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Background: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent C exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. Methods: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Results: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. Conclusions: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

Background: The U.S. Preventive Services Task Force advocates use of a 5A's framework (assess, advise, agree, assist, and arrange) for preventive health recommendations.Purpose: To describe 5A content of patient-physician colorectal cancer (CRC) screening discussions and physician-recommended screening modality and to test if these vary by whether patient previously received screening recommendation.Methods: Direct observation of periodic health examinations in 2007-2009 among average-risk primary care patients aged 50-80 years due for screening. Qualitative content analyses conducted 2008-2010 used to code office visit audio-recordings for 5A and other discussion content.Results: Among study-eligible visits (N=415), 59% contained assistance (i.e., help scheduling colonoscopy or delivery of stool cards), but the assess, advise, and agree steps were rarely comprehensively provided (1%-21%), and only 3% included the last step, arrange follow-up. Almost all physicians endorsed screening via colonoscopy (99%), either alone (69%) or in combination with other tests (30%). Patients nonadherent to a prior physician screening recommendation (31%) were less likely to have the reason(s) for screening discussed (37% vs 65%) or be told the endoscopy clinic would call them for scheduling (19% vs 27%), and more likely to have fecal occult blood testing (FOBT) alone (34% vs 25%) or FOBT and colonoscopy recommended (24% vs 14%), and a screening plan negotiated (21% vs 14%). Significance level is p<0.05 for all contrasts.Conclusions: Most patients due for CRC screening discuss screening with their physician, but with limited application of the 5A's approach. Opportunities to improve CRC screening decision-making are great, particularly among patients who are nonadherent to a prior recommendation from a physician. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adherence to professional society guidelines for follow-up or surveillance care in cancer survivors usually is measured with medical record review. Administrative data represent an alternative approach that may encompass larger numbers of patients with relatively low incremental costs. OBJECTIVES: We sought to determine the feasibility of using claims data to measure guideline adherence. METHODS: By reviewing paper and electronic medical records and claims data of 429 patients with 1 of 5 common cancers who received treatment with curative intent, we compared specific procedure receipt as well as guideline adherence classification as derived from claims and medical record data. Concordance was measured via kappa statistics. MEASURES: Care in the initial 18-month follow-up period was characterized as less than recommended, recommended, or greater than recommended per practice guidelines in both medical record and administrative data. RESULTS: Matching rates for individual procedures varied and were generally highest for certain laboratory tests and lowest for physical examinations. There were generally good-to-excellent levels of agreement (kappa=0.34-0.96) between a patient's classification in claims data and medical record data. No consistent differences in agreement were observed according to insurance type. CONCLUSIONS: In general, claims data capturing procedures and visit use for characterizing guideline adherence was comparable with what was documented in the medical record and suggests that if validated in other settings, administrative data could be used to describe patterns of follow up care. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The high prevalence of systemic lupus erythematosus (SLE) among African American women may be due to environmental exposures, genetic factors, or a combination of factors. Our goal was to assess association of residential proximity to hazardous waste sites and genetic variation in 3 glutathione Stransferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE. METHODS: Residential histories were obtained by interviewing 93 SLE patients from 3 predominantly African American neighborhoods in Boston. Residential addresses and locations of 416 hazardous waste sites in the study area were geocoded using ArcView software. Time-varying Cox models were used to study the effect of residential proximity to hazardous sites, GST genotype, and interaction between genotype and exposure in determining age at diagnosis. RESULTS: The prevalence of SLE among African American women in these neighborhoods was 3.56 SLE cases per 1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was associated with earlier SLE diagnosis (P = 0.03), but there was no association with proximity to 416 hazardous sites. Available data on specific site contaminants suggested that, at a subset of 67 sites, there was higher potential risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni correction). GST genotypes had a significant interaction with proximity (P = 0.03) in analyses limited to these sites. CONCLUSION: There was no independent association between residential proximity to hazardous waste sites and the risk of earlier SLE diagnosis in this urban population. However, analysis of a limited number of sites indicated that the risk of earlier SLE associated with proximity to hazardous sites might be modulated by GST polymorphisms. [ABSTRACT FROM AUTHOR]

Objectives: To assess the disparities in colorectal cancer (CRC) screening between elderly dual Medicare-Medicaid enrollees (or duals), the most vulnerable subgroup of the Medicare population, and nonduals.Data Sources/study Setting: The 1999 Medicare Denominator File, the Medicare Outpatient Standard Analytic Files, and Physician Supplier Part B files. In addition, the 1998 Area Resource File was used as a source for county-level attributes.Data Collection/extraction Methods: CRC screening procedures for 1999-fecal occult blood test (FOBT), flexible sigmoidoscopy (FLEX), colonoscopy with FOBT and/or FLEX (COL-WFF), and colonoscopy only (COL-ONLY)-were extracted from claim records, using diagnostic and procedure codes. Duals (n = 2.5 million) and nonduals (n = 20.2 million) receiving their care through the fee-for-service system were identified from the Denominator file. Hierarchical logistic regression analysis was conducted to adjust for individual- and county-level characteristics.Principal Findings: Compared with nonduals, duals were disproportionately represented by female, older-old, and minority individuals (respectively 74.4 versus 58.5 percent; 19.3 versus 10.8 percent; 35.7 versus 8.0 percent), and CRC screening was significantly lower in duals than in nonduals (5.1 versus 12.2 percent for FOBT adjusted odds ratio [AOR]: 0.48, 95 percent confidence interval [CI]: 0.45-0.51); 0.7 versus 1.9 percent for FLEX, (AOR: 0.55, 95 percent CI: 0.49-0.61); 0.4 versus 0.8 percent for COL-WFF (AOR: 0.60, 95 percent CI: 0.54-0.67); and 1.8 versus 2.5 percent for COL-ONLY (AOR: 0.85, 95 percent CI: 0.80-0.89); p < .001 for all comparisons.Conclusions: Duals are significantly less likely than nonduals to undergo CRC screening, even after adjusting for individual- and county-level covariates. Future studies should evaluate the contribution of comorbidity and low socioeconomic status to these disparities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the risk of systemic lupus erythematosus (SLE) associated with occupational exposure to silica dust and organic solvents in an urban population. METHODS: Women with SLE were identified through both community screening and hospital databases in 4 predominantly African American neighborhoods in Boston. Female control patients were volunteers from the same communities and were screened for the absence of connective tissue disease. Demographic factors, smoking history, and a detailed occupational history, including exposures to specific chemicals, were obtained by in-person interviews. The exposure assessment was based on independent evaluation of the occupational history by 2 reviewers who were blinded to each subject's disease status. The risks associated with exposure to silica and solvents were analyzed using multivariate conditional logistic regression models, adjusted for potential confounders. RESULTS: Ninety-five patients and 191 age- and race-matched controls were included in this analysis. Exposure to silica for longer than 1 year was associated with SLE (odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.7-11.2). An exposure-response effect was seen for longer duration of exposures to silica (P for trend = 0.01). The association between occupational exposure to organic solvents and SLE was not statistically significant (OR 1.04, 95% CI 0.34-3.2). CONCLUSION: Silica exposure from a variety of industrial occupations in urban areas is associated with an increased risk of SLE. A longer duration of exposure to silica dust is associated with greater risks. This study provides further impetus for additional research into the influence of modifiable exposures on the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

BACKGROUND: After potentially curative cancer treatment, patients may receive procedures for routine monitoring for recurrence or for evaluation of symptoms or signs. OBJECTIVE: We sought to characterize surveillance care guideline-recommended and other procedures performed in cancer survivors according to routine versus diagnostic indications. METHODS: This was a retrospective cohort study of paper and electronic medical records between 1990 and 2000 from a large midwestern U.S. integrated health care delivery system of 500 patients who received curative treatment of breast, colorectal, endometrial, lung, or prostate cancer. Our measures were the indications for potential surveillance procedures as recommended by clinical practice guidelines or otherwise. RESULTS: Among 14,670 procedures of interest received, 82.0% were performed for routine surveillance, whereas 10.6% were performed for diagnostic indications and 7.3% had indeterminate indications. Office visits most were often delivered for routine indications (91.6%), followed by guideline recommended tests for local recurrence (range 74.1-98.4%, depending on the specific test and cancer). In general, tests that were not recommended in established guidelines were for the purposes of detection of metastatic recurrence and were less often delivered for routine indications (overall frequency 59.2%, P<0.0001 compared with recommended testing). CONCLUSION: Office visits and testing for local recurrence of cancer generally are performed for routine surveillance, regardless of recommendation by practice guidelines. Because procedures not recommended by practice guidelines were more often for diagnostic purposes, classification of patients as undergoing intensive surveillance may be misleading and may require record review to confirm. [ABSTRACT FROM AUTHOR]

Age at menopause has implications for fertility and risk of hormonally related chronic diseases. Some pesticides disrupt reproductive hormones or are toxic to the ovary, but little is known about the association between pesticide exposure and timing of menopause. Cox proportional hazards modeling was used to examine the association between use of pesticides and age at menopause among 8,038 women living and working on farms in Iowa and North Carolina. Premenopausal women aged 35-55 years were followed from enrollment (1993-1997) to the date of their last menstrual period, or their follow-up interview (1999-2003) if still premenopausal. Women who experienced surgical menopause were censored at the date of surgery. Approximately 62% of the women reported ever mixing or applying pesticides; women who had never used pesticides were the comparison group for all analyses. After control for age, smoking status, and past use of oral contraceptives, the median time to menopause increased by approximately 3 months for women who used pesticides (hazard ratio = 0.87, 95% confidence interval: 0.78, 0.97) and by approximately 5 months for women who used hormonally active pesticides (hazard ratio = 0.77, 95% confidence interval: 0.65, 0.92). Pesticide use may be associated with a later age at menopause. [ABSTRACT FROM AUTHOR]

Background: Health care delivery varies with the level of managed care activity (MCA) in an area, potentially affecting health care for those not participating in managed care programs. However, the extent to which MCA is associated with the use of cancer screening by fee-for-service beneficiaries (FFS) is unclear.Objective: We sought to study colorectal cancer screening among Medicare FFS beneficiaries in relation to levels of Medicare MCA.Research Design: This study linked 1999 Medicare denominator and Part B claims data with the 1998 Area Resource File. After categorizing MCA as low (<10%), moderate (10-29.99%), or high (> or =30%), we assessed the association between colorectal cancer screening among FFS beneficiaries and MCA, controlling for individual demographic variables and county-level attributes of socioeconomic status and physician resources.Subjects: We included Medicare FFS beneficiaries 65 years of age or older with both Part A and Part B coverage for the entire calendar year from large counties in the study.Measures: We measured the likelihood of undergoing fecal occult blood testing (FOBT), flexible sigmoidoscopy (FLEX), or colonoscopy (COL).Results: Compared with Medicare FFS beneficiaries residing in counties with low MCA, those in high MCA counties were significantly more likely to undergo FOBT (adjusted odds ratio [AOR] 1.10, 95% confidence interval [CI] 1.04-1.16), FLEX (AOR 1.11, 95% CI 1.04-1.18), or colonoscopy, after receiving FOBT/FLEX (AOR 1.07, 95% CI 1.02-1.13).Conclusions: From a public health perspective, an association between higher levels of MCA and colorectal cancer screening among those not enrolled in managed care may translate into modest increases in use of colorectal cancer screening and possibly earlier detection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Epstein-Barr virus (EBV) is hypothesized to play a role in the development of systemic lupus erythematosus (SLE). Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important in regulating T cell-mediated immunity, encompassing the first line of response to viral infections, and genetic variation in CTLA-4 has been associated with SLE. This study examined the seroprevalence of EBV in a population-based study of SLE patients from the southeastern United States, and potential interactions with CTLA-4 polymorphisms were assessed. METHODS: Cases comprised 230 subjects recently diagnosed as having SLE (144 African American and 86 white) from university and community-based clinics, and controls comprised 276 age-, sex-, and state-matched subjects (72 African American and 204 white) recruited from driver's license registries. Antibodies to EBV capsid antigen were determined by enzyme-linked immunosorbent assay, with results expressed as positive or negative using the international standardized ratio (ISR) (a ratio of the sample absorbance to a known standard). CTLA-4 genotypes were identified by polymerase chain reaction-based methods. RESULTS: In African Americans, EBV-IgA seroprevalence was strongly associated with SLE (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 3.0-10.6). In whites, the modest association of SLE with EBV-IgA (OR 1.6) was modified by age, in that the strongest association was observed in those older than age 50 years (OR 4.1, 95% CI 1.6-10.4). The seroprevalence of EBV-IgM and that of EBV-IgG were not associated with SLE. Higher EBV-IgG absorbance ratios were observed in SLE patients, with a significant dose response across units of the ISR in African Americans (P < 0.0001). Allelic variation in the CTLA-4 gene promoter (-1661A/G) significantly modified the association between SLE and EBV-IgA (P = 0.03), with a stronger association among those with the -1661AA genotype. CONCLUSION: These findings suggest that repeated or reactivated EBV infection, which results in increased EBV-IgA seroprevalence and higher IgG antibody titers, may be associated with SLE, and that the CTLA-4 genotype influences immune responsiveness to EBV in SLE patients. The observed patterns of effect modification by race, age, and CTLA-4 genotype should be examined in other studies and may help frame new hypotheses regarding the role of EBV in SLE etiology. [ABSTRACT FROM AUTHOR]

