Characteristics of Population Health Physicians and the Needs of Healthcare Organizations.

INTRODUCTION: Healthcare organizations are transitioning from fee-for-service, volume-based care toward value-based care and the Triple Aim. Physicians have critical roles as leaders and practitioners in this emerging field of population health management; however, the competencies required of these physicians are not well described. The purpose of this study is to explore the approaches of healthcare systems to population health-related functions, the competencies needed, and the characteristics of physicians who lead or staff these functions. METHODS: Investigators conducted semistructured interviews with a convenience sample of 14 healthcare executives and 15 Preventive Medicine physicians and a focus group with 9 healthcare executives. Interviews and the focus group were recorded, transcribed, and coded. Themes and notable quotes were identified. Data were collected and analyzed in 2019. RESULTS: Population health was variously defined by the healthcare executives, often naming specific components or activities. The typical population health activities described by healthcare executives (e.g., quality measurement and process improvement) were reported along with the skills of physicians performing these functions (e.g., data analysis, informatics, leadership, business acumen). A total of 2 types of population health physicians were described: the clinician leader and the population health specialist. CONCLUSIONS: This exploratory study identified several useful competencies for population health physicians in healthcare systems. Findings point to opportunities to promote a more systematic approach to population health and to prepare Preventive Medicine and other physicians for population health management positions.

Fetal bisphenol A and ethinylestradiol exposure alters male rat urogenital tract morphology at birth: Confirmation of prior low-dose findings in CLARITY-BPA.

Bisphenol A (BPA) is a contaminant in virtually all Americans. To examine BPA's adverse effects, the FDA-NCTR, NIEHS, and 14 groups of academic scientists formed a consortium: CLARITY-BPA. The purpose of our study was to investigate the effects of a wide range of doses of BPA on fetal development of the NCTR CD-SD male rat urogenital sinus (UGS). Pregnant rats were administered BPA or positive control ethinylestradiol (EE2) daily, via oral gavage, from gestational day 6 through parturition. Tissues were collected on postnatal day 1 and the UGS was analyzed using computer-assisted 3-D reconstruction. Importantly, only low doses of BPA, as well as EE2, significantly changed birth weight and UGS morphology, including an increased size of the colliculus and decreased size of the urethra, consistent with prior reported BPA and EE2 effects. Our findings provide further evidence that BPA mediates nonmonotonic developmental effects on the fetal urogenital sinus.

Experimental BPA Exposure and Glucose-Stimulated Insulin Response in Adult Men and Women.

CONTEXT: Human cross-sectional and animal studies have shown an association of the chemical bisphenol A (BPA) with insulin resistance, type 2 diabetes, and other metabolic diseases, but no human experimental study has investigated whether BPA alters insulin/C-peptide secretion. DESIGN: Men and postmenopausal women (without diabetes) were orally administered either the vehicle or a BPA dose of 50 µg/kg body weight, which has been predicted by US regulators (Food and Drug Administration, Environmental Protection Agency) to be the maximum, safe daily oral BPA dose over the lifetime. Insulin response was assessed in two cross-over experiments using an oral glucose tolerance test (OGTT; experiment 1) and a hyperglycemic (HG) clamp (experiment 2). Main outcomes were the percentage change of BPA session measures relative to those of the control session. RESULTS: Serum bioactive BPA after experimental exposure was at levels detected in human biomonitoring studies. In the OGTT, a strong positive correlation was found between hemoglobin A1c(HbA1c) and the percentage change in the insulinogenic index (Spearman = 0.92), an indicator of early-phase insulin response, and the equivalent C-peptide index (Pearson = 0.97). In the HG clamp study, focusing on the later-phase insulin response to a stable level of glucose, several measures of insulin and C-peptide appeared suppressed during the BPA session relative to the control session; the change in insulin maximum concentration (Cmax) was negatively correlated with HbA1c and the Cmax of bioactive serum BPA. CONCLUSIONS: This exploratory study suggests that BPA exposure to a dose considered safe by US regulators may alter glucose-stimulated insulin response in humans.

Holding thermal receipt paper and eating food after using hand sanitizer results in high serum bioactive and urine total levels of bisphenol A (BPA).

Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.

Prenatal bisphenol A exposure and maternally reported behavior in boys and girls.

