Unite de Recherche Clinique

Paris, France

Unite de Recherche Clinique

Paris, France
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Devillier P.,CNRS Laboratory for Molecular and Pharmacological Mechanisms of Bronchial Obstruction | Chassany O.,University Paris Diderot | Vicaut E.,Unite de Recherche Clinique | De Beaumont O.,Stallergenes SA | And 3 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background: The minimally important difference (MID) has been defined as the smallest improvement considered worthwhile by a patient. The MID has not been estimated for the Rhinoconjunctivitis Total Symptom Score (RTSS). Methods: In a prospective multicentre study, patients consulting for grass-pollen-induced allergic rhinitis (AR) recorded a 15-point global rating of change scale (GRCS) score and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score on a weekly basis and the individual symptom scores comprising the RTSS on a daily basis over two consecutive weeks. The MID in the RTSS was determined with anchor-based methods (using the GRCS and the RQLQ) and a distribution-based method [based on the RTSS' standard deviation (SD)]. Results: The study population comprised 806 patients (253 children, 250 adolescents and 303 adults). During the first week of the study, the mean ± SD RTSSs for these age groups were 6.5 ± 3.3, 6.8 ± 3.4 and 7.0 ± 3.4, respectively. For an improvement of 2 points in the GRCS or 0.5 points in the RQLQ score, the regression analysis yielded MIDs in the RTSS of 1.24 ± 0.17 and 1.12 ± 0.14 in children, 1.33 ± 0.14 and 1.20 ± 0.13 in adolescents and 1.13 ± 0.14 and 0.89 ± 0.12 in adults, respectively. When applying distribution-based methods, the MID ranged from 1.09 to 1.13 (based on 0.33 SDs of the first-week RTSS) and from 1.22 to 1.40 (based on 0.5 SDs of the difference in RTSSs between the first and second weeks). Conclusion: The MID in the RTSS was consistently estimated as 1.1-1.3 (and could conceivably be rounded to 1) in patients with grass-pollen-induced AR. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mohr J.P.,Columbia University | Parides M.K.,Mount Sinai School of Medicine | Stapf C.,Columbia University | Stapf C.,Paris West University Nanterre La Défense | And 18 more authors.
The Lancet | Year: 2014

Background: The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods: Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181. Findings: Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4.10, exceeding the prespecified stopping boundary value of 2.87). At this point, outcome data were available for 223 patients (mean follow-up 33.3 months [SD 19.7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10.1%) patients in the medical management group compared with 35 (30.7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0.27, 95% CI 0.14-0.54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0.0001) and neurological deficits unrelated to stroke (14 vs 1, p=0.0008) in patients allocated to interventional therapy compared with medical management. Interpretation: The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.

Chevalier X.,Henri Mondor Hospital | Ravaud P.,University of Paris Descartes | Maheu E.,University Paris - Sud | Baron G.,University of Paris Descartes | And 11 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Aim To test the efficiency of tumour necrosis factor blockers (adalimumab) in patients with painful refractory (non-responders to analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)) hand osteoarthritis (OA). Methods We performed a randomised, double-blind, placebo-controlled, parallel group, multicentre study. Patients were randomised to: 1/1 adalimumab 40 mg for two subcutaneous injections at a 15-day interval or placebo and monitored for 6 months. The primary outcome was the percentage of patients with an improvement of more than 50% in global pain (Visual Analogue Scale) between week 0 (W0) and week 6 (W6). Secondary outcomes included the number of painful joints, swollen joints, morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, and consumption of analgesics. Analysis on the mean primary outcome measure was done on patients who received at least one injection. Results 99 patients were recruited and 85 patients were randomised. Among them, 37 patients in the placebo group and 41 in the adalimumab group received at least one injection and were evaluated at W6 (n=78) on the main efficacy outcome. Mean age was 62 years, 85% were women, and mean level of pain was 62 mm at W0. At W6, 35.1% in the adalimumab group versus 27.3% in the placebo group had a pain reduction ≥50% (RR 1.12 (95% CI 0.82 to 1.54; p=0.48). There were no statistical differences for all secondary end points. The rate of adverse events was similar in the two groups. Conclusions Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.

Montalescot G.,Group 47 | Van't Hof A.W.,Isala Clinics | Lapostolle F.,Service DAide Medicale Urgente 93 | Silvain J.,Group 47 | And 23 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown.METHODS We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days.RESULTS The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and inhospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used.Conclusions: Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. Copyright © 2014 Massachusetts Medical Society. All rights reserved.

Reynaud Q.,Service de Medecine Interne | Lega J.-C.,University Claude Bernard Lyon 1 | Lega J.-C.,Jean Monnet University | Mismetti P.,Jean Monnet University | And 7 more authors.
Autoimmunity Reviews | Year: 2014

Aim: To evaluate the magnitude of venous and arterial thrombosis risk associated with antiphospholipid antibodies (APLs) in adults without systemic lupus erythematosus (SLE). Methods: Case-control and cohort studies were selected from the MEDLINE and Cochrane Library databases. Two investigators independently extracted data on study design, patient characteristics, venous and arterial events and exposure to APLs, including lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2 Glycoprotein I (β2GpI), anti-prothrombin (aPT), anti-phosphatidyl serine (aPS), and anti-phosphatidyl ethanolamine (aPE). Results: 30 studies were included (16,441 patients). The odds ratio (OR) for venous thrombosis was 6.14 (95% confidence interval [CI] 2.74-13.8) in LA-positive patients (5 studies, 1650 patients) and 1.46 (CI 1.06-2.03) in aCL-positive patients (12 studies, 5375 patients). None of the associations with more recently identified APLs was significant, but fewer studies were available. For arterial thrombosis, the OR for LA and aCL was 3.58 (CI 1.29-9.92) and 2.65 (CI 1.75-4.00) respectively. The associations between β2GpI, aPT and aPS and the risk of arterial thrombosis were also significant, the OR being 3.12 (CI 1.51-6.44), 2.95 (CI 1.31-6.66) and 6.00 (CI 3.07-11.7), respectively. Owing to the heterogeneity of cut-off values for each APL assay, we were unable to perform any sensitivity analysis to determine the optimal value. The presence of low-quality studies may have led to overestimation of the magnitude of the associations. Conclusions: LA and aCL were significantly associated with an increased risk of thrombosis, especially arterial, in patients without SLE. Systematic thromboprophylaxis in high-risk patients with APL should be evaluated. © 2014 Elsevier B.V.

Marzelle J.,University Paris Est Creteil | Presles E.,Unite de Recherche Clinique | Presles E.,French Institute of Health and Medical Research | Becquemin J.P.,University Paris Est Creteil
Annals of Surgery | Year: 2015

Objective: To present results and to identify predictive factors of early outcome after fenestrated and/or branched endovascular repair (f/b-EVAR) for complex aortic aneurysms, abdominal (AAA) and thoracoabdominal (TAAA). Background: Feasibility of f/b-EVAR for complex aneurysms is now established, but little is known aboutwhich patients will benefit from this technique. Methods: Univariate and multivariate analysis of preoperative and intraoperative factors on postoperative mortality and complications was performed on 268 patients (group 1: juxta- and pararenal AAA; group 2: suprarenal and TAAA IV; group 3: TAAA I, II, III) enrolled in a prospective multicenter trial of f/b-EVAR. Results: Thirty-day mortality, in-hospital mortality (IM), and combined mortality and severe complications (CMSC) rates were 6.7%, 10.1%, and 22.0%, respectively. Group belonging (2 or 3 vs 1) was the only preoperative predictive factor of CMSC [hazard ratio (HR) = 2.10; 95% confidence interval (CI): 1.26-3.48; P = 0.0043]. Occurrence of a technical complication and duration of intervention significantly influenced both IM (HR = 4.39; 95% CI: 2.05-9.38; P = 0.0001) and CMSC (HR = 3.07; 95% CI: 1.84-5.11; P < 0.0001). Postoperative events associated with increased IM were spinal cord ischemia (HR = 9.46; 95% CI: 3.98-22.47; P < 0.0001), hemodialysis (HR = 27.44; 95% CI: 12.63-59.61; P < 0.0001), and reintervention (HR = 4.45; 95% CI: 2.03-9.73; P = 0.0002). Conclusions: Although promising, f/b-EVAR still carries a significant rate of mortality and complications,mostly related to the complexity of the procedure. In these complex cases, new strategies should be investigated to improve outcomes. Copyright © 2014 by Lippincott Williams & Wilkins.

