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The management of cancer-related pain in patients with opioid use disorder (OUD) remains complex and often challenging for clinicians and patients. There is currently a paucity of data to guide best practices, and the evidence that exists is variably applied. In this hospital-based questionnaire, we sought to understand the variation in practice patterns among clinicians in palliative medicine, addiction medicine, and hospital medicine, in caring for this complex patient population. Sixty-two questionnaire responses were analyzed and variation was found in management of pain, as well as initiation or titration of buprenorphine and methadone. There was also a significant difference in postdischarge subspecialty follow-up. Furthermore, the findings suggest that buprenorphine and methadone may be underutilized in this population. Patients and clinicians may benefit from additional support and standardization of practices to best manage coexisting cancer-related pain and OUD. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in pain research challenge the concept that animals lack pain senses, showing that they have similar neural pathways to humans and experience pain similarly. Understanding brain circuits for effective pain control is crucial for adjusting pain control to individual patient responses and conditions. Pain management in oncological patients aims to lessen the impact of tumor cell development and its consequences on the immune system. Researchers have focused on improving algological approaches to better respond to patient needs, which requires a deeper understanding of how analgesics work, interact with other drugs, and affect patients' conditions. Opioids, although linked to tumor progression, remain the mainstay for managing oncologic pain. Advancements in understanding pain physiopathology have historically challenged animals' absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient's individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient's demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients. [ABSTRACT FROM AUTHOR]

According to certain findings, heroin addiction represents a significant medical as well as social problem. It is known that with opioid substitution treatment this disease can be overcome or alleviated. However, the application of this treatment does not always give the expected results, so it is necessary to apply additional neuroleptic therapy until the patients are fully stabilized. But the joint application of substitution and neuroleptic therapy can lead to a series of side effects, one of which is the appearance of hyperpolactinemia. The aim of this study is to observe the prevalence of symptoms of hyperprolactinemia in patients with poor response to methadone treatment, treated with neuroleptic therapy. Material and methods: The cross-sectional study evaluated 20 male patients with a mean age of ±24.13 years treated at the Skopje Psychiatric Hospital with high doses of Sol methadone 80-120 mg/day. All patients had a bad agreement on the methadone treatment, so additional therapy was included, tab. Risperidone with an average dose of 2 mg/day. Participants signed an informed consent to participate. Patients were assessed using a semi-structured questionnaire specifically designed for the study. Data consisted of age, sex, and symptoms of hyperprolactinemia: amenorrhea, loss of libido, erectile dysfunction, and gynecomastia. The results of this study were analyzed using descriptive methods, t-test and Pearson's correlation coefficient. The p value of statistical significance was set at p<0.05. Results: The results obtained in our study showed that a certain percentage of methadone patients who were on Risperidone therapy had symptoms of hyperprolactinemia, but the results were without statistical significance p>0.05. Conclusion: although in our study we obtained a small percentage of patients with symptoms of hyperprolactinemia, care must be taken in patients on methadone treatment who are also treated with neuroleptic therapy due to their synergistic effect, we should always keep in mind the possibility of developing hyperprolactinemia. [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]

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]

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]

Background. The subject of this article is the role of forensic toxicology in post-mortem examinations using immunofluorescence methods, its implications and its role in providing conclusive evidence for both criminal and civil proceedings. The aim of the study is to verify the correlation between the mode of death and the ingestion of exogenous substances and, if positive, to identify the category of substances ingested and assess their role in the cause of death. Materials and methods. A laboratory study was carried out, consisting of several phases: pre-analytical phase; analytical phase; post-analytical phase. The variables analyzed were sex, cause of death, age. Abused substances tested: amphetamines, methamphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, tricyclic antidepressants, delta-9-tetrahydrocannabinol (cannabis), alcohol. Conclusions. Retrospective analysis was performed on a total sample of 55 cases. The most relevant data emerged: cocaine with an incidence of 7.3% (4 cases out of 55), amphetamines with 5.4% (3 cases in total). The results of the screening tests were then subjected to confirmatory tests. There is an association between the use of certain exogenous substances and an increased risk of certain causes of death, such as overdose, traffic accidents, cardiovascular deaths, etc. This paper has highlighted the possibility of using first level immunological tests, such as immunofluorescence, to provide preliminary answers to the judicial authority immediately after autopsy, and a quantitative deepening with further second level tests, such as gas chromatography, as a gold standard to determine the cause of death. [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]

Access to treatment and medication for opioid use disorder (MOUD) is essential in reducing opioid use and associated behavioral risks, such as syringe sharing among persons who inject drugs (PWID). Syringe sharing among PWID carries high risk of transmission of serious infections such as hepatitis C and HIV. MOUD resources, such as methadone provider clinics, however, are often unavailable to PWID due to barriers like long travel distance to the nearest methadone provider and the required frequency of clinic visits. The goal of this study is to examine the uncertainty in the effects of travel distance in initiating and continuing methadone treatment and how these interact with different spatial distributions of methadone providers to impact co-injection (syringe sharing) risks. A baseline scenario of spatial access was established using the existing locations of methadone providers in a geographical area of metropolitan Chicago, Illinois, USA. Next, different counterfactual scenarios redistributed the locations of methadone providers in this geographic area according to the densities of both the general adult population and according to the PWID population per zip code. We define different reasonable methadone access assumptions as the combinations of short, medium, and long travel distance preferences combined with three urban/suburban travel distance preference. Our modeling results show that when there is a low travel distance preference for accessing methadone providers, distributing providers near areas that have the greatest need (defined by density of PWID) is best at reducing syringe sharing behaviors. However, this strategy also decreases access across suburban locales, posing even greater difficulty in regions with fewer transit options and providers. As such, without an adequate number of providers to give equitable coverage across the region, spatial distribution cannot be optimized to provide equitable access to all PWID. Our study has important implications for increasing interest in methadone as a resurgent treatment for MOUD in the United States and for guiding policy toward improving access to MOUD among PWID. Author summary: Persons who inject drugs (PWID) such as heroin or other illicit substances are at increased risk of getting or transmitting HIV or hepatitis C (HCV) infection, because limited access to clean syringes and drug injection equipment means that PWID often share contaminated syringes. Public health interventions aimed at reducing injection drug use include medications for opioid use disorder (MOUD) that help to reduce cravings for opioids like heroin and fentanyl. However, resources like MOUD provider clinics are often unavailable to PWID due to factors such as the travel distance from home to clinic, frequent clinic visits, along with social phenomena such as degree of medical mistrust and stigma towards treatment. We use a computational simulation model of PWID social networks and drug use behaviors in Chicago, IL and suburbs to show how the geographic distribution of clinical providers of methadone, an MOUD, impacts the injection frequency of PWID. Our modeling results show that when PWID prefer a low travel distance to methadone providers, distributing providers near areas that have the greatest need is best at reducing syringe sharing behaviors. However, this strategy also decreases access across suburban locales, posing even greater difficulty in regions with fewer transit options and providers. [ABSTRACT FROM AUTHOR]

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference > + 2, < − 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention. [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]

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 for up 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 warmhandoff 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. [ABSTRACT FROM AUTHOR]

Sexual dysfunction caused by opioids is one of the serious problems of drug misusers. This study aimed to evaluate and compare the effect of continuous low-dose sildenafil treatment alongside psychological training on the sexual function of methadone-treated patients. This randomized clinical trial was conducted on methadone-treated men with sexual dysfunction. Patients were randomly divided into two treatment groups: sildenafil 25 mg and psychological training. Sexual Quality of Life-Men, Sexual Self-Efficacy Scale–Erectile, and the International Index of Erectile Function were used before and 4 weeks after the end of the intervention. A total of 67 couples were included in the study (34 psychological interventions vs. 33 sildenafil group). After 4 weeks of treatment, the mean of male erectile function (33.73 ± 8.114 and 27.62 ± 6.238, p = 0.003) and sexual self-efficacy score (78.36 ± 12.713 and 69.62 ± 14.940, p < 0.0001) in the sildenafil group were statistically significant compared to the psychological group, however, the sexual quality score of the two groups was not statistically significant (31.48 ± 9.216 and 31.71 ± 11.333, p = 0.342). The sexual function of methadone-treated men in both groups was significantly improved, yet this difference was significantly greater in the pharmaceutical treatment group than the trainings. As a result, due to the high need for treatment, any type of intervention (medication or psychotherapy) will be effective in these patients. [ABSTRACT FROM AUTHOR]

With opioid overdose rates on the rise, we aimed to develop a county-level risk stratification that specifically focused on access to medications for opioid use disorder (MOUDs) and high overdose rates. We examined over 15 million records from the South Carolina Prescription Tracking System (SCRIPTS) across 46 counties. Additionally, we incorporated data from opioid treatment programs, healthcare professionals prescribing naltrexone, clinicians with buprenorphine waivers, and county-level overdose fatality statistics. To assess the risk of opioid misuse, we classified counties into high-risk and low-risk categories based on their prescription rates, overdose fatalities, and treatment service availability. Statistical methods employed included the two-sample t-test and linear regression. The t-test assessed the differences in per capita prescription rates between high-risk and low-risk counties. Linear regression was used to analyze the trends over time. Our study showed that between 2017 and 2021, opioid prescriptions decreased from 64,223 to 41,214 per 100,000 residents, while fentanyl-related overdose deaths increased by 312%. High-risk counties had significantly higher rates of fentanyl prescriptions and relied more on out-of-state doctors. They also exhibited higher instances of doctor shopping and had fewer medical doctors per capita, with limited access to MOUDs. To effectively combat the opioid crisis, we advocate for improved local healthcare infrastructure, broader treatment access, stricter management of out-of-state prescriptions, and vigilant tracking of prescription patterns. Tailored local strategies are essential for mitigating the opioid epidemic in these communities. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain can lead to several complications. The effectiveness of different opioids in relieving pain after surgery has been widely studied. However, managing pain in patients with opioid addiction is still challenging. This study aimed to examine the impact of ketamine and methadone on postoperative pain in patients with addiction. Methods: This was a non-inferiority randomized clinical trial. All included patients were monitored for morphine use, pain scores, and vital signs every 3 h. The intervention group received 0.5 mg/kg ketamine administered intravenously every 6 h. The control group received 5 mg of methadone intramuscularly every 8 h. The patient received intravenous morphine if their visual analog scale was above 3. All side effects in each group were recorded. Results: Two hundred and twenty patients were included in this study. There were 127 men (57.7%) with an average age of 57.1 ± 19.5 and 93 women (42.3%) with an average age of 57.1 ± 21.0. There were no significant differences in demographic characteristics between the groups. There was no significant difference in the dose or frequency of morphine administration between groups. There was no significant difference between the groups in pain scores and vital signs at different time points. Drug side effects, including delirium and gastrointestinal symptoms, did not differ significantly between the methadone and ketamine groups. Conclusions: Our clinical data support the hypothesis that ketamine is not inferior to methadone in patients with addiction. Future randomize clinical trials are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Objective: To model the potential impact of mobile methadone unit implementation in Louisiana on net medication for opioid use disorder (MOUD) treatment rates. Data Sources/Study Setting: We use secondary Louisiana Medicaid claims data between 2020 and 2021. Study Design: We simulate the impact of mobile methadone units in Louisiana using two approaches: (1) a "Poisson regression approach," which predicts the number of opioid use disorder (OUD) patients that might use methadone at mobile locations based on the underlying association between methadone use and proximity to a brick‐and‐mortar methadone clinic; (2) a "policy approach," which leverages local treatment uptake rates following the expansion of methadone coverage to Louisiana Medicaid beneficiaries in 2020 to estimate methadone use following mobile unit implementation. Models were run in cases where mobile methadone operators could choose their operation locations freely and in a separate instance where they were restricted to serving rural locations. Data Collection: Our analytic sample includes 43,341 Louisiana Medicaid beneficiaries with one or more primary or secondary diagnoses for opioid dependence. Principal Findings: We predict that 10 new mobile methadone units in Louisiana would increase the net MOUD treatment rate in the state by 0.54–2.39 percentage points. If these mobile units delivered Methadone exclusively to rural areas, they could increase rural MOUD treatment by 8.54–13.67 percentage points. Further, roughly 20% of all beneficiaries residing in rural areas being treated with methadone would be an average of 24 miles closer to a methadone treatment provider following mobile unit implementation. Conclusions: Mobile methadone units represent a promising innovation in the delivery of methadone that is likely to increase methadone use, especially in underserved rural locations. However, we find significant variation in their impact conditional on where they choose to operate, and so careful location planning will be required to maximize their benefit. [ABSTRACT FROM AUTHOR]

