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

Author

Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan-Fai, Gottenberg, Jacques-Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, and Becht, Etienne

Published
2024
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4. Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, Becht, Etienne, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, and Becht, Etienne

Published
2024

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

Author

Möckli, Nathalie, Simon, Michael, Denhaerynck, Kris, Trutschel, Diana, Martins, Tania, Meyer-Massetti, Carla, and Zúñiga, Franziska

Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Variability of Primary Sjögren's Syndrome Is Driven by Interferon α and Interferon α Blood Levels Are Associated With the Class II HLA–DQ Locus

Author

Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Celine, Charbit, Bruno, Thorball, Christian W., Jonsson, Roland, Lessard, Christopher J., Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Hélène, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl A., Appel, Silke, Tarn, Jessica R., Quintana‐Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, Gottenberg, Jacques Eric, Dernis, Emmanuelle, Devauchelle‐Pensec, Valerie, Dieude, Philippe, Dubost, Jean‐Jacques, Fauchais, Anne‐Laure, Goeb, Vincent, Hachulla, Eric, Hatron, Pierre Yves, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Salliot, Carinne, Rist, Stephanie, Saraux, Alain, Vittecoq, Olivier, Nocturne, Gaétane, Ravaud, Philippe, Seror, Raphaèle, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Astrom, Kalla, Bousso, Philippe, Bruhns, Pierre, Cumano, Ana, Demangel, Caroline, Deriano, Ludovic, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gelpi, Odile, GompertsBoneca, Ivo, Hasan, Milena, Hercberg, Serge, Lantz, Olivier, Leclerc, Claude, Mouquet, Hugo, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Shorte, Spencer, Soumelis, Vassili, Tangy, Frédéric, Tartour, Eric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie‐Noëlle, Albert, Matthew L., Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie Translationnelle - Translational Immunology lab, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Lausanne University Hospital, University of Bergen (UiB), Oklahoma Medical Research Foundation (OMRF), University of Oklahoma Health Sciences Center (OUHSC), Université de Strasbourg (UNISTRA), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biogen Inc. [Cambridge, MA, USA], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) (grant 806975). The JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Unionand the European Federation of Pharmaceutical Industries and Associations. This work was also supported by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal Skin Disease grant R01-AR-065953). The Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome(ASSESS) national multicenter prospective cohort was formed in 2006 with aFrench Ministry of Health grant (Programme Hospitalier de Recherche Clinique 2005 P060228). The ASSESS cohort is promoted by the French Society of Rheumatology and receives research grants from the French Society of Rheumatology. Dr. Gottenberg’s work was supported by Bristol Myers Squibbfor transcriptomic analysis of the ASSESS and Norwegian cohorts and by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögrenet des syndromes secs). Drs. Trutschel’s and Schwikowski’s work was supported by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs)., Milieu Intérieur Consortium, ASSESS study investigators, and NECESSITY Consortium: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle Seror, Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Odile Gelpi, Ivo GompertsBoneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L Albert, Darragh Duffy, Lluis Quintana-Murci., European Project: 806975,NECESSITY, Clauss, Isabelle, and NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID

Subjects
Proteomics, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's Syndrome, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, HLA-DQ Antigens, Immunology, Humans, Interferon-alpha, Immunology and Allergy, Prospective Studies
Abstract

Objective: Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS. Methods: We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa). Results: Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA–DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells. Conclusion: We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms., Arthritis & Rheumatology, 74 (12), ISSN:2326-5191, ISSN:2326-5205

Published
2022
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15. Positive effect of the INTERCARE nurse‐led model on reducing nursing home transfers: A nonrandomized stepped‐wedge design

Author

Zúñiga, Franziska, primary, Guerbaai, Raphaëlle‐Ashley, additional, Geest, Sabina, additional, Popejoy, Lori L., additional, Bartakova, Jana, additional, Denhaerynck, Kris, additional, Trutschel, Diana, additional, Basinska, Kornelia, additional, Nicca, Dunja, additional, Kressig, Reto W., additional, Zeller, Andreas, additional, Wellens, Nathalie I. H., additional, Pietro, Carlo, additional, Desmedt, Mario, additional, Serdaly, Christine, additional, and Simon, Michael, additional

Published
2022
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19. Organisationale Interventionen zur Förderung der Personen-zentrierten Pflege von Menschen mit Demenz - Studienprotokoll einer systematischen Übersichtsarbeit

Author

Dichter, Martin Nikolaus, Reuther, Sven, Trutschel, Diana, Köpke, Sascha, and Halek, Margareta

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund/Fragestellung: Leitlinien empfehlen psychosoziale Interventionen als Strategien in der Pflege von Menschen mit Demenz. Ein vielversprechender und international empfohlener Ansatz sind organisationale Interventionen zur Person-zentrierte Pflege von Menschen mit Demenz. Diesen wird eine[zum vollständigen Text gelangen Sie über die oben angegebene URL], EbM und Digitale Transformation in der Medizin; 20. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

