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Summary During the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial. To address the novel challenges introduced by these trials, an interdisciplinary panel was convened on behalf of the Transparency Committee of the French National Authority for Health to clarify an approach designed to guarantee a transparent, reproducible, and fair assessment of histology-agnostic treatments for reimbursement by the French National Health Insurance Fund. The requirements of this approach include the need for randomisation, clinically relevant endpoints, appropriate correction for multiple significance testing, characterisation of subgroup heterogeneity, and validation of underlying biomarker assays. A prospectively designated external control is encouraged when the implementation of a direct comparison is deemed infeasible. We also underline the importance of recording outcomes from basket trials in a registry for use as future external controls.

International audience; No abstract available

Purpose The Working Group undertook a critical, comprehensive synthesis of the response shift work to date. We aimed to (1) describe the rationale for this initiative; (2) outline how the Working Group operated; (3) summarize the papers that comprise this initiative; and (4) discuss the way forward. Methods Four interdisciplinary teams, consisting of response shift experts, external experts, and new investigators, prepared papers on (1) definitions and theoretical underpinnings, (2) operationalizations and response shift methods, (3) implications for healthcare decision-making, and (4) on the published magnitudes of response shift effects. Draft documents were discussed during a two-day meeting. Papers were reviewed by all members. Results Vanier and colleagues revised the formal definition and theory of response shift, and applied these in an amended, explanatory model of response shift. Sébille and colleagues conducted a critical examination of eleven response shift methods and concluded that for each method extra steps are required to make the response shift interpretation plausible. Sawatzky and colleagues created a framework for considering the impact of response shift on healthcare decision-making at the level of the individual patient (micro), the organization (meso), and policy (macro). Sajobi and colleagues are conducting a meta-analysis of published response shift effects. Preliminary findings indicate that the mean effect sizes are often small and variable across studies that measure different outcomes and use different methods. Conclusion Future response shift research will benefit from collaboration among diverse people, formulating alternative hypotheses of response shift, and conducting the most conclusive studies aimed at testing these (falsification).

International audience; Background: Patient-Reported Outcomes (PROs) are standardized questionnaires used to measure subjective outcomes such as quality of life in healthcare. They are considered paramount to assess the results of therapeutic interventions. However, because their calibration is relative to internal standards in people's mind, changes in PRO scores are difficult to interpret. Knowing the smallest value in the score that the patient perceives as change can help. An estimator linking the answers to a Patient Global Rating of Change (PGRC: a question measuring the overall feeling of change) with change in PRO scores is frequently used to obtain this value. In the last 30 years, a plethora of methods have been used to obtain these estimates, but there is no consensus on the appropriate method and no formal definition of this value. Methods: We propose a model to explain changes in PRO scores and PGRC answers. Results: A PGRC measures a construct called the Perceived Change (PC), whose determinants are elicited. Answering a PGRC requires discretizing a continuous PC into a category using threshold values that are random variables. Therefore, the populational value of the Minimal Perceived Change (MPC) is the location parameter value of the threshold on the PC continuum defining the switch from the absence of change to change. Conclusions: We show how this model can help to hypothesize what are the appropriate methods to estimate the MPC and its potential to be a rigorous theoretical basis for future work on the interpretation of change in PRO scores.

Objective In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. Methods Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. Results 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). Conclusion A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.

Dating the onset of the continental collision and amalgamation of crustal blocks is at the basis of the reconnaissance of orogenic cycles and yields time constraints for the estimate of rates of accretionary processes over the last 4.5 Gyrs. The Paleoproterozoic Southeastern Churchill Province (SECP) represents the easternmost branch of the Trans-Hudson Orogen, squeezed between the Superior and North Atlantic Cratons (NAC). It comprises a collage of Archean to Paleoproterozoic crustal blocks (Core Zone), and two transpressive orogenic belts (New Quebec and Torngat Orogens), for which crustal amalgamation and associated collisional events are largely undated. We apply a multi-chronometer approach coupled with trace elements geochemistry on supracrustal sequences from the granulitic Tasiuyak Complex accretionary prism and the occidental margin of the NAC (upper plate) to estimate the timing of prograde, peak and retrograde metamorphism in the core of the Torngat Orogen. Our results yield to prograde garnet growth at 1885 ± 12 Ma (Lu-Hf), peritectic prograde monazite growth at 1873 ± 5 Ma (U-Pb), retrograde zircon growth during melt crystallization at 1848 ± 12 Ma, and rutile closure during slow exhumation at 1705 ± 5 Ma in the Tasiuyak Complex. Garnet from the NAC are dated at 2567 ± 4.4 Ma (Lu-Hf) and suggest that the granulite facies metamorphism in the NAC margin largely predates the Torngat Orogeny. We integrate the metamorphic record throughout the SECP to decipher its Paleoproterozoic tectonometamorphic evolution and propose a sequential collisional evolution from ~1.9 to 1.8 Ga.

Objectives To analyze long‐term cognitive status and function after cochlear implantation in profoundly deaf individuals. Design Prospective observational longitudinal study. Setting Ten academic medical centers referent for cochlear implantation. Participants Individuals aged 65 and older who qualified for cochlear implantation (N=70). Measurements Cognitive tests were administered before cochlear implantation and 1 and 5 or more years after cochlear implantation. Evaluation consisted of 6 tests assessing attention, memory, orientation, executive function, mental flexibility, and fluency. Cognitive status was determined as normal, mild cognitive impairment (MCI), or dementia. Speech perception in quiet and noisy conditions was assessed using disyllabic words, and quality of life was assessed using the Nijmegen Cochlear Implant Questionnaire. Results Mean follow‐up was 6.8 years (range 5.5–8.5 years). Speech perception scores and quality of life remained stable from 1 to 7 years after cochlear implantation. Of 31 participants (45%) with MCI before cochlear implantation, 2 (6%) developed dementia during follow‐up, 19 (61%) remained stable, and 10 (32%) returned to normal cognition. None of the 38 with normal cognition developed dementia during follow‐up, although 12 (32%) developed MCI. Conclusion MCI is highly prevalent in older adults with profound hearing loss. Nevertheless, we observed a low rate of progression to dementia, and cognitive function improved in some individuals with MCI at baseline. These results highlight that cochlear implantation should be strongly considered in profoundly deaf individuals, even those with MCI, who may have a specific subtype of MCI, with a possible positive effect of hearing rehabilitation on neurocognitive functioning.

A correction to this paper has been published: https://doi.org/10.1007/s11136-021-02890-6

This study proposes a refined approach for quantification of the vorticity of kinematic flow in natural shear zones. This approach, here called C′-c method, is based on estimation of the angle between the flow apophyses A1 and A2 by performing two independent measurements. The tilting angle of a quartz crystallographic preferred orientation (β) and the orientation of the C′ shear bands (θ). Using these two angles it is possible to quantify the sectional vorticity number using the following formula: Wn = Cos[2(θ-β)]. Data obtained by applying the C′-c method on known shear zones well match the vorticity numbers estimated with other approaches on the same structures. In this study, we applied the C′-c method to the Abloviak Shear Zone (Torngat Orogen) and the Ben Hope Thrust (Caledonides of NW Scotland) obtaining the first vorticity data on these structures. Our data show that the C′-c method can increase the potential range of rocks in which it is possible to estimate kinematic vorticity. Our results also show that the C′-c method can be negatively affected by microscale kinematic flow partitioning, highlighting the importance of a detailed microstructure characterization of the studied rocks before any estimate of kinematic vorticity is attempted.

Purpose To investigate the clinical and virologic-associated and predictive factors of intraocular pressure (IOP) evolution over time and its severity in Fuchs' heterochromic iridocyclitis (FHC). Methods Consecutive patients with both clinical FHC and intraocular synthesis of rubella virus (RV)-specific antibodies were included in this study. Specific ocular production of RV antibodies was confirmed using the quotient of serum/aqueous humor ratio of RV IgGs (Crv) and control antiviral IgGs (Cctl), using quantitative serology methods. Epidemiologic, clinical, biological, and virologic data at referral were collected and correlated with IOP values over time, occurrence, and severity of glaucoma. Results Sixty-eight eyes of 68 patients were included. Mean age at diagnosis was 40.7 ± 11.1 years. Mean follow-up was 4.3 ± 4.3 years. Mean baseline Crv and Cctl values were 12.34 ± 14.67 and 216.70 ± 98.4, respectively. Mean baseline IOP was 17.2 ± 7.2 mm Hg (range, 9-40) and 15.6 ± 5.6 (range, 3-30) 5 years after referral. The predictive factors for pejorative IOP evolution over time and glaucoma severity were male sex (P = 0.03) and decreased Crv (P = 0.04) and presence of iris nodules (P < 0.001) and decreased Cctl (P = 0.02), respectively. Diagnostic delay was associated with increased likelihood of undergoing glaucoma surgery (P = 0.02). Conclusions Time to diagnosis, male sex, presence of iris nodules at baseline, and decreased Crv and Cctl ratios were associated with increased likelihood of pejorative IOP evolution over time. Given the aggressiveness of glaucoma in FHC, these results provide interesting insight into what category of patients should need the closest screening.

International audience; Gambling has an inherent structural monetary component, and financial motive is one of the main motivations for gambling. Despite this, and contrary to other addictive behaviours that involve money such as compulsive buying, gambling has never been studied from a materialism perspective. The objective of the present study was to explore the links between materialism and gambling disorder (GD) and whether this relationship is mediated by financial motives for gambling. We compared 65 pathological gamblers (PGs) seeking treatment to 65 matched non-problem gamblers. The data collection included socio-demographics, gambling characteristics, the Materialism Values Scale, the Gambling Motives Questionnaire-Financial, and the Rosenberg Self-Esteem Scale. The statistical analysis included linear mixed models and Structural Equation Modelling. The level of materialism was significantly higher for the PGs, except for the Centrality dimension. Only one mediated effect was significant, and it concerned an indirect path from Happiness through financial motives. Moreover, Happiness explained most of the variance of the probability of becoming a PG. Contrary to compulsive buying, the PGs seemed to display materialism in a more experiential way that was centred on what possessions can induce secondarily rather than on the possessions themselves. The belief that material possessions are essential to achieving happiness may encourage the PG to gamble, thus contributing to both the development and maintenance of GD. We provided evidence that materialism is a key concept in the comprehension of GD and should be further considered when adapting care strategies.

Purpose To determine the prognostic factors of long-term visual outcome in birdshot retinochoroidopathy (BRC). Methods Design: Retrospective case series. Study Population: Successive HLA-A29+ BRC patients whose latest visit was between May and August 2013 at a single tertiary center (Pitie-Salpetriere Hospital, Paris). Observation Procedure: Endpoint visual status (remission or deterioration) was determined for each patient based on clinical and ancillary data from the latest visit including optical coherence tomography (OCT), automated visual field (AVF), and angiograms. Main Outcome Measure: Epidemiologic, clinical, OCT, AVF, angiographic, and electrophysiological data at baseline were correlated to final visual status. Results Fifty-five patients were included. Mean observation period was 8 years (range: 0.6-23 years). Mean disease duration was 9.8 years (range: 1.2-32.7 years). Female-to-male sex ratio was 1.6:1. Factors of good visual prognosis (remission vs deterioration) included at baseline: late age of disease onset (49.5 vs 45 years, P = .05), presence of vitreous inflammatory reactions >2+ (35.9% vs 6.2%, P = .04), vascular leakage on fluorescein angiograms (FA) (44.4% vs 12.5%, P = .03), absence of macular pigment epithelium atrophy on FA (88.9% vs 62.5%, P = .05), and presence of macular edema on OCT (33.3% vs 6.2%, P = .04). Preserved electrooculography light peak and Arden ratio ( P = .06) and presence of choroidal spots on infracyanine green angiograms (80.0% vs 53.3%, P = .08) seemed associated with the best prognoses. Conclusion This study suggests a series of prognostic factors of long-term visual outcome in BRC. Keeping in mind the insidious evolution of the disease, knowledge of such prognostic factors should help tailor the treatment and monitoring of birdshot patients.

The large scale Paleoproterozoic Trans-Hudson Orogen exposed in Canada is recognized to record one of the first complete Wilson cycle. Although it is considered as a prototype of modern accretionary orogen, the strain pattern, thermal state, and architecture in its wedge are still poorly constrained. Part of it, the accretionary New Quebec Orogen (NQO, 1.82–1.77 Ga) resulted from oblique collision between the Superior Craton lower plate and a composite upper plate including the Kuujjuaq Domain (KD) and the Core Zone, and exposes supracrustal sequences of the Rachel-Laporte Zone (RLZ), a continental forearc basin that evolved in a collisional foreland basin upon collision. We performed an integrated analysis, using petrography, phase equilibria modelling and Lu-Hf garnet, and U-Pb zircon, monazite and rutile chronology on supracrustal rocks in the central segment of the New Quebec Orogen. On the one hand, the RLZ experienced a tight clockwise metamorphic evolution, with a peak at 650 °C/0.7 GPa. Prograde garnet and monazite growth is estimated at 1804 ± 8 Ma and 1796 ± 4 Ma respectively. On the other hand, the metamorphic peak for restitic granulites from the KD is estimated at 790 °C/0.72 GPa and follows isothermal decompression. Geochronology yields ages of 1836 ± 5 Ma for prograde garnet growth, and 1807 ± 4 Ma for crystallization of zircon from anatectic melt, which was followed by rapid cooling recorded by rutile at 1798 ± 16 Ma. We propose that the Lac Turcotte Fault that separates both domains has acted as a tectonometamorphic discontinuity that limits contrasting P-T-t paths. We suggest sequential burial of supracrustal sequences along an apparently continuous Barrovian sequence, with progressive recycling of inner zones in the foreland basin and subsequent involvement of the latter in the orogenic wedge. Refereed/Peer-reviewed

