Confidence in providing methadone maintenance treatment of primary care providers in Vietnam.

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.

Retention of people who inject drugs enrolled in a 'medications for opioid use disorder' (MOUD) programme in Uganda.

BACKGROUND: Injection Drug use is associated with increased HIV risk behaviour that may result in the transmission of HIV and poor access to HIV prevention and treatment. In 2020, Uganda introduced the 'medication for opioid use disorder (MOUD) treatment' for People who inject drugs (PWID). We analysed the 12-month retention and associated factors among PWID enrolled on MOUD treatment in Kampala, Uganda. METHODS: We conducted a retrospective analysis of 343 PWID with OUD who completed 14 days of methadone induction from September 2020 to July 2022. Retention was defined as the number of individuals still in the programme divided by the total number enrolled, computed at 3-, 6-, 9-, and 12 months using lifetable and Kaplan-Meier survival analyses. Cox proportional regression analyses were conducted to assess factors associated with retention in the programme in the first 12 months. RESULTS: Overall, 243 (71%) of 343 participants stabilized at a methadone dose of 60 mg or more. The majority of participants were males (n = 284, 82.8%), and the median (interquartile range, IQR) age was 31 (26-38) years. Most participants (n = 276, 80.5%) lived 5 km or more away from the MOUD clinic. Thirty (8.8%) were HIV-positive, 52 (15.7%) had a major mental illness and 96 (27.9%) had a history of taking alcohol three months before enrollment. The cumulative retention significantly declined from 83.4% (95%CI = 79.0-87.0) at 3months to 71.9% (95%CI = 67.2-76.6) at 6months, 64% 95%CI = 58.7-68.9) at 9months, and 55.2%; 95% CI (49.8-60.3% at 12months. The 12-month retention was significantly higher for participants on methadone doses of 60 mg or more (adj.HR = 2.1, 95%CI = 1.41-3.22), while participants resident within 5 km of the MOUD clinic were 4.9 times more likely to be retained at 12 months, compared to those residing 5 km or more, (adj. HR = 4.81, 95%CI = 1.54-15). Other factors, including predisposing, need, and enabling factors, were not associated with retention. CONCLUSION: Our study demonstrates acceptable 12-month retention rates for people who inject drugs, comparable to previous studies done in both developing and developed countries. Sustaining and improving retention may require enhanced scaling up of MOUD dose to an optimal level in the first 14 days and reducing the distance between participant locale and MOUD clinics.

Intraoperative methadone for day-case gynaecological laparoscopy: A double-blind, randomised controlled trial.

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%, Padjusted >0.99; postoperative nausea and vomiting 29.4% versus 42.9%, Padjusted >0.99; overnight admission 17.7% versus 11.4%, Padjusted >0.99; excess sedation 8.82% versus 8.57%, Padjusted >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.

Effects of tasipimidine premedication with and without methadone and dexmedetomidine on cardiovascular variables during propofol-isoflurane anaesthesia in Beagle dogs.

OBJECTIVE: To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. STUDY DESIGN: Prospective, placebo-controlled, blinded, experimental trial. ANIMALS: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. METHODS: The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 µg kg-1 orally and placebo IV; TMP: tasipimidine 30 µg kg-1 orally and methadone 0.2 mg kg-1 IV; and TMPD: tasipimidine 30 µg kg-1 orally with methadone 0.2 mg kg-1 and dexmedetomidine 1 µg kg-1 IV followed by 1 µg kg-1 hour-1. Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. RESULTS: Tasipimidine induced a significant 20-30% reduction in HR and CO with decreases in MAP (10-15%), tbf (40%) and stO2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored.

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

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

The dynamics of more-than-human care in depot buprenorphine treatment: A new materialist analysis of Australian patients' experiences.

BACKGROUND: Long-acting injectable depot buprenorphine has become an important treatment option for the management of opioid dependence. However, little is known about patients' experiences of depot buprenorphine and its embodied effects. This qualitative study aims to explore patients' experiences of depot buprenorphine treatment, including how it feels within the body, experiences of dosing cycles across time, and how this form of treatment relies on wider ecologies of care beyond the clinical encounter. METHODS: Participants were recruited from sites in Sydney, regional New South Wales, and Melbourne, Victoria, Australia. Thirty participants (16 men, 14 women) participated in semi-structured interviews. Participants had histories of both heroin and prescription opioid consumption, and opioid agonist therapy including daily dosing of buprenorphine and methadone. RESULTS: Our analysis illuminates: (1) how patients' expectations and concerns about treatment are linked to past embodied experiences of withdrawal and uncertainty about the effectiveness of depot buprenorphine; (2) the diverse meanings patients attribute to the depot buprenorphine substrate 'under the skin'; and, (3) how depot buprenorphine is embedded within wider ecologies of care, such as counselling and social supports. CONCLUSION: Our analysis destabilises commonplace assumptions about a linear, causal relationship between the pharmacological action of depot buprenorphine and experiences of treatment. Instead, it highlights patients' variable experiences of depot buprenorphine, tracing the everyday practices, embodied feelings, expectations and wider networks of care that shape patient experiences. We conclude with some reflections on the implications of our analysis for alcohol and other drug treatment, specifically how they might inform the design of client education materials and care.

Methadone dosing at New York State opioid treatment programs following initial revisions to federal regulations.

INTRODUCTION: In March 2020, a temporary federal regulatory exemption for opioid treatment programs (OTPs) was issued, allowing for a greater number of take-home methadone doses than was previously permitted. In the same month, to address financial sustainability, New York State (NYS) Medicaid also transitioned to a bundle reimbursement methodology for OTPs. We examined methadone dosing schedules in NYS before and after these regulatory and financing changes. METHODS: We conducted a retrospective cohort study using NYS OTP patient data from two sources: the client data system for a baseline period (February 2020) and survey data collected after regulatory and financing changes (May 2020 to August 2021, 64 weekly surveys). We compared methadone dosing schedules over time using chi-square tests and Poisson regression. RESULT: At baseline, data were available for 78% (n=77/99) of OTPs including 90.9% (n=26,225/28,839) of their enrolled patients. During the survey period, 99 OTPs completed 93.1% (n=5901/6336) of weekly surveys, with a mean statewide weekly patient census of 38,904 (SD=1214.5). Between February and May 2020, daily dosing significantly decreased from 55.4% to 16.3% of patients (-39.1 percentage points [95%CI: -39.8 to -38.4]), although it significantly increased subsequently (3.33%/4-weeks [95%CI: 3.28, 3.39]). In addition, weekly-to-monthly dosing significantly increased from 26.9% to 54.5% of patients (27.6 percentage points [95%CI: 26.9, 28.4]), although it significantly decreased subsequently (-1.19%/4-weeks [95%CI: -1.23, -1.15]). DISCUSSION: Despite large initial changes, we found a trend toward gradual return to more restrictive dosing schedules. OTPs need further support in leveraging new opportunities to improve methadone treatment and outcomes.

A comparative analysis of opioid-free and opioid-sparing anaesthesia techniques for laparoscopic ovariectomy in healthy dogs.

