METHOD: Twenty-four male Wistar rats were divided into four groups which consist of normal, 1.8 g/kg ethanol (40% v/v), 200 mg/kg Z. zerumbet extract plus ethanol and 400 mg/kg Z. zerumbet plus ethanol. The extract of Z. zerumbet was given once daily by oral gavage, 30 min prior to ethanol exposure via intraperitoneal route for 14 consecutive days. The rats were then sacrificed. Blood and brain homogenate were subjected to biochemical tests and part of the brain tissue was sectioned for histological analysis.
RESULT: Treatment with ethyl-acetate Z. zerumbet extract at 200 mg/kg and 400 mg/kg significantly reduced the level of malondialdehyde (MDA) and protein carbonyl (p
STUDY DESIGN AND SETTING: Scientific databases were systematically searched to identify relevant trials of HCQ/CQ for the treatment of COVID-19 published up to 10 September 2020. The Cochrane risk-of-bias tools for randomized trials and non-randomized trials of interventions were used to assess risk of bias in the included studies. A 10-item Consolidated Standards of Reporting Trials (CONSORT) harm extension was used to assess quality of harm reporting in the included trials.
RESULTS: Sixteen trials, including fourteen randomized trials and two non-randomized trials, met the inclusion criteria. The results from the included trials were conflicting and lacked effect estimates adjusted for baseline disease severity or comorbidities in many cases, and most of the trials recruited a fairly small cohort of patients. None of the clinical trials met the CONSORT criteria in full for reporting harm data in clinical trials. None of the 16 trials had an overall 'low' risk of bias, while four of the trials had a 'high', 'critical', or 'serious' risk of bias. Biases observed in these trials arise from the randomization process, potential deviation from intended interventions, outcome measurements, selective reporting, confounding, participant selection, and/or classification of interventions.
CONCLUSION: In general, the quality of currently available evidence for the effectiveness of CQ/HCQ in patients with COVID-19 is suboptimal. The importance of a properly designed and reported clinical trial cannot be overemphasized amid the COVID-19 pandemic, and its dismissal could lead to poorer clinical and policy decisions, resulting in wastage of already stretched invaluable health care resources.
METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and preprint repository databases (up to February 28, 2021). Random-effects and inverse variance heterogeneity meta-analysis were used to pool the odds ratio of individual trials. The risk of bias was appraised using Version 2 of the Cochrane risk-of-bias tool for randomized trials.
RESULTS: Six randomized controlled trials were included in this analysis with a total of 658 patients who were randomized to receive ivermectin and 597 patients randomized in the control group who did not receive ivermectin. Of six trials, four had an overall high risk of bias. The estimated effect of ivermectin indicated mortality benefits (pooled odds ratio = 0.21; 95% confidence interval 0.11-0.42, n = 1255), with some evidence against the hypothesis of 'no significant difference' at the current sample size.
CONCLUSION: We observed a preliminary beneficial effect on mortality associated with ivermectin use in patients with COVID-19 that warrants further clinical evidence in appropriately designed large-scale randomized controlled trials.