Journal Cover
American Journal of Epidemiology
Journal Prestige (SJR): 2.713
Citation Impact (citeScore): 3
Number of Followers: 171  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0002-9262 - ISSN (Online) 1476-6256
Published by Oxford University Press Homepage  [396 journals]
  • Design Strategy of the Sabes Study: Diagnosis and Treatment of Early HIV
           Infection Among Men Who Have Sex With Men and Transgender Women in Lima,
           Peru, 2013–2017
    • Authors: Lama J; Brezak A, Dobbins J, et al.
      Pages: 1577 - 1585
      Abstract: The Sabes Study evaluated a treatment-as-prevention intervention among cisgender men who have sex with men and transgender women in Lima, Peru—populations disproportionately affected by the human immunodeficiency virus (HIV) epidemic. The intervention was designed to prevent onward transmission of HIV by identifying HIV-negative high-risk individuals, testing them monthly for the presence of HIV, and then rapidly treating those who became HIV-positive. The main outcome of interest was the development of a model predicting the population-level impact of early detection of HIV infection and immediate initiation of antiretroviral therapy in this population. From July 2013 to September 2015, a total of 3,337 subjects were screened for HIV; 2,685 (80.5%) were negative, and 2,109 began monthly testing. We identified 256 individuals shortly after HIV acquisition, 216 of whom were enrolled in the treatment phase of the study. All participants were followed for 48 weeks (follow-up ended in 2017) and were then referred to the Peruvian Ministry of Health to continue receiving free HIV care and treatment. Initial findings from this intervention demonstrate that it is possible to recruit high-risk individuals, screen them for HIV, continue to test those who are initially HIV-negative in order to identify incident cases shortly after acquisition, and then rapidly link them to health care.
      PubDate: Wed, 07 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy030
      Issue No: Vol. 187, No. 8 (2018)
  • Retirements of Coal and Oil Power Plants in California: Association With
           Reduced Preterm Birth Among Populations Nearby
    • Authors: Casey J; Karasek D, Ogburn E, et al.
      Pages: 1586 - 1594
      Abstract: Coal and oil power plant retirements reduce air pollution nearby, but few studies have leveraged these natural experiments for public health research. We used California Department of Public Health birth records and US Energy Information Administration data from 2001–2011 to evaluate the relationship between the retirements of 8 coal and oil power plants and nearby preterm (gestational age of <37 weeks) birth. We conducted a difference-in-differences analysis using adjusted linear mixed models that included 57,005 births—6.3% of which were preterm—to compare the probability of preterm birth before and after power plant retirement among mothers residing within 0–5 km and 5–10 km of the 8 power plants. We found that power plant retirements were associated with a decrease in the proportion of preterm birth within 5 km (−0.019, 95% CI: −0.031, −0.008) and 5–10 km (−0.015, 95% CI: −0.024, −0.007), controlling for secular trends with mothers living 10–20 km away. For the 0–5-km area, this corresponds to a reduction in preterm birth from 7.0% to 5.1%. Subgroup analyses indicated a potentially larger association among non-Hispanic black and Asian mothers than among non-Hispanic white and Hispanic mothers and no differences in educational attainment. Future coal and oil power plant retirements may reduce preterm birth among nearby populations.
      PubDate: Wed, 16 May 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy110
      Issue No: Vol. 187, No. 8 (2018)
  • Invited Commentary: The Power of Preterm Birth to Motivate a Cleaner
    • Authors: Mendola P.
      Pages: 1595 - 1597
      Abstract: This commentary reflects on a natural experiment reported by Casey et al. (Am J Epidemiol. 2018;187(8):1586–1594) that tested the association between living near a coal or oil power plant and preterm birth. They found that retiring power plants resulted in a significant reduction in preterm birth, with larger effects observed for late preterm birth and among non-Hispanic black mothers and infants. Natural experiments, in particular the Utah Valley Steel Mill closure, have played a prominent role in the evidence base for air pollution regulation due to their demonstrated impact on cardiopulmonary effects in adults. Reproductive health, including infant mortality and preterm birth associated with poor air quality, has generally received less attention. Even small reductions in preterm birth can have a large population health impact, both in terms of preventing mortality in the short-term an in preventing lifelong disability among affected infants.
      PubDate: Wed, 16 May 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy108
      Issue No: Vol. 187, No. 8 (2018)
  • The Association of Arsenic Exposure and Arsenic Metabolism With the
           Metabolic Syndrome and Its Individual Components: Prospective Evidence
           From the Strong Heart Family Study
    • Authors: Spratlen M; Grau-Perez M, Best L, et al.
      Pages: 1598 - 1612
      Abstract: Inorganic arsenic exposure is ubiquitous, and both exposure and interindividual differences in its metabolism have been associated with cardiometabolic risk. However, the associations of arsenic exposure and arsenic metabolism with the metabolic syndrome (MetS) and its individual components are relatively unknown. We used Poisson regression with robust variance to evaluate the associations of baseline arsenic exposure (urinary arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident MetS and its individual components (elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, hypertension, and elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort study in American Indian communities (baseline visits were held in 1998–1999 and 2001–2003, follow-up visits in 2001–2003 and 2006–2009). Over the course of follow-up, 32% of participants developed MetS. An interquartile-range increase in arsenic exposure was associated with a 1.19-fold (95% confidence interval: 1.01, 1.41) greater risk of elevated fasting plasma glucose concentration but not with other individual components of the MetS or MetS overall. Arsenic metabolism, specifically lower percentage of monomethylarsonic acid and higher percentage of dimethylarsinic acid, was associated with higher risk of overall MetS and elevated waist circumference but not with any other MetS component. These findings support the hypothesis that there are contrasting and independent associations of arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.
