Methadone Prescribing Regulation for Opioid Use Disorder in Canada: Evidence for an East-West Policy Divide.

Opioid agonist therapy (OAT) is a key element in the response to opioid-related harms in Canada. In May 2018, Health Canada rescinded the requirement for obtaining a federal exemption for methadone prescribing. This comparative analysis examined provincial OAT policies and policy changes in response to this federal policy change. Policies and changes were regionalized; despite having lower rates of opioid-related harms, eastern provinces had looser regulatory regimes compared with western provinces, which became even looser after the federal policy change. Diverse knowledge and policy networks need to be fostered to bridge this east-west divide in substance use care policy.

Managing emergency department patients with opioid use disorder.

As the United States continues to grapple with the opioid crisis, emergency clinicians are on the front lines of managing patients with opioid use disorder. This issue reviews tools and best practices in emergency department management of patients with opioid overdose and opioid withdrawal, and how substance use history will inform treatment planning and disposition. As growing evidence shows that medications for opioid use disorder (MOUD)- buprenorphine, methadone, and naltrexone-can have lasting impacts on patients' addiction recovery, strategies for assessing patient readiness for MOUD and overcoming barriers to emergency department initiation of these medications are reviewed. Newer approaches to buprenorphine dosing (high-dose, low-dose, home induction, and long-acting injectable dosing) are also reviewed.

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.

Mediating effect of craving on the impact of buprenorphine/naloxone and methadone treatment on opioid use: Results from a randomized controlled trial.

BACKGROUND: The relationship between opioid craving and opioid use is unclear. We sought to determine to what extent craving mediated the relationship between opioid agonist therapy and changes in opioid use. METHODS: Data came from a pragmatic, 24-week, pan-Canadian, multi-centric, open-label, randomized controlled trial comparing flexible buprenorphine/naloxone take-home doses to standard supervised methadone models of care for the treatment of prescription-type opioid use disorder. Participants were randomly allocated to buprenorphine/naloxone or methadone models of care. 270 people with prescription-type opioid use disorder were included in analyses. There were 93 women (34.4%) and 2 transgender (0.7%) participants. Most participants were white (67.4%), 45.9% reported unstable living conditions, and 44.8% had psychiatric comorbidities. Generalized linear mixed models followed by mediation analysis estimated the direct effect of treatment group on Timeline Followback-reported next-week opioid use and the indirect effect through past 24-hour opioid craving measured using the Brief Substance Craving Scale at week 2, 6, 10, 14, 18 and 22. RESULTS: Upon mediation analysis, the average direct effect of treatment on opioid use was 0.465 (95 % CI = 0.183 to 0.751, p < 0.001). The average causal mediated effect was 0.144 (95 % CI = 0.021 to 0.110; p < 0.001). Craving accounted for 23.6 % of the effect of treatment on opioid use (p < 0.001). CONCLUSIONS: Past 24-hour craving was associated with increased next-week opioid use; however, craving only partially mediated the effect of buprenorphine/naloxone and methadone on next-week opioid use. Research is needed to develop a comprehensive understanding of factors mediating opioid use during opioid agonist therapy.

Simultaneous determination of methadone and tramadol in serum samples by ultrasonic-assisted micro solid phase extraction and gas chromatography-mass spectrometry.

Ultrasonic-assisted dispersive micro solid phase extraction (UA-DMSPE) is proposed as a fast and easy technique for the extraction and preconcentration of methadone and tramadol from serum samples. Different sorbents including carbon nanotubes, oxidized carbon nanotubes, and TiO2 nanoparticles were compared to extract methadone and tramadol. The best performance was obtained using oxidized carbon nanotubes due to the strong affinity between the drugs and carbon nanotube adsorbents. Final analysis of drugs performed by using gas chromatography-mass spectrometric detection. Different parameters affecting the extraction efficiency, such as the sample volume, amount of adsorbent, desorption solvent type and volume, centrifugation time, and speed were investigated and optimized. The striking features of this technique are correlated to its speed and the small volumes of sample (about 1 mL), desorption solvent (about 50 µL), and adsorbent (about 0.001 g) for analysis of drugs, and finally, milder centrifugation conditions relative to the previously reported adsorbent. The optimal parameters were achieved as follows: pH value was set at 9, the sample volume was adjusted to 1200 µL, the amount of adsorbent used was 1 mg, the extraction time was set at 5 min, and the volume of the desorption solvent was adjusted to 50 µL. The limits of detections (0.5 and 0.8 ng mL-1) and quantifications (1.5 and 2.5 ng mL-1) were obtained for methadone and tramadol, respectively. The developed method also showed good repeatability, relative standard deviation (RSD) of 9.49 % and 7.47 % (n = 5), for the spiked aqueous solution at the concentration level of 10, 50, and 100 ng mL-1 for analytes, and linearity, R ≥ 0.9809. The results showed that UA-DMSPE is a quick, relatively inexpensive, and environmentally friendly alternative technique for the extraction of opiate drugs from serum samples.

