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Murviel-lès-Montpellier, France

Kamar N.,Toulouse University Hospital Center | Kamar N.,French Institute of Health and Medical Research | Kamar N.,University Paul Sabatier | Izopet J.,French Institute of Health and Medical Research | And 26 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia. METHODS: We examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients). Ribavirin therapy was initiated a median of 9 months (range, 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range, 29 to 1200), which was equivalent to 8.1 mg per kilogram of body weight per day (range, 0.6 to 16.3). Patients received ribavirin for a median of 3 months (range, 1 to 18); 66% of the patients received ribavirin for 3 months or less. RESULTS: All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3). At the end of therapy, HEV clearance was observed in 95% of the patients. A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped. A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78%). A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period. A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response. Anemia was the main identified side effect and required a reduction in ribavirin dose in 29% of the patients, the use of erythropoietin in 54%, and blood transfusions in 12%. CONCLUSIONS: This retrospective, multicenter study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients. Copyright © 2014 Massachusetts Medical Society.

Gottenberg J.-E.,University of Strasbourg | Dayer J.-M.,University of Geneva | Lukas C.,Lapeyronie hospital | Ducot B.,University Paris - Sud | And 6 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: To identify a specific pattern of serum cytokines that correlates with the diagnosis, activity and severity of rheumatoid arthritis (RA) in patients with early RA as well as with the level of serum markers of B cell activation. Methods: Serum interleukin (IL)-1β, IL-1 receptor antagonist (IL1-Ra), IL-2, IL-4, IL-6, IL-10, IL-17, IL-21, monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor α and interferon γ levels were measured in the (ESPOIR) Etude et Suivi des POlyarthrites Indifférenciées Récentes early arthritis cohort, which included patients with at least two swollen joints for >6 weeks and <6 months, and no previous corticosteroids or disease-modifying antirheumatic drugs. Serum cytokine levels were compared between patients who met the 1987 American College of Rheumatology criteria for RA (n=578) or had undifferentiated arthritis (UA, n=132) at the 1-year follow-up visit. Results: Serum IL-6 and IL-21 were the only cytokines that discriminated RA from UA on univariate analysis. IL-6 level was associated with RA, whereas erythrocyte sedimentation rate and C-reactive protein were not. Higher proportions of rheumatoid factor and anticyclic citrullinated protein (CCP) positivity, levels of markers of B cell activation, and a higher frequency of rapid radiographic progression were observed in patients with RA with detectable IL-6 or IL-21. Multivariate analysis associated IL-6 and anti-CCP levels with radiographic erosions at enrolment with 1-year radiographic progression. Conclusion: Serum IL-6 concentration is greater in RA than in UA. Increase in serum IL-6 and IL-21 levels is associated with markers of B cell activation, and IL-6 is associated with radiographic progression in patients with RA.

Monnier L.,Institute of Clinical Research of Montpellier i | Wojtusciszyn A.,Lapeyronie hospital | Colette C.,Institute of Clinical Research of Montpellier i | Owens D.,University of Cardiff
Diabetes Technology and Therapeutics | Year: 2011

Background: The present study was designed to define the relative contributions of glucose variability and ambient glycemia to the incidence of asymptomatic hypoglycemia in type 2 diabetes. Methods: Two hundred twenty-two persons with type 2 diabetes were divided into three groups: Group I (n=53) on insulin sensitizers alone, Group II (n=87) on oral hypoglycemic agents (OHAs) to include at least one insulin secretagogue, and Group III (n=82) on insulin alone or in combination with OHAs. Ambient mean glucose concentration (MG) values (in mmol/L) and glycemic variability (SD around the mean glucose value) (in mmol/L) or mean amplitude of glycemic excursions (in mmol/L) were assessed by a continuous glucose monitoring system. Asymptomatic hypoglycemia was recorded over a 48-h period. Poisson regression analysis was used for assessing the potential predictors of hypoglycaemia. Results: The best model fit was obtained with the two following explanatory variables: MG and SD. Hypoglycemia frequency was negatively associated with MG and positively with SD: Log (number of hypoglycemia episodes)=1.37-(0.72×MG)+(1.33×SD). Odds ratios (95% confidence interval) for hypoglycemic risk were significantly different from 1 for MG at 0.96 (0.95-0.97) (P<0.0001) and for SD at 1.08 (1.06-1.10) (P<0.0001). In addition, the risk for hypoglycemia was completely or virtually eliminated when the SD was <1.7mmol/L irrespective of the ambient glucose level and treatment modality. Conclusions: As the risk of asymptomatic hypoglycemia increases in the presence of increased glucose variability, avoidance of excess glucose fluctuations should be an important consideration for either reducing or preventing the risk of hypoglycemia in type 2 diabetes. © 2011, Mary Ann Liebert, Inc.

