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This article summarizes the available evidence on pediatric cochlear implantation to provide current guidelines for clinical protocols and candidacy recommendations in the United States. Candidacy determination involves specification of audiologic and medical criteria per guidelines of the Food and Drug Administration. However, recommendations for a cochlear implant evaluation also should maintain flexibility and consider a child's skill progression (i.e., month-for-month progress in speech, language, and auditory development) and quality of life with appropriately fit hearing aids. Moreover, evidence supports medical and clinical decisions based on other factors, including (a) ear-specific performance, which affords inclusion of children with asymmetric hearing loss and single-sided deafness as implant candidates; (b) ear-specific residual hearing, which influences surgical technique and device selection to optimize hearing; and (c) early intervention to minimize negative long-term effects on communication and quality of life related to delayed identification of implant candidacy, later age at implantation, and/or limited commitment to an audiologic rehabilitation program. These evidence-based guidelines for current clinical protocols in determining pediatric cochlear implant candidacy encourage a team-based approach focused on the whole child and the family system.

To review outcomes of cochlear implantation (CI) in children diagnosed with autism spectrum disorder (ASD).Retrospective case review and parent survey.Tertiary care children's hospital.Thirty children with ASD who underwent CI between 1991 and 2018. Mean age at CI = 3.5 years (0.8-11.8), mean age at diagnosis of ASD = 5.1 years (2.0-15.0) (22/30 diagnosed after CI), mean follow-up = 10.5 years (1.4-21.6). Parents of 7 children returned a survey.Unilateral or bilateral cochlear implantation.Speech perception; expressive communication mode; educational placement; social engagement; consistency of CI use; parent survey of child behavior change.Thirty-three percent of all and 45% of the 22 consistent device users developed measurable open-set speech perception by an average of 4.5 years of device use. Educational placement at last follow-up included 13% mainstreamed without interpreter, 50% Special Education programs, 10% therapeutic residential or day programs, 23% total communication programs, and one home schooled. Spoken language alone was used by 31% and spoken plus sign by 14%, with the remainder using sign alone, augmentative communication devices or no mode of communication. By parent report, 86% showed improvement in social engagement compared to pre-CI. Survey results showed the behaviors most frequently ranked as most affected by CI were communication and attention, while awareness of environment had the lowest (most affected) mean ranking.Findings support a growing body of literature that cochlear implantation has the potential to improve auditory skills, language, and enhance social engagement in some deaf children with autism spectrum disorder.

Partant d’une enquête ethnographique menée dans trois services hospitaliers français entre 2012 et 2018, cet article vise à rendre compte des parcours de soins et de fin de vie en réanimation. Nous montrons que la trajectoire de la maladie se découpe en trois phases – curative, d’attente, palliative – au cours desquelles les soignant·e·s mobilisent des répertoires d’actions sensiblement différents. Oscillant entre une approche clinique et des savoirs informels, ces répertoires produisent des changements ontologiques qui redéfinissent le statut du malade. Le passage du statut de malade curable à celui de malade incurable conduit à une réorganisation de l’arc de travail autour de la fin de vie, et dans lequel les soignant·e·s œuvrent à une définition de la « bonne mort ». Le travail entrepris auprès du malade et de sa famille montre que la prise en charge de la fin de vie reste soumise à l’appréciation des équipes en même temps qu’elle constitue un espace d’échange et de discussion à travers lequel les proches peuvent se réinvestir. Based on an ethnographic survey conducted between 2012 and 2018, this article aims to report on the hospitalization and end-of-life trajectories in intensive care medicine. We show that the trajectory of the disease is divided into three distinct phases – a curative phase, a waiting phase, and a palliative phase – during which the caregivers mobilize significantly different repertoires of action. Oscillating between resuscitative medicine, palliative practices and informal knowledge, these repertoires produce ontological changes that redefine the status of the patient. The passage from the status of curable patient to that of incurable patient leads to a redefinition of the arc of end-of-life work in which the caregivers work towards a definition of the “good death”. The work undertaken with and close to the patient and his or her family shows that end-of-life care remains subject to the appreciation of the teams, while at the same time constituting a privileged space for exchange where the relatives can become involved.

International audience; Fruit des journées d'études organisées les 28 et 29 mars 2019 à Paris dans le cadre de rencontres sous l'égide de l'Association française de sociologie (AFS) entre les chercheur·e·s des réseaux thématiques RT1 « Savoirs, travail et professions » et RT19 « Santé, médecine, maladie et handicap », cet ouvrage collectif a pour objet d'aller voir, au plus près des situations de terrain, ce qui se joue sous le couvert des injonctions à la coopération en santé, tout en prenant en compte leurs effets. Il s'agit par exemple d'observer les effets de la coopération sur les frontières professionnelles, sur l'autonomie des protagonistes, ou encore sur la légitimation ou l'invalidation des savoirs tant professionnels que profanes.Les 32 contributions réunies dans cet ouvrage offrent l'occasion de réinterroger la notion de « coopération » en mobilisant une pluralité d'approches théoriques et méthodologiques. Car même centrée sur les pratiques en santé, cette notion renvoie à un ensemble de significations et d'usages sociaux des plus variés, tant de la part des sociologues que des enquêté·e·s. Inscrite dans des rapports de pouvoir, la coopération suppose des mécanismes de régulation pour perdurer. Aussi, s'interroger sur les logiques sous-jacentes à ces mécanismes est-il particulièrement stimulant en termes de réflexion sur les pratiques et leurs possibles évolutions. Comment et par qui les modalités de la coopération et, à travers elles, l'activité de travail, sont-elles construites ? Qui tente ou est sommé de coopérer, qui s'exécute ou non, et avec quelles motivations ? Comment les pratiques de coopération sont-elles mobilisées, instrumentalisées, affichées ou effacées dans les luttes pour la maîtrise des savoirs et de la division du travail de santé ?C'est notamment à ces questions que cet ouvrage répond, en s'adressant tant aux étudiant·e·s et chercheur·e·s qu'aux professionnel·le·s et aux usager·ère·s du système de santé, et en inaugurant, avec ce premier opus, la nouvelle collection des éditions de l'Irdes : « Sociologie ».