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.

Impact of jail-based methadone or buprenorphine treatment on non-fatal opioid overdose after incarceration.

BACKGROUND: Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS: This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS: MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION: MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.

Estimated Number of Injection-Involved Overdose Deaths in US States From 2000 to 2020: Secondary Analysis of Surveillance Data.

BACKGROUND: In the United States, both drug overdose mortality and injection-involved drug overdose mortality have increased nationally over the past 25 years. Despite documented geographic differences in overdose mortality and substances implicated in overdose mortality trends, injection-involved overdose mortality has not been summarized at a subnational level. OBJECTIVE: We aimed to estimate the annual number of injection-involved overdose deaths in each US state from 2000 to 2020. METHODS: We conducted a stratified analysis that used data from drug treatment admissions (Treatment Episodes Data Set-Admissions; TEDS-A) and the National Vital Statistics System (NVSS) to estimate state-specific percentages of reported drug overdose deaths that were injection-involved from 2000 to 2020. TEDS-A collects data on the route of administration and the type of substance used upon treatment admission. We used these data to calculate the percentage of reported injections for each drug type by demographic group (race or ethnicity, sex, and age group), year, and state. Additionally, using NVSS mortality data, the annual number of overdose deaths involving selected drug types was identified by the following specific multiple-cause-of-death codes: heroin or synthetic opioids other than methadone (T40.1, T40.4), natural or semisynthetic opioids and methadone (T40.2, T40.3), cocaine (T40.5), psychostimulants with abuse potential (T43.6), sedatives (T42.3, T42.4), and others (T36-T59.0). We used the probabilities of injection with the annual number of overdose deaths, by year, primary substance, and demographic groups to estimate the number of overdose deaths that were injection-involved. RESULTS: In 2020, there were 91,071 overdose deaths among adults recorded in the United States, and 93.1% (84,753/91,071) occurred in the 46 jurisdictions that reported data to TEDS-A. Slightly less than half (38,253/84,753, 45.1%; 95% CI 41.1%-49.8%) of those overdose deaths were estimated to be injection-involved, translating to 38,253 (95% CI 34,839-42,181) injection-involved overdose deaths in 2020. There was large variation among states in the estimated injection-involved overdose death rate (median 14.72, range 5.45-31.77 per 100,000 people). The national injection-involved overdose death rate increased by 323% (95% CI 255%-391%) from 2010 (3.78, 95% CI 3.33-4.31) to 2020 (15.97, 95% CI 14.55-17.61). States in which the estimated injection-involved overdose death rate increased faster than the national average were disproportionately concentrated in the Northeast region. CONCLUSIONS: Although overdose mortality and injection-involved overdose mortality have increased dramatically across the country, these trends have been more pronounced in some regions. A better understanding of state-level trends in injection-involved mortality can inform the prioritization of public health strategies that aim to reduce overdose mortality and prevent downstream consequences of injection drug use.

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.

Healthcare staff's perspectives on long-acting injectable buprenorphine treatment: a qualitative interview study.

BACKGROUND: Long-acting injectable buprenorphine (LAIB) formulations are a novel treatment approach in opioid agonist treatment (OAT), which provide patients with a steady dose administered weekly or monthly and thus reduce the need for frequent clinic visits. Several studies have analyzed patient experiences of LAIB but the perspective of OAT staff is unknown. This study aimed to explore how healthcare staff working in OAT clinics in Sweden perceive and manage treatment with LAIB. METHODS: Individual qualitative interviews were conducted with OAT physicians (n = 10) in tandem with nine focus group sessions with OAT nurses and other staff categories (n = 41). The data was analyzed with thematic text analysis. RESULTS: Five central themes were identified in the data: (1) advantages and disadvantages of LAIB, (2) patient categories that may or may not need LAIB, (3) patients' degrees of medication choice, (4) keeping tabs, control and treatment alliance, and (5) LAIB's impact on risk and enabling environments in OAT. Overall staff found more advantages than disadvantages with LAIB and considered that patients with ongoing substance use and low adherence were most likely to benefit from LAIB. However, less frequent visits were viewed as problematic in terms of developing a treatment alliance and being able to keep tabs on patients' clinical status. Clinics differed regarding patients' degrees of choice in medication, which varied from limited to extensive. LAIB affected both risk and enabling environments in OAT. CONCLUSIONS: LAIB may strengthen the enabling environment in OAT for some patients by reducing clinic visits, exposure to risk environments, and the pressure to divert medication. A continued discussion about the prerequisites and rationale for LAIB implementation is needed in policy and practice.

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.

Comparison of analgesic efficacy of tramadol, morphine and methadone in cats undergoing ovariohysterectomy.

OBJECTIVES: The aim of this study was to compare the analgesic efficacy and the effect on physiological variables and behavior of the use of tramadol, methadone and morphine as preoperative analgesia in healthy cats undergoing elective ovariohysterectomy. METHODS: Cats undergoing ovariohysterectomy were randomly assigned to receive one of the following premedication treatments intramuscularly: methadone (0.2 mg/kg; n = 10); morphine (0.2 mg/kg; n = 10); or tramadol (3 mg/kg; n = 10). Induction of anesthesia was done with propofol, and maintenance of anesthesia was done with isoflurane. Intraoperative heart rate, arterial blood pressure, respiratory rate, end-tidal isoflurane concentration and frequency of rescue analgesia (fentanyl 2.5 µg/kg) were compared between groups. Postoperative analgesia was assessed using the UNESP-Botucatu Multidimensional Composite Pain Scale, and perioperative serum glucose, cortisol concentrations and postoperative rescue analgesia were evaluated. RESULTS: Intraoperative rescue analgesia was required in 76.5% of cats at some time during surgery, and 27% of cats required postoperative rescue analgesia up to 6 h after extubation. There were no significant differences between groups with respect to intraoperative and postoperative rescue analgesia, pain scale scores and end-tidal isoflurane concentrations. In the immediate postoperative period, after extubation, most of the patients presented with hypothermia; however, 1-6 h postoperatively, hyperthermia was observed in most of the patients, and was most common in the tramadol group. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of this study, methadone, morphine and tramadol produced satisfactory postoperative analgesia in most of the cats undergoing ovariohysterectomy, and the effects lasted up to 6 h postoperatively. Intraoperative analgesia was not sufficient in most cases. Significant cardiovascular or respiratory effects contraindicating the use of these drugs were not found. Postanesthetic hyperthermia occurred with all opioids studied and was more frequent in the tramadol group.

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.

Fentanyl abuse proportion in methadone maintenance treatment, and patients' knowledge about its risks.

INTRODUCTION: Fentanyl is not yet routinely monitored among methadone maintenance treatment (MMT) patients in Israel. We aimed 1. to evaluate urine fentanyl proportion changes over 3 years and characterize patients' characteristics 2. To study patients' self-report on fentanyl usage, and compare knowledge about fentanyl risk, before and following brief educational intervention. METHODS: Fentanyl in the urine of all current MMT patients was tested every 3 months year between 2021 and 2023, and patients with positive urine fentanyl were characterized. Current patients were interviewed using a fentanyl knowledge questionnaire (effects, indications, and risks) before and following an explanation session. RESULTS: Proportion of fentanyl ranged between 9.8 and 15.1%, and patients with urine positive for fentanyl (September 2023) were characterized as having positive urine for pregabalin, cocaine, and benzodiazepine (logistic regression). Of the current 260 patients (87% compliance), 78(30%) self-reported of fentanyl lifetime use ("Ever"), and 182 "never" use. The "Ever" group had higher Knowledge scores than the "Never", both groups improved following the explanatory session (repeated measure). The "Ever" group patients were found with urine positive for cannabis and benzodiazepine on admission to MMT, they were younger, did not manage to gain take-home dose privileges and had a higher fentanyl knowledge score (logistic regression). CONCLUSIONS: In the absence of routine fentanyl tests, a high knowledge score, shorter duration in MMT, benzodiazepine usage on admission, and current cannabis usage, may hint of the possibility of fentanyl abuse.

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.

Project CHARIOT: study protocol for a hybrid type 1 effectiveness-implementation study of comprehensive tele-harm reduction for engagement of people who inject drugs in HIV prevention services.

BACKGROUND: People who inject drugs (PWID) remain a high priority population under the federal Ending the HIV Epidemic initiative with 11% of new HIV infections attributable to injection drug use. There is a critical need for innovative, efficacious, scalable, and community-driven models of healthcare in non-stigmatizing settings for PWID. We seek to test a Comprehensive-TeleHarm Reduction (C-THR) intervention for HIV prevention services delivered via a syringe services program (SSP). METHODS: The CHARIOT trial is a hybrid type I effectiveness-implementation study using a parallel two-arm randomized controlled trial design. Participants (i.e., PWID; n = 350) will be recruited from a syringe services program (SSP) in Miami, Florida. Participants will be randomized to receive either C-THR or non-SSP clinic referral and patient navigation. The objectives are: (1) to determine if the C-THR intervention increases engagement in HIV prevention (i.e., HIV pre-exposure prophylaxis; PrEP or medications for opioid use disorder; MOUD) compared to non-SSP clinic referral and patient navigation, (2) to examine the long-term effectiveness and cost-effectiveness of the C-THR intervention, and (3) to assess the barriers and facilitators to implementation and sustainment of the C-THR intervention. The co-primary outcomes are PrEP or MOUD engagement across follow-up at 3, 6, 9 and 12 months. For PrEP, engagement is confirmed by tenofovir on dried blood spot or cabotegravir injection within the previous 8 weeks. For MOUD, engagement is defined as screening positive for norbuprenorphine or methadone on urine drug screen; or naltrexone or buprenorphine injection within the previous 4 weeks. Secondary outcomes include PrEP adherence, engagement in HCV treatment and sustained virologic response, and treatment of sexually transmitted infections. The short and long term cost-effectiveness analyses and mixed-methods implementation evaluation will provide compelling data on the sustainability and possible impact of C-THR on comprehensive HIV prevention delivered via SSPs. DISCUSSION: The CHARIOT trial will be the first to our knowledge to test the efficacy of an innovative, peer-led telehealth intervention with PWID at risk for HIV delivered via an SSP. This innovative healthcare model seeks to transform the way PWID access care by bypassing the traditional healthcare system, reducing multi-level barriers to care, and meeting PWID where they are. TRIAL REGISTRATION: ClinicalTrials.gov NCT05897099. Trial registry name: Comprehensive HIV and Harm Prevention Via Telehealth (CHARIOT). Registration date: 06/12/2023.

A multicomponent LC-MS/MS method for drugs of abuse testing using volumetric DBS and a clinical evaluation by comparison with urine.

BACKGROUND: Drug testing commonly use urine as a specimen and immunoassays for screening. The need for supervised urine collection has led to an interest in alternative specimens and a need for using mass spectrometry methods already for screening. In addition, mass spectrometry methods allow for broad multipanel screening which of great value because of the increased number of substances that needs to be covered has increased over time. One alternative specimen of interest for drugs of abuse testing is dried blood spots (DBS) and this work aimed at developing multipanel screening methods based on selected reaction monitoring liquid chromatography - mass spectrometry for both urine and dried finger blood as specimens. MATERIALS AND METHODS: The urine method comprised 37 analytes and utilised salted out liquid/liquid extraction in 96-well format, respectively, and the blood method comprised 35 analytes, a 10 µL volumetric DBS device and a two-step solvent extraction procedure. In both cases stable isotope labelled internal standards were used for almost all analytes. RESULTS: The methods were validated according to forensic standard. The lowest reporting limits were generally set at 100 ng/mL for urine and 1 ng/mL for blood and the accuracy and imprecision were within limits of 15 and 20%. The methods were applied in a clinical study on patients receiving methadone maintenance treatment for opioid dependence. Methadone was detected in all urine and DBS samples, for urine sometimes below the commonly applied screening cutoff limit of 300 ng/mL. In 20 out of 99 cases no other drug was detected in any specimen. The most commonly other detected substances were pregabalin, amphetamine, alprazolam, zopiclone and THCCOOH. Findings in urine and DBS generally agreed well but more positives were detected in DBS. CONCLUSION: Multipanel methods using liquid chromatography - mass spectrometry suitable for clinical drug screening were successfully developed for urine and blood collected by finger-pricking and stored as DBS.