Berlin I.,French Institute of Health and Medical Research | Jacob N.,Hopital Pitie Salpetriere | Coudert M.,Unite de Recherche Clinique | Perriot J.,Dispensaire Emile Roux | And 2 more authors.
Addiction | Year: 2011

Aims To assess the efficacy of nicotine replacement therapies (NRT) when the daily dose was adapted according to saliva cotinine concentrations. Design Randomized, multi-centre, single-blind, controlled trial. Setting Twenty-one smoking cessation clinics in France. Participants A total of 310 smokers with medical comorbidities, motivated to quit, smoking ≥10 cigarettes/day, for whom smoking cessation was mandatory. NRT was administered for 3 months. The standard care group received nicotine patches with monthly dose decreases; buccal absorption NRT could be co-administered at the discretion of the investigator. In the dose adaptation group, the aim was a 100±5% nicotine substitution with respect to smoking state based on the determination of saliva cotinine concentrations. NRT daily doses were prescribed according to the previous week's saliva cotinine concentrations in the dose adaptation group; saliva cotinine concentrations were not provided in the standard care group. Measurements Prolonged abstinence rate (weeks 9-12, main outcome measure), point-prevalence and continuous abstinence rate, saliva cotinine concentration, NRT daily dose, craving for cigarettes. Findings The median daily prescribed NRT dose was 30 and 31mg/day in the first study week and 17.25 and 35.5mg/day during weeks 9-12 in the standard care group and dose adaptation group, respectively. Saliva cotinine remained stable in the dose adaptation group and decreased in the standard care group (P<0.01) by weeks 9-12. The cotinine substitution rate was significantly lower in the standard care group than in the dose adaptation group. Despite differences in NRT doses and cotinine substitution rates, prolonged (standard care group: 26.4%, dose adaptation group: 30.3%), continuous (standard care group: 8%, dose adaptation group: 12%) and point-prevalence abstinence rates were similar. Conclusions In smokers with medical comorbidities and highly motivated to quit, adaptation of the nicotine replacement therapy daily dose according to saliva cotinine does not appear to be substantially superior to standard nicotine replacement therapy use. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Perrot S.,French Institute of Health and Medical Research | Vicaut E.,Unite de Recherche Clinique | Servant D.,Unite Stress et Anxiete | Ravaud P.,University of Paris Descartes
BMC Musculoskeletal Disorders | Year: 2011