Patients with new-onset dyspepsia can be safely and effectively treated with empiric therapy.Approximately 40% of patients with dyspepsia have an underlying disease, while up to 60% have functional dyspepsia.Endoscopy, the gold standard for the diagnostic evaluation of dyspepsia, is recommended for patients who present with alarm factors, who do not respond to empiric therapy or have recurring symptoms, or who are concerned about serious disease.Antisecretory therapy and Helicobacter pylori eradication therapy are the mainstay interventions for uninvestigated dyspepsia, although neither will relieve symptoms in most patients. [ABSTRACT FROM AUTHOR]

Purpose: Farm workers are exposed to crystalline silica, but there are no established questionnaires to assess silica dust exposure from farm work in epidemiologic studies. This study examines aspects of farm work that were used to estimate potential silica dust exposure in a population-based study conducted in the southeastern United States.Methods: We collected work and farming histories through in-person interviews with 620 participants in a population-based case-control study of systemic lupus erythematosus. A dust-exposure matrix was used to develop a telephone interview for 69 participants with potential medium- or high-level exposure, including questions on tasks, frequency, and farm location. Soil systems maps were used to infer soil type (sandy/other). Exposure indices were constructed based on tasks, frequency, and soil type.Results: Thirty-six percent of study participants worked on a farm, but only 52 (8%) were classified in the high (n=16) or medium (n=36) exposure groups based on responses to follow-up interview questions. Exposure indices based on open-ended job descriptions in initial interviews correctly categorized 52% of participants who answered prompted questions on relevant dusty tasks in follow-up interviews.Conclusions: Specific questions on dusty tasks and frequency are needed to accurately assess silica exposure from farm work. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study investigated the effect of alcohol-related disease on hip fracture and mortality. METHODS: A retrospective cohort design was used. The study cohort consisted of hospitalized Medicare beneficiaries with alcohol-related disease (n = 150,119) and randomly matched controls without alcohol-related disease (n = 726,218) identified through the 1988-1989 inpatient claims file. Incidence rates of hip fracture and mortality were examined. RESULTS: During the study period, 20,620 patients developed hip fracture, with 6973 cases among patients with alcohol-related disease and 13,647 cases among patients without alcohol-related disease. After adjustment for potential confounders, patients with alcohol-related disease had a 2.6-fold increased risk of hip fracture relative to patients without alcohol-related disease (95% confidence interval = 2.5, 2.6). Patients with alcohol-related disease had a higher risk of mortality at 1 year after hip fracture. CONCLUSIONS: Alcohol-related disease increases the risk of hip fracture significantly and reduces long-term survival. The present results suggest that patients hospitalized for alcohol-related disease should be targeted for hip fracture prevention programs. [ABSTRACT FROM AUTHOR]