The efficacy and safety of Zuranolone for treatment of depression: A systematic review and meta-analysis.

RATIONALE: Zuranolone, a newly FDA-approved synthetic neurosteroid, shows promise in treating depression. OBJECTIVES: Our aim is to evaluate Zuranolone's efficacy and safety in treating depression. METHODS: Five databases were searched until September 2023 for relevant randomized clinical trials evaluating the efficacy and safety of zuranolone. The potential risk of bias in the included trials was evaluated by the Cochrane Risk of Bias II guideline Data were extracted and pooled using Review Manager Software (RevMan 5.3). RESULTS: An analysis of eight studies highlights Zuranolone's efficacy in treating depression compared to placebo across most of the outcomes. Notably, the 30mg and 50mg doses demonstrated significant improvements in reducing HAM-D scores by over 50% within a 15-day follow-up (RR) of 1.46 (95% CI [1.27, 1.68], p < 0.0001) and 1.14 (95% CI [1.01, 1.3], p = 0.04). Additionally, the HAM-D ≤ 7% score analysis revealed significant enhancements with the 30mg dose over both 15-day (RR = 1.82, 95% CI [1.44, 2.31], p < 0.0001) and 45-day (RR = 1.43, 95% CI [1.16, 1.77], p = 0.0008) durations. Adverse Events Drug Discontinuation demonstrated no overall significant difference (OR = 1.33, 95% CI: [0.79, 2.23], p = 0.282). Further, specific adverse events, such as headache, showed no significant overall difference between Zuranolone and placebo (OR = 1.11, 95% CI: [0.84, 1.47], p = 0.47), with dose-dependent analysis revealing less headache in the 30 mg group. CONCLUSION: Zuranolone demonstrates favorable tolerability and safety, particularly at 30mg and 50mg doses after 15 days, suggesting its potential and effective treatment for depression.

Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Rett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions. OBJECTIVE: To evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients. METHODS: We identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion. Two independent reviewers evaluated the identified studies' titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome, we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3. RESULTS: Among the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200 mg dosage (overall mean difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200 mg dosage (overall mean difference: -0.34, p < 0.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200 mg), vomiting (200 mg), and irritability (200 mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite. CONCLUSION: Trofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200 mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.

Efficacy of dietary nitrate-rich beetroot juice supplementation in patients with chronic obstructive pulmonary disease (COPD): A systematic review and meta-analysis.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease causing airflow obstruction from the lungs reducing exercise tolerance. It is one of the leading causes of respiratory dysfunction worldwide. Nitric Oxide (NO) may have a significant role in this inflammatory reaction to improve exercise capacity. AIM: To evaluate the effect of dietary nitrate ingestion for COPD patients. METHODS: We searched Scopus, PubMed, Cochrane, and Web of Science databases till August 2020 and updated the search in December 2020 using relevant keywords. All search results were screened for eligibility. We extracted the data from the included articles and pooled them as mean difference (MD) with a 95% confidence interval (CI), using Review Manager software (ver. 5.4). RESULTS: A pooled analysis from eight included trials showed no significant difference between dietary nitrate-rich beetroot juice and placebo in systolic blood pressure, diastolic blood pressure, heart rate, 6-min walk test, cycling ergometry endurance time, and maximum rate of oxygen consumption (VO2). On the other hand, nitrate-rich beetroot juice significantly increased the Borg Rating of Perceived Exertion (RPE) scale more than the placebo (MD = -0.77; 95% CI [0.18, 1.37], P = 0.01). CONCLUSION: There is no significant effect of nitrate-rich beetroot juice on cardiovascular events as systolic, diastolic blood pressure, and heart rate, or exercise performance as 6-min walk test, and cycling ergometry endurance time, or maximum rate of oxygen consumption (VO2). On the other hand, nitrate-rich beetroot juice improves the Borg Rating of Perceived Exertion (RPE) scale reflecting an increased exercise and physical activity level.