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University of Technology of Compiègne, France

Nseir S.,University Hospital of Lille | Makris D.,University of Thessaly | Mathieu D.,University Hospital of Lille | Durocher A.,University Hospital of Lille | Marquette C.,University Hospital of Nice
Critical Care | Year: 2010

Introduction: Sedative and analgesic medications are routinely used in mechanically ventilated patients. The aim of this review is to discus epidemiologic data that suggest a relationship between infection and sedation, to review available data for the potential causes and pathophysiology of this relationship, and to identify potential preventive measures.Methods: Data for this review were identified through searches of PubMed, and from bibliographies of relevant articles.Results: Several epidemiologic studies suggested a link between sedation and ICU-acquired infection. Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Furthermore, experimental evidence coming from studies both in humans and animals suggest that sedatives and analgesics present immunomodulatory properties that might alter the immunologic response to exogenous stimuli. Clinical studies comparing different sedative agents do not provide evidence to recommend the use of a particular agent to reduce ICU-acquired infection rate. However, sedation strategies aiming to reduce the duration of mechanical ventilation, such as daily interruption of sedatives or nursing-implementing sedation protocol, should be promoted. In addition, the use of short acting opioids, propofol, and dexmedetomidine is associated with shorter duration of mechanical ventilation and ICU stay, and might be helpful in reducing ICU-acquired infection rates.Conclusions: Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, microcirculatory effects, and immunomodulatory effects are main mechanisms by which sedation may favour infection in critically ill patients. Future studies should compare the effect of different sedative agents, and the impact of progressive opioid discontinuation compared with abrupt discontinuation on ICU-acquired infection rates. © 2010 Nseir et al.; licensee BioMed Central Ltd.

Godefroy O.,University Hospital of Amiens | Azouvi P.,University Hospital of Garches | Robert P.,University Hospital of Nice | Roussel M.,University Hospital of Amiens | And 2 more authors.
Annals of Neurology | Year: 2010

Objective: Disorders of executive functions are among the most frequent cognitive deficits, but they remain poorly defined and are subject to heterogeneous assessment. To address this major issue, the Groupe de Réflexion sur l'Evaluation des Fonctions Exécutives (GREFEX) group has proposed criteria for behavioral and cognitive dysexecutive syndromes and has designed a battery including a specific heteroquestionnaire and 7 cognitive tests. We investigated the frequency of behavioral and cognitive dysexecutive disorders in patients suffering from various diseases and the association of these disorders with loss of autonomy. Methods A total of 461 patients aged between 16 and 90 years with severe traumatic brain injury, stroke, mild cognitive impairment, Alzheimer disease, multiple sclerosis, and Parkinson disease were recruited into this prospective cohort study by 21 centers between September 2003 and June 2006. Behavioral and cognitive dysexecutive disorders were examined using the GREFEX battery. Results A dysexecutive syndrome was observed in 60% of patients, concerning both behavioral and cognitive domains in 26% and dissociated in 34%. All behavioral and cognitive dysexecutive disorders discriminated (p = 0.001, all) patients from controls. The pattern of cognitive syndrome differed (p = 0.0001) according to the disease. Finally, behavioral (odds ratio [OR], 4.6; 95% confidence interval [CI], 2. 3-9.1; p = 0.0001) and cognitive (OR, 3.36; 95% CI, 1.7-6.6; p = 0.001) dysexecutive syndromes and Mini Mental State Examination score (OR, 0.79; 95% CI, 0.68-0.91; p = 0.002) were independent predictors of loss of autonomy. Interpretation This study provided criteria of dysexecutive syndrome and showed that both behavioral and cognitive syndromes contribute to loss of autonomy. Profiles vary across patients and diseases, and therefore systematic assessment of behavioral and cognitive disorders in reference to diagnostic criteria is needed. Copyright © 2010 American Neurological Association.

