate: 27% Cleveland, Mean differences in probability of Houston, Tampa, Education inpatient use in inadequate vs. Tobacco N = 3,260 and south Florida ED use adequate: 0.05; 95% CI, 0.00- 0.09 Alcohol Inadequate: 30% S-TOFHLA ED: 0.05; 95% CI, 0.01-0.10 Marginal: 28% Good Comorbidities Inadequate: 24.5% Adequate: 21% Marginal: 11.2% Mean differences in probability of Adequate: 64.2% marginal vs. adequate inpatient use: 0.04; 95% CI, -0.01 -0.09 ED: 0.04; 95% CI, -0.01-0.09 pharmacy: - - 0.08 - 0.00 0.04; 95% CI, BMI= body mass index; CHF =congestive heart failure; CI =confidence interval; ED =emergency department; FQHC =Federally Qualified Health Center; HIV immunodeficiency virus; HL =health literacy; IRR =incidence rate ratio; LVEF =left =human ventricular ejection fraction; N =number; NR =not reported; NYHA =New York Heart Association; OR =odds ratio; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literac y in Medicine; RR =relative risk; Serum K =Serum K=serum potassium; S -TOFHLA =Short Test of Functional Health Literacy in Adults. 66

89 Table 7. Summary of studies of the relationship between health literacy and emergency department and hospitalization rates (continued) Authors, Year, Outcome Measure Study Design, Variables Used Population and Literacy tool, Results By Health Setting, Health Differences in Results Between in Multivariate Sample Size, Literacy Level Literacy Skill Level Health Lite racy Skill Levels Quality Analysis Control group Race related ED Hope et al., ED visits: Higher cardiovascular - 83 Data NR NYHA RCT participants 2004 visits in patients with worse with CHF in classification prescription label reading skills Indianapolis, IN Medications Cohort P NR; = 0.002 score Reading Ability to read N = 61 standard prescription Fair Literacy level: NR Mean reading score: 1.65 ± 0.56 Murray et al., Age Adequate had a lower risk of based ED use: University - 78 2009 hospitalization for heart failure public clinic Data NR Race practice in Insurance than adequate Hospitalization: Cohort Indianapolis Data NR NYHA class All -cause ED visits (unadjusted) Indiana LVEF N = 192 Prescription label reading score, Hematocrit 1-pt increment: IRR, 0.76; 95% CI, S-TOFHLA CHF score Fair 0.59-0.97 Inadequate: Serum Na, 29.2% Income specific ED visits -failure- Heart Adequate: - Serum K, Cardio (unadjusted) 70.8% myopathy label reading score: Prescription questionnaire IRR, 0.36; 95% CI, 0.19-0.69 Comparison refill adherence All -cause hospitalization prescription label (unadjusted) reading Prescription label reading score: Depression IRR, 0.68; 95% CI, 0.54-0.86 specific Heart -failure- hospitalization (unadjusted): - 0.76 IRR, 0.34; 95% CI, 0.15 ED visits (per child) Children of parents with low HL Child age General, asthma DeWalt et al., 80 Inadequate: 1.53 had a greater incidence of ED and allergy, and 2007 Household visits than those with higher HL: pulmonary clinic Adequate: 1.08 income Retrospective IRR, 1.4; 95% CI, 0.97 -2.0 Parental race at children’s cohort Hospitalizations Parental asthma hospital Children of parents with low HL Inadequate: 0.39 knowledge REALM N = 150 had a greater incidence of Parental smoking Adequate: 0.12 Low: 24% hospitalizations more than with Asthma severity High:76% Fair higher HL: IRR, 4.6; classification 95%, CI 1.8-12 Controller medication use Site of care 67

90 Table 7. Summary of studies of the relationship between health literacy and emergency department and hospitali zation rates (continued) Authors, Year, Study Design, Outcome Measure Population and Variables Used in Literacy tool, Multivariate Results By Health Differences in Results Between Setting, Health Sample Size, Health Literacy Skill Levels Analysis Literacy Level Literacy Skill Level Quality More ER visits in lower HL group; P Elderly outpatients Race ER visits: Cho et al., 81 Ethnicity Data NR at a hospital and an < 0.05 2008 Gender FQHC in Chicago More hospitalizations in lower HL Educational Cross -sectional Hospitalizations: ; P group < 0.05 S-TOFHLA Data NR attainment Inadequate: 50.9% N = 489 Less preventive care in lower health Adequate: 49.1% Preventive care: P < 0.05 literacy group; Data NR Fair Hospital visit past 12 None city - Paasche - Orlow 2 inner Inadequate HL associated with more 79 hospitalization in past 12 mos.: hospitals months et al., 2005 = 0.04 P (unadjusted) NR; Inadequate: 81% Prospective S-TOFHLA Adequate: 52% cohort Inadequate HL not associated with Inadequate: 22% ED visit past 12 months ED visits in past 12 mos.; Adequate: P (unadjusted) = 0.28 Inadequate: 88% N = 73 78% Adequate: 75% Fair Ethnicity Shone et al., New York school Used any urgent care Parent HL level not related to urgent 84 2009 district, where Race Low: 40.9% care > 40% of children Child health Adequate: 41.2% Cross -sectional live in poverty Insurance Used any urgent care; (unadjusted) > 0.999 P Parent employment N = 499 REALM Low: 33% Fair Adequate: 67% 82 > 1 Murphy, 2010 - HL level not related to ER visits ER visits Age positive - HIV Data by HL: NR Education individuals ages 16- compared to none (adjusted): OR, Cross -sectional 24 in Fort 0.98; 95% CI, 0.96-1.01 Lauderdale, hospital Overnight HL level not related to overnight N= 186 Philadelphia, stays > 1 compared to none hospital stay - Data by HL: NR Baltimore, Los (adjusted): OR, 0.97; 95% CI, 0.93- Fair Angeles, and 1.01 Detroit - S-TOFHLA modified Inadequate: 12% Marginal: 3% Adequate: 86% 68

91 Table 8. KQ 1a health literacy studies: strength of evidence grades by health care service outcomes Outcome for Health Literacy Number of Results Studies Studies Overall Grade Hospitalization Moderate 6 Low health literacy associated with increased hospitalization Emergency 9 Low health literacy associated with greater emergency care use Moderate Care Visit report) except in 1 study of urgent care visits (measured by self - Colon Low Larger studies found lower health literacy associated with lower 5 Screening probability of screening Pap Tests Low health literacy associated with decreased probability of 3 Low ever having a Pap test Mammogram 4 Low health literacy associated with less use of mammography; Moderate measures and populations differed across studies Sexually Low Low health literacy associated with greater odds of accepting 1 Transmitted HIV testing Infection Immunization: 4 Low health literacy associated with lower probability of receipt Moderate Influenza of influenza vaccine Immunizat ion: Mixed results Insufficient 2 Pneumococcal Access to Care 9 Mixed results for association with number of physician visits, Insufficient dental and vision visits Access to Low 1 Parental low health literacy associated with having child without Insurance health insurance HIV =human immunodeficiency virus; Pap= Papanicolau. 69

92 Table 9. Summary of studies of the relationship between health literacy and colon cancer screening (KQ 1a) Authors, Year, Study Design, Variables Outcome Measure and Differences in Results Population Literacy tool, Used in Results By Health Setting, Health Between Health Multivariate Sample Size, Literacy Level Analysis Literacy Skill Levels Literacy Skill Level Quality Age Miller et al., No difference between - Self University report of last time 89 limited and adequate -based received colon community 2007 internal medicine groups: RR, 0.99; 95% screening -1.55 clinic -sectional Cross CI, 0.64 Limited: 54% REALM Adequate: 58% N= 50 Limited: 48% Adequate: 52% Fair 81 Cho et al., 2008 Race Elderly outpatients Decreased probability in -report FOBT: NR Self Ethnicity at Hospital and an inadequate compared -sectional Cross Gender FQHC in Chicago with adequate group; < 0.05 P Education N = 489 S-TOFHLA Inadequate:50.9% Fair Adequate: 49.1% report of colon - Self Age Peterson et al., No difference between Community health 87 limited and adequate screening clinic in Nashville, 2007 Sex TN Race groups: OR, 0.67; 95% Cross -sectional Inadequate: 51.7% Insurance -1.83 CI, 0.24 REALM Adequate: 65.7% N = 99 Limited: 29.3% Adequate 70.7% Fair Guerra et al., No differences between 4 community clinics, Ethnicity Self -report FOBT 88 inadequate/marginal 2005 2 university Medicaid Inadequate/Marginal: and adequate groups: practices in PA Education 39% FOBT; P = 0.66 -sectional Cross Income Adequate: 64% Sigmoidoscopy or S-TOFHLA = 0.52 Colonoscopy; P N = 136 Inadequate:36% Sigmoidoscopy or Marginal: 6% Colonoscopy Fair Adequate:58% Inadequate/Marginal: 30% Adequate: 72% White et al., Age Nationally colon -report of Self Adults over 65 years: 86 2008 Gender representative US screen Decreased probability of Race sample living in having colon cancer Cross -sectional Poverty level households Below basic: 38% screening basic/below basic groups; P < 0.05 Insurance Basic: 41% N = 18,100 Health status NAAL Intermediate: 41% Oral reading Basic/below basic: Proficient: 36% Fair fluency 36% Intermediate: 56% Proficient: 12% CI= confidence interval; FOBT =fecal occult blood test; FQHC =federally qualified health center; N =number; NAAL =national assessment of adult literacy; NR =not reported; OR =odds ratio; REALM =Rapid Estimate of Adult Literacy in Medicine; RR= relative risk; S -TOFHLA= Short Test of Functional Health Literacy in Adults. 70

93 le 10. Summary of studies of the relationship between health literacy and Pap tests (KQ 1a) Tab Authors, Year, re Outcome Measu Study Design, Variables Used Differences in Results Population and Literacy tool, Between Health Setting, Health in Multivariate Results By Health Sample Size, Analysis Literacy Skill Levels Literacy Skill Level Literacy Level Quality 81 Race Pap: NR Less Pap screening in Cho et al., 2008 Elderly outpatients at Hospital and an Ethnicity inadequate group than < P adequate group; -sectional Cross FQHC in Chicago Gender 0.05 Education S-TOFHLA N = 489 Inadequate: 51% Adequate: 49% Fair 65) - Pap test (age 18 Age White et al., Adults under 40 Nationally 86 2008 Below basic: 63% representative US Race decreased probability of having a Pap test in sample living in Basic: 67% Gender basic/below basic than Cross -sectional households Intermediate: 70% Poverty level higher groups: < 0.05 P Insurance Proficient: 74% Basic or below NAAL Health status 64 Adults 40- basic: 36% Oral reading no differences by HL Intermediate: 56% N = 18,100 fluency level; P > 0.05 Proficient: 12% Fair Garbers et al., Having a source Ever had a Pap test Less likely to ever have Women recruited 91 2004 of care through their had a Pap test in Having any younger female Inadequate: 80% inadequate compared to health insurance Adequate: 99% marginal and adequate -sectional relatives in 2 Cross Age Marginal: 92.1% women's health Marginal: OR, 0.14; 95% Years in the US N = 205 centers in New -1.41 CI, 0.01 Education York City Pap test within past 3 Inadequate: OR, 0.06; S-TOFHLA years Inadequate: 30% 0.55 95% CI, 0.01- Marginal: 19% Fair Inadequate: 62.3% Adequate: 51% No differences in Pap Adequate: 82.9% test within past 3 years Marginal: 82.1% Marginal: OR, 1.31; 95% CI, 0.44 -3.85 Inadequate: OR, 0.53; 95% CI, 0.21 - 1.35 CI= =federally qualified health center; HL =health literacy; N =number; NAAL =National Assessment confidence interval; FQHC =Short Test of Functional Health Literacy in =not reported; OR =odds ratio; Pap= Papanicolau, S -TOFHLA of Adult Literacy; NR Adults; US =United States. 71

94 Table 11. Summary of studies of the relationship between health literacy and mammography (KQ 1a) Authors, Year, Study Design, Outcome Measure Variables Used Population and Literacy tool, Results By Health in Multivariate Setting, Health Differences in Results Between Sample Size, Literacy Skill Level Health Literacy Skill Levels Analysis Quality Literacy Level Mammography: NR Age Bennett et al., Nationally Lower utilization of mammography 85 representative Race in the below basic/basic group; 2009 P < 0.05 sample of US Gender population 65 and -sectional Income Cross older Nativity N = 2,668 NAAL Below basic: 29.0% Good Basic: 29.5% Intermediate: 38.2 Proficient: 3.3% 81 Mammography: NR Cho et al., 2008 Race Outpatients at Less mammography in inadequate Ethnicity hospital and an group than adequate group; P < 0.05 Cross FQHC in Chicago -sectional Gender Education S-TOFHLA N = 489 Inadequate:50.9% Fair Adequate: 49.1% 65: Decreased probability Nationally White et al., Age Mammogram (age >40) Adults > 86 Gender Below basic:58% 2008 representative US mammography in below basic or P basic group; < 0.05 sample living in Basic: 61% Race -sectional Intermediate:62% households Cross Poverty level Insurance Proficient: 62% NAAL status N = 18,100 Basic or below -reported Self basic: 36% health status, Fair Oral reading Intermediate:56% Proficient: 12% fluency Age Mammogram: NR 3 community health Inadequate HL associated with Guerra et al., 90 2005 only lower odds of ever having a clinics in Education mammogram Acculturation Philadelphia Cross -sectional Insurance S-TOFHLA Ever had a mammogram: status N = 97 Inadequate: 70% OR, 0.88; 95% CI, 0.79-0.98 Adequate: 30% Fair Had last mammogram within 1 yr: OR, 0.99; 95% CI, 0.92-1.05 Had last mammogram within 2 yrs: OR, 1.02; 95% C I, 0.93 - 1.09 - Had mammogram as part of check up: OR, 0.99; 95% CI, 0.92 - 1.06 CI= confidence interval; FQHC =federally qualified health center; HL =health literacy; N =number; NAAL =National Assessment of Adult Literacy; NR =not reported; OR =odds ratio; S -TOFHLA =Short Test of Functional Health Literacy in Adults; yr =year. 72

95 Table 12. Summary of studies of the relationship between health literacy and sexually transmitted infections testing (KQ 1a) Authors, Year, Study Design, Differences in Outcome Measure Population and Variables Used Literacy tool, Results Between Results By Health Setting, Health in Multivariate Health Literacy Skill Sample Size, Literacy Skill Level Literacy Level Levels Analysis Quality Inner city public Age Barragan et al., HIV Test Acceptance: Inadequate HL 93 positively associated 2005 Education NR hospital urgent care center, with acceptance of -sectional Cross Atlanta, GA HIV test compared with adequate group: N = 372 REALM CI, OR, 2.017; 95% Inadequate: 1.190- 3.418 Fair 25% Adequate: 75% CI= confidence interval; HIV =human immunodeficiency virus; HL =health literacy; N =number; NR =not reported; OR =odds ratio; REALM =Rapid Estimate of Adult Literacy in Medicine. 73

96 Table 13. Summary of studies of the relationship between health l iteracy and immunizations (KQ 1a) Authors, Year, Study Design, Outcome Measure Population and Variables Used Literacy tool, Differences in Results Between Results By Health in Multivariate Setting, Health Sample Size, Literacy Level Literacy Skill Level Analysis Health Literacy Skill Levels Quality Increased probability of having a flu White et al., Pneumonia shot Age Nationally 86 2008 representative US Gender shot in basic/below basic group Below basic: 39% < 0.05 P Adults < 40; Race Basic: 42% sample living in = NS P 64; Adults 40- Cross -sectional households Poverty level Intermediate: 38% Adults >65: Decreased probability Insurance Proficient: 27% N = 18,100 NAAL of flu shot; not related to having a Health status, < 0.05) P pneumonia shot ( Basic or below Flu shot Oral reading Fair basic: 36% fluency Below basic: 39% Intermediate: 56% Basic: 37% Proficient: 12% Intermediate: 32% Proficient: 26% Howard et al., Prudential Age Influenza vaccine: NR Influenza vaccine receipt lower in 63 2006 Medicare managed Gender inadequate than adequate: 0.76; P = 0.020 OR, care plan in Race/Ethnicity Pneumococcal vaccine: Cohort Cleveland, Education NR No differences in pneumococcal Houston, Tampa, Income vaccine receipt between inadequate N = 3260 and south Florida Site P 0.85; and adequate: OR, = 0.114 Morbidity Fair S-TOFHLA Smoker No difference between marginal Inadequate: 24.4% and adequate groups Marginal: 11.5% Influenza vaccine: OR, 1.06; Adequate: 64.4% P = 0.707 Pneumococcal vaccine: OR, 0.91; P = 0.445 functioning, Sudore et al., Influenza shot: NR Inadequate less likely to have - Well Age 95 Medicare recipients influenza shot in 12 months: 2006 Race 0.59; 95% CI, 0.41-0.83 OR, Sex living in the -sectional Cross Income community in Marginal less likely to have Memphis and Study site N = 2,512 influenza shot in 12 months: Pittsburgh Health status 1.25 0.94; 95% CI, 0.7- OR, Cardiac disease REALM Fair Stroke Limited: 24% Cancer Adequate: 76% Hypertension Diabetes Obesity Depressive symptoms CI= confidence interval; N =number; NAAL =national assessment of adult literacy; NR =not reported; NS =not significant; OR =odds ratio; REALM =Rapid Estimate of Adult Literacy in Medicine; S -TOFHLA =Short Test of Functional Health Literacy in Adults; US =United States. 74

97 Table 13. Summary of studies of the relationship between health literacy and immunizations (KQ 1a) (continued) Authors, Year, Outcome Measure Study Design, Population and Variables Used Literacy tool, Differences in Results Between Results By Health in Multivariate , Health Setting Sample Size, Health Literacy Skill Levels Literacy Skill Level Analysis Literacy Level Quality Age Nationally Bennett et al., Lower utilization of influenza Influenza vaccination: 85 NR vaccination in below basic and representative Race 2009 group; P < 0.05 Gender sample of US basic -sectional Cross population 65 Income Nativity and older N = 2668 NAAL Below basic: Good 29.0% Basic: 29.5% Intermediate: 38.2 Proficient: 3.3% Table 14. Summary of studies of the relationship between health literacy and access to care and access to insurance (KQ 1a) Authors, Year, Outcome Measure Study Design, Variables Used Population and Differences in Results Literacy tool, Results By Health Between Health Literacy Setting, Health in Multivariate Sample Size, Literacy Level Literacy Skill Level Quality Skill Levels Analysis Age HL not associated with time Number of physician Baker et al., Prudential Medicare 62 Gender 2004 managed care to first physician visit, mean visits Inadequate: 9.8% visits, number of physician Race enrollees in Marginal: 9.3% or no physician visit in the Cohort Cleveland, Houston, Physical and Adequate: 8.1% first year Mental health Tampa, and south -diseases Chronic N = 3,260 Florida Number of physician visits Total physician visits Smoking S-TOFHLA Marginal: OR,1.23; 95% CI, Inadequate: 13.7 Good Alcohol use Inadequate: 24.5% 0.82-1.85 Marginal: 13.5 BMI Marginal: 11.2% Inadequate: OR, 1.23; 95% Adequate: 14.3 Study site Adequate: 64.2% -1.72 CI, 0.88 Months enrolled Mean physician visits Time to first visit Inadequate: 2.2 Marginal: HR, 0.89; 95% CI, Marginal: 2.2 0.78-1.00 Adequate: 2.2 Inadequate: HR, 0.94; 95% CI, 0.84 -1.04 Mea n visits Marginal: NR; P = 0.34 Inadequate: NR; P = 0.38 Mean visits Marginal: NR; P = 0.27 Inadequate: NR; P = 0.62 AOR =adjusted odds ratio; BMI =body mass index; CI =confidence interval; ED =emergency department; HIV =human immunodeficiency virus; HL =health literacy; HR =hazard ratio; mos =months; N =number; NAAL =National Assessment of Adult Literacy; NR =not significant; OR =odds ratio; REALM =Rapid Estimate of Adult Literacy in Medicine; =not reported; NS =Test of Functional Health Literacy in =significant; S -TOFHLA= Short Test of Functional H ealth Literacy in Adults; TOFHLA sig Adults; vs. =versus. 75

98 Table 14. Summary of studies of the relationship between health literacy and access to care and access to insurance (KQ 1a) (continued) Authors, Year, Study Design, Outcome Measure Differences in Results Population and Literacy tool, Variables Used in Results By Health Setting, Health Between Health Literacy Sample Size, Literacy Skill Level Multivariate Analysis Skill Levels Literacy Level Quality New Prudential Howard et al., Inadequate HL not related to Overall use Age 68 Medicare managed- Inadequate: 95% Sex 2005 overall use, outpatient, or Marginal: 96% Race/Ethnicity care enrollees in pharmacy use Cleveland, Houston, Adequate: 97% Cohort Income Tampa, and south Marginal HL used more Education Florida pharmacy services than those Tobacco N = 3,260 Inpatient use with adequate HL Alcohol Inadequate: 35% S-TOFHLA Marginal: 34% Comorbidities Good Inadequate: 24.5% All other use comparisons not Adequate: 27% Marginal: 11.2% significant Adequate: 64.2% Outpatient use ity Mean differences in probabil Inadequate: 90% of use Marginal: 90% Inadequate vs. adequate Adequate: 91% Overall: 0.00; 95% CI, -0.02-0.02 ED use -0.02; 95% CI, Outpatient: Inadequate: 30% -0.05-0.01 Marginal: 28% Pharmacy: -0.03; 95% CI, Adequate: 21% -0.06-0.00 Pharmacy use Mean differences in probability Inadequate: 85% of use Marginal: 85% Marginal vs. adequate Adequate: 88% Overall: 0.00; 95% CI, -0.02-0.03 Outpatient: -0.01; 95% CI, -0.04-0.02 Pharmacy: -0.04; 95% CI, - 0.08 - 0.00 Lindau et al., - time follow - No differences on followed up on Patient Age Clinics in Chicago 96 2006 time after abnormal Race area academic up after an abnormal Pap smear between inadequate HIV status medical center Pap and adequate groups: OR, Cohort Cancer REALM Inadequate: 33% Unemployment 2.05; 95% CI, 0.47 -8.85 Adequate: 66% Inadequate: 35% N = 68 Insurance No differences in predicting Adequate: 65% women's follow -up within one Patient followed up Fair year between inadequate and within one year adequate groups: OR, 3.75; 95% CI, 0.81- 17.4 Inadequate: 67% Adequate: 80% 5 San Francisco bay Race Longer time from dialysis date Grubbs et al., Time from dialysis 97 date to transplant list outpatient dialysis Gender to transplant referral list date 2009 referral date units in inadequate group than Income Retrospective Age at start of dialysis adequate group: HR 4.54; S-TOFHLA Inadequate: 23.5 mos cohort 95% CI, 1.67- 12.5 Support Inadequate: 32.3% Adequate: 15.3 mos Hypertension No difference in time from N = 62 Diabetes Peripheral vascular transplant list referral date to Time from transplant disease Fair 76

99 Table 14. Summary of studies of the relationship between health literacy and access to care and access to insurance (KQ 1a) (continued) Authors, Year, Study Design, Outcome Measure Population and Variables Used in Differences in Results Literacy tool, Results B y Health Multivariate Setting, Health Between Health Literacy Sample Size, Skill Levels Literacy Level Literacy Skill Level Quality Analysis Grubbs et al., Adequate: 67.7% Waitlist date by HL: HR 1.25; Coronary artery list referral date to 97 disease 95% CI, 0.62- 2009 waitlist date 3.45 HIV (continued) Inadequate: 6.6 mos Hepatitis C Adequate: 2.1 mos Congestive heart failure Depression Drug abuse Hibbard et al., Community Age No differences in predicting Choosing a quality 98 2007 Gender choice hospital: NR quality choice of a hospital TOFHLA (passage Education between inadequate and adequate groups; = NS P Cross - B) Comprehension sectional Low: 45% Activation High: 55% N = 303 Fair Sudore et al., -functioning, Well Age Doctor/clinic Less access in 3 of 4 access 95 2006 Medicare recipients Race Insurance for meds measures between limited living in the Sex Composite access and adequate group. - Cross community with Income, measure: NR sectional multiple sources of Study site No doctor/clinic: OR, 0.79; medical care in Health status 1.45 95% CI, 0.43- N = 2,512 Memphis and Cardiac disease Pittsburgh Stroke No insurance for medication: Fair Cancer 5% CI, 0.41-0.81 OR, 0.58; 9 REALM Hypertension Limited: 24% Diabet es Composite access measure: -6th (= 8.8%, 0 Obesity OR, 0.51; 95% CI, 0.35-0.75 grade, + 15.2%, Depressive marginal/7-8th symptoms Marginal group did not differ grade) from adequate group in any Adequate: 76% access measures No doctor/clinic: OR, 0.90; 1.49 95% CI, 0.54- No insurance for medication: OR, 0.97; 95% CI, 0.75-1.25 Composite access measure: - 1.35 OR, 1.05; 95% CI, 0.81 Mancuso et al., Access to asthma Age No difference by HL level Primary care 100 99, care: NR practice in New Race/ethnicity 2006 Cross Sex - York City More difficult to access = 0.58 asthma care; P Comorbidity Access to care due sectional N = 175 TOFHLA to other conditions: Language Fair More difficult access to Inadequate: 10% NR duration Asthma medical care for other Marginal: 8% Asthma severity medical conditions; P = 0.005 Asthma control Adequate: 82% 77

100 Table 14. Summary of studies of the relationship between health literacy and access to care and access to insurance (KQ 1a) (continued) Authors, Year, Study Design, Outcome Measure Differences in Results Population and Literacy tool, Variables Used in Results By Health Between Health Literacy Skill Setting, Health Sample Size, Multivariate Analysis Literacy Level Levels Quality Literacy Skill Level Adults under 40 White, et al., Dental checkup Age, Nationally 86 Below basic: 44% representative US 2008 Gender sample Basic: 59% living in Race Decreased probability of having households Cross -sectional -up for below a vision check Intermediate: 70% Poverty level Proficient: 77% basic/basic HL: NR; P < 0.05 Insurance status NAAL Self -reported health N = 18,100 Basic or below basic: No association with dental status, Vision checkup 36% Below basic: 54% Fair check-ups, P = NS Oral reading fluency Intermediate: 56% Basic: 58% Proficient: 12% 64 Adults 40- Intermediate: 59% Proficient: 58% Decreased probability of dental Prostate screen checkup for below basic/basic; P < 0.05 Below basic: 31% Basic: 34% Intermediate: 31% Adults > 65 Proficient: 26% Dec reased probability of dental check-up, vision check Osteoporosis screen -up, osteoporosis screening, and Below basic: 17% Basic: 13% prostate cancer screening in below basic/basic HL group; Intermediate: 11% Proficient: 7% P < 0.05 No differences by HL related to men's screening for osteoporosis: P = NS 82 The likelihood of receiving Medical care Age Murphy, 2010 positive - HIV medical care was related to received Education individuals ages 16- Cross -sectional Data by HL level: NR 24 in Fort higher HL level Lauderdale, Medical care received 3 or more N= 186 Philadelphia, times (adjusted): OR, 1.09; 95% Baltimore, Los -1.15 CI, 1.04 Fair Angeles, and Detroit -modified TOFHLA Medical care received once or Inadequate: 12% twice (adjusted): OR, 1.06; 95% Marginal: 3% CI, 1.02 -1.09 Adequate: 86% 102 Age ≥ 16 years Parents Yin, 2009 At least 1 child In comparison to HL proficient Gender old living in a US without health group, odds are greater that at onal -secti Cross insurance household (nationally least 1 child is without health Number of children Below basic: 24% living in the home representative insurance (adjusted) Below basic: AOR, 2.4; 95% CI, Basic: 10% N = 6,100 Education sample) -4.9 1.1 Intermediate: 6% Race/ethnicity NAAL - Basic: AOR, 1.7; 95% CI, 0.5 Proficient 3% Fair Country of birth 5.7 Below basic: 11% English proficiency Intermediate: AOR, 1.4; 95% CI, Basic: 18% Income 0.4 Intermediate: 56% -4.2 Region Metropolitan statistical Proficient: 15% area 78

101 Table 15. Summary of studies of the relationship between health literacy and adherence (KQ 1b) Authors, Year, Outcome Measure Differences in Outcomes Study Design, Population and Variables Used in Outcomes By Health Analysis Sample Between Health Literacy Setting, Health Literacy Level Multivariate Analysis Levels Size, Quality Literacy Level Graham et al., Individual’s norm for < 95% adherence to Norms found to mediate Patients at an HIV 104 2007 medication regimen clinic in HIV the relationship between acceptable adherence report of pill counts - (self (investigator controlled as HL and nonadherence Philadelphia, Retrospective over past 3 months) mediator) Pennsylvania cohort Difference between low Low: 60% REALM and adequate groups N = 87 Low: 49% Adequate: 36% (unadjusted): OR, 0.36; Adequate: 51% 95% CI, 0.16- 0.88 Fair No difference in nonadherence (adjusted): OR, 0.36; 95% CI, 0.17- 1.02 Antiretroviral therapy Antiretroviral therapy pill Kalichman et al., HIV positive adults Age 103 pill adherence < 85% 2008 nonadherence greater in in Atlanta, GA Education lower health literacy group (pills counts averaged Years since testing HIV Prospective cohort usted): OR, 3.77; 95% (adj over past 4 months) TOFHLA positive -9.93 CI, 1.46 Lower: 49% HIV symptoms N = 145 Lower: 84% Higher: 51% Depression Higher: 69% Internalized stigma Fair Social support Alcohol use Self - reported Age No difference in Murphy et al., HIV -positive 82 medication adherence Education 2010 medication adherence individuals ages over past 3 days level by HL (adjusted) 16-24 in Fort Cross -sectional Lauderdale, ≥ 90% adherent: OR, 1.00; Inadequate/marginal Philadelphia, N = 186 ≥ 90%: 24% 95% CI, 0.96- 1.05 Baltimore, Los > 0 to < 90%: 41% Angeles, and Fair 0%: 35% > 0% and < 90% adherent: Detroit OR, 1.00; 95% CI, 0.95- Adequate 1.04 -modified TOFHLA ≥ 90%: 36% Inadequate/ > 0 to < 90%: 24% Marginal: 15% 0%: 41% Adequate: 86% CD4 =cluster of differentiation 4; CI =confidence interval; HIV =Human immunodeficiency virus; HL =health literacy; HR =hazard =Short ratio; N =not reported; OR =odds ratio; REALM =Rapid estimate of adult literacy in medicine; S -TOFHLA =number; NR Test of Functional Health Literacy in Adults; TOFHLA =Test of Functional Health Literacy in Adults; VA =veterans administration. 79

102 Table 15. Summary of studies of the relationship between health literacy and adherence (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Differences in Outcomes Population and Variables Used in Outcomes By Health Analysis Sample Setting, Health Between Health Literacy Literacy Level Multivariate Analysis Levels Size, Quality Literacy Level Nonadherence: Osborn et al., Race Patients at 2 HIV Nonadherence to HIV 69 clinics, 1 in 2007 Gender medications in past 4 Higher in low than (companions: Wolf days (self -report) Age Chicago, Illinois 70 adequate group (adjusted): et al., 2007; Income and 1 in OR, 2.12; 95% CI, 1.93- Low: 52% Waite et al., Number of medications in Shreveport, 71 , Osborn et 2.32 2008 Marginal: 19% Louisiana HIV regimen 72 ) al., 2010 Adequate: 30% -HIV comorbid Non REALM No difference between conditions Cross marginal and adequate Low: 11% -sectional Mental illness groups (adjusted): Marginal: 20% 1.55; 95% CI, 0.93- Adequate: 69% OR, N = 204 2.45 Fair Nonadherence (<90% Age Patients at 2 HIV Osborn et al., Nonadherence: - 201072 Insurance coverage 95%) to HIV clinics, 1 in Chicago, Illinois Positively associated with medications in past 4 Employment status (companions: Osborne et al., and 1 in being in the low compared lf-report) days (se Number of medications in 69 Wolf et al., 2007; HIV regimen to adequate group Shreveport, 70 Low: 89% 2007; Number of non-HIV Louisiana (adjusted): OR, 3.3; 95% 71 Waite et al., 2008 Marginal: 80% prescription meds currently CI, 1.3 -8.7 REALM Adequate: 31% taken Cross -sectional Low: 11% No difference between Presence of a comorbid Marginal: 20% chronic condition marginal and adequate N = 204 Adequate: 69% Treatment for a mental group (adjusted): OR, 2.1; -5.5 95% CI, 0.8 health condition Treatment for alcohol or Fair drug use - Orlow et 100% adherence to HIV Gender Patients with HIV Paasche Total adherence: 105 medication regimen and a history of al., 2006 Age Education -report for 3 day (self alcohol problems in No difference between low Randomization group period) Retrospective and adequate group Boston, cohort Ethnicity (adjusted): OR, 1.93; 95% Massachusetts Low: 69% CI, 0.86 -4.31 Homeless status REALM: Marginal: 63% Drank to intoxication past N = 235 No difference between Low: 14% Adequate: 64% 30 days marginal and adequate Marginal: 29% Injected drugs past 6 Fair group (adjusted): OR, Adequate: 57% months Complexity of regimen 1.29; 95% CI, 0.77 - 2.19 80

103 Table 15. Summary of studies of the relationship between health literacy and adherence (KQ 1b) (continued) Outcome Measure Authors, Year, Study Design, Differences in Outcomes Population and Variables Used in Outcomes By Health Analysis Sample Between Health Literacy Setting, Health Literacy Level Multivariate Analysis Literacy Level Size, Quality Levels 71 Nonadherence (adjusted Nonadherence to HIV Stigma concerns related to Waite et al., 2008 - Patients at 2 HIV clinics, 1 in HIV medications (self medications in past 4 - (Companions: not controlling for stigma) -report) report) (investigator Osborn et al., days (self Chicago, Illinois 69 Positively related to being 2007; and 1 in controlled as mediator) 70 Age ; Low: 52% Wolf et al., 2007 in the low compared to the Shreveport, Gender Osborne et al., Marginal: 19% adequate group: OR, 3.3; Louisiana 72 ) Site 2010 Adequate: 30% 95% CI, 1.3-8.7 REALM Employment status Cross -sectional Low: 11% Number of medications in No difference between Marginal: 20% HIV regimen marginal and adequate N = 204 Adequate: 69% Number of non-HIV group: OR, 2.1; 95% CI, prescription medications -5.5 0.8 Fair taken Comorbid chronic condition Nonadherence (adjusted- Treatment for mental controlling for stigma) health condition Treatment for substance No difference between low abuse and adequate group: OR, 2.1; 95% CI, 0.7 -6.5 No difference between low and adequate group: OR, - 1.8 0.7; 95% CI, 0.2 70 Wolf et al., 2007 Patients at 2 HIV HIV treatment knowledge Nonadherence to HIV Nonadherence (adjusted- (companions: clinics, 1 in (investigator controlled as medications in past 4 not controlling for Osborn et al., Chicago, Illinois mediator) -report) days (self - knowledge and self 69 2007; and 1 in - HIV medication self efficacy) Waite et al., Shreveport, efficacy (investigator Low: 52% ; Osborne 200871 Louisiana controlled as mediator) Marginal: 19% Positively related to being 72 ) et al., 2010 Age Adequate: 30% in the low compared to the REALM Insurance coverage oup: OR, 3.3; adequate gr -sectional Cross Low: 11% Employment status 95% CI, 1.3-8.7 Marginal: 20% Number of medications in N = 204 Adequate: 69% HIV regimen No difference between Number of non-HIV marginal and adequate Fair prescription medications group: OR, 2.1; 95% CI, currently taking 0.8 -5.5 Presence of comorbid chronic conditions Nonadherence mediation Treatment for mental analysis (adjusted- health condition past 6 controlling for knowledge months and self -efficacy) Treatment alcohol or drug use past 6 months No difference between low and adequate groups: OR, 2.0; 95% CI, 0.8 -5.3 No difference between marginal and adequate groups: OR, 1.6; 95% CI, 0.6 - 4.7 81

104 Table 15. Summary of studies of the relationship between health literacy and adherence (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Differences in Outcomes Study Design, Variables Used in Outcomes By Health Between Health Literacy Setting, Health Analysis Sample Literacy Level Multivariate Analysis Levels Quality Size, Literacy Level 107 No difference between Chew et al., 2004 Age Preoperative Nonadherence to fasting instructions Marital status clinic of the VA groups in nonadherence to Prospective cohort fasting instructions Number of medications Puget Sound Low: 9% Cognitive functioning (unadjusted): P = 0.80 S-TOFHLA N = 332 Adequate: 8% No difference between Low (Inadequate/ groups in nonadherence to Marginal): 12% Nonadherence to Fair preoperative medication Adequate: 88% preoperative medication instructions (adjusted): OR, instructions: 1.9; 95% CI, 0.8 -4.8 Low: 37% Adequate: 21% 81 failed to Cho et al., 2008 Race/ethnicity Using path analysis, HL Seniors who are Nonadherence: Gender fill prescriptions on time level did not have a (companion: Lee et patients at 1 of 2 160 al., 2009 significant direct effect on Chicago, Illinois Education -report) (self clinics nonadherence (adjusted): -sectional Cross Inadequate/marginal: ≥ 0.05 -0.17, P β = S-TOFHLA NR N = 489 Inadequate/ Adequate: NR marginal: 51% Fair Adequate: 49% 106 Fang et al., 2006 No difference in adherence Patients at Age Adherence to between groups by any of anticoagulation Sex medication as -sectional Cross the measures of missed clinic in San Race/ethnicity measured by self -report doses (adjusted) Francisco, Education 3 of missed doses over N = 179 California Cognitive impairment time periods (last 3 Did not miss a dose in Years on warfarin days, last 2 weeks, > 3 Fair > 3 months (adjusted): S-TOFHLA months) OR, -2.0 0.9; 95% CI, 0.4 Limited: 61% Adequate: 39% No missed doses > past 3 months: Limited: 61% Adequate: 51% 73 Gatti et al, 2008 No difference in medi cation Adults who used Negative beliefs about Self -reported low (companion Johnson adherence (adjusted): 3 pharmacies in medications medication adherence - 74 ) et al., 2010 0.96; 95% CI, 0.6- OR, 1.7 hospitals in Age measured by Morisky 8- Atlanta -efficacy Low self item Medication Cross -sectional Self -report of Adherence Scale REALM hyperlipidemia -8>2) (MMAS N = 275 Inadequate/ REALM mean: Fair Marginal: 60% low adherence group: Adequate: 40% 52.4 (16.8) high adherence group: 50.1 (17.4) 82

105 Table 15. Summary of studies of the relationship between health literacy and adherence (KQ 1b) (continued) Authors, Year, Outcome Measure Differences in Outcomes Study Design, Population and Variables Used in Outcomes By Health Setting, Health Between Health Literacy Analysis Sample Literacy Level Size, Quality Literacy Level Levels Multivariate Analysis Nonadherence: Nonadherence to Age New Prudential Gazmararian et al., 61 cardiovascular Medicare 2006 Race (companions: No difference between low managed care medication refill Gender 64 Wolf et al., 2007; and adequate groups Education adherence (1-year enrollees in 65 Baker et al., 2007; Regimen complexity (adjusted): OR, 1.23; 95% period) Cleveland, OH; Howard et al., Houston, TX; and CI, 0.92 -1.64 63 Low: 45% 2006; Tampa and south 66 Wolf et al., 2005; Marginal: 42% Florida (including No difference between 67 Baker et al., 2008; Adequate: 38% Ft. Lauderdale marginal and adequate Howard et al., groups (adjusted): OR, and Miami) 68 2005; 1.15; 95% CI, 0.82-1.62 62 ) S-TOFHLA Baker et al., 2004 Inadequate: 24% Prospective cohort Marginal: 12% Adequate: 64% N = 1,549 Fair - Race/ethnicity Adherence positively Caregivers’ self Hironaka et al., Caregivers of 108 Caregiver education related to being in the infants who 2009 reported days of Caregiver concerns receive care at 2 inadequate/marginal group adherence to giving Prospective cohort pediatric clinics regarding multivitamins compared to the adequate vitamins to their infants in prior week and possible side effects group (adjusted): OR, 2.4; N = 110 S-TOFHLA Randomized assignment to 4.2 95% CI, 1.37- drops or sprinkle Inadequate/Marginal: Inadequate/ formulation Fair 3.7 days Marginal: 18% Adequate: 2.4 days Adequate: 82% 74 Johnson, 2010 reported - Self moderator: social Potential Adults who used No difference in adherence support medication adherence (companion: Gatti et by HL level: β = 0.072; - 3 pharmacies in 73 Age ) al., 2008 measured by Morisky 8- hospitals in 95% CI, - 0.350-0.494 Sex Atlanta item Medication Cross After adjusting for -sectional Adherence Scale REALM interaction between HL (MMAS -8): NR N = 275 and social support Inadequate/ (moderator): lower HL Marginal: 60% Fair related to better adherence Adequate: 40% at lower levels of social support, higher HL better adherence at higher levels of social support HL: β = -1.827; 95% CI, -3.389- 0.265 HL x social support: β, 0.086; 95% CI, 0.018- 0.154 83

106 Table 16. KQ 1b health literacy studies: strength of evidence grades by health outcomes Strength of Outcome for Health Evidence Number of Studies Grade Literacy Studies Results Mixed results depending on adherence measure, Insufficient 11 Adherence and adjustment for confounding disease state, Self Mixed results in studies conducted within various sub - - efficacy Insufficient 5 populations Mixed results Insufficient Smoking 2 2 No effect on current alcohol consumption. Alcohol and substance Insufficient Positive use relationship between health literacy level and substance use in one study. 3 Mixed results from studies examining exercise, diet, a Healthy lifestyle Insufficient seatbelt use composite measure, and (physical activity, eating habits, and seat belt use) Healthy lifestyle (obesity 5 Mixed results, 4 of 5 studies unadjusted Insufficient and weight) Review of prescription 1 Low health literacy associated with being less likely to Low information read prescription information HIV risk and sexual Mixed results Insufficient 2 behaviors 6 Taking medications Lower health literacy associated with poorer ability to Moderate demonstrate being able to take mediations appropriately appropriately Interpreting labels and 3 Low health literacy associated with poorer ability to Moderate health messages interpret labels and health messages; smaller likelihood of giving an organized health narrative - care 1 Low literacy associated with poorer self - care skill in 1 Asthma self Low study ealth Mental h 10 Results in 8 of 10 studies found association between Low lower health literacy and depression but control for symptomatology confounding was limited Insufficient Chronic disease Mixed results: 3 studies on association with chronic 7 diseases generally and 4 studies on association with outcomes specific diseases HIV severity and 5 Results in 3 studies found no relationship but control Low symptoms for confounding was limited and sample sizes were small Asthma severity and Insufficient 2 Mixed results; only unadjusted analysis of asthma control control Glycemic control: mixed results 5: Insufficient Diabetes control and 5 glycemic related symptoms control, Complications: no relationship 1 compli - cations 84

107 Table 16. KQ 1b health literacy studies: strength of evidence grades by health outcomes (continued) Number Strength of Evidence Outcome for Health Results Literacy Studies of Studies Grade 2 Mixed results Insufficient Hypertension control Prostate cancer control 1 More likely to have higher prostate-specific antigen Low (PSA) test results (worse levels) 1 No relationship with global health status Low Health status: all adults Health status and quality Overall: Moderate 5 Lower overall health status of life: seniors Mental and physical: mental and physical functioning Mixed effects Insufficient Health status and quality Insufficient Mixed results: mental and physical functioning by 5 of life: individuals with disease state and measure specific diseases Mortality: seniors 2 Higher risk of mortality in the lower literacy group; risk High not elevated in the marginal literacy group (1 study) 85

108 -efficacy (KQ 1b) Table 17. Summary of studies of the relationship between health literacy and self Authors, Year, Outcome Measure Differences in Results Population and Study Design, Outcomes By Variables used in Setting, Health Between Health Literacy Analysis Sample Health Literacy Literacy Level Multivariate Analysis Levels Size, Quality Level 82 Outcomes by HL No difference by Age HL in self Murphy, 2010 - HIV - positive individuals ages efficacy in taking HIV Education level: NR -sectional Cross 16-24 in Fort medication regimen score Lauderdale, (adjusted): OR, 0.99; 95% N= 186 -1.03 CI, 0.95 Philadelphia, Baltimore, Los No difference in self - Fair Angeles, and efficacy in keeping medical Detroit appointment (adjusted): TOFHLA -modified OR, 1.01; 95% CI, 0.95- 1.06 Inadequate: 12% Marginal: 3% Adequate: 86% No difference between Age Peterson et al., Mean perception of Patients with 87 -efficacy score self 2007 Sex groups in perception of public health care self coverage at a -efficacy for FOBT Race Cross -sectional (adjusted): P = 0.44 FOBT Insurance status community health Limited: 3.87 clinic in Nashville, N = 99 No difference between Adequate: 3.93 Tennessee groups in perception of REALM Fair -efficacy or self Colonoscopy: Limited: 29% colonoscopy: P = 0.52 Limited: 3.92 Adequate: 3.99 Adequate: 71% Self None efficacy for - Self Women patients - Torres et al., efficacy positively 113 2009 at a family health taking hormone correlated with HL (unadjusted): r = 0.70; P < therapy center in New Cross York City 0.01 -sectional Self -efficacy by s-TOFHLA health literacy level: N = 106 Inadequate: 46% NR Marginal: 18% Fair Adequate: 36% -efficacy for Self von Wagner et al., Age Higher HL level associated Adults in London, 114 Ethnicity participating in CRC 2009 with greater self -efficacy England between screening Employment (adjusted): β = 0.061; 95% 50-69 years of -sectional Cross Gender CI, 0.009 -0.113 age Number of computer links Self -efficacy by N = 96 open health literacy level: -TOFHLA UK Mean NR reading time Mean: 92.2 CRC screening Fair Range: 26-100 knowledge CI= =colorectal cancer; FOBT =fecal occult blood test; HL =health literacy; HIV =Human confidence interval; CRC immunodeficiency virus; N =number; NR =not reported; OR =odds ratio; REALM =rapid estimate of adult literacy in medicine; TOFHLA =Test of Functional Health Literacy in Adults; S -TOFH LA =Short Test of Functional Health Literacy in Adults; UK -S - TOFHLA =British version of the Test of Functional Health Literacy in Adults. 86

109 Table 17. Summary of studies of the relationship between health literacy and self -efficacy (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Outcomes By Differences in Results Study Design, Between Health Literacy Variables used in Setting, Health Health Literacy Analysis Sample Level Multivariate Analysis Levels Size, Quality Literacy Level 70 Wolf et al., 2007 - Perception of self Patients at 2 HIV Higher HIV medication Age (companions: efficacy to properly clinics, 1 in self -efficacy greater in Insurance coverage take and manage HIV Osborn et al., Chicago, Illinois adequate than low group Employment status 69 medication 2007; and 1 in (adjusted): OR, 5.8; 95% Number of medications in 71 Waite et al., 2008 Shreveport, -15.7 CI, 2.0 HIV regimen Low: 61% Osborne et al., Louisiana Number of non-HIV 72 ) Marginal: 20% 2010 No difference HIV prescription medications Adequate: 24% REALM cation self -efficacy medi currently taking -sectional Cross Low: 11% between adequate and Presence of comorbid Marginal: 20% marginal groups chronic conditions N = 204 Adequate: 69% (adjusted): OR, 1.6; 95% Treatment for mental CI, 0.3 -3.2 health condition past 6 Fair months Treatment alcohol or drug use past 6 months 87

110 Table 18. Summary of studies of the relationship between health literacy and health behaviors (KQ 1b) Authors, Year, Outcome Measure Population and Differences in Results Study Design, Between Health Literacy Analysis Sample Variables used in Setting, Health Outcomes By Health Literacy Level Levels Quality Size, Multivariate Analysis Literacy Level 115 Higher HL associated with von Wagner, 2007 National sample Age Don’t smoke greater likelihood of not of British adults Education Inadequate: 29% Cross -sectional smoking (adjusted): OR, Gender Marginal: 32% 1.02; 95% CI, 1.003-1.03 Modified TOFHLA Ethnicity Adequate: 70% N = 719 Inadequate: 6% Income Higher HL associated with Marginal: 6% Fruit and vegetable Fair ≥ greater likelihood of eating Adequate: 89% > 5/day intake 5 fruit/vegetables a day Inadequate: 29% (adjusted): OR, 1.02; 95% Continuous Marginal 39% -1.03 CI, 1.003 measure used in Adequate: 47% analysis HL level not associated with Any exercise in the likelihood of having exercised last week: in the last week (adjusted): Inadequate: 22% OR, 1.00; 95% CI, 0.98-1.02 Marginal: 20% Adequate: 36.6% 64 New Prudential Difference in smoking status Wolf, 2007 Age (never): Smoking Medicare (companions: (adjusted) Gender Inadequate: 47% managed care Gazmararian, Race/ethnicity Marginal: 42% 61 enrollees in 2006; No difference between Language (English or Adequate: 39% 65 Baker et al., 2007; Cleveland, OH; groups in ever vs. never Spanish) Howard et al., X; and Houston, T smoking Site Smoking (former) 63 2006; Tampa and south Education Inadequate: 42% 66 Wolf et al., 2005; Florida (including Inadequate vs. adequate: Annual income Marginal: 45% 67 Baker et al., 2008; Ft. Lauderdale -1.1 OR, 0.9; 95% CI, 0.7 Occupation (white or Adequate: 49% Howard et al., and Miami) Marginal vs. adequate: blue collar) 68 2005; -1.2 OR, 0.9; 95% CI, 0.7 Smoking (current) 62 ) Baker et al., 2004 S-TOFHLA Inadequate: 12% Inadequate: 22% No difference between Marginal: 13% -sectional Cross Marginal: 11% groups in ever vs. quit Adequate: 12% Adequate: 66% smoking N = 2,923 Current alcohol use Inadequate vs. adequate: (none) Fair OR, 0.9; 95% CI, 0.6 -1.3 Inadequate: 75.6% Marginal vs. adequate: Marginal: 64.2% OR, 0.7; 95% CI, 0.5 -1.0 None: 57.9% Differ ence in alcohol Current alcohol use consumption (adjusted) (light to moderate) Inadequate: 23% No difference between Marginal: 34% groups in light/moderate vs. Adequate: 38% no alcohol consumption Current alcohol use Inadequate vs. adequate: (heavy) -2.5 OR, 1.1; 95% CI, 0.5 Inadequate: 2% Marginal vs. adequate: OR, Marginal: 2% Adequate: 4% 1.4; 95% CI, 0.6 - 3.3 BMI= Body Mass Index; CI =confidence interval; HL =health literacy; HIV =Human immunodeficiency virus; INR =International Normalized Ratio; N =not reported; OH =Ohio; OR =odds ratio; REALM =rapid estimate of adult literacy in =number; NR =Test of Functional Health =risk ratio; S -TOFHLA =Short Test of Functional Heal th Literacy in Adults; TOFHLA medicine; RR Literacy in Adults; TX =Texas. 88

111 Table 18. Summary of studies of the relationship between health literacy and health behaviors (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Population and Differences in Results Between Health Literacy Setting, Health Outcomes By Health Variables used in Analysis Sample Multivariate Analysis Literacy Level ity Levels Literacy Level Size, Qual 64 Physical Activity per Wolf, 2007 No difference between week (< 1 time) (companions: groups in heavy vs. no Inadequate: 38% Gazmararian, alcohol consumption 61 Marginal: 25% 2006; 65 al., 2007; Baker et Adequate: 22% Inadequate vs. adequate: Howard et al., -3.0 OR, 1.3; 95% CI, 0.6 63 2006; Physical Activity per vs. adequate: OR, Marginal 66 Wolf et al., 2005; week (1-2 times) -2.8 1.2; 95% CI, 0.5 67 Baker et al., 2008; Inadequate: 15% Howard et al., Marginal: 16% Difference in physical activity 68 2005; Adequate: 15% (adjusted) 62 ) Baker et al., 2004 (continued) Physical Activity per No difference between week (3 times) groups in physical activity 1-2 Inadequate: 14% times per week vs. < 1 time Marginal: 18% Adequate: 15% Inadequate vs. adequate: -1.4 OR, 1.0; 95% CI, 0.7 Physical Activity per Marginal vs. adequate: OR, week (> 4 times) -1.8 I, 0.9 1.3; 95% C Inadequate: 33% Marginal: 41% No difference between Adequate: 48% groups in physical activity 3 times per week vs. < 1 time Seat belt use (always) Inadequat e: 72% Inadequate vs. adequate: Marginal: 78% -1.3 OR, 0.9; 95% CI, 0.7 Adequate: 78% Marginal vs. adequate: OR, 1.0; 95% CI, 0.7 -1.5 Seat belt use (nearly always, sometimes, or No difference between seldom) groups in physical activity Inadequate: 28% greater than 4 times per Marginal: 22% week vs. less than 1 time Adequate: 22% Inadequate vs. adequate: OR, 1.3; 95% CI, 0.9 -1.7 Marginal vs. adequate: OR, 1.0; 95% CI, 0.7 -1.4 No difference between groups in seat belt use (unadjusted): P = 0.13 89

112 Table 18. Summary of studies of the relationship between health literacy and health behaviors (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Differences in Results Population and Health Analysis Sample Outcomes By Variables used in Setting, Health Between Health Literacy Literacy Level Size, Quality Levels Multivariate Analysis Literacy Level 65 Baker et al., 2007 Difference in BMI across New Prudential BMI < 18.5 None groups (unadjusted): P < (companions: Medicare Inadequate: 8% 0.005 Gazmararian, managed care 4% Marginal: 61 2006; enrollees in Adequate: 4% 64 Wolf et al., 2007; Cleveland, OH; Howard et al., Houston, TX; and BMI 18.5 -24.9 68 2005; Tampa and south Inadequate: 59% 67 Baker et al., 2008; Florida (including Marginal: 60% Howard et al., Ft. Lauderdale Adequate: 58% 68 2005; and Miami) 62 ) Baker et al., 2004 S-TOFHLA -29.9 BMI 25.0 Cohort Inadequate: 24% Inadequate: 23% Marginal: 11% Marginal: 24% N = 3,260 Adequate: 64% Adequate: 26% Good BMI > 30.0 Inadequate: 10% Marginal: 12% Adequate: 12% BMI Patients at primary None Huizinga et al. No difference between 10 care clinic at groups in BMI level 2008 < 9th: 31.7 (SD 9.9) Vanderbilt (unadjusted): P = 0.50 -sectional Cross University ≥ 9th: 30.2 (SD 7.8) REALM N = 160 < 9th grade: 23% Fair ≥ 9th grade: 77% 95 Difference in probability of Seniors (70 (BMI > 30) Obesity None 79 - Sudore, 2006 obesity across groups 0-6th grade: 29% year old) in (companion: (unadjusted): OR, 1.51; Pittsburgh, 7th -8th grade: 32% Sudore et al., 167 ) > 9th grade: 23% 2006 1.85 95% CI, 1.23- Pennsylvania and Memphis, -sectional Cross Tennessee N = 2,512 REALM 0-6th grade: 8% Fair 7-8th grade: 15% >9th grade: 76% 9 Rothman, 2006 Adults in a primary None ≥ 30): Obese (BMI No difference between care clinic < HS: 53% groups in percent obese -sectional Cross > HS: 43% (unadjusted): P = 0.31 REALM N = 200 < HS: 23% > HS: 77% Fair 90

113 Table 18. Summary of studies of the relationship between health literacy and health behaviors (KQ 1b) (continued) Year, Authors, Outcome Measure Population and Study Design, Differences in Results Between Health Literacy Setting, Health Variables used in Analysis Sample Outcomes By Health Literacy Level Multivariate Analysis Levels Size, Quality Literacy Level Sharif and Bl ank, Age Higher HL significantly Child BMI Children ages 6-19 119 related to decrease in child Parental BMI 2010 85th ≥ BMI BMI: B, -0.016; 95% CI, Child Eating self - No data reported by HL percentile for age -0.025, -sectional Cross -0.008 efficacy and sex who Parental eating self - received primary N = 78 efficacy care at in an inner -TOFHLA Parental S city academic Good community health center in the Bronx, NY S-TOFHLA Child Adequate: 52% Parent Adequate: 77% 81 Health Promoting Seniors who are Using path analysis, HL Race/ethnicity Cho et al., 2008 patients at 1 of 2 (companion: level did not have a direct Gender Lifestyle Profile relating 160 ) Chicago, Illinois Lee et Education to exercise, nutrition, al., 2009 effect on health behavior ≥ 0.05 clinics and health (adjusted): P Cross -sectional responsibility s-TOFHLA N = 489 Data: NR Inadequate/ marginal: 51% Fair adequate: 49% 120 Read/looked at Age Wolf et al., 2006 Low HL gro up more likely Adults at a primary care clinic in Gender than adequate group to not medication guides and read/look at medication -sectional Cross consumer information Shreveport, Race guides: OR, 2.5; 95% CI, included with Education Louisiana -5.2 1.2 N = 251 Number of prescription REALM prescriptions taken medications No difference between Low: 30% Fair marginal and adequate Low: 17% Marginal: 31% groups in likelihood of Marginal: 22% Adequate: 40% Adequate: 33% reading/looking at medication guides: P = NS, data NR Female inmates in - HIV Risk Behavior in Paasche Orlow, No difference between Age 121 - 2005 groups in HIV risk Rhode Island adult Race past 3 months (self behaviors (adjusted) Problem drinking correctional report of sex without a Cross -sectional shared condom or institute ≤ 6th grade vs. ≥ 9th injection drug N = 423 REALM grade: OR, 2.02; 95% CI, equipment) ≤ 6th grade: 10% 0.83-4.92 ≤ 6th grade: 9% Fair 7th -8th grade: 19% -8th ≤ 6th grade vs. 7th -8th grade: 19% 7th ≥ 9th grade: 71% grade: OR, 1.89; 95% C I, ≥ 9th grade: 72% 0.74 - 4.81 91

114 Table 18. Summary of studies of the relationship between health literacy and health behaviors (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Study Design, Differences in Results Variables used in Setting, Health Outcomes By Health Between Health Literacy Analysis Sample Levels Literacy Level Multivariate Analysis Size, Quality Literacy Level 122 Marteleto, 2008 14-22 years old at Grades completed in Sexual debut: NR An increase in literacy of time of Wave 1 in 2002 one standard deviation Longitudinal Cape Town, South Enrolled in 2002 First pregnancy: NR associated with a 7.5% Africa Age reduction in probability of N = 4,751 (wave 1) Age squared sexual debut (adjusted): P Area Panel Cape Race < 0.05 Fair Study Literacy Income Literacy level not related to evaluation scores: Household shock first pregnancy in either NR Mother's education females or males Father's education (adjusted) Living with mother Probit coefficient Living with father Females: 0.41 Males: - 0.030 Murphy et al., Higher HL positively and alcohol use Drug Age positive - HIV 82 over past 3 months 2010 Education individuals ages associated with substance No data by HL use (adjusted): P = 0.0181 16-24 in Fort Cross -sectional Lauderdale, Philadelphia, N= 186 Baltimore, Los Angeles, and Fair Detroit TOFHLA -modified Inadequate: 12% Marginal: 3% Adequate: 86% 92

115 Table 19. Summary of studies of the relationship between health literacy and the outcome of health care related skills (KQ 1b) uthors, Year, Outcome Measure A Variables used in Study Design, Population and Differences in Results Results By Health Between Health Literacy Setting, Health Multivariate Analysis Sample Levels Literacy Level Analysis Literacy Level Size, Quality Age DRUGS: Requiring Clinic population Difference across groups in Kripalani et al., 123 2006 Education overall DRUGS score with coronary heart observed completion of (unadjusted): P = 0.001 disease in Atlanta, Cognitive functioning 4 tasks: 1. Identify appropriate -sectional GA Cross Inadequate more likely than medication REALM adequate to not be able to 2. Open container N = 152 identify all medications Inadequate: 52% 3. Select correct dose (adjusted): OR, 12.00; 95% CI, Marginal: 29% 4. Report appropriate Good 2.57-56.08 Adequate: 20% timing of doses. No difference between Mean score: marginal and adequate in Inadequate: 92.1 ability to identify all Marginal: 96.3 medications (adjusted): OR, Adequate: 97.7 23.75 - 4.75; 95% CI, 0.95 Raehl et al., Age MedTake Test: ability to Seniors in Amarillo, A higher MedTake Test score 124 2006 -the Number of over - Texas was associated with a higher open and take own REALM score (adjusted): < P medications while counter drugs Cross -sectional 0.01 REALM mean: observed by pharmacist Owned a car in last 55.4 10 years Received food N = 57 MedTake Test assistance in last 10 outcomes: NR years Fair 125 No difference in use of dosing reported use of - Self Experience of ever Parents/ Yin et al., 2007 instrument between health receiving a dosing nonstandardized dosing caregivers of literacy groups (adjusted for all Cross -sectional instrument in a health instrument children at an control variables): OR, 1.5; care setting Emergency Child’s age 95% CI, 0.8-2.8 N = 292 Inadequate/ Department in New Child has regular Marginal: 35% York City Marginal/inadequate greater health care provider Fair Adequate: 19% use than adequate (adjusted Confounders with TOFHLA for control variables except for health literacy: Inadequate: 10% Caregiver’s confounders with HL): OR, 1.9; Marginal: 16% 95% CI, 1.0-3.5 education, country of Adequate: 74% origin, language, -economic socio status AIDS =acquired immune deficiency syndrome; AOR =Body Mass Index; CI= confidence interval; =adjusted odds ratio; BMI DRUGS =Florida; GA =Georgia; HIV =Human immunodeficiency virus; HL =health =Drug Regimen Unassisted Grading Scale; FL literacy; HS =high school; IL =Illinois; INR =International Normalized Ratio; LA =Louisiana; MI =Michigan; N =number; NR =not reported; NY =odds ratio; REALM =rapid estimate of adult literacy in medicine; RR =risk ratio; SD =standard =New York; OR =Test of -TOFHLA= Short Test of Functional Health Literacy in Adults; SES =socio -economic status; TOFHLA deviation; S Functional Health Literacy in Adults; US =United States. 93

116 Table 19. Summary of studies of the relationship between health literacy and the outcome of health care related skills (KQ 1b) (continued) Authors, Year, Outcome Measure sign, Population and Study De Variables used in Differences in Results Results By Health Between Health Literacy Setting, Health Multivariate Analysis Sample Analysis Size, Quality Levels Literacy Level Literacy Level Estrada et al., Age Adults greater than No difference by HL level in Warfarin control 126 measured through INR INR variability (adjusted): P = 50 years old on 2004 warfarin variability: NR 0.06 ≥ 1 month in 2 anticoagulation Prospective management units No difference by HL time INR intensity of Optimal cohort anticoagulation (time in in therapeutic range REALM range): NR (adjusted): P = 0.71 N = 143 ≤ 3rd: 11% -6th: 15% 4th Fair 7th -8th: 26% >8th: 48% Davis et al., Analysis 1 Adults in primary Analysis 1 Misunderstood one or 75 2006 care clinics in Age more prescription label (Analysis 1) Greater misunderstanding in Shreveport, LA; Sex instructions: Jackson, MI; and inadequate compared to Race 76 Wolf et al., 2007 adequate group (adjusted): Chicago, IL Education Inadequate: 63% 2) (Analysis RR, 2.32; 95% CI, 1.26-4.28 Number of Marginal: 51% REALM medications currently Adequate: 38% Cross -sectional Greater misunderstanding in Inadequate: 19% taken daily marginal compared to Marginal: 29% Site Correct demonstration of N = 395 adequate group (adjusted): Adequate: 52% number of pills: RR, 1.94; 95% CI, 1.14-3.2 lysis 2 Ana Fair None Inadequate: 35% Greater demonstration of pills Marginal: 63% in adequate compared to Adequate: 80% inadequate group ( adjusted): RR, 3.02; 95% CI, 1.70-4.89 No difference between marginal and adequate groups in demonstration of pills: RR = NS, data NR Analysis 2 Difference across literacy groups in correctly interpreting primary label (unadjusted) Amoxicillin: P < 0.001 Trimethoprim: P < 0.001 94

117 Table 19. Summary of studies of the relationship between health literacy and the outcome of health care related skills (KQ 1b) (continued) Authors, Year, Outcome Measure Differences in Results Study Design, Variables used in Population and Results By Health Setting, H Multivariate Between Health Literacy ealth Analysis Sample Literacy Level Levels Literacy Level Size, Quality Analysis Davis et al., Guaifenesin: P < 0.001 75 Felodipine: P = 0.03 2006 (Analysis 1) Furosemide: P = 0.09 76 Difference across literacy Wolf et al., 2007 groups in correctly attending to (Analysis 2) auxiliary label (unadjusted) (continued) Amoxicillin: P = 0.13 Trimethoprim: P = 0.14 Guaifenesin: P < 0.001 Felodipine: P = 0.11 Furosemide: P = 0.01 Understanding nutrition Adults in primary Rothman et al., Age Greater understanding of 9 Gender 2006 labels measured through nutrition labels in higher HL care clinic Nutrition Label Survey group (adjusted): P < 0.001 Race/ethnicity -sectional Cross REALM Income Nutritional Label Survey < HS: 23% Education N = 200 score mean (SD): > HS: 77% Insurance status < HS: 51 (16) Presence of chronic Fair > HS: 75 (19) disease Status of being on a specific diet reading Label frequency Race Bailey et In comparison to group with Adults in al, Misinterpretation of 77 medication label adequate HL (adjusted): 2009 Shreveport, La; Age (Companions: instructions: Sex Chicago, IL, and Davis et al., Greater probability of marginal Education Jackson, Michigan 75 , Wolf et al., Low: 43% group misinterpreting 2006 76 ) 2007 REALM: Marginal: 34% medication instructions: AOR, Low: ≤ 6th grade: Adequate: 18% , 1.19 -3.97 2.20; 95% CI -sectional Cross 20% Greater probability of low Marginal: 7th- 8th N = 373 group misinterpreting grade: 29% ≥ 9th Adequate: medication instructions: AOR, Fair grade: 51% 2.90; 95% CI, 1.41 - 6.00 95

118 Table 19. Summary of studies of the relationship between health literacy and the outcome of health care related skills (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Variables used in Differences in Results Population and Results By Health Setting, Health Multivariate Analysis Sample Between Health Literacy evels Analysis L Literacy Level Size, Quality Literacy Level 127 Parent's age In comparison to group with Accuracy in measuring a and Yin et al, 2010 English - Spanish-speaking adequate HL, the odds of dose of medicine using 6 Relationship to child different dosing Cross -sectional making any dosing error Marital status parents whose instruments: NR child received care Language (>20% deviation) was greater N = 302 Ethnicity in those with a high likelihood at public pediatric US birth of limited HL: AOR, 1.7; 95% clinic in NY Good SES -2.8 and in those with CI, 1.1 Newest Vital Sign possible limited HL: AOR, 1.6; Presence of a child in 95% CI, 1.02- 2.6 the house <8 years High likelihood of old In comparison to group with limited literacy: Presence of child in adequate HL, odds of making 40% the household with a a large dosing error (>40% Possible limited chronic medical deviation) was greater in those literacy: 38% problem with a high likelihood of limited Adequate literacy: HL: AOR, 2.3; 95% CI, 1.2- 4.6 22% but no difference in those with possible limit ed HL: AOR, 1.9; 95% CI, 0.95 - 3.7 Comprehension of radio Mothers of Higher literacy level associated Maternal schooling LeVine et al., 128 with greater probability of 2004 kindergarten age Childhood health messages: NR giving an organized health socioeconomic status children in urban narrative (adjusted): < 0.05 P Cross -sectional Comprehension of and rural Nepal Age visual print health Current N = 167 Literacy measured message: NR socioeconomic status as continuous, Husband's schooling Fair composite score of Ability to give an Urban/rural reading organized health-related comprehension narrative: NR and noun definition (in Nepalese) Levels NR Orlow et Age Inpatient adults Poorer probability of mastery - Paasche Mastery of metered dose 79 inhaler technique of metered dose inhaler in hospitalized for Sex al., 2005 severe asthma at 2 inadequate than adequate Ethnicity Cross -sectional Inadequate: 32% group (adjusted): OR, 0.29; inner city hospitals Education P = 0.03 1.00; 95% CI, 0.08- 3% Adequate: 6 Income s-TOFHLA N = 73 History of near fatal Inadequate: 22% asthma Asthma Adequate: 78% Fair hospitalization in prior 12 months 96

119 Table 19. Summary of studies of the relationship between health literacy and the outcome of health care related skills (KQ 1b) (continued) Outcome Measure Authors, Year, Study Design, Differences in Results Variables used in Population and Results By Health Multivariate Setting, Health Be tween Health Literacy Analysis Sample Levels Literacy Level Literacy Level Analysis Size, Quality Orlow et - Paasche Having a physician 79 for asthma care al., 2005 Prior emergency (continued) department visit for asthma last 12 months (subset of confounders used in final model specification NR) - Valverde Gender Adults with HIV in Higher HL related to better Medication Management Waldrop 47 Test (MMT), a mock trial Education et al, 2009 justed): MMT score (ad HIV clinics or AIDS < 0.05 P of medication drug assistance -taking Time since HIV Cross -sectional skills (interpretation of programs in Miami, diagnosis FL Numeracy medication labels and a N = 155 medication insert, TOFHLA (% counting a week’s supply of medication and Fair correct) placing them in an Men: 78% organizer, and Women: 73% determining missed doses and refills) HL data NR 97

120 Table 20. Summary of studies of the relationship between health literacy and the outcome of prevalence of depression and other mental health outcomes (KQ 1b) Outcome Measure Authors, Year, Population and Differences in Outcomes Study Design, Between Health Literacy Variables used in Analysis Sample Setting, Health Outcomes By Health Literacy Level Multivariate Analysis Levels Size, Quality Literacy Level Lincoln et al., - Adults in an inner Time Baseline Depressive 130 2006 city short -term Sex symptomatology inpatient Age ) CES -D: mean (SD Prospective cohort detoxification unit Race Low: 30.9 (11.3) No difference between Education Higher: 34.8 (13.32) groups (adjusted cross - P = sectional analysis): N = 390 REALM Income Low: 46% Primary language ASI -Alc 0.09 Fair Higher: 54% Primary substance of Low: 0.46 (0.34) choice High: 0.48 (0.34) Lower group greater Randomization group (adjusted longitudinal < 0.01 P analysis): Mini -mental status ASI -Drug exam Low: 0.26 (0.13) Baseline outcomes High: 0.26 (0.15) Alcohol addiction severity variable No difference between - groups (adjusted cross sectional analysis): = P 0.88 No difference between groups (adjusted = longitudinal analysis): P 0.86 Drug addiction severity No difference between - groups (adjusted cross sectional analysis: P = 0.11 No difference between groups (adjusted longitudinal analysis): P = 0.35 Depressive Hispanic HIV positive adults Depressive Nokes et al., 131 symptomatology worse in receiving care in 2007 symptomatology: NR San higher health literacy Francisco, Distress over body group (adjusted): P < 0.05 Fresno, Richmond, Cross -sectional changes: NR NYC, Corpus Distress over body Christi N = 489 changes greater in higher REALM health literacy group Fair Mean = 59.1 (SD, (adjusted): β= 2.91, P < 12.9) 0.05 ASI -Alc =Addiction Severity Index - Alcohol; ASI -Drug =Addiction Severity Index - Drugs; BSI =Brief Symptom Index; CES - D=Center for Epidemiology Studies – =chronic obstructive pulmonary disease; HIV =human Depression Scale; COPD immunodeficiency virus; N =number; NALS =national adult literacy survey; NR =not reported; NYC =New York City; OH= Ohio; OR =odds ratio; PHQ =Patient Health Questionnaire; PR =Poisson Regression coefficient; REALM =Ra pid Estimate of Adult Literacy in Medicine; SAHSLA =Short Assessment of Health Literacy for Spanish-speaking Adults; S -TOFHLA= Short Test of Functional Health Literacy in Adults, TX =Texas. 98

121 Table 20. Summary of studies of the relationship between health literacy and the outcome of prevalence of depression and other mental health outcomes (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Study Design, Differences in Outcomes Setting, Health Outcomes By Health Analysis Sample Between Health Literacy Variables used in Literacy Level Multivariate Analysis Levels Literacy Level Size, Quality Bennett et al., Pregnant patients Elevated depressive Mexican nativity Inadequate group more 132 2007 Receiving prenatal Recent marijuana use symptomatology likely than adequate group care in clinics in ≥ 16) (CES-D to have depressive Cross -sectional Philadelphia Inadequate HL: 44% symptomatology N = 99 Marginal HL: 33% (adjusted): PR, 2.39; 95% - S-TOFHLA Adequate HL: 18% CI, 1.07 -5.35 Fair Spanish No difference in Inadequate: 18% depressive Marginal: 15% symptomatology between Adequate: 67% marginal and adequate groups (adjusted): PR, - 4.02 1.73; 95% CI, 0.75 Kalichman et al., HIV positive adults Depression: Mean (SD) None No difference between 103 in Atlanta, GA 2008 Lower: 10.9 (6.6) groups in rate of Higher: 8.7 (7.8) depression (unadjusted): Cross -sectional TOFHLA OR, 0.95; 95% CI, 0.91- Lower: 49% 1.00 N = 145 Higher: 51% Fair Patients at 3 None higher in lower Anxiety Hospital Anxiety and Walker et al., 133 group (unadjusted): P = 2007 rheumatology Depression scales clinics in the United (HAQ and HAD) 0.03 -sectional Cross Kingdom Depression higher in lower Depression, mean N = 363 REALM Lower:8.1 group (unadjusted): P = Lower (< 60): 15% Adequate: 6.5 0.01 Fair Adequate ( ≥ 60): 85% Anxiety, mean Lower: 9.4 Adequate: 7.7 None Difference across groups Adults with Depression, Patient Morris et al., 134 5) diabetes in primary 2006 in depression (PHQ > Health Questionnaire care practices in (unadjusted): P = 0.03 (PHQ) > 5 Inadequate: 40% Vermont -sectional Cross Marginal: 54% Difference across groups S-TOFHLA Adequate: 31% in median depression N = 1,002 Inadequate: 10% score (unadjusted): P = Marginal: 7% Depression, median 0.04 Good Adequate: 83% Patient Health Questionnaire Score Inadequate: 3 Marginal: 5 Adequate: 2 99

122 Table 20. Summary of studies of the relationship between health literacy and the outcome of prevalence of depression and other mental health outcomes (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Differences in Outcomes Study Design, Variables used in Setting, Health Outcomes By Health Between Health Literacy Analysis Sample Literacy Level Multivariate Analysis Levels Size, Quality Literacy Level 79 None Sudore et al., Seniors (70- Depression Difference in probability of 95 0-6th grade: 6% 2006 year old) in depression across groups (companion: Pittsburgh, 7th -8th grade: 3% (unadjusted): OR, 2.54; > 9th grade: 2% Sudore et al., Pennsylvania and 4.42 95% CI; 1.47- 2006167) Memphis, Tennessee -sectional Cross REALM N = 2,512 0-6th grade: 8% 7-8th grade: 15% >9th grade: 76% Fair Depression None Difference between groups New Prudential Howard et al., 68 2005 Medicare managed in rate of depression Inadequate: 19% (companion: (unadjusted): P < 0.0001 Marginal: 14% care enrollees in Gazmararian, Cleveland, OH; Adequate: 12% 61 ; Wolf et al., 2006 Houston, TX; and 64 ; Howard et 2007 Tampa and south 63 ; Wolf et al., 2006 Florida (including 66 ; Baker al., 2005 Ft. Lauderdale and 67 ; et al., 2008 Miami) Baker et al., 62 ) S-TOFHLA 2004 Adequate: 64% Cohort Marginal: 11% Inadequate: 24% N = 3,260 Good 135 Lower HL related to higher D (mean score) Coffman, 2010 - CES Demands of Spanish speaking adults who are immigration depression scores Low HL: 13.9 (9.5) -sectional (adjusted): P = 0.048 recent High HL: 9.7 (8.3) immigrants Cross recruited from two N=99 Latino service agencies Fair SAHLSA ≤ 39 Low HL: Adequate HL: >39 82 Age Psychological distress positive - HIV Murphy, 2010 No difference in BSI Global Severity Index by individuals ages Education as measured by BSI -sectional Cross Global Severity Index 16-24 in Fort HL level (adjusted): No data reported by HL P = 0531 Lauderdale, N= 186 Philadelphia, Baltimore, Los Fair Angeles, and Detroit TOFHLA -modified Inadequate: 12% Marginal: 3% Adequate: 86% 100

123 Table 21. Summary of studies of the relationship between health literacy and the outcome of prevalence of chronic diseases (KQ 1b) Authors, Year, Outcome Measure Population and Differences in Outcomes Study Design, Outcomes By Health Variables used in Setting, Health Between Health Literacy Analysis Sample Multivariate Analysis Literacy Level Literacy Level Levels Size, Quality Self -report of physical, Sen tell and Halpin, National sample Lower health literacy Race 141 mental, or other health 2006 of adults associated with greater odds Education condition that keeps of having a condition that Understand English Cross -sectional respondent from Total NALS keeps respondent from Born in US working: NR score working (adjusted): OR, 1.11; Unemployed N = 23,889 Level 1: 20% 95% CI, 1.08- 1.14 Family income Long-term illness (> 6 Level 2: 27% Income missing Fair months): NR Level 3: 34% Lower health literacy Sex Level 4: 18% associated with greater odds Age Level 5: 2% of having a long- term illness Married (adjusted): OR, 1.04; 95% CI, Get food stamps 1.02-1.04 Live in Metropolitan Statistical Area Region 65 Number of chronic New Prudential None No difference between the Baker et al., 2007 conditions (companion: groups in number of chronic Medicare managed Inadequate: mean 1.7 Gazmararian, care enrollees in conditions (unadjusted): P = 61 (SD=1.2) 0.87 2006; Cleveland, OH; 64 Wolf et al., 2007; Marginal: mean = 1.7 Houston, TX; and Howard et al., (SD=1.2) Tampa and south 63 2006; Adequate: mean = 1.5 Florida (including 66 Wolf et al., 2005; (SD=1.2) Ft. Lauderdale and Baker et al., Miami) 67 2008; Howard et al., S-TOFHLA 68 Inadequate: 24% 2005; Baker et al., Marginal: 11% 62 ) 2004 Adequate: 64% Prospective cohort N = 3,260 Good Rothman et al., Adults in a primary No difference between groups Chronic illness None 9 in percent with chronic illness 2006 care clinic (hypertension, (unadjusted): P = 0.08 coronary artery -sectional Cross REALM disease, high < HS: 23% cholesterol, diabetes, N = 200 > HS: 77% or heart failure) < HS: 52% > HS: 38% Fair ASI -Alc =Addiction Severity Index - Alcohol; ASI -Drug =Addiction Severity Index - Drugs; CES -D =Center for Epidemiology Studies =confidence interval; COPD =Chronic Obstructive Pulmonary Disease; HS =high school; – Depression Scale; CI N=number; NALS =National Adult Literacy Survey; NR =not reported; OH =Ohio; PR =Poisson Regression coefficient; REALM =Rapid Estimate of Adult Literacy in Medicine; S -TOFHLA =Short Test of Functional Health Literacy in Adults; SD =standard deviation; TOFHLA =Test of Functional Health Literacy in Adults; TX =Texas; US =United States. 101

124 Table 21. Summary of studies of the relationship between health literacy and the outcome of prevalence of chronic diseases (KQ 1b) (continued) Authors, Year, Outcome Measure Differences in Outcomes Study Design, Population and Variables use Setting, Health Analysis Sample Between Health Literacy d in Outcomes By Health Levels Size, Quality Literacy Level Multivariate Analysis Literacy Level 66 Wolf et al., 2005 New Prudential Age Hypertension -reported prevalence of Self (companion: Medicare managed Sex Inadequate:50% chronic disease (adjusted) Gazmararian, care enrollees in Race/ethnicity Marginal: 46% 61 2006; Cleveland, OH; Income Adequate: 43% No difference in rates of 64 Wolf et al., 2007; Houston, TX; and Education hypertension between Baker et al., Tampa and south Tobacco Diabetes inadequate and adequate 65 200;7 Florida (including Alcohol consumption Inadequate: 19% groups: OR, 1.20; 95% CI, Howard et al., Ft. Lauderdale and Self -reported Marginal: 15% 0.95-1.50 63 2006; Miami) comorbid conditions Adequate: 13% Baker et al., No difference in probability of 67 2008; S-TOFHLA Coronary artery hypertension between Howard et al., Adequate: 67% disease marginal and adequate 68 2005; Marginal: 11% Inadequate: 6% groups: OR, 1.03; 95% CI, Baker et al., Inadequate: 22% Marginal: 7% 0.80-1.34 62 ) 2004 Adequate: 8% Inadequate group had a Cross -sectional significantly higher rate of Heart failure diabetes than adequate group: Inadequate: 6% N = 2,923 OR, 1.48; 95% CI, 1.09-2.02 Marginal: 4% Adequate: 4% No difference in probability of Fair diabetes between marginal Bronchitis or and adequate groups: OR, emphysema 1.10; 95% CI, 0.75-1.59 Inadequate: 10% Marginal: 10% No difference in coronary Adequate: 14% artery disease between inadequate and adequate Asthma groups: OR, 0.93; 95% CI, Inadequate: 7% 0.59-1.47 Marginal: 8% Adequate: 7% No difference in coronary artery disease between Arthritis marginal and adequate Inadequate: 57% groups: OR, 0.85; 95% CI, Marginal: 57% 0.51-1.43 Adequate: 50% Inadequate group has a higher Cancer probability of heart failure than Inadequate: 4% adequate group: OR, 1.69; Marginal: 7% 95% CI, 1.02- 2.80 Adequate: 6% No difference in heart failure between marginal and adequate groups: OR, 0.97; 95% CI, 0.49- 1.9 0 No difference in bronchitis or emphysema between inadequate and adequate groups: OR, 0.75; 95% CI 0.53 - 1.08 102

125 Table 21. Summary of studies of the relationship between health literacy and the outcome of prevalence of chronic diseases (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Differences in Outcomes Population and Setting, Health Outcomes By Health Between Health Literacy Analysis Sample Variables used in Levels Multivariate Analysis Literacy Level Size, Quality Literacy Level 66 No difference in bronchitis or Wolf et al., 2005 emphysema between m arginal (companion: and adequate groups: OR, Gazmararian, 61 0.81; 95% CI, 0.53-1.22 2006; 64 Wolf et al., 2007; 65 Baker et al., 2007 No difference in asthma Howard et al., between inadequate and 63 2006; adequate groups: OR, 0.96; Baker et al., 1.37 95% CI, 0.62- 67 2008; Howard et al., No difference in asthma 68 2005; between marginal and Baker et al., adequate groups: OR, 1.26; 62 ) 2004 2.01 95% CI, 0.79- (continued) No difference in arthritis between inadequate and adequate groups: OR, 0.98 1.23 95% CI, 0.78- No difference in arthritis between marginal and adequate groups: OR, 1.11; 95% CI, 0.85- 1.44 No difference in cancer between inadequate and adequate groups: OR , 0.91; 95% CI, 0.54- 1.52 No difference in cancer between marginal and adequate groups: OR, 1.38; 95% CI, 0.84 2.27 - New Prudential Howard et al., None Heart Attack Difference between groups in 68 heart attack rate (unadjusted): 2005 Medicare managed Inadequate: 15% (companion: Marginal: 18% P = 0.01 care enrollees in Gazmararian, Cleveland, OH; Adequate: 13% 61 Wolf et al., 2006; No differences between Houston, TX; and 64 Baker et al., 2007 groups in rate of angina Angina Tampa and south 65 Howard et 2007; Florida (including Inadequate: 8% (unadjusted): P = 0.06 63 Wolf et al., 2006; Ft. Lauderdale and Marginal: 12% 66 Baker al., 2005; Miami) Difference between groups in Adequate: 8% 67 Baker et al., 2008; rate of stroke (unadjusted): P 62 ) et al., 2004 S-TOFHLA < 0.0001 Stroke Adequate: 64% Inadequate: 13% Cohort Marginal: 11% Marginal: 9% No differences between Inadequate: 24% Adequate: 7% groups in rate of COPD N = 3,260 (unadjusted): P = 0.06 COPD Good Inadequate: 14% Marginal: 16% Adequate: 18% 103

126 Table 21. Summary of studies of the relationship between health literacy and the outcome of prevalence of chronic diseases (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Study Design, Differences in Outcomes Between Health Literacy Variables used in Outcomes By Health Setting, Health Analysis Sample Literacy Level Literacy Level Levels Multivariate Analysis Size, Quality 79 None Sudore et al., Hypertension Seniors (70- Difference in probability of 95 0-6th grade: 62% year old) in 2006 hypertension across groups (companion: Pittsburgh, -8th grade: 63% 7th (unadjusted): OR, 1.39; 95% Sudore et al., > 9th grade: 55% Pennsylvania and -1.68 CI, 1.25 167 ) Memphis, 2006 Diabetes Tennessee Difference in probability of Cross -sectional 0-6th grade: 25% diabetes across groups 6% REALM 7th -8th grade: 2 (unadjusted): OR, 1.98; 95% N = 2,512 0-6th grade: 8% >9th grade: 15% CI, 1.58 -2.48 7-8th grade: 15% Fair > 9th grade: 76% Limited group higher rate of Heart failure Adults with None Laramee et al., 143 OR, heart failure (unadjusted): diabetes in primary 2007 Limited: 27% 2.05; 95% CI, 1.39-3.02 Adequate: 15% care practices in Cross -sectional Vermont, New Hampshire, and northern New York N = 998 State Fair S-TOFHLA Limited: 17% Adequate: 83% 142 Kim, 2009 Difference in probability of Korean older adults None Self -report of chronic (> 60 years) arthritis between groups disease -sectional Cross (unadjusted): P = 0.003 Korean Functional Arthritis N= 103 Health Literacy test Difference in probability of Low HL: 51.2% (TOFHLA) hypertension between groups High HL: 21.7% High literacy ( Fair ≥5): (unadjusted): P = 0.018 58% Hypertension Low literacy (<5): Difference in probability of Low HL: 44.2% 42% sensory disease between High HL: 21.7% groups (unadjusted): P = 0.086 Sensory disease Low HL: 39.5% in probability of Difference High HL: 23.3% diabetes mellitus between groups (unadjusted): P = Diabetes mellitus 0.808 Low HL: 45.5% High HL: 54.5% Difference in probability of pulmonary disease between Pulmonary disease groups (unadjusted): P = Low HL: 16.3% 0.380 High HL: 10.0% Difference in probability of Heart disease heart disease between groups Low HL: 8.3% High HL: 2.3% (unadjusted): P = 0.397 104

127 Table 22. Summary of studies of the relationship between health literacy and HIV patient symptoms (KQ 1b) Authors, Year, Outcome Measure Study Design, Differences in Analysis Outcomes Between Variables used in Outcomes By Health Population and Setting, Sample Size, Health Literacy Literacy Level Multivariate Analysis Health Literacy Level Quality Levels Orlow RNA) Paasche - Viral load (HIV - Viral load suppressed Gender Patients with HIV and a 105 Low: 63% Age suppression history of alcohol et al., 2006 Marginal: 58% problems in Boston, MA Education Retrospective No difference between Randomization group Adequate: 61% cohort REALM low and adequate Ethnicity groups (adjusted): OR, Low: 14% Homeless status 1.70; 95% CI, 0.79- N = 235 Marginal: 29% Drank to intoxication past 3.65 Adequate: 57% 30 days Fair Injected drugs past 6 No difference between months marginal and adequate Complexity of regimen groups (adjusted): Medication adherence OR, 1.29; 95% CI, 0.77 2.18 - No difference in CD4 CD4 cell count: median Gender Mayben et al., Adults with HIV 145 receiving care at 4 (interquartile range) cell count between Reason for getting tested 2007 Inadequate: 175 (69, Cross -sectional publicly funded clinics in adequate and Marijuana use 272) Houston, TX inadequate groups = 0.35 (adjusted): P Adequate: 247(31, 517) N = 119 TOFHLA Inadequate: 28% Fair Adequate: 72% HIV -positive adults Hispanic Nokes et al., HIV -symptom intensity: -symptom intensity HIV 131 NR greater in higher receiving care in San 2007 health literacy group Francisco, Fresno, Cross -sectional (adjusted): β, 8.62; Richmond, NYC, Corpus P < 0.05 Christi N = 489 REALM Fair Mean = 59.1 (SD, 12.9) Kalichman et al., -positive adults in HIV HIV symptoms: Mean None No difference between 103 Atlanta, GA 2008 (SD) groups in number of Lower: 4.0 (3.2) HIV symptoms -sectional Cross TOFHLA Higher: 4.7 (3.9) (unadjusted): Lower: 49% OR, 1.05; 95% CI, N = 145 Higher: 51% 0.95-1.14 Fair 82 Murphy, 2010 Age -1 Viral load (plasma HIV -positive individuals HIV No relationship RNA): Mean (SD) Education ages 16-24 in Fort between viral load and Cross -sectional Lauderdale, HL (adjusted): P = 0.13 Marginal/ Inadequate: Philadelphia, Baltimore, N= 186 3.82 (1.08) Los Angeles, and Detroit 69 (1.19) Adequate: 3. No relationship Fair TOFHLA -modified between CD4 count CD4 measures Inadequate: 12% and HL (adjusted): P = 0.15 Data NR Marginal: 3% Adequate: 86% CD4 =Classification of Disease, Version 4; CES -D =Center for Epidemiology Studies – Depression Scale; CI =confidence interval; COPD= =Georgia; HIV =human immunodeficiency virus; N =number; NR =not Chronic Obstructive Pulmonary Disease; GA reported; NYC =New York City; OR =odds ratio; PR =Poisson Regression coefficient; REALM =Rapid Estimate of Adult Literacy in Medicine; RNA =Ribonucleic Acid; S -TOFHLA =Short Test of Functional Health Literacy in Adults; SD =standard deviation; TOFHLA =Test of Functional Health Literacy in Adults; TX =Texas. 105

128 Table 23. Summary of studies of the relationship between health literacy and asthma patient symptoms (KQ 1b) Authors, Year, Outcome Measure Variables Study Design, Population and Differences in Outcomes used in Analysis Outcomes By Health Setting, Health Between Health Literacy Sample Size, Multivariate Analysis Quality Literacy Level Literacy Level Levels Shone et al., Parents No difference between groups Asthma is not under Child health 84 in rate of asthma not under insurance of children with good control 2009 Low: 76% Parent’s good control (unadjusted): persistent Cross -sectional employment, Adequate: 82% asthma in P = 0.094 ethnicity, and Rochester New N = 499 Parents’ in low group more race Child's health is York School likely to have child with fair/poor fair/poor District Fair health (adjusted): OR, 3.96; Low: 39% 95% CI, 2.4-6.4 Adequate: 17% REALM Low: 33% Adequate: 67% Albuterol Use (mean None Greater Albuterol use in Parents of DeWalt et al., 80 per week) 2007 children of parents in lower children with days asthma receiving compared to higher health Lower: 2.7 literacy group (unadjusted): -sectional Cross care at 3 clinics Higher: 1.5 P = 0.01 in North Carolina N = 150 Albuterol Use (total Greater total weekly Albuterol REALM mean use per week) Lower: 24% use in children of parents in Fair Lower: 6 doses Higher: 76% lower compared to higher health Higher: 3 doses literacy group (unadjusted): P = 0.03 Appropriate Controller Use No difference between groups Lower: 68% in appropriate controller use Higher: 82% (unadjusted): P = 0.15 CI= confidence interval; N =number; OR =odds ratio; REALM =Rapid Estimate of Adult Literacy in Medicine. 106

129 Table 24. Summary of studies of the relationship between health literacy and diabetes control (KQ 1b) Authors, Year, Study Design, Outcome Measure Populat ion and Differences in Variables used in Analysis Outcomes By Health Multivariate Outcomes Between Setting, Health Sample Size, Literacy Level Analysis Health Literacy Levels Quality Literacy Level No difference in HbA1c HbA1c median Morris et al., Age Adults with 134 2006 Sex levels across groups diabetes in Inadequate: 6.9% Marginal: 6.8% Race primary care (adjusted, continuous -sectional Cross Marital status practices in TOFHLA scores used): Adequate: 6.9% Insurance Vermont P = 0.88 N = 1,002 Income SBP median No difference in SBP S-TOFHLA Inadequate:137 Duration of diabetes Good across groups (adjusted, Inadequate: 10% Diabetes education Marginal: 144 Marginal: 7% continuous TOFHLA Adequate: 138 Depression Adequate: 83% scores used): P = 0.78 Alcohol use DBP median Medication use No difference in DBP Physician practice Inadequate: 76 across groups (adjusted, Marginal: 77 continuous TOFHLA Adequate: 79 scores used): P = 0.39 LDL -cholesterol No difference in LDL- median cholesterol across Inadequate: 99 groups (adjusted, Marginal: 94 continuous TOFHLA Adequate: 99 scores used): P = 0.59 Retinopathy Retinopathy rates Inadequate: 30% Marginal: 34% No difference between Adequate: 18% inadequate and adequate group Nephropathy (adjusted): OR, 1.88; Inadequate: 15% 3.91 95% CI, 0.90- Marginal: 0 Adequate: 9% No difference between marginal and adequate Gastroparesis groups (adjusted): OR, Inadequate: 9% 2.30; 95% CI, 0.63-8.44 Marginal: 6% Adequate: 6% Nephropathy Foot/leg problems No difference between Inadequate: 30% inadequate and Marginal: 30% adequate groups Adequate: 30% (adjusted): OR, 1.05; 2.80 95% CI, 0.39- Cerebrovascular disease No difference between Inadequate: 21% marginal and adequate Marginal: 17 % groups (adjusted): OR, Adequate: 10% 0.99; 95% CI, 0.95 1.03 - C-SDSCA =Chinese version of Summary of Diabetes Self -Care Activities; CI =confidence interval; DBP =diastolic blood pressure; Hb =hemoglobin; HL =health literacy; LDL =Low -density lipoprotein; N =number; OR =odds ratio; REALM =Rapid Estimate of Adult Literacy in Medicine; S -TOFHLA -Spanish= Short Test of Functional Health Literacy in Adults –Spanish; SBP =systolic blood pressure; TOFHLA =Test of Functional Health Literacy in Adults. 107

130 Table 24. Summary of studies of the relationship between health literacy and diabetes control (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Differences in Population and Variables used in Analysis Outcomes By Health Setting, Health Multivariate Outcomes Between Sample Size, Level Literacy Level Literacy Analysis Health Literacy Levels Quality Morris et al., Foot/leg problem rates Coronary artery 134 disease 2006 (continued) Inadequate: 30% No difference between Marginal: 27% inadequate and Adequate: 17% adequate groups (adjusted): OR, 0.52; 95% CI, 0.24- 1.16 No difference between marginal and adequate groups (adjusted): OR, 1.39; 95% CI, 0.47-4.12 Gastroparesis No difference between inadequate and adequate groups (adjusted): OR, 1.92; 6.36 95% CI, 0.58- No difference between marginal and adequate groups (adjusted): OR, 1.98; 95% CI, 0.26-18.07 Cerebrovascular disease No difference between inadequate and adequate groups (adjusted): OR, 0.86; 95% CI, 0.39- 1.91 No difference between marginal and adequate groups (adjusted): OR, 0.65; 95% CI, 1.66-2.57 Coronary artery disease No difference between inadequate and adequate groups (adjusted): OR, 0.76; 95% CI, 0.36 - 1.63 108

131 Table 24. Summary of studies of the relationship between health literacy and diabetes control (KQ 1b)(continued) Authors, Year, Study Design, Outcome Measure Variables used in Differences in Population and Analysis Outcomes By Health Multivariate Outcomes Between Setting, Health Sample Size, Health Liter Literacy Level Analysis Quality Literacy Level acy Levels No difference between Morris et al., 134 2006 marginal and adequate (continued) groups (adjusted): OR, - 3.70 1.12; 95% CI, 0.34 Higher HL associated HbA1c levels Tang et al., Gender Adults with 148 2007 Insurance outcomes: NR with lower HbA1c levels diabetes in (adjusted): P < 0.001 diabetes Duration of diabetes -sectional Cross Patient awareness education survey management score and medical chart center of a public C-SDSCA review (management of hospital in Hong diabetes) Kong N = 149 Chinese S - TOFHLA: Fair Levels NR HbA1c median Education Powell et al., Patients with Difference in HbA1c 149 <4th grade: 8% 2007 Type 2 diabetes Age level between groups P = 0.02 (adjusted): -6th grade: 8% 4th treated in general Race -sectional Cross internal medicine 7th Gender -8th grade: 10% HS: Median: 7.9% clinic Treatment regimen N = 68 REALM < 4th grade: 13% Fair -6th grade: 4th 25% 7th -8th grade: 19% High school: 43% Adult diabetes HL mediated the direct Schillinger et al., Age Log HbA1c: NR 150 relationship between patients (> 30 2006 Primary language other than English years old) treated education and HbA1c -sectional Cross at one of two level in a partial Insurance mediation model primary care Education N = 395 (adjusted path analysis): clinics at San < 0.05 P Francisco Good General Hospital HL mediated the direct S-TOFHLA relationship between Mean = 20.6 education and HbA1c level in a full mediation (SD=12.1) model (adjusted path P = 0.03 analysis): 109

132 Table 24. Summary of studies of the relationship between health literacy and diabetes control (KQ 1b) (continued) Authors, Year, Study Design, Outcome Measure Differences in Variables used in Population and Analysis Outcomes By Health Multiv Setting, Health Outcomes Between ariate Sample Size, Quality Analysis Health Literacy Levels Literacy Level Literacy Level Adults with a HbA1c by HL level: Patient trust No difference between Mancuso et al, 151 NR HL groups in HbA1c diagnosis of type depression 2010 1 or 2 diabetes in diabetes knowledge (adjusted): P = 0.436 -sectional Cross performance of self - 2 urban care activities Midwestern US N=102 primary care clinics Good TOFHLA Inadequate: 16% Marginal: 21% Adequate: 63% 110

133 Table 25. Summary of studies of the relationship between health literacy and hypertension control (KQ 1b) Authors, Year, Study Design, Outcome Measure Population and Differences in Variables used in Analysis Outcomes By Health Multivariate Outcomes Between Setting, Health Sample Size, Analysis Literacy Level Literacy Level Health Literacy Levels Quality Age SBP: mean (SD) The relationship between Patients with Powers et al., 154 HL and blood pressure Race 2008 hypertension level differed in the two receiving primary VA Marital status -sectional Cross Limited: 138.7 (17.8) care in the VA healthcare systems Education (adjusted) (moderator Adequacy of income healthcare system Adequate: 138.4 N = 1,224 (17.5) analysis) and Duke Diabetic status University Medication HL main effect: β = -1.2; Fair Adherence Healthcare system Duke 95% CI, - -2.3 4.8 in Durham, NC. Smoking Limited: 142 (24.9) Adequate: 133 (17.6) Exercise REALM Interaction between HL Participatory VA and healthcare system: decision-making Limited: 38% β = 7.4; 95% CI, 2.5 -12.3 score Adequate: 58% Duke Limited: 28% Adequate: 72% Age Controlled Blood Adults with Category V group has Pandit et al., 155 greater odds of having hypertension 2009 Race Pressure receiving primary Category I: 34% Gender controlled BP than care from clinics in Category II: 49% Category I group Cross -sectional Marital status Category III: 45% Grand Rapids, Employment status (adjusted): RR, 2.68; Category IV: 61% Michigan, 95% CI, 1.54- Insurance coverage 4.70 N = 330 Chicago, Illinois, Category V: 46% Site location (highest) and Shreveport, Fair Louisiana No difference between S - TOFHLA Pandit et al., Number of comorbid 155 Category I: 17% Category II and Category conditions 2009 Category II: 11% (continued) Years treated for V in odds of having controlled BP (adjusted): Category III: 16% hypertension RR, 1.47; 95% CI, 0.53- Category IV: 26% Clinic site Category V: 31% Education 4.05 Category V group has greater odds of having controlled BP than Category III group (adjusted): RR, 1.69; 95% CI, 1.08- 2.63 No difference between Category IV and Category V in odds of having controlled BP (adjusted): RR, 1.10; 95% CI, 0.40 - 3.01 BP =blood pressure; CI =confidence interval; PSA =prostate -specific antigen; REALM =Rapid Estimate of Adult Literacy in Medicine; RR =relative risk; S -TOFHLA =Short Test of Functional Health Literacy in Adults; SD =standard deviation; SBP =systolic blood pressure; VA =veterans administration. 111

134 Table 26. Summary of studies of the relationship between heal th literacy and prostate cancer control (KQ 1b) Authors, Year, Outcome Measure Study Design, in Population and Differences Variables used in Analysis Outcomes By Health Multivariate Setting, Health Outcomes Between Sample Size, Literacy Level Literacy Level Analysis Health Literacy Levels Quality PSA Level > 20 Low group more likely to Wolf et al., Age Patients with 157 mg/mL Race 2006 newly diagnosed have elevated PSA than Marginal: 24% prostate cancer functional group Annual income Cross -sectional Low: 33% (adjusted): OR, 2.5; 95% in 4 outpatient Marital status Functional: 14% -4.2 oncology and CI, 1.5 N = 308 urology clinics in No difference in rates of Chicago area elevated PSA between Good REALM functional marginal and Low: 18% groups (adjusted): OR, Marginal: 33% 1.4; 95% CI, 0.9 -2.2 Functional: 50% =milligram/millileter; OR =prostate -specific antigen; REALM =Rapid Estimate confidence interval; mg/mL CI= =odds ratio; PSA of Adult Literacy in Medicine. between health literacy and health status (KQ 1b) Table 27. Summary of studies of the relationship Outcome Measure Authors, Year, Population and Study Design, Differen ces in Results Variables used in Outcomes By Health Setting, Health Between Health Literacy Analysis Sample Size, Quality Literacy Level Multivariate Analysis Levels Literacy Level No difference between groups Smith and Perceived overall health Age Adults in 159 Smoking status University -affiliated Haggerty, 2003 in perceived general health (adjusted): β = family practice Maternal language Low: mean = 3.3 -0.11; 95% CI, -sectional Cross center in Montreal, Adequate: mean = 3.0 -0.25-0.03 Canada N = 229 REALM Low: 6% Fair Adequate: 94% Race Nationally Bennett et al., Health status Higher health literacy Income 200985 representative levels by health literacy iated with better self assoc - Gender (companion: White sample of US level: NR reported health status 86 ) population, 65 et al., 2008 Age (adjusted): P < 0.05 years and older Nativity -sectional Cross NAAL N = 2,668 Below basic: 29.0% Good Basic: 29.5% Intermediate: 38.2 Proficient: 3.3% ADL =activities of daily living; AQLQ =Asthma Quality of Life Questionnaire; BMI =body mass index; FACT -G=Functional Assessment of Cancer Therapy -General; HR =hazard ratio; HRQoL =health -related quality of life; IADL =instrumental activities of daily living; N =National Assessment of Adult Literacy; NALS =National Adult Literacy Survey; NR =not =number; NAAL reported; OR =odds ratio; PCS =Physical Component Summary; REALM =Rapid Estimate of Adult Literacy in Medicine; SD =standard deviation; SF =short form; S -TOFHLA =Short Test of Functional Health Literacy in Adults; USUnited States; VRQoL =vision -related quality of life. 112

135 y and health status (KQ 1b) Table 27. Summary of studies of the relationship between health literac (continued) Authors, Year, Outcome Measure lts Differences in Resu Study Design, Population and Outcomes By Health Variables used in Between Health Literacy Analysis Sample Setting, Health Levels Size, Quality Multivariate Analysis Literacy Level Literacy Level Analysis 1 Seniors who are Analysis 1 - Health status (self Analysis 1 81 Cho et al., 2008 patients at 1 of 2 Race/ethnicity report) Chicago clinics Gender Levels: NR Using path analysis, higher Cross -sectional Education health literacy level related to S-TOFHLA General health (self - better health status (adjusted): < 0.05 P N = 489 Inadequate/ Analysis 2 report) marginal: 51% Age Levels: NR Fair adequate: 49% Gender Analysis 2 Race -12) Physical health (SF Analysis 2 Education Levels: NR Low health literacy associated 160 Lee, 2009 Marital status Income with lower level of general Social support level Mental health (SF -12) health status(adjusted): < 0.05 P Cross -sectional Levels: NR N = 489 No dif ference between groups in physical health (adjusted): P = NS Fair No difference between groups in mental health (adjusted): = NS P Analysis 1 New Prudential Analysis 1 - Physical HRQoL (SF 1 Analysis 63 Howard, 2006 Medicare Age 12) managed- care Gender Inadequate: mean = Inadequate group poorer Prospective cohort enrollees in Race/ethnicity 41.9 (SD=11.9) physical HRQoL than Cleveland, Education Marginal: mean = 43.6 adequate (adjusted): N = 3,260 < 0.001 P Houston, Tampa, Income (SD=11.7) and south Florida Site 46.2 Adequate: mean = Fair Morbidity (SD=10.7) Marginal group poorer S-TOFHLA Smoker physical HRQoL than Analysis 2 Inadequate: 25% Mental HRQoL (SF -12) adequate (adjusted): 65 P =0.019 Baker et al., 2007 Marginal: 11% Analysis 2 Inadequate: mean 52.1 Adequate: 64% None (SD=10.7) (companions: Marginal: mean = 54.9 Inadequate group poorer Gazmararian, (SD=9.2) mental HRQoL than adequate 61 Wolf et al., 2006; < 0.001 (adjusted): P Adequate: mean 55.5 64 Wolf et al., 2007; (SD=7.9) 66 Baker et 2005; No difference in mental 67 Howard al., 2008; IADL limitation oL between marginal and HRQ 68 et al., 2005; Inadequate: 46% adequate groups (adjusted): Baker et al., = 0.304 P Marginal: 37% 62 ) 2004 Adequate: 24% Inadequate group less likely to Prospective cohort -report health status of self ADL limitation good or better than adequate Inadequate: 9% groups (adjusted): OR, 0.71; N = 3,260 Marginal: 6% = 0.004 P Adequate: 3% Good No differences in self -reported health status of good or better between marginal and adequate groups (adjusted): OR, 0.77; P = 0.060 113

136 Table 27. Summary of studies of the relationship between health literacy and health status (KQ 1b) (continued) Authors, Ye ar, Outcome Measure Differences in Results Study Design, Population and Setting, Health Outcomes By Health Between Health Literacy Variables used in Analysis Sample Literacy Level Levels Size, Quality Multivariate Analysis Literacy Level Analysis 2 Analysis 1 63 Howard, 2006 Significant difference between (continued) 3 HL groups in IADL limitation P (unadjusted): < 0.001 Significant difference between 3 HL groups in ADL limitation P (unadjusted): < 0.001 79 Sudore et al., - report poor health - Seniors (70 Difference in probability of Self None 95 poor health across groups 2006 year old) in 0-6th grade: 33% (companion: (unadjusted): OR, 2.60; 95% 7th -8th grade: 28% Pittsburgh, 167 ) 9th grade: 14% > Sudore, 2006 -3.23 Pennsylvania and CI, 2.09 Memphis, -sectional Cross Tennessee REALM N = 2,512 0-6th grade: 8% 7-8th grade: 15% Fair 9th grade: 76% > 66 Wolf et al., 2005 New Prudential Age Physical function (SF - Inadequate group lower (companion: Medicare managed Sex 36) mean (SD) physical function scores than Gazmararian, care enrollees in Race/ethnicity Inadequate: 67.7 (9.7) adequate group (adjusted): 61 2006; Cleveland, OH; Income Marginal: 73.7 (27.5) -6; 95% CI, -8.4 β, -3.5 64 Wolf et al., 2007; Houston, TX; and Education Adequate: 78.0 (24.6) Baker et al., Tampa and south Tobacco Marginal lower physical 65 2007; Florida (including Alcohol consumption Mental health function scores than adequate Howard et al., Ft. Lauderdale and -reported Self functioning (SF -36) -1.1; 95% group (adjusted): β, 68 2005; Miami) comorbid conditions mean (SD) -1.8 CI, -3.9 Baker et al., Inadequate: 76.2 (20.9) 67 2008; S-TOFHLA Marginal: 81.8 (18.6) Inadequate group lower Howard et al., Inadequate: 22% Adequate: 84.0 (16.1) mental health scores than 68 2005; Marginal: 11% adequate group (adjusted): Baker et al., Adequate: 67% β, -6.7 to -3.1 -4.9; 95% CI, 62 ) 2004 Marginal group lower mental -sectional Cross health score than adequate group (adjusted including N = 2,923 95% CI, -0.9; education): β, -2.9 -1.2 Fair Inadequate group has greater self -reported instrumental activity limitations than adequate group (adjusted including ed): OR, 2.25; 95% CI, 1.74 -2.92 Marginal group has greater instrumental activity limitations than adequate group: OR, 1.65; 95% CI, 1.22 - 2.24 114

137 Table 27. Summary of studies of the relationship between health literacy and health status (KQ 1b) (continued) Outcome Measure Authors, Year, Study Design, Population and Differences in Results Variables used in Setting, Health Outcomes By Health Between Health Literacy Analysis Sample Literacy Level Multivariate Analysis Size, Quality Levels Literacy Level 66 Inadequate group has greater Wolf et al., 2005 -reported activity self (companion: limitations than adequate Gazmararian, 61 group (adjusted included): 2006; 64 Wolf et al., 2007; OR, 2.83; 95% CI, 1.62-4.96 Baker et al., 65 2007; Marginal group has greater Howard et al., activity lim itations than 68 2005; adequate group (adjusted): Baker et al., OR, 2.05; 95% CI, 1.06-3.97 67 2008; Howard et al., Inadequate group has greater 68 2005; limitations due to physical Baker et al., health than adequate group 62 ) 2004 (adjusted): OR, 1.79; 95% CI, (continued) 1.39-2.32 No differences in limitations because of physical health between adequate and marginal groups (adjusted): OR, 1.35; 95% CI, 1.00-1.84 Inadequate group has fewer accomplishments due to physical health than adequate group (adjusted): OR, 1.90; 95% CI, 1.48- 2.45 Marginal has fewer accomplishments than marginal gr oup (adjusted): OR, 1.46; 95% CI, 1.08-1.97 Inadequate group has greater pain interfering with activities than adequate group (adjusted): OR, 2.01; 95% CI, 1.46-2.77 No difference in pain interfering with activities between marginal and adequate groups ( adjusted): OR, 1.23; 95% CI, 0.83 - 1.82 115

138 Table 27. Summary of studies of the relationship between health literacy and health status (KQ 1b) (continued) Authors, Year, Outcome Measure Population and Study Design, Differences in Results Between Health Literacy Setting, Health Outcomes By Health Variables used in Analysis Sample Literacy Multivariate Analysis Literacy Level Levels Level Size, Quality 161 Muir et al., 2008 Glaucoma patients Age VRQoL score (mean) No difference between groups at a Duke eye clinic Race Low: 84 in VRQoL (adjusted): -sectional Cross in Durham, NC Visual acuity Adequate: 76 P = 0.621 Visual field REALM N = 110 Education Physical HRQoL Low HL associat ed with Low: 52% -12): NR (SF poorer physical HRQoL Adequate: 48% Fair (unadjusted): P = 0.002 Mental HRQoL No difference between groups (SF -12): NR in mental HRQoL (unadjusted): P = 0.068 - Hispanic Global physical health Nokes et al., positive adults HIV Physical health rated lower in 131 2007 (scale developed by higher group (unadjusted): receiving care in P = 0.02 San Francisco, investigators): mean (SD) Cross -sectional Fresno, Richmond, Lower: 7.21, (2.42) Corpus NYC, Higher: 6.68, (2.22) Christi N = 489 REALM Fair Mean = 59.1 (SD, 12.9) Asthma severity Adults with asthma Mancuso and Outcome data by health Lower HL related to poorer 100 enrolled in a literacy level: NR AQLQ (adjusting for asthma Rincon, -efficacy asthma self 2006 severity, asthma self Age -efficacy): primary care Cross -sectional P = 0.003 practice in New Education Depressive symptoms York City N = 175 Lower HL related to poorer Asthma knowledge AQLQ (adjusting for asthma TOFHLA Fair -efficacy, Adequate: 82% severity, asthma self Marginal: 8% age and education): P = 0.03 Inadequate: 10% No difference in AQLQ by HL level (adjusting for asthma -efficacy, severity, asthma self age, education, depressive symptoms): P = 0.07 No difference in AQLQ by HL level (adjusting for asthma severity, asthma self -efficacy, age, education, depressive oms, asthma sympt knowledge): P = 0.38 Lower HL related to poorer Physical HRQoL (SF -36) (adjusting for asthma severity and asthma self -efficacy): P = 0.0003 116

139 Table 27. Summary of studies of the relationship between health literacy and health status (KQ 1b) (continued) Authors, Year, Study Design, Outcome Measure Variables used in Differences in Results Population and Analysis Outcomes By Health Multivariate Between Health Literacy Setting, Health Sample Size, Literacy Level Quality Analysis Levels Literacy Level No difference in physical Mancuso and 100 HRQoL (SF -36) by HL level Rincon, 2006 (continued) (adjusting for asthma - severity, asthma self efficacy, age and = 0.11 education): P No difference in physical HRQoL (SF -36) by HL level (adjusting for asthma severity, asthma self - efficacy, age, education and depressive symptoms): P = 0.22 -36 by No difference in SF HL level (adjusting for asthma severity, asthma self -efficacy, age, education, depressive symptoms and asthma knowledge): P = 0.53 data by Outcome Johnston et al., Adult patients at Motor index Having less than adequate 162 health literacy level: Education HL associated with poorer 2005 spinal cord injury clinic in New NR physical morbidity (number Jersey of days physical health "not Cross -sectional good") (adjusted): P < = 0.05 TOFHLA N = 107 Inadequate: 6% No difference between Marginal: 8% Fair groups in mental health Adequate: 86% morbidity (number of days mental heal th "not good") P = 0.90 (adjusted): No difference between groups in SF -12 Physical Component score (adjusted): P = 0.49 No difference between -12 Mental groups in SF Component score (adjusted): P = 0.07 No difference between groups in physical independence (adjusted): P = 0.47 No difference between groups in mobility (adjusted): P = 0.93 117

140 Table 27. Summary of studies of the relationship between health literacy and health status (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Population and Differences in Results Variables used in Analysis Outcomes By Health Between Health Literacy Multivariate Setting, Health Sample Size, Quality Literacy Level Literacy Level Levels Analysis - G mean (SD) FACT Age No difference between Hahn et al., Adult cancer 163 2007 Gender patients in 5 groups on any of the FACT - Chicago-area G scale items (adjusted) Race/ethnicity Physical well-being -sectional Cross cancer centers Work status Low: 17.9 (5.9) No difference between Marital status High: 18.4 (5.8) N = 415 Passage groups on SF -36 including Living arrangement comprehension and excluding biased scale -being Socioeconomic Emotional well Good subtest of items (adjusted) Low: 17.6 (5.2) status Woodcock Prior computer High:17.5 (4.7) Language Difference standard Gamble experience Proficiency utility score (unadjusted): Functional well Cancer diagnosis -being = 0.561 P Battery Stage at diagnosis Low: 15.7 (6.5) Low: 52% High: 16.0 (6.3) Months since High: 48% diagnosis Current SF -36 mean (SD) chemotherapy treatment Physical functioning Performance status Low: 48.7 (26.7) High: 57.2 (27.5) Role -physical Low: 29.7 (38.2) High: 34.8 (42.4) Bodily pain Low: 55.5 (26.9) High: 56.0 (24.9) General health Low: 49. 9 (20.6) High: 53.2 (21.3) Vitality Low: 51.5 (21.4) High: 47.3 (20.5) Mental health Low: 65.5 (19.6) High: 66.9 (20.2) Fair/poor health Low: 53.3% High: 39% Standard Gamble utility score Low: mean = 0.87 (0.20) High: mean = 0.85 (0.23) 118

141 Table 27. Summary of studies of the relationship between health literacy and health status (KQ 1b) (continued) Authors, Year, Outcome Measure Study Design, Differences in Results Population and Variables used in Analysis comes By Health Out Setting, Health Multivariate Between Health Literacy Sample Size, Literacy Level Quality Literacy Level Levels Analysis 142 No difference in physical Kim, 2009 Age - Physical function (SF Korean older 12) Education function by HL level adults (> 60 -sectional Cross Low HL: 40.34 (10.3) (adjusted): P = 0.06 Income years) High HL: 46.71 (9.8) Limitations in activities Korean N= 103 Functional Health worse in low HL group Limitations in activity (adjusted): P = 0.025 Literacy test Low HL: 51.11 (8.6) Fair (TOFHLA) High HL: 44.64 (10.8) High literacy Pain that interfered with ≥5): 58% ( normal work worse in low HL Pain that interfered Low literacy (<5): group (adjusted without with normal work 42% education): P = 0.044 Low HL: 47.08 (10.6) High HL: 40.37 (12.3) Subjective general health worse in low HL group Subjective general (adjusted): P = 0.036 -12) health (SF Low HL: 36.97 (11.5) No difference in mental High HL: 44.88 (12.0) health status by HL level (adjusted): P =0.15 Mental health status (SF -12) Low HL: 45.13 (9.82) High HL: 48.88 (6.53) 119

142 Table 28. Summary of studies on the relationship between health literacy and mortality (KQ 1b) Authors, Year, Out come Measure Study Design, Population and Differences in Results Variables used in Analysis Outcomes By Health Multivariate Setting, Health Between Health Literacy Sample Size, Analysis Quality Literacy Level Literacy Level Levels Baker et al., Analysis 1 cause mortality rate - All Baseline measures: New Prudential 65 Medicare Inadequate: 39% Number of chronic 2007 (Analysis 1) All managed care conditions Marginal: 29% -cause mortality Inadequate group had a enrollees in Physical health Adequate: 19% Baker et al., greater rate than score Cleveland, OH; 67 2008 Houston, TX; and Cardiovascular mortality Mental health score adequate group (Analysis 2) rate IADL limitation Tampa and south (adjusted): HR,1.52; 95% Inadequate: 19% ADL limitation -1.83 CI, 1.26 Florida (including (companion: Smoking Ft. Lauderdale Marginal: 17% Gazmararian, No difference between Adequate: 8% and Miami) Alcohol use 61 Wolf et 2006; marginal and adequate Vigorous physical 64 al., 2007; S-TOFHLA activity groups (adjusted): HR, Cancer mortality rate Howard et al., Inadequate: 24% 1.13; 95% CI, 0.90-1.41 Inadequate: 9% BMI 63 Wolf et 2006; Marginal: 11% Marginal: 5% 66 al., 2005; Adequate: 64% Adequate: 6% Cardiovascular mortality Howard et al., e group had a Inadequat 68 Baker et 2005; Noncardiovascular/ greater rate than the 62 ) al., 2004 noncancer mortality rate adequate group Inadequate: 11% (adjusted): HR, 1.52; 95% Prospective Marginal: 7% CI, 1.16 -2.00 cohort Adequate: 5% Marginal group had a N = 3,260 greater rate than the adequate group Good (adjusted): HR, 1.39; 95% CI, 1.02 -1.90 Cancer mortality No difference between inadequate and adequate groups (adjusted): HR, 1.18; 95% CI, 0.81-1.72 No difference between marginal and adequate groups (adjusted): HR, 0.65; 95% CI, 0.38-1.09 All other causes mortality Inadequate group has a greater rate than the: adequate group (adjusted): HR, 1.87; 95% CI , 1.32 - 2.67 ADL =activities of daily living; AQLQ =Asthma Quality of Life Questionnaire; BMI =body mass index; CI =confidence interval; =Ohio; HR =health -related quality of life; IADL =Instrumental activities of daily living; N =number; OH =hazard ratio; HRQoL OR =Odds ratio; TN =Tennessee; TX =Texas. 120

143 Table 28. Summary of studies on the relationship between health literacy and mortality (KQ 1b) (continued) Authors, Year, Study Design, Outcome Measure Differences in Results Population and Analysis Outcomes By Health Variables used in Between Health Literacy Setting, Health Sample Size, Quality Literacy Level Levels Multivariate Analysis Literacy Level No difference between Baker et al., 65 marginal and adequate 2007 (Analysis 1) groups (adjusted): HR, 1.18; 95% CI, 0.76-1.85 Baker et al., 67 2008 Analysis 2 (Analysis 2) (continued) -cause mortality All (adjusted for all confounders and level of cognitive functioning) Inadequate group has a greater rate than adequate (adjusted): HR, 1.27; 95% -1.5 7 CI, 1.03 No difference between marginal and adequate group (adjusted): HR, 1.08; 95% CI, 0.85 - 1.36 Mortality rate Limited group greater odds Sudore et al., 79 Seniors (70- Demographics: age, 167 of dying than adequate 2006 Limited: 20% year old) in race, gender, income, group (adjusted): HR, 1.75; (companion: Adequate: 11% Pittsburgh, PA, education 95% CI, 1.27- 2.41 Sudore et al., and Memphis, Health status: self - 95 ) 2006 TN rated health, cardiac Limited group greater odds disease, stroke, Prospective of dying than adequate REALM cancer, hypertension, cohort, group (adjusted, excluding Limited: 24% diabetes, obesity retrospective participants with cognitive Adequate: 76% Health-related analysis impairment): HR, 1.94; behaviors: former or 95% CI, 1.37- 2.74 current smoker, N = 2,512 dri nking >1 alcoholic beverage per day Good Poor health care access: lack of a regular doc or clinic, no flu shot within past 12 months, no insurance for medications Psychosocial status: high depressive symptoms, poor personal mastery 121

144 Table 29. Summary of studies of the relationship between health literacy and costs (KQ 1c) Authors, Year, Outcome Measure Study Design, Differences in Results Variables used in Population and Outcomes By Health Setting, Health Multivariate Between Health Literacy Analysis Sample Literacy Level Literacy Level Analysis Size, Quality Levels Age Costs 1 - year period Overall costs (adjusted) Howard, et al., New Medicare 68 No difference between 2005 managed- care Sex inadequate and adequate Overall mean (SD) enrollees in Race/ethnicity (companion: Inadequate: $9,614 ± Cleveland, Income groups: β, $1,551; 95% CI, Gazmararian, $22,536 -$166-$3,267 Houston, Tampa, Education 61 Wolf et al., 2006; and south Florida Marginal: $8,484 ± No difference between Tobacco 64 Baker et 2007; Alcohol marginal and adequate $16,646 65 Howard S-TOFHLA al., 2007; consumption groups: β, $596; 95% CI, Adequate: $7,246 ± 63 Self -reported Wolf et al., 2006; Inadequate: 25% $17,941 -$2,630 -$1,437 66 et al., 2005; comorbid conditions Marginal: 11% Baker et al., Adequate: 64% Inpatient costs (adjusted) Inpatient mean (SD) 67 Howard et 2008; Inadequate: $6,817 ± No difference between 68 Baker al., 2005; $21,049 inadequate and adequate 62 ) et al., 2004 inal: $5,857 ± Marg groups: β, $1,543; 95% CI, $15,240 -$89-$3,175 Prospective cohort No difference between Adequate: $4,656 ± marginal and adequate $16,428 N = 3,260 groups: β, $748; 95% CI, -$1,252-$2,748 Outpatient mean (SD) S-TOFHLA Inadequate: $1,970 ± $3,477 Outpatient costs (adjusted) Marginal: $1,727 ± $2,954 Good No difference between Adequate: $1,805 ± inadequate and adequate $3,188 groups: β, -$213; 95% CI, -$481-$55 ED mean (SD) Costs lower in marginal Inadequate: $189 ± $551 group: β, -$350; 95% CI, Marginal: $182 ± $593 -$679 to -$20 Adequate: $100 ± $360 ED costs (adjusted) Pharmacy mean (SD) Higher costs in inadequate Inadequate: $638 ± group: β, $108; 95% CI, $62 - $1,267 $154 Marginal: $719 ± $998 Higher costs in marginal Adequate: $684 ± $890 CI, $28 - group: β, $80; 95% $132 Pharmacy costs (adjusted) No difference between inadequate and adequate group: β, $27; 95% CI, -$55-$110 No difference between marginal and adequate groups: β, $35; 95% CI, - $62 - $132 CI= -confidence interval; ED =-emergency department; IDR =Instrument for the Diagnosis of Reading; N =number; S - TOFHLA =Short Test of Functional Health Literacy in Adults; SD =standard deviation. 122

145 Table 29. Summary of studies of the relationship between health literacy and costs (KQ 1c) (continued) Authors, Year, Outcome Measure Study Design, Differences in Results Variables used in Population and Between Health Literacy Multivariate Analysis Sample Outcomes By Health Setting, Health Literacy Level Literacy Level Levels Analysis Size, Quality 168 Medicaid Weiss et al. 2004 Total costs, 1 Age -year period, Medicaid costs over a 1-year beneficiaries in mean (range) Ethnic group period higher in low group Retrospective Arizona Health status Low: $10,688 ($0- (adjusted) cohort $95,002) (P = 0.037) IDR Higher: $2,890 ($0- N = 74 Low: 24% 38,957) Higher: 76% Fair Table 30. KQ 1c health literacy studies: strength of evidence grades by costs of health care Strength of Number Outcome for Health Evidence Results Literacy Studies of Studies Grade Costs of health care 2 Mixed results across payment source and patient Insufficient populations 123

146 Table 31. Summary of studies of the relationship between health literacy and disparities (KQ 1d) Outcome Measure Authors, Year, Study Design, Population and Variables used in Differences in Results Between Outcomes By Health Analysis Sample Multivariate Setting, Health Health Literacy Levels Literacy Level Analysis Size, Quality Literacy Level Self report of physical, Sentell and Halpin, Race of National sample Health literacy mediates the 141 Education 2006 adults association of black race on having mental, or other health a condition that keeps you from condition that keeps Understand -sectional Cross Total NALS score work (adjusted): respondent from English Odds associated with black race, Level 1: 20% working Born in U.S.A. N = 23,889 not controlling for health literacy: Level 2: 27% Unemployed Data: NR OR 1.54, 95% CI, 1.29- 1.84 Level 3: 34% Family income Fair Odds associated with black race, Level 4: 18% Income missing Long-term illness controlling for health literacy: Level 5: 2% Sex (greater than 6 1.26 OR 1.04; 95% CI, 0.85- Age months) Married Health literacy mediates the effect Get food stamps Live in Metropolitan Data: NR of black race on having long-term Statistical Area illness (adjusted) Region Odds associated with black race, not controlling for health literacy: 1.49 OR 1.24; 95% CI, 1.03- Odds associated with black race, controlling for health literacy: 1.30 OR, 1.07; 95% CI, 0.89 - 63 Physical HRQoL mean Physical HRQoL (difference in Howard, 2006 New Prudential Age (SF -12) (companion: scores between white and black, Medicare managed Gender White: 44.9 adjusted) Gazmararian, care enrollees in Race/ethnicity 61 Wolf et al., Black: 43.6 2006; Not controlling for health literacy: Cleveland, Ohio, Education 64 Baker et 2007; 0.1 Houston, Texas, Income 65 Wolf et al., 2007; Mental HRQoL mean Controlling for health literacy: - 0.5 Tampa, and south Site 66 Baker al., 2005; (SF -12) Difference between models: Florida (including Morbidity 67 et al., 2008; White: 55.7 (0.6, 95% CI, 0.3 -0.9) Ft. Lauderdale and Smoker Howard et al., Black: 53.0 Miami) 68 Baker et 2005; QoL (difference in Mental HR 62 ) al., 2004 Self -reported health scores between white and black, S-TOFHLA good or higher adjusted) By race: Cohort White: 0.39 Not controlling for health literacy: White: Black: 0.23 0.5 Adequate: 71% N = 3,260 Controlling for health literacy: 0.2 Marginal: 10% Receipt of influenza Difference between models: Inadequate: 19% Fair vaccine -0.5) (0.3, 95% CI, 0.1 Black: White: 0.826 Adequate: 36% - reported health good or higher Self Black: 0.701 Marginal: 12% (difference in scores between Inadequate: 52% white and black, adjusted) Receipt of Not controlling for health literacy: pneumococcal vaccine 0.8 White: 0.48 Controlling for health literacy: 0.6 Black: 0.29 CI= confidence interval; Hb =hemoglobin; HIV =human immunodeficiency virus; HL =health literacy; HR =hazard ratio; HRQoL =health related quality of life; N =number; NAAL =National Assessment of Adult Literacy; NALS =National Adult Literacy Survey; NR =not sufficient; OR =odds ratio; OTC =over the counter; PSA =prostate -specific antigen; =not reported; NS REALM =Rapid Estimate of Adult Literacy in Medicine; SE= standard error; SF -12 =Short Form 12; S -TOFHLA= Short Test of Functional Health Literacy in Adults; US =United States. 124

147 Table 31. Summary of studies of the relationship between health literacy and disparities (KQ 1d) (continued) Outcome Measure Authors, Year, Population and Outcomes By Study Design, Differences in Results Between Variables used in Setting, Health Health Literacy Analysis Sample Size, Quality Multivariate Analysis Level Health Literacy Levels Literacy Level 157 Health literacy mediates the PSA Level > 20 Wolf et al., 2006 Age Patients with newly association between race (African Race ng/mL diagnosed prostate Marginal: 24% Convenience cancer in 4 American versus white) and PSA Annual income outpatient oncology Low: 33% Marital status level (adjusted). and urology clinics N = 308 Functional: 14% Odds associated with African in Chicago area American, not controlling for health Outcomes by race: Good REALM literacy NR Low: 18% (OR, 4.6; 95% CI, 2.0 - 9.5) Marginal: 33% Od ds associated with African Functional: 50% American, controlling for health literacy 9.1) (OR, 3.0; 95% CI, 0.8 - 77 Race HL is a mediator between race and Adults in Misinterpretation of Bailey, 2009 Age medication label gender and misinterpretation of Shreveport, LA; -sectional Cross instructions Sex medication instructions Chicago, IL; and Jackson, MI Education Odds associated with being black Low: 43% N = 373 Marginal: 34% vs. white (adjusted) REALM Not controlling for HL: OR, 1.63; Adequate: 18% ≤ 6th grade: Low: Fair 95% CI, 1.02- 2.61 20% Controlling for HL: OR, 1.22; 95% Marginal: 7th- 8th -2.04 CI, 0.73 29% grade: ≥ 9th Adequate: Odds associated with being male grade: 51% vs. female (adjusted) Not controlling for HL: OR, 1.67; 2.72 95% CI, 1.03- HL: OR, 1.59; 95% Controlling for - 2.60 CI, 0.97 Nationally Race HL mediates the association NR Bennett et al., 85 Income 2009 between race (black vs. white) and representative (companion: White self -reported health status sample of US Gender 86 ) et al. 2008 population 65 Age (adjusted) Nativity years and older Cross -sectional Odds associated with being black Not controlling for HL: β, - 0.34 (SE, NAAL P 0.11) ( < 0.05) N = 2,668 Below basic: for HL: β, -0.24 (SE, Controlling 29.0% 0.04) ( < 0.05) P Good Basic: 29.5% Intermediate: 38.2 Odds associated with being Proficient: 3.3% Hispanic Not controlling for HL: β, 0.02 (SE, 0.14) ( P = NS) Controlling for HL: β,0.21 (SE, 0.07) ( P < 0.05) HL mediates the association between race (black vs. white) and receipt of infl uenza vaccine (adjusted) 125

148 Table 31. Summary of studies of the relationship between health literacy and disparities (KQ 1d) (continued) Outcome Measure Authors, Year, Outcomes By Population and Study Design, Differences in Results Between Variables used in Setting, Health Health Literacy Analysis Sample Multivariate Analysis Level Literacy Level Health Literacy Levels Size, Quality Odds associated with being black Bennett et al., 85 2009 Not controlling for HL: β, -0.24 (SE, (companion: White 0.10) (P < 0.05) 86 ) et al. 2008 Controlling for HL: β, -0.18 (SE, (continued) 0.04) (P < 0.05) Odds associated with being Hispanic - Not controlling for HL: β, 0.04 (SE, 0.16) (P = NS) Controlling for HL: β, 0.08 (SE, 0.07) (P = NS) HL not found to mediate relationship between race/ethnicity and receipt of mammogram (adjusted, comparison is white) Odds associated with being black Not controlling for HL: β, 0.23 (SE, 0.15) (P =NS) Controlling for HL: β, 0.28 (SE, 0.06) (P < 0.05) Odds associated with being Hispanic Not controlling for HL: β, 0.57 (SE, 0.19) (P < 0.05) Controlling for HL: β, 0.70 (SE, 0.07) (P < 0.05) HL not found to mediate the relationship between race/ethnicity and dental checkup (adjusted, comparison is white) Odds associated with being black Not controlling for HL: β, - 0.13 (SE, 0.11) (P =NS) Controlling for HL: β, -0.04 (SE, 0.04) (P = NS) Odds associated with being Hispanic Not controlling for HL: β, 0.19 (SE, 0.14) (P = NS) Controlling for HL (β. 0.35 (SE , 0.05) (P < 0.05)) 126

149 Table 31. Summary of studies of the relationship between health literacy and disparities (KQ 1d) (continued) Authors, Year, Outcome Population by Measure Study Design, Variables used in Outcomes By Differences in Results Health Literacy Analysis Between Health Literacy Multivariate Health Literacy Level and Sample Size, Quality Levels Setting Analysis Level 171 Osborn, 2009 Adults with type I Age HL not found to be a mediator of Data NR or II diabetes Year of diagnosed relationship between African Cross -sectional diabetes American race and HbA1C through REALM Insulin use structural equation modeling N= 383 < 9th grade = 31% African American race ≥ 9th grade = 69% Good Sudore et al., 79 Seniors (70- Mortality rate NR Mortality within subgroups 167 year old) in 2006 Limited: 20% comparing limited group with (companion: Pittsburgh, PA, Adequate: 11% adequate: Interaction between and Memphis, Sudore et al., racial group and HL and sex and 95 ) TN 2006 HL (P > 0.10 for all comparisons implying no moderator effect) Pros pective REALM - White: HR 2.36; 95% CI, 1.63 cohort, Limited: 24% 3.42 retrospective Adequate: 76% Black: HR 1.66; 95% CI, 1.29- analysis 2.29 HR 1.77; 95% CI, 1.20- Male: N = 2,512 2.62 Female: HR 2.27; 95% CI, 1.67- 3.09 Good Race Nonadherence to Osborn et al., Patients at 2 HIV HL mediates association of black 69 2007 Gender white race on adherence vs. HIV medications clinics: 1 in (companions: (adjusted) Age in past 4 days Chicago, IL, and Odds associated with being Wolf et al., Income 1 in Shreveport, 70 Low: 52% black, not controlling for HL: OR, 2007; LA Number of Waite et al., 5.08 Marginal: 19% 2.4; 95% CI, 1.14- medications in HIV 71 ) REALM 2008 Adequate: 30% Odds associated with being regimen Low: 11% black, controlling for HL: OR, Non -HIV comorbid Cross -sectional Marginal: 20% 5.85 1.8; 95% CI, 0.51- conditions Adequate: 69% Mental illness N = 204 Fair 102 HL is a mediator between race Yin, 2009 ≥ 16 Age Parents At least 1 child Gender without health years old living in and health insurance coverage -sectional Cross Number of children a US household insurance (adjusted) Below basic: (nationally living in the home 24% Race/ethnicity not controlling for N = 6,100 Educational representative HL: = 0.03 P Basic: 10% sample) attainment Race/ethnicity controlling for HL: Fair Intermediate: 6% Race/ethnicity = 0.08 P NAAL Proficient: 3% Country of birth Below basic: English proficiency HL is not a mediator between 11% Self -reported Income race and self -report of difficul ty Basic: 18% difficulty Region understanding of medication Intermediate: understanding Metropolitan labels 56% OTC medication statistical area Race/ethnicity not controlling for Proficient: 15% labels HL: = 0.04 P Below basic: Race/ethnicity controlling for HL: 74% P = 0.05 Basic: 43% Intermediate/ proficient: 38% 127

150 Table 32. KQ 1d health literacy studies: strength of evidence grades by disparities across health outcomes Strength of Number of Outcome for Health Evidence Literacy Studies Studies Grade Results 8 Health literacy mediates disparities in specific health Disparities across Black vs. white: outcomes between black and white race in selected Low health outcomes outcomes. Hispanic: Health literacy not found to mediate the relationship Insufficient between Hispanic and white race but little data available. Sex: Ins ufficient Health literacy found to mediate the relationship between males and females in one, study, no other data available. 128

151 Table 33. Overview of numeracy studies Source Also Variables Used in examined Population Numeracy Design Population Multivariate Analysis Levels literacy Quality Score Outcomes Knowledge 74% inadequate 264 patients at Age No Aggarwal et al., 178 4 ambulatory numeracy on 5-item Health care 2007 Race services care clinics Cross numeracy test adapted -sectional Education affiliated with an Fair from Black and Toteson Primary care provider urban academic FH disease medical center in the US None Cavanaugh et al., 398 patients - Knowledge 69% < 9th grade WRAT Yes 174 -efficacy Self 2008 from 2 primary 3, numeracy -sectional Cross care clinics and Behavior Fair 2 endocrinology Disease Diabetes Numeracy Test Quartile 1: 27% clinics at 3 prevalence/ Quartile 2: 25% hospitals in the severity Quartile 3: 26% US Quartile 4 : 23% Age Davids et al., No Accuracy of risk 254 patients in % correct on numeracy 175 Race 2004 perception 2 academic test adapted from -sectional Education Cross general Schwartz and Woloshin Fair Income medicine clinics FH breast cancer in the US 0: 15% Age at menses 1: 17% Age at first live birth 2: 27% Number of breast biopsies 3: 41% 6 items (including 3 Age Medication skill No Estrada et al., 143 patients in 126 anticoagulation 2004 adapted from Schwartz Prospective management and Woloshin) cohort clinics in 1 Fair 0 correct: 13.3% university and 1 1-2 correct: 35% VA-based 3-4 correct: 34.3% hospital in the - 6 correct: 17.5% US 5 Haggstrom and No Age Accuracy of risk NR % with all correct on 207 patients in Schapira, Schwartz and Woloshin a general perception Race 176 2006 numeracy test medicine clinic FH at an academic -sectional Cross Family income Fair Insurance medical center in the US Education Hibbard et 43% low numeracy (less - 303 community al., Skill None Yes 98 2007 dwelling adults than mean = 9 on 15- Use of health care in the US item scale adapted from RCT services Relevant data Lipkus) - analyzed cross sectionally Fair AIDS =acquired immune deficiency syndrome; FH =family history; HgbA1c =glycosylated hemoglobin; HIV =human immunodeficiency virus; HS =high school; NOS =not otherwise specified; NR =not reported; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; SES =socioeconomic status; TOFHLA =Test of Functional Health rd edition. -3 =Wide Range Achievement Test -3 =Veterans Administration; WRAT Literacy in Adults; VA 129

152 Table 33. Overview of numeracy studies (continued) Source Also Variables Used in meracy examined Population Nu Design Multivariate Analysis Levels literacy Outcomes Quality Score Population Age 169 patients in Yes Disease 66% < 9th grade WRAT - Huizinga et al., 10 Gender 2008 3, numeracy prevalence/ an academic Cross -sectional severity primary care Race clinic in the US Income Fair Education REALM th No Lokker et al. 182 caregivers Age - skill Medication < 6 grade on WRAT 179 math: 36% Gender 2009 of patients at Race general th th 6 - -8 grade on WRAT Educational attainment -sectional pediatric clinics Cross math: 47% at 3 academic medical centers Fair Disease Age Diabetes Numeracy Test 383 patients at Osborn et al., Yes 171 2 primary care prevalence and Year of diagnosed Quartile 1 = 27% 2009 and 2 diabetes Quartile 2 = 25% Diabetes severity Cross -sectional 3 = 26% Quartile specialty clinics Insulin use (Numeracy as a Quartile 4 = 22% located at 3 African American race Good mediator of medical centers relationship between race and HgbA1c) Yes None Skill 63% < HS on WRAT -3, 200 patients at Rothman et al., 9 Disease 2006 1 academic numeracy prevalence/ Cross -sectional primary care severity clinic in the US Fair Schwartz et al., No Age Accuracy of risk % correct on numeracy 287 patients at 24 test from Schwartz and perception a Veterans 1997 Income Education hospital in the RCT Woloshin US who Relevant data Frame of information 0: 30% analyzed cross - received a 1: 28% mailed s sectionally urvey 2: 26% Fair 3: 16% Sheridan and No None Accuracy of risk % correct on numeracy 62 medical 172 perception students in 1 Pignone, 2002 test from Schwartz and RCT Woloshin US medical Relevant data school - analyzed cross 0-1: 5% sectionally 2: 18% 3: 77% Fair 130

153 Table 33. Overview of numeracy studies (continued) Also Source Population Numeracy Variables Used in examined Design literacy Population Multivariate Analysis Levels Quality Score Outcomes None Accuracy of risk Sheridan et al., 357 patients in No % correct on numeracy 173 2003 an academic from Schwartz and test perception RCT Woloshin general Relevant data medicine clinic 0: 41% in the US - analyzed cross 1: 30% sectionally 2: 27% Fair 3: 2% 177 No Vavrus, 2006 Gender 277 students Knowledge 57% low numeracy -sectional Cross from 4 school Literacy Fair Household spending (Correctly completed 0-1 districts in the United Republic Parents’ education of 3 calculations on Television in home of Tanzania numeracy test NOS) Siblings Electricity Sewage Waldrop - Vaverde Yes Gender Medication skill 57% correct on applied 155 individuals 47 Time since HIV diagnosis et al., 2009 who are problems subtest of (Numeracy as a patients at HIV Woodcock -Johnson III Education -sectional Cross mediator of the Health literacy or clinics Men: 63% correct relationship participants in Fair Women: 50% correct between gender AIDS drug on and medicati assistance management program in Miami, Florida capacity) 125 No Caregiver education Knowledge, 292 caregivers TOFHLA, NR by Yin et al., 2007 Cross Country of origin -sectional Medication skill numeracy (split at of young children at the Fair median) Language pediatric SES Age of children emergency department in Regular health care provider an urban Experience in health care academic medical center setting in the US 131

154 Table 34. The relationship between numeracy level and use of health care services (KQ 1a) Author, Year, Study Design, Variables Used % Low Results by Numeracy in Multivariate Sample Size, Difference Analysis Quality Level Outcome Numeracy 74% inadequate -date % with up-to Age Up -to -date with -date OR for up-to Aggarwal et al., 178 numeracy on 5- breast cancer Race screening for breast breast cancer 2007 item numeracy screening Education cancer screening (inadequate test adapted Primary care Inadequate: 71% vs. adequate): -sectional Cross from Black and % with up-to -date provider Adequate: 77% OR, 1.43 (0.62-3.33)a survey Toteson colon c ancer Familial OR for up-to - date colon screening - hypercholes -date with colon -to Up N = 264 cancer screening terolemia disease cancer guidelines *Note: sample for (inadequate vs. Inadequate: 46% actual colon adequate): Adequate: 51% screening 152 OR, 0.91 (0.3-2.0)a (women < age 50 who would not be eligible for screening were excluded) Fair a Calculated by research team =randomized controlled trial; vs. OR =versus. =odds ratio; RCT Table 35. KQ 1 numeracy studies: strength of evidence grades by use of health care services and health outcomes Number Results Overall Grade Outcome of Studies Use of 1 Mixed results, no adjustment for confounding Insufficient Healthcare Services Accuracy of 5 Insufficient Perceived risk (n = 2): mixed results depending on length over which Risk risk estimated Perception Perceived treatment benefit (n = 4): mixed results depending on numeracy level categories, 3 of 4 studies suggested low numeracy reduced ac curacy of perceived benefit. Knowledge Mixed results, partially dependent on type of knowledge, sample Insufficient 4 size, and adjustment for confounding - Efficacy Self 1 Lower numeracy associated with lower self - efficacy in unadjusted Insufficient analysis Behavior Insufficient 1 care behavior in unadjusted Lower numeracy not related to self - analysis Skills Skill in taking Mixed results depending on type of skill 6 medication: Insufficient Skill in taking medication (n = 4): mixed results Skill in interpreting information (n = 2) lower numeracy related Skill in interpreting health health information: Low to lower comprehension Disease Insufficient (n = 3 BMI (n = 2), HbA1c (n = 1), illness requiring dietary restriction Prevalence 1): Mixed results and Severity Disparities Numeracy appears to partially mediate the relationship between Low 2 race and HgbA1c (n=1) and between gender and HIV medication management capacity (n=1) BMI= body mass index; HbA1c =glycosylated hemoglobin; HIV =human immunodeficiency virus 132

155 Table 36. The relationship between numeracy level and accuracy of risk perception (KQ 1b) Variables Author, Year, Study Design, % Low Used in Numeracy Difference Results by Sample Size, Multivariate Outcome Numeracy Level Analysis levels by Numeracy Level Quality Lifetime risk Lifetime risk estimation Davids et al., Age Estimation error for % of questions 175 error correct on Race (adjusted) 2004 breast cancer risk estimation error numeracy test Education -Sectional Cross Numeracy (Absolute difference -coefficient for Beta adapted from Income between perceived 0 correct: 40.1 every additional FH breast Schwartz and N = 254 1 correct: 28.3 and Gail model numeracy question cancer Woloshin Note: 18% of incorrect: 0.18; 95% CI, 2 correct: 30.1 calculated breast Age at menses a 0 correct: 15% those invited cancer risks over 0.05-0.30 3 correct: 25.8 Age at first live 1 correct: 17% lifetime and 5 years) birth 5-year risk estimation 2 correct: 27% Fair 5-year estimation Number of error (adjusted): NR 3 correct: 41% error breast biopsies Note: unadjusted Numeracy correlation NS 0 correct: 32.2 1 correct: 24.0 2 correct: 27.8 3 correct: 20.5 Haggstrom and NR % with < 3 Accurate perception Age, Accurate perception of NR Schapira, correct on of breast cancer Race, breast cancer survival 176 2006 Schwartz and survival (compared FH, over 5 years (0-2 Woloshin with 5 -year survival Family income, questions vs. 3 correct; -Sectional Cross numeracy test rates) Insurance, adjusted): OR, 1.19; a Education 95% CI, 0.54 –2.63 N = 207 Accurate perception Accurate perception of Note: 18% of of screening screening those invited mammography mammography benefit benefit (compared (0-2 correct vs . 3 Fair with meta -analysis correct; adjusted): OR, result s) 1.33; 95% CI, 0.50– a 3.57 Sheridan and Correctly stated Ability to correctly None Correctly stated which % of questions 172 which compare treatment treatment correct on Pignone, 2002 treatment provided more benefit provided more numeracy test benefit presented 0-1 vs. 3 correct from Schwartz RCT alternately as ARR, benefit a , 0-1 correct: 33% - 61% (unadjusted): Relevant data RRR, NNT, and Woloshin = 0.03 P 2 correct: 91% - combination analyzed cross 0-1 correct: 5% 3 correct: 94% sectionally Correctly calculated Ability to correctly 2 correct: 18% treatment benefit Correctly calculated calculate treatment 3 correct: 77% N = 62 medical (unadjusted) treatment benefit benefit presented students a 0-1 vs. 3 correct: -71% , 0-1 correct: 0% alternately as ARR, P < 0.01 2 correct: 36% RRR, NNT, Fair 3 correct: 71% combination aCalculated by research team =5-year survival rates; =confidence interval; FH 5-yr survival rate =number =family history; NNT =absolute risk reduction; CI ARR =not significant; OR =randomized controlled trial; RRR =relative risk ratio; =not reported; NS needed to treat; NR =odds ratio; RCT vs. =versus. 133

156 Table 36. The relationship between numeracy level and accuracy of risk perception (KQ 1b) (continued) Author, Year, Variables Used in % Low Study Design, Results by Difference Multivariate Sample Size, Numeracy Analysis levels Numeracy Level Outcome by Numeracy Level Quality Correctly stated which Correctly stated Sheridan et al., Ability to correctly None questions % of 173 which treatment correct on compare treatment 2003 treatment provided benefit presented provided more numeracy test more benefit 0-1 vs. 3 correct alternately as ARR, from Schwartz RCT benefit a 0-1 correct: 35% (unadjusted): - 53% ; and Woloshin Relevant data RRR, NNT, < 0.001 P 2 correct: 63% analyzed cross - combination 0 correct: 41% 3 correct: 88% sectionally Ability to correctly Correctly calculated 1 correct: 30% Correctly calculated treatment calculate treatment benefit 2 correct: 27% N = 357 treatment benefit (unadjusted) benefit presented 3 correct: 2% a 0-1 vs. 3 correct: -45% ; 0-1 correct: 5% alternately as ARR, Fair < 0.001 P 2 correct: 30% RRR, NNT, t: 50% combination 3 correc Ability to correctly Schwartz et al., % of questions Correctly perceived Age, Correctly perceived 24 correct on perceive treatment 1997 treatment benefit Income, treatment benefit 0 correct: 5.8% Education, numeracy test benefit presented RCT 1 correct: 8.9% 0 vs. 1 correct from Schwartz Frame of alternately as ARR Relevant data (adjusted) 2 correct: 23.7 % +/- baseline ris k or information and Woloshin cross analyzed - 3 correct: 40% absolute difference: as RRR +/ - baseline 0 correct: 30% sectionally -3.1%a; OR, 0.77; 95% risk 1 correct: 28% CI, 0.21 –3.33a 2 correct: 26% N = 287 3 correct: 16% 0 vs. 2 correct Fair (adjusted) absolute difference: -17.9% a; OR, 0.14; 95% CI, 0.04- 0.45a 0 vs. 3 correct (adjusted) absolute difference: +34.2%a; OR, 0.08; 95% CI, 0.02 - 0.28a 134

157 Table 37. Relationship between numeracy level and knowledge (KQ 1b) Author, Year, Variables Used Study Design, % Low Numeracy Results by in Multivariate Sample Size, levels Analysis Numeracy Level Difference Quality Outcome Knowledge of breast Aggarwal et al., 74% inadequate Knowledge of Age Knowledge of breast 178 cancer guidelines Race cancer guidelines breast cancer numeracy on 5-item 2007 Inadequate: 25% Education and colorectal (inadequate vs. numeracy test Adequate: 48% adapted from Black -sectional cancer Primary care adequate, adjusted): Cross and Toteson 0.71)a provider screening 0.37 (0.19- Knowledge of colon guidelines FH of disease N = 264 Knowledge of colon cancer guidelines *Note: sample for cancer guidelines Inadequate: 17% actual colon (inadequate vs. Adequate: 35% screening 152 adequate, adjusted): (women < age 50 1.25)a 0.63 (0.29- who would not be eligible for screening were excluded) Fair WRAT None Median Cavanaugh et al., Median Diabetes - 3, numeracy Median diabetes 174 knowledge < 9th grade: 69% 2008 knowledge diabetes 9th grade: 31% DNT Quartile 1 vs. 4 Quartile 1: 52 DNT > knowledge a Cross -sectional ; DNT Quartile 2: 65 (unadjusted): -34 (range 0-100) P P for trend: < 0.001 Diabetes Numeracy DNT Quartile 3: 79 N = 398 DNT Quartile 4: 86 Test (DNT: median % correct) Fair Overall: 65% Quartile 1: 27% Quartile 2: 25% Quartile 3: 26% Quartile 4: 23% 177 Vavrus, 2006 Gender % of 5 57% Low Numeracy NR OR for high general Literacy knowledge health knowledge -sectional Cross Household questions about (correctly completed (low vs. high spending general health 0-1 of 3 calculations numeracy, adjusted): N = 277 Parents’ correctly on numeracy test 0.66a; P > 0.05 answered education NOS) Fair Television in OR for high home % of 5 HIV/AIDS knowledge Siblings knowledge (low vs. high questions about Electricity numeracy, adjusted): Sewage HIV/AIDS 0.36a; P < 0.001 correctly answered a Calculated by research team CI= =Diabetes Numeracy Test; FH =family history; HIV/AIDS =acquired immunodeficiency confidence interval; DNT syndrome/human immunodeficiency virus; NOS =not otherwise specified; NR =not reported; OR =odds ratio; SES =socioeconomic rd edition. vs. =versus; WRAT -3 =Wide Range Achievement Test -3 Test of Functional Health Literacy in Adults; status; TOFHLA= 135

158 Table 37. Relationship between numeracy level and knowledge (KQ 1b) (continued) Author, Year, Variables Used Study Design, % Low Numeracy Results by in Multivariate Sample Size, Numeracy Level Quality ysis Outcome Difference levels Anal 125 Caregiver Odds of poor Yin et al., 2007 Poor knowledge of NR by TOFHLA, % of caregivers with poor knowledge of weight numeracy (split at education weight based dosing Cross Innumerate: 76% -sectional median) Country of origin based dosing knowledge of Numerate: 62% (innumerate vs. Language -based weight SES N = 292 dosing numerate, adjusted): Age of children caregivers of 1.1; 95% CI, 0.6 -2.2 Note: when Regular young children education, healthcare acculturation, and provider Fair SES are not included Experience in in model, result was healthcare setting significant (1.8; 95% CI, 1 - 3.1) -efficacy (KQ 1b) Table 38. Relationship between numeracy and self Variables Author, Year, Study Design, Used in Sample Size, Results by Multivariate Low Numeracy Outcome Numeracy Level Quality Analysis % Difference Cavanaugh et al., None Median self - efficacy - Median self Median Self - efficacy WRAT - 3, numeracy th 174 < 9 DNT Quartile 1 vs. 4: 2008 grade: 69% efficacy for a th -4 for trend: P , grade: 31% 9 DNT Quartile 1: 28 > diabetes self - P = 0.003) ( -sectional Cross artile 2: 28 management DNT Qu Diabetes Numeracy DNT Quartile 3: 31 Measured by N = 398 Test (DNT: median DNT Quartile 4: 32 Perceived correct) % - Fair Diabetes Self Overall: 65% Management Quartile 1: 27% Scale (range 8-40) Quartile 2: 25% Quartile 3: 26% Quartile 4: 23% a Calculated by research team rd edition. =versus; WRAT -3 =Wide Range Achievement Test -3 =Diabetes Numeracy Test; vs. DNT 136

159 Table 39. Relationship between numeracy level and behavior (KQ 1b) Author, Year, Variables Used Study Design, % Low Results by Numeracy Sample Size, in Multivariate Quality Analysis Numeracy Level Difference Outcome Cavanaugh et al., Absolute difference in -3, WRAT Median reported None Self -management 174 2008 numeracy general diet behaviors use of self - behaviors a (Quartile 1 vs. 4): 0 < 9th grade: ; management = 0.21 P Cross -sectional 69% behaviors using General diet 9th grade: > the Summary of Quartile 1: 5 31% Absolute difference in N = 398 Diabetes Self - Quartile 4: 5 specific diet behaviors Care Activities a ; Diabetes (Quartile 1 vs. 4): 0 Fair scale (range 0-7) Specific diet = 0.82 P Numeracy Test Quartile 1: 3.5 (DNT: median Includes the Quartile 4: 3.5 Absolute difference in % correct) following exercise behavior behaviors Exercise a ; Overall: 65% (Quartile 1 vs. 4): +0.75 General diet Quartile 1: 3.5 P = 0.25 Quartile 1: 27% Specific diet Quartile 4: 2.75 Quartile 2: 25% Exercise Absolute difference in Quartile 3: 26% Blood glucose Blood glucose level blood glucose level Quartile 4: 23% level testing testing testing (Quartile 1 vs. 4): Foot care Quartile 1: 7 a = 0.44 ; P 1.5 Quartile 4: 6.5 Absolu te difference in foot Foot care care behavior (Quartile 1 Quartile 1: 5.5 a ; P < 0.001 vs. 4): 2.25 Quartile 4: 3.25 a Calculated by research team rd DNT =Diabetes Numeracy Test; vs. =versus; WRAT -3 =Wide Range Achievement Test - 3 edition. 137

160 Table 40. Relationship between numeracy level and skills (KQ 1b) Author, Year, Variables Study Design, Used in % Low Results by Multivariate Sample Size, Difference Quality Numeracy Level Outcomes Numeracy Analysis Medication Taking Skills % INR tests Estrada et al., Age 6-items Absolute difference Correct medication 126 2004 within range (including 3 in % INR tests within dosing 0 correct: 56% adapted from range (adjusted): operationalized as: Prospect 5-6 correct: 66% Schwartz and NR; P = 0.35 cohort Woloshin) Absolute difference % INR tests within INR variability in INR variability the therapeutic range N = 143 using mean 0 correct: (adjusted): NR; ility (using INR variab sigma score 13.3% P = 0.03 sigma, a composite Note: 11 were 0 correct: 0.80 1-2 correct: capturing number of proxies for 5-6 correct: 0.45 35% measurements, time patients 3-4 correct: since previous 34.3% measure, and Fair 5-6 correct: therapeutic range; 17.5% higher values are worse) th NR Age Lokker et al., Adjusted odds ratios grade on < 6 Poor caregiver 179 for each decrease in understanding of -math: 2009 WRAT Gender numeracy grade OTC cold medicine Race 36% Cross -sectional level Educational labels (i.e. say th th -8 grade on 6 product suitable for attainment N = 182 For caregivers with -math: WRAT -month < 24 -old) th nd -8 grade Caregiver intent to 47% 2 numeracy score Fair use medication in 13- month-old Think suitable: 1.25 a (0.99-1.58) Would use: 1.19 (1.01-1.41)* Adjusted odds ratios for each in increase numeracy grade level For caregivers with th th grade -16 9 numeracy score Think suitable: 1.28 (0.79-2.06) Would use: 1.78 (1.07 - 2.96) a Calculated by research team confidence interval; HIV =human immunodeficiency virus; HS =high school; i.e., example; INR =international normalized CI= =number; NR ratio; NLS =Nutrition Label Survey; N =randomized =not reported; NS =not significant; OTC =over -the -counter; RCT controlled trial; SES =socioeconomic status; TOFHLA =Test of Functional Health Literacy in Adults; vs. =versus; WRAT -3 =Wide Range Achievement Test -3 rd edition. 138

161 Table 40. Relationship between numeracy level and skills (KQ 1b) (continued) Author, Year, Variables Study Design, Used in % Low Results by Sample Size, Multivariate Quality Numeracy Outcomes Numeracy Level Difference Analysis - - Waldrop Adjusted beta NR Gender % correct on 57% correct on Valverde et al., Time since Medication applied coefficient for 47 HIV problems 2009 Management Test relationship (MMT: range 2-16) subtest of between numeracy diagnosis -sectional Cross Woodcock Education and MMT: 0.538; - P < 0.01 Johnson III Health N = 155 literacy Men: 63% correct Fair Women: 50% correct Odds of use of Yin et NR by % of caregivers with Caregiver Use of 125 nonstandardized al.,2007 TOFHLA, poor knowledge of education nonstandardized dosing instrument numeracy (split correct medication Country of dos ing instrument Cross -sectional (innumerate vs. at median) dosing instrument origin Innumerate: 34% numerate, fully (operationalized as Language numerate: 19% N = 292 adjusted): 1.4; 95% reported use of SES caregivers of -2.7 CI, 0.8 nonstandardized Age of young children instrument) children Note: when Regular Fair education, healthcare acculturation, and provider SES are not Experience in included in model, healthcare result was setting significant: 1.9; 95% CI, 1.1 3.4 - Skills in Interpreting Health Information Absolute difference Nutrition label Age Rothman et al., % questions correct 63% < HS on 9 in NLS score WRAT -3, comprehension Gender on 24- item Nutrition 2006 < high school: Label Survey after Race numeracy (adjusted): NR; 61% P < 0.001 Cross Insurance - being given a > high school: Sectional nutrition label to read Income 84% Education N = 200 Clinical disease Specific diet Fair Label reading frequency Hibbard et al., Absolute difference 43% low % questions correct Health Plan None 98 2007 in comprehension numeracy (less on 13- item health Comprehension (low vs. high, than mean = 9 plan knowledge Low numeracy: RCT unadjusted): item on 15- questionnaire after 72%a However, -18.5%a; P < 0.05 scale adapted being given health High numeracy: results of from Lipkus) plan information to 90.5%a interest in this Absolute difference review paper are in choice of higher % Choosing higher Note: interaction cross -sectional quality hospital (low quality hospital by patient vs. high, activation (i.e., N = 303 unadjusted): motivation to -11.8%a; P < 0.01 engage with Fair material) 139

162 Table 40. Relationship between numeracy level and skills (KQ 1b) (continued) Author, Year, Variables Study Design, Used in % Low Results by Sample Size, Multivariate Quality Numeracy Outcomes Numeracy Level Difference Analysis Low numeracy Hibbard et al., 98 2007 Low activation: (continued) 67.7% High activation: 76.3% P for interaction: P < 0.05 High numeracy Low activation: 90.2% High activation: 90.7% P for interaction: NS Choice of higher quality hospital Low numeracy: 59.9% High numeracy: 71.7% Note: interaction by patient activation (i.e., vation to moti engage with material) Low numeracy Low activation: 53% High activation: 66.8% P for interaction: P < 0.05 High numeracy Low activation: 66.3% High activation: 77% P for interaction: P < 0.001 140

163 Table 41. Relationship between numeracy level and disease prevalence and severity (KQ 1b) Author, Year, Variables Used in Study Design, Results by % Low Multivariate Sample Size Numeracy Level Analysis Outcomes Difference Quality Numeracy Absolute Median HbA1c Cavanaugh et al., Median HbA1c Age 3, - WRAT 174 numeracy 2008 Gender difference in < 9th grade: Quartile 1: 7.6% Median HbA1c Race -sectional Cross Income (quartile 1 vs. 4: Quartile 2: 7.1% 69% +0.5%; P = 0.119) 9th grade: > Quartile 3: 7.1% Type of diabetes N = 398 31% Years since In adjusted Quartile 4: 7.1% diagnosis of analysis, every Diabetes diabetes 10% decrease in Fair Numeracy Test % correct DNT Clinic site (DNT: median % questions resulted correct) in an increase in HbA1c of 0.09%; Overall: 65% 95% CI, 0.01%- Quartile 1: 27% 0.16% Quartile 2: 25% Quartile 3: 26% Quartile 4: 23% Age Mean BMI Huizinga et al., BMI (< 9th grade Mean BMI WRAT -3, 10 9th grade, vs. 2008 > Gender < 9th grade: 31.8 numeracy a ; > 9th grade: 27.9 unadjusted): +3.9 Race < 9th grade: = 0.008 P Cross -sectional Income 66% Effect of numeracy > 9th grade: Education 34% on BMI: (adjusted): N = 169 REALM P = 0.01 β = -0.14; Fair Rothman et al., Absolute Illness requiring None - % with self 63% < HS on 9 difference in WRAT -3, dietary restriction reported 2006 percent with illness illness numeracy < HS: 44% requiring diet -sectional Cross HS: 35% > requiring restriction dietary % BMI > 30 HS, (< HS vs. > N = 200 restriction < HS: 48% unadjusted): +9%; P = 0.20 Fair % BMI > 30 HS: 40% > Absolute n % difference i with BMI > 30 (< HS vs. > HS, unadjusted): +8%; = 0.30 P a Calculated by research team BMI= body mass index; CI =confidence interval; DNT =Diabetes Numeracy Test; HbA1c= glycosylated hemoglobin; HS =high -3 =Wide Range Achievement Test school; REALM =Rapid Estimate of Adult Literacy in Medicine; vs. =versus;WRAT -3 rd edition. 141

164 Table 42. Relationship between numeracy level and disparities (KQ 1d) Author, Year, Exposure, Study Design, % Population with Outcome, Sample Size, Limited Literacy Mediator Results of Mediational Analysis Quality Osborn et al., Diabetes Numeracy Exposure: race del results Structural equation mo 171 2009 Test Quartile 1 = 27% Outcome: HgbA1c Correlation between African-American race - Cross Quartile 2 = 25% and numeracy: -0.46 (P < 0.001) sectional Quartile 3 = 26% Mediator: Quartile 4 = 22% numeracy Correlation between numeracy and HgbA1c: N = 383 -0.15 (P < 0.01) Good Correlation between African-American race and HgbA1c Without mediator: 0.12 (P < 0.01) With mediator: 0.10, NS - 57% correct on Path Waldrop Exposure: analysis results gender Valverde et al, Correlation between female gender and applied problems 47 numeracy: subtest of -0.428 (P < 0.01) 2009 -Johnson Woodcock Outcome: - Cross Correlation between numeracy and medication medication III sectional management capacity: 0.644 (P < 0.01) management Men: 63% correct capacity Women: 50% N = 155 Correlation between female gender and correct medication management capacity Mediator: Fair numeracy Without mediator: NR , significant With mediator: 0.073, NS HgbA1c =glycosylated hemoglobin; NR =not reported; NS =not significant. 142

165 o Mitigate the Effects of The Effect of Interventions T Low Health Literacy Introduction This chapter presents the results of our literature search for key question (KQ) 2. The analytic framework for this question is presented in Chapter 2. In brief, KQ 2 asked about effective interventions to mitigate the effects of low health literacy on (a) use of health care services, (b) health outcomes, (c) costs of health care, and (d) health disparities. As we noted in our methods, the best studies to answer this question would have included analyses specific to ever, much of the research about interventions designed individuals with low health literacy. How to mitigate the effects of low health literacy has been done in populations that include a -specific combination of low and high health literacy individuals and failed to perform literacy subgroup anal yses. Instead of excluding a large portion of the intervention literature, we decided to permit inclusion of studies with a combination of low and high literacy individuals and no subgroup analysis, knowing that they may provide only indirect information a bout the effect of interventions on an exclusively low literacy population. For KQ 2, we present our results in two ways. First, where interventions use single strategies to mitigate the effects of low health literacy, we present results by intervention strategy (e.g., alternative document design, alternative numerical presentation, additive or alternative pictorial representation, alternative media, alternative readability, and document design) in an effort to aid intervention developers. The majority of r esults in this section focus on comprehension 180,181 also focus on the use of health care services. following the intervention, although a few Second, where interventions use multiple strategies (preventing conclusions about the active nts), we organize results in accordance with outcomes in our analytic intervention compone framework. Tables presenting selected information about KQ 2 studies are presented at the end of the chapter. These tables provide (1) an overview of included intervention studies (Table 43), (2) detail about the interventions tested in included studies (Table 44), (3) the aggregate strength of evidence of included studies (Tables 46 and 53), (4) results of studies using single strategies to 51), (5) results of anized by strategy (Tables 44, 47- mitigate the effects of low health literacy org studies using multiple strategies to mitigate the effects of low health literacy organized by outcome (Tables 52, 54 -61). Detailed evidence tables appear in Appendix D. Because this report is an update , we needed to integrate findings from our first review in 2004 with those of our current review. To do this, we reorganized findings from the first review using the organizational structure described above and note in each section how results from the first review are similar to or different from current findings and whether they modify our current conclusions. To facilitate conclusions, we provide insights based on observations about the common features of effective interventions. These “cross -cutting” observations are presented at the end of the chapter. Search Results We identified 56 articles reporting on 53 unique studies to include in our updated review. 143

