Background People diagnosed with a co-occurring serious mental illness (SMI; ie, major depressive disorder, bipolar disorder, or schizophrenia) but hospitalized for a nonpsychiatric condition experience higher rates of readmissions and other adverse outcomes, in part due to poorly coordinated care transitions. Current hospital-to-home transitional care programs lack a focus on the integrated social, medical, and mental health needs of these patients. The Thrive clinical pathway provides transitional care support for patients insured by Medicaid with multiple chronic conditions by focusing on posthospitalization medical concerns and the social determinants of health. This study seeks to evaluate an adapted version of Thrive that also meets the needs of patients with co-occurring SMI discharged from a nonpsychiatric hospitalization. Objective This study aimed to (1) engage staff and community advisors in participatory implementation processes to adapt the Thrive clinical pathway for all Medicaid-insured patients, including those with SMI; (2) examine utilization outcomes (ie, Thrive referral, readmission, emergency department [ED], primary, and specialty care visits) for Medicaid-insured individuals with and without SMI who receive Thrive compared with usual care; and (3) evaluate the acceptability, appropriateness, feasibility, and cost-benefit of an adapted Thrive clinical pathway that is tailored for Medicaid-insured patients with co-occurring SMI. Methods This study will use a prospective, type I hybrid effectiveness-implementation, stepped-wedge, cluster randomized controlled trial design. We will randomize the initiation of Thrive referrals at the unit level. Data collection will occur over 24 months. Inclusion criteria for Thrive referral include individuals who (1) are Medicaid insured, dually enrolled in Medicaid and Medicare, or Medicaid eligible; (2) reside in Philadelphia; (3) are admitted for a medical diagnosis for over 24 hours at the study hospital; (4) are planned for discharge to home; (5) agree to receive home care services; and (6) are aged ≥18 years. Primary analyses will use a mixed-effects negative binomial regression model to evaluate readmission and ED utilization, comparing those with and without SMI who receive Thrive to those with and without SMI who receive usual care. Using a convergent parallel mixed methods design, analyses will be conducted simultaneously for the survey and interview data of patients, clinicians, and health care system leaders. The cost of Thrive will be calculated from budget monitoring data for the research budget, the cost of staff time, and average Medicaid facility fee payments. Results This research project was funded in October 2023. Data collection will occur from April 2024 through December 2025. Results are anticipated to be published in 2025-2027. Conclusions We anticipate that patients with and without co-occurring SMI will benefit from the adapted Thrive clinical pathway. We also anticipate the adapted version of Thrive to be deemed feasible, acceptable, and appropriate by patients, clinicians, and health system leaders. Trial Registration ClinicalTrials.gov NCT06203509; https://clinicaltrials.gov/ct2/show/NCT06203509 International Registered Report Identifier (IRRID) DERR1-10.2196/64575
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