Éditeur(s) : HAL CCSD
Résumé : International audience
GYNECOLOGIE OBSTETRIQUE FERTILITE & SENOLOGIE

hal-01653280
https://hal.archives-ouvertes.fr/hal-01653280
DOI : 10.1016/j.gofs.2016.12.017
PUBMED : 28238320

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Background: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. Objectives Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. Study design Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012–2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. Results The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n = 143, 30%) and respiratory failure (n = 116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n = 21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. Conclusions Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions
ISSN: 1386-6532

hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01302409/file/Factors%20associated%20with%20poor%20outcomes.pdf
DOI : 10.1016/j.jcv.2016.04.005

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Holoprosencephaly (HPE) is the most common congenital cerebral malformation, characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been associated with HPE, and are often inherited from an unaffected parent underlying complex genetic bases. It is now emerging that HPE may result from a combination of multiple genetic events, rather than from a single heterozygous mutation. To explore this hypothesis, we undertook whole exome sequencing (WES) and targeted high-throughput sequencing approaches to identify mutations in HPE subjects. We report here two HPE families in which two mutations are implicated in the disease. In the first family presenting two fetuses with alobar and semi-lobar HPE, we found mutations in two genes involved in HPE, SHH and DISP1, inherited respectively from the father and the mother. The second reported case is a family with a 9-year old girl presenting lobar HPE, harbouring two compound heterozygous mutations in DISP1. Together, these cases of digenic inheritance SHH/DISP1 and autosomal recessive HPE suggest that in some families, several genetic events are necessary to cause HPE. This study highlights the complexity of HPE inheritance and has to be taken into account by clinicians to improve HPE genetic counseling.
ISSN: 0009-9163

hal-01259228
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259228
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259228/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259228/file/Complex%20mode%20of%20inheritance%20in%20holoprosencephaly_accepted.pdf
DOI : 10.1111/cge.12722

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.
ISSN: 2326-5205

hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/file/Long-term%20outcomes%20of%20the%20WEGENT%20trial_accepted.pdf
DOI : 10.1002/art.39450

Éditeur(s) : HAL CCSD
Résumé : International audience
Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
ISSN: 2168-6211

hal-01258705
http://hal.univ-brest.fr/hal-01258705
PUBMED : 25621457
DOI : 10.1001/jamapediatrics.2014.3351

Éditeur(s) : HAL CCSD International Medical Press
Résumé : International audience
BACKGROUND: Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA). METHODS: APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event. RESULTS: The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression (n=16), suicides (n=5) and suicide attempts (n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA. CONCLUSIONS: Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.
ISSN: 1359-6535

hal-00875183
https://hal.archives-ouvertes.fr/hal-00875183
DOI : 10.3851/IMP2102
PUBMED : 22544079

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: In the context of recent guidelines on invasive candidiasis (IC), how French intensive care units (ICUs) are managing IC? METHODS: This is a prospective observational multicenter cohort study. During 1 year (2012-2013), 87 French ICUs enrolled consecutive patients with suspected or proven IC (SIC or PIC) and receiving systemic antifungal therapy (SAT). Data were collected up to 28 days after inclusion. RESULTS: We studied 835 patients, 291 with PIC and 544 with SIC. At SAT initiation, patients with SIC were significantly more severe (SAPS II 50.1 ± 18.7 vs. 46.2 ± 18.0). Severe sepsis or septic shock prompted to initiate empiric SAT in 70 % of SIC. Within 4 days in median, the initial SAT was modified in 49 % of patients with PIC vs. 33 % patients with SIC. Modifications were most often motivated by mycological results, and de-escalation was the most frequent change. Regarding compliance to IC management guidelines, echinocandin was used for 182 (62.5 %) patients with PIC, and 287 (52.7 %) of those with SIC; central venous catheter was removed in 87 (54.3 %) of patients with candidaemia, and 43 of the remaining patients received echinocandin; and de-escalation was undertaken after 5 days of SAT in 142 patients, after 10 days in 13 patients. As 20.6 % of SIC were secondarily documented, 403/835 (48 %) patients had finally a proven IC. Candida albicans was the main pathogen (65.3 %), then Candida glabrata (15.9 %). The 28-day mortality rates were 40.0 % in candidaemia, 25.4 % in cIAI, and 26.7 % in deep-seated candidiasis. In the overall population of patients with proven IC, four independent prognostic factors were identified: immunosuppression (Odds Ratio (OR) = 1.977: 1.03-3.794 95 % confidence interval (CI), p = 0.04), age (OR = 1.035; 1.017-1.053 95 % CI; p  extless 0.001), SAPS extgreater46 on ICU admission (OR = 2.894; 1.81-4.626 95 % CI; p  extless 0.001), and surgery just before or during ICU stay (OR = 0.473; 0.29-0.77 95 % CI; p  extless 0.001). CONCLUSION: When SAT is initiated in French ICUs, the IC is ultimately proven for 48 % of patients. Empiric SAT is initiated in severely ill ICU patients. The initial SAT is often adapted, with de-escalation to fluconazole when possible. Mortality rate remains high
ISSN: 2110-5820

hal-01259216
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01259216
DOI : 10.1186/s13613-015-0103-7
PUBMED : 26743881

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. METHODS: We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. RESULTS: Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. CONCLUSION: TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.
ISSN: 1462-0324

hal-01155105
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01155105
DOI : 10.1093/rheumatology/kev129
PUBMED : 26001634

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Objectif Analyser les caractéristiques virologiques et les complications des syndromes grippaux chez les diabétiques en période hivernale. Patients et Méthodes Étude conduite dans 6 hôpitaux (Montpellier, Lyon, Cochin, Bichat, Limoges, Rennes) au cours de 3 saisons grippales (2012-2013, 2013-2014 et 2014-2015), sur 1 451 adultes hospitalisés avec syndrome grippal récent (début ≤ 7 jours), associant un signe respiratoire (toux, dys-pnée) et un signe systémique (fièvre, céphalées, malaise, myalgies). Les virus respiratoires étaient recherchés par RT-PCR sur prélèvement naso-pharyngé ou LBA (Centre National de Référence, Lyon). La vaccination anti-grippale, la présence d'un diabète, les comorbidités, les complications en cours d'hospitalisation (insuffisance rénale, cardiaque, respiratoire, pneumonie, décès) et la durée moyenne de séjour (DMS) étaient enregistrées. Les facteurs de risque de complications ont été étudiés par régression logistique multivariée ajustée sur âge, sexe, infection grippale, vaccination, diabète et antécédents de pathologies rénale, cardiaque ou respiratoire. Résultats Les hospitalisations ont eu lieu dans des services de maladies respiratoires, médecine interne, MIT et réanimation. Un diabète était présent chez 368 sujets (non traités : 15 %, ADO : 41 %, insuline : 27 %, mixte : 17 %). Les diabétiques étaient plus âgés (71 ± 15 vs 65 ± 20 ans, P < 0,001) et présentaient plus souvent un antécédent de pathologie rénale (18 % vs 8 %, P < 0,00001) ou cardiaque (19 % vs 11 %, P < 0,001). Leur couverture vaccinale était meilleure (60 % vs 46 %). Les données virologiques étaient comparables : grippe 38,9 % (76,1 % type A) vs 39,2 % ; (74,1 % type A) ; autres virus respiratoires : 17,0 % vs 19,9 %. La DMS était un peu plus élevée chez les diabétiques (9,1 ± 9 vs 8,9 ± 11, P = 0,015), avec une tendance à un risque de décès plus élevé (6,25 % vs 3,97 %, P 0,07). En analyse multivariée, le diabète était un facteur de risque de complications à type d'insuffisance rénale (OR : 1,66, IC 95 % : 1,10-2,52) mais pas d'insuffisance cardiaque, respiratoire ou de décès. Les complications n'étaient pas modi-fiées par les résultats virologiques. Conclusions Le diabète est un facteur de risque de complications rénales chez les patients hospitalisés avec syndrome grippal
ISSN: 1262-3636

hal-01300779
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01300779
DOI : 10.1016/S1262-3636(16)30020-9

