Novel Therapeutic and Program-Based Approaches to Opioid Use Disorders.

Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key contributors to the complications and mortality associated with opioid use disorder. Medications for opioid use disorder treatment, such as methadone and buprenorphine, are safe and substantially reduce opioid use, infectious complications, and mortality risk, but remain underutilized. Polysubstance use and emerging substances such as xylazine and designer benzodiazepines create additional treatment challenges. Recent clinical and policy innovations in treatment delivery, including telemedicine, bridge clinics, and expanded models for accessing methadone have the potential to increase access to life-saving care for people living with opioid use disorder.

Efficacy of transdermal buprenorphine patch for managing withdrawal symptoms in patients with cancer physically dependent on prescription opioids.

BACKGROUND: The physical dependence on prescription opioids among cancer survivors remains an under-investigated area, with a scarcity of well-designed prospective studies. METHODS: This single-arm, phase-2 clinical trial in Korea assessed the efficacy and safety of a transdermal buprenorphine patch (TBP) in managing physical dependence on prescription opioids in cancer survivors, as confirmed through the DSM-5 criteria or psychiatric consultation for opioid withdrawal. This study involved a 4-phase treatment protocol of screening, induction/stabilization, discontinuation, and monitoring. The primary outcome was the rate of successful opioid discontinuation, as measured by a negative urine-drug screening at 8 weeks. Key secondary outcomes included the resumption of prescribed opioids, changes in both the Clinical Opioid Withdrawal Scale (COWS) and morphine equivalent daily dose (MEDD), and assessments related to the psychological and physiological aspects of dependence and safety. RESULTS: Thirty-one participants were enrolled. In the intention-to-treat population, the success rate of opioid discontinuation was 58%, with only 2 participants experiencing a resumption of prescribed opioids. Significant reductions were observed in MEDD, which decreased from 98 to 26 mg/day (P < .001), and COWS scores, which decreased from 5.5 to 2.8 (P < .001). Desire to use opioids reduced from 7.0 to 3.0 on a 10-point numeric rating scale (P < .001). Toxicities related to TBP were mild and manageable, without severe precipitated withdrawal symptoms. CONCLUSION: TBP may be considered as an alternative therapeutic option in cancer survivors physically dependent on prescription opioids, especially where sublingual formulations are unavailable.

The Associations Between Opioid Use Disorder and Healthcare-Related Outcomes in Vaso-occlusive Crisis.

BACKGROUND: In patients who experience frequent vaso-occlusive crises (VOC), opioid dependence may be due to a need for pain control as opposed to addiction; the implications of opioid use disorder (OUD) in this population are unclear. OBJECTIVE: To compare outcomes in hospitalizations for VOC in those with a history of OUD to those without a history of OUD. DESIGN: A retrospective assessment of hospitalizations for adults in the USA with a primary discharge diagnosis of VOC using the National Inpatient Sample database from 2016 to 2019. We also compared VOC hospitalizations to hospitalizations for all other reasons to assess differences in OUD-associated clinical factors. PARTICIPANTS: In total, 273,460 hospitalizations for VOC; 23,120 (8.5%) of these hospital stays involved a secondary diagnosis of OUD. MAIN MEASURES: Primary outcomes were length of hospital stay and cost. Mortality was a secondary outcome. KEY RESULTS: Hospital length of stay was increased (mean 6.2 vs 4.9 days) in patients with OUD (adjusted rate ratio = 1.24, 95% CI 1.20-1.29, p < 0.001). Mean cost was also higher in those with OUD ($9076) than those without OUD ($8020, p < 0.001). Mortality was decreased in VOC hospitalizations in those with OUD, but the difference was not statistically significant (adjusted OR = 0.64, 95% CI 0.028-1.48, p = 0.30). CONCLUSIONS: OUD is associated with increased length of stay and costs in patients with VOC. While there are many possible explanations, providers should consider undertreatment of pain due to addiction concerns as a potential factor; individualized pain plans to mitigate this challenge could be explored.

HIV Prevalence and HIV Screening History Among a Veterans Association Cohort of People with Opioid and Alcohol Use Disorders.

