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Objectives By removing systematic differences across treatment groups, simple randomization is assumed to protect against bias. However, random differences may remain if the sample size is insufficiently large. We sought to determine the minimal sample size required to eliminate random differences, thereby allowing an unbiased estimation of the treatment effect. Study Design and Setting We reanalyzed two published multicenter, large, and simple trials: the International Stroke Trial (IST) and the Coronary Artery Bypass Grafting (CABG) Off- or On-Pump Revascularization Study (CORONARY). We reiterated 1,000 times the analysis originally reported by the investigators in random samples of varying size. We measured the covariates balance across the treatment arms. We estimated the effect of aspirin and heparin on death or dependency at 30 days after stroke (IST), and the effect of off-pump CABG on a composite primary outcome of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days (CORONARY). In addition, we conducted a series of Monte Carlo simulations of randomized trials to supplement these analyses. Results Randomization removes random differences between treatment groups when including at least 1,000 participants, thereby resulting in minimal bias in effects estimation. Later, substantial bias is observed. In a short review, we show such an enrollment is achieved in 41.5% of phase 3 trials published in the highest impact medical journals. Conclusions Conclusions drawn from completely randomized trials enrolling a few participants may not be reliable. In these circumstances, alternatives such as minimization or blocking should be considered for allocating the treatment.

The main objective of this study was to investigate the impact of implementing a computer-based order entry system without clinical decision support on the number of radiographs ordered for patients seen in the emergency department.Our results show a decrease in the number of radiographs ordered after computer-based order entry system implementation, despite an increase in the number of emergency department admissions.Our study also shows that the time interval between emergency department admission and medical imaging was not affected by this new workflow. Background and objectiveThe adoption of computerized physician order entry is an important cornerstone of using health information technology (HIT) in health care. The transition from paper to computer forms presents a change in physicians' practices. The main objective of this study was to investigate the impact of implementing a computer-based order entry (CPOE) system without clinical decision support on the number of radiographs ordered for patients admitted in the emergency department. MethodsThis single-center pre-/post-intervention study was conducted in January, 2013 (before CPOE period) and January, 2014 (after CPOE period) at the emergency department at Nimes University Hospital. All patients admitted in the emergency department who had undergone medical imaging were included in the study. ResultsEmergency department admissions have increased since the implementation of CPOE (5388 in the period before CPOE implementation vs. 5808 patients after CPOE implementation, p=.008). In the period before CPOE implementation, 2345 patients (44%) had undergone medical imaging; in the period after CPOE implementation, 2306 patients (40%) had undergone medical imaging (p=.008). In the period before CPOE, 2916 medical imaging procedures were ordered; in the period after CPOE, 2876 medical imaging procedures were ordered (p=.006). In the period before CPOE, 1885 radiographs were ordered; in the period after CPOE, 1776 radiographs were ordered (p

Resume Objectifs Desir est une etude de cohorte prospective, longitudinale, multicentrique, francaise de patients souffrant de rachialgie inflammatoire evocatrice de spondyloarthrite, avec un suivi de 10 ans. Le but est d’evaluer les performances des differents systemes de criteres de classification de la spondyloarthrite axiale, et de decrire la frequence et les caracteristiques des signes cliniques de spondyloarthrite axiale. Methodes Les donnees demographiques et les items permettant la classification et le calcul des indices ont ete recueillis, ainsi que les donnees biologiques et d’imagerie. Les donnees a l’inclusion furent analysees. La performance de plusieurs systemes de criteres de classification fut evaluee (LR, rapport de vraisemblance) avec le diagnostic du medecin comme « gold standard ». Concernant la presentation clinique de la spondyloarthrite axiale, une analyse descriptive a ete realisee. Resultats Parmi les patients, 708 sont inclus ; 92 % d’entre eux satisfont a au moins un systeme de criteres de classification : mNY 26 %, 79 % Amor, ESSG 78 %, ASAS 70 % ; le niveau de confiance du medecin est de 6,8 ± 2,7. Parmi les patients, 81 et 83 % remplissent les criteres modifies (y compris IRM) d’Amor ou de l’ESSG. Une atteinte axiale est presente dans 100 % des cas. Les AINS sont pris par 90 % des patients, avec un score d’AINS de 50 ± 46. Un BASDAI superieur a 40 est note dans 60 % des cas et une CRP elevee dans 30 % des cas. L’antigene HLA-B27 est present dans 58 % des cas. Suivant l’ASDAS CRP, 12,7 % des patients ont une maladie inactive, 63 % une activite de la maladie tres elevee ; le BASFI moyen etait de 30. Une atteinte peripherique est presente dans 57 % des cas, avec une arthrite dans 37 % de ceux-ci. Une enthesite est notee chez 49 % des patients, et constitue le premier symptome chez 22,5 % des cas ; la participation de la paroi thoracique anterieure est notee dans 44,6 % des cas, et une dactylite dans 13 %. Parmi les manifestations extra-articulaires supplementaires, le psoriasis est repertorie dans 16 % des cas, une uveite dans 8,5 % et une maladie inflammatoire chronique intestinale (MICI) dans 5,1 %. Le tabagisme est present dans 36,3 % des cas et une hypertension arterielle dans 5,1 % des cas. Conclusion Ces donnees representent la base de l’evaluation du suivi de cette cohorte, permettant de futures etudes specifiques.

Summary Objectives Adverse drug events are the sixth-leading cause of death in Western countries and are also more frequent in emergency departments (EDs). In some hospitals or on some occasions, ED physicians prescribe for patients who they have admitted. These prescriptions are then followed by the wards and can persist for several days. Our objectives were to determine the frequency of prescription errors for patients over 18 years old hospitalized from ED to medical or surgical wards, and whether there exists a relationship between those prescription errors and ED LOS. Methods This was a single center retrospective study that was conduct in the ED of a university hospital with an annual census of 65 000 patients. The population studied consisted of patients over 18 years old hospitalized from ED to medical or surgical wards between January 1st, 2012 and January 21st, 2012. Results Six hundred eight patients were included. One hundred fifty-four (25%) patients had prescription errors. Prescription errors were associated with increased ED length of stay (OR = 2.47; 95% CIs [1.58; 3.92]) and polypharmacy (OR = 1.78; 95% CIs [1.20; 2.66]). Fewer prescription errors were found when the patient was examined in the ED by a consultant (OR = 0.61; 95% CIs [0.41; 0.91]) and when the medical history was known (OR = 0.28; 95% CIs [0.10; 0.88]). Conclusion Prescription errors occurred frequently in the ED. We assume that a clear communication and cooperation between EPs and consultants may help improve prescription accuracy.

Objective Hip fracture is the most devastating osteoporotic fracture, increasing the risk of mortality. Recent data suggest a decrease in incidence of this fracture. Few data are available on potential changes in mortality. We studied the change of inpatient mortality from 2002 to 2008 in France. Methods Data were extracted from the French Hospital National Database. The absolute number of inpatient mortality for hip fracture was described as well as the case fatal rate and mortality rate adjusted on age and gender. Risk factors of inpatient mortality were assessed by multiple regressions. Results Inpatient mortality stay decreased from 3057 to 2350 in patients aged 40 years and over and in both gender. Inpatient mortality stays were more important in women and increased with age, but the case fatal rate was higher in men than in women (5.4 vs. 2.8% in 2008). During the study period, the mortality rate (per 1 000 000) varied from 132 to 88 and from 82 to 64 in women and men, respectively. In the older patients, case fatality and mortality rates decreased significantly during the study period. From 2008 data, age more or equal to 85 years, male gender, stay in intensive care and existence of some chronic or acute disease, especially cardiovascular disease, hepatic disease, renal insufficiency, and infection were significant determinants of inpatient mortality. Conclusion Inpatient mortality after hip fracture decreased in France between 2002 and 2008, although age, male gender and comorbidities were identified as determinants of inpatient mortality.

Resume Objectif La fracture de hanche est la fracture osteoporotique la plus grave, augmentant le risque de mortalite. De recentes donnees suggerent une diminution de l’incidence de ce type de fracture. Peu de donnees concernant les changements potentiels en termes de mortalite sont disponibles. Nous avons etudie les modifications de la mortalite des patients hospitalises de 2002 a 2008 en France. Methodes Les donnees furent extraites de la base nationale de donnees francaises hospitalieres. Le nombre absolu d’hospitalisations pour fracture de hanche avec deces fut releve ainsi que le taux de letalite et le taux de mortalite, ajustes sur l’âge et le sexe. Les facteurs de risque de mortalite des patients hospitalises furent evalues par regressions multiples. Resultats Le nombre d’hospitalisations avec deces a diminue de 3057 a 2350 chez les patients âges de 40 ans et plus dans les deux sexes. Le nombre de sejours avec deces etait plus important chez les femmes et augmentait avec l’âge, mais le taux de letalite etait plus eleve chez les hommes que chez les femmes (5,4 vs. 2,8 % en 2008). Au cours de la periode de l’etude, le taux de mortalite (par 1000 000) varia de 132 a 88 et de 82 a 64 chez les femmes et les hommes, respectivement. Chez les patients plus âges, les taux de letalite et de mortalite ont diminue significativement au cours de la periode de l’etude. A partir des donnees de 2008, l’âge superieur ou egal a 85 ans, le sexe masculin, le sejour en soins intensifs et l’existence d’une maladie aigue ou chronique, particulierement maladie cardiovasculaire, maladie hepatique, insuffisance renale et infection, etaient des determinants significatifs de la mortalite des patients hospitalises. Conclusion La mortalite des patients hospitalises apres fracture de hanche a diminue en France entre 2002 et 2008, bien que l’âge, le sexe masculin et la presence de comorbidites aient ete identifies comme des determinants de la mortalite des patients hospitalises.

Points essentiels La progression rapide de la technologie Web a pour consequence une multiplication des dossiers de soin et de recherche pour un meme patient. Des initiatives comme le dossier medical patient ou le dossier communicant de cancerologie n’ont pas pour vocation initiale de contribuer a la recherche biomedicale. Une reflexion sur la place du dossier patient informatise comme aide a la recherche biomedicale est animee par plusieurs groupes internationaux. Remplir des dossiers multiples est un element limitant dans un contexte de restriction des ressources medicales et paramedicales et de la hausse du seuil d’exigence de qualite des soins et de la recherche biomedicale. Les obstacles a la « reutilisation secondaire » des donnees cliniques des dossiers patients informatises pour la recherche biomedicale sont d’ordre reglementaire, organisationnel et technique. L’approche proposee dans le cadre de l’initiative internationale Integrating the healthcare enterprise par le profil d’integration Retrieve form for data capture est prometteuse. Dans le cadre de registres du cancer, une initiative conjointe de l’Association nord-americaine des registres du cancer et des Centres for disease control a permis une transmission automatisee de comptes rendus d’anatomie pathologiques aux registres, limitant ainsi le deplacement de techniciens des registres dans les structures de soins.

Summary Background Stem-cell transplantation can cure primary immunodeficiencies. However, in patients with pre-existing organ toxicity, patients younger than 1 year, and those with DNA or telomere repair disorders, chemotherapy-based conditioning is poorly tolerated and results in major morbidity and mortality. We tested a novel antibody-based minimal-intensity conditioning (MIC) regimen to assess whether this approach allowed curative donor stem-cell engraftment without non-haemopoietic toxicity. Methods 16 high-risk patients underwent stem-cell transplantation for primary immunodeficiencies with an MIC regimen consisting of two rat anti-CD45 monoclonal antibodies YTH24.5 and YTH 54.12 for myelosuppression, and alemtuzumab (anti-CD52) and fludarabine, and low dose cyclophosphamide for immunosuppression. Donors were matched siblings (n=5), and matched (9) and mismatched (2) unrelated donors. Findings Antibody-based conditioning was well tolerated, with only two cases of grade 3 and no grade 4 toxicity. Rates of clinically significant acute (n=6, 36%) and chronic graft-versus-host disease (GVHD) (n=5, 31%) were acceptable. 15 of 16 patients (94%) engrafted, of whom 11 (69%) achieved full or high-level mixed chimerism in both lymphoid and myeloid lineages, and three achieved engraftment in the T-lymphoid lineage only. One patient needed retransplantation. At a median of 40 months post-transplant, 13 of 16 patients (81%) in this high-risk cohort were alive and cured from their underlying disease. Interpretation Monoclonal antibody-based conditioning seems well tolerated and can achieve curative engraftment even in patients with severe organ toxicity or DNA repair defects, or both. This novel approach represents a shift from the paradigm that intensive chemotherapy or radiotherapy, or both, is needed for donor stem-cell engraftment. This antibody-based conditioning regimen may reduce toxicity and late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor. Funding None.

The term "theranostics" characterizes a particular combination of the coupled use of a drug therapy with a diagnostic test (called "companion diagnostics"). The diagnostic test marks out the technical means used to identify a biomarker which allows for adjusting the use of the new drug.Theranostics promise a significant step forward for the use of personalized medicine, better tailored for patients in terms of efficacy and tolerance. The development process of theranostics is complex since it requires a proper phasing from development to reimbursement, through a collaborative and controlled approach.The task force's recommendations should form the basis for reflection and action amongst the different players in the field of the development of theranostics.All stages of the system meeting heterogeneous and asynchronous rules should be harmonized to allow for simultaneous availability of, and access to the drug and test. Nevertheless, it is necessary to simplify the regulations to enable a better adaptation of theranostics to the speed of innovation.

Resume Par theranostic, on entend une combinaison particuliere de l’utilisation couplee d’un medicament et d’un test diagnostique (parfois nomme « compagnon diagnostique »). Le test diagnostique designe ici le moyen technique utilise pour identifier un biomarqueur qui permet de moduler l’usage du nouveau medicament. Le theranostic constitue un progres significatif pour une medecine plus personnalisee, mieux adaptee aux patients en termes d’efficacite et de tolerance. Toutefois, le developpement des theranostics est complexe car il necessite un phasage a tous les stades, du developpement au remboursement, avec une approche collaborative et maitrisee. Le groupe de travail a emis des recommandations comme base de reflexion et d’action pour les acteurs impliques dans le developpement de theranostics. En effet, toutes les etapes du systeme repondent a des regles heterogenes et asynchrones qu’il conviendrait d’harmoniser pour permettre une mise a disposition simultanee et un acces generalise au medicament et au test. Des simplifications reglementaires sont necessaires pour permettre une meilleure adaptation du theranostic a l’acceleration de l’innovation.

