Prospective Population-based Study Research Articles

Methodology for Biological Sample Collection, Processing, and Storage in the Newcastle 1000 Pregnancy Cohort: Protocol for a Longitudinal, Prospective Population-Based Study in Australia.

Research in the developmental origins of health and disease provides compelling evidence that adverse events during the first 1000 days of life from conception can impact life course health. Despite many decades of research, we still lack a complete understanding of the mechanisms underlying some of these associations. The Newcastle 1000 Study (NEW1000) is a comprehensive, prospective population-based pregnancy cohort study based in Newcastle, New South Wales, Australia, that will recruit pregnant women and their partners at 11-14 weeks' gestation, with assessments at 20, 28, and 36 weeks; birth; 6 weeks; and 6 months, in order to provide detailed data about the first 1000 days of life to investigate the developmental origins of noncommunicable diseases. The study aims to provide a longitudinal multisystem approach to phenotyping, supported by robust clinical data and collection of biological samples in NEW1000. This manuscript describes in detail the large variety of samples collected in the study and the method of collection, storage, and utility of the samples in the biobank, with a particular focus on incorporation of the samples into emerging and novel large-scale "-omics" platforms, including the genome, microbiome, epigenome, transcriptome, fragmentome, metabolome, proteome, exposome, and cell-free DNA and RNA. Specifically, this manuscript details the methods used to collect, process, and store biological samples, including maternal, paternal, and fetal blood, microbiome (stool, skin, vaginal, oral), urine, saliva, hair, toenail, placenta, colostrum, and breastmilk. Recruitment for the study began in March 2021. As of July 2024, 1040 women and 684 partners were enrolled, with 922 infants born. The NEW1000 biobank contains 24,357 plasma aliquots from ethylenediaminetetraacetic acid (EDTA) tubes, 5284 buffy coat aliquots, 4000 plasma aliquots from lithium heparin tubes, 15,884 blood serum aliquots, 2977 PAX RNA tubes, 26,595 urine sample aliquots, 2280 fecal swabs, 17,687 microbiome swabs, 2356 saliva sample aliquots, 1195 breastmilk sample aliquots, 4007 placental tissue aliquots, 2680 hair samples, and 2193 nail samples. NEW1000 will generate a multigenerational, deeply phenotyped cohort with a comprehensive biobank of samples relevant to a large variety of analyses, including multiple -omics platforms. DERR1-10.2196/63562.

Increased risk of clinically relevant neurodevelopmental disorders in survivors of congenital diaphragmatic hernia: a population-based study.

Neurodevelopmental disorders (ND) have been recognized as the most common and potentially most disabling outcome of congenital diaphragmatic hernia (CDH). Our aim was to evaluate the incidence of ND in patients with a history of CDH referred for ND assessment on the basis of clinically relevant symptoms rather than through a screening process. The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who survived the newborn period in Sweden during the observational period from 1st January 1982 until 31st December 2015. In the study period, 641 non-syndromic CDH survivors were identified, and 3080 control cases were selected. Significantly higher incidence of clinically relevant any ND (11.5% vs 5.6%,p < 0.001), ASD (3.9% vs 2.1%,p:0.011), and intellectual disorder (6.6% vs 0.7%,p < 0.001) were observed in CDH compared to controls. When compared with controls, those with CDH were found to have a 2.179 times higher risk to develop any ND (p < 0.001), 1.867 times higher risk for ASD (p = 0.008), and 10.63 times higher for intellectual disorder (p < 0.001). CDH survivors have a higher risk of clinically relevant ND than the general population, independent of the effect of screening.

Association between changes in adherence to the 24-hour movement guidelines with depression and anxiety symptoms among Chinese adolescents: a prospective population-based study

