Efficacy and safety of edaravone in treatment of amyotrophic lateral sclerosis-a systematic review and meta-analysis.

BACKGROUND: Based on the results of randomized, double-blind, placebo-controlled trials, the benefit and safety of edaravone in the treatment of amyotrophic lateral sclerosis remain controversial. We performed a meta-analysis to evaluate the efficacy and safety of edaravone in the treatment of this disease. METHODS: We searched PubMed, the Cochrane Library, and Embase from the inception of electronic data to April 2018. We included randomized, double-blind, placebo-controlled trials reporting amyotrophic lateral sclerosis patients receiving 60-mg intravenous edaravone or intravenous saline placebo for 24 weeks. The primary efficacy evaluation was changed in Amyotrophic Lateral Sclerosis Functional Rating Scale score from baseline to after the trial. Measure of safety was the frequency of investigated adverse events and serious adverse events. Data synthesis and analysis and evaluation of risk of bias were performed using RevMan 5.3 software. Heterogeneity among studies was evaluated with the I2 statistic. RESULTS: A total of 367 patients were analyzed across three randomized controlled trials (183 patients receiving intravenous edaravone; 184 receiving placebo). A difference in ALSFRS-R score between groups at 24 weeks was found (mean difference [MD] = 1.63, 95% confidence interval [CI] 0.26-3.00, P = .02). No differences in the frequency of adverse events (odds ratio [OR] = 1.22, 95% CI 0.68-2.19, P = .50) or serious adverse events (OR = 0.71, 95% CI 0.43-1.19, P = .20) were found. CONCLUSION: Intravenous edaravone is efficacious in amyotrophic lateral sclerosis patients, with no severe adverse effects. Additional reliable randomized controlled trials with larger sample sizes will further assess the efficacy and safety of edaravone in amyotrophic lateral sclerosis. CLINICAL TRIAL REGISTRATION: The systematic review and meta-analysis was registered in the international prospective register of systematic reviews. (PROSPERO registration number: CRD42018096191; http://www.crd.york.ac.uk/PROSPERO .).

The non-linear correlation between the volume of cerebral white matter lesions and incidence of bipolar disorder: A secondary analysis of data from a cross-sectional study.

Cerebral white matter lesions (WML) are major risk factors for bipolar disorder (BD). However, studies on the association between cerebral WML volume and BD risk are limited. This study aimed to investigate the relationship between cerebral WML volume and BD incidence. This is a secondary retrospective analysis of patients (N = 146, 72 males, 74 females, mean age = 41.77 years) who have previously undergone magnetic resonance imaging examinations. Information was obtained from the Dryad database. Univariate analysis, piecewise linear regression model, and multivariable logistic regression model were used for statistical analysis. A non-linear relationship was recognized between the cerebral WML volume and BD incidence, in which the inflection point of the WML volume was 6,200 mm3. The effect sizes and confidence intervals on the left and right sides of the emphasis point were 1.0009 (1.0003, 1.0015) and 0.9988 (0.9974, 1.0003), respectively. Subgroup analysis (WML volume < 6,200 mm3) showed that the cerebral WML volume (for 0.1 mm3 increase) was positively related to the BD incidence (OR = 1.11, 95% confidence interval [CI] (1.03, 1.21)). Here we show that the cerebral WML volume is positively and non-linearly correlated to the BD risk. Volumetric analysis of WML provide a better understanding of the association between WML and the BD risk, and thereby the pathophysiological mechanisms of BD. Graphical abstract: A non-linear relationship between the volume of cerebral white matter lesions (WML) and bipolar disorder (BD) incidence is shown. The cerebral WML volume is positively and non-linearly correlated to the BD risk. The correlation is stronger when the cerebral WML volume was <6,200 mm3.Graphical AbstractA non-linear relationship between the volume of cerebral white matter lesions and bipolar disorder incidence is shown after adjusting for age; sex; lithium, atypical antipsychotic, antiepileptic, and antidepressant drug use; BMI; migraine; smoking; hypertension; diabetes mellitus; substance and alcohol dependency; and anxiety disorder.