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Ivermectin under scrutiny: a systematic review and meta-analysis of efficacy and possible sources of controversies in COVID-19 patients

Shafiee et al., Virology Journal, doi:10.1186/s12985-022-01829-8
Jun 2022  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
Meta analysis including 17 of 104 studies (51 RCTs), finding significantly lower mortality with ivermectin. All seven outcomes favor ivermectin, while statistical significance is reached only for mortality. The conclusion is incorrect, authors find significantly lower mortality. Authors suggest lower risk of bias studies show lower effects, however their analysis is unreliable. For example consider Reis et al., authors give the study a perfect rating in risk of bias analysis, however this study not only has a very high theoretical risk of bias, but shows very high actual bias, randomization failure, blinding failure, and reports conflicting data that is impossible to be correct1.
7 meta analyses show significant improvements with ivermectin for mortality2-7, hospitalization8, recovery4, and cases4.
Currently there are 104 ivermectin for COVID-19 studies, showing 48% lower mortality [35‑59%], 35% lower ventilation [17‑50%], 40% lower ICU admission [12‑58%], 34% lower hospitalization [21‑44%], and 81% fewer cases [71‑87%].
Shafiee et al., 13 Jun 2022, peer-reviewed, 6 authors. Contact: hamidrezamozhgani@gmail.com (corresponding author).
This PaperIvermectinAll
Ivermectin under scrutiny: a systematic review and meta-analysis of efficacy and possible sources of controversies in COVID-19 patients
Arman Shafiee, Mohammad Mobin Teymouri Athar, Omid Kohandel Gargari, Kyana Jafarabady, Sepehr Siahvoshi, Sayed-Hamidreza Mozhgani
Virology Journal, doi:10.1186/s12985-022-01829-8
Background: We conducted a systematic review and meta-analysis to evaluate the efficacy of ivermectin for COVID-19 patients based on current peer-reviewed RCTs and to address disputes over the existing evidence. Methods: MEDLINE (Pubmed), Scopus, Web of Science, Cochrane library, Google scholar and Clinicaltrials.gov were searched for RCTs assessing the efficacy of Ivermectin up to 20 February 2022. A systematic review and meta-analysis of studies was performed based on the PRISMA 2020 statement criteria. Results: 19 and 17 studies were included in this systematic review and meta-analysis, respectively. There was no significant difference in progression to severe disease (log OR − 0.27 [95% CI − 0.61 to 0.08], I2 = 42.29%), negative RT-PCR (log OR 0.25 [95% CI − 0.18-0.68], I2 = 58.73%), recovery (log OR 0.11 [95% CI − 0.22-0.45], I2 = 13.84%), duration of hospitalization (SMD − 0.40 [95% CI − 0.85-0.06], I2 = 88.90%), time to negative RT-PCR (SMD − 0.36 [95% CI − 0.89-0.17], I2 = 46.2%), and viral load (SMD -0.17 [95% CI -0.45 to 0.12], I^2 = 0%). It is worth noting that, based on low-certainty evidence, ivermectin may possibly reduce mortality (log OR − 0.67 [95% CI − 1.20 to − 0.13], I2 = 28.96%). However, studies with a higher risk of bias were more likely to indicate positive effects on the efficacy of this drug, according to our subgroup analyses based on study quality. Conclusion: Ivermectin did not have any significant effect on outcomes of COVID-19 patients and as WHO recommends, use of ivermectin should be limited to clinical trials.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12985-022-01829-8. Additional file1 Funding The authors declare no funding information. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no Competing interests. • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year • At BMC, research is always in progress. Learn more biomedcentral.com/submissions Ready to submit your research Ready to submit your research ? Choose BMC and benefit from: ? Choose BMC and benefit from: Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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' 'https://doi.org/10.1016/j.jclinepi.2021.12.018.', 'journal-title': 'J Clin Epidemiol.'}, { 'key': '1829_CR64', 'doi-asserted-by': 'publisher', 'first-page': '462', 'DOI': '10.18433/jpps31457', 'volume': '23', 'author': 'BM Padhy', 'year': '2020', 'unstructured': 'Padhy BM, Mohanty RR, Das S, Meher BR. Therapeutic potential of ' 'ivermectin as add on treatment in COVID 19: a systematic review and ' 'meta-analysis. J Pharm Pharm Sci. 2020;23:462–9.', 'journal-title': 'J Pharm Pharm Sci'}, { 'key': '1829_CR65', 'doi-asserted-by': 'publisher', 'first-page': '155', 'DOI': '10.1007/BF02602327', 'volume': '1', 'author': 'RA Davidson', 'year': '1986', 'unstructured': 'Davidson RA. Source of funding and outcome of clinical trials. 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JAMA ' 'Intern Med. 2022;182:452–4.', 'journal-title': 'JAMA Intern Med'}], 'container-title': 'Virology Journal', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12985-022-01829-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s12985-022-01829-8/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s12985-022-01829-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 11, 14]], 'date-time': '2022-11-14T01:07:58Z', 'timestamp': 1668388078000}, 'score': 1, 'resource': {'primary': {'URL': 'https://virologyj.biomedcentral.com/articles/10.1186/s12985-022-01829-8'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 6, 13]]}, 'references-count': 68, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2022, 12]]}}, 'alternative-id': ['1829'], 'URL': 'http://dx.doi.org/10.1186/s12985-022-01829-8', 'relation': {}, 'ISSN': ['1743-422X'], 'subject': ['Infectious Diseases', 'Virology'], 'container-title-short': 'Virol J', 'published': {'date-parts': [[2022, 6, 13]]}, 'assertion': [ { 'value': '24 March 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '2 June 2022', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '13 June 2022', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Not applicable.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare that they have no Competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '102'}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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