Background: The Methadone Maintenance Treatment (MMT) program has been proven to be beneficial in reducing illicit opioid use, increasing access to and retention of HIV treatment and other therapies, and reducing HIV transmission, and other drug-related morbidities and mortalities. However, determinants of treatment retention and outcomes for opioid-dependent persons accessing MMT in Kenya are limited. We sought to identify factors contributing to poor treatment outcomes among opioid-dependent persons enrolled in the Mombasa MMT program, between 2017 and 2019. Method: We conducted a retrospective records review for opioid-dependent persons receiving Methadone treatment in the Kisauni MAT clinic enrolled during 2017–2019. We defined poor clinical or health-related treatment outcome as any client Lost-To-Follow-Up (LTFU), turned HIV or Viral hepatitis positive, and/or missed two or more antiretroviral therapy (ART) appointments intake during MMT. Variables abstracted from clinical and pharmacological MMT service delivery tools included socio-demographic characteristics, clinical history, risk factors, and MMT outcomes. Data were analyzed using Epi Info7. We calculated Prevalence Odds Ratios (POR) and 95% Confidence Intervals (CI) to identify factors associated with adverse health outcomes. Results: Of the total 443 eligible records, the mean age was 37 years (SD ± 7.2) and males comprised 90.7%. The majority of females clients, 79.1% (34/43), were aged ≤35 years, 7.0% (3/43) had no education, 32.6% (14/43) were employed, 39.5% (17/43) were HIV positive and 18.6% (8/43) were HCVpositive. Overall, adverse treatment outcomes were at 27.5% (122/443), namely: LTFU at 22.8% (101/443), new HIV cases at 1.0% (4/391), HCV at 1.2% (5/405), and Hepatitis B Virus (HBV) at 1.2% (5/411), and 1.1% (5/443) died. Of HIV-infected clients linked to Comprehensive Care Clinic (CCC), 3.6% (2/56) defaulted from ART, and 25% (2/8) had detectable Viral Load of those retested. Lack of formal education (POR: 2.7, 95% CI: 1.3–5.7), unemployment (POR: 2.4, 95% CI: 1.4–4.0), and being a Non-Injector (POR: 1.7, 95% CI: 1.0–2.9) were negatively associated with treatment retention. Conclusion: Females were younger, and more educated with higher HIV and HCV prevalence. Being a Non-injector, unemployment, and lack of formal education may increase the likelihood of poor treatment outcomes among MMT clients. Closer monitoring of MMT clients with these characteristics is recommended with the integration of CCC into MMT services. [ABSTRACT FROM AUTHOR]

Mental health conditions including substance use disorder are the leading cause of pregnancy-related deaths in the U.S. Unfortunately, fears of child protective services' involvement interfere with maternal self-disclosure of substance use in pregnancy. Seeking to identify more mothers with substance use disorder in pregnancy or at delivery, and responsive to changes to the federal Child Abuse Prevention and Treatment Act (CAPTA), Connecticut requires hospital personnel to submit a deidentified notification to CPS for all newborns with prenatal substance exposure. However, it is unknown whether this approach aligns with maternal self-report on substance use. For the present study, we compared population parameters derived from CAPTA notifications submitted between March-December 2019 with parameters derived from self-report data on substance use in pregnancy from mothers who gave birth during the same timeframe. Results revealed that three times as many mothers self-reported any alcohol or drug use in pregnancy compared to the rate measured with CAPTA notifications. Compared to mothers who self-reported drug use in the third trimester, CAPTA notifications were made for statistically similar rates of Black mothers but half the self-reported rate of White and Hispanic mothers. This disparity reflects that CAPTA notifications were made for twice as many Black mothers as White or Hispanic. Although CAPTA notifications are not punitive in nature, this disparity reveals that the public health aims of this policy are not yet achieved. Significance: Accurate and equitable identification of infants with prenatal substance exposure and their mothers, coupled with non-stigmatized, non-punitive intervention is central to any public health response.The current study relies on 2019 data from Connecticut to understand accuracy and equity in identification of these infants by comparing hospital-based notifications to self-report substance use in pregnancy. We found that hospital approaches to detecting prenatal substance exposure identified twice as many Black mothers as White or Hispanic mothers. Compared to self-reported substance use in pregnancy, which detected equivalent rates of substance use across race groups, White and Hispanic mothers' substance use in pregnancy was under-identified in hospital settings. [ABSTRACT FROM AUTHOR]

Available literature demonstrates that methadone is prone to moderate postmortem redistribution, but subject to high interindividual variability in the central to peripheral blood concentration ratios (C/P). In this case series, 10 cases of chronic methadone users displaying C/P < 1 (range 0.26–0.82) are described. Femoral, cardiac and ante-mortem blood concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are reported for all cases, as well as sex, age, case history, results of the pathological investigation, other toxicological findings and cause and manner of death. EDDP blood concentrations, similar in both central and peripheral blood, as well as antemortem blood concentration results in Case 4, demonstrate that this atypical C/P < 1 finding is attributable to postmortem changes and not analytical or pre-analytical artifacts. Case 4 is a particularly instructive example, with femoral blood concentration (966 ng/mL) approximately twice as high as cardiac blood (499 ng/mL) and ante-mortem blood (418 ng/mL, collected 38 min prior to death)—clearly demonstrating that cardiac blood methadone concentration is more representative of the antemortem blood concentration in this case. In Case 4 and four others, toxicological interpretation based on femoral blood concentration alone would have been misleading. Based on these results and evidence from the literature, it is hypothesized that methadone bioaccumulates in the tissues of chronic users and redistributes from thigh tissues into femoral blood, increasing the concentration postmortem. This case series highlights how femoral blood is not always preserved from postmortem changes and that the analysis of multiple blood sources is necessary to avoid a misleading toxicological interpretation—particularly for cases of chronic methadone users. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate analgesia, sedation and adverse effects of two doses of subcutaneous methadone in dogs undergoing tibial plateau levelling osteotomy. Materials and Methods: Seventeen client‐owned dogs undergoing unilateral tibial plateau levelling osteotomy were randomly allocated to receive either 0.25 mg/kg methadone (eight dogs) or 0.5 mg/kg methadone (nine dogs). All dogs were premedicated with methadone and 2 to 6 mcg/kg dexmedetomidine subcutaneously. They were induced and maintained on a standard protocol. All animals received a second dose of methadone subcutaneously 4 hours after premedication and a 4.4 mg/kg dose of carprofen subcutaneously at 8 hours after premedication. During surgery, blood pressure, heart rate and temperature were assessed every 5 minutes. Postoperatively, sedation scores, temperature, heart rate and Glasgow composite modified pain score – short form were assessed for 12 hours postoperatively. Results: One of 17 (5.9%) dogs had intraoperative hypotension, nine of 17 dogs had intra‐operative bradyarrhythmias and 17 of 17 dogs had intra‐operative hypothermia. No dogs required intra‐operative rescue. Composite modified pain score – short form scores were below the threshold for intervention in 16 of 17 (94.1%) animals. Only one of 17 (5.9%) dogs required rescue analgesia. Median sedation score was 0 by the T8 time point. Adverse events were rare in both groups with only vocalisation and hypothermia reported commonly postoperatively. Clinical Significance: Two doses of methadone at either 0.25 or 0.5 mg/kg administered via subcutaneous injections pre‐operatively and 4 hours later, along with 4.4 mg/kg carprofen subcutaneously 8 hours after the first methadone dose appear to provide sufficient pain control for up to 12 hours in dogs undergoing tibial plateau levelling osteotomy. [ABSTRACT FROM AUTHOR]

