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PubMed | Royal Brompton & Harefield NHS Foundation Trust, Raymond Poincare University Hospital, University of Seville, Ludwig Maximilians University of Munich and 5 more.
Type: Review | Journal: International journal of molecular sciences | Year: 2016

Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease.


North K.N.,Murdoch Childrens Research Institute | North K.N.,University of Sydney | Wang C.H.,Driscoll Childrens Hospital | Clarke N.,University of Sydney | And 12 more authors.
Neuromuscular Disorders | Year: 2014

Over the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies. The International Standard of Care Committee for Congenital Myopathies performed a literature review and consulted a group of experts in the field to develop a summary of (1) the key features common to all forms of congenital myopathy and (2) the specific features that help to discriminate between the different genetic subtypes. The consensus statement was refined by two rounds of on-line survey, and a three-day workshop. This consensus statement provides guidelines to the physician assessing the infant or child with hypotonia and weakness. We summarise the clinical features that are most suggestive of a congenital myopathy, the major differential diagnoses and the features on clinical examination, investigations, muscle pathology and muscle imaging that are suggestive of a specific genetic diagnosis to assist in prioritisation of genetic testing of known genes. As next generation sequencing becomes increasingly used as a diagnostic tool in clinical practise, these guidelines will assist in determining which sequence variations are likely to be pathogenic. © 2013 The Authors.


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.


Tattevin P.,Pontchaillou University Hospital | Tattevin P.,University of Rennes 1 | Cremieux A.-C.,University of Versailles | Cremieux A.-C.,Raymond Poincare University Hospital | And 2 more authors.
Clinical Infectious Diseases | Year: 2014

Background. Concerns have recently emerged about the efficacy and the quality of antibacterial generic products approved for use in humans.Methods. We searched Medline and Embase for original research articles on antibacterial generic products published in English or French before July 2013.Results. We selected 37 original research articles: 15 on -lactams, 10 on glycopeptides, and 12 on other antibacterial agents. The majority of articles (73.0%) were published during 2008-2012. Study designs included analytical chemistry (n = 9), in vitro susceptibility studies (n = 14), animal experiments (n = 6, including 5 using the neutropenic mouse thigh infection model), and clinical studies in humans (n = 15). Of the 37 studies, 14 (37.8%) suggested that some generic products may be inferior to the innovator in terms of purity (n = 2), in vitro activity (n = 3), in vivo efficacy in experimental models (n = 4), clinical efficacy (n = 2), taste (n = 2), or compliance and acceptability in children (n = 1). The majority of in vitro studies (78.6%) found no significant difference between generic products and the innovator. Most (5/6) in vivo studies suggesting a difference between generic products and the innovator were performed in an animal model that is not validated for the evaluation of the efficacy of antibacterial agents. The level of evidence was constantly low in clinical studies.Conclusions. Published data on antibacterial generic products are limited and heterogeneous, thus precluding any attempt to generalize the study results. This systematic review suggests that additional evidence would be needed before considering a revision of the marketing authorization process for antibacterial generic products. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup. com.


Truelle J.-L.,Raymond Poincare University Hospital | Fayol P.,Service Of Psychorehabilitation Center Hospitalier Esquirol | Montreuil M.,Paris 8 University | Chevignard M.,Hopital National de Saint Maurice | Chevignard M.,University Pierre and Marie Curie
Current Opinion in Neurology | Year: 2010

Purpose of review: Despite being the main cause of death and disability in young adults, traumatic brain injury (TBI) is a rather neglected epidemic. Community integration of persons with TBI was, until recently, insufficiently informed by clinical research. Recent findings: To bridge the gap between rehabilitation and community re-entry, the first task is to assess the person, using TBI-specific outcome measures. The second task is to provide re-entry programs, the effectiveness of which is assessed by those measures, using well designed studies. There are very few such studies. However, there are some effective comprehensive programs and others which are specifically targeted dealing mainly with return to work, behavior, and family issues. The complex psychological and environmental components of the disability require individualized and often long-term care. Summary: For persons with severe TBI trying to achieve the best possible community integration a new semiology is required, not just limited to medical care, but also involving social and psychological care that is tailored to the needs of each individual and family, living within his/her environment. Currently, only a minority benefit from well validated programs. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Dinh A.,Raymond Poincare University Hospital | Salomon J.,Raymond Poincare University Hospital | Bru J.P.,Annecy General Hospital | Bernard L.,Raymond Poincare University Hospital | Bernard L.,University of Tours
Scandinavian Journal of Infectious Diseases | Year: 2012

Objective: To analyze the indications for and the efficacy of parenteral fosfomycin, especially against multidrug-resistant (MDR) and pan-resistant bacterial infections.Patients and methods: During a unique crisis in fosfomycin production, the supply of this antibiotic had to be carefully monitored in France over a 10-week period. One hundred and sixteen assessable patients were included in a prospective cohort study.Results: The main indications for use were osteoarthritis, lung infection, urinary tract infection, and bacteraemia. The 2 bacteria most frequently involved were Pseudomonas aeruginosa and methicillin-resistant Staphylococcus. MDR bacteria were seen in 71.5% (83/116) of cases, especially MDR P. aeruginosa (n = 28). Critical situations were common, with 44.0% (51/116) of hospitalizations occurring in an intensive care unit and 22.4% (26/116) of patients with septic shock. The overall outcome was favourable in 76.8% of cases (76/99 assessable patients).Conclusion: This study provided a unique opportunity to describe the use of fosfomycin and assess its efficacy, especially against MDR bacterial infections, even in critical situations. © 2012 Informa Healthcare.