Éditeur(s) : HAL CCSD Springer
Résumé : International audience
Diabetologia
Stockholm, Sweden

hal-01204766
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01204766
DOI : 10.1007/s00125-015-3687-4

Éditeur(s) : HAL CCSD Oxford University Press (OUP): Policy B
Résumé : International audience
AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients
ISSN: 0195-668X

hal-01255874
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01255874
DOI : 10.1093/eurheartj/ehv650
PUBMED : 26685134

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
o abstract
ISSN: 0269-9370

hal-01560146
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560146
DOI : 10.1097/QAD.0000000000001474
PUBMED : 28492398

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction Les péritonites secondaires à levures représentent une part importante des candidoses profondes et de leur traitement. Peu d’outils sont disponibles afin de prédire au mieux les patients susceptible d’avoir une culture du liquide péritonéal positive. L’étude AMARCAND II (10/202–09/2013) a analysé les patients de réanimation recevant un traitement antifongique pour un candidose invasive prouvée ou suspectée. L’analyse des patients ayant un traitement probabiliste pour péritonite à levure suspectée est présentée ici. Patients et méthodes Cent soixante-douze patients parmi les 835 inclus ont été analysés. Les patients ayant une documentation mycologique (groupe D) ont été comparés à ceux ayant une culture à levure négative (groupe ND). La performance du Candida score [1] et du Peritonitis score [2] ont été évalués dans cette population de candidose profonde suspectée. Résultats Parmi les 172 patients, 51 ont eu une péritonite documentée à levure et 121 un culture à levure négative. Les caractéristiques des groupes sont présentées dans le Tableau 1. L’AUC du Peritonitis score était de 0,63 [0,54–0,72] contre 0,40 [0,31–0,49] pour le Candida score, p = 0,005. Pour un Peritonitis score ≥ 3, la sensibilité était de 39,2 %, la spécificité de 81,8 %, la VPP de 47,6 % et la VPN de 76,2 %. Le Candida score ne permettait pas de classer les patients atteints de péritonite à levure. Discussion Peu d’éléments permettent de différencier les patients qui vont avoir une infection documentée des autres. La localisation sus-mésocolique de l’infection et l’antibiothérapie de plus de 48 heures sont les éléments les plus fiables retrouvés. Le Peritonitis score reste intéressant dans ce contexte mais le Candida score n’a aucune utilité
ISSN: 2352-5800

hal-01244999
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01244999
DOI : 10.1016/j.anrea.2015.07.329

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER: We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY: The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. STUDY DESIGN, SIZE, DURATION: This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues. MATERIALS, SETTING, METHODS: Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. MAIN RESULTS AND THE ROLE OF CHANCE: We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. LIMITATIONS, REASONS FOR CAUTION: While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.
ISSN: 0268-1161

inserm-00814146
http://www.hal.inserm.fr/inserm-00814146
DOI : 10.1093/humrep/des360
PUBMED : 23024119

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.
ISSN: 0305-7453

hal-00875284
https://hal.archives-ouvertes.fr/hal-00875284
DOI : 10.1093/jac/dkr208
PUBMED : 21636583

