Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease.

Primary Sjögren disease (pSD) is an autoimmune disease characterized by lymphoid infiltration of exocrine glands leading to dryness of the mucosal surfaces and by the production of autoantibodies. The pathophysiology of pSD remains elusive and no treatment with demonstrated efficacy is available yet. To better understand the biology underlying pSD heterogeneity, we aimed at identifying Consensus gene Modules (CMs) that summarize the high-dimensional transcriptomic data of whole blood samples in pSD patients. We performed unsupervised gene classification on four data sets and identified thirteen CMs. We annotated and interpreted each of these CMs as corresponding to cell type abundances or biological functions by using gene set enrichment analyses and transcriptomic profiles of sorted blood cell subsets. Correlation with independently measured cell type abundances by flow cytometry confirmed these annotations. We used these CMs to reconcile previously proposed patient stratifications of pSD. Importantly, we showed that the expression of modules representing lymphocytes and erythrocytes before treatment initiation is associated with response to hydroxychloroquine and leflunomide combination therapy in a clinical trial. These consensus modules will help the identification and translation of blood-based predictive biomarkers for the treatment of pSD.

How external and agency characteristics are related to coordination in homecare - findings of the national multicenter, cross-sectional SPOTnat study.

BACKGROUND: Homecare client services are often distributed across several interdependent healthcare providers, making proper care coordination essential. However, as studies exploring care coordination in the homecare setting are scarce, serious knowledge gaps exist regarding how various factors influence coordination in this care sector. To fill such gaps, this study's central aim was to explore how external factors (i.e., financial and regulatory mechanisms) and homecare agency characteristics (i.e., work environment, workforce, and client characteristics) are related to care coordination in homecare. METHODS: This analysis was part of a national multicentre, cross-sectional study in the Swiss homecare setting that included a stratified random sample of 88 Swiss homecare agencies. Data were collected between January and September 2021 through agency and employee questionnaires. Using our newly developed care coordination framework, COORA, we modelled our variables to assess the relevant components of care coordination on the structural, process, and outcome levels. We conducted both descriptive and multilevel regression analyses-with the latter adjusting for dependencies within agencies-to explore which key factors are associated with coordination. RESULTS: The final sample size consisted of 1450 employees of 71 homecare agencies. We found that one explicit coordination mechanism ("communication and information exchange" (beta = 0.10, p <.001)) and four implicit coordination mechanisms-"knowledge of the health system" (beta = -0.07, p <.01), "role clarity" (beta = 0.07, p <.001), "mutual respect and trust" (beta = 0.07, p <.001), and "accountability, predictability, common perspective" (beta = 0.19, p <.001)-were significantly positively associated with employee-perceived coordination. We also found that the effects of agency characteristics and external factors were mediated through coordination processes. CONCLUSION: Implicit coordination mechanisms, which enable and enhance team communication, require closer examination. While developing strategies to strengthen implicit mechanisms, the involvement of the entire care team is vital to create structures (i.e., explicit mechanisms) that enable communication and information exchange. Appropriate coordination processes seem to mitigate the association between staffing and coordination. This suggests that they support coordination even when workload and overtime are higher.