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Marseille, France

Pavord I.D.,University of Leicester | Korn S.,Mainz University Hospital | Howarth P.,University of Sfax | Bleecker E.R.,Center for Genomics and Personalized Medicine | And 4 more authors.
The Lancet | Year: 2012

Background Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway infl ammation. Early studies suggest that inhibition of eosinophilic airway infl ammation with mepolizumab- a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish effi cacy, safety, and patient characteristics associated with the response to mepolizumab. Methods We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic infl ammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 09% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratifi ed by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically signifi cant asthma exacerbations, which were defi ned as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506. Findings 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically signifi cant. The rate of clinically signifi cant exacerbations was 240 per patient per year in the placebo group, 124 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<00001), 146 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=00005), and 115 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<00001). Three patients died during the study, but the deaths were not deemed to be related to treatment. Interpretation Mepolizumab is an eff ective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. Funding GlaxoSmithKline.

Meneton P.,French Institute of Health and Medical Research | Kesse-Guyot E.,French National Conservatory of Arts and Crafts | Fezeu L.,French National Conservatory of Arts and Crafts | Galan P.,French National Conservatory of Arts and Crafts | And 2 more authors.
Journal of Hypertension | Year: 2013

OBJECTIVE: To evaluate habitual dietary intakes in patients with established hypertension, dyslipidemia and/or overweight. METHODS: A national sample of 6167 French free-living patients, aged 45-65 years, in whom daily food and nutrient intakes (24-h records) and clinical status were regularly monitored between 1994 and 2002. RESULTS: For each disorder, affected patients have reduced fat and energy intakes compared with nonaffected participants after adjustment for confounding factors. In addition, after further adjustment for energy intake, dyslipidemic patients eat less cheeses, sweets, eggs and appetizers, whereas overweight patients eat less bread and sweets, more yoghurts, vegetables, meats and poultries in comparison to their nonaffected counterparts. By contrast, hypertensive patients drink more wines and less milk, eat less yoghurts, fruits and vegetables, more processed meats than participants without hypertension. Nutrient intakes also reflect these distinctive eating patterns as shown by reduced carbohydrate intake and increased protein and mineral intakes in overweight patients and increased alcohol intake and decreased mineral intakes in hypertensives when compared with nonaffected participants. Among affected patients, antihypertensive and hypolipidemic drug treatments are not associated with additional differences in daily food and nutrient intakes except eggs that are consumed in smaller amounts by treated dyslipidemic patients. CONCLUSION: Hypertensive patients maintain an unhealthy eating pattern that tends to perpetuate their disorder in contrast to dyslipidemic or overweight patients who adopt more protective diets. The origin of this behavioural difference and poor adherence to practice guidelines between hypertensives and other cardiovascular risk patients needs to be investigated. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins.

Morgieve M.,French Institute of Health and Medical Research | N'diaye K.,French Institute of Health and Medical Research | Haynes W.I.A.,French Institute of Health and Medical Research | Granger B.,De Biostatistiques et dInformation Medicale bioSPIM | And 4 more authors.
Psychological Medicine | Year: 2014

Background Cognitive behavioural therapy (CBT) is a successful treatment of obsessive compulsive disorder (OCD). It is known to induce changes in cerebral metabolism; however, the dynamics of these changes and their relation to clinical change remain largely unknown, precluding the identification of individualized response biomarkers. Method In order to study the dynamics of treatment response, we performed systematic clinical and functional magnetic resonance imaging (fMRI) evaluation of 35 OCD patients immediately before a 3-month course of CBT, halfway through and at its end, as well as 6 months after. To sensitize fMRI probing, we used an original exposure task using neutral, generic and personalized obsession-inducing images. Results As expected, CBT produced a significant improvement in OCD. This improvement was continuous over the course of the therapy; therefore, outcome could be predicted by response at mid-therapy (r 2 = 0.67, p < 0.001). Haemodynamic response to the task was located in the anterior cingulate and orbitofrontal cortices and was stronger during exposure to personalized obsession-inducing images. In addition, both the anxiety ratings and the haemodynamic response to the obsession-inducing images in the anterior cingulate and the left but not the right orbitofrontal clusters decreased with symptom improvement. Interestingly, haemodynamic activity continued to decrease after stabilization of clinical symptoms. Conclusions Using an innovative and highly sensitive exposure paradigm in fMRI, we showed that clinical and haemodynamic phenotypes have similar time courses during CBT. Our results, which suggest that the initial CBT sessions are crucial, prompt us to investigate the anatomo-functional modifications underlying the very first weeks of the therapy. © Cambridge University Press 2013.

Adefurin A.,University of Nottingham | Sammons H.,University of Nottingham | Jacqz-Aigrain E.,Clinical Investigation Center | Choonara I.,University of Nottingham
Archives of Disease in Childhood | Year: 2011

Objective: To determine the safety of ciprofloxacin in paediatric patients in relation to arthropathy, any other adverse events (AEs) and drug interactions. Methods: A systematic search of MEDLINE, EMBASE, CINAHL, CENTRAL and bibliographies of relevant articles was carried out for all published articles, regardless of design, that involved the use of ciprofloxacin in any paediatric age group ≤17 years. Only articles that reported on safety were included. Results: 105 articles met the inclusion criteria and involved 16 184 paediatric patients. There were 1065 reported AEs (risk 7%, 95% CI 3.2% to 14.0%). The most frequent AEs were musculoskeletal AEs, abnormal liver function tests, nausea, changes in white blood cell counts and vomiting. There were six drug interactions (with aminophylline (4) and methotrexate (2)). The only drug related death occurred in a neonate who had an anaphylactic reaction. 258 musculoskeletal events occurred in 232 paediatric patients (risk 1.6%, 95% CI 0.9% to 2.6%). Arthralgia accounted for 50% of these. The age of occurrence of arthropathy ranged from 7 months to 17 years (median 10 years). All cases of arthropathy resolved or improved with management. One prospective controlled study estimated the risk of arthropathy as 9.3 (OR 95% CI 1.2 to 195). Pooled safety data of controlled trials in this review estimated the risk of arthropathy as 1.57 (OR 95% CI 1.26 to 1.97). Conclusion: Musculoskeletal AEs occur due to ciprofloxacin use. However, these musculoskeletal events are reversible with management. It is recommended that further prospective controlled studies should be carried out to evaluate the safety of ciprofloxacin, with particular focus on the risk of arthropathy.

Iordache L.,Jean Verdier Hospital | Launay O.,Clinical Investigation Center | Bouchaud O.,Avicenne Hospital | Jeantils V.,Jean Verdier Hospital | And 10 more authors.
Autoimmunity Reviews | Year: 2014

Objectives: 1) To describe autoimmune diseases (AD) in HIV-infected people, and 2) to perform a literature review concerning this issue. Design: 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. Results: The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm3. Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance.These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. Conclusion: In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use. © 2014 Elsevier B.V.

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