Objectives To update a 2004 systematic review of health care service use and health outcomes 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. Data sources We searched MEDLINE®, 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. Review methods We used standard Evidence-based Practice Center methods of dual review of abstracts, full-text articles, abstractions, quality ratings, and strength of evidence grading. We 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 health 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. Health literacy level potentially mediates disparities between blacks and whites. The strength of evidence of numeracy studies was insufficient to low, limiting conclusions 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-experimental 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 few studies. The strength of evidence was moderate for the effect of mixed interventions on 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 justifying appropriate cutoffs for health literacy levels prior to conducting studies; developing tools that measure additional related skills, particularly oral (spoken) health literacy; and examining mediators and moderators of the effect of health literacy. Priorities 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.

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Health literacy interventions and outcomes: an updated systematic review.

We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[ A], odds ratio (OR) = 1.36, P = 5.0 x 10(-10)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

https://genepi.qimr.edu.au/contents/p/staff/Thorleifsson_NatGen_Oct10.pdf

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10-10) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10-9). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10-14, OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10-14, OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. © 2011 Nature America, Inc. All rights reserved.

Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

Health literacy

Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron disease in both familial and sporadic cases. Initial reports indicate that this variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum is associated with transactive response DNA binding protein (TDP-43) proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype is not yet well characterized. We report the clinical and pathological phenotypes associated with pathogenic C9ORF72 mutations in a cohort of 563 cases from Northern England, including 63 with a family history of amyotrophic lateral sclerosis. One hundred and fifty-eight cases from the cohort (21 familial, 137 sporadic) were post-mortem brain and spinal cord donors. We screened DNA for the C9ORF72 mutation, reviewed clinical case histories and undertook pathological evaluation of brain and spinal cord. Control DNA samples (n = 361) from the same population were also screened. The C9ORF72 intronic expansion was present in 62 cases [11% of the cohort; 27/63 (43%) familial, 35/500 (7%) cases with sporadic amyotrophic lateral sclerosis/motor neuron disease]. Disease duration was significantly shorter in cases with C9ORF72-related amyotrophic lateral sclerosis (30.5 months) compared with non-C9ORF72 amyotrophic lateral sclerosis/motor neuron disease (36.3 months, P < 0.05). C9ORF72 cases included both limb and bulbar onset disease and all cases showed combined upper and lower motor neuron degeneration (amyotrophic lateral sclerosis). Thus, clinically, C9ORF72 cases show the features of a relatively rapidly progressive, but otherwise typical, variant of amyotrophic lateral sclerosis associated with both familial and sporadic presentations. Dementia was present in the patient or a close family member in 22/62 cases with C9ORF72 mutation (35%) based on diagnoses established from retrospective clinical case note review that may underestimate significant cognitive changes in late disease. All the C9ORF72 mutation cases showed classical amyotrophic lateral sclerosis pathology with TDP-43 inclusions in spinal motor neurons. Neuronal cytoplasmic inclusions and glial inclusions positive for p62 immunostaining in non-motor regions were strongly over-represented in the C9ORF72 cases. Extra-motor pathology in the frontal cortex (P < 0.0005) and the hippocampal CA4 subfield neurons (P < 0.0005) discriminated C9ORF72 cases strongly from the rest of the cohort. Inclusions in CA4 neurons were not present in non-C9ORF72 cases, indicating that this pathology predicts mutation status.

Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72

Health literacy and adherence to glaucoma therapy.

Primary open-angle glaucoma (POAG, OMIM 137760; Online Mendelian Inheritance in Man; http://www.ncbi.nlm.nih.gov/Omim/provided in the public domain by the National Center for Biotechnology Information, Bethesda, MD) is a leading cause of irreversible visual impairment and blindness worldwide, especially in the elderly and the African-American population.1,2 Many risk factors are associated with the development of POAG, including elevated intraocular pressure, positive family history of glaucoma, refractive error, and African-American race.1–4 POAG is a complex genetic disorder. Three genes—myocilin, optineurin, and WD repeat domain 36 — have been implicated in POAG to date, but together account for less than 10% of POAG cases.5–7 In addition, a role for variants of the CYP1B1 gene in POAG has been reported in the Spanish, French, and Indian populations.8

Although primary open-angle glaucoma is the most common form of glaucoma in the world, pseudoexfoliation glaucoma (XFG; OMIM 177650) is the most common secondary form of open-angle glaucoma associated with pseudoexfoliation syndrome (XFS; OMIM 177650).1 XFS is a systemic disorder in which an unidentified fibrillar substance is produced in ocular and many nonocular tissues.9,10 Its incidence increases with age, and the risk of development XFG in individuals with XFS has been reported to be as high as 60%.9,10 The prevalence appears to be highest among individuals of Scandinavian ancestry and lower among African Americans.11 The reported prevalence of XFG varies among ethnic groups and ranges from 0.4% to 28% of cases of open-angle glaucoma in the United States.11 Recently, variants in the lysyl oxidase like 1 gene (LOXL1) were found to be significantly associated with XFG and XFS in a genome-wide genetic association study.12 Two nonsynonymous coding SNPs in exon 1 of LOXL1, rs1048661 (R141L) and rs3825942 (G153D), were found to confer increased risk of XFG in this and other studied populations.11–16 In the original study, LOXL1 showed marginally significant association with POAG (P = 0.04) in the Icelandic population, but absence of association (P = 0.18) in the Swedish population, suggesting that the relationship between POAG and LOXL1 should be examined in additional populations.12

Both POAG and XFG are complex disorders that share a similar clinical phenotype, glaucomatous optic neuropathy. Similar to POAG, XFG is primarily an open-angle form of glaucoma frequently associated with elevated IOP. Since genetic variants associated with LOXL1 are common in individuals of European ancestry, our goal was to examine whether these variants play a role in POAG in other populations. In this study, we investigated the association between variants of LOXL1 and POAG in the Caucasian, African-American, and Ghanaian (West-African) populations.

Lack of association between LOXL1 variants and primary open-angle glaucoma in three different populations.

Background Increasing emphasis on patient-centered care and other recent developments should make patient expectations increasingly important in ophthalmology. Motivated by the pivotal role of patient expectations in quality-of-care assessments and by the limited knowledge about patients' expectations regarding eye care, we initiated a pilot study using focus groups to determine a relevant set of concerns that patients express as expectations. Methods A total of 6 focus groups were conducted with patients at Duke University Eye Center (Durham, NC). Focus groups ranged in size from 4 to 10 people. The average group size was 6. Results Content analysis of transcripts from the 6 focus groups yielded 22 areas of expectations for eye care, which were classified into 5 categories: communication, interpersonal manner, physician's skill, logistics, and other. The 6 areas that appeared to be of greatest importance to focus group participants were the following: (1) honesty, (2) information about diagnosis and prognosis, (3) explanation in clear language, (4) ophthalmologist's experience and reputation, (5) empathy, and (6) listening and addressing concerns. Conclusions In general, ophthalmology patients in the focus groups emphasized expectations related to communication and interpersonal manner. In contrast to previous studies with primary care patients, however, ophthalmology patients expressed few expectations for technical interventions, such as medication prescriptions, physical examination, or diagnostic testing.

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Patient expectations regarding eye care: focus group results.

DNA copy number variants (CNVs) have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG) is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC). This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1.) (p = 0.017, fisher's exact test). It was validated with array comparative genomic hybridization (arrayCGH) and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio) = 3.5, 95% CI −1.1–12.0). Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6–16.4). Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.

/pdf/galc-deletions-increase-the-risk-of-primary-open-angle-5e0mw0k3xw.pdf

GALC Deletions Increase the Risk of Primary Open-Angle Glaucoma: The Role of Mendelian Variants in Complex Disease

Purpose: Coding variants in the optineurin gene (OPTN, GLC1E) have been reported to play a role in primary open-angle glaucoma (POAG) in various populations. This study investigated the role of OPTN sequence variants in patients with POAG in Ghana (West Africa). Methods: This is a case-control study of unrelated Ghanaian POAG cases and non-glaucomatous controls. Ascertainment criteria for POAG included the presence of glaucomatous optic nerve neuropathy, associated visual field loss, and elevated intraocular pressure (IOP) in both eyes, all in the absence of secondary causes of glaucoma. Controls had normal optic nerves, visual fields, and IOP. All the coding exons of OPTN were polymerase chain reaction (PCR) amplified and sequenced in all 140 cases and 130 controls using an ABI 3730 DNA analyzer. Results: All the coding exons of OPTN were sequenced in 140 POAG patients and 130 controls. Several coding variants were identified including M98K, A134A, V147L, P292P, A301G, S321S, and E322K. Three coding variants (V147L, P292P, and A301G) have not been reported previously. There were no significant differences on the frequencies of all the identified variants between POAG cases and controls in this population. Conclusions: This is the first comprehensive study of OPTN in a single West African population. Our results suggest that coding variants in OPTN may not contribute to the risk for POAG in persons of West African descent. Glaucoma is a group of disorders defined by a

/pdf/optineurin-coding-variants-in-ghanaian-patients-with-primary-24gwe5ur82.pdf

Cecile Santiago-Turla

Papers

Health literacy and adherence to glaucoma therapy.

Lack of association between LOXL1 variants and primary open-angle glaucoma in three different populations.

Patient expectations regarding eye care: focus group results.

GALC Deletions Increase the Risk of Primary Open-Angle Glaucoma: The Role of Mendelian Variants in Complex Disease

Optineurin coding variants in Ghanaian patients with primary open-angle glaucoma.