Clermont-Ferrand, France
Clermont-Ferrand, France

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Costedoat-Chalumeau N.,University of Paris Descartes | Pouchot J.,University of Paris Descartes | Guettrot-Imbert G.,University Of Clermont Ferrand | Leroux G.,University of Paris 13 | And 2 more authors.
Best Practice and Research: Clinical Rheumatology | Year: 2013

Adherence is defined as "the extent to which a person's behaviour coincides with medical or health advice." Poor adherence to therapeutic regimens is a common and expensive problem in patients with chronic diseases including systemic lupus erythematosus (SLE) and is associated with a higher risk of flares, morbidity, hospitalisations and poor renal outcome. Non-adherence to the treatment is multifactorial for most patients and varies according to unintentional or intentional patterns. The rates of non-adherence in SLE patients range from 3% to 76% depending on the assessment methods, which are all subject to limitations. Indeed, poor adherence to therapeutic regimens is difficult to evaluate. Two studies have shown that undetectable blood hydroxychloroquine (HCQ) concentration may be a simple, objective and reliable marker of non-adherence in SLE patients. The accurate diagnosis of non-adherence may prevent one from incorrectly interpreting disease manifestations as a lack of response. It may then avoid an unnecessary or even dangerous treatment escalation. © 2013 Elsevier Ltd. All rights reserved.


Leger J.-M.,University Hospital Pitie Salpetriere | Viala K.,University Hospital Pitie Salpetriere | Nicolas G.,University of Angers | Creange A.,University Hospital Henri Mondor | And 7 more authors.
Neurology | Year: 2013

Objective: To determine whether rituximab 375 mg/m2 was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy). Methods: Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) $4 and visual analog pain scale >4 or ataxia score $2. The primary outcome was mean change in ISS at 12 months. Results: Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m2 rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 ± 2.7 in the rituximab group, and 1.0 ± 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p = 0.027), the self-evaluation scale (p 5 0.016), and 2 subscores of the Short Form-36 questionnaire. Conclusions: Although primary outcome measures provide no evidence to support the use of rituximab in IgM anti-MAG demyelinating neuropathy, there were improvements in several secondary outcomes in per protocol analysis. Level of evidence: This study provides Class I evidence that rituximab is ineffective in improving ISS in patients with IgM anti-MAG demyelinating neuropathy. © 2013 American Academy of Neurology.


Pugazhendhi S.,Wellcome Trust Research Laboratory | Santhanam S.,Wellcome Trust Research Laboratory | Venkataraman J.,Government Stanley Medical College | Creveaux I.,University of Clermont Ferrand | Ramakrishna B.S.,Wellcome Trust Research Laboratory
Gene | Year: 2013

Background: Three mutations (two missense and one frameshift) in the NOD2 gene are associated with Crohn's disease (CD) in a proportion of patients with Crohn's disease in North America, Europe and Australia. These three mutations are not found in Indian patients with CD. We undertook new studies to identify polymorphisms in the NOD2 gene in the Indian population and to detect whether any of these were associated with inflammatory bowel disease (IBD) in this population. Methods: Individual exons of the NOD2 gene were amplified by PCR and subjected to denaturing high performance liquid chromatography (DHPLC) to detect heteroduplex formation. All 12 exons of the NOD2 gene were amplified and Sanger-sequenced to detect polymorphisms in the NOD2 gene. 310 patients with CD, 318 patients with ulcerative colitis (UC) and 442 healthy controls (HC) were recruited for association studies. DNA from these participants was evaluated for the identified eight polymorphisms by Sequenom analysis. Results: Heteroduplex formation was noted by DHPLC in exons 2 and 4 of the NOD2 gene. Sequencing of the entire NOD2 gene data revealed eight polymorphisms - rs2067085, rs2066842, rs2066843, rs1861759, rs2111235, rs5743266, rs2076753, and rs5743291 - of which the latter four were described for the first time in Indians. None of these polymorphisms was associated with CD. The SNPs rs2066842 and rs2066843 were in significant linkage disequilibrium. Both SNPs showed a significant association with UC (P = 0.03 and 0.04 respectively; odds ratio 1.44 and 1.41 respectively). Conclusion: Four NOD2 polymorphisms were identified for the first time in the Indian population. Of 8 NOD2 polymorphisms, none were associated with CD but two were weakly associated with UC. NOD2 polymorphisms do not play a major role in CD genesis in India. © 2012 Elsevier B.V.


