Population Cohort Research Articles

SARS-CoV-2 testing, test positivity and vaccination in social housing residents compared with the general population: a retrospective population-based cohort study

BackgroundThe consideration of unique social housing needs has largely been absent from the COVID-19 response, particularly in tailoring strategies to improve access to testing and vaccine uptake among vulnerable and...

Body adiposity index and other indexes of body composition in predicting cardiovascular disease in the Chinese population: A Cohort study.

The purpose of this study was to compare the ability of four obesity indicators, including waist circumference (WC), body mass index (BMI), body adiposity index (BAI), and waist-to-height ratio (WHtR) on prediction for incident cardiovascular disease (CVD) in Chinese Han population. We analyzed data from a prospective population cohort of 3598 participants aged 35 to 74 years from Jiangsu China. The logistic regression model was used to analyze the association between four obesity indicators and CVD risk. The ROC curve was used to assess and compare the diagnostic performance of four obesity indicators. During 8 years (median 6.3 years) of follow-up time, 82 CVD endpoints were collected during follow up (36 men and 46 women). After adjustment for age, smoking status, alcohol consumption and family history of CVD, in men, WC, BMI, and BAI were associated with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and hypertension. In women, WC, BMI and WHtR were associated with TG, HDL-C, hyperglycemia and hypertension, BAI was only associated with HDL-C, hyperglycemia, and hypertension. ROC curve analysis indicated that BAI have the highest area under the curve to identify CVD, and BMI has the lowest area under the curve to identify CVD in Chinese males. WHtR has the highest area under the curve to identify CVD, and BMI has the lowest area under the curve to identify CVD in Chinese females. CVD risk was more consistently correlated with BAI in Chinese men and more consistently correlated with WHtR and WC in Chinese women.

Digital Exclusion and Cognitive Function in Elderly Populations in Developing Countries: Insights Derived From 2 Longitudinal Cohort Studies.

Cognition disorders not only lead to adverse health consequences but also contribute to a range of socioeconomic challenges and diminished capacity for performing routine daily activities. In the digital era, understanding the impact of digital exclusion on cognitive function is crucial, especially in developing countries. This study aimed to evaluate the association between digital exclusion and cognitive function among elderly populations in developing countries. Using data from CHARLS (China Health and Retirement Longitudinal Study) from 2011 to 2020 and MHAS (Mexican Health & Aging Study) from 2012 to 2021, we defined digital exclusion as self-reported absence from the internet. Cognitive function was assessed through 5 tests: orientation, immediate verbal recall, delayed verbal recall, serial 7s, and figure recall. Cognitive function was assessed in 2 categories: worse cognition (a categorical variable that classifies cognition as either better or worse compared to the entire cohort population) and cognitive scores (a continuous variable representing raw cognitive scores across multiple follow-up waves). Logistic regression analyses and generalized estimating equation (GEE) analyses were used to examine the relationship between cognitive function and digital exclusion, adjusting for potential confounders, including demographics, lifestyle factors, history of chronic diseases, basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and basic cognitive abilities. After excluding participants with probable cognitive impairment at baseline and those who did not have a complete cognitive assessment in any given year (ie, all tests in the cognitive assessment must be completed in any follow-up wave), a total of 24,065 participants in CHARLS (n=11,505, 47.81%) and MHAS (n=12,560, 52.19%) were included. Of these, 96.78% (n=11,135) participants in CHARLS and 70.02% (n=8795) in MHAS experienced digital exclusion. Adjusted logistic regression analyses revealed that individuals with digital exclusion were more likely to exhibit worse cognitive performance in both CHARLS (odds ratio [OR] 2.04, 95% CI 1.42-2.99; P<.001) and MHAS (OR 1.40, 95% CI 1.26-1.55; P<.001). Gender and age did not significantly modify the relationship between digital exclusion and worse cognition (intervention P>.05). The fully adjusted mean differences in global cognitive scores between the 2 groups were 0.98 (95% CI 0.70-1.28; P<.001) in CHARLS and 0.50 (95% CI 0.40-0.59; P<.001) in MHAS. A substantial proportion of older adults, particularly in China, remain excluded from internet access. Our study examined longitudinal changes in cognitive scores and performed cross-sectional comparisons using Z-score standardization. The findings suggest that digital exclusion is linked to an increased risk of cognitive decline among older adults in developing countries. Promoting internet access may help mitigate this risk and support better cognitive health in these populations.

Prostate Cancer Risk Prediction Model Using Clinical and Magnetic Resonance Imaging–Related Findings: Impact of Combining Lesions' Locations and Apparent Diffusion Coefficient Values

Objectives The aims of the study are to develop a prostate cancer risk prediction model that combines clinical and magnetic resonance imaging (MRI)–related findings and to assess the impact of adding Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions-level findings on its diagnostic performance. Methods This 3-center retrospective study included prostate MRI examinations performed with clinical suspicion of clinically significant prostate cancer (csPCa) between 2018 and 2022. Pathological diagnosis within 1 year after the MRI was used to diagnose csPCa. Seven clinical, 3 patient-level MRI-related, and 4 lesion-level MRI-related findings were extracted. After feature selection, 2 logistic regression models with and without lesions-level findings were created using data from facility I and II (development cohort). The area under the receiver operating characteristic curve (AUC) between the 2 models was compared in the PI-RADS ≥3 population in the development cohort and Facility III (validation cohort) using the Delong test. Interfacility differences of the selected predictive variables were evaluated using the Kruskal-Wallis test or chi-squared test. Results Selected lesion-level features included the peripheral zone involvement and apparent diffusion coefficient (ADC) values. The model with lesions-level findings had significantly higher AUC than the model without in 655 examinations in the development cohort (0.81 vs 0.79, respectively, P = 0.005), but not in 553 examinations in the validation cohort (0.77 vs 0.76, respectively). Large interfacility differences were seen in the ADC distribution (P &lt; 0.001) and csPCa proportion in PI-RADS 3–5 (P &lt; 0.001). Conclusions Adding lesions-level findings improved the csPCa discrimination in the development but not the validation cohort. Interfacility differences impeded model generalization, including the distribution of reported ADC values and PI-RADS score-level csPCa proportion.

The association of multidimensional frailty with metabolic syndrome and low-grade inflammation in community-dwelling older adults in the Netherlands: a Lifelines cohort study.

Preventing metabolic syndrome (MetS) and frailty in older adults is crucial for healthy aging. The association between MetS and physical frailty is well-documented, with low-grade inflammation as potential explanation. However, the association between MetS and frailty as a multidimensional concept, and the association of low-grade inflammation with presence of MetS and frailty, is yet unclear. Therefore, we examined these associations low-grade inflammation in a large cohort of community-dwelling older adults. This cross-sectional study was performed among adults aged ≥ 65 years enrolled in the Dutch Lifelines population cohort. MetS was defined according to the Joint Interim Statement of 2009. Frailty was measured by the Groningen Frailty Indicator (GFI), which consists of 15 self-reported items on both physical and psychosocial functioning, with a score ≥ 4 indicating presence of frailty. The association between MetS and its five components and frailty was assessed using logistic regression models. Low-grade inflammation was represented by high-sensitivity C-reactive protein (hsCRP) level. The association of hsCRP level with presence of MetS and frailty was assessed using multinomial logistic regression in a sub-cohort with available hsCRP measurements. Of 11,552 adults (52.1% women) included, the prevalences of MetS and frailty were 28% and 15%, respectively. MetS was positively associated with frailty after adjusting for relevant covariates (OR: 1.37; 95% CI: 1.22-1.53). MetS components elevated blood pressure was most strongly associated with frailty. In the sub-cohort of 3896 participants, high hsCRP was associated with presence of MetS and frailty (OR: 1.31; 95% CI: 1.15-1.51), and MetS alone (OR: 1.44; 95% CI: 1.33-1.56), but not to frailty alone. A higher hsCRP level was associated with a higher score on the physical domain of frailty (b: 0.06; 95% CI: 0.03-0.08). Presence of MetS is associated with presence of frailty indicated by a multidimensional index in a large group of Dutch older adults. Low-grade inflammation, indicated by plasma hsCRP level, was found to be associated with both presence of MetS and frailty and presence of MetS alone. Increased hsCRP levels were associated with the physical component of frailty, but not with frailty as a multidimensional concept.

Abstract 4135352: Neighborhood-level Determinants and Disparities in Incident Type 2 Diabetes in a Population-Based Cohort, 2015–2020

Introduction: Living in an area with high Area Deprivation Index (ADI) is linked to worse cardiovascular disease (CVD) outcomes. However, the association of ADI with type 2 diabetes (T2D), a major CVD risk factor, is incompletely described. This knowledge may guide primary CVD prevention. Method: Rochester Epidemiology Project is a medical record linkage system of persons in southeast Minnesota and southwest Wisconsin. We identified 253,890 persons (aged 4–98 yrs on July 1, 2015) in 9 counties with &gt;90% population coverage. ADI scores, from 2015 home addresses, were grouped into quartiles of low (Q1) to high (Q4) deprivation. We excluded persons with type 1 diabetes (T1D) or history of T2D and identified new T2D cases (2015-2020) using ICD codes, HbA1c and medications. We examined the association between ADI quartile and risk of incident T2D using Cox regression with persons right censored at death, T2D, T1D or last visit. Models were adjusted for age and gender, and reported adjusted hazard ratios (aHR [95% confidence interval]). Results: Age, gender, and race statistically differed across ADI quartiles (Table). Age × ADI interaction was significant ( P &lt;.001). T2D incidence ranged from 6.3 (Q1) to 9.0 (Q4) per 1000 person-years ( P &lt;.001). Women vs. men/non-binary persons (combined due to limited non-binary persons) had 30% lower risk of incident T2D (aHR 0.70 [0.67–0.72]). Risk of incident T2D was higher in persons from higher ADI areas. At median age of 48.6 yrs, the risk was 30% higher in Q2 (aHR 1.3 [1.22–1.38]), 38% higher in Q3 (aHR 1.38 [1.30–1.47]) and 53% higher in Q4 (aHR 1.53 [1.43–1.62]) vs. Q1. Higher ADI was associated with higher incident T2D in younger persons, with risk attenuation with increasing age (Figure). Conclusion: In this population cohort, persons, particularly of younger age, living in more deprived areas had a higher risk of incident T2D. ADI may help identify areas for targeted T2D screening, with implications for CVD screening and prevention.

Abstract 4127413: High-normal Blood Pressure (130-139/85-89mmHg) is Associated with an Increased Risk of Mortality

Background: The relationship between high-normal blood pressure (BP) and mortality lacks high-quality evidence based on large population cohort. The aim of this study was to comprehensively investigate the association of high-normal BP and its trajectory with all-cause and cause-specific mortality. Methods: In a community-based population cohort from the China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project, 3,598,940 participants aged 35-75 years with baseline BP were included. High-normal BP was defined as a systolic blood pressure (SBP) of 130-139 mmHg and/or a diastolic blood pressure (DBP) of 85-89 mmHg at baseline. Four trajectories of BP change were identified in 105,894 participants included in the study, who had more than 2 follow-up BP measurements, using latent mixture modeling. Among them, high-normal-increasing was defined as an increase in SBP from 130-139 at baseline to over 140 at the last follow-up. Findings: Compared with the optimal BP group (SBP &lt; 120 mmHg and DBP &lt; 80 mmHg, [18.1%]), participants with high-normal BP (18.7%) had a 4% increase in all-cause mortality risk (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 1.01-1.07) and a 28% increase in CVD mortality risk (HR 1.28, 95% CI: 1.21-1.34), with the greatest increase in mortality risk observed from hemorrhagic stroke (HR 1.75, 95% CI: 1.55-1.98). Among BP trajectories, compared with participants with optimal-stable BP (25.3%), those with high-normal-increasing BP (3.5%) had a 25% increase in all-cause mortality risk (HR 1.25, 95% CI: 1.00-1.54) and a 67% increase in CVD mortality risk (HR 1.66, 95% CI: 1.21-2.30), with the greatest increase in mortality risk also observed from hemorrhagic stroke (HR 3.15, 95% CI: 1.38-7.20). In our study cohort, approximately 0.7% and 1.3% of all-cause mortality was attributable to the high-normal BP at baseline and high-normal-increasing BP trajectory, respectively. Interpretation: Individuals presenting high-normal BP at baseline or high-normal-increasing BP trajectory afterward exhibited a significantly elevated mortality risk, which is most pronounced for hemorrhagic stroke. Early management of BP in patients with high-normal BP is crucial for the prevention and treatment of hypertension.

Abstract 4118425: Prevalence and Spectrum of Pathogenic Genetic Variants in Korean Cardiomyopathy Patients: Insights from Next-Generation Sequencing

Background and Aim: Next-generation sequencing (NGS) is increasingly used to identify genetic variants associated with cardiomyopathies, which can aid in precise diagnosis and management. This study aimed to elucidate the prevalence and spectrum of pathogenic and likely pathogenic genetic variants in a cohort of Korean population diagnosed with different forms of cardiomyopathy. Methods: This retrospective study analyzed 122 patients diagnosed with cardiomyopathy at three tertiary hospitals in Korea, all of whom underwent NGS to identify genetic variants between December 2017 and October 2023. Detailed patient records, including clinical diagnoses, imaging results, and family histories, were reviewed to correlate genetic findings with phenotypic data. Results: Of the patients, 35 (28.7%) were found to have pathogenic or likely pathogenic variants, and 43 (35.2%) were found to have only variants of uncertain significance. Of the patients with pathogenic or likely pathogenic variants, 16 had hypertrophic cardiomyopathy (HCM) and 16 had dilated cardiomyopathy (DCM), while 3 remained with an uncertain clinical phenotype. In the HCM group, 16 patients exhibited variants predominantly in MYBPC3 (62.5%), followed by MYH7 (12.5%), and others such as TPM1, TNNI3, PRKAG2, and SCN5A (each 6.3%). Additionally, 43.8% of the HCM group had a familial history of sudden cardiac death or cardiomyopathy, with a mean left ventricular mass index (LVMi) of 148.3 ± 70.4 g/m2 and a mean maximal wall thickness of 17.7 ± 3.9 mm. The DCM group showed a different pattern, with TTN variants in 43.8%, LMNA in 18.8%, and others including MYBPC3, RBM20, TTN2, and KCNQ1 (each 6.3%). This group had a mean left ventricular ejection fraction (LVEF) of 27% and a LVMi of 119.7 g/m2. Conclusion: Our findings highlight significant genetic diversity in cardiomyopathies among Korean patients, with distinct genetic backgrounds observed in HCM and DCM. The high prevalence of specific mutations such as MYBPC3 in HCM and TTN in DCM could guide targeted genetic testing and personalized treatment strategies in these populations.

Use of mobile phones to collect data on COVID-19: phone access and participation rates, in Rakai, Uganda

ABSTRACT During the COVID-19 pandemic lockdown, we deployed a rapid, mobile phone-based survey to assess access and participation rates when using mobile phones to collect data on COVID-19 in Rakai, south-central Uganda. We sampled prior Rakai Community Cohort Study (RCCS) participants based on HIV status using mobile phone contacts. We administered a 30-minute phone-based interview to consenting participants to assess their knowledge about different aspects of COVID-19 and their access to care. Our analysis compares the mobile phone survey participation rates with historic participation rates in regular RCCS face-to-face interviews. We supplemented phone survey data with demographic, behavioral, and HIV status data from prior face-to-face RCCS surveys. Phone access in Round 19 of the RCCS was found to be 90.2%, with lower access among older people, and people living with HIV. When including only individuals who participated in the previous RCCS survey round, participation in the face-to-face survey (81.9%) was higher than participation in our phone survey (74.8%, p < .001). Survey participation was higher among people living with HIV compared to HIV-negative individuals (84.0% vs 81.4%, p < .001) in the face-to-face survey, but in the phone survey the reverse was found, with participation rates being higher among HIV-negative individuals compared to people living with HIV (78.0% vs 71.6%, p < .001). It was possible to collect data from an existing population cohort during the lockdown using phones. Phone access was high. Overall participation rates were somewhat lower in the phone survey, notably in people living with HIV, compared to the face-to-face survey.

