This document comprises an AMIA Board of Directors approved White Paper that presents a roadmap for national action on clinical decision support. It is published in JAMIA for archival and dissemination purposes. The full text of this material has been previously published on the AMIA Web site (www.amia.org/inside/initiatives/cds). AMIA is the copyright holder.

There is a pressing need for high-quality, effective means of designing, developing, presenting, implementing, evaluating, and maintaining all types of clinical decision support capabilities for clinicians, patients and consumers. Using an iterative, consensus-building process we identified a rank-ordered list of the top 10 grand challenges in clinical decision support. This list was created to educate and inspire researchers, developers, funders, and policy-makers. The list of challenges in order of importance that they be solved if patients and organizations are to begin realizing the fullest benefits possible of these systems consists of: improve the human-computer interface; disseminate best practices in CDS design, development, and implementation; summarize patient-level information; prioritize and filter recommendations to the user; create an architecture for sharing executable CDS modules and services; combine recommendations for patients with co-morbidities; prioritize CDS content development and implementation; create internet-accessible clinical decision support repositories; use freetext information to drive clinical decision support; mine large clinical databases to create new CDS. Identification of solutions to these challenges is critical if clinical decision support is to achieve its potential and improve the quality, safety and efficiency of healthcare.

Vinculin is a ubiquitously expressed multiliganded protein that links the actin cytoskeleton to the cell membrane. In myocytes, it is localized in protein complexes which anchor the contractile apparatus to the sarcolemma. Its function in the myocardium remains poorly understood. Therefore, we developed a mouse model with cardiac-myocyte-specific inactivation of the vinculin (Vcl) gene by using Cre-loxP technology. Sudden death was found in 49% of the knockout (cVclKO) mice younger than 3 months of age despite preservation of contractile function. Conscious telemetry documented ventricular tachycardia as the cause of sudden death, while defective myocardial conduction was detected by optical mapping. cVclKO mice that survived through the vulnerable period of sudden death developed dilated cardiomyopathy and died before 6 months of age. Prior to the onset of cardiac dysfunction, ultrastructural analysis of cVclKO heart tissue showed abnormal adherens junctions with dissolution of the intercalated disc structure, expression of the junctional proteins cadherin and ␤1D integrin were reduced, and the gap junction protein connexin 43 was mislocalized to the lateral myocyte border. This is the first report of tissue-specific inactivation of the Vcl gene and shows that it is required for preservation of normal cell-cell and cell-matrix adhesive structures.