Population Cohort Research Articles

Assessment of psychological resilience in a large cohort of the general population: Validation and norm values of the RS-5.

Psychological resilience is known as a protective factor against mental health disorders for which valid measures are indispensable. The present work aims to evaluate the Resilience Scale-5 (RS-5) psychometrically, and provide norm values. Data from the Gutenberg Health Study (GHS), encompassing 7,496 participants aged 25 to 86, spanning the years 2017 to 2022, was used. Selectivity, item difficulty, internal consistency, construct and factor validity, as well as factorial invariance were tested. Additionally, correlations and associations with depression, anxiety, and sociodemographic factors were determined. Furthermore, norm values were provided. The RS-5 displayed robust psychometric properties. Participants reported an average resilience score of 28.94 (SD = 5.53, median = 30, IQR = 6, range = 5-35), with those aged ≥75 exhibiting the highest resilience levels (M = 30.21, SD = 5.75, median = 32, IQR = 7). The RS-5 displayed a very good model fit, affirming measurement invariance across sex and age decades. Construct validity found support through anticipated intercorrelations with related psychological constructs. Significant correlations (p < .001) linked higher resilience with female gender, advanced age, higher education, elevated household income, and diminished psychological distress. The RS-5 emerged as a reliable and economic instrument for assessing psychological resilience in individuals aged 25 to 86. The study unraveled distinct sociodemographic characteristics significantly tied to resilience levels within this cohort. In contributing recent norm values tailored to the German population, this research enhances the practical applicability of the RS-5 across diverse contexts and enriches our comprehension of the demographic nuances associated with psychological resilience.

Formal school exclusions over the educational lifecourse in Wales

ABSTRACT For the first time, this paper takes a dynamic approach to studying formal school exclusions and their association with educational outcomes. In particular, we study every instance of school exclusions over a key part of a pupil’s education lifecourse between Year 6 (end of primary school) to Year 11 (end of secondary school). Using a single population cohort of all pupils in maintained schools in Wales, we show that the frequency of formal school exclusions varies over pupils’ lifecourse and identify five main exclusion trajectories, reflecting these variations over time, as follows: no exclusions, low level exclusions, early rise in exclusions, high-level Year 11 exclusions and late rise in exclusions. These general trajectories may suggest differences in the underlying reason for school exclusions that are not necessarily evident in pupils’ official records or as reported by individual schools. We also show the differential impact of these exclusion trajectories on later educational outcomes. Highlighting these different trajectories may be useful to policymakers and practitioners when developing national and local guidance around school exclusions. They may also reflect unknown biases in the likelihood that a pupil gets excluded from school, often a major area of concern in debates around inclusive education.

Contribution of the large-scale population cohort in disease risk prediction model study: taking United Kingdom Biobank as an example

The disease risk prediction model is the basis of precision prevention and an essential reference for clinical treatment decisions. The development of risk prediction models requires the support of a large amount of high-quality data. A large population cohort study is an important basis for this study. The United Kingdom Biobank (UKB), as a mega-population cohort and biobank, has played an essential role in the exploration of disease etiology and research related to disease prevention and control, with its rich baseline and follow-up data and concepts and mechanisms shared globally. This study followed PRISMA guidelines and included 210 articles with corresponding authors from 18 countries, of which 58 (27.62%) were from the UKB. A total of 491 disease risk prediction models were extracted for cancer, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases, respiratory diseases, and other diseases and their subgroups, of which 132 were developed by UKB without validation, 183 were developed by UKB with internal validation, 17 were developed by UKB with external validation, and 159 were developed by external development with UKB validation. A total of 188 models used only macro variables (38.29%), and 303 models combined macro and micro variables (61.71%). Model construction methods included survival outcome models, logistic regression, and machine learning. Survival outcome models were dominated by Cox proportional risk regression models and a few models considering competitive risk, accelerated failure models, or different baseline risk functions. Machine learning models included random forest, XGBoost, CatBoost, support vector machine, convolutional neural network, and other methods. The UKB is an essential resource for multiple disease risk prediction modeling studies.

Characteristics of posterior precortical vitreous pockets visualized by swept-source OCT and en face OCT