BACKGROUND: Veterans face high risk for HIV and substance use, and thus could be disproportionately impacted by the HIV and substance use disorder (SUD) "syndemic." HIV prevalence among veterans with SUD is unknown. OBJECTIVE: To project HIV prevalence and lifetime HIV screening history among US veterans with alcohol use disorder (AUD), opioid use disorder (OUD), or both. DESIGN: We conducted a retrospective cohort analysis using national Veterans Health Administration (VHA) data. PARTICIPANTS: We selected three cohorts of veterans with SUD: (1) AUD, (2) OUD, and (3) AUD/OUD. Included veterans had ICD codes for AUD/OUD from 2016 to 2022 recorded in VHA electronic medical records, sourced from the VA Corporate Data Warehouse (CDW). MAIN MEASURES: We estimated HIV prevalence by dividing the number of veterans who met two out of three criteria (codes for HIV diagnosis, antiretroviral therapy, or HIV screening/monitoring) by the total number of veterans in each cohort. We also estimated lifetime HIV screening history (as documented in VHA data) by cohort. We reported HIV prevalence and screening history by cohort and across demographic/clinical subgroups. KEY RESULTS: Our sample included 669,595 veterans with AUD, 63,787 with OUD, and 57,015 with AUD/OUD. HIV prevalence was highest in the AUD/OUD cohort (3.9%), followed by the OUD (2.1%) and AUD (1.1%) cohorts. Veterans of Black race and Hispanic/Latinx ethnicity, with HCV diagnoses, and aged 50-64 had the highest HIV prevalence in all cohorts. Overall, 12.8%, 29.1%, and 33.1% of the AUD/OUD, OUD, and AUD cohorts did not have history of HIV screening, respectively. CONCLUSIONS: HIV prevalence was high in all SUD cohorts, and was highest among veterans with AUD/OUD, with disparities by race/ethnicity and age. A substantial portion of veterans had not received HIV screening in the VHA. Findings highlight room for improvement in HIV prevention and screening services for veterans with SUD.

Maternal opioid use disorder and infant mortality in Wisconsin, United States, 2010-2018.

OBJECTIVE: The difference in infant health outcomes by maternal opioid use disorder (OUD) status is understudied. We measured the association between maternal OUD during pregnancy and infant mortality and investigated whether this association differs by infant neonatal opioid withdrawal syndrome (NOWS) or maternal receipt of medication for OUD (MOUD) during pregnancy. METHODS: We sampled 204,543 Medicaid-paid births from Wisconsin, United States (2010-2018). The primary exposure was any maternal OUD during pregnancy. We also stratified this exposure on NOWS diagnosis (no OUD; OUD without NOWS; OUD with NOWS) and on maternal MOUD receipt (no OUD; OUD without MOUD; OUD with <90 consecutive days of MOUD; OUD with 90+ consecutive days of MOUD). Our outcome was infant mortality (death at age <365 days). Demographic-adjusted logistic regressions measured associations with odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Maternal OUD was associated with increased odds of infant mortality (OR 1.43; 95% CI 1.02-2.02). After excluding infants who died <5 days post-birth (i.e., before the clinical presentation of NOWS), regression estimates of infant mortality did not significantly differ by NOWS diagnosis. Likewise, regression estimates did not significantly differ by maternal MOUD receipt in the full sample. CONCLUSIONS: Maternal OUD is associated with an elevated risk of infant mortality without evidence of modification by NOWS nor by maternal MOUD treatment. Future research should investigate potential mechanisms linking maternal OUD, NOWS, MOUD treatment, and infant mortality to better inform clinical intervention.

A comparison of the mixed and sequential use of acetaminophen and dexketoprofen in painful vaso-occlusive crises.

PURPOSE: Opioids are widely used to treat painful vaso-occlusive crises (VOC) in sickle cell disease (SCD). However, due to opioids' significant adverse effect profiles, the search for alternative therapies continues from the past to the present. The study aimed to investigate the efficacy of acetaminophen and dexketoprofen in the treatment of painful VOC. METHODS: This study is a single-center, prospective, non-randomized, single-blinded, controlled study. The study comprised two groups: the first administered acetaminophen and dexketoprofen mixed group, while the second received them sequential group. Opioids were used in patients with persistent pain despite these analgesics. Demographic and laboratory information, pain scores, opioid requirement, dose amount, side effects, and length of hospital stay of the patients were recorded. RESULTS: The study comprised 56 (100%) patients with painful VOC, 29 (51.8%) from the mixed group, and 27 (48.2%) from the sequential group. Opioid use was seen in 16 (55.2%) patients in the mixed group and 21 (77.8%) patients in the sequential group (p = 0.074). The median amount of opioid used was significantly lower in the mixed group than in the sequential group (p < 0.001). Also, the median length of hospital stay was significantly lower in the mixed group than in the sequential group (p < 0.001). CONCLUSION: Our study suggests that administering acetaminophen and dexketoprofen in the mix for the treatment of painful VOC in patients with SCD may be a more efficient approach compared to sequential administration. This approach appears to reduce opioid usage and shorten hospital stays.

