Search

ObjectiveTo assess the safety and efficiency of steam vein sclerosis (SVS) of the great saphenous vein (GSV) in a multicentre open prospective cohort study.Design75 consecutive adult patients with GSV reflux, CEAP C2–C5 and vein diameter 4–13 mm.MethodsPatients treated using an SVS™ generator delivering homogenous pulses of superheated steam were followed up at 8 days and 1, 3, 6 and 12 months (clinical, duplex ultrasound, quality of life [QoL] with SF12).Results88 veins were treated in 75 patients. At 6 months, 72/75 (96%) veins were obliterated (95% CI: 89–99) and Kaplan–Meier analysis found an obliteration rate of 96.1% at 12 months. QoL increased at 6 months for both the physical and mental components (p = 0.049 and p

The purpose of the clinical trial guidelines is to harmonise legislation in order to ensure consistency within Europe and thereby promote Europe's attractiveness for clinical research while maintaining or improving the protection of subjects who agree to participate. The French administrative system has hitherto been relatively favourable (with simple notification to a single Ethics Committee per study); it is thus important to maintain competitiveness in these respects, given that, in other areas (the time it takes to establish agreements, recruitment, etc.), other countries have the advantage. At the moment, this Directive has not been entirely transposed into French law. The pilot period established by the Afssaps (French drug agency) has made it possible to determine very quickly how to set things up. For Ethics Committees, the situation is more critical in that many points remain that need to be finalised (selection of members, internal rules, Competent Authority/Ethics Committee relationship, etc.). The Giens workshop issued a number of proposals and it hopes, through the Afssaps)/DGS (French agency of health in government)/LEEM Steering Group (French pharmaceutical companies association), to be able to help establish an efficient system which also correctly protect the patient.

Resume Introduction La commission du medicament et des dispositifs medicaux des hospices civils de Lyon (HCL) est confrontee a la pauvrete des donnees cliniques disponibles lors du referencement de dispositifs medicaux (DM). Les HCL se sont rapproches de differents organismes de Rhone-Alpes pour mettre en place une action visant a inciter les petites et moyennes entreprises (PME) du DM a realiser des etudes cliniques. Nous rapportons les resultats de cette experience qui s’est deroulee entre 2007 et 2010. Methodes Les projets des entreprises eligibles ont ete selectionnes sur la base de leur interet scientifique. Une structure d’accompagnement reglementaire et methodologique a ete mise en place. Resultats Vingt entreprises etaient candidates, 17 ont ete selectionnees. Huit protocoles de recherche clinique ont ete rediges ; quatre etudes cliniques ont ete mises en œuvre. Ces etudes ont ete realisees par des micro-entreprises et concernaient des DM pouvant etre consideres comme des innovations ou des nouveautes substantielles. Les principales causes pour lesquelles les projets n’ont pas conduit a un protocole de recherche ou a une etude etaient : une phase de developpement du DM plus longue que prevue ( n = 3) ; un probleme de faisabilite methodologique ( n = 1) ; la recherche infructueuse d’un investigateur principal ( n = 2) ; ou un choix de l’entreprise ( n = 5). Discussion et conclusions Cette experience pilote a permis de former des PME a la recherche clinique et de generer des etudes cliniques pour l’evaluation de DM. Sa perennisation pourrait inciter les industriels a realiser des essais cliniques de bonne qualite.

Resume La loi no 2005-370 du 22 avril 2005 relative aux droits des patients en fin de vie place le malade au cœur de la decision medicale et lui permet d’exprimer ses souhaits concernant ses soins. Ainsi, de nombreux patients hospitalises expriment le souhait de retourner sur leur lieu de vie. Cependant, beaucoup decedent encore a l’hopital. Pourquoi certains rentrent-ils chez eux et d’autres non ? Quels sont les facteurs pouvant influencer le retour a domicile ? Materiel et methodes Nous avons realise une etude epidemiologique d’observation, prospective, exhaustive et longitudinale incluant des patients en fin de vie, relevant de soins palliatifs, hospitalises et souhaitant regagner leur residence habituelle. Nous avons choisi d’analyser six facteurs predefinis comme potentiellement predictifs d’un retour sur leur lieu de vie. Resultats L’etude menee sur 12 mois a permis de recueillir 132 dossiers : 73 patients rentres a domicile et 59 patients restes hospitalises. La presence d’un entourage « autre » que familial, l’appel a une structure specialisee en soins palliatifs au cours du temps et la presence d’aides pratiques au domicile du patient sont trois facteurs favorisant le retour sur le lieu de vie initial. L’âge, le sexe, la pathologie principale, l’environnement familial, le niveau de fragilite du patient et de sa famille, ne favorisent pas ce retour. Conclusion La connaissance de ces facteurs predictifs permet de guider les equipes soignantes hospitalieres et du domicile dans la prise en charge des patients en fin de vie souhaitant retourner chez eux.