To determine the characteristics of posterior precortical vitreous pockets (PPVPs) and to observe vitreous changes in myopic eyes by swept-source optical coherence tomography (SS-OCT) and en face imaging in a cohort of the Chinese Han population. This was a cross-sectional study. Volunteers (235 participants, 374 eyes) received an SS-OCT examination. The heights and widths of the PPVPs were measured by SS-OCT. The area of the PPVPs was measured on en face images. The relationships between PPVP size and sex, age, axial length (AL) and spherical equivalent (SE) were evaluated. The mean width and height were 6711.64 ± 1241.87 μm and 662.47 ± 326.39 μm, respectively. The area of the PPVPs was 30.296 ± 9.114 mm2. Boat-shaped, oval, and hook-shaped PPVPs were observed in 73.26%, 21.12%, and 5.62% of all eyes, respectively; 73.53% of all PPVPs had channels communicating with Cloquet’s tubes. There was a significant difference in the PPVP width among the participates over and under 50 years old (t = -2.508, P = 0.031). Age had a positive correlation with the PPVP width (r = 0.53, P = 0.001). The PPVP height showed significant differences among the different myopia groups (F = 3.618, P = 0.013). SE had a negative correlation with the PPVP height (r = -0.176, P = 0.001). However, there were no correlations between the AL and the width, height or area of the PPVPs (P = 0.117; P = 0.334; P = 0.057, respectively). Age and myopia affect the size of PPVPs. SS-OCT greatly facilitates visualization of the complex structure of the vitreous.

The Prospective Analysis of Biomarkers in Sepsis: Correlation With Clinical Outcomes.

Background Sepsis is a medical emergency and necessitates immediate diagnosis and treatment to prevent the progression to severe sepsis, septic shock, and potentially mortality. Aim This study aims to study the diagnostic significance of conventional and new markers, interleukin-10 (IL-10), in predicting the severity of sepsis. Methodology A prospective observational study was conducted in the department of surgery in a tertiary care hospital in Pune, India. The study included 100 patients diagnosed with a quick Sequential Organ Failure Assessment (qSOFA) score of ≥2. Serum C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) levels were measured. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic performance of these biomarkers. Results The mean serum CRP level on day 7 was significantly higher than the baseline, day 1, and day 3 groups (p=0.0001). On analysis by repeated measure, the ANOVA test revealed that the mean CRP levels on day 7were significantly higher. The mean PCT levels on day 7, day 3, and day 1 groups were significantly lower than those on day 1, day 2, and day 2, respectively (p=0.0001). The mean p-value of 3.3 g/L CRP was significantly lower on day 1 than that on day 3. IL-10 levels showed a significant upward trend, rising from 5.21 pg/mL at baseline to 7.57 pg/mL by day 7, with a p-value of <0.0001. Our cohort population showed elevated IL-10 values on the day of admission in a total of 15 patients. In our study, we observed that 11 patients with elevated IL-10 levels progressed towardmultiple organ dysfunction syndrome (MODS) and four mortalities. IL-10 is a crucial marker for identifying patients with worsening surgical sepsis. Conclusion IL-10, CRP, and PCT have potential as prognostic markers in assessing and predicting disease severity.The dynamic changes in these biomarkers correlate strongly with clinical outcomes, suggesting their role in guiding treatment decisions.

Changes in Lens Structure in Pathological Myopia, Cataract Surgery and Special Situations

Pathological myopia is a major cause of low vision and blindness worldwide. In patients with pathological myopia, there are changes such as thinning of the lens and increase in equatorial diameter. In various population and clinic-based cohort, case-control and cross-sectional studies, it has been reported that myopic patients have a higher risk of posterior subcapsular cataract, cortical and nuclear cataract. It is known that the modern technique of phacoemulsification and intraocular lens implantation is effective in highly myopic eyes and provides significant improvement in visual acuity. However, complications related to phacoemulsification such as posterior capsule rupture, retinal detachment, progression of existing maculopathy, capsular phimosis, late lens dislocation and transient intraocular pressure elevation occur more frequently in highly myopic patients. As a result, it is extremely important that cataract surgeries of these patients are performed by experienced surgeons and that attention is paid to perioperative and postoperative complications.

