Remdesivir is an antiviral agent that has shown broad-spectrum activity, including against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials investigating the role of remdesivir in coronavirus disease 2019 reported conflicting results. This study aimed to systematically review the best available evidence and synthesize the results. Several electronic databases were searched for candidate studies up to 12 October 2020. Studies eligible for metaanalysis were selected based on the inclusion criteria. Primary outcomes are the recovery and mortality rates, while secondary outcomes are the safety profile of remdesivir. The main effective measures are the rate ratio (RR) and rate difference (RD). Four clinical trials and one observational study were included. Remdesivir treatment for 10 days increased the recovery rate on day 14 by 50% among severe Covid-19 patients (RR ¼ 1.5, 95%CI ¼ 1.33-1.7), while on day 28 it was increased by 14% among moderate and severe Covid-19 patients (RR ¼ 1.14, 95%CI ¼ 1.06-1.22). Additionally, remdesivir decreased the mortality rate on day 14 by 36% among all patients (RR ¼ 0.64, 95%CI ¼ 0.45-0.92) but not on day 28 (RR ¼ 1.05, 95%CI ¼ 0.56-1.97). Nonmechanically ventilated Covid-19 patients showed better response to remdesivir in the recovery (RR ¼ 0.3, 95%CI ¼ 0.13-0.7) and mortality (RR ¼ 2.33, 95%CI ¼ 1.24-4.4) rates on day 14. Remdesivir reduced serious adverse effects by absolute 6% and no significant Grade 3 or 4 adverse effects were reported. At this early stage of the pandemic, there is evidence that remdesivir can be safely administered for hospitalized Covid-19 patients. It improves the recovery rate in both moderate and severe patients but, the optimal effect is achieved for those who are severely affected but not mechanically ventilated.

Aims: Cilostazol (CLS) has shown antidepressant effect in cardiovascular patients, post-stroke depression, and animal models through its neurotrophic and antiinflammatory activities. Consequently, we aimed to investigate its safety and efficacy in patients with MDD by conducting double-blind, randomized, placebo-controlled pilot study. Methods: 80 participants with MDD (DSM-IV criteria) and Hamilton DepressionRating Scale (HDRS) score >20 were treated with CLS 50 mg or placebo twice daily plus escitalopram (ESC) 20 mg once daily for six weeks. Patients were evaluated by HDRS scores (weeks 0, 2, 4, and 6). Serum levels of CREB1, BDNF, 5-HT, TNFα, NF-κB, and FAM19A5 were assessed pre-and post-treatment.Results: Co-administration of CLS had markedly decreased HDRS score at all-time points compared to the placebo group (p < 0.001). Early improvement, response, and remission rates after 6 weeks were significantly higher in the CLS group (90%, 90%, 80%, respectively) than in the placebo group (25%, 65%, 50% respectively) (p < 0.001). Moreover, the CLS group was superior to the placebo group in modulation of the measured neurotrophic and inflammatory biomarkers. Conclusion:CLS is safe and effective short-term adjunctive therapy in patients with MDD with no other comorbid conditions.Trial registration ID:NCT04069819.

Background Being a pandemic and having a high global case fatality rate directed us to assess the evidence strength of hydroxychloroquine efficacy in treating COVID‐19 arising from clinical trials and to update the practice with the most reliable clinical evidence. Methods A comprehensive search was started in June up to July‐18, 2020 in many databases, including PubMed, Embase and others. Of 432 studies found, only six studies fulfilled the inclusion criteria which includes: clinical trials, age>12 years with non‐severe COVID‐19, PCR‐confirmed COVID‐19, hydroxychloroquine is the intervention beyond the usual care. Data extraction and bias risk assessment were done by two independent authors. Both fixed‐effect and random‐effect models were utilized for pooling data using risk difference as a summary measure. The primary outcomes are clinical and radiological COVID‐19 progression, SARS‐CoV‐2 clearance in the pharyngeal swab, and mortality. The secondary outcomes are the adverse effects of hydroxychloroquine. Results Among 609 COVID‐19 confirmed patients obtained from pooling 6 studies, 294 patients received Hydroxychloroquine and 315 patients served as a control. Hydroxychloroquine significantly prevent early radiological progression relative to control with risk difference and 95% confidence interval of ‐0.2 (‐0.36 to ‐0.03). On the other hand, hydroxychloroquine did not prevent clinical COVID‐19 progression, reduce 5‐days mortality, or enhance viral clearance on days 5, 6, 7. Moreover, many adverse effects were reported with hydroxychloroquine therapy. Conclusions Failure of hydroxychloroquine to show viral clearance or clinical benefits with additional adverse effects outweigh its protective effect from radiological progression in non‐severe COVID‐19 patients. Benefit‐risk balance should guide hydroxychloroquine use in COVID‐19. This article is protected by copyright. All rights reserved.