Introduction The objectives of reference centres for rare diseases are multiple and mainly concern disease management and coordination between specialties, but they also have to improve knowledge through epidemiological studies and biomedical research. A first database was created by the hereditary haemorrhagic telangiectasia network to achieve these objectives, but facing a lack of data entered in the first database, we established a new database, named CIROCO (Clinical Investigation for the Rendu-Osler Cohort). This new database was constructed after the first database assessment. Methods We listed all difficulties encountered in the first database. We focused on three themes: database technical characteristics, database design (the number and characteristics of variables and the overall structure) and data entry. Based on this expertise, we defined the characteristics that should lead to an optimization of the database. We then compared the performance of these databases in terms of available data. Results The first database had 1273 fields spread out on 14 forms. A total of 838 patients was entered from 2001 to 2005 and among the 1273 fields, 205 (16%) had no data at all. The new database gathered 362 fields from the first database and 173 new fields. These fields were rearranged into 443 variables. A total of 1410 patients directly seen by the clinicians were entered. For patients seen by clinicians each variable used for defining the disease was available for at least 93% of patients. Conclusion Items to be included in a specific database should be carefully selected in order to achieve good results and an epidemiological utility.

Resume Introduction La prise en charge de l’anemie des patients atteints d’insuffisance renale chronique (IRC) represente un enjeu medicoeconomique important de par la frequence de cette pathologie et le cout des agents stimulant l’erythropoiese (ASE). L’objectif de ce travail etait d’identifier les determinants des couts associes a ces traitements pour determiner, a efficacite comparable, l’ASE le plus efficient. Materiel et methodes Une recherche bibliographique par interrogation de la base de donnees Medline a ete realisee. Resultats Parmi les couts medicaux directs, cinq etudes ont montre que l’acquisition de l’epoetine alfa (EA) par rapport a la darbepoetin alfa (DA) etait moins onereuse. Concernant les couts lies a la voie d’administration, l’injection sous-cutanee (SC) des epoetines permettrait une economie du fait d’une diminution des doses par rapport a la voie intraveineuse (IV). Le passage de l’EA en SC a la DA en IV, chez les patients hemodialyses, etait associe a une reduction du nombre d’injections et a un cout de traitement inferieur par DA que par EA. Les couts lies aux schemas d’administration, notamment ceux lies aux temps infirmier, medical et pharmaceutique, etaient faibles au regard de ceux lies a l’acquisition de l’ASE. Enfin, les couts lies au suivi therapeutique et a la prise en charge des effets indesirables des ASE etaient similaires entre l’EA et la DA. Conclusion Les couts lies aux prix d’acquisition de l’ASE, negocies par la structure de soins, representent la part la plus importante des couts medicaux directs.

– Objective: The aim of the study was to evaluate the role of alcohol drinking and patterns of consumption in oral cancer incidence and mortality in a cohort study using data from the Trivandrum Oral Cancer Screening Study, India. Methods: At baseline, the study participants completed a lifestyle questionnaire including items on frequency and duration of alcohol consumption. They were followed up for oral cancer incidence and mortality. Data from 32 347 subjects, of whom 134 eventually developed oral cancer, were analysed to estimate risk of oral cancer incidence and mortality according to drinking patterns, using a Cox regression model adjusted for age, religion, education, occupation, body mass index (BMI), standard of living index, chewing habits, smoking habits, and vegetable and fruit intake. Results: Current and past drinkers were each associated with significantly increased risk of developing oral cancer. The hazard ratio increased significantly by 49% (95% CI = 1–121%) among current drinkers and 90% (95% CI = 13–218%) among past drinkers. A significant dose–response relationship between intake frequency, duration and oral cancer risk (incidence and mortality) was observed. Conclusions: As with other lifestyle factors, alcohol intake plays an important role in oral carcinogenesis in this population, and understanding this role is relevant to developing public health policies targeting at-risk population.

La directive essais cliniques avait pour but une harmonisation des legislations afin de favoriser la coherence du systeme europeen et par la meme l'attractivite de l'Europe en matiere de recherche clinique tout en maintenant ou renforcant la protection des personnes qui acceptent d'y participer. La situation francaise en matiere administrative etait jusqu'a present relativement favorable (etude a notifier avec deja un seul comite d'ethique par etude), il est donc important de maintenir la competitivite sur ces points sachant que sur d'autres points (delais de mise en place des conventions, recrutement, ...) la situation n'est pas a l'avantage de la France. A l'heure actuelle, la transposition de cette directive n'est pas encore totalement finalisee en droit francais. La periode pilote qui a ete mise en place par l'Afssaps (Agence francaise de securite sanitaire des produits de sante) a permis d'etablir sans delais les modalites de mise en place. Pour les CPP (Comites de Protection des Personnes), la situation est plus critique dans la mesure ou beaucoup de points restent a etablir (choix des membres, reglement interieur, rapport CA/CE [autorites competentes/comites d'ethique]...). L'atelier de Giens a permis de faire naitre un certain nombre de propositions et souhaite par le biais du groupe de pilotage Afssaps / DGS (Direction Generale de la Sante) / LEEM (Les Entreprises du Medicament) continuer a contribuer a la mise en place d'un systeme efficace et protecteur pour les patients.