      PubDate: Thu, 15 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy048
      Issue No: Vol. 187, No. 8 (2018)
  • Amyotrophic Lateral Sclerosis and Exposure to Diesel Exhaust in a Danish
    • Authors: Dickerson A; Hansen J, Gredal O, et al.
      Pages: 1613 - 1622
      Abstract: Previous studies have suggested an increased risk of amyotrophic lateral sclerosis (ALS) and other motor neuron diseases for persons in occupations commonly involving exposure to diesel exhaust (DE). In this study, we investigated the association between occupational exposure to DE and odds of ALS. ALS cases were identified from the Danish National Patient Registry (1982–2013) and individually matched to 100 controls per case on the basis of birth year and sex. Using information on occupational history from 1964 onward obtained from the Danish Pension Fund, we estimated cumulative DE exposures using a job exposure matrix. We evaluated associations using conditional logistic regression analyses and stratified the analyses by sex. Using a 10-year lag period, DE exposure was positively associated with ALS among men who had ever been exposed (adjusted odds ratio (aOR) = 1.20, 95% confidence interval (CI): 1.05, 1.38). For men with greater than 50% probability of DE exposure, we observed a positive association between ALS and highest-quartile exposure during the 5-year (aOR = 1.35, 95% CI: 1.07, 1.70) and 10-year (aOR = 1.41, 95% CI: 1.11, 1.79) lag periods. Our study suggests an association between consistently higher exposures to DE and ALS in men, but not in women. These findings support previous reports of associations between ALS and occupations commonly involving DE exposure.
      PubDate: Sat, 24 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy069
      Issue No: Vol. 187, No. 8 (2018)
  • Population Density in Hiroshima and Nagasaki Before the Bombings in 1945:
           Its Measurement and Impact on Radiation Risk Estimates in the Life Span
           Study of Atomic Bomb Survivors
    • Authors: French B; Funamoto S, Sugiyama H, et al.
      Pages: 1623 - 1629
      Abstract: In the Life Span Study cohort of atomic bomb survivors, differences in urbanicity between high-dose and low-dose survivors could confound the association between radiation dose and adverse outcomes. We obtained data on the population distribution in Hiroshima and Nagasaki before the 1945 bombings and quantified the impact of adjustment for population density on radiation risk estimates for mortality (1950–2003) and incident solid cancer (1958–2009). Population density ranged from 4,671 to 14,378 people/km2 in the urban region of Hiroshima and 5,748 to 19,149 people/km2 in the urban region of Nagasaki. Radiation risk estimates for solid cancer mortality were attenuated by 5.1% after adjustment for population density, but those for all-cause mortality and incident solid cancer were unchanged. There was no overall association between population density and adverse outcomes, but there was evidence that the association between density and mortality differed according to age at exposure. Among survivors who were 10–14 years of age in 1945, there was a positive association between population density and risk of all-cause mortality (per 5,000-people/km2 increase, relative risk = 1.053, 95% confidence interval: 1.027, 1.079) and solid cancer mortality (per 5,000-people/km2 increase, relative risk = 1.069, 95% confidence interval: 1.025, 1.115). Our results suggest that radiation risk estimates from the Life Span Study are not sensitive to unmeasured confounding by urban-rural differences.
      PubDate: Thu, 29 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy066
      Issue No: Vol. 187, No. 8 (2018)
  • Oral Contraceptive Use and Risks of Cancer in the NIH-AARP Diet and Health
    • Authors: Michels K; Brinton L, Pfeiffer R, et al.
      Pages: 1630 - 1641
      Abstract: Although use of oral contraceptives (OCs) is common, their influence on carcinogenesis is not fully understood. We used Cox proportional hazards models to examine OC use (never/<1 year (referent), 1–4, 5–9, ≥10 years) and development of incident cancers across body sites within the same base population: women in the prospective National Institutes of Health-AARP Diet and Health Study (enrolled 1995–1996 and followed until 2011). Adjustment for confounding varied by outcome; all models accounted for age, race, body mass index, and smoking status, and included at least 100,000 women. Any OC use conferred a 3% reduction in the risk for any cancer (hazard ratio = 0.97, 95% confidence interval: 0.95, 0.99). Expected risk reductions that strengthened with duration of use were identified for ovarian and endometrial cancers and were suggested for kidney cancer (all P for trend < 0.05). Non-Hodgkin lymphoma risk (hazard ratio = 0.79, 95% confidence interval: 0.64, 0.97) was reduced with 10 or more years of OC use. There was a 37% reduced risk for bladder cancer and 46% increased risk for pancreatic cancer among long-term OC users who were 60 years of age or younger at baseline. OC use did not influence risks for most other cancers evaluated. Given the high prevalence of use and changing formulations, additional studies are warranted to fully understand the chemopreventive effects of these medications.