Background: Many drugs are implicated in male infertility and screening for medication history is an important for diagnosis and treatment of the problem. The aim is to study amikacin effect on male reproductive system in comparison to gentamicin.Methods: Twenty-five male wister rats weighted 220±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received gentamicin in dose 18.25 mg/kg/day once daily (OD) (therapeutic dose). The second group received gentamicin with double dose of the first group. The third group received amikacin in dose 54.75 mg/kg/day OD (therapeutic dose). The Fourth group received amikacin with double dose of the third group. However, the fifth group served as a control and received normal saline (NS) OD. All treatments were administered intraperitoneally (IP) for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all animals. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.Results: Amikacin and gentamicin negatively affected reproductive organs weights, sperm parameters, serum follicle stimulating hormone and luteinizing hormone (LH) level relative to control (p<0.05). However, serum testosterone level was only affected with gentamicin (p<0.05). A significant difference between gentamicin and amikacin was found in sperm count, testis and epididymis weights and serum testosterone and LH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of both gentamicin and amikacin were dose-dependent.Conclusions: Both gentamicin and amikacin adversely affect andrological function that should be monitored and controlled during application of these drugs.

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Background: Drug-induced reproductive organs toxicities is an important aetiology in investigation of male infertility. The aim is to study levofloxacin effect on male reproductive system in comparison to ciprofloxacin.Methods: Twenty-five male wister rats weighted 230±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received ciprofloxacin with dose 78.23 mg/kg/day in 2 doses (therapeutic dose). The second group received the double dose of the first group ciprofloxacin. The third group received levofloxacin with dose 39.11 mg/kg/day once daily (OD) (therapeutic dose). The Fourth group received the double dose of the third group levofloxacin. However, the fifth group served as a control and received normal saline with carboxymethylcellulose OD. All treatments were administered orally for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all rats. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.Results: Ciprofloxacin and levofloxacin negatively altered reproductive organ weights, sperm parameters and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) level (p<0.05). Additionally, serum testosterone level was significantly deceased in ciprofloxacin-treated group (the double dose) (p<0.05) relative to control. The difference between ciprofloxacin and levofloxacin was significant in seminal vesicle weight and serum LH and FSH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of levofloxacin and ciprofloxacin were dose-dependent.Conclusions: Both ciprofloxacin and levofloxacin adversely affect andrological function that should be monitored and controlled during application of these drugs.

INTRODUCTION Topiramate is an antiepileptic drug that has been used for many labeled and off-labeled indications. It may be useful in reducing withdrawal symptoms of various addictive agents such as alcohol, cocaine, cannabis and smoking. To date, some studies have examined the effectiveness of topiramate for smoking cessation. The present review aims to synthesize the results from those studies and determine topiramate effectiveness in smoking cessation. METHODS A comprehensive search was conducted in the databases: PubMed/ Medline, Cochrane, Egyptian Knowledge Bank, and Google Scholar. All clinical trials that examined the effect of topiramate, compared with the placebo, on smoking cessation rate were included. Statistical analysis using fixed effect models, heterogeneity and sensitivity analysis were conducted using RevMan 5.3. RESULTS Five trials met the inclusion criteria and were included in the metaanalysis. Topiramate non-significantly increased prolonged smoking abstinence rate (OR=1.19, 95% CI: 0.57-2.5) compared with the placebo. On the other hand, topiramate significantly increased the abstinence rate at weeks 4