International audience; Objectives - To analyze long-term cognitive status and function after cochlear implantation in profoundly deaf individuals. Design - Prospective observational longitudinal study. Setting - Ten academic medical centers referent for cochlear implantation. Participants - Individuals aged 65 and older who qualified for cochlear implantation (N=70). Measurements - Cognitive tests were administered before cochlear implantation and 1 and 5 or more years after cochlear implantation. Evaluation consisted of 6 tests assessing attention, memory, orientation, executive function, mental flexibility, and fluency. Cognitive status was determined as normal, mild cognitive impairment (MCI), or dementia. Speech perception in quiet and noisy conditions was assessed using disyllabic words, and quality of life was assessed using the Nijmegen Cochlear Implant Questionnaire. Results - Mean follow-up was 6.8 years (range 5.5-8.5 years). Speech perception scores and quality of life remained stable from 1 to 7 years after cochlear implantation. Of 31 participants (45%) with MCI before cochlear implantation, 2 (6%) developed dementia during follow-up, 19 (61%) remained stable, and 10 (32%) returned to normal cognition. None of the 38 with normal cognition developed dementia during follow-up, although 12 (32%) developed MCI. Conclusion - MCI is highly prevalent in older adults with profound hearing loss. Nevertheless, we observed a low rate of progression to dementia, and cognitive function improved in some individuals with MCI at baseline. These results highlight that cochlear implantation should be strongly considered in profoundly deaf individuals, even those with MCI, who may have a specific subtype of MCI, with a possible positive effect of hearing rehabilitation on neurocognitive functioning.

OBJECTIVEIn large vestibular schwannoma (VS) surgery, the facial nerve (FN) is at high risk of injury. Near-total resection has been advocated in the case of difficult facial nerve dissection, but the amount of residual tumor that should be left and when dissection should be stopped remain controversial factors. The objective of this study was to report FN outcome and radiological results in patients undergoing near-total VS resection guided by electromyographic supramaximal stimulation of the FN at the brainstem.METHODSThis study was a retrospective analysis of a prospectively maintained database. Inclusion criteria were surgical treatment of a large VS during 2014, normal preoperative FN function, and an incomplete resection due to the strong adherence of the tumor to the FN and the loss of around 50% of the response of supramaximal stimulation of the proximal FN at 2 mA. Facial nerve function and the amount and evolution of the residual tumor were evaluated by clinical examination and by MRI at a mean of 5 days postoperatively and at 1 year postoperatively.RESULTSTwenty-five patients met the inclusion criteria and were included in the study. Good FN function (Grade I or II) was observed in 16 (64%) and 21 (84%) of the 25 patients at Day 8 and at 1 year postoperatively, respectively. At the 1-year follow-up evaluation (n = 23), 15 patients (65%) did not show growth of the residual tumor, 6 patients (26%) had regression of the residual tumor, and only 2 patients (9%) presented with tumor progression.CONCLUSIONSNear-total resection guided by electrophysiology represents a safe option in cases of difficult dissection of the facial nerve from the tumor. This seems to offer a good compromise between the goals of preserving facial nerve function and achieving maximum safe resection.

International audience

Background In early rheumatoid arthritis (RA), some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Identifying at the time of diagnosis the characteristics predictive of RRP is of importance. Several matrices predicting this risk have been proposed over the last years. They were limited somewhat in terms of precision or were built using specific populations. Objectives To develop a matrix to predict RRP with better precision and generalizability by pooling databases from various studies. Methods The study is based on the pooling of individual data from cohorts (ESPOIR and Leuven) and clinical trials (BeSt, SWEFOT and ASPIRE). Included patients were adult DMARD-naive patients with recent suspected or confirmed diagnosis of active RA for which the first therapeutic strategy after inclusion was to prescribe MTX or leflunomide in monotherapy for at least 3 months. The main outcome was the presence after one year of RRP defined as an increase in modified Sharp score (vSHS) of at least 5 points between baseline and year one. Baseline characteristics were compared by the presence of RRP to search for predictors. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve (AUC). Calibration and discriminatory power of the model were assessed. Model parameters were extracted to estimate the probability of a RRP for each combination of level of baseline characteristics. Results The data of 1306 patients were pooled. After one year, 236 exhibited RRP (20.6%, CI 95% [18.2–22.9], mean probability of RRP of 0.21). Model of prediction of RRP included as baseline characteristics Rheumatoid Factor (RF) positivity (OR=2.1 CI 95% [1.5–3.0]; p 95% [1.7–3.2]; p 30mg/l (OR=2.1 CI 95% [1.5–3.0]; p 10 (OR=1.5 CI 95% [1.01–2.2]; p=0.048). Model calibration was good (Hosmer and Lemeshow test: p=0.79). AUC was 0.68. The matrix proposes estimated RRP probability for 36 combinations of level of baseline characteristics. Its range goes from patients with a 4.1 fold lower risk of RRP compared to average risk (probability of 0.05 CI 95% [0.03–0.08], patient with CRP 95% [0.39–0.55], patient with CRP >30, with RF, with erosive disease on X-ray, with >10 swollen joints). Conclusions A matrix proposing RRP probability at one year with better precision (i.e. narrower CI 95% than those previously published) in early RA for various combinations of levels of a few common baseline characteristics has been built using several databases. However, discriminating power is not ideal. Further investigations will be needed to fully explore the potential complexity of predicting RRP in early RA. Disclosure of Interest None declared

International audience

Background Postoperative operative pulmonary complications (PPCs) after hepatic surgery are associated with increased length of hospital stays. Intraoperative blood transfusion, extensive resection and different comorbidities have been identified. Other parameters, like time of hepatic ischemia, have neither been clinically studied, though experimental studies show that hepatic ischemia can provide lung injury. The objective of this study was to determinate the risk factors of postoperative pulmonary complications (PPCs) after hepatic resection within 7 postoperative days. Method Ninety-four patients consecutively who underwent elective hepatectomy between January and December 2013. Demographic data, pathological variables, and preoperative, intraoperative, and postoperative variables had been prospectively collected in a data base. The dependant variables studied were the occurrence of PPCs, defined before analysis of the data. Results PPCs occurred in 32 (34%) patients. A multivariate analysis allowed identifying the risk factors for PPCs. On multivariate analysis, preoperative gamma-glutamyltransferase (GGT) elevation OR =5,12 [1,85-15,69] p = 0,002, liver ischemia duration OR = 1,03 [1,01-1,06] p = 0,01 and the intraoperative use of vasopressor OR = 4,40 [1,58-13,36] p = 0,006 were independently associated with PPCs. For every 10 min added in ischemia duration, the OR of the risk of PPCs was estimated to be 1.37 (CI95% = [1.08-1.81], p = 0.01). Conclusion Three risk factors for PPCs have been identified in a population undergoing liver resection: preoperative GGT elevation, ischemia duration and the intraoperative use of vasopressor. PPCs after liver surgery could be related to lung injury induced by liver ischemia reperfusion and not solely by direct infectious process. That could explain why factors influencing directly or indirectly liver ischemia were independently associated with PPCs. Electronic supplementary material The online version of this article (doi:10.1186/s12871-017-0372-9) contains supplementary material, which is available to authorized users.

The objective of this work was to detail the incidence and mortality trends of invasive and in situ breast cancer (BC) in France, especially regarding the development of screening, over the 1990-2008 period. Data issued from nine population-based cancer registries were studied. The incidence of invasive BC increased annually by 0.8 % from 1990 to 1996 and more markedly by 3.2 % from 1996 to 2003, and then sharply decreased until 2006 (-2.3 % per year), especially among women aged 50-69 years (-4.9 % per year). This trend was similar whatever the introduction date of the organized screening (OS) program in the different areas. The incidence of ductal carcinoma in situ steadily increased between 1990 and 2005, particularly among women aged 50-69 years and 70 and older. At the same time, the mortality from BC decreased annually by 1.1 % over the entire study period. This decrease was more pronounced in women aged 40-49 and 50-69 and, during the 1990-1999 period, in the areas where OS began in 1989-1991. The similarity in the incidence trends for all periods of implementation of OS in the different areas was striking. This suggests that OS alone does not explain the changes observed in incidence rate. Our study highlights the importance of closely monitoring the changes in incidence and mortality indicators, and of better understanding the factors causing variation.

La détresse émotionnelle liée au diabète impacte la qualité de vie et l’équilibre métabolique ce qui rend indispensable l’exploration du vécu de la maladie. Nous avons comparé 2 approches de médecine narrative, un atelier d’écriture où le patient écrit « une lettre à son diabète » (LAMD) et le « théâtre du vécu » (TDV) où un récit est transformé en une saynète qui est interprétée par des comédiens professionnels, mise en scène par le patient à l’aide du directeur d’acteurs. Deux groupes de patients diabétiques de type 1 hospitalisés dans le cadre d’un séjour d’éducation thérapeutique ont été randomisés dans une session soit avec LAMD (n = 27) soit avec TDV (n = 28). Deux questionnaires portant sur la détresse émotionnelle liée au diabète (PAID) et sur ses représentations du diabète (IPQR) ont été réalisés en début de programme et 3 mois plus tard et les résultats comparés par un test de Wilcoxon apparié. Une analyse qualitative menée par une psychologue a été effectuée chez 11 patients 3 mois après l’intervention. Nous n’avons pas observé de différence significative sur l’évolution du score des questionnaires entre les 2 approches mais l’analyse qualitative suggère un effet positif des 2 processus narratifs, plus marqué pour le TDV.

Objective: To report the speech performance and sound localization in adult patients 5 years after bilateral simultaneous cochlear implantation and to evaluate the change in speech scores between 1 and 5 years. Design: In this prospective multicenter study, 26 patients were evaluated 5 years after implantation using long straight electrode arrays (MED-EL Combi 40+, standard electrode array, 31 mm). Speech perception was measured using disyllabic words in quiet and noise, with the speech coming from the front and a cocktail party background noise coming from 5 loudspeakers. Speech localization measurements were performed in noise under the same test conditions. These results were compared to those obtained at 1 year reported in a previous study. Results: Five years after implantation, an improvement in speech performance scores compared to 1 year after implantation was found for the poorer ear both in quiet and in noise (+12.1 ± 2.6%, p < 0.001). The lower the speech score of the poorer ear at 1 year, the greater the improvement at 5 years, both in quiet (r = -0.62) and at a signal-to-noise ratio of +15 dB (r = -0.58). The sound localization on the horizontal plane in noise provided by bilateral implantation was better than the unilateral one and remained stable after the results observed at 1 year. Conclusion: In adult patients simultaneously and bilaterally implanted, the poorest speech scores improved between 1 and 5 years after implantation. These findings are an additional element to recommend bilateral implantation in adult patients. The use of both cochlear implants and speech training sessions for patients with poor performance should continue in the period after 1 year following implantation, since the speech scores will improve over time.

Background In patients with rheumatoid arthritis in remission, a disease activity–driven tapering of adalimumab or etanercept relying on progressive injection spacing has not been shown to be equivalent to a maintenance strategy at full dose in terms of disease activity in the Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS) trial. Objectives To evaluate the cost-effectiveness of such a spacing strategy based on the data of the STRASS trial. Methods This is a cost-utility analysis of the STRASS trial, a French multicenter 18-month equivalence randomized open-label controlled trial that included patients at stable dose for at least 1 year, in remission for at least 6 months. Effectiveness was assessed in quality-adjusted life-years (QALYs). Costs involved in the study period were assessed from a payer perspective. The decremental cost-effectiveness ratio (DCER) was calculated in the complete cases sample (n = 98). Several sensitivity analyses were conducted and the impact of missing data on DCER estimate was investigated. An acceptability analysis was performed. Results In the spacing arm, TNF-blockers were stopped for 34.1% of the patients, tapered for 43.2%, and maintained at full dose for 18.2%. The spacing strategy was associated with less QALYs gain (mean difference of −0.158; 95% confidence interval [CI] −0.085 to −0.232) and reduced costs (mean difference of −€8,440; 95% CI −6,507 to −10,212). The estimated DCER of the spacing strategy over the maintenance at full dose was €53,417 saved per QALY lost (95% CI 32,230 to 104,700). Conclusions The spacing strategy appears cost-effective, but the acceptability of such a QALY loss reported to the cost avoided remains to be evaluated, because no consensual threshold has been determined for willingness to accept as compared with willingness to pay.

BackgroundDisease activity may change over time in axial spondyloarthritis (axSpA). The objectives were to identify patterns of disease activity evolution in patients with early axSpA.MethodsPatients from the prospective early axSpA cohort (DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR)) who fulfilled the Assessment in SpondyloArthritis Society (ASAS) criteria for axSpA at baseline and with at least three Ankylosing Spondylitis Disease Activity Score (ASDAS) values available over the 3 years of follow-up were analysed. Statistical analyses: trajectories were estimated by group-based trajectory modelling; predisposing baseline factors for such trajectories were identified by univariate and multivariable multinomial (logit) regression; work disability over time was compared between the trajectories by Cox hazard model.ResultsIn all, 370 patients were analysed: mean disease duration was 1.6 (±0.9) years. The five distinct trajectories of disease activity over the 3 years were (t1) ‘persistent moderate disease activity’ (n=134 (36.2%)); (t2) ‘persistent inactive disease’ (n=66 (17.8%); (t3) ‘changing from very high disease activity to inactive disease’ ((n=29 (7.8%)); (t4) ‘persistent high disease activity’ (n=126 (34.1%)) and (t5) ‘persistent very high disease activity’ (n=15 (4.1%)). After adjustment for other characteristics, t2 was associated with a white-collar job (OR=2.6 (95% CI 1.0 to 6.7)) and t3 with male gender (OR=7.1 (1.6 to 32.2)), higher education level (OR=9.4 (1.4 to 63.4)) and peripheral joint involvement (OR=6.2 (1.23 to 31.32)). Patients from (t4) and (t5) were more often declared work disabled over follow-up (HR=5.2 (1.5 to 18.0) and HR=8.0 (1.3 to 47.9), respectively).ConclusionsTrajectory modelling of disease activity was feasible in early axSpA: more than 30% patients (141/370) were in a trajectory with a persistent high disease activity. Persistent high disease activity trajectories were significantly associated with consequences on work.Trial registration numberNCT01648907.

International audience; Background: The prevention of addictions in young people is a challenge for Mental and Public Health policies, and requires specific risk-screening tools. Specific personality traits, as assessed using the Substance Use Risk Profile Scale (SURPS), could play a key role in the onset and escalation of substance use. This study aimed to examine (1) measurement invariance across age and gender (2) the effects of age and gender on associations between SURPS scores and the most frequently-consumed substances. Methods: Analyses were based on the responses from 5069 participants (aged 14-20 years) from the 2011 ESPAD-France dataset. Substance-use outcomes were experimentation and current frequency of alcohol, tobacco and cannabis use, and drunkenness. Results: Our approach, consisting in analysing measurement and structural invariance and interaction terms, established the stability of (i) SURPS profiles, and (ii) relationships between these scores and substance experimentation and use over a developmental period ranging from mid-adolescence to early adulthood. Measurement invariance across genders was also confirmed despite the absence of scalar invariance for 2 items. Significant interactions between gender and SURPS factors were established, highlighting differential vulnerability, especially concerning Hopelessness and experimentation of alcohol and drunkenness, or Impulsivity and tobacco experimentation. Finally, Anxiety Sensitivity could be protective against substance use, especially for cannabis in girls. Conclusions: Our results suggest the relevance of the SURPS to assess vulnerability towards drug use, and underline the need to consider gender differences in addiction risks.

Inappropriate prescribing in elderly is considered as common (40% of subjects from community from the 3CStudy in France had a inappropriate prescription, using Beer's criteria), and can lead to severe issues. Few studies have assessed inappropriate prescribing for elderly inpatients in acute care, with multiple tools. Our study was designed to assess outcome prescriptions concordance of elderly inpatients, for potentially inappropriate medication use.A retrospective study based on a random sample of 170 inpatients in 2009 was performed at Nantes University Hospital. We used standardized tools, especially general prescriptions rules of the "Collège professionnel des gériatres français", Beers's criteria, the Anticholinergic Risk Scale, concordance for renal function, and search for medication with tight therapeutic edge.Mean age of inpatients was 85.2 ± 4.1 years. Median numbers of prescribing drugs was eight. General prescriptions rules were followed up to 90% of inpatients: no forbidden drug-drug interaction was found. However, more than two psychotropic medications were prescribed for 3.9% of inpatients. At least one drug listed in Beers's criteria were found for 41 (27.0%) inpatients: amiodarone (18 inpatients) and long-term benzodiazepines (seven inpatients). A medication from the anticholinergic risk scale was found for 28 subjects (18.6%): however, for only seven of them, the score was higher than 3. Concordance for renal function was required for 126 inpatients (82.9%) for at least one prescription, 9 (7.1%) patients have a medication overdose according to their renal impairment. Medications with tight therapeutic edge were prescribed for 52 subjects (34.2%): mostly oral anticoagulants (27 subjects). In 15 cases, the dose was underneath the recommended level.Some potentially inappropriate medication uses were revealed by our study. It is essential to spread out results for clinicians, for a better knowledge of these risks.

International audience; Objective. This simulation study was designed to provide data on the performance of Oort's procedure (OP) for response shift (RS) detection (regarding Type-I-Error, power and overall performance), according to sample characteristics, at item-level. A specific objective was to assess the impact of using different information criteria (IC), as alternatives to LRT (Likelihood-Ratio Test), for global assessment of RS occurrence. Methods. Responses to 5 binary items at two times of measurement were simulated. Thirty-six combinations of sample characteristics (sample size (n), "true change", correlations between the two latent variables and presence/absence of uniform recalibration RS (ur)) were considered. A thousand datasets were generated for each combination. RS detection was performed on each dataset following OP. Type-I-Error and power of the global assessment of RS occurrence, as well as overall performance of the OP was assessed. Results. The estimated Type-I-Error was close to 5% for the LRT and lower than 5% for the IC. The estimated power was higher for the LRT as compared to the AIC, which was the highest among the other IC. For the LRT, the estimated power for n = 100 and for the combination of n = 200 and ur = 1 item was below 80%. Otherwise, for other combinations of sample characteristics, the estimated power was above 90%. Conclusion. For the LRT, higher values of power were estimated compared to IC with appropriate values of Type-I-Error. These results were consistent with Oort's proposal to use the LRT as the criterion to assess global RS occurrence.

International audience; Objective. The purpose of Randomized Control Trials (RCTs) can be the assessment of the direct effect of treatment on Health-Related Quality of Life (HRQL). Response shift (RS) theory considers that a change in HRQL scores observed over time cannot be explained solely by a direct effect of a medical condition, it may also result from a change in the way people appraise their HRQL. The RS effect is a potential bias that is liable to compromise efficient assessment of the effect of treatment on HRQL. Study design and setting. We hypothesize a link between the RS effect on HRQL scores, and the level of complexity of HRQL conceptualization. Results. We discuss how the impact of reconceptualization on scores depends on the complexity of the linguistic definition of a subjective construct, and how for reprioritization the impact depends on the dimensionality. The linguistic theory of semantic primes is used to help identify how subjective constructs can be classified according to the complexity of their definitions. Conclusion. Finally, we suggest that the impact of the RS effect on HRQL scores could be avoided (or lessened) if questionnaires were designed with a rule of "the least semantic and psychometric complexity" in mind.

International audience; PURPOSE:Some IRT models have the advantage of being robust to missing data and thus can be used with complete data as well as different patterns of missing data (informative or not). The purpose of this paper was to develop an algorithm for response shift (RS) detection using IRT models allowing for non-uniform and uniform recalibration, reprioritization RS recognition and true change estimation with these forms of RS taken into consideration if appropriate.METHODS:The algorithm is described, and its implementation is shown and compared to Oort's structural equation modeling (SEM) procedure using data from a clinical study assessing health-related quality of life in 669 hospitalized patients with chronic conditions.RESULTS:The results were quite different for the two methods. Both showed that some items of the SF-36 General Health subscale were affected by response shift, but those items usually differed between IRT and SEM. The IRT algorithm found evidence of small recalibration and reprioritization effects, whereas SEM mostly found evidence of small recalibration effects.CONCLUSION:An algorithm has been developed for response shift analyses using IRT models and allows the investigation of non-uniform and uniform recalibration as well as reprioritization. Differences in RS detection between IRT and SEM may be due to differences between the two methods in handling missing data. However, one cannot conclude on the differences between IRT and SEM based on a single application on a dataset since the underlying truth is unknown. A next step would be to implement a simulation study to investigate those differences.

Introduction Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients. Methods We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort (n = 87) was used for validation. Results Fuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P = 0.03) and C3 patients (mean = 51.9 years; P = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P

Purpose : Comparisons of breast cancer characteristics between organized and opportunistic screening have been limited. This study was designed to compare characteristics of cancers detected by either organized or opportunistic screening as well as clinically diagnosed cancers in Loire-Atlantique (a French administrative entity), from 2003 to 2007. Methods : This study is based on data from the population-based Loire-Atlantique Cancer Registry. Stage at diagnosis and prognostic characteristics of carcinomas detected by organized screening were compared, by age-adjusted logistic regressions, to those of cancers detected by opportunistic screening and diagnosed clinically. Analyses were restricted to women aged 50–74 years (the age group targeted by the organized screening program) for the 2003–2007 period. Results : Between 2003 and 2007, 2864 invasive and 400 in situ breast cancer cases were diagnosed in women aged 50–74 years in Loire-Atlantique. Compared to cancers diagnosed clinically, cancers detected by organized screening were more likely to be in situ (13.7% vs. 3.8%), diagnosed at an early stage (74.4% vs. 51.3%), have a low SBR grade (grade 1: 35.4% vs. 18.5%), and be positive for estrogen–progesterone receptors (68.3% vs. 59.0%). The distribution of stage at diagnosis and prognostic characteristics between organized and opportunistic screening were similar. Conclusion : These findings are consistent with the hypothesis that breast cancers are detected early by organized screening. Cancer characteristics were similar between the two screening modes. Estimating the impact of mammography screening on mortality in Loire-Atlantique should be the object of further investigations.

Background Once remission is achieved for patients with rheumatoid arthritis (RA), treatment down-titration should be attempted, for safety issues or economic reasons. One of the proposed strategies, recently tested in the STRASS trial [1], is to progressively space injections of TNF-blockers. Objectives To assess the Incremental Cost-Effectiveness Ratio (ICER) of a strategy of progressive spacing of TNF-blocker injections (S-arm) over another maintaining them at full-dose (M-arm) in RA patients in stable remission. Methods The study was a French multi-centre 18-month equivalence randomized open-label controlled trial. It included patients receiving etanercept (ETA) or adalimumab (ADA) at stable dose for ≥1 year; in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months; and with stable joint damage. In the S-arm, the interval between 2 subcutaneous injections was increased every 3 months by 50% in 4 steps, to a complete stop at step 4. If remission was not maintained, spacing was suspended or reversed to the previous interval. Costs engaged within the study-period, measured in euros, were assessed using a health insurance payer perspective encompassing medical costs (drugs, consultations and medical tests, use of emergency room and hospitalizations) and costs relative to sick leave. Utilities values used to compute Quality Adjusted Life Years (QALYs) were derived from the EQ-5D, using values validated in the French population, assessed at baseline and every 6 months. The ICER was estimated. A probabilistic sensitivity analysis was performed by computing 5000 ICERs (bootstrap). The probability of cost-effectiveness (p of CE) of the maintenance strategy was computed for different Willingness to Pay (WTP) thresholds. Results Analyses were performed on 44 patients in the S-arm and 54 in the M-arm with complete data. In the S-arm, TNF-blockers were stopped for 34.1% of the patients, tapered for 43.2%, maintained at full-dose for 18.2%. After 18 months of follow-up, 62.3% and 45.9% of the patients of the S and M-arm respectively, found their symptomatic state acceptable (p=0.08). Patients in the S-arm gained 1.106 QALYs while it was 1.264 in the M-arm (mean differences in QALYs of -0.158). After 18 months, total mean cost was 12452 euros in the S-arm and 20892 euros in the M-arm (mean cost difference of -8440 euros). The cost of TNF-blockers represented 81.0% and 92.8% of the total cost in the S and M-arms respectively. The estimated ICER was 53417 euros per QALY. The p of CE of the maintenance strategy was 0.02, 0.06, 0.22 and 0.41 for WTP thresholds fixed at 25000, 30000, 40000 and 50000 euros respectively. Conclusions Although 62.3% of the patients found their symptomatic state acceptable, the spacing strategy was found to be less effective based on QALY measures. But, it was also found to be less costly. Thus, the maintenance strategy was assessed as the strategy with the lowest probability of being cost-effective for WTP thresholds ranging from 25000 to 50000 euros. References Fautrel et al, EULAR 2013 and ACR 2013 Disclosure of Interest None declared