Journal Cover
American Journal of Epidemiology
Journal Prestige (SJR): 2.713
Citation Impact (citeScore): 3
Number of Followers: 188  
  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]
    • Pages: 258 - 258
      PubDate: Mon, 07 Jan 2019 00:00:00 GMT
      DOI: 10.1093/aje/kwy244
      Issue No: Vol. 188, No. 1 (2019)
    • Pages: 258 - 258
      PubDate: Mon, 07 Jan 2019 00:00:00 GMT
      DOI: 10.1093/aje/kwy215
      Issue No: Vol. 188, No. 1 (2019)
    • Pages: 259 - 259
      PubDate: Mon, 07 Jan 2019 00:00:00 GMT
      DOI: 10.1093/aje/kwy226
      Issue No: Vol. 188, No. 1 (2019)
    • Pages: 259 - 259
      PubDate: Mon, 07 Jan 2019 00:00:00 GMT
      DOI: 10.1093/aje/kwy217
      Issue No: Vol. 188, No. 1 (2019)
    • Pages: 260 - 260
      PubDate: Mon, 07 Jan 2019 00:00:00 GMT
      DOI: 10.1093/aje/kwy260
      Issue No: Vol. 188, No. 1 (2019)
  • The Origins and Early Evolution of Epidemiologic Research in
           Cardiovascular Diseases: A Tabular Record of Cohort and Case-Control
           Studies and Preventive Trials Initiated From 1946 to 1976
    • Authors: Blackburn H.
      Pages: 1 - 8
      Abstract: This article serves as a ready reference guide to the pioneering formal studies in cardiovascular disease (CVD) epidemiology initiated during 3 decades of the subject’s evolution into an established academic field that contributed to the public health. The article is not intended to be a history of CVD epidemiology or an editorial about its significance. The appended tables include the titles and starting dates of the early studies, the names of their principal investigators, and references to a single defining article from each. The early observational studies of CVD epidemiology provided a widely useful CVD risk-factor paradigm. The early clinical trials justified the more definitive preventive trials of the 1980s and beyond. This early research in populations, along with others in clinics and laboratories, led to greater understanding of the causes of CVD, to a vigorous practice of preventive cardiology, and to national policy and programs of health promotion, all of which were coincident with a 50-year decline in CVD mortality rates.
      PubDate: Sat, 15 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy175
      Issue No: Vol. 188, No. 1 (2018)
  • A Population-Based Matched-Sibling Analysis Estimating the Associations
           Between First Interpregnancy Interval and Birth Outcomes
    • Authors: Regan A; Ball S, Warren J, et al.
      Pages: 9 - 16
      Abstract: The association between a single interpregnancy interval (IPI) and birth outcomes has not yet been explored using matched methods. We modeled the odds of preterm birth, being small for gestational age, and having low birth weight in a second, live-born infant in a cohort of 192,041 sibling pairs born in Western Australia between 1980 and 2010. The association between IPI and birth outcomes was estimated from the interaction between birth order and IPI (with 18–23 months as the reference category), using conditional logistic regression. Matched analysis showed the odds of preterm birth were higher for siblings born following an IPI of <6 months (adjusted interaction odds ratio = 1.22, 95% confidence interval: 1.06, 1.38) compared with those born after an IPI of 18–23 months. There were no significant differences for IPIs of <6 months for other outcomes (small for gestational age or low birth weight). This is the first study to use matched analyses to investigate the association between a single IPI on birth outcomes. IPIs of <6 months were associated with increased odds of preterm birth in second-born infants, although the association is likely smaller than previously estimated by unmatched studies.
      PubDate: Wed, 05 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy188
      Issue No: Vol. 188, No. 1 (2018)
  • Invited Commentary: Promise and Pitfalls of the Sibling Comparison Design
           in Studies of Optimal Birth Spacing
    • Authors: Hutcheon J; Harper S.
      Pages: 17 - 21
      Abstract: Numerous observational studies have shown that infants born after short interpregnancy intervals (the interval between birth and subsequent conception) are more likely to experience adverse perinatal outcomes than infants born following longer intervals. Yet it remains controversial whether the link between short interpregnancy interval and adverse outcomes is causal or is confounded by factors such as low socioeconomic position, inadequate access to health care, and unintended pregnancy. Sibling comparison studies, which use a woman as her own control by comparing exposure and outcome status of her different pregnancies (i.e., comparing sibling offspring), have gained popularity as a strategy to reduce confounding by these difficult-to-measure factors that are nevertheless relatively stable within women. A variant of this approach, used by Regan et al. (Am J Epidemiol. 2019;188(1):9–16) and reported in this issue of the Journal, is a maternally matched design based on a single interpregnancy interval per woman. Using real and simulated data, we highlight underappreciated shortcomings of these designs that could limit the validity of study findings. In particular, we illustrate how the single-interval variant appears to derive estimates from comparisons between different mothers, not within mothers. Future studies of optimal birth spacing using sibling comparison designs should examine in detail the potential consequences of these methodological limitations.
      PubDate: Wed, 05 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy195
      Issue No: Vol. 188, No. 1 (2018)
  • Regan et al. Reply to “Sibling Comparison Design in Birth-Spacing
    • Authors: Regan A; Ball S, Warren J, et al.
      Pages: 22 - 23
      PubDate: Wed, 05 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy187
      Issue No: Vol. 188, No. 1 (2018)
  • Restrictive Immigration Law and Birth Outcomes of Immigrant Women
    • Authors: Torche F; Sirois C.
      Pages: 24 - 33
      Abstract: Unauthorized immigration is one of the most contentious policy issues in the United States. In an attempt to curb unauthorized migration, many states have considered restrictive laws intended to make life so difficult for unauthorized immigrants that they would choose to leave the country. Arizona’s Senate Bill 1070, enacted in 2010, was a pioneering example of these efforts. Using population-level natality data and causal inference methods, we examined the effect of SB1070 on infants exposed before birth in Arizona. Prenatal exposure to the bill resulted in lower birth weight among Latina immigrant women, but not among US-born white, black, or Latina women. The decline in birth weight resulted from exposure to the bill being signed into law, rather than from its (limited) implementation. The findings indicate that the threat of a punitive law, even in the absence of implementation, can have a harmful effect on the birth outcomes of the next generation.
      PubDate: Wed, 24 Oct 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy218
      Issue No: Vol. 188, No. 1 (2018)
  • Acetaminophen (Paracetamol) Exposure During Pregnancy and Pubertal
           Development in Boys and Girls From a Nationwide Puberty Cohort
    • Authors: Ernst A; Brix N, Lauridsen L, et al.
      Pages: 34 - 46
      Abstract: This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Use of acetaminophen was reported 3 times during pregnancy and 6 months postpartum. In total, 54% of mothers indicated use at least once during pregnancy. Between 2012 and 2017, sons and daughters provided information on a wide range of pubertal milestones—including Tanner stages, axillary hair growth, and age at menarche or voice break and first ejaculation—every 6 months from 11 years of age until full sexual maturation. Data were analyzed using a regression model for interval-censored data, providing adjusted mean monthly differences in age at attaining the pubertal milestones according to intrauterine cumulative (weeks) and trimester-specific acetaminophen exposure. Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure (i.e., about 1.5–3 months earlier age at pubic hair, axillary hair, and acne development comparing unexposed with those prenatally exposed for more than 12 weeks). Male pubertal development had no strong association with acetaminophen exposure.
      PubDate: Fri, 07 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy193
      Issue No: Vol. 188, No. 1 (2018)
  • Maternal Smoking During Pregnancy and Timing of Puberty in Sons and
           Daughters: A Population-Based Cohort Study
    • Authors: Brix N; Ernst A, Lauridsen L, et al.
      Pages: 47 - 56
      Abstract: Because early puberty has been linked to diseases later in life, identification of modifiable causes of early puberty is of interest. We explored the possible associations between maternal smoking during pregnancy and pubertal development in sons and daughters. Between 2012 and 2017, 15,819 children from the Danish National Birth Cohort, born during 2000–2003, provided half-yearly information on puberty from the age of 11 years. We estimated adjusted age differences (in months) at attaining various pubertal milestones, including Tanner stages, per 10 daily cigarettes smoked in the first trimester of gestation. In sons, exposure to smoking in utero was associated with earlier genital development (Tanner 2, −1.3 months, 95% confidence interval (CI): −2.5, 0.0; Tanner 5, −3.7 months, 95% CI: −5.3, −2.0), pubic hair development (Tanner 2, −1.8 months, 95% CI: −2.9, −0.6; Tanner 5, −2.9 months, 95% CI: −4.2, −1.7), and voice break (−2.4 months, 95% CI: −3.6, −1.3). In daughters, maternal smoking was associated with earlier breast development (Tanner 2, −3.4 months, 95% CI: −5.3, −1.5; Tanner 5, −4.7 months, 95% CI: −6.5, −2.9), pubic hair development stages 3–5 (Tanner 5, −2.5 months, 95% CI: −4.1, −1.0), and menarche (−3.1 months, 95% CI: −4.0, −2.3). Fetal exposure to tobacco smoke might advance timing of puberty in boys and girls.
      PubDate: Sat, 15 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy206
      Issue No: Vol. 188, No. 1 (2018)
  • Pregnancy Outcomes in Women With Multiple Sclerosis
    • Authors: MacDonald S; McElrath T, Hernández-Díaz S.
      Pages: 57 - 66
      Abstract: Few studies have assessed the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS). We used 2 large US administrative databases, the Truven Health MarketScan Database (2011–2015; Truven Health Analytics Inc., Ann Arbor, Michigan) and the Nationwide Inpatient Sample (2007–2011), to identify delivery cohorts. MS and pregnancy outcomes (infections, cesarean delivery, preterm delivery, poor fetal growth, preeclampsia, chorioamnionitis, postpartum hemorrhage, stillbirth, and infant malformations) were identified during pregnancy and at delivery. We calculated adjusted risk ratios according to MS status and relapse(s) in the year before delivery. Among over 5 million pregnancies, we identified 3,875 pregnancies in women with MS. Women with MS had an increased risk of infections during pregnancy (Truven Health: adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.16, 1.27) and preterm delivery (Truven Health: aRR = 1.19 (95% CI: 1.04, 1.35); Nationwide Inpatient Sample: aRR = 1.30 (95% CI: 1.16, 1.44)). The risks of other outcomes were similar for women with and without MS. In the Truven Health database, risk ratios for the pregnancy outcomes in women experiencing relapses versus those without relapses were between 0.9 and 1.4, and confidence intervals overlapped the null. Overall, women with MS had an increased risk of infections and preterm delivery; however, their risks for other adverse pregnancy outcomes were not elevated. Disease activity before delivery was not a strong predictor of outcomes.
      PubDate: Tue, 28 Aug 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy197
      Issue No: Vol. 188, No. 1 (2018)
  • Alcohol Intake and Colorectal Cancer Risk in the Multiethnic Cohort Study
    • Authors: Park S; Wilkens L, Setiawan V, et al.
      Pages: 67 - 76
      Abstract: To investigate the association of alcohol intake with colorectal cancer risk according to race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage type, and anatomical subsite, we analyzed data from 190,698 black, Native Hawaiian, Japanese-American, Latino, and white persons in Hawaii and California in the Multiethnic Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993–2013). In multivariate Cox regression models, the hazard ratio was 1.16 (95% confidence interval (CI): 1.01, 1.34) for 15.0–29.9 g/day of alcohol and 1.28 (95% CI: 1.12, 1.45) for ≥30.0 g/day among men, and 1.06 (95% CI: 0.85, 1.32) and 1.15 (95% CI: 0.92, 1.43), respectively, among women, compared with nondrinkers (P for heterogeneity according to sex = 0.74). An increased risk was apparent among Native Hawaiians, Japanese Americans, Latinos, and white persons and among individuals with body mass index <25.0 (calculated as weight (kg)/height (m)2), never-users of nonsteroidal antiinflammatory drugs, and those with lower intake of dietary fiber and folate. Beer and wine, but not liquor, consumption was positively related to colorectal cancer risk. The association was stronger for rectum and left-colon tumors than for right-colon tumors. Our findings suggest that the positive association between alcohol and colorectal cancer varies according to race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical subsite of tumors.
      PubDate: Sat, 15 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy208
      Issue No: Vol. 188, No. 1 (2018)
  • Trajectory of Postconcussive Symptoms 12 Months After Deployment in
    • Authors: Ferdosi H; Schwab K, Metti A, et al.
      Pages: 77 - 86
      Abstract: We analyzed data from a cohort of recently deployed soldiers from 2 US Army bases, Fort Carson and Fort Bragg (2009 to 2015). Soldiers with and without a recent history of mild traumatic brain injury (mTBI) on deployment were evaluated within days of return and at 3, 6, and 12 months. Those with mTBI were more likely than those without to endorse ≥1 postconcussive symptom as “severe” and/or “very severe” (47% vs. 21%, baseline; adjusted relative risk (RR) = 1.71, 95% confidence interval: 1.51, 1.93, all time points), which remained significant after adjusting for posttraumatic stress disorder (adjusted RR = 1.34, 95% confidence interval: 1.20, 1.50). Prevalence and relative risks for 3 of the most common baseline symptoms remained constant over time: sleep problems (RR = 2.19), forgetfulness (RR = 2.56), and irritability (RR = 2.73). The pattern was slightly different for headache (baseline, RR = 3.44; 12 months, RR = 3.26), due to increased prevalence of headache in those without mTBI. The prevalence of clinically relevant postconcussive symptoms remained relatively constant over 1 year of follow-up, whether or not symptoms were associated with concussion. Service members with recent mTBI reported more symptoms than those without at all time points.
      PubDate: Fri, 07 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy199
      Issue No: Vol. 188, No. 1 (2018)
  • The Causal Effect of Education on Tooth Loss: Evidence From United Kingdom
           Schooling Reforms
    • Authors: Matsuyama Y; Jürges H, Listl S.
      Pages: 87 - 95
      Abstract: Associations between education and oral health have frequently been reported, but until now there has been no causal evidence. Exploiting exogenous variation in the duration of schooling due to 1947 and 1972 reforms in mandatory schooling in the United Kingdom, we examined the causal relationship between education and tooth loss in older age. We conducted a cross-sectional study using data from waves 3 (2006–2007), 5 (2010–2011), and 7 (2014–2015) of the English Longitudinal Study of Ageing. We used a 2-stage least squares instrumental variable approach and included 5,667 respondents (average age = 67.8 years; 44.4% were men) in the analyses, of whom 819 (14.5%) had no teeth. The schooling reforms increased the duration of education by an average of 0.624 years (95% confidence interval: 0.412, 0.835). For respondents born within ±6 years of the pivotal cohorts, a 1-year increment of education causally reduced the probability of edentulism by 9.1 (95% confidence interval: 1.5, 16.8) percentage points. The effects were stronger for the 1947 reform than for the 1972 reform. Results were robust to broadening of the cohort bandwidth and functional form of the cohort trend. The findings suggest that investment in education produces improved oral health later in life.
      PubDate: Fri, 07 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy205
      Issue No: Vol. 188, No. 1 (2018)
  • Mediators of the Association Between Religious Service Attendance and
    • Authors: Kim E; VanderWeele T.
