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This chapter proposes an optimized innovative information technology as a means for achieving operational functionalities of real-time portable electronic health records, system interoperability, longitudinal health-risks research cohort and surveillance of adverse events infrastructure, and clinical, genome regions – disease and interventional prevention infrastructure. In application to the Dod-VA (Department of Defense and Veteran's Administration) health information systems, the proposed modernization can be carried out as an “add-on” expansion (estimated at $288 million in constant dollars) or as a “stand-alone” innovative information technology system (estimated at $489.7 million), and either solution will prototype an infrastructure for nation-wide health information systems interoperability, portable real-time electronic health records (EHRs), adverse events surveillance, and interventional prevention based on targeted single nucleotide polymorphisms (SNPs) discovery.