Points essentiels • La medecine fondee sur le niveau de preuve (Evidence-based medicine) est nee dans les annees 1980. Elle a pour corollaire de s’appuyer sur une lecture critique des resultats publies. • La declaration « CONSORT » est un outil methodologique qui permet d’ameliorer la qualite des comptes rendus des essais therapeutiques randomises et d’effectuer une lecture critique d’articles portant sur ces essais. L’utilisation de la grille du CONSORT est requise par la plupart des grandes revues internationales pour publication des essais cliniques. Elle est pourtant mal connue et peu utilisee alors que son interet est regulierement demontre. • Nous proposons une traduction complete du « CONSORT » et la creation d’un site Internet ( http://eb.medecine.univ-paris5.fr/moodle ) pour son utilisation, afin de lever la barriere de la langue et d’en faciliter l’acces aux praticiens francophones. • L’utilisation de la grille CONSORT aide le clinicien a realiser une lecture critique des resultats publies dans le but d’exercer une pratique medicale fondee sur le niveau de preuve. • D’autres grilles ont ete proposees a la suite du CONSORT pour les autres domaines de la recherche clinique.

Summary Background Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial. In this study, we compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome. Methods Our prospective, randomised, multicentre study took place between Oct 1, 1999, and March 3, 2003, in 21 medical or multidisciplinary intensive-care units from university or community hospitals in France. Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups. The two groups were treated with the same polymer membrane and bicarbonate-based buffer. 360 patients were randomised, and the primary endpoint was 60-day survival based on an intention-to-treat analysis. Findings Rate of survival at 60-days did not differ between the groups (32% in the intermittent haemodialysis group versus 33% in the continuous renal replacement therapy group [95 % CI −8·8 to 11·1,]), or at any other time. Interpretation These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis.

Objective Two investigations evaluate Bayesian meta-regression for detecting treatment interactions. Study design and setting The first compares analyses of aggregate and individual patient data on 1,860 subjects from 11 trials testing angiotensin converting enzyme (ACE) inhibitors for nondiabetic kidney disease. The second explores meta-regression for detecting treatment interaction on 671 covariates, including the baseline risk, from 232 meta-analyses of binary outcomes compiled from the Cochrane Collaboration and the medical literature. Results In the ACE inhibitor study, treatment effects were homogeneous so meta-regression identified no interactions. Analysis of individual patient data using a multilevel model, however, discovered that treatment reduced glomerular filtration rate (GFR) more among patients with higher baseline proteinuria. The second investigation found meta-regression most effective for detecting treatment interactions with study-level factors in meta-analyses with >10 studies, heterogeneous treatment effects, or significant overall treatment effects. Under all three conditions, 46% of meta-regressions produced strong interactions (posterior probability >0.995) compared with 6% otherwise. Baseline risk was associated with the odds ratio in 6% of meta-analyses, half the rate found using maximum likelihood. Conclusion Meta-regression can detect interactions of treatment with study-level factors when treatment effects are heterogeneous. Individual patient data are needed for patient-level factors and homogeneous effects.

Introduction La fibrodysplasie ossifiante progressive (FOP) est une affection autosomique dominante rare, caracterisee par l’association d’anomalies congenitales des extremites et la survenue d’episodes successifs et cumulatifs d’ossifications musculaires irreversibles, conduisant a une ankylose progressive de l’axe vertebral et des membres. Objectifs La prevalence de la FOP est mal connue, evaluee de facon variable par deux etudes a 0,36 et 0,61 par million d’habitants. L’objectif de ce travail est d’estimer la prevalence a partir de deux systemes de collecte de donnees nationaux complementaires en France : donnees provenant soit de registres (CEMARA et MOC) soit medico-administratives (PMSI) afin notamment d’evaluer les patients non presents dans les registres. Methodes Cette etude a ete realisee a partir du croisement de CEMARA, base de donnees des centres maladies rares, existant depuis 2007 (integrant les patients FOP du registre local du centre de reference MOC etablit en 1990, apres accord des patients et des professionnels les prenant en charge) et du PMSI, base du programme de medicalisation des systemes d’information (donnees de 2006 a 2012). La date choisie pour l’estimation de la prevalence etait le 1er janvier 2012. Les patients decedes avant cette date ont ete exclus de l’etude. Resultats Les resultats preliminaires sont presentes ci-dessous. Les resultats du croisement des deux bases ne seront analyses qu’apres accord de la CNIL en attente. CEMARA et registre du CR MOC : au 01/01/2012, 85 patients vivants sont identifies FOP dans CEMARA et resident en France. Pour 63, le diagnostic avait ete confirme a cette date, 10 avaient deja des symptomes mais sans diagnostic confirme. Pour le reste (12), ces donnees sont manquantes. La prevalence est donc de 1,3 cas par million. Parmi ces 85 patients, 52 % sont des hommes, l’âge moyen est de 29 ans, 44 % ont moins de 20 ans, 48 % entre 20 et 60 ans et 8 % plus de 60 ans. PMSI : au 01/01/2012, 242 patients sont identifies dans le PMSI comme ayant ete hospitalises avec un code diagnostique CIM10 de FOP avant cette date et non decedes a cette date. La prevalence estimee est de 3,7 par million. Il est probable que certains de ces patients aient eu ce code diagnostique par exces. Ce point sera examine apres : (1) appariement des donnees avec la base CEMARA et (2) examen plus precis des donnees issues du PMSI sur ces hospitalisations (autres diagnostics, hospitalisations ulterieures). Parmi ces 242 patients, 44 % sont des hommes, l’âge moyen est de 42 ans, 18 % ont moins de 20 ans, 60 % entre 20 et 60 ans et 22 % plus de 60 ans. Conclusion Cette etude preliminaire permet de montrer pour cette pathologie une prevalence superieure aux etudes anterieures. Elle montre la pertinence du reseau CEMARA ainsi que le potentiel d’exploitation couple aux donnees medico-administratives en France pour les maladies rares. L’etude d’appariement avec le PMSI permettra d’affiner la precision de l’etude qui se situera probablement au-dessus de 1,3 cas par million en France (soit 1/770 000 residents).

The Kaplan-Meier (KM) method is commonly used to estimate the incidence of an event over time. It assumes independence between the event of interest and any competing event that precludes the event of interest to occur. However, when the competing event is death without the event of interest, censoring these patients will affect the incidence of the event of interest by modifying the number of exposed patients, so that KM results will be misleading. Three prospective cohorts were studied: (1) 657 renal transplant recipients, (2) 262 children with acute leukemia who received bone marrow transplants, and (3) 8,353 intensive care patients. The main outcome measures were kidney graft loss, leukemia relapse, and ICU-acquired infection, respectively, with death before the main outcome as the competing event. The incidence of each main outcome was overestimated by the KM method. The magnitude of overestimation ranged from 3% to 30%, and varied with baseline patient characteristics and follow-up duration, with most of this variation being related to the rate of the competing event. A competing-risk approach must be used to analyze the risk of events other than death in cohort studies, particularly when mortality rates are high.

Summary Background Transplantation of allogeneic haemopoietic stem cells can cure several primary immunodeficiencies. This European report focuses on the long-term results of such procedures done between 1968 and December, 1999, for primary immunodeficiencies. Methods The report includes data from 37 centres in 18 countries, which participated in a European registry for stem-cell transplantation in severe combined immunodeficiencies (SCID) and in other immunodeficiency disorders (non-SCID). 1082 transplants in 919 patients were studied (566 in 475 SCID patients, 512 in 444 non-SCID patients; four procedures excluded owing to insufficient data). Minimum follow-up of 6 months was required. Findings In SCID, 3-year survival with sustained engraftment was significantly better after HLA-identical than after mismatched transplantation (77% vs 54%; p=0·002) and survival improved over time. In HLA-mismatched stem-cell transplantation, B(–) SCID had poorer prognosis than B(+) SCID. However, improvement with time occurred in both SCID phenotypes. In non-SCID, 3-year survival after genotypically HLA-matched, phenotypically HLA-matched, HLA-mismatched related, and unrelated-donor transplantation was 71%, 42%, 42%, and 59%, respectively (p=0·0006). Acute graft versus host disease predicted poor prognosis whatever the donor origin except in related HLA-identical transplantation in SCID. Interpretation The improvement in survival over time indicates more effective prevention and treatment of disease-related and procedure-related complications—eg, infections and graft versus host disease. An important factor is better prevention of graft versus host disease in the HLA-non-identical setting by use of more efficient methods of T-cell depletion. For non-SCID, stem-cell transplantation can provide a cure, and grafts from unrelated donors are almost as beneficial as those from genetically HLA-identical relatives.

In France, the prevalence of End-Stage Renal Disease (ESRD) is not precisely known. The sources of information are scattered and not coordinated. Consequently, care is ill adapted to meet the demand. The Multi-Source Information System is the basis of the Renal Epidemiology and Information Network (REIN). It is dedicated to improve and organise our medical and epidemiological knowledge of ESRD and to aid public health decision-making in this area. The proposed approach is based on the datawarehouses. This model allows a unified vision of scattered data into distinct databases, for a better management, be it particular (patient follow-up) or global (regional follow-up), with a finality of aid in decision-making. Several categories of problems were considered: the global conception of the information system, the organisation of the datawarehouse, which offers different viewpoints of the data, the integration of heterogeneous data coming from different sources, data exchange and definition of a specific ontology.

Objectif(s) Creee en 2007, CEMARA est une application permettant l’enregistrement des patients suivis dans les centres de reference et de competences maladies rares (CMR). Elle a pour finalite principale de contribuer a l’elaboration et a l’evaluation des strategies sanitaires visant a ameliorer la prise en charge des patients atteints de maladies rares. Par l’identification d’indicateurs de sante publique, ce recueil participe a une meilleure description de l’epidemiologie des maladies rares. Methode Les CMR recueillent pour chaque patient un set de donnees minimum defini par consensus en 2006 comprenant identification, diagnostic (terminologie Orphanet) et activite de prise en charge medicale (consultations, hospitalisations, avis). Ce recueil s’effectue au cours de la prise en charge des patients au sein des centres de reference ou de competence du reseau participant : 66 centres de reference par plus de 1 600 utilisateurs. Sont definis comme des cas, les patients nes, atteints, avec un diagnostic confirme, probable ou non classable. Resultats Au 31 decembre 2015, le recueil concernait 307 295 patients, 14 275 porteurs sains, et 73 312 non malades (generalement des apparentes). Sont egalement recenses 18 260 fœtus. Parmi les personnes malades, 1,2 % sont declarees decedees (30 % des fœtus). La file active de 2015 a ete de 77 143 patients dont plus de la moitie (environ 40 000) ont ete crees pour la premiere fois au court de l’annee. Le sex-ratio est de 1,097, (p Conclusion Apres huit ans de recueil, et grâce a l’implication des CMR, CEMARA est une ressource unique qui viendra alimenter de maniere de-identifiee la Banque nationale de donnees maladies rares (BNDMR). Elle a permis aux centres de reference participant de mieux suivre leur file active, de publier et de participer a des projets de recherche. Cependant, l’exhaustivite des cas et la saisie systematique des activites est difficile a obtenir. De plus, certains items tels que le deces ou les communes de naissance sont peu renseignes. Ces donnees pourraient etre retrouvees ou redressees grâce au chainage de la BNDMR avec d’autres bases nationales (SNDS, registres…) sous reserve de la possibilite d’utilisation du NIR. De grandes etudes nationales (medico-economiques, parcours de prise en charge…) pourraient egalement etre favorisees.

Objectifs La cystinose, trouble de surcharge lysosomale, est une maladie rare qui, en l’absence de traitement, se compliquait d’une insuffisance renale chronique terminale (IRCT) avant l’âge de 10 ans. Depuis l’arrivee sur le marche en 1998 de la cysteamine, l’IRCT a ete retardee de plusieurs dizaines d’annees et l’esperance de vie a quintuple. L’observance des personnes pour ce medicament est un defi lie a sa pharmacodynamie contraignante (une prise toutes les 6 heures) et aux effets indesirables du traitement (odeur soufree de l’haleine). Les objectifs de notre travail etaient d’evaluer la prevalence de la cystinose en France, l’observance du traitement, et les couts directs pour l’assurance maladie. Methodes Les donnees ont ete obtenues a partir du Systeme national d’informations inter-regimes de l’Assurance maladie (2009–2013) chaine au PMSI (2005–2013) en cooperation avec la Banque nationale de donnees maladies rares (BNDMR). Un cas de cystinose a ete dit prevalent s’il presentait au moins un des criteres suivants : des remboursements du traitement specifique de la cystinose delivre en pharmacie centrale d’hopital, une affection de longue duree specifique de la cystinose (code CIM-10 specifique des maladies metaboliques hereditaires E720a) et un critere composite combinant des donnees hospitalieres, de remboursement du traitement et de motif d’affection longue duree. La prevalence a ete estimee au 31 decembre 2013, l’observance et les couts respectivement sur la periode 2012–2013 et 2013. Resultats Au total, 118 personnes ont ete identifiees comme ayant une cystinose (58 hommes). La prevalence brute observee en France etait de 1,8 cas par million d’habitants (IC95 % : [1,5–2,1]). L’âge moyen etait de 21,2 ± 12,8 ans. Pres de la moitie des cas (47,5 %) presentait une IRCT et cette proportion augmentait avec l’âge (0–9 ans 0 % ; 10–19 ans 29 % ; plus de 20 ans 80 %). Plus de la moitie des patients (52 %) avaient une bonne observance du traitement par cysteamine (≥80 %) ; cependant, cette observance diminuait avec l’âge (0–9 ans 73 % ; 10–19 ans 57 % ; 20–29 ans 48 %). A l’adolescence, une mediocre acceptation des contraintes du traitement se prolonge jusqu’au debut de l’âge adulte. L’observance du traitement chez les dialyses etait adaptee dans seulement 2 cas sur 3. Si la cystinose ne recidive pas sur un greffon, en revanche, le traitement doit etre poursuivi pour prevenir les manifestations musculaires et neurologiques. Or, deux transplantes sur 3 ne paraissent pas compliants. En 2013, le cout global des soins etait de 2,9 millions d’euros soit en moyenne 24,606 euros par patient. Les principaux postes de depenses etaient les medicaments (48 %), l’hospitalisation (33 %) et les transports (9 %). Conclusion La prevalence de la cystinose estimee a partir du SNIIRAM, voisine de 1/500 000, est coherente avec celle de la BNDMR et plus faible que les donnees de la litterature (1/200 000). Un patient transplante sur 3, et plus de la moitie des patients de plus de 20 ans, ont une observance du traitement qui parait mediocre. La base medico-administrative de l’assurance maladie est apparue utile a une approche pharmaco-epidemiologique et economique d’une maladie rare, ici la cystinose, lorsqu’un traitement specifique existe.

Background/Aims: Long-term survival of patients with intestinal failure requiring home parenteral nutrition (HPN) has been only partly shown. Therefore, we described the survival of these patients and explored prognosis factors. Methods: Two hundred seventeen noncancer non-acquired immunodeficiency syndrome adult patients presenting with chronic intestinal failure enrolled from January 1980 to December 1989 in approved HPN programs in Belgium and France; prognosis factors of survival were explored using multivariate analysis. Data were updated in March 1991; not one of the patients was lost to follow-up. Results: Seventy-three patients died during the survey, and the mortality rate related to HPN complications accounted for 11% of deaths. Probabilities of survival at 1, 3, and 5 years were 91%, 70%, and 62%, respectively. Three independent variables were associated with a decreased risk of death: age of patients younger than 40 years, start of HPN after 1987, and absence of chronic intestinal obstruction. In patients younger than 60 years of age included after 1983 with a very short bowel, who could represent suitable candidates for small bowel transplantation, the 2-year survival rate was 90%, a prognosis that compared favorably with recent reports of survival after small bowel transplantation. Conclusions: HPN prognosis compares favorably with recent reports of survival after small bowel transplantation.

The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months). This good prognosis was associated with rapid development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n=100) gave significantly lower survival (52%; median follow-up 47 months). Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients. Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell chimerism was strongly associated with the development of normal B-cell function.

Summary Introduction The aim of this study was to assess the burden of hospitalized wrist fractures between 2002 and 2006 in France. Methods Data were drawn from the French Hospital National Database. The number of admissions and the incidence rates were described as well as the type of entry and discharge from hospital, length of stay, and 2006 in-patients costs. Results Thirty-eight thousand seven hundred and ten and 38,979 hospitalizations for wrist fractures were registered in 2002 and 2006, respectively. The incidence rate of fractures increased with age whatever the year and decreased significantly from 2002 to 2006. Lengths of stay and mean inpatients costs increased with age. The overall in-patients 2006 costs was 79 millions with an average individual cost of 2100 € per hospitalized wrist fractures. Conclusion The incidence of hospitalizations for wrist fractures decreased in 2006 compared to 2002. The number of hospitalizations increased, as a consequence of ageing, (except for wrist fracture in men) with a subsequent increase in cost related to these fractures. The increase with age outlines the role of underlying osteoporosis and the relevance of appropriate care of patients at risk of for such fractures. Level of evidence IV.

Background: Hematopoietic stem cell transplantation remains the only treatment for most patients with severe combined immunodeficiencies (SCIDs) or other primary immunodeficiencies (non-SCID PIDs). Objective: To analyze the long-term outcome of patients with SCID and non-SCID PID from European centers treated between 1968 and 2005. Methods: The product-limit method estimated cumulative survival; the log-rank test compared survival between groups. A Cox proportional-hazard model evaluated the impact of independent predictors on patient survival. Results: In patients with SCID, survival with genoidentical donors (n = 25) from 2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005). Transplantation after year 1995, a younger age, B+ phenotype, genoidentical and phenoidentical donors, absence of respiratory impairment, or viral infection before transplantation were associated with better prognosis on multivariate analysis. For nonSCID PID, in contrast with patients with SCID, we confirm that, in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival was 76% in phenoidentical transplants (n = 23) and worse in mismatched related donor transplants (n = 47; 46%; P = .016). Conclusion: This is the largest cohort study of such patients with the longest follow-up. Specific issues arise for different patient groups. Patients with B-SCID have worse survival than other patients with SCID, despite improvements in each group. For non-SCID PID, survival is worse than SCID, although more conditions are now treated. Individual disease categories now need to be analyzed so that disease-specific prognosis may be better understood and the best treatments planned. (J Allergy Clin Immunol 2010;126:602-10.)

