Reducing Acute Hospitalizations at High-Performing CPC+ Primary Care Practice Sites: Strategies, Activities, and Facilitators.

PURPOSE: Despite evidence suggesting that high-quality primary care can prevent unnecessary hospitalizations, many primary care practices face challenges in achieving this goal, and there is little guidance identifying effective strategies for reducing hospitalization rates. We aimed to understand how practices in the Comprehensive Primary Care Plus (CPC+) program substantially reduced their acute hospitalization rate (AHR) over 2 years. METHODS: We used Bayesian analyses to identify the CPC+ practice sites having the highest probability of achieving a substantial reduction in the adjusted Medicare AHR between 2016 and 2018 (referred to here as AHR high performers). We then conducted telephone interviews with 64 respondents at 14 AHR high-performer sites and undertook within- and cross-case comparative analysis. RESULTS: The 14 AHR high performers experienced a 6% average decrease (range, 4% to 11%) in their Medicare AHR over the 2-year period. They credited various care delivery activities aligned with 3 strategies for reducing AHR: (1) improving and promoting prompt access to primary care, (2) identifying patients at high risk for hospitalization and addressing their needs with enhanced care management, and (3) expanding the breadth and depth of services offered at the practice site. They also identified facilitators of these strategies: enhanced payments through CPC+, prior primary care practice transformation experience, use of data to identify high-value activities for patient subgroups, teamwork, and organizational support for innovation. CONCLUSIONS: The AHR high performers observed that strengthening the local primary care infrastructure through practice-driven, targeted changes in access, care management, and comprehensiveness of care can meaningfully reduce acute hospitalizations. Other primary care practices taking on the challenging work of reducing hospitalizations can learn from CPC+ practices and may consider similar strategies, selecting activities that fit their context, personnel, patient population, and available resources.

Deficits in Enrichment-Dependent Neurogenesis and Enhanced Anxiety Behaviors Mediated by Expression of Alzheimer's Disease-Linked Ps1 Variants Are Rescued by Microglial Depletion.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that presently affects an estimated 5.7 million Americans. Understanding the basis for this disease is key for the development of a future successful treatment. In this effort, we previously reported that mouse prion protein-promoter-driven, ubiquitous expression of familial AD (FAD)-linked human PSEN1 variants in transgenic mice impairs environmental enrichment (EE)-induced proliferation and neurogenesis of adult hippocampal neural progenitor cells (AHNPCs) and in a non-cell autonomous manner. These findings were confirmed in PS1M146V/+ mice that harbor an FAD-linked mutation in the endogenous PSEN1 gene. We now demonstrate that CSF1R antagonist-mediated microglial depletion in transgenic male mice expressing mutant presenilin 1 (PS1) or PS1M146V/+ "knock-in" mice leads to a complete rescue of deficits in proliferation, differentiation and survival of AHNPCs. Moreover, microglia depletion suppressed the heightened baseline anxiety behavior observed in transgenic mice expressing mutant PS1 and PS1M146V/+ mice to levels observed in mice expressing wild-type human PS1 or nontransgenic mice, respectively. These findings demonstrate that in mice expressing FAD-linked PS1, microglia play a critical role in the regulation of EE-dependent AHNPC proliferation and neurogenesis and the modulation of affective behaviors.SIGNIFICANCE STATEMENT Inheritance of mutations in genes encoding presenilin 1 (PS1) causes familial Alzheimer's disease (FAD). Mutant PS1 expression enhances the levels and assembly of toxic Aß42 peptides and impairs the self-renewal and neuronal differentiation of adult hippocampal neural progenitor cells (AHNPCs) following environmental enrichment (EE) that is associated with heightened baseline anxiety. We now show that microglial depletion fully restores the EE-mediated impairments in AHNPC phenotypes and suppresses the heightened baseline anxiety observed in mice expressing FAD-linked PS1. Thus, we conclude that the memory deficits and anxiety-related behaviors in patients with PS1 mutations is a reflection not just of an increase in the levels of Aß42 peptides, but to impairments in the self-renewal and neuronal differentiation of AHNPCs that modulate affective behaviors.