OBJECTIVE: To compare the perioperative analgesic effects of an opioid-free (OFA) and an opioid-sparing (OSA) anaesthetic protocol in dogs undergoing laparoscopic ovariectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 28 client-owned dogs. METHODS: Dogs were allocated to one of two groups. The OFA group was administered intramuscular (IM) dexmedetomidine 5 µg kg-1 and ketamine 1 mg kg-1, followed by two intraoperative constant rate infusions (CRIs) of dexmedetomidine (3 µg kg-1 hour-1) and lidocaine (1 mg kg-1 loading dose, 2 mg kg-1 hour-1). The OSA group was administered IM dexmedetomidine 5 µg kg-1, ketamine 1 mg kg-1 and methadone 0.2 mg kg-1, followed by two intraoperative saline CRIs. In both groups, anaesthesia was induced with intravenous (IV) propofol 2 mg kg-1 and diazepam 0.2 mg kg-1 and maintained with isoflurane. Rescue dexmedetomidine (0.5 µg kg-1) was administered IV if there was a 20% increase in cardiovascular variables compared with pre-stimulation values. Ketorolac (0.5 mg kg-1) was administered IV when the surgery ended. Postoperative analgesia was evaluated using the Short Form-Glasgow Composite Measure Pain Scale and methadone (0.2 mg kg-1) was administered IM if the pain score was ≥ 6/24. Statistical analysis included mixed analysis of variance, Chi-square test and Mann-Whitney U test. RESULTS: There were no significant differences in the intraoperative monitored variables between groups. The OFA group showed a significantly lower intraoperative rescue analgesia requirement (p = 0.016) and lower postoperative pain scores at 3 (p =0.001) and 6 (p < 0.001) hours. No dogs were administered rescue methadone postoperatively. CONCLUSIONS AND CLINICAL RELEVANCE: Although both groups achieved acceptable postoperative pain scores with no need for further intervention, the analgesic efficacy of the OFA protocol was significantly superior to that of the OSA protocol presented and was associated with a lower intraoperative rescue analgesia requirement and early postoperative pain scores.

Erector spinae plane block in dogs undergoing hemilaminectomy: A prospective randomized clinical trial.

OBJECTIVE: To compare the perioperative cumulative opioid consumption and the incidence of cardiovascular complications in dogs undergoing hemilaminectomy in which either an erector spinae plane (ESP) block or systemic opioids were administered. STUDY DESIGN: Prospective randomized clinical trial. ANIMALS: A total of 60 client-owned dogs. METHODS: Dogs were randomized to one of three groups: an ESP block (group ESP), a constant rate infusion of fentanyl (group FNT, positive control) or a single dose of methadone as premedication (group MTD, negative control). Intraoperative nociceptive response was treated with fentanyl [1 µg kg-1, intravenously (IV)] boli. Before closure of the surgical site, morphine (0.1 mg kg-1) was applied to the dura mater. The cumulative dose of opioids was recorded and compared between groups. The incidence of intraoperative bradycardia and/or hypotension and the time to extubation were compared between groups. The short form of the Glasgow Composite Pain Scale (SF-GCPS) was used to score nociception before anaesthetic induction and 1, 2, 6, 12,18 and 24 hours postoperatively. Methadone 0.2 mg kg-1 was administered IV if the SF-GCPS score was ≥ 5. RESULTS: Group MTD required more intraoperative rescue analgesia than groups ESP (p = 0.008) and FNT (p = 0.001). The total cumulative intraoperative dose of fentanyl was higher in groups FNT (p < 0.0001) and MTD (p = 0.002) than in group ESP. The incidence of cardiovascular complications was similar between groups. Extubation time was longer in group MTD (p = 0.03). Postoperatively, the time to first rescue analgesia was longer in group ESP than in group MTD (p = 0.03). The cumulative postoperative opioid consumption and pain scores were similar between groups. CONCLUSIONS AND CLINICAL RELEVANCE: The ESP block resulted in a reduced intraoperative opioid consumption compared with the control positive and negative groups.

Experience of patients on methadone maintenance treatment receiving take-home methadone doses during COVID-19 pandemic: A multi-site study from India.