      PubDate: Wed, 31 Jan 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwx388
      Issue No: Vol. 187, No. 8 (2018)
  • Preterm Birth and Small Size for Gestational Age in Singleton, In Vitro
           Fertilization Births Using Donor Oocytes
    • Authors: Boulet S; Kawwass J, Crawford S, et al.
      Pages: 1642 - 1650
      Abstract: We used 2006–2015 US National Assisted Reproductive Technology Surveillance System data to compare preterm birth and fetal growth for liveborn singletons (24–42 weeks’ gestation) following in vitro fertilization with donor versus autologous oocytes. Using binary and multinomial logistic regression, we computed adjusted odds ratios and 95% confidence intervals for associations between use of donor oocytes and preterm delivery, being small for gestational age (SGA), and being large for gestational age (LGA), stratified by fresh and thawed embryo status and accounting for maternal characteristics and year of birth. There were 204,855 singleton births from fresh embryo transfers and 106,077 from thawed embryo transfers. Among fresh embryo transfers, donor oocyte births had higher odds of being preterm (adjusted odd ratio (aOR) = 1.32, 95% confidence interval (CI): 1.27, 1.38) or LGA (aOR = 1.27, 95% CI: 1.21, 1.33) but lower odds of being SGA (aOR = 0.81, 95% CI: 0.77, 0.85). Among thawed embryo transfers, donor oocyte births had higher odds of being preterm (aOR = 1.57, 95% CI: 1.48, 1.65) or SGA (aOR = 1.22, 95% CI: 1.14, 1.31) but lower odds of being LGA (aOR = 0.87, 95% CI: 0.82, 0.92). Use of donor oocytes was associated with increased odds of preterm delivery irrespective of embryo status; odds of being SGA were increased for donor versus autologous oocyte births among thawed embryo transfers only.
      PubDate: Fri, 09 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy051
      Issue No: Vol. 187, No. 8 (2018)
  • Breastfeeding and Childhood Wheeze: Age-Specific Analyses and Longitudinal
           Wheezing Phenotypes as Complementary Approaches to the Analysis of Cohort
    • Authors: Quigley M; Carson C, Kelly Y.
      Pages: 1651 - 1661
      Abstract: Systematic reviews suggest that breastfeeding is associated with a lower risk of asthma, although marked heterogeneity exists. Using UK Millennium Cohort Study data (n = 10,126 children, born 2000–2002), we examined the association between breastfeeding duration and wheezing in the previous year, first for each age group separately (ages 9 months, 3 years, 5 years, 7 years, and 11 years) and then in terms of a longitudinal wheezing phenotype: “early transient” (wheezing any time up to age 5 years but not thereafter), “late onset” (any time from age 7 years but not beforehand), and “persistent” (any time up to age 5 years and any time from age 7 years). The association between breastfeeding and wheeze varied by age (2-sided P for interaction = 0.0003). For example, breastfeeding for 6–9 months was associated with lower odds of wheezing at ages 9 months, 3 years, and 5 years but less so at ages 7 years and 11 years (adjusted odds ratios = 0.73, 0.78, 0.79, 0.84, 1.06, respectively). There was a strong dose-response relationship for breastfeeding per month and early transient wheeze (adjusted odds ratio for linear trend = 0.961, 95% confidence interval: 0.942, 0.980) but no clear trend for late-onset or persistent wheeze. Our results identified heterogeneity in the association between breastfeeding and wheezing according to age at wheezing and wheezing phenotype.
      PubDate: Tue, 03 Apr 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy057
      Issue No: Vol. 187, No. 8 (2018)
  • An Epigenome-Wide Association Study of Obesity-Related Traits
    • Authors: Dhana K; Braun K, Nano J, et al.
      Pages: 1662 - 1669
      Abstract: We conducted an epigenome-wide association study on obesity-related traits. We used data from 2 prospective, population-based cohort studies: the Rotterdam Study (RS) (2006–2013) and the Atherosclerosis Risk in Communities (ARIC) Study (1990–1992). We used the RS (n = 1,450) as the discovery panel and the ARIC Study (n = 2,097) as the replication panel. Linear mixed-effect models were used to assess the cross-sectional associations between genome-wide DNA methylation in leukocytes and body mass index (BMI) and waist circumference (WC), adjusting for sex, age, smoking, leukocyte proportions, array number, and position on array. The latter 2 variables were modeled as random effects. Fourteen 5′-C-phosphate-G-3′ (CpG) sites were associated with BMI and 26 CpG sites with WC in the RS after Bonferroni correction (P < 1.07 × 10−7), of which 12 and 13 CpGs were replicated in the ARIC Study, respectively. The most significant novel CpGs were located on the Musashi RNA binding protein 2 gene (MSI2; cg21139312) and the leucyl-tRNA synthetase 2, mitochondrial gene (LARS2; cg18030453) and were associated with both BMI and WC. CpGs at BRDT, PSMD1, IFI44L, MAP1A, and MAP3K5 were associated with BMI. CpGs at LGALS3BP, MAP2K3, DHCR24, CPSF4L, and TMEM49 were associated with WC. We report novel associations between methylation at MSI2 and LARS2 and obesity-related traits. These results provide further insight into mechanisms underlying obesity-related traits, which can enable identification of new biomarkers in obesity-related chronic diseases.
