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1.
Pharmacotherapy ; 40(11): 1072-1081, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33044019

RESUMEN

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.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19/mortalidad , Reposicionamiento de Medicamentos , Hospitalización/estadística & datos numéricos , Hidroxicloroquina/uso terapéutico , Uso Fuera de lo Indicado , Anciano , Ensayos Clínicos como Asunto , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Estudios Retrospectivos , Resultado del Tratamiento
2.
Bioorg Med Chem Lett ; 28(8): 1298-1302, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29571571

RESUMEN

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.


Asunto(s)
Antibacterianos/farmacología , Disulfiram/análogos & derivados , Disulfiram/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/toxicidad , Ciprofloxacina/farmacología , Disulfiram/síntesis química , Disulfiram/toxicidad , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Semivida , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Microsomas Hepáticos/efectos de los fármacos , Estructura Molecular , Ratas , Vancomicina/farmacología
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