Background: Opioid analgesia remains a cornerstone of the management of perioperative pain in cardiac surgical patients. Emerging evidence suggests that intermediate and long-term postoperative opioid dependence is underappreciated and associated with adverse patient outcomes. Methadone has emerged in the cardiothoracic and non-cardiothoracic anesthesia literature as an option that may provide lasting analgesic benefit and may be associated with a reduction in overall perioperative opioid requirements. Main body: This study was a systematic literature review and meta-analysis that aimed to provide evidence supporting the use of perioperative or intraoperative methadone in adult cardiac surgical patients, particularly with respect to objective measures of postoperative pain and opioid requirements prior to and at discharge from the hospital. Electronic searches of three research databases were performed: PubMed (1972 to October 2023), Ovid MEDLINE (1946 to October 2023), and EMBASE (1978 to October 2023). This search yielded a total of 190 articles, 7 of which met the relevant inclusion and exclusion criteria. This included five randomized controlled trials and two large retrospective cohort studies. Conclusion: Preoperative or intraoperative methadone led to reduced pain scores at 24 h postoperatively and reduced opioid requirements at discharge. Methadone may be effective at reducing perioperative pain scores and opioid requirements postoperatively, including at discharge. The literature on this subject has important limitations, and further research in larger randomized controlled trials is needed. [ABSTRACT FROM AUTHOR]

Introduction: This case series records a cohort of patients treated with transdermal buprenorphine patches as part of a buprenorphine microdose induction protocol to transition from methadone to buprenorphine in a community setting. This has historically been a difficult process to manage in community settings and this case series explored a method to gradually manage this in an outpatient setting. Method: A retrospective file audit was conducted of the electronic medical records of cohealth Innerspace patients who had undergone buprenorphine microdose induction using transdermal patches. A total of 32 patients were identified. Results: In this case series 23 of the 32 patients successfully transitioned from methadone to sublingual or long‐acting injectable depot buprenorphine preparations utilising the transdermal buprenorphine microdosing technique. All patients in this case series regardless of the success of the transition were retained in treatment. Discussion and Conclusions: A fixed‐dose transdermal buprenorphine patch regimen enabled 23 of 32 patients in this case series transition from methadone to buprenorphine in an outpatient setting. Given the small sample size further research is required to demonstrate the effectiveness of this technique. [ABSTRACT FROM AUTHOR]

Background: Posterior spinal fusion is the most common surgical procedure performed for correction of adolescent idiopathic scoliosis in the United States. Intraoperative methadone has been shown to improve pain control in adult patients undergoing complex spine surgery, and current pediatric studies show encouraging results; however, prospective randomized‐controlled trials are lacking in the pediatric literature. Aims: We conducted a single‐center double‐blind randomized‐controlled trial to compare intraoperative use of methadone to morphine in pediatric patients undergoing posterior spinal fusion. Methods: A total of 47 adolescents undergoing posterior spinal fusion were randomized (stratified by sex) to either a methadone (n = 25) or morphine (n = 22) group. The primary outcome was postoperative opioid consumption. Secondary outcomes included postoperative pain severity, opioid‐related side effects, and ratio of patient‐controlled analgesia injections: attempts as a behavioral index of uncontrolled pain. Results: Patients in the methadone group consumed less total opioid postoperatively (median [interquartile range], 0.3 mg/kg [0.1, 0.5]) than patients in the morphine group (0.3 mg/kg [0.2, 0.6]), median difference [95% confidence interval] −0.07 [−0.2 to 0.02]; (p =.026). Despite the lower amount of opioid used postoperatively, pain scores for the methadone group (3.5 [3.0, 4.3]) were not significantly different from those in the morphine group (4.0 [3.2, 5.0]; p =.250). Groups did not differ on opioid‐related side effects. Conclusions: A two‐dose intraoperative methadone regimen resulted in decreased opioid consumption compared to morphine. Although the clinical significance of these results may be limited, the analgesic equipoise without increased opioid‐related side effects and potential for a lower incidence of chronic pain may tip the balance in favor of routine methadone use for adolescents undergoing posterior spinal fusion. [ABSTRACT FROM AUTHOR]

Optimal pain relief in day-case surgery is imperative to patient comfort and timely discharge from hospital. Short-acting opioids are commonly used for analgesia in modern anaesthesia, allowing rapid recovery after surgery. Plasma concentration fluctuations from repeated dosing of short-acting opioids can cause patients to oscillate between analgesia with potential adverse effects, and inadequate analgesia requiring rescue dosing. Methadone's unique pharmacology may offer effective and sustained analgesia with less opioid consumption, potentially reducing adverse effects. Using a double-blind, randomised controlled trial, we compared post-anaesthesia care unit opioid consumption between day-case gynaecological laparoscopy patients who received either intravenous methadone (10 mg), or short-acting opioids intraoperatively. The primary outcome was post-anaesthesia care unit opioid consumption in oral morphine equivalents. Secondary outcomes included total opioid consumption, discharge opioid consumption, pain scores (0–10) until discharge, adverse effects (respiratory depression, postoperative nausea and vomiting, excess sedation), and rate of admission. Seventy patients were randomly assigned. Patients who received methadone consumed on average 9.44 mg fewer oral morphine equivalents in the post-anaesthesia care unit than the short-acting group (18.02 mg vs 27.46 mg, respectively, 95% confidence interval 0.003 to 18.88, P = 0.050) and experienced lower postoperative pain scores at every time point, although absolute differences were small. There was no evidence of lower hospital or discharge opioid consumption. No significant differences between the methadone and short-acting groups in other outcomes were identified: respiratory depression 41.2% versus 31.4%, P adjusted >0.99; postoperative nausea and vomiting 29.4% versus 42.9%, P adjusted >0.99; overnight admission 17.7% versus 11.4%, P adjusted >0.99; excess sedation 8.82% versus 8.57%, P adjusted >0.99. This study provides evidence that, although modestly, methadone can reduce post-anaesthesia care unit opioid consumption and postoperative pain scores after day-case gynaecological laparoscopy. There were no significant differences in any secondary outcomes. [ABSTRACT FROM AUTHOR]

Background and aims: Ongoing methadone intoxication parallels the generalization of the implemented addiction cession programs, as well as the necessity to sustain an effectively durable addiction treatment course. This study aimed to investigate the predisposing factors and clinical features of methadone intoxication. Methods: During a one-year period (March 2018 to March 2019), patients admitted for methadone intoxication were investigated retrospectively. Demographic data, the consumed methadone dose, electrocardiogram findings, and the level of creatinine phosphokinase (CPK) at admission were collected and entered into a statistical analyzing platform (SPSS version 22) for further statistical testing. Results: Seventy-five eligible patients were investigated. The mean age was 23.63±16.66, 66.7% were male, and 15 patients were children. The unemployment status led to an increased methadone poisoning (MP) incidence (P<0.05). The incidences of an increased CPK or QT segment prolongation were 17% and 7%, respectively. There was not any statistical correlation between the incidence of MP, the demographic and clinical data, as well as the used methadone dose. Moreover, the duration of the QT segment was not statistically influenced by the CPK. Conclusion: MP incidence seems to be influenced by social status. The increase in CPK and QT prolongation was not influenced by the methadone dose. It seems that more studies are required to further investigate the risk and prognostic factors of MP. [ABSTRACT FROM AUTHOR]