      Pages: 96 - 101
      Abstract: Mounting evidence consistently shows associations between religious service attendance and reduced mortality risk, yet research identifying mediators remains limited. Using prospective data from the Health and Retirement Study (2006–2014; n = 5,200 US adults), we evaluated a range of potential mediators. After robust control for confounders (demographic, health, health-behavior, and social factors), among positive psychological factors, we observed mediation through increased life satisfaction (5.27%; P ≤ 0.001) and possibly positive affect (1.52%; P = 0.06) but not optimism, mastery, or purpose. Among dimensions of psychological distress, we observed mediation through reductions in hopelessness (1.92%; P = 0.01), trait anger (1.98%; P = 0.03), state anger (2.23%; P = 0.03), and possibly loneliness (1.21%; P = 0.06), but not cynical hostility or negative affect, and some evidence that increased anxiety (−3.61%; P = 0.008) and possibly depressive symptoms (−1.14%; P = 0.05) increased mortality odds. Among social factors, we observed mediation through contact with friends (10.73%; P = 0.005) but not living with a spouse or contact with children or other family. Among health behaviors, we observed mediation through exercise (5.38%; P ≤ 0.001) and negative mediation through alcohol frequency (−2.55%; P = 0.03) and possibly body mass index (−2.34%; P = 0.08) but not smoking. These results highlight a range of mediators that might underlie the association between religious service attendance and reduced risk of mortality.
      PubDate: Thu, 27 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy211
      Issue No: Vol. 188, No. 1 (2018)
  • Social Isolation and Mortality in US Black and White Men and Women
    • Authors: Alcaraz K; Eddens K, Blase J, et al.
      Pages: 102 - 109
      Abstract: Social isolation is associated with higher mortality in studies comprising mostly white adults, yet associations among black adults are unclear. In this prospective cohort study, we evaluated whether associations of social isolation with all-cause, cardiovascular disease, and cancer mortality differed by race and sex. Adults enrolled in Cancer Prevention Study II in 1982/1983 were followed for mortality through 2012 (n = 580,182). Sex- and race-specific multivariable-adjusted hazard ratios and 95% confidence intervals were estimated for associations of a 5-point social isolation score with risk of death. Social isolation was associated with all-cause mortality in all subgroups (P for trend ≤ 0.005); for the most isolated versus the least isolated, the hazard ratios were 2.34 (95% confidence interval (CI): 1.58, 3.46) and 1.60 (95% CI: 1.41, 1.82) among black men and white men, respectively (P for interaction = 0.40) and 2.13 (95% CI: 1.44, 3.15) and 1.84 (95% CI: 1.68, 2.01) among black women and white women, respectively (P for interaction = 0.89). The association did not differ between black men and black women (P for interaction = 0.33) but was slightly stronger in white women than in white men (P for interaction = 0.01). Social isolation was associated with cardiovascular disease mortality in each subgroup (P for trend < 0.03) but with cancer mortality only among whites (P for trend < 0.0001). Subgroup differences in the influence of specific social isolation components were identified. Identifying and intervening with socially isolated adults could improve health outcomes.
      PubDate: Tue, 16 Oct 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy231
      Issue No: Vol. 188, No. 1 (2018)
  • Risk of Hospitalization for Cancer, Musculoskeletal Disorders, Injuries,
           or Poisonings Surrounding Widowhood
    • Authors: Einiö E; Martikainen P.
      Pages: 110 - 118
      Abstract: Psychological distress has been indicated to affect the risk of death from cardiovascular disease, cancer, and external causes. Mortality from these major causes of death is also known to be elevated after widowhood when distress is at a heightened level. Surprisingly little is known about changes in health other than mental and cardiac health shortly before widowhood. We used longitudinal data on widowed (n = 19,185) and continuously married (n = 105,939) individuals in Finland (1996–2002) to assess the risk of hospitalization for cancer and for external and musculoskeletal causes surrounding widowhood or random dates. We fitted population-averaged logit models using longitudinal data of older adults aged 65 years or over. The results show that hospitalization for injuries had already increased prior to widowhood and clearly peaked after it. The increases were largely related to falls. A similar increasing pattern of findings was not found around a random date for a group of continuously married individuals. Hospitalizations for cancer and musculoskeletal disorders appeared to be unrelated to the process of widowhood. Hospitalizations for poisonings increased after widowhood. The results imply that the process of widowhood is multifaceted and that various types of health changes should be studied separately and before the actual loss.
      PubDate: Wed, 22 Aug 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy184
      Issue No: Vol. 188, No. 1 (2018)
  • Cohort Differences in Cognitive Impairment and Cognitive Decline Among
           Mexican-Americans Aged 75 Years or Older
    • Authors: Downer B; Garcia M, Raji M, et al.
      Pages: 119 - 129
      Abstract: Research suggests that the prevalence and incidence of cognitive impairment among older adults is decreasing. This analysis used data from 9 waves (1993–2016) of the Hispanic Established Populations for the Epidemiologic Study of the Elderly to assess cognitive status and cognitive decline for 2 cohorts of Mexican-Americans aged ≥75 years in 1993–1994 versus 2004–2005. Logistic regression, joint longitudinal survival models, and illness-death models for interval-censored data were used to examine cohort differences in the odds of prevalent cognitive impairment, trajectories of cognitive decline, and the risk of 10-year incident cognitive impairment, respectively. Results indicated that compared with the 1993–1994 cohort, the 2004–2005 cohort had higher odds for prevalent cognitive impairment (odds ratio = 2.51, 95% confidence interval (CI): 1.92, 3.29), particularly among participants with <4 years of education (odds ratio = 2.99, 95% CI: 2.14, 4.18). Conversely, the 2004–2005 cohort exhibited significantly slower rates of cognitive decline (βˆ = 0.50, 95% CI: 0.39, 0.62) and had a significantly lower risk of incident cognitive impairment (hazard ratio = 0.75, 95% CI: 0.62, 0.91) compared with the 1993–1994 cohort. This analysis provides mixed results for cohort trends in the cognitive health of older Mexican-Americans. Continued research is needed to identify risk factors that contribute to these population-level trends.
      PubDate: Fri, 07 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy196
      Issue No: Vol. 188, No. 1 (2018)
  • Associations of Maternal Exposure to Dichlorodiphenyltrichloroethane and
           Pyrethroids With Birth Outcomes Among Participants in the Venda Health
           Examination of Mothers, Babies and Their Environment Residing in an Area
           Sprayed for Malaria Control
    • Authors: Chevrier J; Rauch S, Crause M, et al.
      Pages: 130 - 140
      Abstract: Although effective in controlling malaria, indoor residual spraying results in elevated exposure to insecticides such as dichlorodiphenyltrichloroethane (DDT) and pyrethroids. These chemicals cross the placenta, but no studies have examined their associations with birth outcomes in populations residing in indoor residual spraying areas. We investigated this question in the Venda Health Examination of Mothers, Babies and Their Environment (VHEMBE), a birth cohort study of 751 South African children born between 2012 and 2013. We measured maternal peripartum serum DDT and urine pyrethroid metabolite concentrations and collected data on birth weight, length, head circumference, and duration of gestation. We analyzed the data using marginal structural models with inverse-probability-of-treatment weights, generalized propensity scores, and standard conditional linear regression. Using all 3 analytical methods, p,p′-DDT, o,p′-DDT, and to a lesser extent p,p′-dichlorodiphenyldichloroethylene were related to elevated birth weight, birth length, and head circumference among girls. Changes in gestational duration did not mediate this relationship, suggesting that these exposures accelerate fetal growth, which is consistent with the known estrogenic properties of o,p′-DDT and p,p′-DDT. No associations with pyrethroid metabolites were found. Results suggest that prenatal exposure to DDT is related to elevated birth size. Further studies are needed to elucidate the implications of these findings.
      PubDate: Mon, 09 Jul 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy143
      Issue No: Vol. 188, No. 1 (2018)
  • Associations of Prenatal Exposure to Cadmium With Child Growth, Obesity,
           and Cardiometabolic Traits
    • Authors: Chatzi L; Ierodiakonou D, Margetaki K, et al.
      Pages: 141 - 150
      Abstract: Prenatal cadmium exposure has been associated with impaired fetal growth; much less is known about the impact during later childhood on growth and cardiometabolic traits. To elucidate the associations of prenatal cadmium exposure with child growth, adiposity, and cardiometabolic traits in 515 mother-child pairs in the Rhea Mother-Child Study cohort (Heraklion, Greece, 2007–2012), we measured urinary cadmium concentrations during early pregnancy and assessed their associations with repeated weight and height measurements (taken from birth through childhood), waist circumference, skinfold thickness, blood pressure, and serum lipid, leptin, and C-reactive protein levels at age 4 years. Adjusted linear, Poisson, and mixed-effects regression models were used, with interaction terms for child sex and maternal smoking added. Elevated prenatal cadmium levels (third tertile of urinary cadmium concentration (0.571–2.658 μg/L) vs. first (0.058–0.314 μg/L) and second (0.315–0.570 μg/L) tertiles combined) were significantly associated with a slower weight trajectory (per standard deviation score) in all children (β = −0.17, 95% confidence interval (CI): −0.32, −0.02) and a slower height trajectory in girls (β = −0.30, 95% CI: −0.52,−0.09; P for interaction = 0.025) and in children born to mothers who smoked during pregnancy (β = −0.48, 95% CI: −0.83, −1.13; P for interaction = 0.027). We concluded that prenatal cadmium exposure was associated with delayed growth in early childhood. Further research is needed to understand cadmium-related sex differences and the role of coexposure to maternal smoking during early pregnancy.
      PubDate: Tue, 25 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy216
      Issue No: Vol. 188, No. 1 (2018)
  • Associations of Long-Term Exposure to Ultrafine Particles and Nitrogen
           Dioxide With Increased Incidence of Congestive Heart Failure and Acute
           Myocardial Infarction
    • Authors: Bai L; Weichenthal S, Kwong J, et al.
      Pages: 151 - 159
      Abstract: Although long-term exposure to traffic-related air pollutants such as nitrogen dioxide has been linked to cardiovascular disease (CVD) mortality, little is known about the association between ultrafine particles (UFPs), defined as particles less than or equal to 0.1 μm in diameter, and incidence of major CVD events. We conducted a population-based cohort study to assess the associations of chronic exposure to UFPs and nitrogen dioxide with incident congestive heart failure (CHF) and acute myocardial infarction. Our study population comprised all long-term Canadian residents aged 30–100 years who lived in Toronto, Ontario, Canada, during the years 1996–2012. We estimated annual concentrations of UFPs and nitrogen dioxide by means of land-use regression models and assigned these estimates to participants’ postal-code addresses in each year during the follow-up period. We estimated hazard ratios for the associations of UFPs and nitrogen dioxide with incident CVD using random-effects Cox proportional hazards models. We controlled for smoking and obesity using an indirect adjustment method. Our cohorts comprised approximately 1.1 million individuals at baseline. In single-pollutant models, each interquartile-range increase in UFP exposure was associated with increased incidence of CHF (hazard ratio for an interquartile-range increase (HRIQR) = 1.03, 95% confidence interval (CI): 1.02, 1.05) and acute myocardial infarction (HRIQR = 1.05, 95% CI: 1.02, 1.07). Adjustment for fine particles and nitrogen dioxide did not materially change these estimated associations. Exposure to nitrogen dioxide was also independently associated with higher CHF incidence (HRIQR = 1.04, 95% CI: 1.03, 1.06).
      PubDate: Tue, 28 Aug 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy194
      Issue No: Vol. 188, No. 1 (2018)
  • Association Between the Decline in Pneumococcal Disease in Unimmunized
           Adults and Vaccine-Derived Protection Against Colonization in Toddlers and
           Preschool-Aged Children
    • Authors: Weinberger D; Pitzer V, Regev-Yochay G, et al.
      Pages: 160 - 168
      Abstract: Vaccinating children with pneumococcal conjugate vaccine (PCV) disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccine dosing strategies (e.g., removing doses), it is critical to understand which groups of children contribute most to transmission to adults. We used data from Israel (2009–2016) to evaluate how the buildup of vaccine-associated immunity in children was associated with declines in invasive pneumococcal disease (IPD) due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on IPD in adults were obtained from a nationwide surveillance study carried out in Israel. We compared the trajectory of decline of IPD due to PCV-targeted serotypes in adults with the decline of colonization prevalence and increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage among children in the age range of 36–59 months. This suggests that preschool-aged children, rather than infants, are responsible for maintaining the indirect benefits of PCVs.
      PubDate: Tue, 20 Nov 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy219
      Issue No: Vol. 188, No. 1 (2018)
  • Association Between Age and Plasmodium falciparum Infection Dynamics
    • Authors: Buchwald A; Sorkin J, Sixpence A, et al.
      Pages: 169 - 176
      Abstract: Few data exist on the incidence or duration of natural Plasmodium falciparum infections in high-transmission settings. School-aged children (SAC) carry a disproportionate burden of infections, suggesting either increased incidence or increased duration. We estimated the incidence and duration of unique infections according to age groups. The Mfera Cohort Study (2014–2017) in Malawi had 2 years of follow-up, with 120 participants tested monthly and during sick visits. Blood samples were collected to detect P. falciparum by microscopy and polymerase chain reaction. Positive samples underwent genotyping. Simulation was used to account for high rates of nondetection of infection among low-parasitemia infections, which increase in frequency with age. Adults had significantly fewer unique infections per person per year (median, 2.5) compared with SAC and children younger than 5 years of age (6.3 and 6.6, respectively). Over half of all genotypes were persistent. Infections lasted significantly longer in adults (median, 180 days) and SAC (median, 163 days) compared with children younger than 5 years of age (median, 97 days), after accounting for age-dependent nondetection of infection. SAC acquired new infections at the same rate as children younger than 5 years, but they maintained these infections for longer periods of time, similar to adults. This study provides new insights into P. falciparum infection dynamics that should be considered when designing malaria control strategies.
      PubDate: Tue, 25 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy213
      Issue No: Vol. 188, No. 1 (2018)
  • The Population-Level Impacts of Excluding Norovirus-Infected Food Workers
           From the Workplace: A Mathematical Modeling Study
    • Authors: Yang W; Steele M, Lopman B, et al.
      Pages: 177 - 187
      Abstract: Norovirus is the leading cause of acute gastroenteritis and foodborne disease in the United States. The Food and Drug Administration recommends that food workers infected with norovirus be excluded from the workplace while symptomatic and for 48 hours after their symptoms subside. Compliance with this recommendation is not ideal, and the population-level impacts of changes in food-worker compliance have yet to be quantified. We aimed to assess the population impacts of varying degrees of compliance with the current recommendation through the use of a compartmental model. We modeled the number and proportion of symptomatic norovirus cases averted annually in the US population (using data from 1983–2014) in specific age groups (children aged <5 years, children aged 5–17 years, adults aged 18–64 years, and adults aged ≥65 years) under various scenarios of food-worker exclusion (i.e., proportion compliant and days of postsymptomatic exclusion) in comparison with a referent scenario which assumed that 66.6¯% of norovirus-symptomatic food workers and 0% of postsymptomatic food workers were excluded from work. Overall, we estimated that 6.0 million cases of norovirus have already been avoided annually under the referent scenario and that 6.7 million (28%) more cases might be avoided through 100% compliance with the current recommendations. Substantial population-level benefits were predicted from improved compliance in exclusion of norovirus-infected food workers from the workplace—benefits that may be realized through policies or programs incentivizing self-exclusion.
      PubDate: Fri, 07 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy198
      Issue No: Vol. 188, No. 1 (2018)
  • A Prospective Study of Dairy-Food Intake and Early Menopause
    • Authors: Purdue-Smithe A; Whitcomb B, Manson J, et al.
      Pages: 188 - 196
      Abstract: Early natural menopause, the cessation of ovarian function prior to age 45 years, affects approximately 10% of women and increases risk of cardiovascular disease and other adverse conditions. Laboratory evidence suggests a potential role of dairy foods in the ovarian aging process; however, no prior epidemiologic studies have evaluated how dairy-food intake is associated with risk of early menopause. We therefore evaluated how intakes of total, low-fat, high-fat, and individual dairy foods were associated with early menopause in Nurses’ Health Study II. Women who were premenopausal at the start of follow-up in 1991 were followed until 2011 for early menopause. Food frequency questionnaires were used to assess dietary intake. In Cox proportional hazards models adjusting for age, smoking, and other factors, total baseline dairy-food intake of ≥4 servings/day versus <4 servings/week was associated with 23% lower risk of early menopause (hazard ratio = 0.77, 95% confidence interval: 0.64, 0.93; P for trend = 0.08). Associations appeared to be limited to low-fat dairy foods (for ≥2 servings/day vs. <3 servings/month, hazard ratio = 0.83, 95% confidence interval: 0.68, 1.01; P for trend = 0.02), whereas high-fat dairy-food intake was not associated with early menopause. Low-fat dairy foods may represent a modifiable risk factor for reducing risk of early menopause among premenopausal women.
      PubDate: Tue, 18 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy212
      Issue No: Vol. 188, No. 1 (2018)
  • Identification of the Fraction of Indolent Tumors and Associated
           Overdiagnosis in Breast Cancer Screening Trials
    • Authors: Ryser M; Gulati R, Eisenberg M, et al.
      Pages: 197 - 205
      Abstract: It is generally accepted that some screen-detected breast cancers are overdiagnosed and would not progress to symptomatic cancer if left untreated. However, precise estimates of the fraction of nonprogressive cancers remain elusive. In recognition of the weaknesses of overdiagnosis estimation methods based on excess incidence, there is a need for model-based approaches that accommodate nonprogressive lesions. Here, we present an in-depth analysis of a generalized model of breast cancer natural history that allows for a mixture of progressive and indolent lesions. We provide a formal proof of global structural identifiability of the model and use simulation to identify conditions that allow for parameter estimates that are sufficiently precise and practically actionable. We show that clinical follow-up after the last screening can play a critical role in ensuring adequately precise identification of the fraction of indolent cancers in a stop-screen trial design, and we demonstrate that model misspecification can lead to substantially biased estimates of mean sojourn time. Finally, we illustrate our findings using the example of Canadian National Breast Screening Study 2 (1980–1985) and show that the fraction of indolent cancers is not precisely identifiable. Our findings provide the foundation for extended models that account for both in situ and invasive lesions.
      PubDate: Tue, 16 Oct 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy214
      Issue No: Vol. 188, No. 1 (2018)
  • Reassessing Serosurvey-Based Estimates of the Symptomatic Proportion of
           Zika Virus Infections
    • Authors: Mitchell P; Mier-y-Teran-Romero L, Biggerstaff B, et al.
      Pages: 206 - 213
      Abstract: Since the 2007 Zika epidemic in the Micronesian state of Yap, it has been apparent that not all people infected with Zika virus (ZIKV) experience symptoms. However, the proportion of infections that result in symptoms remains unclear. Existing estimates have varied in their interpretation of symptoms due to other causes and the case definition used, and they have assumed perfect test sensitivity and specificity. Using a Bayesian model and data from ZIKV serosurveys in Yap (2007), French Polynesia (2013–2014), and Puerto Rico (2016), we found that assuming perfect sensitivity and specificity generally led to lower estimates of the symptomatic proportion. Incorporating reasonable assumptions for assay sensitivity and specificity, we estimated that 27% (95% credible interval (CrI): 15, 37) (Yap), 44% (95% CrI: 26, 66) (French Polynesia), and 50% (95% CrI: 34, 92) (Puerto Rico) of infections were symptomatic, with variation due to differences in study populations, study designs, and case definitions. The proportion of ZIKV infections causing symptoms is critical for surveillance system design and impact assessment. Here, we accounted for key uncertainties in existing seroprevalence data and found that estimates for the symptomatic proportion ranged from 27% to 50%, suggesting that while the majority of infections are asymptomatic or mildly symptomatic, symptomatic infections might be more common than previously estimated.
      PubDate: Tue, 28 Aug 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy189
      Issue No: Vol. 188, No. 1 (2018)
  • Development and Validation of a Clinical Prediction Rule to Predict
           Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing
    • Authors: Jackson S; Lydecker A, Magder L, et al.
      Pages: 214 - 221
      Abstract: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among nursing home residents is high. Health-care workers (HCWs) often serve as a vector in MRSA transmission. The ability to identify residents who are likely to transmit MRSA to HCWs’ hands and clothing during clinical care is important so that infection control measures, such as Contact Precautions, can be employed. Using data on demographic and clinical characteristics collected from residents of community nursing homes in Maryland and Michigan between 2012 and 2014, we developed a clinical prediction rule predicting the probability of MRSA transmission to HCWs’ gowns. We externally validated this model in a cohort of Department of Veterans Affairs nursing home residents from 7 states between 2012 and 2016. The prediction model, which included sex, race, resident dependency on HCWs for care, the presence of any medical device, diabetes mellitus, and chronic skin breakdown, showed good performance (C statistic = 0.70; sensitivity = 76%, specificity = 49%) in the development set. The decision curve analysis indicated that this model has greater clinical utility than use of a nares surveillance culture for MRSA colonization, which is current clinical practice for placing hospital inpatients on Contact Precautions. The prediction rule demonstrated less utility in the validation cohort, suggesting that a separate rule should be developed for residents of Veterans Affairs nursing homes.
