Large Population-based Cohort Research Articles

Prospective comparison of risk factors for firearm suicide and non-firearm suicide in a large population-based cohort of current and former US service members: findings from the Millennium Cohort Study

BackgroundSuicide is a leading cause of death among service members and veterans. Among suicide methods, firearms are the most lethal and commonly used method among military populations. Limited research has compared risk factors for the various suicide methods. This study evaluated and compared risk factors for firearm versus non-firearm suicides using data from the Millennium Cohort Study, a large longitudinal military cohort. MethodsUsing a competing risk approach, we identified factors associated with each suicide method. Risk factors included demographics, mental health diagnoses, mental health symptoms, military-specific characteristics, health behaviors, and psychosocial factors. Cause of death was assessed from July 1, 2001, through December 31, 2018. FindingsAmong 201,565 eligible participants with a mean [SD] age of 27.9 [5.2] years, there were 139,789 (69.3%) male, 61,776 (30.7%) female, 15,927 (7.9%) Hispanic, 24,667 (12.3%) non-Hispanic Black, 14,107 (7.0%) Asian, Pacific Islander, American Indian or Multiracial, and 146,736 (72.8%) non-Hispanic White participants. During the study period, 330 died by firearm suicide and 168 died by non-firearm suicide. Overall, effect estimates for risk factors were similar across both methods of suicide. After adjustment, men (HR: 3.69, 95% CI: 2.59, 5.24) and those who screened positive for depression (HR: 1.97, 95% CI: 1.36, 2.87) had an elevated risk for firearm suicide. In contrast, those who self-reported a history of bipolar diagnosis (HR: 3.40, 95% CI: 1.76, 6.55) had significantly increased risk for non-firearm suicide. InterpretationFindings suggest that prevention and intervention strategies overall may not need to be differentiated by specific demographic, military, or health factors. Targeted interventions that consider sex and mental health screens might have relative utility in preventing firearm related suicide risk compared with non-firearm suicide. FundingMilitary Operational Medicine Research Program, Defense Health Program, and Department of Veterans Affairs.

Prevalence and temporal trends of epilepsy in children: A retrospective birth cohort study.

Epilepsy is one of the most common chronic neurologic diseases in children, however, few recent studies examine the prevalence of epilepsy and its evolution over time according to birth or maternal characteristics. To examine the prevalence of epilepsy in children born between 2002 and 2020 and the temporal trends by year of birth, in Ontario, Canada, overall and according to maternal and birth characteristics. We included all in-hospital deliveries between 2002 and 2020 (N=2 343 482) in Ontario, Canada, using linked administrative health dataset. We estimated the overall prevalence of epilepsy diagnosed before the age of 18 years, by birth and maternal characteristics. For temporal trend analyses, we restricted our population to children born up to 2012 (N=1 405 271) and examined the prevalence of epilepsy diagnosed by age 8 by their year of birth, using Poisson regression. The overall prevalence of epilepsy in our cohort was 8.1 per 1000 live births (95% CI 8.0-8.2). Prevalence was higher for boys, for children born preterm, with congenital malformations, from multiple pregnancies, from mothers born in Canada, and for children living in deprived areas. Epilepsy prevalence diagnosed by age 8 increased slightly between 2002 and 2012 cohorts (6.9 (95% CI 6.2-7.6) to 7.3 (95% CI 6.6-8.1) per 1000 live births, respectively). Differences by gestational age as gradient and socioeconomic characteristics were persistent and stable over time, while those by pregnancy plurality and sex decreased. In a large population-based birth cohort in Canada, we observed a slight increase in epilepsy prevalence over time among children born in 2002 and those born in 2012 and persistent disparities by gestational age, socioeconomic position, and maternal immigration status. This study highlights the need for continued surveillance of rates to see if this increasing trend is persistent, to understand the potential causes behind it, and to understand the persistence of these disparities.

Childhood Adversity and Incident Psychotic Experiences in Early Adulthood: Cognitive and Psychopathological Mediators.

Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood. We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula. In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results. Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort

BackgroundThe prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth.MethodsWe analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features.ResultsWe detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e − 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels.ConclusionsCyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

How many future dementia cases would be missed by a high-risk screening program? A retrospective cohort study in a population-based cohort.