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa. However, a coordinated approach to identify and monitor these contaminants and to develop strategies for public health interventions has not yet been made. OBJECTIVES: This commentary summarizes the scientific evidence presented by experts at the First African Endocrine Disruptors meeting. We describe a "call to action" to utilize the available scientific knowledge to address the impact of EDCs on human and wildlife health in Africa. DISCUSSION: We identify existing knowledge gaps about exposures to EDCs in Africa and describe how well-designed research strategies are needed to address these gaps. A lack of resources for research and a lag in policy implementation slows down intervention strategies and poses a challenge to advancing future health in Africa. CONCLUSION: To address the many challenges posed by EDCs, we argue that Africans should take the lead in prioritization and evaluation of environmental hazards, including EDCs. We recommend the institution of education and training programs for chemical users, adoption of the precautionary principle, establishment of biomonitoring programs, and funding of community-based epidemiology and wildlife research programs led and funded by African institutes and private companies. https://doi.org/10.1289/EHP1774.
Environmental Health Perspectives

hal-01616487
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616487
DOI : 10.1289/EHP1774
PUBMED : 28935616

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. DESIGN: Prospective study of 1046 patients at 47 French clinical sites. METHODS: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. RESULTS: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. CONCLUSIONS: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.
ISSN: 0269-9370

hal-00875222
https://hal.archives-ouvertes.fr/hal-00875222
DOI : 10.1097/QAD.0b013e32834e8776
PUBMED : 22089377

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Molecular diagnosis of congenital toxoplasmosis or disseminated toxoplasmosis is based mainly on PCR. The repeated DNA element rep529 has become the main DNA target used in most PCR methods, whether laboratory developed or commercial. In this multicenter study, we evaluated the Toxoplasma ELITe MGB (Elitech) commercial kit by comparison with three reference quantitative PCR assays (RAs) used routinely in three proficient laboratories of the French National Reference Center for Toxoplasmosis network, using Toxoplasma calibrated suspensions diluted to obtain a range of concentrations from 0.1 to 10,000 parasites/ml. These suspensions were extracted with either the DNA extraction kit (EXTRAblood; Elitech) recommended by the manufacturer or the QIAamp DNA minikit (Qiagen). The Toxoplasma ELITe MGB assay was also evaluated on a panel of 128 clinical samples, including 56 amniotic fluid samples, 55 placenta samples, and various other samples, of which 95 originated from patients with proven toxoplasmosis. The ELITe MGB assay amplified low-concentration replicates (<10 parasites/ml) of calibrated suspensions less frequently than the RAs of 2/3 laboratories. Additionally, the combination of EXTRAblood and Toxoplasma ELITe MGB yielded poorer sensitivity than the combination of QIAamp DNA minikit and ELITe MGB for low parasite concentrations (P < 0.001 for 1 parasite/ml). On clinical samples, the sensitivity and the specificity of the commercial assay were 89% and 100%, respectively. The sensitivity ranged from 79% (placenta samples) to 100% (amniotic fluid samples). Overall, this study shows that the Toxoplasma ELITe MGB assay is suitable for the diagnosis of toxoplasmosis from non-cell-rich or non-hemoglobin-rich samples and that the EXTRAblood kit is not optimal.
ISSN: 0095-1137

hal-01526432
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526432
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526432/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01526432/file/Evaluation%20of%20the%20Toxoplasma.pdf
DOI : 10.1128/JCM.02379-16

Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVE: To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. DESIGN: Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months. SETTING: University hospitals. PATIENT(S): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (+/-) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. INTERVENTION(S): Semen analyses and aneuploidy study by FISH were performed at each time point. MAIN OUTCOME MEASURE(S): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. RESULT(S): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD +/- radiotherapy or CHOP/MOPP-ABV. After ABVD +/- radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment. CONCLUSION(S): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.
Fertility and sterility

hal-01477204
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01477204
DOI : 10.1016/j.fertnstert.2016.10.001
PUBMED : 27810161

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. METHODS: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. RESULTS: A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. CONCLUSIONS: In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.
ISSN: 0022-1899

hal-00875299
https://hal.archives-ouvertes.fr/hal-00875299
DOI : 10.1093/infdis/jir211
PUBMED : 21628666