Facteurs pronostiques de survie de la sclérose latérale amyotrophique sous ventilation non invasive (étude rétrospective de 33 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

LA MARECHALERIE DU 16 EME AU 18 EME SIECLE, AU TRAVERS DES OUVRAGES DE FIASCHI, SOLLEYSEL, LAFOSSE ET BOURGELAT

La maréchalerie est une discipline ancienne qui fut certainement à l'origine de la médecine vétérinaire. Son évolution est cependant mal connue. L'objectif de ce travail était de suivre l'évolution de la maréchalerie du 16ème au 18ème siècle en relisant les traités de maîtres incontestés comme Fiaschi, Solleysel, Bourgelat et Lafosse. Chaque ouvrage est analysé dans un premier temps puis l'évolution des pratiques est présentée sous forme de synthèses thématiques. L'examen de ces pièces montre que les pratiques de maréchalerie étaient déjà très élabore es au 16ème siècle. La concurrence existant entre Lafosse et Bourgelat devait conduire à la formalisation de ces connaissances par les deux auteurs.MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF

Prise en charge initiale de la maladie de Parkinson par les médecins généralistes en région Rhône-Alpes

Le choix thérapeutique initial dans la maladie de Parkinson agit non seulement sur la symptomatologie présentée par le patient, mais aussi sur l'évolution de la maladie. L'introduction de la Lévodopa doit être différée, notamment chez le sujet jeune, afin de retarder l'apparition des complications motrices. Néanmoins, un recours systématique au neurologue pour l'initiation thérapeutique paraît difficile étant donné 1' augmentation de la prévalence de la maladie de Parkinson avec le vieillissement de la population. Une prise en charge par les médecins généralistes peut se discuter. Or peu d'études analysent leur pratique face à cette pathologie complexe. Analyser la prise en charge initiale de la maladie de Parkinson réalisée par les médecins généralistes, afin d'évaluer si l'initiation thérapeutique par le médecin généraliste était conforme aux recommandations, au même titre que le neurologue. Nous avons réalisé une étude descriptive rétrospective. Un questionnaire informatisé a été envoyé aux médecins généralistes exerçant une activité libérale en région Rhône-Alpes. Chaque médecin généraliste pouvait renseigner le dossier clinique d'un à trois patients présentant la maladie de Parkinson. Leur prise en charge était comparée à trois consensus, français et européens. Notre étude incluait 99 patients grâce à la participation de 70 médecins généralistes sur les 2607 interrogés. Le traitement de la maladie de Parkinson était initié par le médecin généraliste pour 30% des patients. Sur les 99 patients, 92 avaient eu une consultation neurologique, que ce soit avant ou après l'initiation thérapeutique. Il n'y avait pas de différence statistiquement significative entre les médecins généralistes et les neurologues dans le suivi des recommandations, que ce soit pour les recommandations du texte des experts de 2000 (p 0.210), de la Haute Autorité de Santé de 2012 (p 0.924), ou de l'European Federation of Neurological Societies/Movement Disorder Society de 2013 (p 0.924). La Lévodopa seule était prescrite pour 24 patients (77%) pris en charge par le médecin généraliste (n=30) et 34 patients (49%) pris en charge par le neurologue (n=69). Pour 31 des 42 patients âgés de moins de 65 ans (74%), l'initiation thérapeutique était réalisée par un neurologue. Il prescrivait dans 55% des cas (n=17) un agoniste dopaminergique non dérivé de l'ergot de seigle seul ou en association, alors que les médecins généralistes administraient ce traitement chez un patient (9%) de cette tranche d'âge. Bien que les médecins généralistes respectent les recommandations, la prescription des agonistes dopaminergiques semble sous utilisée. Au vu de l'importance du choix thérapeutique initial dans l'évolution de la maladie, notamment chez le sujet jeune, nous conseillons une prise en charge neurologique précoce. De façon générale, le soin d'un patient parkinsonien doit être axé sur la multidisciplinarité et centré sur le patient et ses aidantsLYON1-BU Santé (693882101) / SudocSudocFranceF

Metallic impurity content behavior during ICRH-heated L-mode discharges in EAST Metallic impurity content behavior during ICRH-heated L-mode discharges in EAST

International audienceThis study uses the diversity of materials at known locations in the Experimental Advanced Superconducting Tokamak (EAST) to extract, local information on which plasma-surface interaction processes are dominant during Ion Cyclotron Resonance Heating (ICRH) (near vs far field effects). Metallic impurity content is indicated by the intensity of impurity line emissions observed with a fast-time-response extreme ultraviolet (EUV) spectrometer, normalized to line-averaged plasma density, i.e. Iimp/ne. Parametric dependencies are explored over scans of ICRH and LH (Lower Hybrid) power and for different toroidal phasings between straps, strap power balance, and magnetic configurations. This diversity of behavior is interpreted as the signature of different physical processes. Before 2017, as only the upper divertor region contained tungsten (W), the W content in the core used to increase a lot when moving from lower (LSN) to upper single null (USN) configurations, and was correlated with the total injected power rather than the ICRH power. Molybdenum (Mo), covering the part of the inner wall facing one ICRF antenna appear sensitive to this antenna power and phasing benchmarked by modelling suggesting a probable interaction due to residual ICRF waves crossing the plasma. Materials close and magnetically-connected to an active antenna show better correlation with ICRF antenna electrical tuning than those which are far away, or not connected. This is particularly the case with W since 2018, because the limiter tiles of the LH launchers were changed from graphite to tungsten. In these latter conditions, it is shown that W sources at the mid-plane (equatorial plane) contribute to a significant fraction of the core contamination by tungsten (25% in ohmic regime, and more during ICRH)

Long-Term Effectiveness, Safety and Tolerability of Fingolimod in Patients with Multiple Sclerosis in Real-World Treatment Settings in France: The VIRGILE Study

Online ahead of printInternational audienceIntroduction: It is important to confirm the effectiveness and tolerability of disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) in real-world treatment settings. This prospective observational cohort study (VIRGILE) was performed at the request of the French health authorities. The primary objective was to evaluate the effectiveness of fingolimod 0.5 mg in reducing the annualised relapse rate (ARR) in patients with RRMS.Methods: Participating neurologists enrolled all adult patients with RRMS starting fingolimod treatment between 2014 and 2016, who were followed for 3 years. Follow-up consultations took place at the investigator's discretion. The primary outcome measure was the change in ARR at month 24 after fingolimod initiation. Relapses and adverse events were documented at each consultation; disability assessment (EDSS) and magnetic resonance imagery were performed at the investigator's discretion.Results: Of 1055 eligible patients, 633 patients were assessable at month 36; 405 (64.0%) were treated continuously with fingolimod for 3 years. The ARR decreased from 0.92 ± 0.92 at inclusion to 0.31 ± 0.51 at month 24, a significant reduction of 0.58 [95% CI - 0.51 to - 0.65] relapses/year (p < 0.001). Since starting fingolimod, 461 patients (60.9%) remained relapse-free at month 24 and 366 patients (55.5%) at month 36. In multivariate analysis, no previous disease-modifying treatment, number of relapses in the previous year and lower EDSS score at inclusion were associated with a greater on-treatment reduction in ARR. The mean EDSS score remained stable over the course of the study. Sixty-one out of 289 (21.1%) patients presented new radiological signs of disease activity. Treatment-related serious adverse events were lymphopenia (N = 21), bradycardia (N = 19), elevated transaminases (N = 9) and macular oedema (N = 9).Conclusions: The effectiveness and tolerability of fingolimod in everyday clinical practice are consistent with findings of previous phase III studies. Our study highlights the utility of fingolimod for the long-term management of patients with multiple sclerosis

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

International audienceBackground and Purpose— Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I 2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None