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Background & Aims: The aim of this study was to assess the analytic validity of self-reported family history of hemochromatosis or iron overload. Methods: A total of 141 probands, 549 family members, and 641 controls participated in the primary care Hemochromatosis and Iron Overload Screening Study. Participants received a postscreening clinical examination and completed questionnaires about personal and family histories of hemochromatosis or iron overload, arthritis, diabetes, liver disease, and heart disease. We evaluated sensitivities and specificities of proband-reported family history, and concordance of HFE genotype C282Y/C282Y in probands and siblings who reported having hemochromatosis or iron overload. Results: The sensitivities of proband-reported family history ranged from 81.4% for hemochromatosis or iron overload to 18.4% for liver disease; specificities for diabetes, liver disease, and heart disease were greater than 94%. Hemochromatosis or iron overload was associated with a positive family history across all racial/ethnic groups in the study (odds ratio, 14.53; 95% confidence intervals, 7.41–28.49; P < .0001) and among Caucasians (odds ratio, 16.98; 95% confidence intervals, 7.53–38.32; P < .0001). There was 100% concordance of HFE genotype C282Y/C282Y in 6 probands and 8 of their siblings who reported having hemochromatosis or iron overload. Conclusions: Self-reported family history of hemochromatosis or iron overload can be used to identify individuals whose risk of hemochromatosis or iron overload and associated conditions is increased. These individuals could benefit from further evaluation with iron phenotyping and HFE mutation analysis. [Copyright &y& Elsevier]

Bivariate mixture modeling was used to analyze joint population distributions of transferrin saturation (TS) and serum ferritin concentration (SF) measured in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Four components (C1, C2, C3, and C4) with successively age-adjusted increasing means for TS and SF were identified in data from 26,832 African Americans, 12,620 Asians, 12,264 Hispanics, and 43,254 whites. The largest component, C2, had normal mean TS (21% to 26% for women, 29% to 30% for men) and SF (43–82 μg/L for women, 165–242 μg/L for men), which consisted of component proportions greater than 0.59 for women and greater than 0.68 for men. C3 and C4 had progressively greater mean values for TS and SF with progressively lesser component proportions. C1 had mean TS values less than 16% for women (<20% for men) and SF values less than 28 μg/L for women (<47 μg/L for men). Compared with C2, adjusted odds of iron deficiency were significantly greater in C1 (14.9–47.5 for women, 60.6–3530 for men), adjusted odds of liver disease were significantly greater in C3 and C4 for African-American women and all men, and adjusted odds of any HFE mutation were increased in C3 (1.4–1.8 for women, 1.2–1.9 for men) and in C4 for Hispanic and white women (1.5 and 5.2, respectively) and men (2.8 and 4.7, respectively). Joint mixture modeling identifies a component with lesser SF and TS at risk for iron deficiency and 2 components with greater SF and TS at risk for liver disease or HFE mutations. This approach can identify populations in which hereditary or acquired factors influence metabolism measurement. [Copyright &y& Elsevier]

Abstract: The US Office of Management and Budget (OMB) guidelines for collecting and reporting race and ethnicity information recently divided the “Asian or Pacific Islander” category into “Asian” and “Native Hawaiian or Other Pacific Islander.” The OMB''s decision to disaggregate the “Asian or Pacific Islander” category was the first step toward providing these communities with information to better serve their needs. However, whether individuals who formerly made up the combined group categorize themselves as the new guidelines intend is a question analyzed in this report. A subset of adults participating in the Hemochromatosis and Iron Overload Screening Study completed both the OMB-minimum and the expanded race and ethnicity measure used in the National Health Interview Survey. We compared responses on the expanded measure contained within the OMB “Asian” definition (Filipino, Korean, Vietnamese, Japanese, Asian Indian, Chinese, and/or Other Asian) to “Asian” responses on the OMB-minimum measure. Mixed heritage Asians less often marked “Asian.” Among mixed heritage Japanese, Chinese, and Filipinos, 27%, 49%, and 52% did not mark “Asian” on the OMB measure, respectively. Eleven percent of single-heritage Filipinos did not mark “Asian.” Many individuals formerly making up the combined “Asian or Pacific Islander” group do not categorize themselves as the revised OMB guidelines intend. This is particularly evident among Filipinos and among Asians of mixed heritage. This research illuminates the reliability and utility of the broad “Asian” category and points to possible consequences of collapsing groups into a single category, i.e., missed information and/or erroneous generalization. [Copyright &y& Elsevier]