The simultaneous identification of drugs has considerable difficulties due to the intricate interplay of analytes and the interference present in biological matrices. In this study, we introduce an innovative electrochemical sensor that overcomes these hurdles, enabling the precise and simultaneous determination of morphine (MOR), methadone (MET), and uric acid (UA) in urine samples. The sensor harnesses the strategically adapted carbon nanotubes (CNT) modified with graphitic carbon nitride (g-C3N4) nanosheets to ensure exceptional precision and sensitivity for the targeted analytes. Through systematic optimization of pivotal parameters, we attained accurate and quantitative measurements of the analytes within intricate matrices employing the fast Fourier transform (FFT) voltammetry technique. The sensor's performance was validated using 17 training and 12 test solutions, employing the widely acclaimed machine learning method, partial least squares (PLS), for predictive modeling. The root mean square error of cross-validation (RMSECV) values for morphine, methadone, and uric acid were significantly low, measuring 0.1827 µM, 0.1951 µM, and 0.1584 µM, respectively, with corresponding root mean square error of prediction (RMSEP) values of 0.1925 µM, 0.2035 µM, and 0.1659 µM. These results showcased the robust resiliency and reliability of our predictive model. Our sensor's efficacy in real urine samples was demonstrated by the narrow range of relative standard deviation (RSD) values, ranging from 3.71 to 5.26%, and recovery percentages from 96 to 106%. This performance underscores the potential of the sensor for practical and clinical applications, offering precise measurements even in complex and variable biological matrices. The successful integration of g-C3N4-CNT nanocomposites and the robust PLS method has driven the evolution of sophisticated electrochemical sensors, initiating a transformative era in drug analysis. [ABSTRACT FROM AUTHOR]

Summary: Background: The use of combinations of α2‐adrenergic agonists and opioids has been published as providing superior sedation than either drug alone. Objectives: The present study aimed to compare the sedative and physiological effects of intravenous (IV) administration of dexmedetomidine alone and in combination with methadone, morphine, tramadol or pethidine in miniature donkeys. Study design: Experimental, crossover Latin square, randomised, blinded study. Methods: Twelve clinically healthy miniature donkeys with a mean age of 6 ± 2 (mean ± SD) years, weight of 94 ± 5 kg and height at withers of 0.80 ± 0.06 m were assigned to six IV treatments. They received either 0.9% saline, 5 μg/kg dexmedetomidine, 5 μg/kg dexmedetomidine and 0.2 mg/kg methadone, 5 μg/kg dexmedetomidine and 0.1 mg/kg morphine, 5 μg/kg dexmedetomidine and 2 mg/kg tramadol or 5 μg/kg dexmedetomidine and 1 mg/kg pethidine, with a washout period of 8 days. The degree of sedation was investigated using a numerical ranking scale of 0–3. Heart rate (HR), respiratory rate (RR), rectal temperature (RT) and intestinal motility were performed before and 5, 10, 15, 30, 45, 60, 75, 90 and 120 min after drug administration. Results: Animals in dexmedetomidine or dexmedetomidine/opioid treatments were sedated for 5–60 min. Sedation was significantly higher in dexmedetomidine/opioid treatments than in dexmedetomidine at 15–30 min (p < 0.05). In all treatments, HR and RR significantly decreased from baseline at 5–75 and 30–60 min, respectively (p < 0.05). Intestinal motility was decreased in dexmedetomidine and dexmedetomidine/opioid treatments at 5–60 and 5–90 min, respectively. Compared to dexmedetomidine, intestinal motility was significantly lower in dexmedetomidine/opioid treatments at 75–90 min. Main limitations: Assessment of only HR and RR are inadequate to describe the cardiorespiratory effects of dexmedetomidine/opioids. Conclusions: The use of combinations of dexmedetomidine/opioids would be considered for superior sedation for 15–30 min after administration in miniature donkeys. No significant differences were detected between opioids in combination with dexmedetomidine in miniature donkeys. [ABSTRACT FROM AUTHOR]

Objective To investigate variation in drug poisoning mortality rates by drug type and occupation in Massachusetts. Methods Death certificates for deaths by drug poisonings occurring between 2010 and 2019 in Massachusetts were coded based on the decedent's occupation. Mortality rates and rate ratios (with all other occupations as the reference group) were calculated based on the occupation of the workers according to drug type. Poisson regression was used to determine significantly elevated mortality rates and trends in drug poisoning deaths by occupation and drug type. Results The rate of drug poisoning deaths increased from 2010 to 2016 after which they plateaued. With respect to specific substances, fentanyl- and cocaine-related deaths increased throughout the surveillance period. For drug poisoning deaths overall, workers in construction trades (3,017); food preparation and serving (1,116); transportation and material moving (1,062) occupations had the highest number of drug poisoning deaths. When adjusting for age, sex, race/ethnicity, and educational attainment, workers in 7 occupations had significantly elevated mortality rate ratios for drug poisonings overall: farming, fishing, and forestry (3.42, P < 0.001); construction trades (2.58, P < 0.001); health care support (1.61, P < 0.001); community and social service (1.60, P < 0.001); food preparation and serving related (1.54, P < 0.001); personal care and service (1.37, P < 0.001); and arts, design, entertainment, sports, and media (1.21, P = 0.010). In many cases, workers in these same occupations had elevated mortality rate ratios for poisonings from specific substances. Health care practitioners and technical occupation workers only had elevated rates for methadone-related poisonings (1.73, P = 0.010). Conclusions These findings highlight that workers in certain occupations have an elevated risk for drug poisonings and that the patterns differ with respect to the drug type. These findings can be useful for providing services to workers in high-risk occupations and in identifying occupational factors that may be related to the risk of drug poisoning death. While previous research has begun to uncover work-related factors that may contribute to opioid use, further work is needed to identify occupational factors that may contribute to psychostimulant and benzodiazepine use. [ABSTRACT FROM AUTHOR]