BackgroundThe 24-hour movement guidelines (24-HMG) include screen time (ST), sleep duration, and physical activity. Previous studies have explored the associations of adherence to the 24-HMG with depression and anxiety symptoms among adolescents, ignoring changes in behaviors. This study aimed to examine whether changes in adherence to the 24-HMG were associated with depression and anxiety symptoms among adolescents.MethodsWe recruited adolescents from Shenzhen, China in 2021 and followed them up 1 year later. Changes in adherence to the individual 24-HMG were categorized into four groups: persistent non-adherence, adherence to non-adherence, non-adherence to adherence, and persistent adherence. Changes in the numbers of adherence to the overall 24-HMG were obtained by subtracting the number of guidelines adhered to in wave 2 from that in wave 1.ResultsWe included 12,570 participants aged 9–18 years with 52.2% boys. Compared with persistent non-adherence for the ST/sleep duration guideline, non-adherence to adherence and persistent adherence were associated with lower depression and anxiety symptoms, but adherence to non-adherence was not. Changes in adherence to the physical activity guideline were not related to outcomes. The β coefficients (95% CIs) for each point increase in changes in the numbers of adherence to guidelines were − 0.58 (− 0.69, − 0.47) and − 0.43 (− 0.53, − 0.33) for depression and anxiety symptoms, respectively. The association of persistently adhering to sleep guideline with anxiety symptoms and the associations of changes in the numbers of adherence to the 24-HMG had sex differences.ConclusionsMaintaining and strengthening healthy movement behaviors to meet more guidelines of the 24-HMG, especially sleep and ST, may be beneficial for preventing depression and anxiety symptoms in adolescents.

Cancer incidence following non-neoplastic medical conditions: a prospective population-based cohort study.

Many non-neoplastic diseases have been established to be tumorigenic, and cancers are sometimes misdiagnosed as non-neoplastic diseases. We conducted a comprehensive registry-based study of site-specific cancer diagnosis risk following the diagnosis of any preceding medical condition (PMC) encoded by the International Classification of Diseases (ICD)-10 classification. We analyzed healthcare data and cancer data for a random population-based sample of 2.5 million individuals living in Finland on January 1, 2000. Hazard ratios for each PMC and cancer pair were estimated using piecewise constant hazard regression models. P-values were corrected for multiple testing with the Bonferroni method. Several lifestyle-related PMCs were associated with the risk of cancer diagnosis, exemplified by chronic obstructive pulmonary disease and subsequent lung cancer diagnosis risk (female hazard ratio [HR] = 9.91, 95% confidence interval [CI]: 9.18-19.7, p-adj. < 0.0001; male HR = 5.69, 95% CI: 5.43-5.96, p-adj. < 0.0001). Diagnosis risk of ill-defined cancers appeared to increase following diagnosis of Alzheimer's disease (AD). We identified rare PMCs of potential interest. A considerable proportion of the statistically significant associations were explainable by tobacco smoking and alcohol use. The enrichment of ill-defined cancer diagnoses in persons with AD, together with the overall inverse association between AD and cancer, may reflect underdiagnosis of cancer in this patient population. Our results provide a useful resource for research on the prevention and early detection of cancer.

Survival rate changes in children with congenital diaphragmatic hernia over the past three decades: a nationwide, population-based prospective nested case-control study.

The survival rate (SR) for neonates born with congenital diaphragmatic hernia (CDH) remains high. Our aim was to investigate the change in SR in children with CDH over the past decades. The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who was born in Sweden during the observational period from 1st January 1982 to 31st December 2015. In the study period, 4654 (99.6%) control children and 684 children with CDH (70.4%, p < 0.001) were with a survival of 2years of age. Any patients who were born with CDH had a overall 5.8 times higher chance for not surviving 2years of age than children without CDH. The SR improved significantly in CDH in the past 3 decades. Significantly higher number of patients were prematurely born in the CDH group than in the controls (23.3 vs 6.1%, p < 0.001). The SR of premature and non-premature born CDH patients has increased significantly over the past 3 decades. The SR of CDH patients were significantly increased in the past 3 decades. The 2-year survival remains 5.8 times higher than those who were not born with CDH. These changes were mainly attributed to the improved SR of premature and non-premature born CDH patients.

Airway management in infants with Robin sequence in the United Kingdom and Ireland: A prospective population-based study.

There is currently no consensus about managing upper airway obstruction (UAO) in infants with Robin sequence (RS), in terms of treatment efficacy or clinical outcomes. This study describes UAO management in UK/Ireland, and explores relationships between patient characteristics, UAO management, and clinical outcomes in the first 2 years of life. Active surveillance of RS throughout UK/Ireland via the British Paediatric Surveillance Unit and nationally commissioned cleft services. Clinical data were collected at initial notification and 12-month follow-up. 173 infants with RS were identified, of which 47% had additional congenital anomalies or an underlying syndrome (non-isolated RS). Two-thirds (n = 119) required an airway intervention other than prone positioning: non-surgical in 84% and surgical (tracheostomy) in 16%. Nasopharyngeal airway (NPA) was the most common intervention, used in 83% (n = 99) for median 90 days (IQR 136). Surgical UAO management was associated with prolonged hospital admission, higher prevalence of neurodevelopmental delay (NDD), lower weight-for-age z-scores, and delayed oral feeding. These findings were not attributable to a higher prevalence of non-isolated RS in this group. Although more commonly associated with non-isolated RS, growth faltering was also identified in 48%, and NDD in 18%, of cases of isolated RS. In UK/Ireland, most infants with RS are managed with NPA, and tracheostomy is reserved for refractory severe UAO. Clinical outcomes and duration of use indicate that NPA is a safe and feasible first-line approach to UAO. Longitudinal assessment of neurodevelopment and growth is imperative, including in children with isolated RS. Current variations in practice reinforce the need for evidence-based treatment guidelines.