166 Study Quality 182 -184 79,133,181,185 -219 and 38 studies as fair quality. Of all 53 studies, we rated 3 as good quality One additional study was rated fair for intermediate outcomes and poor for followup 220 outcomes. Finally, we rated 11 studies as poor quality and excluded them from further 221 -231 review. Characteristics of Included Studies ort on the 42 good- or fair Below we rep -quality studies identified in our updated review. Included studies had a wide variety of designs (Table 43). Across all 42 studies, 27 were si- randomized controlled trials (RCTs), two were cluster randomized trials, and 13 were qua experimental studies. With respect to interventions, 21 used one specific strategy to mitigate the effects of low health literacy and 21 used a mixture of strategies combined into one intervention (Table 44). Of ic low -literacy strategy to enhance patient intervention studies that used one specif comprehension, two focused on alternative document design, three on alternative numerical presentation, eight on additive or alternative pictorial representations, four on alternative media, and seven on a combination of alternative readability and document design. Additionally, one intervention focused on the effects of physician notification about patients’ literacy status on health outcomes. A total of 21 studies involved mixed interventions; these included a combination of the strategies noted above and other strategies to promote improvements in patient knowledge, self -efficacy, behavior, adherence, disease, quality of life, and health care services use. Interventions were tested in study populations with diff erent proportions of individuals with -one studies examined the effect of interventions low health literacy or low numeracy. Twenty -health -literacy subgroups, although many were underpowered for these specifically in low analyses and/or failed to adequately control for confounding. Other studies examined - and high intervention effects in populations that included both low -literacy or - numeracy -health individuals; these studies provide only supportive evidence about the effect of interventions to mitigate the effects of low literacy. Effects of Health Literacy Interventions Using Single Strategies, by Intervention Type Intervention: Alternative Document Design -quality randomized trials addressed the effects of alternative document design on Two fair 185,188 outcomes, including comprehension and choice of higher quality options (Table 45). Both stratified analysis by health literacy subgroups. These studies examined the effects of specific design features including highlighting the common features of comparative information, presenting only essential information, and putting key information first. One study tested simplifying design features in a convenience sample of 303 adults who were 185 This study r andomized asked to examine comparative information about health plans. individuals to six groups, which allowed two major comparisons: (1) the effects of presenting information on 13 features of health plans side by side in random order vs. with common features first, and (2) the effects of presenting a list of info rmation about the plan (no framework) vs. presenting information about four advantages and four disadvantages of the plan (long 144

167 framework) vs. presenting information about two advantages and two disadvantages of the plan (short framework). The investigator s found that presenting common features first provided no - or high- improvements over the side -by-side presentation of information in either low numeracy participants. However, the short framework and the long framework (for high- numeracy participants only) provided small improvement in comprehension (ranging from 0.3- 0.7 points on a comprehension scale with scores ranging from 0 -6). The long framework provided significantly worse comprehension than no framework for those with low numeracy ( -0.5 points on a comprehension scale with scores ranging from 0 -6, P < 0.05). 188 In the other study in this category, which was done by the same group of investigators and appears to have used the same participants, the researchers investigated the effects of limiting and focusing information. In this study, participants received varying amounts of health plan information. Some participants received only the information investigators deemed essential to . Others, however, received decisions about health plan use (i.e., information on cost and quality) both this essential information as well as other nonessential information (i.e., information on quality of hospital food and number of visiting hours per day). Both high- and low -numeracy participants who received only essential information had better comprehension (high numeracy < 0.01) and chose higher quality options P 0.3 on a scale of 0- 3, P < 0.01; low numeracy 0.7, P (high numeracy +19 percentage points, < 0.01) P < 0.01; low numeracy +23 percentage points, than individual s who received both essential and nonessential information. When all information - was presented, putting the essential information first further improved comprehension for low -3, numeracy < 0.01), but not for high- P numeracy individuals (+0.6 points on a scale of 0 individuals. Order had no effect on whether respondents chose higher quality options. Considering this evidence in aggregate, our research team judged the overall strength of evidence for studies examining alternative document design to be insuffi cient (Table 46 and Appendix F), indicating that future studies would have a high likelihood of changing estimates of effect. Studies from our previous review did not change overall conclusions. In our previous 232 on alternative document design. This RCT review, we identified only one study focusing compared illustrated narrative text to bulleted text on genital warts and cervical cancer screening and found no overall differences in comprehension among study arms receiving these presentations. Notably, howe ver, low -literacy participants comprehended illustrated materials better than bulleted information. Intervention: Alternative Numerical Presentation Three fair -quality randomized trials examined the effects of alternative numerical 188,217,219 Each examined a different strategy to improve numerical presentations (Table 47) . presentation. All stratified their analyses by participant numeracy level. 188 The first study was performed in the same population as the studies in the prior section. It examined the ef fects of presenting information on hospital quality so that the higher number (rather than the lower number) of any indicator indicated a better quality. In this study, listing information so that the higher number was better improved the mean number of co rrect responses to comprehension questions (+0.4 on a 0- P < 0.001) and the proportion of 4 scale, individuals choosing a higher quality option (+13 percentage points, P < 0.01). Results varied by numeracy level, however; participants in the low - but not the high -numeracy subgroup achieved benefit from this approach. This study also investigated whether adding symbols to indicate the concepts of “more” or “less” would aid comprehension. We present these results in the next ns. section about pictorial presentatio 145

168 219 The second study examined the effects of presenting information on the baseline risk of heart attack and treatment benefit for a hypothetical cholesterol drug using the same or different denominators. In this factorial randomized trial, a probabilis tic sample of 1,047 American and German adults were randomly assigned first to information about the baseline risk of disease and risk following treatment presented alternately with four different sets of denominators (800/800, 100/800, 800/100, and 100/100). They were then secondarily randomized to either receive icon arrays or not. Presenting the numerical information using the same vs. different denominators = 0.001), with a greater effect among resulted in appreciable improvements in understanding ( P those with low numeracy (+25 percentage points) vs. high numeracy (+16 percentage points, unadjusted for numeracy effect = 0.001). The effect of adding icon arrays is discussed below in P the section on additive pictorial representation. 217 The third study examined the effect of presenting information on the positive predictive value of genetic testing for diabetes and trisomy 21 (i.e., the likelihood of disease given a positive test for either of these diseases) in alternate numerical formats. In this study , a convenience sample of 162 adults was randomized to receive genetic testing information as either conditional probabilities or natural frequencies. In the conditional probabilities arm of the he sensitivity and false positive rates study, information on both the baseline rate of disease and t of the genetic test was presented in percentages. Participants were then asked to calculate the likelihood of diabetes if genetic testing was positive. In the natural frequency arm, on the other hand, information on the baseline rate of disease was presented as x/10,000 people and x, respectively; these presentations sensitivity and false positive rates as y/x and z/10,000- preserve the base rate of disease and reduce the computations individuals must perform to te the likelihood of disease if genetic testing is positive. As hypothesized by investigators, estima natural frequencies improved the accuracy of participants’ estimates of the positive predictive P value of genetic testing (effect size not reported, th similar effects for both high = 0.001) wi - (+24 percentage points) and low - (+27 percentage points) numeracy individuals. However, these results must be interpreted with caution due to the relatively small sample and lack of reporting ics. of baseline group characterist In considering this evidence, our research team felt that the overall strength of evidence was low (Table 46 and Appendix F), indicating that future research may change estimates of effect. refore, it did not modify Our prior review found no studies examining this outcome; the conclusions. Intervention: Additive and Alternative Pictorial Representation 133,186,188,189,195,216,219 -quality studies Eight fair (including two reported by Peters in the same article) investigated the effects of pictorial representation on outcomes, including comprehension, accurate perception of risk, and choice of higher quality options (Table 48). Six i-experimental studies. Six investigated the additive effects of were RCTs and two were quas pictorial information and two examined alternative pictorial representations. Five stratified their analysis by participant health literacy or numeracy level. effects of adding pictorial information, two studies (performed Of the six trials addressing the by the same group and reported in one article) focused on the effect of adding symbols to 188 Both stratified their analyses by numeracy level. One study considered numerical information. in t he preceding section examined the effect of adding symbols to hospital quality information. Numerical information was presented alternately in two formats such that either the higher r indicated better number indicated better quality (higher -number -better) or the lower numbe 146

169 188 quality (lower Symbols were then added to determine their effect on -better). -number comprehension of hospital quality information and choice of higher quality hospitals. The symbols included a plus sign to indicate more patients per nurse, a minus sign to indicate fewer patients per nurse, and no symbol to indicate an average number of patients per nurse. These symbols had no effect on comprehension or hospital choice in the overall sample. However, adding symbols to the lower -number -better condition led to poorer choices (although not poorer 19 comprehension) in high- numeracy participants (percentage choosing higher quality hospital - value not reported) and slightly better choices in the lower -numeracy percentage points, P participants (percentage choosing higher quality hospital +12 percentage points, P value not 188 reported). In a similar study from this same group reported in the same article, participants (1) the effect were randomly assigned to one of five conditions to examine two main outcomes: of adding symbols to essential (with or without nonessential) hospital quality information, and (2) the effect of using black and white circles (i.e., all black, half -black half -white, all white) vs. colored traffic light symbols (i.e., gre en, yellow, red circles) to indicate relative quality. Symbols had no overall effect on comprehension but did increase the number of participants choosing high -quality options (+14 percentage points, P < 0.05). Effects varied by whether symbols accompanied only information essential to quality (i.e., death rates) or both essential and nonessential information (i.e., death rates and satisfaction). Adding symbols to both essential and nonessential information reduced the percentage of low -numeracy participant s choosing high- numeracy participants. The effect of using quality hospitals, but it made no difference for high- black and white circles vs. colored traffic light symbols also differed by numeracy level. A numeracy participants chose high -quality hospitals with colored symbols higher number of high- quality (+16 percentage points, P < 0.05), while fewer low -numeracy participants chose high- hospitals, although the trend was not statistically significant ( -11 percentage points, P not significant). Two studies, including one already mentioned above, addressed the effects of adding icon 216,219 Icon arrays (also known as arrays to numerical information about treatment benefit. pictographs) represent the benefits and/or harms of treatment using a series of dots, human figures, or faces that are shaded to represent the proportion of individuals affected by disease. Both studies stratified analyses by participant numeracy level. The first study examined the effects of adding icon arrays to numerical information in thr ee hypothetical treatment scenarios (aspirin for cardiovascular disease, cholesterol drug for cardiovascular disease, and appendicitis 216 This factorial trial randomized a convenience sample of 171 students and older screening). adults first to alternate n umerical information (absolute risk reduction vs. relative risk reduction) and then to icon arrays or not. The study confirmed its a priori assumption that presenting treatment benefit information as absolute (rather than relative) risk reduction improved understanding for everyone (unadjusted difference +49 percentage points, adjusted P = 0.001). It then showed that adding icon arrays further aided understanding (unadjusted difference +23 percentage points, adjusted P = 0.002). However, improvements with i con arrays differed according to numeracy level, with greater improvements among those with low numeracy in unadjusted analyses. The second study, which was mentioned above in the “Alternative Numerical Presentation” section, examined the effects of adding icon arrays to numerical 219 In information in a single hypothetical treatment scenario (cholesterol drug for heart attack). this factorial randomized trial, a probabilistic sample of 1,047 American and German adults were randomly assigned first to informa tion about the baseline risk of disease and risk following treatment presented alternately with four different sets of denominators. They were then 147

170 secondarily randomized to either receive icon arrays or not. The effects of icon arrays on accuracy of risk perception varied both by the denominators indicating treatment benefit and by participant numeracy. When denominators for the baseline risk and risk following treatment were different, icon arrays improved understanding for both low - (unadjusted differenc e +32 (unadjusted difference +11 percentage points) numeracy percentage points) and high- participants. However, when denominators for baseline risk and risk following treatment were the same, icon arrays provided a more modest benefit in the accuracy of r - isk perception for low literacy participants (unadjusted difference +11 percentage points) and worsened risk perception P values for these in high- literacy participants (unadjusted difference - 16 percentage points). differences were not reported. 133,195 studies examined the effect of adding illustrations to prose. Two other Neither of these studies stratified analysis by literacy level, although one reported that literacy predicted 133 outcomes. This study, a randomized trial of 363 participants (only 4 percent of whom had Rapid Estimate of Adult Literacy in Medicine [REALM] scores below 45), found no overall effect of adding a mind map (a pictorial representation linking key concepts and ideas) to 133 standard arthritis education materials. The other study, a quasi -experimental study enrolling a convenience sample of 130 adults from academic family medicine clinics, showed no effect of adding illustrations to the auxiliary prescription labels indicating “take with water,” “may cause 195 drowsiness,” “take with food,” “no alcohol,” or “take on empty stomach.” The remaining studies examined alternative pictorial representations. Only one stratified ing 140 adults (41 percent of whom were analysis by numeracy. In this Internet study randomiz deemed to have low numeracy because they incorrectly answered the first numeracy question on the Lipkus numeracy scale) to six different conditions, the researchers could determine the effect dot icon arrays for three risk magnitudes (3 percent, 6 percent, 50 of grouped vs. dispersed 186 They determined that there was no overall effect on comprehension among those percent). who received the grouped dot (rather than dispersed dot) icon arrays; however, those with higher numeracy had significantly greater improvements than those with lower numeracy. A different quasi -experimental study examined seven teratogen warning symbols in comparison with a 189 standard symbol. hat the medication The researchers found that participants’ understanding t should not be taken if pregnant and that the medication causes birth defects improved if these P concepts were represented in separate complementary diagrams rather than single diagrams ( value not reported). They also found that adding t ext stating “causes birth defects” increased understanding of all tested symbols. In aggregate, our research team considered the overall strength of evidence for alternative de disparate pictorial representations to be insufficient (Table 46 and Appendix F). Studies ma comparisons and found mixed results, precluding clear conclusions. Our prior review did not modify conclusions; although our prior review found one study of alternative pictorial representations, it was graded as poor quality. Intervention: Al ternative Media Four randomized trials assessed the effects of various types of media on comprehension 184,200,212,213 Three focused on the effects of adding or and/or intent to seek health care (Table 49). substituting various media (e.g., video, computer, or slide show presentations) for printed 200,212,213 184 A fourth examined the effects of adding video to verbal narratives. materials. Three of 184,200,213 four studies stratified results by health literacy status. 148

171 The first study examining the effects of v arious media compared to print materials randomized 233 parents or caretakers of children enrolled in Head Start Programs to one of four presentations of informed consent standard, simplified print, video, computerized―for — 200 -risk studies. -risk and low hypothetical high Compared with standard informed consent, the video and computerized versions had little effect on freely remembered recall of information. However, the computerized version showed a trend toward improving prompted recall P = 0.08) with no difference (percentage of total information remembered +4 percentage points, by health literacy group. Whether such improvements are clinically meaningful is not clear. The comparison of the standard consent and simplified print version is presented below in the section “Alternative Design and Readability Document.” The second study randomized a convenience sample of 232 men at two university hospitals to two different media for delivery of a symptom score assessment for benign prostatic 213 hypertrophy: print or print plus video (which the authors called “multimedia”). The multimedia delivery included a computerized video with reading of the symptom score -coded to questions. Questions were shown on the computer screen during reading and color tten symptom score sheets to be completed by participants. The efficacy of the correspond to wri multimedia version was assessed by two different measures of comprehension: the mean number of errors participants made and the proportion of participants understanding questions (compared to professionally completed scores). Overall, the multimedia version increased comprehension (mean difference in errors - P 1.51, < 0.001; mean difference in percentage understanding +19 not reported), with larger effects am ong participants with low health literacy P percentage points, (defined as less than high school reading skills by the REALM; significance of interaction by health literacy status not reported). It also increased the accuracy of categorical classification of = 0.04). P symptoms in the overall sample (+13 percentage points, The third study examining the effects of various media compared to print materials randomized 90 teenage patients and their parents (all of whom had median REALM and Wide suggesting reading skill at the high school level) to Range Achievement Test [WRAT] scores, standard, simplified — one of three presentations of informed consent for orthodontic treatment print, or simplified print plus a slide show that included images and audiovisual cues 212 As discussed under the section “Alternative representing the elements of informed consent. Readability and Document Design” below, compared with standard informed consent - (readability not reported), the simplified informed consent (which was written at the seventh grade level and included large font, white space, active voice, and cues to action) did not improve recall or comprehension for patients or parents. The addition of a slide show, however, improved the proportion of information adequately recalled by patients (unadjusted absolute difference +11 percentage points, P < 0.05) and the proportion of information adequately recalled and comprehended by parents (unadjusted absolute differences for recall +9 percentage P points, < 0.001). Results should be < 0.05; for comprehension +12 percentage point s, P interpreted with caution, however, because they did not adjust for potentially meaningful baseline differences between study arms. Furthermore, they were not stratified by literacy level. 184 s of adding video to verbal narratives. A single study examined the effect This study randomized a convenience sample of 200 adults from four primary care practices in the United States to a verbal narrative about advanced dementia or a verbal narrative in combination with a 184 Participants who received the verbal narrative plus video had improved 2- minute vid eo. knowledge compared to the verbal narrative alone (unadjusted mean difference +0.9 on a scale us video ranging from 0 -5, P < 0.001) Additionally, those who received the verbal narrative pl 149

172 had a greater preference (which we considered a proxy for intent) for comfort care as an end -of- 8.6). Preference for life strategy (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI], 1.8- comfort care varied by health literacy level, with those who had higher health literacy having higher preference for comfort care. Based on findings from the studies above and their mixed results, our research team judged the strength of evidence to be insufficient (Table 46 and Appendix F). Three studies from our 233 -235 prior review contributed additional information, but didn’t change overall conclusions. In th 233 6 grade level our prior review, one RCT found that both a simple brochure written at the 5- and a video written at a similar level improved compr ehension of colon cancer screening information more than usual care, although neither was superior to the other overall or in 234,235 stratified analyses. Two additional nonrandomized trials found mixed results. One showed that a brochure plus video plus verbal recommendation about mammography improved mammography rates over either a verbal recommendation alone or a brochure plus verbal 234 recommendation. The other confirmed no differences overall or in literacy subgroups in comprehension of information on sleep disorders with a 12- grade brochure vs. a video based on a 235 script written at the 12 th grade level. Intervention: Alternative Readability and Document Design We found seven studies examining the effects of interventions that combined simplification -quality randomized trials (seven of readability with document redesign (Table 50). Six were fair 191,199,200,204,208,212,214 -quality quasi -experimental and one was a fair articles based on six studies) 204 204,208 One focused on an advanced directive, study. one on simplified advice about head 191 214 trauma, and four on simplified one on a simplified Medicaid health plan comparison chart, 199,200,204,212 informed consent (although one of the latter provided only postintervention data, 204 ). Only three of the six with interpretable data stratified results by which limited conclusions 191,200,214 health literacy level. The first study stratifying results by health literacy level examined the effects of a simplified 214 The char t had four key improvements: it listed only Medicaid health plan comparison chart. the differences between health plans, ordered plans from the most to the least generous, grouped or “chunked” cost -sharing and benefit information in rows to allow comparison across plans, and increased font size. Compared to a standard chart, the modified health plan comparison chart provided no significant improvements in comprehension overall or by health literacy group in a convenience sample of 122 Medicaid recipients in Florida. This might be attributable to the high residual document complexity, which was noted to be at a high school level for the simplified chart. The second study stratifying results by health literacy level examined the effects of a 191 This simplified sheet included simplified language, a simplified head trauma advice sheet. reduced number of words, grouping or chunking ideas, and the use of large font sizes and plenty point of white space. Compared with a standard advice sheet, this simplified sheet resulted in a 1- improvement on a compre hension scale with possible scores ranging from 0 -10. There was no interaction by literacy level. The third study stratifying results by health literacy level was mentioned above in the section “Alternative Media.” This RCT randomized 233 parents or careta kers of children enrolled in Head Start Programs to one of four presentations of informed consent —standard, simplified 200 risk and low -risk studies. print, video, computerized―for hypothetical high The simplified - print version of informed consent included in this study employed simple language, chunking of 150

173 ideas, and white space to improve participant understanding. Compared with standard informed consent, the simplified print version had little effect on freely remembered recall of information. -literacy (less than an However, it showed trends toward improving prompted recall in the low -grade reading level on the WRAT) subgroup. Whether such improvements are meaningful eighth is not clear. Results from other studies, which did not stratify data by literacy level, were mixed. Three 199,204,208,212 studies showed no effect on comprehension by three different combinations of reading and document simplification (see Table 44 and Table 50), although one of these showed pleting advanced directives. Both studies had changes in the proportion of participants com 199,204,208 199 features limiting interpretation of findings. For instance, in one study, participants had a mean REALM score of 65 out of 66; this raises the possibility that the same intervention tested -literacy individuals might have appreciably different results. in a population with more low 204,208 Additionally, in the other study, results about completion of advanced directives were -over between study arms with lack of adjustment for relevant confounded because of cross confounders. Based on these findings, our research team judged the overall strength of evidence about alternative readability and document design to be insufficient (Table 46 and Appendix F). Studies found mixed results, which are likely attr ibutable, at least in part, to the components of document redesign and methodological bias. Several studies from our prior review and prior sections of the current review similarly reported mixed results. In our prior review, one study 236 and showed an association between low readability ve readability alone focused on alternati and improved comprehension. Three other studies focused on a combination of alternative 237 -239 In prior sections of this r eview readability and document design and reported mixed results. (see “Alternative Document Design” above), the benefits of document design varied by the components of redesign. Intervention: Physician Notification of Patient Literacy Status -quality cluster randomized trial examined the effects of physici an notification of One fair -efficacy and hemoglobin A1c (HgbA1c), patient literacy status on health outcomes including self 181 (Table 51). -literacy individuals Despite enrolling a population with a high proportion of low Literacy in Adults [TOFHLA] score below 16) and (74 percent had a Test of Functional Health increasing physicians’ use of more than three communication -enhancing strategies (adjusted OR 4.7, 95% CI, 1.4 -16), neither patients’ self -efficacy nor HgbA1c changed in any material way with physician notification. Based on this single study, our research team graded the overall strength of evidence as low (Table 46 and Appendix F). There were no studies from our prior review to modify this assessment. Summary of Interventions Using Single Intervention Design Strategies In summary, the strength of evidence regarding the effect of specific intervention design -health -literacy populations is low (Table 46 and Appendix F). This is features for low attributable, in large part, to differences in the interventions (a nd subsequent results) for studies broadly grouped as follows: alternative document design, alternative numerical presentation, alternative pictorial representation, alternative media, alternative readability and document design, and physician notification of literacy status. Looking closely within intervention categories, we noted that several specific design features -literacy populations in one or a few resulted in improvements in comprehension for low -health 151

174 studies. These features, which bear further st udy in broader populations, include presenting essential information by itself (i.e., information on hospital death rates without other distracting information, such as information on consumer satisfaction); presenting essential information first (i.e., information on hospital death rates before information about consumer satisfaction); presenting information so that the higher number (rather than the lower number) indicates better quality; using the same denominators to present baseline risk and treatment benefit information; adding icon arrays to numerical presentations of treatment benefit; and adding video to verbal narratives. Additionally, in reexamining data from our 2004 review, we noted potential benefit from other design features tested individuall y in one or a few studies; these include using reduced reading level and illustrated narratives. In contrast to the above design features, we noted that a few specific design features resulted in worse comprehension in one or a few studies; these design f eatures also bear further study in broader populations. For instance, one study raised questions about whether colored traffic symbols to denote hospital quality may actually worsen health choices among those with low literacy. Similarly, one study raised questions about whether adding symbols to nonessential quality information (i.e., satisfaction information), may actually draw attention away from the essential information and worsen health choices among those with low health literacy. Effects of Mixed St rategy Interventions, by Analytic Framework KQ 2a. Effect of Mixed Interventions on Use of Health Care Services 194,196,202,203,207 182 quality study and five fair -quality studies addressing the We found one good- effects of mixed strategy interventions on use of health care services (Table 52). Four were 182,194,202,203 196 RCTs, and one used a quasi -experimental one was a cluster randomized trial, 207 design. Two studies provided preventive service education and examined rates of preventive 196,203 182 Three others, one promoting adherence - and two facilitating self services utilization. 202,207 182,207 and examined rates of visits to emergency rooms management, 194 182,202,207 hospitalizations. One additional s tudy examined use of recommended services, but the authors did not describe this outcome in sufficient detail to allow interpretation; thus results are not presented here. Four of the six studies stratified analyses by literacy level. oviding preventive service education, only one stratified analysis by health Of two studies pr literacy level. This cluster randomized trial delivered interventions to both providers and patients. It provided providers with education on literacy and communication strategies and patients with education on colorectal cancer screening. With these interventions, this study showed increases in any colorectal cancer test completion over 18 months (absolute difference 8.9 percentage points, = 0.003). The impact differed by health literacy level, with an absolute P P = 0.002) and 3 difference of 26 percentage points in the low -health -literacy subgroup ( percentage points in the high- P = 0.65) when adjusting only for the -literacy subgroup ( health 196 A second trial providing patients with education on clustering of patients within providers . 203 with significant increases in prostate cancer screening also increased preventive service use, the number of prostate -specific antigen tests ordered after both low -readability patient education (adjusted OR, 7.62, 95% CI, 1.62- 35.83) and cues encouraging patients to talk with their physician (adjusted OR, 5.86, 95% CI, 1.24 -27.81). However, the health benefits of additional nformation about prostate cancer screening are questionable and the authors do not present i 152

175 whether results differed by health literacy level. Rates of digital rectal examinations documented by chart review did not change in this study. Of two studies examining the effects of interventions on emergency room visits, only one -experimental study promoting -quality quasi tified results by health literacy level. This fair stra -management by children (intervention directed at children) reported an overall asthma self entage points, 30 perc reduction in emergency room visits (unadjusted mean difference - < 0.01), with a striking effect in those who showed improvements in reading compared to P 207 0.52). those who did not (adjusted OR, 0.34; 95% CI, 0.22- Smaller reductions in emergency room visits (incidence rate ratio, 0.82; 95% CI, 0.70- 0.95) were noted in one good -quality RCT promoting medication adherence for congestive heart failure (CHF); this study was conducted in an undifferentiated population of individuals, 29 percent of whom were designated as “not 182 -TOFHLA. ) on the S literate” (not otherwise specified Of three studies examining the effects of interventions on hospitalizations, two stratified -quality randomized trial results by health literacy. The best of these two studies was a fair 202 -management. focused on CHF self ported no overall reduction in hospitalizations This study re but significant reductions in a subgroup of individuals of low health literacy (adjusted incidence -quality quasi -experimental study of an asthma self - 0.91). A fair rate ratio, 0.39; 95% CI, 0.16- tervention also reported reductions in hospitalizations (adjusted mean difference - management in 207 A third 15 percentage points, < 0.001), although the effect did not differ by literacy level. P a trend toward reduced good- quality RCT, which did not stratify results by health literacy, noted hospitalizations (incidence rate ratio, 0.39; 95% CI, 0.16- 0.91) with a medication adherence for 182 CHF. Based on these findings, our research team graded the strength of evidence for the effect of room visits and hospitalizations as moderate. This grade is mixed interventions on emergency based on consistent evidence from multiple fair quality studies that adherence and self - - to good- -literacy management interventions reduce emergency room visits and hospitalizations in low subgroups or populations that contain individuals with both low and high numeracy (Table 53 and Appendix F). Our prior review found no studies examining this outcome; it, therefore, did not modify our conclusions. comes KQ 2b. Effect of Mixed Interventions on Health Out Knowledge -quality studies addressing the effects of mixed strategy interventions We identified 10- fair 79,194,197,201,202,205,206,211,215,220 194,201,202 Three were RCTs and the on knowledge (Table 54). 79,197,205,206,211,215,220 Two quasi -experimental remaining seven were quasi -experimental studies . studies measured data about knowledge before or after the intervention only, limiting 201,220 79,206 Of studies with interpretable data, two focused on promoting adherence, conclusions. 194,197,201,202,211,215 and one on promoting six on promoting self -management of chronic illness, 205 215 Only one examined knowledge as the primary outcome. Five examined literacy weight loss. of effectiveness of the as a moderator of intervention effect, testing whether the level 194,197,211,215 intervention differed by health literacy level. In aggregate, studies found mixed results; findings did not seem to be related to study design, pants, or health literacy intervention or disease focus, health literacy level of included partici strategies employed as part of the intervention. Four of eight studies with interpretable 202,205,215,220 202 215 including one RCT and one study that focused on knowledge as the data, 202,205,215,220 primary outcome, found positive effects of their intervention on knowledge. 153

176 However, which components of these interventions were the effective components remained unclear. Additionally, in the one study that found an effect and stratified results by health literacy 215 level, results were greater in those with high health literacy; this may be in part because the small subgroups for low health literacy had insufficient power to detect differences. One -literacy -health -experimental study showed positive effects for the high group additional quasi 197 -health -literacy group at 3- month followup. but not the low Given the mixed findings, our research team judged the overall strength of evidence to be insufficient (Table 53 and Appendix F). However, 14 studies from our prior review (including 12 that examined knowledge as their primary outcome) contributed additional information. Eight have been described above because they addressed specific alternative presentations of health information. One additional study is presented below under the effects of mixed interventions on skill. Five additional studies addressed the effect of mixed interventions on knowledge and are 240 -245 243,244 described here. Four of these five studies, including two RCTs, and one study that 244 stratified results by literacy level, found improvements in knowledge with interventions as diverse as an interactive videodisc program about self -care of fatigue in cancer patients, low - literacy nutrition classes, a cholesterol education video, and a CD -ROM on prostate cancer e remaining nonrandomized trial found no improvement in knowledge with the screening. Th addition of a color medication schedule to verbal teaching. With continued mixed results (9 of 14 studies overall with knowledge improvements), the research team concluded that the overall strength of evidence was still insufficient (Table 53 and Appendix F), with effect estimates that are likely to change substantially with new results. Self -Efficacy We identified nine fair -quality studies addressing the effects of mixed strategy in terventions 187,194,202,209,210 and five were quasi -experimental -efficacy (Table 55). Four were RCTs on self 190,205,207,211,220 190,220 five on promoting self - Two focused on promoting adherence, studies. 187,194,202,207,210,211 205 209 eatment, None one on arthritis tr management, and one on weight loss. -efficacy as its primary outcome; only two examined literacy as a moderator of examined self 194,211 effect. One reported self -efficacy results only postintervention, which limited 220 conclusions. In aggregate, studies found mixed results, which may be related to differences in the intensity 207 187,202,210 and one quasi -experimental study with intensive self - of the intervention. Two RCTs management interventions including frequent and prolonged participant contact showed improvements in self -efficacy. Additionally, one study that targeted both patients and providers (although with less intensive and less prolonged contact for each than other effective 205 However, none of these studies stratified interventions) showed increases in self -efficacy. analyses by literacy level. Other studies with less intensive interventions, including two 190,194,209,211 and no differential effect by health literacy randomized trials, showed negative results 194 level in the one study that performed stratified analysis. Based on these studies, our research team judged the overall strength of evidence to be insufficient (Table 53 and Appendix F). No studies from our prior review addressed this outcome. Behavioral I ntent We found no studies addressing the effects of mixed health literacy interventions on patients’ intent to perform specific health behaviors. Similarly, our prior review found no studies addressing this outcome. 154

177 Skill acy interventions on patients’ We found one study addressing the effects of mixed health liter 218 -quality randomized trial randomized a convenience sample of 56 skill (Table 56). This fair -minute individuals to either a standard nutrition label or a nutrition label information card and 8 video tutorial. Participants wh o received the information card and video tutorial correctly answered a higher proportion of questions on a 12- item food label quiz (adjusted absolute difference + 12 percentage points, P < 0.05), with a greater effect among those with adequate -TOFHLA in an adjusted analysis. Based on findings from this study, our literacy on the s research team judged the overall strength of evidence to be low (Table 53 and Appendix F). Two 245,246 studies from our prior review addressed label -reading skills and found mixed results. This leaves the overall literature inconclusive. Behavior Three fair -quality studies addressed the effect of mixed strategy interventions on actual 187,197,202,210 behaviors (Table 57). -experimental study. All Two were RCTs; one was a quasi ved individual or group counseling that taught self -management behaviors and measured invol aggregate self -management behaviors. Additionally, two studies measured individual self - management behaviors for diabetes (including diet, physical activity, foot care, m edication 187,197,210 Only one analyzed these effects by health adherence, and glucose self -monitoring). 197 literacy level. In aggregate, these studies suggested that self -management interventions including individual and group counseling improved aggregate -management behaviors. However, in the only self 197 improvements were sometimes greater for study to examine effects by health literacy status, those who had adequate health literacy and at other times greater for those with inadequate health literacy in adjusted analyses. Based on these studies, our research team judged the strength of evidence regarding t he effects of self -management interventions on behavior as moderate (Table 53 and Appendix F). Three studies in our prior review also addressed behavior, although their intervention focus 243,245,247 All three had special diet interventions a nd measured dietary change was different. and/or caloric intake. These studies found mixed results, precluding definitive conclusions about -literacy diet interventions on behavior. the effects of low -health dherence Medication A 182 79,197,201,209 and four fair We found one good- quality addressing the effect of -quality studies mixed literacy interventions on adherence to medication regimens (Table 58).Three were 182,201,209 79,197 Three included interventions that -experimental studies. and two were quasi RCTs 182,197,201 79 A fourth was a self -management ecifically to promote adherence. were designed sp intervention that measured medication adherence only postintervention in a subset of patients, 209 was designed to promote arthritis which limited drawing any conclusions. A fifth management. Of studies with interpretable data, only one stratified results by health literacy 197 level. 182,197,201,209 effects were mixed, which In the four studies contributing interpretable data, appeared to be related to both the intensity of the inter vention and the measure of adherence. The 182 quality RCT, good- which involved an intensive intervention focused at both patients and their providers, found improved adherence (+10.9 percent, 95% CI, 5- 16.7) during the intervention vent Monitoring Systems (MEMS) to assess adherence. The effect, period using Medication E 155

178 however, attenuated at 3 months after completion of the intervention (+3.9 percent, 95% CI, 197,201,209 -2.8- 10.7). Three other studies, which used less intensive interventions and measured -report, found no effect, although one showed a trend toward improved adherence by self adherence among a subgroup of individuals who were initially nonadherent (+12 percent, = P for any of the 0.08, when counting as adherent those who disagreed that they missed medications 201 four reasons on the Morisky questionnaire). In the study that stratified results by health 197 results were similar by health literacy group in an adjusted analysis. literacy, ngth of evidence for the Based on the findings above, our research team judged the stre effects of mixed interventions on adherence to be insufficient (Table 53 and Appendix F). Only one study from our previous review measured adherence and found no effect of a color 240 medication schedule. This nonrandomized trial di d not change our conclusion about the overall strength of evidence for this outcome. Disease Prevalence and Severity 79,187,193,194,197,198,210 183 We found one good- quality -quality studies and six fair addressing the effects of mixed strategy interventions on disease prevalence and severity (Table 59). Four were 183,187,193,194,210 79,197,198 and three were quasi -experimental studies. Five measured RCTs 183,187,194,197,198,210 79,193 and two measured symptoms. biomarkers of disease Five stratified results by level of health literacy. In general, studies reported mixed results, which may be attributable, at least in part, to intervention and study design. -management interventions on disease Three studies addressed the effects of diabetes self 187,194,197,210 Two fair -quality RCTs biomarkers (including HgbA1c, blood pressure, and BMI). 187,194,210 found no effect on HgbA1c, blood pressure, or BMI in participants overall or in low - 194 -literacy subgroups in an a djusted analysis. health By contrast, a fair -quality quasi - experimental study found a statistically significant decrease in HgbA1c with no difference in 197 without a control group, effect among health literacy subgroups in an adjusted analysis; however, we can not judge the importance of this finding. Two other studies addressed the effects of diabetes disease management programs (i.e., self - 183,198 management plus pharmacist adjustment of medication) on disease biomarkers. These 198 -experimental studies appeared to test the sam and a randomized e intervention in a quasi 183 The RCT showed a significant decrease in HgbA1c in the low -health -literacy group design. - (adjusted absolute difference - 1.4 percent, 95% CI, - 2.3 to - 0.6) but not in the high- health literacy gro -1.4 to 0.3), although it should 0.5 percent, 95% CI, up (adjusted absolute difference - be noted that the sample size may have been too small to detect small differences in the high - literacy subgroup. Systolic blood pressure was also significantly lowered among all participants 7.6 mmHg, 95% CI, - 13 to - 2.2 mmHg). Exactly which component (adjusted absolute difference - - of this intervention was efficacious remains unclear, although the lack of efficacy of other self management interventions suggests that the pharmacist adjustment of medication may be the critical factor. Additionally, the self -management component in this study employed a wider variety of strategies to mitigate low health literacy (e.g., simple language, simple organizational structure, pictur es, teach -back, repetition) than other studies. 79,193 Two studies addressed the effects of mixed strategy interventions on symptom control, although only one had adequate power to test its effects on disease severity and did not stratify 193 This fair -quality randomized trial, which tested the effects of results by health literacy level. adult basic and literacy education as an adjunct to depression management, showed statistically 156

179 significant reductions in scores on the PHQ item depression scale of -9 (the 9- the Patient Health Questionnaire) over multiple followups. Based on the findings above, our research team judged the strength of evidence separately for -management, disease management, and adult basic and literacy interventions. We concluded self that the -management interventions, moderate for strength of evidence is insufficient for self disease management interventions, and low for adult basic and literacy education interventions (Table 53 and Appendix F). No studies from our prior review included these types of interventions. However, one RCT from our prior review found reduced depression with case 248 management as an adjunct to a standard Head Start program. Furthermore, two RCTs from our 247,249 found no effect of special nutrition education programs on cholesterol (two prior review studies) or blood pressure (one study). Quality of Life 187,202,209,210 182 and three fair One good- RCTs addressed the effects of mixed -quality quality strategy interventions on quality of life (Table 60); however, none used quality of life as the 187,209,210 primary outcome. Two focused on general quality of life - and two focused on disease 182,202 specific quality of life. One measured quality of life only after the intervention in the 182 thereby limiting conclusions. Only one stratified results by health literacy intervention group, 202 level. The three studies providing interpretable data yielded mixed results. Two studies reported no effects of self -validated quality -of-life measures, including -management interventions on well - the mental and physical health subscales of the Medical Outcomes Study Short Form 12 (SF 187,210 202 and the Minnesota Living with Heart Failure scale (MLHF). One of the studies, 12) however, reported reductions in the number of bed day s in the past month (adjusted absolute -1.7 days per month, 95% CI, - 0.1 days per month) for people assigned to an difference 3.3 to - 187,210 A third trial on intensive telephone counseling intervention with 39 patient contacts. arthritis management interve ntion reported mixed effects, with no effects on the Health 209 Assessment Questionnaire (HAQ), but improvements on the mental health subscale of the SF - 36. Based on findings described above, our research team judged the strength of evidence for the effects of mixed interventions on quality of life to be insufficient (Table 53 and Appendix F). Our prior review found no studies examining this outcome; it, therefore, did not modify our conclusions. KQ 2c. Effect of Mixed Interventions on Health Care Costs We f quality RCTs examining the health care costs of mixed health literacy ound two good- interventions. One good- quality RCT examined the cost -effectiveness of its intervention to 182 promote adherence to CHF medication (Table 61). This intensive pharmacist -led intervention, which included patient education and skill building, graphic medication labels, monitoring of adherence, and notification of providers, showed trends toward cost savings ( -$2,960, 95% CI, -$7,603 to $1,338) compared with usual care when consi dering intervention, outpatient, and inpatient costs. Another good- quality RCT examined the labor and total costs (defined as labor plus indirect costs) of its diabetes disease management intervention. This study reported the labor costs for its disease ma nagement program, which employed both clinical pharmacists and diabetes care coordinators who provided more than 13 hours of education, skill building, and medication adjustment per patient, were $25.50 per patient per month (range in sensitivity 157

180 analysis $12.01 to $55.35 per patient per month). Total costs were slightly higher at $36.97 per patient per month (range in sensitivity analysis $16.22 to $88.56 per patient per month). strength of Based on these studies and their mixed findings, our research team graded the evidence for the effects of mixed interventions on health care costs as insufficient (Table 53 and Appendix F). Our prior review found no studies addressing this outcome and did not modify our conclusions. KQ 2d. Effect of Mixed Interventions on Disparities We found no studies addressing the effects of mixed health literacy interventions on patients’ intent to perform specific health behaviors. Similarly, our prior review found no studies addressing this outcome. Summary of Interventions Using Mixed Intervention Strategies The strength of evidence for studies combining multiple strategies to mitigate the effects of low health literacy on outcomes was more variable than for single -feature interventions. We found moderate strength of evidence that studied interventions change health care service use. -management and adherence interventions appear to be effective in Specifically, intensive self reducing emergency room visits and hospitalizations. Additionally, educational interventions and/or cues fo r screening increased colorectal cancer and prostate cancer screening. We note, however, that the health benefits of additional prostate cancer screening are questionable and that increased screening rates could be a marker for poor decision making. Evidence of moderate strength indicates that some interventions change health outcomes. For instance, intensive disease- management programs appear to be effective at reducing disease prevalence. Furthermore, self -management interventions increased self -managemen t behavior; however, in the only study that stratified its analysis by health literacy level, the effect was greater in the high -literacy subgroup than in the low -health -literacy subgroup in adjusted -health - analyses. The effects of other interventions on other health outcomes, including knowledge, self -related skills, quality of life, and cost, were mixed; thus, the strength efficacy, adherence, health of evidence was insufficient. Too few studies addressed the effects of health literacy interventions on the outcomes of behavioral intent and disparities to draw any meaningful conclusions; the strength of evidence is insufficient. Cross- Cutting Observations About Interventions Designed To Mitigate Low Health Literacy Looking at the common features of successf ul interventions can help illuminate features that may be important in making interventions effective at mitigating the effects of low health literacy. Common features across nearly all of the interventions that improved distal outcomes (e.g., self -managem ent, hospitalizations, mortality) were their high intensity, theory basis, pilot - testing before full implementation, emphasis on skill building, and delivery of the intervention 182,183,202,207 by a health professional (e.g., pharmacist, diabetes educator). Examining pathways of effect can also help illuminate factors that may be important in making interventions effective. Six studies in our update examined the impact of interventions on 79,182,187,194,197,202 (Table 44). In addition to changing distal outcomes, three or more outcomes 158

181 196,197,202 these studies reported changes in the following intermediate outcomes: knowledge, self - 182,187,197,202 187 efficacy, or behavior. Although these studies did not perform formal mediation analyses, the change in these in termediate outcomes suggests that changing knowledge, increasing self -efficacy, and changing behavior may be important goals in mitigating the effects of low health literacy. 159

182 Table 43. Summary of included intervention studies Analysis Design Stratified by Quality Population, Health (Sample Literacy Size) Literacy Levels Source Intervention Outcomes Control Score Level literacy Interventions using single strategies for low health a Standard American Yes Comprehension Fair 28% < high school SS - RCT Multimedia AUA Bryant et al., 13 Urological Association on REALM (232) 20092 Mean REALM BPH Symptom Score - SS) score: 59 (AUA a Standard print consent Yes Knowledge Fair 50% Low (1) Simplified print RCT Campbell et al., 200 grade reading form (233) (< 8th consent form 2004 (2) Video consent level on Woodcock (3) Computerized Johnson) Average REALM consent score: 56.3 Coyne et al., RCT No Comprehension Fair Mean REALM : 65 Standard Consent Simplified consent form 199 (226) 2003 Form RCT Natural frequencies Conditional Mean numeracy on Yes Galesic et al., Accuracy of positive Fair 217 2009 predictive value (162) (x/10,000) probabilities (%) 12-pt scale derived Presented to illustrate Presented to illustrate from Lipkus & estimates the positive predictive the positive predictive Schwartz: Overall: 9.7 value of genetic value of genetic testing Older adults: 8.6 for early detection of testing for early Younger adults: diabetes detection of diabetes or trisomy 21 or trisomy 21 10.3 a b c d adjusted for relevant confounders; weighted percents; Read from Table; determined through personal communication with author 12- p= 12- point; ABLE =Adult Basic and Literacy Education; ARR =absolute risk reduction; AUA -SS= American Urological Association -Symptom Score; BPH =benign prostatic hyperplasia; CHD =congestive heart failure; cRCT =cluster randomized controlled trial; FDA =The Federal Drug Administration; =coronary heart disease; CHF HgbA1 c=glycosylated hemoglobin; inadeq.inadequate; info.information; MDs = medical doctors; MIC = modified informed consent; MIC + SS =modified informed consent + slide show; NA= not applicable; NOS =not otherwise specified; PDA =personal digital assistant; pt= point; pts =patients; Quasi-= quasi -experimental study; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy for Adults; RRR =relative risk reduction; S -TOFHLA =short form Test of Functional Health literacy in Adults; TOFHLA =Test of =United States; WRAT =Wide Range Achievement Test. Functional Hea lth Literacy in Adults; US 160

183 Table 43. Summary of included intervention studies (continued) Analysis Stratified by Design Population, Health Quality Literacy (Sample Control Intervention Outcomes Size) Score Literacy Levels Level Source Fair Mean numeracy Factorial Galesic et al., Accuracy of risk Yes Icon arrays Numerical Risk 216 score on 12-pt scale 2009 RCT perception (presented alternately derived from Lipkus (171) as ARR or RRR) & Schwartz: Older adults: 8.6 Students: 10.3 a Garcia RCT Accuracy of risk Yes Numerical information Fair 49% Low numeracy - Numerical information perception (1047) (RRR) plus icon array Retamero and about RRR (including (> median score on 219 Galesic, 2009 (including information information with 9-item scale adapted from Lipkus varying size presented with varying b denominators) sizes of denominators) and Schwartz) b (Germany: 49% , a ) US 48% (1) Common/unique Greene et al., Comprehension Fair 50% Low (score Yes (1) Side - by - side RCT 185 (303) 2008 (random) comparison presentation of less than 10 on DR characteristics Numeracy Test) of characteristics (2) No framework (2a) Short framework (2b) Long framework Fair Greene and Comprehension Simplified Medicaid RCT 57% TOFHLA Cloze Standard Medicaid Yes 214 health plan ≤ 18 (out of Peters, 2009 (122) health plan comparison score chart comparison chart 20) Hwang et al., No - , Comprehension Medication label text + Medication label text: ≤ 6th Fair 5% REALM Quasi 195 2005 pre -post A. Take with water illustration grade 22% REALM 7-8th (130) B. May cause grade drowsiness C. Take with food D. No alcohol E. Take on an empty stomach 161

184 Table 43. Summary of included intervention studies (continued) Analysis Design (Sample Quality Population, Health Stratified by Size) Literacy Levels Control Intervention Outcomes Source Literacy Level Score Standard Consent RCT (90) No Fair Patient: Comprehension (1) Modified informed Kang et al., 212 2009 Median REALM and Form consent for (MIC) (2) Modified informed WRAT scores: high consent + slide show school (MIC + SS) Parent: Note: Interventions Median REALM and WRAT score: high delivered to both patient and parent school Comprehension No Mayhorn and (1) Original symbol, but Original teratogen 42.9% Low literacy Fair -, Quasi Goldsworthy, woman taking pill symbol (REALM, NOS) -only post 189 2007 (2) Cross and skull (slash through (700) bones in pregnant belly pregnant woman) (4) 2 pictures: Original symbol + skull bones in pregnant belly (5) 2 pictures: #4 but more caricatured (6) 1 picture combining original symbol + skull bones in pregnant belly (7) skull bones in pregnant belly + inlay with slash through per son taking pills (1) Ordered cost, quality, RCT Low (score 50% Fair Nonordered, Comprehension, Peters et al., Yes 188 less than 10 on DR (303) non-quality info. nonquality info. 2007 choice of higher Numeracy Test) (2) Cost and quality info. quality option (Study 1) only 162

185 Table 43. Summary of included intervention studies (continued) Design Analysis (Sample Quality Population, Health Stratified by Score Size) Literacy Levels Control Intervention Outcomes Source Literacy Level Low (score Comprehension, RCT Fair 50% Peters et al., Numbers only (1) essential info (e.g. Yes 188 2007 (303) death rates) choice of higher less than 10 on DR (Study 2) quality option accompanied by Numeracy Test) black/white symbols (2) essential info (e.g. death rates) traffic accompanied by symbols (3) essential and non - essential info (e.g. death rates and satisfaction) accompanied by black/white symbols - (4) essential and non essential info (e.g. death rates and satisfaction) accompanied by traffic symbols Peters et al., Yes Comprehension, (1) Higher number is Lower number is RCT Low (score 50% Fair 188 2007 choice of higher better quality, no less than 10 on DR better quality, no (303) (Study 3) symbols symbols Numeracy Test) quality option (2) Lower number is symbols better quality, (3) Higher number is better quality, symbols Seligman et al., No cRCT efficacy - Self Fair 74% TOFHLA Physician notification of Usual Care for 181 inadeq. Diabetes 2005 patients' health literacy HgbA1c (63 MDs, 16% TOFHLA Physician use of status 182 pts) marginal effective communication strategies 163

186 Table 43. Summary of included intervention studies (continued) Analysis Stratified Design Quality Population, Health (Sample by Literacy Literacy Levels Control Score Size) Intervention Level Source Outcomes RCT No Sudore et al., Comprehension Simplified Advanced 40% TOFHLA Fair Standard Advanced 204 (205) Directive < 22 (inadeq. or Directive 2007 Sudore et al., marginal) 208 2008 a Fair Quasi Yes Comprehension Sudore et al., 22% TOFHLA Simplified consent form -, None 192 inadeq. 2006 -only post 18% TOFHLA (204) marginal th a Good 18% ≤ 6 Volandes et al., RCT grade on Yes Verbal narrative about Verbal narrative + video Knowledge 184 advanced dementia (200) Intent 2009 showing features of REALM th grade on 12% 7- 8 advanced dementia REALM Standard Arthritis Fair Walker et al., 15% with REALM < Standard Arthritis RCT Knowledge No 133 Booklet booklet + Mind Map (363) 60 (9th grade) 2007 Fair 41% Low RCT Dispersed dot icon Grouped dot icon array Wright et al., Yes Comprehension 186 (incorrect answer to 2009 (3 different risk (140) array st 1 (3 different risk question on magnitudes: 3%, 6%, magnitudes: 3%, 6%, Lipkus numeracy 50%) 50%) scale) a Yates and RCT Yes Comprehension Simplified head trauma Fair 1.5% REALM < 7th Standard head trauma 191 c grade advice form (200) advice form Pena, 2006 14% REALM 7-8th c grade 164

187 Table 43. Summary of included intervention studies (continued) Design Population, Analysis Quality Health Literacy Stratified (sample Control Intervention by Literacy Score Source Levels size) Outcomes health literacy Interventions using mixed interventions for low Bosworth et al., Fair RCT (588) 38% low literacyd Usual care Tailored adherence Knowledge No 201 Adherence intervention 2005 - , Brock and 55% REALM < 8th Knowledge Fair No Quasi NA Adherence video on 220 grade Smith, 2007 (although pre PDA -post Adherence poor for (51) adherence) - , Weight loss intervention Davis et al., 49% REALM < 6th No Quasi - Knowledge, Self None Fair 205 efficacy -post 2008 grade pre 22% REALM (101) - 7 8th grade RCT (127) Knowledge Fair 41% S - TOFHLA DeWalt et al., Usual care + low Yesa CHF self - management 202 2006 literacy pamphlet on program inadeq. Self -efficacy Behavior CHF Quality of life Use of health care services Educational Intervention Ferreira et al., Fair 31% Low (< 9th cRCT (113 Yes Use of Healthcare Usual Care 196 2005 Services grade on TOFHLA) MDs, for Physicians and measured Note: Patients on Colorectal 1,978 pts) only in 19% of Cancer screening patients a RCT (144) Yes Fair 56% S - TOFHLA Knowledge - Diabetes self Usual care + Gerber et al., 194 2005 computerized quizzes -efficacy management < 22 (inadeq. or Self marginal) on diabetes -related HgbA1c intervention Use of health care concepts Services a Jay et al., RCT (56) Yes Fair 17% Limited Comprehension Nutrition label Standard FDA 218 information card and materials explaining ≤ literacy (score 2009 22) on S TOFHLA video tutorial - nutrition label 165

188 Table 43. Summary of included intervention studies (continued) Design Analysis Quality Population, Health Stratified by (Sample Control Intervention Score Literacy Level Source Size) Literacy Levels Outcomes a Yes Kim et al., Knowledge Fair 23% S - TOFHLA < - Diabetes self Quasi - None , 197 22 (inadeq. or management Behavior pre 2004 -post (92) marginal) HgbA1c intervention (15% inadeq. on TOFHLA) 42% REALM < 6th Kripalani et al., Quasi Self Fair -, No None CHD adherence -efficacy 190 pre -post grade intervention (pill card) 2007 37% REALM 7-8th (242) grade rd RCT (303) Fair Kripalani et al., 38% REALM < 3 (1) Educational Handout, NOS Use of Healthcare No 203 Unclear if prostate Intervention on Prostate Services 2007 grade 18% REALM 4-6th content or other Cancer Screening (2) Cue to Discuss grade content - 8th REALM 7 23% Prostate Cancer screening grade a rd - , (1) Modified Print No control Fair Kripalani et al., 21% REALM < 3 Quasi Knowledge Yes 206 grade post only informed Consent with 2008 (408) 25% REALM 4-6th Oral Overview grade 31% REALM 7-8th grade adherence CHF Adherence Good 29% “not literate” on Usual care RCT (314) Murray et al., No 182 Quality of Life intervention S-TOFHLA (NOS) 2007 Use of Health care Services Cost a Paasche - Orlow Quasi - , Yes Knowledge - Asthma Self Fair 22% S - TOFHLA NA 79 -post et al., 2005 Management pre Adherence Inadeq. (73) Asthma symptom Intervention control 166

189 Table 43. Summary of included intervention studies (continued) Design Analysis Quality Stratified by (Sample Population, Health Literacy Levels Control Intervention Size) Outcomes Score Literacy Level Source a , Robinson et al., NA Quasi Yes Fair Mean Gilmore Oral efficacy - Self - Asthma Self - 207 Management pre -post Reading Test Score: Use of Healthcare 2008 Services (110) Intervention 3.2 NA Rothman et al., Quasi Fair 55% Lower literacy Diabetes Self Yes HgbA1c (and - - , rd 198 other biomarkers) pre Management -post 32% REALM < 3 2004 (159) grade Intervention REALM Score 23% - 6th grade 4 a Rothman et al., Yes HgbA1c (and Diabetes Self RCT (217) hour education - Good 38% REALM < 1 6th 183 2004 session Management other biomarkers) grade Intervention Rothman et al., 250 2006 Rudd et al., RCT (127) efficacy, No Fair 19% REALM < Arthritis Management - Self Arthritis Management high 209 Intervention (arthritis 2009 Intervention + Individual Adherence, school pamphlet, medicine Counseling Quality of Life calendar, hospital map) TOFHLA Schillinger et - RCT (339) No Fair 59% S - < Usual care (1) Diabetes Self efficacy Self 187 22 (inadeq. or Management Program Behavior al., 2008 Schillinger et marginal) Hgba1c (and other (automated telephone 210 al., 2009 biomarkers) delivery) - (2) Diabetes Self Quality of life Management Program (group medical visit delivery) a 26% with low Fair Linear video tutorial Quasi, No control Sobel et al., Yes Knowledge 215 -44 on literacy (0 2009 pre -post about asthma and its REALM) (130) management 33% with marginal -60 on literacy (45 REALM) Wallace et al., Yes - , Knowledge - Diabetes Self NA Fair 29% TOFHLA Quasi 211 2009 -efficacy inadeq. Self pre -post Management 14% TOFHLA Intervention (250) marginal Weiss et al., No RCT (70) Depression Adult Basic and Literacy Fair Mean REALM score: Usual care 193 47 Education (ABLE) Severity 2006 167

190 Table 44. Intervention study detail # of Contact Literacy Individual Theory Pre - time Who Delivered Description Author Tailoring Medium Driven Strategies testing sessions Basic Interventions: Alternative Document Design a Yes (1) Common Greene et al., NA NA Chunking of Researchers NR 1 Print 185 presentation of 2008 ideas information (vs. random presentation) (2) Short Framework (vs. long or no framework) a a (1) Ordered Ordering, Researchers Peters et al., < 1 hour 1 Print Yes NA NA 188 info. (vs. 2007 Essential info. (study 1) unordered only info.) (2) Essential info. (vs. nonessential info.) a determined via personal contact with authors AUA-SS= American Urological Association -Symptom Score; BPH =benign prostatic hyperplasia; avg =average; CHD =coronary heart disease; CHF =congestive heart failure; =hypertension; info. DM etes; HIV =human immunodeficiency virus; hr =hour; HTN =diab =information; med =medicine; min =minute; NA =not applicable; NOS =not otherwise specified; NR =not reported; PCP =primary care provider; PDA =personal digital assistant; Q and A =question and answer; RRR= relative risk reduction; vs. =versus. 168

191 Table 44. Intervention study detail (continued) Individual - Pre Theory Literacy # of Contact Driven time Who Delivered Strategies Author Tailoring Medium sessions Description testing Alternative Numerical Presentation Basic Interventions: a a Self Yes Galesic et al., NA NA Numerical administered - Natural <5 min 1 Print 217 simplification frequencies on computer 2009 (x/10,000) Presented to illustrate the positive predictive value of genetic testing for early detection of diabetes or trisomy 21 a Yes Garcia Same (vs. NA - Numerical NA administered - Print 1 1 - 2 Self simplification Retamero and different) on Computer minutes 219 denominators Galesic, 2009 for baseline risk and treatment benefit a a Peters et al., Yes NA (1) Higher NA Numerical Print 1 < 1 hour Researchers 188 simplification number better 2007 quality (vs. (study (3) lower number better quality) 169

192 Table 44. Intervention study detail (continued) # of Contact Literacy Individual Theory Pre - Description time Who Delivered Medium Tailoring Driven Author sessions testing Strategies Basic Interventions: Additive and Alternative Pictorial Presentation Icon arrays (vs. Galesic et al., Yes NA Print 1 <10 mina Self - administered NA Graphical 216 on computer none) 2009 presentation a Icon arrays (vs. Garcia Print - 1 1 - 2 Self - administered Graphical Yes NA NA presentation minutes Retamero and none) on Computer 219 Galesic, 2009 NR Illustrations No Hwang et al., NA Print 1 Researchers Graphics NA 195 2005 (vs. none) Mayhorn and Yes 7 alternate NA NA Print 1 25 min Researchers Graphics teratogen Goldsworthy, 189 symbols 2007 a a (1) color Yes NA NA Graphics, Color Print 1 < 1 hour Researchers Peters et al., 188 symbols (vs. 2007 -white or black (study (2) no symbols) a a NA (1) symbols to Graphics Yes Peters et al., Print 1 < 1 hour Researchers NA 188 indicate 2007 (study (3) higher/lower quality (vs. none) a a Researchers No NA Print 1 Unknown NA Walker et al., Conceptual Mind map (vs. 133 depiction 2007 none) Wright et al., NR Grouped dot NA NA Graphical Print 1 NR Researchers 186 simplification icon arrays (vs. 2009 dispersed dot) 170

193 Table 44. Intervention study detail (continued) # of Contact Literacy Individual Theory Pre - Description time Who Delivered Strategies Medium Tailoring Driven Author sessions testing Basic Interventions: Alternative Media a a Bryant et al., No NA Video, NA delivery, 1 15 min Researchers Oral Print + Video 213 color 2009 BPH Symptom -coding of Computer Score (vs. Print symptom score Score) answers, Visual demonstration of scoring a (1) Simplified NA Print, Yes NA Campbell et al., 1 < 1 hr Researchers Simple language, 200 consent form 2004 Video, Chunking of (2) Video Computer ideas, consent White space, (3) Compute- Pictures, rized consent Oral delivery Kang et al., (1) Modified grade administered, - Yes NA - Self 1 10 - 15 min. 7th NA Print, 212 for Print; reading level, Slide although informed 2009 show researchers consent form large font, white length of (2) Modified space simple slide show delivered slide informed NOS show language, active consent + slide voice, “action” show cues Suitability Assessment of Materials score: 69% a Verbal Volandes et al., No Yes No Video Oral, Researchers 1 2 min. 184 2009 Video narrative + Video showing features of advanced dementia 171

194 Table 44. Intervention study detail (continued) Individual Theory Literacy Contact # of sessions time Who Delivered Medium Strategies Tailoring Driven Pre - testing Description Author Basic Interventions: Alternative Reading Level and Document Design a (1) Simplified Campbell et al., Yes NA NA Simple language, Print, Researchers < 1 hr 1 200 2004 consent form Chunking of Video, Computer (2) Video ideas, consent White space, (3) Compute- Pictures, rized consent Oral delivery -8th grade 1 NR Researchers 7th Print Coyne et al., Simplified NA No NA 199 reading level, 2003 consent form Simple language, (vs. standard 1 idea per form) paragraph, Large font, White space, Pictures a a 20 min Print 1 Self -administered Yes Simplified NA Greene and Simplified NA 214 Peters, 2009 Medicaid document health plan complexity (high comparison school reading level), font size, chart (vs. focus on standard chart) differences in information ordering Kang et al., (1) Modified NA Yes grade - NA Print, th 7 administered, 1 10 - 15 min. - Self 212 for Print; although informed 2009 Slide reading level, consent form length of researchers large font, white show slide show delivered slide (2) Modified space simple language, active informed NOS show voice, “action” consent + slide cues show Suitability Assessment of Materials score: 69% 172

195 Table 44. Intervention study detail (continued) Literacy - Pre Theory # of Individual Contact Who Delivered Strategies sessions Tailoring time Driven Medium testing Description Author Sudore et al., No Simplified NA NA grade - 5th Print 1 < 30 min Researchers 204 2007 advanced reading level, 208 Sudore, 2008 directive (vs. values standard) clarification questions. Large Font, Graphics Simplified NA No Print, NA Sudore et al., 1 10 min Researchers 6th - grade 192 2006 reading level. consent form Oral Simple language, Large Font, - Teach back a Simplified NA Yates and Pena, Yes Word reduction, Print NA 5 - 10 min Researchers 1 191 Simple language, instruction 2006 Chunking of ideas, sheet (vs. Large Font, standard form White space at same readability) Basic Interventions: Provider Notification of Patient Literacy Status No NA NA NA Print 1 NA Researchers Seligman et al., Provider 181 2005 notification of patient literacy level Mixed Interventions: Adherence Bosworth et al., Adherence No Yes Yes Oral presentation, Telephone ~12 44 min (avg) Nurses 201 2005 intervention for key concepts, HTN information given a (education, skill to family/friend building) Yes NR No Simple language, Self Video on PDA 1 17 min Brock and Smith, Adherence 220 Pictures/Graphics intervention for 2007 HIV (education, skill building) a a Kripalani Adherence Yes Individual Social 1 5 min et al., Pharmacist Yes Pictures, 190 Large Font intervention for 2007 Counseling, Cognitive a CHD (pill card) Theory Print 173

196 Table 44. Intervention study detail (continued) Literacy - Pre Theory # of Individual Contact Who Delivered Strategies sessions Tailoring time Driven Medium testing Description Author Variable, Adherence Yes No (but Yes 6th grade reading Pharmacist 20 - ~10 Murray et al., Patient: a 182 Individual level, - hours patient range not intervention for 2007 a Organization by available counseling, CHF centered Print mental schema, principles) (education, Provider: Lists/short graphic med telephone, paragraphs, labels, skill paging, email Pictures building, monitoring and feedback, provider communication) Mixed Interventions: Self - Management Self Yes Social Pharmacist or Health Individual Yes 6th grade 10 to 16 Not DeWalt et al., 202 a 2006 measured Cognitive counseling, Management Educator readability, Teach a Theory back Print, intervention for CHF Telephone (education, skill building) Self No Yes Yes Computer with Audio/Video, Gerber et al., 2.9 on Self 53.5 min on 194 a a average audio/video Testimonials average Management 2005 Intervention for DM (education, feedback) a a Kim et al., 6th grade reading NA Self None Individual and Noa 4 10 hoursa Diabetes Educators a 197 level group 2004 Management Intervention for counseling DM (NR) Orlow et No Paasche Self N No - Teach back Individual Researcher 1 30 min+ 79 counseling, Management al., 2005 Print Intervention for Asthma (skill building) 174

197 Table 44. Intervention study detail (continued) # of Contact Literacy Individual Theory Medium time Who Delivered Strategies testing Tailoring sessions Driven Pre - Description Author 29 Yes for Self NR No NR Group 68 hrs Trained facilitators, Robinson et 207 asthma, Management al., 2008 NOS counseling no for Intervention for literacy Asthma (literacy education, asthma education, skill building, goal setting, communication training) a a a a 2 Self No Yes Schillinger et al., Yes (1) Telephone Oral presentation Automated Calls, (1) 1 39 (1) 312 min 187 2008 29 Nurse (2) Group (2) 810 min Management (2) PCP, health Schillinger et al., Interventions for Counseling 210 educator 2009 DM (education, skill building) Individual Self Simple language, Researcher 20-45 Wallace et al., 3 Yes Yes No 211 counseling, 2009 Management Conversational minutes Print, based on Intervention for tone, measurement Telephone DM (education, Pictures at 1 site goal setting) Mixed Interventions: Disease Management a a a Individual No No (general Yes Simple language, Rothman et al., Pharmacists Disease ~15 ~336 min 198 counseling, Pictures, Management 2004 principles of Print, Simple Intervention for Social Telephone DM (education, Cognitive organizational trouble-shooting, Theory structure, a applied) med adjustment) Teach Back a a Disease Yes No (general Yes Simple language, Rothman et al., Pharmacists or Individual 463.2 min 13+ 183 Management counseling, Diabetes Care 2004 Pictures, principles of Print, Intervention for Coordinators Simplified Social Telephone DM (education, Cognitive organizational skill building, structure, Theory a Teach Back, applied) med adjustment) Repetition 175

198 Table 44. Intervention study detail (continued) Theory Individual Tailoring Driven Pre-testing # of Contact Literacy Medium Author sessions Description time Who Delivered Strategies Mixed Interventions: Screening Educational Providers: NR Provider: Providers: Yes Ferreira et al., Provider: Provider: Researchers - Provider: 5 - Provider: 4 196 on low Intervention on 6 hr workshops education 5 Patients: Yes 2005 none Patients: No health literacy (although Patient: Colorectal Patient: NR Patient: NR Screening communication followed Video, quality Print strategies, NOSa Patient: Simple improvement languagea principals) a Patient: Health Belief Modela Yes (1) Nonea No Simple language, Researchers Not 1a Print Kripalani et al., 203 2007 Educational measureda Pictures, Large Font, Intervention on Key Concepts, Prostate Q and A Cancer Screening (2) Cue to Discuss Prostate Cancer Screening Mixed Interventions: Other et al., Weight loss No Physician: specific Provider: Researchers Provider: 4 Davis Yes No Provider: 2 205 2008 education hr workshops Intervention (education) Patient: 1 interactions with Patient: 15 Patient: low lit population min st nd -2 1 Video Patient: (education, grade readability, teach back motivation) 218 Nutrition label Card: Yes NR Print, Video Jay et al., 2009 1 ~10 - 15 min Researchers Color, Chunking of No ideas, Video information card Video: NR and video tutorial 176

199 Table 44. Intervention study detail (continued) # of Contact Literacy Individual Theory time Who Delivered Medium Strategies Tailoring testing Driven Pre - Description Author sessions (1) Modified (1) Print Kripalani et al., No No No 1 7 - 8 min on Researchers (1) 8th grade 206 Print Informed averagea 2008 (2) Individual readability, Chunking of ideas Consent with oral education Oral (2) teach back Overview (1) Arthritis Yesa Social Yes 5th to 8th grade Rudd et al., Arthritis Educator ~1 hra Individual 1+a 209 (intervention 2009 readability, Counseling, Cognitive Management Avoidance of Intervention (2) Theorya Print jargon (education, medicine calendar, hospital map) (2) Arthritis Management Intervention + Individual Counseling - Linear video NA, pilot study NR Yes Video 1 6 Sobel et al., 20 min Researchers Specific to content, 215 Video, Small 2009 about asthma number of new and its management concepts Program Staff Adult Basic and Weiss et al., None No Individual grade - NR 18.1 hr 4th Yesa 193 2006 Literacy Counseling, (range 0-74 readability, (although Print, Short Sentences, hr) Education focus on empowerment Large Font, Intervention Computer (education and and locus of White Space, job skill Avoid jargon control) a building) 177

200 Table 45. Single intervention strategies: alternative document design % Population Author, Date of with Limited Study Sample Publication, Literacy/ Quality Size design Control Group Outcomes Difference Intervention Numeracy -by-side Greene et al., RCT (1) Side (1) Common/unique 50% 303 Low (score Mean # Common vs. Side to Side 185 2008 comparison of presentation of less than 10 on responses to (unadjusted) characteristics Fair characteristics DR Numeracy comprehension Subgroup: High Numeracy (2) No framework (2a) Short framework Test) questions Comprehension: -0.3, NS (2b) Long framework (range 0-6) Low Numeracy Subgroup: Comprehension: -0.3, NS Short framewo rk vs. No (unadjusted) High Numeracy Subgroup: Comprehension: +0.7, (P < 0.05) Low Numeracy Subgroup: Comprehension: +0.3, (P < 0.05) Long framework vs. No (unadjusted) High Numeracy Subgroup: Comprehension: +0.5, (P < 0.05) Low Numeracy Sub group: Comprehension: -0.5, (P < 0.05) Info =information; NR =not reported; NS =not significant; RCT =randomized controlled trial; vs. =versus. 178

201 Table 45. Single intervention strategies: alternative document design (continued) Author, Date of % Population with Study Sample Limited Literacy/ Publication, Numeracy Intervention Control Group design Outcomes Difference Quality Size Ordered, all vs Mean # correct Peters et al., 50% Low (score 303 . Control RCT Non - ordered, non - (1) Ordered essential 188 and non-essential info (= (unadjusted) 2007 responses to essential info less than 10 on DR (Study 1) High Literacy Subgroup: comprehension all) numeracy test) Comprehension (2) Essential info only : +0.1, NS questions (range Fair Choice: +5%, NS 0-3) % choosing Low Literacy Subgroup: higher quality Comprehension: +0.6, (P < hospital 0.01) Plan Choice: +9%, NS P for literacy interaction: comprehension: (P < 0.05) Choice: NS Essential only, vs. cont rol (unadjusted): Overall: Comprehension: +0.4, (P < 0.01) Choice: +21%, (P < 0.01) High Numeracy Subgroup: Comprehension: +0.3, (P < 0.01) Choice: +19%, NR Low Numeracy Subgroup: Comprehension: +0.7, (P < 0.01) Choice: +23%, NR P for interaction: comprehension: (P < 0.05) Choice: NS 179

202 Table 46. KQ 2 specific interventions: strength of evidence grades by type of outcome Number of Results Overall Grade Outcome Studies Alternative Insufficient Highlighting common quality features (n 2 RCTs examining = 1): No effect Document multiple Providing a framework for quality features (i.e., Design chunking advantages and disadvantages; n = 1): simplifications Improved comprehension for high literacy, worsened comprehension for low literacy if long rather than short list of features Presenting only essential quality info (i.e., death rates, = 1): Improved comprehension and not satisfaction) (n choice of higher quality plans = 1): Improved l quality info first (n Presenting essentia comprehension for low literacy only, no effect on health plan choice Alternative Low 3 RCTs examining Presenting quality information such that the higher Numerical different numerical number (vs. lower number) is better: Improved Presentation presentations comprehension and choices of higher quality options for low (but not high) numeracy individuals Presenting information about the baseline risk of disease and treatment benefit information with the s. different numbers: Improved accuracy of risk same v perception with greater effect in low vs. high numeracy group Presenting positive predictive values as natural frequencies rather than conditional probabilities: improved comprehension equally for low and high literacy individuals Alternative Insufficient 6 RCTs and = 2): Adding symbols to numerical info (n Pictorial - 2 quasi Mixed effects depending on the symbols and the Representations experimental information to which they were added. studies examining Plus/minus signs to indicate fewer/more had no (1) adding symbols overall effect, a lthough there was an interaction by to numerical whether higher quality was indicated by higher or information, (2) lower numbers. Black and white and colored traffic light circles had no adding icon arrays effect on comprehension, but increased the proportion to numbers, of individuals choosing high quality hospitals. (3) adding However, there was an interaction by (1) whether illustrations to essential (i.e., death rates) or both essential and non- prose, essential (i.e., death rates and satisfaction) quality (4) using different information was presented, and (2) by numeracy level. pictorial Adding icon arrays to numbers (n = 2): representations for Improved understanding of both ARR and RRR same concept presentations when icons were added. Interaction by (1) numeracy level, and (2) whether numbers and icon arrays depicted baseline risk and the risk following treatment with the same or different denominators. 180

203 Table 46. KQ 2 specific interventions: strength of evidence grades by type of outcome(continued) Number of Studies Results Overall Grade Outcome Adding illustrations to prose (n = 2): No effect of mind map added to brochure or illustrations added to simple medication label text Using different pictorial representations for the same = 2): concept (n No overall improvement with grouped (vs. random) icon arrays, although interaction by numeracy level. Some teratogen warning symbols Alternative Media 4 RCT examining Insufficient 3): = Effect of adding or substituting for print (n alternate media; Effect for adding video, computer, or slide show 3 examining adding presentations to print were mixed. Effect for simplified or substituting print were mixed depending on the reading level of the other media for printed materials and study design and quality Effect of adding video to verbal narrative (n = 1): print and 1 examining adding Improved knowledge and preference for comfort care. video to verbal narrative Alternative Insufficient 6 RCTs, 1 quasi - Mixed results depending on degree of simplification, Readability and d study quality literacy level of population, an experimental study Document -only data with post Design Physician Low No effect on patient level outcomes 1 cRCT Notification of Patient Literacy Status RCTs =randomized controlled trials; info= information; vs. =versus; cRCT =cluster randomized controlled trial 181

204 Table 47. Single intervention strategies: alternative numerical presentation % population Author, Date of with Limited Sample Study Publication, Literacy/ Quality Size Difference design Control Numeracy Outcomes Intervention 50% (score < 10 Mean # correct 303 Peters et al., RCT Lower is better, Higher is better vs. Lower is better (1) higher is 188 better, no (unadjusted): responses to on DR 2007 no symbols (Study 3) Comprehension: Numeracy Test) comprehension symbols Overall: +0.4, (P < 0.001) questions (range 0- High literacy Subgroup:+0.2, NS (2) lower is Fair 4) better, symbols Low literacy Subgroup: % choosing higher a, (P < 0.01) +0.7 quality hospital (3) higher is better, symbols Choice: Overall: +13%, (P < 0.01) High Literacy Subgroup: NR (interaction by symbols) Low Numeracy Subgroup: +20% a, (P < 0.05) Symbols vs. No Symbols: Comprehension: Overall: NR, P < 0.10 High Literacy Subgroup: -0.3a, (P < 0.05) a , NR Literacy Subgroup: -0.1 Low Choice: Higher Literacy Subgroup: -7%a, NR Lower Literacy Subgroup: +5%a, NR Higher # better, no symbols vs. Control: High Literacy Subgroup: Comprehension: +0.3, NR Choice: 4% - a b c Weighted percent; Calculated by reviewers; Calculated by research team =randomized controlled trial; vs. =versus. 12- pt=12- point; NR =not reported; NS =not significant; RCT 182

205 Table 47. Single intervention strategies: alternative numerical presentation (continued) Author, % population with Limited Date of Sample Study Literacy/ Publication, Size design Intervention Numeracy Outcomes Quality Control Difference Low Literacy Subgroup: Comprehension: +0.3, NR P < 0.05) Choice: +26%, ( Lower # better + symbols vs. Control (unadjusted): Literacy Subgroup: High Comprehension: -0.2, NR Choice: -19% Low Literacy Subgroup: -0.2, NR Comprehension: Choice: +12%, NR Higher # better + symbols vs. Control (unadjusted): High Literacy Subgroup: -0.1, NR Comprehension: Choice: +1% oup: Low Literacy Subgr Comprehension: +0.5, NR < 0.05) P Choice: +25%, ( Galesic et 162 Natural frequency vs. conditional RCT Information % Accurately Mean numeracy Natural 217 perceiving risk pt scale on 12- al., 2009 probability overall (unadjusted): frequencies about genetic NR, (P = 0.001) testing for derived from (x/10,000) (47 older Fair early detection adults, 115 Lipkus & Presented to High numeracy vs. low numeracy, overall Schwartz: of diabetes or younger illustrate the (unadjusted): NR, (P +0.01) trisomy 21 adults) 9.7 Overall: positive value presented as of genetic Absolute difference in accurate answers conditional Older adults: 8.6 testing for early (% all correct) by numeracy (unadjusted): probabilities detection of (% with Younger adults: diabetes or High numeracy (natural frequency vs. condition, a , NR 10.3 trisomy 21 conditional probability): + 24% Low numeracy (natural frequency vs. a conditional probability): +27% , NR 183

206 Table 47. Single intervention strategies: alternative numerical presentation (continued) % population Author, with Limited Date of Study Sample Publication, Literacy/ Size design Control Numeracy Outcomes Difference Intervention Quality probability of + Absolute difference (younger vs. older, = 0.31) P overall): NR, ( test with disease, probability of negative test with disease) Garcia - % Accurate Numerical Factoria % accurate, same versus different Numerical 1047 49% Low perception of risk Retamero et l RCT information denominators (with or without icon information numeracy (> 219 reduction al., 2009 with different arrays): with the same (534 from median score denominators denominators German, on 9-item scale c , P not reported Fair for baseline Low numeracy: +25% for baseline 513 from adapted from risk and risk and US) Lipkus and c High numeracy: +16% , P not reported treatment treatment Schwartz) benefit benefit Overall effect of denominator: not (800/100 or (800/800 and (Germany: b = 0.001) P reported, adjusted ( , US: 100/800) 100/100) 49% c ) 48% Overall effect of numeracy: adjusted ( P = 0.001) 184

207 and alternative pictorial representation Table 48. Single intervention strategies: additive % Population Author, Date Study Sample of Publication, with Limited Intervention Quality Size Outcomes Literacy design Difference Control No icon Factorial Galesic et al., Icon arrays 171 Mean numeracy: Older adults, high % Accurately 216 arrays (either RCT 2009 numeracy on Icons vs Numerical RRR (unadjusted): perceiving risk a ARR or RRR (59 older 12-pt scale +11%, NS Fair numerical adults, derived from Icons vs Numerical ARR (unadjusted): a presentation) 112 Lipkus & +5%, NS students) Schwartz: Older adults, low numeracy: Icons vs Numerical RRR (unadjusted): Older adults: a +75%, sig 8.6 Icons vs. Numerical ARR (unadjusted): a +30%, sig Students: 10.3 Students, high numeracy: Icons vs Numerical RRR (unadjusted): a +23%,sig - Icons vs Numerical ARR (unadjusted): a 1%, NS Students, low numeracy: Icons vs Numerical RRR (unadjusted): a +24%, NS Icons vs Numerical ARR (unadjusted): a +21%, NS Overall p for numerical format (ARR vs b , (P = 0.001) RRR): +49% b overall p for icon array (yes/no):+23% (P = 0.002) b c a d Calculated by research team Calculated by research team; difference calculated by research team, significance read from figure; Weighted percents; =not otherwise specified; 12- point; ARR =absol ute risk ratio; B&W symbols =black and white symbols; CI =confidence interval; e.g. =example; info =information; NOS pt=12- NR =not reported; NS = not significant; OR =odds ratio; Quasi -= quasi -experimental study; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in =versus. =United States; vs. Medicine; RRR =relative risk ratio; sig =significant; US 185

208 Table 48. Single intervention strategies: additive and alternative pictorial representation (continued) % Population Author, Date Study Sample with Limited Publication, of Outcomes Intervention Size Control Literacy Difference Quality design % Accurate - Garcia Numerical Factorial Accurate estimates difference (when size Numerical 1047 49% Low perception of risk Retamero et RCT information of denominators different; unadjusted): information plus numeracy (> 219 reduction al., 2009 only icon array (534 from median score (including Low numeracy: +32%c, P NR (including German, on 9-item Fair varying sizes High numeracy: +11%c, P NR information 513 from scale adapted of presented with US) from Lipkus denominator) Accurate estimates difference (when size varying sizes of and of denominator same; unadjusted): denominators) Schwartz) Low numeracy: +11%c, P NR (Germany: c, US: High numeracy: -16%c, P NR 49% c ) 48% Interactions between numeracy and icon arrays (P = 0.008) and size of denominators and icon arrays = 0.001) (P Hwang et al., 5% REALM ≤ 130 Medication label - Quasi % correctly Medication Change in Interpretation of Label B with 195 2005 text + illustration 6th grade (post - interpreting label text: illustration: post) prescription label Improved: 5 Fair 22% REALM A. Take with No Change: 87% 7th -8th grade water Worse: 9% (unadjusted P = 0.33) B. May cause Change in Interpretation of Label E with drowsiness illustration Improved: 7% C. Take with No Change: 86% food Worse: 7% (unadjusted P = 1.00) D. No alcohol Note: change in interpretation of labels A, C, D = 0 E. Take on an empty stomach 186

209 Table 48. Single intervention strategies: additive and alternative pictorial representation (continued) % Population Author, Date Study Sample with Limited of Publication, Intervention Size design Literacy Outcomes Difference Quality Control Mayhorn and 42.9% Low 700 Quasi - % Who c orrectly Original (1) Original "Don't take if pregnant" (x versus original Goldsworthy, literacy (post identify symbol teratogen symbol, but symbol 3) 189 (REALM, 2007 only) meaning as “don’t symbol woman taking Symbol 1 +4%, NR NOS) take if pregnant” pill Symbol 2: -8%, NR Fair (slash Symbol 4: +3%, NR % Who correctly through (2) Cross and Symbol 5: +8%, NR identify symbol as pregnant skull bones in -29%, NR Symbol 6: “causes birth woman) pregnant belly Symbol 7: -10%, NR defect” (4) 2 pictures: "Causes birth defects" (x versus original Original symbol symbol 3) + skull bones in Symbol 1: -1%, NR pregnant belly Symbol 2: +14%, NR Symbol 4: +19%, NR (5) 2 pictures: #4 Symbol 5: +14%, NR but more Symbol 6: +4%, NR caricatured Symbol 7: +15%, NR (6) 1 picture Note: addition of text that says “causes combining ease understanding for birth defects” incr original symbol + all skull bones in pregnant belly (7) skull bones in pregnant belly + inlay with slash through person taking pills 187

210 Table 48. Single intervention strategies: additive and alternative pictorial representation (continued) % Population Author, Date Study Sample of Publication, with Limited Intervention Difference Size Control design Outcomes Quality Literacy (1) essential info Numbers RCT Peters et al., 303 Mean # of correct 50% (Median Symbols vs. Numbers (unadjusted): 188 only (e.g. death 2007 split) comprehension rates) (Study 2) questions (range Overall: accompanied by 0-3) Comprehension: NR, NS P < 0.05) Choice: +14%, ( Fair black/white symbols % choosing higher quality High Numeracy Subgroup: (2) essential info hospital Comprehension: NR c , NR (e.g. death Choice: +18% rates) Low Numeracy Subgroup: accompanied by Comprehension: NR traffic symbols c Choice: -5% , NR (3) essential and p for interaction by numeracy: non-essential P < 0.001) Comprehension: ( info (e.g. death Choice: NR rates and satisfaction) Colored vs. B & W symbols (unadjusted): accompanied by black/white Overall: symbols Comprehension: NR d , NS Choice: +3% (4) essential and non-essential High Literacy Subgroup: info (e.g. death Comprehension: NR rates and d Choice: 16% < 0.05) , ( P satisfaction) accompanied by Low Literacy Subgroup: traffic symbols Comprehension: NR d Choice: - 11% , NS 188

211 Table 48. Single intervention strategies: additive and alternative pictorial representation (continued) % Population Author, Date Study Sample of Publication, with Limited Intervention Quality Size Difference design Literacy Outcomes Control Effect of Symbols on Choice: Peters et al., 188 2007 Essential info with B&W symbols (Study 2) (continued) (unadjusted): High Literacy Subgroup: +12%, NR Low Literacy Subgroup: +11%, NR Essential info with traffic light symbols (unadjusted): High Literacy Subgroup: +29%, NR Low Literacy Subgroup: +6%, NR Essential and non -essential info with B&W symbols (unadjusted): High Literacy Subgroup: +7%, NR Low Literacy Subgroup: -9%, NR Essential and non -esse ntial info with traffic light symbols (unadjusted): High Literacy Subgroup: +22%, NR Low Literacy Subgroup: -26%, NR p for interaction (essential vs. non- essential): P < 0.05 p for interaction (literacy level): P < 0.05 189

212 Table 48. Single intervention strategies: additive and alternative pictorial representation (continued) % Population Author, Date Study Sample of Publication, with Limited Intervention Quality Literacy design Outcomes Difference Control Size RCT Lower Peters et al., (1) higher 50% (score < 303 Mean # correct Symbols vs. No Symbols (unadjusted): 188 number is 2007 number is better 10 on DR responses to better (Study 3) quality, no Numeracy comprehension Comprehension: Overall: NR, P < 0.10 quality, no symbols Test) questions (range Fair symbols 0-4) High Literacy Subgroup: c P , ( < 0.05) -0.3 (2) lower number d , NR Low Literacy Subgroup: -0.1 is better quality, % choosing symbols higher quality Choice: hospital Higher Literacy Subgroup: (3) higher c , NR -7% number is better Lower Literacy Subgroup: quality, symbols c , NR +5% Higher # better, no symbols vs. Control (unadjusted): High Literacy Subgroup: Comprehension: +0.3, NR -4% Choice: Low Literacy Subgroup: Comprehension: +0.3, NR Choice: +26%, ( P < 0.05) Lower # better + symbols vs. Control (unadjusted): High Literacy Subgroup: Comprehension: -0.2, NR Choice: -19%, P not reported Low Literacy Subgroup: Comprehension: -0.2, NR Choice: +12%, P , NR 190

213 Table 48. Single intervention strategies: additive and alternative pictorial representation (continued) Author, Date % Population Sample Study with Limited of Publication, design Size Control Literacy Outcomes Difference Quality Intervention Higher # better + symbols vs. Control Peters et al., 188 (unadjusted): 2007 (Study 3) (continued) High Literacy Subgroup: Comprehension: -0.1, NR Choice: +1% Low Literacy Subgroup: Comprehension: +0.5, NR Choice: +25%, (P < 0.05) Overall: Walker et al., Mean Rheumatoid 15% REALM RCT Standard 363 Standard 133 < 60 (9th Arthritis 2007 Arthritis Arthritis booklet -0.11, (unadjusted P > 0.3) grade) + Mind Map Booklet Knowledge Score Fair (range -40 to 40) Note: REALM score predicts change in knowledge, (adjusted P < 0.003) 140 41% Low % Grouped dot RCT Dispersed correctly Wright et al., Grouped vs. dispersed dot icon arrays, 186 adjusted OR comprehension: icon arrays identifying largest dot icon 2009 d 2.26 (95% CI 0.779 to 6.57) (incorrect of 3 displayed arrays (3 different risk Fair answer to 1st risks magnitudes: 3%, Comprehension with grouped dot icon (3 different question on 6%, 50%) array (unadjusted OR high vs. low risk Lipkus numeracy): magnitudes: numeracy 0) 3.830 (95% CI, 1.301-11.28 3%, 6%, scale) 50%) Comprehension with dispersed dot icon array (unadjusted OR high vs. low numeracy): 10.2, CI, NR Interaction term (display by numeracy): NS 191

214 Table 49. Single intervention strategies: alternative media % Population Author, Date of Study Sample Publication, Limited Intervention Sizes design Literacy Outcomes Quality Difference Control Mean number of errors Multimedia Mean symptom score error: RCT 232 28% < high Bryant et al., 213 -1.51 -written): -SS compared on AUA computer version Overall (multimedia school on 2009 ( P < 0.001) Fair professional - REALM of American with health- ≥ HS: P <0.001) -1.24 ( REALM Mean -SS Urological administered AUA 0.03) P < HS: -2.31 ( - % understanding AUA score: 59 Association’s % understanding of questions SS questions (i.e. less BPH symptom overall (multimedia-written): 19% than 2- pt difference score AUA -SS ( P NR) between experimental P ≥ HS: +18% ( NR) derived and interviewer NR) P < HS: +25% ( derived scores) Acc Accuracy of categorical uracy of classification: +13% ( P = 0.04) - assification on AUA cl SS Campbell et al., % of total information remembered % of total information < 50% Low ( RCT Standard 233 (1) Simplified 200 print consent on free recall (adjusted): print consent 2004 8th grade remembered on free Simplified vs. standard: +0.1%, NS Fair form reading level recall form Video vs. standard: 0.1% < NS % of correct answers on (2) Video on Woodcock tandard: -0.1%, NS Computer vs. s prompted recall consent Johnson) Average Note: No interaction by literacy level (3) Computerized REALM score (unadjusted) consent 56.3 % correct answers on prompted recall (adjusted): Simplified vs. standard: +6%, NS Note: Trend toward improvement in low literacy group (unadjusted) Video vs. standard: +3%, NS Computer vs. standard: +4%, ( P = 0.08) a Calculated by research team 2-pt =2-point; AUA -SS= American Urological Association -Symptom Score; BPH =benign prostatic hyperplasia; CI =confidence interval; HL =health literacy; HS =high school; info =information; MIC =modified informed consent; MIC + SS =modified informed consent + slide show; NR =not reported; NS =not significant; OR =odds ratio; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; ref =reference; vs. =versus; WRAT =Wide Range Achieveme nt Test. 192

215 Table 49. Single intervention strategies: alternative media (continued) Author, Date of % Population Study Sample Limited Publication, Difference Sizes design Literacy Outcomes Control Intervention Quality RCT Standard 1) MIC form % with combined recall Combined recall and comprehension Patient: Kang et al., 90 212 (unadjusted): informed 2) MIC + slide info and 2009 of Median Patient: Fair consent comprehension show REALM and a , NS MIC vs. control: +6.5% WRAT scores: (MIC + SS) a , NS -1.2% MIC +SS vs. control: high school Parent: Note: recall improves with MIC + SS P < 0.05), comprehension (10.5%, Median does not (+6.3%, NS) REALM and Parent: WRAT scores: a MIC vs. control: 1.4% , NS high school a MIC + SS vs. control: +10.0 < P , ( Note: 0.05) Intervention Note: recall improves with MIC + SS delivered to a (+8.9 , P < 0.05), so does patient and a comprehension (+11.6% , parent P < 0.001) Mean knowledge: RCT Verbal narrative Volandes et al., Mean knowledge on 5 - 200 ≤ 6th 18% 184 < P Unadjusted difference: +0.9, ( grade on point scale (higher + 2009 0.001) Good REALM Video showing scores better) Overall preference for comfort care: 8th 12% 7- % Preferring comfort features of Unadjusted difference: +22% (95% care grade on advanced CI, 11% to 34%) REALM dementia Adjusted OR: 3.9 (1.8-8.6) Preference for comfort care by HL group: Unadjusted differences: ≤ 6th grade HL: ref 7th -13 to 38%) -8th grade HL: 13% ( ≥ 9th grade HL: 39% (21% to 56%) Adjusted OR: ≤ 6th gra de HL: ref 7th -8th grade HL: 1.7 (0.54- 5.3) ≥ 9th grade HL: 4.1 (1.6 - 10.8) 193

216 Table 50. Single intervention strategies: Alternative readability and document design Author, Date of Sample % Population with Study Publication, Quality Size Control Limited Literacy Outcomes Difference Intervention design 8th % of total Standard % of total information remembered on Campbell et al., (1) RCT < 50% Low ( 233 200 free recall (adjusted): Simplified 2004 information grade reading level print consent print remembered on Woodcock Fair +0.1%, NS Simplified vs. standard: Johnson) form on free consent form recall Note: No interaction by literacy level % of correct (2) Video Average REALM answers on consent score 56.3 prompted recall (3) % correct answers on prompted recall Computerize (adjusted): d consent Simplified vs. standard: +6%, NS Note: Trend toward improvement in low literacy group 199 Standard RCT 44 oncology Simplified : 65 Mean REALM % of answers Overall difference (unadjusted): Coyne et al., 2003 P = 0.21) 3%, ( groups consent form Consent correct to 23 Fair Form comprehensi 226 patients questions on Note: Also measured decision to participate a b Calculated by research team; Read from table Lit =literacy; NR =not reported; NS =Rapid Estimate of Adult =odds ratio; Quasi -= quasi -experimental study; RCT =randomized controlled trial; REALM =not significant; OR Literacy in Medicine; std =standard; TOFHLA =Test of Functional Health Literacy in Adults; WRAT =Wide Range Achievement Test. 194

217 Table 50. Single intervention strategies: Alternative readability and document design (continued) Sample Study % Population with Author, Date of Intervention Size Design Limited Literacy Outcomes Difference Control Publication, Quality 57% TOFHLA Cloze Compre - 122 Full index (unadjusted, out of 9): RCT Revised Greene and Peters, 214 2009 score ≤ 18 (out of 20) Overall: NR Medicaid health hension (# plan Low Lit: +0.1a, NS of correct Fair comparison ans wers) High Lit: +0.7a, NS chart with four key changes: Identifying subindex (unadjusted, out of 6): Overall: NR (1) List only the Low Lit: -0.2a, NS benefits with High Lit: +0.5a, NS differences between plans Synthesizing Subindex (unadjusted, out of 3): (2) Cost - Overall: NR sharing and Lit: +0.3a, NS Low benefit High Lit: +0.1a, NS information in rows rather p for interaction for full and sub-indices < than columns 0.05 (3) Arranged plans from most generous to least generous based on cost - sharing and benefits (instead of alphabetically) (4) Increased font size to 10 (13 for headers) 195

218 Table 50. Single intervention strategies: Alternative readability and document design (continued) % Population with Author, Date of Study Sample Control Size Limited Literacy Intervention Outcomes Difference Design Publication, Quality 212 RCT Standard 90 Patient: 1) Modified Kang et al., 2009 Combined recall and comprehension % with Median REALM and combined informed (unadjusted difference): informed Fair consent form recall of WRAT scores: high consent Patient: (MIC) school info and compre- a , NS 2) Modified Parent: MIC -control: +6.5% hension informed Median REALM and Parent: consent + slide WRAT scores: high show school a , NS MIC -control: 1.4% (MIC + SS) Note: Intervention delivered to patient and parent 192 Sudore et al., 2006 # of passes 22% TOFHLA Quasi - 204 Simplified None Overall # of passes through teach to (post Inadequate goal: through the consent form only) Fair teach-to 1: 28% -goal 2: 53% 18% TOFHLA Marginal consent process 3: 20% required to obtain Unadjusted P for literacy interaction: 0.02; 11% of those with inadequate consent literacy required only 1 pass whereas # of compre- 36% of individuals with adequate hension literacy required only 1 pass statements missed on Adjusted OR for requiring more than 1 the first pass - pass (for each 1-pt decrease in s of TOFHLA): 1.04 (95% CI 1.00 to 1.07) questioning # of comprehension statements missed on first pass questioning: 0: 28% 1: 30% 2 or more: 42% Adjusted OR for missing comprehension (for each 1-pt decrease in s -TOFHLA): 1.04 (95% CI 1.00 to 1.07) 196

219 Table 50. Single intervention strategies: Alternative readability and document design (continued) Author, Date of Sample % Population with Study Intervention Publication, Quality Size Design Outcomes Difference Control Limited Literacy 204 Knowledge (adjusted for baseline RCT Standard Knowledge of Simplified 205 40% Sudore et al., 2007 208 knowledge): +1%, (P = 0.30) Advanced Sudore et al., 2008 TOFHLA advance Advanced Directive Directive directive < 22 (Inadequate or Fair Advance directive completed at 6 Marginal) topics, months (unadjusted): +11%, (P = Advance 0.03) directive completion at 6 months Note: Also measure % of form completed Yates and Pena, Median score: +1 correct: (unadjusted Mean 1.5% REALM < 7th 200 Simplified head RCT Standard 191 comprehensi P < 0.0001) 2006 trauma advice gradeb head trauma on score form (range 0-10) Fair advice form 14% REALM 7th-8th Adjusted OR comprehension gradeb (simplified versus std): 4.14 (2.19 - 7.81) No interaction by literacy level 197

220 a Table 51. Single intervention strategies: physician notification of patient literacy levels % Author, Date of Population Study Sample Publication, Limited Size Control Quality Literacy Intervention Outcomes Difference design cRCT Usual Physician Seligman et al., 74% 63 MDs % of physicians % physicians with intensive use of 181 Care for notification of 2005 TOFHLA 182 pts reporting use of > 3 communication strategies (adjusted OR): patients' health Diabetes Fair Inadequate communication -16.0 4.7, 95% CI, 1.4 literacy status 16% enhancing strategies Note: trends toward differences for TOFHLA - Mean patient Self individual communication strategies of Marginal efficacy using Patient involving family/friends and referring to a Enablement Instrument nutritionist (ra nge 0-12) -efficacy (adjusted): -0.3, Pati ent Self Mean HgbA1c (P = 0.61) HbA1c (adjusted): -0.27, 95% CI, -0.80- 0.27 a Communication strategies include Involving family members or friends; referring to a nutritionist; using pictures of diagrams ; referring to a diabetes educator; reviewed understanding of medications; spending time teaching about diabetes CI= confidence interval; cRCT =cluster randomized controlled trial; HgbA1c =glycosylated hemoglobin; MDs =medical doctors; OR =odds ratio; pts =patients; TOFHLA =Test of Functional Healt h Literacy in Adults. 198

221 Table 52. Effect of mixed interventions on use of health care services Author, Date % Population of Study Control Sample with Limited Publication, Intervention Size Design Literacy Outcome Difference Quality Group RCT Usual Care + DeWalt et al., - 41% S 127 CHF Self - Hospitalization or death: Hospitalization 202 low literacy 2006 Management TOFHLA Overall: IRR (unadjusted) = 0.69 (95% pamphlet on Fair program inadequate CI, 0.40 -1.19) CHF Inadequate literacy subgroup: IRR (adjusted) = 0.39 (95% CI, 0.16- 0.91) Marginal/adequate literacy subgroup: IRR (adjusted) = 0.56 (95% CI, 0.30- 1.04) 113 MDs Difference % of patients for whom cRCT Usual Care Educational in Any Recommendations: 31% Low (< Ferreira et al., 196 = 0.02) P Overall: 6.6%, ( 9th grade on 2005 1978 pts Intervention for any CRC screening a Literacy subgroup results NR Fair is recommended in test Physicians and TOFHLA) Note: Difference in Completion of Any Tests: 18 months following Patients on P Overall: 8.9%, ( = 0.003) measured only visit Colorectal Low Literacy Subgroup: % of patients for whom in 19% of Cancer b 25.7%, (unadjusted P = 0.002) screening is completed patients screening High Literacy Subgroup: 3%, (unadjusted within x timeframe b =0.65) P Gerber et al., Low Literacy Subgroup: Receipt of - 56% S RCT Usual Care + 144 - Diabetes Self 194 Management Change Medical Care (adjusted): -0.29, TOFHLA < 22 computerized 2005 Recommended Medical Fair (Inadequate or Intervention Services (NOS) quizzes on NS High Literacy Subgroup: marginal) - diabetes Change Medical Care (adjusted): -0.07, related NS concepts a b any CRC screening test includes home fecal occult blood testing, sigmoidoscopy, and colonoscopy; adjusted only for effects of clustering of patients within providers =congestive heart failure; CI CHF =colorectal cancer; cRCT =cluster randomized controlled trial; DRE= digital rectal examination; ED =emergency =confidence interval; CRC department; ER =emergency room; IRR =incidence rate ratio; MDs =medical docto rs; NA =not applicable; NOS =not otherwise specified; NR =not reported; NS =not significant; OR =odds ratio; PSA = prostate specific antigen; pts =patients; Quasi =quasi -experimental study; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in =Test of Functional Health Literacy in Adults Medicine; S -TOFHLA =short form Test of Functional Health Literacy in Adults; TOFHLA 199

222 Table 52. Effect of mixed interventions on use of health care services (continued) Author, Date % Population of Study Control Sample with Limited Publication, Intervention Size Quality Design Literacy Outcome Difference Group RCT Handout, NOS 303 38% REALM < Kripalani et al., (1) Educational Education PSA test ordered 203 Unclear if 2007 3rd grade Intervention on PSA test ordered (adjusted OR): 7.62; DRE documented prostate Fair 18% REALM Prostate CI, 1.62 -35.83 content or 4th -6th grade Cancer DRE documented (adjusted OR): 0.85; other content 23% REALM Screening CI 0.21 -3.37 (2) Cue to 7th -8th grade Cue Discuss PSA test ordered (adjusted OR): 5.86; Prostate CI, 1.24 -27.81 DRE documented (adjusted OR): 1.04; Cancer screening CI, 0.29 - 3.76 RCT CHF Usual Care Murray et al., 314 29% “not ED visit ED visits: 182 Adherence 2007 literate” on S - Hospitalization -0.52, Absolute difference(unadjusted): Intervention Good TOFHLA NR (NOS) Incidence rate ratio (unadjusted): 0.82 (0.70 to 0.95) Hospitalizations: -0.21, Absolute difference (unadjusted): NR Incidence rate ratio (unadjusted): 0.81 (95%, CI 0.64 1.04) - < P 29.6%, ( ED visits (unadjusted): - Robinson et -related ED Quasi Asthma Mean Gilmore 110 NA Asthma Self - 207 visits: Oral Reading (pre - Management al., 2008 0.01) Fair Asthma -related Test Score: 3.2 Intervention post) Interaction by literacy subgroup: adjusted hospitalizations: OR for Effect of reading level on ER visits: 0.34 (0.22 - 0.52) Hospitalizations (unadjusted): -14.9%, ( P < 0.001) Interaction by literacy subgroup: adjusted OR for e ffect of reading level on ER visits: 1.31 (0.82 to 2.10) 200

223 Table 53. KQ 2 Mixed interventions: strength of evidence grades by type of outcome Number of Studies Results Overall Grade Outcome Use of 2): Increased use across Moderate Preventive services (n 4 RCTs, 1cRCT, = Healthcare - and 1 quasi literacy levels Services = 2): Reduced use across literacy levels ED visits (n experimental study = 3): Reduced use (or trends Hospitalizations (n toward reduced use) across literacy levels; greater reductions in low literacy population Knowledge Insufficient 3 RCTs and 7 Mixed results with 4 of 8 studies with interpretable data showing an effect on knowledge quasi -experimental studies (including 2 -test only with post data on knowledge, which precluded conclusions) Self Efficacy 4 RCTs and 5 Mixed results depending on intensity of intervention; Insufficient for intensive interventions although these analyses for -experimental quasi vel these interventions weren’t stratified by literacy le studies a Skill Improved label reading skill with greater effect in those 1 RCT Insufficient with high literacy (However, 2 studies from 2004 review found mixed results) Behavior 2 RCTs and 1 Moderate Improved self -management behaviors, greater improvement in adequate literacy group in the 1 study quasi -experimental study that performed analysis stratified by literacy level Adherence 3 RCTs and 2 Insufficient the Mixed results related to the intensity of intervention and measure of adherence quasi -experimental studies (1 with post test only data) - Disease - Self 3): mixed effects on 4 RCTs, 3 quasi - management = Self - management programs (n Prevalence and biomarkers depending on study quality programs: experimental Severity studies Insufficient improved = 2): Disease management programs (n Disease HbA1c in low literacy group, improved BP across management programs: literacy levels moderate Adult basic and = 1): improved Adult Basic and Literacy Education (n literacy education: depression severity across literacy levels low Quality of Life 4 RCTs (1 Mixed results Insufficient measured QoL -test in only post intervention group) Costs 2 RCT Non - significant trend toward reduced cost across Insufficient literacy groups a data from 2004 review modified the overall strength of evidence from low to insufficient =randomized controlled trials; HbA1c RCTs =cluster =glycosylated hemoglobin; BP =blood pressure; QoL =quality of Life; cRCT randomized controlled trial; ED =emergency department 201

224 54. Effect of mixed interventions on knowledge Table Author, Date of Control Sample % Population with Difference Between Control and Publication, Size Group Limited Literacy Outcome Intervention Groups Design Intervention Quality a = 0.49) Overall: 0, (unadjusted P Tailored Usual Care 588 38% low literacy Mean Change in RCT Bosworth et al., 201 Hypertension Adherence 2005 Fair knowledge (score Intervention range 0 - 10) < 0.005) P Overall: NR, (unadjusted 51 Quasi - (pre Brock and - Mean HIV and HIV NA Adherence 55% REALM < 8th 220 grade medication Video on PDA post) Smith, 2007 Fair (although Knowledge (9-pt. scale) poor for adherence) Patient recall of recommendations: Davis et al., Patient recall of MD Quasi - (pre - 49% REALM < 6th None Weight loss 101 205 = P Lose weight +43%, (unadjusted post) grade 2008 recs. to lose weight, intervention Fair 22% REALM 0.02) increase physical Increase physical activity +41%, -8th 7th grade activity or see a (unadjusted P = 0.01) dietician P sted Go to dietician +39%, (unadju = 0.002) - DeWalt et al., Usual Care + TOFHLA - Overall (adjusted): 12% (95% CI, 6 CHF Self - % CHF Knowledge 127 41% S RCT 202 questions correct 18%) 2006 low literacy Management inadeq. Fair pamphlet on program CHF Low Literacy Mean Change in TOFHLA < 22 - RCT Usual Care + 56% S 144 - Diabetes Self Gerber et al., 194 Management Diabetes Knowledge Change Knowledge (adjusted): -0.12, (Inadeq. or marginal) computerized 2005 (scale NR) Fair quizzes on NS Intervention High Literacy diabetes - Change Knowledge (adjusted): +0.3, related concepts NS a b absolute difference calculated by research team Determined through personal communication with author; 9-point scale; adeq. 9-pt. scale= =congestive heart failure; CI =confidence interval; HIPAA =Health Insurance Portability and Accountability Act of 1996; =adequate; CHF HIV =human immunodeficiency virus; HL =health literacy; inadeq. =inadequate; MD rec. =physician’s recommendations; NA =not applicable; NR =not reported; NS =not significant; PDA =personal digital assistant; Qua si-= quasi -experimental study; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; sig =significant; S - =versus. =Test of Functional Health Literacy in Adults; vs. TOFHLA =short form Test of Functional Health Literacy in Adults; TOFHLA 202

225 Table 54. Effect of mixed interventions on knowledge (continued) Author, Date of Control Sample % Population with Difference Between Control and Publication, Intervention Design Size Limited Literacy Outcome Quality Intervention Groups Group Kripalani et al., Correct teach back 1st attempt by Odds of correctly 21% REALM < 3rd Quasi - (post 408 No control 1) Modified 206 Print informed literacy subgroup (adjusted): only) grade teaching back 2008 Fair 25% REALM 4th - 6th 4.869) - 6th grade - 4th consent and HIPAA Consent with 2.259 (1.048- 2.275 (1.049- - 8th grade - grade 7th 4.935) Oral Overview on first information 8th - 4.344 (1.814-10.404) 31% REALM 7th - > 9th grade attempt (relative to grade those with literacy level < 3rd grade Diabetes Self Kim et al Overall (adjusted): % Diabetes Quasi - (pre - TOFHLA < 22 - None ., - 23% S 92 197 Management post) (Inadeq. or marginal) Knowledge Questions 2004 NR, sig Adeq. vs. Inadeq. HL (adjusted): (15% inadeq. on Fair Intervention Correct NR (+), (P < 0.001) TOFHLA) - Orlow - Quasi - (pre - Paasche Asthma Knowledge: NR NA Asthma Self - Asthma Knowledge 73 22% S TOFHLA 79 Management (range 0-10) % post; pre-test et al., 2005 Mastering discharge medication Inadeq. % Mastering Fair 2 weeks): regimen (baseline- only for Intervention discharge medication knowledge) Overall (unadjusted): + 20%, NR; p for interaction by literacy: (P = 0.40) regimen Quasi - 26% with low literacy - Mean knowledge score (post No control Linear video Mean score on 12 pre, 130 Sobel et al., 215 tutorial about asthma knowledge unadjusted): +2.6 b, (P < 0.001) experimental 2009 (0-44 on REALM) Mean knowledge score (post 33% with marginal Fair asthma and its -pre, -post) questions (range 0- (pre management sted) compared to adequate adju literacy (45 -60 on 12) REALM) literacy score: Adequate: reference -0.8 (95% CI, -1.5 to -0.1) Marginal: - 1.5 (95% CI, - 2.3 to - 0.6) Low: Wallace et al., Overall (unadjusted): 6.16%, (P <0.001) % of Diabetes 29% TOFHLA inadeq. Quasi - (pre - 250 NA Diabetes Self - 211 Management post) 14% TOFHLA Knowledge questions 2009 Adequate Literacy subgroup correct Intervention Fair marginal (unadjusted): +6.94%, NR Marginal/inadequate Literacy subgroup (unadjusted): +5.21%, NR Unadjusted P for interaction by literacy level: 0.23 203

226 efficacy Table 55. Effect of mixed interventions on self- Author, Date of % Population Study Sample Publication, with Limited Control Group Size Quality Literacy Intervention Difference Design Outcome = P Overall (unadjusted): +27%, ( Quasi - Davis et al., % patients 49% REALM < None Weight loss 101 205 2008 6th grade 0.01) intervention (pre - reporting Fair 22% REALM confidence in post) -8th grade 7th ability to lose weight DeWalt et al., Overall (adjusted): Mean difference in RCT Usual Care + low -TOFHLA 41% S 127 CHF Self - 202 -efficacy 2 (95% CI, 0.7-3.1) Management CHF self literacy pamphlet inadeq. 2006 on CHF (range of scores Fair program 2(4) - 0 Change in Mean Low Literacy Gerber et al., TOFHLA RCT Usual Care + - 56% S Diabetes Self - 144 194 Management -efficacy (adjusted): computerized < 22 (Inadeq. or Change Self - 2005 Diabetes Self Fair quizzes on 13 +0.52, 0.1 marginal) Intervention efficacy – (score High Literacy -related diabetes range NR) -efficacy (adjusted): Change Self concepts 0.20, NS - Overall (unadjusted): Mean Self Efficacy Kripalani et al., Quasi - < 42% REALM None CHD adherence 242 190 - (pre 6th grade intervention (pill 2007 for Appropriate +2.5, NR 37% REALM card) Medication Use Fair post) -8th grade Scale (score 7th - range 13 39) Asthma Self Overall (unadjusted): Mean Asthma Self Quasi - Mean Gilmore NA Robinson et al., - 110 207 < 0.001) P 10.4, ( Efficacy Scale - 2008 Oral Reading (pre Management Intervention (scale 40 - 100) Fair post) Test Score: 3.2 ATSM -management support; ATSM -GMV =automated telephone self -management support -group medical visits; CHD =coronary heart disease; =automated telephone self CHF =congestive heart failure; CI =confidence interval; GMV =group medical visits; inadeq. =inadequate; mo. =month; NA =not applicable; NR =not reported; NS =not significant; quasi -= quasi -experimental study; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; S -TOFHLA =short form Test of Functional Health Literacy in Adults; TOFHLA =Test of Functional Health Literacy in Adults. 204

227 Table 55. Effect of mixed interventions on self- efficacy (continued) % Population Author, Date of Study Sample Publication, with Limited Control Group Intervention Quality Size Literacy Outcome Difference De sign Arthritis RCT Arthritis < 19% REALM Overall at 12 mo. (adjusted): 127 Rudd et al., efficacy - Mean self 209 NR, ( P = 0.12) 2009 4) Management (score range 1- Management high school Fair Intervention + Intervention Individual (arthritis pamphlet, medicine Counseling calendar, hospital map) 339 - TOFHLA Mean Diabetes ): 6.0 Usual Care (adjusted RCT 59% S Schillinger et usual care (1) Diabetes Self - ATSM 187 -efficacy (0 - self (2.0 to 10.1) 22 (inadeq. or Management al., 2008 < ; -Usual Care (adjusted): 5.5 Schillinger et GMV marginal) Program 100 scale) 210 al., 2009 (1.4 to 9.6) (automated -3.6 to -GMV (adjusted): 0.5 ( ATSM Fair telephone 4.6) delivery) - (2) Diabetes Self Management Program (group medical visit delivery) Quasi - Wallace et al., - Diabetes Self NA 29% TOFHLA 250 Mean diabetes Overall (unadjusted): 211 (pre - 2009 Management inadeq. - self -care self 4.29, (P < 0.001) post) Fair Intervention 14% TOFHLA efficacy (0 –100 Adequate literacy subgroup marginal scale) (unadjusted): 4.8, NR Inadequate literacy subgroup (unadjusted): +3.67, NR Unadjusted P for interaction by literacy subgroup: 0.29 205

228 Table 56. Effect of mixed interventions on skills Author, Date of Control Sample % Population with Difference Between Control and Publication, Intervention Quality Design Limited Literacy Outcome Intervention Groups Group Size Standard RCT Jay et al., Nutrition label intervention- 17% limited literacy 56 control (adjusted): % correct on 12-item 218 b, FDA (P < 0.05) 2009 (score ≤ 22) on S - Overall: + 11.8% information card food label quiz written Fair and video tutorial TOFHLA a Adequate literacy : +23% materials a Inadequate literacy: +1% p for interaction: < 0.05 a absolute difference calculated by research team -TOFHLA =short form Test of Functional Health Literacy in Adults FDA =The Food and Drug Administration; RCT =randomized controlled trial; S 206

229 Table 57. Effect of mixed interventions on behavior % Population Author, Date Study Control Sample with Limited of Publication, Intervention Size Design Literacy Outcome Difference Quality Group % weighing daily at DeWalt et al., RCT Usual Care Overall (adjusted): 127 TOFHLA CHF Self - - 41% S 202 P NR, ( < 0.001) Management program inadequate 2006 12 months + low Fair literacy pamphlet on CHF 23% S -TOFHLA Kim et al., 92 - Quasi - Diabetes Self None # self -care days in Overall (adjusted): NR, sig 197 Adeq. vs. Inadeq. HL (adjusted): < 22 (Inadequate 2004 - (Pre Management last 7 days < 0.001; Inadeq. better) Diet: NR, ( P Intervention or marginal) post) Fair P = 0.022; Adeq. better) Exercise: NR, ( (15% inadequate Foot care: NR, ( P = 0.001; Inadeq. better) on TOFHLA) P = 0.751) Medication adherence: NR, ( -glucose monitoring: NR, Self P = 0.002; Inadeq. better) ( Schillinger et RCT Usual Care (1) Diabetes Self 59% S TOFHLA care days: - Overall # self Mean # of days self 339 - 187 -Usual Care (adjusted): 0.6 (0.4 to 0.9) care behavior Management Program < 22 (inadequate al., 2008 ATSM ; Schillinger et 01 to 0.6) performed in last 7 GMV -Usual Care (adjusted): 0.3 (0. (automated telephone or marginal) 210 al., 2009 days (score range -GMV (adjusted): 0.3 (0.1 to 0.6) ATSM delivery) (2) Diabetes Self - Fair Minutes of moderate physical activity: 0-7) Management Program Mean # minutes -Usual Care (adjusted): 123.9 (14.8 to ATSM (group medical visit engaged in 233.0) moderate or delivery) GMV -Usual Care (adjusted): 69.1 ( -42.1 to vigorous physical 179.4) activity/week ATSM -GMV (adjusted): 54.8 ( -62.1 to 186.3) Minutes of vigorous physical activity: -Usual Care (adjusted): ATSM 32.2 ( -9.8 to 74.2) -Usual Care (adjusted): 23.3 ( GMV -19 to 65.5) ATSM - GMV (adjusted): 8.9 ( - 33.7 to 51.5) Adeq. =adequate; ATSM =automated telephone self -management support; ATSM -GMV =automated telephone self -management support -group medical visits; CHF =congestive heart failure; GMV =group medical visits; HL =health literacy; inadeq =inadequate; NR =not reported; Quasi =quasi -experimental study; RCT =randomized controlled trial; S - TOFHLA =short form Test of Funct ional Health Literacy in Adults; TOFHLA =Test of Functional Health Literacy in Adults. 207

230 Table 58. Effect of mixed interventions on adherence Author, Date of Study Control Sample % population with Publication, Group Intervention Size Design Limited Literacy Outcome Quality Difference a Tailored 38% low literacy RCT Usual care 588 Change in % Bosworth et Overall change (unadjusted): 201 Adherence reporting agreement -0.076%) 0.007% (95% CI, -0.62% al., 2005 to any question in Intervention Fair Change among those initially Morisky adherence adherent (unadjusted): - 2%, P ( = 0.68) scale Change among those initially non- adherent (unadjusted): +12%, ( P = 0.08) b , NR TOFHLA < Overall: +0.7 # days of Medication Quasi - Kim et al., - 23% S None Diabetes Self - 92 197 Management (pre 22 (Inadequate or 2004 Adeq. vs. Inadequate HL - adherence in last = 0.751) (adjusted): NR, ( P post) marginal) week Intervention Fair (15% inadequate on TOFHLA) Murray et al., % of prescribed medication taken: % of prescribed 29% “not literate” RCT Usual Care CHF Adherence 314 182 on S -TOFHLA During intervention (unadjusted): medication taken 2007 Intervention Good +10.9% (95% CI, 5%-16.7%) (according to MEMS (NOS) Post Intervention (unadjusted): cap) +3.9 % ( - 2.8% - 10.7%) Poor adherence, by literacy % with adherence Paasche- - Quasi NA Asthma Self - 22% S 73 -TOFHLA Orlow et al., subgroups (adjusted): less than 50% for - (pre Management Inadequate 79 = 0.45) P NR, p for interaction: ( inhalers or meds 2005 post) Intervention Fair (according to Doser CT or MEMS cap) 208

231 Table 58. Effect of mixed interventions on adherence (continued) Author, Date of Study Control Sample % population with Publication, Size Intervention Limited Literacy Design Outcome Difference Quality Group RCT Arthritis Rudd et al., Arthritis 127 19% REALM < high Mean score on Mean percent change in 209 2009 Management Managemen medication Levine school medication adherence t Intervention Intervention + Fair adherence (unadjusted): Individual (arthritis assessment (range 6 mo: -5.01%, p 0.33 Counseling pamphlet, 0-3, 3 best) 12 mo: -9.09%, p 0.10 medicine calendar, hospital map) b a Determined through personal communication with author; Calculated by team Adeq. =adequate; CHF =congestive heart failure; CI =confidence interval; HL =health literacy; meds =medications; MEMS cap =Medication Event Monitoring System cap; NA =not applicable; NOS =not otherwise specified; NR =not reported; Quasi -= quasi -experimental study; RCT =randomized controlled trial; S -TOFHLA =short form Test of Functional =versus. Health Literacy in Adults; TOFHLA =Test of Functional Health Literacy in Adults; vs. 209

232 Table 59. Effect of mixed interventions on disease prevalence and severity Author, Date of Study Control Sample % Population with Publication, Intervention design Size Limited Literacy Outcome Difference Quality Group - Usual Care + Low Literacy Subgroup (adjusted): Gerber et al., Diabetes Self RCT Mean Change in 144 56% S - TOFHLA < 194 computerized Management Hemoglobin A1C -0.1, NS Change in HgbA1C: 22 (Inadequate or 2005 Fair Mean Change in Systolic Intervention -1 mmHg, NS Change in SBP: marginal) quizzes on and Diastolic Blood diabetes Change in DBP: 3 mmHg, NS - Pressure (mmHg) related Change in BMI: NR, NS Mean Change in Body High Literacy Subgroup (adjusted): concepts Mass Index (kg/m2) Change in HgbA1C: 0.0, NS Change in SBP: +1 mmHg, NS Change in DBP: -7 mmHg, NS -1 kg/m2, NS Change in BMI: Note: in exploratory subgroup analyses of Hgba1c > 9 (n = 26), intervention more effective than control for low literacy (but not high literacy) group 197 Quasi - None Kim et al., 2004 Diabetes Self - Overall (unadjusted): 92 23% S - TOFHLA < Mean HgbA1c Management Fair (pre - 22 (Inadequate or -1.3a, Sig Adeq. vs. Inadeq. HL (adjusted): marginal) Intervention post) (15% inadequate on NR, (P = 0.086) TOFHLA) Paasche - Orlow et Overall: NR score on asthma Mean TOFHLA Quasi - - 22% S 73 NA Asthma Self - 79 - (pre Inadequate Management symptom questionnaire al., 2005 By subgroup: NR Intervention - 6) Fair post) p for interaction: (P = 0.69) (range 0 a Calculated by team ABLE =Adult Basic and Literacy Education; Adeq. =adequate; ATSM =automated telephone self -management support; ATSM -GMV =automated telephone self -management support =body mass index; CI =confidence interval; DBP =diastolic blood pressure; GMV =group medical visit-usual care; HgbA1c= glycosylated -group medical visists; BMI hemoglobin; HL =health literacy; inad =inadequate; NA =not applicable; NR =not reported; NS =not significant; Quasi-= quasi -experimental study; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; SBP =systolic blood pressure; sig =significant; S -TOFHLA =short form Test of Functional Health Literacy in Adults; s =versu =Test of Functional Health Literacy in Adults; vs. TOFHLA 210

233 Table 59. Effect of mixed interventions on disease prevalence and severity (continued) Author, Date of Study Sample % Population with Publication, Control Group Intervention Quality Size Limited Literacy Outcome Difference design Quasi - Diabetes NA Rothman et al., Lower Literacy Subgroup Mean HgbA1c 159 55% Lower Literacy 198 rd Disease - (Pre 32% REALM < 3 2004 (unadjusted): post) Management Fair grade 1.2) -1.9% points (95% CI, -2.5 to - 23% REALM Score Intervention Higher Literacy Subgroup -6th grade 4th (unadjusted): -1.8% points (95% CI, -2.5 to - 1.0) RCT Overall (adjusted): - hour education Diabetes Disease Rothman et al., 217 38% REALM < sixth Mean HgbA1c 1 183 SBP session 2004 grade Management -7.6 mmHg ( -13 to -2.2 mmHg) Good Systolic blood pressure Low literacy subgroup: Intervention HgbA1c (adjusted): -1.4%; 95% CI, -2.3% to -0.6%) High literacy subgroup): HgbA1c (adjusted): 0.5%; 95% CI, 1.4% - 0.3% - - (1) Diabetes Self Usual Care RCT 59% S Schillinger et al., < -TOFHLA HgbA1C Mean Hemoglobin A1C 339 187 Management ; Mean Systolic and diastolic 22 (inadequate or -Usual Care (adjusted): 2008 ATSM Program Schillinger et al., -0.5 to 0.4) marginal) -0.1 ( blood pressure (mmHg) 210 (automated 2009 -Usual Care (adjusted): Mean Body Mass Index GMV 2 ) telephone -0.2 to 0.7) (kg/m 0.2 ( delivery) -GMV (adjusted): ATSM - (2) Diabetes Self -0.3 ( -0.8 to 0.7) Management SBP Program (group ATSM -Usual Care (adjusted): medical visit -3.2 mmHg ( -8.3 to 1.9 mmHg) delivery) GMV -Usual Care (adjusted): -3.9 mmHg ( -9.0 to 1.2 mmHg) ATSM -GMV(adjusted): 0.7 mmHg ( - 4.5 to 5.9 mmHg) 211

234 Table 59. Effect of mixed interventions on disease prevalence and severity (continued) Author, Date of % Population with Control Sample Study Publication, Intervention design Size Limited Literacy Outcome Difference Quality Group Schillinger et al., DBP 187 ; 2008 ATSM -Usual Care(adjusted): Schillinger et al., -1.6 mmHg ( -5.1 to 2.0 mmHg) 210 2009 GMV -Usual Care (adjusted): (continued) -6.6 to 0.4 mmHg) -3.1 mmHg ( ATSM -GMV (adjusted): 1.5 mmHg ( -2.0 to 5.1 mmHg) BMI -Usual Care (adjusted): ATSM 2 ) 0.1 kg/m2 ( -0.4 to 0.5 kg/m -Usual Care (adjusted): GMV 2 -0.5 to 0.5 kg/m 0.02 kg/m2 ( ) ATSM -GMV (adjusted): 2 ( - 0.4 to 0.5) 0.1 kg/m 193 Overall (unadjusted): 70 RCT Usual care Adult Basic and Mean depression severity Mean REALM score Weiss et al., 2006 = 0.25 P 1st follow -up: 0, Literacy score on Patient Health 47 Fair P -3, = 0.03 2nd follow -up: Education (ABLE) Questionnaire (score range 3rd follow -up: -4, P = 0.04 0-27) Note baseline difference in REALM 212

235 interventions on quality of life Table 60. Effect of mixed Author, Date of Sample % population with Study Publication, Design Size Control Group Limited Literacy Outcome Difference Intervention Quality RCT Heart failure- DeWalt et al., - Usual Care + low CHF related Quality of -TOFHLA 41% S CHF Self related quality of life 127 202 literacy pamphlet inadequate 2006 Management program (adjusted): Life by MLHF (range of on CHF -105) 2 (95% CI, 9 to -5) scores 0 Fair Adequate Health Literacy (adjusted) : Subgroup -4.2 (95% CI -14 to 6) Inadequate Health Literacy (adjusted) : Subgroup - 15 to 12 - 1.6, 95% CI 29% “not literate” on Usual Care CHF Adherence 314 RCT Mean score on Chronic Murray et al., Within Intervention Group 182 S-TOFHLA (NOS) Heart Failure 2007 Intervention (unadjusted): +0.39 Good Questionnaire (range from 1 to 7; better functioning = higher) Arthritis Management RCT Arthritis Mean percent change in HAQ < Rudd et al., high 127 19% REALM HAQ scores (range of 209 Intervention + school Management scores at 2009 12 months: scores 0 - 3, 0 best) a *, p 0.45 Fair 6 months: -3.60% Individual Counseling Intervention a 12 months: -2.12% *, p0.64 (arthritis pamphlet, medicine calendar, hospital map) -12 mental health: 22 -Mental health < -TOFHLA 59% S SF12 RCT SF Schillinger et (1) Diabetes Self Usual Care 339 187 ATSM -Usual Care (adjusted): 3.7 al., 2008; (inadequate or scale (score range 0 - Management Schillinger et marginal) 100) (-2 to 9.4) Program (automated 210 al., 2009 -12 Physical health -Usual Care (adjusted): SF GMV telephone delivery) -2.9 ( -8.6 to 2.9) scale (score range 0- - (2) Diabetes Self ATSM 6.5 (0.7 to -GMV (adjusted): - 100) Management 12.4) Mean # days in bed in Program (group last month due to health medical visit delivery) problems a Calculated by research team ATSM =automated telephone self -management support; ATSM -GMV =automated telephone self -management support -group medical visits; CHF =congestive heart failure; CI= =group medical visits; HAQ =the Health Assessment Questionnaire; MLHF =the Minnesota Living with Heart Failure Questionnaire; NOS =not confidence interval; GMV -12 Mental health =not reported; NS =not significant; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; SF otherwise specified; NR scale= 12-item short-form mental health scale; S -TOFHLA =short form Test of Functional Health Literacy in Adults. 213

236 Table 60. Effect of mixed interventions on quality of life (continued) Author, Date of Study Sample % population with Publication, Control Group Intervention Quality Size Design Limited Literacy Outcome Difference Schillinger et Extent to which diabetes -12 physical health: SF 187 al., 2008; limits normal activity ATSM -Usual Care (adjusted): 2.7 Schillinger et (score range 0 - 5, lower (-4.0 to 9.5) 210 al., 2009 = less) GMV -Usual Care (adjusted): (continued) -6.9 to 6.7) -0.1 ( ATSM -GMV(adjusted): 2.9 ( -4 to 9.7) # Bed Days over prior month: - ATSM -Usual Care (adjusted): 0.1) -3.3 to - 1.7 ( GMV -Usual Care(adjusted): 0.6 ( - 1.0 to 2.2) -GMV (adjusted): -2.3 ( ATSM -3.9 -0.4) to Extent limited activity: ATSM -Usual Care: NR, ( P = 0. 02) GMV -Usual Care: NR, NS ATSM - GMV: NR, NS a Calculated by research team ATSM, automated telephone self -management support; ATSM -GMV, automated telephone self -management support -group medical visits; CHF, congestive heart failure; CI, confidence interval; GMV, group medical visits; HAQ, the Health Assessment Questionnaire; MLHF, the Minnesota Living with Heart Failure Questionnaire; NOS, not otherwise specified; NR, not reported; NS, not significant; RCT, randomized controlled trial; REALM, Rapid Estimate of Adult Literacy in Medicine; SF -12 Mental health scale, 12 -item short -form mental health scale; S -TOFHLA, short form Test of Functional Health Literacy in Adults. 214

237 Table 61. Effect of mixed interventions on health care costs % Population Author, Date Study Control ication, with Limited of Publ Group Intervention Sample Size Literacy Outcome Difference design Quality - RCT Usual Care CHF Murray et al., $1338) $2960 (95% CI, 314 29% “not literate” $7603 - Total intervention, - 182 2007 Adherence on S outpatient, and inpatient -TOFHLA (NOS) Intervention Good costs 217 Rothman et al., Labor costs: Labor costs for RCT Usual Care 38% REALM Diabetes 183 intervention delivery; Total + sixth grade < $25.50 per patient per month Disease 2004 Rothman et al., Education costs (labor costs + Management (Sens. analysis $12.01 to $55.35 250 2006 indirect costs) per patient per month) Session Intervention Good Total costs: $36.97 per patient per month (Sens. Analysis $16.22 to $88.56 per patient per month) CHF =congestive heart failure; CI =confidence interval; NOS =not otherwise specified; RCT =randomized controlled trial; REALM =Rapid Estimate of Adult Literacy in Medicine; sens. =sensitivity; S -TOFHLA =short form Test of Funct ional Health Literacy in Ad ults 215

238 Discussion Overview During this systematic review update, the RTI International -University of North Carolina Evidence -based Practice Center (RTI -UNC EPC) identified a moderately large body of literature addressing the relationship between health literacy (including numeracy) and health outcomes. Our two key questions (KQ s) and subquestions were as follows. Outcomes: Are health literacy skills related to (a) use of health care services, (b) health 1. outcomes, (c) costs of health care, and (d) disparities in health outcomes or health care service use? Interventions: For individuals with low health literacy skills, what are effective 2. interventions to (a) improve use of health care services, (b) improve health outcomes, (c) ts of care, and (d) improve health care service use and/or health affect the cos outcomes among different racial, ethnic, cultural, or age groups? 1,50 ,51 These issues parallel the questions addressed in the initial review, published in 2004. published in the field has expanded substantially. The initial The amount of research being review was limited to the relationship between literacy and health outcomes (or interventions); it included a total of 73 articles, 44 addressing outcomes, and 29 addressing interventions. The -quality studies updated review expanded the scope of studies; it included 103 new good - or fair reported in a total of 132 unduplicated articles. Of these, 86 articles addressed the relationship ationship between numeracy and between health literacy and outcomes and 16 examined the rel outcomes. In addition, 45 articles reported on interventions for individuals with low health literacy, split between those testing a single intervention strategy and those testing a mix s. (combination) of intervention strategie In this chapter, we recap the principal findings for KQ 1 and KQ 2 and comment on the applicability of the available bodies of evidence. We then discuss the limitations of both the literature reviewed and our own update. Finally, we present recommendati ons for future research. Principal Findings KQ 1 . Health Literacy and Outcomes Literacy Studies For examining the association between health literacy and health outcomes (KQ 1), we included 86 fair - or good -quality articles (72 studies) in this update. Of these, 24 articles addressed the effect of health literacy on health care service use, 72 on health outcomes, 9 on disparities, and 2 on costs. Overall, the majority of studies were assessed as being of fair quality. Differences in health literacy level w ere associated with use of health care services. Specifically, lower literacy was associated with increased emergency department and hospital use, and breast cancer (mammography), and lower influenza immunization, based on moderate strength of evidence. Evidence for other health care service use was low or insufficient because of inconsistent or limited findings and outcomes. 216

239 The relationship between health literacy and health outcomes was variable. The risk of mortality for seniors was clearly higher with lower health literacy. There was also moderate evidence to support a relationship between lower health literacy and poorer ability to take medications appropriately or interpret labels and health messages and poorer overall health status among seniors. In these studies, the evidence consists of all observational studies generally having a medium risk of bias and results generally in a consistent direction. The evidence for all a small number other outcomes was either low or insufficient because the literature consisted of of studies, poorly designed studies, and/or inconsistent results. These evaluations focused on the relationship between the lowest and highest health literacy groups. The evidence was sparse for evaluating differences between those with mar ginal (a middle category) health literacy and adequate (the highest category) health literacy. The evidence concerning differences by health literacy level in costs of health care (KQ 1c) was low. The two relevant studies examined different payment sources (Medicaid and Medicare), found inconsistent results, and included different patient populations. No studies examined differences in costs among those with private health insurance coverage or no coverage. hip between race and health for a variety of Health literacy was found to mediate the relations outcomes. Outcomes studied included a condition that keeps respondents from working or term illness; misinterpretation of medication labels; prostate -specific antigen having a long- levels among newly diagnosed prostate cancer patients; nonadherence to HIV medications; children having health insurance; and, among seniors, self -reported health status, physical and mental health -related quality of life, and receipt of an influenza vaccine. We cannot know whether hea lth literacy level would also be a mediator of the relationship between race and other health outcomes that have not been tested. Only one study examined whether health literacy level mediated the relationship between Hispanic ethnicity and health outcomes and no relationship was found. In contrast, one study found that health literacy level mediated the relationship between gender and misinterpretation of medication labels. We found no studies that other sociodemographic characteristics evaluated the relationship between age, cultural group, or and health outcomes. Numeracy Studies In this update we reviewed 16 fair -quality studies that examined the relationship between numeracy and various outcomes, including use of health care services, health outcomes, costs, and disparities. Most studies examining the relationship of numeracy to health outcomes were cross -sectional in design. Four studies were randomized controlled trials that analyzed their data in a cross -sectional manner for this analysis; one used a prospective cohort design. In general, the strength of evidence for the relationship between numeracy and outcomes was insufficient or low given the small number of studies, which often had a high risk of bias or collectively gave mixed results. Only one study addressed the relationship between numeracy and use of health care services; this study reported no effect of numeracy on up- to-date screening for breast and colon cancer, but appears to be limited by inadequate power. Similarly, several studies demonstrated that the relationships between numeracy level and accuracy of risk perception (five studies), knowledge (four studies), skill in taking medication (six studies), and disease prevalence and severity (three studies) are mixed. The evidence for the r elationship between numeracy and other health outcomes (e.g., self -efficacy, behavior) was insufficient to draw conclusions. No studies addressed the costs associated with differences in numeracy level. 217

240 However, two studies examined whether numeracy level mediates health disparities and found that numeracy appeared to mediate the relationship between race and hemoglobin A1c and between gender and HIV medication management capacity. Health Literacy and Numeracy S tudies Seven studies addressed the effects of both health literacy and numeracy on various 9,10,47,98,125,126,171 outcomes. Of these seven studies, six performed adjusted analyses on the same outcomes, thereby allowing assessment of whether these exposures affect health outcomes ,126,171 9,47,98,125 All of these studies must be interpreted with caution, however, because differently. the proportion of individuals with low health literacy was small, raising the possibility of ceiling effects, which could obscure effects in the health literacy analyses. One study showed that ability to read nutrition labels was lower in both those with low health literacy skills (less than ninth grade) measured by the Rapid Estimate of Adult Literacy in Medicine (REALM) and low numeracy skills (less than ninth grade) measured by the Wide Range Achievement Test for 9 mathematics (WRAT -math). However, it noted that the outcome was more highly correlated with numeracy (ρ 0.67) than health literacy (ρ 0.52). Similarly, another study showed that both health literacy skills (percent correct on the Short Test of Functional Health Literacy in Adults [S-TOFHLA]) and numeracy (percent correct on the Applied Problems Subtest of the 47 although the Johnson Test) were related to HIV medication management capacity, Woodcock- beta- coefficient was higher for numeracy in a regression model including both literacy and 126 showed that both health literacy skills (measured by the numeracy skill. A third study REALM) and numeracy (measured by a 6 -item hybrid test including 3 -items from Schwarz and Wolos hin and 3 additional items from investigators) were related to the proportion of INR tests within range, although the correlation was higher for numeracy (r 0.12) than for health literacy (r 0.02). In contrast, two other studies found relationships between numeracy and health outcomes, but not between literacy and health outcomes. One of these studies found a relationship between numeracy (measured by the WRAT -math) and body mass index (BMI), but no relationship 10 The other found a relationship between between literacy (measured by the REALM) and BMI. -specific numeracy (measured by the Diabetes Numeracy Test) and HgbA1c, but no diabetes 171 125 Only a single study relationship between literacy and HgbA1c. suggested a stronger relationship between literacy and health outcomes than numeracy and health outcomes. This study showed a greater likelihood of parent’s using nonstandard dosing instruments to dose children’s medicines related to their TOFHLA reading comprehension score (split at the median; adjusted OR, 2.4; 95% CI, 1.3 -4.7) compared with their TOFHLA numeracy score (split at the median; OR, 1.4; 95% CI, 0.8 to 2.7). KQ 2. Interventions To Improve Health Literacy In this update we identified 42 new fair - or good -quality studies addressing the effect of int erventions designed to mitigate the effects of low health literacy. Twenty -one used one specific strategy to mitigate the effects of low health literacy, and21 used a mixture of strategies combined into one intervention. Interventions W ith Single Design Features In general, the strength of evidence regarding the effect of specific design features of interventions for low -health -literacy populations is low or insufficient. This is attributable, in ions (and subsequently results) for studies broadly large part, to differences in the intervent 218

241 grouped in the following design feature categories: alternative document design, alternative numerical presentation, additive and alternative pictorial representation, and improved readability and alternative document design. Looking closely within categories, however, we noted that several specific design features -health -literacy populations in one or a few resulted in improvements in comprehension for low studies. These features, which bear further study in broader populations, include: presenting essential information by itself (i.e., information on hospital death rates without other distracting 188 information, such as information on consumer satisfaction); presenting essential information 188 first (i.e., i nformation on hospital death rates before information about consumer satisfaction); presenting quality information with the higher number (rather than the lower number) indicating 188 better quality; sk of disease and using the same denominators to present the baseline ri 219 216,219 treatment benefit; adding icon arrays to numerical presentations of treatment benefit; and 184 Additionally, reexamining data from our 2004 review within adding video to verbal narratives. ial benefit from using reduced reading level and/or these categories further suggests potent 232,236 illustrated narratives. In contrast, one study raised questions about whether certain design features, such as colored traffic symbols to denote death rates in hospitals of varying quality or symbo ls accompanying nonessential quality information, may actually worsen health choices 188 among those with low health literacy. With a Combination of F eatures Interventions The strength of evidence for studies combining multiple strategies to mitigate the effects of low health literacy on outcomes was more variable that it was for single -feature interventions. We found consistent moderate strength of evidence that studied interventions change health care service use. Specifically, intensive self -management and adherence interventions appear to be effective in reducing emergency department visits and hospitalizations. Additionally, educational interventions and/or cues for screening increased colorectal cancer and prostate cancer screening. We note, however, that the health benefits of additional prostate cancer screening are 251,252 questionable and that increased screening rates could be a marker for poor decisionmaking. We additionally found consistent evidence of moderate strength that some interventions change health outcomes. For instance, intensive disease -management programs appear to be effective at reducing disease prevalence. Furthermore, self -management interventions increased nalysis by health self -management behavior; however, in the only study that stratified its a literacy level, improvements were sometimes greater for those who had adequate health literacy and at other times greater for those with inadequate health literacy in adjusted analyses. The effects of other interventions on other health outcomes, including knowledge, self -efficacy, adherence, health -related skills, quality of life, and cost were mixed; thus, the strength of evidence was insufficient. Components of effective interventions were their high intensity, theory basis, pilottesti ng before full implementation, emphasis on skill building, and delivery of the intervention by a health professional. Interventions that changed distal outcomes appeared to work by intermediately increasing knowledge or self -efficacy or by changing behavio r. Too few studies addressed the effects of literacy interventions on the outcomes of behavioral intent, or disparities to draw any meaningful conclusions; the strength of evidence is insufficient. 219

242 04 Review What This Update Adds to the Literature Included in the 20 Our results expand findings from our 2004 review in several ways. The size of the literature in the 2010 update review, examining the relationship between health literature and health eview and encompasses a larger outcomes (KQ 1) is larger than was available for the earlier r variety of outcomes (Table 62). In the 2004 review, we found that lower health literacy level was related to poorer knowledge of matters related to health outcomes and use of health services. his relationship during the update. In the earlier review, we Therefore, we did not reexamine t recommended that future research examining the relationship between health literacy and health outcomes consistently control for potential confounding variables to more accurately measure the st rength of the relationship between health literacy and the outcome. Unlike the earlier review, in the update, primary study outcomes are generally evaluated using multivariate analysis and control for potential confounding variables, providing a better and less biased estimate of the direction and magnitude of effect for our findings. Based on these more rigorous studies, we identified a relationship between health literacy level and additional health related outcomes. In 2004, we also recommended that studies more closely examine the factors that mediate the relationship between health literacy and health outcomes. In 2004, we had found 158 only one study that directly examined racial disparities. For the update, we found a limited ns to provide evidence of variables that may be on the pathway of body of research that begi effect between health literacy and health outcomes; these include factors such as knowledge, self -efficacy, and beliefs such as stigma related to their disease. New studies suggest that heal th literacy could be a mediator of racial disparities in health outcomes. In 2004, we also recommended that studies stratify outcomes by numeracy level to gain a greater understanding of how these skills may uniquely affect health outcomes and under what conditions numeracy would be a useful indicator for targeting individuals for interventions. For the update, we found a small body of evidence concerning the relationship between numeracy level and health outcomes (Table 63). This is not only useful in and of itself, but it also is the next step in expanding our understanding of the skills that are needed to be health literate. For KQ 2, our findings also expand findings from the 2004 review in several ways. In the l and more varied studies of interventions be 2004 review, we recommended that additiona pursued and that all studies measure the interventions’ effects in a broader range of outcomes and by literacy subgroup. Studies in the current report have largely addressed these recommendations (see Table 64 and Table 65). First, they address more varied interventions and provide insights into the utility of particular intervention design features. In our 2004 report, there were relatively few interventions of any type. Thus, we focused on how interventions af fected outcomes rather than attempting to parse interventions into specific elements. In the current report, we reviewed studies by the specific intervention design features studied (see Table 64); only when that was not possible (i.e., because interventio ns used multiple design features) did we review studies by the outcomes involved (see Table 65). Using this new organizational structure, we identified several intervention design features that bear further study, including some identified through our 2004 review; these include presenting essential information by itself (i.e., information on hospital death rates without other distracting information, such as information on consumer 188 presenting essential information first (i.e., information on hospital death rates satisfaction); 188 before information about consumer satisfaction); presenting quality information with the 188 higher number (rather than the lower number) indicating better quality; adding icon arrays to 216,219 184 t; and using adding video to verbal narratives; numerical presentations of treatment benefi 220

243 232,236 reduced reading level and/or illustrated narratives. We also were able to illuminate what factors may be key in making the mixed interventions effective. Common features across nearly all of the mixed interventions that improved distal outcomes (e.g., self -management, hospitalizations, mortality) were their high intensity, theory basis, pilottesting before full implementation, emphasis on skill building, and delivery of the intervention by a h ealth professional (e.g., pharmacist, diabetes educator; see intervention studies evidence tables in 182,183,202,207 Appendix D). Second, studies in the current report provide insight into the impact of interventions on a r 2004 review, the majority of studies focused only on the broader spectrum of outcomes. In ou outcome of knowledge (see Table 64 and Table 65). In the current review, studies focused on a broader range of outcomes, including disease self -efficacy, behavior, adherence, disease severity, quality of life, preventive services use, emergency department visits, prevalence and hospitalizations, and costs. Additionally, six studies in our update examined the impact of 79,182,187,194,197,202 interventions on three or more outcomes (see intervention s tudies evidence tables in Appendix D); they preliminarily suggest that effective interventions to mitigate the 197,202 increasing self - effects of low health literacy may work by increasing knowledge, 187 182,187,197,202 or changing behavior. efficacy, Third, a little over half the studies examined the effect of interventions by health literacy subgroup. This allows investigators to determine whether the intervention is more or less effective among those with low health literacy and whether interventions might ameliorate health disparities. Limitations Limitations of the Literature Readers should interpret the findings from our systematic review in the context of several ty of limitations. As with all systematic reviews, our results and conclusions depend on the quali the published literature. A limitation across KQ s was heterogeneity in outcomes, populations, and study designs; this level of diversity in the knowledge base precluded us from pooling results statistically. Specific limitations of the literature fo r studies addressing KQ 1 (i.e., the effects of health literacy and/or numeracy on health outcomes) included the following: • Lack of specification of thresholds for distinguishing levels of health literacy that consider the relevance of those levels to (1) the outcomes and population being 253 studied and (2) the body of similar work in the field. • Lack of an analytic framework or logic model for determining the appropriate set of potential confounding variables that need to be included in multivariate models. While studies generally controlled for some sociodemographic variables and other factors, the choice of variables varies across studies. • The potential for over controlling. Many studies included education (which is highly correlated with health literacy) as part of their multivariate model. Additionally, some studies included mediators of the effect of health literacy in their model; this may result in underestimating the aggregate effect of health literacy. Small sample sizes, making it impossible to de termine whether null findings represented a true lack of effect or simply reflected limitations in statistical power. 221

244 Studies conducted in just one clinic or in other narrowly defined patient populations, rendering the applicability of findings to other settings or populations unknown. Only two studies were conducted within nationally representative samples: the National Assessment of Adult Literacy conducted in 2003 and the earlier National Adult Literacy Survey in 1992. Health literacy tools that contin ue to focus primarily on reading ability despite the Institute of 53 Medicine’s call for skills -based health literacy tools (i.e., tools focused on a combination of oral or verbal, navigational, computer, or other skills necessary for individuals to manage their health).At the time of this update review, we identified none in the literature. Thus, we could not determine the relationship between a wider array of skills or abilities and health outcomes. We did, however, find evidence that development of tools that can measure these additional skills 254 has begun. A limited number of studies examining the role of health literacy on health disparities. Most research focused on whether health literacy mediated the relationship between race and health outcomes. Th e limitations of the literature for studies addressing KQ 2 (i.e., the effects of interventions to mitigate low health literacy) included the following : • Lack of an adequate control or comparator group in many studies, limiting the ability to determine the true effect(s) of the intervention. Measurement of multiple outcomes with insufficient attention to ensure that each is • adequately powered to detect a difference. • Testing interventions that combined various design features to mitigate the effect of low hea lth literacy but offering no way to determine the effectiveness of individual components. • Failure to perform adequately controlled subgroup analyses that would elucidate differential effects of interventions in low - and high- -literacy populations. This health is important to the extent that the field’s overall goal is to reduce disparities related to the impact of low health literacy rather than simply to improve outcomes for individuals at all health literacy levels. Failure to report adequately the design features that would allow future content • analyses of effective interventions. Limitations of Our Review In addition to clarifying the limitations of the overall body of literature, we must also acknowledge the limitations of our systematic review and updat e of the 2004 report. First, we included only those studies in which investigators quantitatively measured the literacy of their populations. We may have missed some important studies addressing the relationship of health literacy on health outcomes or imp ortant interventions that either did not measure health literacy or measured it only by self -report. Second, we excluded studies that included only outcomes 255 -260 Our reasoning was that, in our judgment, focused on communication or decisionmaking. patient -physician communication likely moderated rather than mediated the effect of intent for behavior on health outcomes. However, this may have meant we missed outcomes or interventions important to some researc hers, clinicians, and policymakers. Third, we did not conduct dual independent abstraction of all information for review. Rather, a single reviewer abstracted information and a second reviewer checked it; we feel this process was sufficiently rigorous to a llow accurate conclusions, and it is the basic strategy the RTI −UNC EPC has used for this step for more than a decade. We did, however, perform dual review for article inclusion 222

245 and dual rating of the risk of bias of individual studies and the strength of evidence in relation to outcomes, highlighting an overall rigorous process. Fourth, we did not formally integrate the analyses from our 2004 and current reviews, although based on our review of summary materials, we suspect this would have a minimum impact on our overall conclusions. Opportunities for Future Research This update shows that the field of health literacy has advanced since our 2004 review. However, many opportunities remain for important future research. The need for such investigations is con siderable for gaining a better understanding of the outcomes of health care, given levels of health literacy, and for expanding the knowledge base about the impact of interventions intended to improve health literacy. the Relationship Between Health Literacy and Future Research Into Health Outcomes Instrument C utpoints The field will greatly benefit from researchers prespecifying the most relevant cutpoints for distinguishing levels of health literacy within the population being studied, considering how the cutpoints selected compare to those that have been used in measuring similar populations and outcomes. Currently, investigators use cutpoints inconsistently, such that “adequate” and “inadequate” or “low” health literacy levels have different definitions across studies. This problem makes comparing results from these studies difficult. Additionally, the literature as a whole does not lend itself to explaining at what particular level lower health literacy is related to th care. significantly poorer outcomes of heal Furthermore, sometimes a middle group, often referred to as having “marginal health literacy,” is identified; other times, no such group is specified. Sometimes research teams combine the middle health literacy group with the higher health litera cy group; sometimes they combine it with the lower health literacy group. In short, those conducting work in this area in the future should more rigorously defend their choice of inadequate, marginal, and adequate levels of health literacy. Skills -Based Measures Testing skills -based health literacy measures will be an important focus of future research. Our current review expanded the tools that measure health literacy to include those that focus on numeracy. However, we found no tools that measure oral h ealth literacy. New instruments are likely to be available in the near future that can be used as alternative measures of health literacy that capture additional and potentially critical skills. For example, a 2009 Institute of Medicine workshop and result ing report, Measures of Health Literacy, highlight several skills -based measurement tools that are under development —one designed for use in clinics and a second for population- based surveillance. 261 Future research should consider these and other measures that may explain the interplay of a wider range of health literacy skills and outcomes. Future research should also consider capturing changing competencies over time based on greater knowledge or experience (or both), resulting in health literacy levels changing over time. For this type of measurement, prospective research designs will be critical, allowing researchers to measure health literacy at different times while in treatment or after different amounts of experience managing a chronic condition. 223

246 Links Between L ow Literacy and O utcomes Health Additional work is needed to help us understand the pathways between low health literacy and health outcomes. A few studies examined variables that may be in the analytic pathway between health literacy and health outcomes and mediate the relationship between the two— including knowledge, self -efficacy, and beliefs. More research is needed investigating these potential mediators in relation to a wider range of outcomes and populations. Other potential variables t hat warrant serious attention as mediators or moderators of the relationship include measures of education, social support, cultural competency, decisionmaking skills, and trust in the information source. ubgroups Population S Additional research is needed to understand whether health literacy has a differential effect in various subgroups of the population. For example, we lack data evaluating whether the effect of low health literacy would be significantly different in different groups defined by various sociodemographic factors. Of particular interest are the following comparisons: white populations vs. various racial and/or ethnic minority populations, nonelderly vs. elderly individuals, and male vs. female patients. Methodologic Limitations Current work should continue to address the basic methodological deficiencies we found during this update and the problems we noted in the previous review. For instance, researchers need to determine a minimal set of confounding variables to be considered for all mult ivariate analyses; sample sizes need to be larger so that investigators truly have sufficient power to detect differences among the three health literacy levels. esearch Applicability of R The degree to which results from the studies done to date can be a pplied broadly is limited. Considering the “PICOTS” framework (patients/populations, interventions, comparators, outcomes, timeframes, and settings) for considering the generalizability of a body of research, we conclude that the ability of decisionmakers to generalize results from the current body of work is not great. Most current studies were limited to one clinic or one geographic area; thus, we lack evidence that the results would apply in more broadly defined populations or settings. The field needs t o examine the relationships between health literacy and health outcomes in more diverse and representative populations. Future Research I nto Interventions to Mitigate the Effects of Low Health Literacy Opportunities to study interventions to mitigate the e ffects of low health literacy are also substantial. Effective Design of Health -R elated D ocuments Additional work is needed on the design features of documents. As discussed above, we identified several design features of health -related interventions that could mitigate the effects of low health literacy. However, the majority have been examined in only one or a few studies in clinical populations; thus, they warrant further investigation. 224

247 An important question to answer is, “What needs study and what does not?” Our review failed to turn up evidence regarding several document design features widely recommended by experts in the field of health literacy; these include grouping or “chunking” of ideas and teach- 262 back. However, whether these features require s pecific investigation in relation to health literacy when they have been well studied in other fields is not clear. For instance, the field of psycholinguistics has done extensive testing of simplified sentence and document structure and the cohesiveness o f concepts in the text; this body of work, albeit not necessarily stemming from the health sector, may obviate the need for specific testing of these approaches in the health 263 literacy field per se. niques of explicit Furthermore, the educational literature has tested tech instruction that are recommended for poor readers —i.e., instruction that has a clear task and is broken into small steps with practice and feedback at every step and determined that they are — 263 effective. Rather than spending time and energy on additional testing, exploring the extent to which other fields can inform the work of health literacy may be more appropriate. Some design features, however, may warrant explicit testing. Given the evidence from multiple areas of study that motivation increases the effects of comprehension and 98,263,264 behavior, more study of the impact of illustrations, videos, fotonovelas, and other novel approaches that may increase motivation for information- processing through their visual appeal seems warranted. Researchers in health literacy should seek guidance from the health 265 communication literature to guide these efforts. Further testing of techniques based on oral and numerical delivery of information will also be useful. Oral information receives diff erent cognitive processing than written information and has 263 Numbers and graphical -literacy individuals. a naturally simpler syntax that may help low numerical information have many alternative forms of presentation. These have been shown to standing in high -literacy individuals; they should be tested for comprehension among affect under 266 -271 those with lower literacy. Finally, investigation of “work- around” interventions should be undertaken. These can include use of patient advocates, who could accompa ny individuals to medical appointments and facilitate subsequent care. Effective Components of Combination I nterventions Additional work is also needed to determine the effective components of already -tested interventions that have employed a combination of features to mitigate the effects of low health literacy. While a combination of intervention features has repeatedly been shown to ensure the success of interventions, paring away ineffective features could save delivery time and result in more cost -effective delivery. Several possibilities for accomplishing this task exist. For instance, one approach is to conduct a qualitative content analysis of existing interventions. Another approach is to conduct additional trials to test components of effective interventions. A final approach is to conduct a meta -regression; in such analyses, investigators enter data about the features of existing interventions into a statistical program to determine their relative impact on relevant outcomes. While the field may b e too young for this now, meta -regression could be a very useful technique as additional studies with similar intervention features and outcomes become available. To prepare for such a meta- regression, investigators in the field might agree on a useful set of intervention design features to be tested and consistently report on the incorporation of these features into multicomponent interventions. 225

248 Effective Prac tice and Policy Interventions and policy interventions. Additional work is also needed to determine the effect of practice We found almost no studies that addressed such interventions. Implications of This Report for Clinicians and Policymakers In addition to identifying areas for future research, this report informs clinicians and policymake rs. First, it continues to raise awareness that low health literacy has a substantial impact on healthcare service use, health outcomes, cost, and disparities and warrants the attention of both clinicians and policymakers. Second, it highlights effective i nterventions that could be implemented in clinical practice now and/or supported by policy. These interventions have been rated as having moderate strength of evidence in our review and include intensive adherence, self -management, and disease management i nterventions delivered by clinical practitioners. Finally, for policymakers, our update highlights the critical need for research funding to test practice and policy interventions, which to date have gone largely untested. The recent Department of Health and Human Services National Action Plan to Improve Health Literacy helps enumerate these and other critical actions for clinicians and policymakers 52 addressing health literacy. 226

249 Conclusions Our systematic review update confirms that lower health literacy as measured by poorer reading skills is associated with a range of adverse health outcomes. Evidence is beginning to emerge concerning the relationship between poorer numeracy skills and health outcomes but the evidence is still too weak to be confident of a n association. We found no evidence evaluating oral (verbal) health literacy and health outcomes. Rigorous, well -designed studies of interventions to mitigate the effects of low health literacy have been conducted since our earlier review. Future studies i solating one measurable and replicable component of an intervention will, however, be particularly helpful in building this body of evidence. Many studies have now been conducted with a variety of clinic populations. Future research could enhance our confi dence in the more universal applicability of results by including more broadly based and representative samples. 227

250 Table 62. Health outcome study results (KQ 1): summary and comparison of 2004 and 2010 systematic reviews Number of Number of Low Health articles: 2004 articles: 2010 Low Health Literacy Strength of (Number Related (Number Literacy Evidence: Related controlling for Results: controlling for confounding) Results: 2010 confounding) 2010 2004 Study design Outcome Hospitalization Cohort 2 (2) Moderate 4 (3) Increase Increase Cross 0 sectional - 2 (2) Cohort Moderate Increase NA: no 0 4 (3) Emergency care 0 studies sectional - Cross visits 3 (3) - 0 5(5) NA: no Colon screening Decrease Insufficient Cross sectional studies - sectional 1(1) 3(3) Pap tests Decrease Low Cross Decrease Cross sectional 1(1) 4(4) - Decrease Moderate Mammogram Decrease Cross - sectional 1(1) STI (testing) 1(1) Increase Increase Low Immunization: 0 1(1) Cohort Decrease Moderate Decrease - 3(3) sectional Influenza 1(1) Cross Insufficient Immunization: Cohort 0 Mixed 1(1) Decrease 1(1) sectional - Cross Pneumococcal 1(1) Cohort 4(4) No difference 0 Mixed Insufficient Access to care Cross 1(1) - sectional 5(5) Access to sectional 0 1(1) - NA: no Decrease Low Cross insurance studies Cohort Knowledge - Not re 1 (0) NA: analysis NA Decrease 9 (7) not repeated sectional evaluated - Cross Cohort 2 (0) 6 (6) Adherence Mixed Mixed Insufficient 9 (9) Cross 2 (1) - sectional Self - Cross - sectional 0 5 (4) NA: no efficacy Mixed Insufficient studies Cross 3 (1) 2 (2) Mixed sectional Mixed Insufficient Smoking - Alcohol and drug Cross - sectional 1 (1) 2 (2) No difference Mixed Insufficient use Insufficient Mixed NA: no Cross - sectional 0 3 (3 - for some Healthy lifestyle outcomes) studies (physical activity, eating habits, and seat belt use) 0 1 (0) Obesity and NA: no Cohort Mixed Insufficient weight Cross 4 (1) - sectional studies 0 Review of Low Cross -sectional 0 1 (1) NA: no Decrease studies prescription information HIV risk and Insufficient Cohort Mixed NA: no 0 1 (1) 0 1 (1) sectional studies - Cross sexual behavior NA: no Moderate Cohort Decrease Taking 0 1 (1) 0 medications studies -sectional Cross 4 (4) appropriately Moderate Decrease Cross - sectional 0 Interpreting 5 (4) NA: no studies labels and health messages Asthma self care Cross - sectional 1 (1) 1 (1) Decrease Decrease Low Low Mental health Cohort Greater in 8 Decrease 1 (0) 2 (1) Cross 8 (4) sectional - studies symptomatology 4 (2) Chronic disease Cohort Insufficient Mixed 1 (1) 2 (0) No difference 5 (3) sectional - Cross HL =health literacy; NA =not applicable; QoL =quality of life; STI =sexually transmitted infection 228

251 Table 62. Health outcome study results (KQ 1): summary and comparison of 2004 and 2010 systematic reviews (continued) Number of Number of Low Health Low Health articles: 2004 articles: 2010 Literacy Strength of (Number (Number Related Literacy Evidence: controlling for Results: Related controlling for confounding) Outcome Resu lts: 2010 2004 2010 Study design confounding) Mixed Cohort 1 (1) No difference in Low HIV severity and sectional Cross 3 (0) 4 studies symptoms - 4 (3) Asthma severity Cross -sectional 0 2 (1) NA: no Insufficient Mixed and control studies Diabetes control Insufficient Cross - sectional 3 (2) 6 (5) Mixed Mixed and related symptoms Cross - sectional Hypertension 1 (1) 2 (2) No difference Mixed Insufficient control No difference 1 (1) -sectional 1 (1) Prostate cancer Cross Decrease Low control Low Cross - sectional 2 (2) 1 (1) Decrease No difference Health status: all adults 1 (1) Moderate Cohort Decrease 0 Health status Decrease -sectional 1 (0) Cross and QoL 5 (4) seniors: Mental & Insufficient 3 (2) Mixed NA: no Cohort physical studies -sectional 2 (2) Cross 0 functioning: seniors Insufficient 2 (0) Cross - sectional Health status 5 (5) No difference Mixed and QoL: specific diseases Mortality: High Cohort 0 3 (3) NA: no Greater studies seniors No difference 1 (1) Costs 2(2) Cohort Mixed Insufficient Disparities HL partially Cohort Race: Low HL mediates 1 (1) 0 1 (1) Cross Hispanic 5 (5) mediates: racial -sectional racial disparity in 1 study disparities in ethnicity: Low Sex: Low some outcomes, no differences in Hispanic ethnicity, sex differences for 1 outcome 229

252 Table 63. Numeracy outcome study results (KQ 1): summary of 2010 systematic review* Number of articles: 2010 (Number Low Numeracy Literacy Strength of controlling for Outcome Related Results: 2010 confounding) Evidence: 2010 Study design Low Cross 1(1) No effect Use of health care -sectional services Cross - sectional 5(3) Mixed Insufficient Accuracy of risk perception sectional 4(3) Mixed Insufficient - Knowledge Cross Decrease efficacy - sectional 1(0) Cross Insufficient - Self Cross - sectional 1(0) Behavior No effect Insufficient Skills Cohort Taking medication: 1(1) Taking medication (n=4): Insufficient -sectional Cross Mixed 5(4) Interpreting health Interpreting health information (n=2): information: Low Decrease Insufficient Cross - Disease 3(2) Mixed sectional prevalence and severity Low Cross 2(2) Numeracy partially Disparities -sectional mediates the relationship between race and 1 outcome and between gender and 1 outcome *Numeracy studies were not included in the 2004 review n=number Table 64. Results of intervention studies with single design strategies (KQ 2): summary and comparison of 2004 and 2010 systematic reviews * Number of Number of articles Low Health articles Low Health (Number Literacy (Number Strength of Literacy Related stratifying stratifying Study Related Evidence: Results: results by HL results by HL design 2004 Design Strategy level): 200 level): 2010 Results: 2010 2010 4 Alternative 1(1) 2(2) RCT Increased Increased Low Document Design 3(3) RCT 0 Alternative NA Increased Low Numerical Presentation Additive and Insufficient RCT Mixed NA 0 8(5) Quasi 0 Alternative Pictorial Representation (pre/post) RCT 1(1) Insufficient 4(3) Mixed Alternative Media Mixed 2(1) NRCT Insufficient RCT Mixed 2(0) Alternative Mixed 6(3) Readability and Quasi (post) 0 1(1) NRCT Document Design 3(3) Physician Low No effect cRCT 0 1(1) NA Notification of HL (patient outcomes) Level *Studies in 2004 report reorganized into 2010 framework (e.g. single vs. multiple design strategy interventions) for reporting cRCT =cluster randomized controlled trial; HL =health literacy; NA =not applicable; NRCT =non- randomized controlled trial; quasi =quasi -experimental study; RCT =randomized controlled trial 230

253 Table 65. Resu lts of interventions with multiple design strategies: summary and comparison of 2004 and 2010 systematic reviews* Number of Number of articles articles Low Health Low Health (Number Literacy (Number Strength of Literacy stratifying Related stratifying Evidence: Related Results: results by HL results by HL Results: 2010 level): 2004 level): 2010 Study design 2004 Outcome 2010 RCT Knowledge Insufficient 2(1) Mixed Mixed 3(1) Quasi (pre/post) 1(0) 5(2) 1(0) Quasi (post) 2(2) NRCT 0 1(0) efficacy RCT Insufficient 0 Mixed 4(1) - Self NA Quasi (pre/post) 4(0) 0 0 Quasi (post) 1(0) 0 NA 0 NA NA Behavioral Intent RCT Increased Insufficient* 0 Skill Mixed 1(1) 1(1) 0 Quasi (pre/post) 0 NRCT 1(0) RCT Behavior 2 (0) 2(0) Nutrition Self - - Self Quasi (pre/post) 0 1(1) interventions: management management NRCT 1 0 Mixed interventions: interventions: Increased Moderate Nutrition interventions: Insufficient Adherence RCT Insufficient Mixed No effect 0 2(0) 0 1(1) Quasi (pre/post) Quasi (post) 1(1) 0 1 (0) 0 NRCT Disease Self - 3(0) 4(2) RCT No effect - Self Prevalence and 3(3) management: management: 0 Quasi Insufficient Severity Insufficient Disease Disease management: management: Moderate Moderate Adult basic and Adult Basic and Lit. Education: Education: Low Low 0 4(0) NA Mixed Insufficient RCT Quality of Life RCT 0 1(0) NA Increased Moderate Preventive 1(1) 0 service use cRCT Emergency RCT Moderate 0 Reduced 1(0) NA Room Visits 0 Quasi (pre/post) 1(1) Moderate Hospitalization Reduced 2(1) RCT NA 0 1(1) 0 Quasi (pre/post) Cost RCT 0 2(0) NA Mixed Insufficient Disparities 0 0 NA NA Insufficient *Studies in 2004 report reorganized into 2010 framework (e.g. single vs. multiple design strategy interventions) for reporting cRCT =cluster randomized controlled trial; NA =not applicable; NRCT =non-randomized controlled trial; quasi= quasi - experimental study; RCT =randomized controlled trial 231

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267 Mo xey A, O'Connell D, McGettigan P, et al. 270. Describing treatment effects to patients. J Gen Intern Med 2003 Nov;18(11):948- 59. 271. Covey J. A meta -analysis of the effects of presenting treatment benefits in different formats. Med Decis Making 2007 Sep - Oct;27 (5):638 -54. 245

268 . Author Queries Appendix A Queries to Authors for Additional Information Research Objective Questions for Authors Author To determine if a nurse administered patient What strategies did you employ in your Bosworth et al., - 1 intervention specifically to address the 2005 tailored intervention can improve blood problem of low health literacy? pressure control What behavioral theory did you use in the To evaluate the effects of using an Brock & Smith, 2 design of your intervention? 2007 audiovisual animation displayed on a PDA for patient education in a clinical setting To determine whether a novel multimedia testing (either - Did you perform any pre Bryant et al., 3 -SS would be cognitive and usability testing or pilot 2009 computer version of the AUA better understood by patients than the original testing) of your intervention? What was the total contact time with form, and to see whether improvement in participants during the delivery of your understanding varied by literacy level rvention? inte What behavioral theory did you use in the design of your intervention? Did you tailor your intervention to address individual patient characteristics? If so, how? Did you perform any pre- testing (either To compare comprehension of consent Campbell et al., 4 cognitive and usability testing or pilot pothetical research study) information (for a hy 2004 testing) of your intervention? as a function of the medium of presentation, mostly among a low literacy population - What was the total contact time with To compare the efficacy of a heart failure self DeWalt et al., - 5 participants during the delivery of your management program designed for patients 2006 intervention? with low literacy versus usual care What behavioral theory did you use in the f your intervention? design o What strategies did you employ in your Ferreira et al., - care provider directed To test whether health 6 2005 intervention increased colorectal cancer intervention specifically to address the screening rates literacy? problem of low health What behavioral theory did you use in the design of your intervention? Did you perform any pre- testing (either cognitive and usability testing or pilot testing) of your intervention? Galesic et al., What was the total contact time with Experiment 1: To investigate whether icon 7 arrays increase accuracy of understanding participants during the delivery of your 2009 medical risks (either ARR or RRR) intervention? Experiment 2: To investigate whether icon arrays and alternate denominators affect perceived seriousness of risks and helpfulness of treatments; this experiment is erest to SER not of int Did you perform any pre- testing (either To examine whether natural frequencies can Galesic et al., 8 cognitive and usability testing or pilot 2009 improve posterior probability judgments of testing) of your intervention? older adults and of people with lower What was the total contact time with numeracy skills participants during the delivery of your intervention? A-1

