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Sustained compressive injury (SCI) in the brain is observed in numerous injury and pathological scenarios, including tumors, ischemic stroke, and traumatic brain injury-related tissue swelling. Sustained compressive injury is characterized by tissue loading over time, and currently, there are few in vitro models suitable to study neural cell responses to strain-dependent sustained compressive injury. Here, we present an in vitro model of sustained compressive neural injury via centrifugation. Spheroids were made from neonatal rat cortical cells seeded at 4000 cells/spheroid and cultured for 14 days in vitro. A subset of spheroids was centrifuged at 104, 209, 313 or 419 rads/s for 2 minutes. Modeling the physical deformation of the spheroids via finite element analyses, we found that spheroids centrifuged at the aforementioned angular velocities experienced pressures of 10, 38, 84 and 149 kPa, respectively, and compressive (resp. tensile) strains of 10% (5%), 18% (9%), 27% (14%) and 35% (18%), respectively. Quantification of LIVE-DEAD assay and Hoechst 33342 nuclear staining showed that centrifuged spheroids subjected to pressures above 10 kPa exhibited significantly higher DNA damage than control spheroids at 2, 8, and 24 hours post-injury. Immunohistochemistry of β3-tubulin networks at 2, 8, and 24 hours post-centrifugation injury showed increasing degradation of microtubules over time with increasing strain. Our findings show that cellular injuries occur as a result of specific levels and timings of sustained tissue strains. This experimental SCI model provides a high throughput in vitro platform to examine cellular injury, to gain insights into brain injury that could be targeted with therapeutic strategies.

Pharmacotherapy includes a growing number of clinically effective medications for substance use disorder, yet there are significant barriers to its adoption and implementation in routine clinical practice. The Medication Research Partnership (MRP) was a successful effort to promote adoption of pharmacotherapy for opioid and alcohol use disorders in nine substance abuse treatment centers and a commercial health plan. This qualitative analysis of interviews (n = 39) conducted with change leaders at baseline and at the end/beginning of 6-month change cycles explains how treatment centers overcame obstacles to the adoption, implementation, and sustainability of pharmacotherapy. Results show that barriers to adopting, implementing, and sustaining pharmacotherapy can be overcome through incremental testing of organizational change strategies, accompanied by expert coaching and a learning community of like-minded professionals. The greatest challenges lie in overcoming abstinence-only philosophies, establishing a business case for pharmacotherapy, and working with payers and pharmaceutical representatives.

ObjectiveThe Medication Research Partnership (MRP), a collaboration between a national commercial health plan and nine addiction treatment centers, implemented organizational and system changes to promote use of federally approved medications for treatment of alcohol and opioid use disorders.MethodA difference-in-differences analysis examined change over time in the percentage of patients receiving a prescription medication for alcohol or opioid use disorders treated in MRP (n = 9) and comparison (n = 15) sites.ResultsMRP clinics experienced a 2.4-fold increase in patients receiving an alcohol or opioid prescription (13.2% at baseline to 31.7% at 3 years after MRP initiation); comparison clinics experienced significantly less change (17.6% to 23.5%) with an adjusted difference-in-differences of 12.5% (95% CI [5.4, 19.6], p = .001). MRP sites increased the patients with prescriptions to treat opioid use disorder from 17.0% (baseline) to 36.8% (3 years after initiation), with smaller changes observed in comparison sites (23.2% to 24.0%) and a 3-year post-initiation adjusted difference-in-differences of 19% (95% CI [8.5, 29.5], p = .000). Medications for alcohol use disorders increased in both MRP (9.0% to 26.5%) and comparison sites (11.4% to 23.1%).ConclusionsPromoting the use of medications to support recovery required complex interventions. The Advancing Recovery System Change Model, initially developed in publicly funded systems of care, was successfully adapted for commercial sector use. The model provides a framework for providers and commercial health plans to collaborate and increase patient access to medications.

Background: The Confederated Tribes of the Grand Ronde Community of Oregon began a Mobile Medication Unit (MMU) as part of their Great Circle Recovery Opioid Treatment Program (OTP) to address elevated rates of opioid use disorder (OUD) among American Indians and Alaska Natives in Oregon. The MMU provides methadone or buprenorphine for individuals with OUD, enrolled in the OTP, who are living either on the reservation or in surrounding rural communities. An implementation study describes the service through document review and qualitatively assesses patient and staff experiences and the perceived barriers and facilitators to mobile services. Methods: Semi-structured qualitative interviews with patients (n=11), MMU staff (n=5), and the state opioid treatment authority (n=1) gathered details on the initiative's development and operations. Provider interviews probed implementation experiences. Patient interviews focused on their experiences with the MMU and staff, changes in quality of life and recommendations for enhancing treatment. Interviews were transcribed and analysed using a Thematic Analysis approach. Results: Staff themes identified two driving forces (i.e. staff desire for an inclusive approach to wellness that is accessible to all community members; the catalysts for the MMU), two steps toward MMU development (i.e. Tribal approvals and support; the construction and maintenance of community relationships) and two perspectives on MMU implementation and impact (i.e. initial implementation barriers; facilitators and observations of how the MMU reduced stigma associated with agonist therapy). Patients' themes noted the MMU's professional and 'caring' environment, accessible rural locations and general suggestions including culturally responsive ancillary services. Conclusion: The Great Circle MMU enhanced access to opioid agonist therapy for people with OUD (i.e. American Indians/Alaska Natives, and non-natives) living in rural communities. The Confederated Tribes of Grand Ronde operates the first Tribally owned OTP MMU, grounded in cultural humility and committed to Tribal members and the great circle of the larger community. [ABSTRACT FROM AUTHOR]