Childhood-to-adulthood body size trajectory and cancer risk: a prospective cohort study

Abstract Background While excess weight in adulthood and childhood has been associated with increased cancer risk, the link between childhood-to-adulthood body size trajectories and cancer risk requires further investigation. Methods We used data from the UK Biobank, a prospective population-based cohort study. The main exposure was childhood-to-adulthood body size trajectory, constructed from self-reported body at age 10 (categories: thinner, average, and plumper than average) and measured body mass index (BMI) at recruitment (normal weight, overweight, and obese). Primary outcome was obesity-related cancer (13 different cancer types). Results During a median follow-up of 11.7 years, 21,289 participants developed obesity-related cancers. Having a larger body size at age 10 was strongly associated with being overweight or obese in adulthood. Compared to participants with average childhood to normal adulthood body size trajectory, all trajectories ending in overweight or obesity in adulthood were strongly associated with an increased risk of obesity-related cancers. The strength of the association was mostly determined by adulthood BMI, and similar patterns were observed for colorectal, endometrial, kidney, pancreatic and esophageal cancer. However, a larger body size in childhood was associated with a lower risk of postmenopausal breast cancer. Conclusions Although a larger body size in childhood predisposes to overweight and obesity in adulthood, it does not necessarily predispose to an increased obesity-related cancer risk if measures to maintain a healthy weight are taken in adulthood. Key messages • While larger body size in childhood predisposes individuals to overweight and obesity in adulthood, maintaining a healthy weight in adulthood may help mitigate the risk of obesity-related cancers. • Our findings highlight the importance of preventing and reducing overweight and obesity in adulthood for primary cancer prevention.

Plasma levels of sCASP3 predicts carotid intima media thickness progression

Abstract Background Studies on human atherosclerotic plaques have shown that apoptosis is associated with rupture prone plaques and that apoptosis is a key process for fast plaque progression. In line with this, we showed that circulating levels of soluble Caspase-3 (sCaspase-3) predict atherosclerotic events. However, the relationship between circulating levels of apoptosis markers and plaque progression remains to be explored. Purpose Here we aimed to investigate if circulating levels of apoptosis markers could predict mean intima-media thickness in the common carotid artery (IMT-CCA) progression among individuals with atherosclerotic carotid plaques. Methods The Malmö Diet and Cancer (MDC) cardiovascular cohort was used. MDC is a prospective population-based cohort study. Baseline variables (blood, clinical information and carotid ultrasound measurements) were collected between 1991-1994 and the right carotid ultrasound re-examinations were performed between 1994-2001. IMT was measured at by ultrasound at baseline as well as at the re-examinations. The Olink Proximity Extension Assay (SciLifeLab, Uppsala, Sweden) was used to analyze plasma levels of sCaspase-3, sFADD, sCaspase-8, sTRAIL-R2 and sTNFR1 at baseline. Correlation and multiple linear regression analyses, adjusted for age, sex, and cardiovascular risk factors, were employed to evaluate the relationships between apoptosis biomarkers and IMT-CCA as well as average annual change in IMT-CCA. Results In total, 1929 participants (median age 60 years) with an ultrasound confirmed carotid plaque (focal IMT &amp;gt;1.2mm) at baseline were included. Subjects who underwent ultrasound IMT re-examination over a period of &amp;gt;4.5 years were divided into a discovery (n=406) and a validation (n=355) cohort. sCaspase-3 was identified as the marker with the strongest correlation to IMT-CCA at baseline (p=0.02) and upon re-examination (p=0.04), among the five apoptosis markers examined, in both the discovery and validation cohorts. sCaspase-3 also showed a correlation with the average annual change of IMT-CCA (r=0.12, p=8×10-4) in both cohorts. Furthermore, when diving the cohort into tertiles based on plasma levels of sCapase-3, subjects with high levels of sCaspase-3 (3rd tertile) had greater annual changes in IMT-CCA compared to the 1st tertile (p=0.03). Multiple linear regression analyses confirmed that sCapase-3 was associated with the average annual IMT-CCA change in both the discovery (beta=0.14, 95% confidence interval (CI) 0.04–0.24) cohort and the validation cohort (beta=0.11, 95%CI 0.01–0.21). Conclusion Using a large, population-based study with repeated IMT measurements, we demonstrated that circulating levels of sCapase-3 were associated with increasing IMT in the CCA. While further studies are warranted, these results suggest that sCapase-3 levels could serve as potential screening marker to identify individuals at higher risk for plaque progression.

Longitudinal assessment of the impact of prevalent diabetes on hospital admissions and mortality in the general population: a prospective population-based study with 19 years of follow-up

BackgroundHospitalization indicates the presence of severe disease and constitutes a leading cost in health care. We aimed to prospectively assess if prevalent diabetes mellitus contributes to excess all-cause and cause-specific hospital admissions and mortality at the population level.MethodsWe used a Swedish prospective population-based cohort, including 25,642 individuals of whom 4.2% had prevalent diabetes at baseline (mean age 61.2 ± 6.8 years, age range 44.8–73.4 years). We compared the number of hospitalizations and mortality classified according to the main chapters of the 10th revision of the International Classification of Diseases (ICD-10) during follow-up using nationwide inpatient registries, comparing individuals with and without prevalent diabetes, using multivariate adjusted negative binomial regression (incidence rate ratio, IRR) and Cox regression, respectively.ResultsDuring a median follow-up of 19 years, 18,904 subjects were hospitalized at least once [median 3 (IQR 2–6)] and 6767 (26.4%) individuals died. Overall, subjects with diabetes were hospitalized (IRR 1.83, p < 0.001) more often, and had a higher incidence rate of hospital admissions due to endocrine diseases (IRR 14.6, p < 0.001), dermatological diseases (IRR 3.7, p < 0.001), injuries and poisoning (IRR 2.7, p < 0.001), infectious diseases (IRR 2.5, p < 0.001), psychiatric diseases (IRR 2.0, p < 0.001), but also cardiovascular, hematological, genitourinary, neurologic and respiratory diseases compared with non-diabetic individuals. No difference was observed for hospital admissions due to cancer or musculoskeletal disorders. All-cause mortality was higher (HR 1.77, p < 0.001) in individuals with diabetes, with disease-specific mortality being significant only for cardiovascular and endocrine disease-related death.ConclusionsAt the population level, prevalent diabetes increased the hospitalization burden longitudinally due to diseases of most of the ICD-10 main chapters, except for cancer and musculoskeletal disorders. These novel findings challenge the current view on the spectrum of prevalent diabetes-related conditions and may have implications for screening and treatment strategies in diabetes.Permission of graphical illustrationsSource: Pixabay.com. No permission or acknowledgement is required.

Delays in Cardiopulmonary Resuscitation, Defibrillation, and Epinephrine Administration in Out-of-Hospital Cardiac Arrest - Composite Time-Dependent Effects of Prehospital Interventions on 30-Day Favorable Neurological Outcomes and Social Implications From a Prospective Nationwide Population-Based Cohort Study.

Our study investigated the prognostic impacts of the interval between collapse and the initiation of cardiopulmonary resuscitation (CPR), and subsequent intervals to defibrillation or epinephrine administration, on 30-day favorable neurological outcomes following out-of-hospital cardiac arrest (OHCA). This nationwide population-based cohort study used the All Japan Utstein Registry, encompassing OHCA patients in Japan between January 2006 and December 2021. The primary outcome was 30-day favorable neurological outcomes, defined as Cerebral Performance Category 1 or 2. Three-dimensional plots and multivariable logistic regression models were used to assess the time-dependent prognostic impacts of prehospital CPR interventions. In all, 184,731 OHCA patients (86,246 with shockable rhythm and 98,485 with non-shockable rhythm) were included in the study. Three-dimensional plots revealed that the interval between collapse and initiation of CPR, and subsequent intervals to defibrillation or epinephrine, were independently associated with 30-day favorable neurological outcomes in the groups with shockable and non-shockable rhythms, respectively (P<0.05 for all). Among patients with witnessed OHCA, there was a dose-response relationship between delays in the collapse-CPR initiation interval, and subsequent intervals to defibrillation or epinephrine administration, and 30-day favorable neurological outcomes. Our findings provide valuable insights into OHCA management.

Risk factors and evolution of weight loss in Parkinson's disease: A 9-year population-based study

IntroductionWeight loss is considered a common complication of Parkinson's disease (PD), but there are few prospective longitudinal studies on weight loss in patients followed from time of PD diagnosis. We sought to determine the frequency, evolution and risk factors of weight loss in a representative incident PD cohort. MethodsIn this prospective population-based observational study, we followed 180 newly-diagnosed, initially drug-naïve PD patients and 161 controls with repetitive weight examinations over 9 years. We used Cox regression models with adjustment for potential confounders to identify independent risk factors of clinically significant (>10 %) weight loss. ResultsMean % weight change during follow-up was −3.9 (±11.2) in patients and −1.4 (±8.1) in controls (p = 0.016). Clinically significant weight loss was observed in 26.7 % of patients and 10.6 % of controls (RR 2.53; 95 % CI 1.52–4.21; p < 0.001). Age was the only independent baseline risk factor for weight loss (HR 1.06 per year; 95 % CI 1.03–1.10; p < 0.001). Additional time-dependent risk factors were presence of olfactory impairment (HR 2.42; 95 % CI 1.14–5.15; p = 0.021), presence of dyskinesias (HR 3.14; 95 % CI 1.58–6.23; p = 0.001), and cognitive impairment (HR per MMSE unit 0.90; 95 % CI 0.82–0.99; p = 0.036). Dopamine agonist use reduced the risk of weight loss during follow-up (HR 0.44; 95 % CI 0.24–0.82; p = 0.007). ConclusionThe risk of weight loss is more than doubled in the general PD population and associated with both disease-related features and drug-related complications. This suggests a multifactorial nature of weight loss in PD, which is important to consider in research and clinical practice.

Beyond the Heart: The Predictive Role of Coronary Artery Calcium Scoring in Non-Cardiovascular Disease Risk Stratification.

Coronary artery calcium scoring (CACS), a non-invasive measure of coronary atherosclerosis, has significantly enhanced cardiovascular (CV) risk assessment and stratification in asymptomatic individuals. More recently, a higher score for CAC has been associated with an increased risk of non-CV diseases and all-cause mortality. This review consolidated evidence supporting the role of CAC in assessing non-CV diseases, emphasizing its potential in early diagnosis and prognosis. We observed a strong association between CACS and non-CV diseases, viz., chronic obstructive pulmonary disease, pulmonary embolism, pneumonia, diabetes, chronic kidney disease, osteoporosis, metabolic dysfunction-associated steatotic liver disease, nephrolithiasis, stroke, dementia, malignancies, and several autoimmune diseases. Also, CAC may aid in evaluating the risk of CV conditions developing secondary to the non-CV diseases mentioned earlier. Further evidence from prospective studies, intervention trials, and population-based behavioral studies is needed to establish CAC cutoff values and explore preventative care applications, facilitating their broader integration into healthcare practices.

Characterizing the progression from mild cognitive impairment to dementia: a network analysis of longitudinal clinical visits

BackgroundWith the recent surge in the utilization of electronic health records for cognitive decline, the research community has turned its attention to conducting fine-grained analyses of dementia onset using advanced techniques. Previous works have mostly focused on machine learning-based prediction of dementia, lacking the analysis of dementia progression and its associations with risk factors over time. The black box nature of machine learning models has also raised concerns regarding their uncertainty and safety in decision making, particularly in sensitive domains like healthcare.ObjectiveWe aimed to characterize the progression of health conditions, such as chronic diseases and neuropsychiatric symptoms, of the participants in Mayo Clinic Study of Aging (MCSA) from initial mild cognitive impairment (MCI) diagnosis to dementia onset through network analysis.MethodsWe used the data from the MCSA, a prospective population-based cohort study of cognitive aging, and examined the changing association among variables (i.e., participants’ health conditions) from the first visit of MCI diagnosis to the visit of dementia onset using network analysis. The number of participants for this study are 97 with the number of visits ranging from 2 visits (30 months) to 7 visits (105 months). We identified the network communities among variables from three-fold collection of instances: (i) the first MCI diagnosis, (ii) progression to dementia, and (iii) dementia diagnosis. We determine the variables that play a significant role in the dementia onset, aiming to identify and prioritize specific variables that prominently contribute towards developing dementia. In addition, we explore the sex-specific impact of variables in relation to dementia, aiming to investigate potential differences in the influence of certain variables on dementia onset between males and females.ResultsWe found correlation among certain variables, such as neuropsychiatric symptoms and chronic conditions, throughout the progression from MCI to dementia. Our findings, based on patterns and changing variables within specific communities, reveal notable insights about the time-lapse before dementia sets in, and the significance of progression of correlated variables contributing towards dementia onset. We also observed more changes due to certain variables, such as cognitive and functional scores, in the network communities for the people who progressed to dementia compared to those who does not. Most changes for sex-specific analysis are observed in clinical dementia rating and functional activities questionnaire during MCI onset are followed by chronic diseases, and then by NPI-Q scores.ConclusionsNetwork analysis has shown promising potential to capture significant longitudinal changes in health conditions, spanning from the MCI diagnosis to dementia progression. It can serve as a valuable analytic approach for monitoring the health status of individuals in cognitive impairment assessment. Furthermore, our findings indicate a notable sex difference in the impact of specific health conditions on the progression of dementia.

Difference in Risk Factor profile for Abdominal Aortic Aneurysm and Thoracic Aortic Aneurysm

Previous studies suggest partly different risk factor profiles of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), but prospective data are scarce. The purpose of this prospective population-based case-control study was to investigate differences in risk factor profile between TAA and AAA. Participants in two prospective population-based studies, the Västerbotten Intervention Project (VIP) and the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, between 1986 and 2010 underwent cardiovascular risk assessments, including blood samples, oral glucose tolerance test, blood pressure readings and a self-reported health questionnaire. All individuals who were later diagnosed with TAA or AAA were identified. Age, sex, and time-matched controls were selected from the same cohorts, aiming at four controls / case. Adjusted odds ratios for potential risk factors for later diagnosis of TAA and AAA respectively, were estimated by multivariate conditional logistic regression analyses. From total 96,196 individuals with prospectively collected data in the VIP/MONICA cohort, a total of 236 individuals with AAA (181 men and 55 women) and 935 matched controls, and 168 individuals with TAA (115 men and 53 women) and 662 controls were included. The average age at baseline examination was 57.0 ± 5.7 years for AAA cases and controls, and 52.1 ± 8.8 years for TAA cases and controls. Mean time between baseline examination and diagnosis of AAA/TAA was 12.1 and 11.7 years respectively. There was a clear difference in risk factor profile between AAA and TAA. Smoking, hypertension and coronary artery disease were significantly associated with later diagnosis of AAA with highest adjusted odds ratio for a history of smoking (OR 10.3, 95% CI 6.3-16.8). For TAA, hypertension was the only positive risk factor (OR 1.7, CI 1.1-2.7), while smoking was not associated. Diabetes was not associated with either AAA or TAA, neither was self-reported physical activity. In this prospective population-based case-control study risk factor profile differed between AAA and TAA. This suggests a partially different etiology for TAA and AAA.

SARS-CoV-2 memory response in non-hospitalised cases: immunology in the context of a population-based cohort study

Background The study of non-hospitalised COVID-19 cases provides a context for improved understanding of the immune response to existing and new infections. Population-based cohorts provide a unique opportunity to do this in relation to rich longitudinal pre- and pan-pandemic data. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has subsequently followed participants for over 30 years. Methods A study comprising three clinic visits was implemented, in response to the COVID-19 pandemic, amongst ALSPAC participants to measure SARS-CoV-2 specific humoral and cellular responses longitudinally. Here we present data from the first clinic in December 2020 before the start of the UK vaccination campaign and examine associations with a set of exemplar pre- and pan-pandemic health factors. Results We observed humoral and cellular memory immune responses to SARS-CoV-2 infection in mild cases of COVID-19 up to 9 months post-infection. Symptomatic infection elicited a memory immune response of greater magnitude, though there was variation in response in both asymptomatic and symptomatic individuals. We examined health factors associated with severe COVID-19 and found that cardio-metabolomic, respiratory and immune-related health factors associate with a memory immune response of higher magnitude. For example, in older participants (mean age 58 years), higher BMI was associated with an immune memory response of greater magnitude, particularly with anti-S and anti-N binding antibodies. Conclusions We set out to illustrate the use of cohort studies to deliver detailed immunological data and to provide example analyses of how life course health factors can be examined in relation to the immune response following a widespread and novel infection. We expanded this assessment to include longitudinally assessed traits, opening up the potential for the more common use of longitudinal population studies for the better understanding the aetiology of infection outcome.

Effects of childhood adversities on alexithymia features vary between sexes. Results of a prospective population study

ABSTRACT Introduction: Adverse childhood experiences (ACEs) associate with various mental disorders, including personality features. Our understanding of how ACEs influence alexithymia features in the general population is limited. In a prospective population setting, we studied whether ACEs associate with alexithymia, and the role of sex and emotional symptoms in this association. Methods: In a Finnish population-based prospective study, 3,142 individuals aged between 30 and 64 years completed eleven ACE questions and the Toronto Alexithymia Scale in 2000 and 2011, and the Hopkins Symptoms Checklist in 2011. The effect of ACEs on alexithymia and its subdomains – difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and externally oriented thinking (EOT) in 2000 and 2011 – was analysed using repeated measures ANOVA. Results: The number of ACEs and their main component, childhood social disadvantage, associated positively with total alexithymia scores and its subdomains DIF and DDF, and negatively with EOT. After controlling for the effect of depression and anxiety, the strength of these associations was reduced, but the effect of social disadvantage on DIF and EOT remained significant in females. Childhood family conflicts associated positively with DIF in males and negatively with EOT in females. Additionally, maternal mental problems associated positively with DIF and DDF in females. Discussion: In the general population, ACEs, particularly social disadvantage, are associated with adult alexithymia features. Alexithymia features, detectable from youth, may predispose individuals to emotional disturbances caused by childhood adversities. The effect of family conflicts and maternal mental problems on alexithymia features varies between sexes.

Association of aspirin use with risk of intracerebral hemorrhage in patients without history of stroke or transient ischemic attack in the UK Biobank.

The association between aspirin use and the risk of intracerebral hemorrhage (ICH) among individuals without previous stroke events is inconclusive. We investigated the association between regular aspirin use and ICH risk in middle-aged and older adults without previous stroke or transient ischemic attack (TIA). This prospective population-based study included participants older than 40 years with no history of stroke or TIA from the UK Biobank. The main exposure was regular aspirin use. Cox regression analyses and propensity score matching analyses estimated the hazard ratios (HRs) for aspirin use for incident fatal and non-fatal ICH. We conducted pre-specified subgroup analyses for selecting individuals at high risk of ICH when using aspirin. Multiple sensitivity analyses were performed to test the robustness of our results. A total of 449,325 participants were included into final analyses (median (IQR) age 58 (50-63) years, 54.6% females), of whom 58,045 reported aspirin use. During a median follow-up of 12.75 (IQR: 12.03-13.47) years, 1557 (0.3%) incident ICH cases were identified, of which 399 (25.6%) were fatal. Aspirin was not associated with increased risk of overall (hazard ratio (HR): 1.11, 95% confidence interval (CI): 0.95-1.27, P = 0.188), fatal (HR: 1.03, 95% CI: 0.78-1.36, P = 0.846) and non-fatal (HR: 1.12, 95% CI: 0.95-1.33, P = 0.186) ICH. Propensity score matching analysis showed similar results. Subgroup analysis indicated that aspirin use in individuals older than 65 years or with concurrent anticoagulant use was correlated with increased risk of ICH. In this large cohort study of middle-aged and older adults without stroke or TIA events, there was no significant association between aspirin use and ICH risk in the real-world setting. However, it is possible that aspirin use in those aged over 65 years and concurrent anticoagulant treatment may increase the risk of ICH.

Association of RAAS inhibitors on osteoporosis and fracture risk in the hypertensive population–A prospective population-based cohort study in Lanzhou, China

BackgroundRenin-angiotensin-aldosterone system (RAAS) inhibitors appear to benefit bone tissue in antihypertensive treatment. However, the association between RAAS inhibitors and bone metabolism was inconsistent.Methods and study designBased on the study of Risk Evaluation of Cancers in Chinese Diabetic Individuals(REACTION) conducted in 2011, We followed 6,252 Lanzhou residents aged 40–75 years from 2014 to 2016. Finally, 1,625 hypertension cases with complete data were included in the analysis. The study subjects were divided into four groups according to the type of antihypertensive drugs. We employed logistic or multivariate Cox proportional hazards regression to estimate the association between different antihypertensive drug use and osteoporosis, the risk of fracture, and the change in bone mineral density (BMD) level. The association of osteoporosis or the fracture risk by cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated.ResultsThe cross-sectional study showed that there was no significant association between baseline antihypertensive drugs (angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)) use and osteoporosis and fracture. During a mean follow-up of 3.4 years in the longitudinal study, there were 478 new osteoporosis cases and 76 fractures. Compared with patients without antihypertensive drug use, the hazard ratios (HRs) [95% confidence interval (CI)] for the risk of osteoporosis were 1.005(0.651,1.552) and 1.077(0.793,1.462) in ACEI or ARB use (p > 0.05). ACEI or ARB use was also not significantly associated with fracture risk (HR 1.102(0.326,3.726), 0.735(0.251,2.148), p > 0.05). Further analysis showed that the use of ACEI (HR 1.078(0.146,7.950)) or ARB (HR 1.169(0.347,3.939)) was not significantly associated with the improvement of osteoporosis (p > 0.05). In addition, the duration of RAAS inhibitors used showed no apparent correlation with the risk of osteoporosis (≤ 3 years: HR 0.872 (0.516, 1.474), > 3 years: HR 1.151 (0.574, 2.308)), nor with the improvement of osteoporosis and the risk of fracture. Meanwhile, the association mentioned above did not change compared to different RAAS inhibitors.ConclusionsThe use of RAAS inhibitors, including ACEIs and ARBs, was not significantly associated with osteoporosis, risk of fracture, or BMD change.

Association between dynapenic obesity and risk of cardiovascular disease: The Hisayama study.

Dynapenic obesity is a condition characterized by high adiposity levels combined with muscle dysfunction. Although high adiposity and muscle loss/dysfunction are thought to synergistically increase the risk of cardiovascular disease (CVD), few studies have addressed the association between dynapenic and sarcopenic obesity and CVD. We aimed to investigate the association of dynapenic obesity with incident CVD events using the data from a population-based prospective longitudinal study in Japan. A total of 2490 community-dwelling Japanese aged 40-79years (42.5% males, mean age 57.7±10.6years) without a history of CVD were followed up for a median of 24years. Handgrip strength was classified as low, medium, or high by age- and sex-specific tertiles. Body mass index (BMI) levels were categorized as lean (<18.5kg/m2), normal (18.5-24.9kg/m2), or obese (≥25.0kg/m2). Dynapenic obesity was defined as having both low handgrip strength and obesity. The outcomes were defined as the first-ever development of CVD (defined as stroke or coronary heart disease). The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the development of CVD were estimated using a Cox proportional hazards model, in which participants with high handgrip strength and normal BMI were used as a reference group. Mediation analyses used serum high-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment for insulin resistance (HOMA-IR) as mediators. During the follow-up period, 482 participants developed CVD events (324 cases of stroke and 209 of coronary heart disease). The multivariable-adjusted risk of CVD increased significantly among participants with dynapenic obesity compared with the reference group (HR 1.49, 95% CI 1.03-2.17). An analysis by age groups showed a further increase in the risk of CVD among participants with dynapenic obesity aged less than 65years (HR 1.66, 95% CI 1.04-2.65). In mediation analyses for participants aged less than 65years, serum hs-CRP was shown to be a significant mediator explaining 13.8% of the association between dynapenic obesity and the development of CVD, while HOMA-IR explained 12.2% of this relationship. Dynapenic obesity was a significant risk factor for the development of CVD in a general Japanese population. This association was more pronounced among those aged <65years. Inflammation, and possibly glucose metabolism, might partly mediate this association. Our findings suggest that preventing muscle dysfunction as well as appropriate weight control, especially in middle-age, are important for preventing the development of CVD.

Adverse childhood experiences, economic challenges and suicide risk under COVID-19 pandemic: results from U-CORONA study

Purpose The purpose of this study is to examine the synergistic effect of adverse childhood experiences (ACEs) and economic challenges on suicide risk, under the coronavirus disease 2019 (COVID-19) pandemic, using a prospective population-based cohort study. Design/methodology/approach Participants included 435 adults (aged from 18 to 92 years, mean = 53.8) from the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, a population-based longitudinal study in Utsunomiya city, Japan. The baseline survey was conducted in June 2020, between the first and the second wave of the COVID-19 pandemic in Japan. ACEs were assessed using 13 items, and economic challenges due to the COVID-19 were assessed using one item. In the follow-up study, conducted in October 2020 between the second and the third wave of the COVID-19 pandemic in Japan, suicide risk was assessed using six items from the Mini-International Neuropsychiatric Interview via a self-reported questionnaire. Findings This study found positive independent association between ACEs and economic challenges due to COVID-19 and suicide risk. Synergistic effects were also found: the participants with one ACE and economic challenges and those with 2+ ACEs and economic challenges were more likely to be at higher risk of suicide compared to those without ACEs and economic challenges. Originality/value The findings suggest that adults with a higher number of ACEs, in addition to severe economic challenges, were more likely to be at risk for suicide during the COVID-19 pandemic.