BACKGROUND: Methadone take-home doses for opioid dependence treatment are strictly regulated due to diversion and overdose concerns, so patients must visit the clinic daily for dispensing. This was also done in India until the COVID-19 pandemic, when lockdown restriction compelled take- home dispensing of methadone. This study examined experience of patients who received take- home methadone during COVID-19 pandemic in India. METHODS: Observational, cross-sectional design. We contacted all consenting methadone centres in India during the lockdown and selected those that provided take-home doses for the study. Patients who received daily methadone before the lockdown and take-home doses after were interviewed using a study-specific questionnaire. RESULTS: The study had 210 participants. Take-home methadone was dispensed for 2.5 days on average in each dispensing. When taking methadone at home, 3.3% split their dose 25% took less than the prescribed dose to save it for a rainy days, and 3.3% reported an overdose episode. Adherence improved in 58.6% participants after take-home methadone. Participants perceived many benefits from take-home methadone such as reduced hospital visits and travel time to collect methadone, improvement in work, and financial savings. About 54.3% participants reported storing their take-home doses safely, and 1.9% reported that their family consumed methadone by mistake. CONCLUSIONS: Take-home methadone was found to be beneficial to most participants in terms of time saved and improved productivity. Preconceived concerns of providing take-home methadone in terms of its overdose, diversion, or accidental ingestion by others are not commonly seen when individuals are provided take-home doses of methadone.

Higher methadone dose at time of release from prison predicts linkage to maintenance treatment for people with HIV and opioid use disorder transitioning to the community in Malaysia.

BACKGROUND: Incarcerated people with HIV and opioid-dependence often experience poor post-release outcomes in the absence of methadone maintenance treatment (MMT). In a prospective trial, we assessed the impact of methadone dose achieved within prison on linkage to MMT after release. METHODS: From 2010 to 2014, men with HIV (N = 212) and opioid dependence before incarceration were enrolled in MMT within 6 months of release from Malaysia's largest prison and followed for 12-months post-release. As a prospective trial, allocation to MMT was at random and later by preference design (predictive nonetheless). MMT dosing was individually targeted to minimally achieve 80 mg/day. Time-to-event analyses were conducted to model linkage to MMT after release. FINDINGS: Of the 212 participants allocated to MMT, 98 (46 %) were prescribed higher dosages (≥80 mg/day) before release. Linkage to MMT after release occurred in 77 (36 %) participants and significantly higher for those prescribed higher dosages (46% vs 28 %; p = 0.011). Factors associated with higher MMT dosages were being married, on antiretroviral therapy, longer incarceration periods, having higher levels of depression, and methadone preference compared to randomization. After controlling for other variables, being prescribed higher methadone dosage (aHR: 2.53, 95 %CI: 1.42-4.49) was the only independent predictor of linkage to methadone after release. INTERPRETATION: Higher doses of methadone prescribed before release increased the likelihood of linkage to MMT after release. Methadone dosing should be introduced into international guidelines for treatment of opioid use disorder in prisons and further post-release benefits should be explored. FUNDING: National Institute of Drug Abuse (NIDA).

Continuous Wound Irrigation and Intraoperative Methadone Decreases Opioid Use and Shortens Length of Stay After CRS/HIPEC.

BACKGROUND: Epidural analgesia is resource and labor intense and may limit postoperative management options and delay discharge. This study compared postoperative outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with epidural analgesia versus continuous wound infusion system (CWIS) with/without intraoperative methadone. METHODS: A single-institution, retrospective chart review was performed including all patients undergoing open CRS/HIPEC from 2018 to 2021. Patient demographics, surgical characteristics, length of stay, and in-hospital analgesic use were reviewed. In-hospital opioid exposure in morphine milligram equivalents (MME) was calculated. Multivariate analysis (MVA) for mean total and daily opioid exposure was conducted. RESULTS: A total of 157 patients were included. Fifty-three (34%) had epidural analgesia, 96 (61%) had CWIS, and 79 (50%) received methadone. Length of stay was significantly shorter with CWIS + methadone versus epidural (7 vs. 8 days, p < 0.01). MVA showed significantly lower mean total and daily opioid exposure with CWIS+methadone versus epidural (total: 252.8 ± 17.7 MME vs. 486.8 ± 86.6 MME; odds ratio [OR] 0.72, 95% confidence interval [CI] 0.52-0.98, p = 0.04; Daily: 32.8 ± 2.0 MME vs. 51.9 ± 5.7 MME, OR 0.72, 95% CI 0.52-0.99, p ≤ 0.05). The CWIS-only group (n = 17) had a significantly lower median oral opioid exposure versus epidural (135 MME vs. 7.5 MME, p < 0.001) and longer length of stay versus CWIS + methadone (9 vs. 7 days, p = 0.04), There were no CWIS or methadone-associated complications and one epidural abscess. CONCLUSIONS: CWIS + methadone safely offers better pain control with less in-hospital opioid use, shorter length of stay, and decreased resource utilization compared with epidural analgesia in patients undergoing CRS-HIPEC.

