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All Studies   Meta Analysis    Recent:   

Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic

Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012
May 2021  
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Mortality 27% Improvement Relative Risk Mortality (b) 93% HCQ for COVID-19  Smith et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 255 patients in the USA Lower mortality with HCQ (p=0.0024) c19hcq.org Smith et al., medRxiv, May 2021 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now with p < 0.00000000001 from 417 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 102 treatments. c19hcq.org
Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level.
Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.
This study is excluded in the after exclusion results of meta analysis: immortal time bias may significantly affect results.
risk of death, 27.2% lower, RR 0.73, p = 0.002, treatment 19 of 37 (51.4%), control 182 of 218 (83.5%), NNT 3.1, odds ratio converted to relative risk, >3g HCQ and >1g AZ, multivariable cox proportional hazard regression.
risk of death, 92.9% lower, OR 0.07, p < 0.001, inverted to make OR<1 favor treatment, ≥80mg/kg HCQ and >1g AZ, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Smith et al., 31 May 2021, retrospective, USA, preprint, 4 authors.
This PaperHCQAll
Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
Leon G Smith, Nicolas Mendoza, David Dobesh, Stephen M Smith
doi:10.1101/2021.05.28.21258012
All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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Through comprehensive, ' 'longitudinal evaluation and new consideration of all the data, we were able to better ' 'describe and understand factors affecting outcome after ' 'intubation.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>All vital ' 'signs, laboratory values, and medication administrations (time, date, dose, and route) were ' 'collected and organized. Further, each patient’s prior medical records, including PBM data ' 'and available ECG, were reviewed by a physician. These data were incorporated into ' 'time-series database for statistical ' 'analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>By discharge ' 'or Day 90, 78.2% of the cohort expired. The most common pre-existing conditions were ' 'hypertension, (63.5%), diabetes (59.2%) and obesity (50.4%). Age correlated with death. ' 'Comorbidities and clinical status on presentation were not predictive of outcome. Admission ' 'markers of inflammation were universally elevated (&gt;96%). The cohort’s weight range was ' 'nearly 7-fold. Causal modeling establishes that weight-adjusted HCQ and AZM therapy improves ' 'survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ ' 'serum levels.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>This ' 'detailed approach gives us better understanding of risk factors, prognostic indicators, and ' 'outcomes of Covid patients needing IMV. Few variables were related to outcome. By considering ' 'more factors and using new methods, we found that when increased doses of co-administered HCQ ' 'and AZM were associated with &gt;100% increase in survival. Comparison of absolute with ' 'weight-adjusted cumulative doses proves administration ≥80 mg/kg of HCQ with &gt; 1 gm AZM ' 'increases survival in IMV-requiring Covid patients by over 100%. According to our data, HCQ ' 'is not associated with prolongation. Studies, which reported QTc prolongation secondary to ' 'HCQ, need to be re-evaluated more stringently and with controls.</jats:p><jats:p>The weight ' 'ranges of Covid patient cohorts are substantially greater than those of most antibiotic RCTs. ' 'Future clinical trials need to consider the weight variance of hospitalized Covid patients ' 'and need to study therapeutics more thoughtfully.</jats:p></jats:sec>', 'DOI': '10.1101/2021.05.28.21258012', 'type': 'posted-content', 'created': {'date-parts': [[2021, 5, 31]], 'date-time': '2021-05-31T21:15:16Z', 'timestamp': 1622495716000}, 'source': 'Crossref', 'is-referenced-by-count': 5, 'title': 'Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA ' 'Pandemic', 'prefix': '10.1101', 'author': [ {'given': 'Leon G.', 'family': 'Smith', 'sequence': 'first', 'affiliation': []}, {'given': 'Nicolas', 'family': 'Mendoza', 'sequence': 'additional', 'affiliation': []}, {'given': 'David', 'family': 'Dobesh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Stephen M.', 'family': 'Smith', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'issue': '9', 'key': '2021060212302166000_2021.05.28.21258012v1.1', 'doi-asserted-by': 'crossref', 'first-page': 'e0239235', 'DOI': '10.1371/journal.pone.0239235', 'article-title': 'Clinical, laboratory and radiological characteristics and outcomes of ' 'novel coronavirus (SARS-CoV-2) infection in humans: A systematic review ' 'and series of meta-analyses', 'volume': '15', 'year': '2020', 'journal-title': 'PloS One'}, { 'key': '2021060212302166000_2021.05.28.21258012v1.2', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/eci.13362'}, { 'key': '2021060212302166000_2021.05.28.21258012v1.3', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0241955'}, { 'issue': '1', 'key': '2021060212302166000_2021.05.28.21258012v1.4', 'doi-asserted-by': 'crossref', 'first-page': '82', 'DOI': '10.1016/j.ajic.2020.06.008', 'article-title': 'Meta-analysis investigating the relationship between clinical features, ' 'outcomes, and severity of severe acute respiratory syndrome coronavirus ' '2 (SARS-CoV-2) pneumonia', 'volume': '49', 'year': '2021', 'journal-title': 'Am J Infect Control'}, { 'issue': '6', 'key': '2021060212302166000_2021.05.28.21258012v1.5', 'doi-asserted-by': 'crossref', 'first-page': '813', 'DOI': '10.1007/s15010-020-01502-8', 'article-title': 'The epidemiological burden and overall distribution of chronic ' 'comorbidities in coronavirus disease-2019 among 202,005 infected ' 'patients: evidence from a systematic review and meta-analysis', 'volume': '48', 'year': '2020', 'journal-title': 'Infection'}, { 'issue': '11', 'key': '2021060212302166000_2021.05.28.21258012v1.6', 'doi-asserted-by': 'crossref', 'first-page': 'e0241742', 'DOI': '10.1371/journal.pone.0241742', 'article-title': 'Predictors of in-hospital COVID-19 mortality: A comprehensive ' 'systematic review and meta-analysis exploring differences by age, sex ' 'and health conditions', 'volume': '15', 'year': '2020', 'journal-title': 'PloS One'}, { 'key': '2021060212302166000_2021.05.28.21258012v1.7', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.dsx.2020.06.064'}, { 'issue': '6', 'key': '2021060212302166000_2021.05.28.21258012v1.8', 'doi-asserted-by': 'crossref', 'first-page': 'e2012270', 'DOI': '10.1001/jamanetworkopen.2020.12270', 'article-title': 'Clinical Characteristics and Morbidity Associated With Coronavirus ' 'Disease 2019 in a Series of Patients in Metropolitan Detroit', 'volume': '3', 'year': '2020', 'journal-title': 'JAMA Netw Open'}, { 'issue': '1', 'key': '2021060212302166000_2021.05.28.21258012v1.9', 'doi-asserted-by': 'crossref', 'first-page': '47', 'DOI': '10.1016/j.cmi.2020.10.017', 'article-title': 'Clinical course and outcomes of critically ill patients with COVID-19 ' 'infection: a systematic review', 'volume': '27', 'year': '2021', 'journal-title': 'Clin Microbiol Infect'}, { 'key': '2021060212302166000_2021.05.28.21258012v1.10', 'doi-asserted-by': 'publisher', 'DOI': '10.2337/diacare.27.2007.S5'}, { 'key': '2021060212302166000_2021.05.28.21258012v1.11', 'doi-asserted-by': 'publisher', 'DOI': '10.2337/dc09-9029'}, { 'issue': '1', 'key': '2021060212302166000_2021.05.28.21258012v1.12', 'doi-asserted-by': 'crossref', 'first-page': '6', 'DOI': '10.1038/kisup.2012.6', 'volume': '2', 'author': 'Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work ' 'Group. 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The QT Interval in Patients with SARS-CoV-2 Infection Treated ' 'with Hydroxychloroquine/Azithromycin [Internet]. Cardiovascular ' 'Medicine; 2020 Apr [cited 2020 Oct 20]. 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FDA cautions against use of hydroxychloroquine or ' 'chloroquine for COVID-19 outside of the hospital setting or a clinical ' 'trial due to risk of heart rhythm problems. FDA [Internet]. 2020 Apr 30 ' '[cited 2020 May 15]; Available from: ' 'https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or'}], 'container-title': [], 'original-title': [], 'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2021.05.28.21258012', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 6, 2]], 'date-time': '2021-06-02T19:55:23Z', 'timestamp': 1622663723000}, 'score': 1, 'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2021.05.28.21258012'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 5, 31]]}, 'references-count': 47, 'URL': 'http://dx.doi.org/10.1101/2021.05.28.21258012', 'relation': {}, 'published': {'date-parts': [[2021, 5, 31]]}, 'subtype': 'preprint'}
Late treatment
is less effective
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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