Evaluation of a tiered opioid prescription algorithm in an ERAS pathway: exploring opportunities for further refinement.

BACKGROUND: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription. OBJECTIVE: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education. METHODS: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription was defined as >20% of the original prescription left over. Descriptive statistics were used for analysis. RESULTS: The survey response rate was 61% and 59% in the minimally invasive surgery and open surgery cohorts, respectively. Overall, 42.8% of patients reported using no opioids after hospital discharge, 45.2% in the minimally invasive surgery and 38.6% in the open surgery cohort. Furthermore, 74.9% of respondents were over-prescribed, with median age being statistically significant for this group (p=0.004). Finally, 46.4% of respondents expressed no knowledge regarding safe disposal practices, with no statistically significant difference between groups (p>0.99). CONCLUSION: Despite implementation of the tiered discharge opioid algorithm aimed to personalize opioid prescriptions to estimated need, we still over-prescribed opioids. Additionally, despite targeted education, nearly half of all patients who completed the survey did not know how to dispose of their opioid tablets. Additional efforts are needed to further refine the algorithm to reduce over-prescription of opioids and improve disposal education.

Antenatal care of women who use opioids: a qualitative study of practitioners' perceptions of strengths and challenges of current service provision in Scotland.

BACKGROUND: The increasing rise of women using opioids during pregnancy across the world has warranted concern over the access and quality of antenatal care received by this group. Scotland has particularly high levels of opioid use, and correspondingly, pregnancies involving women who use opioids. The purpose of this study was to investigate the different models of antenatal care for women using opioids during pregnancy in three Scottish Health Board Areas, and to explore multi-disciplinary practitioners' perceptions of the strengths and challenges of working with women who use opioids through these specialist services. METHODS: Thirteen semi-structured interviews were conducted with health and social care workers who had experience of providing antenatal and postnatal care to women who use drugs across three Scottish Health Board Areas: NHS Greater Glasgow and Clyde, NHS Lothian, and NHS Tayside. Framework Analysis was used to analyse interview data. The five stages of framework analysis were undertaken: familiarisation, identifying the thematic framework, indexing, charting, and mapping and interpretation. RESULTS: Each area had a specialist antenatal pathway for women who used substances. Pathways varied, with some consisting of specialist midwives, and others comprising a multidisciplinary team (e.g. midwife, mental health nurse, social workers, and an obstetrician). Referral criteria for the specialist service differed between health board areas. These specialised pathways presented several key strengths: continuity of care with one midwife and a strong patient-practitioner relationship; increased number of appointments, support and scans; and highly specialised healthcare professionals with experience of working with substance use. In spite of this, there were a number of limitations to these pathways: a lack of additional psychological support for the mother; some staff not having the skills to engage with the complexity of patients who use substances; and problems with patient engagement. CONCLUSIONS: Across the three areas, there appears to be high-quality multi-disciplinary antenatal services for women who use opioids during pregnancy. However, referral criteria vary and some services appear more comprehensive than others. Further research is needed into the perceptions of women who use opioids on facilitators and barriers to antenatal care, and provision in rural regions of Scotland.

Psychological distress among postpartum women who took opioids during pregnancy: the role of perceived stigma in healthcare settings.

This study examined the relationship between perceived stigma in healthcare settings during pregnancy and psychological distress and well-being in the postpartum period among individuals who took opioids while pregnant. Analyses included 134 birth mothers of opioid-exposed infants. At 0-1 months postpartum, perceived stigma and psychological distress were measured using the Prenatal Opioid use Perceived Stigma scale and measures from the Patient-Reported Outcome Measurement Information System (PROMIS). Food insecurity, housing instability, and Adverse Childhood Experiences (ACEs) were also assessed. Linear and generalized linear mixed-effect models were conducted to compare PROMIS scale scores and unmet needs by stigma, adjusting for site/location, age, race/ethnicity, marital status, education, public insurance, and parity. More than half of participants (54%) perceived stigma in healthcare settings. Individuals reporting stigma had higher depression, anxiety, and anger scores (p < 0.001) indicating greater psychological distress in the postpartum period compared to those reporting no stigma, after controlling for demographic characteristics. In addition, they scored significantly lower on the PROMIS meaning and purpose scale, an indicator of well-being (p = 0.002). Those reporting stigma were more likely to have food insecurity (p = 0.003), three or more ACEs (p = 0.040), verbal or physical abuse during pregnancy (p < 0.001), and less emotional support (p = 0.006) than those who did not. An association was observed between perceived stigma in the prenatal period and psychological distress in the postpartum period, providing support for stigma reduction interventions and education for healthcare providers on trauma-informed care.

Surgical removal of extended-release buprenorphine depot due to adverse reactions.

Extended-release formulations of buprenorphine offer less frequent dosing, provide consistent medication delivery, and improve adherence for treatment of opioid use disorder (OUD). Although buprenorphine is a partial agonist with seemingly less precipitated withdrawal and easier initiation than full opioid agonists used for OUD, its use is not benign and understanding of the different extended-release formulations is necessary. We report a case of a patient that received a long-acting buprenorphine formulation (Sublocade®) administered subcutaneously that presented to the emergency department with tachycardia, hyperglycemia, elevated anion gap, and sustained nausea and vomiting refractory to pharmacotherapy requiring surgical removal of the buprenorphine depot for resolution of nausea and vomiting symptoms.

Federal opioid agonist therapy policy: interrupted time series analysis of the impact of the methadone exemption removal across eight provinces in Canada.

BACKGROUND: Federal deregulation of opioid agonist therapies are an attractive policy option to improve access to opioid use disorder care and achieve widespread beneficial impacts on growing opioid-related harms. There have been few evaluations of such policy interventions and understanding effects can help policy planning across jurisdictions. METHODS: Using health administrative data from eight of ten Canadian provinces, this study evaluated the impacts of Health Canada's decision in May 2018 to rescind the requirement for Canadian health professionals to obtain an exemption from the Canadian Drugs and Substance Act to prescribe methadone for opioid use disorder. Over the study period of June 2017 to May 2019, we used descriptive statistics to capture overall trends in the number of agonist therapy prescribers across provinces and we used interrupted time series analysis to determine the effect of this decision on the trajectories of the agonist therapy prescribing workforces. RESULTS: There were important baseline differences in the numbers of agonist therapy prescribers. The province with the highest concentration of prescribers had 7.5 more prescribers per 100,000 residents compared to the province with the lowest. All provinces showed encouraging growth in the number of prescribers through the study period, though the fastest growing province grew 4.5 times more than the slowest. Interrupted time series analyses demonstrated a range of effects of the federal policy intervention on the provinces, from clearly positive changes to possibly negative effects. CONCLUSIONS: Federal drug regulation policy change interacted in complex ways with provincial health professional regulation and healthcare delivery, kaleidoscoping the effects of federal policy intervention. For Canada and other health systems such as the US, federal policy must account for significant subnational variation in OUD epidemiology and drug regulation to maximize intended beneficial effects and mitigate the risks of negative effects.

Patient's and healthcare provider's experiences with Opioid Maintenance Treatment (OMT): a qualitative evidence synthesis.

BACKGROUND: Opioid Maintenance Treatment (OMT) is the gold standard for people with opioid dependence. However, drop-out rates are high, and many patients do not reach desired outcomes. Understanding patients' and healthcare providers' experiences with the treatment can provide valuable information to improve the quality of OMT and to increase acceptability and accessibility of services. The aim of this systematic review is to explore and synthesise the experiences of OMT among persons with opioid dependence and health care providers, to inform policy makers and practitioners on how to improve OMT outcomes. METHODS: We conducted a qualitative evidence synthesis. We systematically searched in electronic databases (CINAHL, Embase, MEDLINE, and nordic databases) and searched for grey literature. As we identified many studies that met our inclusion criteria, we purposively sampled a manageable number of studies to include in this review. Two researchers independently extracted and coded data from the included studies and used the Andersen's healthcare utilization model to organize and develop codes. We assessed the methodological limitations of the studies, and our confidence in the findings using GRADE CERQual. RESULTS: We retrieved 56 relevant studies and purposively sampled 24 qualitative studies of patients' and healthcare providers' experiences with OMT. Our analyses resulted in six main themes: (1) External stigma prevents engagement and retention in treatment, (2) Being identified as in OMT contributed to an increased experience of stigma (3) Inadequate knowledge and expertise among healthcare providers affected patients' treatment experiences, (4) Quality of communication between personnel and patients impacts patients' engagement with treatment and treatment outcomes, (5) Patients wanted help with many aspects of their lives not just medication, and (6) Balancing positive expectations of OMT with treatment stigma. We found that stigma was an overarching theme across these themes. CONCLUSION: Our findings suggest that OMT could be more beneficial for patients if treatment programs prioritize efforts to diminish societal and OMT provider stigma and find strategies to better address patient needs. Initiatives should focus on improving treatment knowledge among providers, encouraging the use of client perspectives, considering the context of family members, and establishing a more holistic and flexible treatment environment.