Buprenorphine microdosing regimen using transdermal buprenorphine patches to transition from methadone to buprenorphine.

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.

Medications for opioid use disorder associated with reduced readmissions for patients with severe injection-related infections: A matched cohort study.

INTRODUCTION: Hospitalizations due to severe injection-related infections (SIRIs) and patient-directed discharge (PDD) in people who inject drugs (PWID) are increasing, but research on readmission outcomes at PDD is limited. In this retrospective, matched cohort study we evaluated predictors of 30-day readmission by discharge status among PWID. METHODS: Among patients diagnosed with SIRIs at a tertiary hospital, Fisher's exact tests assessed differences in readmission rates by discharge status. Medications for opioid use disorder (MOUD) at discharge was defined as either having a buprenorphine dose dispensed within 24 h of discharge and buprenorphine being included in the discharge summary as a prescription, or a methadone dose dispensed inpatient within 24 h of discharge. Logistic regression analyses evaluated predictors of readmission outcomes. RESULTS: Among 148 PWID with SIRI diagnosis, 30-day readmission rate following PDD was higher than standard discharge (25.7 % vs. 9.5 %, p = 0.016) and MOUD decreased odds of 30-day readmission (OR = 0.32, 95 % CI: 0.12,0.83, p = 0.012). >7 missed days of antibiotic treatment increased odds of 30-day readmission (OR 4.65, 95 % CI: 1.14, 31.72, p = 0.030) within PDD patients. CONCLUSIONS: PDD carries higher 30-day readmission rate compared to standard discharge. Strategies to reduce PDD rates and increase MOUD initiation may improve readmission outcomes.

Flexibilidad en las pautas take home de metadona en los CAD de Madrid Salud durante la pandemia de Covid-19 / Flexibility in the methadone take home guidelines in the CAD of Madrid Salud during the Covid-19 pandemic

El objetivo del estudio fue examinar qué cambios se realizaron en los horarios de dispensación y las pautas take home de metadona solución oral y comprimidos, en los siete Centros de Atención a las Adicciones (CAD) de Madrid Salud, a raíz del estado de emergencia y a lo largo de un año posterior a su entrada. Se realizó un estudio descriptivo longitudinal, obteniendo los datos de la revisión de los informes elaborados por la unidad de farmacia, encargada del suministro y control de la metadona, en tres momentos: febrero de 2020 y marzo de 2021, para las pautas de metadona quincenal; y además en noviembre de 2020 para las de tratamiento con metasedín. Se realizó un análisis de estadística descriptiva, calculándose frecuencias absolutas y relativas, así como el porcentaje de variación entre el primer momento y el último momento de medición. En todos los centros se redujeron los días de dispensación. Las pautas quincenales take home de solución de metadona aumentaron más del 50% en todos los centros, manteniéndose un año después un incremento total del 97%. Las personas en tratamiento de mantenimiento con Metasedín se incrementaron en un 45,3%. Las restricciones de movilidad debido al confinamiento por Covid-19 obligaron a flexibilizar y ampliar el take home. La buena respuesta de las personas en tratamiento ha favorecido el mantenimiento de los cambios, lo que ayuda a la normalización de un tratamiento estigmatizado. (AU)

