Background-The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging.Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) and NHANES 2005-2006, independent of traditional risk factors. Methods and Results-We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer-Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine-adjusted models (nϭ1919; odds ratioϭ1.13; 95% confidence interval, 1.02-1.24; Pϭ0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (nϭ1744; odds ratioϭ1.11; 95% confidence interval, 1.00 -1.23; Pϭ0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (Ͻ3-year follow-up), body mass index Ͼ30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at PՅ0.05. Conclusions-Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during Ͼ10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms.

BackgroundBisphenol A (BPA) is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals, yet human studies remain limited.ObjectiveWe estimated daily excretion of BPA among adults and examined hypothesized associations with serum estrogen and testosterone concentrations.MethodsWe conducted cross-sectional analyses using data from the InCHIANTI Study, a prospective population-based study of Italian adults. Our study included 715 adults between 20 and 74 years old. BPA concentrations were measured by liquid chromatography–mass spectrometry in 24-hr urine samples. The main outcome measures were serum concentrations of total testosterone and 17β-estradiol.ResultsGeometric mean urinary BPA concentration was 3.59 ng/mL [95% confidence interval (CI), 3.42–3.77 ng/mL], and mean excretion was 5.63 μg/day (5th population percentile, 2.1 μg/day; 95th percentile, 16.4 μg/day). We found higher excretion rates among men, younger respondents, and those with increasing waist circumference (p = 0.013) and weight (p = 0.003). Higher daily BPA excretion was associated with higher total testosterone concentrations in men, in models adjusted for age and study site (p = 0.044), and in models additionally adjusted for smoking, measures of obesity, and urinary creatinine concentrations (β = 0.046; 95% CI, 0.015–0.076; p = 0.004). We found no associations with the other serum measures. We also found no associations with the primary outcomes among women, but we did find an association between BPA and SHBG concentrations in the 60 premenopausal women.ConclusionHigher BPA exposure may be associated with endocrine changes in men. The mechanisms involved in the observed cross-sectional association with total testosterone concentrations need to be clarified.

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ObjectiveTo compare all-cause and liver-related hospital resource use in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation in UK patients with hepatic encephalopathy (HE).DesignA UK multicentre, retrospective, observational study. Patients' medical records were reviewed for demographics, clinical outcomes and adverse events (AEs) to rifaximin-α. Details of hospital admissions/attendances in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation were extracted from hospital electronic databases.Setting13 National Health Service centres.Patients207 patients with HE who initiated rifaximin-α between July 2008 and May 2014. Hospital resource use data were available for 145/207 patients.Main outcome measureChange in mean number of liver-related hospital bed days/patient (total and critical care) between the 6 months pre-rifaximin-α and post-rifaximin-α initiation.ResultsComparing the 6 months pre-rifaximin-α and post-rifaximin-α initiation in alive patients at the end of the observation period (N=114): there were significant reductions in the mean number of hospitalisations/patient (liver-related 1.3 to 0.5, p<0.001; all-cause 1.9 to 0.9, p<0.001), hospital bed days/patient (liver-related 17.8 to 6.8, p<0.001; all-cause 25.4 to 10.6, p<0.001), 30-day hospital readmissions/patient (liver-related 0.5 to 0.2, p=0.039; all-cause 0.8 to 0.4, p=0.024) and emergency department (ED) attendances/patient (all-cause, 1.0 to 0.5, p<0.001). The mean critical care bed days/patient reduced significantly for all-cause admissions (1.3 to 0.3, p=0.049); non-significant reduction for liver-related admissions. 4% of patients (9/207) developed AEs.ConclusionsIn UK clinical practice, treatment with rifaximin-α for HE is well-tolerated and associated with significant reductions in hospitalisations, bed days (including critical care), ED attendances and 30-day readmissions.

Background: Bisphenol A (BPA) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. Exposure of animal and cell models to doses of BPA below the recommended tolerable daily intake (TDI) of 50 μg/kg/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans.Objective: We investigated associations between BPA exposure and in vivo estrogenic gene expression in humans.Methods: We studied 96 adult men from the InCHIANTI population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes.Results: The geometric mean urinary BPA concentration was 3.65 ng/mL [95% confidence interval (CI): 3.13, 4.28], giving an estimated mean excretion of 5.84 μg/day (95% CI: 5.00, 6.85), significantly below the current TDI. In age-adjusted models, there were positive associations between higher BPA concentrations and higher ESR2 [estrogen receptor 2 (ER beta)] expression (unstandardized linear regression coefficient = 0.1804; 95% CI: 0.0388, 0.3221; p = 0.013) and ESRRA (estrogen related receptor alpha) expression (coefficient = 0.1718; 95% CI: 0.0213, 0.3223; p = 0.026): These associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. Upper-tertile BPA excretors (urinary BPA > 4.6 ng/mL) had 65% higher mean ESR2 expression than did lower-tertile BPA excretors (0–2.4 ng/mL).Conclusions: Because activation of nuclear-receptor–mediated pathways by BPA is consistently found in laboratory studies, such activation in humans provides evidence that BPA is likely to function as a xenoestrogen in this sample of adults.