9242 SOX11 mutations cause hypogonadotropic hypogonadism through both hypothalamic and pituitary level deficits

Abstract Disclosure: B. Sun: None. S. Stockman: None. M. Stamou: None. L. Plummer: None. K. Salnikov: None. D. Kotan: None. K. Topaloglu: None. S.B. Seminara: None. R. Balasubramanian: None. AbstractPurpose: Human SOX11 mutations cause Coffin-Siris Syndrome (CSS) which is clinically characterized by aplasia or hypoplasia of the distal phalanx/nail of the fifth digit, developmental delay, cognitive impairment, and distinctive facial features. Recent studies show hypogonadotropic hypogonadism (HH) occurs in ∼20% of patients with SOX11 mutations. The genotypic-phenotypic spectrum of SOX11 mutations in patients presenting with Idiopathic Hypogonadotropic Hypogonadism (IHH) is unknown. Methods: Exome sequencing data from 1810 unrelated IHH probands (anosmic and normosmic forms) were reviewed for SOX11 rare sequence variants (RSVs) [minor allele frequency &amp;lt;0.1%]. Rare variant association analysis (RVAS) and domain-based enrichment for SOX11 RSVs was performed between the IHH and gnomAD population cohort. RSVs predicted as pathogenic/likely pathogenic by ACMG criteria were deemed as pathogenic RSVs and detailed phenotypic analysis was undertaken for these variants. Results: A total of 4 pathogenic SOX11 RSVs were identified in 5 IHH cases. RVAS analysis showed that SOX11 inactivating RSVs (frameshift/non-sense) across the entire protein was enriched in the IHH cohort (2 RSVs in 3 IHH cases (p.S303X [de-novo]; p p.S345Afs*13); p&amp;lt;0.0001) while SOX11 missense RSVs was enriched only within the SOX11-HMG domain (2 RSVs in 2 IHH cases (p.G84D [de-novo]; p.P114S; p=0.003). Phenotypic review of individuals with pathogenic SOX11-RSVs revealed a spectrum of endocrine defects including: anosmic and normosmic forms of IHH, growth-hormone (GH) deficiency, neuroimaging defects (pituitary microadenoma and hypothalamic mass), and hypothyroidism. Additionally, we also identified a pathogenic SOX11 HMG domain RSV in a patient with functional HH (p.R100Q). CSS-associated features were present in almost all individuals with pathogenic SOX11 RSVs. Conclusions: This study validates SOX11 mutations as causal for IHH and reiterates the critical importance of the SOX11-HMG domain in disease pathogenesis. The spectrum of endocrine abnormalities in SOX11-related human disorders includes IHH, functional HH, GH deficiency, pituitary lesions, and hypothyroidism. The association of congenital anosmic and normosmic forms of IHH, functional HH, and anatomic abnormalities of the pituitary gland suggest that the pathogenesis of HH in SOX11-disorder may stem from both hypothalamic and pituitary level deficits. Presentation: 6/1/2024

8474 SOX11 mutations cause hypogonadotropic hypogonadism through both hypothalamic and pituitary level deficits

Abstract Disclosure: B. Sun: None. S. Stockman: None. M. Stamou: None. L. Plummer: None. K. Salnikov: None. D. Kotan: None. K. Topaloglu: None. S.B. Seminara: None. R. Balasubramanian: None. AbstractPurpose: Human SOX11 mutations cause Coffin-Siris Syndrome (CSS) which is clinically characterized by aplasia or hypoplasia of the distal phalanx/nail of the fifth digit, developmental delay, cognitive impairment, and distinctive facial features. Recent studies show hypogonadotropic hypogonadism (HH) occurs in ∼20% of patients with SOX11 mutations. The genotypic-phenotypic spectrum of SOX11 mutations in patients presenting with Idiopathic Hypogonadotropic Hypogonadism (IHH) is unknown. Methods: Exome sequencing data from 1810 unrelated IHH probands (anosmic and normosmic forms) were reviewed for SOX11 rare sequence variants (RSVs) [minor allele frequency &amp;lt;0.1%]. Rare variant association analysis (RVAS) and domain-based enrichment for SOX11 RSVs was performed between the IHH and gnomAD population cohort. RSVs predicted as pathogenic/likely pathogenic by ACMG criteria were deemed as pathogenic RSVs and detailed phenotypic analysis was undertaken for these variants. Results: A total of 4 pathogenic SOX11 RSVs were identified in 5 IHH cases. RVAS analysis showed that SOX11 inactivating RSVs (frameshift/non-sense) across the entire protein was enriched in the IHH cohort (2 RSVs in 3 IHH cases (p.S303X [de-novo]; p p.S345Afs*13); p&amp;lt;0.0001) while SOX11 missense RSVs was enriched only within the SOX11-HMG domain (2 RSVs in 2 IHH cases (p.G84D [de-novo]; p.P114S; p=0.003). Phenotypic review of individuals with pathogenic SOX11-RSVs revealed a spectrum of endocrine defects including: anosmic and normosmic forms of IHH, growth-hormone (GH) deficiency, neuroimaging defects (pituitary microadenoma and hypothalamic mass), and hypothyroidism. Additionally, we also identified a pathogenic SOX11 HMG domain RSV in a patient with functional HH (p.R100Q). CSS-associated features were present in almost all individuals with pathogenic SOX11 RSVs. Conclusions: This study validates SOX11 mutations as causal for IHH and reiterates the critical importance of the SOX11-HMG domain in disease pathogenesis. The spectrum of endocrine abnormalities in SOX11-related human disorders includes IHH, functional HH, GH deficiency, pituitary lesions, and hypothyroidism. The association of congenital anosmic and normosmic forms of IHH, functional HH, and anatomic abnormalities of the pituitary gland suggest that the pathogenesis of HH in SOX11-disorder may stem from both hypothalamic and pituitary level deficits. Presentation: 6/1/2024

Better Prediction of Clinical Outcome with Estimated Glomerular Filtration Rate by CKD-EPI 2021.

While the real-world impact of estimated glomerular filtration rate (eGFR) equation change on clinical outcome in a longitudinal cohort setting is limited, external valuation of equation performance should be performed in different population cohorts. This study aimed to compare differential impacts of eGFR values, calculated by 5 equations in a Korean patient population, on clinical outcomes. This retrospective longitudinal follow-up cohort study analyzed 23 246 participants with standardized creatinine/cystatin C assay-based laboratory results. The primary exposure was baseline eGFR calculated by 5 different equations including the recently developed 2021 race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Clinical outcomes including all-cause mortality, renal replacement therapy, and albuminuria were analyzed to estimate the hazard ratio of the eGFR on clinical outcomes. Among the 5 equations, CKD-EPI 2021 with creatinine and cystatin C (CKD-EPI 2021-CrCys) showed an earlier increase in hazard ratios for all clinical outcomes, while CKD-EPI 2012 with cystatin C showed a higher hazard ratio for all-cause mortality at low eGFR. Replacing CKD-EPI 2012 with CKD-EPI 2021-CrCys, 5.4% of patients with mortality and 3.3% of patients who received renal replacement therapy were reclassified to a lower risk stage. The 2021 CKD-EPI equations were acceptable in a Korean population, with better predictive power for clinical outcomes when compared to previous equations. The updated race-free factors for eGFR calculation improved identification of patients at risk for clinical outcomes.

Prevalence of anemia and related factors among Tabari cohort population: a cross-sectional study

BackgroundAnemia presents a considerable public health challenge, standing as a leading contributor to elevated rates of mortality and morbidity. Therefore, this study aimed to investigate the prevalence of anemia and related factors among Tabari cohort population.MethodsThis study involved a cross-sectional investigation carried out during the enrollment phase of the Tabari cohort. The Tabari cohort is a subset of the larger nationwide cohort study known as the “Prospective Epidemiological Research Studies in IrAN” (PERSIAN) cohort. The collected data included general information, anthropometric measurements, medical history and blood samples. Anemia was defined as a hemoglobin level less than 13 mg/dL for men and less than 12 mg/dL for women. Data were analyzed using SPSS V.16.ResultsOut of the 10,073 participants included in the analysis, 1,352 individuals (13.4%) were diagnosed with anemia. In the multiple regression analysis, the odds of anemia were significantly 2.31 times in females compared to males, 3.69 times in urban residents compared to rural residents, 1.41 times in social economic categories of IV and 1.35 in social economic categories of V compared to social economic categories of I, 1.70 times in drug abuse compared to non-drug abuse, 0.71 times in body mass index (BMI) categories of 25–29.9 kg/m² and 0.70 in BMI ≥ 30 kg/m² compared to BMI < 25, 0.77 times for triglycerides(TG) > 150 compared to below 150, 0.76 times for total cholesterol(TC) > 200 compared to below 200, 0.83 times for high waist-to-hip ratio (WHR) compared to low WHR, 1.33 times in low High-density Lipoprotein (HDL) compared to high HDL, 1.18 times in diabetics (DM) compared to non-DM, and 1.37 times in individuals with coronary heart diseases (CHD) compared to healthy individuals.ConclusionAnemia was a prevalent condition among Tabari cohort population. Several conditions including female gender, urban residence, Social economic level of IV and V, drug abuse, low HDL, high WHR, DM, and CHD conditions were significantly associated with increased odds of anemia. Furthermore, BMI categories of 25–29.9 kg/m² and ≥ 30 kg/m², high TC and high TG were significantly associated with decreased odds of anemia among this population.

COVID-19 pandemic, pregnancy care, perinatal outcomes in Eastern Myanmar and North-Western Thailand: a retrospective marginalised population cohort

BackgroundThe COVID-19 pandemic disrupted routine health care and antenatal and birth services globally. The Shoklo Malaria Research Unit (SMRU) based at the Thailand-Myanmar border provides cross border antenatal care (ANC) and birth services to marginalised pregnant women. The border between the countries entered lockdown in March 2020 preventing cross-border access for women from Myanmar to Thailand. SMRU adapted by opening a new clinic during the COVID-19 pandemic in Myanmar. This study explored the impact of the COVID-19 pandemic and response on access to ANC and pregnancy outcomes for marginalised pregnant women in the border regions between Thailand and Myanmar.MethodsA retrospective review of medical records of all pregnancies delivered or followed at antenatal clinics of the SMRU from 2017 to the end of 2022. Logistic regression was done to compare the odds of maternal and neonatal outcomes between women who delivered pre-COVID (2017–2019) and women who delivered in the COVID-19 pandemic (2020–2022), grouped by reported country of residence: Thailand or Myanmar.ResultsBetween 2017 and the end of 2022, there were 13,865 (5,576 resident in Thailand and 8,276 in Myanmar) marginalised pregnant women who followed ANC or gave birth at SMRU clinics. Outcomes of pregnancy were known for 9,748 women with an EGA ≥ 28 weeks. Unknown outcome of pregnancy among women living in Thailand did not increase during the pandemic. However, there was a high (60%) but transient increase in unknown outcome of pregnancy for women with Myanmar residence in March 2020 following border closure and decreasing back to the baseline of 20–30% after establishment of a new clinic. Non-literate women were more likely to have an unknown outcome during the pandemic. There was no statistically significant increase in known stillbirths or maternal deaths during the COVID pandemic in this population but homebirth was over represented in maternal and perinatal mortality.ConclusionDecreasing barriers to healthcare for marginalised pregnant women on the Thailand-Myanmar border by establishment of a new clinic was possible in response to sudden border closure during the COVID-19 pandemic and most likely preventing an increase in maternal and perinatal mortality.

Trajectory of Cognitive Decline Before and After Stroke in 14 Population Cohorts

Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajectory prestroke in stroke survivors with the trajectory of individuals without incident stroke over follow-up. The study used harmonized and pooled data from 14 population-based cohort studies included in the Cohort Studies of Memory in an International Consortium collaboration. These studies were conducted from 1993 to 2019 across 11 countries among community-dwelling older adults without a history of stroke or dementia. For this study, linear mixed-effects models were used to estimate trajectories of cognitive function poststroke relative to a stroke-free cognitive trajectory. The full model adjusted for demographic and vascular risk factors. Data were analyzed from July 2022 to March 2024. Incident stroke. The primary outcome was global cognition, defined as the standardized average of 4 cognitive domains (language, memory, processing speed, and executive function). Cognitive domain scores were formed by selecting the most commonly administered test within each domain and standardizing the scores. The study included 20 860 participants (12 261 [58.8%] female) with a mean (SD) age of 72.9 (8.0) years and follow-up of 7.51 (4.2) years. Incident stroke was associated with a substantial acute decline in global cognition (-0.25 SD; 95% CI, -0.33 to -0.17 SD), the Mini-Mental State Examination, and all cognitive domains (ranging from -0.17 SD to -0.22 SD), as well as accelerated decline in global cognition (-0.038 SD per year; 95% CI, -0.057 to -0.019 SD per year) and all domains except memory (ranging from -0.020 to -0.055 SD per year), relative to a stroke-free cognitive trajectory. There was no significant difference in prestroke slope in stroke survivors compared with the rate of decline in individuals without stroke in all cognitive measures. The mean rate of decline without a previous stroke was -0.049 SD per year (95% CI, -0.051 to -0.047 SD) in global cognition. In this cohort study using pooled data from 14 cohorts, incident stroke was associated with acute and accelerated long-term cognitive decline in older stroke survivors.

A-017 Clinical Performance Evaluation of the Atellica IM High-Sensitivity Troponin I Assay to Aid in Risk Stratification for All-Cause Mortality and Major Adverse Cardiac Events

Abstract Background Cardiac troponin I (cTnI) is the only troponin isoform present in the myocardium, where it binds to actin and inhibits actin and myosin interaction. Upon myocardial injury, cTnI is released into circulation and serial measurements can be used to aid in the diagnosis of acute myocardial infarction (AMI). In addition, in patients presenting with signs and symptoms of acute coronary syndrome (ACS), elevated cTnI levels provide useful prognostic information relative to short and long-term risk of all-cause mortality (ACM) and major adverse cardiac events (MACE). The objective of this study was to evaluate the clinical performance of the Atellica® IM TNIH assay to aid in risk stratification for ACM/MACE*. Methods Patients from 29 emergency departments (ED) across the United States presenting with signs and symptoms suggestive of ACS were followed for 30-, 90-, and 365-day progression to ACM/MACE (consisting of myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization). At each timepoint, the risk (cumulative incidence) and hazard ratios were calculated for populations with baseline cTnI levels ≤ or &amp;gt; the 99th percentile value. Kaplan-Meier curves were generated to display the absolute risk (cumulative incidence) of ACM/MACE outcomes. Analyses were performed for all enrolled patients (entire population) and separately for the entire population excluding those with an adjudicated AMI at presentation. Analyses were performed separately for both serum and plasma (lithium heparin) sample types. Results For the Entire Population cohort, the binary baseline TNIH result (TNIH &amp;gt; overall 99th percentile or ≤ overall 99th percentile) was significantly associated with 30-, 90-, and 365-day cumulative ACM/MACE (p-value&amp;lt;0.0125) for both plasma and serum samples. For plasma samples, risk difference increased from 6.27% at day 30 to 19.62% at day 365. For serum samples, risk difference increased from 6.24% at day 30 to 18.71% at day 365. Cox proportional hazard regression analysis compared the TNIH 99th percentile groups in their hazard of experiencing an ACM/MACE event in the 30-, 90-, and 365-days post ED presentation. For plasma samples, the hazard of ACM/MACE for subjects with cTnI values above the TNIH 99th percentile was relatively constant at each follow-up interval as more than double the rate of subjects below the 99th percentile; hazard ratios ranged between 2.81 (p-value&amp;lt;0.0001) and 3.49-fold (p-value&amp;lt;0.0001) for the three follow up visits. For serum samples, the hazard ratios were between 2.69 (p-value&amp;lt;0.0001) and 3.28-fold (p-value&amp;lt;0.0001) for the three follow up visits. Similar results were obtained for the Entire Population Excluding Subjects with Adjudicated AMI During Initial Presentation cohort. Conclusions The Atellica IM TNIH assay can be used in the detection of myocardial injury and can aid in risk stratification for 30-, 90-, and 365-day all-cause mortality (ACM) and major adverse cardiac events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary syndrome (ACS). *This prognostic claim is not available in the United States.

