Aims To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin–angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. Methods and results All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32–54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61–84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. Conclusions We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.
Background: Medication regimen complexity (MRC) has not been characterized in detail in patients with end-stage renal disease (ESRD). The objective of the present study was to quantify changes over time in the prescription drug burden and MRC in patients with ESRD (before transplantation, on discharge after kidney transplantation [M0], and 4 months [M4] and 12 months [M12] afterward).Methods: We retrospectively studied adult patients having undergone kidney transplantation. The number and types of drug prescribed, the pill burden, and the MRC index (MRCI) at 4 different time points (before transplantation, M0, M4, and M12) were extracted from the patients' medical records. MRCI was calculated by adding each drug score (calculated according to its formulation, dosing frequency, and additional instructions concerning administration). Hence, the MRCI took account of all prescription drugs. A logistic regression model was used to identify factors associated with an elevated MRCI at M12. Results:The median (interquartile range) age of the 354 study participants was 52 years (42-62). Respectively 21%, 42%, 53%, and 38% of the patients were taking 10 or more drugs before transplantation and at M0, M4, and M12. At M12, the 3 most frequently prescribed drug classes were immunosuppressants, cardiovascular system drugs, and drugs acting on the alimentary tract and metabolism. The pill burden and MRCI before transplantation were significantly lower (P < 0.001) than at each time point after transplantation. Diabetes and dyslipidemia were independently associated with an elevated MRCI at M12. Conclusion:In kidney transplant recipients, the drug burden and MRCI were greater at all time points after transplantation than before transplantation. The impact of the drug burden and MRC on medication adherence and clinical outcomes in these patients requires further evaluation.
Background: There are conflicting data on the effects of dysbiosis-inducing drugs, and especially antibiotics (ATBs), on clinical outcomes in patients treated with immune checkpoint inhibitors (ICIs). There is a particular lack of data for patients with melanoma. Methods: We performed a single-center retrospective study of the associations between ATBs and other drugs known to modify the gut microbiota (proton pump inhibitors, nonsteroidal anti-inflammatory drugs, statins, opioids, anti-vitamin K, levothyroxine, vitamin D3, antiarrhythmics, metformin and phloroglucinol), overall survival (OS) and tumor response in consecutive cancer patients (particularly those with melanoma) treated with an ICI (ipilimumab, nivolumab or pembrolizumab) over a 9-year period. Results: A total of 372 patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Overall, 112 patients (30.1%) had received ATBs. ATB use was associated with (1) shorter OS in the study population as a whole [adjusted hazard ratio [95% confidence interval (CI)]: 1.38 (1.00–1.90), p = 0.048] and in patients with melanoma [adjusted hazard ratio (95% CI): 2.60 (1.06–6.39), p = 0.037], and (2) a lower response rate in the study population as a whole [8.1%, versus 31.1% in patients not treated with ATBs; adjusted odds ratio (95% CI): 6.06 (2.80–14.53), p < 0.001] and in patients with melanoma [adjusted odds ratio (95% CI): 4.41 (1.04–22.80), p = 0.045]. Sensitivity analyses that minimized the indication bias did not reveal an association between OS and the presence of an infection requiring ATBs (quantified as the severity of infection, hospitalization for an infection, or ICI discontinuation). Other dysbiosis-inducing drugs were not associated with a difference in OS. Conclusion: Unlike other dysbiosis-inducing drugs, ATBs were associated with poorer clinical outcomes in ICI-treated patients overall and in the subset of patients with melanoma.
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