Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

International audienceAir pollution (indoors and outdoors) is a major issue in public health as epidemiological studies have highlighted its numerous detrimental health consequences (notably, respiratory and cardiovascular pathological conditions). Over the past 15 years, air pollution has also been considered a potent environmental risk factor for neurological diseases and neuropathology. This review examines the impact of air pollution on children's brain development and the clinical, cognitive, brain structural and metabolic consequences. Long-term potential consequences for adults’ brains and the effects on multiple sclerosis (MS) are also discussed. One challenge is to assess the effects of lifetime exposures to outdoor and indoor environmental pollutants, including occupational exposures: how much, for how long and what type. Diffuse neuroinflammation, damage to the neurovascular unit, and the production of autoantibodies to neural and tight-junction proteins are worrisome findings in children chronically exposed to concentrations above the current standards for ozone and fine particulate matter (PM2.5), and may constitute significant risk factors for the development of Alzheimer's disease later in life. Finally, data supporting the role of air pollution as a risk factor for MS are reviewed, focusing on the effects of PM10 and nitrogen oxide

Real-life study to assess effectiveness and safety of eculizumab in patients with neuromyelitis optica spectrum disorders in France: protocol for ECUP4, an observational study

BackgroundEculizumab, a humanized monoclonal antibody targeting the C5 complement protein, has been approved for the treatment of neuromyelitis optica spectrum disorders (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive (Ab+). The aim of this study is to evaluate the long-term effectiveness and safety of eculizumab in French adults with NMOSD and to describe patients' characteristics, disability, and quality of life using data collected in a real-world setting.MethodsThis is the protocol for ECUP4, an ongoing prospective, observational, non-comparative, multicenter study conducted in 32 reference centers in France. Eligible patients must also be enrolled in NOMADMUS, a nested cohort of the French national multiple sclerosis registry (OFSEP). The primary endpoint is the annualized relapse rate. Secondary endpoints include the long-term safety of eculizumab, as well as patients' characteristics, treatment outcomes, disability, pain, visual acuity, and quality of life. Visits and treatments follow routine clinical practice. The case report forms (CRF) comprise data recorded in the context of the NOMADMUS cohort, collected during routine visits. The inclusion period is planned for 3 years, with no limitation on the number of patients enrolled. The maximum follow-up duration will be 5.5 years.ConclusionThe efficacy and safety of eculizumab in patients with AQP4+ NMOSD have been demonstrated in randomized clinical trials that showed a significant reduction in the risk of relapse, with a safety profile consistent with other indications. This study will provide clinical and patient-reported evidence of the benefits of eculizumab, using data from a real-world setting in France.Trial registration numberThis study is registered at the French public repertory Health data Hub, N° F20211228123801. All information can be accessed at: https://www.health-data-hub.fr/

Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)

Sclerosi multipla: epidemiologia

International audienceLa sclerosi multipla (SM) è una malattia neurologica dei giovani adulti (età media all’esordio intorno ai 30 anni) di cui due terzi dei casi è costituito da donne. Gli studi di prevalenza rivelano grandi disuguaglianze nel mondo, con la più alta frequenza in Nord America e in Europa (> 100 per 100 000 abitanti) e la più bassa in Asia e in Africa (2 per 100 000). In totale, attualmente si contano 2,8 milioni di casi nel mondo, di cui circa 120 000 in Francia. Questi numeri aumentano con ogni nuovo studio, probabilmente riflettendo un migliore conteggio dei casi, ma questo aumento è anche possibilmente legato a un aumento dell’incidenza e a un aumento della durata della vita dei pazienti. In termini di incidenza, si stima che vi siano circa 3 000-5 000 nuovi casi di SM ogni anno in Francia e viene diagnosticato 1 caso ogni 5 minuti nel mondo (vale a dire 300 al giorno). La SM è una malattia cronica, poco letale e che spesso dura per diversi decenni. La SM causa un eccesso di mortalità che appare circa 10 anni dopo l’insorgenza della malattia e porta a un riduzione dell’aspettativa di vita di diversi anni rispetto alla popolazione generale. Questo eccesso di mortalità è dovuto alla SM stessa ma anche ad altre cause di decesso, il che sottolinea l’importanza della diagnosi e della gestione delle comorbilità e del rinforzo del ruolo della prevenzione (in particolare oncologica e cardiovascolare) nella gestione complessiva dei pazienti affetti da SM. Infine, benché l’origine della SM sia sempre sconosciuta, si può affermare che è una malattia multifattoriale, dovuta all’influenza di fattori ambientali combinata a una suscettibilità genetica, la cui equazione esatta non è ancora conosciuta fino a oggi

Survimus, une étude multicentrique de la mortalité dans la sclérose en plaques, France

International audienceIntroduction.– En France, environ 80 000 personnes sont atteintes de sclérose en plaques (SEP), maladie chronique et handicapante débutant chez le jeune adulte (moyenne 31 ans). La SEP fait actuellement l’objet de nombreuses recherches, notamment thérapeutiques, et compte tenu de la nocivité potentielle des traitements, il est nécessaire de disposer d’informations précises sur la mortalité des patients. Les objectifs de l’étude Survimus sont de :– mesurer la durée de vie des patients et la comparer à celle de la population française appariée sur la triade âge-sexe-période ;– décrire les causes de décès ;– étudier les facteurs associés au décès ;– repérer d’éventuelles disparités géographiques.Méthodes.– Sont inclus les patients de 15 centres experts, ayant une SEP certaine depuis au moins une année (effectif potentiel : 25 000 patients). La recherche du statut vital à la date de point (premier janvier 2010) est effectuée selon le décret no 98-37 autorisant l’accès aux données relatives au décès des personnes inscrites au Répertoire national d’identification des personnes physiques (RNIPP) dans le cadre des recherches dans le domaine de la santé. Le nombre de décès attendus est estimé à partir des tables de mortalité annuelles par âge et sexe de l’Institut national des études démographiques (Ined).Résultats.– Les résultats préliminaires sur 17 733 patients, avec 1334 décès (7,5 %) recensés dont 52 % directement imputables à la SEP, confortent l’hypothèse d’un âge au décès prématuré et d’une surmortalité globale.Discussion et conclusion.– Les résultats définitifs de cette étude qui s’inscrit dans l’Observatoire français de la SEP (lauréat du projet « Cohortes », Investissements d’Avenir) seront disponibles en septembre 2012

Mortalité dans la sclérose en plaques (mesures, facteurs pronostiques et comparaison à la population générale. Etude de la base de données EDMUS de Rennes)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

A new treatment era in multiple sclerosis: Clinical applications of new concepts

International audienceSeveral clinical courses have been defined in multiple sclerosis (MS), but uncertainty remains as to whether they reflect different neuropathological mechanisms. Two recent concepts have emerged which could influence the treatment strategy adopted in MS:inflammation drives axonal damage;disability progression in MS follows a two-stage process

From medical prescription to patient compliance. A qualitative insight into the neurologist-patient relationship in multiple sclerosis

International audienceBackground: Approximately 12 disease-modifying treatments are available worldwide for patients with relapsing multiple sclerosis (MS). These recent therapeutic advances have led to major changes in patient and neurologist attitudes toward drug prescription. Herein, we aimed to characterize patient choice regarding treatment for MS and identify how neurologists assess and monitor patient compliance during follow-up. Methods: In 29 patients with MS, we observed visits to their neurologist to understand how questions related to compliance were addressed in the doctor-patient relationship. Face-to-face interviews were conducted with 15 of the 29 patients to discuss how they dealt with their drug prescription from a patientcentered perspective. Results: Of the 15 patients with MS, nine were offered a choice of treatment. However, we found that neurologists were not always willing to consider the patients' input. Even if physicians attempt to align treatment choice with patient preferences to ensure compliance, preferences are often assumed rather than solicited from patients. Furthermore, patients may be unwilling to make their own treatment decisions. Various ways for neurologists to assess compliance during visits were also identified. Noncompliance can be considered as a way for patients to communicate their preferences and demonstrate involvement in their drug therapy, and it can lead to a renegotiation of the current treatment course. Conclusions: These findings suggest that the neurologist-patient relationship has a great influence on patient compliance throughout the MS disease course. © 2018 Consortium of Multiple Sclerosis Centers

L'intégration du droit international coutumier dans l'ordre juridique communautaire

International audienc

Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: A 5-year prospective study

International audienceBackground: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy. Objective: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS).Methods: Eight hundred and two patients from 12 MS centres (308 relapsing-remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6-12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after.Results: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea. Conclusion: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS