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Introduction: Overdose deaths from high-potency synthetic opioids, including fentanyl and its analogs, continue to rise along with emergency department (ED) visits for complications of opioid use disorder (OUD). Fentanyl accumulates in adipose tissue; although rare, this increases the risk of precipitated withdrawal in patients upon buprenorphine initiation. Many EDs have implemented medication for opioid use disorder (MOUD) programs using buprenorphine. However, few offer methadone, a proven therapy without the risk of precipitated withdrawal associated with buprenorphine initiation. We describe the addition of an ED-initiated methadone treatment pathway and compared its 72-hour follow-up outpatient treatment engagement rates to our existing ED-initiated buprenorphine MOUD program.Methods: We expanded our ED MOUD program with a methadone treatment pathway. From February 20–September 19, 2023, we screened 20,504 ED arrivals; 5.1% had signs of OUD. We enrolled 61 patients: 28 in the methadone; and 33 in the buprenorphine pathways. For patients who screened positive for opioid use, shared decision-making was employed to determine whether buprenorphine or methadone therapy was more appropriate. Patients in the methadone pathway received their first dose of up to 30 milligrams (mg) of methadone in the ED. Two additional methadone doses of up to 40 mg were dispensed at the time of the ED visit and held in the department, allowing patients to return each day for observed dosing until intake at an opioid treatment program (OTP). We compared 72-hour rates of outpatient follow-up treatment engagement at the OTP (for those on methadone) or at the addiction treatment center (ATC) (for those on buprenorphine) for the two treatment pathways.Results: Of the 28 patients enrolled in the methadone pathway, 12 (43%) successfully engaged in follow-up treatment at the OTP. Of the 33 patients enrolled in the buprenorphine pathway, 15 (45%) successfully engaged in follow-up treatment at the ATC (relative risk 1.06; 95% confidence interval 0.60–1.87).Conclusion: Methadone initiation in the ED to treat patients with OUD resulted in similar 72-hour follow-up outpatient treatment engagement rates compared to ED-buprenorphine initiation, providing another viable option for MOUD.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Introduction: Methadone is a medically necessary and lifesaving medication for many patients with opioid use disorder. To adequately address these patients’ needs, methadone should be offered in the hospital, but barriers exist that limit its continuation upon discharge. The code of federal regulations allows for methadone dosing as an inpatient as well as outpatient dispensing forup to three days to facilitate linkage to treatment. As a quality initiative, we created a new workflow for discharging patients on methadone to return to the emergency department (ED) for uninterrupted dosing.Methods: Our addiction medicine team changed hospital methadone policy to better allow hospitalization as a window of opportunity to start methadone. This necessitated the creation of a warm-handoff process to link patients to methadone clinics if that linkage could not happen immediately on discharge. Thus, our team created the “ED Bridge” process, which uses the “3-day rule” to dispense methadone from the ED post hospital discharge. We then followed every patient we directed through this workflow as an observational cohort for outcomes and trends.Results: Of the patients for whom ED bridge dosing was planned, 40.4% completed all bridge dosing and an additional 17.3% received at least one but not all bridge doses. Established methadone patients made up 38.1% of successful linkages, and 61.9% were patients who were newly started on methadone in the hospital.Conclusion: Improving methadone as a treatment option remains an ongoing issue for policymakers and advocates. Our ED bridge workflow allows us to expand access and continuation of methadone now using existing laws and regulations, and to better use hospitals as a point of entry into methadone treatment.

BACKGROUND: Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in rural mountainous areas. This study aims to investigate factors related to confidence in providing methadone treatment among primary care providers in Vietnam to inform good practice development. METHODS: We conducted a cross-sectional survey with 276 primary care providers who were physicians, physician assistants, nurses, pharmacists or dispensing staff from 67 communes in a mountainous province in Northern Vietnam. Using self-report scales, we measured providers confidence in providing methadone treatment, beliefs in harm reduction, perceived work-related support, perceived stigma and risk in working with drug-using patients, and empathy towards this population. We used multiple linear regression analyses to explore factors associated with providers confidence in providing methadone treatment in the whole sample and to compare two groups of providers who did and did not have experience providing methadone. Potential associated factors were measured at facility and provider levels. RESULT: 114 (41.3%) participants had previously experience in providing methadone treatment. Providers with methadone treatment experiences had higher confidence in and more accurate knowledge of methadone treatment, perceived less stigma of working with drug-using patients, and reported more work-related support than those without experiences. Higher medical education is associated with lower confidence in providing methadone treatment among providers without methadone experiences, but higher confidence among providers with methadone experiences. Better methadone knowledge was associated with greater confidence in providing methadone treatment among inexperienced providers but not among those with experiences. Receiving work-related support was associated with greater confidence in providing treatment in both groups, regardless of their past methadone experiences. CONCLUSION: In rural provinces where methadone treatment has been expanded to primary care clinics, interventions to improve primary care providers confidence should benefit professionals with diverse experiences in providing methadone treatment. Continued training and support at work for providers is essential to ensuring quality in decentralized methadone treatment.

Objective Data Sources and Study Setting Study Design Data Collection/Extraction Methods Principal Findings Conclusions To assess the effectiveness of evidence‐based quality improvement (EBQI) as an implementation strategy to expand the use of medications for opioid use disorder (MOUD) within nonspecialty settings.We studied eight facilities in one Veteran Health Administration (VHA) region from October 2015 to September 2022 using administrative data.Initially a pilot, we sequentially engaged seven of eight facilities from April 2018 to September 2022 using EBQI, consisting of multilevel stakeholder engagement, technical support, practice facilitation, and data feedback. We established facility‐level interdisciplinary quality improvement (QI) teams and a regional‐level cross‐facility collaborative. We used a nonrandomized stepped wedge design with repeated cross sections to accommodate the phased implementation. Using aggregate facility‐level data from October 2015 to September 2022, we analyzed changes in patients receiving MOUD using hierarchical multiple logistic regression.Eligible patients had an opioid use disorder (OUD) diagnosis from an outpatient or inpatient visit in the previous year. Receiving MOUD was defined as having been prescribed an opioid agonist or antagonist treatment or a visit to an opioid substitution clinic.The probability of patients with OUD receiving MOUD improved significantly over time for all eight facilities (average marginal effect [AME]: 0.0057, 95% CI: 0.0044, 0.0070) due to ongoing VHA initiatives, with the probability of receiving MOUD increasing by 0.577 percentage points, on average, each quarter, totaling 16 percentage points during the evaluation period. The seven facilities engaging in EBQI experienced, on average, an additional 5.25 percentage point increase in the probability of receiving MOUD (AME: 0.0525, 95%CI: 0.0280, 0.0769). EBQI duration was not associated with changes.EBQI was effective for expanding access to MOUD in nonspecialty settings, resulting in increases in patients receiving MOUD exceeding those associated with temporal trends. Additional research is needed due to recent MOUD expansion legislation. [ABSTRACT FROM AUTHOR]

Methadone is an opioid receptor agonist with a high potential for abuse. The current study aimed to compare different machine learning models to predict the outcomes following methadone poisoning. This six-year retrospective longitudinal study utilizes National Poison Data System (NPDS) data. The severity of outcomes was derived from the NPDS Coding Manual. Our database was divided into training (70%) and test (30%) sets. We used a light gradient boosting machine (LGBM), extreme gradient boosting (XGBoost), random forest (RF), and logistic regression (LR) to predict the outcomes of methadone poisoning. A total of 3847 patients with methadone exposures were included. Our results demonstrated that machine learning models conferred high accuracy and reliability in determining the outcomes of methadone poisoning cases. The performance evaluation showed all models had high accuracy, precision, specificity, recall, and F1-score values. All models could reach high specificity (more than 96%) and high precision (80% or more) for predicting major outcomes. The models could also achieve a high sensitivity to predict minor outcomes. Finally, the accuracy of all models was about 75%. However, XGBoost and LGBM models achieved the best performance among all models. This study showcased the accuracy and reliability of machine learning models in the outcome prediction of methadone poisoning. [ABSTRACT FROM AUTHOR]

Background and aims: Ukraine's Ministry of Health released urgent COVID‐19 guidelines, allowing for early implementation of take‐home dosing (THD) for opioid agonist therapies (OAT) such as methadone. Enrollment in OAT and retention in the program are the most effective HIV prevention strategies for people who inject drugs (PWID). This study aimed to evaluate the impact of Ukraine's COVID‐19 emergency guidance on OAT treatment enrollment, retention on treatment and mortality. Design and setting: Using Ukraine's national OAT registry for 252 governmental clinics across 25 regions, we conducted a 12‐month comparative prospective cohort survival analysis. This study compared newly enrolled methadone patients within the initial 6 months following the COVID‐19 guidance (COVID) with patients from the preceding year (pre‐COVID) in a country with high adult HIV prevalence (1.2%) that is concentrated in PWID. Participants: In the nation‐wide sample of newly enrolled PWID in Ukraine, comprising 2798 individuals, 1423 were in the COVID cohort and 1375 were in the pre‐COVID cohort. The majority were male (86.7%), with an average age of 39.3 years. Measurements: Primary outcomes were average monthly enrollment per cohort, treatment retention and mortality, with internal time‐dependent predictors, including THD and optimal (> 85 mg) methadone dosing. Results: Relative to the pre‐COVID period, the monthly average patient enrollment was statistically significantly higher during the COVID period (283.7 versus 236.0; P < 0.0001), where patients were more likely to transition to THD and achieve optimal dosing earlier. Significant differences were observed in the proportions of person‐months on THD (41 versus 13%, P < 0.0001) and optimal dosing (38 versus 31%, P < 0.0001) between the COVID and pre‐COVID cohorts. Predictors of treatment retention, expressed as adjusted hazard ratios (aHR), included early THD [aHR = 1.90, 95% confidence interval (CI) = 1.47–2.45], early optimal dosing (aHR = 1.71, 95% CI = 1.37–2.13) and prior methadone treatment (aHR = 1.39, 95% CI = 1.15–1.68). These factors persisted, respectively, in the pre‐COVID (aHR = 2.28, 95% CI = 1.41–3.70; aHR = 1.84, 95% CI = 1.32–2.56; and aHR = 1.36, 95% CI = 1.06–1.74) and COVID (aHR = 1.91, 95% CI = 1.40–2.59; aHR = 1.61, 95% CI = 1.20–2.16; and aHR = 1.49, 95% CI = 1.08–1.94) cohorts. Survival did not differ significantly between the two prospective cohorts. Conclusion: Ukraine's prompt adoption of early take‐home dosing for opioid agonist therapies, such as methadone, following the emergency COVID‐19 guidance appears to have increased enrollment into methadone and improved treatment retention for people who inject drugs without adverse effects on patient survival. [ABSTRACT FROM AUTHOR]

Rationale and objective: Avoidance of opioid withdrawal plays a key role in human opioid addiction. Here, we present a procedure for studying operant negative reinforcement in rats that was inspired by primate procedures where opioid-dependent subjects lever-press to prevent naloxone infusions. Methods: In Experiment 1, we trained rats (n = 30, 15 females) to lever-press to escape and then avoid mild footshocks (0.13–0.27 mA) for 35 days (30 trials/d). Next, we catheterized them and implanted minipumps containing methadone (10 mg/kg/day) or saline. We then paired (4 times, single session) a light cue (20-s) with a naloxone infusion (20 µg/kg, i.v) that precipitated opioid withdrawal. Next, we trained the rats to escape naloxone injections for 10 days (30 trials/d). Each trial started with the onset of the opioid-withdrawal cue. After 20-s, the lever extended, and an infusion of naloxone (1 to 2.2 µg/kg/infusion) began; a lever-press during an 11-s window terminated the withdrawal-paired cue and the infusion. In Experiment 2, we trained rats (n = 34, 17 females) on the same procedure but decreased the footshock escape/avoidance training to 20 days. Results: All rats learned to lever-press to escape or avoid mild footshocks. In both experiments, a subset, 56% (10/18) and 33% (8/24) of methadone-dependent rats learned to lever-press to escape naloxone infusions. Conclusions: We introduce an operant negative reinforcement procedure where a subset of opioid-dependent rats learned to lever-press to escape withdrawal-inducing naloxone infusions. The procedure can be used to study mechanisms of individual differences in opioid negative reinforcement-related behaviors in opioid-dependent rats. [ABSTRACT FROM AUTHOR]

Background: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL). Case presentation: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control. Conclusions: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain. [ABSTRACT FROM AUTHOR]