269 Author Research Objective Questions for Authors Retamero 1) To determine whether participants show - Garcia testing (either - Did you perform any pre denominator neglect in their estimates of risk cognitive and usability testing or pilot and Galesic, 9 2009 ) of your intervention? reduction and whether those with low testing numeracy show more denominator neglect than those with high numeracy 2) To evaluate whether icon array isunderstanding presentation helps reduce m of risk reduction information due to denominator neglect 3) To determine whether US participants show more denominator neglect than German participants To evaluate a multimedia intervention for Gerber et al., How many intervention sessions did you 10 diabetes education targeting low literacy provide for study participants? 2005 What was the total contact time with individuals from a diverse population participants during the delivery of your intervention? To test whether simplifying official Medicaid testing (either Greene and - Did you perform any pre 11 comparison chart improved comprehension cognitive and usability testing or pilot Peters, 2009 testing) of your intervention? and to examine how important literacy and What was the total contact time with numeracy skills were for comprehension participants during the delivery of your intervention? testing (either Did you perform any pre- 1) To test whether comprehension could be Greene et al., 12 cognitive and usability testing or pilot improved by varying the way information was 2008 testing) of your intervention? presented 2) To examine the effect of numeracy on comprehension of CDHP design and informed decision making (i.e. is numeracy of moderator) 13 To determine whether a multimedia What behavioral theory did you use in the Jay et al., 2009 intervention can improve food label design of your intervention? Did you perform any pre- testing (either -income comprehension in a sample of low cognitive and usability testing or pilot patients testing) of your intervention? 14 Kang et al, 2009 1) To investigate the recall and What was the total contact time with comprehension of orthodontic informed icipants during the delivery of your part intervention? consent among patients and their parents with the traditional AAO informed consent form and other methods with improved readability and processability between 2) To investigate the association reading ability, anxiety, and sociodemographic variables, and recall and comprehension 3) To determine how different domains of information are affected by varying degrees of readability and processability A-2

270 Author Questions for Authors Research Objective 15 Kim et al., 2004 To examine the association between health What was the total contact time with literacy and self management behaviors in participants during the delivery of your intervention? patients with diabetes and to determine What strategies did you employ in your - whether diabetes education improves self intervention specifically to address the management behaviors in patients with problem of low heal th literacy? limited compared with adequate health Did you tailor your intervention to address literacy individual patient characteristics? If so, how? What behavioral theory did you use in the design of your intervention? Did you perform any pre- testing (either cognitive and usability testing or pilot testing) of your intervention? How many intervention sessions did you Kripalani et al., To design and evaluate an illustrated 16 for study participants? provide medication schedule (pill card) that depicts a 2007 What was the total contact time with patient's daily medication regimen using pill participants during the delivery of your images and icons intervention? What behavioral theory did you use in the design of your intervention? How many intervention sessions did you -literacy Kripalani et al., To determine the effects of two low 17 provide for study participants? 2007 educational handouts on the frequency of What was the total contact time with subsequent prostate cancer discussion and participants during the delivery of your screening intervention? What behavioral theory did you use in the design of your intervention? To determine whether simplified written Kripalani et al., What was the total contact time with 18 2008 documents, a short verbal description of the participants during the delivery of your intervention? study, and a visual aid to describe the improved participant randomization process comprehension of informed consent and HIPAA Privacy Rule requirements regarding authorization for use and disclosure of protected health information How many intervention sessions did you Murray et al., To determine whether a pharmacist 19 provide for study participants? 2007 intervention improves medication adherence What was the total contact time with and health outcomes compared with usual participants during the delivery of your -income patients with heart failure care for low intervention? Peters et al., What was the total contact time with Examine whether simpler presentations of 20 2007 quantitative information have a larger participants during the delivery of your influence on (on comprehension) among intervention? Did you perform any pre- testing (either consumers with low numeracy compared to cognitive and usability testing or pilot those higher in numeracy testing) of your interven tion? What strategies did you employ in your Robinson et al., To determine the effects of literacy classes 21 inter vention specifically to address the given to asthmatic pediatric patients in an 2008 problem of low health literacy? urban area on reading level, asthma What behavioral theory did you use in the treatment self -efficacy, ED visits and hospitalizations design of your intervention? A-3

271 Author Research Objective Questions for Authors How many intervention sessions did you Rothman et al., To examine the role of literacy in glycemic 22 provide for study participants? control in a cohort of patients with type 2 2004 What was the total contact time with diabetes participants during the delivery of your intervention? What behavioral theory did you use in the design of your intervention? Did you perform any pre- testing (either cognitive and usability testing or pilot testing) of your intervention? s the total contact time with Rothman et al., What wa To examine the role of literacy on the 23 2004 participants during the delivery of your effectiveness of a comprehensive disease intervention? management program for patients with What behavioral theory did you use in the diabetes design of your intervention? testing (either Did you perform any pre- cognitive and usability testing or pilot testing) of your in tervention? To test the efficacy of educational Rudd et al., How many intervention sessions did you 24 provide for study participants? interventions to reduce literacy barriers and 2009 What was the total contact time with enhance health outcomes among patients participants during the delivery of your with inflammatory arthritis intervention? What behavioral theory did you use in the design of your intervention? Did you perform any pre- testing (either cognitive and usability testing or pilot testing) of your intervention? What strategies did you employ in your management Schillinger et al., - Examined the effects of 2 self 25 2009 intervention specifically to address the support (SMS) strategies (automated Schillinger et al., -management support (ATSM) problem of low health literacy? telephone self 26 What behavioral theory did you use in the 2008 and group medical visits (GMV)) across design of your intervention? o the Chronic Care outcomes corresponding t testing (either Did you perform any pre- Model ve and usability testing or pilot cogniti testing) of your intervention? behavioral theory did you use in the What To determine if notifying physicians of their Seligman et al., 27 design of your intervention? patients' limited health literacy affects 2005 physician behavior, physician satisfaction, or efficacy patient self - What behavioral theory did you use in the Sobel et al., To determine whether a low -literacy 28 design of your int ervention? 2009 multimedia tool can improve asthma - American adults knowledge in African Volandes et al., use in the To evaluate the effect of a video decision What behavioral theory did you 29 design of your intervention? support tool on preferences for future medical 2009 Did you tailor your intervention to address care in older people if they develop advanced individual patient characteristics? If so, dementia, and stability of preferences after 6 how? weeks What was the total contac t time with Intervention: Walker et al., 30 To determine the effectiveness of a pictorial participants during the delivery of your 2007 ‘mind map’ together with the Arthritis intervention? Who delivered your intervention? Research Campaign (ARC) booklet for imparting knowledge to participants with rheumatoid arthritis, and to relate this to participant reading ability Health outcome: To investigate the relationship between anxiety/depression and HL A-4

272 Research Objective Author Questions for Authors What was the total contact time with Wallace et al., To evaluate the impact of providing patients 31 with a literacy -appropriate diabetes education 2009 participants during the delivery of your guide accompanied by brief counseling intervention? designed for use in primary care To determine whether literacy education, Weiss et al., How many intervention sessions did you 32 provide for study participants? 2006 provided along with standard depression What behavioral theory did you use in the treatment to adults with depression and design of your intervention? limited literacy, would result in greater Did you perform any pre- testing (either improvement in depression than would cognitive and usability testing or pilot standard depression treatment alone testing) of your intervention? To determine whether low numeracy Wright et al., What was the total contact time with 33 participants would better understand risks participants during the delivery of your 2009 presented using grouped dot or dispersed dot intervention? Did you perform any pre- testing (either displays cognitive and usability testing or pilot testing) of your intervention? Yates & Pena, assess differences in comprehension testing (either Did you perform any pre- To 34 2006 between standard and simplified head injury cognitive and usability testing or pilot testing) of your intervention? advice sheets References 1. Bosworth HB, Olsen MK, Gentry P, Orr M, 6. Ferreira MR, Dolan NC, Fitzgibbon ML, Dudley T, McCant F, et al. Nurse Davis TC, Gorby N, Ladewski L, et al. administered telephone intervention for Health care provi -directed intervention to der -tailored blood pressure control: a patient increase colorectal cancer screening among multifactorial intervention. Patient Educ veterans: results of a randomized controlled Couns. 2005 Apr;57(1):5- 14. trial. J Clin Oncol. 2005 Mar 1;23(7):1548- 54. 2. Brock TP, Smith SR. Using digital videos displayed on personal digital assistants Retamero R, Gigerenzer Galesic M, Garcia- 7. (PDAs) to enhance patient education in G. Using icon arrays to communicate clinical settings. Int J Med Inform. 2007 medical risk s: overcoming low numeracy. 12):829- 35. Nov -Dec;76(11- Health Psychol. 2009 Mar;28(2):210- 6. 3. Bryant MD, Schoenberg ED, Johnson TV, Galesic M, Gigerenzer G, Straubinger N. 8. Goodman M, Owen- Smith A, M aster VA. Natural frequencies help older adults and Multimedia version of a standard medical people with low numeracy to evaluate questionnaire improves patient medical screening tests. Med Decis Making. understanding across all literacy levels. J 71. 2009 May -Jun;29(3):368- 5. Urol. 2009 Sep;182(3):1120- Retamero R, Galesic M. Garcia- 9. 4. Campbell FA, Goldman BD, Boccia ML, Communicating treatment risk reduction to Skinner M. The effect of format people with low numeracy skills: a cross - prehension modifications and reading com cultural comparison. Am J Public Health. on recall of informed consent information by 2009 Dec;99(12):2196- 202. -income parents: a comparison of print, low Gerber BS, Brodsky IG, Lawless KA, 10. video, and computer -based presentations. Smolin LI, Arozullah AM, Smith EV, et al. Patient Educ Couns. 2004 May;53(2):205- - Implementation and evaluation of a low 16. literacy diabetes education computer DeWalt DA, Malone RM, Bryant ME, 5. multimedia application. Diabetes Care. 2005 . A Kosnar MC, Corr KE, Rothman RL, et al 80. Jul;28(7):1574- -management program for heart failure self Greene J, Peters E. Medicaid consumers and 11. patients of all literacy levels: a randomized, informed decisionmaking. Health Care controlled trial [ISRCTN11535170]. BMC g;30(3):25- 40. Financ Rev. 2009 Sprin Health Serv Res. 2006;6:30. A-5

273 12. Greene J, Peters E, Mertz CK, Hibbard JH. 21. Robinson LD, Jr., Calmes DP, Bazargan M. - Comprehension and choice of a consumer The impact of literacy enhancement on directed health plan: an experimental study. -related outcomes among asthma Am J Manag Care. 2008 Jun;14(6):369- 76. underserved children. J Natl Med Assoc. 6. 2008 Aug;100(8):892- 13. Jay M, Adams J, Herring SJ, Gillespie C, randomized trial Ark T, Feldman H, et al. A Rothman R, Malone R, Bryant B, Horlen C, 22. of a brief multimedia intervention to DeWalt D, Pignone M. The relationship improve comprehension of food labels. between literacy and glycemic control in a 31. 2009:25- Preventive medicine management program. diabetes disease- -Apr;30(2):263- Diabetes Educ. 2004 Mar 73. Kang EY, Fields HW, Kiyak A, Beck FM, 14. Firestone AR. Informed consent recall and 23. Rothman RL, DeWalt DA, Malone R, comprehension in orthodontics: traditional Bryant B, Shintani A, Crigler B, et al. vs improved readability and processability Influence of patie nt literacy on the methods. Am J Orthod Dentofacial Orthop. based effectiveness of a primary care- -9. 2009 Oct;136(4):488 e1- 13; discussion diabetes disease management program. 6. Jama. 2004 Oct 13;292(14):1711- Kim S, Love F, Quistberg DA, Shea JA. 15. - Association of health literacy with self 24. Rudd RE, Blanch DC, Gall V, Chibnik LB, management behavior in patients with Wright EA, Reichmann W, et al. A abetes Care. 2004 diabetes. Di randomized controlled trial of an Dec;27(12):2980- 2. intervention to r educe low literacy barriers in inflammatory arthritis management. 16. Kripalani S, Robertson R, Love -Ghaffari 9. Patient Educ Couns. 2009 Jun;75(3):334- MH, Henderson LE, Praska J, Strawder A, et al. Development of an illustrated Schillinger D, Handley M, Wang F, 25. -literacy medication schedule as a low -management Hammer H. Effects of self patient education tool. Patient Educ Couns. support on structure, process, and outcomes 2007 Jun;66(3):3 77. 68- among vulnerable patients wit h diabetes: a three -arm practical clinical trial. Diabetes 17. Kripalani S, Sharma J, Justice E, Justice J, Care. 2009 Apr;32(4):559- 66. Spiker C, Laufman LE, et al. Low -literacy interventions to promote discussion of 26. Schillinger D, Hammer H, Wang F, Palacios prostate cancer: a randomized controlled J, McLean I, Tang A, et al. Seeing in 3 -D: trial. Am J Prev Med. 2007 Aug;33(2):83- examining the reach of diabetes self - 90. management support strategies in a public health care system. Health Educ Behav. Kripalani S, Bengtzen R, Henderson LE, 18. 82. 2008 Oct;35(5):664- - Jacobson TA. Clinical research in low literacy populations: using teach -back to 27. Seligman HK, Wang FF, Palacios JL, assess comprehension of informed consent Wilson CC, Daher C, Piette JD, et al. - and privacy information. Irb. 2008 Mar Physician notification of their diabetes Apr;30(2):13- 9. patients' limited health literacy. A randomized, controlled trial. J Gen Intern 19. Murray MD, Young J, Hoke S, Tu W, Med. 2005 Nov;20(11):1001- 7. Weiner M, Morrow D, et al. Pharmacist intervention to improve medication Sobel RM, Paasche- Orlow MK, Waite KR, 28. adherence in heart failure: a randomized Rittner SS, Wilson EA, Wolf MS. Asthma trial. Ann Intern Med. 2007 May 1-2-3: a low literacy multimedia tool to 25. 15;146(10):714- educate African American adults about asthma. J Community Health. 2009 Peters E, Dieckmann N, Dixon A, Hibbard 20. Aug;34(4):321- 7. JH, Mertz CK. Less is more in presenting quality information to consumers. Med C are 29. Volandes AE, Paasche -Orlow MK, Barry 90. Res Rev. 2007 Apr;64(2):169- MJ, Gillick MR, Minaker KL, Chang Y, et al. Video decision support tool for advance care planning in dementia: randomised controlled trial. Bmj. 2009;338:b2159. A-6

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275 Appendix B. Search Strings May 2009 Search PubMed 173 #1 Search numeracy Search numeracy Limits: Humans, English #2 146 Search "health literacy" 789 #3 Search "health literacy" Limits: Entrez Date from 2003, Humans, English 586 #4 716 #5 Search #2 OR #4 Search literacy 39075 #6 Search "rapid estimate of adult literacy" OR real* 215538 #7 #8 920 Search #6 AND #7 Search "test of functional health literacy" OR tofhl* 295 #9 295 #10 Search #6 AND #9 Search "Hebrew health literacy test" OR HHLT 6 #11 1202 Search "medical achievement reading test" OR MART #12 Search #6 AND #12 23 #13 Search "newest vital signs" OR NVS 203 #14 #15 Search #6 AND #14 6 #16 assessment of health literacy" OR SAHLSA 170 Search "short Search #6 AND #16 170 #17 290 #18 Search "wide range achievement test" OR WRAT Search #6 AND #18 77 #19 #20 Search "nutritional literacy" OR "literacy assessment for diabetes" OR LAD OR SIL 18220 OR "single item numeracy screener" OR DAHL OR "demographic assessment" OR BEHKA OR "brief estimate" OR "diabetes numeracy" OR "medical data interpretation" OR "subjective numeracy" OR "numeracy test" #21 Search #6 AND #20 264 #22 Search #8 OR #10 OR #11 OR #13 OR #15 OR #17 OR #19 OR #21 1661 #23 Search #8 OR #10 OR #11 OR #13 OR #15 OR #17 OR #19 OR #21 Limits: Entrez 729 Date from 2003, Humans, English Search #5 OR #23 1310 #24 #25 Search #5 OR #23 Limits: Editorial, Letter, Case Reports 58 #26 Search #24 NOT #25 1252 PubMed #1 Search "rapid estimate of adult literacy" 104 #2 Search "test of functional health literacy" 290 B-1

276 #3 6 Search "Hebrew health literacy test" Search "medical achievement reading test 0 #4 Search medical achievements reading test 68 #5 Search "newest vital signs" 1 #6 Search "short assessment of health literacy" 170 #7 Search "wide range achievement test" #8 219 #9 Search "literacy assessment for diabetes" 225 3 #10 Search "nutritional literacy" Search "single item numeracy screener" #11 0 #12 Search #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 991 #13 Search #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 473 Limits: Entrez Date from 2003, Humans, English Search #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 #14 5 Limits: Entrez Date from 2003, Humans, Editorial, Letter, Case Reports, English Search #13 NOT #14 468 #15 PubMed #1 Search literacy [tw] 5516 #2 Search literacy [tw] Limits: Entrez Date from 2003, Humans, English 2337 #3 Search literacy [tw] Limits: Editorial, Letter, Case Reports 243 #4 2226 Search #2 NOT #3 Term used in other databases: “health literacy” CINAHL = 34 = 22 NEW Cochrane = 61 = 34 NEW PsycINFO = 65 = 26 ERIC = 34 = 31 Total Unduplicated Database = 2855 B-2

277 December 2009 Search PubMed Queries Result Search #1 213 Search numeracy 169 #2 Search numeracy Limits: Humans, English Search "health literacy" 964 #3 Search ("2009/01/01"[Entrez Date] : "3000"[Entrez Date]) AND ("health #4 110 literacy") Limits: Humans, English Search #2 OR #4 Limits: Humans, English 273 #5 Search literacy #6 41096 #7 Search "rapid estimate of adult literacy" OR real* 232562 968 #8 Search #6 AND #7 Search "test of functional health literacy" OR tofhl* 326 #9 Search #6 AND #9 #10 326 #11 Search "Hebrew health literacy test" OR HHLT 7 Search "medical achievement reading test" OR MART 1300 #12 #13 Search #6 AND #12 26 #14 vital signs" OR NVS 220 Search "newest 8 #15 Search #6 AND #14 Search "short assessment of health literacy" OR SAHLSA 187 #16 Search #6 AND #16 187 #17 Search "wide range achievement test" OR WRAT 302 #18 Search #6 AND #18 83 #19 Search "nutritional literacy" OR "literacy assessment for diabetes" OR LAD OR #20 18849 SIL OR "single item numeracy screener" OR DAHL OR "demographic assessment" OR BEHKA OR "brief estimate" OR "diabetes numeracy" OR OR "numeracy test" "medical data interpretation" OR "subjective numeracy" #21 Search #6 AND #20 282 #22 Search #8 OR #10 OR #11 OR #13 OR #15 OR #17 OR #19 OR #21 1773 #23 Search ("2009/01/01"[Entrez Date] : "3000"[Entrez Date]) AND (#8 OR #10 OR 86 Limits: Humans, English #11 OR #13 OR #15 OR #17 OR #19 OR #21) Search #5 OR #23 #24 342 #25 Search #5 OR #23 Limits: Editorial, Letter, Case Reports 24 #26 Search #24 NOT #25 318 B-3

278 CINAHL -Medline = 37 : “health literacy” limited to English language and non Published Date from: 20090101- 20101231; Exclude MEDLINE "health literacy" Limiters - records; Language: English Search modes - Boolean/Phrase ( ) 37 Cochrane Library “health literacy” 2009 -present= 1 review; 4 clinical trials = 5 total. PsycINFO “health literacy”, 2009- present, English language, no editorials, no letters = 74 "health literacy" Limiters - Published Date from: 20090101- 20101231; Language: English Search modes - Boolean/Phrase ( 74 ) ERIC Main Search: “health literacy”, 2009- present, English language = 9 B-4

279 May 2010 Search PubMed Result Search Most Recent Queries Search numeracy 243 #1 1084 #2 Search "health literacy" Search #1 OR #2 1285 #3 Search literacy 42702 #4 245476 estimate of adult literacy" OR real* #5 Search "rapid Search #4 AND #5 1000 #6 Search "test of functional health literacy" OR tofhl* 154 #7 #8 154 Search #4 AND #7 1 #9 Search "Hebrew health literacy test" OR HHLT Search #4 AND #9 1 #10 Search "medical achievement reading test" OR MART 1358 #11 Search #4 AND #11 28 #12 Search "newest vital signs" OR NVS 261 #13 #14 Search #4 AND #13 11 #15 Search "short assessment of health literacy" OR SAHLSA 49 Search #4 AND #15 49 #16 Search "wide range achievement test" OR WRAT 303 #17 Search #4 AND #17 84 #18 Search "nutritional literacy" OR "literacy assessment for diabetes" #19 19266 OR LAD OR SIL OR "single item numeracy screener" OR DAHL te" OR OR "demographic assessment" OR BEHKA OR "brief estima "diabetes numeracy" OR "medical data interpretation" OR "subjective numeracy" OR "numeracy test" #20 Search #4 AND #19 303 #21 Search #6 OR #8 OR #10 OR #12 OR #14 OR #16 OR #18 OR #20 1522 2561 Search #3 OR #21 #22 #23 Search #22 Limits: Humans, English 2042 #24 Search #23 Limits: Editorial, Letter, Case Reports 93 #25 Search #23 NOT #24 1949 #26 Search (#25) AND "2009/10/01"[Entrez Date] : "3000"[Entrez Date] 106 Sort by: PublicationDate B-5

280 Analogous terms were used to conduct searches in the following databases: CINAHL 39 initially imported 38 after duplicates removed PsycINFO 68 initially imported 53 after duplicates removed Cochrane Library 44 initially imported 41 after duplicates removed ERIC 8 initially imported 6 after duplicates removed Total records = 24 B-6

281 Appendix C . Inclusion/Exclusion Criteria and Study Internal Validity Quality Form Inclusion/Exclusion Criteria: Please mark each abstract or article IN/OUT based on following criteria. For those excluded, provide exclusion reason and any additional pertinent codes listed below. Insert space below Inclusions: Prospective and cross -sectional observational studies of literacy levels and health. Studies must measure 1. literacy at the individual level. 2. Trials of materials developed for low literacy populations or trials of interventions that compare easier to read/understand material versus standard materials. Exclusion Criteria: 1. Studies with no original data 2. SER only 3. Studies that do not measure literacy or health literacy 4. Studies with no health outcomes (ie. descriptive only or have outcomes like likability, satisfaction) 5. Studies examining normal reading development in children 6. Studies about dyslexia 7. Studies on the ba sic experimental science of reading ability (e.g., studies of brain function, MRI, EEG) 8. Non -English language studies 9. Studies answering KQ1 where literacy is measured (not numeracy) and the only study outcome is knowledge. 10. Studies in which the outcome is l imited to dementia or cognitive impairment. 11. Studies published in abstract form only 12. Case- report only 13. Ecological data only 14. Sample size less than 10 15. Unable to obtain the article Intervention studies that do not address low health literacy 16. C-1

282 Study Internal Validity (Risk of Bias) Review Form :_________________________________ Reviewer______________________ REF #, Author, Year Short Title :__________________________________________________________________________ Response Criter ia Question Comments Internal Validity Good 1. Method of Randomization  Computer generated random -RCT only) allocation. (KQ2 Fair Flipped coin  Poor  Pseudo randomization (ie. alternate allocation, by days of week, etc) or randomization approach cannot be determined Participants not randomized NA  2. Allocation Concealment Good  Central randomization (KQ2 -RCT only) Fair Opaque envelopes  Poor  No concealment NA Participants not randomized  No baseline differences (>20% 3. Creation of Comparable  Good qualitatively) among groups Groups regarding inclusion/exclusion criteria Fair Few baseline difference among groups, probably related to  chance  Multiple differences among Poor groups NA Cross -sectional, case- control or  single arm study Low attrition (< 20%) and Low 4. Maintenance of  Good differential loss (<5%) Comparable Groups. If there is only one study arm than (20 -40%) or Fair Moderate attrition consider the overall attrition  Moderate differential loss (5- only. 15%)  Poor High Attrition (>40%) or High differential loss (>15%) NA control. - Cross - sectional, case  Measure valid and reliable. 5. Health Literacy  Good (unless the HL measure is one of Measurement (health literacy, the well known and applied literacy, numeracy, or other) measures (REALM, TOFHLA,WRAT etc., measurement validation should be discussed in the text) Fair Some of the above features  C-2

283 Poor None of the above features  6. Outcome Measurement  Measure valid and reliable Good (i.e. mortality, clinical measure, well validated scale) Some of the above features Fair  (Chart review, partially validated scale) None of the above features. Poor  -report, pain may be an (self validated scale) - exception, non Good  Same measurement applied to 7. Outcome Measurement Equally Applied each group. Measurement at same point in time in each group Some of the above features. Fair  Poor  None of the above features. NA Study includes only one group   Good 8. Blinding of patients and Blinding of patients and providers providers (KQ2 only) Fair Blinding of one of the above.  Poor Blinding of none of the above.  not an NA Study was  RCT/Intervention study: Patients and providers could not be blinded to the treatment arm Yes  Good 9. Blinding of outcome assessors to intervention or exposure status of participants  Poor No NR  NA  statistical Good  10. Appropriate Statistical tests appropriate to the data. Appropriate accounting for testing clustering, if RCT or naturally clustered environment, and multiple comparisons. Fair Some of the above features.  Poor  features. None of the above 11. Intent to Treat Analysis or Intent to treat or other analysis Good  done Sensitivity Analysis done to assess impact of loss to  Poor No analysis completed follow -up NA Cross sectional, single arm study  -control selected or case on outcome measure 12 Appropriate control of Good  Addressed through study design confounding (e.g., randomization) and/or analysis (e.g., through matching, stratification, multivariate analysis or other statistical adjustment) to control Fair Attempt made  confounding, but doesn’t address all relevant confounders. C-3

284  Poor No attempt to control confounders. 13. Sample sufficient by power Good  Yes, for all outcomes reported analysis Fair  Yes, for some outcomes No, not Poor  done Overall Assessment Good  Conclusions are very likely to be 14. Overall study assessment correct given degree of bias Fair  Conclusions are probably correct given degree of bias Poor  Conclusions aren’t certain because bias too large C-4

285 Appendix D. Evidence Tables Glossary of Abbreviations and Acronyms Used in Evidence Tables Abbreviation/ Definition Acronym * Calculated by evidence report authors African - American AA Assessment of Body Change Distress Scale ABCD ABLE Adult Basic Learning Examination Autologous bone marrow transplant ABMT AC Asthma clinic - converting enzyme ACE Angiotensin ADEPT Adherence and Efficacy to Protease Inhibitor Therapy study ADL of daily living Activities AdLit Adolescent Literacy AFDC Aid for Families with Dependent Children AIDS Acquired immune deficiency syndrome ANCOVA Analysis of covariance ANOVA Analysis of variance AOR adjusted odds ratio Asthma Quality of Life Questionnaire AQLQ ARB Angiotensin II receptor blockers Arthritis Research Campaign ARC ARR Absolute Risk Reduction ART Antiretrovial therapy ASI Aic Addition Severity Index - alcohol scale - ASI - drug Addition Severity Index - drug scale Avg average b/c because BA/BS Bachelor of Arts/Bachelor of Science BCT breast - conservation therapy BDI Beck Depression Inventory Body mass index BMI BMQ Beliefs about Medicines Questionnaire blood pressure BP Breast self - exam BSE BSI Brief Symptom Inventory cancer CA CAD coronary artery disease Capillary Affinity Gel Electrophoresis CAGE Cardiovascular Dietary Education System CARDES computer - assisted self interview CASI Clinical breast exam CBE CD Compact disc Cluster Difference 4 CD4 CD - Compact disc — read - only memory ROM - D Center for Epidemiology Studies Depression Scale CES CHART Craig Handicap Assessment and Reporting Technique CHD coronary heart disease CHF congestive heart failure CI Confidence interval cigarettes cigs COMBO combination of 3 risk reduction presentations (RRR + ARR + NNT) COOP/WONCA Dartmouth Primary Care Cooperative Information Project/World Organization of National Colleges, Academies COPD Chronic obstructive pulmonary disease CPAP Continuous positive airway pressure CR C colorectal cancer D-1

286 Abbreviation/ Definition Acronym SDSCA C - Care Activities Chinese version of the Summary of Diabetes Self - Computed Tomography CT dB Decibel Diastolic blood pressure DBP DDS Diabetes Distress Scale Deaconess Informed Consent Comprehension Test DICCT dl Deciliter DM Diabetes mellitus DMHDS Dunedin Multidisciplinary Health and Development Study Deoxyribonucleic Acid DNA DNR Do Not Resuscitate Drug Regimen Unassisted Grading Scale DRUGS E or S English or Spanish ED Emergency department EFNEP and Nutrition Education Program Expanded Food - Functional Assessment of Cancer Therapy - General FACT G fecal occult blood testing FOBT FQHC Federally Qualified Health Centers Family Service Center FSC G Group GA Georgia GED General equivalency degree Generalized Estimating Equation GEE Grady Grady Memorial Hospital, Atlanta, GA HAART Highly active antiretroviral therapy HAQ/HAD Hospital Anxiety and Depression Scale Harbor Harbor - UCLA Medical Center, Torrance, CA HbA1c Glycosylated hemoglobin Hep C hepatitis C Hg Mercury Human immunodeficiency virus HIV HIV/AIDS Human immunodeficiency virus/Acquired Immune Deficiency Syndrome HL health literacy Health maintenance organization HMO health related quality of life HRQoL high school HS Hypertension HTN Instrumental activities of daily living IADL - International Classification of Disease - Ninth Revision 9 ICD - 9 - CM International Classification of Disease - Ninth Revision, Clinical Modification ICD Instrument for the diagnosis of reading IDL Instrument for the Diagnosis of Reading IDR IEP Individualized Educational Plan INR International Normalized Ratio IQ Intelligence quotient IQR Individual Qualification Record IRR Incidence rate ratio Intra - IUD uterine device kcal Kilocalories kg Kilogram KMS Knowledge of Medication Subtest KQ key question Knowledge Scale Questionnaire KSQ l Liter LA Louisiana LAE Los Angeles English speaking (Harbor - UCLA Medical Center) Los Angeles Spanish speaking (Harbor - UCLA Medical Center) LAS LDL Low Density Lipoprotein D-2

287 Abbreviation/ Definition Acronym Mental Component Summary of SF 36 - MCS MD medical doctor Metered dose inhaler MDI medical med MEMS Medical Equipment Management System Milligrams mg MHMC Mercy Hospital and Medical Center MHP mental health problem Medication Knowledge Score MKS Milliliter mL Millimeters mm MMC Medication management capacity MML Marginal Maximum Likelihood mmol Millimoles - Mental State Examination MMSE Mini Mater – University of Queensland Study of Pregnancy MUSP N Number Not applicable NA NAAL National Assessment of Adult Literacy NALS National Adult Literacy Survey NART National Adult Reading Test North Carolina NC ng/mL Nanograms per mililiter NH New Hampshire NLS Nutrition Label Survey NNT number needed to treat NOS not otherwise specified Not reported NR NS Not significant New York NY OAD oral anti - diabetic drug Oral contraceptive pill OCP Ordinary Least Squares OLS Odds ratio OR Probability P Pennsylvania PA PACE Pima County adult education program, Tucson, AZ Pediatric Asthma Caregiver’s Quality of Life Questionnaire PACQLQ Pictorial anticipatory guidance PAG Patient Activiation Measure PAM Papanicolaou smear Pap test Prostate Cancer Knowledge Questionnaire PCKQ primary care physician PCP PMAQ Patient Medication Adherence Questionnaire PORT Patient Outcomes Research Team PR prevalence ratio PSA Prostate - Specific Antigen QLS Questionnaire Literacy Screen r Correlation coefficient RA Research assistant RCT Randomized controlled trial REALM Rapid Estimate of Adult Literacy in Medicine RNA Ribonucleic Acid RR Relative risk RRR Relative risk ratio RSPM Raven Standard Progressive Matrices SBP Systolic blood pressure SD Standard deviation D-3

288 Abbreviation/ Definition Acronym Summary of Diabetes Self Care Activities Measure - SDSCA Socio - economic status SES - 12 Short Form 12 SF - SF Short Form 36 36 SF 36 PCS Medical Outcomes Study Physical Component - SGUQ Standard Gamble Utility Questionnaire Significant Sig SIP Sickness Impact Profile SMOG Readability formula SNAP Nutrition Action Program Stanford SPMSQ Short Portable Mental Status Questionnaire - HIVrev Revised Sign and Symptom Checklist for persons with HIV Disease SSC STD Sexually transmitted diseases STIFLE S - TOFHLA Short Test of Functional Health Literacy in Adults SWOG Southwestern Oncology Group Test of Adult Basic Education TABE TALS Test of Applied Literacy Skills TIPP The Injury Prevention Program TN Tennessee TOFHLA Test of Functional Health Literacy in Adults - TOFHLS S Test of Functional Health Literacy in Adults in Spanish TT Talking Touchscreen tests Statistical hypothesis test - t Texas TX University of California, Los Angeles UCLA UHS Duke University Healthcare System United Kingdom UK - University of Pennsylvania PENN U US United States Veterans Affairs VA Veterans Affairs Healthcare System VAHS - - 25 25 item Visual Function Questionnaire VFQ VRQoL - related quality of life vision vs. versus Vermont VT WAIS R Wechsler Adult Intelligence Scale – Revised - WIC Women, Infants, and Children wk week WRAT Wide Range Achievement Test WRAT3 Wide Range Achievement Test, 3rd edition WRAT - R Wide Range Achievement Test – Revised yr(s) Year(s) D-4

289 Key Question 1: Health literacy outcome studies Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 1 Inclusion: Bailey et al., 2009 18-75 years of age Research objective: Exclusion: To determine the level of adult understanding - reported severe impaired vision, hearing problems, acute illness Self of dosage instructions for a liquid medication or limited English proficiency commonly prescribed for children. Sampling strategy: Study design: Convenience Sample- consecutive adults waiting for an appointment Cross -sectional for themselves or their children in clinic waiting rooms. Study setting: Sample size: family medicine clinics serving 3 Outpatient N = 373 low -income populations in Shreveport, La; Age (mean and range), %: Chicago, IL, and Jackson, Mich 44 (SD = 13.2) Measurement period: Gender, %: August 2004 July 2003 - Female: 67.8% Measurement tools including cutpoints, %: Race/Ethnicity, %: REALM: African -American: 58 ≤ 6th grade Low: White: 42 Marginal: 7th- 8th grade Income, %: Adequate: ≥ 9th grade NR Insurance status, %: NR Education, %: More than HL or GED: 27.8 HS or GED: 43.1 Less than HS: 29.1 Other characteristics, %: NR Health literacy/numeracy levels, %: Literacy Level: Low: 19.8 Marginal: 28.9 Adequate: 51.2 D-5

290 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Those with lower HL levels were more likely to misunderstand Intrepretation of a prescription label for amoxicillin dosing instructions, controlling for other characteristics. HL Understanding of dosage measurement and frequency of use mediates the relationship between racial differences and nding. medication label understa Covariates used in multivariate analysis: Multivariate analysis 1: Race, age, sex, and Effect in no exposure (i.e., adequate literacy) or control group: education Misunderstanding of Medication Label Instructions, %: analysis 2: Race, age, sex, and Literacy level, adequate: 18.3 Multivariate education and HL Effect in exposure (i.e., low/moderate literacy) or intervention: Description of outcome measures: Misunderstanding of Medication Label Instructions, %: Literacy level, low: 43.2 To assess subjects' understanding of prescription labels, each patient was presented with a series of Literacy level, marginal: 34.3 Difference: mock prescription bottles, including one for an oral suspension medicati Difference in Medication Understanding (adjusted): on and asked "How would you give this medicine?" Marginal v Adequate: AOR, 2.20; 95% CI 1.19-3.97 Low v Adequate: AOR, 2.90; 95% CI 1.41-6.00 Data source(s) for outcomes: s: race and gender sig in Model 1 (not Mediation analysi Interview controlling for HL) and not in Model 2 (controlling for HL) Attempts for control for confounding: Multivariate logistic regression models Blinding: Yes; panel of blinded physician reviewers determined whether or not the interpretations were correct Statistical measures used: Bivariate analyses between demographic variables, literacy level, and incorrect interpretation of dosage instructions Mediational analysis, a form of regression, was used to explore the relationship between literacy, race, and the outcome D-6

291 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 2 2004 Baker et al., Included: 3 ; Wolf et (Companions: Gazmararian, 2006 Medicare managed-care enrollee 5 4 Howard et al., Baker et al., 2007; al., 2007; 65+ 8 7 6 Baker et al., 2008; Wolf et al., 2005; 2006; Enrolled in Prudential HealthCare 3 months or more 9 ) Howard et al., 2005; Excluded: Research objective: Not comfortable speaking English or Spani sh Determine whether individuals with Blind or severely impaired vision not correctable with eyeglasses inadequate HL who are newly enrolled in Living in a nursing home Medicare managed care plans in 4 US cities Missed 1 or more screening questions for severe cognitive had lower rates of outpatient physician visits impairment (not able to correctly identify year, month, state, year of than enrollees with adequate HL. their birth, or home address) Study design: pling strategy: Sam Cohort Convenience sample of consecutive new Medicare managed -care Study setting: enrollees In-person in-home interviews with and Sample size: subsequent claims data for enrollees in 3,260 Cleveland, Hou ston, Tampa, and south Age (mean and range), % (SD): Florida (including Ft. Lauderdale and Miami) 65-69: 37.0 Measurement period: 70-74: 27.3 Interviews occurred May 1997-December 75-79: 19.3 1997 80-84: 11.0 Claims data from within 1 year of date of >85: 5.4 enrollment into plan (usually 3 months prior to Adequate HL: 71.6 (5.6) study enrollment) Marginal HL: 74.1 (6.3) -up duration: Follow 75.6 (7.2) Inadequate HL: 1 year Gender, %: Completeness of follow -up: Male: 42.6 N = 3260 completed interview and S -TOFHLA Male by HL status, %: Adequate: 42.1 Marginal: 46.2 Inadequate: 42.2 Race/Ethnicity, %: White: 76.0 Black: 11.8 English- speaking Hispanic: 2.0 Spanish-speaking Hispanic: 9.2 Other: 1.0 Adequate: White: 84 AA: 6.6 Hispa nic English-speaking: 1.6 Hispanic Spanish- speaking: 6.6 Other: 1.2 D-7

292 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: After adjusting for covariates, healthy literacy was not Access to Care: Time to first physician visit following enrollment significantly associated with time to first physician visit, mean Number of outpatient visits first year, enrolled number of physician visits, or no physician visit in the first year. Inadequate health literacy was associated with a significantly No physician visit first year higher rate of ED visits, after adjusting for covariates. ED frequency Effect in no exposure (i.e., adequate literacy) or control group, Covariates used in multivariate analysis: %: Age Gender Total Outpatient Visits, mean (CI): No Physician visit: 8.1 Race Time to first visit: see Kaplan- -reported physical and mental health Meier Curves, Figure 1 Self Total physician visits: 14.3 (13.7-15.0) # chronic diseases Mean ln (visits): Mean 2.23 ( 2.19-2.28) Smoking Current alcohol use ED Visits: Study site Any ED visit: 21.8 Months enrolled first year 1 ED visit: 15.0 Description of outcome measures: 2 or more ED visits: 6.8 No outpatient visits Smoking, %: Total number of outpatient visits Never: 38.3 Former: 49.2 Time to first visit Total number of ED visits Current: 12.6 Current alcohol use, %: Current alcohol use: categorical None: 58.5 None, Light to moderate, Heavy Light to moderate: 37.5 Problem Drinking: Heavy: 4.0 >2 Positive Responses on CAGE: >2 Positive Responses on CAGE:7.9 Number of Chronic Conditions: (hypertension, Number of c diabetes, heart disease, chronic obstructive hronic conditions, mean (SD): Number of chronic conditions: 1.9 (1.4) pulmonary disease or asthma, arthritis, or cancer) Physical Health Summary Scale: 46.4 (10.7) Depression: Geriatric Depression Scale -12 Mental Health Summary Scale: 55.6 (8.0) Physical Health Summary Scale: SF Effect in exposure (i.e., low/moderate literacy) or intervention: y Scale: Mini Mental State Mental Health Summar Exam ean (CI) Total Outpatient Visits (marginal), m Data source(s) for outcomes: No Physician visit: 9.3 Meier Curves, Figure 1 Time to first visit: see Kaplan- Medicare claims data and in-person orally administered survey Total physician visits: 13.5 (12.1-15.0) Attempts for control for confounding: Mean ln (visits): 2.17 (2.07- 2.27) Total Outpatient Visits (inadequate), mean (CI) Multivariate logistic regression No Physician visit: 9.8 Blinding: Time to first visit: see Kaplan- Meier Curves, Figure 1 NR Total physician visits: 13.7 (12.7-14.8) Statistical measures used: 2.28) Chi -square Mean ln(visits): 2.21 ( 2.14- e logistic regression ED Visits (marginal), % Multivariat ANOVA Any ED visit: 27.6 1 ED visit: 15.3 Kaplan-Meier curves and unadjusted Cox 2 or more ED visits: 12.3 proportional hazards models Multivariate survival analysis ED Visits (inadequate), % Linear regression Any ED visit: 30.4 1 ED visit: 17.0 Multivariate polytomous logistic regression 2 or more ED visits: 13.4 D-8

293 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: Marginal: 2 White: 68 Baker et al., 2004 3 ; Wolf et (Companions: Gazmararian, 2006 AA: 12.6 4 5 Howard et al., al., 2007; Baker et al., 2007; Hispanic English-speaking: 2.5 6 8 7 Wolf et al., 2005; Baker et al., 2008; 2006; Hispanic Spanish- speaking: 16.4 9 ) Howard et al., 2005; Other: 0.6 (continued) Inadequate : White: 25.2 AA: 58.6 Hispanic English-speaking: 2.3 speaking: 13 Hispanic Spanish- Other: 1 Income, %: <$10 000: 18.2 $10 000-14 999: 21.6 $15 000-24 999: 25.6 $25 000-34 999: 8.7 $35 000: 10.2 Did not answer/did not know: 15.7 By HL status, %: Adequate: 36.6 <$15,000 Marginal 56 <$15,000 Inadequate 67.1 <$15,000 Insurance status: Medicare: 100% Education, %: Grade school or less: 17.3 Some high school: 18.4 High school: 33.6 More than high school: 30.7 By health literacy status: Adequate: 0-8 years: 7.1 years: 14.9 9-11 12 or GED: 38.3 >12 years: 39.7 Marginal: 0-8 years: 24.2 9-11 years: 25.6 12 or GED: 30.2 >12 years: 20.0 Inadequate: 0-8 years: 40.9 9-11 years: 24.3 12 or GED: 22.8 >12 years: 12.0 D-9

294 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Results Outcomes Smoking (marginal), %: Never: 42.6 Former: 44.8 Current: 12.6 Smoking (inadequate), %: Never: 45.1 Former: 42.9 Current: 12.0 Current alcohol use (marginal): None: 64.7 Light to moderate: 33.3 Heavy: 1.9 Current alcohol use (inadequate): None: 75.1 Light to moderate: 23.3 Heavy: 1.6 > 2 Positive Responses on CAGE, % Marginal: 7.9 Inadequate: 13.7 Number of chronic conditions, mean (SD): Marginal: 2.1 (1.5) Inadequate: 2.2 (1.5) Physical Health Summary Scal e, mean (SD): Marginal: 43.7 (11.7) Inadequate): Mean (SD) = 41.9 (11.9) Marginal: 55.1 (9.2) Mental Health Summary Scale (inadequate): Mean (SD) = 52.1 (10.7) Difference: Total Outpatient Visits: Difference in no physician visit (adjusted), OR (CI): Mar ginal: 1.23 (0.82-1.85) Inadequate: 1.23 (0.88-1.72) Time to first visit, days (adjusted), HR (CI): Marginal: 0.89 (0.78-1.00) Inadequate: 0.94.84-1.04) Mean visits (adjusted): Marginal: ( P = 0.34) Inadequate: ( P = 0.38) Mean visits, natural log (adjusted): P = 0.27) Marginal: ( Inadequate: ( = 0.62) P ED Visits: Any ED Visit (adjusted): Marginal: ( P = 0.01) Inadequate: ( P < 0.001) D-10

295 Study Description Participant Characteristics Author, year: 2 Baker et al., 2004 3 ; Wolf et (Companions: Gazmararian, 2006 4 5 Howard et al., Baker et al., 2007; al., 2007; 8 7 6 Wolf et al., 2005; Baker et al., 2008; 2006; 9 ) Howard et al., 2005; (continued) D-11

296 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes 1 ED visit (adjusted), RR (CI): Marginal: 1.01 (0.76-1.33) Inadequate: 1.07 (0.86-1.33) 2 or more ED visits (adjusted): Marginal: 1.44 (1.01-2.02) Inadequate:1.34 (1.00-1.79) Smoking: Diff across all 3 HL groups (unadjusted): (P < 0.01) Current Alcohol Use: Diff across all 3 HL groups (unadjusted): < 0.01) (P > 2 Positive Responses on CAGE: Diff across all 3 HL groups (unadjusted): (P = NS) Number of Chronic Conditions: Diff across all 3 HL groups (unadjusted): (P = NS) Physical Hea lth Summary Scale: Diff across all 3 HL groups (unadjusted): (P = NS) Mental Health Summary Scale: Diff across all 3 HL groups (unadjusted): (P = NS) D-12

297 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 8 Baker et al., 2008 Included: 3 (Companions: Gazmararian, 2006 ; Wolf et Medicare managed-care enrollee 4 5 ; Howard et al., ; Baker et al., 2007 al., 2007 65+ 9 6 7 ; ; Howard et al., 2005 ; Wolf et al., 2005 2006 Enrolled in Prudential HealthCare 3 months or more 2 ) Baker et al., 2004 Excluded: Measurement tools including cutpoints: Not comfortable speaking English or Spa nish S-TOFHLA: Blind or severely impaired vision not correctable with eyeglasses Adequate Living in a nursing home Marginal Missed 1 or more screening questions for severe cognitive Inadequate impairment (not able to correctly identify year, month, state, year of (cut points NR) their birth, or home address) er publications from the Cut points used in oth Sampling strategy: same study: -care Convenience sample of consecutive new Medicare managed Adequate: 67-100 enrollees Marginal: 56- 66 Sample size: 55 Inadequate: 0- 3191 (69 of original 3620 excluded because of missing data on cognitive functioning) Age (mean and range): NR: not exactly same as full sample in Baker et al. (2004) since sample analysis excludes 69 participants Gender: NR: not exactly same as Baker et al. (2004) since sample analysis excludes 69 participants Race/Ethnicity: NR: not exactly same as Baker et al. (2004) above since sample analysis excludes 69 participants Income: NR: not exactly same as Baker et al. (2004) since sample analysis excludes 69 participants Insurance status, %: Medicare: 100 Education: NR: not exactly same as Baker et al. (2004) since sample analysis excludes 69 participants Other characteristics: NR Health literacy/numeracy levels: NR D-13

298 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Participants with inadequate HL had sig higher mortality rates Mortality than those with adequate literacy, after adjusting for Covariates used in multivariate analysis: demographic characteristics, socioeconomic status, and Age th; when cognitive function was included in model, baseline heal Sex association Race Effect in no exposure (i.e., adequate literacy) or control group: Language Unadjusted (crude) mortality rates, %: Income Adequate: 18.9 Education Effect in exposure (i.e., low/moderate literacy) or intervention: SF -36 physical functioning and mental health Unadj usted (crude) mortality rates, % : component scores Inadequate: 38.4 # of chronic diseases Marginal: 28.4 # of impairments in ADLs Difference: # of impairments in IADLs Difference in mortality rate (adjusted for control variables but City of enrollment not cognitive functioning), HR (CI): Description of outcome measures: Inadequate vs. Adequate: 1.50 (1.24- 1.81) Deaths were identified using matches from the 90-1.42) Marginal vs. adequate: 1.13 (0. National Death Index Difference in mortality rate (adjusted for control variables and Data source(s) for outcomes: cognitive functioning), HR (CI): One -hour in-person orally administered survey and 1.57) Inadequate vs. adequate: 1.27 (1.03- National Death Index data Marginal vs. adequate: 1.08 (0.85-1.36) Attempts for control for confounding: Multivariate Cox models Blinding: NR Statistical measures used: Kaplan-Meier curves, Cox proportional hazards model, chi square, multivariate Cox models D-14

299 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 5 Baker et al., 2007 Included: 3 (Companions: Gazmararian, 2006 ; Wolf et New Medicare enrollees in 4 health plans 6 4 ; Wolf et al., ; Howard et al., 2006 al., 2007 65+ 8 7 ; Howard et al., ; Baker et al., 2008 2005 English or Spanish speaking 2 9 ) ; Baker et al., 2004 2005 Adequate vision Research objective: Knew year, month, state, year born, address Determine whether low literacy levels Excluded: independently predict overall and cause- Could not complete S -TOFHLA for reasons other than poor vision or specific mortality illiterate Study design: Sampling strategy: Prospective cohort Consecutive series of new enrollees Study setting: Sample size: Cleveland, Houston, Tampa, and South 3,260 Florida Age, mean (SD): Measurement period: Adequate H L: 71.6 (5.6) - December 31, Baseline measurement: July 1 Marginal HL: 74.1 (6.3) 1997 Inadequate HL: 75.6 (7.2) uration: Follow -up d Gender, %: Through 2003 Male -up: Completeness of follow Overall: 42.6 NR Adequate HL: 42.1 Measurement tools including cutpoints: Marginal HL: 46.2 S-TOFHLA: Inadequate HL: 42.2% Adequate: 67-100 Race/Ethnicity, %: Marginal: 56- 66 Adequate HL: 55 Inadequate: 0- White: 83.7 AA: 6.6 Hispanic, English -speaking: 1.6 Hispanic, Spanish-speaking: 6.5 Other: 1.6 Marginal HL: White: 68 AA: 12.6 Hispanic English Speaking: 2.5 Hispanic Spanish Speaking: 16.4 Other: 0.5 Inadequate HL: White: 58.1 AA: 25.0 Hispanic, English -speaking: 2.3 Hispanic, Spanish-speaking: 12.9 Other: 1.8% Income, %: <$10,000 Adequate HL: 12.0 Marginal HL: 26.2 Inadequate HL: 34.1 D-15

300 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Inadequate HL com specific mortality (cardiovascular, Mortality; Cause- pared to adequate (adjusted) significantly Cancer, -cause mortality, cardiovascular death and death other) predicts all Covariates used in multivariate analysis: due to all other causes than cardiovascular or cancer but is not Age significantly related to cancer death. In analyses stratified by race/ethnicity, hazar d ratio for Sex Race/ethnicity relationship between HL and mortality was significant among white and black participants but not Latino. Primary language (E or S) Marginal HL compared to adequate (adjusted) significantly Income Education related to higher cardiovascular death but not significantly # Chronic conditions related to cancer death or death due to all other causes than -reported mental and physical health cardiovascular or cancer. Self Instrumental activities of daily living Effect in no exposure (i.e., adequate literacy) or control group, Activities of daily living % (SD): Descriptio n of outcome measures: All cause mortality: 18.9 National Death Index to identify deaths of individuals Cardiovascular death: 7.9 in study and matched to Medicare enrollees in Cancer death: 5.8 -9 codes to determine cause of death study; ICD Death due to other causes: 5.2 (cardiovascular death, cancer death, other) onic conditions, mean: 1.5 (1.2) Number of chr Data source(s) for outcomes: Physical function score, mean: 46.2 (10.7) Death Index, death certificates National Mental health score, mean: 55.5 (7.9) Attempts for control for confounding: IADL limitation: 23.6 Multivariate analysis ADL limitation: 3.0 Blinding: Smoking, %: NA Never: 38.3 Statistical measures used: Former: 49.2 Multivariate analysis, Kaplan- Meier curves, Current: 12.6 multivariate Cox proportional hazards model Current alcohol use, %: None: 58.5 Light to moderate: 37.4 Heavy: 4.0 Vigorous physical activity, times per week, %: >4: 47.2 3: 15.0 1-2: 15.5 <1: 22.3 BMI, %: <18.5: 4.2 18.5-24.9: 57.8 25.0-29.9: 25.9 >30.0: 12.1 Effect in exposure (i.e., low/moderate literacy) or intervention, %: All cause mortality (marginal), %: 8.7 All cause mortality (inadequate), %: 39.5 Cardiovascular death (marginal), %: 16.7 Cardiovascular death (inadequate), %: 19.3 Cancer death (marginal), %: 4.6 Cancer death (inadequate), %: 8.8 Death due to other causes (marginal), % : 7.4 Death due to other causes (inadequate), %: 11.4 D-16

301 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Insurance status, %: Author, year: 5 Medicare: 100 Baker et al., 2007 3 (Companions: Gazmararian, 2006 ; Wolf et Education, %: 6 4 al., ; Howard et al., 2006 ; Wolf et al., 2007 >12 years: 8 7 ; Baker et al., 2008 ; Howard et al., 2005 Adequate HL: 39.7 9 2 ) ; Baker et al., 2004 2005 Marginal HL: 20 (continued) Inadequate HL: 12 Other characteristics: NA Health literacy/numeracy levels, %: Adequate: 64.1 Marginal: 11.2 Inadequate: 24.5 D-17

302 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Number of chronic conditions (marginal) mean (SD): 1.7 (1.2) Number of chronic conditions (inadequate) mean (SD): 1.7 (1.2) score (marginal) mean (SD): 43.6 (11.7) Physical function Physical function score (inadequate) mean (SD): Mean: 41.9 (11.9) Mental health score (marginal) mean (SD): 54.9 (9.2) Mental health score (inadequate) mean (SD): 52.1 (10.7) IADL limitation (marginal), %: 37.4 IADL limitation (inadequate), %: 46.0 ADL limitation (marginal), %: 5.7 ADL limitation (inadequate), %: 8.8 Smoking (marginal), %: Never: 42.6 Former: 44.8 Current: 12.6 Smoking (inadequate), %: Never: 45.1 Former: 42.9 Current: 12.0 Current alcohol use (marginal), %: None: 65.0 Light to moderate: 33.1 Heavy: 1.9 Current alcohol use (inadequate), %: None: 75.1 Light to moderate: 23.3 Heavy: 1.6 Vigorous physical activity, times per week (marginal), %: >4: 41.0 3: 16.7 1-2: 15.3 <1: 27.0 Vigorous physical activity, times per week (inadequate), %: >4: 31.8 3: 13.8 1-2: 14.1 <1: 40.4 BMI (marginal), %: <18.5: 3.6 18.5-24.9: 59.8 25.0-29.9: 23.8 >30.0: 12.8 BMI (inadequate), %: <18.5: 7.8 18.5-24.9: 59.0 25.0-29.9: 23.1 >30.0: 10.1 D-18

303 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: 5 Baker et al., 2007 3 (Companions: Gazmararian, 2006 ; Wolf et 4 6 ; Howard et al., 2006 al., 2007 ; Wolf et al., 7 8 ; Howard et al., ; Baker et al., 2008 2005 9 2 ; Baker et al., 2004 ) 2005 (continued) D-19

304 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Difference: Difference all -cause mortality (adjusted), HR (CI): Marginal HL vs. Adequate HL: 1.13 (0.90- 1.41) Inadequate HL vs. Adequate HL: 1.52 (1.26-1.83) Difference Cardi ovascular death (adjusted): Marginal HL vs. Adequate HL: 1.39 (1.02- 1.90) Inadequate HL vs. Adequate HL; 1.52 (1.16-2.00) Difference Cancer death (adjusted), HR (CI): Marginal HL vs. Adequate HL: 0.65 (0.38- 1.09) Inadequate HL vs. Adequate HL: 1.18 (0.8 1-1.72) Difference All other causes death (adjusted), HR (CI): Marginal HL vs. Adequate HL: 1.18 (0.76- 1.85) Inadequate HL vs. Adequate HL: 1.87 (1.32-2.67) Difference in No. Chronic Conditions (unadjusted): ( P = 0.87). Difference in Physical Function Score (unadjusted): Inadequate HL worse physical health than adequate HL: ( P < 0.001). Difference in Mental Health Score (unadjusted): < P Inadequate HL worse mental health than adequate HL: ( 0.001). itation (unadjusted): Difference in IADL lim Inadequate HL more likely to have IADL limitations than P < 0.001). adequate HL: ( Difference in ADL limitation (unadjusted): Inadequate HL more likely to have ADL limitations than adequate HL: ( P < 0.001). Difference in Smoking (una djusted): Inadequate HL less likely to have ever smoked than adequate HL: ( P < 0.05). Difference in Current Alcohol Use (unadjusted): Inadequate HL less likely to have used alcohol in the past month than adequate HL: ( P < 0.001). Difference in Vigorous P hysical Activity (unadjusted): Inadequate HL less likely to participate in frequent vigorous physical activity than adequate HL: ( P < 0.001). Difference in BMI by Health Literacy Status (unadjusted): Individuals with inadequate HL were more likely to be < 0.005). underweight than individuals with adequate HL: ( P D-20

305 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 10 Included: Barragan et al., 2005 Research objective: 18-65 years Evaluate association between patients' health Offered HIV test by provider literacy and acceptance of HIV testing No known HIV infection Study design: Not tested for HIV in past 6 months -sectional, HIV test acceptors "cases" Cross Well enough to participate and refusers "controls" Able to give consent y setting: Stud Excluded: Inner city public hospital urgent care center, NA Atlanta GA Sampling strategy: Measurement period: ence: Patients seen at urgent care center during 6-month Conveni 6 months from March to Sept 2000 study period and meeting eligibility criteria -up duration: Follow Sample size: NA 372 -up: Completeness of follow n=200 accepted HIV test, n=172 refused HIV test NA Age (mean and range): Measurement tools including cutpoints: Under 40 years, %: REALM: Acceptors: 61 High health literacy: > 6th grade Refusers: 48.8 Low health literacy: ≤ 6th grade Gender, % : ptors, Females: 44 Acce Refusers, Females: 50.6 Race/Ethnicity, % AA: Acceptors: 93.5 Refusers: 94.8 Income, %: < $10,000/yr: Acceptors: 55.5 Refusers: 60.5 Insurance status, %: Private: Acceptors: 13 Refusers:11.6 Public: Acceptors: 18.5 Refusers: 22.1 None: Acceptors: 68.5 Refusers: 66.3 Education, %: ≥High School Acceptors: 67 Refusers: 67.4 D-21

306 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Independent: Literacy In multivariate analysis test acceptors were more likely to have lower health literacy (adjusted for age and education) Dependent: HIV testing refusal or acceptance Effect in no exposure (i.e., adequate literacy) Covariates used in multivariate analysis: or control group: Age and education NR Description of outcome measures: Effect in exposure (i.e., low/moderate literacy) or intervention: -time survey which gathered demographic One NR Difference, OR (CI): information and asked HIV test acceptors and 2.017 (1.190-3.418) nowledge, refusers questions relating to HIV test k HIV transmission knowledge, HIV treatment knowledge, HIV risk perception, and HIV attitudes and beliefs Data source(s) for outcomes: Self -report Attempts for control for confounding: Multivariate analysis Blinding: NA Statistical measures used: Univariate analysis: OR and 95% CI Multivariate analysis: OR and 95% CI D-22

307 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Other characteristics, %: Author, year: 10 High HIV Risk Perception: Barragan et al., 2005 (continued) Acceptors: 66.5 Refusers:72.7 High Health l iteracy/numeracy levels, %: Acceptors: 70.5 Refusers: 80.8 D-23

308 . Key Question 1: Health literacy outcome studies (continued) Evidence Table 1 Study Description Participant Characteristics Author, year: Eligibility criteria: 11 Bennett et al., 2009 Included: 12 (Companion: White et al., 2008 ) NAAL respondent Research objective: Nonincarcerated Assess whether health literacy contributes, 65 years and older through mediation, to racial/ethnic and Excluded: education-related disparities in self -rated Could not be interviewed because of language barriers or mental health status and preventive health behaviors lities disabi among older adults. Sampling strategy: Study design: 4-stage stratified area design (area segments w/ >25% population -sectional Cross black or Hispanic over sampled) Study setting: Sample size: Household data collection of nationally 2,668 representative sample of US population. Age (mean and range), %: Measurement period: Weighted Percentage: March 2003-January 2004 65-74: 55.2 Follow -up duration: 75-84: 36.5 NA 85+: 8.3 Completeness of follow -up: Gender, %: NA Weighted Percentage: tools including cutpoints: Measurement Male: 44.9 National Assessment of Adult Literacy (NAAL) Race/Ethnicity, weighted %: health literacy component. Continuous scale White: 85.3 collapsed into 4 categories: AA: 7.3 Below basic Latino: 5.1 Basic Other: 2.3 Intermediate Income, weighted %: Proficient. >175% poverty threshold: 58.6 -points not provided. Cut 100%-175%: 23.0 Health Literacy enters regression model as a Below pov threshold: 18.4 continuous variable by transforming Item Insurance status: 500 Response Theory Theta scale to a 0- NR metric. Education, weighted %: >High School: 37.3 High School: 38. 5 >High School: 24.3 Nativity, weighted % (SD): US born: 92.2 (0.9) Foreign Born: 7.8 (0.9) Health literacy/numeracy levels, %: NAAL Categories: Below Basic: 29.0 Basic: 29.5 Intermediate: 38.2 Proficient 3.3 D-24

309 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Health Outcome: Self -rated health status - Fair/poor Health literacy is significantly related to self -rated health status, obtaining an influenza vaccination, a mammogram and a dental vs. Excellent/very good/good checkup in a nationally representative senior population in Preventive Measures: Influenza vaccination, adjusted models. mammogram, dental visit in preceding year Health Literacy significantly mediates disparities between (dichotomous) -reported health status and blacks and whites in relation to self Covariates used in multivariate analysis: obtaining an influenza vaccine but not other outcomes. Race equate literacy) or control group: Effect in no exposure (i.e., ad Income NR Gender Effect in exposure (i.e., low/moderate literacy) or intervention: Age Difference: Nativity Adjusted: Description of outcome measures: -reported health status (adjusted): Self Self -rated health status: self report on 5-point scale P Beta 0.23, < 0.05 of Poor, Fair, Good, Very Good, Excellent; Utilization of influenza vaccination: Beta 0.14, P < 0.05 converted to dichotomous Fair/poor vs. P Mammography: Beta 0.17, < 0.05 Excellent/ve ry good/good. Dental checkup: Beta 0.20, < 0.05 P Preventive Measures: dichotomous -self reported Mediation of race, education by Health Literacy Data source(s) for outcomes: Face to Face interviews for NAAL Attempts for control for confounding: Multivariate analysis Blinding: NA Statistical measures used: t analysis Marginal Maximum Likelihood Probi Probit analysis Baron and Kenney mediation criteria Sobel tests D-25

310 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 13 Included: Bennett et al., 2007 Research objective: Singleton pregnancy Assess association between low literacy and English or Spanish speaking depressive symptomatology in pregnant Chose to have the interview conducted in Spanish (indicator of Latinas with limited English language English proficiency) limited proficiency in US inner -city setting. Excluded: Study design: NR Cross -sectional Sampling strategy: Study setting: Convenience sample Patients recruited from Philadelphia District Sample size (n = 99): Health Centers and 4 hospital -based prenatal Inadequate HL (n = 18) care clinics serving primarily Medicaid Marginal HL, (n = 15) recipients Adequate HL, (n = 66) Measurement period: Age, mean (SD): - 9/2004 11/2003 Total: 26.1 (5.44) Follow -up duration: Inadequate HL: 25.8 (4.91) NA Marginal HL: 26.2 (6.63) -up: Completeness of follow Adequat e HL: 26.2 (5.38) NA Gender, %: s including cutpoints: Measurement tool Females: 100 S-TOFHLA (Spanish): Race/Ethnicity, %: 55 Inadequate: 0- Total: Marginal: 56- 66 Latina: 100 Adequate: >67 Mexican: 23 Other Hispanic Nativity: 77 Inadequate HL: Mexican: 50 Marginal HL, %: Mexican: 27 Adequate HL: Mexican: 15 Income, mean in $ (SD): Total: 7,251 (6762) Inadequate HL: 7,631 (9104) Marginal HL: 6,869 (6925) Adequate HL: 7,240 (6294) Insurance status: NR Education, %: < HS education: Total: 47 Inadequate HL: 78 Marginal HL: 53 Adequate HL: 36 D-26

311 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Controlling for 2 effect modifiers, women with inadequate HL Depressive symptoms (CES -D scale) were more likely to have depressive symptoms compared to Covariates used in multivariate analysis: those with adequate HL. A significant difference was not found Mexican nativity between women with marginal and adequate HL. Recent marijuana use Effect in no exposure (i.e., adequate literacy) or control group: Description of outcome measures: Depressive symptomatology was assessed with a Elevated depressive symptomatology Spanish translation of the CES -D. This 20- item (CES-D ≥ 16) instrument has scores ranging from 0 to 60. Adequate HL: N = 12 (18%) Effect in exposure (i.e., low/moderate liter acy) or intervention: Standard categorical cut -point of >16 was used to Elevated depressive symptomatology indicate elevated depressive symptomatology. Data source(s) for outcomes: ≥ 16) (CES-D Self Inadequate HL, N )%): 8 (44%) -reported data collected by in-person interview Attempts for control for confounding: Marginal HL, N (%): 5 (33%) Difference: Logistic regression used to estimate risk of elevated depressive symptomatology among women at Difference in elevated depressive symptomatology ≥ 16) different literacy levels, controlling for variables (CES-D — found to be effect modifiers of health literacy Inadequate 5.35) HL, PR (CI): 2.39 (1.07– HL, PR (CI): 1.73 (0.75-4.02) Marginal vity and recent marijuana use—but not nati associated with depression symptomatology. Other sociodemographic variables identified through literature as known to be related to depressive symptoms among Latinas were excluded from equation. Blinding: NA Statistica l measures used: Bivariate associations: assessed using one-way -square statistic. analysis of variance or chi Fisher’s exact test was used whenever any cell contained fewer than 5 respondents. Poisson regression used in multivariate analysis, of PR (instead of standard logistic calculation regression) to avoid inflation of RR estimate D-27

312 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: Other characteristics: 13 Bennett et al., 2007 Foreign bor n, N (%): (continued) Total: 91 (92) Inadequate HL: 17 (94) Marginal HL: 14 (93) Adequate: 60 (91) Mean years living in United States (SD): Total: 5.34 (5.22) Inadequate HL: 4.47 (5.70) Marginal HL: 5.07 (3.58) Adequate HL: 5.65 (5.44) Parity, N (%): births: 0 previous Total: 31 (31) Inadequate HL: 6 (33) Marginal HL: 4 (27) Adequate HL: 21 (32) ≥ 1 previous births Total: 68 (69) Inadequate HL: 13 (67) Marginal HL: 11 (73) Adequate: 45 (68) Married or living as married, N (%): Total: 59 (60) Inadequate HL: 12 (67) Marginal HL: 8 (53) Adequate HL: 39 (59) Ever homeless, N (%): Total: 4 (4) Inadequate HL: 1 (6) Marginal HL: 0 (0) Adequate HL: 3 (5) Risk indicators Ever used marijuana, N (%): Total: 4 (4.0) Inadequate HL: 0 (0.0) Marginal HL: 1 (6.7) Adequate HL: 3 (4.5) Intimate partner violence, N (%): Total: 9 (9.0) Inadequate HL: 2 (10.5) Marginal HL: 0 (0.0) Adequate HL: 7 (10.6) Elevated depressive symptomatology (CES-D _ 16), N (%): Total: 25 (25) Inadequate HL: 8 (44) Marginal HL: 5 (33) Adequate HL: 12 (18) Health literacy/numeracy levels, %: Inadequate: 18 Marginal: 15 Adequate: 67 D-28

313 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Eligibility criteria: 14 Chew et al., 2004 Included: Research objective: English speaking Determine association between low HL and Excluded: adherence to preoperative instructions. Poor vision Study design: Severe dementia Prospective cohort Sampling strategy: Study setting: Attempted to enroll all patients who presented at clinic during time Preoperative clinic of VA Puget Sound Health period Care System Sample size: period: Measurement 332 Oct 2001 to Jan 2002 Adherence to preoperative fasting instructions: n = 271 -up duration: Follow Adherence to preoperative medication adherence: n = 217 NR Age, mean (SD): -up: Completeness of follow 58.2 (13.1) NR Significantly different between low and adequate HL Measurement tools including cutpoints: Gender, %: sTOFHLA Females: 5 -16 Inadequate HL: 0 Race/Ethnicity, %: Marginal HL: 17-22 White: 81 Adequate HL: 23-36 Black: 10 Other: 9 Income, %: < $20,000: 34 $20,000 - $39,000: 33 > $40,000: 24 Did not Know/Refused: 9 Significantly different between low and adequate HL Insurance status: NR Education, %: ≤ 8th grade: 7 Some HS: 8 High school/GED: 38 > HS: 48 Significantly different between low and adequate HL Other characteristics: Self report excellent/good health, %: Adequate HL: 82 Low HL: 10 Self report fair/poor health, %: Low HL: 82 Inadequate HL: 18 Sig different between low and adequate HL groups Health literacy/numeracy levels, %: Adequate: 88 Marginal: 7.5 Inadequate: 4.5 D-29

314 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Patients with low HL were more likely to be non-adherent to Non -adherence to preoperative fasting instructions Non preoperative medication adherence instructions but this did not -adherence to preoperative medication reach statistical significance instructions Covariates used in multivariate analysis: rol group, Effect in no exposure (i.e., adequate literacy) or cont %: Age Marital status -adherent to fasting instructions (unadjusted): 8 Non -adherent to medication instructions (unadjusted): 21 Number of medications Non Cognitive Effect in exposure (i.e., low/moderate literacy) or intervention, function %: Description of outcome measures: Adherent to preoperative fasting instructions: Self -adherent to fasting instructions (unadjusted): 9 Non report of adherence to instructions on day of surgical -adherent to medication instructions, (unadjusted): 37 Non procedure Difference: = 0.80) P Adherent to fasting instructions (unadjusted): ( Adherent to preoperative medication instructions: Self report adherence to instructions as direct ed at Adherent to medication instructions (adjusted), OR (CI): 1.9 preoperative clinic visit (0.8 -4.8) Data source(s) for outcomes: Self -report Attempts for control for confounding: Multivariate analysis Blinding: Preoperative nurses were masked to patient's literacy test results for pre -op interview used: Statistical measures Multivariate analyses D-30

315 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Eligibility criteria: 15 Included: Cho et al., 2008 16 ) (Companion: Lee et al., 2009 Age > 65 Research objective: Medicare recipient Examine whether 4 intermediate factors > 1 visit to MHMC -affiliated outpatient clinic between 1999 and 2003 (disease knowledge, health behavior, Mentally competent preventive care, and compliance) explain Good vision association between health literacy and health Currently living at home in Illinois status or utilization Good hearing Study design: Able to conduct the interview in English Cross -sectional Excluded: Study setting: NR Outpatients at MHMC in Chicago, or at Mercy Sampling strategy: Family Health Center, an FQHC associated NR with MHMC; interviews occurred in Sample size: participants' homes or in medical center 489 participants Measurement period: Age (mean and range): March 2003-February 2004 NR Follow -up duration: Gender, %: NA Females: 78.7 -up: Completeness of follow Race/Ethnicity, %: NA AA: 59.1 Measurement tools including cutpoints: Income: s-TOFHLA: NR Inadequate (0-16) Insurance status: Marginal (17-22) NR Adequate (23-36) Education (SD): 2.95 (1.49) Scale: 1 = grade/elementary school 2 = some high school 3 = high school diploma/GED 4 = some college 5 = college graduate 6 = graduate degree Other characteristics: Social support Medical co morbidities Functional status Attitudes toward health care Risk and healthy behaviors Access Health literacy/numeracy levels, %: Inadequate/marginal: 50.89 Adequate: 49.11 D-31

316 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Higher health literacy significantly associated with fewer ER Health status Hospitalizations -reported health status, visits, fewer hospitalizations, higher self higher disease knowledge, and more preventive care ER visits Health literacy had direct rather than indirect effect on health Disease knowledge Health behavior , hospitalization and ER visits outcomes including health status Effect in no exposure (i.e., adequate literacy) or control group: Preventive care NR Compliance Effect in exposure (i.e., low/moderate literacy) or intervention: Covariates used in multivariate analysis: NR Race/ethnicity Difference: Gender Educational attainment (Standardized beta coefficients; results in bold/italics are < .05) significant at statistically P Description of outcome measures: Health status: 0.48 Health status: -0.24 Hospitalizations: -rated 5 point Likert scale Self ER visits: -0.35 Hospitalizations: Disease knowledge: 0.61 -report of hospitalizations in the past year; Self Health behavior: 0.07 dichotomized to 1 (>1 hospitalization) or 0 (0 Preventive care: 0.42 hospitalizations) -0.17 Compliance: ER visits: *Health literacy dichotomized as 1 (adequate) or 0 (inadequate -report of visits in the past year; dichotomized - Self or marginal) to 1 (>1 visit) or 0 (0 visits) Disease knowledge 17 question survey Health behavior 9 Likert scale items from Health Promoting Lifestyle Profile Preventive care FOBT/prostate screening in past two years if male, mammography/Pap smear in past two years if female Compliance -report of how often participants forgot to fill Self prescriptions on time; dichotomized to 1 (always) and 0 (not always) Data source(s) for outcomes: Participant self -report during int erview Attempts for control for confounding: Yes - control variables added to path analyses Blinding: NA Statistical measures used: Path analyses using weighted least -squared method with asymptotic covariance matrix D-32

317 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 17 Inclusion: Coffman and Norton, 2010 Research objective: -identification as a Latino Self To explore the relationships of immigration Age 18 years or older demands, health literacy, and depression in a Spanish speaking sample of recent immigrants. Recent immigrant status (15 years or less in the United States) Study des ign: Exclusion: Cross sectional NA Study setting: Sampling strategy: NR Convenience Sample recruited from two Latino service agencies Measurement period: -ins, and networking through newspaper advertisements, walk NR Sample size: -up duration: Follow N = 99 NA Age (mean and range), % (SD): -up: Completeness of follow 35.7 (3.7) NA Gender, %: Measurement tools including cutpoints, %: Female: 76.8 item Short Assessment of Health Literacy 50- Race/Ethnicity, %: for Spanish-speaking Adults (SAHLSA), 100% Latino Spanish language REALM, Highest score: 50 Mexican descent: 54.5 (Low Health Literacy: the lowest quartile). 8 countries in South America (n = 29) and 4 countries in Central America (n = 16). Income, %: Household income, %: < $20,000: 43.5 $20,000 to $30,000: 30.3 > $30,000: 21.2 Insurance status, %: Insurance: Insurance: 14.1 No Insurance: 85.9 Education, %: Mean years of education: 11.4 (SD = 4.3) < high school education: 49.4% Other characteristics, %: Mean years of residence in the United States: 5.1 (SD = 3.7) Little to no written or spoken English proficiency, low: 95% Undocumented legal status: 70% Employed: 66.7% Housewives not seeking employment: 22% Health literacy/numeracy levels, %: Mean SAHLSA Score: 42.0 (SD = 7.5) Low HL: ≤ 39; n = 27 D-33

318 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Low health literacy, controlling for greater immigration demands Depression predicted higher depression scores. Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: Demands of immigration -D score for participants with high health literacy Mean CES Description of outcome measures: (SD): 9.7 (8.3) Depression: Participants completed the 20- item Effect in exposure (i.e., low/moderate literacy) or intervention: Spanish language Center for Epidemiologic Studies Mean depression score for participants with low health literacy: -D). Participants were asked Depression Scale (CES 13.9 (9.5) to rate how often they experienced depressive Reported depression symptoms, low health literacy: 42.3% symptoms in the past week from 0 to 3: Reported depression symptoms among those with low health 0: Rarely or none of the time literacy that were not depressed: 21.9% 1: Some or a little of the time CES -D items that were significantly correlated to lower health 2: Occassionally or a moderate amount of time literacy score included not feeling hopeful about the futere (r = 3: Most or all of the time .3; P = .004) and thinking that life had been a failure (r = .3; P = s indicated less depression, and a score Lower score of 16 or greater was indicative of clinical depression. .002). Data source(s) for outcomes: Difference: -report: Questionnaire Self Difference in depression score (adjusted): P = 0.048) Lower HL vs higher: B = -.22 (SE .11) ( Attempts for control for confounding: Regression Blinding: No Statistical measures used: model Regression D-34

319 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Eligibility criteria: Author, year: 18 Davis et al., 2006 Included: 19 ) (Companion: Wolf et al., 2007 ≥ 18 years old Research objective: Excluded: Examine relationship between patients’ HL Severely impaired vision and abilities to understand and demonstrate Hearing problems instructions found on container labels of Illness too severe to participate common prescription medications Inability to speak English Study design: Sampling strategy: Cross -sectional Convenience sample of consecutive patients presenting to the Study setting: clinics 3 primary care clinics in Shreveport LA (public Sample size: hospital), Jackson MI (FQHC), and Chicago, 395 IL (FQHC) Age (range): Measurement period: 44.8 (19-85) July 2003 (Shreveport) Gender, %: Jackson and Chicago) July 2004 ( Female: 67.8 -up duration: Follow Race/Ethnicity, %: NA AA: 47.4 -up: Completeness of follow White: 48.4 NA Income: Measurement tools including cutpoints: NR REALM Insurance status, %: 0-44: sixth grade or less (low literacy) Uninsured for medication: 22.8 45-60: seventh to eighth grade (marginal) Education, %: 61-66: ninth grade and above (adequate) < HS: 28.4 Other characteristics: Mean # prescription medications: 1.4 Health literacy/numeracy levels, %: Inadequate: 19.0 Marginal: 28.6 Adequate: 52.4 D-35

320 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes Describe results: Main outcomes: L, participants with Compared with those who had adequate H Understanding medication label instructions Attention to auxiliary warning label instructions low or marginal HL were sig more likely to misunderstand one or more prescription labels and participants with low literacy Demonstration of correct administration Covariates used in multivariate analysis: were significantly less likely to correctly demonstrate how to follow label instructions. Age Sex (i.e., adequate literacy) or control group, Effect in no exposure Race %: Education Misunderstood one or more prescription labels: Adequate: 37.7 Number of medications currently taken daily Site Correct demonstration of number of pills: Description of outcome measures: Adequate: 80.2 Effect in exposure (i.e., low/moderate literacy) or intervention, Understanding medication label instructions: %: response to the question "How would you take this Misunderstood one or more prescription labels, %: medicine?" as rated (correct or incorrect) by three Marginal: 51.3 physicians Attention to auxiliary warning label instructions: "yes" Low: 62.7 or "no," based on whether behavior was noted by Correct demonstration of number of pills: reviewer Marginal: 62.8 Demonstration of correct administration: response to Low: 34.7 the question “Show me how many pills you would Difference: take [of this medicine] in one day” using candy pills Difference misunderstanding prescription medication label for demonstration instructions (adjusted) RR (CI): Data source(s) for outcomes: (1.14 Marginal vs. adequate: 1.94 -3.27) -demon strated Structured interview and patient Low vs adequate: 2.32 (1.26- 4.28) interpretation of medication labels Difference in correct demonstration of label instructions Attempts for control for confounding: (adjusted) RR (CI): Logistic regression 4.89) Low vs. adequate: 3.02 (1.70- Blinding: Marginal vs. adequate: RR NS (data not reported) Outcomes assessors blinded Statistical measures used: Chi square Multivariate analysis D-36

321 Key Question 1: Health lite racy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: criteria: Eligibility 20 Included: DeWalt et al., 2007 Research objective: Child 3 to 12 yrs old Determine if parental literacy is related to ED Clinical diagnosis of asthma for 3+ months d days of school visits, hospitalizations, an History of recurrent episodes of wheezing or coughing missed for children with asthma. Previous visit with physician in clinic no more than 12 months prior Study design: to index visit Retrospective cohort study Undergoing treatment for asthma w ith 1 or more of following: inhaled Study setting: bronchodilators, inhaled cortico-steroids or oral leukotriene inhibitors Study conducted in 3 outpatient pediatrics Excluded: clinics (general, asthma and allergy, and Diagnosis of severe developmental delay pulmonary) at NC Children’s Hospital, public Cystic fibrosis children’s hospital of NC Severe neurological impairment Measurement period: Those not accompanied by primary caregiver on day of study January 2004 to March 2005 Sampling strategy: Follow -up duration: Convenience NR Sample size: -up: Completeness of follow N = 150 NR Higher Parental Literacy, n = 114 Measurement tools including cutpoints: Low Parental Literacy, n = 36 REALM Age, mean (SD): Higher literacy: > 8th grade literacy level Entire sample ≤ 8th grade literacy level Low literacy: Child: 7.7 (2.8) Parent: 35 (8.7) Higher Parental Literacy: Child: 7.7 (2.8) Parent: 35 (7.5) Low Par ental literacy: Child: 7.7 (2.8) Parent: 35 (12) Gender: NR Race/Ethnicity, %: Parental Race: Entire sample: AA: 47 Caucasian: 45 Higher Parental Literacy: AA: 39 Caucasian: 52 Low Parental Literacy: AA: 69 Caucasian: 25 Income, %: Household income of < $15,000/yr Entire Sample: 27 Higher Health Literacy: 21 Low Health Literacy: 44 D-37

322 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Results Outcomes Describe results: Main outcomes: Children of parents with low literacy were more likely to have Classification of Asthma Severity Albuterol Use use of moderate or severe persistent asthma and had greater Controller Medication Use rescue medications. They were also more likely to require ED visits or hospitalization than children of parents with higher ED Visits literacy Hospitalization Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: Moderate/Severe Persistent Child age Household income Asthma: 35% Albuterol Use (mean days per week): 1.5 Parental race Albuterol Use (total mean use per week): 3 doses Parental asthma knowledge Appropriate Controller Use: 82% Parental smoking ED Visits (per child): 1.08 Asthma severity classification Controller medication use Hospitalizations: 0.12 Site of care Effect in exposure (i.e., low/moderate literacy) or intervention, %: ion of outcome measures: Descript ent Moderate/Severe Persist Questions were asked with an open-ended response format. Asthma: 56 Albuterol Use (mean days per week): 2.7 Severity and medication use were based on recall Albuterol Use (total mean use per week: 6 doses over past 2 weeks. Appropriate Controller Use: 68 ED visits and hospitalizations were based on recall ED Visits (per child): 1.53 over past 12 months. - Hospitalizations: 0.39 RA classified severity of illness based on self reported symptoms using questions based on Difference: NHLBI asthma severity guidelines from 2002. Difference Moderate/Severe Persistent Asthma ( unadjusted): = 0.03) P ( Sociodemographic data were self -reported. Difference Albuterol Use (unadjusted): ( = 0.01) P Data source(s) for outcomes: P = 0.03) Difference Total Weekly Albuterol Use: ( Self -report by interviewer = 0.15) P Difference Appropriate controller use: ( Administered questionnaire ED Visits (adjusted): IRR, 1. Attempts for control for confounding: Multivariate Poisson regression Blinding: NR Statistical measures used: Multivariate Poisson regression. D-38

323 Key Question 1: Health litera cy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Insurance status, %: 20 DeWalt et al., 2007 Child’s Insurance: (continued) Entire sample: Medicaid: 57 Private: 43 High er Parental Literacy: Medicaid: 43 Private: 57 Low Parental Literacy: Medicaid: 86 Private: 14 Education: NR Other characteristics, %: Parental smoking: Entire sample: 28 Higher Parental Literacy: 26 Low Parental Literacy: 33 Controller medication use if persistent Asthma: Entire sample: 80 Higher Parental Literacy: 68 Low Parental literacy: 82 Health literacy/numeracy levels, %: Low Parental Literacy: 24 Higher Parental Literacy: 76 D-39

324 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 21 Estrada et al., 2004 Included: Research objective: > 50 years old Examine association between low literacy and ≥ 1 month Been on warfarin numeracy in patients taking warfarin with Excluded: anticoagulation control and other processes of Unable to speak care Non -English speaking Study design: Did not consent to participate Prospective cohort Sampling strategy: Study setting: Convenience Anticoagulation management units: 1 based at Sample size: a university and 1 based at a VA hospital N=143 Measurement period: Participants were 3.9 years younger than eligible patients who refused or were excluded, = 0.03 P November 1998-May 1999 Follow -up duration: Age, mean (SD): Mean: 91 days (SD 18.9) 65.3 (9.8) Completeness of follow -up: Gender, %: 100% Female: 37.8 Measurement tools including cutpoints: Race/Ethnicity, %: Literacy: REALM Nonwhite: 29.4 Numeracy: 6 item test; Schwartz 3-item (1997) Income: and 3 items developed by study researches NR nticoagulation therapy specific to a Insurance status: VA patients: 36 University -based clinic: 4 patients said they could not afford medication, so it was provided to them. Education, %: ≤ 3rd grade: 3.5 4-6th grad: 7.0 7-8th grade: 10.5 >8th grade: 79.0 Other characteristics, %: Indications for anticoagulation therapy: Atrial fibrillation: 39.2 Valvular heart disease: 16.8 s thrombosis: 16.8 Venou Neurologic condition: 11.2 Length of time on wafarin: < 6 months: 19.6 6 - 12 months: 14 > 1 yr: 66.4 INR goal: 2-3: 79.7 of patients 2.5 - 3.5 or other: 20.3 of patients D-40

325 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: After adjusting for age, low numeracy skil ls were associated Primary outcomes: with greater INR variability, while the optimal intensity of Variability of the INR anticoagulation (time in range) was similar among patients at Optimal intensity of anticoagulation Secondary outcomes: different literacy or numeracy levels % INR tests within patients therapeutic range Numeracy skills were associated with the time spent above the Maximum INR value patients therapeutic INR range (unadjusted). Neither low literacy nor numeracy were associated with any other # dose changes secondary outcomes examined. Dose change Effect in no exposure (i.e., adequate literacy) or control group: # missed visits 6 correct: 56% Covariates used in multivariate analysis: % INR tests within range: 5- Age INR variability using mean sigma score: 5-6 correct: 0.45 Effect in exposure (i.e., low/moderate literacy) or intervention: Description of outcome measures: INR variability: measured by computing the % INR tests within range: 0 correct: 56% deviation in the patient's INR from his/her INR variability using mean sigma score: 0 correct:0.80 Difference: therapeutic range over tim e. A wider INR range Difference in INR variability: indicates poorer anticoagulation and is one of the Higher amo = ng patients at lower literacy levels (adjusted): P strongest predictors of bleeding risk. Optimal intensity of anticoagulation (time in range): 0.06 P Higher among patients with lower numeracy skills (adjusted): estimates the amount of time a patients INR is within his/her therapeutic range = 0.03 Data sourc e(s) for outcomes: Optimal intensity of anticoagulation (time in range): -report and medical record review Self The optimal intensity of anticoagulation (time in range) (adjusted) was similar among patients at different literacy, P = Attempts for control for confounding: = 0.35 0.71 or numeracy levels, P Multiple linear regression Blinding: Provider's making adjustments to warfarin dosage were not informed of patients' literacy or numeracy assessments measures used: Statistical Relationship between literacy or numeracy levels and INR variability, time in range, and secondary outcomes was measured with the Spearman rank test. Multiple linear regression D-41

326 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Health literacy/numeracy levels, %: Author, year: 21 6-items (including 3 adapted from Schwarz and Woloshin): Estrada et al., 2004 0 correct: 13.3 (continued) 1-2 correct: 35 3-4 correct: 34.3 5-6 correct: 17.5 D-42

327 Table 1. Key Question 1: Health literacy outcome studies (continued) Evidence Study Description Participant Characteristics Author, year: criteria: Eligibility 22 Included: Fang et al., 2006 objective: Research ≥ 18 years Assess if literacy is associated with warfarin Visual acuity knowledge, adherence and control Basic reading ability Study design: Excluded: -sectional Cross NR Study setting: Sampling strategy: Anticoagulation clinic at San Francisco Consecutive General Hospital Eligible patients receiving care in an anticoagulation clinic Measurement period: Sample size: March 2002 to June 2003 179 Follow -up duration: Limited literacy: n = 109 NA Adequate literacy: n = 70 -up: Completeness of follow Age, mean (range): NR 65.6) Limited literacy: 63.3 (61.0- Measurement tools including cutpoints: Adequate literacy: 53.8 (50.4- 57.1) Numeracy: Gender, %: 4 warfarin-specific questions developed by Females: investigators Limited literacy: 52.3 Literacy: Adequate literacy: 38.6 s-TOFHLA (English or Spanish) Race/Ethnicity, %: Limited health literacy: 0- 22 Latino: Adequate health literacy: 23-26 Limited literacy: 45.9 Adequate literacy: 15.7 Asian -Pacific Islander: Limited literacy: 28.4 Adequate literacy:18.6 White: Limited literacy: 10.1 Adequate literacy: 35.7 AA: Limited literacy:12.8 Adequate literacy: 22.9 Income: NR Insurance status: NR Education, %: ≤8th grade: Limited literacy: 50.5 Adequate literacy: 7.1 High sc hool (some/all): Limited literacy: 30.3 Adequate literacy: 30 D-43

328 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Warfarin (numeracy) knowledge Knowledge (adjusted) Self reported adherence to medication Limited literacy was significantly associated with 3 of 4 International Normalized Ratio (INR) control numeracy questions Adherence and INR control (adjusted) Covariates used in multivariate analysis: - Age Limited health literacy was not significantly associated with self Sex Reported adherence or INR control Race/ethnicity Effect in no exposure (i.e., adequate literacy) or control group, %: Education Knowledge (adjusted): Cognitive impairment Numeracy Question 1: 25.7 Number of years on warfarin Numeracy Question 2: 35.7 Description of outcome measures: Numeracy Numeracy Question 3: 18.6 -related questions 4 warfarin-specific numeracy Numeracy Question 4: 18.6 Adherence Self -reported adherence (adjusted): Missed a dose within the last 3 d: 17.1 Validated questionnaire reporting 1) last time a pill Missed a dose within the last 2wk: 14.3 was missed, 2) any missed dose with the last 2 Did not miss a dose weeks, 3) any missed dose within the last 3 days in >3 mo: 51.4 INR control (adjusted): INR control Proportion of person- Person -time in therapeutic INR range: 43.2 time within target therapeutic Effect in exposure (i.e., low/moderate literacy) or intervention, range over total person-time of follow -up Data source(s) for outcomes: %: Knowledge (adjusted): Warfarin target range was obtained from clinic -report Numeracy Question 1: 70.6 database all other data was self Numeracy Question 2: 73.4 Attempts for control for confounding: Numeracy Question 3: 50.5 Multivariate analysis Nume racy Question 4: 71.6 Blinding: Self -reported adherence (adjusted): NA Missed a dose within the last 3 d: 6.5 Statistical measures used: Bivariate analysis: t Missed a dose within the last 2wk: 12.0 us variables -tests for continuo Did not miss a dose in > 3 mo: 61.1 and chi squared tests for categorical variables Univariate analysis: Simple logistic regression to INR control (adjusted): -time in therapeutic INR range: 45.0 Person determine the association between health literacy and warfarin knowledge as well as self Difference(adjusted), OR (CI): -reported adherence to medication Knowledge: multivariate logistic regression Multivariate analysis: Numeracy Question 1: 2.6 (1.1 -6.1) to control for confounders Numeracy Question 2: 1.9 (0.8 - 4.4) Generalized linear models: To determine if health Numeracy Question 3: 3.2 (1.3 -7.7) -14.0) literacy was related to INR range (i.e., to warfarin Numeracy Question 4: 5.7,(2.3 control) Self -reported adherence: Missed a dose within the last 3 days: 0.5 (0.1-2.1) Missed a dose within the last 2 weeks: 0.7 (0.3-2.2) Did not miss a dose in >3 months: 0.9 (0.4-2.0) INR control (adjusted): 1.4) Person - time in therapeutic INR range: 1.0 (0.7 - D-44

329 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Participant Characteristics Study Description ≥College: Author, year: 22 Limited literacy: 19.3 Fang et al., 2006 (continued) Adequate literacy: 62.9 Other characteristics: Low cognitive function (s -CASI <17): Limited literacy, %: 19.3 Adequate literacy, %: 1.4 Years on warfarin: Limited literacy: 4.4 Adequate literacy: 2.9 Health literacy/numeracy levels, %: Limited: 60.9 Adequate: 39.1 D-45

330 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 23 Included: Garbers and Chiasson, 2004 Research objective: For young female relatives: Examine independent association between Self -identified as Latina or Hispanic inadequate functional health literacy in ≥ 18 yrs Spanish among low -income Latinas aged 40 ≥ 40 living in New Had a female relative York city and older and cervical cancer screening For participants: behavior. Self -identified as Latina or Hispanic Study design: ≥ 40 yrs Cross -sectional Spoke Spanish as primary language Study setting: Excluded: In-person interview at participants' homes. For participants Women were recruited for study through Refusal to complete the Spanish S -TOFHLA younger female relatives who were Sampling strategy: approached as they waited for prenatal or Convenience family planning appointments at 2 women's Sample size: health centers in New York City 205 Measurement period: Age, mean: July 2003 Nov 2002 - 51 Follow -up duration: ference between inadequate, marginal and adequate Significant dif NA literacy groups Completeness of follow -up: Gender, %: NA Females: 100 ools including cutpoints: Measurement t Race/Ethnicity, %: TOFHLA -S Hispanic: 100 Inadequate score 0 - 59 Income: - 74 Marginal score 60 NR Adequate score 75 - 100 Insurance status, %: Uninsured: 57.8 Medicaid/Medicare: 32.3 Private insurance: 9.8 Education, %: No formal education: 5.9 Elementary school only: 44.4 Some high school: 18.5 High school graduate or more: 31.2 Significant difference between inadequate, marginal and adequate literacy groups Other characteristics: Years in the US: 17.9 Significant diff erence between inadequate, marginal and adequate literacy groups No regular source of health care, %: 40.5 No visit to health care provider in the last yr, %: 22 Health literacy/numeracy levels, n (%): Inadequate Literacy: 61 (30) Marginal Literacy: 39 (1 9) Adequate literacy: 105 (51) D-46

331 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Ever had a Pap test Compared to those with adequate and marginal health literacy, Pap test within past 3 years women with inadequate functional health literacy in Spanish Covariates used in multivariate analysis: were significantly less likely to ever have had a pap test Effect in no exposure (i.e., adequat e literacy) or control group: care Having source of Having any health insurance Ever had a Pap test (unadjusted), n (%): Age Adequate HL: 104 (99) Marginal HL: 35 (92.1) Years in US Pap test within past three years (unadjusted), n (%): Education Description of outcome measures: Adequate HL: 87 (82.9) 20 minute survey developed for purposes of study Marginal HL: 32 (82.1) Effect in exposure (i.e., low/moderate literacy) or intervention: plus medical record review for randomly selected subset of 10% of participants Ever had a Pap test (unadjusted), n (%): Inadequate HL: 48 (80) Data source(s) for outcomes: Pap test within past three years (Unadjusted), n (%): Self port -re Inadequate HL: 38 (62.3) Medical chart review for 10% of participants Attempts for control for confounding: Difference: Ever had a Pap test (Adjusted), OR (CI): Logistic regression Adequate HL: Ref Blinding: NA Marginal HL: 0.14 (0.01-1.41) Inadequate HL: 0.06 (0.01- 0.55) Statistical measures used: Pap test within past three years (Adjusted), OR (CI): Chi square tests for categorical variables Adequate HL: Ref Analysis of variance for continuous variables Marginal HL: 1.31 (0.44-3.85) Bivariate analysis Logistic regression Inadequate HL: 0.53 (0.21- 1.35) D-47

332 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 24 Replied when their number was called at pharmacy Gatti et al., 2009 Research objective: Had a phone number To examine the relationships among health ≥ 18 years old literacy, beliefs about medications, and Were picking up a prescription for themselves medication adherence in a population with Used the GMH or DGHC pharmacy as their primary pharmacy inadequate health literacy skills Had been a patient at GMH or DGHC for at least 6 months Study design: Were comfortable speaking English -sectional Cross Did not have a vision impairment beyond 20/200 ng: Study setti -Cog Were able to pass the mini Participants recruited from three outpatient ling strategy: Samp pharmacies at Grady Memorial Hospital, and Convenience sample from the DeKalb Grady Health Center Sample size: pharmacy in Atlanta, GA N = 275 Measurement period: Age (mean): October 2006 June 2006 - 54 Follow -up duration: Gender, %: N/A Female: 73.1 Completeness of follow -up: Race/Ethnicity, %: (91.4%) 275/301 African American: 86.2 Measurement tools including cutpoints, %: Caucasian or white: 5.1 -66) REALM (0 Other: 8.7 60 < high school reading level: 0- Income, %: 66 high school reading level: 61- < $10,000/yr: 63.7 Insurance status, %: NR Education, %: At least a HL diploma or GED: 72.4% Other characteristics, %: Married: 17.2% Divorced/separated: 39.2% Widowed: 18.3% Single/never married: 25.3% Unemployed: 26.8% Employed full -time: 8.5% Employed part -time: 15.8% Other: 48.9% Number of prescriptions: 3.5 (SD 2.5) nary artery disease: 20.1% Coro Hypertension: 72.1% Diabetes: 31.2% Hyperlipidemia: 43.9% Cancer: 3.9% Depression: 44.7% Health literacy/numeracy levels, %: High school: 40.3% < high school: 59.7% (mean REALM score of 51.3, SD 17.1) D-48

333 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Describe results: Main outcomes: -reported medication adherence Health literacy was not a significant predictor of medication Self adherence in bivariate relationships and when other potential Covariates used in multivariate analysis: predictors of adherence were controlled in the model. Health literacy and "patient and regimen Effect in no exposure (i.e., adequate literacy) or control group: characteristic covariates" including negative beliefs REALM mean in high adherence group: 50.1 (17.4) -efficacy, self about medications, age, low self -report Effect in exposure (i.e., low/moderate literacy) or intervention: of hyperlipidemia Description of outcome measures: mean in low adherence group: 52.4 (16.8) REALM -reported medication adherence - measured by Self Difference: Morisky 8 -item Medication Adherence Scale Difference in medication adherence (adjusted): OR = 0.96; P -1.7 ( 95%CI, 0.6 =0.88) with (MMAS -8), which has a score range of 0- 8, lower score representing better adherence; score dichotomized into high adherence: 0-2 and low adherence: 3-8 Data source(s) for outcomes: Patient self -report via survey instruments during 50 minute interview Attempts for control for confounding: Mult ivariable logistic regression Blinding: N/A Statistical measures used: Chi -square Wilcoxon tests Multivariable logistic regression D-49

334 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 3 Included: Gazmararian, 2006 4 (Companions: Wolf et al., 2007; Baker et al., Medicare managed-care enrollee 7 6 5 Wolf et al., 2005; Howard et al., 2006; 2007; 65+ 9 8 Howard et al., 2005; Baker et al., 2008; Enrolled in Prudential HealthCare 3 months or more 2 ) Baker et al., 2004 ICD-9 -CM code and pharmacy claims related to 1 of 4 diagnoses: Research objective: coronary heart disease, hypertension, diabetes mellitus, or Examine relationship between HL and hyperlipidemia medication refill adherence among Medicare Inpatient and outpatient claims - lar managed care enrollees with cardiovascu Excluded: related conditions Not comfortable speaking English or Spanish Study design: Bli nd or severely impaired vision not correctable with eyeglasses Cohort Living in a nursing home Study setting: Missed 1 or more screening questions for severe cognitive In-person in-home interviews with and impairment (not able to correctly identify year, month, state, year of subsequent claims data for enrollees in their birth, or home address) Cleveland, Houston, Tampa, and south Continuou sly enrolled < 1 year Florida (including Ft. Lauderdale and Miami) Spent prolonged period in the hospital (> 100 days) Measurement period: Sampling strategy: Interviews occur red May 1997-December Convenience sample of consecutive new Medicare managed -care 1997 enrollees Claims data from within 1 year of date of Sample size: enrollment into plan (usually 3 months prior to 1,549 study enrollment) Age (mean and range), %: -up duration: Follow 65-69: 34.5 1 year 70-74: 28.0 -up: Completeness of follow 75-79: 19.7 -TOFHLA and 3260 completed both S 80-84: 12.1 interview; of these, 1711 were exc luded >85: 5.6 because they did not meet criteria for this sub- Gender, %: analysis Female: 58 Measurement tools including cutpoints: Race/Ethnicity, %: S-TOFHLA: White: 76.7 Adequate: 67-100 Black: 11.9 66 Marginal: 54- Hispanic: 10.3 53 Inadequate: 0- Other: 1.2 Income: NR Insurance status, %: Medicare: 100 Education, %: Grade school or less: 17.5 Some HS: 19.5 HS: 33.1 > HS: 29.8 Other characteristics, %: Regimen complexity: < 3: 48.5 > 3: 51.5 D-50

335 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: In adjusted analysis, a sig association between HL level and Cardiovascular medication refill adherence Covariates used in multivariate analysis: refill adherence was not found. Effect in no exposure (i.e., adequate literacy) or control group, Age Race %: Adequate: Gender Low Adherence (CMG > 20%): 37.8 Education Regimen complexity e Adherence (CMG < 20%): 62.2 Adequat Effect in exposure (i.e., low/moderate literacy) or intervention, Description of outcome measures: %: Cardiovascular medication refill adherence - measured by CMG from pharmacy claims data Marginal: during 1 yr after enrollment; CMG: # of days Low Adherence (CMG > 20%): 41.2 medication unavailable between prescription fills, Adequate Adherence (CMG < 20%): 58.8 divided by number of days between the first Inadequate: Low Adherence (CMG > 20%): 45.4 Data source(s) for outcomes: Medicare and pharmacy claims data and one-hour Adequate Adherence (CMG < 20%): 54.6 in-person orally administered survey Difference: Difference in refill adherence (adjusted), OR (CI): Attempts for control for confounding: Marginal vs. adequate: 1.15 (0.82-1.61) Multivariate logistic regression Inadequate vs. adequate: 1.21(0.91-1.62) Blinding: NR Difference in refill adherence (adjusted controlling for Statistical measures used: adherence complexity), OR (CI): re, logistic regression Chi -squa Marginal vs adequate: 1.15 (0.82-1.62) Inadequate vs. adequate: 1.23 (0.92 - 1.64) D-51

336 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Cognitive health: Author, year: 3 Severe dementia: 1.6 Gazmararian, 2006 4 Baker et al., (Companions: Wolf et al., 2007; Mild dementia: 22.4 6 7 5 Wolf et al., 2005; Howard et al., 2006; Normal: 76.0 2007; 9 8 Howard et al., 2005; Baker et al., 2008; Health literacy/numeracy levels, %: 2 ) Baker et al., 2004 Adequate: 64.2 (continued) Marginal: 11.8 Inadequate: 24.0 D-52

337 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 25 Graham et al., 2007 Included: Research object ive: -old ≥ 18 years Assess relationship between literacy and HIV On antiretroviral therapy for ≥ 3 months medication adherence Receiving treatment from 1 of 2 U - Penn HIV clinics Study design: Excluded: -sectional Cross NR Study setting: Sampling strategy: -Penn HIV clinics in Recruited from U Pharmacy records examined for those recruited sequentially on Philadelphia, PA arrival for regular clinic appointments Measurement period: Sample size: Feb to June 2003. A retrospective 87 month examination of the previous 3- Age, median (IQR): pharmacy records <95% adherence: 44 (37-48) Follow -up duration: -53) ≥95% adherence: 46 (37 NA Gender, %: -up: Completeness of follow Females: NA <95% adherence: 24 Measurement tools including cutpoints: ≥95% adherence: 27 ≤61: Low health literacy (i.e., <9th REALM Race/Ethnicity, %: grade level) <95% adherence: Black: 88 White: 12 ≥95% adherence: Black: 69 White: 31 Income, %: <$10,0000: <95% adherence: 64 ≥95% adherence: 47 Insurance status: NR Education, %: High school <95% adherence: 60 ≥95% adherence: 69 Other characteristics: Median CD4 count (interquartile range) <95% adherence: 303 cells/cm3 (163-537) ≥95% adherence: 363 cells/cm3 (248 -470) Undetectable viral load (<50 c/ml), %: <95% adherence: 45 ≥95% adherence: 73 Health literacy/numeracy levels: NR D-53

338 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Individuals with adequate literacy had significantly better Independent: Literacy medicati Dependent: Adherence to HIV medication on adherence than those with low literacy in unadjusted analysis. In multivariate model, literacy was not Covariates used in multivariate analysis: NA found to be significantly related to adherence, controlling for Description of outcome measures: potential mediating effect of adherence norm (knowledge). adequate literacy) or control group, Adherence assessed via a validated time to Effect in no exposure (i.e., %: pharmacy refill surrogate measure to a single index drug over the prior 3 months ≥95% adherence: 64 Adherence defined as: (days supply dispensed / # Effect in exposure (i.e., low/moderate literacy) or intervention, days between refills) x 100% %: ≥95% adherence: 40 Data source(s) for outcomes: Difference: Pharmacy records Difference in 95% adherence (unadjusted): ( < 0.05) P Attempts for control for confounding: rolling for Difference in 95% Adherence (adjusted) cont Demographic variables assessed: adherence norm (possible mediator): ≥ 9th grade literacy, OR Age -5.79) (CI): 2.38 (0.98 Race History of drug and alcohol use Cognitive function Level of schooling completed Income Insurance type Socia l support Medical factors assessed: Current HIV viral loads CD4 counts Prior and current psychiatric diagnoses Blinding: NA Statistical measures used: Adherence was include as a continuous variable ≥95% or not. and dichotomized as Association between health literacy and adherence was assessed using chi squared and a REALM cut off of 61 representing a 9th grade reading level Wilcoxon rank sum tests Logistic regression D-54

339 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 26 Grubbs et al., 2009 Included: Research objective: Patients on maintenance hemodialysis (at least 9 months) Determine relationship between health literacy Self identified as black or white and referral for transplant evaluation in Between 21-75 yrs old patients on hemodialysis Never had a kidney transplant Study design: Excluded: rospective chart review, interview Ret Mental Status <18 Mini Study setting: Vision impaired (<20/100) 5 San Francisco Bay area outpatient dialysis Sampling strategy: units Convenience sample Measurement period: Sample size: April 2008 July 2007- 62 Follow -up duration: Age, mean (SD): NA 52.4 (12.2) -up: Completeness of follow Gender, %: NA Males: 66.1 Measurement tools including cutpoints: Race/Ethnicity, %: sTOFHLA: Black:72.6 Inadequate health literacy: 0-22 White: 27.4 Adequate health literacy: 23-36 Income, %: < 30,000: 54.8 Insurance status, %: Medicaid: 11.3 Medicare: 11.3 Medicare/Medicaid: 41.9 Private: 12.9 Private +Medicare: 14.5 VA: 8.1 Education, %: >HS: 61.3 HS equiv: 25.8

340 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Results Outcomes Main outcomes: Describe results: -list Access to kidney transplant wait Inadequate health literacy was associated with lower hazard of being referred for transplant evaluation but not for being wait - Covariates used in multivariate analysis: Demographics (race, gender, income age at start of listed dialysis) Effect in no exposure (i.e., adequate literacy) or control group, mean time (SD): Comorbid conditions (HTN, diabetes, peripheral vascular disease, CAD, HIV, Hep c, CHF, Time from dialysis date to referral date: 15.3 (44.7) mos Time from referral date to waitlist date: 2.1 (4.1) mos depression, drug abuse) Effect in exposure (i.e., low/moderate literacy) or intervention, Support (someone to help with appointments or mean time (SD): medications) Description of outcome measures: Time from dialysis date to referral date: 23.5 (44.8) mos Time from referral date to waitlist date: 6.6 (9.2) mos Dichotomous for referral for transplant evaluation Difference, HR (CI): Mean time from dialysis to referral date Difference in mean time from dialysis date to referral date Data source(s) for outcomes: (adjusted): Chart review, transplant center staff Attempts for control for confounding: 8.2 mos, 0.22 (0.08-0.60) Multivariate analyses Difference in time from referral date to waitlist (adjusted): 1.61) Blinding: 4 mos, 0.80 (0.39- NA ures used: Statistical meas Cox proportional Hazards modeling D-56

341 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 27 Included: Guerra et al., 2005 Research objective: 50 yrs and older Explore as sociation between functional health No prior history of colorectal cancer literacy and reported usage of colorectal Excluded: cancer screening tests NR Study design: Sampling strategy: -sectional Cross Convenience Study setting: Sample size: -based 4 community clinics, 2 university 136 practices in Pennsylvania Age (range): Measurement period: Total: 61 (50-98) June 2001-August 2002 Inadequate or Marginal Health Literacy, %: Follow -up duration: 50-59: 37 NA 60-69: 39 -up: Completeness of follow ≥70: 25 NA Adequate Health Literacy, %: Measurement tools including cutpoints: 50-59: 46 sTOFHLA: 60-69: 34 Inadequate Health Literacy: 0- 16 0: 20 ≥7 Marginal Health Literacy: 17-22 Gender, %: 36 Adequate Health Literacy: 23- Female: Total: 49 Inadequate or Marginal Health Literacy: 42 Adequate Health Literacy: 46 Race/Ethnicity, %: Total: Latino: 47 AA: 20 White: 33 Inadequate or Marginal Health Literacy: Latino: 84 AA: 14 White: 2 Adequate Health Literacy: Latino: 21 AA: 24 White: 55 Income, %: Total: Income < 10,000: 39 Inadequate or Marginal Health Literacy: 79 Adequate Health Literacy: 14 Insurance status, %: Total: Insured: 89 Uninsured: 11 Medicaid: 18 D-57

342 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Had colorectal screening tests sTOFHLA scores were not significant predictors of colon Covariates used in multivariate analysis: screening behaviors after adjustment. Effect in no exposure (i.e., adequate literacy) or control group, Ethnicity %: Medicaid Insurance status FOBT: 64 Education Sigmoidoscopy or Colonoscopy: 72 Effect in exposure (i.e., low/moderate literacy) or intervention, Income %: Description of outcome measures: Colorectal screening instrument (self report) FOBT: 39 Sigmoidoscopy or Colonoscopy: 30 adapted from an instrument to measure knowledge, Difference: attitudes, beliefs, and influences about screening FOBT: (Unadjusted) OR (CI): 2.75 (1.28- 5.97), (adjusted) ( = P mammography developed for low literate women 0.66) Data source(s) for outcomes: Sigmoidoscopy or Colonoscopy (Unadjusted) OR (CI): 6.15 Interview (2.69-14.24) (adjusted): ( P = 0.52) Attempts for control for c onfounding: Multivariate analyses Blinding: NR Statistical measures used: ANCOVA D-58

343 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Inadequate or Marginal Health Literacy: Author, year: 27 Insured:79 Guerra et al., 2005 Uninsured: 21 (continued) Medicaid: 37 Adequate Health Literacy: Insured: 95 Uninsured: 5 Medicaid: 5 Education, %: Total: 8th grade or less: 27 Inadequate or Marginal Health Literacy: 57 Adequate Health Literacy: 6 Other characteristics: NA Health literacy/numeracy levels: Mean STIFLE: 25.9 (0-36) Inadequate Health Literacy (N=36), %: 36 Marginal Health Literacy, %: 6 Adequate Health Literacy, %: 58 D-59

344 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Study Description haracteristics C Author, year: Eligibility criteria: 28 Guerra et al., 2005 Included: Research objective: Women > 40 years Explored association between functional Hispanic ethnicity health literacy and behavior about No history of breast cancer mammography and self -breast examination in Spanish or English speaking a sample of Latinas attending community Excluded: health clinics in Philadelphia. NR Study design: Sampling strategy: -section al Cross Convenience Study setting: Sample size: 3 Community health clinics in Philadelphia 97 Measurement period: Age mean (range): April to September 2001 All women: 58.0 (41-85) -up duration: Follow nt difference between adequate and Inadequate literacy Significa NA groups -up: Completeness of follow Gender, %: NA Females: 100 Measurement tools including cutpoints: Race/Ethnicity, %: sTOFHLA: Hispanic:100 Inadequate score 0-16 Income (N = 71), %: Marginal score 17-22 <$10,000: 63 Adequate score 23- 36 >$10,000 37 Insurance status (N = 97), %: Uninsured: 26 Education (N = 94), %: < high school: 75 High school diploma or GED: 12 Some education beyond high school: 13 Significant difference between adequate and inadequate groups Other characteristics: Acculturation scale 1 -5 (SD), (N=85): 1.69 (0.5) Significant difference between adequate and inadequate groups Health literacy/numeracy levels, %: Mean sTOFHLA score: 17 Inadequate functional health literacy: 70 Adequate functional health literacy: 30 D-60

345 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Describe results: outcomes: Main After adjusting for demographic characteristics, functional Ever had a mammogram health literacy was only associated with a greater odds of Had last mammogram within 1 yr had a mammogram having ever Had last mammogram within 2 yrs -up Had mammogram as part of check Difference, OR (CI): Adjusted results: Check own breasts for lumps Perform self breast exam at least monthly 1.27) Ever had a mammogram: 1.14 (1.02- Covariates used in multivariate analysis: 1.08) Had last mammogram within 1 yr: 1.01 (0.95- Education Had last mammogram within 2 yrs: 0.98 (0.91-1.07) Age -up: 1.01 (0.94-1) Had mammogram as part of check culturation Ac Insurance status Description of outcome measures: Structured 60-item breast cancer screening questionnaire Data source(s) for outcomes: Self -report Attempts for control for confounding: Logistic regression adjusted for education, age, acculturation, insurance status Blinding: NA Statistical measures used: Adjusted logistic regression models D-61

346 Table 1. Key Question 1: Health literacy outcome studies (continued) Evidence Study Description Participant Characteristics Author, year: criteria: Eligibility 29 Hahn et al., 2007 Included: Research objective: ≥ 18 yrs old Examine relationship between literacy and Cancer diagnosis HRQoL using a multimedia touch screen English language preference program that assesses HRQoL. Adequate visual, auditory and physical capabilities Study design: Excluded: Cross -sectional < 20/70 vision when tested with a Rosenbaum vision card Study setting: Sampling strategy: -area cancer centers Five Chicago Convenience Measurement period: Sample size: NR 415 -up duration: Follow Low, n = 214 NA High, n = 201 Completeness of follow -up: Age, mean (SD): NA Total: 54.3 (13.4) Measurement tools including cutpoints: Low: 56.3 (12.9) Passage comprehension subtest of Woodcock High: 52.1 (13.8) Language Proficiency Battery: Gender, %: Low < 7th grade Total: ≥ 7th grade High Female: 66.9 Low: 67.8 High: 66.2 Race/Ethnicity, %: Total: White: 29.8 Black: 57.6 Other: 12.6 Low: White: 18.2 Black: 71.5 Other: 10.3 High: White : 42.3 Black: 43.3 Other: 14.4 Income: NR Insurance status: NR Education, %: Total:

347 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Describe results: Main outcomes: by 3 different tests) There were no statistically significant differences in any of the HRQoL (measured HRQoL scores between the high and low literacy groups. Covariates used in multivariate analysis: Age Effect in no exposure (i.e., adequate literacy) or control group, Gender mean (SD ): FACT Race/ethnicity -G: Physical well-being: 18.4 (5.8) Work status Social/family well-being: 20.8 (5.6) Marital status -being: 17.5 (4.7) Living arrangement Emotional well Functional well SES -being: 16.0 (6.3) SF -36: Prior computer experience Physical functioning: 57.2 (27.5) Cancer diagnosis Role -physical: 34.8 (42.4) Stage at diagnosis Bodily pain: 56.0 (24.9) Months since diagnosis health: 53.2 (21.3) General Current chemotherapy treatment Performance status Vitality: 47.3 (20.5) Description of outcome measures: Social functioning: 59.5 (26.2) -emotional: 48.7 (43.9) Three measures of HRQoL: Role - -item questionnaire with 5 Likert -G: 27 The FACT Mental health 66.9 (20.2) type response categories. Number (%) with fair/poor health: 79 (39.3) Standard gamble utility score: 0.85 (0.23) Scores total HRQoL and dimensions of physical, social/ family, emotional and functional well -being. Effect in exposure (i.e., low/moderate literacy) or intervention, mean (SD): Higher scores = better HRQoL. FACT -36: 36-item measure of 8 health concepts: SF -G: Physical well-being: 17.9 (5.9) physical functioning, role-physical, bodily pain, Social/family well-being: 20.3 (5.9) general health, vitality, social functioning, role- Emotional well emotional and Mental Health, and two higher order -being: 17.6 (5.2) dimensions. It contains multiple response formats Functional well -being: 15.7 (6.5) -type, true/false). Higher scores = (yes/no, Likert -36: SF better HRQoL. Physical functioning: 48.7 (26.7) Role The SGUQ: a preference- based measure of HRQoL -physical: 29.7 (38.2) bodily pain: 55.5 (26.9) that reflects the patient’s value for her/his current General health: 49.9 (20.6) health state. Utility scores range from 0 (current Vitality: 51.5 (21.4) Social functioning: 61.4 (25.7) health = to death) t o 1 (current health = to perfect health). Negative scores are possible. -emotional: 49.3 (43.9) Role Data source(s) for outcomes: Mental health: 65.5 (19.6) Number (%) with fair/poor health: 114 (53.3) -administer Multimedia TT: participants self As text appears on the screen, it is questionnaires. Standard gamble utility score, mean (sd): 0.87 (0.20) also read out loud as patients listen through their Difference: headset. -G (adjusted): no sig difference between Difference FACT Attempts for control for confounding: groups including and excluding biased scale items Multivariable linear regression Difference SF -36 (adjusted): no sig difference between groups < P *Covariates that met a screening criterion of ( including and excluding biased scale items 0.25) in bivariate regressions were selected for a Diffe rence Standard Gamble utility score (unadjusted): P = 0.561) ( multivariable model, and then removed individually P tention criterion, < using backward elimination (re = 0.023). Sig Difference mean Vitality score (adjusted): 4.6, ( P 0.05) difference does not hold when biased scale items removed = P Difference mean Social functioning score (adjusted): 5.1, ( Blinding: 0.030) NA D-63

348 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Low: 29 Hahn et al., 2007

349 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Statistical measures used: -sum -test or Wilcoxon rank Bivariate relationships: t test for continuous variables, Pearson chi -square statistic or Fisher’s exact test for nominal variables, -Haenszel chi and Mantel -square statistic for ordinal variables. HRQoL scores by literacy level D-65

350 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 30 Included: Hibbard et al., 2007 Research objective: 64 years of age) Adults (18- Examine contribution of health literacy, Excluded: numeracy, and patient activation to the NR ative health care comprehension of compar Sampling strategy: performance reports and their use in making Convenience an informed choice Sample size: Study design: 303 Cross -sectional Age (range): Study setting: (18 37 -64) Community Gender: Measurement period: Females: 48% NR Race/Ethnicity: -up duration: Follow NR NA Income, %: Completeness of follow -up: < 25,000: 74 NA Insurance status, %: Measurement tools including cutpoints: Health Insurance: 45 TOFH LA (passage B only) Education, %: Numeracy: 11 item measure from Lipkus, High school or less: 45 Samsa and Rimer, plus 4 items on interpreting Some college or more: 55 risk magnitude Other characteristics, %: Good to excellent health: 40 Fair to poor health: 24 Health literacy/numeracy levels, %: (Calculated) TOFHLA Low Health Literacy: 45 High Health Literacy: 55 Low Numeracy: 43 High Numeracy: 57 D-66

351 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Describe results: Main outcomes: Numeracy and literacy predict comprehension but do not Choosing a high performing hospital Covariates used in multivariate analysis: predict quality choice. In a path analysis, higher numeracy and literacy predict better comprehension, which in turn predicts a Age better quality choice. Making a better qualit Gender y hospital choices is Education related to activation level, separate from comprehension. Comprehension Effect in no exposure (i.e., adequate literacy) or control group: Activation NR Description of outcome measures: Effect in exposure (i.e., low/moderate literacy) or intervention: Quality Choice: Experiment of choosing a higher NR Difference: quality hospital based on performance measures Com Quality Choice (adjusted): prehension: how well a patient understood -0.023, Literacy: P = NS information in the data display = NS P Numeracy: 0.032, Data source(s) for outcomes: Activation X Numeracy: ( = NS) P Interview Activation X HL: ( P = NS) Attempts for control for confounding: Path analysis (adjusted): Multivariate analyses HL predicts comprehension: ( < 0.001) P Blinding: Numeracy predicts comprehension: ( P < 0.001) NA Comprehension predicts Quality Choice: ( < 0.001) P Statistical measures used: Multivariate Logistic regression analysis Path D-67

352 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 31 Included: Hironaka et al., 2009 Research objective: 7 months Caregivers and infants age 5- Determine whether limited caregiver HL is English or Spanish associated with adherence to - a daily multi Excluded: vitamin with iron regimen in infants. History of conditions associated with iron deficiency anemia Study design: Use of vitamin or iron supplements within 1 month prior to Nested Cohort enrollment Study setting: Premature, multiple gestations Phone calls and home visits to caregivers BW < 2500 g using 2 urban pediatric primary care clinics Sampling strategy: Measurement period: Convenience, drawn from 150 in RCT (67% of those eligible) June 2005-March 2006 Sample size: -up duration: Follow Total: 110 dyad 3 months Families: pleteness of follow -up: Com Limited HL:20 NR Adequate HL: 90 Measurement tools including cutpoints: Age, mean (SD): sTOFHLA: Caregiver: 30.2 (6.55) Limited HL = marginal or inadequate HL Limited HL: 30.2 (6.17) -16 Inadequate HL: 0 Adequate HL: 30.1 (6.67) Marginal HL: 17-22 Gender, %: Adequate HL: 23-36 Female: Caregiver: 91.8 Limited HL: 95.0 Adequate HL: 91.1 icity, %: Race/Ethn (Child's race) Black: 48.2 Hispanic: 30.0 Other: 17.3 White: 4.6 Limited HL: Black: 55.0 Hispanic: 20.0 Other: 20.0 White: 5.0 Adequate HL: Black: 46.7 Hispanic: 32.2 Other: 16.7 White: 4.4 Income: NR Insurance status, %: Public: 86.4 Limited HL: 80.0 Adequate HL: 87.8 D-68

353 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Caregivers with limited HL were twice as likely to report high Adherence to administration of adherence to a daily multivitamin with iron regimen in infants as Multivitamin with iron: 32.7% caregivers with adequate HL Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: Race/ethnicity Avg # of days adherent per wk: 2.4 Caregiver ed Effect in exposure (i.e., low/moderate literacy) or intervention: Caregiver concerns regarding multivitamins, side Avg # of days adherent per wk: 3.7 effects Difference, OR (CI): Randomized assignment to drops or sprinkle High adherence (adjusted): lim ited HL versus adequate HL: formulation 2.13 (1.2-3.78 0) Description of outcome measures: High adherence (adjusted-adding control for concerns to Answer to questions regarding model): 2.4 (1.37-4.2) Infant's adherence to multi -vitamin and iron regimen on 5-7 days of preceding week. High adherence: administration of vitamin and iron on 5-7 days of preceding wk. Data source(s) for outcomes: Interview from biweekly data collection over the 3- mo period Attempts for control for confounding: Multivariate analyses Blinding: NA Statistical measures used: GEE multiple Logistic regression D-69

354 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Education, %: 31 Hironaka et al., 2009 Caregiver < HS: 17.3 Research objective: Limited HL: 25.0 Determine whether limited caregiver HL is Adequate HL: 15.6 associated with adherence to a daily multi - Other characteristics, %: vitamin with iron regimen in infants. Caregiver born outside US: 66.4 Study design: Limited HL: 90.0 Nested Cohort Adequate HL: 61.1 Study setting: Health literacy/numeracy levels, %: Phone calls and home visits to caregivers Limited HL: 18.2 using 2 urban pediatric primary care clinics Measurement period: June 2005-March 2006 Follow -up duration: 3 months -up: Completeness of follow NA D-70

355 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 32 Included: Hope et al., 2004 Research objective: Diagnosis of CHF by a patient’s primary care physician Study association of medication adherence, 50 years or older knowledge, and skills (including literacy - Ability to speak English ability to read labels) with ED visits Ability to hear at normal spe aking levels, access to a telephone Study design: Plans to receive medical care and prescription medications at Cohort Wishard Health Service Study setting: Excluded: Patients in study enrolled in control group of Dementia or 5+ errors on the Short Portable Mental Status an ongoing randomized trial of participants Questionnaire with CHF in Indianapolis, Indiana Not prescribed 1+ medication from common drug classes used to Measurement period: treat CHF 3/2/2001 - 6/30/2004 -related questions about their quality Unwilling to respond to health -up duration: Follow of life and adherence 6 months Sampling strategy: Completeness of follow -up: NR NR Sample size: Measurement tools including cutpoints: 61 Literacy was defined as the ability to read Age, mean (SD): standard prescription and auxiliary labels, and 65.4 (8.7) was 1 of 3 components of medication skills Gender, %: measure. Females: 72.1 Other components of this measure were: Race/Ethnicity, %: dexterity (ability to open child-resistant and AA: 49.2 s and a child easy open 40-dr container White: 49.2 -oz bottle) and ability to distinguish resistant 4 American IndiaNAlaska Native: 1.6 Colors of tablets and capsules Income: NR Insurance status: NR Education, %: More than 12 years: 8.9 12 years: 28.6 Less than 12 years: 62.5 Other characteristics, %: NYHA Classification I = 35 II = 46.7 III/IV = 18.3 No. medications 1 - 10 = 60.7 11+ = 39.3 Hea lth literacy/numeracy levels: NR Mean reading score (SD): 1.65 (0.56) D-71

356 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: -cause cardiovascular -related and CHF -specific label Better prescription- -reading skills (literacy) were All associated with fewer ED visits, = 0.002. P ED visits Effect in no exposure (i.e., adequate literacy) or control group: used in multivariate analysis: Covariates NR NYHA classification Effect in exposure (i.e., low/moderate literacy) or intervention: Number of medications NR Race Difference: Reading score P ( = 0.002) Description of outcome measures: The primary outcomes were all -cause -related and CHF -specific ED visits cardiovascular e used -9 codes wer -month period. ICD during the six to determine ED visits with a diagnosis of CHF and a cardiac diagnosis Data source(s) for outcomes: NR (medical records?) Attempts for control for confounding: Multivariate analysis Blinding: NA Statistical measures used: regression Multivariate log-linear D-72

357 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 9 Howard et al., 2005 Included: 3 ; Wolf et (Companions: Gazmararian, 2006 managed-care enrollees Medicare 5 4 ; Howard et al., al., 2007 ; Baker et al., 2007 65 years or older 3 months after he/she enrolled in Prudential 8 7 6 ; ; Wolf et al., 2005 ; Baker et al., 2008 2006 HealthCare 2 9 ) ; Baker et al., 2004 Howard et al., 2005 Excluded: Research objective: Not comfortable speaking English or Spanish Examine impact of low health literacy on Blind or severely impaired vision not correctable with eyeglasses cal care use and costs medi Living in a nursing home Study design: Severe cogniti ve impairment Cohort Sampling strategy: Study setting: Convenience sample of consecutive new Medicare managed -care In-person in-home interviews with and enrollees subsequent claims data for new Medicare Sample size: care enrollees in Cleveland, managed- 3,260 Houston, Tampa, and south Florida (including Age (range), %: Ft. Lauderdale and Miami) 65-69: 37.0 Measurement period: 70-74: 27.3 New enrollees in Prudential Medicare 75-79: 19.3 managed care plans between December 1996 80-84: 11.0 and August 1997. >85: 5.4 Interviews occurred 3 months following Mean by HL level (SD): enrollment. Adequate: 71.6 (7.2) Claims data from within 1 year of date of Marginal: 74.1 (6.3) enrollment into the managed- care plan Inadequate: 75.6 (5.6) (usually 3 months prior to study enrollment) Gender: Follow -up duration: Female: 57.4 1 year By HL status, %: -up: Completeness of follow Female: 3487 enrolled, 3,260 completed sTOFHLA Adequate: 57.9 and interview Marginal: 53.8% Measurement tools (cutpoints NR): Inadequate: 57.8% S-TOFHLA: Race/Ethnicity,%: Adequate White: 76.0 Marginal Black: 11.8 Inadequate speaking Hispanic: 2.0 English- Spanish-speaking Hispanic: 9.2 Other: 1.0 By HL status: Adequate: White: 84 AA: 6.6 Hispanic English-speaking: 1.6 Hispanic Spanish- speaking: 6.6 Other: 1.2 D-73

358 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: utilization Healthcare Participants with inadequate HL used sig more inpatient and ED services than those with adequate HL but no sig differences Healthcare costs were found in overall use outpatient or pharmacy use Covariates used in multivariate analysis: ig more pharmacy (adjusted). Patients with marginal HL used s Age services than those with adequate HL. All other use Sex comparisons were not sig (adjusted). Race/ethnicity Participants with inadequate and marginal HL had sig higher Income ED costs than those with adequate HL. Participants with Education marginal HL had sig lower outpati ent costs than participants Tobacco with adequate literacy (after adjusting for covariates). All other Alcohol consumption comparisons were not sig. -reported comorbid conditions (heart attack, Self Similar results were found in models comparing inadequate angina, stroke, high blood pressure, chronic and adequate groups not controlling for education or comorbid obstructive pulmonary disease, cancer, diabetes, conditions. arthritis, depression) Effect in no exposure (i.e., adequate literacy) or control group, Description of outcome measures: %: Healthcare utilization: percent using any inpatient, Adequate Use: outpatient, ED, or pharmacy services. Overall: 97 Healthcare costs: total, inpatient, outpatient, ED, Inpatient: 27 and pharmacy services. Outpatient: 91 source(s) for outcomes: Data ED: 21 -hour in-person orally Medicare claims data and one Pharmacy: 88 administered survey Costs (SD): Attempts for control for confounding: Overall: $7,246 ($17 941) Multivariate logistic regression Inpatient: $4,656 ($16 428) Blinding: Outpatient:$,1805 ($3188) NR ED: $100 ($360) Statistical measures used: Pharmacy: $684 ($890) 1-way ANOVA Smoking: -square Chi Never: 38 Modified 2-part regression model (Mullahy) Former: 49 Current: 13 Drinking, %: None: 58 Light to Moderate: 37 Heavy: 4 Comorbid Conditions, %: Heart Attack: 13 Angina: 8 Stroke: 7 High Blood Pressure: 45 COPD: 18 Asthma: 7 Cancer: 6 Diabetes: 13 Arthritis: 5 0 Depression: 12 D-74

359 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: Marginal: 9 White: 68 Howard et al., 2005 3 ; Wolf et (Companions: Gazmararian, 2006 AA: 12.6 4 5 ; Howard et al., al., 2007 ; Baker et al., 2007 Hispanic English-speaking: 2.5 6 8 7 ; Wolf et al., 2005 ; ; Baker et al., 2008 2006 Hispanic Spani sh-speaking: 16.4 9 2 ) ; Baker et al., 2004 Howard et al., 2005 Other: 0.6 (continued) Inadequate: White: 25.2 AA: 58.6 Hispanic English-speaking: 2.3 Hispanic Spanish- speaking: 13 Other: 1 Income, %: <$10 000: 18.2 $10 000-14 999: 21.6 $15 000-24 999: 25.6 $25 000-34 999: 8.7 $35 000: 10.2 Did not answer/did not know: 15.7 By HL status: Adequate, <$15,000: 33 Marginal, <15,000: 47 Inadequate, <$15,000: 54 Insurance status, %: Medicare: 100 Education, %: Grade school or less: 17.3 Some high school: 18.4 High school: 33.6 More than high school: 30.7 By HL sta tus: >12 years of school completed: Adequate: 39.7 Marginal: 20 Inadequate: 12 0-8 years of school completed: Adequate: 7.1 Marginal: 24.2 Inadequate: 40.9 Other characteristics: NR Health literacy/numeracy levels, %: Adequate: 64.2 Marginal: 11.2 Inadequate: 24.5 D-75

360 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Inadequate All: 95 Effect in exposure (i.e., low/moderate literacy) or intervention: Inpatient: 35 Outpatient: 90 ED: 30 Pharmacy: 85 Costs (SD): Overall: $9,614 ($22536) Inpatient: $6,817 ($21049) Outpatient: $1,970 ($3477) ED: $189 ($551) Pharmacy:$638 ($1267) Smoking, %: Never: 45 Former: 43 Current: 12 Drinking, %: None: 75 Light to Moderate: 23 Heavy: 2 Comorbid Conditions: Attack: 15 Heart Angina: 8 Stroke: 13 High Blood Pressure: 51 COPD: 14 Asthma: 7 Cancer: 5 Diabetes: 19 Arthritis: 58 Depression: 19 Marginal - Use, %: Overall: 96 Inpatient: 34 Outpatient: 90 ED: 28 Pharmacy: 85 Marginal - Costs (SD): Overall: $8,484 ($16646) Inpatient: $5,857 ($15240) Outpatient: $1,727 ($2954) ED: $182 ($593) Pharmacy: $719 ($998) Smoking, %: Never: 43 Former: 45 Current: 13 D-76

361 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: 9 Howard et al., 2005 3 ; Wolf et (Companions: Gazmararian, 2006 4 5 al., 2007 ; Howard et al., ; Baker et al., 2007 6 8 7 ; Baker et al., 2008 ; ; Wolf et al., 2005 2006 2 9 ) ; Baker et al., 2004 Howard et al., 2005 (continued) D-77

362 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes Drinking, %: None: 64 Light to Moderate: 33 Heavy: 2 Comorbid Conditions, %: 18 Heart Attack: Angina:12 Stroke: 9 High Blood Pressure: 48 COPD: 16 Asthma: 8 Cancer: 7 Diabetes: 16 Arthritis: 58 Depression: 14 +AU1 Difference (CI): Differences in probability of use (adjusted) Inadequate vs adequate overall: 0.00 ( 0.02) -0.02- Inpatient use: 0.05 (0.00-0.09) Outpatient: -0.02 ( -0.05 -0.01) ED: 0.05 (0.01- 0.10) Pharmacy: -0.03; 95% CI, - 0.06 -0.00 Differences in probability of use (adjusted) Marginal vs adequate overall: 0.00 ( -0.02- 0.03) -0.01-0.09) Inpatient use: 0.04 ( Outpatient: -0.01 ( -0 .02) -0.04 -0.01- ED: 0.04 ( 0.09) -0.04 ( -0.08-0.00) Pharmacy: Differences in costs (adjusted) - Inadequate vs adequate: Overall: $1,551 ( -$166-$3267) Inpatient use: $1,543 ( $3175) -$89- Outpatient: -$213 ( -$481-$55) ED: $108 ($62- $154) Pharmacy $27; 95% CI, -$55 -$110 Differences in costs (adjusted) - Marginal vs adequate: -$1437 -$2630) Overall: $596 ( -$1252 -$2748) Inpatient use: $748 ( -$350 ( -$679-- $20) outpatient: ED: $80 ($28-$132) Pharmacy: $35 ( -$132) -$62 Comparisons across 3 groups (unadjusted): ( P = 0.01) Smoking: Drinking: ( P = 0.23) D-78

363 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: 9 Howard et al., 2005 3 (Companions: Gazmararian, 2006 ; Wolf et 4 5 ; Baker et al., 2007 ; Howard et al., al., 2007 7 8 6 ; Wolf et al., 2005 ; Baker et al., 2008 ; 2006 9 2 ; Baker et al., 2004 ) Howard et al., 2005 (continued) D-79

364 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Comorbid conditions: Heart Attack: ( P = 0.01) Angina: ( P = 0.06) Stroke: ( P < 0.0001) = 0.01) High Blood Pressure: ( P COPD: ( = 0.06) P P = 0.65) Asthma: ( P Cancer: ( = 0.15) Diabetes: ( P = 0.0002) Arthritis: ( P = 0.0002) < 0.0001) Depression: ( P D-80

365 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 6 Howard et al., 2006 Included: 3 (Companions:Gazmararian, 2006 ; Wolf et al., Medicare managed-care enrollee 5 4 7 2007 ; ; Baker et al., 2007 ; Wolf et al., 2005 65+ 9 8 ; ; Howard et al., 2005 Baker et al., 2008 Enrolled in Prudential HealthCare 3 months or more 2 ) Baker et al., 2004 Excluded: Research objective: Not comfortable speaking English or Spanish Explore impact of HL on differences in health Blind or severely impaired vision not correctable with eyeglasses status and vaccination by educational Living in a nursing home attainment and race Missed 1 or more screening questions for severe cognitive Study design: impairment (not able to correctly identify year, month, state, year of Cohort their birth, or home address) Study setting: Sampling strategy: In-person in-home interviews with and -care Convenience sample of consecutive new Medicare managed subsequent clai ms data for enrollees in enrollees Cleveland, Houston, Tampa, and south Sample size: Florida (including Ft. Lauderdale and Miami) Analysis by educational level, N: 3,260 Measurement period: Analysis by race (limited to black and white), N: 2,850 Interviews occurred May 1997-December Age (mean and range), %: 1997 Full sample: -up duration: Follow 65-69: 37.0 NA 70-74: 27.3 -up: Completeness of follow 75-79: 19.3 NA 80-84: 11.0 Measurement tools including cutpoints: >85: 5.4 S-TOFHLA: White: Adequate 65-74: 61 Marginal 75-84: 33 Inadequate 85+: 6 Black: 65-74: 66 75-84: 29 85+: 5 Gender, %: Male by education: HS degree: 42 No HS degree: 44 Male by race: White: 42 Black: 34 Race/Ethnicity, %: By education: HS degree: White: 86 Black: 7 Hispanic: 4 Other: 3 D-81

366 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Compared to those with adequate HL, enrollees with inadequate Physical and mental health status HL had sig worse physical and mental health status and were sig receipt of vaccinations Covariates used in multivariate analysis: less likely to report receiving an influenza vaccine. No sig nces were found between marginal and adequate HL differe Age groups. Gender Race/ethnicity Difference: Education 12 (adjusted), β: - Difference in Physical Health SF < 0.001 P -2.53, Inadequate/Adequate: Income P -1.35, Marginal/Adequate: =0.019 Site Difference in Mental Health SF - 12 (adjusted), β: Morbidity Inadequate/Adequate: -1.41, < 0.001 P Smoker Marginal/Adequate: 0.46, = 0.304 P Description of outcome measures: -reported health status of good or better Difference in self Health status: (adjusted), OR: Physical health SF -12 P = 0.004 Inadequate/Adequate: 0.71, -12 Mental health SF = 0.060 Marginal/Adequate: 0.77, P Self -reported health status (fair or poor vs. good, Difference in receipt of influenza vaccine (adjusted), OR: very good, or excellent) Inadequate/Adequate: 0.76, P = 0.020 Receipt of vaccination: = 0.707 Marginal/Adequate: 1.06, P Self -reported receipt of influenza vaccination Difference in recipt of pneumodoccal vaccine (adjusted), OR: -reported receipt of pneumococcal vaccination Self = 0.114 P Inadequate/Adequate: 0.85, Data source(s) for outcomes: = 0.445 P Marginal/Adequate: 0.91, In-person survey Difference in Physical Health SF -12 score (adjusted) between Attempts for control for confounding: model not controlling for HL vs model controlling for HL (CI): Multivariate logistic regression By education level: 0.7 points (0.4-0.9) Blinding: By race: 0.6 points (0.3-0.9) NR Difference in Mental Health SF -12 score (adjusted) between model Statistical measures used: not controlling for HL vs model controlling for HL (CI): -square, multivariate logistic regression, ordinary Chi By education level: 0.3 points (0.1-0.5) least squares regression By race: 0.3 points (0.1-0.5) Difference in probability of self -reported health status of good or better (adjusted) between model not controlling for H L vs model controlling for HL (CI): By education level: 0.02 (0.01- 0.03) 0.03) By race: 0.02 (0.01- Difference in probability of receipt of influenza vaccine (adjusted) between model not controlling for HL vs model controlling for HL (CI): By education lev el: 0.010 (0.001-0.020) By race: 0.009 ( -0.001-0.020) Difference in probability of receipt of pneumococcal vaccine (adjusted) between model not controlling for HL vs model controlling for HL (CI): -0.002 -0.022) By education level: 0.010 ( By race: 0.003 ( - 0 .007 - 0.013) D-82

367 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: No H S degree: 6 White: 59 Howard et al., 2006 3 (Companions:Gazmararian, 2006 ; Wolf et al., Black: 20 4 7 5 2007 ; Baker et al., 2007 ; Wolf et al., 2005 ; Hispanic: 18 9 8 ; ; Howard et al., 2005 Baker et al., 2008 Other: 3 2 ) Baker et al., 2004 Income, %: (continued) By education HS degree: Missing: 16 0-10,000: 11 10,000-15,000: 19 15,000-25,000: 28 25,000-35,000: 11 35,000+: 14 No HS degree: Missing: 16 0-10,000: 30 10,000-15,000: 25 15,000-25,000: 21 25,000-35,000: 4 35,000+: 3 Insurance status, %: Medicare: 100 Education, %: Full sample: Grade school or less: 17.3 Some HS: 18.4 HS grad: 33.6 More than HS: 30.7 White: Grade school or less: 10 Some HS: 18 HS grad: 38 More than HS: 35 Black: or less: 33 Grade school Some HS: 28 HS grad: 24 More than HS: 15 Health literacy/numeracy levels,%: By education: HS degree: Adequate: 78 Marginal: 9 Inadequate: 13 D-83

368 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: No HS degree: 6 Adequate: 40 Howard et al., 2006 3 (Companions:Gazmararian, 2006 ; Wolf et al., Marginal: 16 7 5 4 ; 2007 ; Baker et al., 2007 ; Wolf et al., 2005 Inadequate: 45 9 8 ; Howard et al., 2005 ; Baker et al., 2008 By race: 2 ) Baker et al., 2004 White: (continued) Adequate: 71 Marginal: 10 Inadequate: 19 Black: Adequate: 36 Marginal: 12 Inadequate: 52 D-84

369 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: criteria: Eligibility 33 Included: N Huizinga et al., 2008 Research objective: Excluded: Examine association between numeracy skills Age < 18 years and weight status as measured by BMI Non -English speaking Study design: Dementia Cross -sectional Corrected visual acuity equal to or worse than 20/50 by Rosenbaum Study setting: Pocket Vision Screener are clinic at Vanderbilt Academic primary c Sampling strategy: University Medical Center Convenience sample (referred by clinic staff) Measurement period: Sample size: July 2006 - August 2007 169, no comp arisons -up duration: Follow Age, mean (SD): NA 46 (16) -up, (%): Completeness of follow Low Numeracy: 45.1 160/169 (95) High Numeracy: 47.6 Measurement tools including cutpoints: Gender, %: -3 Numeracy: WRAT Female: 70 Literacy: REALM Low Numeracy: 70 High Numeracy: 70 Race/Ethnicity, %: White: 66 Low Numeracy: 52 High Numeracy: 93 Income, %: <$20,000: 16 Low Numeracy: 23 High Numeracy: 4 Insurance status: NR Education, %: -school or GED: 91 High Low Numeracy: 87 High Numeracy: 98 Other characteristics, %: Dyslipidemia: 26 Hypertension: 38 CAD: 8 Diabetes: 17 NR by numeracy subgroup Health literacy/numeracy levels: Numeracy: All participant s, mean (SD): 89.1 (16) < 9th grade (66% of participants), mean (SD): 80.9 (11) > 9th grade (34% of participants), mean (SD): 105 (9.1) D-85

370 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Lower numeracy was significantly associated with higher BMI. BMI Literacy was not significantly associated with BMI Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: Age Numeracy > 9th grade: Sex BMI (SD): 27.9 (6.0) Race Income Literacy > 9th grade: BMI (SD): 30.2 (7.8) Years of education REALM score Effect in exposure (i.e., low/moderate literacy) or intervention: Description of outcome measures: Nu meracy < 9th grade: BMI (SD): 31.8 (9.0) BMI calculated from height and weight Data source(s) for outcomes: Literacy < 9th grade: -report by patient after measurement by clinic Self BMI (SD): 31.7 (9.9) staff Difference: = 0.008 P BMI (low versus high Num) (unadjusted): +3.9, ts for control for confounding: Attemp Beta coefficient for effect of Numeracy on BMI: (adjusted for Linear regression = cation): P age, sex, race, income, and years of edu -0.14, Blinding: 0.01 NR P BMI (low versus high Lit) (unadjusted): +1.5, = 0.50 Statistical measures used: Spearman's rank correlation Wilcoxon rank sum Linear regression D-86

371 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: Health Literacy: 33 Huizinga et al., 2008 All participants, mean (SD): 61.0 (8.7) (continued) < 9th grade (22.5% of participants) > 9th grade (77.5% of participants ) D-87

372 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 34 Inclusion: Johnson et al., 2010 Research objective: NA To explore whether social support helps Exclusion: patients with limited HL adhere to their Cognitive impairment (Mini -Cog Assessment) medication regimens. Had poor vision (worse than 20/100) Study design: <18 years of age -sectional Cross ≥6 months. Had not been a pharmacy patient for dy setting: Stu Sampling strategy: 3 pharmacies at Grady Memorial Hospital in Convenience sample; A standardized telephone script was used to Atlanta, GA (intervention site) and a recruit patients already enrolled in the PILL Study. Pharmacy community -based satellite pharmacy in supervisors helped identify pharmacists who might be available for Decatur, GA (control site) interviews Measurement period: Sample size: NR 275 Pharmacy Patients Follow -up duration: Age (mean and range), % (SD): NA Mean: 53.91 (12.50) -up: Completeness of follow Gender, %: NA Female: 73.1 luding cutpoints, %: Measurement tools inc Race/Ethnicity, %: REALM: Race: 0-44: limited health literacy Black/African American: 86.2 45-66: adequate health literacy White: 5.1 Other: 8.7 Ethnicity: Hispanic: 1.8 -Hispanic: 98.2 Non Income, %: income, %: Annual household <$10,000: 63.7 ≥$10,000: 36.3 Insurance status, %: NR Education, %:

373 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Describe results: Main outcomes: Adherence to medication regimens Social support was associated with better medication adherence for patients with adequate HL but not those with Covariates used in multivariate analysis: Age limited HL (P< 0.05). Sex Effect in no exposure (i.e., adequate literacy) or control group: Multiple linear regression Analyses: Greater social support was Description of outcome measures: associated with better medication adherence, but only for Adherence: A modified 8-item version of the Morisky -1.827; SE = 0.793; patients with adequate health literacy (β = Adherence Scale. R^2 = 0.000; CI, - 3.389 to - P 0.265; < 0.05). Social support: the Enriched Social Support At the highest level of social support, patients with adequate nt (ESSI), which measures different types Instrume rence than those health literacy reported better medication adhe of social support. reporting inadequate/marginal health literacy. Data source(s) for outcomes: Effect in exposure (i.e., low/moderate literacy) or intervention: Researchers conducted four focus groups with Having as much contact as you would like with someone in patients (two at the intervention site and two at the whom you can trust and confide was associated with better control site) and face-to -face interviews with -literacy patients medication adherence for inadequate/marginal ched conducted 30-min pharmacists. Resear < 0.05). ( P interviews at the pharmacies. Patients in both of the limited-literacy focus groups said Attempts for control for confounding: relatives began helping them after they were hospitalized for Linear regression analyses medication overdoses or interactions. Blinding: Difference: NR The difference between inadequate/marginal and adequate Statistical measures used: health literacy changed for different values of social support, as Regression indicated by the interaction observed between social support Descriptive statistics and health literacy (β = 0.086; SE, 0.035; R^2 change = 0.020; Chi -square tests CI, 0.018 to 0.154; P < 0.05) D-89

374 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Participant Characteristics Study Description Author, year: Social support: 34 Johnson et al., 2010 Low: 48.0 (continued) High: 52.0 Mean (SD): 22.24 (6.18) Medication adherence (n = 272): Low: 68.4 High: 31.6 Mean (SD): 4.95 (1.82) Health literacy/numeracy levels, %: REALM, n = 273 Inadequate/marginal, %: 59.7 Adequate, %: 40.3 Mean (SD): 51.31 (17.09) D-90

375 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Eligibility criteria: Author, year: 35 Included: Johnston et al., 2005 Research objective: Spinal Cord Injury (prioritizing those that do not currently have Describe levels of health literacy in spinal cord comobidity) injury patients and to investigate its possible 18+ years old associations with morbidity, health-related Community living quality of life, functional independence, Excluded: community participation, and life satisfaction. Less than 6 months after injury Study design: Extremely poor vision -sectional Cross Inability to speak English or Spanish Study setting: Unintelligible speech New Jersey outpatient Spinal Cord Injury Uncontrolled psychiatric illness center Lack of cooperation Measurement period: Sampling strategy: NR Convenience Follow -up duration: Sample size: NA 107 -up: Completeness of follow Age, mean (SD): NA 39.1 (11.16) Measurement tools including cutpoints: Gender, %: Adequate: 75 and above Males: 82.2 Inadequate/Marginal: 74 and below Race/Ethnicity, %: White: 66.4 AA: 26.2 Asi an/Pacific Islander: 2.8 Other/Unclassified: 4.7 Income, median annual income (n = 104): $10,000-$14,999 Insurance status: NR Education, %: 1st -8th grade: 1.9 9th -11th grade: 16.8 Grade 12 or GED: 26.2 College 1 to 3 years: 29 College 4 yrs or more: 26.2 Other characteristics, %: Marital status: Never been married: 65.4 Married: 19.6 Divorced: 10.3 Separated: 1.9 Widowed: 2.8 Years since injury, mean/median (SD): 11.36/8.71 (9.56) ASIA Impairment Scale: Motor complete, sensory and motor 56.4 Motor complete, sensory complete: 20.2 Motor incomplete, major deficit: 14.9 Motor incomplete, less deficit: 8.5 Normal 0.0 D-91

376 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Results Outcomes Main outcomes: Describe results: Mobidity (days limited per month) alth mobidity, but associations HL was related to physical he with other outcomes were not significant. Physical Effect in no exposure (i.e., adequate literacy) or control group: Mental NR -12 SF Effect in exposure (i.e., low/moderate literacy) or intervention: Physical Component Summary Mental Component Summary NR CHART (handicap/participation) Difference: Mobidity (days limited per month) Physical independence - Mobility Difference in number of days physical health "not good", β: P < =0.05 0.25, Occupation - Difference in number of days mental health "not good", β: Social Integration 0.02, P = 0.90 Economic self -suf SF -12 Covariates used in multivariate analysis: P -0.09, Difference in Physical Component Summary Scale, β: Motor index = 0.49 Education Summary Scale, β: 0.23, Difference in Mental Component = P Description of outcome measures: 0.07 # of days that Mobidity (days limited per month) - CHART (handicap/participation) physical or mental health "not good" in the last 30 Difference in Physical independence, β: P = 0.47 -0.09, days 0.04, Difference in Physical independence(curvilinear): - = P -12: Physical and Mental sub-scales SF 0.70 - questionnaire to assess health-related QoL - Difference in Mobility, β: = 0.93 P 0.01, Physical Component Summary β: 0.23, Difference in Occupation, = 0.06 P ummative - raw scores transformed to create Raw s P Difference in Social Integration, β: 0.21, = 0.11 mean of 50 and standard deviation of 10 - sufficiency, β: 0.06, P Difference in Economic self = 0.64 Mental Component Summary = 0.28 P Difference in CHART total, β: 0.13, Raw P -0.04, Difference in Satisfaction with Life Scale Mean, β: = raw scores transformed to create mean Summative- 0.78 of 50 and standard deviation of 10 CHART (handicap/participation) - includes subscales listed below; ranging between 0 and 100; and a total score. Physical independence Mobility Occupation Social Integration -sufficiency Economic self CHART total Satisfaction with Life Scale Mean - Diener's Satisfaction with Life Scale, 5 statements on overall life satisfaction with responses ranging from 1 (strongly disagree to 7 (strongly disagree). Data source(s) for outcomes: -report Self Attempts for control for confounding: Multivariate analysis (Linear regression) D-92

377 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Health literacy/numeracy levels, mean/median (SD): Author, year: 35 Johnston et al., 2005 Inadequate: 6.5 (continued) ginal: 7.5 Mar Adequate: 86 Numeracy: 39.6/42.0 (9.4) Literacy: 44.1/47.0 (8.6) D-93

378 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 36 Included: Kalichman et al., 2008 Research objective: 18 years old Examine relationship between health literacy Proof of positive HIV status and antiretroviral treatment adherence among Antiretroviral prescription bottle HIV patients. Currently taking antiretroviral meds Study design: Excluded: Cross -sectional NR Study setting: Sampling strategy: Research program office in Atlanta, GA and Convenience -up phone calls follow Sample size: Measurement period: 145 NR Age, mean (SD): -up duration: Follow 44.9 (6.3) 4 months Gender, %: -up: Completeness of follow Males: 69 NR Race/Ethnicity, %: Measurement tools including cutpoints: AA: 93 TOFHLA (Scores divided into higher and lower White: 6 literacy; specific cut points not specified, but Other: 1 used median scores of 90% correct to define Income: higher/lower) NR Insurance status: NR Education, mean years (SD): 12.3 (2.1) Other characteristics: NR Health literacy/numeracy levels: TOFHLA median score, % correct: 90 D-94

379 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: HL level not significantly related to HIV symptoms, depression, Antiretroviral therapy adherence or alcohol score (unadjusted). Covariates used in multivariate analysis: Lower health literacy was associated with poorer antiretroviral Age Education treatment adherence, after adjusting for other factors including education. Years since testing HIV positive Effect in no exposure (i.e., adequate literacy) or control group, HIV symptoms mean (SD): Depression HIV symptoms: 4.7 (3.9) Internalized stigma Depression: 8.7 (7.8) Social support Alcohol Score: 1.4 (1.9) Alcohol use Antiretroviral Therapy adherence, %: Description of outcome measures: symptoms: experience with 14 common HIV HIV <80% pills taken: 60 symptoms (symptoms not described) <85% pills taken: 69 <90% pills taken: 77 Depression: frequency of 13 cognitive and affective symptoms of depression during past 7 days using Effect in exposure (i.e., low/moderate literacy) or intervention, mean (SD): items from Centers for Epidemiological Studies HIV symptoms: 4.0 (3.2) Depression Scale Depression: 10.9 (6.6) Data source(s) for outcomes: HIV symptoms: self Alcohol Score: 0.95 (1.5) -report Antire Depression: self troviral Therapy adherence: -report Pills taken: Alcohol Use: self -report Antiretroviral Therapy adherence: Monthly <80%: 78 unannounced telephone-based pill counts to <85%: 84 patients, pharmacy information from pill bottles. <90%: 91 Difference, OR (CI): Attempts for control for confounding: Difference HIV symptoms (unadjusted): 1.05 (0.95-1.14) Multivariate analysis Blinding: Difference Depression (unadjusted): 0.95 (0.91-1.00) Difference Alcohol Score (unadjusted): 1.16 (0.96-1.41) NR Statistical measures used: Difference < 80% pills taken (unadjusted): 2.45 (1.17- 5.12) Difference 85% Adherence (adjusted): 3.77 (1.46-9.93) Hierarchical logistic regression Difference < 90% pills taken (unadjusted): 3.18 (1.17 - 8.62) D-95

380 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. S tudy Description Participant Characteristics Author, year: Eligibility criteria: 37 Inclusion: Kim, 2009 Research objective: ≥ 60 Age s of health To investigate the relationship No apparent communicative or cognitive impairment problems literacy to chronic medical conditions and Willing to participate in the study the functional health status among Exclusion: -dwelling Korean older adults community Severe vision problem not correctable with glasses Study design: Did not know year they were born, current month, year, and place they live Cross -sectional Sampling strategy: Study setting: Convenience sample -dwelling older adults recruited Community Sample size: at community -based senior welfare center s N =103 in Daegu, Busan, and Kyungpook Age (mean and range), %: provinces in Korea High literacy: 70.98 (SD 4.28) Measurement period: Low literacy: 73.15 (SD 5.14) September 2007 June 2007 - Gender, %: -up duration: Follow Female: 58.3 N/A Race/Ethnicity, %: -up: Completeness of follow NR NA Income, % (SD): Measurement tools including cutpoints, %: Korean currency: Won Korean Functional Health Literacy test High literacy: 809,000 Won (632,000 Won) (based on the TOFHLA and previously Low literacy: 397,000 Won, (425,000 Won) -15 validated) score ranges from 0 Insurance status, %: (cutpoints not defined) NR Education, % (SD): High literacy: 10.22 years (2.74) Low literacy: 7.05 years ( 4.17) Health literacy/numeracy levels, %: Mean score 5.48 (SD 3.53) Score categories: > 5: 41 = 5: 19 < 5: 43 High literacy ( ≥5): 60 Low literacy (<5): 43 D-96

381 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Older individuals with low health literacy had higher rates of arthritis Chronic disease and hypertension (unadjusted). They were more likely to have Functional health status limitations in activity and lower subjective health controlling for all Activity limitations confounders including education. In adjusted models not controlling Covariates used in multivariate analysis: for education, lower health literacy was also associated with poorer Age physical function and pain that interferred wi th normal work activity. Education Effect in no exposure (i.e., adequate literacy) or control group: Income Arthritis: 21.7% Description of outcome measures: Hypertension: 21.7% chronic disease - measured by self -report Sensory disease: 23.3% divided into physical functional health status - Diabetes mellitus: 54.5% health status, mental health status, functional Pulmonary disease: 10.0% status, and subjective general health status; Heart disease: 2.3% measured using the subscales of the Medical Physical function: 46.71, SD 9.81 Outcomes Study 12- item Short -Form Health Mental health status: 48.88, SD 6.53 Survey Limitations in activity: 44.64, SD 10.75 activity limitations - measured by assessing Pain that interfered with normal work activities: 40.37, SD 12.33 IADLs, ADLS, and limited activities because of Subjective general health: 44.88, SD 12.01 physical health in the past four weeks Effect in exposure (i.e., low/moderate literacy) or intervention: scores for all of the scales were converted to a Arth ritis: 51.2% normalized score with mean of 50 and SD of 10 Hypertension: 44.2% Data source(s) for outcomes: Sensory disease: 39.5% Patient self -report via survey instruments Diabetes mellitus: 45.5% for confounding: Attempts for control Pulmonary disease: 16.3% Linear regression Heart disease: 8.3% Blinding: Physical function: 40.34, SD 10.29 NA Mental health status: 45.13, SD 9.82 Statistical measures used: Limitations in activity: 51.11, SD 8.59 Chi -square Pain that interfered with normal work activities: 47.08, SD 10.62 Linear regression Subjective general health: 36.97, SD 11.46 Difference: difference in rates of chronic conditions (unadjusted): P = 0.003) Arthritis: ( P Hypertension: ( = 0.018) All other chronic conditions: ( P = NS) Adjusted for age, education and income: Difference in physical function: ( = 0.06) P Difference in mental health status: ( P = 0.15) Difference in limitations in activity: ( P = 0.025) P Difference in pain that interfered with normal work activities: ( = 0.215) P = 0.036) Difference in subjective general health: ( Adjusted for age and income: P = 0.006) Difference in physical function: ( P = 0.18) Difference in mental health status: ( Difference in limitations in activity: ( P = 0.005) Difference in pain that interf ered with normal work activities: ( P = 0.044) Difference in subjective general health: ( P = 0.010) D-97

382 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 38 Included: Kripalani et al., 2006 Research objective: Documented diagnosis of CHD or a history of coronary artery Evaluate effects of low literacy, medication Bypass graft surgery, percutaneous transluminal coronary regimen complexity, and sociodemographic angioplasty, or myocardial infarction characteristics on MMC Excluded: Study design: n another adherence study Currently participating i Cross -sectional Too ill to complete the enrollment interview Study setting: Does not manage own medications Patients served at General Medical Clinic at Already using a medication pill card that graphically illustrated their Grady Memorial Hospital in Atlanta, GA regimen Measurement period: No mailing address or telephone number NR Routinely filled prescriptions outside of the Grady pharmacy system Follow -up duration: Unable to communicate in English NA Worse than 20/60 vision Completeness of follow -up: Significant psychiatric illnesses, overt delirium, or dementia NA Sampling strategy: Measurement tools including cutpoints: Convenience REALM: Sample size: ≤ 6th grade (score 0 to 44): inadequate 152 literacy Age (mean and range): -8th grade (score 45 to 60): marginal 7th Gender, %: literacy Females: 54.6 ≥ 9th grade (61 to 66): high literacy Race/E thnicity, %: AA: 94.1 Caucasian: 3.9 Hispanic/Latino: 1.3 Other: 0.7 Income: NR Insurance status: NR Education: Years of education (SD): 10.7 (3.6), Range 0-20 Other characteristics, %: Employment: Unemployed: 17.1 Full -time: 0.7 Part -time: 5.9 Retired/disabled: 76.3 Marital status: Married: 16.4 Separated: 11.8 Divorced: 23.7 Widowed: 30.9 Single/never married: 16.4% D-98

383 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: MMC In univariate analyses, total DRUGS scores and specifically, Covariates used in multivariate analysis: el. ability to identify medications, increased with literacy lev Age Literacy was not related to other 3 components of DRUGS Years of schooling (open container, indicate dose, and report timing). Cognitive function (MMSE) In logistic regression models, those with inadequate literacy Description of outcome measures: were significantly less likely to identify all of their medications, MMC assessed using Drug Regimen Unassisted compared wit h those with adequate literacy skills, while a sig Grading difference was not found between those with marginal and Scale (DRUGS). DRUGS requires subjects to adequate scores. perform 4 tasks with each of their medications: Effect in no exposure (i.e., adequate literacy) or control group, Identify appropriate medication mean (SD): Adequate literacy Open container Overall DRUGS score: Select correct dose Report appropriate timing of doses. Mean (SD): 97. 7 (4.3) Scores range from 0 to 100, weighting each of 4 Components of DRUGS: tasks equally. Identify: 99.2 (2.9) DRUGS provides an overall measure of Open: 99.2 (4.5) management capacity but can also indicates specific Dose: 98.3 (7.5) areas of difficulty. Timing: 94 (12) Data source(s) for outcomes: Unable to identify all medications: 7% DRUGS assessment (participant performs tasks and Effect in exposure (i.e., low/moderate literacy) or intervention, interviewer records score) mean (SD): Attempts for control for confounding: Marginal literacy Multivariable logistic regression Overall DRUGS score: Blinding: Marginal HL: 96.3 (4.9) Yes Inadequate HL: 92.1 (8.7) Statistical measures used: Components of DRUGS: DRUGS score and its 4 components and patient Marginal HL: characteristics and regimen size were compared Identify: 92 (17) Whitney and Kruskal using Mann- -Wallis tests for Open: 100 (0) nonparametric data. Dose: 97.6 (7.3) DRUGS scores were dichotomized and compared Timing: 95.4 (8.1) them across patient and regimen characteristics Inadequate HL: ng chi usi -square and or Fisher’s exact tests. Identify, mean: 76.9 (28.4) Significant factors from univariate analyses included Open, mean: 99.7 (1.7) in multivariable logistic regression models. Dose, mean: 96.1 (10.2) Full models were reduced using a backward mean: 95.6 (8.3) Timing, elimination approach with likelihood ratio tests. Unable to identify all medications: Two alternate modeli ng strategies were also Marginal HL: 25 preformed: one without years of schooling and Inadequate HL: 57 another treated continuous variables as such. Difference: Difference in overall DRUG score: (Unadjusted): ( = 0.001) P DRUG components separately measured (Open, Dose,Timing) = NS) P (Unadjusted): ( Difference inabil ity to identify all medications, (adjusted including ed): Marginal, OR (CI): 4.75 (0.95 - 23) D-99

384 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 39 Laramee et al., 2007 Included: Research objective: Adults with diabetes Assess relationship between HL and heart Excluded: failure among diabetics Significant cognitive impairments Study design: Sampling strategy: Cross -sectional Convenience sample Study setting: Sample size: Patients attending non-academic primary care 998 practices in VT, northern NY and northern NH Limited HL (n = 171) interviewed in their homes Adequate HL (n = 827) Measurement period: Age (range): - 3/2005 7/2003 65 (22- 93) Follow -up duration: Gender, %: NA Females: 54 -up: Completeness of follow Race/Ethnicity, %: NA White: 97 Measurement tools including cutpoints: Income , %: sTOFHLA < $30,000: 59 22 Limited (inadequate or marginal): 0- Insurance status, %: Adequate 23-36 Uninsured: 2 Limited literacy includes sTOFHLA score <23, Education, %: blind or otherwise unable to complete test HS grad: 75 Other characteristics, %: Married or living as married: 63 Health literacy/numeracy levels, %: Limited: 17 Adequate: 83 D-100

385 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Heart failure Diabetes patients with limited literacy were significantly more Covariates used in multivariate analysis: likely to have heart failure than those with adequate literacy. Effect in no exposure (i.e., adequate literacy) or control group, NA %: Description of outcome measures: Heart failure: 15 -administered Heart failure measured through Self Questionnaire, modified from the iteracy) or intervention: Comorbidity Effect in exposure (i.e., low/moderate l inadequate/marginal Charlson Index Data source(s) for outcomes: Heart failure: 27 -report Difference: Self Difference in Heart failure rate (unadjusted), OR (CI): 2.05 Attempts for control for confounding: (1.39-3.02) None Blinding: NA Statistical measures used: Chi -square tests D-101

386 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participa nt Characteristics Author, year: Eligibility criteria: 16 Lee et al., 2009 Included: 15 (Companion: Cho et al., 2008 ) 65 and older Research objective: Medicare recipient Examine whether social support interacts with One or more outpatient visit between 1999- 2003 HL in affecting the health status of older adults Cognitively intact, good vision Study design: Good hearing -sectional Cross English speaking Study setting: Not living in a nursing home. 1 hospital and 1 Community Health Center in Excluded: Chicago NR Measurement period: Sampling strategy: 1999-2003 Convenience -up duration: Follow Sample size: NA 489 -up: Completeness of follow Age (mean and range): NA 77.8 Measurement tools including cutpoints: Gender, %: sTOFHLA: Females: 79.6 16 Inadequate Health Literacy: 0- Race/Ethnicity, %: Marginal Health Literacy: 17-22 AA: 54.4 36 Adequate Health Literacy: 23- Income: NR Insurance status, %: Medicare: 100 Education, %:

387 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Health status Low HL was sig negatively associated with self -reported Covariates used in multivariate analysis: general health and not sig associated with physical and mental Age health st atus. Greater social support had a sig and pos association with general, physical, and mental health in high HL Gender group but was only associated with a better mental health Race outcome in the low HL group. Education Effect in no exposure (i.e., adequate literacy) or control group: Marital status NR Income Effect in exposure (i.e., low/moderate literacy) or intervention: Social support level NR Description of outcome measures: Difference: General health, measured by: 5 point Likert scale Difference in low HL (adjusted), β (SE): Compared with your peers, how would you rate your General health: < 0.05 P -0.259 (0.115), health? Mental health and physical health measured P Physical Health: - 0.107 (0.112), = NS through SF12 Mental Health: -0.182 (0.111), = NS P Data source(s) for outcomes: HL and social support interaction (adjusted): Interview General health, β (SE): Attempts for control for confounding: = NS P Low HL x social support: 0.82 (0.071), Multivariate analyses P < 0.01 High HL x social support: 0.280 (0.084), Blinding: Physical health, β (SE): NR Low HL x social support: 0.79 (0.066), P = NS Statistical measures used: P < 0.001 High HL x social support: 0.308 (0.089), OLS regression and stratified OLS Mental health, β (SE): Low HL x social support: 0.213 (0.074), P < 0.01 < 0.001 High HL x social support: 0.367 (0.073), P D-103

