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Saint-Sauveur-en-Rue, France

Papazian L.,Assistance Publique Hopitaux de Marseille | Roch A.,Assistance Publique Hopitaux de Marseille | Charles P.-E.,CHU de Dijon | Penot-Ragon C.,Assistance Publique Hopitaux de Marseille | And 16 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

IMPORTANCE: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE: To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallelgroup, multicenter trial performed in 26 intensive care units in France from January 2010to March 2013. For power to detect an 8%absolute reduction in the day-28 mortality rate,we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping ruleswere an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS: Participants were randomized to receive simvastatin (60mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcomewas day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95% CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057758. Source

Bardou M.,CHU de Dijon | Quenot J.-P.,Medical Intensive Care Unit | Barkun A.,McGill University
Nature Reviews Gastroenterology and Hepatology | Year: 2015

Bleeding from stress-related mucosal disease in critically ill patients remains an important clinical management issue. Although only a small proportion (1-6%) of patients admitted to an intensive care unit (ICU) will bleed, a substantial proportion exhibit clinical risk factors (mechanical ventilation for >48 h and a coagulopathy) that predict an increased risk of bleeding. Furthermore, upper gastrointestinal mucosal lesions can be found in 75-100% of patients in ICUs. Although uncommon, stress-ulcer bleeding is a severe complication with an estimated mortality of 40-50%, mostly from decompensating an underlying condition or multiorgan failure. Although the vast majority of patients in ICUs receive stress-ulcer prophylaxis, largely with PPIs, some controversy surrounds their efficacy and safety. Indeed, no single trial has shown that stress-ulcer prophylaxis reduces mortality. Some reports suggest that the use of PPIs increases the risk of nosocomial infections. However, several meta-analyses and cost-effectiveness studies suggest PPIs to be more clinically effective and cost-effective than histamine-2 receptor antagonists, without considerable increases in nosocomial pneumonia. To help clinicians use the most appropriate strategy for treatment of patients in the ICU, this Review presents the latest information on all aspects of stress-related mucosal disease. © 2015 Macmillan Publishers Limited. All rights reserved. Source

Chavanet P.,CHU de Dijon
Medecine et Maladies Infectieuses | Year: 2013

Background: Methicillin-resistant Staphylococcus aureus (MRSA) accounts for 10-40% of hospital-acquired pneumonia, and even more in intensive care units. The current guidelines for the treatment of MRSA nosocomial pneumonia include vancomycin and linezolid. The authors of 2 prospective randomized trials comparing vancomycin and linezolid in nosocomial pneumonia had concluded to the non-inferiority of linezolid. A slight superiority of linezolid was observed in the MRSA pneumonia subgroup, in terms of clinical success and survival, but no definite conclusion could be drawn. Methods: A prospective randomized study was made to compare a fixed linezolid dose to dose-optimized vancomycin for the treatment of bacteriologically proven MRSA nosocomial pneumonia (ZEPHyR Study). Results: Among the 165 patients treated by linezolid (57.6%) in the PP population, 95 were clinically cured at the end of the study, compared to 81 of the 174 patients treated by vancomycin (46.6%) (IC 95% of the difference 0.5%-21.6%, P= 0.042). Nephrotoxicity in the mITT population reached 8.4% in the linezolid group compared to 18.2% in the vancomycin group. Conclusion: LNZ was superior to vancomycin for the treatment of MRSA nosocomial pneumonia. © 2013 Elsevier Masson SAS. Source

Two thirds of the patients hospitalized for an acute coronary syndrome (ACS) show disorders of glucose metabolism (diabetes, impaired fasting glucose, impaired glucose intolerance).Every patient hospitalized for an ACS whose HbA1c is equal or above 6.5% must be considered as diabetic.Each patient hospitalized for an ACS whose HbA1c is less than 6.5% should have measurement of plasma glucose fasting and after an oral glucose load between the 7th and the 28th day following the ACS in order to detect a disorder of glucose metabolism.During the hospitalization in cardiac intensive care unit, a treatment with insulin will be started when plasma glucose is. ≥. 1.80. g/L (10.0. mmol/L). In a patient with previously known diabetes, a treatment with insulin will also be started when preprandial plasma glucose is 1.40. g/L (7.8. mmol/L).Insulin treatment in cardiac intensive care unit will be performed by continuous IV infusion of insulin including bolus for meals. Insulin dosage will be determined according to the capillary glucose monitoring.After the hospitalization in cardiac intensive care unit, it is often possible to stop insulin treatment, which may be replaced by other antidiabetic treatments.The choice of the optimal antidiabetic treatment depends on the metabolic profile of the patient (insulin-resistance, insulin deficiency). This choice is not always easy and referral to an endocrinologist/diabetolgist may be needed.Because of the increased cardiovascular mortality associated with hypoglycemias, the long-term use of insulin or insulin-secretory agents (sulfonylureas, glinides) must be limited.During and in the immediate follow-up of an ACS, referral to an endocrinologist/diabetologist is recommended in case of diagnosis of diabetes, when HbA1c. ≥. 8%, when long-term treatment with insulin has been initiated and in case of frequent or severe hypoglycemias. © 2016 Elsevier Masson SAS. Source

Fortinsky K.J.,University of Toronto | Bardou M.,CHU de Dijon | Barkun A.N.,McGill University
Gastrointestinal Endoscopy Clinics of North America | Year: 2015

Nonvariceal upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality worldwide. Mortality from UGIB has remained 5-10% over the past decade. This article presents current evidence-based recommendations for the medical management of UGIB. Preendoscopic management includes initial resuscitation, risk stratification, appropriate use of blood products, and consideration of nasogastric tube insertion, erythromycin, and proton pump inhibitor therapy. The use of postendoscopic intravenous proton pump inhibitors is strongly recommended for certain patient populations. Postendoscopic management also includes the diagnosis and treatment of Helicobacter pylori, appropriate use of proton pump inhibitors and iron replacement therapy. © 2015 Elsevier Inc. Source

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