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Epidemiologists often compare the observed number of deaths in a cohort with the expected number of deaths, obtained by multiplying person-time accrued in the cohort by mortality rates for a reference population (ideally, a reference that represents the mortality rate in the cohort in the absence of exposure). However, if exposure is hazardous (or salutary), this calculation will not consistently estimate the number of deaths expected in the absence of exposure because exposure will have affected the distribution of person-time observed in the study cohort. While problems with interpretation of this standard calculation of expected counts were discussed more than 2 decades ago, these discussions had little impact on epidemiologic practice. The logic of counterfactuals may help clarify this topic as we revisit these issues. In this paper, we describe a simple way to consistently estimate the expected number of deaths in such settings, and we illustrate the approach using data from a cohort study of mortality among underground miners. [ABSTRACT FROM AUTHOR]

In cohort mortality studies, there often is interest in associations between an exposure of primary interest and mortality due to a range of different causes. A standard approach to such analyses involves fitting a separate regression model for each type of outcome. However, the statistical precision of some estimated associations may be poor because of sparse data. In this paper, we describe a hierarchical regression model for estimation of parameters describing outcome-specific relative rate functions and associated credible intervals. The proposed model uses background stratification to provide flexible control for the outcome-specific associations of potential confounders, and it employs a hierarchical “shrinkage” approach to stabilize estimates of an exposure’s associations with mortality due to different causes of death. The approach is illustrated in analyses of cancer mortality in 2 cohorts: a cohort of dioxin-exposed US chemical workers and a cohort of radiation-exposed Japanese atomic bomb survivors. Compared with standard regression estimates of associations, hierarchical regression yielded estimates with improved precision that tended to have less extreme values. The hierarchical regression approach also allowed the fitting of models with effect-measure modification. The proposed hierarchical approach can yield estimates of association that are more precise than conventional estimates when one wishes to estimate associations with multiple outcomes. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premenopausal women from the Study of Women's Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: −11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations. [ABSTRACT FROM AUTHOR]

Exposure to air pollution during pregnancy has been suggested to be a risk factor for preterm birth; however, epidemiologic evidence remains mixed and limited. The authors examined the association between ambient levels of particulate matter <2.5 µm in aerodynamic diameter (PM2.5) and the risk of preterm birth in North Carolina during the period 2001–2005. They estimated the risks of cumulative and lagged average exposures to PM2.5 during pregnancy via a 2-stage discrete-time survival model. The authors also considered exposure metrics derived from 1) ambient concentrations measured by the Air Quality System (AQS) monitoring network and 2) concentrations predicted by statistically fusing AQS data with process-based numerical model output (the Statistically Fused Air and Deposition Surfaces (FSD) database). Using the AQS measurements, an interquartile-range (1.73 µg/m3) increase in cumulative PM2.5 exposure was associated with a 6.8% (95% posterior interval: 0.5, 13.6) increase in the risk of preterm birth. Using the FSD-predicted levels and accounting for prediction error, the authors also found significant adverse associations between trimester 1, trimester 2, and cumulative PM2.5 exposure and preterm birth. These findings suggest that exposure to ambient PM2.5 during pregnancy is associated with increased risk of preterm birth, even in a region characterized by relatively good air quality. [ABSTRACT FROM AUTHOR]

Recent studies finding that small-for-gestational-age (SGA) birth is associated with increased adiposity in childhood and adulthood have been based on analyses "adjusting" for height, weight, or body mass index (BMI; weight (kg)/height (m)²) measured concurrently with the adiposity measurement. To assess the potential for bias due to overadjustment for a causal mediator, we compared 2 approaches to analyzing the association between SGA birth and adiposity outcomes (skinfold thicknesses and bioelectrical impedance measurement of body fat) at age 11.5 years using the same data set in a cohort of Belarusian children followed from birth in 1996-1997 to age 11.5 years in 2008-2010. We 1) studied the association of SGA birth with adiposity, adjusting for baseline covariates only, and 2) made additional regression adjustment for concurrent height, weight, or BMI. The first approach yielded negative associations between SGA birth and all adiposity outcomes. Additional adjustment for concurrent weight or BMI reversed (i.e., to positive) the SGA-adiposity association. To explore the latter anthropometric measures as causal mediators, we also used marginal structural models to estimate the controlled direct effect of SGA birth. That effect was similar to the effect seen with the first approach when modeled on height, was null when modeled on BMI, but was confounded by differences in lean mass versus fat mass when modeled on weight. [ABSTRACT FROM AUTHOR]