Healthcare provider perspectives on emergency department-initiated buprenorphine/naloxone: a qualitative study.

BACKGROUND: Take-home buprenorphine/naloxone is an effective method of initiating opioid agonist therapy in the Emergency Department (ED) that requires ED healthcare worker buy-in for large-scale implementation. We aimed to investigate healthcare workers perceptions of ED take-home buprenorphine/naloxone, as well as barriers and facilitators from an ED healthcare worker perspective. METHODS: In the context of a take-home buprenorphine/naloxone feasibility study at a tertiary care teaching hospital we conducted a descriptive qualitative study. We conducted one-on-one in person or telephone interviews and focus groups with ED healthcare workers who cared for patients given take-home buprenorphine/naloxone in the feasibility study at Vancouver General Hospital from July 2019 to March 2020. We conducted 37 healthcare worker interviews from December 2019 to July 2020. We audio recorded interviews and focus groups and transcribed them verbatim. We completed interviews until we reached thematic saturation. DATA ANALYSIS: We inductively coded a sample of transcripts to generate a provisional coding structure and to identify emerging themes, which were reviewed by our multidisciplinary team. We then used the final coding structure to analyze the transcripts. We present our findings descriptively. RESULTS: Participants identified a number of context-specific facilitators and barriers to take-home buprenorphine/naloxone provision in the ED. Participants highlighted ED conditions having either facilitative or prohibitive effects: provision of buprenorphine/naloxone was feasible when ED volume was low and space was available but became less so as ED volume increased and space decreased. Similarly, participants noted that patient-related factors could have a facilitative or prohibitive effect, such as willingness to wait (willing to stay in the ED for study-related activities and buprenorphine/naloxone initiation activities), receptiveness to buprenorphine/naloxone, and comprehension of the instructions. As for staff-related factors, time was identified as a consistent barrier. Time included time available and time required to initiate buprenorphine/naloxone (including time building rapport). Healthcare worker familiarity with buprenorphine/naloxone was noted as either a facilitating factor or a barrier, and healthcare workers indicated that ongoing training would have been advantageous. Many healthcare workers identified that the ED is an important first point of contact for the target patient population. CONCLUSION: Integrating a buprenorphine/naloxone program into ED care requires organizational supports (e.g., for managing buprenorphine/naloxone within limitations of ED volume, space, and time), and ongoing education of healthcare workers to minimize identified barriers.

Withdrawal interference scale: a novel measure of withdrawal-related life disruption in opioid use disorder and alcohol use disorder.

Background: Hyperkatifeia describes amplified emotional and motivational withdrawal due to addiction-related sensitization of brain-stress-systems. Hyperkatifeia has been proposed as a target for addiction treatment development. However, translation of basic research in this area will require new tools designed to measure hyperkatifeia and related phenomena outside of laboratory settings.Objectives: We define a novel concept, withdrawal interference, and introduce a new tool - the Withdrawal Interference Scale (WIS) - which measures the impact of withdrawal on daily life among individuals with OUD or AUD.Methods: Described are the combined results of three separate cross-sectional studies. The structural validity, convergent validity, construct validity, trans-diagnostic (AUD/OUD) configural, metric, and scalar invariance, internal consistency, and composite reliability of WIS was tested among three independent samples of 1) treatment-seeking adults with OUD (n = 132), 2) treatment-seeking adults with AUD (n = 123), and 3) non-treatment-seeking adults with OUD (n = 140). Males numbered 218 and females were 163.Results: WIS exhibited structural validity (1 factor), convergent validity (average variance extracted .670-.676), construct validity, trans-diagnostic configural (χ2/df = 2.10), metric (Δχ2 = 5.70, p = .681), and scalar invariance (Δχ2 = 12.34, p = .338), internal consistency (α .882-928), and composite reliability (.924-.925).Conclusion: These results suggest WIS is a valid and reliable instrument for measuring withdrawal-related life disruption in AUD and OUD. Further, given our findings of transdiagnostic measurement invariance, WIS scores of individuals with AUD and OUD can be meaningfully compared in future statistical analyses.

Withdrawal catastrophizing scale: initial psychometric properties and implications for the study of opioid use disorder and hyperkatifeia.

Background: Discovery of modifiable factors influencing subjective withdrawal experience might advance opioid use disorder (OUD) research and precision treatment. This study explores one factor - withdrawal catastrophizing - a negative cognitive and emotional orientation toward withdrawal characterized by excessive fear, worry or inability to divert attention from withdrawal symptoms.Objectives: We define a novel concept - withdrawal catastrophizing - and present an initial evaluation of the Withdrawal Catastrophizing Scale (WCS).Methods: Prospective observational study (n = 122, 48.7% women). Factor structure (exploratory factor analysis) and internal consistency (Cronbach's α) were assessed. Predictive validity was tested via correlation between WCS and next-day subjective opiate withdrawal scale (SOWS) severity. The clinical salience of WCS was evaluated by correlation between WCS and withdrawal-motivated behaviors including risk taking, OUD maintenance, OUD treatment delay, history of leaving the hospital against medical advice and buprenorphine-precipitated withdrawal.Results: WCS was found to have a two-factor structure (distortion and despair), strong internal consistency (α = .901), and predictive validity - Greater withdrawal catastrophizing was associated with next-day SOWS (rs (99) = 0.237, p = .017). Withdrawal catastrophizing was also correlated with risk-taking behavior to relieve withdrawal (rs (119) = 0.357, p < .001); withdrawal-motivated OUD treatment avoidance (rs (119) = 0.421, p < .001), history of leaving the hospital against medical advice (rs (119) = 0.373, p < .001) and buprenorphine-precipitated withdrawal (rs (119) = 0.369, p < .001).Conclusion: This study provides first evidence of withdrawal catastrophizing as a clinically important phenomenon with implications for the future study and treatment of OUD.

The Perceived Role of Withdrawal in Maintaining Opioid Addiction among Adults with Untreated Opioid Use Disorder: A Survey of Syringe Exchange Program Participants.

Background: Withdrawal is believed to play a central role in the brain disease model of addiction. However, little research describes withdrawal-motives among untreated individuals in community settings. Methods: This cross-sectional study surveyed syringe exchange program participants (n = 139) with untreated opioid use disorder (OUD) in Columbus, Ohio from January 10th to March 25th, 2023, to assess their perceptions of the role of withdrawal in OUD maintenance, treatment delay, and OUD's refractoriness to buprenorphine. Participants responded to a survey including DSM-5 OUD criteria, demographics, and questions about substance use and opioid withdrawal. Participant ages ranged from 21 to 65 years with a mean age of 37.5 years and standard deviation of 8.1. The racial distribution of the sample was as follows: 81% White/Caucasian, 12% Black/African American, 3% Native American or Alaskan Native. Results: Sixty-six percent of participants agreed, or strongly agreed that opioid withdrawal was "the most important reason" they had been unable to stop using opioids. Almost seventy-one percent agreed, or strongly agreed that worry about opioid withdrawal had caused them to "put off or delay" OUD treatment. Although all participants had active, untreated OUD at the time of recruitment, most (85%) had previously tried buprenorphine, and the majority (78%) reported having experienced buprenorphine-precipitated withdrawal. Conclusions: Among this community sample of individuals with untreated OUD, withdrawal was perceived to have an important role in maintaining OUD, including by motivating OUD treatment delay. Prior buprenorphine-precipitated withdrawal was common, suggesting aversion to withdrawal might possibly be associated with OUD's refractoriness to buprenorphine.

Expanding Public Health Initiatives Through Community Pharmacies and Student Pharmacists: A Programmatic Case Study.