      PubDate: Mon, 14 May 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy025
      Issue No: Vol. 187, No. 8 (2018)
  • Sex Differences in Attaining Cigarette Smoking and Nicotine Dependence
           Milestones Among Novice Smokers
    • Authors: Sylvestre M; Chagnon M, Wellman R, et al.
      Pages: 1670 - 1677
      Abstract: There may be sex differences in the response to nicotine, according to findings of studies in animals; however, sex differences in the natural course of cigarette smoking and nicotine dependence are documented in few studies. Prevalent (n = 240 girls; n = 184 boys) and incident (n = 231 girls; n = 184 boys) cigarette smokers from the Nicotine Dependence in Teens Study were followed up to 5 years after first puff, from age 12 to 18 years (1999–2005). We used Cox proportional hazards models to compare time to development of 3 cigarette-use (i.e., whole cigarette; 100 cigarettes lifetime; regular smoking), and 3 nicotine-dependence symptom (i.e., “really need a cigarette”; mentally addicted; physically addicted) milestones across sex. Girls were at higher risk than boys of attaining all milestones; hazard ratios (95% confidence intervals) ranged from 1.35 (1.06, 1.72) for 100 cigarettes lifetime to 1.74 (1.44, 2.10) for “really need a cigarette.” Among nonregular smokers, 26% (8%; 43%) and 25% (6%; 44%) more girls than boys reported “really need a cigarette” 1 and 2 years, respectively, after first puff. Preventive interventions may need adjustment to incorporate these findings. Additional research should clarify the relative contribution of biological and social underpinnings of these sex differences.
      PubDate: Wed, 07 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy045
      Issue No: Vol. 187, No. 8 (2018)
  • Prognostic Association of Major Frailty Domain Trajectories With 5-Year
           Mortality in Very Old Adults: Results From the PARTAGE Cohort Study
    • Authors: Agrinier N; Erpelding M, Labat C, et al.
      Pages: 1678 - 1685
      Abstract: We aimed to identify trajectories of nutrition, cognitive function, and autonomy over time among very old adults and to assess their impact on mortality. A cohort of subjects aged ≥80 years (in 2007–2008) who were followed for 5 years in 72 Italian and French nursing homes was used for post hoc analyses. Body mass index (BMI; weight (kg)/height (m)2), Mini-Mental State Examination (MMSE) score, and Katz Index of Independence in Activities of Daily Living (ADL) score were assessed at 4 time points. Information on vital status was collected during follow-up. Latent trajectory and Cox models were used. In the 710 subjects included, the mean age at inclusion was 88.0 (standard deviation, 4.8) years, and 78.9% were female. We identified 7 composite trajectories based on BMI, MMSE, and ADL values. As compared with the reference group (trajectory 7—stable overweight; preserved cognitive function and autonomy), 2 trajectories presented increased hazards of dying: trajectory 1 (stable overweight; moderately impaired, then declining, cognitive function and autonomy (adjusted hazard ratio = 1.79, 95% confidence interval (CI): 1.26, 2.55)) and trajectory 6 (stable normal BMI; slight cognitive decline; and moderate, then degrading, loss of autonomy (adjusted hazard ratio = 1.67, 95% CI: 1.15, 2.44)). The C-index was 0.81 (95% CI: 0.72, 0.88). Repeated monitoring of BMI, MMSE score, and ADL in very old adults provides trajectories that produce better prognostic information than simple baseline assessment.
      PubDate: Thu, 15 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy050
      Issue No: Vol. 187, No. 8 (2018)
  • Educational Mobility Across Generations and Depressive Symptoms Over 10
           Years Among US Latinos
    • Authors: Ward J; Robinson W, Pence B, et al.
      Pages: 1686 - 1695
      Abstract: Few studies have collected intergenerational data to assess the association between educational mobility across multiple generations and offspring depression. Using data from the Sacramento Area Latino Study on Aging (1998–2008), we assessed the influence of intergenerational education on depressive symptoms over 10 years among 1,786 Latino individuals (mean age = 70.6 years). Educational mobility was classified as stable-low (low parental/low offspring education), upwardly mobile (low parental/high offspring education), stable-high (high parental/high offspring education), or downwardly mobile (high parental/low offspring education). Depressive symptoms were measured with the Center for Epidemiological Studies–Depression Scale (CES-D); higher scores indicated more depressive symptoms. To quantify the association between educational mobility and CES-D scores over follow-up, we used generalized estimating equations to account for repeated CES-D measurements and adjusted for identified confounders. Within individuals, depressive symptoms remained relatively stable over follow-up. Compared with stable-low education, stable-high education and upward mobility were associated with significantly lower CES-D scores (β = −2.75 and −2.18, respectively). Downwardly mobile participants had slightly lower CES-D scores than stable-low participants (β = −0.77). Our results suggest that sustained, low educational attainment across generations may have adverse mental health consequences, and improved educational opportunities in underresourced communities may counteract the adverse influence of low parental education on Latino depression.
