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Preview: American Journal of Epidemiology - current issue

American Journal of Epidemiology Current Issue

Published: Tue, 28 Nov 2017 00:00:00 GMT

Last Build Date: Fri, 15 Dec 2017 07:47:19 GMT


Kenneth Warren and the Great Neglected Diseases of Mankind Programme: The Transformation of Geographical Medicine in the US and BeyondBy Conrad Keating

Tue, 28 Nov 2017 00:00:00 GMT

ISBN 978-3-319-50145-1, Springer International Publishing, Cham, Switzerland (Telephone: 800-777-4643, E-mail:, Website:, 2016, 150 pp., $29.99 Hardcover

A Decade of War: Prospective Trajectories of Posttraumatic Stress Disorder Symptoms Among Deployed US Military Personnel and the Influence of Combat Exposure

Wed, 27 Sep 2017 00:00:00 GMT

Posttraumatic stress disorder (PTSD) is a common psychiatric disorder among service members and veterans. The clinical course of PTSD varies between individuals, and patterns of symptom development have yet to be clearly delineated. Previous studies have been limited by convenience sampling, short follow-up periods, and the inability to account for combat-related trauma. To determine the trajectories of PTSD symptoms among deployed military personnel with and without combat exposure, we used data from a population-based representative sample of 8,178 US service members who participated in the Millennium Cohort Study from 2001 to 2011. Using latent growth mixture modeling, trajectories of PTSD symptoms were determined in the total sample, as well as in individuals with and without combat exposure, respectively. Overall, 4 trajectories of PTSD were characterized: resilient, pre-existing, new-onset, and moderate stable. Across all trajectories, combat-deployed service members diverged from non–combat-deployed service members, even after a single deployment. The former also generally had higher PTSD symptoms. Based on the models, nearly 90% of those without combat exposure remained resilient over the 10-year period, compared with 80% of those with combat exposure. Findings demonstrate that although the clinical course of PTSD symptoms shows heterogeneous patterns of development, combat exposure is uniformly associated with poor mental health.

Best Practices for Gauging Evidence of Causality in Air Pollution Epidemiology

Wed, 06 Sep 2017 00:00:00 GMT

The contentious political climate surrounding air pollution regulations has brought some researchers and policy-makers to argue that evidence of causality is necessary before implementing more stringent regulations. Recently, investigators in an increasing number of air pollution studies have purported to have used “causal analysis,” generating the impression that studies not explicitly labeled as such are merely “associational” and therefore less rigorous. Using 3 prominent air pollution studies as examples, we review good practices for how to critically evaluate the extent to which an air pollution study provides evidence of causality. We argue that evidence of causality should be gauged by a critical evaluation of design decisions such as 1) what actions or exposure levels are being compared, 2) whether an adequate comparison group was constructed, and 3) how closely these design decisions approximate an idealized randomized study. We argue that air pollution studies that are more scientifically rigorous in terms of the decisions made to approximate a randomized experiment are more likely to provide evidence of causality and should be prioritized among the body of evidence for regulatory review accordingly. Our considerations, although presented in the context of air pollution epidemiology, can be broadly applied to other fields of epidemiology.

Estimating the Comparative Effectiveness of Feeding Interventions in the Pediatric Intensive Care Unit: A Demonstration of Longitudinal Targeted Maximum Likelihood Estimation

Sat, 24 Jun 2017 00:00:00 GMT

Longitudinal data sources offer new opportunities for the evaluation of sequential interventions. To adjust for time-dependent confounding in these settings, longitudinal targeted maximum likelihood based estimation (TMLE), a doubly robust method that can be coupled with machine learning, has been proposed. This paper provides a tutorial in applying longitudinal TMLE, in contrast to inverse probability of treatment weighting and g-computation based on iterative conditional expectations. We apply these methods to estimate the causal effect of nutritional interventions on clinical outcomes among critically ill children in a United Kingdom study (Control of Hyperglycemia in Paediatric Intensive Care, 2008–2011). We estimate the probability of a child’s being discharged alive from the pediatric intensive care unit by a given day, under a range of static and dynamic feeding regimes. We find that before adjustment, patients who follow the static regime “never feed” are discharged by the end of the fifth day with a probability of 0.88 (95% confidence interval: 0.87, 0.90), while for the patients who follow the regime “feed from day 3,” the probability of discharge is 0.64 (95% confidence interval: 0.62, 0.66). After adjustment for time-dependent confounding, most of this difference disappears, and the statistical methods produce similar results. TMLE offers a flexible estimation approach; hence, we provide practical guidance on implementation to encourage its wider use.

Racial and Ethnic Disparities in the Incidence of Esophageal Cancer in the United States, 1992–2013

Wed, 21 Jun 2017 00:00:00 GMT

Racial and ethnic disparities in the incidence of esophageal cancer have not been thoroughly characterized with quantitative health-disparity measures. Using data from 1992–2013 from 13 US cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities according to histological type, based on a variety of disparity metrics. The age-standardized incidence rate of squamous cell carcinoma (SCC) was highest among black persons, while adenocarcinoma mainly affected white men. The rate of SCC decreased over time in all racial/ethnic groups, and this was most pronounced in black persons (by 5.7% per year among men and 5.0% among women). The adenocarcinoma rate rose among non-Hispanic whites and among black men. Racial/ethnic disparities in the incidence of total esophageal cancer decreased over time, which was due mainly to reduced disparities in SCC. The 2 absolute disparity measures—range difference and between-group variance—for adenocarcinoma rose by 3.2% and 6.8% per year, respectively, in men and by 1.8% and 5.3% per year, respectively, in women. This study demonstrates decreased racial/ethnic disparities in the incidence of esophageal SCC over time in the United States, while disparities increased in adenocarcinoma incidence as measured on the absolute scale.

Epidemiologic Risk Factors for In Situ and Invasive Breast Cancers Among Postmenopausal Women in the National Institutes of Health-AARP Diet and Health Study

Fri, 16 Jun 2017 00:00:00 GMT

Comparing risk factor associations between invasive breast cancers and possible precursors may further our understanding of factors related to initiation versus progression. Accordingly, among 190,325 postmenopausal participants in the National Institutes of Health-AARP Diet and Health Study (1995–2011), we compared the association between risk factors and incident ductal carcinoma in situ (DCIS; n = 1,453) with that of risk factors and invasive ductal carcinomas (n = 7,525); in addition, we compared the association between risk factors and lobular carcinoma in situ (LCIS; n = 186) with that of risk factors and invasive lobular carcinomas (n = 1,191). Hazard ratios and 95% confidence intervals were estimated from multivariable Cox proportional hazards regression models. We used case-only multivariable logistic regression to test for heterogeneity in associations. Younger age at menopause was associated with a higher risk of DCIS but lower risks of LCIS and invasive ductal carcinomas (P for heterogeneity < 0.01). Prior breast biopsy was more strongly associated with the risk of LCIS than the risk of DCIS (P for heterogeneity = 0.04). Increased risks associated with use of menopausal hormone therapy were stronger for LCIS than DCIS (P for heterogeneity = 0.03) and invasive lobular carcinomas (P for heterogeneity < 0.01). Associations were similar for race, age at menarche, age at first birth, family history, alcohol consumption, and smoking status, which suggests that most risk factor associations are similar for in situ and invasive cancers and may influence early stages of tumorigenesis. The differential associations observed for various factors may provide important clues for understanding the etiology of certain breast cancers.

TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences

Mon, 12 Jun 2017 00:00:00 GMT

The prevalence of fusions of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific–related gene (ERG), or TMPRSS2:ERG, in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess oncoprotein encoded by the ERG gene as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study (2004–2006). Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patient characteristics. We found that 47 of 262 (18%) prostate cancers were ERG-positive, and being negative for ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2:ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2:ERG fusions in prostate cancer to be highest in men of European descent (49%), followed by men of Asian (27%) and then African (25%) descent. The lower prevalence of TMPRSS2:ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.

