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Ivermectin for Prevention and Treatment of COVID-19 Infection A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines https://journals.lww.com/americanther… Background The antiparasitic ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials. A 2018 application for ivermectin use for scabies gives a direct cost of $2.90 for 100 12-mg tablets. Most trials were registered, self-funded, and undertaken by clinicians We assessed Efficacy of ivermectin treatment in reducing mortality Chemoprophylaxis Data sources Databases up to April 25, 2021 Sifted for studies, extracted data, and assessed risk of bias Meta-analyses were conducted and certainty of the evidence was assessed GRADE approach https://training.cochrane.org/grade-a… https://bestpractice.bmj.com/info/too… GRADE (Grading of Recommendations, Assessment, Development and Evaluations) Reproducible and transparent framework for grading certainty in evidence 100 organisations worldwide officially endorsing GRADE GRADE has four levels of evidence, certainty in evidence very low low moderate high Decreasing confidence Risk of bias Imprecision Inconsistency Indirectness Publication bias Increases confidence Very large magnitude of effect Clear dose-response gradient Residual confounding is likely to decrease rather than increase the magnitude of effect Data sources 24 randomized controlled trials N = 3,406 participants Ivermectin reduced risk of death compared with no ivermectin Meta-analysis of 15 trials (n = 2,438) Average risk ratio 0.38 Moderate-certainty evidence (Confirmed using DerSimonian–Laird method and Biggerstaff–Tweedie method) Ivermectin verses no ivermectin in hospital patients Ivermectin, 2.3% No ivermectin, 7.8% Ivermectin prophylaxis reduced COVID-19 infection 3 trials, n = 738 Average reduction 86% Low-certainty evidence (due to study design limitations and few included trials) Clearly favored ivermectin use improvement deterioration Severe adverse events Rare among treatment trials Evidence of no difference was assessed as low certainty Conclusions Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally. Current NIH recommendations https://www.covid19treatmentguideline… there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19 The sample size of most of the trials was small Various doses and schedules of ivermectin were used Some of the randomized controlled trials were open-label Patients received various concomitant (confounding) medications (e.g., doxycycline, hydroxychloroquine, azithromycin, zinc, corticosteroids) The severity of COVID-19 in the study participants was not always well described The study outcome measures were not always clearly defined Ivermectin for preventing and treating COVID‐19 (April, 2021) https://www.cochranelibrary.com/cdsr/…

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