Published
2019
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20. Multivariate statistical methods to analyse multidimensional data in applied life science : [kumulative Dissertation]

Author

Trutschel, Diana

Abstract

Angewandte Lebenswissenschaften benötigen computergestützte Methoden, insbesondere seitdem die Komplexizität der Daten zunimmt. Für die Datenanalyse ist es wichtig, Studien durchdacht zu konzipieren und geeignete Methoden für die Analyse zu wählen, um valide Ergebnisse für wissenschaftliche Entscheidungen zu erhalten. Benutzerfreundliche Programme, die komplizierte Methoden aufbereiten und zugänglich machen, sind dabei unverzichtbar geworden. Der Fokus dieser Dissertation liegt auf der methodologischen Erarbeitung solcher Verfahren und deren Anwendung bei der Analyse von Daten in realen Studien. Die Herausforderungen werden am Beispiel von zwei Lebenswissenschaften aufgezeigt: Metabolomik, eine Schlüsseldisziplin in der Systembiologie, und Gesundheitsversorgung mit dem Teilbereich Pflegewissenschaft. Obwohl beide Wissenschaften verschiedene Fragestellungen zu beantworten versuchen, sind die methodische Vorgehensweise ebenso wie die mathematischen Lösungsansätze ähnlich und die Daten werden häufig mit Hilfe von multivariaten Methoden untersucht., Applied life sciences require computational methods, especially, since the complexity of data has grown. For data analysis carefully designed studies and appropriate methods are important to make conclusions on basis of valid results. User-friendly applications to make difficult methods available for practitioners are essential. In this thesis the focus is on a methodological point of view as well as showing the application of provided methods in analysing data of real studies. The challenges are shown within two applied life sciences: metabolomics, a key discipline in system biology, and Nursing science as one part of health care. Both scientific fields have their own research questions with different aims. But no matter how different the research question and apparent data characteristics are, patterns within solutions reoccur and often requires multivariate methods for the data analysis.

Published
2019
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21. REDEZEIT: Praktikabilität und Effektivität von sozialer Unterstützung für pflegende Angehörige via Telefon - eine randomisiert kontrollierte Studie

Author

Dichter, Martin N., Albers, Bernd, Trutschel, Diana, Katharina, Wermke, Seismann-Petersen, Swantje, Halek, Margareta, and Berwig, Martin

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund und Fragestellung: Bei einer geschätzten Inzidenz von 1.9% leben mehr als eine Millionen Menschen mit einer Demenz (MmD) in Deutschland [ref:1]. Im Fall von Pflegebedürftigkeit übernehmen pflegende Angehörige den größten Teil der Pflege von MmD[zum vollständigen Text gelangen Sie über die oben angegebene URL], Brücken bauen – von der Evidenz zum Patientenwohl; 19. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

Published
2018

24. Providing an R-package for sampling cluster randomized trails data to show the impact of implementation errors on effect estimation within stepped wedge design studies

Author

Trutschel, Diana, Reuther, Sven, Holle, Daniela, and Verde, Pablo Emilio

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: A simulation can be a tool to explore methodological challenges of used study designs or data analysing methods. Here, we provide an R-package for sampling multidimensional distributed data within cluster randomized trails, for stepped wedge design (SWD) trails as well as cross-over and[for full text, please go to the a.m. URL], 16. Deutscher Kongress für Versorgungsforschung (DKVF)

Published
2017
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26. Die Auswirkung von Kontaminationen auf die Schätzung von Interventionseffekten in Crossover Stepped-Wedge-Designs - Ergebnisse einer Computer Simulation in R

Author

Reuther, Sven, Trutschel, Diana, Halek, Margareta, Bartholomeyczik, Sabine, and Verde, Pablo Emilie

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund und Fragestellung: Das Design einer Stepped-Wedge-cluster randomisierten Studie (SWD) ist eine besondere Form des Cross-Over Designs, das vermehrt in der Versorgungsforschung angewendet wird, um die Effektivität von Interventionen zu untersuchen (Leontjevas et al. 2013; Zwijsen et al.[zum vollständigen Text gelangen Sie über die oben angegebene URL], Gemeinsam informiert entscheiden; 17. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin

Published
2016

30. PS02.08: Differences regarding the provision of caseconferences in dementia- specialized versusnon-specialized care units: Results from across-sectional study

Author

Palm, Rebecca, Trutschel, Diana, Simon, Michael, Bartholomeyczik, Sabine, and Holle, Bernhard

Subjects
ddc:610
Abstract

Background: The aim of dementia-specializedcare units (DSCUs) is to provide high qualitycare for residents with dementia and severechallenging behavior in nursing homes. In GermanyDSCUs receive additional funding to finance higherstaffing ratios and implement dementia specificcare interventions. One of these interventions iscase conferences, a measure to develop a commonunderstanding of the case. They are an importantprerequisite for planning, providing and evaluatingtailor-made interventions. Because of their betterresources, we expect that DSCUs provide caseconferences more often than non-DSCUs.

Published
2015

31. PS01.35: Defining the delayed treatment effect ofdementia specific case conferences in nursinghomes – new territory in mixed method research

Author

Holle, Daniela, Reuther, Sven, Roes, Martina, Graf, Rabea, Segschneider-Rosier, Ute, Trutschel, Diana, and Halek, Margareta

Subjects
ddc:610
Abstract

Objective: Measuring the effect of psychosocialintervention in dementia research is often a challenge because researchers must address complexinterventions and heterogeneous care settings.The ongoing FallDem-study is a stepped-wedged,cluster randomized controlled trial evaluatingthe effect of dementia specific case conferences(DSCC) in 12 nursing homes (Reuther et al. 2014;Holle et al. 2014). Due to the complexity of aDSCC it can be expected that the treatment effectdoesn´t reach 100% effectiveness at the start ofthe intervention. Nursing staff must learn how toconduct DSCC and time is necessary to adopt thepractice to the new knowledge. As such a delayin treatment effect has a great influence on theestimation of the effect size, clear knowledge isneeded about the time point at which a DSCCshows its full effect size to avoid methodologicalpitfalls

Published
2015

32. Quality of Life in People With Severe Dementia and Its Association With the Environment in Nursing Homes: An Observational Study.

Author

Palm, Rebecca, Trutschel, Diana, Sorg, Christian G G, Dichter, Martin N, Haastert, Burkhard, and Holle, Bernhard

Subjects
*COGNITION disorders diagnosis, *DIAGNOSIS of dementia, *TREATMENT of dementia, *ELDER care, *DEMENTIA patients, *MATHEMATICAL models, *NURSING care facilities, *SCIENTIFIC observation, *QUALITY of life, *RESEARCH, *THEORY, *DISABILITIES, *STATISTICAL significance
Abstract

Background and Objectives Theoretical models propose the environment as a factor influencing the quality of life (QoL) of nursing home residents with dementia. This study investigates whether the observed QoL differs depending on the type of care unit. Research Design and Methods DemenzMonitor is an exploratory, observational study involving annual data collection in German nursing homes (2012–2014). For this analysis, we selected residents with a recorded diagnosis of dementia and severe cognitive impairment. QoL was measured with the proxy assessment QUALIDEM. Four care unit types were investigated: large integrated, large segregated, small integrated, and small segregated. Results We did not find a significant difference between the care units. During the 2 years, the observed QoL was not affected by any of the care unit types in a statistically significant or clinically relevant manner. However, a significant interaction effect between time and care unit types was found. Discussion and Implications Structural and organizational characteristics of care units, which in turn have implications for residents characteristics and the quality of care, may influence the QoL of residents. This may explain the interaction we observed. [ABSTRACT FROM AUTHOR]

Published
2019
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37. Variability of Primary Sjogren's Syndrome Is Driven by Interferon alpha and Interferon alpha Blood Levels Are Associated With the Class II HLA-DQ Locus

Author

Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Celine, Charbit, Bruno, Thorball, Christian W., Jonsson, Roland, Lessard, Christopher J., Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Helene, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl A., Appel, Silke, Tarn, Jessica R., Quintana-Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, and Gottenberg, Jacques Eric

Subjects
disease-activity, signatures, pathways, innate, cells, autoantibody production, clinical phenotypes
Abstract

Objective Primary Sjogren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS. Methods We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-alpha (IFN alpha) and IFN gamma protein concentrations using digital single molecular arrays (Simoa). Results Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFN alpha and not by IFN gamma protein levels. IFN alpha protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFN alpha protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA-DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells. Conclusion We identified the predominance of IFN alpha as a driver of primary SS variability, with IFN alpha demonstrating an association with HLA gene polymorphisms.

38. Variability of Primary Sjögren's Syndrome Is Driven by Interferon-α and Interferon-α Blood Levels Are Associated With the Class II HLA-DQ Locus.

Author

Trutschel D, Bost P, Mariette X, Bondet V, Llibre A, Posseme C, Charbit B, Thorball CW, Jonsson R, Lessard CJ, Felten R, Ng WF, Chatenoud L, Dumortier H, Sibilia J, Fellay J, Brokstad KA, Appel S, Tarn JR, Quintana-Murci L, Mingueneau M, Meyer N, Duffy D, Schwikowski B, and Gottenberg JE

Subjects
Humans, Interferon-alpha, Proteomics, Prospective Studies, HLA-DQ Antigens genetics, Sjogren's Syndrome
Abstract

Objective: Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS., Methods: We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa)., Results: Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA-DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells., Conclusion: We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Published
2022
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