Research protocols are usually kept confidential to protect intellectual and commercial interests. But secrecy can also hide deviations that affect the validity of results and threaten the integrity of medical research

Resume Objectif Evaluer l’activite d’un secteur d’orientation courte (SOC) comportant 9 lits destines a accueillir uniquement les patients des urgences pour lesquels une demarche diagnostique et/ou un traitement specifique doit etre debute en attendant qu’une place se libere dans le service approprie. Methodes Pendant les 29 mois suivant la creation du SOC (de fevrier 2001 a juin 2003), nous avons analyse des parametres fournis mensuellement par le departement d’informatique medicale : nombre de patients ayant ete hospitalises au SOC, âge, sexe, diagnostic principal selon les donnees du codage PMSI, duree de sejour, nombre de deces, nombre de sorties directes a domicile, nombre de transferts vers un service de specialite, qualification des services receveurs. Resultats Mille huit cent quarante patients d’âge moyen 73 ans ont ete hospitalises dans le SOC. Les motifs d’admission les plus frequents etaient une surinfection bronchopulmonaire (16 %), un bilan de malaise (14 %), un accident vasculaire cerebral (12 %), une maladie thromboembolique (11 %) et une insuffisance cardiaque (10 %). La duree moyenne de sejour dans le SOC etait de 3,7 jours (inferieure a 48 heures pour 46 % des hospitalisations). Dans 40 % des cas, les patients ont pu retourner directement a leur domicile. Dans 62 % des cas, le transfert du patient vers un service de specialite s’est fait dans les 48 heures. Le fonctionnement du SOC comporte certaines specificites (contacts telephoniques personnalises repetes, lettres de transfert rapides, cooperation difficile avec quelques services, etc.). Conclusion Le SOC rend service aux patients en accelerant leur prise en charge adaptee aux urgences, en permettant une mutation plus rapide, en permettant aux services de specialite de ne prendre en charge que les patients relevant de leur specialite. Il permet une adequation entre les pathologies des patients et les competences des services de specialite medicale.

Background. The aim of the present study was to determine the influence of the venous drainage site on insulin homeostasis in simultaneous pancreas-kidney (SPK) transplant recipients. Methods. The study included 12 SPK patients with portal venous drainage (P) and 11 SPK patients with systemic venous drainage (S) of pancreas allograft. All of the participants presented similar characteristics. The euglycemic hyperinsulinemic clamp was performed using a 0.4-mU/kg/min insulin infusion. An infusion of [6,6-(2)H 2 ] glucose was used to determine glucose turnover at the basal state and during the clamp to determine liver and peripheral tissue sensitivity to insulin. Results. Minor changes in glycemia and insulinemia were shown: fasting plasma glucose was significantly higher in the SPK-P group and insulinemia was higher in the SPK-S group. Hepatic glucose production was similar in both groups. During the clamp, insulin levels were higher in SPK-S recipients, but hepatic glucose production was suppressed in both groups. Glucose use was lower in SPK-S recipients than in SPK-P recipients, 3.32±1.41 mg/kg/min and 4.70±1.64 mg/kg/ min, respectively (P

Resume Objectifs. – Rechercher les facteurs de risque d’infection a Escherichia coli resistant a amoxicilline–acide clavulanique chez des patients de reanimation chirurgicale. Type d’etude. –Prospective d’observation. Patients et methodes. – Cent trente-trois patients ayant presente 135 infections a E. coli lors de leur sejour en reanimation. Une analyse univariee puis une analyse multivariee ont ete realisees. Resultats. – L’exposition anterieure a l’amoxicilline est le seul facteur de risque significativement associe a une infection a E. coli resistant a l’amoxicilline–acide clavulanique. Conclusion. – Les cliniciens doivent eviter l’utilisation d’amoxicilline–acide clavulanique de facon probabiliste chez les patients susceptibles d’avoir une infection a E. coli et qui ont recu au prealable de l’amoxicilline.

To determine risk factors of infections with piperacillin/tazobactam-resistant Escherichia coli in critical care patients.Prospective, consecutive sample survey study.Surgical intensive care unit (ICU) in a university hospital.A consecutive series of 133 patients from whom culture results were positive for E. coli during their ICU stay.None.Multivariate logistic regression analysis identified the following significant independent factors associated with the emergence of a piperacillin/tazobactam-resistant Escherichia coli: prior use of amoxicillin (odds ratio, 4.15) and amoxicillin/clavulanate (odds ratio, 3.25).Treatment with amoxicillin or amoxicillin/clavulanate is a major risk factor for the detection of piperacillin/tazobactam-resistant E. coli in ICU patients.

International audience; INTRODUCTION:Endovascular treatment of large, wide-necked intracranial aneurysms with coils is associated with low rates of initial angiographic occlusion and high rates of recurrence. The Pipeline™ Embolization Device has shown high rates of complete occlusion in uncontrolled clinical series.METHODS:The study is a prospective, controlled, randomized, multicenter, phase 2 open-label trial. Intention-to-treat population includes age ≥18, unruptured saccular aneurysm located in the intra-dural area, neck diameter ≥4 and ≤10 mm, sac diameter ≥7 mm and ≤20 mm, "dome/neck" ratio is ≥1, diameter of the parent artery ≥2 mm and ≤5 mm, and no prior treatment of the aneurysm. Site can only participate if five patients have been previously treated with the Pipeline device. The primary end point of the study is complete occlusion of the aneurysm on angiogram performed 12 months after the endovascular procedure. Complete aneurysm occlusion is defined as the absence of visible blood flow, grade 1 according to the Raymond scale for the standard procedure group and grade 4 according to the grading scale of Kamran for the flow diverter group.RESULTS:The trial is currently enrolling and results of the data are pending the completion of enrollment and follow-up.CONCLUSION:This paper details the trial design of the French EVIDENCE phase 2 trial, a blinded, controlled randomized trial of wide-neck intra-dural aneurysms amenable to either traditional endovascular strategy or flow diversion with Pipeline device.

