Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

Harm Reduction for Opioid Use Disorder: Strategies and Outcome Metrics.

Tweet: The authors discuss harm reduction strategies and associated outcome metrics in relation to the ongoing opioid crisis.

Government Direct-to-Consumer Education to Reduce Prescription Opioid Use: A Cluster Randomized Clinical Trial.

Importance: Direct-to-consumer education reduces chronic sedative use. The effectiveness of this approach for prescription opioids among patients with chronic noncancer pain remains untested. Objectives: To evaluate the effectiveness of a government-led educational information brochure mailed to community-dwelling, long-term opioid consumers to reduce prescription opioid use compared with usual care. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from July 2018 to January 2019 in Manitoba, Canada. All adults with long-term opioid prescriptions were enrolled (n = 4225). Participants were identified via the Manitoba Drug Program Information Network. Individuals receiving palliative care or with a diagnosis of cancer or dementia were excluded. Data were analyzed from July 2019 to March 2020. Intervention: Participants were clustered according to their primary care clinic and randomized to the intervention (a codesigned direct-to-consumer educational brochure sent by mail) or usual care (comparator group). Main Outcomes and Measures: The main outcome was discontinuation of opioid prescriptions at the participant level after 6 months, ascertained by pharmacy drug claims. Secondary outcomes included dose reduction (in morphine milligram equivalents [MME]) and/or therapeutic switch. Reduction in opioid use was assessed using generalized estimating equations to account for clustering, with prespecified subgroup analyses by age and sex. Analysis was intention to treat. Results: Of 4206 participants, 2409 (57.3%) were male; mean (SD) age was 60.0 (14.4) years. Mean (SD) baseline opioid use was comparable between groups (intervention, 157.7 [179.7] MME/d; control, 153.4 [181.8] MME/d). After 6 months, 235 of 2136 participants (11.0%) in 127 clusters in the intervention group no longer filled opioid prescriptions compared with 228 of 2070 (11.0%) in 124 clusters in the comparator group (difference, 0.0%; 95% CI, -1.9% to 1.9%). More participants in the intervention group than in the control group reduced their dose (1410 [66.0%] vs 1307 [63.1%]; difference, 2.8% [95% CI, 0.0%-5.7%]). Receipt of the brochure led to greater dose reductions for participants who were male (difference, 3.9%; 95% CI, 0.1%-7.7%), aged 18 to 64 years (difference, 3.7%; 95% CI, 0.2%-7.2%), or living in urban areas (difference, 5.9%; 95% CI, 1.9%-9.9%) compared with usual care. Conclusions and Relevance: In this cluster randomized clinical trial, no significant difference in the prevalence of opioid cessation was observed after 6 months between the intervention and usual care groups; however, the intervention resulted in more adults reducing their opioid dose compared with usual care. Trial Registration: ClinicalTrials.gov Identifier: NCT03400384.

Implementing Canada's first national virtual phone based overdose prevention service: lessons learned from creating the National Overdose Response Service (NORS).

The opioid epidemic remains one of the largest public health crises in North America to date. While there have been many diverse strategies developed to reduce the harms associated with substance use, these are primarily concentrated within a few large urban centers. As a result, there have been increased calls for equitable access to harm reduction services for those who cannot or choose not to access in-person harm reduction services. In December 2020, Canada's National Overdose Response Service (NORS) a telephone based overdose response hotline and virtual supervised consumption service, was established in collaboration with various agencies and people with lived and living experience of substance use (PWLLE) across Canada to expand access to harm reduction services using novel Opioid Response Technology. In this manuscript we explore the lessons learned from the establishment and continued operation of the service exploring topics related to the initial establishment of the service, securing a phone line, routing technology, EMS dispatch solutions, peer and volunteer recruitment, legal and ethical support, policy and procedure development, securing funding, and marketing. Furthermore, we detail how this service has grown and changed in response to the various needs of service users.

State-level policies and receipt of CDC-informed opioid thresholds among commercially insured new chronic opioid users.