Homozygosity for the C282Y mutation of the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. The authors describe and apply methodology developed for the analysis of phenotypic and genotypic data from 46,136 non-Hispanic Caucasians, a subset of the multi-ethnic cohort enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. For analysis of the distribution of transferrin saturation (TS), mixtures of normal distributions were considered and the expectation-maximization (EM) algorithm was applied for parameter estimation. Maximized log-likelihoods were compared, and significance was assessed by resampling. Sensitivity, specificity, and predictive values from the modeled subpopulations were compared with the actual observed genotypes for C282Y and H63D mutations in the HFE gene. A strong association between HFE genotype and TS subpopulations was found in these data collected from different geographic regions, confirming the external validity of the statistical approach when applied to population-based data. It was concluded that mixture modeling of phenotypic data may provide a clinical guide for screening with gender-specific thresholds to identify potential samples for genetic testing. [Copyright &y& Elsevier]

Objective: This study assesses the variability in requirements among six institutional review boards (IRBs) and the resulting protocol variations for a multicenter mailed survey. Study Design and Setting: We utilized a cross-sectional mailed survey to gather information on long-term psychosocial outcomes of prophylactic mastectomy among women at six health maintenance organizations, all of which are part of the Cancer Research Network. In the context of this collaborative study, we characterized the impact of the different sites'' IRB review processes on the study protocol and participation. Results: IRB review resulted in site differences in physician consent prior to participant contact, invitation letter content and signatories, and incentive type. The review process required two to eight modifications beyond the initial application and resulted in unanticipated delays and costs. Conclusion: Site-to-site variability in IRB requirements may adversely impact scientific rigor and delay implementation of collaborative studies, especially when not considered in project planning. IRB review is an essential aspect of research but one that can present substantial challenges for multicenter studies. [Copyright &y& Elsevier]

: ObjectiveTo determine the association between changes in visual acuity (VA) and frequent falls in older women.: DesignProspective cohort study.: ParticipantsTwo thousand two elderly community-residing women participating in the Study of Osteoporotic Fractures with measurements of VA at baseline and a follow-up examination 4 to 6 years later (mean of 5.6 years).: MethodsBinocular VA with habitual correction was measured under standard illumination using Bailey–Lovie charts at baseline and fourth examinations. Change in VA was stratified into 5 categories: no change or VA gain, loss of 1 to 5 letters, loss of 6 to 10 letters, loss of 11 to 15 letters, and loss of >15 letters. A separate analysis considered decline in VA as the loss of ≥10 letters (≥2 lines) on the Bailey–Lovie acuity measure between baseline and follow-up examinations.: Main outcome measuresData on falls were obtained from postcards sent every 4 months after the follow-up examination. Frequent falling was defined as ≥2 falls during a 1-year period after the follow-up examination.: ResultsCompared with women with stable or improved VA, women with declining acuity had significantly greater odds of experiencing frequent falling during the subsequent year. Odds ratios after adjustment for baseline acuity and other confounders were 2.08 (95% confidence interval [CI]: 1.39–3.12) for loss of 1 to 5 letters, 1.85 (95% CI: 1.16–2.95) for loss of 6 to 10 letters, 2.51 (95% CI: 1.39–4.52) for loss of 11 to 15 letters, and 2.08 (95% CI: 1.01–4.30) for loss of >15 letters. In the analysis of visual decline defined as a loss of ≥10 letters, heightened risk of frequent falling was evident in each of 2 subgroups defined by splitting the sample on baseline VA, with borderline significant evidence of a more pronounced effect in those women with baseline VA of 20/40 or worse (P value for interaction, 0.083).: ConclusionsLoss of vision among elderly women increases the risk of frequent falls. Prevention or correction of visual loss may help reduce the number of future falls. [Copyright &y& Elsevier]