Bonnefond A.,French National Center for Scientific Research |
Bonnefond A.,University of Lille Nord de France |
Clement N.,French Institute of Health and Medical Research |
Clement N.,University of Paris Descartes |
And 45 more authors.
Nature Genetics | Year: 2012
Genome-wide association studies have revealed that common noncoding variants in MTNR1B (encoding melatonin receptor 1B, also known as MT 2) increase type 2 diabetes (T2D) risk. Although the strongest association signal was highly significant (P < 1 - 10 g 20), its contribution to T2D risk was modest (odds ratio (OR) of g1/41.10g1.15). We performed large-scale exon resequencing in 7,632 Europeans, including 2,186 individuals with T2D, and identified 40 nonsynonymous variants, including 36 very rare variants (minor allele frequency (MAF) <0.1%), associated with T2D (OR = 3.31, 95% confidence interval (CI) = 1.78g6.18; P = 1.64 - 10 g 4). A four-tiered functional investigation of all 40 mutants revealed that 14 were non-functional and rare (MAF < 1%), and 4 were very rare with complete loss of melatonin binding and signaling capabilities. Among the very rare variants, the partial- or total-loss-of-function variants but not the neutral ones contributed to T2D (OR = 5.67, CI = 2.17g14.82; P = 4.09 - 10 g4). Genotyping the four complete loss-of-function variants in 11,854 additional individuals revealed their association with T2D risk (8,153 individuals with T2D and 10,100 controls; OR = 3.88, CI = 1.49g10.07; P = 5.37 - 10 g 3). This study establishes a firm functional link between MTNR1B and T2D risk. © 2012 Nature America, Inc. All rights reserved.
Timsit J.-F.,Joseph Fourier University |
Mimoz O.,University of Poitiers |
Mourvillier B.,Bichat Claude Bernard University Hospital |
Souweine B.,University Clermont Ferrand |
And 17 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012
Rationale: Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. Objectives: To determine if chlorhexidine- impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. Methods: Ina 2:1:1 assessor-masked randomizedtrial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. Measurements and Main Results: A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. Conclusions: A large randomized trial demonstrated that chlorhexidine gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials.gov (NCT 01189682). Copyright © 2012 by the American Thoracic Society.
Tattevin P.,Pontchaillou University Hospital |
Tattevin P.,University of Rennes 1 |
Saleh-Mghir A.,University of Versailles |
Saleh-Mghir A.,Raymond Poincare University Hospital |
And 10 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013
Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8×107 CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 μg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 μg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) μg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P<0.02 for each comparison) and in the spleen (P<0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America. Copyright © 2013, American Society for Microbiology.
Duchateau F.-X.,Beaujon University Hospital |
Gueye P.,Lariboisiere University Hospital |
Curac S.,Beaujon University Hospital |
Tubach F.,Bichat Claude Bernard University Hospital |
And 5 more authors.
Intensive Care Medicine | Year: 2010
Purpose: Guidelines for advanced life support of cardiac arrest (CA) emphasize continuous and effective chest compressions as one of the main factors of cardiopulmonary resuscitation (CPR) success. The use of an automated load distributing chest compression device for CPR is promising but initial studies on survival show contradictory results. The aim of this study was to evaluate the effects of AutoPulse™ on blood pressure (BP) in out-of-hospital CA patients. Methods: This prospective study included adult patients presenting with in refractory out-of-hospital CA. Invasive arterial BP produced by AutoPulse™ was compared to BP generated by manual CPR (Active Compression Decompression). Systolic, diastolic and mean BP and end-tidal carbon dioxide were recorded before and after initiating the automated band device for each patient. The comparison of diastolic BP produced by manual CPR versus automated chest compressions was the primary end point. Results: Hemodynamics in 29 patients are reported and analyzed. Median diastolic BP increased after starting AutoPulse™ from 17[11-25] mmHg to 23[18-28] mmHg (P < 0.001). Median systolic BP increased from 72[55-105] mmHg to 106[78-135] mmHg (P = 0.02). Mean BP increased from 29[25-38] mmHg to 36[30-15] mmHg (P = 0.002). On the other hand, End-Tidal CO2 did not increase significantly with AutoPulse™ (21[13-36] vs. 22[12-35] mmHg, P = 0.80). Conclusions: In patients with out-of-hospital CA, the use of AutoPulse™ is associated with an increased diastolic BP compared to manual chest compressions. While its benefit to survival has yet to be demonstrated, the increase in diastolic and mean BP is a promising outcome for AutoPulse™ use. © 2010 Copyright jointly held by Springer and ESICM.