Background: Many people with opioid use disorder who stand to benefit from buprenorphine treatment are unwilling to initiate it due to experience with or fear of both spontaneous and buprenorphine-precipitated opioid withdrawal (BPOW). An effective means of minimizing withdrawal symptoms would reduce patient apprehensiveness, lowering the barrier to buprenorphine initiation. Ketamine, approved by the FDA as a dissociative anesthetic, completely resolved BPOW in case reports when infused at a sub-anesthetic dose range in which dissociative symptoms are common. However, most patients attempt buprenorphine initiation in the outpatient setting where altered mental status is undesirable. We explored the potential of short-term use of ketamine, self-administered sublingually at a lower, sub-dissociative dose to assist ambulatory patients undergoing transition to buprenorphine from fentanyl and methadone. Methods: Patients prescribed ketamine were either (1) seeking transition to buprenorphine from illicit fentanyl and highly apprehensive of BPOW or (2) undergoing transition to buprenorphine from illicit fentanyl or methadone and experiencing BPOW. We prescribed 4–8 doses of sublingual ketamine 16 mg (each dose bioequivalent to 3–6% of an anesthetic dose), monitored patients daily or near-daily, and adjusted buprenorphine and ketamine dosing based on patient response and prescriber experience. Results: Over a period of 14 months, 37 patients were prescribed ketamine. Buprenorphine initiation was completed by 16 patients, representing 43% of the 37 patients prescribed ketamine, and 67% of the 24 who reported trying it. Of the last 12 patients who completed buprenorphine initiation, 11 (92%) achieved 30-day retention in treatment. Most of the patients who tried ketamine reported reduction or elimination of spontaneous opioid withdrawal symptoms. Some patients reported avoidance of severe BPOW when used prophylactically or as treatment of established BPOW. We developed a ketamine protocol that allowed four of the last patients to complete buprenorphine initiation over four days reporting only mild withdrawal symptoms. Two patients described cognitive changes from ketamine at a dose that exceeded the effective dose range for the other patients. Conclusions: Ketamine at a sub-dissociative dose allowed completion of buprenorphine initiation in the outpatient setting in the majority of patients who reported trying it. Further research is warranted to confirm these results and develop reliable protocols for a range of treatment settings. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions More evidence for patterns of healthcare utilisation and associated costs among people receiving opioid agonist therapy (OAT) is needed. We investigated primary and secondary healthcare usage and costs among methadone and buprenorphine recipients in England.We conducted a cohort study using the Clinical Practice Research Datalink GOLD and Aurum databases of patients who were prescribed OAT between 1 January 2007 and 31 July 2019. The cohort was linked to Hospital Episode Statistics admitted patient care, outpatient and emergency department data, neighbourhood‐ and practice‐level Index of Multiple Deprivation quintiles and mortality records. Negative binomial regression models were applied to estimate weighted rate ratios (wRR) of healthcare utilisation. Total and mean costs were calculated using Unit Costs of Health and Social Care and the National Healthcare Service Payment by Results National Tariffs.Among 12,639 patients observed over 39,016 person‐years, we found higher rate of hospital admissions (wRR 1.18; 1.08–1.28) among methadone compared with buprenorphine recipients. The commonest hospital discharge diagnoses among methadone patients were infectious diseases (19.2%), mental and behavioural disorders (17.0%) and drug‐related poisoning (16.5%); the three commonest among buprenorphine patients were mental and behavioural diseases (21.5%), endocrine (13.8%) and genitourinary system diseases (13.1%). Methadone patients had similar mean costs compared with buprenorphine patients (cost difference: £539.01; 432.11–1006.69).Differences in healthcare utilisation frequency for methadone versus buprenorphine recipients were observed. The differences in associated costs were mainly driven by hospital admissions. These findings offer valuable insights for optimising care strategies and resource allocation for OAT recipients. [ABSTRACT FROM AUTHOR]

To mitigate COVID-19 exposure risks in methadone clinics, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued a temporary modification of regulations in March 2020 to permit, with state concurrence, extended take-home methadone doses. The modification allowed for up to 28 days of take-home methadone for stable patients and 14 days for those less stable. Using both interrupted time series and difference-in-differences methods, this study examined the association between the policy change and fatal methadone overdoses, comparing states that permitted the expansion of take-home doses with states that did not. The findings suggest the pandemic emergency take-home policy did not increase methadone-involved mortality. [ABSTRACT FROM AUTHOR]

