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International audience; This paper focuses on the particular situation of an advanced cancer patient whose condition has taken a chronic turn. We argue that chronicity of this kind sometimes falls at the frontier of Evidence Based Medicine because the uncertainty about the patient's condition can lead physicians to resort to clinical trials or non-licensed drugs to prevent the disease from progressing. This situation leaves plenty of scope for individual adjustments between patients and their doctors. Advanced cancer is regarded here not just as a biological event but as a chronic illness and a 'negotiated reality'. We argue that the chronicity of advanced cancer patients' situation broadens the patients' scope for 'work', and we have called this specific type of patient's work 'decision-making work'. This paper is based on a case study focusing on Patrick, a middle-aged Frenchman with metastatic lung cancer who underwent oncological treatment for seven years and was strongly determined to find new therapeutic options even if this meant having to go abroad. He actively orchestrated his therapeutic itinerary by reorganising his relationships with the medical world and coordinating the physicians' work. His particular social position enabled Patrick to bypass some of the current medical rules and to reorganise the usual pattern of distribution of medical responsibilities. The chronicity of his condition placed him at the very frontier of the health care system.

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International audience; Autism spectrum disorder (ASD) is often grouped with other brain-related phenotypes into a broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers need to decide which genes to test in individuals with ASD phenotypes, which requires an understanding of the level of evidence for individual NDD genes that supports an association with ASD. Consensus is currently lacking about which NDD genes have sufficient evidence to support a relationship to ASD. Estimates of the number of genes relevant to ASD differ greatly among research groups and clinical sequencing panels, varying from a few to several hundred. This Roadmap discusses important considerations necessary to provide an evidence-based framework for the curation of NDD genes based on the level of information supporting a clinically relevant relationship between a given gene and ASD.

International audience; Since their first use for treating rheumatoid arthritis (RA) in the late 1940s, glucocorticoids (GCs) have been representing a substantial part of the therapeutic arsenal for RA. However, even if GCs are still widely prescribed drugs, their toxicity is discussed controversially, so obtaining consensus on their use in RA is difficult. Hence, the most recent European League Against Rheumatism and American College of Rheumatology recommendations on early arthritis and RA management advocate the use of GCs as adjunct treatment to conventional synthetic disease-modifying antirheumatic drugs, at the lowest dose possible and for the shortest time possible. However, the recommendations remain relatively vague on dose regimens and routes of administration. Here, we describe literature data on which the current recommendations are based as well as data from recent trials published since the drafting of the guidelines. Moreover, we make proposals for daily practice and provide suggestions for studies that could help clarifying the place of GCs in RA management. Indeed, numerous items, including the benefit/risk ratio of low-dose and very low-dose GCs and optimal duration of GCs as bridging therapy, remain on the research agenda, and future studies are needed to guide the next recommendations for RA.

International audience; The Research Committee of the European Society of Pediatric Urology will present a series of short educational communications related to evidence-based medicine. The aim of the series is to emphasize the importance of grading evidence, thereby determining the best clinical practice for patients. The goal of this series is to guide the clinician in using tools for setting up a clinical question, finding appropriate information, searching appropriate databases, and evaluating the results in relation to the patient in mind. This first part will serve as an introduction or background. Following publications will cover the topics of hierarchy of evidence, information acquisition, clinical appraisal tools, and applications in clinical practice [3].

Background The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). Methods A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. Results A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. Conclusions To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm. Electronic supplementary material The online version of this article (10.1186/s13023-018-0980-6) contains supplementary material, which is available to authorized users.

Introduction Clinical decision support systems (CDSS) implementing clinical practice guidelines (CPGs) have 2 main limitations: they target only patients for whom CPGs provide explicit recommendations, and their rationale may be difficult to understand. These 2 limitations result in poor CDSS adoption. We designed AntibioHelp® as a CDSS for antibiotic treatment. It displays the recommended and nonrecommended antibiotics, together with their properties, weighted by degree of importance as outlined in the CPGs. The aim of this study was to determine whether AntibioHelp® could increase the confidence of general practitioners (GPs) in CPG recommendations and help them to extrapolate guidelines to patients for whom CPGs provide no explicit recommendations. Materials and Methods We carried out a 2-stage crossover study in which GPs responded to clinical cases using CPG recommendations either alone or with explanations displayed through AntibioHelp®. We compared error rates, confidence levels, and response times. Results We included 64 GPs. When no explicit recommendation existed for a particular situation, AntibioHelp® significantly decreased the error rate (−41%, P value = 6x10−13), and significantly increased GP confidence (+8%, P value = .02). This CDSS was considered to be usable by GPs (SUS score = 64), despite a longer interaction time (+9–22 seconds). By contrast, AntibioHelp® had no significant effect if there was an explicit recommendation. Discussion/Conclusion The visualization of weighted antibiotic properties helps GPs to extrapolate recommendations to patients for whom CPGs provide no explicit recommendations. It also increases GP confidence in their prescriptions for these patients. Further evaluations are required to determine the impact of AntibioHelp® on antibiotic prescriptions in real clinical practice.

