Etude de la sécurité d'emploi de la 3,4-diaminopyridine

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Enquête sur le prise en charge de la douleur dans les établissements de santé de la région Bretagne (évaluation de la mise en place du plan triennal de lutte contre le douleur 1998-2000 (DESPharm. hospitalière et des collectivités))

RENNES1-BU Santé (352382103) / SudocSudocFranceF

Effect of oral citrulline supplementation on whole body protein metabolism in adult patients with short bowel syndrome A pilot, randomized, double-blind, cross-over study

International audienceBACKGROUND & AIMS: As citrulline is produced by small intestine, plasma citrulline concentration is decreased and may become essential in patients with short bowel syndrome (SBS). In a rat model of SBS, citrulline supplementation enhanced muscle protein synthesis. The aim of the study was to determine whether citrulline impacts whole body protein metabolism in patients with SBS. METHODS: Nine adults with non-malignant SBS (residual small bowel 90 ± 48 cm; mean ± SD) who were in near-normal nutritional status without any artificial nutrition, were recruited long after surgery. They received 7-day oral supplementation with citrulline (0.18 g/kg/day), or an iso-nitrogenous placebo in a randomized, double-blind, cross-over design with a 13-day wash-out between regimens, and an intravenous 5-h infusion of L-[1-13C]-leucine in the postabsorptive state to assess protein metabolism after each regimen. RESULTS: Plasma citrulline concentration rose 17-fold (25 ± 9 vs. 384 ± 95 μmol/L) and plasma arginine 3-fold after oral citrulline supplementation (both p < 4 × 10-6). Supplementation did not alter leucine appearance rate (97 ± 5 vs. 97 ± 5 μmol kg-1.h-1; p = 0.88), leucine oxidation (14 ± 1 vs. 12 ± 1 μmol kg-1.h-1; p = 0.22), or non-oxidative leucine disposal (NOLD), an index of whole-body protein synthesis (83 ± 4 vs. 85 ± 5 μmol kg-1.h-1; p = 0.36), nor insulin or IGF-1 plasma concentrations. In each of the 3 patients with baseline citrulline<20 μmol/L, citrulline supplementation increased NOLD. Among the 7 patients with plasma citrulline <30 μmol/L, the effect of supplementation on NOLD correlated inversely (r2 = 0.81) with baseline plasma citrulline concentration. CONCLUSION: 1) Oral citrulline supplementation enhances citrulline and arginine bioavailability in SBS patients. 2) Oral citrulline supplementation does not have any anabolic effect on whole body protein metabolism in patients with SBS in good nutritional status, in the late phase of intestinal adaptation, and with near-normal baseline citrulline homeostasis. 3) Whether oral citrulline would impact whole body protein anabolism in severely malnourished SBS patients in the early adaptive period, and with baseline plasma citrulline below 20 μmol/L, warrants further study. Registered under ClinicalTrials.gov Identifier no. NCT01386034

Oral citrulline does not affect whole body protein metabolism in healthy human volunteers: results of a prospective, randomized, double-blind, cross-over study

International audienc

Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole.

International audienceBACKGROUND: Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. METHODS: Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. RESULTS: 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37-55] vs. 30 [15-55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p = 0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14-53] vs. 54 [19-130] and 95 [73-170] mmoles/l, p < 0.01) for all periods. The number of NAB was significantly lower with rabeprazole than with omeprazole (median 1 [1,2] vs. 2 [1-3], p = 0.04). Variances of 24-h data (pH above 3 and 4, median pH, [H+] concentrations) were significantly lower with rabeprazole than with omeprazole (p < 0.0001). CONCLUSIONS: In asymptomatic obese subjects the gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. TRIAL REGISTRATION: ClinicalTrial.gov: NCT01136317

Dietary Proteins Contribute Little to Glucose Production, Even Under Optimal Gluconeogenic Conditions in Healthy Humans

International audienceDietary proteins are believed to participate significantly in maintaining blood glucose levels, but their contribution to endogenous glucose production (EGP) remains unclear. We investigated this question using multiple stable isotopes. After overnight fasting, eight healthy volunteers received an intravenous infusion of [6,6-²H₂]-glucose. Two hours later, they ingested four eggs containing 23 g of intrinsically, uniformly, and doubly [¹⁵N]-[¹³C]-labeled proteins. Gas exchanges, expired CO₂, blood, and urine were collected over the 8 h following egg ingestion. The cumulative amount of dietary amino acids (AAs) deaminated over this 8-h period was 18.1 ± 3.5%, 17.5% of them being oxidized. The EGP remained stable for 6 h but fell thereafter, concomitantly with blood glucose levels. During the 8 h after egg ingestion, 50.4 ± 7.7 g of glucose was produced, but only 3.9 ± 0.7 g originated from dietary AA. Our results show that the total postprandial contribution of dietary AA to EGP was small in humans habituated to a diet medium-rich in proteins, even after an overnight fast and in the absence of carbohydrates from the meal. These findings question the respective roles of dietary proteins and endogenous sources in generating significant amounts of glucose in order to maintain blood glucose levels in healthy subjects

Analysis of cost-effectiveness of chemotherapeutic agents and new therapies for the management of unresectable and metastatic melanoma

International audienceBackground: The advent of targeted therapies and immunotherapies has revolutionized metastatic melanoma (MM) management but their use is associated with high daily costs compared to chemotherapies: €2 for dacarbazine versus €175 for immunotherapies and €413 for targeted therapies. While overall survival (OS) has increased, healthcare expenditures are expected to double by 2030.Objectives: The aim of this study was to estimate the median OS and costs for MM patients in order to evaluate the effectiveness of new biological or targeted therapies (NT) used since 2013 compared to chemotherapies.Materials & methods: This was a retrospective monocentric cost-effectiveness analysis performed in CHU Nantes (Nantes University Hospital). All MM patients treated with conventional chemotherapy as first-line treatment between 2008 and 2012 were included (CHEMO group). The same number of patients treated with NT as first-line between 2013 and 2017 were included (NT group).Results: In total, 161 patients were included in each group. The mean age at diagnosis was 64.7±2.4 years in the CHEMO group and 65.3±2.4 years in the NT group (not significant). The men/women ratio was 1.48 and 1.27, respectively, (not significant). The median OS was 158 days in the CHEMO group and 395 days in the NT group (p<0.001). Treatment cost was €10,280/patient versus €94,676/patient, respectively. The mean incremental cost-effectiveness ratio was €90,184/LY (95% CI: €59,637; €166,395).Conclusion: Our study assessed clinical and economic features associated with MM management before and after the advent of NT. Costs and life expectancy have increased. NT appears to be cost-effective

Activités pharmaceutiques relatives aux essais cliniques de médicaments et dispositifs médicaux réalisées au sein des établissements de santé – guide professionnel

Background and objectivesThe hospital pharmacist, in charge of the pharmaceutical aspects of clinical trials plays a central role in the management and the proper use of investigational health products (IHP), in accordance with the Good Clinical Practices and Public Health Code. The working group “Clinical trials” of the CPCHU (French University Hospitals Pharmacists’ Commission) aimed to prepare national guidelines to describe the activities and involvement of the pharmacists, whatever the type of health care institution.MethodologyAfter an analysis of the existing literature, form and content requirements were set and the structure was established. The chapters were written in subgroups, with systematic revision and validation in plenary.ResultsThe professional guidelines are composed of 109 pages and are available as an interactive pdf file on the SFPC and CNCR websites. Topics covered in the guidelines are divided into 4 chapters, and include inserts of specific recommendations and/or some illustrations. There are 374 references, including 329 regulatory texts, and 5 appendices.Discussion–conclusionThese guidelines are a part of process of dissemination, standardization and securing practices, in order to help hospital pharmacists in the management of IHP and in the development or improvement of their own performance systems in terms of quality. Its pedagogical format also makes it a training tool for students, compounders and senior pharmacists. Its regular updating is necessary

Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study.

International audienceCONTEXT: The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown. OBJECTIVE: To test the efficacy of hydrocortisone therapy in trauma patients. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France. INTERVENTION: Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response. MAIN OUTCOME MEASURE: Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death. RESULTS: One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, -9%; 95% CI, -16% to -3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, -5% to 11%; P = .44). CONCLUSION: In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00563303