      PubDate: Mon, 14 May 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy056
      Issue No: Vol. 187, No. 8 (2018)
  • Neighborhood Disadvantage and Body Mass Index: A Study of Residential
    • Authors: Rachele J; Kavanagh A, Brown W, et al.
      Pages: 1696 - 1703
      Abstract: Natural experiments, such as longitudinal observational studies that follow-up residents as they relocate, provide a strong basis to infer causation between the neighborhood environment and health. In this study, we examined whether changes in the level of neighborhood disadvantage were associated with changes in body mass index (BMI) after residential relocation. This analysis included data from 928 residents who relocated between 2007 and 2013, across 4 waves of the How Areas in Brisbane Influence Health and Activity (HABITAT) study in Brisbane, Australia. Neighborhood disadvantage was measured using a census-derived composite index. For individual-level data, participants self-reported their height, weight, education, occupation, and household income. Data were analyzed using multilevel, hybrid linear models. Women residing in less disadvantaged neighborhoods had a lower BMI, but there was no association among men. Neighborhood disadvantage was not associated with within-individual changes in BMI among men or women when moving to a new neighborhood. Despite a growing body of literature suggesting an association between neighborhood disadvantage and BMI, we found this association may not be causal among middle-aged and older adults. Observing associations between neighborhood socioeconomic disadvantage and BMI over the life course, including the impact of residential relocation at younger ages, remains a priority for future research.
      PubDate: Wed, 17 Jan 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwx390
      Issue No: Vol. 187, No. 8 (2018)
  • Does Socioeconomic Status Modify the Association Between Preterm Birth and
           Children’s Early Cognitive Ability and Kindergarten Academic Achievement
           in the United States'
    • Authors: Beauregard J; Drews-Botsch C, Sales J, et al.
      Pages: 1704 - 1713
      Abstract: Being born preterm and being raised in poverty are each linked with adverse cognitive outcomes. Using data from 5,250 singletons born in the United States in 2001 and enrolled in the Early Childhood Longitudinal Study, Birth Cohort, we examined whether household socioeconomic status (SES) modified the association between preterm birth (PTB) and children’s scores on cognitive assessments at age 2 years and reading and mathematics assessments at kindergarten age. Gestational age was measured from birth certificates and categorized as early preterm, moderate preterm, late preterm, early term, and term. SES was measured at age 9 months using a composite of parental education, occupation, and income. PTB was associated with 0.1- to 0.6-standard deviation-deficits in 2-year cognitive ability and kindergarten mathematics scores and with 0.1- to 0.4-standard-deviation deficits in kindergarten reading scores. Children living in the lowest (versus highest) SES quintile scored 0.6 standard deviations lower on 2-year cognitive ability, 1.1 standard deviations lower on kindergarten reading, and 0.9 standard deviations lower on kindergarten mathematics. The association between PTB and cognitive outcomes did not differ by postnatal SES. However, children who were both born preterm and lived in lower-SES households had the poorest performance on all 3 outcomes and therefore may represent a uniquely high-risk group.
      PubDate: Fri, 11 May 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy068
      Issue No: Vol. 187, No. 8 (2018)
  • Longitudinal Associations Between Respiratory Infections and Asthma in
           Young Children
    • Authors: Ramette A; Spycher B, Wang J, et al.
      Pages: 1714 - 1720
      Abstract: We examined temporal dependencies between repeated assessments of respiratory tract infections (RTIs) and asthma in children in the Leicester Respiratory Cohort, Leicestershire, United Kingdom. Information associated with asthma (i.e., doctor diagnosis, health care visits, wheeze frequency) and RTIs (i.e., cold duration and frequency, cough with colds, ear infections) in the previous 12 months was assessed repeatedly at ages 1, 4, and 6 years for children born between April 1996 and April 1997. We determined associations between contemporaneous and lagged measures of asthma and RTIs, using structural equation modelling. In 1,995 children, asthma was positively associated with contemporaneous infections. Asthma at age 6 years was positively associated with asthma at age 4 years (regression coefficient = 0.87; 95% confidence interval (CI): 0.76, 0.97), but not with asthma at age 1 year (regression coefficient = −0.01; 95% CI: −0.14, 0.11). We found no evidence for direct protective effect of infections at age 1 year on asthma either at age 4 (regression coefficient = −0.20; 95% CI: −0.51, 0.10) or 6 (regression coefficient = 0.24; 95% CI: −0.04, 0.52) years. Adjusting for potential confounders did not qualitatively change those relationships. Based on our findings, we suggest that asthma at age 6 years is directly influenced by asthma history and only indirectly, if at all, by earlier infection episodes. We found little support for a protective effect of preschool infections on asthma at early school age.
      PubDate: Tue, 13 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy053
      Issue No: Vol. 187, No. 8 (2018)
  • Serum Metabolomic Profiling of All-Cause Mortality: A Prospective Analysis
           in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study
    • Authors: Huang J; Weinstein S, Moore S, et al.