OBJECTIVES: To evaluate the association of state-level policies on receipt of opioid regimens informed by Centers for Disease Control and Prevention (CDC) morphine milligram equivalent (MME)/day recommendations. DESIGN: A retrospective cohort study of new chronic opioid users (NCOUs). SETTING: Commercially insured plans across the United States using IQVIA PharMetrics® Plus for Academics database with new chronic use between January 2014 and March 2015. PARTICIPANTS: NCOUs with ≥60-day coverage of opioids within a 90-day period with ≥30-day opioid-free period prior to the date of the first qualifying opioid prescription. INTERVENTIONS: State-level policies including Prescription Drug Monitoring Program (PDMP) robustness and cannabis policies involving the presence of medical dispensaries and state-wide decriminalization. MAIN OUTCOME MEASURES: NCOUs were placed in three-tiered risk-based average MME/day thresholds: low (>0 to <50), medium (≥50 to <90), and high (≥90). Multinomial logistic regression was used to estimate the association of state-level policies with the thresholds while adjusting for relevant patient-specific factors. RESULTS: NCOUs in states with medium or high PDMP robustness had lower odds of receiving medium (adjusted odds ratio [AOR] 0.74; 95 percent confidence interval [CI]: 0.62-0.69) and high (AOR 0.74; 95 percent CI: 0.59-0.92) thresholds. With respect to cannabis policies, NCOUs in states with medical cannabis dispensaries had lower odds of receiving high (AOR 0.75; 95 percent CI: 0.60-0.93) thresholds, while cannabis decriminalization had higher odds of receiving high (AOR 1.24; 95 percent CI: 1.04-1.49) thresholds. CONCLUSION: States with highly robust PDMPs and medical cannabis dispensaries had lower odds of receiving higher opioid thresholds, while cannabis decriminalization correlated with higher odds of receiving high opioid thresholds.

Opioid Coprescription Through Risk Mitigation Guidance and Opioid Agonist Treatment Receipt.

Importance: At the onset of the COVID-19 pandemic, the government of British Columbia, Canada, released clinical guidance to support physicians and nurse practitioners in prescribing pharmaceutical alternatives to the toxic drug supply. These alternatives included opioids and other medications under the risk mitigation guidance (RMG), a limited form of prescribed safer supply, designed to reduce the risk of SARS-CoV-2 infection and harms associated with illicit drug use. Many clinicians chose to coprescribe opioid medications under RMG alongside opioid agonist treatment (OAT). Objective: To examine whether prescription of hydromorphone tablets or sustained-release oral morphine (opioid RMG) and OAT coprescription compared with OAT alone is associated with subsequent OAT receipt. Design, Setting, and Participants: This population-based, retrospective cohort study was conducted from March 27, 2020, to August 31, 2021, included individuals from 10 linked health administrative databases from British Columbia, Canada. Individuals who were receiving OAT at opioid RMG initiation and individuals who were receiving OAT and eligible but unexposed to opioid RMG were propensity score matched at opioid RMG initiation on sociodemographic and clinical variables. Data were analyzed between January 2023 and February 2024. Exposure: Opioid RMG receipt (≥4 days, 1-3 days, or 0 days of opioid RMG dispensed) in a given week. Main Outcome and Measures: The main outcome was OAT receipt, defined as at least 1 dispensed dose of OAT in the subsequent week. A marginal structural modeling approach was used to control for potential time-varying confounding. Results: A total of 4636 individuals (2955 [64%] male; median age, 38 [31-47] years after matching) were receiving OAT at the time of first opioid RMG dispensation (2281 receiving ongoing OAT and 2352 initiating RMG and OAT concurrently). Opioid RMG receipt of 1 to 3 days in a given week increased the probability of OAT receipt by 27% in the subsequent week (adjusted risk ratio, 1.27; 95% CI, 1.25-1.30), whereas receipt of opioid RMG for 4 days or more resulted in a 46% increase in the probability of OAT receipt in the subsequent week (adjusted risk ratio, 1.46; 95% CI, 1.43-1.49) compared with those not receiving opioid RMG. The biological gradient was robust to different exposure classifications, and the association was stronger among those initiating opioid RMG and OAT concurrently. Conclusions and Relevance: This cohort study, which acknowledged the intermittent use of both medications, demonstrated that individuals who were coprescribed opioid RMG had higher adjusted probability of continued OAT receipt or reengagement compared with those not receiving opioid RMG.

How do we understand the value of drug checking as a component of harm reduction services? A qualitative exploration of client and provider perspectives.

BACKGROUND: Mortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered. METHODS: We conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: "clients" (individuals who use drugs and receive harm reduction services) and "providers" (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis. RESULTS: We found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels. CONCLUSION: This study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

Opioid use disorder in pediatric populations: considerations for perioperative pain management and precision opioid analgesia.

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain. Studies indicate that lower repetitive methadone doses can decrease the incidence of chronic persistent surgical pain (CPSP). Ongoing research explores genetic components influencing severe surgical pain, inadequate opioid analgesia, and opioid use disorder. This new genetic research coupled with better utilization of opioids in the perioperative setting provides hope in personalizing surgical pain management, reducing pain, opioid use, adverse effects, and helping the fight against the opioid pandemic. EXPERT OPINION: The opioid and analgesic pharmacogenomics approach can proactively 'tailor' a perioperative analgesic plan to each patient based on underlying polygenic risks. This transition from population-based knowledge of pain medicine to individual patient knowledge can transform acute pain medicine and greatly reduce the opioid epidemic's socioeconomic, personal, and psychological strains globally.

Strengthening Protocols for Rapid Response to Disruptions in Access to Prescription Opioids: Considerations for State and Territorial Health Agencies.

Prescription opioid disruptions pose a danger and lead to adverse health outcomes for patients taking prescription opioids for pain or medication for opioid use disorder. State and territorial health agencies are uniquely positioned to respond to disruptions and potentially prevent risks associated with service disruptions. Responding to disruptions in access to prescription opioids necessitates a multifaceted, collaborative approach that prioritizes care continuity and patient well-being. State and territorial health agencies may benefit from developing and exercising a formal response protocol that outlines roles and activities during these types of events, strengthening capacity to rapidly respond and serve patient needs.

Perioperative pain optimization in the age of the opioid epidemic.

PURPOSE OF REVIEW: The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services. RECENT FINDINGS: There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder. SUMMARY: Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.

Substance use patterns, sociodemographics, and health profiles of harm reduction service recipients in Burlington, Vermont.

BACKGROUND: Understanding current substance use practices is critical to reduce and prevent overdose deaths among individuals at increased risk including persons who use and inject drugs. Because individuals participating in harm reduction and syringe service programs are actively using drugs and vary in treatment participation, information on their current drug use and preferred drugs provides a unique window into the drug use ecology of communities that can inform future intervention services and treatment provision. METHODS: Between March and June 2023, 150 participants in a harm reduction program in Burlington, Vermont completed a survey examining sociodemographics; treatment and medication for opioid use disorder (MOUD) status; substance use; injection information; overdose information; and mental health, medical, and health information. Descriptive analyses assessed overall findings. Comparisons between primary drug subgroups (stimulants, opioids, stimulants-opioids) of past-three-month drug use and treatment participation were analyzed using chi-square and Fisher's exact test. RESULTS: Most participants reported being unhoused or unstable housing (80.7%) and unemployed (64.0%) or on disability (21.3%). The drug with the greatest proportion of participants reporting past three-month use was crack cocaine (83.3%). Fentanyl use was reported by 69.3% of participants and xylazine by 38.0% of participants. High rates of stimulant use were reported across all participants independent of whether stimulants were a participant's primary drug. Fentanyl, heroin, and xylazine use was less common in the stimulants subgroup compared to opioid-containing subgroups (p < .001). Current- and past-year MOUD treatment was reported by 58.0% and 77.3% of participants. Emergency rooms were the most common past-year medical treatment location (48.7%; M = 2.72 visits). CONCLUSIONS: Findings indicate high rates of polysubstance use and the underrecognized effects of stimulant use among people who use drugs-including its notable and increasing role in drug-overdose deaths. Crack cocaine was the most used stimulant, a geographical difference from much of the US where methamphetamine is most common. With the increasing prevalence of fentanyl-adulterated stimulants and differences in opioid use observed between subgroups, these findings highlight the importance and necessity of harm reduction interventions (e.g., drug checking services, fentanyl test strips) and effective treatment for individuals using stimulants alongside MOUD treatment.

Piloting an Opioid Risk Screening Tool in Clinical Practice.

Background: Despite much research and many interventions, the opioid epidemic continues to plague the United States. According to the Centers for Disease Control and Prevention (2021), 136 people die daily from both prescription and illicit opioids. Objective: The goal of this pilot quality improvement project is to examine how the implementation of the Opioid Risk Tool (ORT) in clinical practice might impact the beliefs and attitudes of nurse practitioners (NPs) toward prescribing opioid therapy. Methods: A pre-post design was utilized. A convenience sample recruited participants from a private NP Facebook group. The intervention included a prerecorded presentation on the ORT and the use of the ORT for 8 weeks. Results: While 46 NPs completed the presurvey, only 19 NPs completed the postsurvey. Statistical results did not yield significance, but there were several significant clinical trends discovered. Conclusion: Utilizing the ORT to screen for opioid misuse risks has been shown to improve providers' confidence in opioid prescribing. ORT guides providers in discerning patient risk for developing dependence on opioids. Implications for Nursing: Screening for opioid misuse risk is feasible. ORT adds to the clinical context in deciding a course of treatment in pain management.

Opioid stewardship program implementation in rural and critical access hospitals in Arizona.

OBJECTIVE: The objective of this study is to examine rural hospitals' status in implementing opioid stewardship program (OSP) elements and assess differences in implementation in emergency department (ED) and acute inpatient departments. DESIGN: Health administrator survey to identify the number and type of OSP elements that each hospital has implemented. SETTING: Arizona critical access hospitals (CAHs). PARTICIPANTS: ED and acute inpatient department heads at 17 Arizona CAHs (total of 34 assessments). MAIN OUTCOME MEASURES: Implementation of 11 OSP elements, by department (ED vs inpatient) and prevention orientation (primary vs tertiary). RESULTS: The percentage of implemented elements ranged from 35 to 94 percent in EDs and 24 to 88 percent in acute care departments. Reviewing the prescription drug monitoring program database and offering alternatives to opioids were the most frequently implemented. Assessing opioid use disorder (OUD) and prescribing naloxone were among the least. The number of implemented elements tended to be uniform across departments. We found that CAHs implemented, on average, 67 percent of elements that prevent unnecessary opioid use and 54 percent of elements that treat OUD. CONCLUSIONS: Some OSP elements were in place in nearly every Arizona CAH, while others were present in only a quarter or a third of hospitals. To improve, more attention is needed to define and standardize OSPs. Equal priority should be given to preventing unnecessary opioid initiation and treating opioid misuse or OUD, as well as quality control strategies that provide an opportunity for continuous improvement.

Acceptability and anticipated effectiveness of a safe supply of opioids, among people who inject opioids in King County, WA.

BACKGROUND: Opioid overdose mortality in the US has exceeded one million deaths over the last two decades. A regulated opioid supply may help prevent future overdose deaths by reducing exposure to the unregulated opioid supply. We examined the acceptability, delivery model preference, and anticipated effectiveness of different regulated opioid models among people in the Seattle area who inject opioids. METHODS: We enrolled people who inject drugs in the 2022 Seattle-area National HIV Behavior Surveillance (NHBS) survey. Participants were recruited between July and December 2022 using respondent-driven sampling. Participants who reported injecting opioids (N = 453) were asked whether regulated opioids would be acceptable, their preferred model of receiving regulated opioids, and the anticipated change in individual overdose risk from accessing a regulated opioid supply. RESULTS: In total, 369 (81 %) participants who injected opioids reported that a regulated opioid supply would be acceptable to them. Of the 369 who found a regulated opioid supply to be acceptable, the plurality preferred a take-home model where drugs are prescribed (35 %), followed closely by a dispensary model that required no prescription (28 %), and a prescribed model where drugs need to be consumed on site (13 %), a model where no prescription is required and drugs can be accessed in a community setting with a one-time upfront payment was the least preferred model (5 %). Most participants (69 %) indicated that receiving a regulated opioid supply would be "a lot less risky" than their current supply, 20 % said, "a little less risky", 10 % said no difference, and 1 % said a little or a lot more risky. CONCLUSION: A regulated opioid supply would be acceptable to most participants, and participants reported it would greatly reduce their risk of overdose. As overdose deaths continue to increase in Washington state pragmatic and effective solutions that reduce exposure to unregulated drugs are needed.