Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Carbon-based catalysts: Synthesis and applications

This paper summarizes the main results obtained by the Fuel Combustion Group in three applications: (1) carbon-based catalysts for the selective catalytic reduction (SCR) process of NOx, (2) Pt and Pt–Ru catalysts for direct alcohol fuel cells, (3) carbon-supported catalysts for the electroreduction of CO2. Concerning the first aspect, low-cost catalysts able to work at lower temperatures have been prepared and compared with commercial catalysts; for the second one, new catalysts for methanol and ethanol electrochemical oxidation exhibiting current densities that are double those of the commercial ones have been developed; as regards the third one, carbon-supported catalysts for the electroreduction of CO2 based on Fe and Pd were synthesized and tested. Formic acid was obtained as the main product on all Fe/C electrodes

Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study

Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0\ue2\u80\u937 [low mortality score] vs 8\ue2\u80\u9315 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38\uc2\ub75%] of 343 patients died vs 57 [60\uc2\ub76%] of 94; absolute difference 22\uc2\ub71% [95% CI 11\uc2\ub70\ue2\u80\u9333\uc2\ub73]; adjusted hazard ratio [HR] 0\uc2\ub745 [95% CI 0\uc2\ub733\ue2\u80\u930\uc2\ub762]; p<0\uc2\ub70001). Among those receiving appropriate therapy, 135 (39%) received combination therapy and 208 (61%) received monotherapy. Overall mortality was not different between those receiving combination therapy or monotherapy (47 [35%] of 135 vs 85 [41%] of 208; adjusted HR 1\uc2\ub763 [95% CI 0\uc2\ub767\ue2\u80\u933\uc2\ub791]; p=0\uc2\ub728). However, combination therapy was associated with lower mortality than was monotherapy in the high-mortality-score stratum (30 [48%] of 63 vs 64 [62%] of 103; adjusted HR 0\uc2\ub756 [0\uc2\ub734\ue2\u80\u930\uc2\ub791]; p=0\uc2\ub702), but not in the low-mortality-score stratum (17 [24%] of 72 vs 21 [20%] of 105; adjusted odds ratio 1\uc2\ub721 [0\uc2\ub756\ue2\u80\u932\uc2\ub756]; p=0\uc2\ub762). Interpretation Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to CPE. Combination therapy was associated with improved survival only in patients with a high mortality score. Patients with BSIs due to CPE should receive active therapy as soon as they are diagnosed, and monotherapy should be considered for those in the low-mortality-score stratum. Funding Spanish Network for Research in Infectious Diseases, European Development Regional Fund, Instituto de Salud Carlos III, and Innovative Medicines Initiative