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

Background and aim: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use. Design, setting and participants: This was a population‐based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada. All individuals with at least one OAT dispensation in BC between 1 January 2014 and 31 August 2021 took part. Measurements: To assess changes in OAT prescribing practices over time, we calculated initiation doses, dose titration intervals, maintenance doses and take‐home dosing intervals stratified by medication [methadone, buprenorphine–naloxone and slow‐release oral morphine (SROM)] according to recommended guidelines. Findings A total of 265 410 OAT episodes (57.5% on methadone, 34.5% on buprenorphine–naloxone and 8.0% on SROM) were initiated during the study period. Compared with the guideline recommendation, observed initiation doses were higher among all medications from 2014 (2017 for SROM) to 2021 (buprenorphine–naloxone: 14–29%; methadone: 53–66%; SROM: 26–55%). Titration intervals were shorter for all medications, consistent with guidelines for buprenorphine–naloxone (26–49%), but shorter than recommended for methadone or SROM (28–51% and 12–41%, respectively). Higher maintenance dosing was observed for methadone (68–78%) and SROM (3–21%). Take‐home allowances extending beyond the recommended guideline length increased across medications (buprenorphine–naloxone: 18–35%; methadone: 50–64%; SROM: 34–39%). Changes in prescribing patterns were similar for first‐time OAT initiators. Conclusion: In British Columbia, Canada, from 2014 to 2021, prescribers of opioid agonist treatment (OAT) appeared to initiate both new and experienced OAT clients at higher doses than guideline recommendations, titrate them more rapidly and maintain clients at higher doses. Take‐home dose allowances also gradually increased. [ABSTRACT FROM AUTHOR]

Driving the overdose epidemic, a significant proportion of adult and adolescent patients seen in neurology practice and hospital settings has substance use disorder. Fortunately, there are effective treatments available, in particular for opioid addiction. Some elements of treatment can be delivered directly in medical office-based settings, while others are best provided from within specialized addiction treatment facilities. In this article, we review the nature of substance use disorders, and the various treatment approaches that can be utilized to stabilize patients and facilitate their building a strong recovery foundation. Some interventions discussed may be directly provided by a physician identifying the disorder, while others involve collaboration with specialized addiction treatment centers and recovery support entities. [ABSTRACT FROM AUTHOR]

The rates of opioid use and opioid related deaths are escalating in the United States. Despite this, evidence-based treatments for Opioid Use Disorder are underutilized. There are three medications FDA approved for treatment of Opioid Use Disorder: Methadone, Buprenorphine, and Naltrexone. This article reviews the history, criteria, and mechanisms associated with Opioid Use Disorder. Pertinent pharmacology considerations, treatment strategies, efficacy, safety, and challenges of Methadone, Buprenorphine, and Naltrexone are outlined. Lastly, a practical decision making algorithm is discussed to address pertinent psychiatric and medical comorbidities when prescribing pharmacology for Opioid Use Disorder. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. Material and Methods: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six‐year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. Results: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7–14 (group I), 14.3–38.6 (group II), 40–90 (group III) and 90.9–1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9–39.1]) and group IV (aOR 37.8 [7.6–188.2]) but not in group II (aOR 1.5 [0.4–5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. Conclusions: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40. [ABSTRACT FROM AUTHOR]

Purpose: Refractory cancer-induced bone pain (CIBP) affects a patient’s functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort. Methods: Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days. Results: Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR: d = − 1.2, p = 0.003, OOR: d = − 0.8, p = 0.015) and worst pain (MR: d = − 0.9, p = 0.042, OOR: d = − 0.6, p = 0.048) and total pain interference score (MR: d = − 1.1, p = 0.042, OOR: d = − 0.7, p = 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group (d = − 0.8, p = 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group (d = 0.9, 95% CI 0.1,1.7, p = 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study. Conclusion: This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort. Trial registration: ACTRN12621000141842 registered 11 February 2021. [ABSTRACT FROM AUTHOR]