The objective of the study was to examine the changes made in the dispensing schedules and oral solution methadone take home doses and tablets, in the seven Addiction Care Centers (CAD) of Madrid Salud, because of the state of emergency, and which ones remain one year later. A longitudinal descriptive study was conducted, obtaining the data from the review of the reports prepared by the pharmacy unit, responsible for supply and control of methadone, at three times: February 2020 and March 2021, for the two weeks methadone doses; in addition, people treated with Metasedín were included in November 2020. A descriptive statistical analysis was performed, calculating absolute and relative frequencies, as well as the percentage of variation between the first moment and the last moment of measurement. Dispensing days were reduced in all centers. Two weeks methadone solution take home doses increased by more than 50% in all centers, maintaining a total increase of 97% one year later. People in Metasedín maintenance treatment increased by 45.3%. Mobility restrictions due to confinement by Covid-19 forced to make more flexible and expand the take home. The good response of people in treatment has favored maintaining the changes, which helps to normalize a stigmatized treatment. (AU)

Satisfacción y experiencia de pacientes en tratamiento con sustitutivos opioides en España. Estudio PREDEPO / Patients’satisfaction and experience in treatment with opioid substitution therapy in Spain. The PREDEPO study

El objetivo es comparar la satisfacción, experiencia, objetivos y opinión de los pacientes con trastorno por consumo de opioides (TCO) en base a su tratamiento sustitutivo de opioides (TSO) actual (metadona o buprenorfina/naloxona (B/N)). El estudio PREDEPO es un estudio observacional, transversal, multicéntrico desarrollado en España que incluyó pacientes adultos, diagnosticados de TCO y en TSO, quienes contestaron una encuesta sobre su tratamiento actual. Se incluyeron 98 pacientes (B/N:50%, metadona:50%): edad media de 47 ± 8 años y el 80% varones. A nivel de la satisfacción con su tratamiento, los resultados fueron similares entre grupos. El factor “muy/bastante satisfactorio” que se reportó con mayor frecuencia fue “poder repartir las dosis en varios momentos del día” (44% B/N vs. 63% metadona; p = ,122). Se encontraron diferencias significativas en “tener que recoger la medicación diariamente” donde una menor proporción en el grupo B/N contestaron “muy/bastante molesto” versus el grupo metadona (19% vs. 52%, p = ,032). Los objetivos reportados por la mayoría de los pacientes fueron similares entre grupos (“no sentir más síndrome de abstinencia”, “disminuir o dejar definitivamente mi consumo de drogas”, “mejorar mi estado de salud” y “dejar de pensar en consumir todos los días”) excepto en “no tener más problemas de dinero” (72% B/N vs. 92% metadona; p = ,012). Estos resultados evidencian que existen expectativas no cubiertas con los TSO actuales y la necesidad de nuevos tratamientos que disminuyan la carga de la enfermedad, eviten la necesidad de una dosificación diaria y reduzcan el estigma, mejorando así el manejo del paciente, su adherencia y calidad de vida. (AU)

The aim of this study was to compare patients’ satisfaction, experience, objectives, and opinion based on their current opioid substitution therapy (OST) (buprenorphine/naloxone (B/N) or methadone). The PREDEPO study is an observational, cross-sectional, multicentric study performed in Spain. Adult patients diagnosed with opioid use disorder (OUD) receiving OST were included. They were asked to fill in a questionnaire regarding their current OST. A total of 98 patients were enrolled (B/N: 50%, methadone: 50%). Mean age was 47 ± 8 years old and 80% were male. Treatment satisfaction was similar between groups. The most frequently reported factor for being “very/quite satisfied” was “being able to distribute the dose at different times throughout the day” (44% B/N vs. 63% methadone; p = .122). A significantly lower proportion of patients in the B/N group versus the methadone group reported that having to collect the medication daily was “very/quite annoying” (19% vs. 52%, p = .032). Treatment objectives reported by the majority of patients were similar between groups (“not feeling in withdrawal anymore”, “reduce/definitely stop drug use”, “improve my health”, and “stop thinking about using daily”) except for “not having money problems anymore” (73% B/N vs. 92% methadone; p = .012). These results suggest there are several unmet expectations regarding current OST. There is a need for new treatments that reduce the burden of OUD, avoid the need for daily dosing, and are less stigmatizing which in turn could improve patient management, adherence and, quality of life. (AU)

The Role of Pharmacogenomics in Opioid Prescribing.

