Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial

ContextWhile oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans.MethodsIn this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges.DiscussionThis is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials

Une intervention en centres d’hébergement et de soins de longue durée visant à réduire les problèmes de santé mentale liés au travail

Une intervention visant la diminution des contraintes de l’environnement psychosocial du travail et de leurs effets sur la santé mentale a été mise en place à l’hiver 2002. Cette intervention se résume en cinq étapes : l’engagement du milieu et la constitution d’une équipe d’intervention, l’identification des contraintes, l’élaboration des plans d’action, l’actualisation des plans d’action et l’évaluation de l’intervention. La recherche se déroule dans douze centres d’hébergement et de soins de longue durée (CHSLD) et inclut l’ensemble du personnel soignant en contact direct avec la clientèle (N = 493). Un devis quasi-expérimental avec quatre groupes expérimentaux, huit groupes témoins et des mesures avant et après l’intervention a été utilisé.La description des phases de développement et d’implantation de la démarche d’intervention est présentée ainsi que l’évaluation à 12 mois des effets de l’intervention sur la prévalence des contraintes psychosociales au travail et des problèmes de santé mentale.An intervention aimed at reducing adverse occupational psychosocial factors and their mental health effects was begun during the winter of 2002. This intervention can be summarized in five steps: commitment of stakeholders and setting up of an intervention team, identification of adverse occupational psychosocial factors, development of an action plan, implementation of the action plans, and evaluation of the intervention. The study was conducted in twelve residential and extended care centres (CHSLD) and included all care-giving staff in direct contact with patients (N= 493). A quasi-experimental design was used with four experimental groups and eight control groups, and with pre- and post-intervention measurements.The description of the intervention’s development and implementation phases and the evaluation at 12 months of the effects of the intervention on the prevalence of occupational psychosocial factors and mental health problems are presented.En el invierno 2002 se ha establecido una intervención con objetivo de disminuir las coacciones del ambiente psicosocial del trabajo y de sus efectos sobre la salud mental. Esta intervención se resume en cinco etapas : la compromisión del medio y la constitución de un equipo de intervención, la identificación de las coacciones, la elaboración de los planes de acción, la actualización de los planes de acción y la evaluación de la intervención. La investigación se desarolla en doce centros de alojamiento y de cuidados a largo plazo (CHSLD) e incluye el conjunto del personal sanitario en contacto directo con la clientela (N= 493). Un presupuesto casi experimental de cuatro grupos experimentales, ocho grupos de control y medidas pre and post-intervención fueron utilizados.La descripción de las fases de desarrollo y de implantación de los trámites de intervención están presentados así como la evaluación después de 12 meses de los efectos de la intervención sobre la prevalencia de las coacciones psicosociales en el trabajo y de los problemas de salud mental

Effect of the nanoparticle synthesis method on dendronized iron oxides as MRI contrast agents

Équipe 401 : Nanomatériaux pour la vie et développement durableInternational audienceAqueous suspensions of dendronized iron oxide nanoparticles (NPs) have been obtained after functionalization, with two types of dendrons, of NPs synthesized either by coprecipitation (leading to naked NPs in water) or by thermal decomposition (NPs in situ coated by oleic acid in an organic solvent). Different grafting strategies have been optimized depending on the NPs synthetic method. The size distribution, the colloidal stability in isoosmolar media, the surface complex nature as well as the preliminary biokinetic studies performed with optical imaging, and the contrast enhancement properties evaluated through in vitro and in vivo MRI experiments, have been compared as a function of the nature of both dendrons and NPs. All functionalized NPs displayed good colloidal stability in water, however the ones bearing a peripheral carboxylic acid function gave the best results in isoosmolar media. Whereas the grafting rates were similar, the nature of the surface complex depended on the NPs synthetic method. The in vitro contrast enhancement properties were better than commercial products, with a better performance of the NPs synthesized by coprecipitation. On the other hand, the NPs synthesized by thermal decomposition were more efficient in vivo. Furthermore, they both displayed good biodistribution with renal and hepatobiliary elimination pathways and no consistent RES uptake

Correction to: Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy

An amendment to this paper has been published and can be accessed via the original article