Life-Course Socioeconomic Trajectories and Biological Aging: The Importance of Lifestyles and Physical Wellbeing

Background/Objectives: Studies investigating the associations between life-course socioeconomic status (SES) and biological aging (the difference between biological and chronological age, Δage) have mostly been focused on epigenetic clocks and on a limited number of mediators. The aim of this study was to investigate this relationship using a blood-based aging clock, as well as the potential mediation of different factors including lifestyles or their proxies and physical and mental wellbeing. Methods: A deep-learning aging clock based on 36 blood markers was deployed, in a large Italian population cohort: the Moli-sani study (N = 4772; ≥35 years; 48% men). SES was defined as an eight-level trajectory over the life course, which was tested with Δage in linear models incrementally adjusted for age, sex, and prevalent health conditions. Moreover, the proportion of associations explained by diverse potential mediators, including diet, smoking, physical activity, alcohol, body mass index (BMI), and physical and mental quality of life (QoL) was estimated. Results: Compared to participants with a stably high SES, those showing an educational and financial downward trajectory were older than their CA (β (95%CI) = 1.28 (0.73–1.83) years), as were those with a stably low SES (0.75 (0.25–01.25) years). These associations were largely explained by the tested mediators (overall proportion: 36.2% and 66.3%, respectively), prominently by physical QoL (20.7% and 41.0%), BMI (16.8% and 34.3%), lifestyle (10.6% and 24.6%), and dietary inflammatory score (5.3% and 9.2%). Conclusions: These findings indicate that life-course socioeconomic inequalities are associated with accelerated biological aging, suggesting physical wellbeing and pro-inflammatory lifestyles as potential public health targets to slow down this process in susceptible socioeconomic strata of the population.

Cardiovascular risk factors and all-cause mortality in older age (15-year cohort study)

Cardiovascular diseases (CVD) occupy a leading position in the structure of all-cause mortality. Prospective and interventional studies have identified the major risk factors for CVD and shown their associations with the risk of cardiovascular outcomes and all-cause death. The impact on the individual risk of death may vary by age, sex, study design, and may be population-specific. We aimed to study the contribution of major CVD risk factors to the 15-year risk of all-cause death in the Russian (Siberian) population cohort aged 45–69 years.Material and methods. A random population sample (men and women 45–69 years old, n = 9360) was examined at baseline in 2003–2005 (Novosibirsk, Russian branch of the HAPIEE project) and re-examined twice in 2006–2008 and 2015–2018. Current analysis included individuals without baseline CVD (n = 8087), the average follow-up period – 15.6 (SD 0.69) years. The fatal events were registered based on death certificates from the Population Registration Bureau (ZAGS), and using the data received at serial examinations and postal interview. We analyzed the association between CVD risk factors and all-cause death using multivariate Cox regression.Results. In a cohort aged 45–69, in the adjusted model, 15-year risk of all-cause death was positively associated with age (HR = 1.08; 95 % CI 1.07–1.09), male sex (HR = 1.46; 95 % CI 1.24–1.71), hypertension (HT) (HR = 1.39; 95 % CI 1.25–1.55), smoking (HR = 2.37; 95 % CI 2.08–2.70), high WHR (HR = 1.19; 95 % CI 1.06–1.33), and type 2 diabetes (T2DM) (HR = 1.52; 95 % CI 1.34–1.73), and it was negatively associated with elevated total cholesterol (TC) or LDL-C in blood. In age- and sex-adjusted model, the risk was additionally associated with high triglycerides (HTG), obesity and elevated fasting plasma glucose (FPG). In men, the risk of death was independently associated with age, HT, smoking, low HDL-C, high WHR, and T2DM. In women, the risk of death was independently associated with age, HT, T2DM smoking, and, in age-standardized models, obesity, high WHR, and hyperglycemia.Conclusions. In a population cohort of 45 years and older, among CVD risk factors male sex, HT, smoking, central obesity, and T2DM independently contributed to the risk of all-cause death. Among lipid parameters, low HDL-C and high TG levels increased the risk of death in men. Associations between cardiovascular risk factors and the risk of all-cause death in older people have the patterns specific for older age; these features are important to take into account in a strategy to reduce mortality in the population.