Risk prediction models aim to identify those at high risk to receive targeted interventions. We aimed to identify the proportion of future dementia cases that would be missed by a high-risk screening program. We identified validated dementia risk prediction models from systematic reviews. We applied these to European Prospective Investigation of Cancer Norfolk, a large population-based cohort of 30,387 individuals with 29 years of linked healthcare data. A maximum of 16.0% (14.7,17.2) and 31.9% (30.2,33.5) of cases arose from the highest risk decile and quintiles, respectively. For every 1000 people considered to be at high risk, a maximum of 235 (215, 255) developed dementia. Seven in every 10 cases of dementia arose from people at normal risk, and eight in every 10 people at high risk did not develop dementia. Individual-level prevention approaches targeted at high-risk groups are unlikely to produce large reductions in disease incidence at the population level. Dementia, a significant public health challenge, is not an inevitability of aging; risk reduction is possible. Several dementia risk prediction models have been validated in the general population, and these aim to identify people at high risk of the disease who can then be targeted with primary prevention interventions. An alternative prevention approach is to focus on interventions that reduce risk across the population, irrespective of risk status. In our study, seven out of every ten people who developed dementia during 29 year follow-up were classed as 'normal-risk' (rather than 'high risk') at baseline. Eight out of every ten people who were at high risk at baseline did not go on to develop dementia. Even if effective, dementia risk reduction efforts based upon targeted high-risk approaches are unlikely to reduce incidence of disease at the population level.

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study.

Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study

Background:Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections.Methods:The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).Results:Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12–1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26–1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99–1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11–1.27) and mortality (HR 1.37. 95% CI 1.29–1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19–2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident.Conclusions:PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required.Funding:This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People’s Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Religious Belief Among Women in Australia: Characteristics and Role in Influencing Children's Health-Related Quality of Life and Lifestyle.

Religiosity can be an important factor in women's health-related behaviour, attitudes, and decision-making. Evidence however, regarding the religiosity of mothers and its influence on child health, is scarce. Based on a large population-based cohort in Australia, we aim to examine the religiosity of women in Australia and the association of maternal religiosity with children's health-related quality of life (HRQOL) and lifestyle. Our findings indicate that (1) maternal religious involvement was higher for women with higher education levels, ascertained religious values in decision-making, and abstinence from binge drinking in the household, (2) maternal religiosity positively influenced their children's HRQOL, (3) children of mothers who were more religious had less worries or fewer school-work problems, but the children of mothers with stronger religious beliefs used more internet/computer during the week but had less time playing games on weekends. This study provides additional specificity to inform future health interventions in religious community contexts to enhance the positive influence of maternal religious belief for better development of their children.

COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study

BackgroundInformation on the magnitude and duration of antibody levels after COVID-19 vaccination in different groups may be useful for prioritizing of additional vaccinations. MethodsSerum samples were collected every six months in a prospective cohort study among adults in the Netherlands. Geometric mean concentrations (GMCs) of antibodies against the receptor binding domain of the SARS-CoV-2 spike protein were calculated after the primary series, first, and second booster vaccinations. Effects of age (18–59 vs 60–85 years) and medical risk conditions on GMC 2–6 weeks and 21–25 weeks after each vaccination, and on waning during 3–25 weeks after each vaccination, were estimated by linear regression. ResultsWe included 20,640, 15,229 and 8,392 samples collected after primary, first and second booster vaccination, respectively. GMCs at 2–6 and 21–25 weeks after primary series were lower in participants with older age or medical risk conditions. After the first booster, older age was associated with lower GMC at 2–6 weeks and at 21–25 weeks. Waning after the first and second boosters (only 60–85) was not associated with age or medical risk conditions. ConclusionsSince antibody differences by age and medical risk groups have become small with increasing number of doses, other factors such as COVID-19 disease severity rather than antibody levels are useful for prioritization of additional vaccinations.

Examining the influence of Covid-19 restrictions, a nurse strike, and SARS-CoV-2 coinfection on bacteremia mortality: A Danish population-based cohort study (2019–2022)

ObjectivesBacteremia is an acute severe infection with high mortality. Changes in healthcare services and coinfections with SARS-CoV-2 may have affected the mortality for bacteremia during the COVID-19 pandemic, which has been reported for other major diseases. In this study we examine the all-cause bacteremia mortality amidst the COVID-19 pandemic. MethodsA population-based cohort study comprised of laboratory confirmed bacteremia episodes in the Capital Region, Denmark (March 2019–February 2022). Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI) for all-cause bacteremia mortality associated with the Covid-19 restriction period, a strike period, and coinfection with SARS-CoV-2, adjusted for possible confounders. ResultsA total of 14,912 bacteremia episodes were identified in 12,693 patients during the study period. The 30- and 90-day all-cause mortality were 19 % and 27 %, respectively. The fully adjusted HR for 30- and 90-day all-cause mortality associated with the Covid-19 restriction period were 0.91 (95 % CI, 0.84 to 0.99) and 0.90 (95 % CI, 0.84 to 0.96), respectively, compared to the remaining time period. The corresponding HRs associated with SARS-CoV-2 coinfection were 1.29 (95 % CI, 1.11 to 1.50) and 1.36 (95 % CI, 1.20 to 1.55) compared to patients without coinfection. The association between the national nurse strike and all-cause bacteremia mortality was inconclusive. ConclusionsIn this large population-based cohort study, a significant reduction in all-cause mortality for bacteremia was observed during the Covid-19 restriction period in Denmark, while coinfection with SARS-CoV-2 seem to be a substantial risk factor for all-cause bacteremia mortality.

Long-term survival outcomes of systemic therapy in patients with isolated and mixed medullary thyroid cancer

BackgroundMedullary thyroid carcinoma (MTC) is an uncommon thyroid cancer with limited treatment options for advanced disease. A small subset exhibits mixed MTC histology with both medullary and well-differentiated components. We investigated survival outcomes with systemic therapy in isolated versus mixed MTC using a large population-based cohort. MethodsPatients diagnosed with MTC from 2000 to 2019 were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The overall and thyroid cancer-specific survivals were compared between isolated (n = 1814) and mixed (n = 113) MTC cohorts. The impact of postoperative systemic therapy on survival was analyzed. ResultsNo significant difference in 10-year overall survival was observed between isolated (77.4 %) and mixed (75.2 %) MTC in a cohort of 1927 patients. Median overall survival was similar between isolated (136.9 months) and mixed MTC (129.0 months), p = 0.81. While systemic therapy improved 10-year survival in isolated MTC (83.2 % vs. 76.9 %, p < 0.001), no benefit was seen in mixed MTC (76.4 % vs. 74.2 %, p = 0.82). Multivariate analysis confirmed survival gains with systemic therapy for isolated (HR = 0.763, 95%CI = 0.590–0.987, p = 0.040) but not mixed MTC (HR = 0.909, 95%CI = 0.268–3.079, p = 0.88). ConclusionsIn this large population-based study, no significant survival difference was observed between isolated and mixed MTC. Systemic therapy was associated with improved survival in isolated MTC, but not in the mixed subtype. These findings suggest a differential treatment response that warrants further investigation in prospective studies and may inform histology-tailored management strategies for mixed MTC.

Racial and Ethnic Disparities in Cervical Insufficiency, Cervical Cerclage, and Preterm Birth.

Background: The frequency of cervical insufficiency differs among the major racial and ethnic groups, with limited data specific to Asian American and Native Hawaiian/Pacific Islander (AANHPI) subpopulations. We assessed cervical insufficiency diagnoses and related outcomes across 10 racial and ethnic groups, including disaggregated AANHPI subgroups, in a large population-based cohort. Study Design: We performed a retrospective cohort study of all singleton births between 20-42 weeks' gestation in California from 2007 to 2018. Logistic regression models were performed to estimate the odds of cervical insufficiency and, among people with cervical insufficiency, the odds of cerclage and preterm birth according to self-reported race and ethnicity. Results: Among 5,114,470 births, 38,605 (0.8%) had a diagnosis code for cervical insufficiency. Compared with non-Hispanic White people, non-Hispanic Black people had the highest odds of cervical insufficiency (adjusted odds ratio [aOR] 3.07; 95% confidence interval [CI], 2.97, 3.18), for cerclage placement and higher odds for preterm birth. Disaggregating AANHPI subgroups showed that Indian people had the highest odds (aOR 1.94; 95% CI, 1.82, 2.07) of cervical insufficiency and had significantly higher odds of cerclage without increased odds of preterm birth; Southeast Asian people had the highest odds of preterm birth. Conclusion: Within a large, diverse population-based cohort, non-Hispanic Black people experienced the highest rates of cervical insufficiency, and among those with cervical insufficiency, had among the highest rates of cerclage and preterm birth. Among AANHPI subgroups specifically, Indian people had the highest rates of cervical insufficiency and cerclage placement, without increased rates of preterm birth; Southeast Asian people had the highest rates of preterm birth, without increased rates of cerclage. Disaggregating AANHPI subgroups identifies important differences in obstetric risk factors and outcomes.

Association between posterior occlusal support and tooth loss in a population-based cohort: The OHSAKA study

ObjectivesThis study aimed to assess the association between posterior occlusal support (POS) and the risk of tooth loss in older adults aged ≥75 years. MethodsThis longitudinal study analyzed 94,422 participants who participated in multiple dental check-ups provided as part of the public healthcare services in Osaka, Japan, from 2018 to 2022. The participants were categorized into nine groups (A1–3, B1–4, and C1 and C2) according to their POS status using the Eichner index at baseline. The dental charts were compared between the initial and final assessments to assess tooth loss. Logistic regression analysis was used to examine the association between POS status and tooth loss, adjusted for several covariates, including age, sex, body mass index, periodontal status, oral hygiene, history of diabetes, history of hypertension, attendance at the annual dental check-up, and observational period. Furthermore, stratified logistic regression analyses were conducted using anterior or posterior tooth loss. ResultsAfter controlling for confounders, POS status was associated with tooth loss. The odds ratios (ORs) with A1 as the reference were 1.74 in A2, 2.55 in A3, 3.40 in B1, 4.74 in B2, 5.79 in B3, 6.00 in B4, 4.44 in C1, and 3.00 in C2, respectively. The ORs for anterior tooth loss were higher than those for posterior tooth loss, with the highest OR observed in B4 (21.4). ConclusionsThis large population-based cohort study showed that a decreased POS was a risk indicator for tooth loss; furthermore, the risk increased even further in the anterior teeth region.

Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies

Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts. In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards. We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451[60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities. Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections. Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.

Cohorte Cantabria - A biomedical research tool open to the world.

The contribution of large population-based study cohorts to the knowledge of disease risk factors and causes is unquestionable. The Framingham Cohort, a paradigm for the population-based studies that changed the history of medicine, emerged after the antibiotic revolution, the decrease in infection-related mortality, and the boom in cardiovascular morbidity and mortality.

Risk of carpal tunnel syndrome among patients with osteoarthritis: a US population-based study

BackgroundCarpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States.MethodsPatients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression.ResultsAfter applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21–7.49) in the OA cohort and 1.44 (95% CI 1.38–1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54–4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint.ConclusionsOA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS.

Psychiatric adverse events following COVID-19 vaccination: a population-based cohort study in Seoul, South Korea.

