Barriers and Facilitators to Harm Reduction for Opioid Use Disorder: A Qualitative Study of People With Lived Experience.

STUDY OBJECTIVE: Although an increasing number of emergency departments (ED) offer opioid agonist treatment, naloxone, and other harm reduction measures, little is known about patient perspectives on harm reduction practices delivered in the ED. The objective of this study was to identify patient-focused barriers and facilitators to harm reduction strategies in the ED. METHODS: We conducted semistructured interviews with a convenience sample of individuals in Massachusetts diagnosed with opioid use disorder. We developed an interview guide, and interviews were recorded, transcribed, and analyzed in an iterative process using reflexive thematic analysis. After initial interviews and coding, we triangulated the results among a focus group of 4 individuals with lived experience. RESULTS: We interviewed 25 participants with opioid use disorder, 6 recruited from 1 ED and 19 recruited from opioid agonist treatment clinics. Key themes included accessibility of harm reduction supplies, lack of self-care resulting from withdrawal and hopelessness, the impact of stigma on the likelihood of using harm reduction practices, habit and knowledge, as well as the need for user-centered harm reduction interventions. CONCLUSION: In this study, people with lived experience discussed the characteristics and need for user-centered harm reduction strategies in the ED that centered on reducing stigma, treatment of withdrawal, and availability of harm reduction materials.

"Just give them a choice": Patients' perspectives on starting medications for opioid use disorder in the ED.

OBJECTIVES: Medications for opioid use disorder (MOUD) prescribed in the emergency department (ED) have the potential to save lives and help people start and maintain recovery. We sought to explore patient perspectives regarding the initiation of buprenorphine and methadone in the ED with the goal of improving interactions and fostering shared decision making (SDM) around these important treatment options. METHODS: We conducted semistructured interviews with a purposeful sample of people with opioid use disorder (OUD) regarding ED visits and their experiences with MOUD. The interview guide was based on the Ottawa Decision Support Framework, a framework for examining decisional needs and tailoring decisional support, and the research team's experience with MOUD and SDM. Interviews were recorded, transcribed, and analyzed in an iterative process using both the Ottawa Framework and a social-ecological framework. Themes were identified and organized and implications for clinical care were noted and discussed. RESULTS: Twenty-six participants were interviewed, seven in person in the ED and 19 via video conferencing software. The majority had tried both buprenorphine and methadone, and almost all had been in an ED for an issue related to opioid use. Participants reported social, pharmacological, and emotional factors that played into their decision making. Regarding buprenorphine, they noted advantages such as its efficacy and logistical ease and disadvantages such as the need to wait to start it (risk of precipitated withdrawal) and that one could not use other opioids while taking it. Additionally, participants felt that: (1) both buprenorphine and methadone should be offered; (2) because "one person's pro is another person's con," clinicians will need to understand the facets of the options; (3) clinicians will need to have these conversations without appearing judgmental; and (4) many patients may not be "ready" for MOUD, but it should still be offered. CONCLUSIONS: Although participants were supportive of offering buprenorphine in the ED, many felt that methadone should also be offered. They felt that treatment should be tailored to an individual's needs and circumstances and clarified what factors might be important considerations for people with OUD.

Cell cycle defects in polyhomeotic mutants are caused by abrogation of the DNA damage checkpoint.

Polycomb group (PcG) genes are required for heritable silencing of target genes. Many PcG mutants have chromatin bridges and other mitotic defects in early embryos. These phenotypes can arise from defects in S phase or mitosis, so the phenotype does not show when PcG proteins act in cell cycle regulation. We analyzed the cell cycle role of the proximal subunit of Polyhomeotic (PhP) in Drosophila. Time-lapse imaging reveals that chromatin bridges formed during mitosis are able to resolve but sometimes result in chromosome breakage. Chromosome bridging is also observed in canonical cell cycles occurring in larval brains and is therefore not unique to the rapid embryonic cycles. PhP colocalizes with chromatin in S phase but not in mitosis in early embryos, indicating a direct role in DNA synthesis. Time lapse imaging of ph(p) mutants reveals an acceleration of S phase, showing that ph(p) regulates S phase length. Like ph(p) mutations, mutations in DNA damage checkpoints result in S phase acceleration. Consistent with this model, mutations in ph do not affect DNA synthesis rates, but exhibit impaired ability to block cell cycle progression following exposure to gamma-rays. Our data show that the mitotic defects of ph(p) are caused by defects in the DNA damage response that occurs after DNA replication in S phase, and we propose that PhP has a direct role in DNA damage repair.

The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein.

The cohesin complex is a key player in regulating cell division. Cohesin proteins SMC1, SMC3, Rad21, and stromalin (SA), along with associated proteins Nipped-B, Pds5, and EcoI, maintain sister chromatid cohesion before segregation to daughter cells during anaphase. Recent chromatin immunoprecipitation (ChIP) data reveal extensive overlap of Nipped-B and cohesin components with RNA polymerase II binding at active genes in Drosophila. These and other data strongly suggest a role for cohesion in transcription; however, there is no clear evidence for any specific mechanisms by which cohesin and associated proteins regulate transcription. We report here a link between cohesin components and trithorax group (trxG) function, thus implicating these proteins in transcription activation and/or elongation. We show that the Drosophila Rad21 protein is encoded by verthandi (vtd), a member of the trxG gene family that is also involved in regulating the hedgehog (hh) gene. In addition, mutations in the associated protein Nipped-B show similar trxG activity i.e., like vtd, they act as dominant suppressors of Pc and hh(Mrt) without impairing cell division. Our results provide a framework to further investigate how cohesin and associated components might regulate transcription.

Polycomb group mutants exhibit mitotic defects in syncytial cell cycles of Drosophila embryos.

The Polycomb Group (PcG) of epigenetic regulators maintains the repressed state of Hox genes during development of Drosophila, thereby maintaining the correct patterning of the anteroposterior axis. PcG-mediated inheritance of gene expression patterns must be stable to mitosis to ensure faithful transmission of repressed Hox states during cell division. Previously, two PcG mutants, polyhomeotic and Enhancer of zeste, were shown to exhibit mitotic segregation defects in embryos, and condensation defects in imaginal discs, respectively. We show that polyhomeotic(proximal) but not polyhomeotic(distal) is necessary for mitosis. To test if other PcG genes have roles in mitosis, we examined embryos derived from heterozygous PcG mutant females for mitotic defects. Severe defects in sister chromatid segregation and nuclear fallout, but not condensation are exhibited by Polycomb, Posterior sex combs and Additional sex combs. By contrast, mutations in Enhancer of zeste (which encodes the histone methyltransferase subunit of the Polycomb Repressive Complex 2) exhibit condensation but not segregation defects. We propose that these mitotic defects in PcG mutants delay cell cycle progression. We discuss possible mitotic roles for PcG proteins, and suggest that delays in cell cycle progression might lead to failure of maintenance.