Nomogram for predicting 10-year postoperative recurrence of stage I gastric cancer.

With the advancement of various auxiliary examination techniques, the detection rate of stage I gastric cancer has gradually increased, and its clinical first-choice treatment is surgery. Although patients with stage I gastric cancer generally have a good postoperative survival rate, there is still a certain probability of recurrence. Given the large number of gastric cancer cases, there is a vast population of patients with stage I disease. We are aiming to identify the risk factors for postoperative recurrence of stage I gastric cancer and to establish a reliable predictive model to assess the risk of recurrence in the population for clinical practice. In this retrospective cohort study, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to investigate predictive factors for recurrence among stage I gastric cancer patients who underwent curative gastrectomy between 2000 and 2018. The cohort was divided into training and validation sets for the development and validation of a nomogram. Prognostic factors were evaluated through univariate and multivariate Cox regression analyses. Significant variables identified by the concordance index (C-index) and calibration plots were used to construct nomograms predicting the probability of 5- and 10-year recurrence. Risk factors for recurrence included sex, age, race, histology, tumor size, American Joint Committee on Cancer Tumor (AJCC T) and primary site, which were used to construct the nomogram. The C-index for both the training and validation cohorts indicated that the nomogram possessed good calibration and discrimination abilities in predicting the probability of 5- and 10-year recurrence after curative surgery for stage I gastric cancer. This study established a reliable predictive model for recurrence following curative gastrectomy in stage I gastric cancer based on a population cohort. The findings of this study have the potential to significantly impact clinical practice by providing clinicians with tools for personalized risk assessment and for making informed treatment decisions.

Physiological responses to heat exposure in a general population cohort in Denmark: the Lolland-Falster Health Study.

Rising global temperatures due to climate change pose a health risk. Mortality and morbidity increase during heat events affects various organ systems. While warmer countries face higher risks, even colder regions show elevated mortality during hot periods. This study examines physiological responses to heat exposure using data from the general Danish population cohort Lolland-Falster Health Study (LOFUS) during the summers of 2016-2019. In this cross-sectional study, we analysed health data from 3804 individuals aged ≥15 years. Data were analysed across organ systems: cardiovascular system, lung function, renal system, inflammation, coagulation, and liver function. Meteorological data from the Danish Meteorological Institute provided information on temperature and humidity. Heat exposure was defined as one day ≥28°C heat index the day prior to examination. Adjusted multiple linear regression was applied to analyse differences between the two groups. There were 46 of 368 days with temperatures ≥28°C heat index. In total, 396 participants were heat-exposed (exposure group), while 3408 constituted the unexposed group. Heat exposure was associated with lower systolic blood pressure (-3.82 mm Hg [-5.72; -1.93]), higher heart rate (1.71 beats/min [0.45; 2.98]), lower oxygen saturation (-0.28% [-0.45; -0.10]), higher sodium (0.56 mmol/l [0.33; 0.79]), and higher urine albumin (0.14 mg/l [0.02; 0.27]). No significant differences were observed in inflammation, coagulation, or liver function. This study reveals early physiological responses to heat with one day of heat exposure ≥28°C, particularly in the cardiovascular, pulmonary, and renal systems. These findings underline the need for tailored strategies to mitigate health risks associated with rising temperatures.

ECMO versus IABP for patients with STEMI complicated by cardiogenic shock undergoing primary PCI: a Chinese National Study and propensity-matched analysis

ObjectiveThis study investigated the association between the utilization of extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) and in-hospital mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock undergoing primary percutaneous coronary intervention (PCI). MethodsData encompassing 9635 cases of STEMI complicated by cardiogenic shock and treated with primary PCI using ECMO/IABP support were retrieved from the Chinese Cardiovascular Association database (2019–2021). We conducted an analysis to assess the in-hospital survival disparities among percutaneous mechanical circulatory device recipients and explore the potential advantages of ECMO through multivariable logistic regression analysis within a propensity score–matched (1:2) cohort population. ResultsECMO was administered to 2028 patients, whereas IABP was used in 7607 patients. Patients supported by ECMO showed a lower in-hospital mortality than those supported by IABP (7.2% versus 15.1%, p < 0.001). Within the propensity-matched (case: control = 1:2) cohort, we noted a 34% reduced risk of in-hospital mortality among patients supported by ECMO compared with those supported by IABP (7.7% versus 11.7%; odds ratio = 0.66; 95% CI, 0.53–0.80; p < 0.001) independent of age, sex, systolic blood pressure, obesity, smoke, hypertension, diabetes, dyslipidemia, family history of coronary artery disease, coronary artery disease, stroke, atrial filiation, peripheral artery disease, chronic kidney disease, vascular lesion sites, 3A-grade hospital, and regional distributions in China. ConclusionAmong patients undergoing primary PCI for STEMI complicated by cardiogenic shock, ECMO was associated with better in-hospital survival than IABP.

Assessing the association between cigarette smoking and blood C-reactive protein levels using restructured cohort data

IntroductionCigarette smoke exposure is known to induce inflammation, leading to elevated levels of inflammatory markers such as white blood cell (WBC) count and C-reactive protein (CRP). Despite extensive research on this relationship, longitudinal studies are limited. We aimed to explore the association between cigarette smoke exposure and WBC count and CRP levels by restructuring community cohort data. MethodsData from a community cohort of the Korean population, followed biennially from 2001 to 2018, were utilized. Smoking status was determined through self-administered questionnaires. WBC and CRP levels were measured in a central laboratory with stringent quality control. Cohort data were restructured into pairs representing before and after measurements. We analyzed smoking effects on WBC and CRP using pairwise before-after tests based on changes in smoking status. Furthermore, parallel group analyses comparing changes in smoking status to no change were conducted. ResultsAnalysis included 4336 pairs for WBC and 3068 pairs for CRP from 10,030 participants. Pairwise analysis showed a significant decrease in WBC transitioning from current smoker to non-smoker and an increase from non-smoker to current smoker. Parallel group analysis demonstrated a significant decrease in WBC transitioning from current smoker to non-smoker compared to remaining current smoker, and an increase from non-smoker to current smoker compared to remaining non-smoker. CRP did not exhibit significant associations in either analysis. ConclusionsIn a community cohort, cigarette smoking was associated with elevated WBC count. However, CRP levels did not consistently reflect inflammation associated with cigarette smoking.

Impact of frailty in older people on health care demand: simulation modelling of population dynamics to inform service planning.

As populations age, frailty and the associated demand for health care increase. Evidence needed to inform planning and commissioning of services for older people living with frailty is scarce. Accurate information on incidence and prevalence of different levels of frailty and the consequences for health outcomes, service use and costs at population level is needed. To explore the incidence, prevalence, progression and impact of frailty within an ageing general practice population and model the dynamics of frailty-related healthcare demand, outcomes and costs, to inform the development of guidelines and tools to facilitate commissioning and service development. A retrospective observational study with statistical modelling to inform simulation (system dynamics) modelling using routine data from primary and secondary health care in England and Wales. Modelling was informed by stakeholder engagement events conducted in Hampshire, England. Data sources included the Royal College of General Practitioners Research and Surveillance Centre databank, and the Secure Anonymised Information Linkage Databank. Population prevalence, incidence and progression of frailty within an ageing cohort were estimated using the electronic Frailty Index tool, and associated service use and costs were calculated. Association of frailty with outcomes, service use and costs was explored with multistate and generalised linear models. Results informed development of a prototype system dynamics simulation model, exploring population impact of frailty and future scenarios over a 10-year time frame. Simulation model population projections were externally validated against retrospective data from Secure Anonymised Information Linkage. The Royal College of General Practitioners Research and Surveillance Centre sample comprised an open cohort of the primary care population aged 50 + between 2006 and 2017 (approx. 2.1 million people). Data were linked to Hospital Episode Statistics data and Office for National Statistics death data. A comparable validation data set from Secure Anonymised Information Linkage was generated. Electronic Frailty Index score calculated annually and stratified into Fit, Mild, Moderate and Severe frailty categories. Other variables included age, sex, Index of Multiple Deprivation score, ethnicity and Urban/rural. Frailty transitions, mortality, hospitalisations, emergency department attendances, general practitioner visits and costs. Frailty is already present in people aged 50-64. Frailty incidence was 47 cases per 1000 person-years. Frailty prevalence increased from 26.5% (2006) to 38.9% (2017). Older age, higher deprivation, female sex, Asian ethnicity and urban location independently predict frailty onset and progression; 4.8% of 'fit' people aged 50-64 years experienced a transition to a higher frailty state in a year, compared to 21.4% aged 75-84. Individual healthcare use rises with frailty severity, but Mild and Moderate frailty groups have higher overall costs due to larger population numbers. Simulation projections indicate frailty will increase by 7.1%, from 41.5% to 48.7% between 2017 and 2027, and associated costs will rise by £5.8 billion (in England) over an 11-year period. Simulation modelling indicates that frailty prevalence and associated service use and costs will continue to rise in the future. Scenario analysis indicates reduction of incidence and slowing of progression, particularly before the age of 65, has potential to substantially reduce future service use and costs, but reducing unplanned admissions in frail older people has a more modest impact. Study outputs will be collated into a commissioning toolkit, comprising guidance on drivers of frailty-related demand and simulation model outputs. This study is registered as NCT04139278 www.clinicaltrials.gov. This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 16/116/43) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 44. See the NIHR Funding and Awards website for further award information.