Background: Fibromyalgia is a common disease, but little is known on its real prevalence in France. This epidemiological study aimed to assess fibromyalgia (FM) prevalence in the French metropolitan population, based on a multi-step sampling analysis, combining national screening and clinical confirmation by trained specialists. Methods. a sampling method on the entire national territory was used: patients over 18 years of age accepting to take part in the study were contacted by telephone using the LFES Questionnaire, a screening test for FM. The, for patients detected by the LFESQ, a visit with a FM-trained rheumatologist was proposed to confirm FM, based on 1990 ACR criteria. Each detected patient completed the following self-questionnaires: SF36, HADS, stress VAS, Co-morbidities and Regional pain score. Results: 3081 patients were contacted in 5 representative French regions, of which 232 patients were screened for FM. A fibromyalgia diagnosis was then confirmed by rheumatologist in 20 cases (17 female and 3 male, 56.9 13.2 years). The final estimated FM prevalence was 1.6 (CI95: 1.2%; 2.0%). No significant difference was detected between the patients accepting (CS+) and refusing (CS-) rheumatologist visit for the SF36 score, regional pain score, stress VAS scale and co-morbidities. In patients detected for FM by the LFESQ, we found a statistically significant decrease in quality of life and a statistically significant increase in stress level in patients with a confirmed diagnosis (FM+) (6.3 1.9) compared to patients with an invalidated diagnosis (FM-) (4.4 2.8; p = 0.007). The study also demonstrated a significant association, independently of ACR criteria, between the diagnosis of FM and several factors such as regional pain score > 10, elevated stress level, low SF36 scale score and presence of gastro-intestinal disorder co-morbidities. Conclusion: Fibromyalgia is a common condition; the 1.6% prevalence calculated in the French population in our study corroborates the figures published in the European literature. Our results also suggest that criteria such as regional pain score, stress level or SF36 quality of life, could represent useful tools in fibromyalgia diagnosis. © 2011 Perrot et al; licensee BioMed Central Ltd.

Berlin I.,University Pierre and Marie Curie | Grange G.,Maternite Port Royal | Jacob N.,Hopital Pitie Salpetriere | Tanguy M.-L.,Unite de Recherche Clinique
BMJ (Online) | Year: 2014

Objective: To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design: Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants: 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks' gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions: Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures: The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air =8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results: Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self reported median compliance rate was 85% (interquartile range 56-99%) in the nicotine patch group and 83% (56-95%) in the placebo patch group, assessed at 1016 visits. The mean birth weight was 3065 g (SE 44 g) in the nicotine patch group and 3015 g (SE 44 g) in the placebo patch group (P=0.41). Diastolic blood pressure was significantly higher in the nicotine patch group than in the placebo patch group. The frequency of serious adverse events was similar between the groups, although more non-serious adverse reactions, mainly of skin, occurred in the nicotine patch group. Conclusion: The nicotine patch did not increase either smoking cessation rates or birth weights despite adjustment of nicotine dose to match levels attained when smoking, and higher than usual doses.

Dessap A.M.,Center Hospitalo University Henri Mondor | Katsahian S.,Unite de Recherche Clinique | Roche-Campo F.,Center Hospitalo University Henri Mondor | Varet H.,Unite de Recherche Clinique | And 9 more authors.
Chest | Year: 2014

BACKGROUND: Pulmonary edema may alter alveolar bacterial clearance and infectivity. Manipulation of fluid balance aimed at reducing fluid overload may, therefore, influence ventilator-associated pneumonia (VAP) occurrence in intubated patients. The objective of the present study was to assess the impact of a depletive fluid-management strategy on ventilator-associated complication (VAC) and VAP occurrence during weaning from mechanical ventilation. M ETHODS: We used data from the B-type Natriuretic Peptide for the Fluid Management of Weaning (BMW) randomized controlled trial performed in nine ICUs across Europe and America. We compared the cumulative incidence of VAC and VAP between the biomarkerdriven, depletive fluid-management group and the usual-care group during the 14 days following randomization, using specific competing-risk methods (the Fine and Gray model). R ESULTS: Among the 304 patients analyzed, 41 experienced VAP, including 27 (17.8%) in the usual-care group vs 14 (9.2%) in the interventional group ( P= 5 .03). From the Fine and Gray model, the probabilities of VAC and VAP occurrence were both significantly reduced with the interventional strategy while adjusting for weaning outcome as a competing event (subhazard ratios [25th-75th percentiles], 0.44 [0.22-0.87], P =5 .02 and 0.50 [0.25-0.96], P= 5 .03, respectively). CONCLUSIONS: Using proper competing risk analyses, we found that a depletive fluidmanagement strategy, when initiating the weaning process, has the potential for lowering VAP risk in patients who are mechanically ventilated. © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS.

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