This study investigates the association between the treatment with heparin and mortality in patients admitted with Covid-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with Covid-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1447 had been discharged home from the hospitals, 201 were still admitted, and 126 had been transferred to hospitals not included in the study. Median follow up time was 8 (IQR 5–12) days. Heparin had been used in 1734 patients. Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI) 0.55 (0.37–0.82) p = 0.003. This association remained significant when saturation of oxygen < 90%, and temperature > 37 °C were added to de model with OR 0.54 (0.36–0.82) p = 0.003, and also when all the other drugs were included as covariates OR 0.42 (0.26–0.66) p < 0.001. The association between heparin and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized controlled trials to assess the causal effects of heparin in different therapeutic regimes are required.
This study investigates the association between the treatment with hydroxychloroquine and mortality in patients admitted with COVID-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with COVID-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with hydroxychloroquine, azithromycin, heparin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1449 had been discharged home from the hospitals, 240 were still admitted, and 85 had been transferred to hospitals not included in the study. Median follow-up time was 8 (IQR 5–12) days. Hydroxychloroquine had been used in 1857 patients. Hydroxychloroquine was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI): 0.44 (0.29–0.67). This association remained significant when saturation of oxygen < 90% and temperature > 37 °C were added to de model with OR 0.45 (0.30–0.68) p < 0.001, and also when all the other drugs, and time of admission, were included as covariates. The association between hydroxychloroquine and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized-controlled trials to assess the causal effects of hydroxychloroquine in different therapeutic regimes are required.
Background Azithromycin has been widely used in the management of COVID-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and meta-analysis summarizes the available evidence to date on the beneficial and adverse effects of azithromycin in patients with COVID-19. Methods The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated with and without azithromycin, indexed until 5 July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials and MedRXivs. We used random-effects models to estimate pooled effect size from aggregate data. Results The initial search produced 4950 results. Finally, 16 studies, 5 RCTs and 11 with an observational design, with a total of 22 984 patients, were included. The meta-analysis showed no difference in mortality for those treated with or without azithromycin, in observational studies [OR: 0.90 (0.66–1.24)], RCTs [OR: 0.97 (0.87–1.08)] and also when both types of studies were pooled together [with an overall OR: 0.95 (0.79–1.13)]. Different individual studies also reported no significant difference for those treated with or without azithromycin in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects. Conclusions The results presented in this systematic review do not support the use of azithromycin in the management of COVID-19. Future research on treatment for patients with COVID-19 may need to focus on other drugs.
The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.
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