Co-Developing Theories of Change for Improved Community-Based Violence Intervention Evaluation.

BACKGROUND: Community-based violence intervention (CVI) programs are considered important strategies for preventing community violence and promoting health and safety. Mixed and inconclusive results from some prior CVI evaluations-and our general lack of understanding about the reasons for such varied findings-may be explained in part by misalignment of program theories of change and evaluation measures. Further, most prior evaluations have focused solely on deficit-based outcomes; this narrow focus is inconsistent with the premise of CVI and may fail to capture improvements in health and wellbeing that are on the hypothesized pathway from intervention to violence reduction. METHODS: This paper describes the process and results of co-developing a theory of change for community-based youth firearm violence intervention and prevention programs in Washington state through a community-researcher partnership. We followed a multi-step iterative process, involving 1) CVI program documentation review, 2) individual meetings, and 3) a day-long workshop. RESULTS: The theory of change included 6 key domains: 1) root causes, 2) promotive factors, 3) activities, 4) inter-mediate outcomes, 5) longer-term outcomes, and 6) multi-level context (youth/family, staff/organizational, community, and societal). Root causes were social and structural drivers of community violence. Promotive factors were assets and resources among the community, youth/their families, and community organizations that promote health and safety. Activities were supports and services the program provided to youth and their families, staff, and potentially the broader community. Inter-mediate and longer-term outcomes were the changes among youth, their families, staff, and the community that resulted from program activities. Inter-mediate outcomes may be felt within 6 months to 1 year and longer-term outcomes may be felt after 1-2 years and beyond. CONCLUSIONS: The theory of change we co-developed provides a common lens to conceptualize, compare, and evaluate CVI programs in Washington state and may support more rigorous and equity-centered evaluations.Study type: original investigation. LEVEL OF EVIDENCE: N/A.

Pirtobrutinib: A novel non-covalent BTK inhibitor for the treatment of adults with relapsed/refractory mantle cell lymphoma.

OBJECTIVE: To provide a comprehensive review of the pharmacokinetics, pharmacodynamics, safety, and efficacy of a new Food and Drug Administration (FDA) approved Bruton's tyrosine kinase inhibitor (BTKi), pirtobrutinib for relapsed/refractory mantle cell lymphoma (r/r MCL). DATA SOURCES: A literature search was conducted through PubMed MEDLINE, ClinicalTrials.gov, and the FDA website (January 2018-January 2023) using the following key terms: lymphoma, non-covalent, Bruton's tyrosine kinase (BTK), and relapse. Relevant English language monographs, studies, and abstracts conducted in humans were reviewed and considered. DATA SUMMARY: Pirtobrutinib, a novel non-covalent BTKi, was granted accelerated approval for treatment of r/r MCL on January 27th, 2023, based on an open-label, multi-center phase 1/2 BRUIN trial. In phase l, 61 patients with r/r MCL received seven dose levels of pirtobrutinib (25-300 mg). There was no reported maximum tolerated dose or dose-limiting toxicities during this study period. In phase 2, 56 r/r MCL evaluable efficacy patients received pirtobrutinib 200 mg daily. The overall response rate (ORR) was 52% (95% CI 38-65). Additionally, patients who received a previous covalent BTKi, ORR was 52% (95% CI 38-66). Neutropenia was the most common adverse reaction reported as a grade 3 or higher. CONCLUSION: Pirtobrutinib has demonstrated safety and efficacy in heavily pre-treated adult patients with r/r MCL. Advantages of this drug include its usage in patients whose malignancy is resistant to current BTKi, tolerability, and response rate. Multiple clinical trials are underway to determine the efficacy of pirtobrutinib in other B-cell malignancies.

Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

Moving From Transactional to Relational: How Funders Can Work in Partnership With Black, Indigenous and People of Color Communities.

BACKGROUND: The Racial Equity Coalition (REC) formed to address persistent educational disparities. The coalition was composed of 14 Black, Indigenous and People of Color (BIPOC) organizations that provide culturally integrative youth services. OBJECTIVES: REC, with support from United Way of King County, engaged in participatory research to identify commonalities and shared struggles to inform collective action. Participatory research aligns with REC's commitment to equitable participatory processes. This article focuses on REC's experiences with funders. The objective was to understand what creates positive and challenging experiences with funders, and to identify recommendations for funders to become more culturally responsive. METHODS: A research committee was formed including representatives of nine REC organizations and United Way of King County staff. The committee conducted interviews with each of the 14 REC organizations and conducted thematic analysis of interview transcripts. Through participatory analysis, the committee drafted narratives that were further refined through a series of research retreats attended by all REC organizations. RESULTS: Recommendations were to incentivize collaboration, listen to communities to create culturally responsive definitions of success and measurement strategies, arrive at mutually agreed upon approaches with organizations, honor the connections BIPOC organizations have with their communities, and provide unrestricted funding to allow BIPOC organizations greater agency. CONCLUSIONS: A major challenge for BIPOC organizations is navigating White dominant culture that too often shows up in funding requirements. Having to fit dominant culture standards stifles BIPOC organizations' abilities to meet community needs and the responsiveness of their approaches. REC identified recommendations for funders to be more culturally responsive and community centered.

Evaluating Pharmacist-Driven Interventions in a Primary Care Setting to Improve Proportion of Days Covered and Medication Adherence.

BACKGROUND: Medication nonadherence is the leading cause of poor health outcomes and increased risk of hospitalizations. Previous studies have shown that pharmacist interventions can help improve medication adherence and CMS quality measures. OBJECTIVE: The purpose of this study was to examine the impact of clinical pharmacists' interventions on medication adherence and PDC scores for ACEi/ARBs, statins, and noninsulin antidiabetic medications in the primary care setting. METHODS: This observational study was conducted at four primary care clinics to evaluate PDC scores pre- and post-pharmacist interventions from April 2020 to December 2020. Eligible patients were Humana Part D beneficiaries with a baseline PDC score <85%. The primary outcome of this study was to evaluate the average change in final PDC scores, and 1-month change in PDC scores following a pharmacist intervention. Secondary outcomes were number and types of adherence barriers identified, interventions provided by the pharmacist, and barriers and interventions category (pharmacy, patient or physician-related). RESULTS: A total of 89 barriers were identified and 208 interventions were completed. A statistically significant difference in the average change of final PDC score from baseline was seen among those on ACEi/ARBs (72.5 to 78.0, p = 0.004) and statins (73.3 to 76.6, p < 0.001). Similarly, a statistically significant change was observed from baseline to 1-month PDC among those on ACEi/ARBS (72.5 to 75.4, p = 0.001) and statins (73.3 to 74.9, p < 0.001). Conclusion: Pharmacists located in a primary care setting improved medication adherence and PDC score for patients on ACEIs/ARBs and statins.