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Cottin V.,University Claude Bernard Lyon 1 | Crestani B.,Competence Center for Rare Lung Diseases | Valeyre D.,Hopital University Avicenne | Wallaert B.,Lille University Hospital Center | And 19 more authors.
European Respiratory Review | Year: 2014

Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines. © ERS 2014.


Legriel S.,Center Hospitalier Of Versailles Andre Mignot Hospital | Azoulay E.,CHU Saint Louis | Resche-Rigon M.,CHU Saint Louis | Lemiale V.,CHU Saint Louis | And 14 more authors.
Critical Care Medicine | Year: 2010

Objectives: Few outcome data are available about convulsive status epilepticus managed in the intensive care unit. We studied 90-day functional outcomes and their determinants in patients with convulsive status epilepticus. Design: Two hundred forty-eight convulsive status epilepticus patients admitted to 18 intensive care units in 2005-2007 were included in a prospective observational cohort study. The main outcome measure was a Glasgow Outcome Scale score of 5 (good recovery) on day 90. Main results: Convulsive status epilepticus occurred out of hospital in 177 (67%) patients, and all but 15 patients were still seizing at medical team arrival. The median time from convulsive status epilepticus onset to anticonvulsant drug initiation was 40 mins (interquartile range, 5-80). Total seizure duration was 85 mins (interquartile range, 46.5-180). Convulsive status epilepticus was refractory in 49 (20%) patients. The most common causes of convulsive status epilepticus were anticonvulsive agent withdrawal (36.4%) in patients with previous epilepsy and stroke (27.7%) in inaugural convulsive status epilepticus. Mechanical ventilation was needed in 210 (85%) patients. On day 90, 42 (18.8%) patients were dead, 87 (38.8%) had marked functional impairments (Glasgow Outcome Scale score, 2-4), and 95 (42.4%) had a good recovery (Glasgow Outcome Scale score, 5). Factors showing independent positive associations with poor outcome (Glasgow Outcome Scale score, <5) were older age (odds ratio, 1.04/year; 95% confidence interval, 1.02-1.05; p = .0005), cerebral insult (odds ratio, 2.70; 95% confidence interval, 1.37-5.26; p = .007), longer seizure duration (odds ratio, 1.72/120 min; 95% confidence interval, 1.05-2.86; p = .03), on-scene focal neurologic signs (odds ratio, 2.08; 95% confidence interval, 1.03-4.16; p = .04), and refractory convulsive status epilepticus (odds ratio, 2.70; 95% confidence interval, 1.02-7.14; p = .045). Conclusions: Ninety days after intensive care unit admission for convulsive status epilepticus, half the survivors had severe functional impairments. Longer seizure duration, cerebral insult, and refractory convulsive status epilepticus were strongly associated with poor outcomes, suggesting a role for early neuroprotective strategies. © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


PubMed | CHU La Pitie Salpetriere, CHU Amiens, CHU Bichat, Groupe Hospitalier Sud and 3 more.
Type: Journal Article | Journal: Trials | Year: 2017

Ventilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units. Compared to a long duration (LD) of antibiotic therapy, a short duration (SD) has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant (MDR) pathogen emergence, with the exception of documented VAP of non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA). These results have led the American Thoracic Society to recommend SD therapy for VAP, except for PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. We aimed to assess the non-inferiority of a short duration of antibiotics (8days) versus prolonged antibiotic therapy (15days) in PA-VAP.The impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia (iDIAPASON) trial is a randomized, open-labeled non-inferiority controlled trial, conducted in 34 French intensive care units (ICUs), comparing two groups of patients with PA-VAP according to the duration (8days or 15days) of effective antibiotic therapy against PA. The primary outcome is a composite endpoint combining day 90 mortality and PA-VAP recurrence rate during hospitalization in the ICU. Furthermore, durations of mechanical ventilation and hospitalization, as well as number and types of extrapulmonary infections or acquisition of MDR pathogens during the hospitalization in the ICU will be recorded. Recurrence with predefined criteria (clinical suspicion of VAP associated with a positive quantitative culture of a respiratory sample) will be evaluated by two independent experts.Demonstrating that an SD (8days) versus LD (15days) therapy strategy in PA-VAP treatment is safe and not associated with an increased mortality or recurrence rate could lead to a change in practices and guidelines in the management of antibiotic therapy of this frequent ICU complication. This strategy could lead to decreased antibiotic exposure during hospitalization in the ICU and in turn reduce the acquisition and the spread of MDR pathogens.ClinicalTrials.gov: NCT02634411 . Registered on 19 November 2015.


Van Belle E.,Heart Catheterization Laboratory | Van Belle E.,Lille University | Juthier F.,Heart Catheterization Laboratory | Juthier F.,Lille University | And 23 more authors.
Circulation | Year: 2014

BACKGROUND-: Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. METHODS AND RESULTS-: TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1-Q3=178-490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural grade 2 were identified including femoral delivery (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter (P=0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11; P=0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR


Cottin V.,University of Lyon | Le Pavec J.,University Paris - Sud | Prevot G.,Service de Pneumologie | Mal H.,CHU Bichat | And 3 more authors.
European Respiratory Journal | Year: 2010

This study aims to describe the haemodynamic and survival characteristics of patients with pulmonary hypertension in the recently individualised syndrome of combined pulmonary fibrosis and emphysema. A retrospective multicentre study was conducted in 40 patients (38 males; age 68±9 yrs; 39 smokers) with combined pulmonary fibrosis and emphysema, and pulmonary hypertension at right heart catheterisation. Dyspnoea was functional class II in 15%, III in 55% and IV in 30%. 6-min walk distance was 244±126 m. Forced vital capacity was 86±18%, forced expiratory volume in 1 s 78±19%, and carbon monoxide diffusion transfer coefficient 28±16% of predicted. Room air arterial oxygen tension was 7.5±1.6 kPa (56±12 mmHg). Mean pulmonary artery pressure was 40±9 mmHg, cardiac index 2.5±0.7 L·min -1·m -2 and pulmonary vascular resistance 521±205 dyn·s·cm -5. 1-yr survival was 60%. Higher pulmonary vascular resistance, higher heart rate, lower cardiac index and lower carbon monoxide diffusion transfer were associated with shorter survival. Patients with combined pulmonary fibrosis and emphysema syndrome and pulmonary hypertension confirmed by right heart catheterisation have a dismal prognosis despite moderately altered lung volumes and flows and moderately severe haemodynamic parameters. Copyright©ERS Journals Ltd 2010.


PubMed | Lyon University Hospital Center, Tourcoing Hospital, Laboratoire Of Bacteriologie Virologie, CHU Bichat and Limoges University Hospital Center
Type: | Journal: Antiviral research | Year: 2016

Human cytomegalovirus (HCMV) resistance to antiviral drugs is a major drawback of repeated or long-duration treatment in immunocompromised patients. Resistance testing is usually performed by genotypic assays. For accurate interpretation of these assays, the role of new mutations in HCMV resistance has to be assessed. Two previously unknown UL54 single point mutations (D515Y and V787A) were characterized for phenotypic drug-resistance by marker transfer analysis using bacterial artificial chromosome (BAC) mutagenesis. Increases in 50% inhibitory concentrations of ganciclovir and foscarnet were found for both mutated recombinant strains showing that mutations D515Y and V787A induce resistance to both antivirals. Importantly, none of those impacted the viral growth kinetics. For a better understanding of their molecular resistance mechanisms, a 3D homology model was used to localize the mutated amino-acids in functional domains of UL54 and predict their impact on UL54 function and resistance. However, 3D homology model analysis has limits and phenotypic characterization using BAC-HCMV is still essential to measure the role of unknown mutations.


Lucon A.,Service de Cardiologie | Oger E.,Service de Cardiologie | Oger E.,French Institute of Health and Medical Research | Bedossa M.,University of Rennes 1 | And 13 more authors.
Circulation: Cardiovascular Interventions | Year: 2014

