Reducing the harms of xylazine: clinical approaches, research deficits, and public health context.

OBJECTIVES: Xylazine has emerged as a consistent part of the unregulated drug supply in recent months. We discuss major domains of xylazine's harm, current knowledge deficits, clinical and harm reduction strategies for minimizing harm, and xylazine's public health and policy context. As an interdisciplinary team from across the USA, we have pooled our knowledge to provide an overview of xylazine's current and emerging contexts. METHODS: To inform this essay, the pertinent literature was reviewed, clinical knowledge and protocols were shared by multiple clinicians with direct expertise, and policy and public health context were added by expert authors. RESULTS: We describe xylazine's major harm domains-acute poisoning, extended sedation, and wounds, along with anemia and hyperglycemia, which have been reported anecdotally but lack as clear of a connection to xylazine. Current successful practices for xylazine wound care are detailed. Understanding xylazine's epidemiology will also require greater investment in drug checking and surveillance. Finally, approaches to community-based wound care are discussed, along with an orientation to the larger policy and public health context. CONCLUSIONS: Addressing the harms of xylazine requires interdisciplinary participation, investment in community-based harm reduction strategies, and improved drug supply surveillance. The relatively unique context of xylazine demands buy-in from public health professionals, harm reduction professionals, clinicians, basic science researchers, policymakers and more.

The End of the X-waiver: Excitement, Apprehension, and Opportunity.

With the passage of the MAT act (Mainstreaming Addiction Treatment) and the MATE Act (Medication Training and Expansion), the Drug Enforcement Agency "X-waiver" program governing the office-based prescription of buprenorphine for opioid use disorder has been immediately eliminated. The move was championed by vocal organizations with a rightful concern about buprenorphine access but was opposed by most physicians. Nonetheless, buprenorphine can now be prescribed like any schedule 3 medication. Studies show that despite rising opioid overdoses, buprenorphine prescription increases have been slow to rise and are particularly absent in rural communities. The elimination of the X-waiver may theoretically improve buprenorphine prescribing rates for opioid use disorder in rural areas, by nurse practitioners and physician assistants, and by resident physicians in teaching programs. It may also help decrease discrimination against individuals with opioid use disorder in postacute-care settings like nursing homes, physical rehabilitation centers, and in prisons and jails. Concerns include the elimination of the only focused opioid use disorder education many physicians receive (X-waiver courses) and a literature base showing that interest, rather than the X-waiver itself, remains the biggest barrier to recruiting more buprenorphine prescribers. Concerns also exist over the harms of precipitated withdrawal when buprenorphine is initiated inappropriately. The change of the elimination of the X-waiver brings about a new opportunity for Family Medicine and its parent organizations to champion the inclusion of opioid use disorder treatment within the chronic disease care models well-known to our integrated care settings.

Gender Dynamics in Substance Use and Treatment: A Women's Focused Approach.

Gender impacts substance use initiation, substance use disorder development, engagement with treatment, and harms related to drug and alcohol use. Using the biopsychosocial model of addiction, this review provides a broad summary of barriers and facilitators to addiction services among women. It also reviews substance use among pregnant and parenting women and approaches to care. Given the increasing rates of substance use among women, there is a need to implement and scale-up gender-responsive addiction programming and pursue advocacy at the policy level that addresses the root drivers of substance use inequities among women.

An Exploratory Study to Assess Individual and Structural Level Barriers Associated With Poor Retention and Re-engagement in Care Among Persons Living With HIV/AIDS.

BACKGROUND: Retention in care is the most challenging step along the HIV care continuum. Many patients who engage in care and achieve viral suppression have care interruptions, characterized by moving in and out of care ("churn"). Poor retention has clinical consequences and contributes to new HIV transmissions, but how to predict or prevent it remains elusive. This study sought to understand the relationship between individual- and structural-level barriers, and poor retention for persons living with HIV/AIDS in Atlanta, GA. METHODS: We administered a survey, through interviews, with HIV-infected patients continuously retained in care for 6 years ("continuously retained," n = 32) and patients with recent gaps in care ("unretained" n = 27). We assessed individual-level protective factors for successful engagement (self-efficacy, resilience, perceived social support, and disclosure), risk factors for poor engagement (substance use, mental illness, and stigma), and structural/systemic-level barriers (financial and housing instability, transportation, food insecurity, communication barriers, and incarceration history). Chi-square and Mann-Whitney U tests were used to compare the 2 populations. RESULTS: Both continuously retained and unretained populations had high rates of prior viral suppression but few unretained patients were virologically suppressed upon return to care (11%). Younger age, crack cocaine use, food insecurity, financial instability, housing instability, and phone number changes in the past year were significantly more likely to be present in the unretained population. CONCLUSIONS: Our findings suggest the need for targeted risk assessment tools to predict the highest-risk patients for poor retention whereby public health interventions can be directed to those individuals.

Exploring transitions within a project-based Housing First setting: qualitative evaluation and practice implications.

The Housing First (HF) approach is a model of housing that entails the provision of immediate, permanent, low-barrier, supportive housing to chronically homeless individuals either in separate apartments within a larger community (known as scattered-site HF) or in a single building (known as project-based HF). One recent innovation is the application of project-based HF with chronically homeless individuals with alcohol problems. Although initial studies have shown its effectiveness, there is currently no research on residents' and staff 's experiences living and working in a project-based HF program. The purpose of this article was to document these experiences and highlight strengths and challenges of project-based HF programs. Using data collected from naturalistic observations, agency documentation, one-on-one resident interviews, and a staff focus group, we delineated transitional periods, including moving into project-based HF, community-building, managing day-to-day, and transitions from project-based HF. Findings are interpreted to help health care policymakers and providers envision the role of project-based HF in comprehensive public health efforts and to integrate lessons learned into their own clinical practice.

Where harm reduction meets housing first: exploring alcohol's role in a project-based housing first setting.

BACKGROUND: Housing first (HF) programmes provide low-barrier, nonabstinence-based, immediate, supportive and permanent housing to chronically homeless people who often have co-occurring substance-use and/or psychiatric disorders. Project-based HF programmes offer housing in the form of individual units within a larger housing project. Recent studies conducted at a specific project-based HF programme that serves chronically homeless individuals with alcohol problems found housing provision was associated with reduced publicly funded service utilisation, decreased alcohol use, and sizable cost offsets. No studies to date, however, have qualitatively explored the role of alcohol use in the lives of residents in project-based HF. METHODS: We collected data in a project-based HF setting via naturalistic observation of verbal exchanges between staff and residents, field notes taken during staff rounds, and audio recorded staff focus groups and resident interview sessions. Qualitative data were managed and coded using a constant comparative process consistent with grounded theory methodology. The goal of the analysis was to generate a conceptual/thematic description of alcohol's role in residents' lives. RESULTS: Findings suggest it is important to take into account residents' motivations for alcohol use, which may include perceived positive and negative consequences. Further, a harm reduction approach was reported to facilitate housing attainment and maintenance. Residents and staff reported that traditional, abstinence-based approaches are neither desirable nor effective for this specific population. Finally, elements of the moral model of alcohol dependence continue to pervade both residents' views of themselves and the community's perceptions of them. CONCLUSIONS: Findings suggest it is necessary to set aside traditional models of alcohol use and approaches to better understand, align with, and address this population's needs. In doing so, we might gain further insights into how to enhance the existing project-based HF approach by applying more tailored, alcohol-specific, harm reduction interventions.

Fluorescence measurements of nucleotide association with the Na(+)/K(+)-ATPase.

The Na(+)/K(+)-ATPase, a membrane-associated ion pump, uses energy from the hydrolysis of ATP to pump 3 Na(+) ions out of and 2 K(+) into cells. The dependence of ATP hydrolysis on ATP concentration was measured using a fluorescence coupled-enzyme assay. The dependence on concentration of nucleotide association with the ATPase was examined using ADP and ATP-induced quenching of the fluorescence of ATPase labeled with Cy3-maleimide (Cy3-ATPase) or Alexa Fluor 546 carboxylic acid, succinimidyl ester (AF-ATPase). The kinetics of ATP hydrolysis in the presence of Na(+) and K(+) exhibited negative cooperativity with a Hill coefficient (n(H)) of 0.66 and a half-maximal concentration (K(0.5)) of 61 microM; in the absence of K(+), n(H) was 0.58 and K(0.5) was 13 microM. Nucleotide-induced fluorescence quenching exhibited negative cooperativity with an n(H) of 0.3-0.5. These results suggest that negative cooperativity observed in ATP hydrolysis is attributable to negative cooperativity in nucleotide association to the ATPase. Interaction between AF-ATPase and ATP labeled with Alexa Fluor 647 (AF-ATP) showed significant Förster resonance energy transfer (FRET). These results indicate that the ATPase exists as oligoprotomeric complexes in this preparation, and that this aggregation has significant effects on enzyme function.