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.
Oral vinorelbine and cisplatin with concurrent radiotherapy after induction chemotherapy with cisplatin and docetaxel for patients with locally advanced non-small cell lung cancer: The GFPC 05-03 study
Descourt R.,Institut Universitaire de France |
Vergnenegre A.,University of Limoges |
Barlesi F.,Aix - Marseille University |
Lena H.,University of Rennes 1 |
And 10 more authors.
Journal of Thoracic Oncology | Year: 2011
The aim of this multicenter phase II trial was to evaluate the combination of oral vinorelbine and cisplatin with radiotherapy (RT) after cisplatin-docetaxel induction chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC). Patients and Methods: Patients with previously untreated, inoperable, histologically or cytologically confirmed stage IIIA or IIIB NSCLC, with performance status ≤1 and weight loss ≤10% received two cycles of induction CT with cisplatin (75 mg/m2) and docetaxel (75 mg/m2) every 3 weeks. Patients with a tumor response or stabilization continued to receive cisplatin (80 mg/m2) and oral vinorelbine (40 mg/m2) on days 1 and 8 for two cycles, with concomitant thoracic RT (2 Gy/d, 5 d/wk, and total dose 66 Gy). Results: Fifty-six patients were enrolled. All patients (n = 38) who received CT-RT were assessable for the tumor response. There were no complete responses. In the intent-to-treat analysis, the response rates were 32.1% after induction CT and 41.1% after CT-RT. The median progression-free and overall survival times were 9.2 months (95% confidence interval: 7-14) and 20.8 months (95% confidence interval: 13.7-24.1), respectively. Adverse effects of RT-CT were grades 3 to 4 neutropenia (four patients) and grade 3 esophageal toxicity (one patient). No treatment-related deaths occurred. CONCLUSION:: The oral vinorelbine-cisplatin combination with concurrent RT is feasible and has a favorable risk-benefit ratio in stage IIIA/IIIB NSCLC. Copyright © 2011 by the International Association for the Study of Lung Cancer.
PubMed | University of Nice Sophia Antipolis, Hopital dInstruction des Armees, University of Caen Lower Normandy, Institute Of Recherche Biomedicale Des Armees and Institut Universitaire de France
Type: | Journal: Frontiers in physiology | Year: 2016
In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate.
PubMed | Institute Paoli Calmettes, Montpellier University, Center Henri Becquerel, University of Nantes and 10 more.
Type: Case Reports | Journal: Haematologica | Year: 2015
Central nervous system involvement by malignant cells is a rare complication of Waldenstrm macroglobulinemia, and this clinicopathological entity is referred to as the Bing-Neel syndrome. There is currently no consensus on the diagnostic criteria, therapeutic approaches and response evaluation for this syndrome. In this series, we retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenstrm macroglobulinemia in 36% of patients. When Waldenstrm macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenstrm macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm(3). Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenstrm macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies.
PubMed | Etablissement francais du sang Center Atlantique, British Petroleum, University of Monastir, Sanguine and Hopital dinstruction des armees
Type: Journal Article | Journal: Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine | Year: 2015
Hematologic diseases are a significant part of health disorders in Benin. As an example, anemia is the second cause of hospitalization, measuring up to 7.9% all over the country (National Plan of Sanitary Development, 2009-2018). By contrast, there is only one active hematologist in the country. Thanks to two partnerships, on one hand between the health sciences faculty in Cotonou (Benin) and the medicine one in Tours (France), and on the other hand between the Beninese Blood Transfusion National Agency and the French Blood Establishment, a first blood transfusion and hematology formation was held in Cotonou on December 2014. Among other benefits, was created an hematology-transfusion network in order to facilitate relations between Beninese hospital doctors, with the support of the two French partner institutions. The article describes this progress.
Ekouevi D.K.,French Institute of Health and Medical Research |
Azondekon A.,Hopital dInstruction des Armees |
Dicko F.,Hopital Gabriel Toure |
Malateste K.,French Institute of Health and Medical Research |
And 8 more authors.
BMC Public Health | Year: 2011
Background: The IeDEA West Africa Pediatric Working Group (pWADA) was established in January 2007 to study the care and treatment of HIV-infected children in this region. We describe here the characteristics at antiretroviral treatment (ART) initiation and study the 12-month mortality and loss-to-program of HIV-infected children followed in ART programs in West Africa. Methods. Standardized data from HIV-infected children followed-up in ART programs were included. Nine clinical centers from six countries contributed to the dataset (Benin, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal). Inclusion criteria were the followings: age 0-15 years and initiated triple antiretroviral drug regimens. Baseline time was the date of ART initiation. WHO criteria was used to define severe immunosuppression based on CD4 count by age or CD4 percent < 15%. We estimated the 12-month Kaplan-Meier probabilities of mortality and loss-to-program (death or loss to follow-up > 6 months) after ART initiation and factors associated with these two outcomes. Results: Between June 2000 and December 2007, 2170 children were included. Characteristics at ART initiation were the following: median age of 5 years (Interquartile range (IQR: 2-9) and median CD4 percentage of 13% (IQR: 7-19). The most frequent drug regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitors (62%). During the first 12 months, 169 (7.8%) children died and 461(21.2%) were lost-to-program. Overall, in HIV-infected children on ART, the 12-month probability of death was 8.3% (95% Confidence Interval (CI): 7.2-9.6%), and of loss-to-program was 23.1% (95% CI: 21.3-25.0%). Both mortality and loss-to program were associated with advanced clinical stage, CD4 percentage < 15% at ART initiation and year (2005) of ART initiation. Conclusion: Innovative and sustainable approaches are needed to better document causes of death and increase retention in HIV pediatric clinics in West Africa. © 2011 Ekouevi et al; licensee BioMed Central Ltd.