Aspergillus fumigatus infection in hospitalized immunocompromised patients often raises suspicion regarding the potential for hospital acquisition. Hospital staff have an important responsibility in implementing preventive measures, especially since the advent of current legislation concerning hospital-acquired infections. There have been high expectations that molecular typing methods might determine the source of Aspergillus fumigatus, a ubiquitous mould. The aim of the present epidemiological study, was therefore, to identify the origin(s) of Aspergillus infection in six well-documented patients. All the clinical strains (N=33), and those from hospital (N=14) and home environments (N=34) were isolated according to a standardized protocol and typed by sequence-specific DNA primer analysis. The results confirmed the huge biodiversity of the A. fumigatus population, and consequently the difficulty in ascertaining a hospital source of the infection, as opposed to infections due to other Aspergillus species less frequently encountered.

Background The fate of clinical research projects funded by a grant has been investigated, but there is no information on the projects which did not receive funding. The fate of these projects is not known: do they apply for and/or receive funding from other sources or are they carried out without specific funding? Purpose The aim of the study was to describe all clinical research projects submitted to a French national funding scheme (PHRC 2000) and to assess project initiation, completion and publication status taking into account whether or not they received funding. Methods This study is a retrospective cohort. The initial project characteristics were retrieved from the submission files and follow-up information was collected from the primary investigator. The percentages of projects started, completed and published were studied. Results A total of 481 projects were studied. Follow-up information was obtained for 366. Overall, 185 projects were initiated (51%); 139 of them were funded by the PHRC 2000 or other sources. The most commonly cited reason for not initiating a project was a lack of funding. Subsequently, 121 of the projects initiated were completed (65%). Accrual difficulties were the main reason cited to explain why studies were stopped prematurely or were still ongoing. Finally, 88 of the completed projects were published (73%). Amongst the completed projects, the only factor explaining publication was the statistical significance of the results. Conclusions Obtainment of funding was a determining factor for project initiation. However, once initiated, the funding did not influence completion or publication.

International audience; Background: Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. Primary objective: To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Methodology: Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. Results: A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Conclusion: Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. Trial Registration: ClinicalTrials.gov Identifier #NCT01507480.

The genotypes of 52 strains of Aspergillus fumigatus isolated from 12 patients with invasive aspergillosis were investigated using three typing methods (random amplified polymorphic DNA, sequence-specific DNA polymorphism, and microsatellite polymorphism) combined with multilocus enzyme electrophoresis. Isolates were from patients hospitalized in three different geographic areas (Lyon, France; Grenoble, France; and Milan, Italy). In each case, the genetic polymorphism of several colonies (two to five) within the first respiratory clinical sample was studied. For the 52 isolates tested, random amplified polymorphic DNA identified 8 different genotypes, sequence-specific DNA polymorphism identified 9 different types, and microsatellite polymorphism identified 14 types. A combination of these results with multilocus enzyme electrophoresis study identified 25 different types within the sample studied. We identified 3 patients (of the 12 studied) who carried a single genotype; 6 patients were infected by two genotypes, 1 patient had four genotypes, while the last patient had five. A combination of typing methods provided better discrimination than the use of a single method. Typing methods revealed a population structure within each geographical site, suggesting that the epidemiology of A. fumigatus should be considered separately for each of these geographic areas. This study demonstrates the usefulness of combining several typing methods in reaching an understanding of the epidemiology of A. fumigatus and clarifies whether it is sufficient to type one isolate from each specimen to determine the strain involved in invasive aspergillosis.

Background. The prevalence and significance of vesicoureteral reflux (VUR) after kidney transplantation in adults varies between authors and there have been few reports in children. Methods. We conducted a retrospective study in a single-centre paediatric cohort. Fifty-five of the 84 children who underwent kidney transplantation over a 5-year period were checked with routine cystography after a median of 8 months post-transplantation. Graft function and urinary-tract infections were assessed during the first 6 years after transplantation. Results. VUR into the graft was present in 58% of the patients. Graft function and incidence of urinary-tract infections were similar in the two groups, independent of VUR. After having excluded infections attributed to the presence of a catheter, actuarial survival rates without pyelonephritis and without pyelonephritis following a first lower urinary-tract infection were worse in patients with VUR (P=0.017 and P=0.0039 respectively). None of the eight patients with VUR treated with antibiotic prophylaxis after a first acute pyelonephritis (APN) episode presented subsequent APN after 4.4 ± 3.3 years on therapy. Conclusions. VUR to the graft occurred in more than half paediatric renal transplant recipients. This condition was associated with an increased risk of APN. Long-term antibiotic prophylaxis seems to be able to prevent APN in transplanted children with VUR.

Among 1454 persons whose stool samples (n=5692) were submitted to a reference laboratory for microsporidia assessment from 1993 to 1996, microsporidia were identified in 338 persons: 261 persons infected with human immunodeficiency virus (HIV), 16 transplant patients, and 61 others. Intestinal microsporidiosis appears to be an endemic disease in HIV-positive persons (prevalence, 0.1%) and a sporadic disease in HIV-negative persons (prevalence