Dougados M.,University of Paris Descartes | Braun J.,Rheumazentrum Ruhrgebiet | Szanto S.,Debrecen University | Combe B.,Lapeyronie hospital | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: Patients with advanced ankylosing spondylitis (AS) experience disability because of reduced spinal mobility and pulmonary function impairment. This placebo-controlled study evaluated the effect of etanercept (ETN) in patients with advanced AS. Methods: A multicentre randomised double-blind placebo-controlled trial of 12 weeks' duration was performed. Patients had definite (modified New York criteria), active (Bath AS Disease Activity Index (BASDAI) ≥40), severe (radiological intervertebral bridges) AS refractory to non-steroidal anti-inflammatory drugs and were antitumour necrosis factor naive. They were treated with ETN 50 mg once weekly or identical placebo (PBO). Results: Of the 95 patients screened, 82 were randomised to receive ETN (n=39) or PBO (n=43). At baseline the disease was active (mean BASDAI 61.0±13.4, C reactive protein (CRP) 20.7±25.5 mg/l) and severe (mean Bath AS Metrology Index (BASMI) 5.7±1.3, mSASSS 36.5±20.5);forced pulmonary vital capacity (FVC) was 3.3±0.7 l. Improvement in BASDAI (normalised net incremental area under the curve between baseline and week 12, primary end point) was significantly greater in the ETN group than in the PBO group (-19.8±16.5 vs-11.0±16.4, p=0.019). Moreover, at week 12, ETN gave better results than PBO for the BASDAI (-26.4±19.7 vs -14.4±19.7;p=0.008), total back pain (-29.2±24.0 vs-14.9±24.0;p=0.010), BASFI (-21.7±17.6 vs-10.1±17.6;p=0. 004), BASMI (-0.6±0.6 vs -0.2±0.6;p=0.011), CRP level (-15.7±14.2 vs -1.3±14.2;p<0.001) and FVC (+160±280 ml vs -20±280 ml;p=0.006). Conclusions: ETN has short-term efficacy for patients with advanced AS, as was previously reported for less advanced disease. The efficacy is observed for the main symptoms (pain) and on markers of inflammation (CRP), as well as disease severity in terms of spinal mobility and pulmonary function.

Thomas E.N.,Lapeyronie hospital | Blotman F.,Lapeyronie hospital
Rheumatology International | Year: 2010

The objective of the study was to determine the current evidence to support guidelines for aerobic exercise (AE) and fibromyalgia (FM) in practice, and to outline specific research needs in these areas. Data sources consisted of a PubMed search, 2007 Cochrane Data Base Systematic review, 2008 Ottawa panel evidence-based clinical practice guidelines, as well as additional references found from the initial search. Study selection included randomized clinical trials that compared an aerobic-only exercise intervention (land or pool based) with an untreated control, a non-exercise intervention or other exercise programs in patients responding to the 1990 American College of Rheumatology criteria for FM. The following outcome data were obtained: pain, tender points, perceived improvement in FM symptoms such as the Fibromyalgia Impact Questionnaire total score (FIQ), physical function, depression (e.g., Beck Depression Inventory, FIQ subscale for depression), fatigue and sleep were extracted from 19 clinical trials that considered the effects of aerobic-only exercise in FM patients. Data synthesis shows that there is moderate evidence of important benefit of aerobic-only exercise in FM on physical function and possibly on tender points and pain. It appears to be sufficient evidence to support the practice of AE as a part of the multidisciplinary management of FM. However, future studies must be more adequately sized, homogeneously assessed, and monitored for adherence, to draw definitive conclusions. © Springer-Verlag 2009.

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