Population-representative Cohort Research Articles

Celiac risk doubles in patients with alopecia areata: a nationwide case -control study.

Both alopecia areata (AA) and celiac disease are common immune-mediated diseases. Despite accumulating evidence of bi-directional associations between the two disorders, data remains unclear and inconsistent. In this study we explored the association between alopecia areata and celiac disease in a large representative population cohort. Patients with alopecia areata diagnosed during 2005-2019 were compared with age and gender matched healthy controls for celiac autoimmunity. A total of 33,401 patients with alopecia areata and 66,802 controls were included in the analysis. Overall, 754 patients (0.85) had celiac disease. Compared to controls, celiac prevalence increased twofold among AA patients (1.1% Vs 0.6%, Odds ratio (OR) 1.95, 95% Confidence Interval (CI) 1.69-2.25). Higher prevalence rates were observed among all age groups, with the highest risk in AA patients older than 40 years and older. Alopecia areata may be associated with a significant increased risk for celiac disease, suggesting early diagnostic and preventive measures.

Preadolescent individual, familial, and social risk factors associated with longitudinal patterns of adolescent alcohol, cannabis, and other illicit drug use in a population-representative cohort.

The aim of this exploratory study was to identify developmental patterns of adolescent concurrent alcohol, cannabis, and other illicit drug use and their preadolescent individual, familial, and social risk factors in a population-representative cohort from the province of Quebec, Canada (N = 1,593; 48.4% male). Age 12-17 years self-reports of alcohol, cannabis, and other illicit drug use were collected. Latent growth modeling was used to analyze developmental patterns of single- or polysubstance use (SU/PSU), and multinomial regression examined their association with risk factors assessed at age 10-12 years. Five developmental patterns were revealed, including nonusers (12.8% sample) and four classes reflecting different levels of SU/PSU (5.8%-37.5%), varying in severity based on onset, frequency, and type of substances used. Boys and girls were similarly represented throughout SU/PSU patterns. In comparisons with nonusers, several preadolescent risk factors were associated with increasing severity of SU/PSU. Possibly indexing fearlessness/disinhibition, low internalizing symptoms were common to all adolescent users. An earlier onset of substance use and increasing use of substances throughout adolescence were linked with having deviant peers for all user classes but later-onset users. Preadolescents manifesting externalizing problems and exposed to family adversity in addition to the above risk factors showed the earliest onset and most frequent adolescent SU/PSU, especially those also exposed to less appropriate parenting. Consistent with the developmental model of substance use, the nature, number, and severity of preadolescent risk factors distinguished between the type and severity of SU/PSU patterns in adolescence and call for a consistent strategy of universal, selective, and indicated preventive interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Preadolescent Individual, Familial, and Social Risk Factors Associated With Longitudinal Patterns of Adolescent Alcohol, Cannabis, and Other Illicit Drug Use in a Population-Representative Cohort

Supplemental Material for Preadolescent Individual, Familial, and Social Risk Factors Associated With Longitudinal Patterns of Adolescent Alcohol, Cannabis, and Other Illicit Drug Use in a Population-Representative Cohort