This study investigated the source of infection and strain relatedness of Aspergillus fumigatus isolates from bronchial colonisation and invasive aspergillosis (IA) in four transplant patients. Environmental isolates from the patient's home and from the hospital and infecting isolates were obtained for patient A who developed IA. Clinic environmental and colonising isolates were obtained for patient B. Sequential isolates were obtained from various organs from patient C who developed IA and also from patient D who had a bronchitic aspergillosis that developed into IA. Ninety-one A. fumigatus isolates were analysed by three typing methods: multi-locus enzyme electrophoresis (MLEE), random amplified polymorphic DNA (RAPD) and sequence-specific DNA primers (SSDP). The three combined typing methods demonstrated a greater differentiation of isolates than the typing methods used separately or in pairs. This demonstrated the genotypic variability of A. fumigatus and facilitated better epidemiological analysis. Large polymorphisms were demonstrated for each patient isolate between and colonies within various samples. The relatedness of the isolates suggested nosocomially acquired aspergillosis for patient B, but the source of infection for patient A remained unclear. The results suggested at least three multiple infections among the four patients. This study enabled the identification of the source of infection and strain relatedness, which in turn facilitates the development of preventive measures for patient management in the future.

Within the framework of the Millennium Programme, we have started the design and building of novel equipment with the aim at facilitating and diversifying the experimental conditions on Institut Laue-Langevin (ILL) and ILL–CRG instruments. We anticipate new devices for applying external parameters (pressure, temperature, magnetic or electric fields, etc.), handling the neutron beam polarisation (RF wide-band flipper, TOF-Cryopad, etc.) or carrying multi-task experiments. The facilities already in operation are briefly reviewed: 3 K cryogen-free cryostat hosting the Paris–Edinburgh pressure cell, 3 K pulse-tube top-loading cryostat with 700 K high-temperature insert, 2 K Joule–Thomson cryogen-free cryostat for Eulerian cradles, 20 mK dilution fridge for the recently acquired 15 T cryomagnet and a low-temperature gas-injection sample stick for Orange cryostats.

International audience; Purpose Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year. Methods A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trials (RCT) comparing bevacizumab with ranibizumab in patients with neovascular AMD. Odds ratio (OR) and mean difference (MD) estimates were synthesized under fixed-and random-effects models. Heterogeneity was assessed using the Q statistic and I-2. Results Five RCTs were included, representing 2,686 randomised patients. The meta-analysis confirmed the non-inferiority of bevacizumab compared to ranibizumab for change in visual acuity at 1 year (MD 0.57 letters, -1.80 to 0.66, p = 0.37, I-2 = 0 %). Better anatomical results were found for ranibizumab. Bevacizumab was associated with a 34 % increase in the number of patients with at least one serious systemic adverse event (OR 1.34, 1.08 to 1.66, p = 0.01, I-2 = 0 %). Conclusions The pooled evidence confirmed that, compared with ranibizumab, bevacizumab was associated with equivalent effects on visual acuity at 1 year and with a higher risk of systemic serious adverse events. The current available data do not show which types of adverse events occur more frequently. In practice, bevacizumab should be used under a risk-management plan until further studies have been carried out to assess accurately the increased risk of systemic adverse events.

Journal of Neuroradiology - In Press.Proof corrected by the author Available online since mardi 1 avril 2014

The aim of this prospective and randomized study was to determine whether misoprostol, an analogue of PGE1, could decrease the incidence and the number of rejection episodes and could improve the renal function over a 12-month follow-up, when given at 400 micrograms/day for 12 months in renal transplant patients. Given the known side-effects and the additive cost of misoprostol, a benefit of the therapy should be a decrease of at least 50% in the incidence of rejection episodes in the treated group. Therefore, 60 consecutive renal transplant patients were randomized to receive misoprostol or to receive aluminium and magnesium hydroxide. Patients received steroids, azathioprine, antithymocyte globulins, and cyclosporin A (CsA). CsA was randomly started on day 0 or on day 8. At 12 months, no difference in the incidence of rejection episodes was observed: 63.3% in the 30 patients of the misoprostol + group versus 70.0% in the misoprostol-group (P = 0.558 Mantel-Cox). The renal function, assessed by plasma creatinine, inulin, and para-aminohippuric acid clearances, was not significantly different between misoprostol + and misoprostol-groups. No episode of CsA nephrotoxicity was observed in any patient of group one or group two. At 12 months, the mean dosage of CsA was 4.9 +/- 0.28 mg/kg/day in the misoprostol + group versus 4.52 +/- 0.23 mg/kg/day in the misoprostol-group and the trough level was not significantly different between the two groups. The graft survival rate at 12 months was 86.7% in the Misoprostol + group and 83.33% in the misoprostol-group.(ABSTRACT TRUNCATED AT 250 WORDS)

International audience; Although most of the people in good health questioned about the subject said they would like to die at home, in the western world between 60 and 80% of deaths occur in hospital. Most authors consider that the indispensable conditions for a return home are the patient's desire and presence of the family and caregivers with the appropriate skills. The assessment of other factors predictive of a return home is inadequate. The aim of this study is to clarify how the return home is influenced by the vulnerability of the patient at the end of life, and by that of the family and caregivers. We carried out a multicentric, observational, prospective, exhaustive and longitudinal epidemiological study (three months follow-up), including 146 patients hospitalized at the end of their life and desiring to return home. For these patients the caregivers respected their freedom to choose to die at home in over half the cases (56%). Their overall vulnerability (personal, family context and caregivers) had a significant influence on the return home. This overall vulnerability was in fact identified as applying in 40% of the clinical situations, and made the possibility of a return home 50% less likely.