Buscail H.,University Of Clermont Ferrand | Perrier S.,University Of Clermont Ferrand | Josse C.,University of Burgundy
Materials and Corrosion | Year: 2011

The Inconel 601 alloy oxidation was performed in air, in the temperature range 1000-1150°C, during 90h. Kinetic results show that the parabolic behavior is always followed in this temperature range. The Arrhenius plot of the kp values shows two different activation energies. Between 1000 and 1050°C the activation energy is Ea1=160±10kJ/mol. In the 1050-1150°C temperature range a higher value is calculated E a2=252±20kJ/mol. The Ea2 value and the X-ray diffraction (XRD) results and scanning electron microscope (SEM) energy dispersive X-ray spectroscopy (EDS) examinations are in accordance with a scale growth mechanism limited by a growing Cr2O3 scale acting as a diffusion barrier. In the 1000-1050°C temperature range the activation energy is lower and the structural analyses show that the oxide scale is not only composed of Cr2O3. Then, the oxide scale is composed of titanium oxides (TiO2 and Ti2Cr7O 17) and chromia mixed together. A doping effect of the chromia scale by titanium can be envisaged. Our results also show the presence of some Mn 1.5Cr1.5O4 at the external interface. This external subscale spalls off easily during cooling after the highest temperature oxidation tests. Nevertheless, XRD results and SEM-EDS observations show that the Cr2O3 scale remains very adherent on the substrate and can give a good oxidation protection. This good adherence can be related to the presence of a low amount of aluminum in the Inconel 601 alloy composition. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gremeaux V.,Pole reeducation readaptation | Benaim C.,Pole reeducation readaptation | Poiraudeau S.,Service de reeducation et readaptation | Herisson C.,Montpellier University Hospital Center | And 2 more authors.
Joint Bone Spine | Year: 2013

Objectives: To evaluate the medium-term impact of education workshops on low back pain (LBP) in the setting of a thermal spa on: fear-avoidance beliefs, disability, pain, and satisfaction. Methods: Randomized prospective alternate-month design-type study including 360 individuals having thermal spa therapy for LBP: 188 in the intervention group (three standardized education workshops lasting 1. h. 30 each and usual thermal therapy for 3. weeks), 172 in the control group (usual thermal therapy and non-standardized verbal information). The principal analysis criterion was the difference in the fear-avoidance beliefs (physical FABQ) score between baseline and 6. months after the therapy; secondary criteria were: evolution of disability (Quebec Scale) and pain intensity (Visual Analogue Scale), and satisfaction with the information received. Results: There was a significant reduction in the physical FABQ score at 6. months (. P<. 0.05), and this reduction was more marked in the intervention group (-5.8. ±. 0.7 vs. -2. ±. 0.72. points out of 24; P<. 0.0001). Disability and pain significantly decreased in both groups (. P<. 0.05), with no difference between groups. These workshops also had a significant effect on satisfaction with the information received. Conclusion: Standardized education workshops have a beneficial impact on LBP and contribute to an improvement in the medical services provided during spa therapy by reducing the effect of fear-avoidance beliefs as well as relieving pain. Extending the use of such workshops could contribute to enhance the positive impact of spa therapy in the management of chronic disabling diseases. © 2012 Société française de rhumatologie.


Futier E.,Departement dAnesthesie et Reanimation | Futier E.,University Of Clermont Ferrand | Constantin J.-M.,Departement dAnesthesie et Reanimation | Constantin J.-M.,University Of Clermont Ferrand | And 18 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Lung-protective ventilation with the use of low tidal volumes and positive end-expiratory pressure is considered best practice in the care of many critically ill patients. However, its role in anesthetized patients undergoing major surgery is not known. METHODS: In this multicenter, double-blind, parallel-group trial, we randomly assigned 400 adults at intermediate to high risk of pulmonary complications after major abdominal surgery to either nonprotective mechanical ventilation or a strategy of lung-protective ventilation. The primary outcome was a composite of major pulmonary and extrapulmonary complications occurring within the first 7 days after surgery. RESULTS: The two intervention groups had similar characteristics at baseline. In the intention-to-treat analysis, the primary outcome occurred in 21 of 200 patients (10.5%) assigned to lung-protective ventilation, as compared with 55 of 200 (27.5%) assigned to nonprotective ventilation (relative risk, 0.40; 95% confidence interval [CI], 0.24 to 0.68; P=0.001). Over the 7-day postoperative period, 10 patients (5.0%) assigned to lung-protective ventilation required noninvasive ventilation or intubation for acute respiratory failure, as compared with 34 (17.0%) assigned to nonprotective ventilation (relative risk, 0.29; 95% CI, 0.14 to 0.61; P=0.001). The length of the hospital stay was shorter among patients receiving lung-protective ventilation than among those receiving nonprotective ventilation (mean difference, -2.45 days; 95% CI, -4.17 to -0.72; P=0.006). CONCLUSIONS: As compared with a practice of nonprotective mechanical ventilation, the use of a lung-protective ventilation strategy in intermediate-risk and high-risk patients undergoing major abdominal surgery was associated with improved clinical outcomes and reduced health care utilization. (IMPROVE ClinicalTrials.gov number, NCT01282996.). Copyright © 2013 Massachusetts Medical Society.


Peyrot N.,University of Reunion Island | Thivel D.,University of Clermont Ferrand | Isacco L.,University of Clermont Ferrand | Morin J.-B.,Jean Monnet University | And 2 more authors.
Medicine and Science in Sports and Exercise | Year: 2012

Purpose: This study tested the hypothesis that the increase in walking economy (i.e., decrease in net metabolic rate per kilogram) after weight loss in obese adolescents is induced by a lower metabolic rate required to support the lower body weight and maintain balance during walking. Methods: Sixteen obese adolescent boys and girls were tested before and after a weight reduction program. Body composition and oxygen uptake while standing and walking at four preset speeds (0.75, 1, 1.25, and 1.5 m•s) and at the preferred speed were quantified. Net metabolic rate and gross metabolic cost of walking-versus-speed relationships were determined. A three-compartment model was used to distinguish the respective parts of the metabolic rate associated with standing (compartment 1), maintaining balance and supporting body weight during walking (compartment 2), and muscle contractions required to move the center of mass and limbs (compartment 3). Results: Standing metabolic rate per kilogram (compartment 1) significantly increased after weight loss, whereas net metabolic rate per kilogram during walking decreased by 9% on average across speeds. Consequently, the gross metabolic cost of walking per unit of distance-versus-speed relationship and hence preferred walking speeds did not change with weight loss. Compartment 2 of the model was significantly lower after weight loss, whereas compartment 3 did not change. Conclusions: The model showed that the improvement in walking economy after weight loss in obese adolescents was likely related to the lower metabolic rate of the isometric muscular contractions required to support the lower body weight and maintain balance during walking. Contrastingly, the part of the total metabolic rate associated with muscle contractions required to move the center of mass and limbs did not seem to be related to the improvement in walking economy in weight-reduced individuals. © 2012 by the American College of Sports Medicine.


Coutant F.,University of Clermont Ferrand
Nature Reviews Rheumatology | Year: 2016

Dendritic cells (DCs) are central regulators of the balance between immunity and tolerance, and alteration of the specialized DC system is a common feature of both systemic and tissue-specific autoimmune diseases. Increasing evidence indicates that the heterogeneity and the remarkable functional diversity of DC subsets might be differentially affected in autoimmune disorders, which accounts for different pathologies. This Review discusses recent findings that support this concept and provides a new conceptual overview of the altered function and distribution of DCs in autoimmune disorders. The discussion will focus on systemic lupus erythematosus — a prototype of a multi-organ disease — as well as rheumatoid arthritis and idiopathic inflammatory myopathies, pathologies characterized by tissue-specific lesions. Studies on these diseases have revealed common and disease-specific changes in DC distribution and in critical DC functions, such as phagocytosis, cytokine secretion and migration. An improved understanding of the roles of altered DC distribution and/or disturbed key functions in these autoimmune diseases will pave the way for the development of new therapies aiming at reducing immunogenicity and at enhancing the tolerogenic capacity of DCs. Although some tolerogenic DCs have already been introduced in the clinic, the successful translation of other DC-based therapies will require considerable research efforts. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Macaire J.-J.,University of Tours | Fourmont A.,University of Tours | Argant J.,University of Lyon | Breheret J.-G.,University of Tours | And 2 more authors.
Holocene | Year: 2010

Minimum rates of solid (SSY) and dissolved (DSY) sediment yield (SY) were evaluated in t/km2 per yr from sediments stored in the Sarliève palaeolake (French Massif Central) for seven phases of the Lateglacial and Holocene up to the seventeenth century. The catchment (29 km2), mainly formed of limestones and marls, is located in an area rich in archaeological sites in the Massif Central. The respective impacts of human activities and climate on SY were compared by quantification of human settlements through archaeological survey and palynological data. During the Lateglacial and early Holocene up to about 7500 yr cal. BP, variations in SSY and DSY rates were mainly related to climate change with higher rates during colder periods (Younger Dryas and Preboreal) and lower rates during warmer periods (Bölling-Alleröd and Boreal). However, CF1 tephra fallout induced a sharp increase in SY during the Alleröd. During the middle and late Holocene after 7500 yr cal. BP, SSY and DSY greatly increased (by factors of 6.5 and 2.8, respectively), particularly during the Final Neolithic at about 5300 yr cal. BP when the climate became cooler and more humid. After this date, at least 75% of the SSY increase and more than 90% of the DSY increase resulted from human activities, but SSY rates showed little variation during Protohistoric and Historic Times up to the seventeenth century. SSY and DSY rates and DSY/SSY ratio indicate that catchment soils began to form during the Lateglacial and Preboreal, thickened considerably during the Boreal and Atlantic, finally thinning (rejuvenation) mainly as the result of human-induced erosion during the sub-Boreal and sub-Atlantic. Increased mechanical erosion during the late Holocene also induced an increase in chemical erosion. © The Author(s) 2010.


Futier E.,Montpellier University | Futier E.,University of Clermont Ferrand | Constantin J.-M.,University of Clermont Ferrand | Jaber S.,Montpellier University
Minerva Anestesiologica | Year: 2014

Postoperative pulmonary and extrapulmonary complications adversely affect clinical outcomes and healthcare utilization, so that prevention has become a measure of the quality of perioperative care. Mechanical ventilation is an essential support therapy to maintain adequate gas exchange during general anesthesia for surgery. Mechanical ventilation using high tidal volume (VT) (between 10 and 15 mL/kg) has been historically encouraged to prevent hypoxemia and atelectasis formation in anesthetized patients undergoing abdominal and thoracic surgery. However, there is accumulating evidence from both experimental and clinical studies that mechanical ventilation, especially the use of high VT and plateau pressure, may potentially aggravate or even initiate lung injury. Ventilator-associated lung injury can result from cyclic alveolar overdistension of non-dependent lung tissue, and repetitive opening and closing of dependent lung tissue resulting in ultrastructural damage at the junction of closed and open alveoli. Lung-protective ventilation, which refers to the use of lower VT and limited plateau pressure to minimize overdistension, and positive end-expiratory pressure to prevent alveolar collapse at end-expiration, was shown to improve outcome in critically ill patients with acute respiratory distress syndrome (ARDS). It has been recently suggested that this approach might also be beneficial in a broader population, especially in critically ill patients without ARDS at the onset of mechanical ventilation. There is, however, little evidence regarding a potential beneficial effect of lung protective ventilation during surgery, especially in patients with healthy lungs. Although surgical patients are frequently exposed to much shorter periods of mechanical ventilation, this is an important gap in knowledge given the number of patients receiving mechanical ventilation in the operating room. This review developed the benefits of lung protective ventilation during surgery and general anesthesia and offers some recommendations for mechanical ventilation in the surgical context.

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