Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
Smith et al.,
Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic,
medRxiv, doi:10.1101/2021.05.28.21258012 (Preprint)
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.
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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.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Smith et al., 31 May 2021, retrospective, USA, preprint, 4 authors.
Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.05.28.21258012; this version posted May 31, 2021. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.
Observational Study on 255 Mechanically Ventilated Covid Patients at the
Beginning of the USA Pandemic
Leon G. Smith1, Nicolas Mendoza1, David Dobesh2, & Stephen M. Smith1
1 – Smith Center for Infectious Diseases & Urban Health, East Orange, New
Jersey
2 – Saint Barnabas Medical Center, Livingston, New Jersey
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
medRxiv preprint doi: https://doi.org/10.1101/2021.05.28.21258012; this version posted May 31, 2021. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.
Abstract
Introduction: This observational study looked at 255 COVID19 patients
who required invasive mechanical ventilation (IMV) during the first two
months of the US pandemic. Through comprehensive, longitudinal
evaluation and new consideration of all the data, we were able to better
describe and understand factors affecting outcome after intubation.
Methods: 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.
Results: 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 (>96%). The cohort’s
weight range was nearly 7-fold. Causal modeling establishes that weightadjusted HCQ and AZM therapy improves survival by over 100%. QTc
prolongation did not correlate with cumulative HCQ dose or HCQ serum
levels.
Discussion: 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 >100% increase in survival. Comparison
of absolute with weight-adjusted cumulative doses proves administration
≥80 mg/kg of HCQ with > 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.
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.
2
medRxiv preprint doi: https://doi.org/10.1101/2021.05.28.21258012; this version posted May 31, 2021. The copyright holder for this preprint
(which was not..
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