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Contexte : La réforme de la première année des études de santé définie dans le décret du 4 novembre 2019 a mis fin à la première année commune aux études de santé (PACES) pour introduire un nouveau système ayant pour objectif de diversifier l’accès aux formations de médecine, maïeutique, odontologie, pharmacie et kinésithérapie (MMOP-K) par différents parcours de formation antérieurs. À l’Université de Bordeaux a été mis en place un double système avec un parcours accès spécifique santé (PASS) et des licences accès santé (L.AS). La voie L.AS étant minoritaire en cette première année de mise en place de la réforme, nous avons centré notre analyse sur les étudiant·es en PASS en 2020–2021 et l’accès à la filière médecine. Méthodes : Cette première année de PASS a été évaluée au regard des résultats académiques aux épreuves écrites des deux semestres (nombre d’UE validées, validation/échec du PASS, admissibilité dans la filière médecine) et aux épreuves orales (réussite aux mini entretiens multiples, admission dans la filière médecine). Résultats et conclusion : Nous avons identifié le niveau scolaire à l’entrée à l’Université, mesuré par la mention au bac, comme étant le principal facteur de réussite pour la validation du PASS et la réussite à l’admission dans la filière médecine. Le déterminant social est également associé à la validation du PASS, indépendamment du niveau scolaire. Les résultats montrent également que l’hétérogénéité des résultats en fonction de l’option disciplinaire et du site géographique est essentiellement liée à des disparités de niveaux scolaires à l’entrée en PASS.

Teleconsultation has become a new means of using care which has taken off significantly since the COVID crisis, The pooling of the technological environment within the TC makes it possible to set up practice reviews by reusing the data collected. Our aim was to evaluate the relevance of antibiotic therapy during teleconsultations carried out on the national teleconsultation platform "Qare" in 4 common infections. 143,428 TCs with structured prescriptions were analyzed, with an appropriate prescription in more than 82% of cases, higher than in the literature. The use of data makes it possible to quickly assess practices and inform doctors to improve their practices.

Teleconsultation has become a new means of using care which has taken off significantly since the COVID crisis, The pooling of the technological environment within the TC makes it possible to set up practice reviews by reusing the data collected. Our aim was to evaluate the relevance of antibiotic therapy during teleconsultations carried out on the national teleconsultation platform “Qare” in 4 common infections. 143,428 TCs with structured prescriptions were analyzed, with an appropriate prescription in more than 82% of cases, higher than in the literature. The use of data makes it possible to quickly assess practices and inform doctors to improve their practices.

Protectionists have been accused of unraveling the multilateralist world order. The United States pulling out of the Trans-Pacific Partnership Agreement, the renegotiation of the North American Fre...

PurposeThe benefits of trade liberalization on upskilling and skill-based wage premiums for high-skilled workers have recently been questioned in policy circles, in part because of rising income inequality and populist movements in developed economies such as the USA. The purpose of this paper is to determine the effects of trade liberalization on the relative supply and demand for skills.Design/methodology/approachThrough the systematic review of the literature on trade and skill acquisition, this paper isolates a total of 25 articles published over the past two decades.FindingsKey findings demonstrate the importance of the relative development of the trading partner, with more developed countries experiencing higher upskilling, while less developed countries experience deskilling. Technology, geographic level of analysis, sector and gender were also found to be important influences on human capital acquisition associated with international trade.Originality/valueOverall, the authors find support for the idea that trade with developing countries places pressure on low-skill jobs in developed countries but increases the demand for educated workers. The implications of shifts in skills for public policy-making and in terms of the skill premium on wages are discussed.

In virtual reality (VR), immersion can be created through synchronous visuomotor stimulations and enhanced by adding auditory or kinesthetic stimulations. Multiple patterned vibrations applied at the lower limbs might be a way to induce kinesthetic perception of gait motion that could be combined with VR stimulations to add the perception of self-motion. However, gait motion perception using multiple vibrations has not yet been evaluated. The objective of the study was to quantify the perception of gait motion while applying multiple, patterned vibrations to the lower limbs in healthy individuals. Twenty young healthy participants (25.1 ± 4.4 years) experienced multiple vibrations in 1-min trials. Stimulation consisted of a vibration pattern based on the sequence of muscle lengthening during a 2-s gait cycle. Stimulation was applied on participants in a standing position, under 11 experimental conditions controlling visual information (eyes open/closed), vibration frequency (40-80 Hz), and number and location of the joints stimulated (hips, knees, ankles isolated or combined two by two). Perception of gait motion was quantified for each condition using a 10-point visual analog scale (VAS, 0: "no perception", 10: "Perception of gait movements"). All participants except one achieved a score higher than 5/10 in at least one condition. Great variability was found for perception of gait motion within participants and conditions (VAS ranging from 0 to 9.6/10). Differences were found between conditions (p

Spinal cord injury (SCI) leads to a loss of sensitive and motor functions. Currently, there is no therapeutic intervention offering a complete recovery. Here, we report that repetitive trans-spinal magnetic stimulation (rTSMS) can be a noninvasive SCI treatment that enhances tissue repair and functional recovery. Several techniques including immunohistochemical, behavioral, cells cultures, and proteomics have been performed. Moreover, different lesion paradigms, such as acute and chronic phase following SCI in wild-type and transgenic animals at different ages (juvenile, adult, and aged), have been used. We demonstrate that rTSMS modulates the lesion scar by decreasing fibrosis and inflammation and increases proliferation of spinal cord stem cells. Our results demonstrate also that rTSMS decreases demyelination, which contributes to axonal regrowth, neuronal survival, and locomotor recovery after SCI. This research provides evidence that rTSMS induces therapeutic effects in a preclinical rodent model and suggests possible translation to clinical application in humans. Electronic supplementary material The online version of this article (10.1007/s13311-020-00915-5) contains supplementary material, which is available to authorized users.

Objectives: To summarize significant research contributions published in 2019 in the field of computerized clinical decision support and select the best papers for the Decision Support section of the International Medical Informatics Association (IMIA) Yearbook. Methods: Two bibliographic databases were searched for papers referring to clinical decision support systems (CDSSs) and computerized provider order entry (CPOE) systems. From search results, section editors established a list of candidate best papers, which were then peer-reviewed by external reviewers. The IMIA Yearbook editorial committee finally selected the best papers on the basis of all reviews including the section editors’ evaluation. Results: A total of 1,378 articles were retrieved. Fifteen best paper candidates were selected, the reviews of which resulted in the selection of three best papers. One paper reports on a guideline modeling approach based on clinical decision trees, both clinically interpretable and suitable for implementation in CDSSs. In another paper, authors promote the use of extended Timed Transition Diagrams in CDSSs to formalize consistently recurrent medical processes for chronic diseases management. The third paper proposes a conceptual framework and a grid for assessing the performance of predictive tools based on the critical appraisal of published evidence. Conclusions: As showed by the number and the variety of works related to decision support, research in the field is very active. This year’s selection highlighted pragmatic works that promote transparency and trust required by decision support tools.

International audience; Inertial measurement units (IMUs) have been increasingly popular in rehabilitation research. However, despite their accessibility and potential advantages, their uptake and acceptance by health professionals remain a big challenge. The development of an IMU-based clinical tool must bring together engineers, researchers and clinicians. This study is part of a developmental process with the investigation of clinicians’ perspectives about IMUs. Clinicians from four rehabilitation centers were invited to a 30-minute presentation on IMUs. Then, two one-hour focus groups were conducted with volunteer clinicians in each rehabilitation center on: 1) IMUs and their clinical usefulness, and 2) IMUs data analysis and visualization interface. Fifteen clinicians took part in the first focus groups. They expressed their thoughts on: 1) categories of variables that would be useful to measure with IMUs in clinical practice, and 2) desired characteristics of the IMUs. Twenty-three clinicians participated to the second focus groups, discussing: 1) functionalities, 2) display options, 3) clinical data reported and associated information, and 4) data collection duration. Potential influence of IMUs on clinical practice and added value were discussed in both focus groups. Clinicians expressed positive opinions about the use of IMUs, but their expectations were high before considering using IMUs in their practice.

Background Using a mobile phone while performing a postural and locomotor tasks is a common, daily situation. Conversing or sending messages (SMS) while walking account for a significant share of accidental injuries. Therefore, understanding the consequences of using a mobile phone on balance and walking is important, all the more so when these postural and locomotor tasks are aggravated by a disease. Research question Our objective was to conduct a scoping review on the influence of a dual-task situation – generated by the use of mobile phone – on users' postural and/or locomotor tasks. Methods The literature search was conducted in English on PubMed/Medline and CINHAL databases, using keywords associated with postural and locomotor tasks and with the use of mobile phone. Study location, population, number of subjects, experimental design, types of phone use, evaluated postural-locomotor tasks and expected effects were then analyzed. Results and significance 46 studies were included in this work, 24 of which came from North America. All studies compared postural and locomotor tasks with and without the use of a smartphone. Ten studies also compared at least 2 groups with different characteristics. Only 4 studies included pathological subjects. Various modalities were tested, and most studies focused on walking. Results show that the use of smartphones slows down movement and induces a systematic imbalance, except when listening to music. The dual task of "using the smartphone during a postural or locomotor tasks" induces systematic disturbances of balance and movement, which must be taken into account in the rehabilitation approach. Future studies will have to extend the knowledge regarding pathological situations.

We would like to thank Dr Loustaud-Ratti and colleagues for their interest in our work regarding a case of post-Liver Transplantation (LT) Sinusoidal Obstruction Syndrome (SOS) induced by Mycophenolate Mofetil (MMF).1 We completely agree with the first comment from these authors concerning the increasing incidence of nodular regenerative hyperplasia which may, among other causes, be a late evolution of SOS with an average incidence of 2.3.

Introduction Slow waves and spindles are essential oscillations occurring during NREM sleep that may be disrupted by moderate to severe traumatic brain injury (TBI). We investigated these oscillations in the acute and chronic trauma stage. Methods Four groups were tested with whole-night polysomnography: hospitalized patients with acute TBI (n=10, 29.7±13.8y) or severe orthopedic injuries (n=15, 39.9±17.1y), chronic TBI including 9 returning from the acute TBI group (n=43, 31.9±13.5y), and healthy controls (n=36, 30.5±12.7y). Characteristics for slow waves (density, amplitude, slope, frequency, duration) and spindles (density, amplitude, frequency, duration) were quantified over N2 and N3 sleep for the first three sleep cycles, and groups were compared using one-way ANOVAs. Results One-way ANOVAs showed group effects only for slow wave density (F=4.11 to 6.04, p=0.009 to 0.0008)) and spindle density (F=3.3 to 8.8, p=0.02 to 0.00003). These effects were present for the 2nd and 3rd sleep cycles, but not the 1st. More specifically, slow wave density in acute TBI was higher than in controls, and returned to normal levels in the chronic stage. Conversely, spindle density in acute TBI was lower than in controls and returned to normal levels in the chronic stage. No group difference was observed for the orthopedic group. Conclusion Our results suggest that immediately after a severely disruptive event such as a TBI, the brain needs additional deeper sleep to recover, resulting in more slow waves but also in less spindles. These changes are only present in the 2nd and 3rd sleep cycles, reflecting an absence of the expected dissipation of slow waves, which may suggest increased homeostatic sleep pressure due to the brain injury. Limits to interpretation include the hospital environment and medication, but the absence of changes in the orthopedic group under similar conditions emphasizes the effect of the brain injury itself. Support Canadian Institutes of Health Research (CIHR) and Fonds de Recherche Québec-Santé (FRQS)

Introduction Diminuer l’asymetrie locomotrice est un objectif important de la readaptation post-AVC. La marche est consideree asymetrique lorsque le ratio entre les deux cotes (valeur la plus elevee au numerateur) est superieur a 1,05 pour le temps d’appui (AsymA) et 1,06 pour le temps d’oscillation (AsymO, Patterson et al., 2010). L’hypothese est que l’asymetrie evaluee en laboratoire pourrait etre differente de celle adoptee en milieu ecologique. L’objectif de notre travail est de determiner l’effet du milieu d’evaluation sur l’asymetrie locomotrice post-AVC. Materiel et methodes Vingt-cinq personnes avec une hemiparesie chronique ont marche a vitesse confortable durant 615 m au sein d’un laboratoire et d’un centre commercial. Deux capteurs inertiels (APDM, Opal) etaient places aux tibias. Les evenements de marche, detectes dans les signaux, ont permis d’estimer les parametres temporaux, l’AsymA et l’AsymO. Resultats Deux participants presentaient une AsymA ou une AsymO dans un milieu mais pas dans l’autre, alors que les autres participants presentaient une AsymA (16) et/ou une AsymO (18) dans les deux milieux. Tout au long du parcours, l’AsymA et l’AsymO etaient similaires entre le laboratoire (en moyenne [ET] : 1,15 [0,09] et 1,34 [0,27]) et le milieu ecologique (1,14 [0,09] et 1,32 [0,26]). Les temps d’appui etaient plus longs en laboratoire qu’en milieu ecologique (+3 % environ). Discussion L’asymetrie temporelle evaluee en laboratoire reflete bien celle adoptee par les personnes post-AVC en milieu ecologique, alors que les temps d’appui sont affectes par le milieu d’evaluation. L’estimation de l’asymetrie spatiale est en cours de developpement.

Introduction La contemplation et la perception d’une œuvre d’art au complet implique le regard et l’orientation de la tete. Cette derniere depend des informations proprioceptives du cou. L’application des vibrations sur les muscles du cou stimulent ces informations, et peut generer des reponses posturales. Nous voulons determiner si l’application de vibrations nucales modifie l’exploration visuelle d’une œuvre d’art, et comment la tâche d’exploration affecte les reponses posturales aux vibrations. Materiel et methode Vingt adultes en bonne sante porteront un systeme de suivi du regard (Tobii) et l’application App Balance de mesure de l’equilibre. En position debout, ils exploreront trois tableaux (largeur > 1 m) et identifieront 7 details. L’exploration se fera sans ou avec vibrations nucales (gauches et droites) (VB115, TechnoConcept) de maniere randomisee. Un test d’exploration visuelle de type papier-crayon (test des cloches) sera egalement effectue en position assise. Analyse Les tableau seront divises en 7 colonnes ; la 1re colonne exploree, les temps de fixation et le nombre de visite sur chaque colonne, ainsi que l’activite posturale seront compares entre les differentes conditions. Resultats attendus L’application de vibrations nucales modifiera l’exploration visuelle. Les reponses posturales aux vibrations seront attenuees lors de l’exploration, du fait du meilleur ancrage visuel fourni par l’exploration. Discussion Les personnes avec des deficits de la perception visuelle pourraient beneficier de ce type d’intervention, en situation ecologique. Les donnees des sujets en bonne sante aideront a interpreter les resultats de ces patients recrutes dans une future etude.

Discipline Clinique. Introduction et but de l’etude Malgre les recommandations indiquant qu’il est primordial d’utiliser la nutrition enterale (NE) lorsque le tube digestif est viable, l’utilisation de la nutrition parenterale (NP) reste la methode la plus utilisee en hematologie. Le but etait d’evaluer la faisabilite et l’impact de la nutrition enterale chez des patients admis pour autogreffe de moelle. Materiel et methodes Etude observationnelle menee dans un CH dont les donnees ont ete recueillies prospectivement. La promotion de la NE a ete decidee en equipe, mais la proposition a chaque patient etait laissee au libre choix de l’hematologue referent qui demandait l’accord du patient. Les objectifs nutritionnels etaient de 30–35 kcal/kg/j. Les donnees cliniques (poids, appetit par EPA, echelle visuelle analogique de bien-etre) et biologiques (albumine, prealbumine, CRP) etaient recueillies entre j-1 et j + 1 de la greffe, puis a la sortie d’aplasie. Un questionnaire etait donne au personnel du service pour evaluer sa perception de la NE. Les resultats etaient exprimes en mediane [extremes] comparees par un test de Mann–Whitney. Resultats et analyse statistique Entre decembre 2017 et mai 2018, 18 patients (9H/9F, âge 60,5 ans [36–70] ont ete traites par autogreffe pour myelome (n = 11), lymphome (n = 6) ou Waldenstrom (n = 1). Une patiente decedee precocement n’a pas ete inclue. Le support nutritionnel etait assure par NE (n = 5), NP (n = 9) ou sans support (n = 4). Sur les 13 patients n’ayant pas eu de NE, 7 avaient refuse la NE, et c’etait le choix du medecin pour 6. Les caracteristiques initiales des patients etaient identiques quelque soit le support nutritionnel recu, sauf le poids initial plus eleve dans le groupe sans support (97 kg vs 65 kg pour NE et 74 kg pour NP ; p = 0,03). L’evolution apres versus avant greffe est indiquee dans le Tableau 1 . Les questionnaires ont ete renseignes par 16 professionnels du service (5 medecins, 11 IDE/AS), 62 % exprimaient une image negative de la NE et 69 % s’estimaient mal a l’aise avec cette prise en charge. Conclusion Malgre une difficulte de mise en place de la NE chez les patients autogreffes en lien avec une reserve des patients et des equipes soignantes, l’utilisation de la NE ameliore le statut nutritionnel et devrait etre privilegiee.

Introduction Lors de la marche, les forces de reaction au sol (FRS) expriment le comportement dynamique du centre de gravite du corps a savoir l’acceleration et la deceleration lineaire de celui-ci. Ceci s’exprime au niveau du sol par un patron biphasique (force horizontale) et triphasique (force verticale, et medio-laterale). Ces patrons, mesures chez le sujet hemiparetique par des plateformes de force dans un contexte de laboratoire clinique, sont alteres en amplitude et en duree. Ils sont des indicateurs de la severite des deficits fonctionnels. Dans le milieu ecologique ou la locomotion n’est pas contrainte par un parcours lineaire, il n’existe a date aucune methode validee et non-encombrante permettant la mesure de ces FRS. L’objectif principal de ce projet est le developpement d’une methode minimalement encombrante et precise afin de pourvoir mesurer les FRS dans les plans frontal et sagittal en milieu ecologique. Materiel et methodes Deux capteurs inertiels (APDM) disposes sur les jambes en distal sont utilises a l’interieur et exterieur du laboratoire de recherche lors de plusieurs conditions de marche (symetrique et asymetrique, plan incline, et escalier). Le systeme VICON a servi de referent cinematique alors qu’un tapis roulant instrumentes a 2 voies constituait le referent cinetique. Un modele non-lineaire entraine par identification a ete utilise pour predire les FRS grâce aux donnees des capteurs inertiels. Resultat Les FRS, predites de maniere preliminaires sur 3 sujets, demontrent une erreur quadratique moyenne inferieur a 8 % pour la courbe verticale. Les autres donnees sont en cours d’analyse. Conclusion Les resultats sont prometteurs et il est prevu d’appliquer la methode aux donnees collectees de 36 sujets hemiparetiques evalues dans un milieu ecologique.

Resume Objectifs La prevention des effets indesirables lies aux medicaments (EIM) est devenue un important enjeu de sante publique. La pharmacovigilance a pour objet l’identification, l’analyse et la prevention des risques lies aux EIM. L’objectif du projet VigiTermes est de developper des methodes innovantes pour une detection plus precoce des EIM. Materiel et methodes Les methodes mises en œuvre appartiennent a l’ingenierie des connaissances, l’ingenierie multilingue, le traitement automatique du langage et a la fouille de texte. Resultats Le principal resultat du projet est la mise en place d’une architecture logicielle destinee a la recherche et l’analyse des articles decrivant les EIM sur le serveur bibliographique PubMed. Il s’agit de la premiere application de ce type destinee a la pharmacovigilance. Les autres resultats sont en rapport avec la detection statistique des signaux, la modelisation des medicaments et des EIM au moyen d’ontologies, la recherche d’information dans les bases de donnees de pharmacovigilance et l’application de methode de traitement automatique des langues en japonais appliquee a des cas de pharmacovigilance. Discussion Des developpements sont en cours afin de mettre les resultats du projet sous forme operationnelle pour une exploitation par les autorites reglementaires et les laboratoires pharmaceutiques. L’amelioration de l’interface graphique devrait faciliter l’aide a la decision pour les professionnels responsables des questions liees a la pharmacovigilance. Conclusion Notre ambition est de continuer l’integration des composants sur la plateforme commune afin de proposer aux pharmacovigilants l’outil le plus complet et le plus efficace pour la detection, ainsi que le suivi et la consolidation des signaux de pharmacovigilance.

Resume L’hypertension intracrânienne benigne (HICB) est caracterisee par une augmentation de la pression intracrânienne en l’absence de processus expansif intracrânien, de thrombose veineuse ou d’hydrocephalie. Contrairement a ce que pourrait laisser penser son appellation, elle met en jeu le pronostic visuel. Nous rapportons le cas d’une jeune fille de 15 ans qui a presente un tableau initial compatible avec une meningite virale, bien qu’il n’ait pas comporte de syndrome meninge franc. La pression du liquide cephalorachidien (LCR) etait de 70 cm d’eau. Il n’existait pas de dilatation ventriculaire. L’evolution etait marquee par une atteinte du nerf abducens (VI), une baisse d’acuite visuelle et un œdeme papillaire bilateral. Le diagnostic retenu etait celui d’HICB secondaire, de cause inconnue malgre un bilan exhaustif. Apres 8 semaines de traitement par acetazolamide per os et un traitement par ponctions lombaires iteratives, l’evolution etait favorable. Il n’y a pas eu de recidive apres 1 an de recul. Cette observation illustre les risques lies a une affection peu connue et improprement denommee benigne, dont la prise en charge symptomatique et etiologique est primordiale pour la preservation de la fonction visuelle.

International audience; On November 21, 2004 an Mw6.3 intraplate earthquake occurred at sea in the French Caribbean. The aftershock sequence continues to this day and is the most extensive sequence in a French territory in more than a century. We recorded aftershocks from day 25 to day 66 of this sequence, using a rapidly-deployed temporary array of ocean bottom seismometers (OBS). We invert P- and S-wave arrivals for a tomographic velocity model and improve aftershock locations. The velocity model shows anomalies related to tectonic and geologic structures beneath the Les Saintes graben. 3D relocated aftershocks outline faults whose scarps were identified as active in recent high-resolution marine data. The aftershocks distribution suggests that both the main November 21 event and its principal aftershock, on February 14, 2005, ruptured Roseau fault, which is the largest of the graben, extending from Dominica Island to the Les Saintes archipelago. Aftershocks cluster in the lower part of the Roseau fault plane (between 8 and 12.6 km depth) that did not rupture during the main event. Shallower aftershocks occur in the Roseau fault footwall, probably along smaller antithetic faults. We calculate a strong negative Vp anomaly, between 4 and 8 km depth, within the graben, along the Roseau fault plane. This low Vp anomaly is associated with a high Vp/Vs ratio and may reflect a strongly fracturated body filled with fluids. We infer from several types of observation that fault lubrication is the driving mechanism for this long-lasting aftershock sequence.

Introduction Les donnees issues du Programme de medicalisation du systeme d’information etant utilisees dans de nombreux domaines, les etablissements de sante doivent mesurer la qualite du codage, analyser les erreurs de codage. Nous presentons les etapes de mise en œuvre d’un audit sur la qualite du codage clinique dans le cadre d’un codage decentralise. Methodes Pour realiser un audit, il faut definir : le nombre de sejours audites (un minimum de 200 sejours est recommande, une stratification de l’echantillon est possible : par codeur, pathologies, services…) ; un codage de reference (realise par un seul codeur, un binome clinicien/codeur, obtenu par une methode de consensus…) ; les indicateurs de l’audit (exactitude et completude du codage, changement de groupage et de valorisation) ; la typologie des erreurs. Resultats L’audit a ete realise sur 250 sejours tires au sort : 50 sejours par pole/technicienne d’information medicale (TIM) avec une stratification par service. Les trois medecins seniors ont analyse 247 sejours, leur codage a ete considere comme le « gold standard ». Une analyse globale et sur le codage des diagnostics (11 changements de diagnostic principal, 12 mauvaises hierarchisations des diagnostics, ajout et suppression de diagnostics associes) a ete realisee. Un typage des erreurs a ete realise : mauvaise comprehension clinique, 32 non-respect des consignes de codage, 22 imprecisions des codes utilises. Discussion/Conclusion La variabilite inter-juges, frequente dans le codage, rend souhaitable l’obtention d’un codage de reference par consensus entre codeurs. Pour un audit a realiser regulierement cette methodologie chronophage est difficilement applicable. Pour beneficier de l’expertise des medecins : chaque medecin a audite les sejours du pole dont il avait la responsabilite : l’effet medecin n’est pas analyse. Typer les erreurs est parfois difficile : des diagnostics associes manquants correspondent-ils a une omission volontaire (diagnostics ininteressants pour la valorisation) ou a une incomprehension clinique ? Pour une amelioration continue de la qualite du codage, les resultats de l’audit serviront de support de formation des techniciennes.

Annales Francaises d'Oto-Rhino-Laryngologie et de pathologie cervico-faciale - Vol. 125 - N° 2 - p. 105-108

Proteomic microarrays show a wide range of applications for the investigation of DNA–protein, enzyme–substrate as well as protein–protein interactions. Among many challenges to build a viable “protein microarray”, the surface chemistry that will allow to immobilised various proteins to retain their biological activity is of paramount importance. Here we report a chemical functionalisation method allowing immobilisation of oligo-peptides onto silica surface (porous silica, glass, thermal silicon dioxide). Substrates were first derivatised with a monofunctional silane allowing the elaboration of dense and uniform monolayers in highly reproducible way. Prior to the oligo-peptides grafting, this organic layer was functionalised with an amino-polyethyleneglycol. The coupling step of oligo-peptides onto functionalised supports is achieved through activation of the C-terminal function of the oligo-peptides. Chemical surface modifications were followed by FTIR spectroscopy, AFM measurements and fluorescence scanning microscopy. A systematic study of the oligo-peptide grafting conditions (time, concentration, solvent) was carried out to optimise this step. The oligo-peptides grafting strategy implemented in this work ensure a covalent and oriented grafting of the oligo-peptides. This orientation is ensured through the use of fully protected peptide except the terminal primary amine. The immobilized peptides will be then deprotected before biological recognition. This strategy is crucial to retain the biological activity of thousands of oligo-probes assessed on a microarray.

Cette etude a ete realisee au CHU de Rennes, afin de determiner le taux d'allaitement maternel des nouveau-nes hospitalises des les premiers jours de vie, ainsi que les facteurs associes au choix d'allaiter ou non dans ces conditions de transfert. Patients et methodes. - Trois cent vingt femmes ayant accouche dans une maternite du CHU de Rennes et dont l'enfant avait du etre transfere en neonatalogie ont ete interrogees sur leur choix d'alimentation du nouveau-ne au moyen d'un questionnaire. Resultats.- Trois cent huit femmes ont repondu au questionnaire. Cinquante et un pour cent d'entre elles ont choisi d'allaiter, taux proche de la population globale des parturientes du CHU (52 %). Les facteurs sociodemographiques associes au choix d'allaiter etaient un niveau socioculturel eleve, le fait qu'une femme ait elle-meme ete allaitee, et une experience anterieure d'allaitement (RR = 5,2 ; p < 10 -8 ). Differentes variables concernant l'information des femmes etaient associees au choix d'allaiter. C'etait le cas d'une information sur l'allaitement maternel donnee lors des cours de preparation a l'accouchement (RR = 1,7; p < 10 -5 ) ou lors d'un entretien individuel cible sur l'allaitement maternel d'un nouveau-ne malade (RR = 1,5; p < 10 -2 ), et du simple conseil d'allaiter donne par le corps soignant (RR = 2; p

Medical decision making, such as choosing which drugs to prescribe, requires to consider mandatory constraints, e.g. absolute contraindications, but also preferences that may not be satisfiable, e.g. guideline recommendations or patient preferences. The major problem is that these preferences are complex, numerous and come from various sources. The considered criteria are often conflicting and the number of decisions is too large to be explicitly handled. In this paper, we propose a framework for encoding medical preferences using a new connective, called ordered disjunction symbolized by ~×. Intuitively, the preference "Diuretic~×Betablocker means: "Prescribe a Diuretic if possible, but if this is not possible, then prescribe a Betablocker". We give an inference method for reasoning about the preferences and we show how this framework can be applied to a part of a guideline for hypertension.

BACKGROUND The end-stage LIVER disease and RALtegravir-Agence Nationale de Recherche sur le Sida et les hepatites (LIVERAL-ANRS) 148 study aimed to evaluate the safety, efficacy, and pharmacokinetic parameters of raltegravir (RAL) in human immunodeficiency virus (HIV)-infected patients with end-stage liver disease (ESLD) (substudy 1) and to assess the lack of pharmacokinetic interaction between RAL and the immunosuppressive regimen introduced after liver transplant (substudy 2). METHODS All patients received 400 mg RAL twice daily plus 2 nucleoside reverse transcriptase inhibitors. Liver function and immunovirological parameters were monitored throughout the study. Serial blood samples were drawn to explore RAL pharmacokinetics. Plasma concentrations of protein unbound, total RAL, and RAL glucuronide were determined by liquid chromatography-tandem mass spectrometry. RESULTS Ten patients with ESLD were analyzed in substudy 1. Despite an increased RAL exposure, RAL was well tolerated in all patients and no patient had to stop RAL therapy because of adverse events. Four patients were analyzed in substudy 2. No pharmacokinetic interaction was observed between cyclosporine, mycophenolic acid, and RAL. RAL tolerability was excellent; there were no episodes of acute rejection or opportunistic infection. HIV-RNA levels remained controlled and CD4 cell counts remained stable in all patients throughout the study. CONCLUSIONS The results of the substudy 1 support RAL administration to patients with ESLD. Substudy 2 assesses the safety, tolerability, and efficacy of RAL therapy in HIV-infected patients after liver transplant. RAL might be recommended as a suitable antiretroviral therapy in HIV-infected patients undergoing liver transplant.

Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures.Wilson's disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients.In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67%) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied.Mean LS and FN Z-score was normal (-0.37 ± 1.20 at LS and -0.06 ± 1.20 at FN). BMI19 kg/m(2) and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51%) and VF in 7 (8%) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF.Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.

Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and Europe indicates that 3- to 5-year survival in HIV/HCV-coinfected liver recipients is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected transplant patients (liver, kidney and heart) was similar to that of non-HIV-infected patients. Preliminary experience with lung transplantation and combined kidney and pancreas transplantation is also satisfactory. Infections in HIV-infected recipients during the post-transplant period are similar to those seen in non-HIV-infected patients, although the incidence rates of tuberculosis and fungal infections seem to be higher. HIV-infected patients who are being evaluated for SOT should follow the same recommendations as those used for non-HIV-infected patients in order to prevent infections during the pre-transplant period. After transplantation, HIV-infected SOT recipients must follow recommendations on post-SOT and anti-HIV immunization and on antimicrobial prophylaxis. The recommended antiretroviral regimen is one based on raltegravir or dolutegravir plus two nucleos(t)ide reverse transcriptase inhibitors (tenofovir + emtricitabine or abacavir + lamivudine), because it can prevent pharmacokinetic interactions between antiretroviral drugs, immunosuppressive drugs and some of the antimicrobial agents used to treat or prevent post-transplant infections. In this manuscript, we review current recommendations for preventing infections both before and after transplantation. We also analyse the incidence, aetiology and clinical characteristics of opportunistic and non-opportunistic bacterial, mycobacterial, fungal and viral infections in HIV-infected SOT recipients during the post-transplant period.

No standardized representation of drug indications is currently available that could be used in drug knowledge bases. We describe an object-oriented representation of indications that should make it possible to develop new tools for selecting drugs and checking prescriptions in computerized drug prescription systems. The model was developed using the results of a lexical and semantic analysis of drug indications, collected into a single file and processed using natural language processing software. It distinguishes both the diseases for which the drug may be given and the efficiency of the drug for a given indication. Two aspects of the model were evaluated: the differences if two independent evaluators filled the attributes independently and the loss of information induced by the use of the model. A system based on this model, making it possible for the physician to select all the drugs satisfying various criteria, is also presented.

SUMMARY Antibodies specific for cytochrome CYP2D6, formally known as liver-kidney-microsome type-1 antibodies (LKM-1), are characteristically found in a subgroup of patients presenting autoimmune hepatitis. They are also found in some patients with chronic HCV infection. These autoantibodies are usually detected by indirect immunofluorescence, immunoblotting and ELISA tests. In an attempt to set up a more sensitive detection assay we developed a quantitative immunoprecipitation radioligand assay using a 35S-methionine-labelled CYP2D6 antigen obtained by in vitro transcription and translation synthesis. All 16 sera from AIH-2 patients strongly bound to this CYP2D6 antigen. Two of the nine sera (22%) from AIH-2 patients that presented only liver cytosol-1 antibodies also bound to CYP2D6. All 24 sera from HCV patients that were positive for LKM-1 antibodies by indirect immunofluorescence were also positive using this CYP2D6 radioligand assay. Lastly, all 15 sera from HCV patients negative for LKM-1 antibodies were negative by this test. The present results support the view that this quantitative radioligand assay is more sensitive than immunoblotting and ELISA CYP2D6 assays, and that it could be used in combination with indirect immunofluorescence assay.

Drug prescription has to satisfy three quality criteria. Orders have to be adapted to the patient state, be compatible with all the other drugs of the prescription, and in compliance with the recommendations described in clinical practice guidelines (CPGs). Computer provider order entry systems (CPOEs) have been developed to secure drug orders and they address the first two criteria. Clinical decision support systems (CDSSs) have been developed to improve the implementation of CPGs and promote evidence-based medicine. This chapter first introduces the different medication errors. Then, the general architecture of CPOEs (user interface, drug database, interface with electronic medical records (EMRs) and inference engine) is presented. The main modalities of entering drug orders are described. Alert generation for contra-indications, or drug-drug interactions, are detailed. CDSSs are tools to provide patient-specific recommended treatments. They rely on a knowledge base embedding CPGs. The translation process of CPGs from their original narrative format to a structured formalized representation is described. The difficulty of text translation is emphasized and documentary tools such as GEM that help formalize guideline content are described. The main guideline representation formalisms, Arden Syntax, decision trees, EON and GLIF, are presented. Then, ways of operating CDSSs are described, from the totally automated alert-based mode, to various documentary approaches where the user navigates through a structured knowledge base. Finally, examples of clinical decision support systems currently routinely used are given.

It has been demonstrated that aspirations could occur during respiratory failure, explained by a lack of co-ordination between swallowing and ventilation. To test this hypothesis, we examined the co-ordination of ventilation and swallowing in a completely unrestrained rat model during different level of hypercapnia, during hypoxia, and during tachypnea.A total of 50 male Wistar rats (250-350 g) were studied in a barometric plethysmograph to analyze swallowing and ventilation during swallowing, at different gas concentration [room air (G1), 10% of O2 and 0% of CO2 (G2), 21% of O2 and 5% of CO2 (G3), 21% of O2 and 10% of CO2 (G4), tachypnea (G5)].During hypoxia, there was no difference between G2 and G1 regarding the swallowing parameters and ventilatory parameters. During hypercapnia, there was an increase in swallowing during inspiration in G4 (16 ± 20%P0.01) compared with G1. The analysis of ventilatory parameters during swallowing showed an increase in tidal volume (VT) and mean inspiratory time (VT/TI) (P0.001) with no change in respiratory cycle duration (TTOT), inspiratory time (TI), and expiratory time (TE) when compared with G1. During tachypnea (G5), the VT decreased (P0.05) without any change in VT/TI.Our results on animal demonstrated that hypercapnia increased swallowing during inspiration, which was not the case for tachypnea or hypoxia, and could explain some aspirations during respiratory failure.

Apres avoir lu ce chapitre, vous devriez : pouvoir expliquer quels sont les grands principes de la planification sanitaire et du financement des depenses hospitalieres ; connaitre la place de la loi hopital 2007 et de la loi Hopital Patient Sante Territoire ; avoir compris le principe general du PMSI ; connaitre la constitution des recettes et les tarifs par sejour hospitalier ; les notions de RUM, RSS, RSA ; pouvoir expliquer le principe de l’algorithme de groupage, les GHM, GHS et l’echelle des tarifs ; connaitre le principe de l’etat previsionnel des recettes et des depenses ; savoir quels sont les elements necessaires au pilotage de la tarification a l’activite, les indicateurs ; connaitre les elements de son evaluation, le role de la Haute Autorite de Sante et l’ONDAM ; pouvoir expliquer quelles sont les principales differences et similitudes avec les systemes de tarification developpes dans d’autres pays.

Introduction La severite de la maladie de Wilson (MW) depend etroitement du cuivre libre et par consequent toxique qui s’accumule dans le foie et le cerveau. Le cuivre echangeable (CuEXC) est un nouveau dosage de ce cuivre libre. Le REC (rapport CuEXC/cuivre total) est d’un grand interet dans le diagnostic de la MW ainsi que dans le depistage familial de la maladie. Objectif Determiner si le CuEXC est un marqueur de la severite de la maladie et en particulier de l’atteinte extra-hepatique. Materiel et methodes Quarante-huit nouveaux patients atteints de la MW ont ete evalues de facon prospective avec des scores hepatique, neurologique (UWDRS : Unified Wilson Disease Rating Score), ophtalmologique et neuro-radiologique (IRM cerebrale). Trois presentations phenotypiques ont ete distinguees : pre-symptomatique, hepatique (H) et extra-hepatique (EH). Le CuEXC a ete evalue en plus des dosages cupriques habituels (cupremie, cuprurie/24 h et ceruloplasminemie) avant le debut du traitement chelateur. Les groupes H et EH ont ete compares et des correlations entre les parametres biologiques et les differents scores ont ete recherchees. Resultats Les patients du groupe EH ont un CuEXC significativement plus eleve que ceux du groupe H ( p 2,08 μmol/L est associe a une atteinte EH (Se : 85,7 % ; Sp : 94,1 %). Le CuEXC est significativement correle a l’importance de l’anneau de Kayser-Fleischer ( p = 0,01), au score neurologique UWDRS ( p = 0,001) et a la diffusion des lesions sur l’IRM cerebrale ( p = 0,04). Il reflete donc la severite de l’atteinte extra-hepatique. En revanche, le CuEXC n’est pas correle au score hepatique. Conclusion Le dosage du cuivre echangeable CuEXC se revele etre un marqueur important dans la prise en charge de la MW. Une valeur > 2,08 μmol/L doit faire rechercher une atteinte extra-hepatique (cornee, neurologique) meme si la presentation clinique de la maladie apparait purement hepatique. Le suivi de cette cohorte devrait nous permettre de savoir si le CuEXC est un marqueur pronostic de la MW et s’il est predictif de la reponse au traitement medical.

Little information is available on erythrocytapheresis in children with sickle cell disease, and no comparison has ever been made with manual exchanges in a long-term blood exchange program. We matched a historical cohort of five patients who received 60 erythrocytapheresis procedures with five who received 124 manual exchanges. Long-term erythrocytapheresis was feasible and well-tolerated even in children of low weight. In a long-term approach, automated exchanges were more efficient in maintaining a low HbS level, and exchanges could be spaced out. This approach appears especially useful in the cases where the HbS level must be maintained below 30%.