Sexuality and Gender Diversity Among Adolescents in Australia, 2019-2021

Sexuality- and gender-diverse (SGD) young people experience substantial health disparities relative to cisgender heterosexual peers. Little is known about SGD adolescents younger than 15 years. To describe SGD prevalence and associated factors in a population-representative cohort of younger adolescents in Australia. This prospective cohort study was part of the Future Proofing Study, with enrollment of year 8 students at 134 Australian secondary schools from 2019 to 2021 and annual follow-ups for 5 years. Data were analyzed from June 20, 2023, to June 6, 2024. Outcomes of interest were baseline self-reported gender and sexuality identities, individual characteristics, and mental health and disability diagnoses, as well as school characteristics. Among 6388 participants, median (IQR) age was 13.9 (13.6-15.8), with a range of 10.7 to 17.5 years. Most participants attended school in a major city (76.0%), were born in Australia (91.4%), and spoke English at home (93.7%). Approximately half (3122 participants; 48.9% [95% CI, 45.2%-59.0%]) identified as female or girls, and 46.5% (2973 participants; 95% CI, 39.8%-53.4%) identified as male or boys. The overall proportion of transgender identity was 3.3% (95% CI, 2.7%-3.9%), with 23 participants (0.4%) identifying as transgender boys, 10 participants (0.2%) identifying as transgender girls, 117 participants (1.8%) identifying as transgender nonbinary, and 59 participants (0.9%) identifying as another transgender identity. The overall proportion of sexuality diversity was 12.0% (95% CI, 10.4%-13.8%). The proportion of cisgender participants who were sexuality-diverse (13.0% [95% CI, 11.4%-14.8%] of girls and 4.7% [95% CI, 3.7%-5.9%] of boys) was lower than the proportion among gender-diverse participants, which ranged from 30.0% (95% CI, 9.3%-64.1%) of transgender girls to 91.5% (95% CI, 81.3%-96.4%) of those with another diverse gender identity. Gender diversity and sexuality diversity were strongly associated (odds ratio [OR], 66.24; 95% CI, 38.23-114.80), and both were negatively associated with age (gender diversity: OR per 1-year older, 0.61; 95% CI, 0.49-0.76; sexuality diversity: OR per 1-year older, 0.78; 95% CI, 0.65-0.93) and positively with mental health diagnosis (gender diversity: OR, 2.41; 95% CI, 1.79-3.24; sexuality diversity: OR, 2.50; 95% CI, 2.10-2.98), and disability diagnosis (gender diversity: OR, 2.39; 95% CI, 1.68-3.40; sexuality diversity: OR, 1.96; 95% CI, 1.64-2.36). While there were significant associations between individual and school characteristics and responses to gender and sexuality identity items, patterns of association differed, with no consistent association with economic disadvantage. This cohort study of young adolescents found higher rates of SGD than among samples of older adolescents. The significant associations with younger age, poorer mental health, and disability underscored the urgent need for inclusive programs to promote a safe and welcoming environment in schools, health care settings, and communities.

Socioeconomic inequities in alcohol-attributable mortality by sex/gender and age in Canada: A 13-year population-representative cohort study.

Individuals with low socioeconomic position (SEP) experience greater rates of alcohol-attributable mortality, contributing to health inequities in mortality and life expectancy. We examined the association between SEP and alcohol-attributable mortality by sex/gender and age in Canada. Census records from the 2006 Canadian Census Health and Environment Cohort (ages 12+; n=5,038,790) were linked to mortality data from 2006-2019. SEP was measured by educational attainment and household income. Poisson and Fine and Gray sub-distribution hazard models estimated rate differences (RD) per 100,000 person-years and hazard ratios (HR). Both educational attainment and household income were inversely associated with alcohol-attributable mortality. Absolute SEP inequities were greater among men than women, with a RD of 30.81 (95% CI: 28.04, 33.57) for men and 9.86 (95% CI: 8.49, 11.22) for women when comparing the lowest to the highest income quintile. Age-stratified analyses showed absolute SEP inequities were most pronounced in middle and older adulthood, above age 30 for women and age 50 for men, with smaller RDs in ages 12-29. Relative SEP inequities were similar in women and men, with greater HRs at younger ages. Public health policies addressing social determinants and population-level alcohol policies should consider patterning of SEP inequities by sex/gender and age group.

What Benefits Does Local Sports Club Membership Confer On Community-Dwelling Older People In Ireland?

Abstract Background There is a strong culture of sports club membership amongst older people in Ireland. It has been suggested that this confers health benefits due to increased physical activity and social connection, but studies examining this are currently lacking. The aim of this study therefore was to assess the relationship of sports club membership with markers of health and well-being in a large population-representative cohort of older people. Methods Over 3,500 participants ≥65 years at Wave 5 (mean 74 years, 54% female) of the Irish Longitudinal Study on Ageing were included. Sports club membership (GAA, soccer, rugby, tennis, golf) was elicited by self-report. Depressive symptoms (Centre for Epidemiological Studies Depression Scale), loneliness (UCLA Scale), and quality of life (Control Autonomy Self-Realization Please Scale) were assessed with internationally validated scales. Physical Activity was by self-report and mobility impairment was defined as Timed-Up-and-Go≥14s. The associations between sports club membership and these outcomes were assessed with regression models adjusted for age, sex, education, polypharmacy, chronic disease burden and heart disease. Results One fifth (708/3,510) of participants were a member of a local sports club. Sports club membership was associated with lower rates of depressive symptoms (Odds ratio 0.51 (95% CI 0.34,0.75)), lower levels of loneliness (Beta = -0.28 (95% CI -0.46, -0.10)) and better quality of life (Beta= 0.93 (95% CI 0.49,1.38)) in fully-adjusted models. Sports club members spent more days doing moderate physical activity per week (2.0 (95% CI 1.85,2.21) vs 1.64 (95% CI 1.54,1.73); p<0.001) and had lower likelihood of mobility impairment (Adjusted Odds Ratio 0.49 (95% CI 0.36,0.68)). Conclusion Sports Club Membership is prevalent amongst community-dwelling older people in Ireland and is associated with lower rates of loneliness, depressive symptoms and mobility impairment, and better quality of life. Older sports club members should be encouraged to maintain this activity where feasible.

Differential Association of Preadolescent Risk Factors Across Developmental Patterns of Adolescent Concurrent Gambling Participation and Substance Use.

Early risk factors for gambling participation (GP) and substance use (SU) in adolescents have usually been studied separately, although these disorders were integrated into the same clinical category over a decade ago. This exploratory study aimed to investigate the early individual, parental, familial and social risk factors associated with developmental patterns of adolescent GP and SU in a population-representative cohort (N = 1594, 51.2% boys). Using a person-centered strategy and multiple assessments from age 12 to 17, six developmental patterns describing joint GP and SU courses were revealed. Non-substance users/non-gamblers served as the reference class in an integrated longitudinal-multivariate analysis framework examining 15 distinct risk factors. Results showed that a core of risk factors were common to all trajectory-classes of substance users with or without GP. For a similar level of SU, most of the risk factors associated with non-gambling users also affected their gambling peers. However, additional risk factors were specifically related to GP. Thus, substance users who also gamble were affected by a greater number of risk factors than non-gambling substance users. Findings are consistent with a developmental syndrome of addiction, which posits a shared etiology between different expressions of addiction as well as differences in risk factors that lead to distinct trajectories of addictive behaviors. They highlight the importance of considering both GP and SU for a comprehensive assessment of adolescents' level of risk with regard to addictive behaviors.

P139 THE GUT MICROBIOME AS A PREDICTOR OF INCIDENT HYPERTENSION: DATA FROM A POPULATION SAMPLE OF 3055 INDIVIDUALS WITH A FOLLOW-UP OF 20 YEARS

Background and Objective: Our goal was to examine the previously unknown long-term association between gut microbiome composition and incident hypertension in a representative population cohort. Methods: We collected fecal samples from a population sample of 3,055 non-hypertensive Finns (mean age 43.1 years; 60.8% women) in 2002. These individuals were followed up for incident hypertension until 31 December 2021 using nationwide register data. The samples were sequenced using shotgun metagenomics. We examined associations between gut microbiome composition and incident hypertension using Cox regression (alpha diversity and microbial taxa), permutational multivariate ANOVA (beta diversity) and Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC; microbial taxa) models adjusted for conventional hypertension risk factors. Results: Altogether, 587 cases of incident diabetes occurred over the median follow-up of 19.8 years. Gut microbiome alpha diversity (Shannon index; p=0.98) and beta diversity (R2=0.49%; p=0.99) were not associated with incident hypertension. Furthermore, the associations between microbial taxa and incident hypertension were non-significant. In Cox regression models (Figure), two species reached an FDR-corrected P-value <0.1: Eubacterium G Ventriosum (hazard ratio per 1-SD increase 0.89; 95% CI 0.83-0.96; P=0.07) and Hespellia Stercorisuis (hazard ratio 1.16; 95% CI 1.05-1.27; P=0.098). In ANCOM-BC models, three species reached an FDR corrected P-value of <0.1: Merdousia sp000438015 (log2 fold change 0.32±0.09; P=0.06), Mitsuokella multacida (log2 fold change -0.32±0.09; P=0.06), and Scybalousia sp900543675 (log2 fold change -0.28±0.09; P=0.07). Conclusions: In this first-ever analysis on the association between the gut microbiome and long-term hypertension incidence, we observed that the associations between overall gut taxonomic composition and incident hypertension are weak. In addition, only a few microbial taxa reached a borderline level of significance with inconsistent results between two statistical methods. These findings suggest that the gut microbiome is not a strong predictor of future hypertension.