Koskas P.,Bretonneau Hospital |
Henry-Feugeas M.C.,Bichat Claude Bernard University Hospital |
Feugeas J.P.,University Paris Diderot |
Poissonnet A.,Bretonneau Hospital |
And 3 more authors.
Journal of Geriatric Psychiatry and Neurology | Year: 2014
Objective: To examine the diagnostic ability of the Lawton Instrumental Activities Daily Living (IADLs) scale and the Activities Daily Living (ADLs) scale as a sensitive tool to Alzheimer's disease (AD) in community-dwelling elderly people. Design: In an old age memory outpatient center, among patients with a clinical diagnosis of AD dementia or no dementia supported by at least 6 months of follow-up, we looked back at the baseline Lawton IADL scale (short version IADL-4 item), ADL scale, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MOCA) values. Results: There were 109 patients with AD and 53 nondemented individuals (81.4 ± 4.6 years). The sensitivity of ADL scale or IADL-4 item or the MMSE was low (52%-57%). The most efficient AD classification used both the IADLs-4 item and the MOCA with a threshold score of 20. Besides age and memory scores, the main correlates of IADLs scale or ADLs scale were executive, neuropsychiatric, vascular, and extrapyramidal scores. Conclusion: Our results suggest that the Lawton IADLs-4 item scale and ADLs scale lack sensitivity to AD dementia in elderly people and support a better sensitivity of MOCA rather than MMSE and IADLs-4 item/ADLs at the expense of specificity. © The Author(s) 2014.
Vandekerckhove L.P.R.,Ghent University |
Wensing A.M.J.,University Utrecht |
Kaiser R.,University of Cologne |
Brun-Vezinet F.,Bichat Claude Bernard University Hospital |
And 18 more authors.
The Lancet Infectious Diseases | Year: 2011
Viral tropism is the ability of viruses to enter and infect specific host cells and is based on the ability of viruses to bind to receptors on those cells. Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. In most European countries, HIV tropism is identified with tropism phenotype testing. New data support genotype analysis of the HIV third hypervariable loop (V3) for the identification of tropism. The European Consensus Group on clinical management of tropism testing was established to make recommendations to clinicians and clinical virologists. The panel recommends HIV-tropism testing for the following groups: drug-naive patients in whom toxic effects are anticipated or for whom few treatment options are available; patients who have poor tolerability to or toxic effects from current treatment or who have CNS pathology; and patients for whom therapy has failed and a change in treatment is considered. In general, an enhanced sensitivity Trofile assay and V3 population genotyping are the recommended methods. Genotypic methods are anticipated to be used more frequently in the clinical setting because of their greater accessibility, lower cost, and faster turnaround time than other methods. For the interpretation of V3 loop genotyping, clinically validated systems should be used when possible. Laboratories doing HIV tropism tests should have adequate quality assurance measures. Similarly, close collaboration between HIV clinicians and virologists is needed to ensure adequate diagnostic and treatment decisions. © 2011 Elsevier Ltd.
Koskas P.,Bretonneau Hospital |
Henry Feugeas M.C.,Bichat Claude Bernard University Hospital |
Saad S.,Bretonneau Hospital |
Belqadi S.,Bretonneau Hospital |
And 2 more authors.
Alzheimer Disease and Associated Disorders | Year: 2011
Background: The French government gave a consensual definition of reinforced care units for Behavioral and Psychological Symptoms in Dementia (BPSD) within the project "Plan Alzheimer 2008/2012." These Cognitive and Behavioral Units (CBU) differ in resources from the traditional reference units for BPSD management, the Acute Psychogeriatric Units (APU). However, a better understanding of their operational specificities may enhance the CBU and APU synergies. Objectives: To describe one of the first CBU experiments, with regard to preexisting BPSD management in an APU in the same geriatric hospital. Participants: A total of 129 patients with BPSD, 35 from the CBU and 94 admitted to the APU before opening the colocated CBU. Results: Patients from the CBU often showed comorbidities and a lower nutritional status, but these conditions were more frequent in the APU (P≤10). Severe dementia, night time and aberrant motor behavior, and agitation were more frequent in the CBU (P≤0.0015). In both the units, about 80% of patients were improved without increased use of psychotropic medications and there was a high discharge rate back home of about 30%. Conclusions: These findings that are still preliminary support a particular role for the CBU for elderly patients showing the most advanced dementia and disruptive BPSD. Colocated APU and CBU may allow for more effective integration of medical and psychiatric care in elderly patients with BPSD with frequent comorbidities. Copyright © 2011 by Lippincott Williams & Wilkins.