International audience; Résultats : les effets différenciés des techniques de modification du vivant. 1. Médicalisation et effacement de la personne humaine.2. Incertitudes médicales et mobilisation du registre profane3. Adopter une « attitude du vivant » : effacement de la technique médicaleRéférences Révélés récemment par l'épidémie de Covid-19, les services des réanimation sont étudiés depuis plusieurs années par les sciences humaines, éthiques.

International audience; Today in France, more than one in every two people die in public hospital (Lalande and Veber,2009). Among them, some 25% die in a Intensive Care Units (ICU) intented for reception ofpatients whose vital prognosis is committed in the very short term. Most often considered as atraumatic experience by families (Legrand, 2010), the failure of current medicine to cope withdeath questions the place of dying in these services where the preservation of life is a priority,sometimes, "at any price" (Paillet, 2007). From an ethnographic study of three adult ICU, we willdiscuss practices that structure and accompany the life-end trajectory in these units. We will seethat these practices are ambivalent, because they are situated between two normativerepertoires (life support / life-end), but also because they take place, most often, at the bordersof a medical practice that tends precisely to put the death at a distance.; Aujourd’hui en France, plus d’une personne sur deux meurt dans un établissement de santé(Lalande et Veber, 2009). Parmi elles, environ 25 % décèdent dans un service de réanimation,dédié à l’accueil de patients dont le pronostic vital est engagé à très court terme. Le plus souventvécu comme une épreuve par les familles (Legrand, 2010), le constat d’un échec a priori de lamédecine actuelle interroge la place et la prise en charge du mourir dans ces services où lapréservation de la vie est une priorité, parfois " à tout prix " (Paillet, 2007). À partir d'une étudeethnographique de trois services de réanimation adulte, on s’intéressera ici aux pratiquesd’accompagnement du mourir en réanimation, pratiques dont on verra l’ambivalencepuisqu’elles s’inscrivent à l’articulation de répertoires normatifs en tension (maintien en vie /accompagnement du mourir), mais aussi en ce qu’elles prennent forme, le plus souvent, auxfrontières d’une médecine qui tend précisément à mettre la mort à distance.

Objective: Determine safety and effectiveness of cochlear implantation of children under age 37 months, including below age 12 months. Study Design: Retrospective review. Setting: Tertiary care children's medical center. Patients: 219 children implanted before age 37 mos; 39 implanted below age 12 mos and 180 ages 12–36 mos. Mean age CI = 20.9 mos overall; 9.4 mos (5.9–11.8) and 23.4 mos (12.1–36.8) for the two age groups, respectively. All but two ≤12 mos (94.9%) received bilateral implants as did 70.5% of older group. Mean follow-up = 5.8 yrs; age last follow-up = 7.5 yrs, with no difference between groups. Interventions: Cochlear implantation. Main outcome measures: Surgical and anesthesia complications, measurable open-set speech discrimination, primary communication mode(s). Results: Few surgical complications occurred, with no difference by age group. No major anesthetic morbidity occurred, with no critical events requiring intervention in the younger group while 4 older children experienced desaturations or bradycardia/hypotension. Children implanted under 12 mos developed open-set earlier (3.3 yrs vs 4.3 yrs, p ≤ 0.001) and were more likely to develop oral-only communication (88.2% vs 48.8%, p ≤ 0.001). A significant decline in rate of oral-only communication was present if implanted over 24 months, especially when comparing children with and without additional conditions associated with language delay (8.3% and 35%, respectively). Conclusions: Implantation of children under 37 months of age can be done safely, including those below age 12 mos. Implantation below 12 mos is positively associated with earlier open-set ability and oral-only communication. Children implanted after age 24 months were much less likely to use oral communication exclusively, especially those with complex medical history or additional conditions associated with language delay.

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International audience; Acerca de los protocolos “cuando los necesitamos...”: la asimilación del marco de buenas prácticas como desafío profesional en el ámbito hospitalarioEste artículo analiza las estrategias de los profesionales de salud en el contexto de racionalización de la atención médica. Basado en un estudio etnográfico realizado en tres unidades de reanimación, este articulo nos enseña cómo las enfermeras y las auxiliares de salud asimilan los dispositivos de gestión con respecto a sus propias categorizaciones normativas. Si no se opone a los cambios, adoptan actitudes de asentimiento, disensión y simulación frente a las recomendaciones, protocolos y procedimientos de gestión. Con este medio, intentan de mantener su “profesionalismo desde adentro”.; This article analyzes the adaptation’s strategies of healthcare professionals in the context of rationalizing care caused by the reforms of the French health-care system. Based on an ethnographic investigation conducted in three intensive care units (ICUs), it shows how nurses and nursing-auxiliaries assimilate management procedures according to their own normative categorizations. Far from opposing the "conduct of change", they adopt attitudes of assent, dissent and simulation of recommendations, protocols, and managerial procedures. In this way, they try to maintain the "professionalism from within".; Cet article analyse les stratégies déployées par les personnels soignants face à la rationalisation des soins. À partir d’une enquête ethnographique menée dans trois services de réanimation adulte, il montre comment les infirmier.e.s et les aides-soignant.e.s s’approprient les dispositifs de gestion au regard de leurs propres catégorisations normatives. Loin de s’opposer à la « conduite du changement », ils adoptent des attitudes d’assentiment, de dissentiment et de simulation à l’égard des recommandations, protocoles, procédures et fiches techniques et dont l’enjeu consiste finalement au maintien d’un professionnalisme « par le bas ».

