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Marseille, France

Goncalves A.,Institute Paoli Calmettes | Goncalves A.,French Institute of Health and Medical Research | Goncalves A.,Aix - Marseille University | Viens P.,Institute Paoli Calmettes | And 20 more authors.
Bulletin du Cancer | Year: 2011

The expected increase in cancer incidence emphasizes the need for specific training in this area, including either family physician or specialized oncologists. In France, the fourth to sixth years of medical teaching include both theoretical classes at the university and daily actual practice at the hospital. Thus, clinical rotations are thought to play a major role in the training of medical students and also largely participate to the choice of the student of his/her final specialty. Pedagogic quality of these rotations is dependent on multiple parameters, including a rigorous planification of the expected learning. Here, we reported a systemic planification of learning activities for medical students during an oncology rotation at the Paoli- Calmettes Institute in Marseille, France, a regional comprehensive cancer center. This planification includes an evaluation of learning requirements, definition of learning objectives, selection of learning methods and choice of methods of assessment of the students' achievement of these objectives as well as the learning activity itself. ©John Libbey Eurotext.


Hazekamp M.G.,Leids Universitair Medisch Centrum | Gomez A.A.,Leids Universitair Medisch Centrum | Koolbergen D.R.,Leids Universitair Medisch Centrum | Hraska V.,Deutsches Kinderherzzentrum | And 6 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2010

Objectives: Optimal surgical management for patients with transposition of the great arteries (TGA), ventricular septal defect (VSD) and left ventricular outflow obstruction (LVOTO) remains controversial. Although the Rastelli operation has been the most widely performed surgical procedure during the past decades, several studies have shown its suboptimal long-term prognosis. Other operations have been developed to improve results. This study was performed to compare the outcomes of the different surgical approaches for patients with TGA, VSD and LVOTO, as well as to determine risk factors for mortality and re-intervention. Methods: Records from 146 patients undergoing surgery from 1980 to 2008 from eight European hospitals were reviewed. Median age at operation was 21.5 months (range 0.2-165.1 months), and median weight was 10.0 kg (range 2.0-41.0 kg). Surgical procedures involved were the Rastelli procedure (82), arterial (24) and atrial (5) switch operation with relief of LVOTO, Réparation à l'Etage ventriculaire (REV) procedure (7) and the Metras modification (24), as well as the Nikaidoh procedure (4). Results: The overall survival was 88%, 88% and 58% at 1, 10 and 20 years, respectively. The overall event-free survival was 80%, 45% and 26% at 1, 10 and 20 years, respectively. The REV procedure and the Metras modification were found to have the best long-term results in both survival and event-free survival rates. Multivariate analysis revealed year of operation, non-commitment of the VSD and prolonged cardiopulmonary bypass (CPB) time as risk factors for mortality while age at surgery, year of operation and type of corrective surgery were risk factors for re-intervention. Conclusions: Different surgical approaches have been developed for patients with TGA, VSD and LVOTO. The REV procedure and the Metras modification were observed to have favourable long-term results in survival and event-free survival rates. Aortic translocation techniques such as the Nikaidoh procedure seem promising, but further studies will be needed to confirm this in the long term. © 2010 European Association for Cardio-Thoracic Surgery.


Delplanque M.,Paris West University Nanterre La Defense | De La Simone M.,Paris West University Nanterre La Defense | Burdin V.,French Institute of Health and Medical Research | Skalli W.,Arts et Metiers ParisTech | And 3 more authors.
IRBM | Year: 2012

In order to reduce the failure rate due to a poor understanding of mechanical causes, the new diagnostics and pretreatments of osteoarticular pathologies are turning increasingly to methods assessing the 3D morphology of the joints, its kinematics and its impact on the adjacent joints. The goal of the TecSan HIPEOS project is to provide, in combination with the EOS™ system, a set of clinical tools to better understand the structural and kinematic 3D consequences of musculoskeletal diseases in order to optimize the decision, the surgery and functional recovery. The TecSan HIPEOS project has led to clinically validated applications (sterEOS™), that integrate the 3D approach in clinical practice for the diagnosis, the post-operative control and follow-up of the hip joint based on a static and/or a functional approach of the joint. Other prototype tools have been developed and used to establish proofs of concept and to open interesting perspectives for future applications including surgical planning and pseudokinematic studies. The article summarizes the results obtained both in terms of product innovation and clinical validation. © 2012 Elsevier Masson SAS. All rights reserved.


Zhao W.,French Institute of Health and Medical Research | Fakhoury M.,French Institute of Health and Medical Research | Brochard K.,Hopital Mere et Enfant | Niaudet P.,Hopital Necker Enfants Malades | And 5 more authors.
Journal of Clinical Pharmacology | Year: 2010

The objective was to develop a population pharmacokinetic-pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal-transplant patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal-transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8-A9, UGT2B7, and ABCC2. Population pharmacokinetic analysis was performed with the NONMEM and was validated using bootstrap visual predictive check. The pharmacokinetic data were best described by a 2-compartment model with Erlang distribution to describe the absorption phase. The covariate analysis identified body weight as an individual factor influencing central volume of distribution and concomitant immunosuppressive medication and identified body weight and UGT2B7 802C>T genotype as individual factors influencing apparent oral clearance (CL/F) of MMF. CL/F in cyclosporine-MMF-treated patients was 33% higher than in tacrolimus-MMF-treated patients. The CL/F was significantly lower in patients with UGT2B7 802 C/C genotype compared with patients with UGT2B7 802 C/T and 802T/T genotypes, and this effect was independent of concomitant immunosuppressive medication or body weight. The population pharmacokinetic- pharmacogenetic model of mycophenolic acid was validated. Body weight, concomitant medication, and UGT2B7 genotype contribute significantly to the interindividual variability of MMF disposition in pediatric renal-transplant patients. © The Author(s) 2010.


Cailliez M.,Hopital de la Timone Enfants | Jacqz-Aigrain E.,French Institute of Health and Medical Research
British Journal of Clinical Pharmacology | Year: 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • MMF has been proposed as a treatment of steroid-dependent nephrotic syndrome and in the recent years, several studies have suggested its positive effect in preventing relapses. WHAT THIS PAPER ADDS • The population pharmacokinetics of MPA was first evaluated in children with idiopathic nephrotic syndrome and data fitted well with a two-compartment model with first-order absorption and lag time. • Body weight and serum albumin had a significant impact on oral clearance. • A three-point (T0, T1 and T4h) Bayesian estimator of AUC0-12 was developed. AIMS: To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC0-12). METHODS: The pharmacokinetic model of MMF was described from 23 patients aged 7.4 ± 3.9 years (range 2.9-14.9) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment model with lag-time and first-order absorption and elimination was developed. The final model was validated using visual predictive check. Bayesian estimator was validated using circular permutation method. RESULTS: The population pharmacokinetic parameters were apparent oral clearance 9.7 l h-1, apparent central volume of distribution 22.3 l, apparent peripheral volume of distribution 250 l, inter-compartment clearance 18.8 l h-1, absorption rate constant 5.16 h-1, lag time 0.215 h. The covariate analysis identified body weight and serum albumin as individual factors influencing the apparent oral clearance. Accurate Bayesian estimation of AUC0-12 was obtained using the combination of three MPA concentrations measured just before (T 0), 1 and 4 h (T1 and T4) after drug intake with a small error of 0.298 μg h-1 ml-1 between estimated and reference AUC0-12. CONCLUSIONS: The population pharmacokinetic model of MPA was developed in children with INS. A three-point (T0, T1 and T4h) Bayesian estimator of AUC 0-12 was developed and might be used to investigate the relation between MPA pharmacokinetic and pharmacodynamics in children with INS and determine if there is any indication to monitor MPA exposure in order to improve patient outcome based on individual AUC-controlled MMF dosing. © 2010 The Authors.

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