Groupe Hospitalier Of Linstitut Catholique Lillois

Lille, France

Groupe Hospitalier Of Linstitut Catholique Lillois

Lille, France

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Hezode C.,University Paris Est Creteil | Fontaine H.,University of Paris Descartes | Dorival C.,University Pierre and Marie Curie | Zoulim F.,University of Lyon | And 32 more authors.
Gastroenterology | Year: 2014

Background & Aims We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. Methods In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral responses 12 weeks after therapy and safety. This observational study did not allow for direct comparison of the 2 regimens. Results Among patients given telaprevir, 74.2% of relapsers, 40.0% of partial responders, and 19.4% of null responders achieved SVR12. Among those given boceprevir, 53.9% of relapsers, 38.3% of partial responders, and none of the null responders achieved SVR12. In multivariate analysis, factors associated with SVR12 included prior response to treatment response, no lead-in phase, HCV subtype 1b (vs 1a), and baseline platelet count greater than 100,000/mm3. Severe adverse events occurred in 49.9% of cases, including liver decompensation, severe infections in 10.4%, and death in 2.2%. In multivariate analysis, baseline serum albumin level less than 35 g/L and baseline platelet counts of 100,000/mm3 or less predicted severe side effects or death. Conclusions Relatively high percentages of real-life, treatment-experienced patients with HCV genotype 1 infection and cirrhosis respond to the combination of peginterferon and ribavirin with telaprevir or boceprevir. However, side effects are frequent and often severe. Baseline levels of albumin and platelet counts can be used to guide treatment decisions. number: NCT01514890. © 2014 by the AGA Institute.

Thevenon J.,Center de Genetique et Center de Reference Anomalies du Developpement et Syndromes Malformatifs | Callier P.,Laboratoire Of Cytogenetique | Andrieux J.,Cytogenetique | Delobel B.,Groupe Hospitalier Of Linstitut Catholique Lillois | And 19 more authors.
European Journal of Human Genetics | Year: 2013

Speech sound disorders are heterogeneous conditions, and sporadic and familial cases have been described. However, monogenic inheritance explains only a small proportion of such disorders, in particular in cases with childhood apraxia of speech (CAS). Deletions of <5Mb involving the 12p13.33 locus is one of the least commonly deleted subtelomeric regions. Only four patients have been reported with such a deletion diagnosed with fluorescence in situ hybridisation telomere analysis or array CGH. To further delineate this rare microdeletional syndrome, a French collaboration together with a search in the Decipher database allowed us to gather nine new patients with a 12p13.33 subtelomeric or interstitial rearrangement identified by array CGH. Speech delay was found in all patients, which could be defined as CAS when patients had been evaluated by a speech therapist (5/9 patients). Intellectual deficiency was found in 5/9 patients only, and often associated with psychiatric manifestations of various severity. Two such deletions were inherited from an apparently healthy parent, but reevaluation revealed abnormal speech production at least in childhood, suggesting variable expressivity. The ELKS/ERC1 gene, which encodes for a synaptic factor, is found in the smallest region of overlap. These results reinforce the hypothesis that deletions of the 12p13.33 locus may be responsible for variable phenotypes including CAS associated with neurobehavioural troubles and that the presence of CAS justifies a genetic work-up. © 2013 Macmillan Publishers Limited. All rights reserved.

Hezode C.,French Institute of Health and Medical Research | Fontaine H.,French Institute of Health and Medical Research | Dorival C.,University Pierre and Marie Curie | Larrey D.,Liver Unit IRB INSERM1040 | And 32 more authors.
Journal of Hepatology | Year: 2013

Background & Aims In phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme. Methods 674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16. Results A high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic decompensation) (6.4%), and a difficult management of anaemia (erythropoietin and transfusion use in 50.7% and 12.1%) were observed. Independent predictors of anaemia <8 g/dl or blood transfusion were: female gender (OR 2.19, 95% CI 1.11-4.33, p = 0.024), no lead-in phase (OR 2.25, 95% CI 1.15-4.39, p = 0.018), age ≥65 years (OR 3.04, 95% CI 1.54-6.02, p = 0.0014), haemoglobin level (≤12 g/dl for females, ≤13 g/dl for males) (OR 5.30, 95% CI 2.49-11.5, p = 0.0001). Death or severe complications were related to platelets count ≤100,000/mm3 (OR 3.11, 95% CI 1.30-7.41, p = 0.0105) and albumin <35 g/dl (OR 6.33, 95% CI 2.66-15.07, p = 0.0001), with a risk of 44.1% in patients with both. However, the on-treatment virological response was high. Conclusions The safety profile was poor and patients with platelet count ≤100,000/mm3 and serum albumin <35 g/L should not be treated with the triple therapy. © 2013 European Association for the Study of the Liver.

PubMed | Groupe Hospitalier Of Linstitut Catholique Lillois, Bordeaux University Hospital Center, CHU de Hautepierre, Center Hospitalier and 13 more.
Type: Journal Article | Journal: Journal of medical genetics | Year: 2014

Intellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation.We report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases.We identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders.With a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes implicated in ID and autism.

Charkaluk M.L.,French Institute of Health and Medical Research | Charkaluk M.L.,Groupe Hospitalier Of Linstitut Catholique Lillois | Charkaluk M.L.,University Pierre and Marie Curie | Truffert P.,French Institute of Health and Medical Research | And 7 more authors.
Early Human Development | Year: 2011

Aim: To study the predictive value of a developmental assessment at 2. years corrected age (CA) for schooling at age 8 in children born very preterm and free of disability or delay; to identify other factors associated with schooling in this population. Methods: 244 children born before 33. weeks in 1997, part of the population-based EPIPAGE cohort study, free of disability or delay, had their developmental quotient (DQ) evaluated with the Brunet-Lezine scale at 2. years CA. The mental processing composite (MPC) score was evaluated at age 5 with the K-ABC battery. Data on schooling were obtained at age 8 by postal questionnaire. Schooling was considered appropriate if the child was attending age-appropriate grade level in a regular classroom environment without support at school. Results: Schooling was appropriate for 172 (70%) children. The predictive value of a DQ ≥ 100 for appropriate schooling was 0.80 [0.75;0.85]. In children with a DQ at age 2 < 100, schooling varied significantly according to their MPC score at age 5 whereas it didn't in children with a DQ ≥ 100. In multivariate analysis, the rate of appropriate schooling was significantly related to global DQ at age 2 (p< 0.01), gestational age ≥ 29 weeks (p< 0.05), head circumference at age 2 (p< 0.05) and mother's educational level (p< 0.05). Conclusion: A DQ ≥ 100 cannot be solely used for the prediction of appropriate schooling at age 8. Mother's educational level, gestational age and head circumference at age 2 could be taken account. These factors could be used to individualise follow-up. © 2011 Elsevier Ltd.

Rossez Y.,University of Lille Nord de France | Rossez Y.,French National Center for Scientific Research | Maes E.,University of Lille Nord de France | Maes E.,French National Center for Scientific Research | And 14 more authors.
Glycobiology | Year: 2012

Helicobacter pylori infects more than half of the world's population. Although most patients are asymptomatic, persistent infection may cause chronic gastritis and gastric cancer. Adhesion of the bacteria to the gastric mucosa is a necessary prerequisite for the pathogenesis of H. pylori-related diseases and is mediated by mucin O-glycans. In order to define which glycans may be implicated in the binding of the bacteria to the gastric mucosa in humans, we have characterized the exact pattern of glycosylation of gastric mucins. We have identified that the major component was always a core 2-based glycan carrying two blood group H antigens, whatever was the blood group of individuals. We have also demonstrated that around 80 of O-glycans carried blood group A, B or H antigens, suggesting that the variation of gastric mucin glycosylation between individuals is partly due to the blood group status. This study will help better understanding the role of O-glycans in the physiology and homeostasis of gastric mucosa. Overall, the results reported here give us the necessary background information to begin studies to determine whether individuals who express certain carbohydrate epitopes on specific mucins are predisposed to certain gastric diseases. © 2012 The Author.

Boudet S.,University of Lille Nord de France | Boudet S.,Groupe Hospitalier Of Linstitut Catholique Lillois | Peyrodie L.,University of Lille Nord de France | Peyrodie L.,School of Advanced Engineering Studies | And 8 more authors.
Computer Methods and Programs in Biomedicine | Year: 2012

Adaptive Filtering by Optimal Projection (AFOP) is an automatic method for reducing ocular and muscular artifacts on electro-encephalographic (EEG) recordings. This paper presents two additions to this method: an improvement of the stability of ocular artifact filtering and an adaptation of the method for filtering electrode artifacts. With these improvements, it is possible to reduce almost all the current types of artifacts, while preserving brain signals, particularly those characterising epilepsy. This generalised method consists of dividing the signal into several time-frequency windows, and in applying different spatial filters to each. Two steps are required to define one of these spatial filters: the first step consists of defining artifact spatial projection using the Common Spatial Pattern (CSP) method and the second consists of defining EEG spatial projection via regression. For this second step, a progressive orthogonalisation process is proposed to improve stability. This method has been tested on long-duration EEG recordings of epileptic patients. A neurologist quantified the ratio of removed artifacts and the ratio of preserved EEG. Among the 330 artifacted pages used for evaluation, readability was judged better for 78% of pages, equal for 20% of pages, and worse for 2%. Artifact amplitudes were reduced by 80% on average. At the same time, brain sources were preserved in amplitude from 70% to 95% depending on the type of waves (alpha, theta, delta, spikes, etc.). A blind comparison with manual Independent Component Analysis (ICA) was also realised. The results show that this method is competitive and useful for routine clinical practice. © 2012 Elsevier Ireland Ltd.

Cao H.,University of Lille Nord de France | Cao H.,School of Advanced Engineering Studies | Peyrodie L.,University of Lille Nord de France | Peyrodie L.,School of Advanced Engineering Studies | And 11 more authors.
Gait and Posture | Year: 2013

Expanded Disability Status Scale (EDSS) is the most widely used clinical scale to evaluate levels of multiple sclerosis (MS). As MS can lead to disruptions in the regulation of balance and the disability can be evaluated by force platform posturography, we have developed in this study a new strategy to estimate EDSS from posturographic data. 118 volunteers with EDSS ranging from 0 to 4.5 participated in this study, with eyes closed. By using second-order polynomial regression models, EDSS was estimated from two postural sway parameters, respectively, the length and the surface and four recurrence quantification analysis (RQA) parameters: percentage of recurrence (%Rec), Shannon entropy (Ent), mean diagonal line length (LL) and trapping time (TT). In addition, all four RQA parameters were calculated for position, instantaneous velocity and acceleration of the center of pressure. In order to select the most accurate method for estimating EDSS, four statistical indices (percentage of agreement, underestimation and overestimation, as well as Mean error) were calculated comparing clinical and estimated EDSS scores. The results demonstrate that estimations of EDSS from surface, %Rec and LL of position, best agreed with clinical scores. This study emphasizes the possibility of distinguishing EDSS scores using postural sway and RQA parameters. © 2012 Elsevier B.V.

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