Summary Bariatric surgery is recognized as the most clinically and cost‐effective treatment for people with severe and complex obesity. Many people presenting for surgery have pre‐existing low vitamin and mineral concentrations. The incidence of these may increase after bariatric surgery as all procedures potentially cause clinically significant micronutrient deficiencies. Therefore, preparation for surgery and long‐term nutritional monitoring and follow‐up are essential components of bariatric surgical care. These guidelines update the 2014 British Obesity and Metabolic Surgery Society nutritional guidelines. Since the 2014 guidelines, the working group has been expanded to include healthcare professionals working in specialist and non‐specialist care as well as patient representatives. In addition, in these updated guidelines, the current evidence has been systematically reviewed for adults and adolescents undergoing the following procedures: adjustable gastric band, sleeve gastrectomy, Roux‐en‐Y gastric bypass and biliopancreatic diversion/duodenal switch. Using methods based on Scottish Intercollegiate Guidelines Network methodology, the levels of evidence and recommendations have been graded. These guidelines are comprehensive, encompassing preoperative and postoperative biochemical monitoring, vitamin and mineral supplementation and correction of nutrition deficiencies before, and following bariatric surgery, and make recommendations for safe clinical practice in the U.K. setting.

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International audience; Partant de l'analyse des carrières et des trajectoires individuelles, cette communication interroge comment le choix du service hospitalier représente, pour ses acteurs, des stratégies de mobilité sociale mais aussi professionnelle.

International audience; Partant d'une enquête ethnographique menée entre 2012 et 2017 dans trois services de réanimation adulte, cette communication propose d'interroger les voies d'articulation entre une logique de classement et de gestion nouvellement introduite à l'hôpital et les incertitudes - cliniques, sociologiques et organisationnelles - qui structurent les pratiques professionnelles tout au long de la trajectoire de la maladie en réanimation.Axe envisagé : « Institutions du champ sanitaire ou médico-social »

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Several adult patients with low vision have come to the Advanced Low Vision Clinic at the Corporal Michael Crescenz Department of Veterans Affairs Medical Center (CMCVAMC), in Philadelphia, Pennsylvania, and to the Bucks County Association for the Blind and Visually Impaired, in Newton, Pennsylvania, with a diagnosis of hemianopic loss secondary to a stroke in the visual cortex; brain tumors; or traumatic brain injury. Prism placement for peripheral field loss allows patients to have enhanced peripheral awareness and an increased peripheral field depending on the type of prism used (Brillant, 1999). To determine prism placement, a low vision optometrist evaluates the patient. The evaluation consists of trials of different types of prism systems, including Fresnel, Gottlieb, Onufryk, and Eli Peli. When a preference for a particular prism system is shown, it is temporarily placed. The optometrist confers with the orientation and mobility (O&M) specialist to discuss patient goals and a plan of care. The O&M specialist performs an evaluation and provides visual scanning training as well as instruction in the functional use of prisms. This report describes the process used in these centers for assessing and placing the prism for these individuals. Prior to prism placement, a full visual field test is completed using a Zeiss, Octopus, or Goldman perimeter, which accurately define the visual field loss. The optometrist and O&M specialist review the results of this test to determine the plan of care for the patient. An Esterman visual field test is completed if the patient is interested in driving again. The Esterman test measures the visual field with both eyes open, as this is required by states that permit driving only if an individual has a visual field of 120 degrees across the horizontal meridian. Prism placement is first tested with a 20-40D Fresnel prism cut to the shape of the spectacle lens in the area of field loss with the prism's base facing in the direction of vision loss. The prism is placed by the optometrist to bisect the pupil so its edge can be seen without scanning into the prism. The edge is then trimmed with iridectomy scissors to the edge of the pupil. The patient then scans into the edge and is asked to count fingers within 10-15 degrees of the non-seeing field. The individual is then asked to ambulate and to detect objects in the non-seeing field. For example, if the non-seeing field is temporal, the scan would be to the left or right to view a painting on the wall, a doorway, or a person passing to the side. If the prism edge is causing diplopia, it is trimmed again to the edge of the dilated pupil. In another method of prism placement, an individual is asked to look straight ahead at his or her nose (if the nose can be seen). If they cannot see their nose, then they are asked to look towards the center of their face, then bring a Post-it note (a small self-adhesive piece of paper) along the plane of their glasses from the non-seeing area into the plane of where they can just see the edge of the Post-it note. They then move the Post-it note back 1 millimeter (mm) until they can no longer see it. When viewing straight ahead, they should not see the edge of the Post-it note. A permanent marker pen such as a Sharpie can then be used to mark the eyeglass lens for later placement of the Fresnel prism (Giorgi, Woods, & Peli, 2009). Choosing the strength of the prism depends on the size of the defect and the individual's tolerance. As a general rule of thumb, the number of degrees the image is moved is half the dioptric power of the prism. Therefore, a 30-diopter prism will move the image approximately 15 degrees. The base of the prism is always placed towards the area of the defect in order to move the image towards the seeing area. The base is marked on the Fresnel prism for orientation. The clinician places the prism to the edge of the defect as described above (Warren & Barstow, 2011). …

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This thesis on The Manufacturing of Care in Intensive Care Units aims to show how provision of care for patients requiring highly technical treatment is part of a categorization which is both sociological and anthropological. From a socio-historical approach which aims to retrace how a medical practice of emergency and uncertainty was built up, this involves identifying the professional substructures and the conditions under which the care segment of intensive care has emerged. This approach leads us to question more specifically the evolution of this segment within the framework of the modernization of public hospitals. The standardization undertaken by public authorities invites us to reconsider singular care practices which are grappling with the medical uncertainty resulting from the provision of care to patients whose lives are in danger.These practices are singular in relation to 'emergency routines' which are applied in work supervision, as well as in relation to the patients admitted for treatment. This singularity applies also to the moral behaviour which leads the handling of 'human materials'. The manufacturing of care in intensive care units thus invites us to grasp the socio-anthropological issues which the gradual opening of services to the public reveals a little more each day., Cette thèse sur la « fabrique des soins en réanimation » a pour ambition de montrer comment la prise en charge de patients « techniqués » relève d’une catégorisation à la fois sociologique et anthropologique. Partant d’une approche sociohistorique visant à retracer la constitution d’une médecine d’urgence et d’incertitude, il s’agit d’identifier les soubassements professionnels et les conditions d’émergence d’un segment soignant de réanimation. Cette approche conduit à interroger plus précisément l’évolution de ce segment dans le cadre de la modernisation de l’hôpital public. La prolifération normative engagée par les autorités publiques invite à reconsidérer des pratiques soignantes singulières aux prises avec l’incertitude médicale qui résulte de la prise en charge de patients dont le pronostic vital est engagé. Singulières au regard des patients admis dans les unités, les pratiques soignantes le sont aussi compte tenu des « routines de l’urgence » convoquées dans le contrôle du travail. Enfin, elles le sont également en raison des conduites morales qui commandent au maniement des « matériaux humains ». La fabrique des soins de réanimation invite ainsi à saisir les enjeux socioanthropologiques qui se dévoilent un peu plus chaque jour à travers l’ouverture progressive des services aux publics.

Thomas Hall, the mid-seventeenth-century minister at Kings Norton, Worcestershire, was an avid collector and reader of books. The article explores the evidence provided by his surviving books and library lists to analyse how he acquired his books, what types of books he collected and how he categorized them. It then investigates the books themselves to establish his reading and commonplacing practices, making particular use of his copious underlinings and marginal annotations. This reveals an emphasis on practical outcomes for his reading: in equipping him to understand Scripture, advance his pastoral ministry and provide him with material for the polemical works in which he sought to refute the ideas of the heretical sects that emerged in the 1640s and 1650s and advance what he saw as the cause of true religion. Throughout he displays a strong belief in the power of books to promote the struggle for godly reformation.

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International audience; Sessions jointes RT1 (Savoirs, travail, professions) et RT19 (Santé, Médecine, Maladie et Handicap).

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Introduction: CD20-TCB (RG6026) is a novel T-cell-engaging bispecific (TCB) antibody with a '2:1' molecular format that comprises two fragment antigen binding regions that bind CD20 (on the surface of B cells) and one that binds CD3 (on the surface of T cells). CD20-TCB offers the potential for increased tumor antigen avidity, rapid T-cell activation, and enhanced tumor cell killing versus other bispecific formats. The safety, tolerability, pharmacokinetics, biomarkers, and antitumor activity of CD20-TCB are currently being investigated in a multicenter Phase I dose-escalation trial (NP30179; NCT03075696). We recently presented preliminary clinical data demonstrating promising clinical activity in relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) patients with indolent or aggressive disease (Dickinson et al. ICML 2019). Here, we present preliminary blood and tissue biomarker analyses to explore modes of action, support optimal biological dose selection, and identify potential outcome predictors. Methods: For biomarker analyses, we performed immune profiling of peripheral blood by flow cytometry, analyzed plasma cytokine levels by ELISA, and characterized baseline and on-treatment tumor biopsies by immunohistochemistry/immunofluorescence assays and RNA sequencing. Biomarker data were obtained from 122 patients dosed with 0.005-25mg CD20-TCB. Results: CD20-TCB infusion led to a rapid and transient reduction in T cells in the peripheral circulation (T-cell margination) in all patients. T-cell margination reached nadir 6 hours after the first CD20-TCB infusion, and showed a strong association with CD20-TCB dose and receptor occupancy (RO%; as determined by Djebli et al. ASH 2019). Interestingly, rebound of T cells 160 hours after the first CD20-TCB infusion was associated with response to treatment. Responding patients showed long-term T-cell activation after the first infusion of CD20-TCB at doses from 0.6mg and above. T-cell activation was demonstrated by 2-4-fold elevation of T-cell activation markers such as Ki67, HLA-DR, PD-1, ICOS, OX40, and 4-1BB, which was sustained up to Cycle 5 (105 days). Analysis of paired pre- and on-treatment tumor biopsies (n=6) obtained before and 2-3 weeks after the first dose of CD20-TCB showed evidence of T-cell-mediated tumor cell killing. Analysis of archival and pre-treatment tumor biopsies (n=80) revealed that clinical responses were achieved irrespective of the amount of tumor T-cell infiltration at baseline. In contrast, preliminary baseline bulk tumor RNA sequencing data (n=46) showed upregulation of gene signatures associated with cell proliferation/Myc and T-cell subsets (effector vs exhausted-like) in non-responding patients. Conclusions: In this study, we demonstrated the mode of action of CD20-TCB, a novel bispecific antibody with promising clinical activity in R/R NHL. We also demonstrated that biomarker data on T-cell activation can support dose finding in conjunction with pharmacokinetics. Additional analysis is ongoing to evaluate response predictors and better characterize the population that will benefit most from T-cell mediated therapies. Disclosures Bröske: Roche: Employment, Equity Ownership. James:A4P Consulting Ltd: Consultancy. Belousov:Roche: Employment. Gomez:F. Hoffmann-La Roche Ltd: Employment. Canamero:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Ooi:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Grabole:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Wilson:F. Hoffmann-La Roche Ltd: Employment. Korfi:F. Hoffmann-La Roche Ltd: Consultancy. Kratochwil:F. Hoffmann-La Roche Ltd: Employment. Morcos:Roche: Employment, Equity Ownership. Ferlini:Roche: Employment, Equity Ownership. Thomas:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Dimier:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Moore:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Bacac:Roche: Employment, Equity Ownership, Patents & Royalties: Patents, including the one on CD20-TCB. Weisser:Pharma Research and Early Development Roche Innovation Center Munich: Employment, Equity Ownership, Patents & Royalties. Dickinson:Merck Sharpe and Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: CD20-TCB (also known as RG6026, RO7082859) is a full-length, fully humanized, immunoglobulin G1 (IgG1), T-cell-engaging bispecific antibody with two fragment antigen binding (Fab) regions that bind to CD20 (on the surface of B cells) and one that binds to CD3 (on the surface of T cells) (2:1 format). The 2:1 molecular format of CD20-TCB, which incorporates bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells, redirects endogenous non-specific T cells to engage and eliminate malignant B cells. CD20-TCB is an investigational agent.

CD20-TCB (RG6026) is a novel T-cell-engaging bispecific (TCB) antibody with a '2:1' molecular format comprising two fragment antigen binding regions that bind CD20 (on the surface of B cells) and one that binds CD3 (on the surface of T cells). CD20-TCB offers the potential for increased tumor antigen avidity, rapid T-cell activation, and enhanced tumor cell killing versus other bispecific formats, and the ability to combine with another CD20-targeted agent. Preclinical studies of concurrent therapy with CD20-TCB plus obinutuzumab (G) in diffuse large B-cell lymphoma (DLBCL) models demonstrate strong and sustained tumor regression driven by multiple mechanisms of action. These include induction of direct tumor cell death and antibody-dependent cellular cytotoxicity/cellular phagocytosis mediated by G, as well as recruitment of T-cells into the tumor and T-cell cytotoxicity mediated by CD20-TCB. NP30179 (NCT03075696) is a multicenter Phase I/Ib dose-escalation trial investigating the safety, tolerability, pharmacokinetics, biomarker responses, and anti-tumor activity (assessed by objective response rate [ORR] and complete response [CR] rate per modified Lugano 2014 criteria) of CD20-TCB in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) patients (pts). For the first time, we report preliminary data from Arm B, evaluating dual CD20-targeted therapy with concurrent CD20-TCB and G. All pts receive a single dose of 1000mg G as pre-treatment (Gpt) 7 days before the start of CD20-TCB therapy (Cycle 1) to mitigate cytokine release syndrome (CRS). From Cycle 2 onwards, 1000mg G is administered on the same day as CD20-TCB, which constitutes the start of an initial 28-day dose-limiting toxicity (DLT) window, in 3-weekly cycles. Pts receive escalating doses of CD20-TCB, guided by a model implementing the Bayesian continuous reassessment method with overdose control. As of May 22, 2019, a total of 28 pts with R/R aggressive (a) NHL (DLBCL/primary mediastinal large B-cell lymphoma/transformed follicular lymphoma [FL]/mantle cell lymphoma/Richter´s transformation; n=22) or FL (n=6) had received concurrent G in combination with CD20-TCB doses ranging from 0.6 to 16mg for 8-12 cycles. Median age was 65 years (range, 34-81), 15 (54%) were male, 19 (68%) were refractory to prior therapy, and median prior lines of therapy was 2 (range, 1-6). Twenty-three CRS events (according to Lee criteria, Lee et al. Blood 2014) occurred in 16 (57%) pts (maximum Grade [Gr]: Gr 1, 5 [18%]; Gr 2, 9 [32%]; Gr 3, 1 [4%]; Gr 4, 1 [4%]). CRS events were confined to Cycle 1 in all but two pts. Neurotoxicity was rare (Gr 1, 4 [14%]; Gr 2, 2 [7%]; Gr 3, 1 [4%]) and all events resolved. Apart from CRS, the most frequent adverse events were anemia (all Gr, 6 [21%]; Gr 3, 3 [11%]), thrombocytopenia (all Gr, 6 [21%]; Gr ≥3, 3 [11%]; no hemorrhages reported), neutropenia (all Gr, 4 [14%]; Gr ≥3, 3 [11%]), pyrexia (all Gr, 4 [14%], all Gr 1-2), and hypokalemia (all Gr, 4 [14%]; Gr ≥3, 1 [4%]). No DLTs were reported and no new safety signals were observed. The overall safety profile overlapped with that reported in the single arm of the same study. Twenty-one pts reached their first response assessment or withdrew early and were eligible for efficacy analysis. Overall, the ORR and CR rate by investigator assessment was 48% [10/21 pts] and 43% [9/21], respectively (aNHL: ORR, 38% [6/16]; CR, 31% [5/16]; FL: ORR and CR, 80% [4/5]). CD20-TCB exposure and receptor occupancy (RO%) increased dose-dependently across the investigated dose range, and consistent with the RO%-efficacy model (Djebli et al. ASH 2019), clinically relevant CD20-TCB RO% and increased clinical activity was observed at a dose of 16mg when combined with concurrent G. In the 16mg cohort that included 10 R/R pts, 70% of whom were refractory to prior therapy and median prior lines of therapy was 4, the ORR and CR rate were 90% (9/10 pts) and 80% (8/10), respectively (aNHL: CR, 71% [5/7]; FL: CR, 100% [3/3]), and all CRs were ongoing at the time of abstract submission. This is the first study to demonstrate that CD20-TCB can be safely combined with an anti-CD20 monoclonal antibody and further supports the promise of the '2:1' format for allowing combination therapy with therapeutic levels of other anti-CD20 antibodies, such as G. CD20-TCB plus G provides highly promising clinical activity in heavily pre-treated R/R B-cell NHL. Updated clinical and biomarker data will be presented. Disclosures Morschhauser: Janssen: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Carlo-Stella:AstraZeneca: Honoraria; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; Rhizen Pharmaceuticals: Research Funding; Boehringer Ingelheim: Consultancy; Novartis: Consultancy, Research Funding; Janssen Oncology: Honoraria; Takeda: Other: Travel, accommodations; Sanofi: Consultancy, Research Funding; Genenta Science srl: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Amgen: Honoraria; MSD: Honoraria; Janssen: Other: Travel, accommodations; Celgene: Research Funding; BMS: Honoraria. Salles:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; BMS: Honoraria; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Educational events. Hutchings:Janssen: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Celgene: Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Iacoboni:Celgene: Honoraria; Janssen: Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Honoraria; Roche: Honoraria. Sureda:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Gilead: Honoraria; Novartis: Honoraria. Crump:Servier: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Kite/Gilead: Consultancy. Martinez-Lopez:Novartis: Honoraria, Other: Advisory boards; Janssen: Honoraria, Other: Advisory boards and Non-Financial Support ; Incyte: Honoraria, Other: Advisory boards; VIVIA Biotech: Honoraria; Celgene: Honoraria, Other: Advisory boards and Non-Financial Support ; Amgen: Honoraria, Other: Non-Financial Support ; F. Hoffmann-La Roche Ltd: Honoraria; BMS: Honoraria, Other: Advisory boards. Thomas:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Morcos:Roche: Employment, Equity Ownership. Ferlini:Roche: Employment, Equity Ownership. Keelara:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Bröske:Roche: Employment, Equity Ownership. Bacac:Roche: Employment, Equity Ownership, Patents & Royalties: Patents, including the one on CD20-TCB. Dimier:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Moore:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Weisser:Pharma Research and Early Development Roche Innovation Center Munich: Employment, Equity Ownership, Patents & Royalties. Dickinson:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck Sharpe and Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: CD20-TCB (also known as RG6026, RO7082859) is a full-length, fully humanized, immunoglobulin G1 (IgG1), T-cell-engaging bispecific antibody with two fragment antigen binding ('Fab') regions that bind to CD20 (on the surface of B cells) and one that binds to CD3 (on the surface of T cells) (2:1 format). The 2:1 molecular format of CD20-TCB, which incorporates bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells, redirects endogenous non-specific T cells to engage and eliminate malignant B cells. CD20-TCB is an investigational agent.

Sous la direction de Isabelle Grand, Salvador Juan et Julien Vignet.Autre forme du titre du chapitre : La modernisation de l’hôpital public en France : l’idéal technocratique de normalisation. Ouvrage préparé et écrit par le GURVITCH, Groupe universitaire de recherche sur les valeurs et l'idéologie technocratiques, classe hégémonique.; International audience

Historians have often made negative judgements in assessing the pastoral role of Presbyterian clergymen during the English Revolution. Recent scholarship has posited a far more nuanced picture of their achievements at parish level, cautioning against taking their own gloomy polemic as factual evidence, and showing instances of progress and outright success alongside the well-known setbacks and failures. This study examines the pastoral ministry of Thomas Hall of Kings Norton, Worcestershire, a particularly rigid Presbyterian, showing his theory and, where possible, his practice of pastoral care. It reveals his endeavours, frustrations, successes and failures as he wholeheartedly embraced the challenge to bring about further Protestant reformation from the roots upwards. In contrast to much of the historiography, Hall’s ministry demonstrates that it was his Calvinist doctrine that drove his remarkably positive attitude and inclusive pastoral approach, while he considered his Presbyterian ecclesiolo...

Objective To evaluate the characteristics and outcomes of pediatric cochlear implant recipients diagnosed with Usher syndrome (US). Study design Retrospective study of consecutive pediatric cochlear implant recipients (1991-2010). Setting Tertiary care children's hospital. Patients Children who received a cochlear implant who were diagnosed with US either before or after implantation. Main outcome measures Electroretinography and ophthalmologic findings, cochlear anatomy based on preoperative imaging, age of independent ambulation, age at implantation, speech perception level, and communication method. Results Approximately 26 (3.7%) of 712 cochlear implant recipients were diagnosed with US based on the results of electroretinography and/or genetic testing. Preoperative imaging revealed no evidence of cochlear malformations. Average age of independent ambulation was 21.9 months (range, 12-30). Average age at implantation was 3.3 years (range, 6 mo to 11.6 yr). Mean follow-up after implantation was 7.8 years (range, 10 mo to 15.6 yr). Open-set speech perception was present in 92% of children, with use of a primarily oral communication mode in 69.2%. Conclusion In this large series of patients with the diagnosis of US who have undergone cochlear implantation, CT and MRI imaging were normal. Significant delay in independent ambulation was present in this population secondary to abnormal vestibular function associated with US Type I. A majority of children developed significant open-set speech perception and oral communication skills. Implantation of US children provides them with the opportunity to develop useful hearing and oral communication.

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International audience; " Là, quand les gens s'effondrent devant toi, tu as envie de pleurer avec eux... ". Le travail émotionnel des soignant-e-s enréanimation.

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Several authors proposed that all elements of Beck's cognitive triad (1976) mediate the associations between inference style as described in the hopelessness model (Abramson, Alloy, & Metalsky, 1989) and depressive symptoms. Results of a 3-wave longitudinal study indicate only a partial mediation model with all elements of the cognitive triad being associated with all inference styles, with depressive symptoms fitting the data best. Controlling for direct and indirect effects, no individual element of the cognitive triad mediates the association between inference styles and depressive symptoms. The partial mediation model is not stable across sex or clinical vs subclinical samples. In general, the data supports the integration of all three elements of the cognitive triad into the hopelessness model.

Caloric restriction (CR) slows aging in many species and protects some animals from age-related hearing loss (ARHL), but the effect on humans is not yet known. Because rhesus monkeys are long-lived primates that are phylogenically closer to humans than other research animals are, they provide a better model for studying the effects of CR in aging and ARHL. Subjects were from the pool of 55 rhesus monkeys aged 15-28 years who had been in the Wisconsin study on CR and aging for 8-13.5 years. Distortion product otoacoustic emissions (DPOAE) with f2 frequencies from 2211 to 8837 Hz and auditory brainstem response (ABR) thresholds from clicks and 8, 16, and 32 kHz tone bursts were obtained. DPOAE levels declined linearly at approximately 1 dB/year, but that rate doubled for the highest frequencies in the oldest monkeys. There were no interactions for diet condition or sex. ABR thresholds to clicks and tone bursts showed increases with aging. Borderline significance was shown for diet in the thresholds at 8 kHz stimuli, with monkeys on caloric restriction having lower thresholds. Because the rhesus monkeys have a maximum longevity of 40 years, the full benefits of CR may not yet be realized.

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Importance Randomized clinical trials are needed to compare effectiveness and cost-effectiveness of different low-vision (LV) programs. Objective To determine the value of adding LV rehabilitation with a therapist compared with LV services without intervention. Design, Setting, and Participants A randomized clinical trial was conducted from September 27, 2010, to July 31, 2014, of 323 veterans with macular diseases and best-corrected distance visual acuity (BCDVAbetter-eye) of 20/50 to 20/200. Masked interviewers administered questionnaires by telephone before and after LV treatment. Using an intention-to-treat design, participants were randomized to receive LV devices with no therapy or LV devices with a rehabilitation therapist providing instruction and homework on the use of LV devices, eccentric viewing, and environmental modification. Visual ability was measured in dimensionless log odds units (logits) (0.14-logit change in visual ability corresponds to ability change expected from a 1-line change in visual acuity). Interventions Low-vision devices without therapy and LV devices with therapy. Main Outcomes and Measures Comparison of changes (baseline to 4 months) in overall visual ability and in 4 functional domains (reading, visual information, visual motor, and mobility) estimated from responses to the Veterans Affairs Low Vision Visual Functioning Questionnaire (higher scores indicates more ability or less difficulty in performing activities), and comparison of MNREAD changes (baseline to end of treatment) in maximum reading speed, critical print size, and reading acuity (higher number indicates lower visual acuity). Results Of the 323 participants, 314 were male (97.2%); mean (SD) age, 80 (10.5) years. Basic LV was effective in improving visual ability. However, the LV rehabilitation group improved more in all visual function domains except mobility. Differences were 0.34-logit reading (95% CI, 0.0005 to 0.69; P = .05), 0.27-logit visual information (95% CI, 0.01 to 0.53; P = .04), 0.37-logit visual motor (95% CI, 0.08 to 0.66; P = .01), and 0.27-logit overall (95% CI, 0.06 to 0.49; P = .01). For MNREAD measures, there was more improvement in reading acuity (difference, −0.11 logMAR, 95% CI, −0.15 to −0.07; P P = .005), but not critical print size for the LV rehabilitation group (−0.06 logMAR; 95% CI, −0.12 to 0.002; P = .06). In stratified analyses, the LV rehabilitation group with BCDVAbetter-eye worse than 20/63 to 20/200 improved more in visual ability (reading, visual motor, and overall). Differences were 0.56-logit reading ability (95% CI, 0.08-1.04; P = .02), 0.40-logit visual motor (95% CI, 0.03-0.78; P = .04), 0.34-logit overall (95% CI, 0.06-0.62; P = .02). There was no significant difference between treatment groups for those with BCDVAbetter-eye of 20/50 to 20/63. Conclusions and Relevance Both basic LV alone and combined with LV rehabilitation were effective, but the added LV rehabilitation increased the effect only for patients with BCDVAbetter-eye worse than 20/63 to 20/200. Basic LV services may be sufficient for most LV patients with mild visual impairment. Trial Registration clinicaltrials.gov Identifier:NCT00958360

