Weaning buprenorphine in pregnant patients.

OBJECTIVE: Evaluate maternal and neonatal outcomes after buprenorphine wean compared to patients maintained on buprenorphine throughout pregnancy. METHODS: Prospective cohort study of pregnant patients with opioid use disorder enrolled in a multidisciplinary treatment program between 2015 and 2022. All patients were offered Medications to treat Opioid Use Disorder (MOUD) primarily with buprenorphine. Patients had at least 2 prenatal visits and negative urine drug tests (UDT) prior to weaning. The experimental group underwent a buprenorphine wean greater than 20% of their baseline dose. The control group was maintained on buprenorphine throughout the pregnancy. Relapse was defined as patient reported use or positive UDT during weekly assessments. Mass spectrophotometer was used for detection of drugs in samples. Fisher's exact tests were used to compare outcomes in weaned and control groups. RESULTS: 334 of 456 (73%) patients were treated with buprenorphine during pregnancy, with 39 in the experimental group and 295 in the control group. The mean dose for buprenorphine was similar between the groups (wean: 10.6 mg ± 5.6 vs. control: 10.3 mg ± 4.6, p = 0.76) but was significantly lower at delivery (wean: 4.4 ± 4.6 mg vs. control: 13.0 ± 4.7, p < 0.0001). Mean gestational age at initiation of the buprenorphine wean was 22.7 weeks. 10 of 39 (26%) who weaned were able to completely discontinue buprenorphine prior to delivery. Demographic data was similar between the groups, including overdose history. Overdose history at time of enrollment had a higher trend in the non-weaning group. neonatal opioid withdrawal syndrome (NOWS) treatment was significantly lower in the wean group (23 vs. 47%, p = 0.006), as was highest Finnegan score (9.6 ± 4.5 vs. 12.3 ± 4.0, p = 0.0003). Birthweight percentile was significantly higher in the wean group (44.3 ± 29.9 vs. 34.8 ± 24.4, p = 0.03). Gestational age at delivery, mode of delivery, and complications (HTN, DM, preterm labor, or short cervix) at delivery did not significantly differ between the groups. CONCLUSION: Despite counseling to stay on buprenorphine, there are patients who desire to wean. The NOWS rate in the weaned cohort was significantly lower than the controls with no observed increase in maternal or neonatal morbidity. There were no maternal overdoses or deaths during the pregnancy. Larger studies are needed to evaluate this approach.

Barriers and facilitators for family physicians prescribing opioid agonist therapy in Saskatchewan.

OBJECTIVE: To explore barriers and facilitators for family physicians in Saskatchewan prescribing opioid agonist therapy (OAT). DESIGN: Self-administered postal survey. SETTING: Family medicine practices in Saskatchewan. PARTICIPANTS: A total of 218 Saskatchewan family physicians who were not authorized to prescribe OAT as of June 2022. MAIN OUTCOME MEASURES: Descriptive and inferential statistics of physicians' self-reported barriers to and facilitators of prescribing OAT for opioid use disorder (OUD). RESULTS: Most respondents (84.8%) had some comfort with diagnosing OUD. However, more than half (58.3%) did not feel confident or knowledgeable about prescribing OAT. Barriers to OAT prescribing included lack of time, incomplete training requirements, lack of interest, insufficient funding or support, feeling overwhelmed, and perceiving that OAT does not work and thus is not necessary. Physicians working in core neighbourhoods and those receiving fee-for-service compensation reported the least available time to prescribe OAT. Conversely, physicians working in interdisciplinary team settings had increased time for OAT prescribing compared with physicians in other settings. Having a close personal relationship with someone with OUD was correlated with increased comfort in diagnosing OUD as well as with knowledge about and confidence in prescribing OAT. Themes identified as facilitators to increasing OAT prescribing included the addition of resources and supports, increased training, more awareness about OUD and OAT, enhanced compensation, and altered prescribing regulations. CONCLUSION: Despite the presence of several real and perceived barriers limiting OAT prescribing by Saskatchewan family physicians, there are family physicians interested in providing this therapy. Increased clinical resources and support, including increased interdisciplinary practice, are actionable steps that should be considered by policy decision makers to address this issue. Additionally, increased OUD and OAT education, which includes the perspectives of those with lived experience of OUD, would help address physician confidence, knowledge, and awareness in this area.

Development of Opioid Use Disorder After Breast Reconstruction: Effects of Nicotine Exposure.

INTRODUCTION: After undergoing breast reconstructive surgery, patients are typically prescribed opioids. Smoking tobacco increases rate of opioid metabolism and is associated with development of opioid use disorder (OUD). The aim of this study was to determine whether patients who smoke have an increased risk of OUD after breast reconstructive surgery. Given that OUD is a known risk factor for injection drug use and intravenous drug use increases risk of acquiring blood-borne diseases including human immunodeficiency virus (HIV) and hepatitis, the secondary aim was to determine if these patients are also at increased risk of acquiring these communicable diseases associated with OUD. METHODS: A retrospective analysis was conducted using TriNetX, a multi-institutional deidentified database. Individuals included underwent a breast reconstructive surgery and received postoperative opioid treatment. The exposed group included patients who smoke. The control group did not smoke. Risk of developing OUD, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV from 12 to 36 months after surgery was compared between groups. Patients with preexisting OUD or associated diseases were excluded. Cohorts were matched to control for confounding factors including age, sex, race, mental health history, and concomitant substance use. RESULTS: There were 8648 patients included in the analysis. After matching, 4324 patients comprised the exposure group, and 4324 patients remained in the control group. Preoperative smoking was significantly associated with increased risk of OUD at 12, 24, and 36 months after breast reconstruction (36 months: odds ratio [OR], 2.722; confidence interval [CI], 2.268-6.375). Smoking was also associated with increased risk of HIV and HCV at all time points after surgery (36 months HIV: OR, 2.614; CI, 1.977-3.458; 36 months HCV: OR, 3.718; CI, 2.268-6.375) and increased risk of HBV beginning at 24 months after surgery (36 months HBV: OR, 2.722; CI, 1.502-4.935). CONCLUSIONS: Individuals who smoke have an increased risk of developing OUD, HIV, HCV, and HBV after breast reconstructive surgery. This risk persists for at least 3 years after surgery. Additional research and clinical interventions focusing on early identification of OUD, prevention efforts, and harm reduction strategies for patients who smoke or have nicotine dependence undergoing breast reconstruction are warranted.

Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Users' Acceptability and Perceived Efficacy of mHealth for Opioid Use Disorder: Scoping Review.

BACKGROUND: The opioid crisis continues to pose significant challenges to global public health, necessitating the development of novel interventions to support individuals in managing their substance use and preventing overdose-related deaths. Mobile health (mHealth), as a promising platform for addressing opioid use disorder, requires a comprehensive understanding of user perspectives to minimize barriers to care and optimize the benefits of mHealth interventions. OBJECTIVE: This study aims to synthesize qualitative insights into opioid users' acceptability and perceived efficacy of mHealth and wearable technologies for opioid use disorder. METHODS: A scoping review of PubMed (MEDLINE) and Google Scholar databases was conducted to identify research on opioid user perspectives concerning mHealth-assisted interventions, including wearable sensors, SMS text messaging, and app-based technology. RESULTS: Overall, users demonstrate a high willingness to engage with mHealth interventions to prevent overdose-related deaths and manage opioid use. Users perceive mHealth as an opportunity to access care and desire the involvement of trusted health care professionals in these technologies. User comfort with wearing opioid sensors emerged as a significant factor. Personally tailored content, social support, and encouragement are preferred by users. Privacy concerns and limited access to technology pose barriers to care. CONCLUSIONS: To maximize benefits and minimize risks for users, it is crucial to implement robust privacy measures, provide comprehensive user training, integrate behavior change techniques, offer professional and peer support, deliver tailored messages, incorporate behavior change theories, assess readiness for change, design stigma-reducing apps, use visual elements, and conduct user-focused research for effective opioid management in mHealth interventions. mHealth demonstrates considerable potential as a tool for addressing opioid use disorder and preventing overdose-related deaths, given the high acceptability and perceived benefits reported by users.

Non-scheduled short-acting opioid to taper off opioids?

This commentary discusses the issues related to the current pharmacotherapy using super long-acting opioids (for the potential convenience for both patients and medical providers) for opioid addiction and argues for the potential to use a non-scheduled short-acting opioid to taper off opioids to reduce total number of patients on opioids and ultimately reduce opioid-related death. This article also proposes to develop short-acting opioids for addiction management instead of the current long-acting regimen. The authors further suggest that dezocine, a previously FDA approved medication for perioperative pain management and a non-scheduled opioid, be brought back to clinical practice in the US as a potential alternative addiction management medication, especially for those who are highly motivated to quit opioids completely using a taper off strategy.

The effect of morphine administration on GluN3B NMDA receptor subunit mRNA expression in rat brain.

Opioid addiction is critically dependent on the activation of N­methyl­D­aspartate (NMDA) receptors, which are widely found in the mesocorticolimbic system. Meanwhile, opioid addiction may affect the expression level of NMDA receptor subunits. The existence of GluN3 subunits in the NMDA receptor's tetramer structure reduces the excitatory current of the receptor channel. We evaluated the changes in the mRNA expression pattern of the GluN3B subunit of the NMDA receptor in rat brains following acute and chronic exposure to morphine. Chronic, escalating intraperitoneal doses of morphine or saline were administered twice daily to male Wistar rats for six days. Two other groups were injected with a single acute dose of morphine or saline. The mRNA level of the GluN3B subunit of the NMDA receptor in the striatum, hippocampus, and nucleus accumbens (NAc) was measured by real­time PCR. mRNA expression of the GluN3B subunit was considerably augmented (3.15 fold) in the NAc of animals chronically treated with morphine compared to the control group. The difference between rats that were chronically administered morphine and control rats was not statistically significant for other evaluated brain areas. In rats acutely treated with morphine, no significant differences were found for GluN3B subunit expression in the examined brain regions compared to the control group. It was concluded that chronic exposure to morphine notably increased the GluN3B subunit of the NMDA receptor in NAc. The extent of the impact of this finding on opioid addiction and its features requires further evaluation in future studies.

Characterization of peer support services for substance use disorders in 11 US emergency departments in 2020: findings from a NIDA clinical trials network site selection process.

INTRODUCTION: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs. METHODS: A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis. RESULTS: A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided "general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding. CONCLUSIONS: The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.

Patient and pharmacist perspectives on opioid misuse screening and brief interventions in community pharmacies.

BACKGROUND: Pharmacy-based screening and brief interventions (SBI) offer opportunities to identify opioid misuse and opioid safety risks and provide brief interventions that do not overly burden pharmacists. Currently, such interventions are being developed without patient input and in-depth contextual data and insufficient translation into practice. The purpose of this study is to qualitatively explore and compare patient and pharmacist perceptions and needs regarding a pharmacy-based opioid misuse SBI and to identify relevant SBI features and future implementation strategies. METHODS: Using the Consolidated Framework for Implementation Research, we conducted semi-structured interviews with 8 patients and 11 pharmacists, to explore needs and barriers to participating in a pharmacy-based SBI. We recruited a purposive sample of English-speaking patients prescribed opioids for chronic or acute pain and pharmacists practicing in varied pharmacies (small independent, large-chain, specialty retail) settings. We used an inductive content analysis approach to analyze patient interview data. Then through a template analysis approach involving comparison of pharmacist and patient themes, we developed strategies for SBI implementation. RESULTS: Most patient participants were white, older, described living in suburban areas, and were long-term opioid users. We identified template themes related to individual, interpersonal, intervention, and implementation factors and inferred applications for SBI design or potential SBI implementation strategies. We found that patients needed education on opioid safety and general opioid use, regardless of opioid use behaviors. Pharmacists described needing patient-centered training, protocols, and scripts to provide SBI. A short-self-reported screening and brief interventions including counseling, naloxone, and involving prescribers were discussed by both groups. CONCLUSIONS: Through this implementation-focused qualitative study, we identified patient needs such as opioid safety education delivered in a private and convenient format and pharmacist needs including training, workflow integration, protocols, and a time-efficient intervention for effective pharmacy-based SBI. Alternate formats of SBI using digital health technologies may be needed for effective implementation. Our findings can be used to develop patient-centered pharmacy-based SBI that can be implemented within actual pharmacy practice.

Public Health Interventions and Overdose-Related Outcomes Among Persons With Opioid Use Disorder.

Importance: Given the high number of opioid overdose deaths in the US and the complex epidemiology of opioid use disorder (OUD), systems models can serve as a tool to identify opportunities for public health interventions. Objective: To estimate the projected 3-year association between public health interventions and opioid overdose-related outcomes among persons with OUD. Design, Setting, and Participants: This decision analytical model used a simulation model of the estimated US population aged 12 years and older with OUD that was developed and analyzed between January 2019 and December 2023. The model was parameterized and calibrated using 2019 to 2020 data and used to estimate the relative change in outcomes associated with simulated public health interventions implemented between 2021 and 2023. Main Outcomes and Measures: Projected OUD and medications for OUD (MOUD) prevalence in 2023 and number of nonfatal and fatal opioid-involved overdoses among persons with OUD between 2021 and 2023. Results: In a baseline scenario assuming parameters calibrated using 2019 to 2020 data remained constant, the model projected more than 16 million persons with OUD not receiving MOUD treatment and nearly 1.7 million persons receiving MOUD treatment in 2023. Additionally, the model projected over 5 million nonfatal and over 145 000 fatal opioid-involved overdoses among persons with OUD between 2021 and 2023. When simulating combinations of interventions that involved reducing overdose rates by 50%, the model projected decreases of up to 35.2% in nonfatal and 36.6% in fatal opioid-involved overdoses among persons with OUD. Interventions specific to persons with OUD not currently receiving MOUD treatment demonstrated the greatest reduction in numbers of nonfatal and fatal overdoses. Combinations of interventions that increased MOUD initiation and decreased OUD recurrence were projected to reduce OUD prevalence by up to 23.4%, increase MOUD prevalence by up to 137.1%, and reduce nonfatal and fatal opioid-involved overdoses among persons with OUD by 6.7% and 3.5%, respectively. Conclusions and Relevance: In this decision analytical model study of persons with OUD, findings suggested that expansion of evidence-based interventions that directly reduce the risk of overdose fatality among persons with OUD, such as through harm reduction efforts, could engender the highest reductions in fatal overdoses in the short-term. Interventions aimed at increasing MOUD initiation and retention of persons in treatment projected considerable improvement in MOUD and OUD prevalence but could require a longer time horizon for substantial reductions in opioid-involved overdoses.

Withdrawal during outpatient low dose buprenorphine initiation in people who use fentanyl: a retrospective cohort study.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients' withdrawal experiences.

Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h2 = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h2 = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.