We evaluated alternative approaches to assessing and correcting for nonresponse bias in a longitudinal survey. We considered the changes in substance-use outcomes over a 3-year period among young adults aged 18-24 years (n = 5,199) in the United States, analyzing data from the National Epidemiologic Survey on Alcohol and Related Conditions. This survey collected a variety of substance-use information from a nationally representative sample of US adults in 2 waves: 2001-2002 and 2004-2005. We first considered nonresponse rates in the second wave as a function of key substance-use outcomes in wave 1. We then evaluated 5 alternative approaches designed to correct for nonresponse bias under different attrition mechanisms, including weighting adjustments, multiple imputation, selection models, and pattern-mixture models. Nonignorable attrition in a longitudinal survey can lead to bias in estimates of change in certain health behaviors over time, and only selected procedures enable analysts to assess the sensitivity of their inferences to different assumptions about the extent of nonignorability. We compared estimates based on these 5 approaches, and we suggest a road map for assessing the risk of nonresponse bias in longitudinal studies. We conclude with directions for future research in this area given the results of our evaluations. [ABSTRACT FROM AUTHOR]

This study's objective was to investigate healthy aging in older French adults 5 years after a period of daily nutritional-dose supplementation with antioxidant nutrients. The study was based on the double-blind, randomized trial, Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) Study (1994-2002) and the SU.VI.MAX 2 Follow-up Study (2007-2009). During 1994-2002, participants received a daily combination of vitamin C (120 mg), β-carotene (6 mg), vitamin E (30 mg), selenium (100 µg), and zinc (20 mg) or placebo. Healthy aging was assessed in 2007-2009 by using multiple criteria, including the absence of major chronic disease and good physical and cognitive functioning. Data from a subsample of the SU.VI.MAX 2 cohort, initially free of major chronic disease, with a mean age of 65.3 years in 2007-2009 (n = 3,966), were used to calculate relative risks. Supplementation was associated with a greater healthy aging probability among men (relative risk = 1.16, 95% confidence interval: 1.04, 1.29) but not among women (relative risk = 0.98, 95%confidence interval: 0.86, 1.11) or all participants (relative risk = 1.07, 95%confidence interval: 0.99, 1.16). Moreover, exploratory subgroup analyses indicated effect modification by initial serum concentrations of zinc and vitamin C. In conclusion, an adequate supply of antioxidant nutrients (equivalent to quantities provided by a balanced diet rich in fruits and vegetables) may have a beneficial role for healthy aging. [ABSTRACT FROM AUTHOR]

The timing of a child's first acute lower respiratory infection (ALRI) is important, because the younger a child is when he or she experiences ALRI, the greater the risk of death. Indoor exposure to particulate matter less than or equal to 2.5 µm in diameter (PM2.5) has been associated with increased frequency of ALRI, but little is known about how it may affect the timing of a child's first ALRI. In this study, we aimed to estimate the association between a child's age at first ALRI and indoor exposure to PM2.5 in a low-income community in Dhaka, Bangladesh. We followed 257 children from birth through age 2 years to record their age at first ALRI. Between May 2009 and April 2010, we also measured indoor concentrations of PM2.5 in children's homes. We used generalized gamma distribution models to estimate the relative age at first ALRI associated with the mean number of hours in which PM2.5 concentrations exceeded 100 µg/m3. Each hour in which PM2.5 levels exceeded 100 µg/m3 was independently associated with a 12% decrease (95% confidence interval: 2, 21; P = 0.021) in age at first ALRI. Interventions to reduce indoor exposure to PM2.5 could increase the ages at which children experience their first ALRI in this urban community. [ABSTRACT FROM PUBLISHER]

Higher dietary intakes of flavonoids and proanthocyanidins have been associated with a lower risk of several cancers. Few prospective epidemiologic studies have examined individual flavonoids and proanthocyanidins in relation to prostate cancer. We examined these associations in a prospective US cohort of 43,268 men with a mean age of 70 years who completed detailed self-administered questionnaires in 1999–2000. During a mean follow-up of 7.8 years, 3,974 total prostate cancers, including 567 high-grade cases and 362 advanced cases, were ascertained. Cox proportional hazards regression models were used to calculate multivariable-adjusted relative risks and 95% confidence intervals. Residual energy-adjusted total flavonoids (for fifth quintile vs. first quintile, relative risk = 1.11, 95% confidence interval: 1.01, 1.23; P for trend = 0.02) and several subclasses were positively associated with overall prostate cancer risk, mostly limited to the top quintile and the first 2 years of follow-up. The associations for total flavonoids, flavan-3-ols, and proanthocyanidins with high-grade prostate cancer risk varied by follow-up time. During follow-up from 2002 to 2009, we observed suggestive inverse trends with higher total flavonoids (P for trend = 0.05) and proanthocyanidins (P for trend = 0.04) with high-grade prostate cancer, but not with advanced prostate cancer. Although evidence is limited, a possible role of total flavonoids and proanthocyanidins in prostate cancer tumor progression deserves further study. [ABSTRACT FROM PUBLISHER]

We assessed the relation of experiences of racism to the incidence of obesity and the modifying impact of residential racial segregation in the Black Women's Health Study, a follow-up study of US black women. Racism scores were created from 8 questions asked in 1997 and 2009 about the frequency of “everyday” racism (e.g., “people act as if you are dishonest”) and of “lifetime” racism (e.g., unfair treatment on the job). Residential segregation was measured by linking participant addresses to 2000 and 2010 US Census block group data on the percent of black residents. We used Cox proportional hazard models to estimate incidence rate ratios and 95% confidence intervals. Based on 4,315 incident cases of obesity identified from 1997 through 2009, both everyday racism and lifetime racism were positively associated with increased incidence. The incidence rate ratios for women who were in the highest category of everyday racism or lifetime racism in both 1997 and 2009, relative to those in the lowest category, were 1.69 (95% confidence interval: 1.45, 1.96; Ptrend < 0.01) and 1.38 (95% confidence interval: 1.15, 1.66; Ptrend < 0.01), respectively. These associations were not modified by residential segregation. These results suggest that racism contributes to the higher incidence of obesity among African American women. [ABSTRACT FROM AUTHOR]

Happiness is among the most fundamental of all human goals. Although the short-term association between physical activity and happiness is well known, the long-term associations are not. Data from the National Population Health Survey cycles conducted between 1994/1995 and 2008/2009 (cycles 1 through 8) were analyzed. Happy respondents were classified as physically active or inactive at baseline and then were followed up in subsequent cycles to examine their likelihood of becoming unhappy. Individuals who changed their activity level also were examined. After controlling for potential confounding factors, the authors found that leisure-time physical activity (LTPA) was associated with reduced odds of unhappiness after 2 years and 4 years. People who were inactive in 2 consecutive cycles were more than twice as likely to be unhappy as those who remained active in both cycles after 2 years. Compared with those who became active, inactive participants who remained inactive were also more likely to become unhappy. A change in LTPA from active to inactive was associated with increased odds of becoming unhappy 2 years later. This study suggests that LTPA has a long-term association with happiness. Changes in LTPA are associated with subsequent mood status. [ABSTRACT FROM AUTHOR]

This study evaluated the association of arsenic exposure, as measured in urine, with diabetes prevalence, glycated hemoglobin, and insulin resistance in American Indian adults from Arizona, Oklahoma, and North and South Dakota (1989–1991). We studied 3,925 men and women 45–74 years of age with available urine arsenic measures. Diabetes was defined as a fasting glucose level of 126 mg/dL or higher, a 2-hour glucose level of 200 mg/dL or higher, a hemoglobin A1c (HbA1c) of 6.5% or higher, or diabetes treatment. Median urine arsenic concentration was 14.1 µg/L (interquartile range, 7.9–24.2). Diabetes prevalence was 49.4%. After adjustment for sociodemographic factors, diabetes risk factors, and urine creatinine, the prevalence ratio of diabetes comparing the 75th versus 25th percentiles of total arsenic concentrations was 1.14 (95% confidence interval: 1.08, 1.21). The association between arsenic and diabetes was restricted to participants with poor diabetes control (HbA1c ≥8%). Arsenic was positively associated with HbA1c levels in participants with diabetes. Arsenic was not associated with HbA1c or with insulin resistance (assessed by homeostatic model assessment to quantify insulin resistance) in participants without diabetes. Urine arsenic was associated with diabetes control in a population from rural communities in the United States with a high burden of diabetes. Prospective studies that evaluate the direction of the relation between poor diabetes control and arsenic exposure are needed. [ABSTRACT FROM PUBLISHER]