Teterycz D.,University of Geneva | Ferry T.,University of Geneva | Lew D.,University of Geneva | Stern R.,University of Geneva | And 5 more authors.
International Journal of Infectious Diseases | Year: 2010

Background: Comparisons of different staphylococci in orthopedic implant infections have rarely been reported. In this study we assessed total joint arthroplasty infections and other orthopedic implant infections due to methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and coagulase-negative staphylococci (CoNS). Methods: This was a retrospective study performed at the Geneva University Hospitals for the period January 1996 to June 2008. Results: There were 44 infections due to MRSA, 58 due to MSSA, and 61 due to CoNS. Overall cure was achieved in 57% (25/44) of MRSA infections, 72% (42/58) of MSSA infections, and 82% (50/61) of CoNS infections, after a minimum follow-up of 1 year. In the subgroup of arthroplasty infections only, cure was achieved in 39% (7/18) of MRSA, 60% (15/25) of MSSA, and 77% (30/39) of CoNS episodes. In multivariate analysis, arthroplasty (odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6) and MRSA infections (OR 0.3, 95% CI 0.1-0.9) were inversely associated with overall cure for all implants. CoNS infection (OR 3.0, 95% CI 1.2-8.0) and the insertion of a new implant (OR 4.5, 95% CI 1.6-13.1) were associated with higher cure results. Methicillin resistance, immunosuppression, sex, age, duration of antibiotic therapy, one-stage revision, rifampin use, and total number of surgical interventions did not influence cure. MRSA-infected patients had more post-infection sequelae than patients with MSSA or CoNS (Chi-square test 13/44 vs. 93/119, OR 3.4, 95% CI 1.3-8.9, p= 0.004). Conclusions: In orthopedic implant infections, S. aureus is more virulent than CoNS. MRSA has the worst outcome and CoNS the best. © 2010 International Society for Infectious Diseases.


Perez C.,University of Geneva | Huttner A.,University of Geneva | Assal M.,University of Geneva | Bernard L.,University of Geneva | And 5 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2010

Objectives: No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (≤7 days) with that of patients receiving bursectomy plus longer-course antibiotic therapy (>7 days). Patients and methods: Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. Results: We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with ≤7 days, 8-14 days of antibiotic treatment (OR 0.6; 95% CI 0.1-2.9) or >14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). Conclusions: In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


PubMed | Raymond Poincare University Hospital and University of Versailles
Type: | Journal: European journal of neurology | Year: 2017

Respiratory disorders are a major cause of morbidity and mortality in multiple sclerosis (MS). Mainly reported in walking patients, they are poorly explored when walking is severely impaired. To characterize respiratory impairment in patients with advanced MS.From 2012 to 2015, patients with MS with an Expanded Disability Status Scale (EDSS) score of 7 who were referred for functional and rehabilitation evaluation underwent pulmonary function tests to study lung volumes, cough efficacy and respiratory muscle pressures.Among 73 patients with a median EDSS score of 8 [7.5; 8.5], 72.6% had impaired respiratory function with a mean vital capacity (VC) of 57.9 33.5% of theoretical value. Severe impairment (VC < 50%) was found for 34 (46.6%) patients. Cough was impaired in 45 (61.6%) patients, with a mean cough peak flow of 3.14 1.9 L/s and severe impairment (cough peak flow < 2.67 L/s) in 27 (37.0%) patients. Overall, the results suggested predominant expiratory muscle dysfunction and non-predominant diaphragm impairment. EDSS score was correlated with VC but not with any other clinical data.Restrictive respiratory failure is frequent in severely impaired patients with MS, predominantly involves expiratory muscles, does not involve diaphragm weakness and is associated with cough impairments.


PubMed | French Institute of Health and Medical Research and Raymond Poincare University Hospital
Type: | Journal: The AAPS journal | Year: 2017

This study aimed at describing the pharmacokinetics and the concentration-effect relationships of fludrocortisone and hydrocortisone on urinary sodium/potassium excretion in healthy volunteers. This was a placebo-controlled, randomized, double blind, crossover study, of oral fludrocortisone and intravenous hydrocortisone, given alone or in combination, in 12 healthy male volunteers. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics and pharmacokinetic-pharmacodynamic relationships on urinary sodium/potassium ratio for each drug. A one-compartment model was used to describe fludrocortisone and hydrocortisone pharmacokinetics. Mean plasma half-life was 1.40h (95%CI [0.80;2.10]) for fludrocortisone and 2.10h (95%CI [1.78;2.40]) for hydrocortisone. Clearance was 40.8L/h (95%CI [33.6;48]) for fludrocortisone and 30L/h (95%CI [25.3;34.7]) for hydrocortisone. An indirect response model was used to describe effects on urinary sodium/potassium ratio. Fludrocortisone plasma concentrations showed a wider inter-individual dispersion than hydrocortisone plasma concentrations. Urinary sodium/potassium ratio variability was also higher with fludrocortisone as compared to hydrocortisone. The plasma concentration of drug producing 50% of maximal inhibition of urinary sodium/potassium (IC

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