388 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) St udy Description Participant Characteristics Eligibility criteria: Author, year: 40 LeVine et al., 2004 Included: Research objective: n kindergarten or class 1 of primary Mothers who have children i Explore whether literacy skills influence school mothers' ability to understand health Excluded: messages in text and radio and health NR narrative skills Sampling strategy: Study design: Convenience sampling from a cluster of households in center of Cross -sectional study designated neighborhood in each community. Study setting: Interviewers canvassed the neighborhood, from center outward, for Patan (urban) and Godavari (rural) Nepal women w ith designated characteristics until a sample of at least 80 Measurement period: women - June 1998 October 1996 Sample size: -up duration: Follow 167 NA Age (mean and range) (SD): Completeness of follow -up: Patan: 30.8 (4.9) Range: 22- 59 NA 38 Godavari: 28 (3.9) Range: 20- Measurement tools including cutpoints: , % : Gender Literacy measured as continuous and a Females: 100 composite score of reading comprehension Race/Ethnicity: and noun definition. NR Reading comprehension: assessed in Nepali, Income: using 6 health-related texts graded by difficulty NR of comprehension according to school grade Insurance status: -secondary levels 1, 3, 5, 7, 9 and first post NR year. Comprehension assessed through Educati on: questions based on texts. Score was grade NR level at which able to answer 50% of Other characteristics: questions. Scores were converted into a NR continuous scale of 0 –6. Health literacy/numeracy levels: Noun definitions: assessed by asking NR participant to define 10 nouns for common objects, such as ‘‘dog,’’ with the question, is a ?’’ Responses were scored for the ‘‘What presence of superordinate category membership (‘‘a dog is an animal’’). Scores were the mean number of objects for which a superordinate term like was given. D-104

389 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Higher literacy composite score was predictor of better Comprehension of printed health messages understanding of print and radio health Comprehension of radio health messages messages and giving more organized health narrative. Health narrative skills Effect in no exposure (i.e., adequate literacy) or control group: Covariates used in multivariate analysis: Maternal schooling NR Childhood SES Effect in exposure (i.e., low/moderate literacy) or intervention: Age NR Current SES Difference: Comprehension of audio radio health messages (adjust Husband's schooling ed), β P (SE): 1.11 (0.18), < 0.001 Urban/rural dummy Comprehension of visual print health messages (adjusted), β Description of outcome measures: (SE): 1.08 (0.21), P < 0.001 Comprehension of radio health messages: Tape Probability of giving an organized health narrative: logic played of 3 health messages that were recording estimate: 0.73, < 0.01 P broadcast regularly on the radio (use of oral rehydration salts, family planning, vaccinations). Content of each message was divided into idea units. Participant recall was evaluated. Responses were coded for idea uni ts mentioned, total number of which constituted a score (scores 0-29). Comprehension of printed health messages: Participants presented with 3 radio messages to read and recall was evaluated. Responses were coded for idea units (scores 0 -27). Health nar rative skills: This task was designed to simulate the response to questioning in a health clinic. Participants were asked to recount a health problem they, one of their children, or a relative, had. Interviewers were instructed to ask mostly general questi ons (e.g., and then what happened?) to move the narrative along. If a participant seemed to provide too short an account or was missing a lot of important information, interviewers asked more specific questions. A maximum of 10 specific questions was allow ed. Narratives were dichotomized as organized or disorganized. Data source(s) for outcomes: Participant performance on assessments and self - report in interview Attempts for control for confounding: Multivariate logistic regression Blinding: NA Statistical measures used: Multinomial regression, logistic regression. Analysis of comprehension of visual print messages limited to sample with HS ed. D-105

390 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: ty criteria: Eligibili 41 Included: Lincoln et al., 2006 Research obje ctive: Inpatient detox admission Examine relationship between low HL and Age greater than 17 addiction severity, depressive symptoms, and Report of alcohol, heroin, or cocaine as substances of 1st or 2nd mental health functioning in adults with alcohol choice and drug dependence over 2-year period. Excluded: Study design: Having a primary care provider and having seen provider on at least Prospective cohort one occasion in past 2 years Study setting: Pregnan cy m inpatient 35-bed inner -city short -ter Mini -Mental State examination score less than 21 detoxification unit Lack of fluency in English Measurement period: Less than 3 contacts available to facilitate follow -up March 1999 June 1997 - Specific plans to leave Boston in 2 years Follow -up duration: Sampling strategy: NR Convenience Completeness of follow -up: Sample size: NR 390 Measurement tools including cutpoints: Age, mean (SD): REALM 36 (7.64) Low Literacy: 8th grade and below Gender, %: grade and above Higher Literacy: 9th Males: 76 Race/Ethnicity, %: Black: 53 White: 35 Hispanic: 6 Other: 6 Income, %: <$19,000: 58 $20,000-49,000: 34 >$50,000: 9 Insurance status: NR Education, mean (SD): Years formal education: 11.98 (1.98) Other characteristics, %: Primary Substa nce of Choice: Alcohol: 37 Cocaine: 36 Heroin: 27 Health literacy/numeracy levels, %: Low Literacy: 46 Higher Literacy: 54 D-106

391 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes Describe results: Main outcomes: -D, mean (SD): 33.03 (12.56) Lower literacy among alcohol and drug dependent individuals is CES not associated with any mental health outcomes in cross Addition Severity Index -alcohol scale (ASI -Aic), sectional analy sis but is associated with higher degree of mean (SD): 0.47 (0.34) depressive symptoms in longitudinal models. Adding use of -drug), mean Addition Severity Index -drug scale (ASI health care (SD): 0.26 (0.14) Effect in no exposure (i.e., adequate literacy) or control group, -36 (MCS), Mental Component Summary of SF mean (SD): mean (SD): 31.18 (12.75) CES -D: 34.82 (13.32) Covariates used in multivariate analysis: ASI -Alc: 0.48 (0.34) Time ASI -Drug: 0.26 (0.15) Sex MCS: 29.67 (12.39) Age Effect in exposure (i.e., low/moderate literacy) or intervention, Race mean (SD): Education CES -D: 30.91 (11.26) Income ASI -Alc: 0.46 (0.34) Primary language -Drug: 0.26 (0.13) ASI Primary substance of choice MCS: 33.02 (12.97) Randomization group Difference: -mental status exam Mini -D: Difference in CES Baseline outcomes variable cross sectional): ( (Adjusted- = 0.09) P Description of outcome measures: < 0.01) P (Adjusted-longitudinal): ( -D: measures depressive symptoms with higher CES -Alc: ASI indicating greater levels of distress. Range scores cross sectional): ( P = 0.88) (Adjusted- from 0 to 60 with a score ≥ 16 interpreted as a P (Adjusted-longitudinal): ( = 0.86) clinically significant level of distress. -Drug: ASI -Drug: assesses addiction severity with ASI cross sectional): ( (Adjusted- = 0.11) P composite scores ranging from 0 to 1. = 0.35) P (Adjusted-longitudinal): ( h composite -Alc: assesses addiction severity wit ASI MCS: scores ranging from 0 to 1. P (Adjusted- cross sectional): ( = 0.42) MCS: assesses mental health- related quality of life, sted (Adju = 0.14) P -longitudinal): ( scores ranging from 0 to 100 with higher scores indicating higher quality of life. Data source(s) for outcomes: Self -report Attempts for control for confounding: Multivariate analysis Blinding: NA Statistical measures used: Regression including controlling for time D-107

392 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 42 Included: Lindau et al., 2006 Research objective: Self -identified English speaking Examine relationship between literacy and Excluded: patient adherence to follow -up < 18 years old recommendations after abnormal pap smear. Missing data Study design: Sampling strategy: Prospective cohort Convenience y setting: Stud Sample size: Clinics at Chicago area academic medical 68 center Age (range), %: Measurement period: Adequa te Health Literacy: - December 1999 January 18-24: 34 Follow -up duration: 25-30: 25 One year 31-39: 27 Completeness of follow -up: 40-49: 14 Patients that did not come back after Inadequate Health Literacy: enrollment were classified in the 'did not follow 18-24: 46 up' category 25-30: 17 Measurement tools including cutpoints: 31-39: 20 REALM: 40-49: 17 ≥ 9th grade: ≥ 61 Adequate, Gender, %: Females: 100 Race/Ethnicity, %: Adequate Health Literacy: AA: 52 Hispanic: 21 White: 18 Other: 9 Inadequate Health Literacy: AA: 67 Hispanic: 29 White: 4 Other: 0 Insurance status, %: Adequate Health Literacy: Medicaid: 64 Private: 27 Self pay/no insurance: 9 Inadequate Health Literacy: Medicaid: 92 Private: 8 Self pay/no insurance: 0 Education: NR D-108

393 . Key Question 1: Health literacy outcome studies (continued) Evidence Table 1 Outcomes Results Main outcomes: Describe results: -up HL not statistically significant in predicting women's on-time On -time patient follow Patient follow -up -up within 1 -up after an abnormal Pap smear or follow follow Duration of time to follow -up year. literacy) or control group: Effect in no exposure (i.e., adequate Covariates used in multivariate analysis: -up, mean (SD): 89.3 (53.4) Recommended days to follow Age HIV status Patient followed up on time, %: 66 Patient followed up within one year, %: 80 Cancer -up, %: Days to follow Race 0-60: 26 Unemployment 61-120: 26 Insurance status 121-180: 20 Description of outcome measures: -up - 365: 28 181 On -time patient follow -up Patient follow HIV Positive: 36 Duration of time to follow Effect in exposure (i.e., low/moderate literacy) or intervention: -up Data source(s) for outcomes: Recommended days to follow -up: mean (SD): 87.6 (62.0) Patient charts Patient followed up on time, %: 33 Attempts for control for confounding: Patient followed up within one year, %: 67 -up, %: Days to follow Multivariate analysis Blinding: 0-60: 31 No 61-120: 7 Statistical measures used: 121-180: 31 Logistic regression 181 - 365: 31 Cox proportional hazards regression HIV Positive: 25 Difference: Difference in recommended days to follow up (unadjusted): ( P = 0.99) Difference in Patient followed up on time (adjusted), OR (CI): 2.05 (0.47- 8.85) Difference in patient followed up within one year (adjusted), OR (CI): 3.75, 95% (0.81-17.4) Difference in HIV status (unadjusted): ( P = 0.45) D-109

394 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Other characteristics: Author, year: 42 Lindau et al., 2006 Adequate Health Literacy (continued) Unemployed: 50 Inadequate Health Literacy Unemployed: 63 Health literacy/num eracy levels, %: Adequate literacy: 65 Inadequate literacy: 35 Subjective health literacy: Adequate: 59 Inadequate: 41 D-110

395 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 43 Mancuso and Rincon, 2006 Included: 44 (Companion: Mancuso and Rincon, 2006 ) Adults enrolled in an observational study Research objective: Require daily asthma medications Measure association between health literacy Completed TOFHLA and asthma outcomes and to assess if effect Excluded: of health literacy is mediated through NR covariates Sampling strategy: Study design: Convenience Prospective cohort Sample size: Study setting: 175 Cornell Internal Medicine Associates, a Age (mean and range) (SD): ary care practice serving patient of prim 42 (10) diverse socioeconomic groups from all areas Gender, %: of New York City. Females: 83 Measurement period: Race/Ethnicity, %: 1995-1999 White: 20 -up duration: Follow AA: 31 2 years Latino: 41 -up: NR Completeness of follow Mixed/other: 8 Measurement tools including cutpoints: Income: TOFHLA NR Adequate literacy: ≥75 Insurance status, %: Inadequate/Marginal literacy: <74 Medicaid: 45 Education, %: College graduate: 33 High school graduate: 42 Less than High School: 25 Other characteristics, % (SD): Duration Asthma: 21 years (14) Prior hospitalization asthma: 50 Daily corticosteroids inhaler: 78 Daily beta antagonist inhaler: 93 Daily beta antagonist oral: 6 Described access to care as very difficult: 8 Health literacy/numeracy levels, %: Adequate lit eracy: 82 Marginal literacy: 8 Inadequate literacy: 10 D-111

396 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: AQLQ Health Literacy is not statistically significantly related to asthma and more general health outcomes variables after controlling -36 PCS SF for asthma knowledge and depressive symptoms. Resource utilization for asthma ntrol group, Effect in no exposure (i.e., adequate literacy) or co Covariates used in multivariate analysis: % (SD): Asthma severity Duration Asthma: 20 years (14) -efficacy Asthma self Prior hospitalization asthma: 48 Age Daily corticosteroids inhaler: 78 Education Daily beta antagonist inhaler: 93 Depressive symptoms Daily beta antagonist oral: 6 Asthma knowledge Access to care very difficult: 8 Description of outcome measures: iteracy) or intervention, Effect in exposure (i.e., low/moderate l - 32 item well established scale measuring AQLQ % (SD): asthma symptoms Duration Asthma: 25 years (15) SF - physical component summary scores -36 PCS Prior hospitalization asthma: 59 for functional status Daily corticosteroids inhaler: 75 Resource utilization for Asthma - self report of ED Daily beta antagonist inhaler: 93 -report visits, self Daily beta antagonist oral: 3 Data source(s) for outcomes: Access to care very difficult: 9 -36, and ED visits: self report AQLQ, SF Difference: Attempts for control for confounding: P = 0.06) Difference in duration asthma (unadjusted): ( Multivariate analysis Difference in prior hospitalization asthma (unadjusted): ( = P Blinding: 0.23) NA = 0.68) P Daily corticosteroids inhaler (unadjusted): ( Statistical measures used: = 0.88) P Daily beta antagonist inhaler (unadjusted): ( e analysis: t tests, analysis of variance, and Bivariat P Daily beta antagonist oral (unadjusted): ( = 0.46) chi -squared tests. Access to care very difficult (unadjusted): ( P = 0.76) Multivariate analysis for continuous and Difference in AQLQ (adjusted), β: dichotomous outcomes. Mixed effects models with Controlling for asthma severity: 0.69, P =0.005 random subject effects were used for analysis of = 0.003 P -efficacy: 0.61, Controlling for 1. and Asthma self outcomes that were continuous. Forward stepwise Controlling for 2. and age, education: 0.52, = 0.03 P ession. regr = 0.07 Controlling for 3. and depressive symptoms: 0.40, P Controlling for 4. and asthma knowledge: 0.20, P = 0.38 36 PCS (adjusted), β: - Difference in SF Controlling for asthma severity: 6.69, P = 0.0005 -efficacy: 6.29, P = 0.0003 Controlling for 1. and Asthma self Controlling for 2. and age, education: 3.00, P = 0.11 Controlling for 3. and depressive symptoms: 2.23, P = 0.22 P Controlling for 4. and asthma knowledge: 1.21, = 0.53 Difference in treated in ED (adjusted), β: Controlling for asthma severity: 0.93, P = 0.04 Controlling for 1. and Asthma self -efficacy: 0.94, P = 0.03 Controlling for 2. and age, education: 1.11, P = 0.02 Controlling for 3. and depressive symptoms: 1.01, P = 0.04 = 0.07 Controlling for 4. and asthma knowledge: 0.95, P D-112

397 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 44 Included: Mancuso and Rincon, 2006 43 (Companion: Mancuso and Rincon, 2006 ) Require daily asthma medications, but not daily oral corticosteroids Research objective: Completed TOFHLA Measure health literacy and its association Excluded: with asthma patients' assessments of care NR and their desire to participate in making Sampling strategy: decisions about their treatment. Convenience Study design: Sample size: -sectional Cross 175 Study setting: Age, mean (SD): Cornell Internal Medicine Associates, a 42 (10) primary care practice in New York City. Gender, %: Measurement period: Females: 83 NR Race/Ethnicity, %: Foll -up duration: ow White: 19 NA AA: 31 -up: Completeness of follow Latino: 41 NA Mixed/other: 9 Measurement tools including cutpoints: Income, %: TOFHLA Per household member: Adequate literacy: ≥75 ≤$12,000: 59 Inadequate/Marginal literacy: <74 Insurance status, %: Medicaid: 45 Education, %: High school graduate: 73 Other characteristics, %: Prior hospitalization asthma: 50 Daily corticosteroids inhaler: 78 Asthma exacerbations more than once/month: 62 Medical conditions in addition to asthma: 28 Health literacy/numeracy levels, %: Adequate literacy: 82 Marginal literacy: 8 Inadequate literacy: 10 D-113

398 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes Main outcomes: Describe results: Less satisfied with asthma status ith asthma Lower HL was associated with less satisfaction w status, worse results from care for asthma, more difficult More difficult to access to asthma care Worse results from care for asthma access to medical care for other medical conditions, and want to have less participation in treatment decision making. More difficult access to medical care for other Effect in no exposure (i.e., adequate literacy) or control group: medical conditions NR Worse results from care for other medical conditions Does not want to part Effect in exposure (i.e., low/moderate literacy) or intervention: Covariates used in multivariate analysis: NR Covariates used in models predicting satisfaction Difference: with asthma status, difficulty of accessing asthma Difference (effect of) marginal/inadequate HL on (adjusted): P = 0.002) Less satisfied with asthma status: ( care, results from asthma care, decision making P More difficult to access asthma care: ( = 0.58) participation: = 0.005) P rom care for asthma: ( Worse results f Sex Race/ethnicity More difficult access to medical care for other medical conditions: ( P = 0.005) Language P = Worse results from care for other medical conditions: ( Asthma duration 0.001) Asthma severity Does not want to participate in making treatment decisions, OR Asthma control 13-0.65) (CI): 0.29 (0. Covariates used Description of outcome measures: Satisfaction with asthma status: "Overall, how satisfied are you with the status of your asthma?" Responses: very satisfied to very dissatisfied on a 5- point scale Access to asthma care:"How difficult is it for you to get care for your as thma?" Responses: Data source(s) for outcomes: -report Patient self Attempts for control for confounding: Multivariate analysis Blinding: NR Statistical measures used: Multivariate analysis D-114

399 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Eligibility criteria: 45 Inclusion: Mancuso, 2010 Research objective: ≥ 18 years To examine if health literacy and patient trust English Ability to speak fluent in one's health care provider impacts gylcemic Diagnosis of type 1 or 2 diabetes control in an uninsured population diagnosed HbA1c test with a 6 month period with diabetes. Primary healthcare provider that had been following and had seen Study design: the participants at least twice in the past year. Cross -Sectional Exclusion: Study setting: A diagnosis of end-stage renal disease, psychotic disorder, 2 urban mid-western US primary care clini cs dementia, or blindness Measurement period: NR Sampling strategy: Follow -up duration: NA Convenience sample Completeness of follow -up: Sample size: NA N = 102 Measurement tools including cutpoints, %: Age (mean and range), %: TOFHLA (0 -100): Mean (SD): 52.0 (9.10) 59 Inadequate: 0- Range: 26-67 Marginal: 60- 74 Gender, %: Adequate: 75-100 Female: 61% Race/Ethnicity, %: Race, %: Non -Hispanic Caucasian: 13 Non -Hispanic Black/African American: 79 Hispanic/Latino American: 6 Other: 2 Income, %: NR Insurance status, %: Uninsured: 100% Education, %: Education: <7th grade:1.0 Junior hs (9th grade): 8.8 Partial hs (10th or 11th grade): 23.5 HS graduate: 37.3 Partial college/specialized trai ng (at least 1 year): 21.6 College or university graduate: 7.8 Other characteristics, %: Diabetes type: Type 1: 3.9 Type 2: 96.1 Duration of diabetes in years: < 1: 10.8 1-5: 50.0 6-10: 25.5 12-18: 8.8 20-23: 2.9 D-115

400 . Key Question 1: Health literacy outcome studies (continued) Evidence Table 1 Outcomes Results Main outcomes: Describe results: HL was not a sig predictor of HbA1c. However, HL was sig HbA1c correlated with other included variables including age, Covariates used in multivariate analysis: Patient trust measured through Health Care socioeconomic status, and diabetes knowledge. Relationship Trust Scale), depression (measured Effect in no exposure (i.e., adequate literacy) or control group: NR through Center for Epidemiological Studies Depression Scale), diabetes knowledge (measured Effect in exposure (i.e., low/moderate literacy) or intervention: NR through Diabetes Knowledge Test), and performance of self -care activities (measured Difference: Health literacy (measured as a continuous variable) (adjusted): -Care Activities) through Summary of Diabetes Self = 0.436) P B = -0.063 (0.080) ( Description of outcome measures: Diabetes outcome was assessed by HbA1c measured at one point in time over past 6 months. ≤ 7%. Adequate glycemic control was a HbA1c of Inadequate glycemic control was a HbA1c of > 7%. Data source(s) for outcomes: HbA1c obtained from provider Attempts for control for conf ounding: Multiple regression analysis Blinding: NR Statistical measures used: Cronbach's alpha was calculated and determine the reliabilityh of the TOFHLA, HCR Trust Scale, DKT, SDSCA, and CES-D Multiple regression analysis; correlation coefficients Pearso n's r and Spearman rho D-116

401 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Participant Characteristics Study Description Diabetes treatment: Author, year: 45 Oral medications: 63.7 Mancuso, 2010 (cont inued) Insulin: 19.6 Oral medications and insulin: 14.7 Diet: 2.0 Diabetes complications (comorbidities): Hypertension: 81.4 Depression: 27.5 HbA1c: ≤ 7.0 (controlled diabetes): 35.3 > 7.0 (uncontrolled diabetes): 64.7 Health literacy/numeracy levels, %: TOFHLA (0 -100), %, mean (SD), range: Inadequate: 15.7; 31.3 (20.20); 0-56 Marginal: 20.6; 67.7 (4.00); 61 -74 Adequate: 89.5 (6.50); 76- 100 D-117

402 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 46 Included: Marteleto et al., 2008 Research objective: Young people in Cape Town, 14-22 years old at time of Wave 1 Study effects of literacy/numeracy on sexual Excluded: debut and pregnancy. NR Study design: Sampling strategy: Longitudinal 2 stage probability sample of households; up to 3 youth per Study setting: household Metropolitan Cape Town South Africa Sample size: Measurement period: Age 14- 22: Wave 1: 2002 Wave 1: 4,751 Wave 2: 2003-2004 Wave 3 or 4: 3,916 Wav e 3: 2005 Age 14- 16: Wave 4: 2006 Wave 1: 1,591 -up duration: Follow Wave 3 or 4: 1,413 3-4 years Age (mean and range): -up: Completeness of follow Separate analyses done in 14- 22 and 14- 16, means not provided Attrition: 18% Gender, %: Measurement tools including cutpoints: Male: Cape Area Panel Study Literacy and Wave 1: 46.6 (calculated) Numeracy evaluation - scores standardized, Wave 3: 46.2 (calculated) enter probit regressions as continuous Race/Ethnicity, %: variables Weighted Percentage: Black/Af rican: 28.2 Colored: 53.2 White: 18.6 Income: Wave 1: (South African rands/month) African: Male: 372 Female: 353 Colored: Male: 888 Female: 865 White: Male: 3,972 Female: 3,917 Wave 3: (South African rands/month) African: Male: 372 Female: 354 Colored: Male: 892 Female: 870 White: Male: 3,950 Female: 4,008 D-118

403 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Sexual debut Higher literacy/numeracy scores significantly predict lower Pregnancy probability of sexual debut; Literacy/numeracy scores not Covariates used in multivariate analysis: statistically significant in predicting pregnancy. Grades completed Effect in no exposure (i.e., adequate literacy) or control group: NR Enrolled in 2002 Age Effect in exposure (i.e., low/moderate literacy) or intervention: NR Age since 14 Race Difference: Income An increase in literac y/numeracy exam score by one standard Household shock deviation results in a 7% reduction in probability of sexual P debut, < 0.05. Mother's education Father's education First pregnancy probit coefficient (adjusted): Living with mother Females: 0.41 (not sig at 0.05 level or better) Living with father Males: -0.030 (not sig) Description of outcome measures: Sexual debut: dichotomous Pregnancy: dichotomous Data source(s) for outcomes: Cape Area Panel Survey Attempts for control for confounding: Multivariate analysis Blinding: NR Statistical measures used: Probit regressions D-119

404 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Insurance status: Author, year: 46 NR Marteleto et al., 2008 Research objective: Education: Study effects of literacy/numeracy on sexual Wave 1: (number of grades completed) debut and pregnancy. African: Study design: Male: 6.83 Longitudinal Female: 7.43 Study setting: Colored: Metropolitan Cape Town South Africa Male: 7.63 Measurement period: Female: 8.07 Wave 1: 2002 White: Wave 2: 2003-2004 Male: 8.02 e 3: 2005 Wav 8.13 Female: Wave 4: 2006 Wave 3: (number of grades completed) Follow -up duration: African: 3-4 years Male: 6.89 Completeness of follow -up: Female: 7.42 Attrition: 18% Colored: Male: 7.64 Female: 8.09 White: Male: 8.12 Female: 8.10 Other characteristics: NR Health literacy/numeracy levels: Wave 1: (standardized scores) African: Male: -0.68 -0.52 Female: Colored: Male: -0.03 Female: -0.05 White: Male: 1.17 Female: 1.07 Wave 3: (standardized scores) African: Male: -0.63 -0.54 Female: Colored: Male: -0.02 Female: -0.04 White: Male: 1.23 Female: 1.0 D-120

405 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 47 Included: Mayben et al., 2007 Research objective: Diagnosed with HIV in past 3 years Assess relationship between HL and CD4 cell Accessible med records counts at time of HIV diagnosis Excluded: Study design: <18 years old Cross -sectional Not able to communicate in English or Spanish Study setting: Blind, too sick to participate Patients receiving care at 4 publicly funded Did not receive care at one of the four clinics health care facilities in Houston, TX Katrina evacuee Measurement period: Cognitively impaired NR Sampling strategy: -up duration: Follow Convenience sample NA ze: Sample si Completeness of follow -up: 119 NA Inadequate, n = 33 Measurement tools including cutpoints: Adequate, n = 86 TOFHLA Age (range), %: Inadequate (combined inadequate and 18-29: 22 marginal): 0 - 74 30-39: 28 100 Adequate: 75 - 40-49: 34 >50: 16 Gender, %: Females: 36 Race/Ethnicity, %: Black: 53 White: 33 Other/mixed: 14 Hispanic: 28 Not Hispanic: 72 Income: NR Insurance status: NR Education, %:

406 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Health literacy was not associated with CD4 cell count at Delayed diagnosis of HIV (measured by CD4 count upon initial diagnosis) diagnosis. Interaction terms of health literacy and reason Covariates used in multivariate analysis: tested, and health literacy and gender were also not significantly associated with initial CD4 cell count in separate Gender analyses. Reason for getting tested Effect in no exposure (i.e., adequate literacy) or control group: Marijuana Median CD4 cell count: 247 Description of outcome measures: Interquartile range: 31, 517 Initial CD4 cell count was abstracted from medical records and was defined as first CD4 cell count Effect in exposure (i.e., low/moderate literacy) or intervention: Median CD4 cell count: 175 recorded after diagnosis of HIV infection. Initial CD4 200 Interquartile range: 69, 272 cell counts were stratified into 3 categories (0– Difference: cell/mm3, 201– 350 cells/mm3, 350 cells/mm3) P Difference (adjusted): ( = 0.35) based on clinical parameters and cross -tabulated with health literacy. Data source(s) for outcomes: Medical record Attempts for control for confounding: Multivariable regression Blinding: NA Statistical measures used: Univariable and multivariable linear regression. CD4 cell counts were natural log transformed in regression analyses. P < 0.25 in univariable Explanatory variables with a regression analysis were placed into a multivariable regression model and then selectively removed at P > 0.10 to determine final model. D-122

407 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 48 Included: Miller et al., 2007 Research objective: speaking English- Determine association between health literacy 50+ years and colorectal cancer screening (CRC) Excluded: screening behavior. Obvious cognitive or physical impairments that would interfere with Study design: ability to complete survey -sectional Cross Sampling strategy: Study setting: Convenience sample Private setting associated with Wake Forest Sample size: -based internal medicine University community 50 clinic. Limited, n = 24 Measurement period: Adequate, n = 26 38,231 Age, mean (SD): Follow -up duration: Total: 62.5 NA Limited: 62.9 (10.5) -up: Completeness of follow Adequate: 62.2 (9.2) NA Gender, %: Measurement tools including cutpoints: Female: 72 REALM Limited: 71 Limited: < 9th grade Adequate: 73 Adequate: 9th + Race/Ethnicity, %: Total AA: 58 White: 42 Limited: AA:75 White: 25 Adequate: AA: 42 White: 58 Income, %: Total: <$25,000: 87 Limited: <$25,000: 79 $25,000 +: 8 Adequate: <$25,000: 81 $25,000 +: 15 Insurance status, %: Limited: Uninsured: 25 Medicare: 46 Medicaid: 38 Commercial/Military: 21 D-123

408 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Receipt of screening (according to There was no significant difference in self -reported receipt of CRC screening guidelines) screening between limited literacy and high literacy patients. Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: CRC Screening current, n (%): Age Description of outcome measures: Yes: 15 (58) -report of last time received screening, if ever. cy) or intervention: Self Effect in exposure (i.e., low/moderate litera CRC Screening current, n (%): Completed screening defined as: Yes: 13 (54) FOBT within last year flex sig within 5 years Difference: colonoscopy within 10 years. Difference (adjusted), RR (CI): 0.99 (0.64 -1.55) Dat a source(s) for outcomes: In-person survey administered by study staff Attempts for control for confounding: To construct logistic regression model, examined bivariate association of literacy level and receipt of CRC screening with each possible covariate. Variables sig at 5% level from bivariate analyses were included in final multivariable logistic regression model. Given that education is highly correlated with literacy, they did not include education in multivariable model. Blinding: Literacy and demographic data were collected at completion of survey to keep surveyor blinded to literacy level. Statistical measures used: Chi -square Fisher's Exact tests Logistic regression Exact logistic regression performed using network method described by Mehta et al. Estimates of adjusted RR for receipt of CRC screening obtained using Cochran-Mantel -Haenszel methods since multivariable modeling resulted in at most only one other covariate additional to literacy level. D-124

409 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Adequate: 48 Miller et al., 2007 Uninsured: 15 (continued) Medicare: 54 Medicaid: 54 Commercial/Mil itary: 23 Education, %: Limited: HS: 0 Adequate: HS: 46 Other characteristics, %: Frequency of medical visits Limited < 4/yr: 33 4+/yr: 67 Adequate: < 4/yr: 20 4+/yr: 80 Health literacy/numeracy levels, %: Limited: 48 Adequate: 52 D-125

410 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: criteria: Eligibility 49 Included: Morris et al., 2006 Research objective: Diabetes diagnosis Explore whether low HL among diabetic adults Adult is related to being less likely to achieve Excluded: mmended goals for A1C, systolic blood reco Major cognitive impairment pressure, diastolic blood pressure, and low Poor vision or other physical impairment that could affect HL density lipoprotein and having more assessment complications related to their diabetes Sampling strategy: Randomized subsample from list of participants in Vermont Diabetes Study design: tem until reached 15% participation across all Information Sys -sectional Cross member primary care practices. Study setting: Sample size: Patients in a region-wide sample of primary 1,002 tices in Vermont. care prac Age ( range): Measurement period: 66 (56- 79) July 2003 - March 2005 Gender, %: Follow -up duration: Males: 46 NA Race/Ethnicity, %: Completeness of follow -up: White: 97 NA Income, %: Measurement tools including cutpoints: Annual income >$30,000: 59 sTOFHLA: Insurance status, %: Inadequate Literacy: 0-16 Private insurance: 58 Marginal Literacy: 17-22 Medicare: 60 36 Adequate Literacy: 23- Medicaid: 21 Military/VA: 5 No insurance: 2 Education, %: Some high school or less: 25 High school graduate: 36 College graduate/some college: 31 Graduate education: 9 Other characteristics, %: Married/living as married: 63 Alcohol intake: > 1 drink/week: 20 Years with diabetes, median (IQR): 6.8 (3-14) Attended diabetes class: 35 Treatments for diabetes: Diet alone: 24 Oral hypoglycemic alone: 57 Insulin alone: 9 Insulin and oral agent: 9 Hypertension medications: 83 Cholesterol medications: 59 D-126

411 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: HL is not associated with glycated hemoglobin, blood pressure, A1C lipid levels or self reported diabetes complications in a cross - Systolic Blood Pressure sectional study of older adults with diabetes under relatively Diastolic Blood Pressure good glycemic control. -cholesterol LDL in no exposure (i.e., adequate literacy) or control group: Effect Diabetes Complications A1C, median: 6.9 Retinopathy SBP, median: 138 Nephropathy DBP, median: 79 Gastroparesis -cholesterol, median: 99 LDL problems Foot/leg Complications from Diabetes: Cerebrovascular disease Retinopathy, %: 18 Coronary artery disease Nephropathy, %: 9 Depression, Patient Health Questionnaire-9: >9, Gastroparesis, %: 6 dictomous Foot/leg problems, %: 30 Depression Score-Patient Health Questionnaire(0- Cere brovascular disease, %: 10 27), median (IQR): 2 (0-6) Coronary artery disease, %: 17 Covariates used in multivariate analysis: Depression, Patient Health Questionnaire > 5, %: 31 Age Depression, Patient Health Questionnaire Score, median (IQR): Sex -6) 2 (0 Race Effect in exposure (i.e., low/moderate literacy) or intervention: status Marital A1C Insurance quate: median 6.9 Inade Income Marginal: median 6.8 Duration of diabetes SBP Education Inadequate: median 137 Depression Marginal: median 144 Alcohol use DBP Medication use specific to each outcome Inadequate: median 76 Physician practice Marginal: median 77 Description of outcome measures: -cholesterol LDL Glycated hemoglobin (A1C) Inadequate: median 99 Systolic Blood Pressure Marginal): median 94 Diastolic Blood Pressure Complications from Diabetes (Inadequate), %: esterol -chol LDL Retinopathy: 30 Diabetes Complications - self report of: Retinopathy, Nephropathy, Gastroparesis, Foot/leg Nephropathy: 15 problems, Cerebrovascular disease, Coronary artery Gastroparesis: 9 disease Foot/leg problems: 30 Depression, Patient Health Questionnaire Cerebrovascular disease: 21 Depression Score-Patient Health Questionnaire Coronary artery disease: 30 e(s) for outcomes: Data sourc Complications from Diabetes (Marginal), %: - lab values A1C Retinopathy: 34 Systolic Blood Pressure - lab value; Nephropathy: 0 lab value; Diastolic Blood Pressure - Gastroparesis: 10 LDL - lab values -cholesterol Foot/leg problems: 44 self report of: Diabetes Complications - disease: 17 Cerebrovascular Retinopathy Coronary artery disease: 27 Nephropathy Gastroparesis Foot/leg problems Cerebrovascular disease Coronary D-127

412 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Health literacy/numberacy levels: Author, year: 49 Morris et al., 2006 Inadequate Literacy: 10 (continued) y: 7 Marginal Literac Adequate Literacy: 83 D-128

413 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Attempts for control for confounding: Depression, Patient Health Questionnaire >5: Inadequate: 40 Multivariate analysis Marginal: 54 Blinding: NR Depression, Patient Health Questionnaire Score Inadequate, median: 3 Statistical measures used: Marginal, median: 5 Regression analysis was used to measure association between HL and A1C, SBP, DBP, Low Difference: Difference in DBP (adjusted, TOFHLA measured as Density Lipoproteins. = 0.39) P continuous): ( Multivariate logistic regression was used to measure association between HL and self -reported -cholesterol (adjusted, TOFHLA measured as Difference in LDL = 0.59) continuous): ( P retinopathy, neuropathy, gastroperesis, foot and leg lar disease, and coronary ulcerations, cerebrovascu Diabetes Complications (Adjusted) = 0.09) Adequate vs. Inadequate: ( Difference in Retinopathy P artery disease. Difference in Retinopathy Adequate vs. Marginal: ( = 0.21) P Bivariate analysis examined relationship between Difference in Nephropathy Adequate vs. Inadequate: ( P = 0.93) HL and depression. Difference in Nephropathy Adequate vs. Marginal: ( P = 0.53) Difference in Gastroparesis Adequate vs. Inadequate: ( P = 0.28) Difference in Gastroparesis Adequate vs. Marginal: ( = 0.55) P Difference in Foot/leg problems Adequate vs. Inadequate: ( P = 0.11) Difference in Foot/leg problems Adequate vs. Marginal: ( P = 0.55) Difference in Cerebrovascular dis ease Adequate vs. Inadequate: ( = 0.72) P Difference in Cerebrovascular disease Adequate vs. Marginal: P = 0.54) ( Difference in Coronary artery disease Adequate vs. Inadequate: ( P = 0.49) Difference in Coronary artery disease Adequate vs. Inadequate: ( = 0 .85) P Difference in Depression, Patient Health Questionnaire- 9 Score > 5 across literacy categories (unadjusted): ( P = 0.03) Difference in Depression Score-Patient Health Questionnaire = 0.04) across literacy categories (unadjusted): ( P D-129

414 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 50 Included: Muir et al., 2008 Research objective: ≥18 Assess relationship between health literacy Glaucoma diagnosis and vision-related quality of life (VRQol), Presence of visual field tests in the medical record general HRQoL and mental HRQol Excluded: Study design: Refused to participate Cross -sectional survey and medical chart Low cognitive status review Sampling strategy: Study setting: All patients at clinic at time of study Glaucoma patients at the Duke University Eye Sample size: Center 195 Measurement period: Multivariate analysis: N=110 1-time survey administered between July 2000 Age (mean and range), %: and June 2001 ≤65: 28 Follow -up duration: 66-73: 22 NA 74-80: 26 Completeness of follow -up: >80: 23 NA Gender, %: Measurement tools including cutpoints: Female: 59 REALM: Race/Ethnicity, %: Low: ≤ 8th grade White: 55 ≥ 9th grade Adequate: Black: 42 Income: NR Insurance status: NR Education, %: ≥HS: 75

415 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: In bivariate analysis, low health literacy was associated with 1. VRQoL l HRQoL physical HRQoL but not menta 2. General HRQol In multivariate analysis, health literacy was not related to total 3. Mental HRQol VRQoL (with and without education in model) but was related Covariates used in multivariate analysis: to subscale component "dependency". It was not significantly Age related to any other subscale components. Race Effect in no expos Visual acuity ure (i.e., adequate literacy) or control group: 1. VRQoL (VFQ -25), mean (SD): 76 (18) Visual fields SF morbid 2. General HRQoL: NR -12 score (as a surrogate for co- 3. Mental HRQoL: NR conditions) Description of outcome measures: Effect in exposure (i.e., low/moderate literacy) or intervention: -25), mean (SD): 84 (18) VRQoL: 25-item Visual Function Questionnaire 1. VRQoL (VFQ 2. General HRQoL: NR -25) (VFQ 3. Total score based on following subscales: Mental HRQoL: NR General health Difference: Difference (unadjusted) General vision 1. VRQoL: ( P < 0.001) Near vision 2. General HRQoL: ( = 0.0002) P Distance vision = 0.068) P 3. Mental HRQoL: ( Driving = 0.621) P Difference total VFQoL score (adjusted): ( Peripheral vision = Difference VFQoL subscale-dependency (adjusted): ( P Color vision 0.040) Ocular pain -12) (unadjusted): ( P = 0.002) Differe nce Physical QoL (SF Role limitations P Difference Mental QoL (unadjusted): ( = 0.068) Dependency Social Data source(s) for outcomes: Self -report Attempts for control for confounding: Multivariate analysis: controlled for agenrace, visual acuity, visual field, and education. A second model excluded education. Blinding: NA istical measures used: Stat Relationship between VRQoL and HL was measured using bivariate analysis and linear regression for the multivariate analysis D-131

416 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 51 Murphy et al., 2010 Inclusion: Research objective: -positive HIV Investigates association between HL and Ages 16-24 etroviral medications among adherence to antir speaking English- HIV positive adolescents. Engaged in 2 of the following: currently prescribed antiretroviral Study design: medications, or told by physician to be on antiretroviral medications -sectional Cross (whether taking them or not); ever had sexual intercourse; ever tried Study setting: alcohol/drugs Five U.S. sites, primarily through the At least one behavior had to be at problem level: adherence < 90% Adolescent Trials Network: FORT Lauderdale, t month, unprotected intercourse within the last 3 months, in the las FL; Philadelophia, PA; Baltimore, MD; and Los or screening at problem level for alcohol and/or drug. ite was located Angeles, CA; 1 non-network s Exclusion: in Detroit, MI NA Measurement period: Sampling strategy: NR Convenience sample -up duration: Follow Sample size: NA N = 186 (missing data for some analyses) Completeness of follow -up: NA Age (mean and range), %: Measurement tools including cutpoints, %: Mean (SD): 20.5 (2.3) -TOFHLA: cut points not provided but The S Range: 16-24 inadequate and marginal combined for Gender, %: analyses. Four items from t he numeracy Male: 49.5% section of the original TOFHLA were added to Female: 47.3% -TOFHLA for the study. Multivariate the S Transgender/transsexual: 3.2% analysis included reading score only. Race/Ethnicity, %: African American/Black only: 78.0% European American only: 3.2% Hispanic only: 11.3% Mixed race/ethnicity: 7.5% Income, %: Monthly income ($): Mea n (SD): 644.30 (626.50) Median: 506.00 Range: 5.00- 4000 Insurance status, %: NR Education, %:

417 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Among HIV -efficacy to -positive adolescents health literacy was not sig Medication adherence, viral -load, self associated with: medication adherence, viral load, self adherence to medication regimens and medical -efficacy for care received. adherence; ER visits, or overnight hospital stays, adjusting for age Covariates used in multivariate analysis: and education but HL was positively associated with medical care received. Age and education level Effect in no exposure (i.e., adequate literacy) or control group: Description of outcome measures: Univariate Analysis: Adherence: Participants completed the diabetic - -care practice instrument, adapted for HIV self Average percentage adherence of all medications taken over past itive adolescents, assessing illness 3 days,n (%): pos management, and Module 1 of the pediatric ≥ 90%: 30 (35.7) adherence questionnaire for current HIV > 0 to < 90%: 20 (23.7) medications and number of missed doses over the 0%: 34 (40.5) last 3 days. Log10 viral load: Alcohol, smoking and substance abuse: N: 158 Participants completed the alcohol, sm oking and Mean (SD): 3.69 (1.19) substance involvement screening test (ASSIST), Median: 3.93 which assessed drug and alcohol use for the past 3 5.88 Range: 1.40- mos. Geometric mean: 4,855 Mental status: Participants completed the brief Effect in exposure (i.e., low/moderate literacy) or intervention: symptom inventory measures mental status. en over past Average percentage adherence of all medications tak -efficacy: Self Self -efficacy for health promotion and 3 days, n(%): risk reduction assessed confidence in taking ≥ 90% (adherent): 4 (23.5) medications and keeping health care 7 (41.2) appointments. 6 (35.3) Lboratory evaluations: Included CD4+ measures Log10 viral load: and plasma HIV -1 RNA (viral load) N: 27 Data source(s) for outcomes: Mean (SD): 3.82 (1.08) -assisted Self -report (questionnaires), computer Median: 3.73 personal interviews, and Laboratory test (CD4+ Range: 1.70- 5.67 -1 RNA (viral load) measures and plasma HIV Geometric: 6572 Attempts for control for confounding: Difference: Regression modeling Difference avg % adherence of all meds taken over past 3 days Blinding: adherent (adjusted): >= 90% adherent: OR, 1.00; compared to 0% NR 1.05 95% CI, 0.96- Statistical measures used: >0% and < 90% adherent: OR, 1.00; 95% CI, 0.95-1.04 Log10 viral load (adjusted): B = -0.007 ( P = 0.13) Cronbach's alpha, the Fisher -Freeman-Halton P = 0.15) CD4 count (adjusted): B = 2.78 ( exact test = 0531) BSI GSI (adjusted): B = 0.186 ( P Wilcoxon rank sums test, logistic regression = 0181) Total substance involvement (adjusted): B = 0.433 ( P modeling 4 Self efficacy adherence to HIV medication regimen score >= (adjusted): OR, 0.99; 95% CI, 0.95-1.03 Self efficacy adherence to keep medical appointment score >= 4 (adjusted): OR, 1.01; 95% CI, 0.95 -1.06 ER visits (adjusted): OR, 0.98; 95% CI, 0.96-1.01 Overnight hospital stay >= (adjusted):OR, 0.97; 95% CI, 0.93 -1.01 Medical care received 3 or more times (adjusted): OR, 1.09; 95% CI, 1.04 -1.15 Medical care received once or twice (adjusted): OR, 1.06; 95% CI, 1.09 1.02 - D-133

418 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Overnight or longer hospital stay during the past 3 months: Author, year: 51 Number of participants with overnight stay: 17 Murphy et al., 2010 (continued) Mean (SD): 1.1 (0.3) Median: 1 Ra nge: 1-2 Health literacy/numeracy levels, %: -modified: TOFHLA Inadequate: 11.8 Marginal: 2.7 Adequate: 85.5 D-134

419 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 52 Included: Murray et al., 2009 Research objective: 50 yo+ Determine factors independently Congestive heart failure diagnosis Associated with clinical exacerbation of heart Wishard pharmacy Use failure over 12 months as well as relative Prescribed an ACE, ARB, beta blocker, diuretic, digoxin, or strengths of their associations aldosterone antagonist Study design: Not planning to use pill box Prospective cohort Telephone access Study setting: Able to hear normal conversation -based public clinic practice in University Excluded: Indianapolis, Indiana Dementia Measurement period: Sampling strategy: Jun 2004 Feb 2001- Cohort obtained from usual care arm of an RCT -up duration: Follow Sample size: 1 yr 192 -up: Completeness of follow Age, mean (SD): NR 63.2 (8.9) Measurement tools including cutpoints: Gender, %: sTOFHLA: Females: 66.7 16 Inadequate Health Literacy: 0- Race/Ethnicity, %: Marginal Health Literacy: 17-22 Black: 51.6 Adequate Health Literacy: 23- 36 White 46.9 Other: 1.6 Income, %: Adequate income: 63.5 Insurance status, %: Medicare: 56.8 Medicaid: 36.5 Education, mean years (SD): 10.6 (2.7) Other characteristics: NA Health literacy/numeracy levels, % (SD): sTOFHLA adequate: 70.8 Prescription reading score: 1.5 (0.7) Comparison task score: 17.1 (5.5) Prescription label reading test: No correct responses: 0 Accurately read and interpret prescr iption instructions: 2 Cognitive test: Letter - comparison tests (max score 42) and pattern - comparison tests (max score 30) D-135

420 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: All cause ED visits Prescription label reading skills were associated with lower incidence of all cause and heart failure specific emergency care -failure specific ED visits Heart and all cause h ospitalization. Participants with adequate health All cause hospitalizations literacy had a lower risk of hospitalization for heart failure Heart failure specific hospitalizations Effect in no exposure (i.e., adequate literacy) or control group: Covariates used in multivariate analysis: NR Insurance Effect in exposure (i.e., low/moderate literacy) or intervention: NYHA class NR LVEF Diffe rence: Refill adherence All Cause ED visits (unadjusted), IRR (CI): Prescription label reading score Prescription label reading score, 1 pt increment: 0.76 (0.59- Hct 0.97) Race Heat failure specific ED visits (unadjusted): Prescription label onnaire score Chronic Heart Failure questi reading score: 0.36 (0.19-0.69) Serum Na All cause hospitalization (unadjusted): Income adequacy Prescription label reading score: 0.68 (0.54-0.86) Serum K Heart failure specific hospitalization (unadjusted): sTOFHLA Kansas City cardiomyopathy questionnaire 0.76) 0.34 (0.15- Age Comparison task score Depression Description of outcome measures: Clinical exacerbations (ED and hospitalizations) over 12 months Data source(s) for outcomes: Medical records, participant charts, verified by research assistants at participant visits and endpoints adjudicated by RN as abstractor using previously validated methodology Attempts for control for confounding: Multivariate analyses Blinding: NR Statistical measures used: Log-Linear Regression, step-wise inclusion of independent -square vars, chi D-136

421 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 53 Nokes et al., 2007 Included: Research objective: ≥18 Determine influence of health literacy on HIV positive depressiv e symptoms, HIV symptom intensity Excluded: and distress over body changes attributed to NR HIV among persons with HIV/AIDS Sampling strategy: Study design: Convenience -sectional Cross Sample size: Study setting: 489 HIV positive patients receiving care at Age, mean (SD): Infectious disease clinics or community -based 42.6 (8.77) in 6 US cities (San Francisco, organizations Gender: Fresno, Richmond, New York City, Corpus NR Christi) Race/Ethnicity, %: Measurement period: AA: 50 6-month period from 2002-2003 Hispanic/Latino: 25 Follow -up duration: -Hispanic: 20 White/ Non NA Income, %: Completeness of follow -up: "Barely adequate": 54 NA Insurance status, %: Measurement tools including cutpoints: Uninsured: 37 REALM: Possible range: 0- ured as a 66; meas Education, %: continuous variable Some HS: 40 >HS: 30 Other characteristics, %: HIV Positive: 59 Aids: 37 Health literacy/numeracy levels, mean (SD): 59.1 (12.9) D-137

422 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: Physical health Higher HL was significantly related to greater body change distress, symptom intensity and depressive symptoms in step- Depressive symptoms Distress over body changes nalyses. wise regression a Effect in no exposure (i.e., adequate literacy) or control group: -symptom intensity HIV Physical health, mean (SD): 6.68 (2.22) Covariates used in multivariate analysis: Data on other outcomes not provided Hispanic Effect in exposure (i.e., low/moderate literacy) or intervention: measures: Description of outcome Physical health: global health status rating scale Physical health, mean (SD): 7.21 (2.42) Data on other outcomes not provided developed by investigators Difference: Depressive symptoms: Center for Epidemiology -D) Studies Depression Scale (CES Physical health (mean difference): 0.53 Correlation analysis: Distress over body changes: Assessment of Body Depressive symptoms: .09, P < 0.05 Change Distress Scale (ABCD) < 0.05 Distress over body changes: .11, P HIV -symptom i ntensity: Revised Sign and Symptom = 0.01 -symptom intensity: .16, HIV P Checklist for persons with HIV Disease (SSC - Step s ted ), β: -wise regression (adju HIVrev) Depressive symptoms: 4.26, P < 0.05 Data source(s) for outcomes: P Distress over body changes: 2.91, < 0.05 -report Self < 0.05 -symptom intensity: 8.62, HIV P Attempts for control for confounding: -wise multiple regression Step Blinding: NR Statistical measures used: Bivariate correlation analysis -wise linear regression using list wise deletion Step on the predictor variables D-138

423 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 54 Osborn et al., 2007 Included: 55 and Waite et (Companions: Wolf et al., 2007 HIV -infected patients on one or more antiretroviral medications 56 ) al., 2008 Excluded: Research objective: HIV patients on current ART regimen for < 2 weeks Examine mediating effect of limited HL on Diagnosis of dementia relationship between race and HIV -medication Blindness or severely impaired vision not correctable with adherence. eyeglasses dy design: Stu Deafness or hearing problems uncorrectable with a hearing aid Cross -sectional Too ill to participate in the survey Study setting: Sampling strategy: Outpatient infectious disease clinics at Convenience Northwestern Memorial Hospital, Chicago Sample size: or Louisiana State University Health Sciences 204 Center, Shreveport, LA Age, mean (SD): Measurement period: 40.1 (9.2) June to September 2001 Gender, %: -up duration: Follow Females: 20.1 NA Race/Ethnicity, %: -up: Completeness of follow AA: NA Total: 45.1 Measurement tools including cutpoints: Marginal/low HL: 52 REALM Non 4.3 -AA Marginal or low HL: 1 ≤ 6th grade: Low literacy (score of 0 to 44) Income, %: 7th - 8th grade: Marginal literacy (score of 45 Annual Income: to 60) < $10,000: 39.7 - 66) ≥ 9th grade: Adequate (score of 61 $10,000-$11,999: 23 $12,000-$17,999: 9.8 ≥ $18,000: 27.5 Insurance status, %: Private: 27.5 Medicare: 19.6 Medicaid or free care: 52.9 Education, %: < HS: 12.3 HS graduate: 26 > HS: 61.8 Number of HIV medications in regimen: 1-2 medicines: 29.9 ≥3 medicines: 70.1 ≥1 non -HIV comorbid conditions: 52.5 Adherence to HIV -medication in past 4 days: Non -AA: 76.8 AA: 60.1 Health literacy/numeracy levels, %: Low: 11.3 Marginal: 20.1 Adequate: 68. D-139

424 Evidence Key Question 1: Health literacy outcome studies (continued) Table 1. Outcomes Results Main outcomes: Describe results: Low HL was a significant predictor of nonadherence but Medication Adherence Covariates used in multivariate analysis: By adding HL to mediation adherence marginal HL was not. model, coefficient for black race changed from being Gender statistically sig to not and coefficient decreased in size, from an Age odds of 2. Income Effect in no exposure (i.e., adequate literacy) or control group, Number of medications in regimen %: -HIV comorbid condition Non Nonadherence to HI V-medication in past 4 days: Mental illness Adequate literacy: 30 Description of outcome measures: Effect in exposure (i.e., low/moderate literacy) or intervention, Patients reported any missed doses in past 4 days %: through reviewing names and color photographs of -medication in past 4 days: Nonadherence to HIV common HIV medications included in a revised Low literacy: 52.2 version of the PMAQ Difference: Patients rated as having proper adherence if no Model 1 - -medication without literacy Nonadherence to HIV missed doses during time period were reported. level (adjusted), OR (CI): Data source(s) for outcomes: AA: 2.4 (1.14 5.08) -report Self Model 2 - Nonadherence to HIV -medication with literacy level Attempts for control for confounding: (adjusted), OR (CI): Multivariate regression -5.85) AA: 1.8 (0.51 Blinding: Marginal HL: 1.55 (0.93-2) NR Statistical measures used: Within Intervention Group (unadjusted) : +0.39 -square and t Chi -tests to test bivariate associations. Multivariate regression: to analyze mediational effect of HL on racial differences in HIV -medication adherence. First, relationship between race and adherence established after adjusting for covariates and potential interaction effects (Model 1). Next, relationship between literacy and adherence tested, which was confirmed in a prior study using this same cohort. Finally, literacy was added to Model 1 as a mediator (Model 2). D-140

425 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 57 Included: Osborn et al., 2009 Research objective: Diagnosis or type I or II diabetes, age 18-85 years, English- speaking To examine whether health literacy, numeracy Exc luded: and diabetes specific numeracy mediate the Previous diagnosis of dementia, psychosis, or blindness association between African American race Pts with a corrected visual acuity of 20/50 or worse using and A1C level Rosenbaum Screener Study design: Sampling strategy: -sectional Cross Convenience sampling Stu dy setting: Sample size: Two primary care and 2 diabetes specialty N = 383 clinics located at 3 medical centers. Quartile (Q) by DNT Measurement period: Q1, n = 104 March 2004 to Q2, n = 97 November 2005 8 Q3, n = 9 Follow -up duration: Q4, n = 84 NA Age (mean and range), %: -up: Completeness of follow Total, median NA (range) = 56 (47-64) Measurement tools including cutpoints, %: By DNT quartile DNT: Q1, Q2, Q3, Q4 (cutpoints not explained 67) Q1 = 61 (51 - but lower quartile indicates lower diabetes Q2 = 57 (49 - 66) related numeracy) Q3 = 56 (47 - 62) REALM Q4 = 50 (41 - 56) < 9th grade Gender, %: ≥ 9th grade Female: 50% -3 WRAT By DNT quartile < 9th grade Q1: 60% ≥ 9th grade Q2: 44% Q3: 50% Q4: 45% Race/Ethnicity, %: Total White: 65% Nonwhite: 35% By DNT quartile Q1 White: 31% Nonwhite: 69% Q2 White: 67% Nonwhite: 33% Q3 White: 79% Nonwhite: 21% D-141

426 Key Question 1: Health literacy outcome studies (continued ) Evidence Table 1. Outcomes Results Main outcomes: Describe results: recent in medical record A1C: most Model 1: younger age, using insulin, having been diagnosed with diabetes for more years, and African American race were Covariates used in multivariate analysis: Covariates in Model 1: associated with sig higher A1C levels and accounted for 17% of the variability in A1C levels. Age Sex Model 2: African American race was associated with limited P < 0.001), limited general numeracy literacy skills (r = -0.39, Years of ed P skills (r = - 0.43, < 0.001), and limited DNT skills (r = -0.46, Annual income < 0.001). AA race did not have a sig direct effect on A1C (r = P Insulin use 0.10, P = NS). Of the skills measures, only DNT significantly Diabetes type directly predicted A1C levels. Higher DNT was associated with Years of diagnosed diabetes lower A1C levels (r = -0.15, P <0.01) Race Model 3--literacy and general numeracy removed from the Covariates in Models 2 and 3 (sig variables from model : AA race associated with lower DNT (r = -0.47, Model 1): P < 0.001). Lower DNT associated with higher A1C level Age (r = -.17, < 0.01). Direct effect of AA race on A1C not P Year of diagnosed diabetes measured Insulin use Effect in no exposure (i.e., adequate literacy) or control group: African American race NR Description of outcome measures: Effect in exposure (i.e., low/moderate literacy) or intervention: Glycemic control was assessed by most recent A1C AIC (%) value in patient's medical record. 96% were -9.0) Q1: 7.6 (6.5 obtained within 6 months of the participant -8.3) Q2: 7.2: (6.3 A1C and evaluation and median time between Q3: 7.2 (6.5 -8.0) evaluation was 15 days. -8.2) Q4: 7.2 (6.4 Data source(s) for outcomes: ( P = 0.24) Chart review Difference: Attempts for control for confounding: Model 2 Structural equation modeling P = < 0.001, CFI Overall model fit, X2 (12, n = 383) = 485.47, Blinding: 0.464, RMSEA = 0.32 (90% CI, 0.30 –0.35). NR Test of significance of individual paths: Statistical measures used: = NS P REALM, Three structural equation models were estimated. = NS P General numeracy, Model 1 tested whether Af rican American race < 0.01 DNT, P predicted higher A1C levels after controlling for potential confounders. Model 2 tested whether Model 3 P = 0.99, = 0.07, CFI Overall model fit, X2 (3, n = 383) = 6.91, African American race predicted low HL skills, low general numeracy skils, and low DNT, and whether RMSEA = 0.06 (90% CI, 0.00 –0.12). < 0.001 P Test of significance of individual paths: DNT, these variables, in turn, predicted A1C levels. Model 3: Sig HL and numeracy predictors from Model 2 and potential confounders. D-142

427 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Q4 Author, year: 57 Osborn et al., 2009 White: 89% (continued) Nonwhite: 11% Income, %: Total <$20,000: 44% By DNT quartile Q1: <$20,000: 80% Q2: <$20,000: 49% Q3: <$20,000: 23% Q4: <$20,000: 20% Insurance status, %: Has Private Insurance Total: 48% By DNT quartile Q1: 31% Q2: 40% Q3: 59% Q4: 67% Education, %: Total

428 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 58 Inclusion: Osborn et al., 2010 Research objective: Prescribed 1 or more antiretroviral medications To develop and validate a brief assessment of Receiving medical care through outpatient infectious disease clinics at health knowledge and action in the context of Northwestern Memorial Hospital in Chicago, Illinois and Louisiana State HIV treatment, referred to as the Brief iversity Health Sciences Center in Shreveport, Louisiana Un Estimate of Health Knowledge and Action-HIV Exclusion: e BEHKA-HIV and version (BEHKA-HIV). Th Had been on current regimen for less than 2 weeks REALM were evaluated as predictors of Too ill to participate medication adherence. Had one or more of the following conditions, as noted in the medical Study design: ly impaired vision not recored: (1) dementia; (2) blindness or severe Cross sectional correctable with eyeglasses; (3) deafness or hearing problems Study setting: uncorrectable with a hearing aid. Outpatient infectious disease clinics at Sampling strategy: Northwestern Memorial Hospital in Chicago, Convenience sample Illinois and Louisiana State University Health Sample size: Scie nces Center in Shreveport, Louisiana N = 204 Measurement period: Age (mean and range), %: NR; however, participants were recruited from Mean (SD): 40.1 (9.2) June to September 2001. Gender, %: Follow -up duration: Female: 20.1 NA Race/Et hnicity, %: -up: Completeness of follow African -American: 45.1 NA Income, %: Measurement tools including cutpoints, %: ≤ $800/month: 39.7 Household income REALM: Insurance status, %: ≤ 3rd grade pronunciation: 0-18 Correct words Uninsured: 27.5 reading level (low literacy) Education, %: 6th 19-44 Correct words pronunciation: 4th- At least some college education: 60 grade reading level (low literacy) Other characteristics, %: 45-60 Correct word pronunciation: 7th or 8th Unemployed: 55.9 grade reading level (marginal literacy) Receiving treatment for a non- HIV related chronic illness: 52.5 ≥ 9 th grade 61-66 Correct word pronunciation: Receiving mental health serves: Nearly one-third (adequate literacy) Receiving treatment for alcohol or illicit drug use in the past 6 mos: 9.3 Taking 3 or more HIV medications: Over 70 Health literacy/numeracy levels, %: REALM: ≥ 9th grade (adequate): 6 8.6 7th -8th grade (marginal): 20.1 ≤ 6th grade (low): 11.3 D-144

429 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Low but not marginal HL was significantly associated with poor Adherence -r eported HIV medication non-adherence. HIV knowledge and action self Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: Brief Estimate Health Knowledge and Action-HIV (BEHKA- Age HIV), %: Insurance coverage Employment status 6-8 (adequate): 31.8 Number of medications in HIV regimen Adherence: 90.9% of patients scoring 6- Number of non-HIV prescription meds currently -HIV (adequate) 8 on the BEHKA taken were adherent to their current regimen Adherence in relation to REALM score: NR Presence of a comorbid chronic condition Treatment for a mental health condition in the past 6 Effect in exposure (i.e., low/moderate literacy) or intervention: months Brief Estimate Health Knowledge and Action-HIV (BEHKA- Treatment for alcohol or drug use in past 6 months. HIV), %: Description of outcome measures: 4-5 (marginal): 34.1 Patient Medication Adherence Questionnaire 0-3 (low): 34.1 -reported any recent missed (PMAQ): Patients self e: Adherenc doses of HIV medication using pages that contained 3 on the BEHKA 51.0% of patients scoring 0- -HIV (low) were names and color photographs of common HIV adherent to their current regimen included in a revised version of the medications 82.3% of patients scoring 4- 5 on the BEHKA -HIV (marginal) PMAQ; Patients were required to identify their were adherent to their current regimen medication and then report on a missed dose in the Adherence in relation to REALM score not reported past 4 days for each antiretroviral agent. Difference: Brief Estimate Health Knowledge and Action-HIV Difference in non-adherence (adjusted): Version (BEHKA-HIV): 8 -item ass essment of HIV 5.5 Marginal HL vs adequate: OR, 2.1; 95% CI, 0.8- treatment knowledge and action; 3 items were Low HL vs adequate: OR, 3.3; 95% CI, 1.3- 8.7 associated with knowledge and 5 with action. The BEHKA-HIV scores ranged from 0 to 8, and patients were classified as low, marginal, or adequate on the BEHKA-HIV. Higher scores corresponded with fewer missed doses of a regimen. Data source(s) for outcomes: -person interviews: -report, in Self Patient Medication Adherence Questionnaire (PMAQ) Brief Estimate Health Knowledge and Action-HIV Version (BEHKA-HIV) Attempts for control for confounding: Mul tivariate logistic regression models Blinding: NR Statistical measures used: Cronbach's alpha -specific likelihood ratios (SSLRs) Stratum Chi square, logistic regression - D-145

430 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteri stics Author, year: Eligibility criteria: 59 Included: Paasche-Orlow et al., 2005 Research objective: English speaking Identify educational factors (including literacy) housed in general facility population associated with HIV risk behaviors among Age 18+, not yet sentenced incarcerated women. able to competently provide verbal consent Study design: Excluded: Cross -sectional study NR Study setting: Sampling strategy: Rhode Island Adult Correctional Institute Consecutive request to enroll during a 2 week period Measurement period: Sample size: Within 4 days of arrival, February 4, 2004 to 423 July 19, 2004 Age, mean (range): Follow -up duration: Total: 34 (18-64) NA Gender, %: Completeness of follow -up: Females: 100 NA Race/Ethnicity, %: Measurement tools including cutpoints: Caucasian: 63 M (score 0 REAL -66) AA: 25 Cut points: Hispanic: 10 ≤ 6th Grade (0 -44) Income: 60) - 8th Grade (45- 7th NR ≥ 9th Grade (61 -66) Insurance status: NA Education, %: ≤ 8th grade: 9 - 11th grade: 46 9th HS graduate: 45 Other characteristics, %: Received special Education: 26 Had Individualized Educational Plan:15 History of problem drinking: 37 Health literacy/numeracy levels, %: ≤ 6th Grade: 10 7th - 8th Grade: 19 ≥ 9th Grade: 71 D-146

431 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Desc ribe results: HIV Risk Behavior No significant association between literacy level and HIV risk behavior. Covariates used in multivariate analysis: Age Effect in no exposure (i.e., adequate literacy) or control group: Race HIV Risk Behavior, % (n): - 8th Grade: 19 (42) 7th Problem drinking measures: Description of outcome ≥ 9th Grade: 72% (162) HIV risk: dichotomous variable based on response Effect in exposure (i.e., low /moderate literacy) or intervention: to question, "During the last 3 months, have you had HIV Risk Behavior, % (n): sex without using a condom OR have you shared ≤ 6th Grade: 9 (21) any part of injection drug equipment (needle, Difference: syringe, cotton, cooker, or rinse water) at least on ce Difference in odds of reporting HIV Risk behavior (adjusted), a month?" OR (CI): Data source(s) for outcomes: 4.81) - 8th Grade: 1.89 (0.74 - 7th Self -report data from in-person interview. -4.92) ≥ 9th Grade: 2.02 (0.83 Attempts for control for confounding: Multivariate logistic regression Blinding: NR Statistical measures used: Fisher exact test -sample t tests Two ANOVA Bi-variate logistic regression related primary independent variables (health literacy and other education variables) and demographic variables to HIV risk behavior. Multivariate logistic regression added race, age, and problem drinking to the model. D-147

432 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 60 Included: Paasche-Orlow et al., 2006 Research objective: 2 or more positive responses to CAGE questionnaire or physician ationship between health Investigate rel assessment of alcohol abuse or dep endency literacy and antiretroviral adherence and HIV - Fluent in English or Spanish RNA Suppression in HIV patients with a -Mental State Examination score >21 Mini history of alcohol problems. No plans to move from Boston area within 2 years Study design: Excluded: Longitudinal Those that did not complete health literacy assessment Study setting: Not on Antiretroviral therapy Boston Conducted research interview in Spanish Measurement period: Sampling strategy: July 1997-August 2001 Convenience -up duration: Follow Sample size: Up to 3 years 235 -up: Completeness of follow Age, mean (IQR): NR 42 (9) Measurement tools including cutpoints: Gender, %: REALM Males: 79 <6th grade: Race/Ethnicity, %: 7th - 8th grade: Black: 45 >9th grade: White: 38 Other: 17 Income: NR Insurance status: NR Education, %: High school graduate or equivalent degree: 63 Other characteristics: Homeless, %: 23 Nested adherence trial status: Not in nested trial, %: 42 Intervention subject in nested trial, %: 30 Control subject in nested trial, %: 28 Alcohol consumption, median drinks/day (IQR): 6 (9) Drank to intoxication in past 30 days, %: 33 Injected drugs past 6 months, %: 19 ASI alcohol score, median (IQR): 0.1 (0.3) ASI drug score, median (IQR): 0.1 (0.2) Health literacy/numeracy levels, %: <6th grade: 14 7th - 8th grade: 29 >9th grade: 57 D-148

433 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: HL was not associated with a lower odds of adherence or 100% Adherence at baseline, %: 64 virologic Viral load suppressed at baseline visit, %: 60 suppression in this longitudinal analysis of HIV - Covariates used in multivariate analysis: infected patients with a history of alcohol problems. Gender Effect in no exposure (i.e., adequate literacy) or control group, %: Age Education 100% adherence: 64 Randomization group Viral load suppressed: 61 Effect in exposure (i.e., low/moderate literacy) or intervention, Ethnicity Homeless status %: Drank to intoxication past 30 days ≤ 6th grade): 69 100% adherence ( 100% adherence (7th-8th grade): 63 Injected drugs past 6 months Viral load suppressed ( ≤ 6th grade): 63 Complexity of regimen Model predicting HIV -RNA Suppression also uses Viral load suppressed (7th-8th grade): 58 medication adherence as covariate Difference: Difference in 100% Adherence (adjusted), OR (CI): Description of outcome measures: ≥ 9th grade: 1.93 (0.86 vs. ≤ 6th grade -4.31) 100% Adherence: dictomous; 3 -day ART adherence -2.19) 7th ≥ 9th grade: 1.29 (0.77 -8th grade vs. (100% adherent vs. <100% adherent) Viral load suppressed at baseline visit: measured Difference in HIV -RNA Suppression (adjusted), OR (CI): using branched- -3.65) chain DNA techniques; detection ≤ 6th grade vs. ≥ 9th grade: 1.70 (0.79 -2.18) -8th grade vs. threshold 500 copies/mL; viral load suppression 7th ≥9th grade: 1.29 (0.77 defined as having undetectable Data source(s) for outcomes: -report 100% Adherence at baseline: self questionnaire Viral load suppressed at baseline visit: lab values Attempts for control for confounding: Multivariate analysis Blinding: NA Statistical measures used: Bivariate analysis to assess the associations between characteristics and HL. Compared across HL groups using Chi -squared for categorical variables and Kruskall -Wallis test for continuous variables. Longitudinal logistic regression models used to examine association between HL and each main outc ome over time. A GEE approach used an independence working correlation matrix to account for correlation due to analyzing repeated measure from the same subject over time. D-149

434 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 61 Included: Paasche-Orlow, 2005 Research objective: Age 18 or older To assess whether inadequate health literacy Admitted with a physician diagnosis of asthma exacerbation to 2 and retaining discharge is a barrier to learning inner -city academic medical centers and medication instructions and appropriate Excluded: metered-dose inhaler technique among Other chronic lung disease asthmatics. o corticosteroids Contraindication t Study design: Patients or physicians who declined consent post test) Quasi -experimental (pre- Investigators' patients Study setting: Discharged to location other than home Two inner -city hospitals Sampling strategy: Measurement period: Convenience April 2001 - October 2002 Sample size: Fo llow -up duration: 73 2 weeks --baseline Note: adherence data only available on 46 (63%) Completeness of follow -up: characteristics not given for these individuals to compare to full 77% sample Note: patients who did not f/u were more likely Age, mean (SD): to be younger, female, AA, high school grad, 40.9 (10.9) be hospitalized in the last 12 months, and Gender, %: have lower Female: 66 Measurement tools including cutpoints: Race/Ethnicity, %: sTOFHLA: AA: 79 Inadequate: ≤ 16/36 Income, %: Adequate: >16/36 asthma scores ≥ $19,000: 65 Income Insurance status: NR Education, %: High School graduate or GED: 60 Other characteristics, %: Asthma -related health care use: Hospital visit past 12 mo: 58 ED visit past 12 mo: 77 Near -fatal asthma: 42 Cigarette smoking history: Never: 44 Past: 27 Current: 29 Asthma: Physician for asthma care, %: 51 Asthma knowledge score, mean (SD): 6.9 (2.0) Heal th literacy/numeracy levels: Inadequate: 22% D-150

435 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results results: Describe Main outcomes: Outcomes: Inadequate health literacy was associated with poor ≥ mean) asthma medication knowledge Better ( asthma medication knowledge, poor MDI technique, and ≥ mean) Metered Dose Inhaler technique Better ( hospitalization. Asthma knowledge appeared to mediate Mastery of discharge regimen after one round relationship between inadequate literacy and MDI technique. Poor (< 50%) adherence to corticosteroid therapy equate health literacy was not a barrier to Intervention: Inad ≥ mean) asthma symptom control Better ( learning key asthma management skills in a one-on -one 30 Covariates used in multivariate analysis: minute asthma education session. Age Note: power is a significant limitation to this conclusion, Sex however. Ethnicity Effect in no exposure (i.e., adequate literacy) or c ontrol group: Education -related health care use, %: Asthma Income Hospital visit past 12 mo: 52 History of near fatal asthma ED visit past 12 mo: 75 Hospitalization in prior 12 mo. -fatal asthma: 37 Near Having a physician for asthma care Cigarette smoking history, %: Prior ED visit for Asthma last 12 mo. Never: 46 Note: given sample size, model should hold only 4 Past: 30 covariates Current: 25 Description of outcome measures: Better asthma medication knowledge: Asthma Physician for asthma care, %: 53 Medication Knowledge Questionnaire, 10-item Asthma knowledge score (at baseline), mean: 7.2 developed by investigators based upon existing Mastery of Metered Dose Inhaler technique (at baseline), %: asthma knowledge scales, professional opinion, and 63% (read from chart) the desire for each item to be directly related to Intervention: Mastery of Metered Dose Inhaler technique (at baseline), %: 32 ≥mean score] vs. medication use; dichotomous (yes [ no]). (read from chart) Better Metered Dose Inhaler techniqu e: score 0-6 Mastery of Discharge Regimen (at baseline), %: 75 (read from chart; based on assessed technique meeting 6 criteria average of 76 Inad Lit; 73 AdLit) (shaking, exhaling prior, lips around mouthpiece, full Poor Adherence (baseline): NR deep breath without triggering indicator, hold Asthma Symptom control (baseline): NR ≥mean score breathe 5 seconds); dichotomous (yes [ Effect in exposure (i.e., low/moderate literacy) or intervention: =4] vs. no]). -related health care use, %: Asthma Mastery of discharge regimen after 1 round: Hospital visit past 12 mo: 81 dichotomous (yes. vs. no) 88 ED visit past 12 mo: Poor adherence to corticosteroid therapy: using Near -fatal asthma: 63 Doser CT which records the numeracy of actuations Cigarette smoking history, %: for inhaled steroid (poor adherence < 50%: Never: 38 dichotomous (yes vs. no)) and MEMS Caps which Past: 19 e pill bottle opened for record the number of times th Current: 44 oral steroids (poor adherence <50%). Physician for asthma care, %: 44 Better asthma symptom control: using 6 symptom Asthma knowledge score (at baseline), mean: 5.2 Mastery of Metered Dose Inhaler technique (at baseline), %: 32 items in Asthma Control Questionnaire: (read from chart) ≥mean score] vs. no]). dichotomous (yes [ Data source(s) for outcomes: Better ( edge ≥mean) asthma medication knowl Better ( ≥mean) Metered Dose Inhaler technique Mastery of discharge regimen after one round Poor (<50%) adherence to corticosteriod therapy ≥mean) asthma symptom control Better ( Attempts for control for confounding: Multivariate analysis D-151

436 Evid ence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: 61 Paasche-Orlow, 2005 (continued) D-152

437 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Results Outcomes INTERVENTION: Blinding: ery of Metered Dose Inhaler technique (after single round Mast Yes, to outcome assessors at 2 weeks No to patient education), %: 64 (avg 59 Inad Lit; 73 AdLit) Statistical measures used: Better Metered Dose Inhaler technique (at 2-week follow -up), Wilcoxon rank sum, matched pairs signed rank, and %: 88 (read from chart; avg 86 Inad Lit; 90 AdLit) x2 for bivariate. Understanding of Discharge Regimen after single round Logistic regression models for adjusted analyses. education, %: 69 Mastery of Discharge Regimen (at 2 week follow -up), %: 95 (read from chart; average 92 Inad Lit; 98 AdLit) Poor Adherence (at 2 week follow -up, available on 46 participants), %: 48 Asthma Symptom Control (at 2 week follow -up): NR Difference: Difference in Cigarette smoking history (unadjusted): ( P = 0.31) P = Difference in Physician for asthma care (unadjusted): ( 0.53) Difference in Asthma knowledge score (at baseline) (unadjusted): -2.0, P < 0.01 OR (adjusted) (CI): 0.08 (0.02- 0.38) Difference in Mastery of Metered Dose Inhaler technique (at baseline) (adjusted), %: - P = 0.03 31 (read from chart), OR (CI)l 0.29 (0.08- 1.00) Intervention: Difference in Mastery of Metered Dose Inhaler technique (at 2- week follow -up): (unadjusted), %: 56, NR; p for interaction by literacy, = 0.02 P Difference in Understanding of Discharge Regimen (at 2-week -up) (unadjusted), %: + 20, NR; p for interaction by follow P = 0.40 literacy, Difference in Adherence (at 2 week follow -up, available on 46 participants) by literacy sub group (adjusted): NR, P for interaction, P = 0.45 Asthma Symptom Control (at 2 week follow -up) by literacy = 0.84 subgroup: NR, P for interaction, P D-153

438 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 62 Included: Pandit et al., 2009 Research objective: ≥ 18 yrs old Determine whether there is an association Diagnosis of hypertension in their medical record between hypertension control and HL level. Had a clinic appointment during st udy period Study design: Excluded: -sectional Cross Did not speak English Study setting: Clinic nurse determined they were too ill or cognitively impaired to Patients receiving care from primary care participate and Rapids, MI, safety net clinics in Gr Sampling strategy: Chicago, IL, or Shreveport, LA Convenience Measurement period: Sample size: July 2006 and August 2007 330 -up duration: Follow Category I, n = 56 NA Category II, n = 37 Completeness of follow -up: Category III, n = 51 NA Category IV, n = 84 Measurement tools including cutpoints: Category V, n = 102 S-TOFHLA (scores range from 0 to 100) Age (mean and range) (SD): Scores are typically placed in one of three Total : 53.6 (12) literacy categories: inadequate, Category I: 60 (10.5) marginal,adequate. However, in this study, Category II: 55.9 (13.6) they divided scores into five categories to Category III: 54.6 (9.4) "provide a larger spectrum of literacy skills." Category IV: 52.3 (11.8) They created the categories based on the S - Category V: 49.7 (12) TOFHLA frequency distribution: Gender, %: 30 Category I: 0– Female 50 Category II: 31– Total: 67.9 70 Category III: 51– Category I: 50 Category IV: 71– 90 Category II: 75.7 Category V: 91– 100 III: 68 Category Category IV: 69.9 Category V: 74.5 Race/Ethnicity, %: AA Total: 78.5 Category I: 89.3 Category II: 83.3 Category III: 84.3 Category IV: 81.7 Category V: 67.6 Income: NR Insurance status, %: Total: Private: 10 Medicare: 18.8 Medicaid: 27.3 None/free care: 43.9 D-154

439 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Hypertension control Lower HL level was sig associated with a lower probability of having controlled BP. Covariates used in multivariate analysis: control group, Effect in no exposure (i.e., adequate literacy) or Age %: Race Controlled Blood Pressure Gender Marital status Category III: 45.1 Category IV: 60.7 Employment status coverage Insurance Category V: 45.1 Site location Effect in exposure (i.e., low/moderate literacy) or intervention, %: Number of comorbid conditions Controlled Blood Pressure Years treated for hypertension Category I: 33.9 Clinic site Category II: 48.6 Education Difference: Description of outcome measures: Hypertension control was measured by blood Difference hypertension control compared to Categrory V (adjusted), OR (CI): pressure readings which were recorded from medical chart and considered controlled if less than Category I: 2.68 (1.54-4.70) Category II: 1.47 (0.53-4.05) 140 mmHg systolic and less than 90 mmHg diastolic Category III: 1.69 (1.08-2.63) (or < 130 mm Hg systolic and < 80 mm Hg diastolic -3.01) for patients Category IV: 1.10 (0.40 Data source(s) for outcomes: Medical chart review Attempts for control for confounding: Multivariate logistic regression Blinding: NR Statistical measures used: -square Chi Student’s t -tests Multivariate logistic regression D-155

440 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Category I: Author, year: 62 Private: 10.7 Pandit et al., 2009 (continued) Medicare: 14.3 Medicaid: 32.1 None/free care: 42.9 Category II: Private: 13.5 Medicare: 24.3 Medicaid: 24.3 None/free care: 37.8 Category III: Private: 7.8 Medicare: 21.6 Medicaid: 33.3 None/free care: 37.3 Category IV: Private: 11.9 Medicare: 20.2 Medicaid: 19 None/free care: 48.8 Category V: Private: 7.8 Medicare: 16.7 Medicaid: 29.4 None/free care: 46.1 Education: 8, n = 45 Grades 1 - Grades 9 -11, n = 45 HS, n = 103 >HS, n = 96 Other characteristics, %: Employment: Total: -time: 20.9 Full Part -time: 13.3 Unemployed/ retired: 65.8 Category I: -time: 8.9 Full Part -time: 14.3 Unemployed/ retired: 76.8 Category II: Full -time: 21.6 Part -time: 10.8 Unemployed/ retired: 67.6 Category III: Full -time: 9.8 Part -time: 19.6 Unemployed/ retired: 70.6 D-156

441 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Category V: 62 Pandit et al., 2009 Full -time: 27.5 (continued) Part -time: 9.8 Unemployed/ retired: 62.7 Site: Total: Chicago: 30.6 Grand Rapids: 36.1 Shreveport: 33.3 Category I: Chicago: 25 Grand Rapids: 30.4 Shreveport: 44.6 Category II: Chicago: 24.3 Grand Rapids: 45.9 Shreveport: 29.7 Category III: Chicago: 33.3 Grand Rapids: 35.3 Shreveport: 31.4 Category IV: Chicago: 35.7 Grand Rapids: 35.7 Shreveport: 28.6 Category V: Chicago: 30.4 Grand Rapids: 36.3 Shreveport: 33.3 Health literacy/numeracy levels, %: Category I: 17 Category II: 11 Category III: 15.5 Category IV: 25.5 Category V: 31 D-157

442 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 63 Included: Peterson et al., 2007 Research objective: ≥50 years -old ith Determine if health literacy is associated w Receive primary care at clinic reported self -efficacy for completing colorectal English- speaking cancer screening and with receipt of colorectal Have TennCare (TN's Medicaid program) or Medicare cancer tests. Excluded: Study design: NR -sectional Cross Sampling strategy: Study setting: Convenience sample Patients at a community health clinic in Sample size: Nashville, TN, located in a medically 99 nity adjacent to a public underserved commu Limited HL, n = 29 housing project Adequate HL, n = 70 Measurement period: mean (SD): Age, - 6/2005 9/2004 59.5 (7.8) Follow -up duration: Limited HL: 60 (8.8) NA Adequate HL: 60 (7.5) -up: Completeness of follow Gender, %: NA Female: 56 Measurement tools including cutpoints: Limited HL: 55 REALM: Adequate HL: 40 -60) ≤8th (score of 0 Limited HL: Race/Ethnicity, %: ≥9th (score of 61 Adequate HL: -66) Total: White: 66 Black: 32 American IndiaNAlaskan native: 1 Asian: 1 Hispanic Ethnicity: 1 Limited HL: White: 48 Black: 52 Adequate HL: White: 73 Black: 24 American IndiaNAlaskan native: 1 Asian: 1 Hispanic Ethnicity: 1 Income, %: Total: ≤$15,000: 65 $15,000-30,000: 19 >$30,000- 50,000: 9 >$50,000-75,000: 2 >$100,000- 150,000: 1 Don't know/refused: 4 D-158