International audience; The number of patients on chronic anticoagulant or antiplatelet therapy requiring endoscopic urological surgery is increasing worldwide. Therefore, there is a strong demand to standardize the perioperative treatment of this cohort of patients, both from a surgical and cardiological point of view, balancing the risks of bleeding versus thrombosis, and the important possible clinical and medical legal repercussions therein. Although literature is scarce and the quality of evidence quite low, in line with other surgical specialties, guidelines and recommendations for the management of urological patients have begun to emerge. The aim of this review is to analyze current available literature and evidence on the most common endoscopic procedures performed in this high-risk group of patients, focusing on the perioperative management. In particular, to analyze the most frequently performed endoscopic procedures for the treatment of benign prostate enlargement (transurethral resection of the prostate, Thulium, Holmium and greenlight laser prostatectomy), bladder cancer (transurethral resection of the bladder), upper urinary tract urothelial cancer, and nephrolithiasis. Despite the lack of randomized studies, regardless of individual patient considerations, studies would support continuation of acetylsalicylic acid, which is recommended by cardiologists, in patients with intermediate/high risk of coronary thrombosis. In contrast, multiple studies found that bridging with light weight molecular weight heparin can potentially lead to more bleeding than continuation of the anticoagulant(s) and antiplatelet therapy, and caution with bridging is advised. All urologists should familiarize themselves with emerging guidelines and recommendations, and always be prepared to discuss specific cases or scenarios in a dedicated multidisciplinary team.

International audience; Cholesterol-lowering drugs are often prescribed to patients with type 2 diabetes mellitus despite uncertainty about the benefits of this treatment in the prevention of cardiovascular complications. We here systematically review (PRISMA guidelines) the results of high-quality double blind trials testing whether cholesterol-lowering drugs (statins and fibrates) reduce mortality and cardiovascular complications specifically in type 2 diabetics. Trials with premature termination without pertinent medical justification or using nonrandomized subgroups of diabetics were excluded from the review. Only four trials met our predefined inclusion criteria. Among the 3 statin trials, CARDS was discontinued 2 years before the anticipated end and in the absence of significant effect on both overall and cardiovascular mortality, suggesting that the trial should not have been prematurely stopped. The two other statin trials showed no significant effect on the primary endpoint (relative risk 0.92, 95% CI 0.77 to 1.10 in 4D and 0.90, 95% CI 0.73 to 1.12 in ASPEN) and on both cardiovascular and overall mortality. Finally, the fibrate trial (FIELD) showed no significant benefit on the primary endpoint (relative risk 0.89, 95% CI 0.75 to 1.05) and mortality (relative risk 1.11, 95% CI 0.95 to 1.29). Because of a huge medical heterogeneity between patients in the selected trials, it was consensually decided to stop the analysis at this stage. This review does not support the use of cholesterol-lowering drugs (such as statin and fibrate) to reduce mortality and cardiovascular complications in type 2 diabetics. Official guidelines should be re-examined and reformulated by experts independent from the pharmaceutical industry.

International audience; PURPOSE OF REVIEW: Asthma is a heterogeneous disease constituted by overlapping separate syndromes. This review discusses recent published data relevant to asthma and severe asthma classification, resting either on the 'candidate' approach based on criteria chosen by experts or on the 'exploratory' approach based on unsupervised statistical methods. RECENT FINDINGS: Following the 'candidate' approach, groups of experts recently reviewed the classification of severe asthma to be applicable in low-income, milddle-income, and high-income countries and provided a systematic algorithm to diagnose severe refractory asthma. The concept of asthma endotypes involving different biological mechanisms has recently being proposed. Results from the 'exploratory' approach support the clinical heterogeneity in severe asthma and the need for new approaches for the classification of asthma severity. The novel childhood and adult asthma phenotypes recently identified using the exploratory approach were supported by first evidence of validity (replication in independent studies, assessment of their discriminative properties, and effect on clinical prognosis). SUMMARY: Research on asthma phenotypes has increased exponentially in the last year. The main focus has been on severe asthma, likely due to its clinical and socioeconomic burden. Interestingly, many of the phenotypes identified are stable across populations and methodological approaches. Further analyses on the asthma phenotypes are needed to address their stability over time and their relevance from clinical and etiological perspectives.

International audience; Systematic reviews and meta-analyses constitute one of the central pillars of evidence-based medicine. However, clinical trials are poorly reported which delays meta-analyses and consequently the translation of clinical research findings to clinical practice. We propose a Center of Excellence in Research Reporting in Neurosurgery (CERR-N) and the creation of a clinically significant computational ontology to encode Randomized Controlled Trials (RCT) studies in neurosurgery. A 128 element strong computational ontology was derived from the Trial Bank ontology by omitting classes which were not required to perform meta-analysis. Three researchers from our team tagged five randomly selected RCT's each, published in the last 5 years (2004-2008), in the Journal of Neurosurgery (JoN), Neurosurgery Journal (NJ) and Journal of Neurotrauma (JoNT). We evaluated inter and intra observer reliability for the ontology using percent agreement and kappa coefficient. The inter-observer agreement was 76.4%, 75.97% and 74.9% and intra-observer agreement was 89.8%, 80.8% and 86.56% for JoN, NJ and JoNT respectively. The inter-observer kappa coefficient was 0.60, 0.54 and 0.53 and the intra-observer kappa coefficient was 0.79, 0.82 and 0.79 for JoN, NJ and JoNT journals respectively. The high degree of inter and intra-observer agreement confirms tagging consistency in sections of a given scientific manuscript. Standardizing reporting for neurosurgery articles can be reliably achieved through the integration of a computational ontology within the context of a CERR-N. This approach holds potential for the overall improvement in the quality of reporting of RCTs in neurosurgery, ultimately streamlining the translation of clinical research findings to improvement in patient care.

International audience; OBJECTIVES: To assess the current 'real-world' management of hospitalised patients with lower-extremity peripheral artery disease (LE-PAD) and to assess the 1-year outcome. DESIGN, MATERIALS AND METHODS: The prospective and multicentre registry COhorte des Patients ARTériopathes (COPART) recruited consecutive patients from the departments of vascular medicine of three academic hospitals in Southwestern France. RESULTS: Among the 940 patients, 27.4% had intermittent claudication (IC), 9.3% ischaemic rest pain, 54.3% ulceration or gangrene and 9.3% acute limb ischaemia (ALI). Patients with IC were younger and more likely to be men, with a history of smoking (89.5%) and chronic obstructive pulmonary disease (17%). Among those with IC, 8.9% had bypass surgery and 41.5% were treated with percutaneous angioplasty. Those with tissue loss had higher rates of cardiovascular disease (CVD) risk factors and co-morbidities. At entry to the study, the level of control of the CVD risk factors was poor. The 1-year mortality rate was of 5.7% in patients with IC, 23.1% in patients with ischaemic rest pain, 28.7% in patients with tissue loss and 23% in those with ALI. Compliance with evidence-based medicine and pharmacological treatment was sub-optimal. CONCLUSION: This registry underscores the differences in patient profiles in the daily clinical setting, compared to those enrolled in several trials.

International audience; Objectives: To develop recommendations about prognosis and follow-up of psoriatic arthritis (PsA) with peripheral joint involvement in everyday clinical practice. Methods: The strategy was as following: (a) The choice of five questions, by the scientific committee according to the Delphi method, considered as a basis for the recommendations; (b) the Systematic Literature Research based on Medline, Cochrane and abstracts from the annual meetings of SFR, EULAR and ACR. An expert committee composed with 68 rheumatologists elaborated and validated the recommendations, specifying the strength and the degree of agreement for each of them. Results: The questions selected were: (1) How can articular and cutaneous disease activity of PsA be assessed in usual clinical practice? (2) Which parameters are predictive for functional, radiological and fatal outcome in PsA? (3) Which clinical and biological parameters are useful for the follow-up of PsA? At which frequency? (4) Which X-rays are useful for the follow-up of PsA? At which frequency? (5) How can the response to treatments be assessed in PsA? The literature search identified 1181 abstracts and 123 articles were included and analyzed. Seven recommendations, whose strength ranged from B to D, were drafted and validated by a final vote of the expert committee. Conclusion: Seven recommendations about follow-up of patients with PsA for daily practice were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with PsA. (C) 2009 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

International audience; OBJECTIVE: Since the first paper published by Matzel et al., in 1995, on the efficacy of sacral nerve stimulation (SNS) in patients with faecal incontinence, the indications, the contraindications, the stimulation technique and follow up of implanted patients have changed. The aim of this article was to provide a consensus opinion on the management of patients with faecal incontinence treated with SNS. METHOD: Recommendations were based on a critical review of the literature when available and on expert opinions in areas with insufficient evidence. RESULTS: We have reviewed the indications and contraindications, proposed an algorithm for patient management showing the place of SNS. The temporary test technique, the implantation technique, the patient follow up and the approach in case of treatment failure were discussed. CONCLUSION: We hope not only to provide a guide on patient management to clinical practitioners interested in SNS but also to harmonize our practices.

ObjectiveThe eumusc.net project is an initiative founded by the European Community and the European League Against Rheumatism. One aim of the project was to facilitate equal standards for musculoskeletal health across Europe. The aim of this work-package was to develop patient-centred and consensus based standards of care (SOC) for osteoarthritis (OA), which should be available in a professional and a patient version.MethodsA systematic review concerning guidelines dealing with OA was conducted. Furthermore, experts in musculoskeletal diseases were contacted to ensure that ‘grey’ literature was not excluded. Documents that fulfilled predefined inclusion/exclusion criteria were included and all interventions for OA were extracted and categorised. Based on this list of interventions, a three round Delphi exercise with an international and multidisciplinary expert panel, including patient research partners, was performed to achieve expert consensus.ResultsSix documents were included and used for further analysis. Out of them, 46 interventions have been extracted and 10 consensus based SOC were formulated. In addition, a patient version, written in a lay-understandable wording and in the format of checklist questions was developed. An example is SOC 5: “People with OA should achieve optimal pain control using pharmacological and non-pharmacological means.” The matching patient-centred checklist question reads: “Do I know how to control pain associated with OA?”ConclusionsThe SOC for OA will be available in the 23 languages of the European Union to enhance unified information to patients and professionals and to further harmonise the treatment/care of OA within Europe.

International audience; The human auditory cortex includes several interconnected areas. A better understanding of the mechanisms involved in auditory cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. In human, it is difficult to track in vivo neuronal connectivity. We investigated the interarea connection in vivo in the auditory cortex using a method of directed coherence (DCOH) applied to depth auditory evoked potentials (AEPs). This paper presents simultaneous AEPs recordings from insular gyrus (IG), primary and secondary cortices (Heschl's gyrus and planum temporale), and associative areas (Brodmann area [BA] 22) with multilead intracerebral electrodes in response to sinusoidal modulated white noises in 4 epileptic patients who underwent invasive monitoring with depth electrodes for epilepsy surgery. DCOH allowed estimation of the causality between 2 signals recorded from different cortical sites. The results showed 1) a predominant auditory stream within the primary auditory cortex from the most medial region to the most lateral one whatever the modulation frequency, 2) unidirectional functional connection from the primary to secondary auditory cortex, 3) a major auditory propagation from the posterior areas to the anterior ones, particularly at 8, 16, and 32 Hz, and 4) a particular role of Heschl's sulcus dispatching information to the different auditory areas. These findings suggest that cortical processing of auditory information is performed in serial and parallel streams. Our data showed that the auditory propagation could not be associated to a unidirectional traveling wave but to a constant interaction between these areas that could reflect the large adaptive and plastic capacities of auditory cortex. The role of the IG is discussed.

Clinical practice guidelines (CPGs) are documents giving recommendations based on expert reasoning, weighing up the pros and cons of treatments on the basis of the available evidence. We propose a new approach to the construction of clinical decision support systems (CDSS), making use of the evidence-based medical reasoning used by experts in CPGs. In this study, we determined whether this approach could retrieve the recommendations for antibiotic prescription for empirical treatment in primary care.We manually extracted, from CPGs, all the properties of antibiotics underlying recommendations for their prescription or non-prescription. We then used these properties to establish an algorithm in the form of a sequence of conditions, leading to a list of recommended antibiotics. The optimal sequence was determined by studying, for each sequence, the degree of similarity between the list of antibiotics recommended in CPGs and the list obtained with the algorithm.12 antibiotic properties were used in the form of conditions in an algorithm. For 95% of clinical situations, 10 sequences retrieved the recommended treatment.This algorithm could be used in a CDSS for antibiotic treatment and would be useful for experts drawing up CPGs.

International audience; The aim of this report was to propose a definition for erosive disease in the context of inflammatory arthritis in light of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria for use in clinical practice and studies. A EULAR task force was formed including 16 rheumatologists and one rheumatology fellow. The process was both evidence based and consensus based, and included, between March 2010 and April 2012, analyses of data from two cohorts, two face-to-face meetings, one online voting and one teleconference. The Leiden Early Arthritis Cohort and the French ESPOIR cohort were used for the evidence-based part. The outcome measures, which were initiation of methotrexate therapy, or any disease-modifying antirheumatic drug therapy within the first year of disease and arthritis persistency over 5 years, were studied with the aim to give the best definition of erosive disease. A decision was made to select a definition with a high specificity and focus on patients who did not otherwise fulfil the 2010 ACR/EULAR RA criteria (

International audience

International audience; Progress in the medical treatment of patients with heart failure with systolic dysfunction, cardiac resynchronization therapy, internal cardiac defibrillators and multidisciplinary management programmes has resulted in dramatic improvements in survival and quality of life; however, this progress has led to an increase in the prevalence of advanced heart failure. In the context of organ shortage for cardiac transplantation, the technological developments in left ventricular assist devices, shown in recent positive clinical studies, provide real hope for patients with advanced heart failure. This article summarizes the most recent clinical studies concerning left ventricular assist devices and discusses for whom and when a left ventricular assist device should be proposed.

International audience; PURPOSE OF REVIEW: A recent and large multicentre study reports that ICU patients receive less than half of the recommended energy requirement. This review aims at clarifying whether underfeeding is scientifically justified or sustained by evidence-based medicine. RECENT FINDINGS: There is evidence that optimal nutrition improves clinical outcome of critically ill patients. The deleterious effect of overfeeding ICU patients is now well acknowledged, but underfeeding is not scientifically justified in ICU patients. Total energy expenditure in ICU patients is variable and methods to predict resting energy expenditure are questionable in these patients. SUMMARY: There is a need to measure energy expenditure in clinical practice. When not possible, the current guidelines on artificial nutrition (i.e. 25 kcal/kg per day) should be applied in order to limit underfeeding.

International audience; The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers), instead of survival, in determining treatment efficacy in patients with lung cancer. Initially, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer. Some intermediate criteria can be early predictors, if not surrogates, for survival, despite limitations in their potential application: these include time to progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers. Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.

International audience; The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

International audience; The presence of a pacemaker or an implantable cardioverter-defibrillator was historically considered a contraindication to magnetic resonance imaging (MRI), due to the risks for both patient and device: reed-switch closure responsible for asynchronous pacing, inhibition of pacing, rapid ventricular pacing, heating on the lead tip or even device displacement... However, many recent studies demonstrate that if MRI is crucial for the management of the patient, it can be performed under specific monitoring and scanning conditions and after device reprogramming. The growing implication of device constructors in constructing a MRI safety device will perhaps extend in the future the indications of this imaging modality in implanted patients.

Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. Conclusion The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.

Background The purpose of the study was to evaluate systematic reviews of research into two public health priorities, tobacco consumption and HIV infection, in terms of the reporting of data related to the applicability of trial results (i.e., whether the results of a trial can be reasonably applied or generalized to a definable group of patients in a particular setting in routine practice, also called external validity or generalisability). Methods All systematic reviews of interventions aimed at reducing or stopping tobacco use and treating or preventing HIV infection published in the Cochrane database of systematic reviews and in journals indexed in MEDLINE between January 1997 and December 2007 were selected. We used a standardized data abstraction form to extract data related to applicability in terms of the context of the trial, (country, centres, settings), participants (recruitment, inclusion and exclusion criteria, baseline characteristics of participants such as age, sex, ethnicity, coexisting diseases or co-morbidities, and socioeconomic status), treatment (duration, intensity/dose of treatment, timing and delivery format), and the outcomes assessment from selected reviews. Results A total of 98 systematic reviews were selected (57 Cochrane reviews and 41 non-Cochrane reviews); 49 evaluated interventions aimed at reducing or stopping tobacco use and 49 treating or preventing HIV infection. The setting of the individual studies was reported in 45 (46%) of the systematic reviews, the number of centres in 21 (21%), and the country where the trial took place in 62 (63%). Inclusion and exclusion criteria of the included studies were reported in 16 (16%) and 13 (13%) of the reviews, respectively. Baseline characteristics of participants in the included studies were described in 59 (60%) of the reviews. These characteristics concerned age in about half of the reviews, sex in 46 (47%), and ethnicity in 9 (9%). Applicability of results was discussed in 13 (13%) of the systematic reviews. The reporting was better in systematic reviews by the Cochrane Collaboration than by non-Cochrane groups. Conclusions Our study highlighted the lack of consideration of applicability of results in systematic reviews of research into 2 public health priorities: tobacco consumption and HIV infection.

International audience; Everolimus has proven efficacy for prevention of rejection in adult de novo renal and cardiac transplant recipient in combination with ciclosporine and corticosteroids. Therapeutic drug monitoring (TDM) with target trough concentration (C0) value from 3 to 8 µg/L has been proposed. Through a systematic review of the literature, this work explored a level of recommendation for this TDM. Everolimus exhibits both wide interindividual pharmacokinetic variability and poor relationship between dose and exposure. A good relationship has been reported between C0 values and global exposure to the drug (i.e. AUC). Although C0 > 3 µg/L has been associated with a decreased incidence of rejection, the upper limit of 8 µg/L has never been formally validated. No clinical trial testing other exposure indices or comparing efficacy and/or toxicity of everolimus therapy with and without TDM has been published so far. Consequently the level of recommendation for everolimus monitoring is "recommended".

International audience; Objectives: To develop recommendations about treatment (except anti-TNF agents) of psoriatic arthritis with peripheral joint involvement (PsA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed. Methods: The recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points of interest. Then, a literature task force looked for relevant publications in the following: Cochrane, Pubmed, and Ovid databases and abstracts from the French Society for Rheumatology, European League against Rheumatism and American College of Rheumatology. Based on the data from these publications, recommendations were drafted and then validated by a group of 68 experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts. Results: The evidence extracted from 73 selected papers was presented to experts during interactive workshops. At the end of the workshops, the experts drafted six recommendations, which were then validated by a final vote including all participants. These six recommendations displayed various strength from B to D. Conclusion: These recommendations should help to improve practice uniformity and, ultimately, to improve the management of PsA in France. (C) 2009 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.

International audience; OBJECTIVE: To propose French recommendations for the clinical, biological and radiological diagnosis of peripheral psoriatic arthritis (PsA) in daily practice based on data from the literature and expert opinion. METHOD: The strategy was the following: the choice of four questions, concerning this topic by the scientific committee according to the Delphi method, forming the basis of the recommendations. The Systematic literature research based on Medline, Cochrane and abstracts from the annual meetings of the French society of rheumatology (SFR), American college of rheumatology (ACR) and European ligue against rheumatism (EULAR). An experts committee of rheumatologists elaborated, validated specifying the strength and the degree of agreement of each recommendation. RESULTS: The questions selected were: (1) What clinical data should be collected to assist in the diagnosis of psoriatic arthritis? (2) What laboratory tests, immunological tests, and genetic tests should be performed to assist in the diagnosis of psoriatic arthritis? (3) What are the radiological investigations useful in the diagnosis of psoriatic arthritis? (4) What classification and/or diagnosis criteria can assist in the diagnosis of psoriatic arthritis? A literature search identified 1627 abstracts and 33 articles were included and analyzed. Four recommendations relative to the diagnosis were drafted and validated by a final vote of the experts committee. CONCLUSION: Recommendations concerning the diagnosis of PsA for daily practice were developed and validated on the basis of data from the literature and expert opinion. They should help to establish the diagnosis of PsA in daily practice.

International audience; Given the large amount of medical literature of varying methodological quality, care must be taken when translating the results of randomised controlled trials into clinical practice. To assist in this translation process, we provide a method that involves answering three main questions: 'Can I trust the results?' 'How do I understand the results?' and 'To whom do the results apply?' To answer the first question, we describe important items that help in judging the reliability of the findings. For the second question, we address the clinical and statistical significance of results by looking at the size and precision of the effect. Finally, we raise the issue of external validity and of reporting adverse effects to determine which patients may best benefit from the new intervention.

International audience; A highlight of the congress was an interactive and inclusive discussion of the existing gaps between clinical neurology and epidemiology and the ways of bridging these gaps. Some perceptions, challenges and scientific issues between experimental and non-experimental neuroepidemiology were brought to light. Recognizing that all study designs have advantages and disadvantages, panelists stressed that studies should aim to complement each other while answering important research- or practice-related questions. Advocated strategies included introducing more epidemiology into the medical school or residency curriculum, developing consistency in the reporting of epidemiological data to improving the strength and utility of the evidence, as well as nurturing collaborations that recognize the usefulness of both experimental and non-experimental epidemiological studies. These strategies will in the end benefit clinical practice. Indeed, clinical knowledge improves with experience and critical scientific evidence that can change perceptions, yet, individualized disease management will probably always remain an art rather than an exact science. Nevertheless, strong epidemiological studies and collaborations can influence government and public health policies. Bridging the gap between neuroepidemiological research and practice - whether through improved communication, education or basic science- is clearly a pressing challenge that requires our concerted and sustained effort.

The aging of the world population is a new medical challenge for the 21st century. There has been a striking increase in the proportion of elderly people, especially the very old, over the past decades. The elderly are living longer due, in part, to improved standards of living and the availability of social aid and medical care. Although some people reach a very old age completely free of physical ailments, most elderly people have several chronic diseases. Modern pharmacotherapy can slow down and delay the consequences of these ailments up to the eighth decade of life, but thereafter the complications of these diseases will usually become clinically significant. This often results in the administration of several drugs simultaneously. Clinical Pharmacology & Therapeutics (2008); 85, 1, 94–97 doi:10.1038/clpt.2008.214

International audience; Processed meat intake may be involved in the etiology of colorectal cancer, a major cause of death in affluent countries. The epidemiologic studies published to date conclude that the excess risk in the highest category of processed meat-eaters is comprised between 20% and 50% compared with non-eaters. In addition, the excess risk per gram of intake is clearly higher than that of fresh red meat. Several hypotheses, which are mainly based on studies carried out on red meat, may explain why processed meat intake is linked to cancer risk. Those that have been tested experimentally are (i) that high-fat diets could promote carcinogenesis via insulin resistance or fecal bile acids; (ii) that cooking meat at a high temperature forms carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons; (iii) that carcinogenic N-nitroso compounds are formed in meat and endogenously; (iv) that heme iron in red meat can promote carcinogenesis because it increases cell proliferation in the mucosa, through lipoperoxidation and/or cytotoxicity of fecal water. Nitrosation might increase the toxicity of heme in cured products. Solving this puzzle is a challenge that would permit to reduce cancer load by changing the processes rather than by banning processed meat.

International audience; The combination of chemotherapy and surgery is a standard of care for non-small cell lung cancer, as shown by the recently published "Standards, Options et Recommandations" (SOR) by the Fédération des Centres de Lutte contre le Cancer. This document was approved by the INCa, the SPLF, the Ligue contre le Cancer, the IFCT. However, the respective position of chemotherapy and surgery remains debated. Most trials of preoperative chemotherapy were closed when the positive studies of adjuvant chemotherapy were published. Therefore, the trials of preoperative chemotherapy lack strength to conclude on the validity of the concept. Confirmation will come from meta-analyses. Two meta-analyses based on published data have been yet published, and are positive.

International audience; OBJECTIVES: To develop recommendations about pharmacotherapy (excluding biotherapeutic agents) in patients with axial forms of ankylosing spondylitis (AS) seen in everyday clinical practice. METHODS: The recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points about which recommendations were needed. Then, a literature task force looked for relevant publications in the following: Cochrane, PubMed, and Ovid databases; and abstracts from the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on the data in these publications, recommendations were drafted then validated by a group of experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts. RESULTS: The four focal points were the best strategy for using nonsteroidal anti-inflammatory drugs, role for systemic glucocorticoid therapy, role for glucocorticoid injections into the sacroiliac joints and entheses, and role for slow-acting drugs (e.g., methotrexate, sulfasalazine, leflunomide, thalidomide, and pamidronate). Of the 661 promising publications identified by the literature search, 173 were found to be relevant. The evidence in these 173 papers was reported to experts during interactive workshops. At the end of the workshops, the experts drafted recommendations, which were then validated by having all panel participants vote during a final meeting. There were seven recommendations, whose strength ranged from A to D. CONCLUSION: Seven recommendations about pharmacotherapy in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS in France.

International audience; OBJECTIVE: To develop recommendations regarding imaging studies for the diagnosis and follow-up of patients with axial forms of ankylosing spondylitis (AS) seen in everyday practice. METHODS: Evidence from the literature and expert opinion were used to develop the recommendations. Using the Delphi consensus procedure, a scientific committee selected five areas of interest, about which scientific evidence was sought by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. Based on this evidence, a panel of experienced rheumatologists drafted recommendations, using expert opinion if needed to supplement gaps in evidence. For each recommendation, the level of evidence and the extent of agreement among the experts were specified. RESULTS: The five areas of interest dealt with the usefulness of imaging studies for the diagnosis, follow-up, prognostic evaluation, and assessment of treatment responses in patients with AS. The literature search retrieved 144 articles based on titles and abstracts. After elimination of articles that did not include an analysis of the radiological evaluation of AS, 73 articles were left for review. Eight recommendations were drafted then validated by having all panel participants vote during a final meeting. CONCLUSION: Eight recommendations about the use of imaging studies in patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.

International audience; OBJECTIVE: To develop French recommendations about the clinical and laboratory follow-up of patients with axial ankylosing spondylitis (AS) seen in everyday practice. METHODS: The recommendations were developed based on evidence from the literature and on expert opinion. A Delphi consensus procedure was used by a scientific committee to select five focal points, about which evidence was obtained by searching Medline and the databases maintained by the French Society for Rheumatology, European League against Rheumatism, and American College of Rheumatology. The results of the literature review were used by a panel of experienced rheumatologists to draft and to validate the recommendations, using expert opinion if needed to supplement gaps in published knowledge. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: The three focal points selected using the Delphi procedure dealt with choosing the best clinical and laboratory parameters for monitoring patients with AS; whether follow-up benefits from the use of composite indices (e.g., the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the BAS Functional Index [BASFI] and the BAS Metrology Index [BASMI]); and the clinical and laboratory parameters that predict functional or structural outcomes in patients with AS. The literature search retrieved 1510 relevant articles based on titles and abstracts, of which 322 were selected for in-depth review. Five recommendations about the clinical and laboratory follow-up of patients with AS were developed then validated by having all panel participants vote during a final meeting. CONCLUSION: Recommendations about the clinical and laboratory follow-up of patients with AS were developed. They can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of patients with AS.

National audience; OBJECTIVES: The aim of this study was to assess the reliability and validity of tests assessing medical students' ability to read medical journal articles critically. METHODS: All third-year students at our medical school (n=125) took three tests between December 2004 and June 2005 as part of a program to teach critical appraisal of medical literature. Each test required students to write a 250-word structured abstract and to answer a set of 6 to 8 appraisal questions. Interrater reliability was assessed with the intra-class correlation coefficient for the first test. Validity was assessed 1) by calculating the correlation coefficient between the mean scores on the three critical appraisal tests and 2) by calculating the correlation coefficient between these tests and eight other tests in other subjects that the students took over the same period. RESULTS: Interrater reliability was satisfactory for the overall score (ICC=0.72) and for the score for the questions alone (ICC=0.73). It was only moderate, however, for the structured abstract test (ICC=0.53) and varied markedly from question to question (ICC range: 0.29-0.86). Intertest correlations were all statistically significant (p

International audience

International audience; BACKGROUND: Thromboprophylaxis in elderly patients, including post-acute care patients, is at variance with scientific evidence. The purpose of this study was to determine whether a multifaceted intervention was followed by a decrease in deep venous thrombosis (DVT). METHODS: A prospective preintervention-postintervention study was conducted in 1373 patients (preintervention phase, n = 709; postintervention phase, n = 664), aged 65 years or older, enrolled in 33 hospital-based post-acute care facilities in France. An evidence-based guideline addressing pharmacologic and mechanical prophylaxis was implemented through a multifaceted intervention. The main outcome measure was any DVT diagnosed at routine comprehensive ultrasonography performed by registered angiologists. RESULTS: A DVT was found in 91 patients (12.8%) in the preintervention phase and in 52 patients (7.8%) in the postintervention phase (P = .002). The decrease in DVT involved the calf (7.1% vs 3.6%; P = .005) and the proximal venous segments (5.8% vs 4.2%; P = .18) and remained significant after adjusting for risk factors (adjusted odds ratio of any DVT, 0.58; 95% confidence interval, 0.39-0.86). Pharmacologic prophylaxis with either low-molecular-weight heparin at the high-risk dose, unfractionated heparin, and vitamin K antagonist was similar in the 2 study groups, whereas patients in the postintervention group were more likely to use graduated compression stockings (27.4% vs 34.6%; P = .004) and less likely to receive low-molecular-weight heparin at the low-risk dose (24.7% vs 18.5%; P = .006), which was not recommended by our guideline. CONCLUSIONS: A multifaceted intervention addressing venous thromboembolism prophylaxis in post-acute care patients can be followed by a significant decrease in the rate of any DVT in elderly patients. More active interventions are needed to enforce compliance with evidence-based guidelines.

In 2008 the national ranking examination (NRE) will include a test on critical reading of scientific articles. This decision has provoked controversy about whether reproducible correction is possible. The aim of our study was to assess the consistency of grading between this two-part test (critical analysis and summarizing, analyzed separately), and the more classic tests.Eight graders, all instructors at the Tours Medical School, corrected papers for each of the 3 tests. Papers for the critical reading test came from medical school final examinations and for the standard test from a practice examination. The instructors worked in pairs: each pair read 30 papers for each test, and both members separately graded each paper. The final grade was the mean of the two grades. The consistency of grading between the 4 pairs was estimated by Kendall's coefficient of concordance.Kendall's coefficients of concordance were estimated at 0.94 (95% CI=[0.86; 0.97]) for the standard test, at 0.92 (95% CI=[0.81;0.97]) for the critical analysis test, and at 0.75 (95% CI=[0.62; 0.84]) for the summaries. Pairwise comparisons estimated the difference in concordance between the standard test and the summary at 0.18 (95% CI=[0.08; 0.32]) and that between the standard and critical reading test at 0.01 (95% CI= [-0.07; 0.12]). Finally the difference in concordance between the 2 new tests - summary and critical reading - was estimated at -0.17 (95% CI=[-0.32; -0.04]).The focus should be on the difficulty of reproducible correction of the summaries, to set up methods for appropriate correction and adequate grading. The elaboration of detailed scoring templates, including numerous items and specifying in which part of the summary each item must be placed, should help to improve the reproducibility of this test's correction.

International audience; OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

International audience; OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

International audience; Literature, specifically MEDLINE, is among the main sources of information used to detect whether a drug may be responsible for Adverse Drug Reactions cases. The aim of our work is to automate the search of publications that correspond to a given Adverse Drug Reactions case: (i) by defining a general pattern for the queries used to search MEDLINE and (ii) by determining the threshold number of publications capable to confirm or infirm the Adverse Drug Reaction. We applied our algorithm to a set of 620 cases from a French pharmacovigilance database. We obtained a precision of 93%, recall 70%. We determined a threshold of 3 publications to confirm an Adverse Drug Reaction case.

BackgroundLarge-scale genomic studies based on transcriptome technologies provide clusters of genes that need to be functionally annotated. The Gene Ontology (GO) implements a controlled vocabulary organised into three hierarchies: cellular components, molecular functions and biological processes. This terminology allows a coherent and consistent description of the knowledge about gene functions. The GO terms related to genes come primarily from semi-automatic annotations made by trained biologists (annotation based on evidence) or text-mining of the published scientific literature (literature profiling).ResultsWe report an original functional annotation method based on a combination of evidence and literature that overcomes the weaknesses and the limitations of each approach. It relies on the Gene Ontology Annotation database (GOA Human) and the PubGene biomedical literature index. We support these annotations with statistically associated GO terms and retrieve associative relations across the three GO hierarchies to emphasise the major pathways involved by a gene cluster. Both annotation methods and associative relations were quantitatively evaluated with a reference set of 7397 genes and a multi-cluster study of 14 clusters. We also validated the biological appropriateness of our hybrid method with the annotation of a single gene (cdc2) and that of a down-regulated cluster of 37 genes identified by a transcriptome study of anin vitroenterocyte differentiation model (CaCo-2 cells).ConclusionThe combination of both approaches is more informative than either separate approach: literature mining can enrich an annotation based only on evidence. Text-mining of the literature can also find valuable associated MEDLINE references that confirm the relevance of the annotation. Eventually, GO terms networks can be built with associative relations in order to highlight cooperative and competitive pathways and their connected molecular functions.

International audience

The characterization of estrogen receptor beta (ERbeta) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and the mitogenic effects of estrogen in these tissues (such as breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERbeta expression in cancer as compared with benign tumors or normal tissues, whereas ERalpha expression persists. The loss of ERbeta expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERalpha target genes by ERbeta or ERbeta-specific gene induction could explain that ERbeta has a differential effect on proliferation as compared with ERalpha. ERbeta may exert a protective effect and thus constitute a new target for hormone therapy, such as ligand specific activation. The potential distinct roles of ERalpha and ERbeta expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review.

International audience; Analysis of brain structure in Turner syndrome (TS) provides the opportunity to identify the consequences of the loss of one X chromosome on brain anatomy and to characterize the neural bases underlying the specific cognitive profile of TS subjects which includes deficits in spatial-numerical processing and social cognition. Fourteen subjects with TS and fourteen controls were investigated using voxel-based analysis of high resolution anatomical and diffusion tensor images and using sulcal morphometry. The analysis of anatomical images provided evidence for macroscopical changes in cortical regions involved in social cognition such as the left superior temporal sulcus and orbito-frontal cortex and in a region involved in spatial and numerical cognition such as the right intraparietal sulcus. Diffusion tensor images showed a displacement of the grey-white matter interface of the left and right superior temporal sulcus and revealed bilateral microstructural anomalies in the temporal white matter. The analysis of fiber orientation suggests specific alterations of fiber tracts connecting posterior to anterior temporal regions. Last, sulcal morphometry confirmed the anomalies of the left and right superior temporal sulci and of the right intraparietal sulcus. Our results thus provide converging evidence of regionally specific structural changes in TS that are highly consistent with the hallmark symptoms associated with TS.

“Death by parenteral nutrition” was the title of the controversial editorial published in the June issue of Intensive Care Medicine by P.E. Marik and M. Pinsky [1]. One might believe that a real event was being described by the authors. Imagine our astonishment, which quickly turned to dismay, when we read the words: “…a poison or toxin is a substance that through its chemical action usually kills, injures or impairs an organism… and by this definition TPN meets all criteria of a poison/toxin, in the critically ill patient receiving parenteral nutrition.” We are surprised and perturbed that the authors have missed some important issues regarding the nutrition of patients in intensive care units (ICUs), exchanging sensationalism for sound scientific discussion.

International audience; This paper explores service users' experiences of a 'person-centred' mental health service. We describe the development of a model of social psychiatry that places the emphasis on the experiences of the person within social and political contexts. This establishes the foundations of a 'person-centred' approach, the values of which are described briefly. The results of interviews with 20 people are presented, in which their experiences of the service are explored in detail. These interviews reveal the struggle that lies at the heart of the professional-service user dialectic, which relates to issues of institutional power, roles and responsibility, and which places professional staff in conflict with the very notion of 'person-centredness'. No matter how 'person-centred' a mental health service may strive to be, there remain serious obstacles to the full realization of this approach. Despite this critique, there were many things that were valued by those who used the service. More detailed qualitative studies are required to explicate the complex relationships and paradoxes that emerged.