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Introduction: Sickle cell disease (SCD) is an inherited disorder of red cells complicated by acute vaso-occlusion (VOC) and chronic organ damage in adults leading to a shortened lifespan. Improved management of SCD patients has resulted in increasing life expectancy so that the prevalence of malignancy in patients with SCD may be increasing. Patients with SCD often have comorbidities related to their disease that may limit their ability to receive cancer treatments and result in worse outcomes. Available literature describing cancer in SCD patients is limited to case reports and small retrospective reviews. This study describes a cohort of adult patients with SCD with a malignancy and the effect on their SCD. Methods: The Adult Hemoglobinopathy Resource Center at Washington University has provided care for adult SCD patients throughout the St. Louis, Missouri metropolitan area since 1990. All patients have confirmed SCD (Hgb SS, Hgb SC, Hgb Sβ+, Hgb Sβ0, Hgb SC Harlem, Hgb S Other) and have been seen at least once since 2011 or are known to have died were included in this study. A retrospective chart review of these SCD patients was conducted and medical records were reviewed for malignancies. Demographic data and SCD history included: gender, SCD genotype, baseline Hgb, and hydroxyurea use. Cancer treatment history data included: age at and date of diagnosis, cancer screening, type and stage of malignancy, date and cause of death, complications of cancer treatments, and the number of hospitalizations/emergency departments visits for VOC in the year before and after cancer diagnosis. Categorical variables were analyzed using Fisher's exact test and continuous variable analyzed using student t-test. Patients were grouped into Hgb SS and non-Hgb SS for analysis to explore differences in outcomes. Overall survival (OS) was calculated based on date of diagnosis to date of death or censored at July 7, 2016. Commonly cited oncology literature was reviewed for the median OS for each malignancy based on stage. Each patient's actual survival was compared to the expected median OS for their respective malignancy. OS was classified as better or worse if actual survival time was at least equivalent to or shorter than cited median OS, respectively. Results: From October 2011 to December 2015, 397 patients have been evaluated and 15 are known to have died. Of the surviving patients, the mean age is 35 yrs (range 18-76); 199 are female (52.1%), and 183 are male (47.9%). The hemoglobinopathies include SS-245, SC-106, Sβ+-24, Sβ0-5, SC Harlem-1, and unconfirmed-1. Overall, 85 patients have died since 1994. Eleven patients (Hgb SS-6, Hgb SC-3 and Hgb Sβ+-2) were found to have diagnoses of twelve malignancies. The diagnoses and number of patients include non-small cell lung-3, breast-2, and one each of germ cell tumor, Hodgkin lymphoma, colon, and papillary thyroid, extra-adrenal metastatic paraganglioma, tongue base squamous cell and prostate cancers. The incidence of malignancy in our cohort was 2.3% and the median age at cancer diagnosis was 41.8 yrs (range 19-68). Patients with Hgb SS trended towards having cancer diagnosed at a later age compared to non-Hgb SS patients (ages 52.3 vs 35.8 yrs respectively, p=0.1). Hgb SS patients had a lower baseline Hgb (p=0.00005) and higher frequency of hydroxyurea use (p=0.012) compared to non-Hgb SS patients at the time of cancer diagnosis. The median OS of patients was at least equivalent to expected OS in 2 out of 6 patients with Hgb SS and 4 out of 5 patients non-Hgb SS disease (p=0.16). Initial therapy consisted of surgery (5), radiation therapy (3, 1 curative and 2 palliative intent) and chemotherapy (4). Chemotherapy was indicated as standard of care but not administered to 4 patients secondary to comorbidities. There was no significant difference in VOC/year in the year before compared to the year after cancer diagnosis. Malignancy was identified by age appropriate cancer screening in 3 out of 4 applicable patients. Conclusions: In adults with SCD, malignancy occurred in 2.3% of patients over about 25yrs. There was not an observed increase in pain crises requiring in-hospital or emergency department evaluations after cancer diagnosis. Patients with SCD should complete age appropriate cancer screening for early detection. There is a modest trend towards worse outcomes for patients with Hgb SS disease compared to the general population and compared to Hgb SC/Sβ+. Disclosures Blinder: CSL Behring: Honoraria; Novartis: Honoraria; Janssen: Honoraria.

Summary Eating disorders have both psychological and physiological elements and so require treatment that combines expertise in both. Professionals who treat patients with an eating disorder need to have knowledge of the nutritional effects and physiological consequences of the illness. This is rare within a predominantly mental health setting. The extreme dieting behaviour in anorexia nervosa leading to the severe weight loss and symptoms of semi-starvation; binge-eating behaviour, seen in cases in bulimia nervosa and binge eating disorder; and the patient’s distorted beliefs about nutrition and dietary requirements all underpin the need for the expertise provided by dietitians. They now have an essential role within the multi-disciplinary assessment and treatment programmes for all three major eating disorders.