Home-based exercise in autoimmune myasthenia gravis: A randomized controlled trial.

The tolerance of exercise and its effects on quality of life in myasthenia gravis are not currently backed up by strong evidence. The aim of this study was to determine whether exercise as an adjunct therapy is well tolerated and can improve health-related quality of life (HRQoL) in stabilized, generalized autoimmune myasthenia gravis (gMG). We conducted a parallel-group, multi-center prospective RCT using computer-generated block randomization. Adults with stabilized, gMG, and no contra-indication to exercise, were eligible. Participants received usual care alone or usual care and exercise. The exercise intervention consisted of 3-weekly 40 min sessions of an unsupervised, moderate-intensity home rowing program over 3 months. The primary endpoint was the change in HRQoL from randomization to post-intervention. Assessor-blinded secondary endpoints were exercise tolerance and effects on clinical, psychological and immunological status. Of 138 patients screened between October 2014 and July 2017, 45 were randomly assigned to exercise (n = 23) or usual care (n = 20). Although exercise was well tolerated, the intention-to-treat analysis revealed no evidence of improved HRQoL compared to usual care (MGQOL-15-F; mean adjusted between-groups difference of -0.8 points, 95%CI -5.4 to 3.7). Two patients hospitalized for MG exacerbation were from the usual care group.

Association between Hospitalization and Change of Frailty Status in the GAZEL Cohort.

OBJECTIVES: To assess the relationship between changes of frailty status and intervening hospitalizations, using information of the GAZEL cohort, matched with the data of the French National Health Data System. DESIGN: Observational cohort study. PARTICIPANTS: Community-dwelling adults of the GAZEL cohort (n = 12145; aged between 58 and 73 years in 2012). MEASUREMENTS: Frailty was determined with the Strawbridge questionnaire in 2012, 2013 and 2014. Data regarding hospitalizations (notably their number, length of stay, emergency department use, and main diagnosis) were collected from the French National Health Data System. The relationship between intervening hospitalizations and changes of frailty status over time was assessed with multivariate Markov models. RESULTS: The prevalence of frailty was 14% in 2012 and 2013 and 17% in 2014. A total of 2715 changes in frailty status were observed from 2012 to 2014. At least one hospitalization was recorded for 1453 people (12%) between the 2012 and 2013 questionnaires, and 1472 (13%) between the 2013 and 2014 questionnaires. No association was found between intervening hospitalizations and changes of frailty status (aHR 1.14 [0.97-1.35] for robust to frail transition and aHR 0.89 [0.73-1.08] for frail to robust transition). However, repeated hospitalizations, hospitalizations after emergency department use, surgery and several diagnosis groups were significantly associated with transitions towards frailty or its recovery. CONCLUSION: Hospitalizations encompass a wide range of clinical situations, some of them being associated with incident frailty. An early recognition of these situations could help to better prevent and manage frailty in the early old age.

[Non-inferiority and equivalence trials: Key methodological issues]. / Essais de non-infériorité et d'équivalence : les points clés de leur méthodologie.

Non-inferiority and equivalence trials aim to promote new treatments that are not expected to be superior to existing ones in a given indication. In order to compensate for a possible loss of efficacy, the new treatment should offer other advantages compared to the reference treatment, a better safety of use for example. Their methods somewhat differ from those of superiority trials, often better known to the medical community. This article presents the key points of the methodology of non-inferiority and equivalence trials in order to inform the readers of such trials about the issues and critical points. The general methodology (hypotheses, decision rules, number of subjects required, and strategy of analysis) is presented using examples and graphic illustrations. The issues and critical points are identified and discussed, in particular the choice of the comparator and of the margin of non-inferiority.

The effect of transcranial direct current stimulation (tDCS) on locomotion and balance in patients with chronic stroke: study protocol for a randomised controlled trial.

BACKGROUND: Following stroke, patients are often left with hemiparesis that reduces balance and gait capacity. A recent, non-invasive technique, transcranial direct current stimulation, can be used to modify cortical excitability when used in an anodal configuration. It also increases the excitability of spinal neuronal circuits involved in movement in healthy subjects. Many studies in patients with stroke have shown that this technique can improve motor, sensory and cognitive function. For example, anodal tDCS has been shown to improve motor performance of the lower limbs in patients with stroke, such as voluntary quadriceps strength, toe-pinch force and reaction time. Nevertheless, studies of motor function have been limited to simple tasks. Surprisingly, the effects of tDCS on the locomotion and balance of patients with chronic stroke have never been evaluated. In this study, we hypothesise that anodal tDCS will improve balance and gait parameters in patients with chronic stroke-related hemiparesis through its effects at cortical and spinal level. METHODS/DESIGN: This is a prospective, randomised, placebo-controlled, double-blinded, single-centre, cross-over study over 36 months. Forty patients with chronic stroke will be included. Each patient will participate in three visits: an inclusion visit, and two visits during which they will all undergo either one 30-min session of transcranial direct current stimulation or one 30-min session of placebo stimulation in a randomised order. Evaluations will be carried out before, during and twice after stimulation. The primary outcome is the variability of the displacement of the centre of mass during gait and a static-balance task. Secondary outcomes include clinical and functional measures before and after stimulation. A three-dimensional gait analysis, and evaluation of static balance on a force platform will be also conducted before, during and after stimulation. DISCUSSION: These results should constitute a useful database to determine the aspects of complex motor function that are the most improved by transcranial direct current stimulation in patients with hemiparesis. It is the first essential step towards validating this technique as a treatment, coupled with task-oriented training. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02134158 . First received on 18 December 2013; last updated on 14 September 2016. Other study ID numbers: P120135 / AOM12126, 2013-A00952-43.

Late Functional Changes Post-Severe Traumatic Brain Injury Are Related to Community Reentry Support: Results From the PariS-TBI Cohort.

OBJECTIVES: To explore late functional changes after a traumatic brain injury and their relation to patients' characteristics and reentry support. DESIGN: Prospective follow-up of an inception cohort of adults with severe traumatic brain injury recruited in 2005-2007 in the Parisian area, France. One and 4-year assessments were performed by trained neuropsychologists. One-to-4-year change in the Glasgow Outcome Scale-Extended defined 3 groups: "improvement," "stability," and "worsening." Relationships between these groups and patients' characteristics were analyzed. RESULTS: Among 504 recruited patients and 245 four-year survivors, 93 participated in both evaluations. Overall Glasgow Outcome Scale-Extended improved by 0.4. Forty percent of the sample improved, 44% were stable, and 16% worsened. Being in a more unfavorable group was related to preinjury alcohol abuse and to higher anxiety and depression at 4 years. Attendance to a specialized community reentry unit was related to higher chances of being in the "improvement" group in univariate analyses and after adjustment for age, time to follow command, preinjury alcohol and occupation, and mood disorders (adjusted odds ratio [OR] = 4.6 [1.1-20]). CONCLUSION: Late functional changes were related to psychosocial variables and to reentry support. The effect of reentry support on late recovery needs to be confirmed by further investigations.

Should Sensory Impairment Be Considered in Frailty Assessment? A Study in the GAZEL Cohort.

OBJECTIVES: The assessment of sensory difficulties is sometimes included in the screening of frailty in ageing population. This study aimed to compare the prevalence of frailty and associated risk of adverse outcomes depending on whether sensory difficulties participated in the definition of frailty. DESIGN: Prospective cohort study - GAZEL cohort. SETTING: France. PARTICIPANTS: The 13,128 subjects who completed a questionnaire in 2012. MEASUREMENTS: According to the Strawbridge questionnaire, subjects were considered frail if they reported difficulties in two domains or more among physical, nutritive, cognitive and sensory domains. The risk of adverse health outcomes was assessed by using logistic regression models (hospitalisations, onset of difficulty in performing movements of everyday life) and multivariate Cox proportional hazards models (mortality). RESULTS: Mean age was 66.8 +/- 3.4 years and 73.8% were males. The prevalence of frailty varied from 4.4 to 14.2% depending on whether the sensory domain was excluded or included. During follow-up, 182 deaths (1.4%), 479 hospitalisations (3.6%) and 703 cases of new disability (8.0%) were observed. Both definitions of frailty predicted the onset of difficulties to perform everyday movements, with 2 to 3-fold increase in the risk. The inclusion of the sensory domain in the definition made frailty predictive of hospitalisations (Odds Ratio 1.31 [1.01-1.70]) but the association with mortality was only observed when sensory difficulties were ignored (Hazard Ratio 2.28 [1.32-3.92]). CONCLUSION: The inclusion of a sensory domain into a frailty screening instrument has a major impact in terms of prevalence and modifies the risk profile associated with frailty. In order to develop the use of frailty screening instruments in clinical practice, further researches will need to carefully evaluate the impact on risk prediction of the different domains involved.

A comprehensive picture of 4-year outcome of severe brain injuries. Results from the PariS-TBI study.

OBJECTIVES: Survivors of severe traumatic brain injury have a great variety of impairments and participation restrictions. Detailed descriptions of their long-term outcome are critical. We aimed to assess brain injury outcome for subjects with traumatic brain injury in terms of the International classification of functioning, disability and health. MATERIALS AND METHODS: Four-year follow-up of an inception cohort of adults with severe traumatic brain injury by using face-to-face interviews with patients and proxies. RESULTS: Among 245 survivors at 4 years, 147 were evaluated (80% male, mean age: 32.5±14.2 years at injury); 46 (32%) presented severe disability, 58 (40%) moderate disability, and 40 (28%) good recovery. Most frequent somatic problems were fatigue, headaches, other pain, and balance. One quarter of subjects had motor impairments. Rates of cognitive complaints ranged from 25 to 68%, the most frequent being memory, irritability, slowness and concentration. With the Hospital Anxiety and Depression Scale, 43% had anxiety and 25% depression. Overall, 79% were independent in daily living activities and 40 to 50% needed help for outdoor or organizational activities on the BICRO-39. Most had regular contacts with relatives or close friends but few contacts with colleagues or new acquaintances. Subjects spent little time in productive activities such as working, studying, looking after children or voluntary work. Quality of life on the QOLIBRI scale was associated with disability level (P<0.0001). CONCLUSION: Management of late brain injury needs to focus on cognitive difficulties, particularly social skills, to enhance patient participation in life.

Global ultrasound assessment of structural lesions in osteoarthritis: a reliability study by the OMERACT ultrasonography group on scoring cartilage and osteophytes in finger joints.

OBJECTIVE: Ultrasonography is sensitive for the evaluation of cartilage pathology and degree of osteophytes in patients with hand osteoarthritis (OA). High consistency of assessments is essential, and the OMERACT (Outcome Measures in Rheumatology) ultrasonography group took the initiative to explore the reliability of a global ultrasonography score in patients with hand OA using semiquantitative ultrasonography score of cartilage and osteophytes in finger joints. METHODS: Ten patients with hand OA were examined by 10 experienced sonographers over the course of two days. Semiquantitative scoring (0-3) was performed on osteophytes (carpo-metacarpal 1, metacarpo-phalangeal (MCP) 1-5, proximal interphalangeal 1-5 and distal interphalangeal 2-5 joints bilaterally with an ultrasonography atlas as reference) and cartilage pathology (MCP 2-5 bilaterally). A web-based exercise on static cartilage images was performed a month later. Reliability was assessed by use of weighted κ analyses. RESULTS: Osteophyte scores were evenly distributed, and the intraobserver and interobserver reliabilities were substantial to excellent (κ range 0.68-0.89 and mean κ 0.65 (day 1) and 0.67 (day 2), respectively). Cartilage scores were unevenly distributed, and the intraobserver and interobserver reliability was fair to moderate (κ range 0.46-0.66 and mean κ 0.39 (day 1) and 0.33 (day 2), respectively). The web-based exercise showed acceptable agreement for cartilage being normal (κ 0.47) or with complete loss (κ 0.68), but poor for the intermediate scores (κ 0.22-0.30). CONCLUSIONS: Use of the present semiquantitative ultrasonography scoring system for cartilage pathology in hand OA is not recommended (while normal or total loss of cartilage may be assessed). However, the OMERACT ultrasonography group will endorse the use of semiquantitative scoring of osteophytes with the ultrasonography atlas as reference.

EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice.

A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.

[Use of social and health primary care services for older people with complex needs: Comparison of three types of gerontological coordination]. / Utilisation des services d'aide et de soins à domicile pour les personnes âgées en situations complexes : comparaison entre trois types de coordination gérontologique.

BACKGROUND: Older people with complex needs live mainly at home. Several types of gerontological coordinations have been established on the French territory to meet their needs and to implement social and primary health care services. But we do not have any information on the use of these services at home as a function of the coordination method used. METHODS: We compared the use of home care services for older people with complex needs in three types of coordination with 12 months' follow-up. The three coordinations regrouped a gerontological network with case management (n=105 persons), a nursing home service (SSIAD) with a nurse coordination (n=206 persons) and an informal coordination with a non-professional caregiver (n=117 persons). RESULTS: At t0, the older people addressed to the gerontological network had less access to the services offered at home; those followed by the SSIAD had the highest number of services and of weekly interventions. Hours of weekly services were two-fold higher in those with the informal coordination. At t12, there was an improvement in access to services for the network group with case management and an overall increase in the use of professional services at home with no significant difference between the three groups. CONCLUSION: The use of social and primary health care services showed differences between the three gerontological coordinations. The one-year evolution in the use of home services was comparable between the groups without an explosion in the number of services in the network group with case management.

Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise.

OBJECTIVE: To standardize ultrasound (US) in enthesitis. METHODS: An initial Delphi exercise was undertaken to define US-detected enthesitis and its core components. These definitions were subsequently tested on static images taken from spondyloarthritis patients in order to evaluate their reliability. RESULTS: Excellent agreement (>80%) was obtained for including hypoechogenicity, increased thickness of the tendon insertion, calcifications, enthesophytes, erosions, and Doppler activity as core elementary lesions of US-detected enthesitis. US definitions were subsequently obtained for each elementary component. On static images, the intraobserver reliability showed a high degree of variability for the detection of elementary lesions, with kappa coefficients ranging from 0.13-1. The interobserver kappa values were variable, with the lowest kappa coefficient for enthesophytes (0.24) and the highest coefficient for Doppler activity at the enthesis (0.63). CONCLUSION: This is the first consensus-based US definition of enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work.

Predictive factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI): results from the PariS-TBI study.

OBJECTIVES: To assess outcome and predicting factors 1 year after a severe traumatic brain injury (TBI). METHODS: Multi-centre prospective inception cohort study of patients aged 15 or older with a severe TBI in the Parisian area, France. Data were collected prospectively starting the day of injury. One-year evaluation included the relatives-rating of the Dysexecutive Questionnaire (DEX-R), the Glasgow Outcome Scale-Extended (GOSE) and employment. Univariate and multivariate tests were computed. RESULTS: Among 257 survivors, 134 were included (mean age 36 years, 84% men). Good recovery concerned 19%, moderate disability 43% and severe disability 38%. Among patients employed pre-injury, 42% were working, 28% with no job change. DEX-R score was significantly associated with length of education only. Among initial severity measures, only the IMPACT prognostic score was significantly related to GOSE in univariate analyses, while measures relating to early evolution were more significant predictors. In multivariate analyses, independent predictors of GOSE were length of stay in intensive care (LOS), age and education. Independent predictors of employment were LOS and age. CONCLUSIONS: Age, education and injury severity are independent predictors of global disability and return to work 1 year after a severe TBI.

The reliability of musculoskeletal ultrasound in the detection of cartilage abnormalities at the metacarpo-phalangeal joints.

OBJECTIVE: To assess the reliability of ultrasound (US) in detecting cartilage abnormalities at the metacarpo-phalangeal (MCP) joints in people with cartilage pathology. METHODS: Nine expert ultrasonographers initially achieved consensus on definitions and scanning protocols. They then examined the second to fifth MCP joints of the dominant hand of eight people with hand osteoarthritis (OA). US examinations were conducted in two rounds, with independent blinded evaluations of cartilage lesions. Global cartilage abnormalities were assessed by applying a dichotomous (presence/absence) score; in addition, the following lesions were evaluated using the same scoring system: loss of anechoic structure and/or thinning of the cartilage layer, and irregularities and/or loss of sharpness of at least one cartilage margin. Reliability was assessed using kappa (k) coefficients. RESULTS: Thirty-two joints were examined. Intra-observer k values ranged from 0.52 to 1 for global cartilage abnormalities; k values ranged from 0.54 to 0.94 for loss of anechoic structure and/or thinning of cartilage layer and from 0.59 to 1 for irregularities and/or loss of sharpness of at least one cartilage margin. Values of k for inter-observer reliability were 0.80 for global cartilage abnormalities, 0.62 for loss of anechoic structure and/or thinning of cartilage layer, and 0.39 for irregularities and/or loss of sharpness of at least one cartilage margin. CONCLUSION: US is a reliable imaging modality for the detection of cartilage abnormalities in patients with cartilage pathology in the MCP joints. The analysis of specific cartilage measures showed more variable results that may be improved by modifying definitions and further standardization of US techniques.

Intermittent self-catheterization habits and opinion on aseptic VaPro catheter in French neurogenic bladder population.

STUDY DESIGN: Interventional, multi-center, open-label, randomized and crossover study. OBJECTIVES: The study objectives were to describe the current catheterization habits of the French neurogenic bladder patients using intermittent catheterization (IC), and to evaluate the ease of use, reliability and patients' comfort and patients' acceptance of the new 'no-touch', presumably easy-to-use VaPro catheter. SETTING: Patients were recruited from 11 centers in France. METHODS: In total, 106 men and women (age 18-65 years) with neurogenic bladder using IC at least four times a day were randomized into two groups. All subjects were trained to use the approved 'no-touch' method. A questionnaire evaluating patients' experiences was distributed before the start of the trial and after each 15-day period of catheter use, that is, VaPro vs conventional catheter. RESULTS: The majority of patients in this French IC user panel had very strong catheterization habits: 2/3 of them had been using IC for >2 years with high ease of use and comfort. Nevertheless, >50% of patients would recommend the VaPro catheter to other people who need IC. More than three out of four patients felt confident and more secure with the new catheter. Men and spinal cord injury (SCI) patients were significantly more positive about the VaPro catheter than women and patients without SCI, respectively. CONCLUSION: The VaPro catheter is an acceptable and reliable alternative to the existing hydrophilic-coated 'no-touch' catheter. SPONSORSHIP: This study was sponsored by Hollister France Inc.

[Management of neurogenic bladder patients in France: a survey carried out by the French-speaking neurourology study group (GENULF)]. / Prise en charge des patients ayant une vessie neurologique en France: une enquête du groupe d'études de neuro-urologie de langue française (GENULF).

OBJECTIVE: To design and run a survey aiming at investigating urologists' and physiatrists' clinical practices in France when managing neurogenic bladder patients. PATIENTS AND METHODS: Three thousand one hundred and eighty questionnaires were sent to the members of four French societies involved in treating neurogenic bladder dysfunction. Questions were focused on consultations, clinical follow-up and patient management. RESULTS: Two hundred and seventy-four urologists and 109 physiatrists completed the questionnaire. The frequency of systematic follow-up differed between urologists (6 months) and physiatrists (12 months). Upper urinary tract imaging and systematic urodynamic follow-up were usually performed yearly. The latter was carried out by 56% urologists and 83% physiatrists. Urinary retention was essentially treated by intermittent catheterization. Less than 15% of urologists and physiatrists were treating bacteriuria. Symptomatic urinary infections were treated for 11 to 12 days (men) and for 8 to 9 days (women). To treat their patients, both specialists used self-catheterization education and botulinum toxin A injections. CONCLUSION: Our survey showed differences in approach between urologists and physiatrists in the management of patients with neurogenic bladder dysfunction. Their clinical practice was most of the time in line with national and international guidelines.

Ultrasound evaluation of fluid in knee recesses at varying degrees of flexion.

OBJECTIVE: Various methods are utilized in daily practice to obtain optimal information on effusion in the knee. Our aim is to investigate which scanning position provides the best information about synovial fluid in the knee by using ultrasound and to evaluate the magnitude of difference for measuring synovial fluid in 3 major recesses (suprapatellar, medial parapatellar, and lateral parapatellar) of the knee according to various degrees of flexion. METHODS: Sonographers in 14 European centers documented bilateral knee joint ultrasound examinations on a total of 148 knee joints. The largest sagittal diameter of fluid was measured in scans corresponding to the 3 major recesses at different (0°, 15°, 30°, 45°, 60°, and 90°) degrees of flexion of the knee. The difference of measurement of effusion according to transducer position, knee position, and the interaction between them was investigated by analysis of variance followed by Tukey's test. RESULTS: No correlation was noted between patient characteristics and ultrasound detection of effusion. The sagittal diameter of synovial fluid in all 3 recesses was greatest at 30° flexion. Analysis of variance and Tukey's test revealed that the suprapatellar scan and 30° flexion is the best combination for detecting effusion as confirmed by receiver operator characteristic curve analysis. CONCLUSION: The suprapatellar scan of the knee in 30° flexion was the most sensitive position to detect fluid in knee joints. Sagittal diameter of fluid in all 3 recesses increased with the knee in the 30° flexed position as compared to the extended position.

Which knee and probe position determines the final diagnosis of knee inflammation by ultrasound? Results from a European multicenter study.

PURPOSE: To investigate which knee and probe position best identifies knee inflammation and to determine a cut-off level for abnormal synovial effusion. MATERIALS AND METHODS: 18 experienced sonographers (all rheumatologists) performed ultrasound examinations of the knee joint in patients with knee symptoms and in healthy controls. Each sonographer performed longitudinal suprapatellar ultrasound scans using 9 different configurations at each knee: Midline, parapatallar lateral and parapatellar medial from midline in neutral position (0°) with and without quadriceps muscle contraction and in 30° flexion of the knee. The presence of synovial effusion (SE), the effusion measured in millimeters and the presence of synovial hypertrophy (SH) was noted. RESULTS: A total of 298 knees of 149 subjects (129 patients and 20 controls) were examined. The detection of SH is more sensitive and specific than the detection of SE, independently of the knee and probe position, for the final diagnosis of abnormality. The detection of both synovial hypertrophy and effusion in the knee in neutral position (0°) with quadriceps contraction and with the probe in the midline position, are the best independent predictors for knee abnormalities. Knee effusion > 3.2 mm measured with the probe in the lateral aspect of the knee is the best diagnostic characteristics for predicting pathological SE. CONCLUSION: The best combination for detecting SH and SE is obtained by placing the probe in the midline position with the knee in 0° with quadriceps contraction. A cut-off value for pathological effusion may be obtained in the lateral aspect of the knee.

Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs.

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

[Severe stroke: prognosis, intensive care admission and withhold and withdrawal treatment decisions]. / AVC graves : pronostic, critères d'admission en réanimation et décisions de limitations et arrêt de traitements.

INTRODUCTION: Stroke can produce irreversible brain damage of massive proportion leading to severe disability and poor quality of life. Resuscitation and mechanical ventilation of these patients remain controversial because of the high mortality and severe disability involved. STATE OF ART: When prognosis is very poor, do-not-resuscitate orders (DNR orders) and withhold or withdrawal of treatment may be discussed. Studies have shown that DNR orders are relatively frequent in acute stroke: up to 30% of all patients, and 50% of which are given upon admission. DNR orders are closely associated with severity of the neurological deficit and age. Precise estimates of withhold and withdrawal of treatment are not available, but terminal extubations in severe stroke could contribute to 40,000 to 60,000 acute stage deaths per year. Little is known about the decision making process and palliative care in these situations. The neurological prognosis is the main explicit criterion. However, evaluation of neurological outcome is highly uncertain and difficult, and does not always reflect quality of life. Several studies have raised the issue of this disability paradox. Thus, physician estimation of prognosis has a profound impact on decisions for life sustaining therapies, and may lead to self-fulfilling prophecies in case of false appreciation of published evidence. Other criteria could influence the withhold and withdrawal of treatment decision, such as social conditions and patient values. PERSPECTIVES AND CONCLUSION: Decisions for life-sustaining therapies in severe stroke are always difficult and often based on subjective and uncertain criteria. We have to improve prognosis estimation and our understanding of patient preferences to promote patient-centered care. An ethical approach may guide these complex decisions.

Outdoor sports and risk of ultraviolet radiation-related skin lesions in children: evaluation of risks and prevention.

BACKGROUND: Excessive ultraviolet (UV) radiation exposure can cause skin cancers, skin photoageing and cataracts. Children are targeted by sun-protection campaigns because high sun exposure and sunburn in childhood increase the risk of melanoma in adulthood. Little information is available about UV radiation risk and exposure in children who take part in outdoor sports. OBJECTIVE: To evaluate the risk of developing UV radiation-induced skin lesions run by children who practise outdoor sports, and UV radiation exposure and sun-protection measures during a soccer tournament. METHODS: Firstly, we evaluated the relationship between melanocytic naevus - a skin lesion linked with exposure to UV radiation - and outdoor sports in 660 11-year-old children. Secondly, we used the occasion of a 1-day soccer tournament held in the spring to evaluate UV radiation-protective measures used by soccer players and the public. We also evaluated the UV radiation index and cloud cover during the tournament, and calculated the UV radiation dose and minimal erythema dose depending on skin phototype. RESULTS: The naevus count and acquired naevus count measured over the 2 years of the study were higher in the 344 children who practised outdoor sports. Sun-protective measures were insufficient for soccer players and the public. CONCLUSIONS: This study shows that outdoor sports increase the risk of developing UV radiation-induced skin lesions in childhood. During a 1-day soccer tournament held in the spring, children and their parents were inadequately protected against the sun. These results suggest that sun-protection campaigns should be aimed at children who practise popular outdoor sports.