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The goals of treating withdrawal are to alleviate unnecessary distress, maintain the therapeutic alliance between patient and provider, facilitate treatment of the primary reason for admission and increase the patient's engagement in longterm addiction management. According to a 2010 systematic review,21 there was no statistically significant difference in completion of opioid detoxification between the opioid agonists buprenorphine and methadone (odds ratio 1.64, 95% confidence interval [CI] 0.68-3.79). As such, choosing between them should take into account the patient's preference and commitment to longterm addiction treatment, comorbid medical conditions, potential adverse effects (e.g., QTc prolongation), medication interactions (e.g., with some antiretroviral medications) and availability of outpatient providers able to continue the opioid agonist therapy.21 Methadone initiated at 10- 30 mg daily and slowly titrated to a total daily dose of 20-40 mg is usually sufficient to treat withdrawal symptoms.18,20 Alternatively, buprenorphine may be initiated, according to standard protocols, once moderate opioid withdrawal is evident (Figure 1).22 Buprenorphine initiated too early can precipitate withdrawal. Interviews with providers have commonly identified concerns about deception and manipulation on the part of patients with opioid use disorder who report pain.34,35 At the same time, patients with opioid use disorder fear that they will be labelled as \"drug seekers,\" that their pain will go undertreated, that the underlying condition will go undiagnosed or that their opioid agonist therapy will be discontinued.34,36 Elements of an effective initial pain encounter include reviewing both patient and provider expectations regarding pain management, acknowledging prior difficult interactions, reassuring the patient that the pain will be addressed and that opioid agonist therapy will be continued or substituted if necessary, and reviewing the medication schedule. Involving the patient in decisions about pain management is particularly relevant for those with opioid use disorder and may prevent some of the stressful doctor-patient interactions related to opioids that both parties dislike.26,27,37 The analgesic effect of buprenorphine is also shorter than its effects on withdrawal and craving. Given its high affinity for the opioid ì receptor, buprenorphine effectively blocks the actions of most other opioids, thereby complicating acute pain management.41 Several strategies have been described to overcome this problem, predominantly based in expert opinion. The first is to continue daily buprenorphine and add short-acting opioids titrated to pain control. High-dose opioids, and possibly patient-controlled analgesia, will likely be needed.26,39,41-43 A second strategy uses the inherent analgesic properties of buprenorphine by giving the total daily dose divided three or four times daily.26,42 Doses of 4-8 mg every six to eight hours have been used to treat moderate to severe pain.41,43 A third strategy is to discontinue buprenorphine and use short-acting opioids to treat the acute pain. The blocking effects of buprenorphine wear offover 24-72 hours, so the patient must be carefully monitored for signs of overdose, given that the initial opioid dose will be much higher than ultimately needed.22 After the need for acute pain management has resolved, buprenorphine can be reintroduced.

To identify individual and site-related factors associated with frequent emergency department (ED) buprenorphine/naloxone (BUP) initiation. BUP initiation, an effective opioid use disorder (OUD) intervention, varies widely across Canadian EDs. We surveyed emergency physicians in 6 Canadian provinces from 2018 to 2019 using bilingual paper and web-based questionnaires. Survey domains included BUP-related practice, demographics, attitudes toward BUP, and site characteristics. We defined frequent BUP initiation (the primary outcome) as at least once per month, high OUD prevalence as at least one OUD patient per shift, and high OUD resources as at least 3 out of the following 5 resources: BUP initiation pathways, BUP in ED, peer navigators, accessible addiction specialists, and accessible follow-up clinics. We excluded responses from sites with <50% participation (to minimize non-responder bias) and those missing the primary outcome. We used univariate analysis to identify associations between frequent BUP initiation and factors of interest, stratifying by OUD prevalence. We excluded 3 responses for missing BUP initiation frequency and 9 for low response rate at one ED. Of the remaining 649 respondents from 34 EDs, 374 (58%) practiced in metropolitan areas, 384 (59%) reported high OUD prevalence, 312 (48%) had high OUD resources, and 161 (25%) initiated BUP frequently. Age, gender, board certification and years in practice were not associated with frequent BUP initiation. Site-specific factors were associated with frequent BUP initiation (high OUD resources [OR 6.91], high OUD prevalence [OR 4.45], and metropolitan location [OR 2.39],) as were individual attitudinal factors (willingness, confidence, and responsibility to initiate BUP.) Similar associations persisted in the high OUD prevalence subgroup. Individual attitudinal and site-specific factors were associated with frequent BUP initiation. Training to increase physician confidence and increasing OUD resources could increase BUP initiation and benefit ED patients with OUD.