OPINION STATEMENT: Pharmacogenomics is increasingly important to guide objective, safe, and effective individualised prescribing. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person's genetic profile. Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice. This narrative review examines the literature surrounding opioid pharmacogenomics and its applicability to the palliative care cancer population. There is currently limited intersection between the fields of palliative care and pharmacogenomics, but growing evidence presents a need to build linkages between the two disciplines. Pharmacogenomic evidence guiding opioid prescribing is currently available for codeine and tramadol, which relates to CYP2D6 gene variants. However, these medications are prescribed less commonly for pain in palliative care. Research is accelerating with other opioids, where oxycodone (CYP2D6) and methadone (CYP2B6, ABCB1) already have moderate evidence of an association in terms of drug metabolism and downstream analgesic response and side effects. OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable. Current evidence indicates that incorporation of pharmacogenomic testing into opioid prescribing practice should focus on the CYP2D6 gene and its actionable variants. Although opioid pharmacogenomic tests are not widely used in clinical practice, the progressively reducing costs and rapid turnover means greater accessibility and affordability to patients, and thus, clinicians will be increasingly asked to provide guidance in this area. The upsurge in pharmacogenomic research will likely discover more actionable gene variants to expand international guidelines to impact opioid prescribing. This rapidly expanding area requires consideration and monitoring by clinicians in order for key findings with clinical implications to be accessible, meaningfully interpretable and communicated.

Association Between Increased Dispensing of Opioid Agonist Therapy Take-Home Doses and Opioid Overdose and Treatment Interruption and Discontinuation.

Importance: During the COVID-19 pandemic, modified guidance for opioid agonist therapy (OAT) allowed prescribers to increase the number of take-home doses to promote treatment retention. Whether this was associated with an increased risk of overdose is unclear. Objective: To evaluate whether increased take-home doses of OAT early in the COVID-19 pandemic was associated with treatment retention and opioid-related harm. Design, Setting, and Participants: A retrospective propensity-weighted cohort study of 21 297 people actively receiving OAT on March 21, 2020, in Ontario, Canada. Changes in OAT take-home dose frequency were assessed between March 22, 2020, and April 21, 2020, and individuals were observed for up to 180 days to assess outcomes (last date of follow-up, October 18, 2020). Exposures: Exposure was defined as extended take-home doses in the first month of the pandemic within each of 4 cohorts based on OAT type and baseline take-home dose frequency (daily dispensed methadone, 5-6 take-home doses of methadone, daily dispensed buprenorphine/naloxone, and 5-6 take-home doses of buprenorphine/naloxone). Main Outcomes and Measures: Primary outcomes were opioid overdose, interruption in OAT, and OAT discontinuation. Results: Among 16 862 methadone and 4435 buprenorphine/naloxone recipients, the median age ranged between 38 and 42 years, and 29.1% to 38.2% were women. Among individuals receiving daily dispensed methadone (n = 5852), initiation of take-home doses was significantly associated with lower risks of opioid overdose (6.9% vs 9.5%/person-year; weighted hazard ratio [HR], 0.73 [95% CI, 0.56-0.96]), treatment discontinuation (51.0% vs 63.6%/person-year; weighted HR, 0.80 [95% CI, 0.72-0.90]), and treatment interruption (19.0% vs 23.9%/person-year; weighted HR, 0.80 [95% CI, 0.67-0.95]) compared with no change in take-home doses. Among individuals receiving daily dispensed buprenorphine/naloxone (n = 662), there was no significant difference in any outcomes between exposure groups. Among individuals receiving weekly dispensed OAT (n = 11 010 for methadone; n = 3773 for buprenorphine/naloxone), extended take-home methadone doses were significantly associated with lower risks of OAT discontinuation (14.1% vs 19.6%/person-year; weighted HR, 0.72 [95% CI, 0.62-0.84]) and interruption in therapy (5.1% vs 7.4%/person-year; weighted HR, 0.69 [95% CI, 0.53-0.90]), and extended take-home doses of buprenorphine/naloxone were significantly associated with lower risk of interruption in therapy (9.5% vs 12.9%/person-year; weighted HR, 0.74 [95% CI, 0.56-0.99]) compared with no change in take-home doses. Other primary outcomes were not significantly different between groups. Conclusions and Relevance: In Ontario, Canada, during the COVID-19 pandemic, dispensing of increased take-home doses of opioid agonist therapy was significantly associated with lower rates of treatment interruption and discontinuation among some subsets of patients receiving opioid agonist therapy, and there were no statistically significant increases in opioid-related overdoses over 6 months of follow-up. These findings may be susceptible to residual confounding and should be interpreted cautiously.