To explore the association between intraoperative methadone use, postoperative pain, and opioid consumption after coronary artery bypass grafting (CABG) surgery. Retrospective cohort study. Single academic medical center. Patients undergoing isolated CABG over a 5-year period. None. Demographic data, comorbidities, and intraoperative anesthetic medications were recorded. Primary study outcomes were average and maximum pain scores and morphine milligram equivalent consumption on the first 2 postoperative days (PODs). Linear mixed-effects regression models were used to examine the effect of intraoperative methadone use on study outcomes. Among 1,338 patients, 78.6% received intraoperative methadone (0.2 mg/kg). Patients who did not receive methadone had higher average (estimated [Est], 0.48; 95% confidence interval [CI], 0.22-0.73; p < 0.001) and maximum postoperative (Est, 0.49; 95% CI, 0.23-0.75; p < 0.001) pain scores over PODs 0 to 2. For postoperative opioid consumption, there was a significant intraoperative methadone use–time interaction effect on postoperative opioid use (odds ratio [OR], 2.21; 95% CI, 1.74-2.80; p < 0.001). Across PODs 0 to 2, patients who received intraoperative methadone had a faster decline in postoperative opioid use than those who did not receive intraoperative methadone. Patients who did not receive intraoperative methadone were extubated slightly faster (OR, 0.82; 95% CI, 0.72-0.93; p < 0.01). Our data suggest that the use of intraoperative methadone is safe, reduces postoperative pain, and expedites weaning from postoperative opioids after CABG surgery. [ABSTRACT FROM AUTHOR]

Opioid withdrawal is common among hospitalized patients. Those with substance use disorders exhibit higher rates of patient-directed discharge. The literature lacks information regarding the patient perspective on opioid withdrawal in the hospital setting. In this study, we aimed to capture the patient-reported experience of opioid withdrawal during hospitalization and its impact on the desire to continue treatment for opioid use disorder after discharge. We performed a single-center qualitative study involving semi-structured interviews of hospitalized patients with opioid use disorder (OUD) experiencing opioid withdrawal. Investigators conducted in-person interviews utilizing a combination of open-ended and dichotomous questions. Interview transcripts were then analyzed with open coding for emergent themes. Nineteen interviews were performed. All participants were linked to either buprenorphine (79%) or methadone (21%) at discharge. Eight of nineteen patients (42%) reported a patient-directed discharge during prior hospitalizations. Themes identified from the interviews included: (1) opioid withdrawal was well-managed in the hospital; (2) patients appreciated receiving medication for opioid use disorder (MOUD) for withdrawal symptoms; (3) patients valued and felt cared for by healthcare providers; and (4) most patients had plans to follow-up for opioid use disorder treatment after hospitalization. In this population with historically high rates of patient-directed discharge, patients reported having a positive experience with opioid withdrawal management during hospitalization. Amongst our hospitalized patients, we observed several different individualized MOUD induction strategies. All participants were offered MOUD at discharge and most planned to follow-up for further treatment. [ABSTRACT FROM AUTHOR]

Background: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood. Aims: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use. Materials & Methods: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS‐I for observational studies. Certainty of evidence was assessed using GRADE. Results: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta‐analysis as they reported a different outcome and studied an opioid antagonist. Meta‐analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31–4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15–3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52–130.61; I2 = 0%), but both indicated an increased risk. Conclusion: In this systematic review and meta‐analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence. [ABSTRACT FROM AUTHOR]

Methadone is a synthetic long-acting opioid that is increasingly used in the replacement therapy of opioid-addicted patients, including pregnant women. However, methadone therapy in this population poses challenges, as it induces cognitive and behavioral impairments in infants exposed to this opioid during prenatal development. In animal models, prenatal methadone exposure results in detrimental consequences to the central nervous system, such as: (i) increased neuronal apoptosis; (ii) disruption of oligodendrocyte maturation and increased apoptosis and (iii) increased microglia and astrocyte activation. However, it remains unclear whether these deleterious effects result from a direct effect of methadone on brain cells. Therefore, our goal was to uncover the impact of methadone on single brain cell types in vitro. Primary cultures of rat neurons, oligodendrocytes, microglia, and astrocytes were treated for three days with 10 µM methadone to emulate a chronic administration. Apoptotic neurons were identified by cleaved caspase-3 detection, and synaptic density was assessed by the juxtaposition of presynaptic and postsynaptic markers. Apoptosis of oligodendrocyte precursors was determined by cleaved caspase-3 detection. Oligodendrocyte myelination was assessed by immunofluorescence, while microglia and astrocyte proinflammatory activation were assessed by both immunofluorescence and RT-qPCR. Methadone treatment increased neuronal apoptosis and reduced synaptic density. Furthermore, it led to increased oligodendrocyte apoptosis and a reduction in the myelinating capacity of these cells, and promoted the proinflammatory activation of microglia and astrocytes. We showed that methadone, the most widely used drug in opioid replacement therapy for pregnant women with opioid addiction, directly impairs brain cells in vitro, highlighting the need for developing alternative therapies to address opioid addiction in this population. [ABSTRACT FROM AUTHOR]