Background Patients with opioid use disorder (OUD) frequently leave the hospital as patient directed discharges (PDDs) because of untreated withdrawal and pain. Short-acting opioids can complement methadone, buprenorphine, and non-opioid adjuvants for withdrawal and pain, however little evidence exists for this approach. We described the safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with OUD at an academic hospital in Philadelphia, PA. Methods From August 2021 to March 2022, a pharmacist guided implementation of a pilot sOAT protocol consisting of escalating doses of oxycodone or oral hydromorphone scheduled every four hours, intravenous hydromorphone as needed, and non-opioid adjuvants for withdrawal and pain. All patients were encouraged to start methadone or buprenorphine treatment for OUD. We abstracted data from the electronic health record into a secure platform. The primary outcome was safety: administration of naloxone, over-sedation, or a fall. Secondary outcomes were PDDs and respective length of stay (LOS), discharges on methadone or buprenorphine, and discharges with naloxone. We compared secondary outcomes to hospitalizations in the 12 months prior to the index hospitalization among the same cohort. Results Of the 23 cases, 13 (56.5%) were female, 19 (82.6%) were 40 years or younger, and 22 (95.7%) identified as White. Twenty-one (91.3%) regularly injected opioids and four (17.3%) were enrolled in methadone or buprenorphine prior to hospitalization. sOAT was administered at median doses of 200–320 morphine milligram equivalents per 24-h period. Naloxone administration was documented once in the operating room, over-sedation was documented once after unsanctioned opioid use, and there were no falls. The PDD rate was 44% with median LOS 5 days (compared to PDD rate 69% with median LOS 3 days for prior admissions), 65% of sOAT cases were discharged on buprenorphine or methadone (compared to 33% for prior admissions), and 65% of sOAT cases were discharged with naloxone (compared to 19% for prior admissions). Conclusions Pilot implementation of sOAT was safe. Compared to prior admissions in the same cohort, the PDD rate was lower, LOS for PDDs was longer, and more patients were discharged on buprenorphine or methadone and with naloxone, however efficacy for these secondary outcomes remains to be established.

IntroductionOpioid use disorder (OUD) during pregnancy is associated with increased rates of adverse perinatal, foetal and neonatal health events. Opioid agonist treatment (OAT) can substantially reduce the risk of these potential harms. In British Columbia (BC), methadone and buprenorphine/naloxone are first-line treatment options for pregnant people with OUD. However, the comparative effectiveness of these regimens during pregnancy remains poorly understood, particularly in terms of how dosage may impact clinical outcomes. This protocol outlines a proposed population-based retrospective study to evaluate the comparative effectiveness of methadone compared with buprenorphine/naloxone during pregnancy on perinatal and neonatal health outcomes.Methods and analysisWe propose to conduct a retrospective observational study using population-based data from individuals who received methadone or buprenorphine/naloxone during pregnancy between 1 April 2010 and 31 March 2022. Data will be collected from 10 linked population-level administrative databases. We will emulate target trials using intention-to-treat and per-protocol approaches. We will use a pooled logistic regression approach to assess the impact of methadone versus buprenorphine/naloxone on time to OAT episode discontinuation and a dose-response marginal structural model to evaluate neonatal health at delivery. An exploratory observational analysis will also be conducted to describe the impact of methadone vs buprenorphine exposure during the first trimester of pregnancy on congenital malformations and anomalies.Ethics and disseminationThis study has been determined to meet the criteria for exemption per Article 2.5 of the 2018 Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Study databases have been made available by the BC Ministries of Health and Mental Health and Addiction as part of the provincial opioid overdose public health emergency response. Results will be disseminated to policymakers, clinical partners, community programmes and people with lived and living experience of substance use and published in peer-reviewed journals.

Prescribing of buprenorphine and naloxone in the emergency department (ED) has been shown to be an effective intervention. The purpose of this study was to determine the frequency of prescribing of naloxone and buprenorphine and the sub-groups that may be more or less likely to receive treatment. We used a national electronic health record database to identify patients with opioid poisoning or overdose presenting between January 2019-December 2021. Patients who were prescribed naloxone or buprenorphine were identified in this dataset and then further segmented based on self-identified gender, age, racial and ethnic identity, income categories, and social vulnerability index in order to identify sub-groups that may be less likely to be prescribed treatment. We found 74,004 patients in the database whom we identified as presenting to the ED with an opioid poisoning or overdose. Overall, 22.8% were discharged with a prescription for naloxone, while 0.9% of patients were discharged with buprenorphine products. Patients were less likely to receive naloxone prescriptions if they were female, White or Pacific Islander, non-Hispanic, not between the ages of 18-65, and non-English speaking. We found the same pattern for buprenorphine prescriptions except that the results were not significant for ethnicity and English-speaking. Despite evidence supporting its use, buprenorphine is not prescribed from the ED in a substantial proportion of patients. Naloxone is prescribed to a higher percentage, although still a minority of patients receive it. Some sub-groups are disadvantaged in the prescribing of these products. Further study may assist in improving the prescribing of these therapies.

Background Opioid use disorder (OUD) remains a significant public health issue as the number of opioid-related overdose deaths continues to reach new highs each year. Buprenorphine/Naloxone is a medication that has been shown to be highly effective for the treatment of OUD. However, the clinical management of patients on this medication is challenging as many patients discontinue treatment prematurely. We conducted a qualitative study focusing on experienced prescribers of buprenorphine to learn about what they believe are key challenges in prescribing this medication to patients with OUD and related strategies for improving treatment outcomes. Methods We conducted two rounds of interviews with 12 prescribers who were either trained as a primary care physician, nurse practitioner, or physician assistant. These prescribers were recruited from an academically-based treatment program, a community health center, and a commercial substance use disorder treatment facility. Interview data were coded and analyzed in accordance with a grounded theory approach. Results Key findings and related recommendations emerged for patient monitoring, integration of behavioral health with prescribing, patient volume requirements, and use of telehealth. Conclusion The interviews generated a number of recommendations for improving patient outcomes from buprenorphine treatment. Some of these recommendations can be implemented quite readily whereas others entail more substantial resources and time commitments.

An analysis of 2016–2019 Medicare claims data for patients with opioid use disorder showed that receipt of medications to treat OUD was more frequent among White patients than among Black and Hispanic patients.

AbstractObjectiveTo compare the risk of mortality among people with opioid use disorder on and off opioid agonist treatment (OAT) in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply.DesignPopulation based retrospective cohort study.SettingIndividual level linkage of five health administrative datasets capturing drug dispensations, hospital admissions, physician billing records, ambulatory care reports, and deaths in British Columbia, Canada.Participants55 347 people with opioid use disorder who received OAT between 1 January 1996 and 30 September 2018.Main outcome measuresAll cause and cause specific crude mortality rates (per 1000 person years) to determine absolute risk of mortality and all cause age and sex standardised mortality ratios to determine relative risk of mortality compared with the general population. Mortality risk was calculated according to treatment status (on OAT, off OAT), time since starting and stopping treatment (1, 2, 3-4, 5-12, >12 weeks), and medication type (methadone, buprenorphine/naloxone). Adjusted risk ratios compared the relative risk of mortality on and off OAT over time as fentanyl became more prevalent in the illicit drug supply.Results7030 (12.7%) of 55 347 OAT recipients died during follow-up. The all cause standardised mortality ratio was substantially lower on OAT (4.6, 95% confidence interval 4.4 to 4.8) than off OAT (9.7, 9.5 to 10.0). In a period of increasing prevalence of fentanyl, the relative risk of mortality off OAT was 2.1 (95% confidence interval 1.8 to 2.4) times higher than on OAT before the introduction of fentanyl, increasing to 3.4 (2.8 to 4.3) at the end of the study period (65% increase in relative risk).ConclusionsRetention on OAT is associated with substantial reductions in the risk of mortality for people with opioid use disorder. The protective effect of OAT on mortality increased as fentanyl and other synthetic opioids became common in the illicit drug supply, whereas the risk of mortality remained high off OAT. As fentanyl becomes more widespread globally, these findings highlight the importance of interventions that improve retention on opioid agonist treatment and prevent recipients from stopping treatment.

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners’ clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants’ attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author’s Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.

The rate of opioid analgesic overdose is proportional to the number of opioid prescriptions and the dose prescribed. This review considers the epidemiology, mechanisms, and management of opioid analgesic overdose. Opioid analgesic overdose is a preventable and potentially lethal condition that results from prescribing practices, inadequate understanding on the patient's part of the risks of medication misuse, errors in drug administration, and pharmaceutical abuse. 1 , 2 Three features are key to an understanding of opioid analgesic toxicity. First, opioid analgesic overdose can have life-threatening toxic effects in multiple organ systems. Second, normal pharmacokinetic properties are often disrupted during an overdose and can prolong intoxication dramatically. 3 Third, the duration of action varies among opioid formulations, and failure to recognize such variations can lead to inappropriate treatment decisions, sometimes with lethal results. 2 , . . .