Background-Pulmonary hypertension (PH) is associated with poor prognosis in patients with severe aortic stenosis. The aim of this multicenter study was to describe clinical outcome after transcatheter aortic valve implantation. Methods and Results-The FRANCE 2 Registry included all patients undergoing transcatheter aortic valve implantation in France in 2010 and 2011. Patients were divided into 3 groups depending on systolic pulmonary artery pressure (sPAP) estimated in transthoracic echocardiography: group I, sPAP <40 mm Hg (no PH); group II, sPAP 40 to 59 mm Hg (mildto- moderate PH); and group III, sPAP =60 mm Hg (severe PH). Patients were followed up for 1 year. A total of 2435 patients whose pre-transcatheter aortic valve implantation sPAP was reported were included. A total of 845 were in group I (34.7%), 1112 in group II (45.7%), and 478 in group III (19.6%). Procedural success, early complications, and 30-day mortality were statistically similar across sPAP groups. One-year mortality was higher in groups II and III (group I, 22%; group II, 28%; and group III, 28%; P=0.032). Mild-to-moderate and severe PH were identified as an independent factor of all-cause mortality. The major adverse cardiovascular event rates did not differ according to sPAP. New York Health Association functional class improved significantly in all groups. Conclusions-PH (sPAP =40 mm Hg) in patients with aortic stenosis undergoing transcatheter aortic valve implantation was associated with increased 1-year mortality especially when severe (sPAP =60 mm Hg) but not with increased 30-day mortality, and functional status was significantly improved regardless of PAP level. © 2014 American Heart Association, Inc.


Pieroni L.,Groupe Hospitalier Pitie Salpetriere | Delanaye P.,University of Liège | Boutten A.,CHU Bichat | Bargnoux A.-S.,Montpellier University Hospital Center | And 7 more authors.
Clinica Chimica Acta | Year: 2011

Chronic kidney disease definition is based on glomerular filtration rate (GFR) estimations which are derived from creatinine-based equations. The accuracy of GFR estimation is thus largely dependent of those of serum creatinine assays. International recommendations highlight the need for traceable creatinine assays. The French Society of Clinical Biochemistry conducted a study for measuring accuracy of creatinine enzymatic methods. This evaluation involved 25 clinical laboratories. Creatinine was measured in serum pools ranging from 35.9 ± 0.9±mol/L to 174.5 ± 3.1±mol/L (IDMS determination) using 12 creatinine enzymatic methods. For all creatinine values greater than 74.4 ± 1.4±mol/L, the bias and imprecision did not exceed 5% and 5.9%, respectively. For the lowest value (35.9 ± 0.9±mol/L), the bias ranged from -1.8 to 9.9% (with one exception). At this level, the imprecision ranged from 1.9 to 7.8%. The true performances of the assays (couples of bias and relative standard deviation), were evaluated using Monte-Carlo simulations. Most of the assays fall within the maximum Total Error of 12% at all concentrations. This study demonstrates substantial improvements in the calibration, traceability and precision of the enzymatic methods, reaching the NKDEP recommendations. Moreover, most of these assays allowed accurate creatinine measurements for creatinine levels lower than 40±mol/L. © 2011 Elsevier B.V.


PubMed | University of Nantes, CHU Bichat, Cemka Eval, French Institute of Health and Medical Research and Sanofi S.A.
Type: Journal Article | Journal: Diabetes therapy : research, treatment and education of diabetes and related disorders | Year: 2016

The objective of this study was to document the initiation of insulin therapy in patients with type 2 diabetes mellitus (T2DM) and its maintenance as a function of time after initiation in a French nationwide representative cohort.A retrospective cohort study was conducted on a random sample of~600,000 beneficiaries registered in the French national health insurance database. Newly insulin treated T2DM patients were selected. Persistence was defined as remaining on insulin without discontinuation (defined over a 6 or a 12-month period).Among 1909 initiations identified in 2012/2013 (basal scheme: 61.8%, basal/rapid: 15%, other schemes: 23.2%) the average age (standard deviation) at initiation was, respectively, 67.5 (14.2), 61.8 (18.1) and 63.2 (18.4) years. Insulin was initiated by general practitioners in 39.3% and prescribed without other antidiabetic drugs in 32.0%. Persistence was studied in 1969 patients initiating insulin in 2011/2012. Among survivors, nearly 25% stopped insulin during the first year (18.4% for basal scheme). Patients discontinuing insulin were younger [64.7years (18.5) vs 67.3years (14.3) p=0.0003] and less often male (45.8% vs 55.7%, p<0.0001). A proportion of 20.2% did not receive any antidiabetic drug over 12months after discontinuation. These high percentages were only partly explained by transient intensive insulin regimens in acutely ill patients identifiable in the database.We observed a high rate of early discontinuation of insulin in T2DM patients (but lower with basal insulin scheme). Further real world studies are warranted to identify factors associated with this poor persistence.This study was supported by Sanofi-France.

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