Lefort H.,Service medical durgence |
Mendibil A.,Service medical durgence |
Romanat P.E.,hopital dinstruction des Armees |
Tourtier J.-P.,Service medical durgence
Annales Francaises de Medecine d'Urgence | Year: 2013
Fascia iliaca block is a safe and reliable block that is quite useful in prehospital emergency situations. This loco-regional analgesia can be used in the field. The block is used for pain relief in diaphysal femoral fracture, but also in hip bone lesions. The contra-indications are numerous for outcomes trauma and must be observed. The patient must be clearly informed about the technical procedure. This procedure is easy to realize, requiring little equipment. It consists in an injection of a single shot of local anaesthetic into an anatomical compartment containing nerves: femoral, lateral femoral cutaneous and obturator nerve. Analgesia results directly from the action of the local anaesthetic on sensitive fibres, and indirectly due to muscle relaxation. As for any regional anaesthesia, basic conditions of security are required with the immediate availability of the necessary resources in case of adverse and immediate complications (malaise, systemic toxicity and allergy). We present the realization of fascia iliaca block in prehospital setting. © 2013 Société française de médecine d'urgence and Springer-Verlag France.
Martinaud C.,Hopital dInstruction des Armees |
Brisou P.,Hopital dInstruction des Armees |
Mozziconacci M.-J.,Institute Paoli Calmettes
American Journal of Hematology | Year: 2010
The World Health Organization (WHO) has added detection of the JAK2 tyrosine kinase mutation, JAK2 V617F, in the diagnostic work up for myeloproliferative neoplasms (MPNs), especially for polycythemia vera (PV) and essential thrombocythemia (ET). The rational use of this new marker requires the determination of accurate thresholds of clinical significance and thus implies clarification of the presence or not of JAK2 V617F in healthy individuals. The aim of this study was to determine JAK2 V617F mutation levels in healthy subjects with no clinical or biological signs indicative of MPN. Results in 198 healthy subjects indicate that a very accurate quantification of JAK2 V617F is feasible when the analysis is performed with a highly sensitive and reliable RQ-PCR assay, and that the JAK2 V617F mutation may be detectable in very rare cases of healthy volunteers with no clinical symptoms of MPNs or blood disorder, but only at levels around the analytical threshold of the assay (0.035%) and far below the commonly accepted positivity cutoff (1%).
Dujardin G.,French Institute of Health and Medical Research |
Commandeur D.,Hopital dInstruction des Armees |
Le Jossic-Corcos C.,French Institute of Health and Medical Research |
Ferec C.,French Institute of Health and Medical Research |
Corcos L.,French Institute of Health and Medical Research
Journal of Cystic Fibrosis | Year: 2011
Background: Cystic fibrosis is caused by mutations of the Cystic Fibrosis Transmembrane conductance Regulator gene (CFTR). Among the 1795 reported mutations, 221 (12.31%) are believed to affect pre-mRNA splicing. Nevertheless, not all splicing mutations have been demonstrated, by functional assays, to affect splicing in living cells. Methods: We have used a minigene-based approach, coupled to site-specific mutagenesis, to analyze the effects of presumptive pre-mRNA splicing mutations. Results: We show here that the intron 11 1811+1G>C and the intron 12 1898+3A>G mutations strongly affected CFTR pre-mRNA splicing. The encoded proteins are predicted to be defective, which would thus participate in the disease phenotype of carrier individuals. Conclusions: These results further validate the minigene strategy for the study of presumptive splice mutations, and report unanticipated defects in splicing. Such assays should improve the analysis of genotype-phenotype correlations. © 2011 European Cystic Fibrosis Society.
Vareil M.-O.,Center Hospitalier University Pellegrin |
Tandonnet O.,Hopital dEnfants |
Chemoul A.,Hopital dInstruction des Armees |
Bogreau H.,Institutde Medecine Tropicale Du Service Of Sante Des Armees |
And 8 more authors.
Emerging Infectious Diseases | Year: 2011
Plasmodium falciparum malaria is usually transmitted by mosquitoes. We report 2 cases in France transmitted by other modes: occupational blood exposure and blood transfusion. Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever.