Liao, Duanping

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Background The etiologies of ischemic stroke remain undetermined in 15% to 40% of patients. Apart from atrial fibrillation, other arrhythmias are less well‐characterized as risk factors. Premature cardiac contractions are known to confer long‐term cardiovascular risks, like myocardial infarction. Ischemic stroke as cardiovascular risk outcome remains a topic of interest. We examined the prospective relationships in the Atherosclerosis Risk in Communities ( ARIC ) study, to determine whether premature atrial ( PAC ) or ventricular ( PVC ) contractions are associated with increased risk for incident ischemic stroke. Methods and Results We analyzed 14 493 baseline stroke‐free middle‐aged individuals in the ARIC public‐use data. The presence of PAC or PVC at baseline was assessed from 2‐minute electrocardiogram. A physician‐panel confirmed and classified all stroke cases. Average follow‐up time was 13 years. Proportional hazards models assessed associations between premature contractions and incident stroke. PAC s and PVC s were identified in 717 (4.9%) and 793 (5.5%) participants, respectively. In all, 509(3.5%) participants developed ischemic stroke. The hazard ratio ( HR ) (95% confidence interval [ CI ]) associated with PVC was 1.77 (1.30, 2.41), attenuated to 1.25 (0.91, 1.71) after adjusting for baseline stroke risk factors. The interaction between PVC and baseline hypertension was marginally significant ( P =0.08). Among normotensives, having PVC s was associated with nearly 2‐fold increase in the rate of incident ischemic stroke ( HR 1.69; 95% CI 1.02, 2.78), adjusting for stroke risk factors. The adjusted risk of ischemic stroke associated with PAC s was 1.30 (95% CI 0.92, 1.83). Conclusions Presence of PVC s may indicate an increased risk of ischemic stroke, especially in normotensives. This risk approximates risk of stroke from being black, male, or obese in normotensives from this cohort.