Supplementary Material for: Cerebrovascular Accident Risk in a Population with Periodic Limb Movements of Sleep: A Preliminary Meta-Analysis

<b><i>Background and Purpose:</i></b> Periodic limb movements of sleep (PLMS) are usually comorbid with hypertension, tachycardia, and coronary arterial diseases, which are also risk factors for cerebrovascular accidents (CVA). However, evidence about the relationship between CVA and PLMS is still weak. The aim of this study was to investigate (1) the prevalence of CVA in patients with PLMS, and (2) the severity of PLMS in patients with or without CVA through a meta-analysis. <b><i>Methods:</i></b> The electronic databases of PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov were searched. The inclusion criteria were (1) articles investigating comorbidity between PLMS and CVA, and (2) clinical trials in humans. <b><i>Results:</i></b> This meta-analysis included (1) 9,823 patients with PLMS and 9,416 controls from 5 studies to analyze the prevalence of CVA in PLMS, and (2) 158 patients with PLMS with CVA and 88 PLMS controls without CVA from 3 studies to analyze the severity of PLMS with and without CVA. The results showed (1) significantly higher comorbidity rates of CVA in the patients with PLMS than in the controls without PLMS (OR 1.267, <i>p</i> = 0.019), and (2) higher PLM index in the patients with CVA than in the controls (Hedges’ <i>g</i> = 0.860, <i>p</i> = 0.001; means difference: 4.435, <i>p</i> = 0.016). <b><i>Conclusions:</i></b> The results revealed (1) a worse severity of PLMS in the patients with CVA, and (2) increased prevalence of CVA in the patients with PLMS. Based on our results, the patients had a higher prevalence of CVA within 8 years of a diagnosis of PLMS compared to those without PLMS by about 1.3-fold. Whether (1) patients with PLMS receiving treatment have a similar incidence of stroke to those without PLMS, and (2) secondary stroke prevention can lower the severity of PLMS or whether those with severe PLMS have a higher risk of stroke is still inconclusive. Future studies investigating the prevalence of CVA in patients with PLMS should use a follow-up period of over 8 years

Supplementary Material for: Mortality and lithium-protective effects after first-episode mania diagnosis in bipolar disorder: A nationwide retrospective cohort study in Taiwan

Introduction: This study aimed to estimate all-cause mortality in patients after a first episode mania (FEM) and examine whether six guideline-recommended medications can reduce mortality. Methods: The cohort included population-based FEM samples and matched controls from Taiwan, spanning 2007 to 2018. The primary outcomes assessed were all-cause/suicide-related mortality, while the secondary outcome focused on mortality associated with pharmacological treatments. We compared mortality in post-FEM patients and age-/sex-matched controls without any diagnosed bipolar disorders, and patients with and without psychopharmacological treatment using Cox regression analysis, respectively. Statistics were presented with time-to-event adjusted hazard ratios (AHR) and 95% confidence intervals (CIs). Results: The study included 54,092 post-FEM patients and 270,460 controls, totaling 2,467,417 person-years of follow-up. Post-FEM patients had higher risks of all-cause mortality (AHR 2.38, 95% CI 2.31–2.45) and suicide death (10.80, 5.88-19.84) than controls. Lithium (0.62, 0.55–0.70), divalproex (0.89, 0.83–0.95), and aripiprazole (0.81, 0.66–1.00) were associated with reduced all-cause mortality compared to non-users. There were no significant all-cause mortality differences for quetiapine (0.95, 0.89–1.01), risperidone (0.92, 0.82–1.02), and paliperidone (1.24, 0.88–1.76) users. When accounting for drug action onset times in sensitivity analyses, only lithium significantly reduced all-cause mortality (AHR range 0.65–0.72). There were 35 and 16 suicide deaths in post-FEM patients and controls, respectively. No drug had a significant effect on suicide deaths (lithium: 6; divalproex: 7; aripiprazole: 0; quetiapine: 10; risperidone: 4; paliperidone: 1). Conclusion: Post-FEM patients had a higher risk of all-cause/suicide-related mortality, and lithium treatment might reduce all-cause mortality