443 Table 1. Key Question 1: Health literacy outcome studies (continued) Evidence Outcomes Results Main outcomes: Describe results: -efficacy or being Literacy was not associated with reported self Colorectal cancer screening Self -efficacy (FOBT and colonoscopy) up to date with CRC testing. Effect in no exposure (i.e., adequate literacy) or control group: Appropriate receipt of CRC screening (FOBT, colonoscopy, sigmoidoscopy) -efficacy, mean (SD): Self Covariates used in multivariate analysis: FOBT: 3.93 (0.34) Colonoscopy: 3.99 (0.32) Age Up -to -date CRC screening, %: 65.7 Sex Effect in exposure (i.e., low/moderate literacy) or intervention: Race Self Insurance status -efficacy, mean (SD): Description of outcome measures: FOBT: 3.87 (0.41) -efficacy for obtaining and Colonoscopy: 3.92 (0.39) Perception of self Up -to -date CRC screening, %: 51.7 completing FOBT measured through 8 questions. Difference: Perception of self efficacy for obtaining and Self commpleting colonoscopy meas ured through 13 -efficacy difference (adjusted): = 0.44) FOBT: ( P questions regarding a respondent's ability to = 0.52) P Colonoscopy: ( schedule a colonoscopy, complete the preparation Up -date CRC screening difference (adjusted), OR (CI): 0.67 -to for colonoscopy and overcome (0.24-1.83) Any concerns about the test. Responses to self - efficacy statements were on a five-point Likert scale strongly disagree to 5=strongly ranging from 1= agree. Perception scale was validated Up to date on CRC testing: either FOBT in last year, colonoscopy at any time or flexible sigmoidoscopy in the last 5 years. Data source(s) for outcomes: Structured interview (in person or telephone) Attempts for control for confounding: Multivariate regression to control for potential confounding from demographic characteristics Blinding: NA Statistical measures used: Bivariate analyses Multivariate linear regression to estimate the effect of HL on reported self -efficacy, controlling for sociodemographic variables. Logistic regression to estimate the effect of HL on receipt of CRC tests, controlling for sociodemograhics D-159

444 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Limited HL: Author, year: 63 Peterson et al., 2007 ≤$15,000: 79 (continued) $15,000-30,000: 14 >$30,000- 50,000: 3 Don't know/refused: 3 Adequate HL: ≤$15,000: 59 $15,000-30,000: 21 >$30,000- 50,000:11 >$50,000-75,000: 3 >$100,000- 150,000: 1 Don’t know/refused: 4 Insurance status, %: Total: Medicaid: 56 Medicare: 11 Both: 32 Limited HL: Medicaid: 34 Medicare: 14 Both: 52 Adequate HL: Medicaid: 64 Medicare: 10 Both: 24 Education, %: Total: ≤8th: 14 -12th: 44 > 9th 12th: 41 Limited HL: ≤8th: 38 -12th: 48 9th >12th: 14 Adequate HL: ≤8th: 4 9th -12th: 43 >12th: 53 Other characteristics: Health literacy/numeracy levels, %: Limited HL: 29 Adequate HL: 71 D-160

445 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 64 Included: al., 2007 Powell et Research objective: Type 2 diabetes Explore relationship among health literacy and Excluded: ' readiness to take health actions patients Not able to complete study materials independently among individuals with type 2 diabetes. Sampling strategy: Study design: Convenience -sectional Cross Sample size: Study setting: 68 General internal medicine clinic that Age, median (IQR): predominately serves a low -income, medically 60) 55 (51- underserved population Gender, %: Measurement period: Males: 21 tudy period (specific month not 1-month s Race/Ethnicity, %: specified) AA: 66 -up duration: Follow Income: NA NR -up: Completeness of follow Insurance status: NA NR Measurement tools including cutpoints: Education, %: REALM: <4th grade: 4 <4th grade -6th grade: 10 4th -6th grade 4th grade: 13 7th -8th 7th -8th grade >9th grade: 72 High school Other characteristics, median (IQR): Years with diabetes: 7 (3 -15.5) Most recent A1C, %: 8.24 (7.6 -10) Health literacy/numeracy levels, %: REALM: < 4th grade: 13.2 4th -6th grade: 25 7th -8th grade: 19.1 High school: 42.6 D-161

446 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: No significant relationship between Diabetes Health Belief Diabetes Health Belief Model scale score teracy was clinically and Most recent hemoglobin A1C level Model scale score and HL. Lower li Covariates used in multivariate analysis: statistically significant in predicting H1C levels. Effect in no exposure (i.e., adequate literacy) or control group: Education Age Diabetes Health Belief Model Score, mean (SD): Race HS: 42.0 (4.5) knowledge 7th -8th grade: 41.2 (3.9) Diabetes -6th grade: 38.8 (3. 9) Most recent A1C 4th Description of outcome measures: Median HbA1C%: 11- HS: 7.9 Diabetes Health Belief Model scale score - question health beliefs questionnaire that -8th grade: 9.6 7th 4th -6th grade: 8.3 operationalizes the Health Belief Model for Effect in exposure (i.e., low/moderate literacy) or intervention: individuals with diabetes. Patients read questions n Likert scale regarding their belief in Diabetes Health Belief Model Score: and respond o <4th grade, mean (SD): 37.7 (4.8) a given statement regarding diabetes and its management. Median HbA1C (IQR): <4th grade, %: 8.3 (7.7-9.3) Most recent hemoglobin A1C level - an indicator of patient's current level of glycemic control ference: Dif Difference in Health Belief Model Scores across HL levels Data source(s) for outcomes: = 0.29) P (adjusted): ( -report Diabetes Health Belief Model: self Difference in Hemoglobin A1C across HL levels (adjusted): ( P A1C: medical record = 0.02) Attempts for control for confounding: Multivariate analysis Blinding: NR Statistical measures used: Relationship between Diabetes Health Belief Model and HL was measured using bivariate analysis and linear regression for the multivariate analysis. Relationship between A1C and HL was measure using bivariate analysis and linear regression for the mutlivariate analysis. D-162

447 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 65 Included: Powers et al., 2008 Research objective: -9 codes (401.0, 401.1, or Diagnosis of hypertension based on ICD Examine association between literacy and 401.9) blood pressure in pri mary care patients with A filled prescription for hypertensive meds in previous year hypertension and to determine if relationship Excluded: was consistent across 2 distinct healthcare Spouse participating in study delivery systems. Not living in 8 county catchments area Study design: Receiving kidney dialysis -sectional Cross ient of an organ transplant Recip Study setting: Planning a pregnancy Primary care clinics in VAHS and UHS in Hospitalization for stroke Durham, NC. Myocardial infarction Measurement period: Coronary artery revascularization in prior 3 months March 2002 to April 2003 VAHS: Metastatic cancer UHC: May 2004 to December 2005 Dementia Follow -up duration: Residence in nursing home or receiving home healthcare NA Difficulty speaking or understanding English -up: Completeness of follow Severe hearing or speech impairment NA Sampling strategy: Measurement tools including cutpoints: Convenience REALM Sample size: 60): limited < 9th grade (score of 0 - 1224 - 66): adequate ≥ 9th grade (score of 61 Age (range): 62.3 yrs (21-92) Gender, %: Female: 35 Race/Ethnicity, %: White: 52.5; Black: 47.2 Income, %: Adequate: 80; Inadequate: 20 Insurance st atus: NR Education, %: 0 - 9th grade:10.6 10th - 12th grade: 32.7 Some College/Vocational: 25 College graduate: 31.7 Other characteristics: making score Participatory decision- VAHS, mean (SD): 26.0 (5.6) UHS, mean (SD): 26.1 (5.0) Health literacy/numeracy levels: VAHS, %: Limited: 38.4; Adequate: 58.3 UHS, %: Limited: 27.5; Adequate: 72.5 D-163

448 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Descr Main outcomes: ibe results: Not sig difference between limited and adequate literacy in SBP DBP relation to SBP. However, interaction between literacy and Covariates used in multivariate analysis: healthcare system was sig suggesting larger differences in SBP according to literacy level for patients in UHS than VAHS. Age Similar interaction effects were not found in relation to DBP or Race BP control. Marital status Effect in no exposure (i.e., adequate literacy) or control group, Education Adequacy of income mean (SD): Diabetic status VAHS – SBP: 138.4 (17.5) Medication Adherence UHS – SBP: 133 (17.6) VAHS – DBP: 75.5 (11.1) Smoking UHS – DBP: 77.2 (10.6) Exercise VAHS in control: 141 (41.1) Participatory decision- making score - BP UHS Description of outcome measures: - BP in control: 237 (51.4) Blood pressure readings were abstracted from Effect in exposure (i.e., low/moderate literacy) or intervention, individuals' medical record at the time of study entry. mean (SD): Clinic nurses using standard automated devices – SBP: 138.7 (17.8) VAHS obtained the patient's resting seated BP prior to their – SBP: 142 (24.9) UHS visit with the primary care provider. – DBP: 75.5 (11.9) VAHS Data source(s) for outcomes: – DBP: 79.7 (11.8) UHS Medical record abstraction VAHS 8) - BP in control: 99 (43. Attempts for control for confounding: - BP in control: 76 (43.4) UHS Multiple linear regression Difference: P = -2.3), -4.8 -1.2 ( Difference in systolic BP (adjusted), β (CI): Blinding: NA NS Statistical measures used: Difference in systolic BP (adjusted): Literacy by Healthcare Multiple linear regression: relationship between system (interaction), ( ≥ 9th grade and VAHS, ref): 7.4 (2.5 - 12.3), = 0.003 P literacy and healthcare system with the primary outcome SBP after controlling for potential confounders. An interaction term of literacy and health system was included in the model to test whether association between literacy and SBP differed across healthcare systems. Logistic regression used to examine relationship between literacy and healthcare system on DBP and BP control outcome. D-164

449 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 66 Raehl et al., 2006 Included: Research objective: Conversational English To test whether the REALM and sTOFHLA are Adequate hearing ription predictors of intended oral presc Age 65+ years medication adherence among older adults Corrected vision of 20/200 or better Study design: Excluded: -sectional Cross -English speaking Non Study setting: Inadequate corrected vision or hearing 3 Comprehensive retirement communities and Alexia an adult day care center, Amarillo TX -reported diagnosis of Alzheimer's disease or dementia Self Measurement period: Sampling strategy: 1-time assessment, date not reported NR -up duration: Follow Sample size: NA 57 Completeness of follow -up: Age (range) (SD): NA 79.49 (65-91) (7.26) Measurement tools including cutpoints: Gender, %: REALM: Females: 72 < 3rd grade (0-18) Race/Ethnicity, %: 4th -6th grade (19-44) White: 81 7th -8th grade (45-60) Hispanic: 9 > 9th grade (61-66) AA: 5 sTOFHLA: Other: 5 Inadequate (0-16) Income: Marginal (17-22) NR Adequate (23-36) Insurance status, %: Received Medicaid in last 10 years: 25 Education, (range) (SD): 11.33 years(0- 17) (3.88) Other characteristics: Geriatric Depression Scale (GDS), (SD), range: 10.39 (6.90), 0-26 MMSE: 25.14 (3.56), 16-30 Former occupation professional/technical, %: 42 Married, %: 26 Owned a car in last 10 years, %: 77 Received food assistance in last 10 years, %: 16 Lives alone, %: 66 Health literacy/numeracy levels, mean (SD) and range: REALM: 55.42 (18.25), 0- 66 sTOFHLA: 17.32 (13.14), 0 36 D-165

450 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: In multivariate model, participants with h igher REALM scores Medication adherence Covariates used in multivariate analysis: had sig higher scores on MedTake Test, measure of Age medication adherence (controlling for sTOFHLA score and educational achievement, among other variables). Relationship Gender between MedTake and STOFHLA was not sig. Marital status Effect in no exposure (i.e., adequate literacy) or control group: Education NR MMSE Effect in exposure (i.e., low/moderate literacy) or intervention: GDS NR Number of drugs Difference: Owned a car in last 10 years Composite MedTake Test (adjusted) Received Medicaid in last 10 years REALM (continuous), β: 0.666, P <0.01 each point increase in Received food assistance in last 10 years higher MedTake Test REALM score, participants had a 0.666 Manages medications indepe ndently score. Receives legal help β : <0.1, P = NS sTOFHLA (continuous), Active DNR Description of outcome measures: Medication adherence measured by the MedTake Test: pharmacist observes subject opening prescription medication containers and demonstrating intended medication taking ability for their own drugs; pharmacist gives score of 0-100% based on accuracy of dose, indication, regimen, and coingestion with food or water; total score is a composite mean of individual drug scores Data source(s) for outcomes: Patient demonstration Attempts for contr ol for confounding: Multivariate linear regression Blinding: NR Statistical measures used: Pearson's correlation, Cramer's V, Spearman rank correlation coefficient, multivariate linear regression D-166

451 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: criteria: Eligibility 67 Included: Rothman et al., 2006 Research objective: 80 Adult patients 18- Examine relationship between health literacy Excluded: and the understanding of food labels. Poor vision Study design: Dementia -sectional Cross Psychiatric illness Study setting: -English speaking Non Academic primary care clinic Sampling strategy: Measurement period: Convenience April 2005 June 2004 - Sample size: -up duration: Follow 200 NA Age, mean (SD): Completeness of follow -up: 43 (14.6) NA Gender, %: Females: 72 Measurement tools including cutpoints: Race/Ethnicity, %: REALM to measure literacy White: 67 ≥HS level (9th grade or above) Black: 25 WRAT -3 to measure numeracy Other: 8

452 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Main Outcome of this study is comprehension of Lower literacy and numeracy skills sig associated with poorer labels, which is not a relevant outcome for nutrition performance on NLS, controlling for potential confounders. No this review. However, descriptive analysis measure statistically sig difference existed in presence of chronic other outcomes by HL: disease, obesity or reading food levels between higher and Chronic illness lower literacy or numeracy. Effect in no exposure (i.e., adequate literacy) or control group, Obesity %: Read food labels Literacy: Covariates used in multivariate analysis: Chronic illness: 38 Age Obese: 43 Gender Read food labels: 89 Race/ethnicity Numeracy: Income Chronic illness: 35 Education Insurance status Obese: 40 Presence of chronic disease Read food labels: 93 Status of being on a specific diet in exposure (i.e., low/moderate literacy) or intervention, Effect %: Label reading frequency Literacy: Description of outcome measures: Chronic illness: dichotomous variable indicating if Chronic illness: 52 patient had a chronic illness that required dietary Obese: 53 restriction, includes hypertension, coronary artery Read food labels: 87 Numeracy: disease, high cholesterol, diabetes, and heart Chronic illness: 44 failure. Obese: 48 Obese: BMI ≥30, dichotomous Read food labels: 86 Read food labels: dichotomous Difference: NLS: questions related to understanding real food Literacy: labels, both literacy and numeracy evaluations < 0.001 P Difference in NLS score (adjusted): data NR, for outcomes: Data source(s) Difference in percent with chronic illness (unadjusted): Self report P ( = 0.08) Attempts for control for confounding: Difference in percent obese (unadjusted): ( P = 0.31) Yes in relation to NLS P = 0.71) Difference in percent reads food labels (unadjusted): ( Blinding: Numeracy: NR < 0.001 Difference in NLS score (adjusted): data NR, P Statistical measures used: Difference in percent with chronic illness (unadjusted): t-tests P = 0.20) ( Wilcoxon rank -sum tests for continuous variables = 0.30) P Difference in percent obese (unadjusted): ( Fisher's exact test or Chi square test for categorical = 0.11) P Difference in percent reads food labels (unadjusted): ( variables Multin omial logistic regression D-168

453 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 68 Included: Schillinger et al., 2006 Research objective: Visited 1 of 2 primary care clinics in prior 12 months Determine whether literacy mediates At least 1 visit to primary care physician in prior 6 months relationship between education and glycemic Had recorded HbA1C in database control among diabetes patients. > 30 years old Study design: Spoke English or Spanish Cross sectional Type 2 diabetes Study setting: Excluded: Two primary care clinics at San Francisco -stage renal disease End General Hospital Psychotic disorder Measurement period: Dementia June - December 2000 Blindness w-up duration: Follo Sampling strategy: NA Convenience Completeness of follow -up: Sample size: NA 395 Measurement tools including cutpoints: Age (mean) (SD): s-TOFHLA 57.9 (11.4) no cut points, used as continuous variable Gender: NR Race/Ethnicity, %: Asian/Pacific Islander: 18.5 Black: 25.3 Hispanic: 42.3 White: 13.9 Income, %: Less than $5,000: 24.3 $5,000 - 9,999: 44.5 $10,000-<20,000: 21.8 $20,000-<30,000: 5.3 $30,000+: 4.1 Insurance status, %: None: 30.6 Me dicare: 37.0 Medi -Cal: 23.3 Commercial: 9.1 Education, %: Some high school or less: 46.8 High school/GED: 24.1 College/technical school: 29.1 Other characteristics, %: Primary language other than English: 51.7% Health literacy/numeracy levels, mean (SD): 20.6 (12.1) D-169

454 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: -income population with diabetes, literacy mediated In low HbA1C rela Covariates used in multivariate analysis: tionship between education and HbA1C. Ethnicity Effect in no exposure (i.e., adequate literacy) or control group: NR Primary language other that English Effect in exposure (i.e., low/moderate literacy) or intervention: Insurance Education NR Full mediation model: age, immigration status, type Difference: of health insurance Effect of education partially mediated through HL: t) of Literacy Score on Log HbA1C: (P < 0.05) Description of outcome measures: Difference (Effec HbA1C Higher literacy associated with greater glycemic control - measure of patients' glycemic control over approximately 3 month period. Effect of education fully mediated through HL: Difference (effect) of Literacy Score on Log HbA1C: ( = 0.03) P Mean (SD): 8.5 (1.9) Higher literacy associated with greater gl ycemic control Log transformed to correct for non-normal Both specifications including HL improved model. distribution. Data source(s) for outcomes: HbA1C - Value obtained from San Francisco General Hospital database, which used ion- exchange chromatography to measure HbA1C. Attempts for control for confounding: Multivariate analysis Blinding: NA Statistical measures used: Path Analysis: Analyses compared 2 competing models —a direct effects model and a mediational model —to explain patients' glycemic control. Direct effects model: relationship between educational attainment and HbA1C (w/out literacy). Mediational model: est imated strength of the direct relationshop between educational attainment and HbA1C when HL added into model to allow expression of a relationship between HL scores and HbA1C. D-170

455 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 69 Included: Sentell and Halpin, 2006 Research objective: NA Understand effect of adult literacy on Excluded: explanatory power of education and race in Below 18 years old predicting health status among US adults Blind Study design: Mentally retarded -sectional Cross Sampling strategy: Study setting: Random, nationally representative, with over sampling of AA and NALS administered in-person Hispanic Measurement period: Sample size: 1992 23,889 -up duration: Follow Age (mean and range), %: NA >25: 15 Completeness of follow -up: 25 to 34: 23 NA 35 to 44: 22 Measurement tools including cutpoints: 45 to 54: 14 Total NALS score combining prose, document, 55 to 64: 11 and numeracy domains 65+: 15 Level 1: <224 Gender, %: 274 Level 2: 225- Males: 48 Level 3: 275- 324 Race/Ethnicity, %: 374 Level 4: 326- White: 68 Level 5: 375+ Black: 18 Hispanic: 7 Other: 7 Income, %: <$5,000: 19 $5,000-9,999: 16 $10,000-14,999: 14 $15,000-19,999: 11 $20,000-29,999: 16 $30,000-39,999: 10 $40,000-49,999: 6 $50,000-74,000: 5 $75,000-99,999: 1 $100,000+: 1 Income missing: 23 Insurance status: Education, %: None: 1 Elementary: 1 Middle School: 7 Some High School: 15 GED/High School Diploma: 58 BA/BS: 13 Postgraduate: 6 D-171

456 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: keeps from work Higher HL is associated with lower odds of having condition Condition term illness. Long-term illness that keeps you from work as well as having long- Covariates used in multivariate analysis: Adding HL to the models predicting these two health status Race ures partially mediates the effect of race and reduces the meas Education size Understand English Effect in no exposure (i.e., adequate literacy) or control group: Born in USA. NR Unemployed Effect in exposure (i.e., low/moderate literacy) or intervention: NR Family income Missing Difference, OR (CI): Difference in having a condition that keeps you from work Sex (adjusted): 0.90 (0.88-0.92) Age Married Difference in having a long-term illness (adjusted): 0.96 (0.94- Get food stamps 0.98) Live in Metropolitan Statistical Area Difference in being black on having a condition that keeps you Region from work (adjusted): Model without HL: 1.54 (1.29- Description of outcome measures: 1.84) Model with HL: 1.04 (0.85- 1.26) Self -report: Condition keeps from work: "Do you have a physical, mental, or other health condition Difference in being black on having long-term illness (adjusted) Model without HL: 1.24 (1.03- 1.49) that stops your participation fully in work, school, housework, or other? Model with HL: 1.07 (0.89- 1.30) Long-term illness: Do you have a long-term illness (6 months or more)? ta source(s) for outcomes: Da - in person survey NALS Attempts for control for confounding: Multivariate analysis Blinding: NR Statistical measures used: Multivariate logistic regression Odds ratios represent the effect of a 10- point NALS literacy scale increase on the original compared to the level below it. D-172

457 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Part icipant Characteristics Study Description Author, year: Other characteristics, %: 69 Born in USA: 89 Sentell and Halpin, 2006 (continued) Unemployed: 7 Married living with spouse: 49 Food Stamps: 9 Live in Metropolitan Statistical Area: 77 Census region: Northeast: 21 Midwest: 24 South: 34 West: 21 teracy/numeracy levels, %: Health li Level 1: 20 Level 2: 27 Level 3: 34 Level 4: 18 Level 5: 2 D-173

458 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Eligibility criteria: 70 Inclusion: Sharif and Blank, 2010 bjective: Research o Children ages 6-19 To test the relationship between child health BMI >or= 85th percentile for age and sex literacy and BMI in overweight children Receiving primary care at study site Study design: Enrolled with one legal guardian Cross -sectional Exclusion: Study setting: Developmental impairment Primary care pediatrics Hemodynamically siginificant heart disease clinic in an inner city academiccommunity Neuromuscular disorders health center in the Bronx, NY Sampling strategy: Measurement per iod: Convenience NR Sample size: -up duration: Follow N = 78 Children from 69 families NA Age (mean and range), %: Completeness of follow -up: Median=11.5 ( 10-16) NA Gender, %: Measurement tools including cutpoints, %: NR STOFHLA Race/Ethnicity, %: Adequate HL: >or=23 AA: 35 Latino: 62 White: 3 Income, %: NR Insurance status, %: Medicaid: 78 Non -medicaid: 22 Education, %: Median (range) Grade school: 6 (5-11) Other characteristics, % (SD): Child BMI: 30.9 (5.1) Child BMI Z -score: 2.3 (0.4) Parental BMI: 33.3 (8.5) Parental education: < 12th grade: 24 12th grade: 40 >12th grade: 36 Child eating self -efficacy: 3.4 (1.0) Parent eating self -effiicacy: 3.1 (1.1) Health literacy/numeracy levels, %: Child STOFHLA (mean , SD): 22.9 (9.0) (52% adequate HL) Parental STOFHLA (mean, SD): 29.1 (8.6) (77% adequate HL) D-174

459 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: BMI -Z score Child health literacy was negatively and independently Covariates used in multivariate analysis: -Z score in overweight children. correlated with BMI Age Effect in no exposure (i.e., adequate literacy) or control group: NA Parental BMI Effect in exposure (i.e., low/moderate literacy) or intervention: Child -efficacy -eating self Child STOFHLA accounted for 13% of the relationship between -efficacy Parental eating self BMI Z -efficacy, child self -score and child age, parental BMI, Parental STOFHLA and child STOFHLA Description of outcome measures: value) P Beta scores ( BMI Z -scores calculated using weight, height, age, < 0.0001) P Child STOFHLA= -0.43 ( gender Chld eating self -efficacy= P -0.39 ( < 0.0001) Data source(s) for outcomes: Child age= = 0.055) -0.21 ( P Measured directly Parental BMI= 0.27 ( P = 0.006) Attempts for control for confou nding: Difference: Regression analysis Child BMI Z -score Blinding: For every one point incr ease in child's HL score (adjusted), the NR 0.025 to - -score decreased by 0.016 points (95% CL, - BMI Z Statistical measures used: Descriptive statisitcs followed by bivariate analysis 0.008) followed by a regression model D-175

460 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 71 Included: Shone et al., 2009 Research objective: Parents of children with persistent asthma, who began elementary Determine relationship between numeracy school within school district in 2006, 2007, or 2008 interpret levels and ability to correctly Excluded: treatment benefits No health literacy data Study design: Parent conducted interview in Spanish -sectional Cross Sampling strategy: Study setting: Convenience Rochester City School District in New York, Sample size: where over 40% of children live in poverty 499 Measurement period: Adequate HL: (n = 335) NR Low HL: (n = 164) -up duration: Follow Age (mean and range): NA Total: 7 years (3-10) Completeness of follow -up: Gender: NA NR including cutpoints: Measurement tools Race/Ethnicity, %: REALM: Total: Low HL: < 9th grade Black: 63.3 Adequate: ≥ 9th grade White: 12.4 Other: 24.4 Parent is: Hispanic: 21.9 Adequate HL Black: 67.2 White: 14.6 Other: 18.2 Low HL: Black: 55.5 White: 7.9 Other: 36.6 Income: NR Insurance status, %: Child has public insurance: Total: 87.4 Adequate HL: 85.3 Low HL: 91.9 Education: NR Other characteristics, %: Pare nt employed: Total: 65.8 Adequate HL: 72.7 Low HL: 51 D-176

461 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: -free days over two weeks Number of symptom In bivariate analyses, parent HL level was not related to Use of any urgent care in past yr diffe rent use of preventive asthma medicines or urgent care for health care need in past yr Unmet the child, or BMQ concerns for the child. In adjusted analyses, low HL did significantly predict perception of child's health as Parent experiences with reading/ filling out medical more likely to be fair/poor, greater worry about child's health, forms low er PACQoL, greater perceived need for asthma medicines, Parent perception of child's overall health lower expectations about asthma treatment, and perception of Parent perception of asthma control Covariates used in multivariate analysis: worse interactions with providers about the child’s asthma. HL Child health insurance and parent was not related to BMQ concerns. Employment, literacy) or control group, ethnicity, and race Effect in no exposure (i.e., adequate Description of outcome measures: %: -free days over 2 wks, use of Self -report: # symptom Used any preventive medicines: 66.9 any urgent care in past yr, unmet health care need Used any urgent care: 41.2 in past yr (parent had to delay or not get health care Any unmet health care need: 22.1 for child when parent felt care was needed; or delay Child's health is fair/poor: 17.3 or not get prescriptions for child when parent felt Worry more than other parents: 42.8 they were needed), parent experiences with reading/ Asthma is not under good control: 82.4 filling out medical forms ee days, mean (SD): 8.02 (4.76) Number of symptom fr Parent perception of child's overall health Parent quality of life, mean (SD): 5.41 (1.17) (excellent/good, fair/poor), parent perception of Treatment expectations, mean (SD): 3.06 (0.64) asthma control, and degr ee of parent worry about Interactions with provider, mean (SD): 4.14 (0.52) the child's health Parent beliefs about when to seek care, mean (SD): 3.83 (0.86) PACQLQ: parent -reported QoL, 13 items about icines, mean (SD): 16.56 (3.86) BMQ need for med impairment related to child’s asthma during past wk BMQ concerns, mean (SD): 14.17 (3.70) (emotional function and activity Items are scored on Effect in exposure (i.e., low/moderate literacy) or intervention, a 7-point Likert scale. %: ent Other subscales used to measure depend Used any preventive medicines: 71.3 variables (previously validated): Used any urgent care: 40.9 Perceived need for asthma meds (e.g., ‘‘My child’s Any unmet health care need: 18.9 life would be impossible without their controller Child's health is fai r/poor: 39 medicines’’) Worry more than other parents: 60.7 Parent beliefs about asthma meds (BMQ) (e.g., ‘‘My Asthma is not under good control: 75.6 child’s controller medicines are a mystery to me’’’) . Number of symptom free days, mean (SD): 8.01 (4.98) Higher scores greater need or concern. Parent quality of life (SD): 5.18 (1.36) Treatment expectations, degree of parent optimism Treatment expectations, mean (SD): 2.82 (0.62) or pessimism about child’s asthma treatment (e.g., an (SD): 3.85 (0.5) Interactions with provider, me ‘‘I expect that my child can fully participate in gym Parent beliefs about when to seek care, mean (SD): 3.90 (0.84) and normal physical activity") Higher scores more BMQ need for medicines, mean (SD): 18.15 (3.89) positive expectations. BMQ concerns, mean (SD): 14.80 ( 4.11) Ten items that describe parent perception of Difference: interactions with providers regarding child’s asthma. Difference (unadjusted): = 0.357) P Used any preventive medicines: ( Higher scores represent greater worry or concern. P any urgent care: ( Used > 0.999) Four items measuring parent beliefs about when to = 0.483) P Any unmet health care need: ( seek care for child’s asthma. Higher scores indicate Asthma not under good control: ( P = 0.094) greater inclination to seek care P = 0.99) Number of symptom free days: ( Data source(s) for outcomes: = 0.353) P Parent beliefs about when to seek care: ( In-person interviews during home visits (CI): 0.69 ( β Difference in BMQ concerns, Std. -0.21- 1.35) Attempts for control for confounding: Multivariate regression D-177

462 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Health literacy/numeracy levels, %: Author, year: 71 Shone et al., 2009 Adequate: 67 (continued) Low: 33 Health literacy/numeracy levels, %: Adequate: 67 Low: 33 D-178

463 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Difference (adjusted): Blinding: Child's health is fair/poor, OR (CI): 3.96 (2.4- 6.4) NR Worry more than other parents, OR (CI): 1.85 ( 1.2 -2.8) -0.097 ( Statistical measures used: - -0.004) -0.51 Parent quality of life, Std. β (CI): -test) to identify - -0.7) -0.3 -0.15 ( (CI): β Treatment expectations, Std. Bivariate analyses (chi -square and t -0.2 ( -0.3 - -0.1) associations between parent HL and dependent Interactions with provider, Std. β, (CI): measures. BMQ need for medicines, Std. β (CI): 0.15 (0.4 -0.2) Multivariate logistic and linear regression analyses MQ concerns, Std. Difference in B 1.35) -0.21- (CI): 0.69 ( β of dependent variables that were sig in bivariate analyses at a level of P <0.10. D-179

464 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 72 Included: Smith and Haggerty, 2003 Research objective: 18-85 years old Assess whether health literacy is associated Had clinical encounters in English -perceived health status with self Excluded: Study design: Too ill Cro sectional ss- Poor vision Study setting: Sampling strategy: University -affiliated family practice center in Convenience sample Montreal, Canada Sample size: Measurement period: 229 December 1997 November 1997 - Low, n = 15 Follow -up duration: Adequate, n = 214 NA Age: Completeness of follow -up: Mean: 47 NA 18-85 Range: Measurement tools including cutpoints: Gender, %: REALM Females: 61 Low: 44) ≤ 6th (0 - Race/Ethnicity: Adequate: > 6th grade (45+) NR Income: NR Insurance status: NR Education, mean: 13.5 years Other characteristics, %: Maternal language: English: 51 French: 12 Other: 37 Current smoker: 26.6 Health literacy/numeracy levels, %: Low: 6.5 Ade quate: 93.5 D-180

465 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Perceived general health Perceived general health was not significantly different between literacy groups. Covariates used in multivariate analysis: Age Effect in no exposure (i.e., adequate literacy) or control group: Smoking status Perceived overall health: (mean score): 3.0 Maternal language Effect in exposure (i.e., low/moderate literacy) or intervention: Perceived overall health (mean score): 3.3 Description of outcome measures: Difference: COOP/WONCA Charts, based on Nelson's COOP P Charts, measure primary care patients' perceptions erceived general health (adjusted), β (CI): 0.03) -0.25- of their overall health and well -being. Each category -0.11 ( P Not sig at < 0.05 is illustrated with a pictogram and accompanying qualitative words. Patients are asked to rate each health dimension during the last two weeks on a scale from 1 (excellent) to 5 (poor). To differentiate between current and overall health, they also asked patients to rate their health "today." Has been validated against other measures. Perceived overall health measured on a scale from 1 excellent - 5 poor Data source(s) for outcomes: In person interview administered by study staff Attempts for control for confounding: Multivariable linear regression Blinding: No Statistical measures used: analysis and multivariable linear Correlation regression controlling for observed confounders. To -literacy patients, multivariable modeling profile low used to find the best explanatory model D-181

466 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Eligibility criteria: 73 Sudore et al., 2006 Included: 74 (companion: Sudore et al., 2006 ) Medicare eligible Research objective: Community dwelling Assess relationship between limited literacy 79 Age 70- and mortality in elders. Residence in designated study zip codes Study design: Excluded: Prospective cohort, retrospective analysis Difficulty walking one quarter of a mile Study setting: Difficulty climbing a flight of stairs 79 year olds including Random sample of 70- Difficulty performing basic activities of daily living white Medicare beneficiaries and black Cinical dementia residents in designated ZIP code areas Inability to communicate with the interviewer surrounding U of Pitt sburgh and U of Sampling strategy: Brochures mailed to random sample of residents in designated zip Tennessee, Memphis codes; then all eligible residents were contacted by phone to request Measurement period: participation. Recruited: 3,075, of these, 563 HL not assessed for Baseline exam: May 1997-June 1998 various reasons Literacy assessment: 1999 Sample size: Mortality data: July 1999-August 2004 2,512 Follow -up duration, mean, median: Age, mean, range (SD): 5.1 years, 4.2 years 75.6, 71-82 (2.8) Completeness of follow -up: Gender, %: NR Female: 52.0 tools including cutpoints: Measurement Male: 48.0 REALM: Race/Ethnicity, %: < 3rd grade (0-18) Black: 38.1 4th -6th grade (19-44) Income, %: -8th grade (45-60) 7th > $50,000: 17.5 > 9th grade (61-66) $25,000-$50,000: 33.3 $10,000-$25,000: 37.4 <$10,000: 11.9 Insurance status, %: Lack insurance for medications: 36.0% Education, %: Postgraduate: 12.9 College: 13.1 Vocational/some college: 23.9 High school: 27.8 < High school: 22.1 Health literacy/numeracy levels, %: Limited literacy (<9th grade): 23.7 ≥9th grade): 76.3 Adequate literacy ( D-182

467 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Compared to participants with adequate literacy, those with -cause mortality All Covariates used in multivariate analysis: limited literacy had a higher risk of death in fully adjusted and Demographics: age, race, gender, income, ed. partially adjusted models. Similar results were found in sub- -rated health, cardiac disease, Health status: self populations identified by race, sex, and income. stroke, cancer, hypertension, Effect in no exposure (i.e., adequate literacy) or control group, Diabetes, obesity. %: Health-related behaviors: Either f ormer smoker Adequate literacy, died: 10.6 (>100 cigarettes in lifetime) or current smoker Effect in exposure (i.e., low/moderate literacy) or intervention, %: Drinking >1 alcoholic beverage per day Poor health care access: lack of a regular doc or Limited literacy, died,: 19.7 clinic, no flu shot within the past 12 months, no ins Difference: Association between HL and mortality (adjusted): to cover meds Partial adjustments, HR (CI): ymptoms, Psychosocial status: high depressive s Demographics: 1.83 (1.34-2.50) poor personal mastery Health status: 1.86 (1.47-2.35) Description of outcome measures: All -cause mortality 2.67) Health-related behaviors: 2.12 (1.69- Poor health care access: 2.01 (1.59-2.55) Data source(s) for outcomes: -2.47) -cause mortality identified by: Poor psychological status: 1.96 (1.56 All Notification of death during attempts to contact Fully adjusted: 1.75 (1.27-2.41) Adjusted, after excluding participants with incident cognitive participants or by proxy, spouse, relative, or friend Hosp impairment, HR (CI): ital records Local obituaries 2.74) 1.94 (1.37- Sub -population analysis: association between HL (0-8th grade Social Security Death Index data vs. higher) and mortality (unadjusted), HR (CI): (all deaths subsequently confirmed by White: 2.36 (1.63-3.42) Attempts for control for confounding: Multivariable logistic regression Black: 1.66 (1.28-2.29) Blinding: Men: 2.01 (1.51-2.67) NR Women: 1.77 (1.20-2.62) ≥HS: HR, 2.27 (1.67 -3.09) Statistical measures used:

468 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 74 Sudore et al., 2006 Included: 73 (Companion: Sudore et al., 2006 ) Medicare eligible Research objective: speaking English- Determine relationship between health -dwelling Community literacy, demographics and access to health Part of health ABC Study care Excluded: Study design: -reported difficulty walking 1/4 mile Self -sectional (participants part of larger Cross Climbing a flight of stairs -Health ABC Study) prospective cohort study Performing basic activities of daily living Study setting: Clinical dementia In-clinic assessment in Memphis (49%) and Sampling strategy: Pittsburgh (51%) areas All persons in ABC study who participated in the clinic interview -functioning, Medicare recipients living in Well Sample size: e sources of the community with multipl 2,512 medical care Age (mean and range) (SD): Measurement period: 76 (2.8) One time (1999/2000) Range: 71-82 Follow -up duration: Gender, %: NA Males: 48 Completeness of follow -up: Race/Ethnicity, %: NA Black: 38 Measurement tools including cutpoints: White: 62 REALM: Income, %: 0-6th grade <$10,000: 12 7-8th grade Insurance status, %: ≥9th grade Medicare eligible: 100 Education, %:

469 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Health status Those with lower HL had significantly wor se health status in Poor health unadjusted analyses. including poor health, hypertension, Hypertension diabetes, obesity, and depression In relation to access to health care measures, lowest literacy Diabetes Obesity group had significantly less access than the highest literacy group on 3 out of Depression 4 measures. 7th-8th grade literacy group did Access to care including: not differ significantly from higher literacy group in any access measures No doctor/clinic 6th grade versus ≥9th grade sig after education Outcomes for 0- No influenza shot in 12 months added to the models. No insurance for medication Effect in no exposure (i.e., adequate literacy) or c ontrol group, Composite access measure is any of the 3 above %: ariate analysis: Covariates used in multiv >9th grade Demographics (age, race, sex, income) Health Status: Study site Poor health: 13.9 Self -rated health status Hypertension: 54.7 Comorbidities (cardiac disease, stroke, cancer, Diabetes: 14.6 hypertension, diabetes, obesity, high depressive Obesity: 23.0 symptoms) Depression: 1.6 Description of outcome measures: Access: Dichotomous for yes/no outcomes No doctor/clinic: NR Data source(s) for outcomes: No influenza shot in 12 months: NR Health status measured through self -reported No insurance for medications: NR physician diagnosis, clinical data, and medication Composite access measure: NR use. Effect in exposure (i.e., low/moderate literacy) or intervention, Obesity measured through BMI. %: Depression measured through CES -D 7th -8th grade Survey self report Health Status: Attempts for control for confounding: Poor health: 28.0 Multivariate analysis Hypertension: 63.2 Blinding: Diabetes: 25.6 NR Obesity: 32.1 Statistical measures used: Depression: 2.9 Analysis of variance for continuous variables Access: Chi -square for dichotomous variables No doctor/clinic: NR Logistic regression for multivariate analysis No influenza shot in 12 months: NR No insuranc e for medications: NR Composite access measure: NR 0-6th grade Health Status: Poor health: 32.6 Hypertension: 61.8 Diabetes: 24.5 Obesity: 29.3 Depression: - 5.7 Access: No doctor/clinic: NR No influenza shot in 12 months: NR No insurance for medications: NR Composite access measure: NR D-185

470 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: 74 Sudore et al., 2006 73 (Companion: Sudore et al., 2006 ) (continued) D-186

471 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Difference: Poor health (unadjusted): 0-6th and 7-8th grade versus ≥ 9th grade: OR, 2.60, 95% CI, 2.09- 3.23 Hypertension (unadjusted): 0-6th and 7-8th grade versus ≥ 9th grade, OR (CI): 1.39 (1.25 - 1.68) Diabetes Mellitus (unadjusted): 0-6th and 7-8th gr ade versus ≥ 9th grade, OR (CI): 1.98 (1.58 - 2.48) Obesity (unadjusted): 0-6th and 7-8th grade versus ≥ 9th grade, OR (CI): 1.51 (1.23 - 1.85) Depression (unadjusted): 0-6th and 7-8th grade versus ≥ 9th grade, OR (CI): 2.54 (1.47 - 4.42) Access: No doctor/clinic (adjusted), OR (CI): 0-6th grade versus ≥ 9th grade: 1.27 (0.69 -2.33) 7-8th grade versus ≥ 9th grade: 1.11 (0.67 -1.86) No influenza shot in 12 months (adjusted), OR (CI): 0-6th grade versus ≥ 9th grade: 1.70 (1.20 -2.41) 7-8th grade versus ≥ 9 th grade: 1.06 (0.80-1.41) No insurance for medication (adjusted), OR (CI): 0-6th grade versus ≥ 9th grade: 1.73 (1.23 -2.43) 7-8th grade versus ≥ 9th grade: 1.03 (0.80 -1.33) Composite access measure (adjusted), OR (CI): 0-6th grade versus ≥ 9th grade: 1.95 (1.33-2.85) 1.23) 7 - 8th grade versus ≥ 9th grade: 0.95 (0.74 - D-187

472 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 75 Tang et al., 2008 Included: Research objective: Type 2 DM Determine if health literacy is associated with ≥18 HbA1C levels Able to read and wrote Chinese Study design: Able to give informed consent Cross nal survey -sectio Excluded: And medical chart review < 20/100 vis ion Study setting: Unintelligible speech Diabetes education management Overt psychiatric illness Center of a public hospital in Hong Kong Sampling strategy: Measurement period: Convenience 30 min interviews from Sept 2005 to Feb 2006 Sample size: Follow -up duration: 149 NA Age (range): Completeness of follow -up: 59.8 (27-90) NA Gender, %: Measurement tools including cutpoints: Females: 45.6 -TOFHLA Chinese S Race/Ethnicity: (validation part of the study) NR (assumed 100% Chinese) 58 Inadequate: 0- Income: Marginal: 59- 66 NR Adequate: 67-100 Insurance status, %: No insurance: 66.4 %: Education, No formal:12.8 Primary: 43 Junior secondary: 28.9 Senior secondary: 10.7 ≥ College: 4.7 Other characteristics, %: Receiving diabetes education: 63.1 Diabetes treatment: Diet only: 8.7 Diet and oral anti -diabetic drug (OAD): 85.2 Diet, OAD and insulin therapy: 2.7 Diet and insulin therapy: 3.4 Health literacy/numeracy levels: NR D-188

473 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Higher HL was significantly associated with lower HbA1C levels HbA1C in adjusted model. Covariates used in multivariate analysis: Effect in no exposure (i.e., adequate literacy) or control group: Gender NR Insurance Effect in exposure (i.e., low/moderate literacy) or intervention: Duration of diabetes NR Patient awareness score Difference: C-SDSCA (management of diabetes) 0.12, HbA1C level (adjusted): B, - < 0.001 P Description of outcome measures: HbA1C Data source(s) for outcomes: Medical records Attempts for control for confounding: Univariate analysis of variables associated with followed by step-wise multivariate HbA1C regression analysis Blinding: NA Statistical measures used: Univariate: Spearman's coefficient (rs) was used to examine whether there was an association between health literacy, complication awareness factors and level HbA1C Multivariate: Stepwise regression analysis to examine factors predictive of patients' HbA D-189

474 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characterist ics Author, year: Eligibility criteria: 76 Torres and Marks, 2009 Included: Research objective: NR Examine relationships among heal th literacy, Excluded: -efficacy, and behavioral intent concerning self NR hormone therapy. Sampling strategy: Study design: Convenience Cross -sectional Sample size: Study setting: 106 Nagle Family Health Center, Washington Age, mean (SD): Heights/Inwood section of New York City 52.58 (5.35) Measurement period: Gender: August to September, 2005 Females: 100% Follow -up duration: Race/Ethnicity, %: NA Hispanic: 75 Completeness of follow -up: White: 23 NA Black: 2 Measurement tools including cutpoints: Income: NR sTOFHLA: Insurance status: NR 16 Inadequate: 0- Education, %: 22 Marginal: 17- Elementary school: 13 Adequate: 23-26 High School or GED: 60 Some college: 19 Bachelor's degree: 4 No response: 4 Other characteristics, %: Length of time with current providers: Less than one month: 1 1-6 months: 14 7-11 months: 44 1-2 years: 35 3-5 years: 4 More than 5 years: 1 No response: 1 Discussion about hormone therapy with provider: Yes: 9 No: 37 Don’t recall/No response: 54 status: Marital Married: 52 Single: 8 Widowed: 10 Divorced or separated: 30 Health literacy/numeracy levels, %: Mean (SD): 19.66 (7.15) Inadequate: 46 Marginal: 18 Adequate: 36 D-190

475 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Self -Efficacy (SD): 26.85 (7.81) A statistically significant (unadjusted) positive correlation between health literacy and self -efficacy was observed. Behavioral intent regarding hormone therapy In adjusted model, self -efficacy and health literacy explain 75% Covariates used in multivariate analysis: of variance in behavioral intent, controlling for age, knowledge Age one therapy, education, marital status, and race. of horm Current knowledge of hormone therapy Effect in no exposure (i.e., adequate literacy) or control group: Education Marital status NR Race Effect in exposure (i.e., low/moderate literacy) or intervention: Description of outcome measures: NR Difference: Self -efficacy: 11 question scale rating self - confidence or belief in one's ability to make Self efficacy correlated with health literacy (unadjusted): 0.70, < 0.01 P decisions Behavioral intent: Health literacy explains 9% of R2 variance Behavioral intent concerning hormone therapy: 0- 10 when entered as step 2 of stepwise regression after self - scale rating certainty with which woman would < 0.05). Direction of P efficacy explained 66% (adjusted): ( choose hormone therapy relationship not presented. Data source(s) for outcomes: Survey questionnaire Attempts for control for confounding: Multivariate analysis Blinding: NR Statistical measures used: Bivariate correlations Pearson's correlation tests Stepwise regression D-191

476 Evidence Table 1: Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Eligibility criteria: 77 Included: von Wagner, 2009 Research objective: Aged 50-69 years Aimed to document association between No prior participation in the screening health literacy and willingness and ability to Excluded: seek information about new CRC screening NR -efficacy program in UK. Aimed to assess self Sampling strategy: for sc reening to determine impact of health lit Investigators invited 144 members from Health Behavior Research Study design: Centre Participant Panel; 86 (60%) agreed to participate; 12 Cross -sectional participants recruited by snowballing from primary recruits Study setting: Sample size: Study sessions were conducted in a private Total Sample: 96 room at the Department of Epidemiology, 144 Recruited from Participant Panel, 86 agreed to participate University College London 12 From snowball sample Measurement period: 2 Excluded (prior screening participation; over age 70) Participants reported on key demographi c Age, mean (SD), range, median: characteristics (age, gender, education, Table 54.2 (4.3) - employment, race and ethnicity) 59.8 (4.3) - In text Information seeking: Participants read Range: 52-69 information about the UK CRC screening Median: 59 program and FOBT screening kit using an Gender, %: interactive com Females: 66.7 -up duration: Follow Race/Ethnicity, %: NA Non -white: 19.8 -u p: Completeness of follow Income: NA NR Measurement tools including cutpoints: Insurance status: UK -TOFHLA NR Education, %:

477 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Information seeking: number of times participants Information-seeking (unadjusted): accessed information links in an interactive # links open (SD): 7.19 (3.25) computer menu Range: 0-11 Effort (average reading time per information link): Median: 7 Divided the total amount of time participants spent in Participants wi th lower health literacy scores opened fewer = 0.07 P links, r = 0.18, the information menu by the number of Covariates used in multivariate analysis: Processing Effort (unadjusted), mean (SD): Demographics (age, gender, ethnicity and Reading time per link: 00:34 (00:25) employment status) Range: 00:13-02:52 Description of outcome measures: Median: 00:25 Information seeking: numerical count Health literacy scores were significantly associated with Effort: numerical average reading time; participants with lower health literacy scores took < 0.001 P longer to read individual informational links, r= - 0.57, Comprehension: composite scale (3 questions Comprehension (unadjusted), mean (SD): inal analyses b/c >80% answered excluded from f CRC screening knowledge 3.30 (1.64) them correctly) Range: 0-7 -efficacy: 5 -point ordinal scale (1=strong Self Median: 3 disagree 5=strong agree) No significant association between health literacy and CRC Data source(s) for outcomes: = 0.64 screening knowledge, r = -0.05, P Information seeking: computer clicks (clicking on Self -efficacy (unadjusted), mean (SD): links pops up new windows) Perceived ability to take part in BCSP 17.85 (2.03) -effica Comprehension and self -report cy: survey self Range: 9-15 Attempts for control for confounding: Median: 18.5 [reported range and median seem questionable Multivariate linear regression given median is larger than upper bound of range] Blinding: Health Literacy is significantly associated with self -efficacy, r = NA 0.33, ( < 0.001) P Statistical measures used: Information seeking (adjusted), β (CI): Bivariate analyses Participants with lower health literacy opened fewer links: 0.079 Multivariate linear regression (0.001- 0.157) Dichotomized race and ethnicity (white vs. non- Effort (adjusted), β (CI): white) and employment status (employed vs. retired Participants with lower health literacy take more time per link, β or unemployed) in multivariate analyses -0.473) -1.457- (CI): -0.965 ( Tested for impact of outliers (defined as standard Self - efficacy for CRC screening participation (adjusted), β (CI): residuals >2) Performing well on the UK -TOFHLA was predictive of higher self -efficacy for participating in CRC screening: 0.041 (0.007- 0.076) Effect in no exposure (i.e., adequate literacy) or control group: NA Effect in exposure (i.e., low/moderate literacy) or intervention: NA Difference: NA D-193

478 Evidence Table 1. Key Question 1: Health literacy outcome studie s (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 56 Waite et al., 2008 Included: 54 (companions: Osborn et al., 2007 ; Wolf et Receiving one or more antiretroviral medications 55 ) al., 2007 Excluded: Research objective: Patient on regimen for less than 2 weeks ble Examine whether social stigma is possi Patients with blindness or impaired vision not correctable with mediator to relationship between literacy and glasses, dementia, deafness or hearing problems not correctable -reported HIV medication adherence. self with hearing aid, or too ill to participate in survey Study design: Sampling strategy: Cross -sectional -infected patients receiving medical care Consecutive series of HIV Study setting: at one of the infectious disease clinics Infectious disease clinics in Shreveport, Sample size: Louisiana and Chicago, Illinois 204 Measurement period: Age, mean: June - September, 2001 40.1 low Fol -up duration: Gender, %: NA Males: 79.9 Completeness of follow -up: Race/Ethnicity, %: NA AA: 45.1 Income, %: Measurement tools including cutpoints: <$800/month: 39.7 REALM: Insurance status, %: 44 low: 0 - Uninsured: 27.5 60 Marginal: 45 - Education, %: 66 Adequate: 61 - Some college education: 60 Other characteristics, %: Unemployed: 55.9 Also being treated for non-HIV related chronic illness: 52.5 Mental health services: nearly one-third Substance abuse: 9.3 Health literacy/numeracy levels, %: Low: 11.3 Marginal: 20.1 Adequat e: 68.6 D-194

479 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: t medication Patients with low literacy were more likely to repor Medication adherence nonadherence until stigma is entered into the model, then Covariates used in multivariate analysis: significance of literacy disappears, indicating that perceived Stigma concerns social stigma mediates the relationship between health literacy Age and medication adherence. Gender Effect in no exposure (i.e., ade quate literacy) or control group: Site Non -adherence in past 4 days Employment status Number of medications in HIV regimen 1 or more missed doses, %: 30 Number of non-HIV prescription medications taken Effect in exposure (i.e., low/moderate literacy) or intervention: -adherence in past 4 days Comorbid chronic condition Non Marginal: Treatment for mental health condition 1 or more missed doses: 19.5 Treatment for substance abuse Description of outcome measures: Low: - Administered Patient 1 or more missed doses : 52.2 Medication adherence Medication Adherence Questionnaire, asked to Difference: Adjusted: identify the medications in their current regimen, as Model 1: -report any recent missed doses (in last well as self four days) using pages that contained names and (Model does not include social stigma) Difference in Adherence (Low vs. Adequate), OR (CI): 3.3 (1.3- color photographs of common HIV medications 8.7) Data source( s) for outcomes: Difference in Adherence (Marginal vs. Adequate), OR (CI): 2.1 Patient survey (self -report) -5.5) (0.8 Attempts for control for confounding: Multivariate analysis Model 2: health literacy) (Model does not include Blinding: No Statistical measures used: Logistic regression Mediation analysis D-195

480 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 78 Waldrop -Valverde et al., 2009 HIV positive, > or = 18 yrs Research objective: Receiving antiretorviral treatment (ART) or "in process" for first To test the relationship between health literacy course of ART, no history of head injury or loss of conciousness cation management and numeracy to medi lasting more than 30 mins, no presence of psychotic symptoms at capacity among HIV positive men and women, of enrollment, not used heroin, cocaine or marijuana in the past time and to test whether health literacy and/or 12 mts numeracy mediated the effects of gender on Sampling strategy: the outcome Convenience Study design: Sample size: Cross -sectional N=155 Study setting: Male (n=90) HIV clinics or participants in AIDS drug Female (n=65) program in Miami, Florida assistance Age (mean and range), %: Measurement period: NR other than no sig difference between men and women NR Gender, %: Follow -up duration: Female: 58 NA hnicity, %: Race/Et Completeness of follow -up: Black: NA Among Men: 81 Measurement tools including cutpoints, %: Among Women: 95 Health Literacy: Income, %: TOFHLA, Range 0-50 and the % correct was NR calculated Insurance status, %: NR Numeracy: Education, % (SD): Applied problems subset of Woodcock Men: 11.7 yrs (2.6) Johnson III Women: 11.3 yrs (1.8) 63 items Other characteristics, %: Cut point: when the participant responds Regular place to stay: incorrectly to the last 6 consecutively Men: 84 administered items or when the final item is Women: 99 administered. Yrs since HIV diagnosis, % (SD): Scores convented to Z scores with a mean of Men: 8.6 (7.0) 0 and a SD of 1 Women: 11.1 (6.2) Health literacy/numeracy levels, %: Health Literacy (% TOFHLA correct): Men: 78 Women: 73 Numeracy (Applied problems Z -score): Men: -0.81 Women: -1.32 D-196

481 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Describe results: Main outcomes: MMT score outcome (hierarchical multiple regression model): Medication Management Test (MMT): Step 1 regressors: years of ed, time since HIV d MMT % correct: iagnosis and Men: 65% gender; explained 14% of variance in outcome (P < 0.001) Step 2 (adding TOFHLA to step 1 variables); adding health Women: 58% ( = NS) P literacy accounted for additional 21% of variance (P < 0.001) Covariates used in multivariate analysis: Step 3 Final model (adding numeracy to step 2): accounted for Included only variables found to be sig related to an additional 12% of the variance. The final model explained a MMT: Gender, education and time since HIV total of 48% of the variance in MMT scores diagnosis Health literacy and numeracy were positively and significantly Regression analysis includes health literacy and associated with MMT numeracy Women were less likely to understand medication instructions Path analysis includes numeracy and excludes as assesse d by the MMT and so path analysis conducted to health literacy. determine if numeracy mediated differences between men and Description of outcome measures: women in MMT performance. Found that the relationship Medication Management Test (MMT): between gender and MMT performance is mediated by Measures ability to understand ART medication numeracy instructions literacy) or control group: Effect in no exposure (i.e., adequate 8 items with a totoal of 16 points, There were 5 NR "mock" HIV medications with labels. Effect in exposure (i.e., low/moderate literacy) or intervention: Test score based on answers to questions about the NR medication labels, the loperamide insert, the ability Difference: to correctly count out and place a week's supply of Difference in MMT score Health literacy: β = 0.210 ( < 0.05) P pills in a medication organizer and to determine Numeracy (applied problems: β = 0.538 ( P < 0.01) missed doses and refills. Total % correct used in the analysis Mediator Path analysis: Data source(s) for outcomes: Differe nce in Medication Management Capacity Directly measured Female: Indirect effect on numeracy: -0.428 ( < 0.01) P Attempts for control for confounding: P Direct effect on Medication Management Capacity: 0.073 ( = Hierarchical multiple regression to examine whether health lit and numeracy are associated with the NS) outcome. Path analysis to examine mediator Numeracy: Direct effect on Medication Management Capacity: 0.644 ( P < analysis. Blinding: 0.01) NR Statistical measures used: ng the Hierarchical multiple regression testi association of health literacy and numeracy with MMT scores. Mediation effects were tested using path analytic techniques D-197

482 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 79 Included: Walker et al., 2007 Research objective: Patients diagnosed by their Rheumatologist as having rheumatoid Intervention: arthritis and willing to take part in the study Determine effectiveness of a pictorial ‘mind Excluded: map’ together with ARC booklet for imparting NA knowledge to participants with rheumatoid Sampling strategy: arthritis, and to relate this to participant Convenience sample reading ability Sample size: Study des ign: 363 RCT Intervention, n = 175 Study setting: Control, n = 188 Participants recruited in three Age, mean (SD): hospital Rheumatology departments in the Intervention: 61.96 (12.23) UK. Control: 61.57 (11.64) Measurement period: Gender, % F: NR Overall: 70.5 Follow -up duration: Intervention: 71.4 1 week Control: 69.7 -up: Completeness of follow Race/Ethnicity: NR NR Income: NR Measurement tools including cutpoints: Insurance status: NR For the intervention: Education, %: REALM as a continuous variable HS or equiv: 85 7th –8th: apprx.: 11 < 7th: < 4 Other characteristics: Disease duration, Mean (SD) Intervention: 13.7 (10.27) Control: 12.76 (10.85) English is 1st language: 97% Health literacy/numeracy levels: Overall REALM < 60, %: 15 REALM < 45, %: 4 REALM score, Mean (SD) Intervention: 62.26 (9.12) Control: 63.28 (7.96) For the health outcomes of Depression and Anxiety: REALM ≥60: good readers REALM < 60: poor readers D-198

483 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Describe results: Main outcomes: No statistically signifi cant difference in knowledge gained KSQ between participants who received mind map and booklet and Anxiety those who received booklet only. People with higher REALM Depression scores gained more knowledge, regardless of whether they Covariates used in multivariate analysis: were in intervention or control. None Poor readers were significantly more anxious and more Description of outcome measures: KSQ: The KSQ was adapted from an existing depressed than the good readers. rheumatoid arthritis knowledge questionnaire for use Effect in no exposure (i.e., adequate literacy) or control group: in clinical settings. Eight sections comprised 40, KQ2 (Control group) ts. Scoring system was +1 if true/false statemen Increase in knowledge, mean (CI): 6.56 (3.36-8.75) 1 if correct, 0 if not completed or don’t know, and - KQ1 (good reader)* incorrect. Possible scores ranged from -40 to +40. -7.0*) Depression, mean (CI): 6.5 (5.9 KSQ administered pre-intervention and post - Anxiety, mean (CI): 7.7 (7.1-8.2*) intervention by telephone. *read from a figure Depression and Anxiety: Patients performed Effect in exposure (i.e., low/moderate literacy) or intervention: Hospital A nxiety and Depression scale (HAQ and KQ2 (Intervention group) HAD) See Zigmond Acta Psychiatric Scand 1983; Increase in knowledge, mean (CI): 6.45 (3.78-10) 67: 361-70. See Fries. Arthritis Rheum 1980; 23: KQ1 (poor reader)* 137-45. -9.5*) Depression, mean, (CI): 8.1 (6.8 Data source(s) for outcomes: Anxiety, mean, (CI): 9.4 (7.9-10.8*) KSQ: pre -intervention, not clear if administered as a *read from a figure written survey or interview; post -intervention, Difference: interviewed by telephone. KQ2 HAQ/HAD: it isn't clear if administered as written Difference in increase in knowledge between intervention and survey or interview. control groups: Mann- Whitney U -statistic -0.11, (unadjusted P > 0.3) Attempts for control for confounding: Note: REALM score predicts change in knowledge, (adjusted P Randomization ANOVA < 0.003) Blinding: KQ1 Anxiety: ( P = 0.03) NR = 0.01) Depressed: ( P Statistical measures used: Whitney U test used to compare mean Mann- increases in knowledge between the intervention and control groups. Univariate analysis of variance with difference between KSQ scores as the dependent variable and REALM score, age,intervention group, depression D-199

484 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 80 Weiss and Palmer, 2004 Included: Research objective: Enrolled in a Medicaid managed-care plan based on medical need Determine effectiveness of a pictorial ‘mind ≥ 18 years old or medical indigence, English or Spanish speaking, map’ together with ARC booklet for imparting Excluded: knowledge to participants with rheumatoid Enrolled due to pregnancy ate this to participant arthritis, and to rel Sampling strategy: reading ability -generated, random sample Computer Study design: Sample size: Secondary analysis of cross -sectional survey, 74 retrospective review of records Age (mean and range): Study setting: 49.9 (21-77) Medicaid subjects in Arizona Gender, %: Measurement period: Females: 28.4 1992 Race/Ethnicity, %: Follow -up duration: Hispanic: 52.1 NA Wh ite: 37 Completeness of follow -up: Other: 10.9 NA Income: Measurement tools including cutpoints: NR IDR: scores 0 -8, equivalent to grade reading Insurance status, %: level. Medicaid: 100 ≤ 3rd grade Low literacy: Education, mean (SD): ≥ 4th grade Higher literacy: -13) 9.1 (4), (0 Other characteristics: Unemployed, %: 78.4 Self -Assessment of Health, %: Excellent: 6.8 Good: 23.3 Fair: 45.2 Poor: 24.7 Lang. of Best Reading Skill: English: 72.9 Spanish: 27 Health literacy/numeracy levels, %: Low: 24.32 Higher: 75.68 D-200

485 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Main outcomes: Describe results: Total medical care charges Participants in low literacy group generated higher charges for health care than those in higher literacy group, after controlling Covariates used in multivariate analysis: for potential confounders. A separate analysis predicting effect Age Ethnic group of education (not controlling for health lit) found education not significant. Health status (Education used in separate analysis and found not Effect in no exposure (i. e., adequate literacy) or control group: to be a significant predictor of costs) Total charges, mean (range): $2,890 ($0- $38,957) Description of outcome measures: Inpatient charges, mean (range): $824 ($0-$18,135) Effect in exposure (i.e., low/moderate literacy) or intervention: Sum of health plan billing charges: hospital, ED, Total charges, mean (range): $10,688 ($0-$95,002) home, and physician care, short -term nursing Inpatient charges, mean (range) $7,038 ($0-$76,884) outpatient and inpatient charges for laboratory, Difference: radiographs, pharmacy, and durable medical Difference between high and low literacy groups (adjusted): ( P equipment. = 0.037) Data source(s) for outcomes: In person interviews, billing records Attempts for control for confounding: Multivariable analysis Blinding: NA Statistical measures used: t-tests measured differences in health care costs between low - and higher literacy groups. Multivariable analysis to control for potential confounders D-201

486 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 12 White et al., 2008 Included: 11 (companion: Bennett et al., 2009 ) ≥ 16 Research objective: Living in a US household Assess relationship between health literacy Excluded: and utilization of preventive health services Inmates among nationally representative US sample Unable to be interviewed because of a language barrier Study design: Unable to be interviewed because of a m ental illness Cross -sectional survey Sampling strategy: Study setting: 4-stage stratified area design to select a nationally representative Nationally representative US sample living in sample households Sample size: Measurement period: 18,100 90 minute interviews from March 2003 to Age (mean and range), %: January 2004 Mean age: 44 years Follow -up duration: 16-39 years: 44 NA 40-64 years: 41% -up: eness of follow Complet >65 years: 15 NA Gender, %: Measurement tools including cutpoints: Females: 52 NAAL: measures functional health literacy Race/Ethnicity, %: (prose, quantitative, and document literacy) White: 71 Grouped into below basic, basic, intermediate Black: 11 and proficient literacy level Hispanic: 12 Oral Reading Fluency instrument: Reading Other: 6 aloud, in English 150-200 words measured as Income, %: correct words read/minute Below poverty: 17 100-175% poverty: 18 >175% poverty: 64 Insurance status, %: Uninsured: >18 Education: NR Other characteristics, %: Reported poor health: 4 Reported fair health: 11 Reported good to excellent health: 86 Average oral reading fluency: 154 words read correctly/minute Health literacy/numeracy levels, %: Basic or below basic: 36 Intermediate: 53 Proficient: 12 D-202

487 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: -up, vision Adults under 40: Low health literacy was related to decreased Preventive health care (dental check -up, and probability of having a pap smear and a vision check check, osteoporosis screening, colon cancer screening, pneumonia shot, flu shot, pap smear, an increased probability of having a flu shot. It was not <0.05 P -ups, associated with dental check mammogram, prostate cancer screening) Effect in no exposure (i.e., adequate literacy) or control group: Covariates used in multivariate analysis: NA Age Effect in exposure (i.e., low/moderate literacy) or intervention: Gender NA Race Difference: Poverty level NA Insurance status Self -reported health status Oral reading fluency Description of outcome measures: Self -report Data source(s) for outcomes: Interview Attempts for control for confounding: Marginal maximum likelihood probit regression analyses Blinding: NA Statistical measures used: MML probit regression analyses: Represents each respondent's literacy proficiency as a probability distribution rather than assigning a literacy score D-203

488 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: Eligibility criteria: 7 Included: Wolf et al., 2005 3 Wolf et al., (companions:Gazmararian, 2006; Medicare managed-care enrollee 5 4 Howard et al., Baker et al., 2007; 2007; 65+ 8 6 Howard et al., Baker et al., 2008; 2006; Enrolled in Prudential HealthCare 3 months or more 2 9 ) Baker et al., 2004; 2005; Excluded: Research objective: Not comfortable speaking English or Spanish Investigate relationship between health Blind or severely impaired vision not correctable with eyeglasses literacy and functional health status among Living in a nursing home cohort of new Medicare managed care Missed 1 or more screening questions for severe cognitive enrollees from 4 US cities impairment (not able to correctly identify year, month, state, year of Study design: their birth, or home address) Cross -sectional Sampling strategy: Study setting: -care Convenience sample of consecutive new Medicare managed In-person in-home interviews with and enrollees subsequent claims data for enrollees in Sample size: Cleveland, Houston, Tampa, and south 2,923 Florida (including Ft. Lauderdale and Miami) Age (mean and range): Measurement period: 71 Interviews occurred May 1997-December By health literacy level: 1997 Adequate, %: Follow -up duration: - 44.3 65-69 NA - 28.2 70-74 -up: NA Completeness of follow 75-79 - 17.3 Measurement tools including cutpoints: - 8.0 80-84 S-TOFHLA: > 85 - 2.2 Adequate Marginal, %: Marginal - 29.4 65-69 Inadequate 70-74 - 26.1 75-79 - 23.9 80-84 - 15.2 5.6 > 85 - Inadequate, %: 65-69 - 24.5 70-74 - 25.6 75-79 - 22.5 80-84 - 16 Gender, %: Female by HL status: Adequate: 58.4 Marginal: 53.6 Inadequate: 59.0 D-204

489 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Descr Main outcomes: ibe results: Self -rated physical and mental health functioning In adjusted models, in relation to chronic conditions, enrollees with -reported chronic conditions inadequate HL were sig more likely to report having diabetes and Self -reported physical funtion and heart failure, significantly lower self of daily living limitations Activity Covariates used in multivariate analysis: mental health scores, and were more li kely to have limitations in IADLs, ADLs, limitations because of physical health, fewer Age Sex accomplishments because of physical health, and pain that Race/ethnicity interfered with work. Those with marginal HL did not report any Income increased prevalence of chronic diseases compar ed to those with Education adequate HL, showed reduced physical and mental health Tobacco functioning only in models that did not adjust for eduction, and were more likely to have limitations in IADLs, ADLs, and limitations Alcohol consumption n fully adjusted and fewer accomplishments due to physical health i Self -reported comorbid conditions models. Site Effect in no exposure (i.e., adequate literacy) or control group: Description of outcome measures: Hypertension, %: 43.3 Self -rated physical and mental health functioning Diabetes, %: 12.8 measured by Medical Outcomes Study 36-Item Coronary artery disease, %: 7.6 -36 subscales SF Chronic conditions (hypertension, diabetes, Heart failure, %: 3.8 coronary artery disease, heart failure, bronchitis or Bronchitis or emphysema, %: 13.5 - emphysema, asthma, arthritis, cancer) self Asthma, %: 7.3 reported in in- person interview Arthritis, %: 50.1 limitations measured by, instrumental Activity Canc er, %: 6.0 activities of daily living, activities of daily living, Physical function mean score: 78.0+24.6 limitations in activity because of physical health, Mental health mean score: 84.0+16.1 fewer accomplishments because of physical Smoking, %: health, and pain that "quite a bit" or "extremely" Never: 38.6 ormal work activities interfered with n Former: 49.0 Data source(s) for outcomes: Current: 12.4 In-person orally administered survey Current alcohol use, %: Attempts for control for confounding: None: 57.9 Multivariate logistic regression Light to moderate: 38.0 Blinding: Heavy: 4.1 NR BMI, %: Statistical measures used: <18.5: 4.3 Chi -square, logistic regression, linear regression 18.5-24.9: 56.8 25.0-29.9: 26.8 >30.0: 12.1 Effect in exposure (i.e., low/moderate literacy) or intervention: Inadequate -Prevalence of self -reported conditions, %: Hypertension: 49.9 Diabetes: 18.7 Coronary artery disease: 5.6 Heart failure: 6.1 Bronchitis or emphysema: 9.7 Asthma: 6.6 Arthritis: 57.3 Cancer: 4.2 Smoking, %: Never: 46.7 Former: 41.6 Current: 11.7 D-205

490 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Participant Characteristics Study Description Author, year: Race/Ethnicity, %: 7 Wolf et al., 2005 By HL status: 3 Wolf et al., (companions:Gazmararian, 2006; Adequate: 5 4 2007; Baker et al., 2007; Howard et al., White: 83.6 8 6 Howard et al., Baker et al., 2008; 2006; AA: 6.5 2 9 ) Baker et al., 2004; 2005; Hispanic English-speaking: 1.8 (continued) Hispanic Spanish- speaking: 7.0 Other: 1.1 Marginal: White: 66.1 AA: 13. 0 Hispanic English-speaking: 2.7 speaking: 17.9 Hispanic Spanish- Other: 0.3 Inadequate : White: 57.1 AA: 25.6 Hispanic English-speaking: 2.6 speaking: 13.8 Hispanic Spanish- Other: 0.9 Income, %: Income <$15,000 by HL status: Adequate: 31.9 Marginal 46. 8 Inadequate 54.8 Insurance status, %: Medicare: 100 Education, %: By HL status: >12 years of school completed: Adequate: 39.5 Marginal: 20.4 Inadequate: 22.1 0-8 years of school completed: Adequate: 7.3 Marginal: 24.7 Inadequate: 41.8 Other characteristics: Health literacy/numeracy levels, %: Adequate: 66.5 Marginal: 11.3 Inadequate: 22.2 D-206

491 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes Current alcohol use, %: None: 75.6 Light to moderate: 22.9 Heavy: 1.5 BMI, %: <18.5: 7.5 18.5-24.9: 56.3 25.0-29.9: 25.0 >30.0: 11.2 Physical function mean score: 67.7+29.7 Mental health mean score: 76.2+20.9 Marginal - Prevalence of self -reported conditions, %: Hypertension: 46.2 Diabetes: 15.2 Coronary art ery disease: 6.7 Heart failure: 3.7 Bronchitis or emphysema: 9.7 Asthma: 8.2 Arthritis: 56.5 Cancer: 7.0 Smoking, %: Never: 42.1 Former: 44.9 Current: 13.0 Current alcohol use, %: none: 64.2 Light to moderate: 33.9 Heavy: 1.8 BMI, %: <18.5: 4.0 18.5-24.9: 56.2 25.0-29.9: 25.5 >30.0: 14.3 Physical function mean score (unadjusted): 73.7+27.5 Mental health mean score (unadjusted): 81.8+18.6 Difference: Difference in prevalence of chronic disease (adjusted), OR (CI): Inadequate/Adequate: -1.50) Hypertension: 1.20 (0.95 Diabetes: 1.48 (1.09-2.02) Coronary artery disease: 0.93 (0.59-1.47) Heart failure: 1.69 (1.02-2.80) Bronchitis or emphysema: 0.75 (0.53 -1.08) Asthma: 0.96 (0.62- 1.37) Arthritis: 0.98 (0.78 -1.23) Cancer: 0.91 (0.54-1.52) Marginal/Adequate, OR (CI): Hypertension: 1.03 (0.80-1.34) Diabetes: 1.10 (0.75-1.59) Coronary artery disease: 0.85 (0.51-1.43) 1.90) Heart failure: 0.97 (0.49 - D-207

492 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Charact eristics Author, year: 7 Wolf et al., 2005 3 (companions:Gazmararian, 2006; Wolf et al., 4 5 Howard et al., Baker et al., 2007; 2007; 8 6 Baker et al., 2008; Howard et al., 2006; 2 9 Baker et al., 2004; ) 2005; (continued) D-208

493 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Outcomes Results Bronchitis or emphysema: 0.81 (0.53 - 1.22) Asthma: 1.26 (0.79- 2.01) Arthritis: 1.11 (0.85 -1.44) Cancer: 1.38 (0.84-2.27) Differences in self -reported physical and mental health (adjusted including ed), β (CI): Inadequate/Adequate - Physical function: - 6 ( -8.4 --3.5) Ment al health: -4.9 ( -6.7 --3.1) Marginal/Adequate: -3.9 Physical function: -1.1 ( -1.8) -2.9 Mental health: -0.9 ( -1.2) -reported activity limitations (adjusted Differences in self including ed), OR (CI): Inadequate/Adequate: IADLS: 2.25 (1.74 -2.92) ADLs: 2.83 (1.62 -4.96) Limitations because of physical health: 1.79 (1.39-2.32) Fewer accomplishments: 1.90 (1.48-2.45) Pain interfering with activities: 2.01 (1.46- 2.77) Marginal/Adequate: IADLS: 1.65 (1.22 -2.24) ADLs: 2.05 (1.06-3.97) Limitations because of physi cal health: 1.35 (1.00-1.84) Fewer accomplishments: 1.46 (1.08-1.97) 1.82) Pain interfering with activities: 1.23 (0.83 - D-209

494 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics year: Author, Eligibility criteria: 81 Included: Wolf et al., 2006 Research objective: ≥ 18 yrs old Assess relationship between literacy and Excluded: medication guide and patient information Severe visual or hearing impairment leaflet use. Too ill to participate Study design: Non -English speaking -sectional Cross Sampling strategy: Study setting: Convenience Patients at Primary Care Clinic at Louisiana Sample size: State University Health Sciences Center 251 Measurement period: ≤ 6th grade: 74 July 2003 -8th grade: 78 7th -up duration: Follow ≥ 9th grade: 99 NA Age, (mean and range) ( SD): -up: Completeness of follow ≤ 6th grade: 50.0 (15.5) NA -8th grade: 47.6 (15) 7th Measurement tools including cutpoints: ≥ 9th grade: 44.9 (14.2) REALM: Gender, % : ≤ 6th grade: low Female: 7th -8th grade: marginal ≤ 6th grade: 60.8 ≥ 9th grade: adequate 7th -8th grade: 70.5 ≥ 9th grade: 78.8 Race/Ethnicity, %: AA: ≤ 6th grade: 89.2 7th -8th grade: 76.9 ≥ 9th grade: 40.4 White: ≤ 6th grade: 9.5 7th -8th grade: 20.5 ≥ 9th grade: 56.6 Other: ≤ 6th grade: 1.3 7th -8th grade: 2.6 ≥ 9th grade: 4 Income: NR Insurance status, %: Payment source for medication: Private: ≤ 6th grade: 5.4 7th -8th grade: 6.4 ≥ 9th grade: 12.1 Medicaid: ≤ 6th grade: 5.4 7th -8th grade: 7.7 ≥ 9th grade: 9.1 D-210

495 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Results Outcomes Main outcomes: Describe results: Use of Medication Guides Patients with lower literacy were less likely to report having looked at Medication Guide or informational leaflet information Number of prescriptions taken Covariates used in multivariate analysis: included with their prescription medications. Effect in no exposure (i.e., adequate literacy) or control group: Age Read medication guides? Gender Race ≥ 9th grade: 32.9% # Medication taken daily: Education Number of prescriptions taken ≥ 9th grade: mean (SD): 2.8 (0.21) Description of outcome measures: Effect in exposure (i.e., low/moderate literacy) or intervention: Medication guide use was assessed by a single Read medication guides? survey item, "Do you ever look at the written ≤ 6th grade, %: 16.7 7th -8th grade, %: 21.8 materials that come with your prescription # Medication taken daily: medications?" ≤ 6th grade, mean (SD): 2.9 (0.62) Data source(s) for outcomes: -8th grade, mean (SD): 3.5 (0.40) In-person interview 7th Difference: Attempts for control for confounding: Difference in whether Read medication guides low vs reference Multiple logistic regression (authors do not specify if reference is marginal/adequate or just Blinding: adequate: (adjusted), OR (CI): 2.5 (1.2-5.2) NR Difference in # medications taken daily (u nadjusted): ( P = NS) Statistical measures used: Bivariate: Student’s t test, chi -square test Multiple logistic regression: D-211

496 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Author, year: Out of Pocket: 81 Wolf et al., 2006 ≤ 6th grade: 58.1 (continued) 7th -8th grade: 71.8 ≥ 9th grade: 63.6 Other: ≤ 6th grade: Education, %: Grades 1 -8: ≤ 6th grade: 21.6 7th -8th grade: 6.4 ≥ 9th grade: 4 -11: Grades 9 ≤ 6th grade: 42 -8th grade: 37.2 7th ≥ 9th grade: 20.2 HS/GED: ≤ 6th grade: 33.8 7th -8th grade: 43.6 ≥ 9th grade: 40.4 >HS: ≤ 6th grade: 2.7 7th -8th grade: 12.8 ≥ 9th grade: 35.4 Other characteristics: Health literacy/numeracy levels, %: ≤ 6th grade: 29.5 7th -8th grade: 31 ≥ 9th grade: 39.5 D-212

497 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: criteria: Eligibility 82 Included: Wolf et al., 2006 Research objective: English- speaking Evaluate association between literacy and Men newly diagnosed with prostate cancer who have not, or only PSA level in men newly diagnosed with recently, begun treatment prostate cancer Excluded: Study design: Blind or severely impaired vision not correctable with eyeglasses, Cross -sectional deaf or hearing problems Study setting: Uncorrectable with a hearing aid, too ill to participate, did not Four outpatient oncology and urology clinics in understand the questions. Chicago area hospitals Sampling strategy: Measurement period: Convenience NR Sample size: Follow -up duration: 308 NA Functional, n = 153 Completeness of follow -up: Marginal, n = 101 NA Low, n = 54 Measurement tools including cutpoints: Age, mean (SD): REALM: 66.5 (8.4) ≤ 6th grade: low < 65 yrs: 7th -8th grade: marginal Functional, %: 56 ≥ 9th grade: functional Marginal, %: 28.6 Low, %: 15.4 65-74 yrs: Functional, %: 40.7 Marginal, %: 37.9 Low, %: 21.4 > 74 yrs: Functional, %: 56.5 Marginal, %: 30.4 Low, %: 13 Gender: Male: 100% Race/Ethnicity, %: AA: Total: 68.5 Functional: 35.7 Marginal: 41.4 Low: 22.9 White: Functional:80 Marginal: 12.9 Low: 7.1 Income, %: < $10,000: Functional: 53.2 Marginal: 27.4 Low: 19.4 D-213

498 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Results Outcomes Main outcomes: Describe results: PSA level at diagnosis (20.0 ng/mL or less vs > 20.0 Low HL was found to be a significant predictor of having ng/mL) elevated PSA but marginal HL was not. Health literacy was ultivariate analysis: Covariates used in m found to be a confounder/mediator for association between Age race and PSA level and contributed to a 35% reduction in Race association between race and PSA level. Annual income Effect in no exposure (i.e., adequate literacy) or control group, Marital status %: Description of outcome measures: PSA Level > 20 ng/mL PSA level at diagnosis was obtained from medical Functional: 13.5 record reviews. Elevated PSA levels defined as > Effect in exposure (i.e., low/moderate literacy) or intervention, than 20 ng/mL according to clinical criteria for “high- %: risk” prostate cancer PSA Level > 20 ng/mL Data source(s) for outcomes: Marginal: 24.1 Medical records Low: 33.3 Attempts for control for confounding: Difference: Multiple logistic regression Difference in PSA Level > 20 ng/mL (adjusted), OR (CI): Blinding: Marginal HL vs functional HL: 1.4 (0.9-2.2) NR Low HL vs function HL: 2.5 (1.5-4.2) Statistical measures used: Race mediator analysis, OR (CI): -square, median, and Student t tests Chi 9.1) AA (adjusted): 3.0 (0.8- Logistic regression analysis: Model fit w as assessed 9.5) AA (adjusted model without HL): 4.6 (2.0- -statistics from the receiver operating with c -Lemeshow characteristic curves and Hosmer square tests. Models adjusted for goodness - -fit chi -of clustering D-214

499 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Study Description Participant Characteristics Author, year: $19,999: - $10,000 82 Wolf et al., 2006 Functional: 40.4 (continued) Marginal: 40.4 Low: 19.3 $20,000-$29,999: Functional: 45.5 Marginal: 39.4 Low: 15.2 ≥ $30,000: Functional: 54.6 Marginal: 29.5 Low: 15.9 Insurance status: NR Education: NR Other characteristics, %: Marital Status: Not currently married: Functional: 54.4 Marginal: 29.8 Low: 15.8 Married: Functional: 48.2 Marginal: 37.5 Low: 14.3 Health literacy/numeracy levels, %: Low: 17.53 Marginal: 32.79 Functional: 49.68 D-215

500 Evidence Table 1. Key Question 1: Health literacy outcome studies (continued) Study Description Participant Characteristics Eligibility criteria: Author, year: 19 Wolf et al., 2007 Included: 18 (Companion: Davis et al., 2006 ) 18 or older Research objective: Excluded: Investigate how patients approached and Blindness or severely impaired vision not correctable with interpreted prescription drug label instructions, eyeglasses and document nature of misunderstanding impairment not correctable with hearing aid Deafness or hearing that may contribute to high prevalence of Too ill to participate medication error. Non -English speaking Study design: Sampling strategy: -person cognitive interviews Qualitative/In Convenience Study setting: Sample size: 3 primary care clinics in Shreveport, 395 Louisiana, Jackson, Michigan, and Chicago, IL Age (mean and range) (SD): Measurement period: 45 (14) (19-85) Consecutive summers beginning July 2003 Gender, %: -up duration: Follow Male: 32 NA Race/Ethnicity, %: Completeness of follow -up: AA: 47 NA White: 48 Measurement tools including cutpoints: Income: REALM NR Low: 0-44 status, %: Insurance 60 Marginal: 45- Lacked prescription drug coverage: 71 Adequate: 61-66 Education, %: Grades 1 -8: 4 Grades 9 -11: 24 Completed High School/GED: 43 High School: 29 Other characteristics, %: Physician most likely source of medication information: 71 Shreveport: 57 Jackson: 25 Chicago: 18 Health literacy/numeracy levels, %: Low: 19 Marginal: 29 Adequate: 52 D-216

501 Key Question 1: Health literacy outcome studies (continued) Evidence Table 1. Outcomes Results Main outcomes: Describe results: Differences in health literacy are associated with patient Misunderstanding of 1 or more dosage instructions Correctly interpreted primary label instructions understanding of prescription bottle medication instructions. Effect in no exposure (i.e., adequate literacy) or control group, Amoxicillin %: Trimethoprim Misunderstanding of 1 o