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1.
Pharmacotherapy ; 40(11): 1072-1081, 2020 11.
Article in English | MEDLINE | ID: mdl-33044019

ABSTRACT

INTRODUCTION: Hydroxychloroquine (HCQ) for coronavirus disease 2019 (COVID-19) is presently being used off-label or within a clinical trial. OBJECTIVES: We investigated a multinational database of patients with COVID-19 with real-world data containing outcomes and their relationship to HCQ use. The primary outcome was all-cause mortality within 30 days of follow-up. METHODS: This was a retrospective cohort study of patients receiving HCQ within 48 hours of hospital admission. Medications, preexisting conditions, clinical measures on admission, and outcomes were recorded. RESULTS: Among patients with a diagnosis of COVID-19 in our propensity-matched cohort, the mean ages ± SD were 62.3 ± 15.9 years (53.7% male) and 61.9 ± 16.0 years (53.0% male) in the HCQ and no-HCQ groups, respectively. There was no difference in overall 30-day mortality between the HCQ and no-HCQ groups (HCQ 13.1%, n=367; no HCQ 13.6%, n=367; odds ratio 0.95, 95% confidence interval 0.62-1.46) after propensity matching. Although statistically insignificant, the HCQ-azithromycin (AZ) group had an overall mortality rate of 14.6% (n=199) compared with propensity-matched no-HCQ-AZ cohort's rate of 12.1% (n=199, OR 1.24, 95% CI 0.70-2.22). Importantly, however, there was no trend in this cohort's overall mortality/arrhythmogenesis outcome (HCQ-AZ 17.1%, no HCQ-no AZ 17.1%; OR 1.0, 95% CI 0.6-1.7). CONCLUSIONS: We report from a large retrospective multinational database analysis of COVID-19 outcomes with HCQ and overall mortality in hospitalized patients. There was no statistically significant increase in mortality and mortality-arrhythmia with HCQ or HCQ-AZ.


Subject(s)
COVID-19 Drug Treatment , COVID-19/mortality , Drug Repositioning , Hospitalization/statistics & numerical data , Hydroxychloroquine/therapeutic use , Off-Label Use , Aged , Clinical Trials as Topic , Cohort Studies , Databases, Factual , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Male , Middle Aged , Mortality/trends , Retrospective Studies , Treatment Outcome
2.
Bioorg Med Chem Lett ; 28(8): 1298-1302, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29571571

ABSTRACT

Sixteen disulfides derived from disulfiram (Antabuse™) were evaluated as antibacterial agents. Derivatives with hydrocarbon chains of seven and eight carbons in length exhibited antibacterial activity against Gram-positive Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A comparison of the cytotoxicity and microsomal stability with disulfiram further revealed that the eight carbon chain analog was of lower toxicity to human hepatocytes and has a longer metabolic half-life. In the final analysis, this investigation concluded that the S-octylthio derivative is a more effective growth inhibitor of Gram-positive bacteria than disulfiram and exhibits more favorable cytotoxic and metabolic parameters over disulfiram.


Subject(s)
Anti-Bacterial Agents/pharmacology , Disulfiram/analogs & derivatives , Disulfiram/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Ciprofloxacin/pharmacology , Disulfiram/chemical synthesis , Disulfiram/toxicity , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Half-Life , Hep G2 Cells , Humans , Microbial Sensitivity Tests , Microsomes, Liver/drug effects , Molecular Structure , Rats , Vancomycin/pharmacology
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