The objectives of reference centres for rare diseases are multiple and mainly concern disease management and coordination between specialties, but they also have to improve knowledge through epidemiological studies and biomedical research. A first database was created by the hereditary haemorrhagic telangiectasia network to achieve these objectives, but facing a lack of data entered in the first database, we established a new database, named CIROCO (Clinical Investigation for the Rendu-Osler Cohort). This new database was constructed after the first database assessment.We listed all difficulties encountered in the first database. We focused on three themes: database technical characteristics, database design (the number and characteristics of variables and the overall structure) and data entry. Based on this expertise, we defined the characteristics that should lead to an optimization of the database. We then compared the performance of these databases in terms of available data.The first database had 1273 fields spread out on 14 forms. A total of 838 patients was entered from 2001 to 2005 and among the 1273 fields, 205 (16%) had no data at all. The new database gathered 362 fields from the first database and 173 new fields. These fields were rearranged into 443 variables. A total of 1410 patients directly seen by the clinicians were entered. For patients seen by clinicians each variable used for defining the disease was available for at least 93% of patients.Items to be included in a specific database should be carefully selected in order to achieve good results and an epidemiological utility.

International audience

Patients with painful conditions often suffer from sleep disturbances. However, changes in sleep pattern per se could also influence pain tolerance. Untreated obstructive sleep apnea (OSA) causes major disturbances in sleep pattern. The aim of this study was to assess whether continuous positive airway pressure (CPAP) treatment in elderly patients with OSA would result in improved pain tolerance.Randomized, double-blind crossover study.Geriatric sleep center based in Antoine Charial University Hospital (Lyon, France).A total of 13 consecutive OSA patients aged 70 and older randomly assigned CPAP treatment (lowCPAP versus highCPAP). Eleven patients completed the study.Overnight sleep recording, electrical pain tolerance assessment, and visual analog scale for sleep quality were performed.Both low- and highCPAP treatment significantly improved respiratory parameters. However, compared with baseline, the electrical pain tolerance score was significantly enhanced (analgesic effect) only under highCPAP treatment (21.2 ± 10.9 versus 28.4 ± 16.0; P = .03).The treatment of OSA with CPAP would have an analgesic effect. This would represent a unique outcome attributed to CPAP treatment. Given the high prevalence of both OSA and chronic pain conditions in the elderly; our findings could hold many implications for very large segments of the elderly population.

The database revealed severity factors relating to human papillomavirus (HPV) type and age at diagnosis. While not exhaustive, the database is easy to use and could serve for a European multicentre epidemiological study.To propose a database as a starting point for a national registry and to estimate prognostic factors in recurrent respiratory papillomatosis (RRP).This was a retrospective study carried out in a tertiary care teaching hospital. From January 2005 to July 2007, epidemiological, clinical and treatment information on patients undergoing endoscopy for RRP in the department was entered in a database. Data were collected on three forms: the first comprised information about disease history before assessment in the department, the second about the disease and its treatment in the department, and the third about evolution after treatment.Data on 72 patients were entered into an RRP database between January 2005 and July 2007. In all, 82% had already been treated for RRP in a different centre; 24 had juvenile-onset (JORRP) and 48 adult-onset (AORRP) papillomatosis. Cidovir injections had been administered to 91% of the patients. Histology found nine cases of dysplasia, one of carcinoma in situ and one of invasive carcinoma. Subglottic and tracheal locations were significantly more frequent in JORRP than in AORRP, as were the maximum Derkay scores and annual numbers of endoscopies. Patients with type 11 HPV had significantly more endoscopies per year than those with type 6.

Management of anaemia in chronic renal insufficiency (CRI) represents an important medico-economic challenge because of the great number of patients and the cost of the erythropoiesis-stimulating agent (ESA). The aim of this study was to identify determinants of the costs associated with these treatments in order to choose, with equal efficacy, the most efficient ASE.A bibliographic research was realised by Medline database interrogation.Among the direct medical costs, five studies showed that acquisition of epoetine alfa (EA) compared to darbepoetin alfa (DA) was less expensive. Concerning the costs associated with the route of administration, the subcutaneous injection (SC) of epoetine allowed a gain in costs because of the decrease of doses compared to the intravenous (IV) route. The switch from EA in SC to DA in IV, for hemodialysis patients, was associated with a reduction of the number of injections and with a treatment's cost lower by DA than by EA. Costs related to the regimen of administration, notably those related to nursing, medical and pharmaceutical time, were negligible towards those associated to the acquisition of the ASE. Finally, the costs of the therapeutic follow-up and treatment of the adverse effects of the ASE were similar between the EA and the DA.The costs associated with the prices of acquisition of the ASE, negotiated by the structure of care, represent the most important part of the direct medical costs.