      Pages: 1721 - 1732
      Abstract: Tobacco use, hypertension, hyperglycemia, overweight, and inactivity are leading causes of overall and cardiovascular disease (CVD) mortality worldwide, yet the relevant metabolic alterations responsible are largely unknown. We conducted a serum metabolomic analysis of 620 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985–2013). During 28 years of follow-up, there were 435 deaths (197 CVD and 107 cancer). The analysis included 406 known metabolites measured with ultra-high-performance liquid chromatography/mass spectrometry–gas chromatography/mass spectrometry. We used Cox regression to estimate mortality hazard ratios for a 1-standard-deviation difference in metabolite signals. The strongest associations with overall mortality were N-acetylvaline (hazard ratio (HR) = 1.28; P < 4.1 × 10−5, below Bonferroni statistical threshold) and dimethylglycine, 7-methylguanine, C-glycosyltryptophan, taurocholate, and N-acetyltryptophan (1.23 ≤ HR ≤ 1.32; 5 × 10−5 ≤ P ≤ 1 × 10−4). C-Glycosyltryptophan, 7-methylguanine, and 4-androsten-3β,17β-diol disulfate were statistically significantly associated with CVD mortality (1.49 ≤ HR ≤ 1.62, P < 4.1 × 10−5). No metabolite was associated with cancer mortality, at a false discovery rate of <0.1. Individuals with a 1-standard-deviation higher metabolite risk score had increased all-cause and CVD mortality in the test set (HR = 1.4, P = 0.05; HR = 1.8, P = 0.003, respectively). The several serum metabolites and their composite risk score independently associated with all-cause and CVD mortality may provide potential leads regarding the molecular basis of mortality.
      PubDate: Tue, 30 Jan 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy017
      Issue No: Vol. 187, No. 8 (2018)
  • A Randomized Controlled Trial to Measure Spillover Effects of a Combined
           Water, Sanitation, and Handwashing Intervention in Rural Bangladesh
    • Authors: Benjamin-Chung J; Amin N, Ercumen A, et al.
      Pages: 1733 - 1744
      Abstract: Water, sanitation, and handwashing interventions may confer spillover effects on intervention recipients’ neighbors by interrupting pathogen transmission. We measured geographically local spillovers in the Water Quality, Sanitation, and Handwashing (WASH) Benefits Study, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention versus those of control participants. Geographically defined clusters were randomly allocated to a compound-level intervention (i.e., chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control arm. From January 2015 to August 2015, in 180 clusters, we enrolled 1,799 neighboring children who were age matched to trial participants who would have been eligible for the study had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples and measured soil-transmitted helminth infections and caregiver-reported diarrhea and respiratory illness. Neighbors’ characteristics were balanced across arms. Detectable Escherichia coli prevalence in tubewell samples was lower for intervention participants’ neighbors than control participants’ (prevalence ratio = 0.83; 95% confidence interval: 0.73, 0.95). Fecal indicator bacteria prevalence did not differ between arms for other environmental samples. Prevalence was similar in neighbors of intervention participants versus those of control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors’ tubewell water contamination but did not affect neighboring children’s health.
      PubDate: Tue, 27 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy046
      Issue No: Vol. 187, No. 8 (2018)
  • Timing of Birth as an Emergent Risk Factor for Rotavirus Hospitalization
           and Vaccine Performance in the Postvaccination Era in the United States
    • Authors: Lopman B; Dahl R, Shah M, et al.
      Pages: 1745 - 1751
      Abstract: Rotavirus vaccines were introduced in the United States in 2006, and in the years since they have fundamentally altered the seasonality of rotavirus infection and have shifted disease outbreaks from annual epidemics to biennial epidemics. We investigated whether season and year of birth have emerged as risk factors for rotavirus or have affected vaccine performance. We constructed a retrospective birth cohort of US children under age 5 years using the 2001–2014 MarketScan database (Truven Health Analytics, Chicago, Illinois). We evaluated the associations of season of birth, even/odd year of birth, and interactions with vaccination. We fitted Cox proportional hazards models to estimate the hazard of rotavirus hospitalization according to calendar year of birth and season of birth assessed for interaction with vaccination. After the introduction of rotavirus vaccine, we observed monotonically decreasing rates of rotavirus hospitalization for each subsequent birth cohort but a biennial incidence pattern by calendar year. In the postvaccine period, children born in odd calendar years had a higher hazard of rotavirus hospitalization than those born in even years. Children born in winter had the highest hazard of hospitalization but also had greater vaccine effectiveness than children born in spring, summer, or fall. With the emergence of a strong biennial pattern of disease following vaccine introduction, the timing of a child’s birth has become a risk factor for rotavirus infection.
      PubDate: Tue, 13 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy054
      Issue No: Vol. 187, No. 8 (2018)
  • Development, Construct Validity, and Predictive Validity of a Continuous
           Frailty Scale: Results From 2 Large US Cohorts
    • Authors: Wu C; Geldhof G, Xue Q, et al.
      Pages: 1752 - 1762
      Abstract: Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale proposed by Fried et al. has been the most widely used. We aimed to develop a continuous frailty scale that could overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (n = 4,243) and Health and Retirement Study (n = 7,600), both conducted in the United States. Frailty was conceptualized as a continuous construct, assessed by 5 measures used in the FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between the 5 indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across 2 cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and continued to be associated with outcomes among robust and prefrail persons classified by the FP scale.
      PubDate: Tue, 24 Apr 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy041
      Issue No: Vol. 187, No. 8 (2018)
  • Competing Effects of Indirect Protection and Clustering on the Power of
           Cluster-Randomized Controlled Vaccine Trials
    • Authors: Hitchings M; Lipsitch M, Wang R, et al.
      Pages: 1763 - 1771
      Abstract: Power considerations for trials evaluating vaccines against infectious diseases are complicated by indirect protective effects of vaccination. While cluster-randomized controlled trials (cRCTs) are less statistically efficient than individually randomized controlled trials (iRCTs), a cRCT’s ability to measure direct and indirect vaccine effects may mitigate the loss of efficiency due to clustering. Within cRCTs, the number and size of clusters affects 3 determinants of power: the effect size being measured, disease incidence, and intracluster correlation. We simulated trials conducted in a collection of small communities to assess how indirect protection and clustering affected the power of cRCTs and iRCTs during an emerging epidemic. Across diverse parameters, we found that within the same trial population, cRCTs were never more powerful than iRCTs, although the difference can be small. We also identified 2 effects that attenuated the loss of cRCT power traditionally associated with increased cluster size. First, if enrollment of fewer, larger clusters was performed to achieve higher vaccine coverage within vaccinated communities, this increased the effect to be measured and, consequently, power. Second, the greater rate of imported transmission in larger communities may increase the attack rate and similarly mitigate loss of power relative to a trial in many, smaller communities.
      PubDate: Wed, 07 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy047
      Issue No: Vol. 187, No. 8 (2018)
  • Antiretroviral Therapy and Mortality in Rural South Africa: A Comparison
           of Causal Modeling Approaches
    • Authors: Oldenburg C; Seage G, Tanser F, et al.
      Pages: 1772 - 1779
      Abstract: Estimation of causal effects from observational data is a primary goal of epidemiology. The use of multiple methods with different assumptions relating to exchangeability improves causal inference by demonstrating robustness across assumptions. We estimated the effect of antiretroviral therapy (ART) on mortality in rural KwaZulu-Natal, South Africa, from 2007 to 2011, using 2 methods with substantially different assumptions: the regression discontinuity design (RDD) and inverse-probability–weighted (IPW) marginal structural models (MSMs). The RDD analysis took advantage of a CD4-cell-count–based threshold for ART initiation (200 cells/μL). The 2 methods yielded consistent but nonidentical results for the effect of immediate initiation of ART (RDD intention-to-treat hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.35, 1.26; RDD complier average causal effect HR = 0.56, 95% CI: 0.41, 0.77; IPW MSM HR = 0.49, 95% CI: 0.42, 0.58). Although RDD and IPW MSM estimates have distinct identifying assumptions, strengths, and limitations in terms of internal and external validity, results in this application were similar. The differences in modeling approaches and the external validity of each method may explain the minor differences in effect estimates. The overall consistency of the results lends support for causal inference about the effect of ART on mortality from these data.
      PubDate: Fri, 23 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy065
      Issue No: Vol. 187, No. 8 (2018)
  • Multilevel Regression and Poststratification: A Modeling Approach to
           Estimating Population Quantities From Highly Selected Survey Samples
    • Authors: Downes M; Gurrin L, English D, et al.
      Pages: 1780 - 1790
      Abstract: Investigators in large-scale population health studies face increasing difficulties in recruiting representative samples of participants. Nonparticipation, item nonresponse, and attrition, when follow-up is involved, often result in highly selected samples even in well-designed studies. We aimed to assess the potential value of multilevel regression and poststratification, a method previously used to successfully forecast US presidential election results, for addressing biases due to nonparticipation in the estimation of population descriptive quantities in large cohort studies. The investigation was performed as an extensive case study using baseline data (2013–2014) from a large national health survey of Australian males (Ten to Men: The Australian Longitudinal Study on Male Health). Analyses were performed in the open-source Bayesian computational package RStan. Results showed greater consistency and precision across population subsets of varying sizes when compared with estimates obtained using conventional survey sampling weights. Estimates for smaller population subsets exhibited a greater degree of shrinkage towards the national estimate. Multilevel regression and poststratification provides a promising analytical approach to addressing potential participation bias in the estimation of population descriptive quantities from large-scale health surveys and cohort studies.
      PubDate: Mon, 09 Apr 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy070
      Issue No: Vol. 187, No. 8 (2018)
  • Years of Life Lost Due to Influenza-Attributable Mortality in Older Adults
           in the Netherlands: A Competing-Risks Approach
    • Authors: McDonald S; van Wijhe M, van Asten L, et al.
      Pages: 1791 - 1798
      Abstract: We estimated the influenza mortality burden in adults aged 60 years or older in the Netherlands in terms of years of life lost, taking into account competing mortality risks. Weekly laboratory surveillance data for influenza and other respiratory pathogens and weekly extreme temperature served as covariates in Poisson regression models fitted to weekly mortality data, specific to age group, for the period 1999–2000 through 2012–2013. Burden for age groups 60–64 years through 85–89 years was computed as years of life lost before age 90 (YLL90), using restricted mean lifetime survival analysis and accounting for competing risks. Influenza-attributable mortality burden was greatest for persons aged 80–84 years, at 914 YLL90 per 100,000 persons (95% uncertainty interval: 867, 963), followed by persons aged 85–89 years (787 YLL90/100,000; 95% uncertainty interval: 741, 834). Ignoring competing mortality risks in the computation of influenza-attributable YLL90 would lead to substantial overestimation of burden, from 3.5% for persons aged 60–64 years to 82% for those aged 80–89 years at death. Failure to account for competing mortality risks has implications for the accuracy of disease-burden estimates, especially among persons aged 80 years or older. Because the mortality burden borne by the elderly is notably high, prevention initiatives may benefit from being redesigned to more effectively prevent infection in the oldest age groups.
      PubDate: Tue, 06 Feb 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy021
      Issue No: Vol. 187, No. 8 (2018)
  • Relative Performance of Propensity Score Matching Strategies for Subgroup
    • Authors: Wang S; Jin Y, Fireman B, et al.
      Pages: 1799 - 1807
      Abstract: Postapproval drug safety studies often use propensity scores (PSs) to adjust for a large number of baseline confounders. These studies may involve examining whether treatment safety varies across subgroups. There are many ways a PS could be used to adjust for confounding in subgroup analyses. These methods have trade-offs that are not well understood. We conducted a plasmode simulation to compare relative performance of 5 methods involving PS matching for subgroup analysis, including methods frequently used in applied literature whose performance has not been previously directly compared. These methods varied as to whether the overall PS, subgroup-specific PS, or no rematching was used in subgroup analysis as well as whether subgroups were fully nested within the main analytical cohort. The evaluated PS subgroup matching methods performed similarly in terms of balance, bias, and precision in 12 simulated scenarios varying size of the cohort, prevalence of exposure and outcome, strength of relationships between baseline covariates and exposure, the true effect within subgroups, and the degree of confounding within subgroups. Each had strengths and limitations with respect to other performance metrics that could inform choice of method.
      PubDate: Thu, 15 Mar 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy049
      Issue No: Vol. 187, No. 8 (2018)
  • Sensitivity Analyses for Misclassification of Cause of Death in the
           Parametric G-Formula
    • Authors: Edwards J; Cole S, Moore R, et al.
      Pages: 1808 - 1816
      Abstract: Cause-specific mortality is an important outcome in studies of interventions to improve survival, yet causes of death can be misclassified. Here, we present an approach to performing sensitivity analyses for misclassification of cause of death in the parametric g-formula. The g-formula is a useful method to estimate effects of interventions in epidemiologic research because it appropriately accounts for time-varying confounding affected by prior treatment and can estimate risk under dynamic treatment plans. We illustrate our approach using an example comparing acquired immune deficiency syndrome (AIDS)-related mortality under immediate and delayed treatment strategies in a cohort of therapy-naive adults entering care for human immunodeficiency virus infection in the United States. In the standard g-formula approach, 10-year risk of AIDS-related mortality under delayed treatment was 1.73 (95% CI: 1.17, 2.54) times the risk under immediate treatment. In a sensitivity analysis assuming that AIDS-related death was measured with sensitivity of 95% and specificity of 90%, the 10-year risk ratio comparing AIDS-related mortality between treatment plans was 1.89 (95% CI: 1.13, 3.14). When sensitivity and specificity are unknown, this approach can be used to estimate the effects of dynamic treatment plans under a range of plausible values of sensitivity and specificity of the recorded event type.
      PubDate: Tue, 06 Feb 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy028
      Issue No: Vol. 187, No. 8 (2018)
  • Prenatal Exposure to Acetaminophen and Risk for Attention Deficit
           Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic
           Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies
    • Authors: Masarwa R; Levine H, Gorelik E, et al.
      Pages: 1817 - 1827
      Abstract: Acetaminophen is the analgesic and antipyretic most commonly used during pregnancy. Evidence of neurodisruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, Embase, and Cochrane databases for relevant studies up to January 2017. Data were independently extracted and assessed by 2 researchers. Seven eligible retrospective cohorts included 132,738 mother-child pairs, with follow-up periods ranging from 3 to 11 years. The pooled risk ratio for ADHD was 1.34 (95% confidence interval (CI): 1.21, 1.47; I2 = 72%); for ASD, the risk ratio was 1.19 (95% CI: 1.14, 1.25; I2 = 14%), and for hyperactivity symptoms, it was 1.24 (95% CI: 1.04, 1.43; I2 = 93%). In meta-regression analysis, the association between exposure and ADHD increased with the child’s age upon follow-up (β = 0.03, 95% CI: 0.00, 0.07) and with the mean duration of exposure (β = 0.00, 95% CI: 0.00, 0.01). The available data is of observational nature only. Studies differed widely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD, and hyperactivity symptoms. These findings are concerning; however, results should be interpreted with caution given that the available evidence consists of observational studies and is susceptible to several potential sources of bias.
      PubDate: Tue, 24 Apr 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy086
      Issue No: Vol. 187, No. 8 (2018)
           IN LIMA, PERU, 2013–2017”
    • Pages: 1828 - 1828
      PubDate: Wed, 01 Aug 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy135
      Issue No: Vol. 187, No. 8 (2018)
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