Methadone (R,S‐methadone) can prolong the QT interval. R‐methadone inhibits cardiac potassium channel function less than S‐methadone. We tested if switching from methadone to R‐methadone would reduce corrected QT (QTc) intervals in methadone maintenance treatment (MMT) patients. Nine patients, with automatically read QTc intervals ≥450 ms, were required to detect a 20 ms (clinically relevant) reduction in QTc intervals with 15 ms standard deviation (SD) and 90% power. Nine stabilized MMT patients, using median (range) 70 (40–120) mg methadone, were included. Data (ECG recordings, serum samples, and withdrawal symptoms) were collected both before drug intake (Cmin) and at 3 h after drug intake (Cmax), and were collected on the day before the switch from methadone to equipotent R‐methadone dose and at 14 and 28 days after the switch. A cardiologist calculated QTc intervals retrospectively. Serum electrolytes and methadone concentrations were measured. Mean QTc intervals at Cmin were 472 ms and 422 ms on methadone (automatically and manually read) and 414 ms on R‐methadone (manually read). Mean (SD) change in QTc intervals was −8 (10) ms (p = 0.047) at Cmin but non‐significant at Cmax. R‐methadone showed a concentration‐dependent relationship with QTc intervals. Switching to R‐methadone reduced QTc intervals, but far less than the 20 ms considered clinically relevant. [ABSTRACT FROM AUTHOR]

Despite the increasing popularity of methadone maintenance treatment (MMT) in Vietnam, little is known regarding the substance use patterns of Vietnamese MMT patients. With it being almost 15 years since the inception of MMT in Vietnam, it felt timely to undertake a systematic review on this topic. We conducted a systematic review of the peer-reviewed literature regarding substance use among MMT patients in Vietnam with three main objectives: 1) identify which types of substances are being used, 2) identify the extent of use (i.e., prevalence), and 3) identify knowledge gaps regarding drug use patterns. After systematically searching four bibliographic databases (PubMed, Web of Science, ScienceDirect, and PsycINFO), we included 20 studies involving 6,653 participants, published between 2012-2021 with 14 unique samples. Findings indicate that, on average, 81% of MMT patients used tobacco, 47% used alcohol, 32% used heroin, 24% engaged in injection drug use, and 12% used illicit drugs. These results suggest that substance use is an active issue among Vietnamese MMT patients that warrants closer attention. These data can be used by providers to inform which/how interventions are targeted at MMT patients in Vietnam and help lower the number of overdoses seen across the country. [ABSTRACT FROM AUTHOR]

The article discusses research by Arpit Parmar, Radhika Chakraborty, and Yatan P. S. Balhara, reported in the April 2024 issue of the Indian Journal of Psychiatry, focusing on the current status of harm reduction initiatives in India. Topics include the history of harm reduction in India, the Indian status of harm reduction compared to global standards, and the strategies of harm reduction services in the country, highlighting the need for improved support and funding for these services.

Families Facing the Future (FFF) is an intervention designed specifically for families with a parent in methadone treatment. FFF is unique because it addresses prevention for children and recovery for parents in a single intervention. The primary goals of the program are to prevent parents' relapse, help them cope with relapse if it occurs, and teach parenting skills in order to reduce the likelihood of substance use among their children. FFF has been implemented as an adjunct to treatment in several Opioid Treatment Programs, but has not been widely adopted due to various implementation barriers. The aims of this study, therefore, were to (1) assess the perceived feasibility of implementing FFF and (2) identify/describe barriers to implementing FFF. An online survey was used to assess implementation feasibility, while individual qualitative interviews were conducted to explore specific barriers to implementation. Data collection from a total of 40 participants (20 patients and 20 providers) was conducted from August 2022 to October 2022 at two Opioid Treatment Programs in Florida. Analyses revealed high feasibility scores, indicating that FFF was viewed by both patients and providers as a practical intervention to implement. Despite strong perceived feasibility of the intervention, qualitative findings identified several implementation barriers with respect to difficulty attending parent training sessions, aversion to in-home visits, and lack of funding (inability to provide patient incentives/bill insurance). This study provides evidence that while patients and providers view FFF as having high feasibility, significant implementation barriers exist. This paper fills a void in the literature by informing if and which modifications might be necessary to facilitate wider adoption of FFF in real-world Opioid Treatment Program settings. [ABSTRACT FROM AUTHOR]

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OBJECTIVE To compare median Sophia Observation withdrawal Symptoms scale (SOS) scores between intravenous methadone dosing scheduled every 6 hours or every 8 hours for iatrogenic withdrawal syndrome (IWS). METHODS This single-center, retrospective chart review evaluated patients aged 4 weeks through 18 years treated with intravenous methadone for IWS. Children admitted to the pediatric intensive care unit (PICU) of a tertiary care children's hospital between August 2017 and July 2021 and treated for IWS for at least 48 hours were eligible for inclusion. Methadone dosing schedules were compared, with a primary outcome of median Sophia Observation withdrawal Symptoms (SOS) score during the first 24 hours after cessation of continuous fentanyl infusion. Secondary outcomes included PICU and general pediatric unit lengths of stay, extubation failure rates, and mortality. RESULTS Twenty patients met inclusion criteria, with 9 in the 6-hour dosing group. There was no difference in median SOS score, extubation failure, length of stay, or mortality between the 2 groups. CONCLUSIONS During the first 24 hours after cessation of continuous fentanyl, there appears to be no difference in IWS severity, as determined by bedside nurse scoring, between patients treated with intravenous methadone every 6 hours compared with every 8 hours. [ABSTRACT FROM AUTHOR]

The article discusses a study by Xiong and colleagues, published in the issue which showed that some policy changes in the U.S. have expanded access to medications for opioid use disorder (MOUD). Topics include concern on the decline in physician prescribing, increase in opioid-involved poisoning deaths in Washington State from 2019 to 2023, and the only reason a person should not be on MOUD.

The monitoring of essential and toxic elements in patients with Opioid Use Disorder (OUD) undergoing methadone treatment (MT) is important, and there is limited previous research on the urinary levels of these elements in MT patients. Therefore, the present study aimed to analyze certain elements in the context of methadone treatment compared to a healthy group. In this study, patients with opioid use disorder undergoing MT (n = 67) were compared with a healthy group of companions (n = 62) in terms of urinary concentrations of some essential elements (selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), calcium (Ca)) and toxic elements (lead (Pb), cadmium (Cd), arsenic (As), and chromium (Cr)). Urine samples were prepared using the acid digestion method with a mixture of nitric acid and perchloric acid and assessed using the ICP-MS method. Our results showed that the two groups had no significant differences in terms of gender, education level, occupation, and smoking status. Urinary concentrations of Se, Cu, and Fe levels were significantly lower in the MT group compared to the healthy subjects. However, the concentrations of Pb, Cd, As, Mn, Cr, and Ca in the MT group were higher than in the healthy group (p < 0.05). No significant difference was established between the levels of Zn in the two groups (p = 0.232). The results of regression analysis revealed that the differences between the concentration levels of all metals (except Zn) between two groups were still remained significant after adjusting for all variables (p < 0.05). The data obtained in the current study showed lower urinary concentrations of some essential elements and higher levels of some toxic elements in the MT group compared to the healthy subjects. These findings should be incorporated into harm-reduction interventions. [ABSTRACT FROM AUTHOR]

Effective management of postoperative pain is essential to ensure patient welfare, reduce morbidity and optimize recovery. Opioids are effective in managing moderate to severe pain in horses but concerns over their adverse effects on gastrointestinal (GI) motility and associated increased colic risk limit their widespread use. Studies investigating the impact of systemic opioids on both GI motility and colic incidence in horses have yielded inconclusive outcomes. Therefore, this retrospective study aims to assess the influence of systemic administration of butorphanol, morphine, and methadone on post-anaesthetic colic (PAC) incidence. Horses undergoing general anaesthesia for nongastrointestinal procedures that were hospitalized for at least 72 h postanaesthesia were included in this study. Anaesthetised horses were stratified by procedure type into horses undergoing diagnostic imaging without surgical intervention, emergency or elective surgery. In addition, patients were grouped by opioid treatment regime into horses receiving no opioids, intraanaesthetic, short-(<24 h) or long-term (>24 h) postoperative opioids. Administered opioids encompassed butorphanol, morphine and methadone. The number of horses showing signs of colic in the 72 h after anaesthesia was assessed for each group. A total of 782 horses were included, comprising 659 undergoing surgical procedures and 123 undergoing diagnostic imaging. The overall PAC incidence was 15.1%. Notably, horses undergoing diagnostic imaging without surgery had a significantly lower PAC rate of 6.5% compared to those undergoing surgery (16.7%, p = 0.0146). Emergency surgeries had a significantly lower PAC rate of 5.8% compared to elective procedures (18%, p = 0.0113). Of the 782 horses, 740 received intraoperative opioids and 204 postoperative opioids, 102 of which long-term (≥24 h). Neither intraoperative (p = 0.4243) nor short-term postoperative opioids (p = 0.5744) increased PAC rates. Notably, only the longterm (≥24 h) administration of morphine significantly increased PAC incidence to 34% (p = 0.0038). In contrast, long-term butorphanol (5.3% PAC, p = 0.8482) and methadone (18.4% PAC, p = 0.6161) did not affect PAC rates. In summary, extended morphine administration was the only opioid treatment associated with a significantly increased risk of PAC. [ABSTRACT FROM AUTHOR]

QT prolongation is related to the development of ventricular arrhythmias such as Torsade de Pointes (TdP) that can lead to sudden cardiac death. Several drugs used in the treatment of patients with advanced cancer may induce QT prolongation due to their interference with cardiac ion channels. Some patients may be at higher risk if predisposing factors are present. Herein we present the case of a patient with advanced cancer under anti-tumor treatment with radical intention that developed a reversible drug-induced QT prolongation when simultaneously treated with methadone, haloperidol and fluoxetine that presented with chest pain and bradycardia. An approach to cancer patients at risk for drug-induced QT prolongation is discussed highlighting the need of a thorough medication review with a special focus in the patient with polypharmacy. [ABSTRACT FROM AUTHOR]

Background: Emergence delirium in children following strabismus surgery is a distressing and potentially dangerous condition and is likely attributable to visual disturbances, pain, and anesthetic gases. We explored whether a single intraoperative dose of methadone could reduce emergence delirium. Methods: Our study was an institutional review board-approved prospective, controlled, before-and-after investigation. Inclusion criteriawere age<18 years and American Society of Anesthesiologists (ASA) classification 1 or 2. Patientswere excluded for obesity, documented sleep apnea, significant neurologic disease, or inpatient status. Control group patients were recruited sequentially, and the anesthetic was performed per preference. The study group was recruited similarly and received an intravenous dose of methadone 0.15 mg/kg at induction. The primary outcome was peak score on the Pediatric Anesthesia EmergenceDelirium (PAED) scale. Secondary outcomes included time to anesthetic emergence, postoperative pain scores, postanesthesia care unit (PACU) length of stay, and postdischarge respiratory complications. Results: Forty-nine control group and 55 study group patients were recruited. No significant differences were found between groups for age, sex, weight, ASA classification, or duration of surgery. The control group received more preoperative midazolam, intraoperative fentanyl, and intraoperative ketorolac. Compared to the control group, the study group had42%and85%reductions in peak and severe PAED scale scores, respectively, in the PACU and required less rescue pain medications. Anesthetic emergence time and length of stay were not different between the groups. No significant postoperative complications occurred. Conclusion: Emergence delirium following outpatient pediatric strabismus surgerywas substantially mitigated by the use of intraoperative methadone without affecting PACU throughput. No significant complications occurred. Further study is warranted to corroborate routine use of this drug for emergence delirium. [ABSTRACT FROM AUTHOR]

Background: A considerable inter‐individual variability has been reported in the relationship between methadone doses applied and serum concentrations achieved in methadone maintenance treatment. However, the underlying causes for this variability are not fully understood. Objectives: We investigated the influence of genetic, pathophysiological and pharmacological factors on serum methadone concentration‐to‐dose ratio (CDR) and discussed the clinical implications of the findings. Methods: We used data from two retrospective laboratory databases and a prospective cohort study to investigate the impact on methadone CDR of hepatic cytochrome P450 enzyme system (CYP) genetic polymorphisms, age, sex, concomitant medication, liver fibrosis and body mass index through linear mixed model analyses. Findings: A positive association was found between CDR and the homozygous CYP2B6*6 genotype, concurrent treatment with CYP3A4 inhibitors and body mass index. CDR was lower among women and during concomitant use of CYP inducers. CDR was not associated with age or the degree of liver fibrosis in our investigations. Conclusions: This research work supports the need for individually tailored dosage considering the various factors that influence methadone CDR. The gained knowledge can contribute to reducing the risks associated with the treatment and optimizing the desired outcomes. [ABSTRACT FROM AUTHOR]

In Hong Kong, the percentage of older drug users has increased over the last two decades. However, the motivations behind their drug-use behaviours have received little research attention. This study focuses on older drug users who are enrolled in methadone treatment programmes but still use illicit drugs (mixed use). Some studies in the criminological literature and government discourse consider drug users to be passive and lacking self-control. However, in-depth interviews in with 25 older mixed users (aged over 50 years) in Hong Kong revealed that mixed use is one of the various strategies they actively employ to improve their self-perceived quality of life. Using the framework of the selective optimization with compensation model, this study (1) describes the strategies older mixed users adopt as active agents to improve their self-perceived quality of life while coexisting with their addiction; and (2) explains how these strategies were affected and constrained by Hong Kong's prohibitionist drug policy. I infer that prohibitionist drug policies that emphasize on total drug abstinence may fail to cater to the needs of older drug users who have undergone several relapses and treatments in their lifetimes and do not think they can give up using drugs. This study also provides evidence to show how some drug users may act as active agents to manage and coexist with their addiction, and their agency seems to be constrained by the wider drug policy implemented in Hong Kong. [ABSTRACT FROM AUTHOR]

This study focused on the development of chitosan and CNTs enhanced glassy carbon electrodes (CS/CNT/GCE) as a methadone electrochemical biosensor and its application to athlete doping testing in biological and food samples. SEM, FTIR, and XRD analysis results indicated the successful synthesis of CS/CNT-modified GCE. An electrochemical study of modified electrodes using the methods of cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) revealed an improvement in the sensitivity, stability, and selectivity of the CS/CNT/GCE within methadone determination due to a synergistic effect between CS and CNT. The CS/CNT/GCE showed a robust and broad linear range of 40 to 1000 µM, a sensitivity of 0.03204 µA/µM, and a detection limit of 0.019 µM for methadone detection. In this investigation, genuine pear samples and blood serum samples from five athletes were utilized to examine the application of the created methadone sensor, and the results showed substantial recovery values (above 96.00%) and good precision (RSD value less than 4.76%). These results demonstrated that the CS/CNT/GCE sensor was dependable and precise for measuring methadone concentrations in biological and food samples. [ABSTRACT FROM AUTHOR]

The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed. [ABSTRACT FROM AUTHOR]

Methadone and buprenorphine/naloxone are opioid agonist therapies for opioid use disorder treatment. Genetic factors contribute to individual differences in opioid response; however, little is known regarding genetic associations with clinical outcomes in people receiving opioid agonist therapies. Participants diagnosed with opioid use disorder, principally consisting of prescription opioids (licit or illicit), were randomized to methadone or buprenorphine/naloxone for 24 weeks of daily treatment (NCT03033732). Urine was collected at 12 biweekly study visits and analyzed for non‐treatment opioids. Variants in genes involved in methadone metabolism (CYP2B6, CYP2C19, and CYP3A4), buprenorphine metabolism (CYP3A4 and UGT2B7), and μ‐opioid receptor function (OPRM1) were genotyped and analyzed for their association with the number of non‐treatment opioid‐free urine screens. Primary analyses focused on the last 12 weeks (6 study visits, post‐titration) of treatment among those reporting White ethnicity. Additional sensitivity and exploratory analyses were performed. Among methadone‐treated participants (n = 52), the OPRM1 rs1799971 AA genotype (vs. G‐genotypes, i.e., having one or two G alleles) was associated with greater opioid‐free urine screens (incidence rate ratio = 5.24, 95% confidence interval (CI) = 2.43–11.26, P = 0.000023); longitudinal analyses showed a significant genotype‐by‐time interaction over the full 24 weeks (12 study visits, β = −0.28, 95% CI = −0.45 to −0.11, P = 0.0015). Exploratory analyses suggest an OPRM1 rs1799971 genotype effect on retention. No evidence of association was found between other genetic variants, including in metabolic variants, and non‐treatment opioid‐free urine screens in the methadone or buprenorphine/naloxone arms. Those with the OPRM1 rs1799971 G‐genotypes may have a poorer response to methadone maintenance treatment, an effect that persisted through 24 weeks of treatment. [ABSTRACT FROM AUTHOR]

Introduction: Methadone ameliorates opioid withdrawal among hospitalized patients with opioid use disorder (OUD). To continue methadone after hospital discharge, patients must enroll in an opioid treatment program (OTP) per federal regulations. Uncontrolled opioid withdrawal is a barrier to linkage from hospital to OTP. Aim: Describe a federally compliant In-Hospital Methadone Enrollment Team (IN-MEET) that enrolls hospitalized patients with OUD into an OTP with facilitated hospital to OTP linkage. Setting: Seven hundred-bed university hospital in Aurora, CO. Program Description: A physician dually affiliated with a hospital's addiction consultation service and a community OTP completes an in-hospital, face-to-face medical assessment required by federal law and titrates methadone to comfort. An OTP-affiliated nurse with hospital privileges completes a psychosocial evaluation and provides case management by arranging transportation and providing weekly telephone check-ins. Program Evaluation Metrics: IN-MEET enrollments completed, hospital to OTP linkage, and descriptive characteristics of patients who completed IN-MEET enrollments compared to patients who completed community OTP enrollments. Results: Between April 2019 and April 2023, our team completed 165 IN-MEET enrollments. Among a subset of 73 IN-MEET patients, 56 (76.7%) presented to the OTP following hospital discharge. Compared to community OTP enrolled patients (n = 1687), a higher percentage of IN-MEET patients were older (39.7 years, standard deviation [SD] 11.2 years vs. 36.1 years, SD 10.6 years) and were unhoused (n = 43, 58.9% vs. n = 199, 11.8%). Compared to community OTP enrolled patients, a higher percentage of IN-MEET patients reported heroin or fentanyl as their primary substance (n = 53, 72.6% vs. n = 677, 40.1%), reported methamphetamine as their secondary substance (n = 27, 37.0% vs. n = 380, 22.5%), and reported they injected their primary substance (n = 46, 63.0% vs. n = 478, 28.3%). Conclusion: IN-MEET facilitates hospital to OTP linkage among a vulnerable population. This model has the potential to improve methadone access for hospitalized patients who may not otherwise seek out treatment. [ABSTRACT FROM AUTHOR]

Methadone is an effective and long-lasting analgesic drug that is also used in medication-assisted treatment for people with opioid use disorders. Although there is evidence that methadone activates μ-opioid and Toll-like-4 receptors (TLR-4s), its effects on distinct immune cells, including mast cells (MCs), are not well characterized. MCs express μ-opioid and Toll-like receptors (TLRs) and constitute an important cell lineage involved in allergy and effective innate immunity responses. In the present study, murine bone-marrow-derived mast cells (BMMCs) were treated with methadone to evaluate cell viability by flow cytometry, cell morphology with immunofluorescence and scanning electron microscopy, reactive oxygen species (ROS) production, and intracellular calcium concentration ([Ca2+]i) increase. We found that exposure of BMMCs to 0.5 mM or 1 mM methadone rapidly induced cell death by forming extracellular DNA traps (ETosis). Methadone-induced cell death depended on ROS formation and [Ca2+]i. Using pharmacological approaches and TLR4-defective BMMC cultures, we found that µ-opioid receptors were necessary for both methadone-induced ROS production and intracellular calcium increase. Remarkably, TLR4 receptors were also involved in methadone-induced ROS production as it did not occur in BMMCs obtained from TLR4-deficient mice. Finally, confocal microscopy images showed a significant co-localization of μ-opioid and TLR4 receptors that increased after methadone treatment. Our results suggest that methadone produces MCETosis by a mechanism requiring a novel crosstalk pathway between μ-opioid and TLR4 receptors. [ABSTRACT FROM AUTHOR]