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Critical appraisal of multidrug therapy in the ambulatory management of patients with COVID-19 and hypoxemia

Gkioulekas et al., Preprints
Dec 2023  
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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 22 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
Reanalysis of 119 hypoxemic COVID-19 outpatients treated with multidrug regimens that may include ivermectin, doxycycline, zinc, vitamins C/D, hydroxychloroquine, and azithromycin. Authors combine case series from the US, Zimbabwe, and Nigeria, using a self-controlled case series method and external controls, showing statistically significant reductions in hospitalization and mortality, with improved results with the more aggressive protocols.
Gkioulekas et al., 8 Dec 2023, preprint, 3 authors.
This PaperIvermectinAll
Critical appraisal of multidrug therapy in the ambulatory management of patients with COVID-19 and hypoxemia
Eleftherios Gkioulekas, Peter A Mccullough, Colleen Aldous
This critical appraisal is focused on three published case series of a total of 119 COVID-19 patients with hypoxemia who were successfully treated in the United States, Zimbabwe, and Nigeria with similar off-label multidrug treatments that may include ivermectin, nanosilver, doxycycline, zinc, and vitamins C and D, resulting in rapid recovery of oxygen levels. We investigate whether these treatment protocols were successful in preventing hospitalizations and deaths. We use a simplified self-controlled case series method to investigate the association of treatment with the existence of a hospitalization rate reduction effect. To show the association of treatment with the existence of a mortality rate reduction effect, we make conservative comparisons of the treatment case series with several external control groups using the exact Fisher test. A novel statistical technique, based on the Sterne interval and the Bayesian factor, is used to assess the resilience of these results with respect to selection bias. The existence of statistically significant hospitalization rate reduction is shown for two of the three case series with the most aggressive treatments, and it is resilient against both random and systemic selection bias. Combining all three case series allows us to show the existence of statistically significant mortality rate reduction, and it is more likely than not that random selection bias does not overturn this finding. These results, combined with an extensive literature review, show that the efficacy of these multidrug treatments is supported by the Bradford Hill criteria of strength of association, temporality, biological gradient, consistency, and biological plausibility.
Informed Consent Statement: Not applicable. The study is a analysis of previously published data. Conflicts of Interest: The authors declare no conflict of interest. Abbreviations The following abbreviations are used in this manuscript:
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