Background. The incidence of oral cavity cancer (OCC) is not well documented because it is rarely described in accord with the anatomic definition but is usually grouped with oropharyngeal subsites. We studied the incidence of OCC in developed and in developing countries. Methods. The age-standardized and age-specific incidence rates of OCC were calculated for the period 1998-2002, using the topographic definition used by the Union Internationale Contre le Cancer (UICC), based on data from CI5-IX. Results. The highest rates are observed in Pakistan, Brazil, India, and France and were consistent with country-specific risk factors and their prevalence. Conclusions. In developing countries, people are exposed to a wider range of risk factors, starting at younger ages, and primary prevention measures and policies are needed. Awareness of professionals must be improved to identify people at risk and target them for prevention and to minimize the consequences of OCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010

International audience; Heparin-induced thrombocytopenia is a severe drug adverse effect with possible dramatic consequences. The risk is 0.1% to 5%. The costs of heparin-induced thrombocytopenia in France were estimated using the Programme Médicalisé des Systèmes d'Information (PMSI) national discharge database. Hospitalizations with heparin-induced thrombocytopenia were identified using diagnostic codes. Costs were assessed from the perspective of the French Sickness Fund or hospitals. Heparin-induced thrombocytopenia could be the reason of admission or could occur during the stay and lead to a different tariff or to additional costs associated with extra length of stay. Direct costs were also estimated from experts' opinions. A sensitivity analysis was performed from data collected in 1 center. During 2005, 445 hospitalizations with heparin-induced thrombocytopenia codes were identified. For 45 patients, the main diagnosis was heparin-induced thrombocytopenia; for the remaining 400 patients, heparin-induced thrombocytopenia occurred during the hospital stay. Tariffs and extra costs were used to estimate an overall average cost of 3230 for heparin-induced thrombocytopenia. For patients with heparin-induced thrombocytopenia as main diagnosis, the average cost was 3400; for the patients with heparin-induced thrombocytopenia that occurred during the stay, 1910 was due to an increased of the tariff and 3348 to an increased length of stay. Estimated direct costs of an episode were 3350 to 3700. Different methods were used to arrive at an estimated cost of 3500 for a heparin-induced thrombocytopenia episode for inpatients. One limitation of the study is that heparin-induced thrombocytopenia tends to be underreported by physicians during hospitalization.

To measure the ability of the Observation-based Nocturnal Sleep Inventory (ONSI) to detect the presence or absence of sleep apnea syndrome (SAS) in older adults.Cross-sectional blinded study.University hospital-based geriatric sleep center.All participants aged 70 and older were referred by physicians for suspicion of SAS.ONSI performed by nurses; overnight polysomnography. SAS was defined as an apnea-hypopnea index of 15 events or more per hour of sleep.A total of 121 consecutive patients were evaluated for study participation. Six were excluded because of technical difficulties with polysomnography or too-frequent awakenings related to medical conditions. One hundred eleven patients completed the validation process. Polysomnography identified 68 patients as having SAS and 43 patients as not having SAS. The nurse-administered ONSI demonstrated good levels of sensitivity (90%), specificity (81%), positive predictive value (88%), and negative predictive value (83%) in screening older adults for SAS.The ONSI is the first valid SAS screening tool proposed for older persons in hospitals and nursing homes. This study demonstrates that the ONSI provides accurate information; is a simple, easy-to-use bed-side tool; and is highly sensitive and specific in screening SAS when compared with overnight polysomnography results.

Object The purpose of this study was to evaluate the long-term efficacy of microvascular decompression (MVD) and to identify the factors affecting outcome in patients treated for primary trigeminal neuralgia (TN). Only the cases with a clear-cut neurovascular conflict (vascular contact and/or compression of the root entry zone of the trigeminal nerve) found at surgery and treated with “pure” MVD (decompression of the root without any additional lesioning or cutting of the adjacent rootlets) were retained. Methods The study included 362 patients who were followed up over a period of 1 to 18 years (median follow-up 7.2 years). A Kaplan–Meier survival analysis was generated at 1 and 15 years of follow-up for all of the considered factors. According to Kaplan–Meier analysis, the success rate (defined as pain-free patients without any medication) was 91% at 1 year and estimated to be 73.38% after 15 years of follow-up. Results None of the following patient-related factors played any significant role in prognosis: sex, patient age at surgery, history of systemic hypertension, duration of neuralgia before surgery, or history of failed trigeminal surgery. Patients with atypical neuralgia (a baseline of permanent pain) had the same outcome as those with a typical (purely spasmodic) presentation. In addition, the side and topography of the trigeminal nerve did not play a role, whereas involvement of all three divisions of the nerve had a negative effect on outcome. Concerning anatomical factors, neither the type of the compressive vessel nor its location along or around the root was found to be significant. However, the severity of compression was important—the more severe the degree of compression, the better the outcome (p = 0.002). The authors also found that presence of focal arachnoiditis had a negative influence on outcome (p = 0.002). Conclusions Pure MVD can offer patients affected by a primary TN a 73.38% probability of long-term (15 years) cure of neuralgia. The presence of a clear-cut and marked vascular compression at surgery (and possibly—although not yet reliably—on preoperative magnetic resonance imaging) is the guarantee of a higher than 90% success rate.

Objective To evaluate growth and bone mineralization in very low birth weight (VLBW) infants fed preterm formula (PF) or term formula (TF). Study design In a double-blind prospective study, 49 preterm infants of gestational age 33 weeks or less were randomly fed PF or TF for 2 months after discharge, then all of the infants were fed TF for the next 2 months. Anthropometric and dual-energy x-ray absorptiometry data were collected at discharge and at 2 months and 4 months after discharge. Anthropometric data also were collected at 12 months postterm. Results Four months after discharge, both body weight (6139 ± 1254 g vs 5540 ± 863 g; P = .03) and bone mineral content (104.4 ± 29.2 g vs 87.5 ± 17.1 g; P = .01) were significantly higher in the PF group compared with the TF group. At 12 months postterm, mean body weight, length, and head circumference remained higher in the PF group than in the TF group, and body mass index was similar and within the normal range in the 2 groups. Conclusions At 4 months after discharge, growth and mineralization were better in the VLBW infants who were fed PF during the first 2 months after discharge compared with those who were fed TF, suggesting that PF may be particularly valuable at this early stage of development.