Abstract 4136743: Current Oral Anticoagulation Use Among Patients With Atrial Fibrillation and Risk Factors Associated With Inadequate Treatments: A Report From a UK Population Cohort Study

Background: The worldwide prevalence of atrial fibrillation (AF) continues to grow with approximately 60 million cases each year. Aim: To understand demographic and clinical attributes of patients receiving adequate DOAC (direct oral anticoagulant) treatment, DOAC undertreatments, or no OAC (oral anticoagulant) treatments, thus providing valuable perspectives into the current landscape of stroke prevention in AF within the UK. Methods: We used the Clinical Practice Research Datalink (CPRD) Aurum database from January 2020 to March 2021 for this retrospective observational study. Patients’ characteristics from various cohorts (standard dose [SD], low dose [LD] per label, LD inconsistent per label prescribing, and untreated) were evaluated based on OAC treatment. Duration of index OAC treatment, time to discontinuation and incidence rates across OAC treated cohorts were assessed. A machine learning method (Elastic Net) identified factors associated with being undertreated or untreated. Results: The final sample included 13,341 patients (mean age 78.5 and female 47%). Within a 180-day timeframe post-diagnosis, 76% of patients received OAC treatment, while 24% did not receive any OAC therapy. Among those treated with DOAC (n=9947), 74% were administered SD (n=7238), 18% received LD per labels (n=1756) and 10% were inappropriately prescribed LD of DOACs (n=953). Both LD cohorts tended to have shorter duration of OAC therapy (figure) and higher discontinuation rates (per 100 person-years; LD per label: 42.97; LD not per label: 39.11) compared to the SD cohort (SD: 31.67). Patients who were untreated were associated with elevated bleeding risk factors such as renal disease and prior bleeding history; patients who received inappropriate LD were associated with age above 75, renal disease, GI conditions with PPI (proton pump inhibitor) concomitant treatments when compared to SD cohort. Conclusions: In our study, a considerable proportion of AF patients remained untreated/undertreated and were associated with bleeding risk factors, highlighting the unmet needs within this population. Exploring potential alternative treatment options with enhanced safety profiles could offer substantial benefits to patients in need.

Elevated serum growth differentiation factor 15 and decorin predict the fibrotic progression of metabolic dysfunction-associated steatotic liver disease.

Mitochondrial dysfunction with oxidative stress contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. We aimed to evaluate the fibrosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers. From a population-based general cohort, 144 subjects with MASLD were recruited in the development group and underwent magnetic resonance imaging-based liver examinations, anthropometric and laboratory tests. As an external validation group, 41 patients enrolled in a biopsy-evaluated MASLD cohort participated in this study. Liver fat content and stiffness were measured by magnetic resonance (MR) imaging-proton density fat fraction and MR elastography (MRE), respectively. Serologic stress biomarkers were quantitated by ELISA. Multivariate regression showed that waist-to-height ratio, growth differentiation factor-15 (GDF15), γ-glutamyltransferase, decorin, and alkaline-phosphatase were independent predictors of hepatic fibrosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95% CI)) of the metabolic stress index for fibrosis (MSI-F) was 0.912 (0.85‒0.98) and 0.977 (0.92‒1.00) in development and validation groups, respectively. MSI-F also had better diagnostic accuracy (82.6‒92.4%) than other fibrosis indices in the both study cohorts. MSI-F consistently differentiated fibrosis severities across cohorts of MRE-evaluated general population and biopsy-proven patients with MASLD, while other indices showed no or less discrimination. MSI-F, as a novel non-invasive index based on a stress-stimulated protective hormone GDF15 and decorin, effectively predicted hepatic fibrosis. Furthermore, MSI-F may serve as pre-screening tool to increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.

Lead exposure and physical frailty in patients with type 2 diabetes mellitus: cross-sectional results from the METAL study.

Chronic lead exposure continues to be a global environmental concern. Previous studies reported high levels of lead exposure in people with diabetes. Frailty is one of the vital comorbidities of type 2 diabetes mellitus (T2DM); however, researchers have not determined whether lead exposure is a risk factor for frailty in people with T2DM. This cross-sectional study explored the association between blood lead levels and frailty in a Shanghai diabetic population cohort. Individuals who met ≥3 of 5 predefined criteria (weight loss, exhaustion, low physical activity, slow walking speed and low grip strength) were defined as frailty. A total of 884 participants with T2DM (50.6% men, mean age 70.6 ± 7.4 years) were included. Among them, 147 (16.6%) patients were frail, and the median (interquartile range) concentration of blood lead was 16.0 µg/L (12.0-23.0). Compared with the participants within the lowest quartile of serum lead, positive associations of the 2nd and 4th lead quartiles with frailty were observed (OR, 95% CI; 1.70 1.01-2.84 and 1.72 1.03-2.88, respectively) after adjusting for age, sex and body mass index (BMI). After further adjustment for drinking status, smoking status, diet, education, blood pressure, triglycerides and glycosylated hemoglobin, the associations of serum lead with frailty were still significant for the 4th and 2nd-4th quartiles of lead (1.71, 1.01-2.91 and 1.57, 1.02-2.41, respectively). In the subgroup analyses, we found positive associations of serum lead with frailty in elderly individuals (1.77, 1.13-2.79), those with obesity (2.14, 1.02-4.51), those with unhealthy diets (2.52, 1.26-5.04), and those without hyperlipidemia (2.09, 1.12-3.88), although the interactions were not statistically significant (P for interaction all >0.05). This work provides evidence of an association between chronic lead exposure and physical frailty in a diabetic population in a Chinese cohort. Future prospective and mechanistic studies are warranted to confirm our findings.

Morphometric evaluation of the proximal tibiofibular joint among patients with knee joint pain: A pilot study and literature review

Objectives: The proximal tibiofibular joint (PTFJ) serves as a crucial stabilizing component of the entire knee joint complex. Morphometric analysis of the PTFJ can lead to clinically significant conclusions for orthopedic specialists and physiotherapists. The aim of the study was to assess the values of the inclination angle of the PTFJ in the sagittal and coronal planes using magnetic resonance imaging in patients with knee pain. Material and Methods: Measurements of the inclination angle were conducted on 48 patients divided into three groups: Those with damaged medial meniscus (M), those with knee joint cartilage damage (Ca), and the control group (C), in which no deviations from normality were observed in the analyzed imaging study. Results: The mean values of the tibiofibular joint inclination angle in the frontal plane were as follows: (C) 16.927° ± 1.778; (Ca) 16.822° ± 2.537; (M) 14.958° ± 1.760. In the sagittal plane, the corresponding values were: (C) 38.155° ± 1.524; (Ca) 39.392° ± 1.927; (M) 37.471° ± 1.165. Although the mean tibiofibular joint inclination angle was lowest in the group with medial meniscus injury when compared to the control group, these differences did not reach statistical significance. Conclusion: Measuring and observing the variety of PTFJ inclination angles among patients are conducive to better understanding its influence on knee pain. The differences in the PTFJ inclination angle between groups in our pilot study were not statistically significant. Consequently, the study necessitates replication within a substantial population cohort.

BIOM-19. METHYLATION PROFILING OF PLASMA CELL-FREE DNA IN PEDIATRIC BRAIN TUMOR PATIENTS

Abstract BACKGROUND Circulating tumor DNA (ctDNA) assays are being evaluated to inform clinical decisions in cancer care in adult patients, but the study in pediatric brain tumor patients is rare partly due to very low levels of ctDNA in blood. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks and morbidity. The aim of this study is to utilize methylomes from plasma ctDNA for non-invasive diagnosis in pediatric brain tumor patients. METHODS Using cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), which with low input DNA requirement, we measured methylation profiles of plasma samples from 77 pediatric brain tumor patients and 16 patients with non-neoplastic diseases like epilepsy. Binomial GLMnet classifiers of tumor or tumor subtype were built, in 2000 iterations of 60% training sets. Performance was evaluated in 40% test sets. RESULTS. These 77 pediatric brain tumor patients were a mixture of the most common pediatric brain tumors, include circumscribed astrocytic gliomas (N=23), glioneuronal tumors (N=16), embryonal tumor (N=9), ependymal tumor (N=7), pediatric type diffuse high grade glioma (N= 5), glioma NOS (N=4), mesenchymal tumor (N=4) and other pediatric brain tumors (N=9). The methylation profile differentiated brain tumors from non-neoplastic diseases with 82.9% accuracy (precision = 92.6%, sensitivity = 86.2%, specificity = 66.7 %). For subtype analysis, the methylation profile detected circumscribed astrocytic glioma from non-neoplastic diseases with 85.7% accuracy (precision = 87.5%, sensitivity = 87.5 %, specificity = 83.3 %), and glioneuronal tumors from non- neoplastic diseases with 83.3% accuracy (all precision, sensitivity, and specificity = 83.3 %). CONCLUSIONS The results suggest that methylation profiling of plasma cell-free DNA has the potential to discriminate between pediatric brain tumor patients and patients with non- neoplastic diseases. Larger population cohorts to train even more accurate classifiers will be needed.

