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Objective To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. Methods From 2003 to 2005, 813 patients were included if they had early arthritis ( Results In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. Conclusions We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Resume Objectif L’objectif de cette etude est de presenter l’evolution des donnees d’incidence et de mortalite du cancer des organes genitaux externes de l’homme dans l’Herault a partir des donnees du Registre des tumeurs de l’Herault (RTH) sur une periode de 30 ans. Materiel et methodes A partir de la base de donnees du RTH, nous avons etudie l’evolution des tumeurs germinales du testicule (TGT) et du cancer du penis (CP) sur 30 ans (de 1987 a 2016). Nous avons analyse les donnees d’incidence et de mortalite de ces tumeurs. Nous avons compare ces resultats aux donnees francaises, europeennes et mondiales. Resultats En 30 ans d’enregistrement nous avons recense 725 cas de TGT et 175 cas de CP. Le taux standardise sur la population mondiale (TSM) d’incidence des TGT a double entre 1987 et 2016 (4,2/100 000 en 1987 et 9,3/100 000 en 2016). Il a ete multiplie par 2,63 dans la population des patients de 30 a 44 ans. On observe une baisse du taux de mortalite avec un TSM a 0,8/100 000 en 1987, et 0,4/100 000 en 2016. Le TSM d’incidence des CP est stable entre 1987 et 2016 (TSM entre 0,4 et 0,9/100 000). La mortalite est stable avec un TSM entre 0,1 et 0,3/100 000 entre 1987 et 2016. Conclusion L’incidence des TGT a fortement augmente dans l’Herault durant les 30 dernieres annees alors que l’on observe une diminution de la mortalite. La proportion des tumeurs germinales seminomateuses augmente ; elle est passee de 53 % a 60 % en 30 ans dans l’Herault. L’incidence et la mortalite du CP etaient stables dans l’Herault durant les 30 dernieres annees.

Resume Objectifs On observe dans l’Herault une nette augmentation de l’incidence des cancers urologiques. Le registre des tumeurs de l’Herault (RTH) a recueilli 1961 tumeurs urologiques en 2016, soit 21,4 % de l’ensemble des tumeurs de l’Herault pour cette annee-la. La creation d’un registre specialise en onco-urologie nous est apparue necessaire. L’objectif de cet article est de decrire le fonctionnement de RHESOU et de donner quelques exemples de resultats. Materiel et methodes En novembre 2018, RHESOU (Registre de l’herault specialise en onco-urologie) a ete cree sur le meme mode de fonctionnement qu’un registre. Il permet de completer les donnees du RTH sur beaucoup d’autres parametres oncologiques. Pour chaque type de cancer urologique et genital masculin et urologique feminin, une fiche de recueil a ete realisee pour recueillir le maximum de donnees presentes dans le dossier des cas signales. Cette etude a evalue les donnees concernant les patients domicilies dans l’Herault pour l’annee 2017. Resultats Nous avons denombre pour l’annee 2017, 970 cancers de la prostate, 581 tumeurs de vessie, 212 cancers du rein, 51 tumeurs de la voie excretrice superieure, 28 cancers du testicule et 9 cancers du penis. Le recueil de ces donnees permet de creer des requetes et de fournir des analyses pertinentes et detaillees sur les cancers urologiques et genitaux masculins. Nous rapportons les donnees analysees sur le rein, la vessie et la prostate. Conclusions RHESOU est un outil accessible pour permettre une vue d’ensemble sur les cancers en urologie dans l’Herault et leur prise en charge. Avec l’apparition de nouveaux traitements, il saura s’adapter en permettant une evolution des fiches. Niveau de preuve 3.

Poly(ADP-ribose) polymerase 1 inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA) in both the metastatic and adjuvant setting. Therefore, we need to reassess the frequency of gBRCA1 and gBRCA2 in order to redefine the criteria for women and tumor phenotype that should be tested.We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with breast cancer and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected breast cancer patients with gBRCA.We performed a meta-analysis of studies of unselected breast cancer that analyzed the relative contribution of gBRCA1 versus gBRCA2 among unselected breast cancer cases in gBRCA carriers. We then performed a meta-analysis of gBRCA carriage in unaffected individuals from genome-wide population studies, the gnomAD databank, and case-control studies.TheThis meta-analysis showed that gBRCA2 carriage is predominant in unselected breast cancer patients and unaffected individuals. ER+ tumors among women with gBRCA-related breast cancer are predominant and have been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA breast cancer in most clinical trials, breast cancer should be considered, regardless of ER status, for

International audience; Purpose: The metabolic changes associated with cachexia – sarcopenia syndrome might down-regulate antitumor immunity. We hypothesized that this syndrome reduces efficiency of immune checkpoint inhibitors (ICPI) in non-small cell lung cancer (NSCLC).Methods: The records of 142 consecutive NSCLC patients receiving first- or second-line anti-Programmed cell death protein 1) ICPI were reviewed. Response evaluation according to Response Evaluation Criteria in Solid Tumors 1.1 was performed at the eighth week of immunotherapy. Pretreatment cachexia was defined as a body-weight loss of 5% or more in the previous 6 months. Sarcopenia was estimated with the third lumbar skeletal muscle mass index (mSMI) and was evaluated before immunotherapy and at the eighth week. A decrease by 5% or more of the mSMI was considered as an evolving sarcopenia. The endpoints were disease control rate (DCR), progression-free (PFS) and overall survival (OS).Logistic regression model and Cox model took into account others covariables known to influence ICPI efficiency, particularly Programmed Death –Ligand 1 tumor cell score, Eastern Cooperative Oncology Group performance status and common somatic mutational status.Results: In multivariate analysis, cachexia – sarcopenia syndrome reduced the probability of achieving a disease control and were associated with a shorter survival. Patients without cachexia had a better probability to achieve disease control in comparison with those who did not experience cachexia (59.9 % and 41.1 %, respectively; odds ratio 95 % (confidence interval [95 %CI]): 2.60 (1.03–6.58)). Patients with cachexia had a shorter OS when compared with those without cachexia (hazard ratios [HR] (95 %CI): 6.26 (2.23–17.57)). Patients with an evolving sarcopenia had a shorter PFS and OS, with HR (95 %CI): 2.45 (1.09–5.53) and 3.87 (1.60–9.34) respectively.Conclusion: Cachexia – sarcopenia syndrome negatively influences patients’ outcome during anti-PD-1 ICPI therapy

Multimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response. The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis, the ESPOIR cohort, and its possible impact on the therapeutic response.We included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed. Each patient was assigned scores of binary aMMI (0=no comorbidity, 1=at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying antirheumatic drug (DMARD) according to the aMMI. We collected data from the visit preceding the first DMARD initiation and the visit after at least 3 months of treatment. The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated.Analyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI=0 or 1, respectively (non-significant), achieved CDAI low disease activity. Similar results were found with counted and weighted aMMI. Therapeutic maintenance was significantly better with binary aMMI=1 than binary aMMI=0 (OR at 10 years=14.0 [CI 95% 3.3-59.4]). Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point.In the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.

Resume Objectifs L’asthme est la premiere pathologie chronique de l’enfant ; son controle et son traitement restent insuffisants. Notre objectif etait d’evaluer si l’utilisation du Childhood Asthma Control Test (C-ACT) en medecine generale avait un impact sur l’adaptation du traitement de fond. Methodes Notre etude quantitative, prospective, comparait 2 groupes de medecins generalistes. Tous ont eu les memes rappels sur l’asthme de l’enfant. Le C-ACT etait presente au groupe C-ACT uniquement. Les medecins du groupe controle devaient travailler de maniere habituelle, sans C-ACT. Les medecins incluaient des enfants asthmatiques de 6 a 11 ans les consultant pour leur asthme ou tout autre motif. Le critere de jugement principal etait l’adaptation du traitement de fond de l’asthme selon les paliers du Global INitative for Asthma (GINA). Les evaluations du groupe controle etaient comparees au C-ACT auto-administre sur internet apres la consultation. Resultats D’avril a octobre 2014, 61 medecins ont inclus 179 patients en 2 groupes comparables. Bien que non statistiquement significatif, avec le C-ACT, les medecins identifiaient 45 % d’asthmes non controles (contre 31 %). Lorsque le motif de consultation n’etait pas lie a l’asthme, ils en depistaient 25 % (contre 15 %). Les medecins utilisant le C-ACT faisaient 2 fois moins d’adaptations therapeutiques non recommandees par le GINA : 8 % contre 16 %. Dans le groupe controle, 25 % des evaluations etaient discordantes avec le C-ACT internet rempli par le patient. Apres correction par le C-ACT internet de ces evaluations initiales imprecises, il y avait en realite 25 % d’adaptations non recommandees : 3 fois plus que dans le groupe C-ACT (p = 0,014). Conclusion Utiliser le C-ACT en medecine generale permet de mieux evaluer le controle de l’asthme de l’enfant et de mieux adapter le traitement de fond.

Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for gBRCA1/2. Objective: We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with BC and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected BC patients with gBRCA1/2.Design: We performed a meta-analysis of studies of unselected BC that analyzed the relative contribution of gBRCA1 versus gBRCA2 and ER+ tumors among gBRCA1/2 carriers. We then performed a meta-analysis of gBRCA1/2 carriage in unaffected individuals, from genome-wide population studies, the gnomAD databank, and case–control studies. Results: The BRCA2 gene was involved in 54% of BC in unselected patients with gBRCA1/2 (n=108,699) and 59% of unaffected individuals (n=238,973) as compared with 38% of gBRCA1/2 family cohorts (n=29,700). The meta-analysis showed that 1.66% (95% CI 1.08-2.54) and 1.71% (95% CI 1.33-2.2) of unselected BC patients carried a gBRCA1 and gBRCA2, respectively. In unaffected individuals, the frequency of heterozygosity for gBRCA1 and gBRCA2 was estimated at 1/434 and 1/288, respectively. Nearly 0.5% of unaffected individuals in the studied populations carried a gBRCA1/2. Overall, 58% of breast tumors occurring in women carrying a gBRCA1/2 were ER+ (n=86,870).Conclusion: This meta-analysis showed that gBRCA2 carriage is predominant in unselected BC and in unaffected individuals. ER+ tumors among women with gBRCA1/2-related BC is predominant and has been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA1/2 BC in both the adjuvant and metastatic setting, BC should be considered regardless of ER status for BRCA1/2 screening for therapeutic purposes.

Background Flap surgery for deep pelvic pressure ulcers has already shown its effectiveness. Most studies relating to the postoperative period assessed complications rates and associated risk factors, but none focused on delayed wound healing. The objective of this study was to describe wound healing delay after primary flap surgery in patients with spinal cord injury (SCI) and to assess associated risk factors. Methods This observational retrospective study based on medical charts included all persons with SCI operated for primary flap surgery for pelvic PU in the Herault department of France between 2006 and 2014. Overall, 100 biomedical, psychological, socioeconomics and care management factors were studied. The primary outcome was wound healing delay, defined as time from surgery to complete cutaneous closure. Results 85 patients were included. Median healing time was 48 days (R: 20–406). Healing rate was 70% at 3 months and 90% at 4 months. After a multivariate analysis three factors were significantly associated with delayed wound healing: duration of hospitalization in the acute care unit (HR = 2.68; p = 0.004), local post-operative complication (HR = 10.75; p = 0.02), and post-operative sepsis (HR = 2.18; p = 0.02). Conclusion After primary skin flap surgery for PU in persons with SCI, delayed wound healing is related to local or general complications as well as care management organization. The risk of delayed wound healing justifies the implementation of a coordinated pre-operative management to prevent complications and a structured care network for an earlier transfer to a SCI rehabilitation center.

Resume Objectif Dans le but de connaitre ce que les medecins specialistes attendent de la chimiotherapie du cancer du poumon (stade 3b et 4), nous les avons confrontes a un auto-questionnaire en ligne decrivant cinq situations differentes de prescription. Methode Trente specialistes experts ont ete invites ; 22 ont repondu (73 %). Pour chacune des differentes situations cliniques, il etait demande a l’expert de se positionner sur 3 items : curabilite, allongement de la survie, soulagement des symptomes. Le jugement porte sur chaque item se faisait sur une echelle de Likert impaire, entre −2 « pas du tout probable » et 2 « tout a fait probable ». Resultats Pour la curabilite, le pourcentage de reponse −2 differait significativement en fonction de la situation clinique (test de Fisher : p Conclusion Ce que les medecins specialistes attendent de la chimiotherapie differe en fonction du pronostic presuppose. A la situation de plus mauvais pronostic correspond l’attente la plus forte en termes de soulagement des symptomes et la plus faible en termes de curabilite.

Resume Objectif L’objectif de l’etude etait de determiner la performance diagnostique de l’IRM dans la distinction des lesions endometriales begnines et malignes chez les patientes menopausees atteintes de metrorragies postmenopausiques ou d’un epaississement endometrial asymptomatique. Patientes et methodes Il s’agissait d’une etude prospective, de 2016 a 2018, incluant les patientes menopausees atteintes de metrorragies postmenopausiques ou d’un epaississement endometrial asymptomatique, en dehors d’un traitement par tamoxifene ou d’un traitement hormonal substitutif. Une IRM pelvienne comprenant des sequences morphologiques (T1, T2, T1 post-gadolinium) et fonctionnelles (diffusion, perfusion) a ete realisee. Les donnees des IRM ont ete comparees aux resultats anatomopathologiques. Resultats Sur 61 patientes incluses, 42 ont beneficie d’un prelevement de l’endometre ; il y avait 15 cancers de l’endometre (25 %), une hyperplasie atypique (1,6 %) et 35 lesions benignes (58 %). L’âge moyen etait de 63 ans. La presence d’un endometre epais (p Conclusion L’IRM pelvienne est performante pour differencier les lesions endometriales begnines et malignes chez les patientes menopausees atteintes de metrorragies postmenopausiques ou d’un epaississement endometrial asymptomatique.

International audience

According to clinical guidelines, the occurrence of very early-onset breast cancer (VEO-BC) (diagnosed ≤ age 30 years) or VEO ovarian cancer (VEO-OC) (diagnosed ≤ age 40 years) in families with BRCA1 or BRCA2 mutation (BRCAm) prompts advancing the age of risk-reducing strategies in relatives. This study aimed to assess the relation between the occurrence of VEO-BC or VEO-OC in families with BRCAm and age at BC or OC diagnosis in relatives. We conducted a retrospective multicenter study of 448 consecutive families with BRCAm from 2003 to 2018. Mean age and 5-year–span distribution of age at BC or OC in relatives were compared in families with or without VEO-BC or VEO-OC. Conditional probability calculation and Cochran–Mantel–Haenszel chi-square tests were used to investigate early-onset cancer occurrence in relatives of VEO-BC and VEO-OC cases. Overall, 15% (19/245) of families with BRCA1m and 9% (19/203) with BRCA2m featured at least one case of VEO-BC, 8% (37/245) and 2% (2/203) featured at least one case of VEO-OC, respectively. The cumulative prevalence of VEO-BC was 5.1% (95% CI 3.6–6.6) and 2.5% (95% CI 1.4–3.6) for families with BRCA1m and BRCA2m, respectively. The distribution of age and mean age at BC diagnosis in relatives did not differ by occurrence of VEO-BC for families with BRCA1m or BRCA2m. Conditional probability calculations did not show an increase of early-onset BC in VEO-BC families with BRCA1m or BRCA2m. Conversely, the probability of VEO-BC was not increased in families with early-onset BC. VEO-BC or VEO-OC occurrence may not be related to young age at BC or OC onset in relatives in families with BRCAm. This finding—together with a relatively high VEO-BC risk for women with BRCAm—advocates for MRI breast screening from age 25 regardless of family history.

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.

BACKGROUND This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by chemotherapy and cetuximab. METHODS In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D0) D7, and D21 of treatment for CTC detection by CellSearch®, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan–Meier method and compared with the log-rank test (P < 0.05). RESULTS At D0, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D0, D7, and D21, respectively. Median PFS time was significantly lower in (a) patients with increasing or stable CTC counts (36/54) from D0 to D7 with EPISPOTEGFR (3.9 vs 6.2 months; 95% CI, 5.0–6.9; P = 0.0103) and (b) patients with ≥1 CTC detected with EPISPOT or CellSearch® (37/51) (P = 0.0311), EPISPOT or FCM (38/54) (P = 0.0480), and CellSearch or FCM (11/51) (P = 0.0005) at D7. CONCLUSIONS CTCs can be detected before and during chemotherapy in patients with rHNSCC. D0–D7 CTC kinetics evaluated with EPISPOTEGFR are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC. ClinicalTrials.gov Identifier NCT02119559

International audience

Resume Introduction Un nombre important de patients atteints d’un cancer de la prostate (CP) est diagnostique et traite. L’objectif de cette etude est d’analyser, deux ans apres traitement, l’incontinence urinaire (IU) et les dysfonctionnements sexuels (DS) pouvant affecter les patients. Methodes Cette etude a suivi tous les cas de CP localise, diagnostiques entre 2008–2009, chez les hommes d’âge ≤ 65 ans en vie deux ans apres traitements. Quatre cent trente-sept personnes ont ete incluses dans l’enquete. Les donnees ont ete collectees par un questionnaire et par croisement avec les donnees du registre des cancers. Une analyse descriptive et comparative de la persistance des sequelles a deux ans a ete effectuee. Resultats A deux ans du traitement, l’IU a persiste pour 48,8 %, 41,2 % ont eu recours a des protections urinaires ; 39,2 % portaient au moins une protection/jour ; 55,2 % ont eu des difficultes financieres a l’achat des protections. Au total, 22,7 % n’ont pas consulte de specialiste pour l’IU. Les DS ont persiste pour 82,8 % ; 30,4 % n’ont pas consulte de specialiste. Les DS ont eu un impact negatif sur la vie sexuelle des patients et de leurs partenaires. Apres ajustement sur le stade, seule la prostatectomie est significativement associee a la persistance de l’IU et de la DS. Conclusion Le pourcentage de patients ayant une IU et/ou une DS persistante reste eleve. La persistance de ces sequelles a ete associee a la prostatectomie. Les differences de toxicites entre traitements doivent etre presentees aux patients avant toute prise en charge afin d’engager le patient dans une demarche de decision partagee.

Purpose of Review Since healthcare costs have continued to rise, health-economic approaches in perioperative medicine tend to create potential benefits. However, a review of the perioperative literature reveals that there are only few published economic analyses. The aim of the present review is to explore the health-economic researches in the field of perioperative medicine.

Background: Health inequalities have increased over the last 30 years. Our goal was to investigate the relationship between low individual socioeconomic status and poor breast cancer prognosis. Our hypothesis was: low socioeconomic status patients have a higher risk of being diagnosed with late stage breast cancer than high socioeconomic status ones due to delayed diagnosis. Methods: We conducted a matched case–control study on 619 women with breast cancer, living in the Herault, a French administrative area. Both Cases and Controls were recruited among invasive cases diagnosed in 2011 and 2012 and treated in Herault care centers. Cases were defined as patients with advanced stages. Controls were composed of early stage patients. Individual socioeconomic status was assessed using a validated individual score adapted to the French population and health care system. Results: We observed that low socioeconomic status patients have a 2-fold risk of having late stage breast cancer regardless of cancer characteristics and detection mode (screening vs. clinical signs). Conclusion: One reason explaining those results could be that low socioeconomic status patients have less regular follow-up which can lead to later and poorer diagnosis. Follow-up is improved for women with a better awareness of breast cancer. Health policy makers could reduce health inequalities by reducing the delay in breast cancer diagnosis for low socioeconomic status women.

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.

This article presents a semiparametric method for estimating receiver operating characteristic surface under density ratio model. The construction of the proposed method is based on the adjacent-category logit model and the empirical likelihood approach. A bootstrap approach for the VUS estimator inference is presented. In a simulation study, the proposed estimator is compared with the existing parametric and nonparametric estimators in terms of bias, standard error, and mean square error. Finally, a real data example and some discussions on the proposed method are provided.

International audience; BACKGROUND AND PURPOSE:Vitamin D deficiency is a recognized risk factor for multiple sclerosis (MS) and is associated with increased disease activity. It has also been proposed that the lower the vitamin D levels are, the higher is the handicap.METHODS:To refine the links between vitamin D insufficiency and disability in MS patients, a retrospective cohort analysis was performed including 181 patients prospectively followed without previous vitamin D supplementation, and age, gender, age at MS onset, MS type, MS activity, Expanded Disability Status Scale (EDSS) were analysed in correlation with plasma vitamin D levels.RESULTS:Vitamin D levels were significantly higher in relapsing-remitting MS than in progressive forms of MS in multivariate analyses adjusted for age, ethnicity, gender, disease duration and season (P = 0.0487). Overall, there was a negative correlation between vitamin D level and EDSS score (P = 0.0001, r = -0.33). In relapsing-remitting MS, vitamin D levels were only correlated with disability scores for EDSS < 4 (P = 0.0012). Patients with >20 ng/ml of vitamin D were 2.78 times more likely to have an EDSS < 4 (P = 0.0011, 95% confidence interval 1.49-5.00).CONCLUSION:Data support previous work suggesting that vitamin D deficiency is associated with higher risk of disability in MS. Vitamin D levels also correlated with the degree of disability in fully ambulatory patients with relapsing-remitting MS. These additional results support the pertinence of randomized controlled trials analysing the interest of an early vitamin D supplementation in MS patients to influence evolution of disability.

International audience; Chronic kidney disease concerns 10 to 14 % of Western populations, and these people are at increased risk of mortality. Treating those patients who reach end-stage renal disease is socially and financially costly and requires considerable medical efforts. While the number of nephrologists per inhabitant in France seems to be preserved over time, the increasing prevalence of end-stage renal disease and improvement in early referral of chronic kidney disease patients results in increased workload for renal physicians. In order to reduce the consequences of chronic kidney disease at both, individual and societal levels, promoting primary prevention (elimination of risk factors), secondary prevention (early management of patients) or tertiary prevention (optimal treatment of functional disabilities related to chronic kidney disease) seems relevant. Some of these actions could narrow the gap between current medical practices and recommendations or prevent new end-stage renal disease cases with an acceptable cost-effectiveness ratio. New approaches might be necessary to better control the disease and overcome current limitations such as resistance to treatments.; La maladie rénale chronique affecte 10 à 14 % des populations occidentales et s’accompagne d’un risque accru de mortalité. Le traitement des patients atteignant le stade d’insuffisance rénale terminale est financièrement et socialement coûteux et nécessite un effort médical conséquent. Alors que le nombre de néphrologues par habitant en France semble conservé au fil du temps, l’augmentation de la prévalence de l’insuffisance rénale terminale et la prise en charge précoce de la maladie rénale chronique entraînent une augmentation de la charge de travail. En vue de réduire les conséquences de la maladie rénale chronique au niveau individuel et de la société, des actions de prévention primaire (suppression des facteurs de risque), secondaire (prise en charge précoce des patients) ou tertiaire (traitement optimal des invalidités fonctionnelles liées à la maladie) semblent pertinentes. Dans certains cas, la mise en place de ces actions permettrait de rapprocher les pratiques médicales actuelles des recommandations ou de permettre, avec un rapport coût-efficacité acceptable, de prévenir des cas d’insuffisance rénale terminale. De nouvelles approches pourraient cependant être nécessaires pour mieux contrôler la maladie et dépasser certaines limitations comme la résistance aux traitements.

Objective The aim of the study was to evaluate dynamic contrast-enhanced magnetic resonance (MR) imaging in the characterization of parotid gland tumors. Methods Fifty-five parotid lesions in 55 patients were retrospectively included. Two observers interpreted 2 reading protocols derived from all MR imaging in 2 distinct sessions, independently and blinded. Benign versus malignant distinction was carried out for protocol 1 (without contrast administration) and protocol 2 (with dynamic contrast-enhanced sequence). Histopathological results after surgical resection were used as the criterion standard. Diagnostic accuracy was compared between protocols using McNemar test. A P values of less than 0.05 indicated significant difference. Results There was no intraobserver statistical discordance between protocols for both observers (P = 0.27 and P = 1). Interobserver reliability showed moderate agreement for protocol 1 (κ = 0.591; 95% confidence interval [CI], 0.376-0.806) and 2 (κ = 0.463, 95% CI, 0.226-0.701). Intraobserver reliability showed moderate agreement for observer 1 (κ = 0.507; 95% CI, 0.279-0.736) and 2 (κ = 0.477; 95% CI, 0.241-0.712). Conclusions Magnetic resonance imaging protocol including dynamic sequence for the characterization of parotid gland lesion yielded nonsignificant increases in sensitivity, specificity, or positive predictive values, and negative predictive values over noninjected protocol.

L’evolution demographique, les maladies chroniques en constante augmentation, l’organisation sous-optimale de la prise en charge des patients ont conduit a une hausse substantielle des depenses de sante. Le systeme de sante doit necessairement s’adapter pour prendre en compte ces evolutions dans un contexte de budget contraint. Une des reformes consiste en la necessite de mettre en place un parcours de soins organise et coordonne autour du medecin traitant qui orientera le patient vers un parcours efficient, limitant ainsi la surconsommation de soins inutiles. Le sujet fait debat sur son perimetre, son contenu et ses modalites organisationnelles. L’objectif de ce travail est de proposer une methodologie permettant de definir une tarification par parcours comme outil de regulation. Pour cela, en introduction nous revenons sur le contexte francais et international du parcours de soins. Une reflexion autour du perimetre et du contenu de celui-ci est ensuite proposee afin d’en estimer le cout puis d’etablir une tarification par parcours. Un exemple de modelisation du parcours de soins dans le cas du diagnostic du cancer de la prostate est presente a titre illustratif.

Objectives To bring a neonatal classification system of unilateral cleft lip and palate and to correlate this classification with the distribution of the permanent lateral incisor and maxillary growth. Design Retrospective with longitudinal follow-up. Setting Tertiary. Patients A total of 112 individuals with treated unilateral cleft lip and palate and 30 controls. Main Outcome Measures Unilateral cleft lip and palate neonatal casts were classified anatomically in four categories, in which Class 1 corresponds to a maxillary arch with a narrow alveolar cleft; Class 2 corresponds to a balanced form; Class 3 corresponds to a wide cleft and short maxilla; and Class 4 corresponds to a wide cleft and long maxilla. The classification was correlated with the distribution of the permanent lateral incisor. Maxillary growth was evaluated using a cephalometric analysis after the age of 10 years. Results Clinical classification of unilateral cleft lip and palate found 10 cases of Class 1 (8.9%), 34 cases of Class 2 (30.4%), 46 cases of Class 3 (41.1%), and 22 cases of Class 4 (19.6%). The permanent lateral incisor was most often present in narrower clefts (Classes 1 and 2); whereas, large clefts (Classes 3 and 4) were relatively more frequently associated with an agenesis of the permanent lateral incisor ( P = .019). Maxillary growth impairment was most severe in Class 3, with a mean sella-nasion-A point angle at 71.9° ± 4.6° ( P < .001). Conclusions Using the cleft width, arch form, and shape of the nasal septum, unilateral cleft lip and palate can be classified into four different classes at birth, which can all give information about permanent lateral incisor agenesis and maxillary growth.

Amyotrophic lateral sclerosis (ALS) is an incurable paralytic disorder primarily typified by the selective and progressive degeneration of motoneurons in the brain and spinal cord. ALS causes muscle wasting and atrophy, resulting eventually in respiratory failure and death within 3–5 years of diagnosis. Vitamin D is a potent secosteroid hormone with diverse biological functions that include protection against neuronal damage. The detrimental consequences of vitamin D dietary deficiency have been documented in other neurodegenerative diseases. However, the protective effect of vitamin D on motoneuron and the influence of its levels on disease course remains elusive. Here we found that the biologically active form of vitamin D significantly potentiated the effect of neurotrophic factors and prevented motoneurons from a Fas-induced death, while electrophysiological properties of motoneurons were not affected. In ALS patients, we report that a severe vitamin D deficiency accelerates by 4 times the rate of decline and were associated with a marked shorter life expectancy. Our findings support a neuroprotective function of vitamin D on motoneurons and propose vitamin D as a reliable prognostic factor of ALS.

Survival curves are a popular tool for representing the association between a binary marker and the risk of an event. The separation between the survival curves in patients with a positive marker (high-risk group) and a negative marker (low-risk group) reflects the prognostic ability of the marker. In this article, we propose an alternative graphical approach to represent the discriminative capacity of the marker-a receiver operating characteristic (ROC) curve, tentatively named prognostic ROC curve-obtained by plotting 1 minus the survival in the high-risk group against 1 minus the survival in the low-risk group. The area under the curve corresponds to the probability that a patient in the low-risk group has a longer lifetime than a patient in the high-risk group. The prognostic ROC curve provides complementary information compared with survival curves. However, when the survival functions do not reach 0, the prognostic ROC curve is incomplete. We show how a range of possible values for the area under the curve can be derived in this situation. A simulation study is performed to analyze the accuracy of this methodology, which is also illustrated by applications to the survival of patients with brain metastases and survival of kidney transplant recipients.

Introduction Le diagnostic pre-implantatoire (DPI) permet d’analyser le contenu genetique d’un embryon humain obtenu par fecondation in vitro (FIV). Cette technique presente l’avantage majeur de pouvoir proposer a un couple presentant un risque eleve de transmettre une maladie genetique grave et incurable au moment du diagnostic, la caracterisation de la mutation ou du desequilibre chromosomique provenant de l’affection dont il est porteur, avant l’implantation des embryons. Une analyse cout-efficacite a ete menee (etude observationnelle financee via un appel d’offre DGOS STIC) : les resultats montrent que la strategie avec DPI est largement dominante et devrait etre adoptee. D’apres les recommandations des societes savantes, l’analyse d’impact budgetaire (AIB) doit completer une evaluation economique de type cout-efficacite ou cout-utilite : la question de l’accessibilite suivant logiquement celle de l’efficience. L’objectif poursuivi par une telle analyse est d’estimer les consequences financieres, a court ou moyen terme de la mise en place d’une strategie de sante sur le budget du payeur. Methodes La perspective retenue est celle de l’Assurance maladie obligatoire dont le budget pluriannuel sera affecte par la generalisation de la strategie etudiee. L’horizon correspond a la duree de prise en charge d’un couple dans le parcours DPI avec pour terme l’accouchement le cas echeant. La methodologie consiste a comparer le cout de la strategie evaluee avec celle de la strategie actuelle. Pour y parvenir, il est necessaire d’identifier et de definir les populations d’interet que sont la population cible (population eligible) et la population rejointe (population effectivement traitee). L’estimation de ces populations est une etape cruciale : une grande rigueur doit y etre consacree et plusieurs hypotheses sont posees. Ce travail fastidieux est gage de la pertinence de la taille des populations estimees. La problematique dans l’analyse ici menee reside dans la generalisation de la pratique du DPI (car deja repandue dans la pratique courante) et le cout qu’elle engendre. Des lors, nous proposons une AIB comparant le scenario 1 correspondant a la prise en consideration de la contrainte d’un nombre limite de DPI realisables par an et le scenario 2 correspondant a la situation dans laquelle aucune contrainte ne porte sur le nombre de DPI realisables annuellement. Une fois ces populations estimees, les ressources financieres des deux strategies peuvent etre evaluees a l’echelle populationnelle. Resultats Les donnees de couts de prise en charge estimees pour l’etude cout-efficacite, auxquelles nous avons applique de nouvelles modalites en lien avec l’AIB, sont utilisees. A partir de celles-ci, un cout de prise en charge par annee du DPI a ete deduit. Le scenario 1 est moins couteux que le scenario 2 : le differentiel maximum entre les deux scenarios sur un an est de l’ordre de 11 millions d’euros et de 33 millions d’euros sur trois ans. Lorsque l’on s’interesse aux evenements medicaux (fausse couche spontanee precoce, IMG, diagnostic prenatal et avortement spontane tardif) et aux couts evites, on constate que la prise en charge de toute la patientele cible permet d’economiser la somme de 5 025 112 € sur trois ans. Conclusion L’ensemble des parametres impactant les depenses et l’organisation de la prise en charge du DPI ont ainsi ete mis en avant. Il revient desormais au decideur d’orienter son choix, un choix eclaire des arguments avances dans cette analyse.

Introduction L’incidence des translocations chromosomiques equilibrees dans la population generale est de 0,16 % et une anomalie de structure chromosomique est mise en evidence au cours d’un bilan de fausses couches a repetition dans 5 a 10 % des cas. Un desequilibre de la translocation peut egalement engendrer une formule chromosomique viable chez le fœtus. De fait, cette anomalie de structure est parfois mise en evidence sur signes echographiques et sera alors suivi d’une IMG. Parfois, c’est suite a la naissance d’un enfant avec retard mental qu’est pose retrospectivement le diagnostic chez l’un des parents. Le diagnostic pre-implantatoire (DPI) permet d’eviter ces risques. Il est realise sur un embryon biopsie au 3e jour apres une procedure de FIV. Il permet de transferer uniquement les embryons sains. Cette technologie est couteuse, autorisee en France depuis 2000, et cinq centres seulement sont habilites. Cette etude propose d’evaluer l’efficience de la strategie de prise en charge incluant le DPI et de la comparer a la prise en charge sans DPI. Methodes Une etude observationnelle financee via un appel d’offre DGOS STIC a ete proposee. Pour des raisons ethiques, il n’a pas ete possible de randomiser les couples. Ainsi, les donnees du parcours incluant le DPI ont ete observees et le parcours sans DPI a ete obtenu via l’interrogation des bases de donnees nationales et avis d’experts le cas echeant. Le ratio cout-efficacite incremental d’un enfant vivant, de phenotype et de formule chromosomique normaux est propose. Le point de vue retenu est celui de l’AMO (Assurance maladie obligatoire) et de la collectivite. L’horizon temporel est l’accouchement et les couts directs ont ete recueillis. La methodologie des arbres de decision est retenue pour cette analyse. Le cout et l’efficacite moyenne sont estimes via les simulations de Monte-Carlo. Une analyse de sensibilite est proposee afin d’evaluer la robustesse des resultats. Resultats Au total, 376 cycles de 191 couples ont ete analyses. Le taux d’enfants nes sans anomalie est de 76,7 % par grossesse versus 3,1 % pour les couples ne beneficiant pas de DPI. La majeure partie de la difference est expliquee par un fort taux de fausse couche dans le groupe sans DPI (70 % versus 22 %). Dix mille trajectoires ont ete simulees. Le cout moyen de la prise en charge pour obtenir une grossesse du point de vue AMO est de 32 481 € [IC MC 95 % : 32 180–32 738] versus 1028 € [IC MC 95 % : 840–1228] dans le bras sans DPI. Le ratio cout-incremental est de 42 947 € [38 060–49 998] par enfant supplementaire ne vivant et normal. L’analyse de sensibilite et le graphique de Tornado, montre une robustesse des resultats. Le point de vue collectif conduit a un ratio de 49 730 €. Conclusion La strategie DPI est dominante. En effet, on obtient un ratio cout-efficacite non pas pour une unite de vie supplementaire comme cela est fait habituellement, mais pour une vie supplementaire en plein etat de sante a la naissance. Le ratio obtenu est largement en deca du seuil de 50 000 € par annee de vie gagnee. Cette strategie permet d’optimiser les ressources allouees au systeme de sante, notamment lorsque l’on considere le cout de la prise en charge des patients atteints sur une vie, mais offre egalement a ces couples une prise en charge medicale sans qu’ils aient a se decider face au dilemme d’une possible interruption de grossesse ou de la garde d’un enfant porteur d’anomalie genetique.

International audience

In France, cervical screening is opportunistic and approximately 40% of women do not attend regular screening programs. The aim of this study was (1) to assess the prevalence of human papillomavirus (HPV) cervical infection and of cytological abnormalities in a population of young pregnant women with poor adherence to cervical cancer screening and (2) to evaluate the adherence to a screening strategy combining HPV testing and cytology during pregnancy. For this purpose, pregnant women benefited from a cervical smear associated with HPV DNA detection. High-risk HPV types were detected and identified using the HC2 assay and the INNO-LiPA HPV genotyping Extra assay. Two hundred forty-seven women (mean age 26.6 ± 5.1 years) were enrolled. Among them, 76.8% did not attend regular cervical cancer screening programs. High-risk HPV types were detected in 50 (20.2%) samples, HPV 16 being the most frequent (N = 12; 14.5%), with multiple HPV infection in 17 samples (27%). Nine (3.6%) abnormal cervical smears were diagnosed. Follow-up of women with abnormal cytology and/or infection with high-risk HPV was obtained in 29 cases (55.8%), showing 12 persistent high-risk HPV infections. Nine women had colposcopy with a final diagnosis of four normal cervixes, three cervical intraepithelial neoplasia grade 1 and two cervical intraepithelial neoplasia grade 2. Overall, women adherence to the free post-partum follow-up visit was 53.5%. This study suggests that a screening program combining HPV testing with cervical cytology during pregnancy may be one option to target young women with poor adhesion to regular cervical cancer screening. J. Med. Virol. 86:536–545, 2014. © 2013 Wiley Periodicals, Inc.

Receiver operating characteristic (ROC) research has been limited to binary choice. Recently, the method was generalized based on the Lehmann assumption also known as the proportional hazards specification. This model accommodates a variety of research questions such as covariate adjustments. By applying this method to three-class ROC analysis, simple analytical forms of ROC surface and volume under the surface were derived without and with covariates. Furthermore, the model parameters and the corresponding asymptotic variances were evaluated. Simulation studies were performed to assess the validity of our proposed method in finite samples and extension work for dimension higher than three-class is considered.

Results of trials and meta-analyses comparing pegylated interferon (PEG-IFN)-α2a and PEG-IFN-α2b for the treatment of chronic hepatitis C are conflicting.Our objective was to determine which PEG-IFN (α2a or α2b), in association with ribavirin, is the most effective for the treatment of chronic hepatitis C by performing an updated meta-analysis.MEDLINE (1950-2012) and EMBASE (1974-2012) databases, as well as the Cochrane Central Register of controlled trials and the Cochrane Database of Systematic Reviews, were searched. Reference lists of retrieved articles were scanned, and proceedings of major international conferences were manually searched for abstracts. Randomized clinical trials and non-randomized clinical studies comparing PEG-IFN-α2a with PEG-IFN-α2b in association with ribavirin in adult patients with chronic hepatitis C were included. Studies including HIV-positive patients or liver transplant recipients were excluded. The data extraction from each study was conducted independently by two authors, with disagreements resolved by consensus or by a third reviewer. The trial quality of randomized clinical trials was assessed by taking into account generation of allocation sequence, allocation concealment, efficacy of randomization, investigator blindness, description of withdrawals and dropouts and adherence to the intention-to-treat principle. Two meta-analyses were performed, the first including randomized clinical trials only, and the second including both randomized and non-randomized clinical studies. The primary outcome measure was frequency of sustained virological response (SVR). Heterogeneity and publication bias were systematically taken into account.This meta-analysis included 26 studies, 11 randomized and 15 non-randomized, with a total of 18,260 patients: 8,125 treated with PEG-IFN-α2a and 10,135 treated with PEG-IFN-α2b. In the meta-analysis that included randomized trials only, the SVR was significantly higher for patients treated with PEG-IFN-α2a than for those treated with PEG-IFN-α2b for genotypes 1 and 4 [odds ratio (OR) 1.45; 95 % CI 1.09-2.06; p = 0.013] and for all genotypes (OR 1.34; 95 % CI 1.05-1.72; p = 0.02). In the meta-analysis including both randomized and non-randomized studies, the SVR was significantly higher for PEG-IFN-α2a than for PEG-IFN-α2b for all genotypes (OR 1.24; 95 % CI 1.10-1.40; p0.001) and for genotypes 1 and 4 (OR 1.25; 95 % CI 1.14-1.36; p0.001); for genotypes 2 and 3, the SVR was greater for treatment with PEG-IFN-α2a than with PEG-IFN-α2b, with the difference tending towards significance (OR 1.15; 95 % CI 0.98-1.35; p = 0.08). A certain degree of heterogeneity was present amongst the various studies included in this meta-analysis. Publication bias was detected (particularly for analyses including only randomized controlled trials) and taken into account using appropriate statistical methods.Current evidence suggests that PEG-IFN-α2a and ribavirin is associated with a higher SVR than PEG-IFN-α2b and ribavirin in patients mono-infected with hepatitis C, particularly for genotypes 1 and 4.

Elderly people are at increased risk of influenza and pneumococcal diseases. Influenza increases clinical pneumococcal disease incidence. Pneumococcal vaccination could therefore be a supplement to influenza vaccination. This study evaluated all-cause mortality and antibiotic consumption according to elderly people’s influenza and pneumococcal vaccination status. Its goal was to demonstrate that vaccination with both Influenza and pneumococcal vaccines decrease all-cause mortality and antibiotic consumption. From 2004-10-01 to 2004-12-31 (3 mo), elderly people (≥ 65 y) who lived in the Gard department (South of France) were offered both vaccinations. Among the 68,897 subjects followed-up one year after this vaccination campaign, 21,303 (30.9%) were vaccinated with both vaccines, 18,651 (27.1%) with influenza vaccine alone, 3,769 (5.5%) with pneumococcal vaccine alone; 25,174 (36.5%) subjects were unvaccinated. Mortality rate (per 1,000 inhabitants-year) adjusted on gender, age and prior underlying chronic disease was 17.9 (95% CI: 16.3–19.6), 20.8 (19.0–22.8), 22.5 (19.0–26.6) and 24.7 (22.7–26.8), respectively. It was 42.1 (38.8–45.8) in elderly people with underlying chronic disease who received both vaccines vs. 58.1 (53.7–62.9) in unvaccinated elderly people. The decrease in mortality rate was 27.0% (20.0–34.0) in subjects who received both vaccines and 16.0% (6.0–24.0) in those who received influenza vaccine. No significant reduction in mortality rate was seen with the pneumococcal vaccine alone. Influenza and/or pneumococcal vaccinations did not decrease antibiotic consumption that drastically increases during the winter period. An additive effect was observed in the prevention of all-cause mortality with influenza and pneumococcal vaccines given together in elderly people, including in those with underlying chronic disease.

International audience; OBJECTIVE:Propensity score (PS) analysis allows an unbiased estimate of treatment effects but assumes that all confounders are measured. We assessed the impact of omitting confounders from a PS analysis on clinical decision making.STUDY DESIGN AND SETTING:We conducted Monte Carlo simulations on hypothetical observational studies based on virtual populations and on the population from a large randomized trial (CRASH-2). In both series of simulations, PS analysis was conducted with all confounders and with omitted confounders, which were defined to have different strengths of association with the outcome and treatment exposure. After inverse probability of treatment weighting, we calculated the absolute risk differences and numbers needed to treat (NNT).RESULTS:In both series of simulations, omitting a confounder that was moderately associated with the outcome and exposure led to negligible bias on the NNT scale. The bias induced by omitting strongly positive confounding variables remained less than 15 patients to treat. Major bias and reversed effects were found only when omitting highly prevalent, strongly negative confounders that were similarly associated with the outcome and exposure with odds ratios greater than 4.00 (or

The aim of this case-control study was to compare two different statistical methods in the identification of dietary patterns by use of principal component analysis (PCA) and variable clustering (VC) and to examine their association with the risk of breast cancer (BC).A dose-response association was then performed by the use of an adaptation of free knot spline function in logistic models.A "Western" pattern was revealed by PCA and VC and was then shown to be associated with a nonsignificant increase of BC risk. Only PCA identified a "meat/alcohol" pattern. Above the spline threshold, BC risk increased significantly (OR ≥ s vs.s = 2.56, 95% CI 1.54-4.27). When we used PCA, a "Mediterranean" pattern was identified, but no association between BC risk and this pattern was shown. VC split the "Mediterranean" dietary pattern in two: "raw vegetables and olive oil" and "fish." Above the spline threshold, the "fish" pattern tended to protect against BC risk (OR ≥ s vs.s = 0.77, 95% CI 0.58-1.01), whereas an excess of raw vegetables and olive oil increased BC risk (OR 1 se = 1.22, 95% CI = 1.06-1.32).Some results from the PCA and the VC methods were similar, whereas others were different but gave complementary results.

Objectives The French Society of Rheumatology has initiated a large national multicenter, longitudinal, prospective follow-up of patients presenting with early inflammatory back pain in order to set up a database to facilitate several investigations on diagnosis, prognosis, epidemiology, pathogenesis and medico-economics in the field of early inflammatory back pain and spondyloarthritis. Methods Patients were recruited if they had inflammatory back pain of more than 3 months and less than 3 years. Patients will be followed every 6 months during the first 2 years then every year during at least 5 years. Apart from information collected on a Case Report Form (demographics, disease activity, severity, co-morbidities, socio-economics, treatments, radiological and MRI evaluation of the spine and the pelvis according to the local investigators, and for some centers bone densitometry and ultrasonography of entheses), the digital X-rays and MRI of the spine and pelvis are stored using a specific software (Carestream) and the biological samples (DNA, RNA, sera, urines) are centralized at the Biological Resources Center (Bichat Hospital). Results The recruitment period of the 708 patients (mean age: 34 ± 9 years, female 54%, HLA-B27 positive: 57%) in the 25 centers was 26 months (from December 2007 to April 2010). The modified New York criteria, Amor criteria, ESSG criteria and axial ASAS criteria were fulfilled by 26%, 77%, 76% and 67% of the patients at entry, respectively. A history or current symptoms suggestive of peripheral arthritis, acute anterior uveitis and inflammatory bowel disease were observed in 21%, 9% and 4% of the patients, respectively. The disease was active (BASDAI: 45 ± 20) despite an NSAID intake in 66% of the patients. Conclusion This large cohort should facilitate the conduct of researches in different areas (clinical, medico-economics, translational) in order to improve our knowledge on the pathogenesis and natural history of axial spondyloarthritis.

Background: To evaluate the prognostic impact of HER2 overexpression in patients with pT1a-b, node negative, breast cancers. Patients and Methods: A population of1127 patients whose diseases were staged as pT 1a-b, pN0 and who were treated in the Languedoc-Roussillon (ONCO LR Southern French regional network) from 1999 to 2004, was identified. 95% of patients had conservative management, no patient received adjuvant trastuzumab, 5% received chemotherapy and 80% anti-estrogen endocrine therapy. HER 2 status was retrospectively assessed by immunohistochemistry in 671 patients (122 pT1a/549 pT1b). Kaplan-Meier method was used to estimate disease-free survival (DFS). Cox proportional hazard models were used to determine associations between HER2 status and disease-free survival adjusting on variables significantly linked to it. Results: 9-year Overall survival was 95%. HER2 overexpression (3+) was observed in 5.2% of the patients (n=35). HER2 3+ category was most frequently identified in the following sub groups: pT1a lesion (12.3% vs 3.6%; p: 0.0001), mastectomies (14% vs 4.4%; p:0.023), Grade 2–3 (91% vs 50%; p According to the immunohistochemical phenotype DFS5 were 95%, 94%, 85%, 73.6% for ER+/PR+/HER2− (n:502/75%), ER-/PR-/ HER2− (n:134/20%), ER+/PR+/HER2 3+ (n:15/2%) and ER-/PR-/ HER2 3+ tumors (n:20/3%), respectively (p:0.02). In univariate analysis, HER2 positive tumors (p:0.017), phenotype classification (p:0.02) and adjuvant treatment (p:0.013) were significant prognostic factors. In multivariate analysis, only patients with HER2 3+ tumors had higher risks of recurrence (hazard ratio [HR], 2.41; 95% CI: [1.06−5.53]; p Discussion: Node-negative, pT1a-b, breast cancer patients overexpressing HER2 have a significant risk of recurrence at 6 years median follow-up. In our series of small breast tumors, HER2 status seems to be a better prognostic factor than ER status. In patients with hormone receptor-positive diseases, HER2 positivity is associated with a worse DFS despite an anti-estrogen treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-16.

Resume Objectifs La Societe francaise de rhumatologie a mis en place une importante etude prospective, nationale, multicentrique, longitudinale, de suivi d’une cohorte de patients avec rachialgie inflammatoire recente, afin de constituer une base de donnees pour faciliter la recherche sur le diagnostic, le pronostic, l’epidemiologie, la physiopathogenie et les aspects medicoeconomique des rachialgies inflammatoires recentes et des spondylarthropathies. Methodes Les patients recrutes devaient avoir une rachialgie inflammatoire evoluant depuis plus de trois mois et moins de trois ans. Ils seront suivis tous les six mois pendant les deux premieres annees, puis chaque annee pendant au moins cinq ans. En plus des informations colligees sur un questionnaire individuel (caracteristiques demographiques, activite de la maladie, severite, comorbidites, aspects socioeconomique, traitements, radiographies standard et IRM du rachis et du pelvis par les investigateurs locaux, et pour certains centres, osteodensitometrie osseuse et echographie des entheses), les radiographies numerisees et l’IRM du rachis et du pelvis sont stockees grâce a un logiciel specifique (Carestream). Les echantillons biologiques (ADN, ARN, serum, urines) sont centralises au centre de ressources biologiques (CRB) de l’hopital Bichat. Resultats La periode de recrutement des 708 patients (moyenne d’âge : 34 ± 9 ans, femmes 54 %, HLA-B27 positif : 57 %) dans les 25 centres a ete de 26 mois (de decembre 2007 a avril 2010). Les criteres de New York modifies, les criteres d’Amor, les criteres ESSG et les criteres rachidiens de l’ASAS etaient remplis par respectivement 26 %, 77 %, 76 % et 67 % des patients a l’inclusion. Des antecedents de symptomes evocateurs d’arthrite peripherique, une uveite anterieure aigue et une maladie inflammatoire chronique de l’intestin etaient presents respectivement chez 21 %, 9 % et 4 % des patients. La maladie etait active (BASDAI : 45 ± 20 mm) malgre les AINS pris par 66 % des patients. Conclusion Cette grande etude devrait faciliter la realisation de travaux de recherche dans differents domaines (clinique, medicoeconomiques, recherche translationnelle) afin d’ameliorer notre connaissance sur la physiopathologie et l’evolution naturelle des spondylarthropathies axiales.

Prenatal diethylstilbestrol (DES)-exposed mice have raised the suspicion of a transgenerational effect in the occurrence of genital malformation in males. This nationwide cohort study in collaboration with a French association of DES-exposed women studied 529 families and showed that a significant proportion of boys born to DES daughters exhibited hypospadias with no other molecular defects identified.

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis.

Background In France, lung cancer is the third most common cancer and the third leading cause of cancer death in women. The main objective of this study is to analyse specificities of lung cancer in the female population in an administrative district in France, focusing on histology, staging and trends over time. Methods Incidence data from 1987 to 2004 were extracted from the Herault cancer registry. The variables of interest considered at diagnosis were stage, histology and age. Mortality data were extracted from the CepiDc–Inserm database for the same period. Results Among the 6,650 patients studied, 16.8% were women. 18.3% of whom were aged less than 50 at diagnosis, (9.9% of men, p Conclusion This population-based study confirmed the specific features of lung cancer in women: younger age at diagnosis, adenocarcinoma and stage at diagnosis with poor prognosis. These results raise the question of possible differences to lung cancer susceptibility between males and females.