Prenatal exposure to gonadal hormones plays a major role in the normal development of the male and female brain and sexually dimorphic behaviors. Hormone-dependent differences in brain structure and function suggest that exposure to exogenous endocrine disrupting chemicals may be associated with sex-specific alterations in behavior. Bisphenol A (BPA) is an environmental chemical that has been shown to alter estrogen, androgen, and thyroid hormone signaling pathways. Epidemiological and experimental studies suggest associations between prenatal exposure to BPA and child behavior, however data are inconsistent, and few studies have examined school age children. We examined BPA concentration in spot urine samples from women at mean 27 weeks of pregnancy in relation to child behavior assessed at age 6-10 years using the parent-completed Child Behavior Checklist (CBCL). We report associations between maternal BPA urinary concentrations and several CBCL scores in 153 children (77 boys and 76 girls). We observed a significant interaction between maternal urinary BPA and sex for several behaviors (externalizing, aggression, Anxiety Disorder, Oppositional/Defiant Disorder and Conduct Disorder traits), but no significant associations between BPA and scores on any CBCL scales. However in analyses restricted to children of mothers with detectable prenatal urinary BPA (n=125), BPA was associated with moderately increased internalizing and externalizing behaviors, withdrawn/depressed behavior, somatic problems, and Oppositional/Defiant Disorder traits in boys. In addition we observed a significant interaction between BPA and sex for several behaviors (externalizing, withdrawn/depressed, rule-breaking, Oppositional/Defiant Disorder traits, and Conduct Disorder traits). These results suggest that prenatal exposure to BPA may be related to increased behavior problems in school age boys, but not girls.

Reproductive parameters in young men living in Rochester, New York.

OBJECTIVE: To describe semen quality and reproductive hormone concentrations of young men living in Rochester, New York, and to compare these with published data from similar European and Japanese populations. DESIGN: Cross-sectional study. SETTING: University and college campuses in the Rochester, New York, area. PATIENT(S): Unselected young college students (n = 222). INTERVENTION(S): A physical examination, blood and semen samples, and completion of a brief questionnaire. MAIN OUTCOME MEASURE(S): Semen parameters and serum reproductive hormone levels. RESULT(S): Subjects were aged 18-22 years (median age, 19.5 years), predominantly Caucasian (81%), and nonsmokers (79%), with a mean (SD) body mass index of 25.5 (4.2) kg/m(2). Overall, median sperm concentration was 52 × 10(6)/mL (5th-95th percentiles: 7-181 × 10(6)/mL), median total sperm count was 158 × 10(6) (14-587 × 10(6)), and 23.1% and 15.8% of men had a sperm concentration below 20 × 10(6)/mL and 15 × 10(6)/mL, respectively. Few men had serum hormones falling outside clinically normal ranges. Median sperm concentrations and reproductive hormone levels were comparable to those seen in young men in Denmark, Finland, and Japan. CONCLUSION(S): Our study provides the first data in 70 years on semen quality and reproductive hormones in young men in the United States with unknown fertility. These data suggest that, overall, reproductive parameters in our study population of young college students from the northeastern United States are similar to those of young European and Japanese men.

Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation.

Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000µg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0-24h), we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose-response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-µg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes.

Non-monotonic dose effects of in utero exposure to di(2-ethylhexyl) phthalate (DEHP) on testicular and serum testosterone and anogenital distance in male mouse fetuses.

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant. Epidemiological studies suggest that DEHP decreases masculinization of male fetuses. Numerous rat studies report DEHP reduces fetal testosterone production at doses greatly exceeding human exposure. We fed pregnant CD-1 mice 0.5-500,000 µg/kg/day DEHP from gestation day (GD) 9-18 and examined mothers and male fetuses on GD 18. We assessed non-monotonic dose-response by adding a quadratic term to a simple linear regression model. Except at the 500,000 µg/kg/day dose, DEHP stimulated an increase in maternal and fetal serum testosterone and increased anogenital distance (AGD). Non-monotonic dose-response curves were noted for AGD and maternal, and testis testosterone (P values 0.013-0.021). Because data from our highest dose (500,000 µg/kg/day) did not differ significantly from controls, this dose could have been incorrectly assumed to be the NOAEL had we only tested very high doses, as is typical in studies for regulatory agencies.

Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001-2008.

BACKGROUND: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women. OBJECTIVE: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study. METHODS: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001-2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance, and glycosylated hemoglobin A1c. RESULTS: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance. DISCUSSION: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.

Socioeconomic factors and phthalate metabolite concentrations among United States women of reproductive age.

INTRODUCTION: Relatively little is known about the socioeconomic correlates of phthalate metabolite urine concentrations among the general population, exposures of increasing public health concern, particularly for women of reproductive age. METHODS: We pooled data from the 2001-2008 cycles of the National Health and Nutrition Examination Survey to examine the associations between phthalate metabolite concentrations (including the molar sum of four di-2-ethylhexyl phthalate (DEHP) metabolites, the molar sum of two dibutyl phthalate (DBP) metabolites, and metabolites of benzylbutyl phthalate (BzBP) and diethyl phthalate (DEP)) with socioeconomic indicators (including ethnicity, education, income, and food security status) among women 20 to 39 years age. We also derived a socioeconomic status summary measure using factor analysis and investigated its associations with metabolite concentrations. RESULTS: In fully adjusted models, the lowest quartile of overall socioeconomic status was associated with 1.83 (95% CI=1.54-2.17) times the concentrations of mono-benzyl phthalate (MBzP), and 0.72 (95% CI=0.54-0.98) times the concentrations of (molar sum) DEHP metabolites compared with the highest quartile of overall socioeconomic status. This latter association was driven primarily by educational attainment. All Non-White ethnicities combined had 1.24 (95% CI=1.09-1.40) times the concentrations of (molar sum) DBP metabolites, 1.32 (95% CI=1.12-1.56) times the mono-ethyl phthalate (MEP) concentrations, and 0.82 (95% CI=0.71-0.96) the concentrations of MBzP of Non-Hispanic Whites. CONCLUSIONS: Biomarkers of phthalate exposure vary with socioeconomic factors in women of reproductive age in the United States. Given the public health concern surrounding phthalate exposure, more research is needed to elucidate the reasons for these differences.

Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York.

BACKGROUND: In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents and humans. Whether AGD is related to semen quality in human is unknown. OBJECTIVE: We examined associations between AGD and semen parameters in adult males. METHODS: We used multiple regression analyses to model the relationships between sperm parameters and two alternative measures of AGD [from the anus to the posterior base of the scrotum (AGD(AS)) and to the cephalad insertion of the penis (AGD(AP))] in 126 volunteers in Rochester, New York. RESULTS: AGD(AS), but not AGD(AP), was associated with sperm concentration, motility, morphology, total sperm count, and total motile count (p-values, 0.002-0.048). Men with AGD(AS) below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5-21.6) to have a low sperm concentration (< 20 × 106/mL). For a typical study participant, sperm concentrations were 34.7 × 106/mL and 51.6 × 106/mL at the 25th and 75th percentiles of (adjusted) AGD(AS). CONCLUSIONS: In our population, AGD(AS) was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive function. Our results suggest, therefore, that the androgenic environment during early fetal life exerts a fundamental influence on both AGD and adult sperm counts in humans, as demonstrated in rodents.

Bisphenol A data in NHANES suggest longer than expected half-life, substantial nonfood exposure, or both.

BACKGROUND: It is commonly stated in the literature on human exposure to bisphenol A (BPA) that food is the predominant BPA exposure source, and that BPA is rapidly and completely cleared from the body. If this is correct, BPA levels in fasting individuals should decrease with increased fasting time. OBJECTIVES: We set out to investigate the relationship between urine BPA concentration and fasting time in a population-based sample. METHODS: We modeled log BPA urine concentration as a function of fasting time, adjusted for urine creatinine and other confounders, in 1,469 adult participants in the 2003-2004 National Health and Nutrition Examination Survey. We estimated the BPA "population-based half-life" (pop(1/2)) for a fasting time of 0-24 hr, < 4.5 hr, 4.5-8.5 hr, and > 8.5 hr. RESULTS: The overall pop(1/2) for the 0- to 24-hr interval was 43 hr [95% confidence interval (CI), 26-119 hr]. Among those reporting fasting times of 4.5-8.5 hr (n = 441), BPA declined significantly with fasting time, with a pop(1/2) of 4.1 hr (95% CI, 2.6-10.6 hr). However, within the fasting time intervals of 0-4.5 hr (n = 129) and 8.5-24 hr (n = 899), we saw no appreciable decline. Fasting time did not significantly predict highest (> 12 ng/mL) or lowest (below limit of detection) BPA levels. CONCLUSIONS: Overall, BPA levels did not decline rapidly with fasting time in this sample. This suggests substantial nonfood exposure, accumulation in body tissues such as fat, or both. Explaining these findings may require experimental pharmacokinetic studies of chronic BPA exposure, further examination of BPA levels and effects in fat, and a search for important nonfood sources.

Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males.

BACKGROUND: Phthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes. OBJECTIVES: Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance. METHODS: Subjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). RESULTS: In model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values