Evidence has suggested an increased risk of psychiatric manifestations following viral infections including coronavirus disease-2019 (COVID-19). However, psychiatric adverse events (AEs) after COVID-19 vaccination, which were documented in case reports and case series, remain unclear. This study is aimed to investigate the psychiatric AEs after COVID-19 vaccination from a large population-based cohort in Seoul, South Korea. We recruited 50% of the Seoul-resident population randomly selected from the Korean National Health Insurance Service (KNHIS) claims database on 1, January, 2021. The included participants (n = 2,027,353) from the Korean National Health Insurance Service claims database were divided into two groups according to COVID-19 vaccination. The cumulative incidences per 10,000 of psychiatric AEs were assessed on one week, two weeks, one month, and three months after COVID-19 vaccination. Hazard ratios (HRs) and 95% Confidence interval (CIs) of psychiatric AEs were measured for the vaccinated population. The cumulative incidence of depression, anxiety, dissociative, stress-related, and somatoform disorders, sleep disorders, and sexual disorders at three months following COVID-19 vaccination were higher in the vaccination group than no vaccination group. However, schizophrenia and bipolar disorders showed lower cumulative incidence in the vaccination group than in the non-vaccinated group. Depression (HR [95% CI] = 1.683 [1.520-1.863]), anxiety, dissociative, stress-related, and somatoform disorders (HR [95% CI] = 1.439 [1.322-1.568]), and sleep disorders (HR [95% CI] = 1.934 [1.738-2.152]) showed increased risks after COVID-19 vaccination, whereas the risks of schizophrenia (HR [95% CI] = 0.231 [0.164-0.326]) and bipolar disorder (HR [95% CI] = 0.672 [0.470-0.962]). COVID-19 vaccination increased the risks of depression, anxiety, dissociative, stress-related, and somatoform disorders, and sleep disorders while reducing the risk of schizophrenia and bipolar disorder. Therefore, special cautions are necessary for administering additional COVID-19 vaccinations to populations vulnerable to psychiatric AEs.

The contribution of rare and common genetic variants to risk of prostate cancer and second primary cancer after prostate in the UK Biobank.

10604 Background: It has been estimated that up to 40% of prostate cancer may be attributed to inherited genetic susceptibility, yet very few variants have been consistently associated with risk and/or adverse outcomes after diagnosis. Moreover, because prostate cancer survival is generally good, risk of developing a second primary cancer (SPC) is an important concern. Identifying men at greater genetic risk of developing an SPC will lead to improved post-diagnostic cancer surveillance practices and lifestyle behavior modifications. Methods: The current investigation leverages genetic and phenotypical data from the UK Biobank (UKB) to examine inherited genetic factors, including rare pathogenic mutations (RPMs) and polygenic risk scores (PRS) with prostate cancer risk and SPC. The individual and joint contribution of (RPM in 26 cancer susceptibility genes and trans-ethnic PRS previously derived for 11 different cancer sites with both risk of prostate cancer and also SPCs among men diagnosed after primary prostate cancer. Cox regression models were used to estimate Hazard Ratio (HR) for prostate cancer, adjusted for age and ancestry. Cumulative incidence of SPC by person-year among prostate cancer patients was estimated from the age of diagnosis and compared with that in men without cancer. Results: Among 228,472 men in the UKB, 17,547 were diagnosed with prostate cancer. RPMs in five genes ( ATM, BRCA2, CHEK2, HOXB13 and PTEN) were significantly associated with prostate cancer risk. The rate of prostate cancer among RPM carriers was 15.59% compared with 7.72% in non-carriers (HR=2.26, 95% CI=1.97-2.59). The top decile of PRSProstate was associated with a 9.99-fold increase in risk of prostate cancer (95% CI=9.08-11). Having a diagnosis of prostate cancer had a significantly increased risk for two SPCs (bladder and kidney) and reduced risk for lung cancer, p&lt;0.001. Those that developed SPC of bladder cancer had significantly higher PRSBladder, p=5.91E-06. The number of RPM carriers (n=77) among SPC bladder cancers was prohibitively small to precisely estimate risk. Conclusions: In this large population-based cohort, both RPMs in largely DNA damage repair genes and PRS contribute to risk of prostate cancer and PRS with second primary bladder cancer among men with prostate cancer. These data both contribute to our understanding of the genetic susceptibility to prostate cancer and reinforce the need for refinement of genetic screening panels.

Long-term cardiovascular outcomes in survivors of 20 adult solid tumors: Large population-based matched cohort study.

11177 Background: The past few decades have seen notable advancements in how cancer is diagnosed and treated, with improvements in cancer survival. Cardiovascular diseases (CVDs) are the major life-limiting comorbidity among cancer survivors. Evidence is scarce on the risks of specific CVDs in survivors of a wide range of solid tumors, hindering informed strategies for prevention and management. Thus, we evaluated a large population-based U.S. electronic health records database. Methods: This large retrospective cohort study was conducted by using the TriNetX dataset between January 2008 and December 2022. All adult patients (&gt;18 years) with a diagnosis of 20 most common solid tumors alive 12 months after diagnosis were matched with controls without a cancer history in a 1:1 ratio with these a priori identified potential confounders: demographics, BMI, nicotine dependence, comorbidities, labs, and medications. The primary outcome was the first incidence of CVD like heart failure (HF), major adverse cardiovascular events (MACE; unstable angina, myocardial infarction, or coronary artery intervention), or venous thromboembolism (VT), and cerebrovascular events (CVE; stroke, transient ischemic attack, cerebral infarction, carotid intervention). Hazard ratios (HR) were calculated to assess the outcomes. Results: 890126 individuals with a solid tumor of interest followed up at least 1 year later were identified and matched to 1787244 controls. The VT risk was higher among survivors of 18 out of 20 specific solid cancer types than controls. HRs ranged from HR 3.68( 95% CI 3.48-3.89) for kidney cancer and HR 1.27 (95% CI 1.21–1.35) in patients after pancreatic cancer. HRs for VT were more prominent without prior CVDs. Higher risks of CVDs were the most common immuno -and chemotherapy. Higher risk of HF was observed in lung (HR 1.46, 95% CI 1.32–1.89), liver (HR 1.22, 95% CI 1.18–1.26), and ovarian (HR 2.01, 95% CI 1.64–2.45) cancers and in patients younger than 55 years. Pericarditis and arrhythmia were common in lung, bile duct, and stomach cancers. A greater risk of arrhythmia was also observed in lung, kidney, and thyroid cancers, whereas CVE was observed in CNS cancers. Conclusions: Survivors of site-specific solid tumors are at a higher medium to long-term risk of one or more CVDs than the general population. Notably, substantial variations in risk were observed across different cancer primary sites. The outcomes underscore the importance of heightened monitoring for CVDs after a cancer diagnosis.

New-onset atrial fibrillation, cardiovascular outcomes and all-cause mortality in patients with newly diagnosed cancer: A large population-based matched cohort study.

11184 Background: Studies have shown an association between atrial fibrillation (AF) and cancer, but the relationship is incompletely studied. there is also a paucity of data regarding the specific association between cancer type and AF risk . Notably, the longitudinal associations of new-onset AF with adverse cardiovascular (ACV) outcomes in Newly Diagnosed Cancer Patients remain unclear. Thus, through a comprehensive nationwide population-based study, we assessed the associations between new-onset AF and subsequent risks of ACV events and all-cause mortality. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adults (&gt;18 years) with any new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients without AF. The primary outcome was new ACV events like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), ischemic heart disease (IHD), and cerebrovascular events (CVE; cerebral infarction, carotid intervention, stroke, transient ischemic attack. The secondary outcome was all-cause mortality. Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare group outcomes. Results: Among the new diagnoses, 52,606 developed AF, and 374,959 remained AF free during the follow-up. After PSM, both cohorts (51,567 each) were well-matched. The mean follow-up duration was 4.8 (± 2.7) years. Among newly diagnosed cancer patients, those with incident AF had higher risk of MACE (HR 1.56; 95% CI 1.49–2.16), HF (HR 3.10; 95% CI 2.76–4.36), IHD (HR 1.68; 95% CI 1.41–2.01), CVE (HR 2.93; 95% CI 2.13–4.04), and all-cause mortality (HR 2.56; 95% CI 1.89–3.78) compared with those without incident AF. We noted a higher incidence rate during the initial months after the diagnosis of AF for both sexes. During the first year, the association with any ACV events (men: HR 2.78, 95% CI, 1.85–3.20; women: HR 1.81, 95% CI, 1.31–2.67) was more substantial than that following AF diagnosis for both sexes. New ‐onset AF was strongly associated with metastatic cancer. In sensitivity analysis, we excluded individuals with &lt;1 year of follow-up results were consistent, and all statistically significant associations remained unchanged. Conclusions: cancer patients who developed AF had significantly higher risks of subsequent adverse cardiovascular events and greater all-cause mortality. AF was strongly associated with metastatic disease. Our findings highlight the importance of strategies for AF prevention to mitigate macrovascular complications in all newly diagnosed cancer patients.