BACKGROUND: Community pharmacies are critical to the public health infrastructure in the United States and provide reliable information for public health concerns. Public health agencies curate educational materials that community pharmacy teams can disseminate. Student pharmacists participate in experiential learning at community pharmacies which could be utilized for dissemination of these resources. OBJECTIVES: The objectives of this project were to: (1) design a model for dissemination of public health information at community pharmacies; and (2) evaluate both the dissemination model's reach within communities and student pharmacist learnings from engagement in the model. METHODS: We engaged student pharmacists in a model to disseminate information at community pharmacies for two Centers for Disease Control and Prevention initiatives about Opioid Use Disorder Anti-Stigma and Antibiotic Stewardship Education. The number of pharmacies and student pharmacists who participated from 2021-2023 were retrospectively reviewed to demonstrate programmatic reach. A retrospective text mining of student assignments was conducted to evaluate student experiences. Descriptive statistics were used to report quantitative data. An inductive, rapid content analysis was completed for qualitative data. RESULTS: Across three years, 333 student pharmacists participated. Students reached 121 community pharmacies, 139 practicing pharmacist preceptors, and over 2000 patients with education and resources. Eleven student learning points emerged from the qualitative analysis. These included learnings around opioid use disorder and antibiotic stewardship. Students also acknowledged that there are public health needs present in communities and that community pharmacy teams are well-positioned to address these needs. CONCLUSION: Engaging student pharmacists to distribute curated information from public health authorities, to both pharmacist preceptors and patients at community pharmacies, is one way to educate future pharmacists, pharmacy teams, and communities on public health priorities. Pharmacies can serve as key venues in communities for dissemination of reliable public health information.

Take-home naloxone administered in emergency settings: feasibility of intervention implementation in a cluster randomized trial.

BACKGROUND: Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT). METHODS: We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019-2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events. RESULTS: At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported. CONCLUSION: Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned. TRIAL REGISTRATION: ISRCTN13232859 (Registered 16/02/2018).

Impact of Depressive Symptom Severity on Buprenorphine/Naloxone and Methadone Outcomes in People With Prescription-Type Opioid Use Disorder: Results From a Pragmatic Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD). METHOD: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24. RESULTS: Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use. CONCLUSIONS: Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27th, 2017, prior to participants enrollment.

Contraception and Healthcare Utilization by Reproductive-Age Women Who Use Drugs in Rural Communities: a Cross-Sectional Survey.

BACKGROUND: Women who use drugs (WWUD) have low rates of contraceptive use and high rates of unintended pregnancy. Drug use is common among women in rural U.S. communities, with limited data on how they utilize reproductive, substance use disorder (SUD), and healthcare services. OBJECTIVE: We determined contraceptive use prevalence among WWUD in rural communities then compared estimates to women from similar rural areas. We investigated characteristics of those using contraceptives, and associations between contraceptive use and SUD treatment, healthcare utilization, and substance use. DESIGN: Rural Opioids Initiative (ROI) - cross-sectional survey using respondent-driven sampling (RDS) involving eight rural U.S. regions (January 2018-March 2020); National Survey on Family Growth (NSFG) - nationally-representative U.S. household reproductive health survey (2017-2019). PARTICIPANTS: Women aged 18-49 with prior 30-day non-prescribed opioid and/or non-opioid injection drug use; fecundity determined by self-reported survey responses. MAIN MEASURES: Unweighted and RDS-weighted prevalence estimates of medical/procedural contraceptive use; chi-squared tests and multi-level linear regressions to test associations. KEY RESULTS: Of 855 women in the ROI, 36.8% (95% CI 33.7-40.1, unweighted) and 38.6% (95% CI 30.7-47.2, weighted) reported contraceptive use, compared to 66% of rural women in the NSFG sample. Among the ROI women, 27% had received prior 30-day SUD treatment via outpatient counseling or inpatient program and these women had increased odds of contraceptive use (aOR 1.50 [95% CI 1.08-2.06]). There was a positive association between contraception use and recent medications for opioid use disorder (aOR 1.34 [95% CI 0.95-1.88]) and prior 6-month primary care utilization (aOR 1.32 [95% CI 0.96-1.82]) that did not meet the threshold for statistical significance. CONCLUSION: WWUD in rural areas reported low contraceptive use; those who recently received SUD treatment had greater odds of contraceptive use. Improvements are needed in expanding reproductive and preventive health within SUD treatment and primary care services in rural communities.