AbstractIntroductionShared decision‐making (SDM) is a method of care by which patients and clinicians work together to co‐create a plan of care. Electronic health record (EHR) integration of SDM tools may increase adoption of SDM. We conducted a “lightweight” integration of a freely available electronic SDM tool, CV Prevention Choice, within the EHRs of three healthcare systems. Here, we report how the healthcare systems collaborated to achieve integration.MethodsThis work was conducted as part of a stepped wedge randomized pragmatic trial. CV Prevention Choice was developed using guidelines for HTML5‐based web applications. Healthcare systems integrated the tool in their EHR using documentation the study team developed and refined with lessons learned after each system integrated the electronic SDM tool into their EHR. CV Prevention Choice integration populates the tool with individual patient data locally without sending protected health information between the EHR and the web. Data abstraction and secure transfer systems were developed to manage data collection to assess tool implementation and effectiveness outcomes.ResultsTime to integrate CV Prevention Choice in the EHR was 12.1 weeks for the first system, 10.4 weeks for the second, and 9.7 weeks for the third. One system required two 1‐hour meetings with study team members and two healthcare systems required a single 1‐hour meeting. Healthcare system information technology teams collaborated by sharing information and offering improvements to documentation. Challenges included tracking CV Prevention Choice use for reporting and capture of combination medications. Data abstraction required refinements to address differences in how each healthcare system captured data elements.ConclusionTargeted documentation on tool features and resource mapping supported collaboration of IT teams across healthcare systems, enabling them to integrate a web‐based SDM tool with little additional research team effort or oversight. Their collaboration helped overcome difficulties integrating the web application and address challenges to data harmonization for trial outcome analyses.
Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by
HLA-DRB1*04
subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers