The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

Sex Differences in the Development of an Opioid Addiction-Like Phenotype: A Focus on the Telescoping Effect.

Background: Women develop addiction and drug-related health consequences after fewer years of drug use than men; this accelerated time course, or telescoping effect, has been observed clinically for multiple drugs, including opioids. Preclinical studies indicate that this is a biologically based phenomenon; however, these studies have focused exclusively on cocaine, and none have considered health effects. Methods: In this study, we used a rat (Sprague Dawley) model to determine sex differences in the time course for the development of an opioid addiction-like phenotype, as defined by the development of physical dependence (withdrawal-induced weight loss) and an increase in motivation for fentanyl (under a progressive-ratio schedule). Effects were determined following either 10 days (optimized, experiment 1) or 3 days (threshold, experiment 2) of extended-access fentanyl self-administration (24 hours/day, fixed ratio 1, 2- to 5-minute trials/hour) or following short-access fentanyl self-administration (subthreshold, experiment 3; fixed ratio 1, up to 40 infusions/day). Opioid-related adverse health effects were also determined (experiment 4). Results: Motivation for fentanyl was similarly increased in males and females following 10 days of extended-access self-administration (experiment 1), was transiently increased in females, but not males, following 3 days of extended-access self-administration (experiment 2) and was not increased in either sex following short-access self-administration (experiment 3). Females developed fentanyl-associated adverse health effects more readily than males (experiment 4), with particularly robust differences during extended-access self-administration and withdrawal. Conclusions: As with findings in humans, female rats developed opioid addiction-like features and adverse health consequences more readily than male rats. These data provide support for a biologically based telescoping effect in females for opioids, particularly for opioid-related adverse health consequences.

In this issue, we explore how female rats develop signs of opioid addiction and related health issues faster than male rats, a phenomenon known as the telescoping effect. This study expands on previous research by using a rat model to assess addiction-like behaviors and health consequences following different withdrawal period and durations of fentanyl self-administration. The findings underline the biological underpinnings of sex differences in addiction trajectories, previously demonstrated in humans but not yet studied in opioids until now.

Feasibility and Acceptability of a Trauma-informed Intervention to Leverage Caregivers in Preventing Opioid Use Among Youth Involved in the Legal System.

Youth in the legal system (YILS) report high rates of substance use (SU), complex family/social relationships, and chronic trauma. The current study tested the feasibility of a prevention intervention, Trust-based Relational Intervention® (TBRI®), that leverages family systems by strengthening connection and providing emotional and instrumental guidance and support. TBRI includes the primary TBRI Intervention, comprised of Caregiver Training, Youth Training, and joint youth-caregiver Nurture Groups, and TBRI Family Coaching. With a sample of eight youth-caregiver dyads, the study adopted a mixed-methods design with a multi-informant approach to fulfill two goals: (1) testing TBRI as a prevention intervention for opioid use (OU), other SU, and related issues, and (2) testing the feasibility and acceptability of the TBRI Intervention by virtual delivery. Session attendance and completion rates demonstrated feasibility of recruiting and retaining participants and intervention fidelity. Preliminary results were reported on intervention outcomes, including OU and other SU, illegal activities, and educational attainment. Pre- and post-intervention comparisons showed decreases in youth negative urgency, conduct problems, and hyperactivity. Caregiver and staff participants responded favorably to TBRI and its virtual delivery; youth were more capable of expressing their needs and acknowledged the importance of families in preventing problems after discharge from secure facilities. While acknowledging sufficiency of intervention content, caregivers expressed the desire for more sessions. Results demonstrate the feasibility and acceptability of a trauma-informed, attachment-based prevention intervention for youth and families in contact with the legal system. TBRI is a promising approach for preventing the initiation or escalation of OU among YILS.

Predictive Model for Opioid Use Disorder in Chronic Pain: A Development and Validation Study.

BACKGROUND/OBJECTIVE: There are several questionnaires for the challenge of anticipating opioid use disorder (OUD). However, many are not specific for chronic non-cancer pain (CNCP) or have been developed in the American population, whose sociodemographic factors are very different from the Spanish population, leading to scarce translation into clinical practice. Thus, the aim of this study is to prospectively validate a predictive model for OUD in Spanish patients under long-term opioids. METHODS: An innovative two-stage predictive model was developed from retrospective (n = 129) and non-overlapping prospective (n = 100) cohorts of real-world CNCP outpatients. All subjects used prescribed opioids for 6 or more months. Sociodemographic, clinical and pharmacological covariates were registered. Mu-opioid receptor 1 (OPRM1, A118G, rs1799971) and catechol-O-methyltransferase (COMT, G472A, rs4680) genetic variants plus cytochrome P450 2D6 (CYP2D6) liver enzyme phenotypes were also analyzed. The model performance and diagnostic accuracy were calculated. RESULTS: The two-stage model comprised risk factors related to OUD (younger age, work disability and high daily opioid dose) and provided new useful information about other risk factors (low quality of life, OPRM-G allele and CYP2D6 extreme phenotypes). The validation showed a satisfactory accuracy (70% specificity and 75% sensitivity) for our predictive model with acceptable discrimination and goodness of fit. CONCLUSIONS: Our study presents the results of an innovative model for predicting OUD in our setting. After external validation, it could represent a change in the paradigm of opioid treatment, helping clinicians to better identify and manage the risks and reduce the side effects and complications.

Differences in prescribing patterns of opioid dependence drugs among patients with primary alcohol use problems and opioid use disorders within New York State by social determinant factors, 2005-2018.

BACKGROUND: The increase in alcohol use problems and opioid use disorder (OUD) highlights the need for research on effective medication treatments for patients with dual diagnoses. OBJECTIVES: This study analyzed trends and social disparities in prescribing OUD medications for patients who initially had alcohol use problems and later received their first OUD diagnosis. METHODS: This study utilized merged data from the New York State Office of Addiction Services and Supports and the Medicaid to analyze individuals aged 18 and older who initially had primary alcohol use problems and later had OUD for the first time between 2005 and 2018. It examined the rates of new buprenorphine and naltrexone prescriptions across various demographic and socioeconomic groups. RESULTS: Among 27,029 clients, the average rate of new buprenorphine was 64.23 per 1,000 clients (95% CI [61.30, 67.15]), with upward trends. The 18-35 age group had the highest buprenorphine utilization (111.48 per 1,000 clients), and highest increase rates compared to other age groups. The White non-Hispanic group had the highest rates of buprenorphine (119.23 per 1000 clients) and showed larger increase over time compared to other race/ethnicity groups. Disabled patients showed slower increasing rates of buprenorphine compared to other groups. Upward trends were observed in naltrexone. All observed differences were statistically significant (P<0.05). CONCLUSIONS: Trends showed increased use of OUD medications, with varying rates of buprenorphine utilization across different ages, races, and employment statuses. Despite this, the rates of receiving new buprenorphine remained low, suggesting a need for innovative methods to expand access to treatments.

Perspectives of physicians and doulas on shared decision-making and decision counseling in the treatment of pregnant women with opioid use disorders.

INTRODUCTION: Research about the application of shared decision-making (SDM) in the context of Medication Assisted Treatment (MAT) for pregnant women with opioid use disorder (OUD) is limited. The objectives of our study were to 1) examine facilitators of and barriers to SDM for the initiation of MAT in clinical practice and 2) evaluate the receptivity of clinicians and doulas involved in the care of women with OUD to the use of an online software application to facilitate SDM about MAT. METHODS: This qualitative study utilized semi-structured interviews with consenting physicians and doulas who provided care for pregnant women with OUD between November 2021 and May 2022. Participants were asked about factors influencing SDM in practice. In addition, the study asked participants about the feasibility of using the Jefferson Decision Counseling Guide© (JDCG) to educate pregnant women with OUD as to the benefits and risks of undergoing MAT versus no treatment and to help patients clarify their treatment preference. The study recorded the interview and transcribed it verbatim using Rev. transcription services. The study used thematic analyses to code the data and identify key barriers and facilitators of SDM and perceptions of the SDM tool. RESULTS: Nineteen participants completed interviews. The study identified several barriers to SDM including time constraints, lack of decision counseling tools at points of care, and patients presenting in an actively high state or withdrawing. Peer workers or other trained personnel, giving patients more time, and comfort in decision counseling are examples of facilitators identified by the participants of the study. Participants believed that the counseling tool could facilitate conversations with patients and should be integrated into the workflow. CONCLUSION: In this qualitative study, we identified several barriers and facilitators of SDM to initiate MAT for pregnant women with OUD. Our findings indicate that there are challenges and opportunities for healthcare systems to increase SDM in this marginalized patient population. Feedback from participants highlighted their receptivity to the use of SDM tools to facilitate meaningful conversations in various settings that can guide decision making about care.

Attributes of higher- and lower-performing hospitals in the Consult for Addiction Treatment and Care in Hospitals (CATCH) program implementation: A multiple-case study.

INTRODUCTION: Six hospitals within the New York City public hospital system implemented the Consult for Addiction Treatment and Care in Hospitals (CATCH) program, an interprofessional addiction consult service. A stepped-wedge cluster randomized controlled trial tested the effectiveness of CATCH for increasing initiation and engagement in post-discharge medication for opioid use disorder (MOUD) treatment among hospital patients with opioid use disorder (OUD). The objective of this study was to identify facility characteristics that were associated with stronger performance of CATCH. METHODS: This study used a mixed methods multiple-case study design. The six hospitals in the CATCH evaluation were each assigned a case rating according to intervention reach. Reach was considered high if ≥50 % of hospitalized OUD patients received an MOUD order. Cross-case rating comparison identified attributes of high-performing hospitals and inductive and deductive approaches were used to identify themes. RESULTS: Higher-performing hospitals exhibited attributes that were generally absent in lower-performing hospitals, including (1) complete medical provider staffing; (2) designated office space and resources for CATCH; (3) existing integrated OUD treatment resources; and (4) limited overlap between the implementation period and COVID-19 pandemic. CONCLUSIONS: Hospitals with attributes indicative of awareness and integration of OUD services into general care were generally higher performing than hospitals that had siloed OUD treatment programs. Future implementations of addiction consult services may benefit from an increased focus on hospital- and community-level buy-in and efforts to integrate MOUD treatment into general care.

Prenatal opioid exposure significantly impacts placental protein kinase C (PKC) and drug transporters, leading to drug resistance and neonatal opioid withdrawal syndrome.

Background: Neonatal Opioid Withdrawal Syndrome (NOWS) is a consequence of in-utero exposure to prenatal maternal opioids, resulting in the manifestation of symptoms like irritability, feeding problems, tremors, and withdrawal signs. Opioid use disorder (OUD) during pregnancy can profoundly impact both mother and fetus, disrupting fetal brain neurotransmission and potentially leading to long-term neurological, behavioral, and vision issues, and increased infant mortality. Drug resistance complicates OUD and NOWS treatment, with protein kinase regulation of drug transporters not fully understood. Methods: DNA methylation levels of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, along with protein kinase C (PKC) genes, were assessed in 96 placental samples using the Illumina Infinium MethylationEPIC array (850K). Samples were collected from three distinct groups: 32 mothers with infants prenatally exposed to opioids who needed pharmacological intervention for NOWS, 32 mothers with prenatally opioid-exposed infants who did not necessitate NOWS treatment, and 32 mothers who were not exposed to opioids during pregnancy. Results: We identified 69 significantly differentially methylated SLCs, with 24 hypermethylated and 34 hypomethylated, and 11 exhibiting both types of methylation changes including SLC13A3, SLC15A2, SLC16A11, SLC16A3, SLC19A2, and SLC26A1. We identified methylation changes in 11 ABC drug transporters (ABCA1, ABCA12, ABCA2, ABCB10, ABCB5, ABCC12, ABCC2, ABCC9, ABCE1, ABCC7, ABCB3): 3 showed hypermethylation, 3 hypomethylation, and 5 exhibited both. Additionally, 7 PKC family genes (PRKCQ, PRKAA1, PRKCA, PRKCB, PRKCH, PRKCI, and PRKCZ) showed methylation changes. These genes are associated with 13 pathways involved in NOWS, including ABC transporters, bile secretion, pancreatic secretion, insulin resistance, glutamatergic synapse, and gastric acid secretion. Conclusion: We report epigenetic changes in PKC-related regulation of drug transporters, which could improve our understanding of clinical outcomes like drug resistance, pharmacokinetics, drug-drug interactions, and drug toxicity, leading to maternal relapse and severe NOWS. Novel drugs targeting PKC pathways and transporters may improve treatment outcomes for OUD in pregnancy and NOWS.

Revisiting dezocine for opioid use disorder: A narrative review of its potential abuse liability.

AIMS: Opioid use disorder (OUD) remains a serious public health problem. Opioid maintenance treatment is effective but under-utilized, hard to access under existing federal regulations, and, once patients achieve OUD stability, challenging to discontinue. Fewer than 2% of persons with OUD stop using opioids completely. There have been calls from public advocacy groups, governmental agencies, and public health officials for new treatments for OUD. Dezocine, a non-scheduled opioid previously used in the United States and currently widely prescribed in China for pain management, could be a candidate for a novel OUD treatment medication in the U.S. Nonetheless, to date, there have been no reviews of the clinical and preclinical literature detailing dezocine's abuse potential, a key consideration in assessing its clinical utility. DISCUSSION: There are no English language reports of human abuse, dependence, or overdose of dezocine, despite years of extensive clinical use. There are a few case reports of dezocine abuse in the Chinese literature, but there are no reports of overdose deaths. Dezocine is perceived as an opioid and is "liked" by opioid-experienced human and non-human primates, properties that are not dose-dependent and are mitigated by ceiling effects-higher doses do not result in more "liking." There is little withdrawal, spontaneous or precipitated, in humans, monkeys, rats, or mice treated chronically with dezocine alone. However, at some doses, dezocine can precipitate withdrawal in humans and monkeys dependent on other opioids. In rodents, dezocine reduces the severity of morphine withdrawal and the rewarding properties of other opioids. CONCLUSIONS: Although dezocine is reinforcing in humans and monkeys with prior or concurrent opioid use within a restricted dose range, there are only a few anecdotal reports of dezocine abuse despite of the long history of use in humans. Given the evidence of dezocine's limited abuse potential, it could be useful both as a treatment for OUD. However, in-depth studies would be required for dezocine to be re-considered for clinical use.

An Assertive Community Intervention to Engage Youth with Opioid Use Disorder and Their Families.

Medications for opioid use disorder (MOUD) are the most effective treatment for OUD. Many patients struggle with adherence, but young adults face unique developmental barriers and experience higher relapse rates. The Youth Opioid Recovery Support (YORS) intervention is a developmentally informed behavioral approach to increase medication adherence through assertive outreach, family involvement, low-barrier access to extended-release MOUD, and contingency management. Early studies have shown promising results, and a randomized controlled trial is underway. Here we describe the implementation of YORS using case examples, offer guidance on adapting YORS to real-world clinical settings, and explore future directions for research and practice.

Barriers and facilitators to implementing treatment for opioid use disorder in community hospitals.

INTRODUCTION: Methadone and buprenorphine are effective treatment for opioid use disorder (OUD), yet they are vastly under-utilized across US hospitals. To inform a national trial assessing the effectiveness of implementation strategies to increase adoption of an inpatient hospital-based opioid treatment (HBOT) model (NCT04921787), we explored barriers and facilitators to expanding medication for opioid use disorder (MOUD) within community hospitals across the United States. METHODS: From November 2021 to March 2022, we used purposeful and snowball sampling to identify and interview participants involved in inpatient care of patients with OUD from twelve community hospitals. We conducted semi-structured interviews on providers' experiences and perspectives on current treatment approaches as well as potential influences on MOUD expansion in their hospitals. We used thematic analysis to identify key barriers and facilitators that could impact implementation of an HBOT model, and organized these findings based on the Consolidated Framework for Implementation Research (CFIR). RESULTS: From qualitative interviews with 57 participants (30 physicians, 7 pharmacists, 6 nurses, and 14 professionals involved in the care of patients with OUD), we identified key barriers and facilitators mapped to CFIR's internal and outer settings. The most salient inner setting domains included tension for change and relative priority, compatibility, available resources, organizational culture, access to knowledge and information, relational connections and communications, and information technology infrastructure. Outer setting domains included policies and laws, financing, and partnerships and connections. CONCLUSIONS: Identifying potential barriers and facilitators can inform hospital-specific strategies to support implementation of HBOT. Implementation strategies that address barriers such as staff availability, knowledge, and attitudes may support increased HBOT adoption. On a broader scale, national policy changes such as increased financing and public reporting of quality metrics would address other barriers we identified and may also encourage hospitals to adopt HBOT models.

Self-Reported Illicitly Manufactured Fentanyl Use and Associated Health and Substance Use Risks in the United States, 2022.

OBJECTIVE: Illicitly manufactured fentanyl (IMF) has emerged as a catalyst of the recent drug epidemic in the United States. To devise more targeted and effective prevention and treatment strategies, it is crucial to understand the demographics of the population who consumes IMF and their health and associated substance use risks. Therefore, this study explores the sociodemographic characteristics, health diagnoses, and drug injection practices of individuals reporting IMF use. METHODS: Data were derived from the 2022 National Survey on Drug Use Health, based on a nationally representative sample of non-institutionalized individuals aged 12 and older in the United States. Focusing on 306 adults who reported ever using IMF, we examined their sociodemographic characteristics, health diagnoses, and substance-related behaviors in comparison to adults with a drug use disorder who did not report IMF use, using logistic regression analyses. RESULTS: The majority of U.S. adults reporting IMF use were aged 35-64, male, non-Hispanic White, with a high school education or lower, never married, and had an annual household income below $40,000. Compared to adults with a drug use disorder who did not report IMF use, they were more likely to report heart conditions (AOR = 2.67, 95% CI = 1.29-5.54) and Hepatitis B or C (AOR = 8.35, 95% CI = 4.05-17.02). Nearly half of this group had an opioid use disorder (OUD) in the past year, and 65.7% (95% CI = 56.7-74.8) reported a history of injecting drugs. CONCLUSIONS: To effectively curb the current drug epidemic, incorporating effective treatment for OUD and harm reduction strategies is crucial.

Correlates of fentanyl preference among people who use drugs in Rhode Island.

BACKGROUND: Fentanyl is increasingly pervasive in the unregulated drug supply and is a driver of drug overdose deaths in the United States. The aims of this study were to characterize and identify correlates of fentanyl preference among people who use drugs (PWUD) in Rhode Island (RI). METHODS: Using bivariate analysis, we examined associations between fentanyl preference and sociodemographic and psychosocial characteristics at baseline among participants enrolled in the RI Prescription Drug and Illicit Drug Study from August 2020-February 2023. Fentanyl preference was operationalized based on responses to a five-point Likert scale: "I prefer using fentanyl or drugs that have fentanyl in them." Participants who responded that they "strongly disagree," "disagree," or were "neutral" with respect to this statement were classified as not preferring fentanyl, whereas participants who responded that they "agree" or "strongly agree" were classified as preferring fentanyl. RESULTS: Among 506 PWUD eligible for inclusion in this analysis, 15% expressed a preference for fentanyl or drugs containing fentanyl as their drug of choice. In bivariate analyses, preference for fentanyl was positively associated with younger age, white race, lifetime history of overdose, history of injection drug use, past month enrollment in a substance use treatment program, past month treatment with medications for opioid use disorder, and preferences for heroin and crystal methamphetamine (all p < 0.05). Descriptive data yielded further insight into reasons for fentanyl preference, the predominant having to do with perceived effects of the drug and desire to avoid withdrawal symptoms. CONCLUSIONS: Only a relatively small subset of study participants preferred drugs containing fentanyl. Given the increased prevalence of fentanyl contamination across substances within the unregulated drug market, the result for PWUD is increasingly less agency with respect to choice of drug; for example, people may be forced to use fentanyl due to restricted supply and the need to mitigate withdrawal symptoms, or may be using fentanyl without intending to do so. Novel and more effective interventions for PWUD, including increased access to age-appropriate harm reduction programs such as fentanyl test strips and overdose prevention centers, are needed to mitigate fentanyl-related harms.

Incidence, Timing and Social Correlates of the Development of Opioid Use Disorder Among Clients Seeking Treatment for an Alcohol Use Problem: Changes Over the Three Waves of the Opioid Epidemic.

Introduction: Opioid use disorder (OUD) and opioid overdose (OD) have shown to be strongly associated with alcohol use disorder (AUD). As a potential target population for secondary prevention, we examined the incidence and timing of OUD/OD among clients seeking treatment for alcohol problems and how this has changed over the three waves of the opioid epidemic corresponding to the primary opioid involved in fatal ODs, prescription painkillers (2007-2009), heroin (2010-2012), and fentanyl (2013-2016). We also examined social determinants of health as predictors of OUD/OD. Methods: Clients (N = 59,186) presenting for a first treatment for alcohol use problems were extracted from the Client Data System (CDS) of the New York State Office of Addiction Services and Support (OASAS) and New York State (NYS) Medicaid Data Warehouse. Using this cohort, we employed the Kaplan-Meier method to determine the survival probabilities for patients admitted in each of the three waves of the epidemic. Results: Patients in Cohort 3 (2013-2016) were diagnosed with OUD/OD more rapidly than patients in Cohort 1 (2007-2009) or Cohort 2 (2010-2012), although the overall estimated OUD/OD rate was comparable across the three cohorts. Discussion: These findings provide a useful estimate of the incidence and the expected time frame of an opioid use disorder in clients with an alcohol use problem. Moreover, it suggests that as the opioid epidemic progressed, OUD/OD developed more rapidly but the overall prevalence did not increase.

Personalized medicine and opioid use disorder.

Opioid use disorder (OUD) is a major public health problem affecting millions of people worldwide. Although OUD is a chronic and relapsing disorder, a variety of pharmacological and non-pharmacological interventions are available. Medication-assisted treatment of OUD generally relies on competition for opioid receptors against the addictive substance. The mechanisms of this competition are to block or inactivate the opioid receptor or activate the receptor with a substance that is intermittent or long acting. Methadone and buprenorphine are two United States Food and Drug Administration-approved medications that have long-term positive effects on the health of opioid-dependent individuals. Although clinical studies of drugs generally demonstrate efficacy in thousands of people and toxicity is excluded, it cannot be predicted whether the given drug will cause side effects in one of the patients at the treatment dose. Individual differences can be explained by many biological and environmental factors. Variations in genes encoding drug metabolism or cellular drug targets significantly explain the variability in drug response between individuals. Therefore, for the effects of candidate genes to be accepted and included in individual treatment protocols, it is important to repeat studies on individuals of different ethnic backgrounds and prove a similar effect.

Collaborating to heal addiction and mental health in primary care (CHAMP): A protocol for a hybrid type 2a trial.

BACKGROUND: The gold-standard treatment for opioid use disorder (OUD) is medication for OUD (MOUD). However, less than a quarter of people with OUD initiate MOUD. Expanding the Collaborative Care Model (CoCM) to include primary care patients with OUD could improve access to and initiation of MOUD. This paper presents the methods and baseline sample characteristics of a Hybrid Type 2a trial comparing the effectiveness of CoCM for OUD and co-occurring mental health symptoms (MHS) to CoCM for MHS only. METHOD: 42 primary care clinics were cluster randomized and 254 primary care patients with OUD and elevated MHS were enrolled. Recruitment was terminated early by the Data and Safety Monitoring Board for futility. Participants completed research assessments at baseline, 3 months, and 6 months. The multiple primary outcomes were past-month number of days of nonmedical opioid use and SF12 Mental Health Component Summary (MCS) scores. RESULTS: MCS scores were over a standard deviation below the national mean (M = 34.5). Nearly half (47.6 %) of participants had previously overdosed in their lifetimes. Three quarters (76.0 %) were already being prescribed MOUD at baseline, only 30.4 % reported non-medical use of opioids, and only 33.9 % reported being bothered by opioid cravings. CONCLUSION: The unexpectedly high proportion of enrollees already prescribed MOUD at baseline indicates that most patients were in the maintenance rather than acute phase of treatment. Challenges identifying and enrolling patients in the acute phase of OUD treatment implies that intervention effectiveness will depend on its success preventing the discontinuation of MOUD rather than initiating MOUD.

Overdose Detection Among High-Risk Opioid Users Via a Wearable Chest Sensor in a Supervised Injecting Facility: Protocol for an Observational Study.

BACKGROUND: Opioid overdose is a global health crisis, affecting over 27 million individuals worldwide, with more than 100,000 drug overdose deaths in the United States in 2022-2023. This protocol outlines the development of the PneumoWave chest biosensor, a wearable device being designed to detect respiratory depression in real time through chest motion measurement, intending to enhance early intervention and thereby reduce fatalities. OBJECTIVE: The study aims to (1) differentiate opioid-induced respiratory depression (OIRD) from nonfatal opioid use patterns to develop and refine an overdose detection algorithm and (2) examine participants' acceptability of the chest biosensor. METHODS: The study adopts an observational design over a 6-month period. The biosensor, a small device, will be worn by consenting participants during injecting events to capture chest motion data. Safe injecting facilities (SIF) in Melbourne, Victoria (site 1), and Sydney, New South Wales (site 2), which are legally sanctioned spaces where individuals can use preobtained illicit drugs under medical supervision. Each site is anticipated to recruit up to 100 participants who inject opioids and attend the SIF. Participants will wear the biosensor during supervised injecting events at both sites. The biosensor will attempt to capture data on an anticipated 40 adverse drug events. The biosensor's ability to detect OIRD will be compared to the staff-identified events that use standard protocols for managing overdoses. Measurements will include (1) chest wall movement measured by the biosensor, securely streamed to a cloud, and analyzed to refine an overdose detection algorithm and (2) acute events or potential overdose identified by site staff. Acceptability will be measured by a feedback questionnaire as many times as the participant is willing to throughout the study. RESULTS: As of April 2024, a total of 47 participants have been enrolled and data from 1145 injecting events have already been collected, including 10 overdose events. This consists of 17 females and 30 males with an average age of 45 years. Data analysis is ongoing. CONCLUSIONS: This protocol establishes a foundation for advancing wearable technology in opioid overdose prevention within SIFs. The study will provide chest wall movement data and associated overdose data that will be used to train an algorithm that allows the biosensor to detect an overdose. The study will contribute crucial insights into OIRD, emphasizing the biosensor's potential step forward in real-time intervention strategies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57367.

Identifying Provider Barriers to the Implementation of Opioid Harm Reduction Methods: An Initial Narrative Review.

According to the Centers for Disease Control and Prevention, the opioid epidemic remains a major issue in the United States, with over 80,000 deaths attributed to opioids in 2021. This public health crisis continues to impact communities across the country, highlighting the need for intervention and reflecting the nation's failed attempts at prohibition through criminalization to reduce opioid use. Harm reduction methodshave proven to be effective in preventing adverse health outcomes and promoting the overall well-being of individuals with opioid use disorders. However, significant gaps remain in the universal implementation by healthcare providers. This review evaluated the PICOT question: What barriers exist among providers in implementing evidence-based harm reduction methods for adults aged 18 years and older, with and without opioid use disorders? A literature search was conducted across databases using key words which included: "Health care provider," "Physician," "Pharmacist," "Harm reduction," "Harm reduction programs," "Naloxone," "Buprenorphine-naloxone induction," "Methadone," "Naloxone take home kits," "Stigma," "Barriers," "Negative perception," "Refusal." The inclusion criteria focused on identifying provider barriers, specifically regarding opioid use. . The review revealed 3 major barriers that exist among providers to prevent harm reduction: stigma, lack of education and knowledge, and lack of access to resources for long-term management. Recognizing these barriers among providers can help organizations develop targeted interventions to overcome them, leading to widespread adoption of opioid harm reduction methods. The results provide an initial narrative review of the current evidence at the time of the authors search to inform practice, policy, and future research.

Incidence of buprenorphine-precipitated opioid withdrawal in adults with opioid use disorder: A systematic review.

BACKGROUND AND AIMS: Buprenorphine is an evidence-based treatment for opioid use disorder, and the risk of precipitated withdrawal contributes to its underuse. The goal of this systematic review was to determine the incidence of buprenorphine-precipitated withdrawal in adults with opioid use disorder. METHODS: This systematic review was registered on PROSPERO (CRD42023437634). We searched Medline, Embase Classic + Embase, and Cochrane CENTRAL from inception to 10 November 2023, and included original research that reported the incidence of sublingual buprenorphine-precipitated withdrawal in adults with opioid use disorder. Primary screening was completed by four independent reviewers. Full text review, data extraction and risk of bias assessments using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2 tool were completed by two independent reviewers. The primary outcome was precipitated withdrawal. Secondary outcomes were baseline opioids used, induction dose, initial Clinical Opiate Withdrawal Scale (COWS) score, location of induction, definition and severity of precipitated withdrawal and adverse events. The range of incidence of precipitated withdrawal across studies was described. RESULTS: Our search yielded 10 197 unique citations. Twenty-one cohort and five randomized trials met inclusion criteria (n = 4497, range 20-1293). The overall incidence of precipitated withdrawal ranged from 0 to 13.2%. Nine studies defined precipitated withdrawal; definitions were inconsistent. Most patients used heroin at baseline. The most common initial dose of buprenorphine was between 2 mg and 8 mg (range: 0.075 mg-24 mg). Initial minimum COWS score ranged from 5 to 13. Induction locations included home, inpatient, emergency department, pre-hospital, outpatient and residential units. Of the fifteen studies with cases of precipitated withdrawal, nine studies did not report the severity of withdrawal experienced. Other induction-related adverse events varied. The overall quality of included studies was poor. CONCLUSIONS: The best available evidence suggests the incidence of buprenorphine-precipitated withdrawal in adults with opioid use disorder is low and should not be a barrier to use.

A Scoping Review of Evidence-Based Interventions and Health-Related Services for Youth Who Use Nonmedical Opioids in Canada and the United States.

PURPOSE: This scoping review synthesizes the characteristics and outcomes of recent evidence-based treatments and services for youth with nonmedical opioid use/opioid use disorder in the context of the ongoing opioid crisis in Canada and the United States. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews guidelines, empirical health databases were searched for literature describing treatments or health-related services for nonmedical opioid use/opioid use disorder among youth (ages 12-25). Two independent reviewers conducted study screening, selection, and data extraction. A deductive content analysis further synthesized the interventions' characteristics following the Consolidated Framework for Implementation Research and an inductive content analysis synthesized the interventions' efficacy/effectiveness outcomes. RESULTS: Twenty-five articles met inclusion from 2,761 screened; 88% described opioid agonist treatment (alone or in combination with nonpharmacological treatment). Following the Consolidated Framework for Implementation Research, commonly identified adaptable characteristics included treatment decision-making processes, integrated health and social services, and treatment settings. Efficacy/effectiveness outcomes most frequently included substance use and treatment engagement. DISCUSSION: This study informs future development, implementation, and evaluation of practices and policies that could be tailored to improve the quality of opioid agonist treatment for youth at risk of significant harms from nonmedical opioid use.