Although recent studies suggest that 13% of young adults, including at least one-fourth of African Americans, experience parental incarceration, little research has examined links between parental incarceration and physical health. Using data from the National Longitudinal Study of Adolescent Health (1994–2008) and gender-based theories of stress, the authors examined whether parental incarceration is associated with increased body mass index among women but not men. Panel analysis spanning adolescence and adulthood, controlling for stressful life events, internalizing behaviors, and a range of individual, familial, and neighborhood characteristics, reveals that body mass index for women who have experienced parental incarceration is 0.49 units (P < 0.004) higher than that for women whose parents have never been incarcerated. This association is not evident among men. Similarly, in change score models between waves II and IV, women experiencing parental incarceration have a 0.92-unit increase in body mass index (P < 0.026) relative to women who did not have a parent undergo incarceration. In supplemental analysis examining if gender differences in incarceration stress response (externalizing vs. internalizing) explain these findings, the authors found that obesity status moderates the relation between depression and parental incarceration. Results suggest a stress internalization process that, for the first time, links parental incarceration with obesity among women. [ABSTRACT FROM AUTHOR]

Inconsistent evidence of the hypothesized favorable effects of high job control on health may have resulted from a failure to treat job control as a multifactor concept. The authors studied whether the 2 components of job control, decision authority and skill discretion, were differentially associated with cause-specific mortality in 13,510 Finnish forest company employees with no history of severe illness. Surveys on work characteristics were carried out in 1986 and 1996, and the respondents were followed up until the end of 2005 by use of the Statistics Finland National Death Registry. During a mean follow-up of 15.5 years, 981 participants died. In the analyses adjusted for confounders, employees with high and intermediate levels of skill discretion had a lower all-cause mortality risk than those with low skill discretion, with hazard ratios of 0.84 (95% confidence interval (CI): 0.69, 1.02) and 0.81 (95% CI: 0.69, 0.96), respectively. In contrast, high decision authority was associated with elevated risks of all-cause, cardiovascular, and alcohol-related mortality, with hazard ratios of 1.28 (95% CI: 1.06, 1.54), 1.49 (95% CI: 1.11, 2.02), and 2.03 (95% CI: 1.03, 4.00), respectively. The results suggest that job control is not an unequivocal concept in relation to mortality; decision authority and skill discretion show different and to some extent opposite associations. [ABSTRACT FROM AUTHOR]

Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified. [ABSTRACT FROM PUBLISHER]

Almost 10% of all births are preterm, and 2.2% are stillbirths. Recent research has suggested that environmental factors may be a contributory cause of these adverse birth outcomes. The authors examined the relation between ambient temperature and preterm birth and stillbirth in Brisbane, Australia, between 2005 and 2009 (n = 101,870). They used a Cox proportional hazards model with livebirth and stillbirth as competing risks. They also examined whether there were periods in pregnancy where exposure to high temperatures had a greater effect. Higher ambient temperatures in the last 4 weeks of the pregnancy increased the risk of stillbirth. The hazard ratio for stillbirth was 0.3 at 12°C relative to the reference temperature of 21°C. The temperature effect was greatest at less than 36 weeks of gestation. There was an association between higher temperature and shorter gestation, as the hazard ratio for livebirth was 0.96 at 15°C and 1.02 at 25°C. This effect was greatest at later gestational ages. These results provide strong evidence of an association between increased temperature and increased risk of stillbirth and shorter gestation. [ABSTRACT FROM PUBLISHER]