Summer temperature and emergency room visits due to urinary tract infection in South Korea: a national time-stratified case-crossover study

BackgroundAlthough urinary tract infection (UTI) is a common and severe public health concern, and there are clear biological mechanisms between UTI and hot temperatures, few studies have addressed the association between hot temperatures and UTI.MethodsWe designed a time-stratified case-crossover study using a population-representative sample cohort based on the National Health Insurance System (NHIS) in South Korea. We obtained all NHIS-based hospital admissions through the emergency room (ER) due to UTI (using a primary diagnostic code) from 2006 to 2019. We assigned satellite-based reanalyzed daily summer (June to September) average temperatures as exposures, based on residential districts of beneficiaries (248 districts in South Korea). The conditional logistic regression was performed to evaluate the association between summer temperature and UTI outcome.ResultsA total of 4,436 ER visits due to UTI were observed during the summer between 2006 and 2019 among 1,131,714 NHIS beneficiaries. For 20% increase in summer temperatures (0–2 lag days), the odd ratio (OR) was 1.06 (95% CI: 1.02–1.10) in the total population, and the association was more prominent in the elderly (people aged 65 y or older; OR:1.11, 95% CI: 1.05–1.17), females (OR: 1.12, 95% CI: 1.05–1.19), and people with diabetes history (OR: 1.14, 95% CI: 1.07–1.23). The effect modification by household income was different in the total and elderly populations. Furthermore, the association between summer temperature and UTI increased during the study period in the total population.ConclusionsOur results are consistent with the hypothesis that higher summer temperatures increase the risk of severe UTIs, and the risk might be different by sub-populations.

Perspectives from cystinosis: access to healthcare may be a confounding factor for variant classification.

Genetic variability persists across diverse populations, and it may impact the characterization of heritable diseases in different ancestral groups. Cystinosis is a metabolic disease caused by pathogenic variants in the CTNS gene causing the cellular accumulation of cystine. We attempted to assess the currently poorly characterized prevalence of cystinosis by employing a population genetics methodology. However, we encountered a significant challenge due to genetic variations across different populations, and the consideration of potential disparities in access to healthcare made our results inconclusive. Pathogenic CTNS variants were identified in a representative global population cohort using The Human Gene Mutation Database (HGMD) and the 1000 Genomes (1KG) database. The c.124G>A (p.Val42Ile) variant was reported to be pathogenic based on an observation in the white population presenting with atypical phenotypes, but it would be reclassified as benign in the African ancestral group if applying the ACMG allele frequency guideline due to its high allele frequency specifically in this population. Inclusion or exclusion of this c.124G>A (p.Val42Ile) variant results in a significant change in estimated disease prevalence, which can impact the diagnosis and treatment of affected patients with a broad range of phenotypic presentations. This observation led us to postulate that pathogenic manifestations of the disease may be underdiagnosed due to variable expressivity and systemic inequities in access to care, specifically in the African subpopulation. We call for a more cautious and inclusive approach to achieve more equitable care across diverse populations.

Subjective hearing and memory problems are associated with dementia and cognition in later life.

Subjective hearing and memory problems are detectable earlier than objective measures of sensory loss and cognitive decline, which are known to be related to an increased risk of dementia in later life. Using a population-representative cohort of 6006 individuals (aged 50-75) we examined whether participants who self-reported hearing and short-term memory issues showed greater rates of dementia within 17 years of follow-up. A sub-cohort was tested for audiometric threshold and cognition after 14 years. Hearing and memory problems were associated with a greater risk of dementia (hazard ratios [HRs]=1.42 [95% confidence interval: 1.11-1.81], 1.57 [1.30-1.90]), and poorer cognition 14 years later. The risk was greatest in those reporting both problems (HR=1.99 [1.42-2.80]). At follow-up, the level of hearing loss was associated with lower cognitive scores. Self-reports of hearing and short-term memory problems are associated with poorer cognitive performance and a greater risk of dementia. Subjective assessments may have predictive power over more than a decade. In a sample of older adults subjective hearing and memory problems were associated with dementia risk.Cross-sectionally, the audiometric screening threshold was associated with cognitive test scores.Subjective sensory and memory loss questions are easy to implement and show good predictive power.

Incident pregnancy and mental health among adolescent girls and young women in rural KwaZulu-Natal, South Africa: an observational cohort study

ABSTRACT Pregnancy can place adolescent girls and young women (AGYW) at risk of poor mental health. However, evidence linking youth pregnancy to mental health in resource-limited settings is limited, especially where HIV incidence is high. We analysed a population-representative cohort of AGYW aged 13–25 in rural KwaZulu-Natal to assess how adolescent pregnancy predicts subsequent mental health. Among 1851 respondents, incident pregnancy (self-reported past-12-month) rose from 0.7% at age 14% to 22.1% by 18. Probable common mental disorder (CMD; 14-item Shona Symptom Questionnaire) prevalence was 19.1%. In adjusted Poisson regression recent pregnancy was associated with slightly higher probable CMD (adjusted prevalence ratio [aPR] 1.19, 95%CI 0.96–1.49), and stronger association among 13–15 year-olds (aPR 3.25, 95%CI 1.50–7.03), but not with HIV serostatus. These findings suggest a possible incremental mental health impact of being pregnant earlier than peers, pointing to the need for age-appropriate mental health interventions for AGYW in resource-limited settings.

Childhood blood-lead level predicts lower general, non-selective hippocampal subfield volumes in midlife

Millions of adults and children are exposed to high levels of lead, a neurotoxicant, each year. Recent evidence suggests that lead exposure may precipitate neurodegeneration, particularly if the exposure occurs early or late in life, with unique alterations to the structure or function of specific subfields of the hippocampus, a region involved in memory and Alzheimer’s disease. It has been proposed that specific hippocampal subfields may thus be useful biomarkers for lead-associated neurological disease. We turned to a population-representative New Zealand birth cohort where the extent of lead exposure was not confounded by social class (the Dunedin Study; born 1972–1973 and followed to age 45) to test the hypothesis that early life lead exposure (blood-lead level at age 11 years) is associated with smaller MRI-assessed gray matter volumes of specific subfields of the hippocampus at age 45 years. Among the 508 Dunedin Study members with childhood lead data and adult MRI data passing quality control (93.9 % of those with lead data who attended the age-45 assessment wave, 240[47.2 %] female), childhood blood-lead levels ranged from 4 to 31 µg/dL (M[SD]=10.9[4.6]). Total hippocampal volumes were lower among adults with higher childhood blood-lead levels (b=-102.6 mm3 per 5 ug/dL-unit greater blood-lead level, 95 %CI: −175.4 to −29.7, p=.006, β=-.11), as were all volumes of the 24 hemisphere-specific subfields of the hippocampus. Of these 24 subfields, 20 demonstrated negative lead-associations greater than β=-.05 in size, 14 were statistically significant after adjustment for multiple comparisons (pFDR<.05), and 9 remained significant after adjustment for potential confounders and multiple comparisons. Children exposed to lead demonstrate smaller volumes across all subfields of the hippocampus in midlife. The hypothesis that lead selectively impairs specific subfields of the hippocampus, or that specific subfields may be markers for lead-associated neurological disease, requires further evaluation.

Long-term recreational exercise patterns in adolescents and young adults: Trajectory predictors and associations with health, mental-health, and educational outcomes.

Individual and societal factors influencing the formation of long-term recreational exercise habits during the transition from adolescence to young adulthood are not well explored. Using data from the Longitudinal Survey of Australian Youth (LSAY), a population-representative cohort study of Young People followed from age 15 to 25, we aimed to (1) model longitudinal recreational exercise trajectories from age 16 to 24, (2) examine predictors at age 15 of entering these trajectories, and (3) explore the association between the trajectories and health, mental health and educational achievement outcomes measured at the final study wave (age 25). Self-reported recreational exercise frequency data from 9353 LSAY participants were analysed using group-based trajectory modelling. We modelled the evolution of two patterns of recreational exercise behaviour: daily exercise, as per public health guidelines (Model 1); and at least once weekly exercise (Model 2). Model 1 trajectories were guideline-adherent exercisers (17.9% of the sample), never guideline exercisers (27.5%), guideline drop-outs (15.2%) and towards guideline (39.4%); Model 2 trajectories were weekly exercise (69.5% of the sample), decreasing (17.4%), increasing (4.8%), and infrequent (8.3%). For both models, at age 15, trajectory membership was predicted by gender, self-efficacy, time spent participating in sport, time spent watching TV, parental socioeconomic status, and academic literacy. At age 25, people in the guideline-adherent exerciser trajectory (model 1) reported better general health relative to other trajectories, Those in the weekly exerciser trajectory (model 2) had better general health and reduced rates of psychological distress, were happier with life and were more optimistic for the future relative to participants in less than weekly trajectory groups. Exercise-promoting interventions for Young People should specifically address the needs of females, people with low self-efficacy, reluctant exercisers, higher academic achievers, and those experiencing socioeconomic disadvantage.

Child support grant expansion and cognitive function among women in rural South Africa: Findings from a natural experiment in the HAALSI cohort.

Cash transfers are a promising but understudied intervention that may protect cognitive function in adults. Although South Africa has a rapidly ageing population, little is known about the nature of association between cash transfers and cognitive function in this setting. We leveraged age-eligibility expansions to South Africa's Child Support Grant (CSG) to investigate the association between duration of CSG eligibility and cognitive function of biological mothers of child beneficiaries in South Africa. We analysed 2014/2015 baseline data from 944 women, aged 40-59 years with at least one CSG-eligible child, enrolled in the population-representative HAALSI cohort in Agincourt, South Africa. Duration of CSG eligibility for each mother was calculated based on the birth dates of all their children and the CSG age-eligibility expansion years (2003-2012). Cognitive function was measured using a cognitive battery administered at the HAALSI baseline interview. Linear regression was used to estimate the association between duration of CSG eligibility, dichotomized as low (≤10 years) and high (>10 years) eligibility, and cognitive function z-scores of the mothers. High vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores in the full sample [β: 0.15 SD units; 95% CI: 0.04, 0.26; p-value = 0.01]. In mothers with one to four lifetime children, but not five or more, high vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores [β: 0.19 SD units; 95% CI: 0.05, 0.34, p-value = 0.02]. Government cash transfers given to support raising children may confer substantial protective effects on the subsequent cognitive function of mothers. Further studies are needed to understand how parity may influence this relationship. Our findings bring evidence to policymakers for designing income supplementation programmes to promote healthy cognitive ageing in low-income settings.

Abdominal Body Composition Reference Ranges and Association With Chronic Conditions in an Age- and Sex-Stratified Representative Sample of a Geographically Defined American Population.

Body composition can be accurately quantified from abdominal computed tomography (CT) exams and is a predictor for the development of aging-related conditions and for mortality. However, reference ranges for CT-derived body composition measures of obesity, sarcopenia, and bone loss have yet to be defined in the general population. We identified a population-representative sample of 4900 persons aged 20 to 89 years who underwent an abdominal CT exam from 2010 to 2020. The sample was constructed using propensity score matching an age and sex stratified sample of persons residing in the 27-county region of Southern Minnesota and Western Wisconsin. The matching included race, ethnicity, education level, region of residence, and the presence of 20 chronic conditions. We used a validated deep learning based algorithm to calculate subcutaneous adipose tissue area, visceral adipose tissue area, skeletal muscle area, skeletal muscle density, vertebral bone area, and vertebral bone density from a CT abdominal section. We report CT-based body composition reference ranges on 4649 persons representative of our geographic region. Older age was associated with a decrease in skeletal muscle area and density, and an increase in visceral adiposity. All chronic conditions were associated with a statistically significant difference in at least one body composition biomarker. The presence of a chronic condition was generally associated with greater subcutaneous and visceral adiposity, and lower muscle density and vertebrae bone density. We report reference ranges for CT-based body composition biomarkers in a population-representative cohort of 4649 persons by age, sex, body mass index, and chronic conditions.

Association between maltreatment, hair cortisol concentration, positive parent-child interaction, and psychosocial outcomes in Chinese preschool children.

Children now are facing an increasing risk of early life stress (ELS), which leads to detrimental psychosocial outcomes. Behavior studies suggested that positive parental interactions might moderate the negative impact of ELS, but the related biological alteration remains unclear. This study aims to investigate whether positive parent-child interactions moderate the association between maltreatment (as a severe form of ELS) and hair cortisol concentration (HCC), as well as between HCC and psychosocial outcomes in young children. Participants were 6-year-old Chinese children (N = 257, Mage = 6.2, 121 were male) selected by stratified cluster random sampling from a Shanghai population representative cohort. Proximal 3cm hair strands were analyzed using liquid chromatography coupled with tandem mass spectrometry for HCC. Children's psychosocial outcome was evaluated using the parental report Strengths and Difficulties Questionnaire (SDQ). Parents also reported the frequency of positive parent-child interactions using the Chinese Parent-Child Interaction Scale (CPCIS) as well as the history of maltreatment. Multi-level logistic regression models adjusting for individual, kindergarten, and district confounders were used to evaluate the associations between maltreatment, HCC, and psychosocial outcomes. Interactions terms tested whether more frequent positive parent-child interactions moderates the association between maltreatment and HCC, as well as between HCC and psychosocial outcomes. Maltreated children exhibited higher levels of HCC (B = 1.20, 95% CI: 0.38,2.02; p = 0.004), and children with higher HCC exhibited poorer psychosocial outcomes (B = 0.34, 95% CI: 0.18,0.51; p < 0.001). Positive parent-child interactions did not have a moderating effect on the association between maltreatment and HCC, but they demonstrated a moderating effect on the association between increased HCC and psychosocial outcomes (interaction term: B = -0.42, 95% CI: -0.75,-0.10; p = 0.01). These findings provide evidence that positive parental interaction may serve as a moderator between chronic cortisol exposure and psychosocial problems. It highlights the importance of frequent parent-child interactions, especially among children under a high risk of ELS.

Annual risk of hepatitis E virus infection and seroreversion: Insights from a serological cohort in Sitakunda, Bangladesh.

Hepatitis E virus (HEV) is a major cause of acute jaundice in South Asia. Gaps in our understanding of transmission are driven by non-specific symptoms and scarcity of diagnostics, impeding rational control strategies. In this context, serological data can provide important proxy measures of infection. We enrolled a population-representative serological cohort of 2,337 individuals in Sitakunda, Bangladesh. We estimated the annual risks of HEV infection and seroreversion both using serostatus changes between paired serum samples collected 9months apart, and by fitting catalytic models to the age-stratified cross-sectional seroprevalence. At baseline, 15% (95 CI: 14-17%) of people were seropositive, with seroprevalence highest in the relatively urban south. During the study, 27 individuals seroreverted (annual seroreversion risk: 15%, 95 CI: 10-21%), and 38 seroconverted (annual infection risk: 3%, 95CI: 2-5%). Relying on cross-sectional seroprevalence data alone, and ignoring seroreversion, underestimated the annual infection risk five-fold (0.6%, 95 CrI: 0.5-0.6%). When we accounted for the observed seroreversion in a reversible catalytic model, infection risk was more consistent with measured seroincidence. Our results quantify HEV infection risk in Sitakunda and highlight the importance of accounting for seroreversion when estimating infection incidence from cross-sectional seroprevalence data.

Long-term association of ultra-short heart rate variability with cardiovascular events

Heart rate variability (HRV) is a cardiac autonomic marker with predictive value in cardiac patients. Ultra-short HRV (usHRV) can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events in the general population is undetermined. We aimed to validate usHRV measured using ≤ 15-s ECGs (using RMSSD, SDSD and PHF indices) and investigate its association with atrial fibrillation, major adverse cardiac events, stroke and mortality in individuals without cardiovascular disease. In the National Survey for Health and Development (n = 1337 participants), agreement between 15-s and 6-min HRV, assessed with correlation analysis and Bland–Altman plots, was very good for RMSSD and SDSD and good for PHF. In the UK Biobank (n = 51,628 participants, 64% male, median age 58), after a median follow-up of 11.5 (11.4–11.7) years, incidence of outcomes ranged between 1.7% and 4.3%. Non-linear Cox regression analysis showed that reduced usHRV from 15-, 10- and 5-s ECGs was associated with all outcomes. Individuals with low usHRV (< 20th percentile) had hazard ratios for outcomes between 1.16 and 1.29, p < 0.05, with respect to the reference group. In conclusion, usHRV from ≤ 15-s ECGs correlates with standard short-term HRV and predicts increased risk of cardiovascular events in a large population-representative cohort.

Rhabdoid tumors in patients conceived following ART: is there an association?

In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT. Anecdotal evidence suggests an association of ART with RT. This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). RTs are very rare malignancies and our results are based on a small number of children with RT_ART. This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. N/A.