Lanoix J.-P.,Amiens University Hospital |
Gaudry S.,Bichat Claude Bernard University Hospital |
Flicoteaux R.,Bichat Claude Bernard University Hospital |
Ruimy R.,Bichat Claude Bernard University Hospital |
Wolff M.,Bichat Claude Bernard University Hospital
International Journal of Tuberculosis and Lung Disease | Year: 2014
BACKGROUND: Although tuberculosis (TB) is not a major public health issue in low-burden countries, severe cases are still a matter of concern. OBJECTIVE: To assess the risk factors for mortality due to TB in a low-burden setting. DESIGN: A retrospective study of 97 patients hospitalised with active TB in the intensive care unit (ICU) of the Bichat-Claude Bernard Hospital, Paris, France, from 2000 to 2009. RESULTS: The mean age was 47.4 ± 14.7 years; 40 patients were human immunodeficiency virus (HIV) infected, with a median CD4 cell count of 74 cells/mm3. The survival analysis showed that 21 patients died during their time in the ICU. The observed risk factors for ICU mortality were organ failure, high Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment scores, and concomitant non-tuberculous infection. In multivariate analysis, only SAPS II score was significantly associated with mortality. CONCLUSION: Risk factors identified in this study are different from those in high-burden countries, and were not associated with the site of TB disease. There was no difference in TB presentation between HIV-infected and non-HIV-infected patients, and HIV was not a mortality risk factor. Low-burden countries still experience high death rates due to severe TB. © 2014 The Union.
Cecile M.,Bichat Claude Bernard University Hospital |
Feugeas H.,Bichat Claude Bernard University Hospital
Alzheimer's Disease Research Journal | Year: 2011
The wide availibility of computed Xray tomography after the 1970s has allowed early enhancement of the hippocampal atrophy in Alzheimer's disease. More recently, three dimensional MR sequences have allowed identification of a more detailed and complex spatial pattern of mesiotemporal atrophy in this condition. Sole asessment of the hippocampus volume or any other single structure from the mesiotemporal lobe was not accurate at discriminating AD from normal aging, vascular cognitive impairment or Lewy bodies disease; conversely, the detailed spatial MR pattern of mesiotemporal atrophy now provides a macroscopic signature of AD. The severity of this complex MR atrophy parallels that of AD pathology; thus, as expected, it is already quite advanced by the time cognitive decline becomes clinically detectable. The currently used clinical definitions of AD lack any specific markers of AD and this pathognomic structural signature of Alzheimer pathology helps in vivo unmasking the pathogenic heterogeneity of such a clinically defined syndrome. The typical forms which combine concordant clinical and brain structural presentations are relatively unfrequent; late-onset Alzheimer's-like cognitive impairment frequently lacks any brain structural evidence of advanced Alzheimer's pathology but demonstrate an unexpected high frequency of neurologically "silent" cerebrovascular changes. Persistent errors in the diagnosis of vascular cognitive impairment have delayed focus on these cerebrovascular changes. However, recent advances in vascular cognitive impairment, use of functional rather than structural cerebrovascular MR examinations, now enhance the contribution of altered intracranial dynamics to the "Alzheimer's syndrome" and especially that of large artery stiffening. © 2011 Nova Science Publishers, Inc.
Delaroche L.,Bichat Claude Bernard University Hospital |
Yazbeck C.,Bichat Claude Bernard University Hospital |
Yazbeck C.,French Institute of Health and Medical Research |
Gout C.,Bichat Claude Bernard University Hospital |
And 3 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2013
Objective: Sperm morphology plays a significant role in assisted reproductive technologies and is associated with high implantation rates. The objective of this study was to evaluate the outcome of intracytoplasmic morphologically selected sperm injection (IMSI) after repeated failures of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques. Study design: In a prospective study in which couples acted as their own controls, 75 infertile couples were offered IMSI after at least two previous IVF or ICSI failures. The main outcome measures were embryo quality and number of blastocysts obtained. Results: The percentage of top quality embryos obtained at day 2 was increased in IMSI compared to IVF/ICSI cycles (89.8% versus 79.8%; p = 0.009). Extended embryo culture was possible in 41.3% of IMSI cycles versus 26.7% of IVF/ICSI cycles (p = 0.04), and the mean number of blastocysts obtained was higher in IMSI cycles (1.5 ± 1.9) than in IVF/ICSI cycles (1.0 ± 1.2) (p = 0.03). Moreover, IMSI resulted in clinical pregnancy and birth rates of respectively 29.3% and 18.6%. Conclusion: After two or three IVF/ICSI failures, IMSI seems to give better embryo quality and more blastocysts, which allow more embryo transfers at the blastocyst stage. This study supports the use of sperm ultramorphology examination as an independent test to be proposed after repeated IVF or ICSI failures. © 2012 Elsevier Ireland Ltd.