      PubDate: Mon, 22 Oct 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy220
      Issue No: Vol. 188, No. 1 (2018)
  • Propensity Score–Based Estimators With Multiple Error-Prone
    • Authors: Hong H; Aaby D, Siddique J, et al.
      Pages: 222 - 230
      Abstract: Propensity score methods are an important tool to help reduce confounding in nonexperimental studies. Most propensity score methods assume that covariates are measured without error. However, covariates are often measured with error, which leads to biased causal effect estimates if the true underlying covariates are the actual confounders. Although some groups have investigated the impact of a single mismeasured covariate on estimating a causal effect and proposed methods for handling the measurement error, fewer have investigated the case where multiple covariates are mismeasured, and we found none that discussed correlated measurement errors. In this study, we examined the consequences of multiple error-prone covariates when estimating causal effects using propensity score–based estimators via extensive simulation studies and real data analyses. We found that causal effect estimates are less biased when the propensity score model includes mismeasured covariates whose true underlying values are strongly correlated with each other. However, when the measurement errors are correlated with each other, additional bias is introduced. In addition, it is beneficial to include correctly measured auxiliary variables that are correlated with confounders whose true underlying values are mismeasured in the propensity score model.
      PubDate: Wed, 24 Oct 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy210
      Issue No: Vol. 188, No. 1 (2018)
  • Interpretation and Potential Biases of Mendelian Randomization Estimates
           With Time-Varying Exposures
    • Authors: Labrecque J; Swanson S.
      Pages: 231 - 238
      Abstract: Mendelian randomization (MR) is used to answer a variety of epidemiologic questions. One stated advantage of MR is that it estimates a “lifetime effect” of exposure, though this term remains vaguely defined. Instrumental variable analysis, on which MR is based, has focused on estimating the effects of point or time-fixed exposures rather than “lifetime effects.” Here we use an empirical example with data from the Rotterdam Study (Rotterdam, the Netherlands, 2009–2013) to demonstrate how confusion can arise when estimating “lifetime effects.” We provide one possible definition of a lifetime effect: the average change in outcome measured at time t when the entire exposure trajectory from conception to time t is shifted by 1 unit. We show that MR only estimates this type of lifetime effect under specific conditions—for example, when the effect of the genetic variants used on exposure does not change over time. Lastly, we simulate the magnitude of bias that would result in realistic scenarios that use genetic variants with effects that change over time. We recommend that investigators in future MR studies carefully consider the effect of interest and how genetic variants whose effects change with time may impact the interpretability and validity of their results.
      PubDate: Sat, 15 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy204
      Issue No: Vol. 188, No. 1 (2018)
  • Effects of Multiple Forms of Information Bias on Estimated Prevalence of
           Suicide Attempts According to Sexual Orientation: An Application of a
           Bayesian Misclassification Correction Method to Data From a Systematic
    • Authors: Salway T; Plöderl M, Liu J, et al.
      Pages: 239 - 249
      Abstract: Multiple epidemiologic studies demonstrate a disparity in suicide risk between sexual minority (lesbian, gay, bisexual) and heterosexual populations; however, both “exposure” (sexual minority status) and outcome (suicide attempts) may be affected by information bias related to errors in self-reporting. We therefore applied a Bayesian misclassification correction method to account for possible information biases. A systematic literature search identified studies of lifetime suicide attempts in sexual minority and heterosexual adults, and frequentist meta-analysis was used to generate unadjusted estimates of relative risk. A Bayesian model accounting for prior information about sensitivity and specificity of exposure and outcome measures was used to adjust for misclassification biases. In unadjusted frequentist analysis, the relative risk of lifetime suicide attempt comparing sexual minority with heterosexual groups was 3.38 (95% confidence interval: 2.65, 4.32). In Bayesian reanalysis, the estimated prevalence was slightly reduced in heterosexual adults and increased in sexual minority adults, yielding a relative risk of 4.67 (95% credible interval: 3.94, 5.73). The disparity in lifetime suicide attempts between sexual minority and heterosexual adults is greater than previously estimated, when accounting for multiple forms of information bias. Additional research on the impact of information bias in studies of sexual minority health should be pursued.
      PubDate: Wed, 05 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy200
      Issue No: Vol. 188, No. 1 (2018)
  • Addressing Extreme Propensity Scores via the Overlap Weights
    • Authors: Li F; Thomas L, Li F.
      Pages: 250 - 257
      Abstract: The popular inverse probability weighting method in causal inference is often hampered by extreme propensity scores, resulting in biased estimates and excessive variance. A common remedy is to trim patients with extreme scores (i.e., remove them from the weighted analysis). However, such methods are often sensitive to the choice of cutoff points and discard a large proportion of the sample. The implications for bias and the precision of the treatment effect estimate are unclear. These problems are mitigated by a newly developed method, the overlap weighting method. Overlap weights emphasize the target population with the most overlap in observed characteristics between treatments, by continuously down-weighting the units in the tails of the propensity score distribution. Here we use simulations to compare overlap weights to standard inverse probability weighting with trimming, in terms of bias, variance, and 95% confidence interval coverage. A range of propensity score distributions are considered, including settings with substantial nonoverlap and extreme values. To facilitate practical implementation, we further provide a consistent estimator for the standard error of the treatment effect estimated using overlap weighting.
      PubDate: Wed, 05 Sep 2018 00:00:00 GMT
      DOI: 10.1093/aje/kwy201
      Issue No: Vol. 188, No. 1 (2018)
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