Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals

107noneObjectives: To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals.Methods: Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions.Results: Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%-100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence.Conclusions: Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking. (c) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.nonePapst, L.*; Beović, B.; Pulcini, C.; Durante-Mangoni, E.; Rodríguez-Baño, J.; Kaye, K.S.; Daikos, G.L.; Raka, L.; Paul, M.; Abbo, L.; Abgueguen, P.; Almirante, B.; Azzini, A.M.; Bani-Sadr, F.; Bassetti, M.; Ben-Ami, R.; Beović, B.; Béraud, G.; Botelho-Nevers, E.; Bou, G.; Boutoille, D.; Cabié, A.; Cacopardo, B.; Cascio, A.; Cassir, N.; Castelli, F.; Cecala, M.; Charmillon, A.; Chirouze, C.; Cisneros, J.M.; Colmenero, J.D.; Coppola, N.; Corcione, S.; Daikos, G.L.; Dalla Gasperina, D.; De la Calle Cabrera, C.; Delobel, P.; Di Caprio, D.; Durante Mangoni, E.; Dupon, M.; Ettahar, N.; Falagas, M.E.; Falcone, M.; Fariñas, M.C.; Faure, E.; Forestier, E.; Foti, G.; Gallagher, J.; Gattuso, G.; Gendrin, V.; Gentile, I.; Giacobbe, D.R.; Gogos, C.A.; Grandiere Perez, L.; Hansmann, Y.; Horcajada, J.P.; Iacobello, C.; Jacob, J.T.; Justo, J.A.; Kernéis, S.; Komnos, A.; Kotnik Kevorkijan, B.; Lebeaux, D.; Le Berre, R.; Lechiche, C.; Le Moxing, V.; Lescure, F.X.; Libanore, M.; Martinot, M.; Merino de Lucas, E.; Mondain, V.; Mondello, P.; Montejo, M.; Mootien, J.; Muñoz, P.; Nir-Paz, R.; Pan, A.; Paño-Pardo, J.R.; Patel, G.; Paul, M.; Pérez Rodríguez, M.T.; Piroth, L.; Pogue, J.; Potoski, B.A.; Pourcher, V.; Pyrpasopoulou, A.; Rahav, G.; Rizzi, M.; Rodríguez-Baño, J.; Salavert, M.; Scheetz, M.; Sims, M.; Spahija, G.; Stefani, S.; Stefos, A.; Tamma, P.D.; Tattevin, P.; Tedesco, A.; Torre-Cisneros, J.; Tripolitsioti, P.; Tsiodras, S.; Uomo, G.; Verdon, R.; Viale, P.; Vitrat, V.; Weinberger, M.; Wiener-Well, Y.Papst, L.; Beović, B.; Pulcini, C.; Durante-Mangoni, E.; Rodríguez-Baño, J.; Kaye, K. S.; Daikos, G. L.; Raka, L.; Paul, M.; Abbo, L.; Abgueguen, P.; Almirante, B.; Azzini, A. M.; Bani-Sadr, F.; Bassetti, M.; Ben-Ami, R.; Beović, B.; Béraud, G.; Botelho-Nevers, E.; Bou, G.; Boutoille, D.; Cabié, A.; Cacopardo, B.; Cascio, A.; Cassir, N.; Castelli, F.; Cecala, M.; Charmillon, A.; Chirouze, C.; Cisneros, J. M.; Colmenero, J. D.; Coppola, N.; Corcione, S.; Daikos, G. L.; Dalla Gasperina, D.; De la Calle Cabrera, C.; Delobel, P.; Di Caprio, D.; Durante Mangoni, E.; Dupon, M.; Ettahar, N.; Falagas, M. E.; Falcone, M.; Fariñas, M. C.; Faure, E.; Forestier, E.; Foti, G.; Gallagher, J.; Gattuso, G.; Gendrin, V.; Gentile, I.; Giacobbe, D. R.; Gogos, C. A.; Grandiere Perez, L.; Hansmann, Y.; Horcajada, J. P.; Iacobello, C.; Jacob, J. T.; Justo, J. A.; Kernéis, S.; Komnos, A.; Kotnik Kevorkijan, B.; Lebeaux, D.; Le Berre, R.; Lechiche, C.; Le Moxing, V.; Lescure, F. X.; Libanore, M.; Martinot, M.; Merino de Lucas, E.; Mondain, V.; Mondello, P.; Montejo, M.; Mootien, J.; Muñoz, P.; Nir-Paz, R.; Pan, A.; Paño-Pardo, J. R.; Patel, G.; Paul, M.; Pérez Rodríguez, M. T.; Piroth, L.; Pogue, J.; Potoski, B. A.; Pourcher, V.; Pyrpasopoulou, A.; Rahav, G.; Rizzi, M.; Rodríguez-Baño, J.; Salavert, M.; Scheetz, M.; Sims, M.; Spahija, G.; Stefani, S.; Stefos, A.; Tamma, P. D.; Tattevin, P.; Tedesco, A.; Torre-Cisneros, J.; Tripolitsioti, P.; Tsiodras, S.; Uomo, G.; Verdon, R.; Viale, P.; Vitrat, V.; Weinberger, M.; Wiener-Well, Y

Search for new physics in events with same-sign dileptons and jets in pp collisions at root s=8 TeV

2014