Application of an Individual-Based Transmission Hazard Model for Estimation of Influenza Vaccine Effectiveness in a Household Cohort

Fri, 09 Jun 2017 00:00:00 GMT

Household cohort studies are an important design for the study of respiratory virus transmission. Inferences from these studies can be improved through the use of mechanistic models to account for household structure and risk as an alternative to traditional regression models. We adapted a previously described individual-based transmission hazard (TH) model and assessed its utility for analyzing data from a household cohort maintained in part for study of influenza vaccine effectiveness (VE). Households with ≥4 individuals, including ≥2 children <18 years of age, were enrolled and followed during the 2010–2011 influenza season. VE was estimated in both TH and Cox proportional hazards (PH) models. For each individual, TH models estimated hazards of infection from the community and each infected household contact. Influenza A(H3N2) infection was laboratory-confirmed in 58 (4%) subjects. VE estimates from both models were similarly low overall (Cox PH: 20%, 95% confidence interval: −57, 59; TH: 27%, 95% credible interval: −23, 58) and highest for children <9 years of age (Cox PH: 40%, 95% confidence interval: −49, 76; TH: 52%, 95% credible interval: 7, 75). VE estimates were robust to model choice, although the ability of the TH model to accurately describe transmission of influenza presents continued opportunity for analyses.

Measurement Error Due to Patient Flow in Estimates of Intensive Care Unit Length of Stay

Fri, 09 Jun 2017 00:00:00 GMT

Clinical endpoints measured in terms of duration, such as intensive care unit (ICU) length of stay (LOS), are widely used in randomized clinical trials (RCTs) and observational research. In analyses of patient-level data from a recent RCT, in which ICU LOS was the primary endpoint, and in administrative data, we showed that additional ICU time is often accrued by patients after they are deemed ready for discharge. This “immutable” time (which cannot plausibly be altered by interventions under study) varies by day, week, and year, adding on average one-third of a day to total LOS. We then used statistical simulations, informed by the administrative data and RCT, to assess the impact of immutable time on the measurement and statistical comparison of patients’ ICU LOS. These simulations demonstrated that immutable time combines with clinically necessary ICU time (neither of which is likely to be normally distributed) to produce overall LOS distributions that might either mask true treatment effects or suggest false treatment effects relative to analyses of time to discharge readiness. The extent and direction of bias were complex functions of the statistical method used, mortality rates and distributions, and the magnitude of immutable time relative to intervention-associated reductions in LOS.

Neonatal Outcomes Associated With Placental Abruption

Thu, 08 Jun 2017 00:00:00 GMT

Placental abruption (early separation of the placenta) is associated with preterm birth and perinatal mortality, but associations with other neonatal morbidities remain understudied. We examined the association between abruption and newborn outcomes. We analyzed 223,341 singleton deliveries from the Consortium on Safe Labor study, a retrospective, multisite, observational study (2002–2008) of electronic medical records in the United States. Adjusted relative risks, incidence rate ratios, and 99% confidence intervals were estimated. Direct effects attributable to abruption were examined by conditioning on intermediates (preterm birth and small for gestational age) with sensitivity analyses. Incidence of abruption was 1.6% (n = 3,619). Abruption was associated with an elevated risk of newborn resuscitation (relative risk (RR) = 1.5, 99% confidence interval (CI): 1.5, 1.6), apnea (RR = 5.8, 99% CI: 5.1, 6.5), asphyxia (RR = 8.5, 99% CI: 5.7, 11.3), respiratory distress syndrome (RR = 6.5, 99% CI: 5.9, 7.1), neonatal intensive care unit admission (RR = 3.4, 99% CI: 3.2, 3.6), longer intensive care length of stay (incidence rate ratio = 2.0, 99% CI: 1.9, 2.2), stillbirth (RR = 6.3, 99% CI: 4.7, 7.9), and neonatal mortality (RR = 7.6, 99% CI: 5.2, 10.1). In sensitivity analyses, there was a direct effect of abruption associated with increased neonatal risks. These findings expand our knowledge of the association between abruption and perinatal and neonatal outcomes.

Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study

Fri, 02 Jun 2017 00:00:00 GMT

Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13–1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission.