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

Dites-le avec des fleurs

Comment l’anthropologie construit-elle ses objets lorsque ceux-ci, comme la fleur, sont investis de représentations plus qu’ils n’en sont le support ? Lorsqu’ils sont des productions sociales originales dans lesquelles s’enchevêtrent des enjeux autant territoriaux, politiques, identitaires qu’idéologiques ou symboliques ? La fleur, appréhendée ici comme un révélateur d’une diversité d’approches, invite non seulement à une plongée au cœur de problématiques associées à l’environnement, mais surtout elle offre un bouquet de développements anthropologiques contemporains, où se reflète autant la vitalité de la discipline que la fécondité de démarches interdisciplinaires. L’apport décisif de l’anthropologie tient in fine dans sa faculté de re-totaliser son objet dans des univers de sens articulés

Anthropologie et eau(x)

L’eau est l’une des ressources qui a la capacité de lier différents domaines du social : le rapport à la nature et au milieu, l’organisation du territoire, les institutions, les relations de pouvoir, les systèmes de valeurs et les identités. Étudier l’eau signifie appréhender, à partir de l’appropriation d’une ressource, les réseaux sociaux, économiques, politiques, culturels ainsi que les formes de dépendance, d’exclusion, de solidarité ou de conflit. Au-delà de l’apparente « naturalité » de l’eau, bien d’autres dynamiques se cachent derrière la gestion hydraulique. Ce dossier s’attache à montrer les apports divers de la recherche en anthropologie sur l’eau. L’eau est appréhendée comme un médiateur relationnel, ce qui en fait un objet heuristique de l’enquête ethnologique alimentant une réflexion globale sur les dynamiques sociales dans le monde contemporain

Reply to the comment of Brinster et al. “Acquired hemophilia, rheumatoid arthritis, and TNFα antagonists”

Comment on:- Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid arthritis. [Joint Bone Spine. 2015]- Acquired hemophilia, rheumatoid arthritis, and TNFα antagonists: Comment on the article "Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid arthritis" by Banse et al., Joint Bone Spine 2015;82:200-2. [Joint Bone Spine. 2015]International audienceCorrespondanc

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6.35 years (SD 4.50) were included. The incidence of perioperative severe critical events was 5.2% (95% CI 5.0-5.5) with an incidence of respiratory critical events of 3.1% (2.9-3.3). Cardiovascular instability occurred in 1.9% (1.7-2.1), with an immediate poor outcome in 5.4% (3.7-7.5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0.88, 95% CI 0.86-0.90; p<0.0001), medical history, and physical condition (1.60, 1.40-1.82; p<0.0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0.99, 0.981-0.997; p<0.0048 for respiratory critical events, and 0.98, 0.97-0.99; p=0.0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia