OBJECTIVE: To understand providers perceptions of how a patients experience of racism may impact the successful implementation of a brief posttraumatic stress disorder (PTSD) treatment in the safety net integrated primary care setting. To conduct a developmental formative evaluation prior to a hybrid type I effectiveness-implementation trial. DATA SOURCES AND STUDY SETTING: From October 2020 to January 2021, in-depth qualitative interviews were conducted with integrated primary care stakeholders (N = 27) at the largest safety net hospital in New England, where 82% of patients identify as racial or ethnic minorities. STUDY DESIGN: Interviews with clinical stakeholders were used to (a) contextualize current patient and provider experiences and responses to racism, (b) consider how racism may impact PTSD treatment implementation, (c) gather recommendations for potential augmentation to the proposed PTSD treatment (e.g., culturally responsive delivery, cultural adaptation), and (d) gather recommendations for how to shift the integrated primary care practice to an antiracist framework. DATA COLLECTION/EXTRACTION METHODS: Interview data were gathered using remote data collection methods (video conferencing). Participants were hospital employees, including psychologists, social workers, primary care physicians, community health workers, administrators, and operations managers. We used conventional content analysis. PRINCIPAL FINDINGS: Clinical stakeholders acknowledged the impact of racism, including racial stress and trauma, on patient engagement and noted the potential need to adapt PTSD treatments to enhance engagement. Clinical stakeholders also characterized the harms of racism on patients and providers and provided recommendations such as changes to staff training and hiring practices, examination of racist policies, and increases in support for providers of color. CONCLUSIONS: This study contextualizes providers perceptions of racism in the integrated primary care practice and provides some suggestions for shifting to an antiracist framework. Our findings also highlight how racism in health care may be a PTSD treatment implementation barrier.

BACKGROUND: Posttraumatic stress disorder (PTSD) disproportionally affects low-income, racial and ethnic minoritized communities, where prevalence is high, yet access to evidence-based treatments (EBTs) is low. As such, there is a need to identify effective, feasible, and scalable interventions for PTSD. Stepped care approaches that include brief, low-intensity treatments are one approach to improving access yet have not been developed for adults with PTSD. Our study aims to test the effectiveness of a step one PTSD treatment in primary care while gathering information on implementation to maximize sustainability in the setting. METHODS: This study will be conducted in integrated primary care in the largest safety net hospital in New England using a hybrid type 1 effectiveness-implementation design. Eligible trial participants are adult primary care patients who meet full or subthreshold criteria for PTSD. Interventions include Brief clinician-administered Skills Training in Affective and Interpersonal Regulation (Brief STAIR) versus web-administered STAIR (webSTAIR) during a 15-week active treatment period. Participants complete assessments at baseline (pre-treatment), 15 weeks (post-treatment), and 9 months (follow-up) post-randomization. We will assess feasibility and acceptability post-trial using surveys and interviews with patients, study therapists, and other key informants, and will assess the preliminary effectiveness of interventions in terms of PTSD symptom change and functioning. CONCLUSION: This study will provide evidence for the feasibility, acceptability, and preliminary effectiveness of brief, low-intensity interventions in safety net integrated primary care, with the aim of including these interventions in a future stepped care approach to PTSD treatment. CLINICAL TRIAL NUMBER: NCT04937504.

MLL gene rearrangements (MLLr) are a common cause of aggressive, incurable acute lymphoblastic leukemias (ALL) in infants and children, most of which originate in utero. The most common MLLr produces an MLL-AF4 fusion protein. MLL-AF4 promotes leukemogenesis by activating key target genes, mainly through recruitment of DOT1L and increased histone H3 lysine-79 methylation (H3K79me2/3). One key MLL-AF4 target gene is PROM1, which encodes CD133 (Prominin-1). CD133 is a pentaspan transmembrane glycoprotein that represents a potential pan-cancer target as it is found on multiple cancer stem cells. Here we demonstrate that aberrant PROM1/CD133 expression is essential for leukemic cell growth, mediated by direct binding of MLL-AF4. Activation is controlled by an intragenic H3K79me2/3 enhancer element (KEE) leading to increased enhancer-promoter interactions between PROM1 and the nearby gene TAPT1. This dual locus regulation is reflected in a strong correlation of expression in leukemia. We find that in PROM1/CD133 non-expressing cells, the PROM1 locus is repressed by polycomb repressive complex 2 (PRC2) binding, associated with reduced expression of TAPT1, partially due to loss of interactions with the PROM1 locus. Together, these results provide the first detailed analysis of PROM1/CD133 regulation that explains CD133 expression in MLLr ALL.