American Journal of Epidemiology

BackgroundIt is critical public health concern to identify safety signals originating from wide-scale immunization efforts. Such safety signals may be identified from spontaneous reports and other data sources. Although some work has been done on the best methods for vaccine safety surveillance, there is a scarcity of information on how these perform in analyses of real-world data. MethodsWe use four administrative claims databases and one electronic health record (EHR) database to evaluate the...

The doubly-ranked non-linear Mendelian randomization method can yield biased estimates when instrument strength varies across individuals due to gene-environment (GxE) interactions. We propose a simple strategy to mitigate this bias by modelling GxE interactions and removing the fitted GxE component from the exposure before stratification by the doubly-ranked method. In simulations, the proposed GxE correction strategy eliminated GxE-induced bias with null, linear and non-linear exposure-outcome...

BackgroundHealth status influences uptake of COVID-19 vaccination, with vaccinated individuals generally being healthier than their unvaccinated counterparts. However, the extent to which this healthy vaccinee effect biases vaccine effectiveness estimates remains unclear. This study investigated how different levels of the healthy vaccinee effect may impact these estimates. MethodsThree national, matched, retrospective cohort studies were conducted on the population of Qatar from February 5, 20...

BackgroundStressful life events (SLEs) across the life course have been associated with cognitive decline, but evidence on their cumulative impact and potential modifiers remains limited. We aimed to examine the associations between SLE exposure in childhood, adulthood, or both life stages and cognitive trajectories, and to investigate whether these associations vary by sex and level of education. MethodsWe used data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally...

BackgroundSynthetic cohorts created by combining two cohorts can be useful when no single data set includes both the exposure and outcome data of interest. We estimate the effects of depression in early adulthood on later-life memory outcome using two nationally representative cohorts separately and in a synthetic sample. MethodsWe used the National Longitudinal Study of Youth 1979 (NLSY; N=5,747) and the Health and Retirement Study (HRS; N=6,846) and a synthetic cohort combining exposure data ...

BackgroundThe long preclinical phase of dementia can bias estimated effects of baseline exposures on dementia incidence. We demonstrate simulations informed by reverse Mendelian randomization (MR) findings to quantify the age-specific magnitude of reverse causation bias in analyses in observational studies of the effects of body mass index (BMI) on dementia. MethodsWe simulated longitudinal trajectories of BMI and dementia risk from ages 45 to 90 years, calibrating to published evidence on age-...

OBJECTIVEUsing two cohorts and synthetic datasets, we estimated effects of prospectively reported alcohol use on memory outcomes across middle age. METHODSData were from National Longitudinal Study of Youth 1979 (NLSY79, n=7540, alcohol reports from ages 18-26), Health and Retirement Study (HRS age 50-56 at enrollment, n=13,090), and a synthetic cohort matching early life exposure information from 3,259 NLSY79 participants to later life memory information from 5,451 HRS participants. Covariate-...

PurposeThe COVID-19 pandemic coincided with worsening U.S. drug overdose mortality and widening racial and ethnic disparities. We estimated race/ethnicity-specific excess overdose deaths at the state level during 2020-2023 and examined how these burdens scale with population size. MethodsWe analyzed annual overdose deaths from 2014-2023 for five racial/ethnic groups in 47 states and the District of Columbia. Pre-pandemic trends (2014-2019) were fit using a generalized growth model, and deaths e...

ObjectivesGrowth Mindset and Grit have been proposed as key psychological resources for resilience and adaptation, yet their manifestation and social distribution in later life remain underexplored. This study examines the structure, distribution, and correlates of Growth Mindset and Grit in older adulthood using proxy indicators in the English Longitudinal Study of Ageing (ELSA). MethodsProxy indicators reflecting learning behaviour, personality traits, affect, and beliefs were used to derive ...

COVID-19 has been shown to cause a range of harmful long-term effects on nearly every organ system1-3. These findings are based on retrospective studies comparing COVID-19 patients to patients with similar medical histories and demographics but no COVID-19 diagnosis4-16. However, concerns have emerged that these comparisons may be biased if COVID-19 patients had unrelated health conditions or other factors not recorded in their medical records17-21. Here, using a massive dataset of 14.4 billion ...

BackgroundVaccines can prevent severe disease by preventing infection or by reducing progression among those who become infected. Vaccine effectiveness against progression given infection is often used to quantify this second mechanism, but it conditions on infection, which is itself affected by vaccination. As a result, this estimand lacks a clear causal interpretation and may behave non-intuitively over time. MethodsWe introduce a conceptual framework that models protection against infection ...

BackgroundThe Global Youth Tobacco Survey (GYTS) is widely used to monitor tobacco use among adolescents worldwide. However, inconsistent analytical approaches particularly in handling complex survey designs and predictor selection limit comparability across countries, survey waves, and software platforms. Although much of the GYTS literature relies on proprietary tools such as SAS and SPSS, practical and transparent guidance on implementing reproducible, theory-informed analyses remains limited...

IntroductionWhile longitudinal studies aid in understanding and preventing long-latency disorders like dementia, evidence for cadmiums role in these conditions is still limited. We evaluated associations between cadmium exposure and incident Alzheimers disease (AD) and all-cause dementia in US adults. MethodsNational Health and Nutrition Examination Survey (NHANES) III (1988-1994) and continuous NHANES (1999-2016) data were linked with Medicare claims to identify incident AD and dementia cases ...

Hybrid controlled trials (HCTs) incorporate real-world data into randomized controlled trials (RCTs) by augmenting the internal control arm with patients receiving the same treatment in routine care. Beyond increasing power, HCTs may improve recruitment by supporting unequal randomization ratios that increase patient access to experimental treatments. However, HCT validity is threatened by bias from unmeasured confounding due to lack of randomization of external controls, leading to outcome non-...

BackgroundViral interference, in which infection with one pathogen reduces susceptibility to another, may influence respiratory virus dynamics. Inference from surveillance data is complicated by time-varying testing behavior that can induce correlated detection patterns independent of biological interaction. MethodsWe developed a multi-pathogen renewal model augmented with a ratio penalty that constrains interference estimates to be consistent with observed log-odds ratios of pathogen positivit...

BackgroundRoutinely collected health data are increasingly used to generate real-world evidence for therapeutic decision-making. Yet, stakeholders, including clinicians, pharmaceutical industry representatives, patient advocacy groups, and statisticians, prioritize different aspects of data quality, analysis, and interpretation. Without explicit consideration of these perspectives, analyses risk being fragmented, misaligned with end-user needs, or lacking transparency. MethodsWe developed a sta...

The early childhood environment influences later mental health, but it remains unclear which aspects are most important for reducing inequalities. We quantified how socioeconomic inequalities in mental health at 5 and 17 years (y) would change under hypothetical interventions on five aspects of the early childhood environment. We analysed parent-reported data from the UK Millennium Cohort Study (n=15513). Socioeconomic circumstances (SEC) were assessed using maternal education at 9 months. Menta...

IntroductionMortality and smoking rates vary over time across the US. The Cancer Intervention and Surveillance Modeling Network--Lung Working Group (CISNET-LWG) has developed a smoking history generator to describe the effects smoking on health. This work further refines these parameters and quantifies effects on life expectancy MethodsData from the National Health Interview Survey (NHIS) and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS) were used to estimate smoking his...

Mendelian randomization is currently mainly implemented through the use of genetic variants as instrumental variables to investigate the causal effect of an exposure on an outcome of interest. Mendelian randomization studies are robust to confounding bias and reverse causation, but they remain susceptible to selection bias; for example, this can happen if the exposure or outcome are associated with selection into the study sample. Negative controls are sometimes used to detect biases (typically ...

PurposeMost spatio-temporal models identify COVID-19 sociodemographic and socioeconomic risk factors using methods that assume a single spatial dependency pattern across the city, which may not reflect reality. The purpose of this study is to apply a spatially and temporally localized Bayesian model to identify COVID-19 risk factors that account for localized context. MethodsFor this study, a spatio-temporal localized Bayesian Hierarchical Model (ST-LCAR) was used to assess the relationships be...