Reactive oxygen species (ROS) have a negative impact on sperm DNA, leading to the formation of oxidative products such as 8-oxo-7,8-dihydroxyguanosine. This compound causes fragmentation and, thus, has a mutagenic effect. Patient treatment with oral antioxidant vitamins is, therefore, standard practice for male infertility, in an attempt to decrease formation of ROS and improve fertility. In this study, the DNA fragmentation index and the degree of sperm decondensation were measured using the sperm chromatin structure assay before and after 90 days treatment with antioxidant vitamins associated with zinc and selenium. Antioxidant treatment led to a decrease in sperm DNA fragmentation (–19.1%, P < 0.0004), suggesting that at least part of the decay was linked to ROS. However, it also led to an unexpected negative effect: an increase in sperm decondensation with the same order of magnitude (+22.8%, P < 0.0009). The opening of interchain disulphide bridges in protamines may explain this aspect, as antioxidant vitamins, especially vitamin C, are able to open the cystin net, thus interfering with paternal gene activity during preimplantation development. This observation might explain the discrepancy observed concerning the role of these antioxidant treatments in improving male fertility.

The aim of this paper was to assess oral presentation bias at a national level. This was a retrospective cohort study with initial characteristics of the approved protocols extracted from the committee's archives, and follow-up characteristics obtained from a questionnaire mailed to the principal investigators. A representative sample of French research ethics committees (25/48), the only committees legally endorsed for ethical authorisation in biomedical research, were studied. All completed research protocols, which had been approved in 1994 by these committees, were included. Initial characteristics (design, study size, investigator) of completed studies and follow-up information (direction of results, rates of publication and rates of oral presentation) were collected. Complete information on results and their dissemination was available for 248 completed non-confidential protocols. Half of these (49%) were declared as orally presented. The observed ranking for strategies to disseminate results was the following: orally presented and published, published only, neither orally presented nor published and orally presented only. Confirmatory results were more often orally presented, with an adjusted OR of 6.4 (95% CI 2.69 to 15.22). Other associated variables are the following: national/international scope of the study, protocol writer's university status, adverse events and interim analysis. There is a trend to submit or accept confirmatory results for oral presentations: meetings are a biased representation of research, and oral presentation bias could even be higher than publication bias.

Background and Purpose— The intensity of the inflammatory response may be related to the volume of acute infarction. Ultra-small superparamagnetic particles of iron oxide (USPIO) may enable assessment of neuroinflammation. We aimed to assess whether the intensity of the inflammatory response might be related to the subacute ischemic lesion volume. Methods— We enrolled patients who presented with acute anterior circulation stroke. MRI was performed at day 0, day 6, and day 9. The MRI protocol included T1-weighted imaging, gradient-echo T2*-weighted imaging, diffusion-weighted imaging, perfusion-weighted imaging and MR angiography. Blood-brain barrier disruption was defined as post-gadolinium enhancement on T1-weighted images. USPIO was administered after day 6 MRI. USPIO enhancement ratios were defined as the ratio between USPIO-related signal volume on day 9 T1-weighted imaging (respectively T2*-weighted imaging) and day 6 diffusion-weighted imaging infarct volume. The relationship between day 6 infarct volume and the enhancement ratio was assessed using Pearson and Spearman correlation tests. Results— The protocol was completed in 10 patients. Signal alterations after USPIO injection was observed in 9/10 patients on day 9 T1-weighted imaging and in 5/10 patients on day 9 T2*-weighted imaging. USPIO-related MRI enhancement was heterogeneous. Lesion volume on day 6 diffusion-weighted imaging had no impact on USPIO enhancement at day 9 according to the Pearson correlation test ( P =0.39) or Spearman test ( P =0.25). There was no relationship between blood-brain barrier disruption and USPIO enhancement. Conclusions— USPIO MRI enhancement is heterogeneous and not clearly related to subacute lesion volume.

Background Public funding is aimed at facilitating the initiation, completion and publication of research study protocols. However, no evaluation is made to investigate the impact of grant success on the conduct of biomedical research. It is therefore of great interest to compare the fate of funded protocols versus not funded: Are they initiated? Are they completed? Did the results confirm the hypothesis? Were they published? The objective was to investigate the fate of protocols submitted for funding, whether they were funded or not. Methods Retrospective cohort study of protocols submitted for funding to the Greater Lyon regional scientific committee in 1997. Initial characteristics of protocols (design, study size, investigator status) were abstracted from archives, and follow-up characteristics (initiation, completion and publication) from a mailed questionnaire to the principal investigators. Results Among the 142 submitted protocols, follow-up information was available for 114 (80%). As a whole, 38% of studies were funded by the Greater Lyon research committee. The rate of initiation varied from 62% for studies with no acknowledged funding to 100% for studies with both committee and other simultaneous funding. When initiated, the rate of completion was 62% for studies with at least one funding and 40% for studies without acknowledged funding. When completed, publication was reached for 77% of studies with either committee or external funding, for 58% of studies without acknowledged funding and for 37% of studies with both committee and external funding. Conclusion Some protocols submitted for funding were initiated and completed without any funding declared. To our understanding this mean that not all protocols submitted really needed funding and also that health care facilities are unaware that they implicitly financially support and pay for biomedical research.