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

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

Polygenic Risk Scores and Hearing Loss Phenotypes in Children

Monogenic causes of childhood hearing loss are well established, as are polygenic risk contributions to age-related hearing loss. However, an untested possibility is that polygenic risk scores (PRS) also contribute to childhood hearing loss of all severities, alongside environmental and/or monogenic causes. To examine the association between a PRS for adult hearing loss and childhood hearing loss phenotypes. This cross-sectional study used a unique population-based dataset spanning normal hearing to profound loss, combining 2 contemporaneous population cohorts in Australia. This included the Child Health CheckPoint, a national population-based cross-sectional study nested within the Longitudinal Study of Australian Children, and the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), a statewide population-based longitudinal data bank open to every child with congenital hearing loss in Victoria, Australia. The analysis took place from March to August 2023. Genotype data were generated from saliva- or blood-derived DNA using global single-nucleotide variations arrays. Based on genotype data, PRS was computed using published UK Biobank genome-wide association study results for self-reported hearing difficulty in individuals aged 40 to 69 years. Hearing outcomes were classified by laterality (bilateral, unilateral), severity (mild, moderate, severe or worse) and types (sensorineural, conductive, mixed, auditory neuropathy, atresia). Analyses included multinominal logistic regressions of PRS with hearing outcomes. Overall, 1488 CheckPoint study children (49.8% boys, aged 11-12 years) and 527 VicCHILD study children (55.2% boys, aged 0-13 years) with hearing and genotype data were included. A 1-SD increment in PRS was associated with higher odds of mild (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), moderate (OR, 5.1; 95% CI, 3.2-8.1), and severe or worse (OR, 5.3; 95% CI, 3.9-7.3) unilateral hearing loss compared with normal hearing. Similarly, the PRS was associated with increased odds of mild, moderate, and severe or worse bilateral hearing loss (per-SD ORs, 3.9-6.6) and all hearing loss types (per-SD ORs, 8.5-10.6). In this cross-sectional study, a PRS initially developed for adult hearing difficulty was associated with wide-ranging childhood hearing loss phenotypes, partly explaining hearing phenotype variations despite shared genetic and environmental factors (eg, preterm birth). Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS and predicting high-risk children.

Diet-Wide Association Study for the Incidence of Type 2 Diabetes in Three Population-Based Cohorts

Background: Dietary factors are well-known modifiable risk factors for type 2 diabetes (T2D), but many studies overlook the interrelationships between these factors, even though foods are often consumed together and contain a variety of nutrients. Objectives: In this study, we employed a diet-wide association study approach to investigate the links between various dietary factors and T2D onset, taking into account complex dietary patterns. Methods: We analyzed 16,666 participants without T2D from three Korean population-based cohorts: the Multi-Rural Communities Cohort (n = 8302), the Atherosclerosis Risk of a Rural Area Korean General Population cohort (n = 4990), and the Kanghwa cohort (n = 3374). A two-step approach was employed. In the first step, robust Poisson regression analysis was used for the initial screening (false discovery rate-adjusted p-values &lt; 0.05). In the second step, a hierarchical cluster analysis was conducted of all dietary factors, followed by mutual adjustment of the screened factors within each cluster to account for interrelationships. Results: The 11 food clusters screened were cooked rice with beans, rice cakes, breads/spreads, bread products, cheese and pizza/hamburger, grain powder, snack/confections, nuts and roasted beans, soy milk, traditional beverages, and non-native fruit. These factors were similarly distributed across three of the seven clusters in each cohort. After mutual adjustment, cooked rice with beans (p-value ≤ 2.00 × 10−7 in all three cohorts) and non-native fruits (p-value ≤ 5.91 × 10−3 in two cohorts) remained significantly associated with lower T2D risk in more than one cohort. Conclusions: The inverse association of cooked rice with beans, not observed with other types of cooked rice, and that of non-native fruits, suggest that incorporating beans into rice and eating various fruits may be an effective strategy for preventing diabetes.

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study.

This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding. Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

Association between major dietary patterns and obesity phenotypes in southwest China: baseline survey results from Hechuan

BackgroundThis study aimed to identify the main dietary patterns in Hechuan and clarify how they are associated with obesity phenotypes.MethodsA cross-sectional study was conducted based on a baseline survey of a general population cohort study in southwest China. A semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary habits of the participants in the past year. Principal component analysis was conducted to identify the main dietary patterns, and multinomial logistic regression analysis was conducted to describe the association between the major dietary patterns and obesity phenotypes.ResultsThree major dietary patterns were identified. The participants who followed the wheaten food dietary pattern had a higher likelihood of having metabolically normal obesity (MHO) (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.02–1.08), metabolically abnormal normal weight (MUNW) (OR 1.08, 95%CI 1.00–1.16), and metabolically abnormal obesity (MUO) (OR 1.07, 95%CI 1.04–1.11). Specifically, those with the highest wheaten food dietary pattern were 1.60 times more likely to have MHO (OR 1.60, 95%CI 1.25–2.05), 2.62 times more likely to have MUNW (OR 2.62, 95%CI 1.28–5.37), and 2.01 times more likely to have MUO (OR 2.01, 95%CI 1.51–2.69) than those with the lowest wheaten food dietary pattern.ConclusionThe wheaten food dietary pattern may increase the risk of obesity and metabolic abnormalities. Therefore, timely interventions should be carried out for this group of people.

Characteristics of sagittal spinopelvic alignment in Thai population: a cross-sectional study.

The prevalence of spinal deformity is a significant health concern often associated with the aging process. It is primarily attributed to the thickening of spinal joints, ligament pathologies, or the narrowing of the spinal canal, leading to compression of the spinal cord and nerve roots, and subsequently causing musculoskeletal problems. When considering corrective surgery for adult spinal deformities, it is crucial for spine surgeons to take into account the standard values of sagittal spinopelvic alignment. Notably, there is currently a lack of specific data on this aspect within the Thai population. Therefore, our study was focused on evaluating the alignment in the Thai population. To analyze sagittal spinopelvic alignment parameters in the asymptomatic Thai population and compare them with other populations. This study was designed as a cross-sectional analysis involving 194 participants, wherein the sagittal spinopelvic parameters were evaluated utilizing radiographic images. The measurements of the sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT) were determined by averaging the assessments conducted by two orthopedic residents and a spine surgeon. In addition, participants' demographic information was obtained through questionnaires, and further analysis was performed on age, gender, and body mass index data. The study also encompassed the determination of correlations between various parameters and the comparison of these parameters with other populations. The body mass index (BMI) of the study participants demonstrated significant associations with several spinal parameters. Specifically, BMI showed significant correlations with sagittal vertical axis (SVA) (r = 0.2, p = 0.09), pelvic incidence (PI) (r = 0.4, p < 0.01), lumbar lordosis (LL) (r = 0.2, p = 0.02), sacral slope (SS) (r = -0.2, p = 0.02), and pelvic tilt (PT) (r = 0.2, p = 0.02). The SS exhibited a statistically significant decline with increasing age (p = 0.04). Furthermore, the mean SVA, PI, LL, SS, and PT differed significantly between the study participants and the Indian population. In addition, the SS was notably lower when compared to the European population. The study revealed the spinopelvic parameters in a cohort of healthy Thai population and observed a correlation between their body mass index (BMI) and pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), and pelvic tilt (PT). Notably, the average SS among Thai adults was found to be statistically lower than that of individuals from Indian, European Caucasian, Asian, and Mexican populations. These insights hold potential value as a reference when strategizing surgical interventions for Thai patients with spinal deformities.