Objectifs Recenser retrospectivement et prospectivement aupres des chirurgiens et oncologues pediatres, toutes observations de cancers pediatriques syndromiques. Des syndromes malformatifs augmentant le risque de cancer ont permis historiquement d’identifier des genes de predisposition. On observe que les malformations et maladies du developpement sont plus frequentes dans la population d’enfants atteints de cancer que dans la population generale, suggerant qu’une cause genetique unique puisse occasionnellement expliquer l’ensemble du phenotype. Les cancers syndromiques sont neanmoins peu recenses, et les associations fortuites peu distinguees des associations significatives. Materiels et Methodes Ces cas seront recenses sur la base de donnees CEMARA, en y precisant les echantillons biologiques constitutionnels et tumoraux disponibles. Ils feront l’objet d’etudes specifiques, orientees par des associations syndromiques decouvertes comme recurrentes ou par des associations semblant hautement significatives. Resultats/ Conclusion Ce projet biologique a vocation a s’etendre a toute equipe de recherche impliquee dans les thematiques «oncogenetique» et/ou «maladie du developpement». Il se construira autour d’un consortium scientifique reunissant les equipes ainsi identifiees.

Rationnel Des travaux preliminaires ont montre une efficacite du recepteur antagoniste de l’interleukine (IL) –1 Anakinra dans la forme systemique d’arthrite juvenile idiopathique (FS-AJI). Objectifs Evaluer l’efficacite et la tolerance de l’anakinra dans la FS-AJI. Etudier la pharmacocinetique et l’effet du traitement sur differents parametres accessoires. Methode Essai multicentrique randomise contre placebo. Objectif principal : demontrer la superiorite d’un traitement par anakinra (2 mg/kg en une sous-cutanee par jour, maximum 100 mg) sur un placebo en comparant a un mois deux groupes de 12 patients. Reponse : jugee sur une amelioration d’au moins 30 % du score composite de Giannini (prenant en compte l’atteinte articulaire, l’evaluation de l’activite de la maladie par les parents et le medecin, le score fonctionnel CHAQ et la VS), une disparition de la fievre et des signes systemiques, une negativation ou une reduction d’au moins 50 % de la CRP et de la VS comparativement a J1. Analyse en intention de traiter. Objectifs secondaires : analyse sur 12 mois de l’efficacite et de la tolerance du traitement, de la possibilite de diminuer la dose de corticoides apres le premier mois. Marqueurs accessoires d’efficacite du traitement dont pharmacocinetique. Resultats Le taux de repondeurs a 1 mois (objectif principal) etait significativement plus eleve sous Anakinra (8/12 repondeurs) que sous placebo (1/12). Sur l’ensemble de l’etude, cinq effets indesirables graves ont ete repertories dont une atteinte ileocolique apres 2 mois s’averant etre une maladie de Crohn ; trois infections et un tassement vertebral n’ont pas requis l’interruption du traitement. Dans 7 cas, le traitement a ete interrompu pour injections trop douloureuses (2 cas, sous placebo), manque d’efficacite ou poussee de la maladie a la decroissance de la corticotherapie (4 cas), hepatite cytolytique transitoire (1 cas). L’etude des criteres secondaires de jugement suggere un interet de la pharmacocinetique et de l’etude du profil d’expression de certains genes. Conclusion Premier essai controle demontrant l’efficacite d’un traitement anti-IL-1 dans la FS-AJI.

Two new thermostable aldosterone binding globulins were partially characterised in plasma (ABG-TS) and urine (ABD-TSu) of normal humans. Analysis comprised ultrafiltration, dialysis, incubation at 37°C preceding or following DEAE cellulose chromatography (pH gradient), and Sephadex G75 chromatography. Both compounds had a molecular weight and isoelectric point similar to that of the already described plasma thermolabile ABG. In studies on the effect of potassium canrenoate, with physiologic range, on aldosterone ABG binding in vivo in 4 out of 7 and in vitro in 9 hypertensives, a decrease, probably due to a specific competitive displacement of aldosterone, was observed. The transmission of high ABG capacity, as reflecting high plasma ABG concentration, was studied in three generations of 40 French Canadian families from the Montreal area. Samples were taken from 304 relatives (aged 2 1 2 −84 ) of two known essential hypertensive (EH) parents, and also from 290 controls (aged 4–65). Relatives with values similar to controls were designated “normal” in contrast to relatives carrying the high ABG binding trait designated “affected”. In “affected” relatives, total mid-afternoon to early evening plasma aldosterone was similar to that of normal relatives or controls but the free fraction was less (P