Passeron T.,University Hospital of Nice
Journal of the European Academy of Dermatology and Venereology | Year: 2013

Melasma is an acquired, symmetrical hypermelanosis of the face. The pathogenesis of melasma is complex and the treatment is often challenging with frequent relapses. Genetic background, exposure to ultraviolet radiation, and female sex hormones are classical influencing factors. To the light of the recent literature, other factors could promote melasma lesions. Moreover, there are increasing evidences showing that melanocytes are not the only cells involved, and that other players probably have a key role in the development and the relapses of melasma. Identifying those associated factors should provide new targets for a more efficient treatment of melasma and a better prevention of the relapses. © 2012 The Author.

Paul C.,University Paul Sabatier | Lacour J.-P.,University Hospital of Nice | Tedremets L.,Medicum Ltd | Kreutzer K.,Stadtische Kliniken Bielefeld | And 5 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Background Secukinumab is a fully human anti-interleukin-17A monoclonal antibody. Objective Determine the efficacy, safety and usability of secukinumab administered via autoinjector/pen. Methods This phase III trial randomized subjects with moderate to severe plaque psoriasis to secukinumab 300 mg, 150 mg or placebo self-injection once weekly to Week 4, then every 4 weeks. Co-primary end points at Week 12 were ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) and clear/almost clear skin by investigator's global assessment 2011 modified version (IGA mod 2011 0/1). Secondary end points included autoinjector usability, assessed by successful, hazard-free self-injection and subject-reported acceptability on Self-Injection Assessment Questionnaire. Results Week 12 PASI 75 and IGA mod 2011 0/1 responses were superior with secukinumab 300 mg (86.7% and 73.3%, respectively) and 150 mg (71.7% and 53.3%, respectively) vs. placebo (3.3% and 0%, respectively) (P < 0.0001 for all). All subjects successfully self-administered treatment at Week 1, without critical use-related hazards. Subject acceptability of autoinjector was high throughout 12 weeks. Adverse events were higher with secukinumab (300 mg, 70.0%; 150 mg, 63.9%) vs. placebo (54.1%), with differences largely driven by mild/moderate nasopharyngitis. Conclusion Secukinumab delivered by autoinjector/pen is efficacious, well-tolerated and associated with high usability in moderate to severe plaque psoriasis. © 2014 European Academy of Dermatology and Venereology.

Sciurba F.C.,University of Pittsburgh | Ernst A.,Beth Israel Deaconess Medical Center | Herth F.J.F.,University of Heidelberg | Strange C.,Medical University of South Carolina | And 6 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: Endobronchial valves that allow air to escape from a pulmonary lobe but not enter it can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with pulmonary hyperinflation related to advanced emphysema. METHODS: We compared the safety and efficacy of endobronchial-valve therapy in patients with heterogeneous emphysema versus standard medical care. Efficacy end points were percent changes in the forced expiratory volume in 1 second (FEV1) and the 6-minute walk test on intention-to-treat analysis. We assessed safety on the basis of the rate of a composite of six major complications. RESULTS: Of 321 enrolled patients, 220 were randomly assigned to receive endobronchial valves (EBV group) and 101 to receive standard medical care (control group). At 6 months, there was an increase of 4.3% in the FEV1 in the EBV group (an increase of 1.0 percentage point in the percent of the predicted value), as compared with a decrease of 2.5% in the control group (a decrease of 0.9 percentage point in the percent of the predicted value). Thus, there was a mean between-group difference of 6.8% in the FEV1 (P = 0.005). Roughly similar between-group differences were observed for the 6-minute walk test. At 12 months, the rate of the complications composite was 10.3% in the EBV group versus 4.6% in the control group (P = 0.17). At 90 days, in the EBV group, as compared with the control group, there were increased rates of exacerbation of chronic obstructive pulmonary disease (COPD) requiring hospitalization (7.9% vs. 1.1%, P = 0.03) and hemoptysis (6.1% vs. 0%, P = 0.01). The rate of pneumonia in the target lobe in the EBV group was 4.2% at 12 months. Greater radiographic evidence of emphysema heterogeneity and fissure completeness was associated with an enhanced response to treatment. CONCLUSIONS: Endobronchial-valve treatment for advanced heterogeneous emphysema induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation. (Funded by Pulmonx; ClinicalTrials.gov number, NCT00129584.) Copyright © 2010 Massachusetts Medical Society.

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