93 research outputs found
Comment les médecins généralistes de la Communauté Urbaine du Mans suivent-ils les grossesses des patientes qu'ils définissent à risque par leurs caractéristiques psycho-socio-économiques?
La précarité constitue un risque pour les grossesses. Les médecins généralistes sont directement impliqués dans leur dépistage et leur prise en charge. Quelle est leur définition des femmes à risque psycho-socio-économique et comment les suivent-ils? Quels sont les freins à leurs interventions? Comment proposent-ils de les perfectionner? Nous avons réalisé une étude qualitative auprès de 15 médecins de la Communauté Urbaine du Mans choisis pour un échantillonnage en variation maximale. Les entretiens, semi-structurés, ont été retranscrits, doublement codés et analysés sous forme thématique. Ils retenaient les critères habituels de la littérature, et en citaient de nouveaux : la fragilité du conjoint ou du couple, le placement des enfants, la notion de plusieurs pères dans une fratrie, ou la femme de moins de 17 ans immature, isolée ou déscolarisée. Ils citaient les situations de violence conjugale en notant qu elles leur échappaient sûrement. Leurs attitudes étaient élaborées et précisaient le cadre des recommandations. Leur suivi était plus cadré, soutenant et basé sur une relation de confiance. Ils préconisaient l entretien prénatal précoce. Ils travaillaient avec les autres intervenants du secteur médico-social et coordonnaient le suivi. Leurs interventions étaient limitées dans les situations d addiction, les contextes où les habitudes culturelles étaient très présentes et les mineures isolées. L établissement du lien avec les autres professionnels était souvent difficile. Ils proposaient alors des perspectives telles qu un carnet d adresse, une facilité dans la prise des rendez-vous et pourquoi pas la création d une PASS dédiée à la périnatalité.The precariousness constitutes a risk for the pregnancies. The general practitioners are directly involved in their screenings and their cares. What is the definition about psychology and socioeconomic risks for women. How do they follow them? Which are brakes in their interventions? How they propose to improve them? We realized a qualitative study with 15 doctors of the Urban Community of Le Mans, chosen in a sample with a lot of diversity. The interviews, semi-structured, were retranscribed, doubling coded and analyzed under thematic shape.They retained the usual criteria of the literature, and quoted from new: the fragility of the spouse or the couple, the placement of the children, the notion of several fathers in a sibship, or the immature woman of less than 17 years, alone or without school. They quoted the situations of conjugal violence by noting that they escaped them certainly. Their attitudes were elaborated and specified the executive of the recommendations. Their follow-up was more centred, supported and based on a relationship of trust. They recommended the early antenatal interview. They worked with the other participants of the medical and social sector and coordinated the follow-up. Their interventions were limited in the situations of addictions, the contexts where the cultural habits were very present and the isolated minors. The establishment of the link with the other professionals was often difficult. They proposed then perspectives such as an address book, an ease in the made an appointment and why not the creation of one PASS dedicated to the perinatal period.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF
Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma.
Multiple myeloma (MM) is an incurable cancer characterized by the proliferation and accumulation of monoclonal plasma cells in the bone marrow. The monoclonal anti-CD38 daratumumab has taken a central place in the different treatment regimens for newly diagnosed and relapsed, refractory myeloma. In this study, we correlated the NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and potential fratricide induced by daratumumab with CD38-expression levels on both effector and target cells. We show that CD38 expression can be modulated by adding all-trans retinoic acid (ATRA) or interferon-α to MM cells to further fine-tune these effects. In addition, we observed that ADCC becomes inefficient when fratricide occurs and both ADCC and fratricide depend on the balance between CD38 expression on effector and target cells. However, the addition of adjuvants (retinoic acid or interferon-α) to myeloma cells or the inhibition of fratricide using a CD38-blocking nanobody on NK-cells can reverse this balance towards ADCC and thus promote lysis of target cells by ADCC. ATRA and interferon-α increased the CD38 expression at the surface of MM cells about three-fold and two-fold, respectively. This increase was of interest for MM cells with low CD38 expression, that became susceptible to daratumumab-mediated ADCC after preincubation. A CD38-blocking nanobody prevented the binding of daratumumab to these NK-cells and blunted the fratricidal effect on effector NK cells. In conclusion, our study highlights the importance of a balanced CD38 expression on target and effector cells and attempts to alter this balance will affect the susceptibility of MM cells towards daratumumab-mediated ADCC
GOLIAH (Gaming Open Library for Intervention in Autism at Home): a 6-month single blind matched controlled exploratory study
BackgroundTo meet the required hours of intensive intervention for treating children with autism spectrum disorder (ASD), we developed an automated serious gaming platform (11 games) to deliver intervention at home (GOLIAH) by mapping the imitation and joint attention (JA) subset of age-adapted stimuli from the Early Start Denver Model (ESDM) intervention. Here, we report the results of a 6-month matched controlled exploratory study.MethodsFrom two specialized clinics, we included 14 children (age range 5–8 years) with ASD and 10 controls matched for gender, age, sites, and treatment as usual (TAU). Participants from the experimental group received in addition to TAU four 30-min sessions with GOLIAH per week at home and one at hospital for 6 months. Statistics were performed using Linear Mixed Models.ResultsChildren and parents participated in 40% of the planned sessions. They were able to use the 11 games, and participants trained with GOLIAH improved time to perform the task in most JA games and imitation scores in most imitation games. GOLIAH intervention did not affect Parental Stress Index scores. At end-point, we found in both groups a significant improvement for Autism Diagnostic Observation Schedule scores, Vineland socialization score, Parental Stress Index total score, and Child Behavior Checklist internalizing, externalizing and total problems. However, we found no significant change for by time × group interaction.ConclusionsDespite the lack of superiority of TAU + GOLIAH versus TAU, the results are interesting both in terms of changes by using the gaming platform and lack of parental stress increase. A large randomized controlled trial with younger participants (who are the core target of ESDM model) is now discussed. This should be facilitated by computing GOLIAH for a web platform.Trial registration Clinicaltrials.gov NCT0256041
The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report
The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities
Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials
Background
Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response.
Methods
We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab.
Findings
In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.
Interpretation
Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.
Funding
UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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