Self-harm and suicide during and after opioid agonist treatment among primary care patients in England: a cohort study.

BACKGROUND: The first 4 weeks after initiation and cessation of opioid agonist treatment for opioid dependence are associated with an increased risk of all-cause mortality and overdose. We aimed to investigate whether the rate of self-harm and suicide among people who were prescribed opioid agonist treatment differs during initiation, cessation, and the remainder of time on and off treatment. METHODS: We did a retrospective cohort study and used health-care records from UK Clinical Practice Research Datalink, linked to mortality and hospital admission data, for adults (age 18-75 years at cohort entry) who were prescribed opioid agonist treatment at least once in primary care in England between Jan 2, 1998, and Nov 30, 2018. We estimated rates and adjusted risk ratios (aRRs) of hospital admissions for self-harm and death by suicide, comparing time during and after treatment, as well as comparing stable periods of time on treatment with treatment initiation, cessation, and the remaining time off treatment. FINDINGS: Between Jan 2, 1998, and Nov 30, 2018, 8070 patients (5594 [69·3%] men and 2476 [30·7%] women) received 17 004 episodes of opioid agonist treatment over 40 599 person-years. Patients were mostly of White ethnicity (7006 [86·8%] patients). 807 episodes of self-harm (1·99 per 100 person-years) and 46 suicides (0·11 per 100 person-years) occurred during the study period. The overall age-standardised and sex-standardised mortality ratio for suicide was 7·5 times (95% CI 5·5-10·0) higher in the study cohort than in the general population. Opioid agonist treatment was associated with a reduced risk of self-harm (aRR in periods off treatment 1·50 [95% CI 1·21-1·88]), but was not significantly associated with suicide risk (aRR in periods off treatment 1·21 [0·64-2·28]). Risk of self-harm (aRR 2·60 [95% CI 1·83-3·70]) and suicide (4·68 [1·63-13·42]) were both elevated in the first 4 weeks after stopping opioid agonist treatment compared with stable periods on treatment. INTERPRETATION: Stable periods of opioid agonist treatment are associated with reduced risk of self-harm, emphasising the importance of improving retention of patients in treatment. The first month following cessation of opioid agonist treatment is a period of increased risk of suicide and self-harm, during which additional psychosocial support is required. FUNDING: Medical Research Council.

Implementing a Methadone Delivery System in New York City in Response to COVID-19.

Opioid agonist medication, including methadone, is considered the first-line treatment for opioid use disorder. Methadone, when taken daily, reduces the risk of fatal overdose; however, overdose risk increases following medication cessation. Amid an overdose epidemic accelerated by the proliferation of fentanyl, ensuring continuity of methadone treatment during the COVID-19 pandemic is a vital public health priority. (Am J Public Health. 2021;111(12):2115-2117. https://doi.org/10.2105/AJPH.2021.306523).