Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Comprehensive Implementation of Shared Decision Making in a Neuromedical Center Using the SHARE TO CARE Program

Constanze Stolz-Klingenberg,1 Claudia Bünzen,1 Marie Coors,2 Charlotte Flüh,3 Klarissa Hanja Stürner,4 Kai Wehkamp,5,6 Marla L Clayman,7,8 Fueloep Scheibler,1,9 Jens Ulrich Rüffer,9,10 Wiebke Schüttig,2 Leonie Sundmacher,2 Daniela Berg,4 Friedemann Geiger1,9,11 1National Competency Center for Shared Decision Making, University Hospital Schleswig-Holstein, Kiel, Germany; 2Chair of Health Economics, Technical University of Munich, Munich, Germany; 3Department of Neurosurgery, University Hospital Schleswig-Holstein, Kiel, Germany; 4Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany; 5Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany; 6Department of Medical Management, MSH Medical School Hamburg, Hamburg, Germany; 7Center for Healthcare Organization and Implementation Research (CHOIR), Veterans Administration, Bedford, MA, USA; 8Department of Population and Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, MA, USA; 9SHARE TO CARE Patientenzentrierte Versorgung GmbH, Cologne, Germany; 10TakePart Media+Science GmbH, Cologne, Germany; 11Department of Psychology, MSH Medical School Hamburg, Hamburg, GermanyCorrespondence: Constanze Stolz-Klingenberg, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, Haus 9, Kiel, 24105, Germany, Tel +49 431 500 20208 ; +49 151 17271928, Email [email protected]: SHARE TO CARE (S2C) is a comprehensive, multi-module implementation program for shared decision making (SDM). It is currently applied at the University Hospital Schleswig-Holstein in Kiel, Germany, and among general practitioners at the Federal State of Bremen. This study examines the results of the full implementation of S2C in terms of effectiveness within the Kiel Neuromedical Center comprising the departments of neurology and neurosurgery.Method and Design: The S2C program consists of four combined intervention modules: 1) multimodal training of physicians; 2) a patient activation campaign including the ASK-3 method; 3) digital evidence-based patient decision aids; and 4) SDM support by nurses, e.g., as decision coaches. The SDM level before and immediately after implementation was retrospectively assessed in consecutively selected patients on the subscale “Patient Decision Making” of the Perceived Involvement in Care Scale (PICSPDM). Mean scores were compared with t-tests.Results: Eighty-nine percent of all physicians (N = 56) completed the SDM training. We developed a total of 12 evidence-based digital decision aids in the center, educated two decision coaches to support patients’ decision processes by using decision aids. Physicians adjusted patients’ pathways to incorporate the use of decision aids. Patients (n = 261) reported a significant increase in participation (p< 0.001; Hedges’ g = 0.49) in medical decision making.Conclusion: The S2C program has been successfully implemented within the entire Neuromedical Center. Patients reported a medium to small increase of perceived involvement in decision making demonstrating the effectiveness of the implementation. For future research, it might be interesting to investigate the sustainability of the effects of S2C. In addition, it seems useful to complement the patient-based evaluation with observer-based data.Keywords: shared decision making intervention, decision aids, physician training, patient activation, neurology, neurosurgery, SD