Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

Opioid-related deaths and their counterpart by occurrence era, age group and coimplicated drugs: Scotland vs. England and Wales.

AIMS: Compare by occurrence era and age group how opioid-related deaths (ORDs) and their counterpart evolved in Scotland vs. England and Wales during 2006-2020. For Scotland, compare coimplication rates between ORDs and non-ORDs for any benzodiazepine, cocaine or gabapentin/pregabalin, and consider whether coimplication in ORDs depended on opioid-specificity. METHODS: Cross-tabulations of drug misuse deaths (DMDs) obtained by 3 yearly occurrence era (2006-2008 to 2018-2020) and age group (under 25, 25-34, 35-44, 45-54, 55+ years) for England and Wales and subdivided by whether at least 1 opiate was mentioned on death certificate (DMD-Os or not); and of Scotland's opioid-related deaths (ORDs vs. non-ORDs) together with (i) coimplication by any benzodiazepine, cocaine or gabapentin/pregabalin; and (ii) opioid-specificity of ORDs. ORD is defined by heroin/morphine, methadone or buprenorphine being implicated in DMD. RESULTS: Per era between 2012-2014 and 2018-2020, Scotland's ORDs increased by 54% and non-ORDs by 34%. Increase in DMD-Os in England and Wales was more modest. Cocaine was implicated in 83% of Scotland's 2690 non-ORDs during 2006-2020; and any benzodiazepine in 53% of 8409 ORDs. However, in 2018-2020, coimplication rates in 2926 ORDs (880 non-ORDs) were 81% (33%) for any benzodiazepine, 30% (74%) for cocaine and 38% (22%) for gabapentin/pregabalin. Coimplication rate in 2018-2020 for any benzodiazepine was lowest at 70% (616/877) for heroin/morphine ORDs; and, by age group, at 66% (160/241) for ORDs aged 55+ years. CONCLUSIONS: Drug testing to inform users, shared intelligence between police and public health for earlier detection of changes in supply and monitoring of prescribed daily-dose of methadone are urgent.

Activity space during treatment with medication for opioid use disorder: Relationships with personality, mood, and drug use.

INTRODUCTION: Activity space in people with substance use disorders (SUDs) has been assessed for theoretical reasons and for detection/prevention of relapse. In this observational study, we relate passively obtained activity space measures to mental states and behaviors relevant to the success of treatment for opioid use disorder. Our long-term goal is to use such data to assess risk in real time and to recognize when SUD patients might benefit from a just-in-time intervention. METHODS: We used GPS data from 238 urban residents in the first 16 weeks of stabilization on medication for opioid use disorder to test preregistered hypotheses about activity space (distance traveled, number of locations, time spent moving, and psychosocial-hazard levels of neighborhoods where participants spent time) in relation to certain static variables (personality, mood propensities) and time-varying treatment-relevant behaviors such as craving and use of opioids and cocaine. RESULTS: The most consistent findings were that 1) mobility decreased over the course of the study; 2) neuroticism was associated with overall lower mobility; 3) trait-like positive mood (averaged from momentary ratings) was associated with higher mobility; 4) participants who used cocaine more frequently had lower mobility; 5) early in treatment, participants spent less time moving (i.e., were more sedentary) on days when they were craving. Some of these findings were in the expected direction (i.e., the ones involving neuroticism and positive mood), and some were opposite to the expected direction (i.e., we expected cocaine use to be associated with higher mobility); others (e.g., changes in mobility over time or in relation to craving) involved nondirectional hypotheses. CONCLUSIONS: Real-time information that patients actively provide is valuable for assessing their current state, but providing this information can be burdensome. The current results indicate that certain static or passively obtained data (personality variables and GPS-derived mobility information) are relevant to time-varying, treatment-relevant mental states and drug-related behavior, and therefore might be useful when incorporated into algorithms for detecting need for intervention in real time. Further research should assess how population-specific these relationships are, and how these passive measures can best be combined with low temporal-density, actively-provided data to obtain valid, reliable assessments with minimal burden.

Risks of returning to opioid use at treatment entry and early in opioid use disorder treatment: Role of non-opioid substances.

OBJECTIVE: Patients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome. METHODOLOGY: We combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use. The trials compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks. RESULTS: When treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine (OR 1.41 [1.18-1.69]) and amphetamine (OR 1.70 [1.27-2.26]) was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group. CONCLUSION: Substance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions.

Non-Prescribed Substance Use during the First Month of Treatment by People Receiving Depot Buprenorphine for Opioid Use Disorder.

Background: Non-prescribed substance use (NPSU) during the treatment of opioid use disorder (OUD) is a recognized phenomenon. The use of non-prescribed substances is associated with discontinuing treatment and drop-out can occur within the early weeks of treatment, before benefit from treatment occurs. Recent developments in treatment include long-acting, slow-release depot buprenorphine injections. This article focuses on NPSU during the first month of treatment with depot buprenorphine, addressing the frequency with which it occurs, the substances used, and reasons for use. Methods: 70 semi-structured interviews (held at three time-points) were conducted with 26 patients initiating depot buprenorphine as part of a longitudinal qualitative study. Analysis prioritized content and framework analyses. Findings: 17/26 participants self-reported NPSU at various times during the first month of treatment. NPSU typically involved heroin, crack-cocaine and some use of benzodiazepines and/or cannabis. Participants' reasons for heroin use were connected to their subjective accounts of opioid withdrawal symptoms, the management of pain, and experimentation (to test the blockade effect of buprenorphine). Frequency of heroin use was typically episodic rather than sustained. Participants associated crack-cocaine use with stimulant-craving and social connections, and considered their use of this substance to be difficult to manage. Conclusions: Patients' initial engagement with treatment for OUD is rarely examined in qualitative research. This study highlights how NPSU amongst patients receiving new forms of such treatment continues to be a challenge. As such, shared decision-making (between providers and patients) regarding treatment goals and NPSU should be central to the delivery of depot buprenorphine treatment programmes.

Percentage of negative urine drug screens as a clinically meaningful endpoint for RCTs evaluating treatment for cocaine use.

BACKGROUND: This study examined a threshold based on the percentage of cocaine-negative (CN) urine drug screens (UDS) collected during treatment as a potential meaningful endpoint for clinical trials. We hypothesized that individuals providing at least 75% CN UDS would have better long-term outcomes than those providing less than 75% CN UDS. METHODS: Two separate pooled datasets of randomized clinical trials conducted at different institutions were used for analyses: one composed of eight trials (N = 760) and the other composed of three trials (N = 416), all evaluating behavioral and/or pharmacological treatments for cocaine use. UDS were collected at least once per week (up to three times per week) during the 8- or 12-week treatment period across all trials, with substance use and psychosocial functioning measured up to 12 months following treatment. Chi-squares and ANOVAs compared within-treatment and follow-up outcomes between the groups. RESULTS: Compared to those who did not achieve the threshold, participants who achieved the 75%-CN threshold were retained in treatment longer and had a longer period of continuous abstinence, and were more likely to report problem-free functioning. Additionally, participants who achieved the 75%-CN threshold were more likely to report sustained abstinence and better psychosocial functioning throughout a follow-up period up to 12 months than those who did not achieve the threshold. CONCLUSIONS: A threshold of 75%-CN UDS is associated with short- and long-term clinical benefits. Future clinical trials may consider this a meaningful threshold for defining treatment responders.

Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies.

BACKGROUND: Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes. METHODS: We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109). FINDINGS: We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use). INTERPRETATION: Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses. FUNDING: Australian National Health and Medical Research Council.

Urine Drug Test Results Among Adolescents and Young Adults in an Outpatient Office-Based Opioid Treatment Program.

PURPOSE: Urine drug testing (UDT) is an important feature of outpatient treatment for opioid use disorder, but associations with patient characteristics among adolescent and young adult patients are unknown. This study assessed UDT results in office-based opioid treatment and characteristics associated with treatment compliance. METHODS: This was a retrospective study of adolescent and young adult patients enrolled in office-based opioid treatment between January 1, 2009, and December 31, 2020. UDT results were described as positive results or expected and unexpected results. Expected results were negative UDTs for opioids, marijuana (THC [tetrahydrocannabinol]), or cocaine/methamphetamine, or a positive UDT for buprenorphine. Unexpected results were positive UDTs for opioids, THC, or cocaine/methamphetamine, or a negative UDT for buprenorphine. Treatment compliance was defined as ≥75% of UDTs provided being expected results. Counts and percentages described UDT results. Regressions evaluated associations between patient characteristics (retention time, age, sex, race/ethnicity, insurance, and comorbid mental health diagnoses) with treatment compliance, and assessed change of positivity rates for UDTs over time. RESULTS: A total of 407 patients were included. Overall, 305 patients (74.9%) demonstrated treatment compliance. Rates of expected UDT results increased with longer retention time (p <.001), except for methamphetamine. Buprenorphine expected results ranged from 77.0% to 96.5%. Diagnosis of stimulant use disorder was associated with decreased compliance (p = .04), while diagnoses of depression, anxiety, nicotine use disorder, and post-traumatic stress disorder were associated with increased compliance (p ≤.04). DISCUSSION: Proportion of expected UDT results increased with retention time. Diagnosis of specific mental health conditions affected treatment compliance. Further research regarding long-term health outcomes is needed.

Impulsivity and Treatment Outcomes in Individuals with Cocaine Use Disorder: Examining the Gap between Interest and Adherence.

Background: Impulsivity is implicated in the development and maintenance of Cocaine Use Disorder (CUD). Less work has examined impulsivity's role on interest in initiating treatment, treatment adherence, or treatment response. No pharmacotherapies are approved for CUD, so efforts to understand and bolster the effects of psychotherapy are important in guiding and refining treatment. The present study examined the impact of impulsivity on interest in treatment, treatment initiation, treatment adherence, and treatment outcomes in individuals with CUD. Methods: Following the completion of a larger study on impulsivity and CUD participants were offered 14 sessions of (12 weeks) Cognitive Behavioral Relapse Prevention (CBT-RP). Before starting treatment, participants completed seven self-report and four behavioral measures of impulsivity. Sixty-eight healthy adults (36% female) with CUD (aged 49.4 ± 7.9) expressed an interest in treatment. Results: Greater scores on several self-report measures of impulsivity, and fewer difficulties with delayed gratification were associated with increased interest in treatment in both males and females. 55 participants attended at least 1 treatment session, while 13 participants did attend a single session. Individuals who attended at least one treatment session scored lower on measures of lack of perseverance and procrastination. Still, measures of impulsivity did not reliably predict session attendance nor the frequency of cocaine-positive urine samples throughout treatment. Males attended nearly twice as many treatment sessions as females despite nonsignificant associations between impulsivity in males and the number of sessions attended. Conclusions: Greater impulsivity in individuals with CUD was associated with expressing an interest in treatment, but not treatment adherence or response.

Interest in treatment with injectable diacetylmorphine among people who use opioids in Baltimore City, Maryland (USA).

INTRODUCTION: Treatment for opioid use disorder (OUD) with diacetylmorphine is an evidence-based form of drug treatment, but it is not available in the United States (US). Better understanding acceptability of treatment with injectable diacetylmorphine among people who use opioids (PWUO) in the US may expedite future initiatives designed to engage persons in this form of treatment should it become available. The purpose of this research is to examine factors associated with interest in treatment with injectable diacetylmorphine among a sample of PWUO in the US. METHODS: Data are from a cross-sectional study of PWUO in Baltimore City, Maryland. Participants were given a brief description of treatment with injectable diacetylmorphine and then asked to rate their level of interest. We used Poisson regression with robust variance to assess factors associated with interest in treatment with injectable diacetylmorphine. RESULTS: The average age of participants was 48 years, 41% were women, and most (76%) identified as non-Hispanic, Black. The most commonly used substances were non-injection heroin (76%), opioid pain relievers (73%), and non-injection crack/cocaine (73%). Two-thirds of participants (68%) indicated interest in treatment with injectable diacetylmorphine. Factors significantly associated with interest in injectable diacetylmorphine treatment included: having at least a high school education (adjusted prevalence ratio [aPR]: 1.23; 95% confidence interval [CI]: 1.04-1.45), not having health insurance (aPR: 1.23; 95% CI: 1.06-1.44), having ever overdosed (aPR: 1.20; 95% CI: 1.01-1.42), and past utilization of medications for opioid use disorder (aPR: 1.22; 95% CI: 1.01-1.47). Recent non-injection cocaine use was inversely associated with interest in treatment with injectable diacetylmorphine (aPR 0.80; 95% CI: 0.68-0.94). CONCLUSION: The majority of participants reported interest in treatment with injectable diacetylmorphine. Given worsening trends in the addiction and overdose crisis in the US, treatment with injectable diacetylmorphine should be considered as another evidence-based option for treating OUD.KEY MESSAGESInterest in treatment with injectable diacetylmorphine was high among a sample of people who use opioids in the United States.Factors associated with increased interest in treatment with injectable diacetylmorphine included having at least a high school education, having ever overdosed, and not having health insurance.Past utilization of medications for opioid use disorder was associated with interest in treatment with injectable diacetylmorphine.

Marker events associated with adherence to HIV/AIDS treatment in a cohort study.

OBJECTIVE: To analyze how clinical and social events may impact adherence to antiretroviral treatment for HIV. METHODS: This is a historical cohort study with 528 patients who underwent treatment for HIV in a specialized care service in Alvorada, RS. A total of 3429 queries executed between the years 2004 and 2017 were analyzed. For each visit, data on treatment characteristics and the patients' clinical picture were collected. Adherence, as measured by patients' self-report, was the endpoint of the study. The logistic regression model via generalized estimating equations was used for estimating the associations. RESULTS: 67.8% of the patients analyzed have up to 8 years of education and 24.8% have a history of crack and/or cocaine use. Among men, being asymptomatic [odds ratio (OR) = 1.43; 95%CI 1.05-1.93], having more than 8 years of education (OR= 2.32; 95%CI 1.27-4.23), and never having used crack (RC = 2.35; 95%CI 1.20-4.57) were associated with adherence. For women, being older than 24 years (CR = 1.82; 95%CI 1.09-3.02), never having used cocaine (CR = 2.54; 95%CI 1.32-4.88) and being pregnant (RC = 3.28; 95%CI 1.83-5.89) increased the odds of adherence. CONCLUSIONS: In addition to defined sociodemographic characteristics, one-off events that may occur in the trajectory of patients on long treatment, such as starting a new pregnancy and not having symptoms, can impact patients' chances of treatment adherence.

Neurobiological Dysfunctional Substrates for the Self-Medication Hypothesis in Adult Individuals with Attention-Deficit Hyperactivity Disorder and Cocaine Use Disorder: A Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Study.

Objectives: Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with attention-deficit hyperactivity disorder with cocaine use disorder (ADHD-CoUD). Materials and Methods: We included 19 ADHD-CoUD patients (84.2% male; age: 32.11 years [7.18]) and 16 CoUD patients (68.7% male; age: 36.63 years [8.12]). All subjects underwent a fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. Results: The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, than CoUD subjects and healthy controls (HCs). Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD patients had a more preserved metabolic connectivity than CoUD patients in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviors (i.e., anterior default mode network [ADMN], executive network [ECN], and anterior salience network [aSAN]). Conclusions: We demonstrated distinct neuropathological substrates underlying substance-use behaviors in ADHD-CoUD and CoUD patients. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD patients might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioral deficits).

Retention in Office-Based Opioid Treatment and Impact on Emergency Department Use in Adolescents and Young Adults With Opioid Use Disorder.

PURPOSE: Longer retention in medication treatment (MT) of addiction is associated with improved health outcomes among adults with opioid use disorder. MT remains underutilized among adolescents and young adults (AYA); factors associated with MT retention are not well-defined and effect of retention on treatment outcomes is unknown. This study examined patient characteristics associated with retention in an office-based opioid treatment program for AYA patients and determined the impact of retention time on emergency department (ED) utilization. METHODS: This was a retrospective study of AYA patients from January 1, 2009, to December 31, 2020. Retention time was the difference between first and last appointment, analyzing follow-up periods of one and two years. Linear regression assessed factors associated with retention. Negative binomial regression showed effect of retention on ED utilization. RESULTS: A total of 407 patients were included. Factors positively associated with retention were diagnosis of anxiety, depression, and nicotine use disorder, White race, private insurance, and Medicaid insurance; however, stimulant/cocaine use disorder was negatively associated (one-year follow-up, p ≤ .028; two-year follow-up, p ≤ .017). Longer retention was associated with reduced risk of ED utilization at one-year (incident rate ratio = 0.84, 95% confidence interval: 0.72-0.99; p = .03) and two-year follow-ups (incident rate ratio = 0.86 95% confidence interval: 0.77-0.96; p = .008). DISCUSSION: Diagnosis of anxiety, depression, nicotine use disorder, and stimulant/cocaine use disorder, and insurance and race can influence retention in MT. Longer retention in MT was associated with lower ED visits, decreasing health care utilization. MT programs should evaluate various interventions to optimize opportunities for increasing retention among their patient cohorts.

Transitioning off methadone: A qualitative study exploring why patients discontinue methadone treatment for opioid use disorder.

INTRODUCTION: Patients who discontinue methadone for opioid use disorder are at increased risk of overdose and death. We know little about how patients make the decision to stop treatment. This study explored reasons why patients discontinue methadone treatment. METHODS: We conducted 20 individual semi-structured patient interviews and two staff focus groups, each with five participants, at two opioid treatment programs in Baltimore, MD, in the United States from June 2021 to May 2022. Patient interviews and staff focus groups covered three domains: 1) reasons why patients may want to discontinue methadone; 2) perspectives about the ideal length of methadone treatment; and 3) changes that could improve retention. We used a modified grounded theory approach to code interviews, identify emergent themes, and develop a conceptual model. RESULTS: We identified three themes related to patients' internal relationships to methadone: patients (1) viewed methadone as a bridge to opioid-free recovery, (2) believed that long-term methadone damages the body, and (3) felt that methadone increases craving for cocaine; and three themes related to their external relationships with opioid treatment programs and society at large: patients (4) viewed daily dosing as burdensome, (5) feared methadone inaccessibility could trigger relapse, and (6) experienced stigma from friends, family, and peers. Patients with internal reasons planned to stop as soon as possible and asked for education about perceived side effects and treatment for cocaine craving to promote retention. Patients with external reasons were willing to continue for longer and asked for adaptive take-home policies and reduced societal stigma around methadone. CONCLUSIONS: Patients want to discontinue methadone either because of their internal relationship to methadone and its real or perceived side effects, or because of their external experiences with opioid treatment programs and societal stigma of methadone. To improve retention, clinical and policy changes should consider responses to both of these categories of reasons.

Daily opioid and stimulant co-use and nonfatal overdoses in the context of social disadvantage: Findings on marginalized populations.

OBJECTIVE: Opioids and stimulants are increasingly implicated in overdose deaths, particularly among minoritized groups. We examined daily opioid and cocaine co-use, nonfatal overdoses, and naloxone carrying among minoritized people who inject drugs (PWID). METHODS: The study derived data from 499 PWID in Baltimore City, MD, recruited using street-based outreach between 2016 and 2019. Participants reported overdoses; sociodemographic characteristics; and use of nonmedical prescription opioids, heroin, cocaine, and naloxone. RESULTS: Among the participants, the mean age was 46, 34 % were female, 64 % self-identified as Black, and 53 % experienced recent homelessness. Black PWID, compared to White PWID, were as likely to use opioids and cocaine daily but were 61 % less likely to have naloxone. After controlling for sociodemographic characteristics, women (aOR:1.88, 95%CI: 1.14, 3.11), persons experiencing homelessness (aOR:3.07, 95%CI: 1.79, 5.24), and those who experienced a recent overdose (aOR:2.14, 95%CI: 1.29, 3.58) were significantly more likely to use opioids and any form of cocaine every day. In a subanalysis of only female PWID, females engaged in sex work (aOR:2.27, 95%CI: 1.02, 5.07) and females experiencing recent homelessness (aOR:5.82, 95%CI: 2.50, 13.52) were significantly more likely to use opioids and cocaine daily. Furthermore, females (aOR:1.69, 95%CI:1.03, 2.77), persons experiencing homelessness (aOR:1.94, 95%CI:1.16, 3.24), and those with higher educational attainment (aOR:2.06, 95%CI:1.09, 3.91) were more likely to often/always carry naloxone, while Black PWID were less likely to have naloxone (aOR:0.39, 95%CI:0.22, 0.69). CONCLUSIONS: These findings highlight the need for targeted naloxone distribution and other harm-reduction interventions among minoritized groups in urban areas.

Self-report and urine drug screen concordance among women with co-occurring PTSD and substance use disorders participating in a clinical trial: Impact of drug type and participant characteristics.

BACKGROUND: Self-report measures are important in substance use assessment, yet they are susceptible to reporting errors. Urine drug screens (UDS) are often considered a more valid alternative. However, collecting in-person UDS may not always be feasible, contributing to the need to understand factors that influence the validity of self-reported substance use. METHODS: In this secondary analysis of data from 295 women with co-occurring PTSD and substance use disorders (SUD) who participated in a clinical trial testing behavioral interventions, we examined concordance and discordance between self-reported drug use and associated UDS results. Generalized linear mixed models were used to examine the impact of treatment type and participant characteristics on the associations between self-reported drug use and UDS results. RESULTS: Findings revealed higher disagreement between self-report and UDS for opioids and sedatives (ranging from.77 to.90) and lower disagreement rates for cannabis and cocaine (ranging from.26 to.33). Treatment type was not a significant moderator of the associations between self-report and UDS across all drugs. Among those with a positive opioid UDS, those who reported employment in the past three years were more likely to self-report no opioid use compared to their counterparts without employment in the past three years. CONCLUSIONS: Findings add to the literature that supports the validity of self-reported cannabis and cocaine use. The greater discrepancies between self-report and UDS test results of opioids and sedatives suggest adjunctive UDS may be required, although a variety of factors other than inaccurate self-report may be associated with this discrepancy.

Predictors of crystal methamphetamine use initiation or re-initiation among people receiving opioid agonist therapy: A prospective cohort study.

BACKGROUND: In the context of the ongoing opioid crisis in the United States and Canada, opioid agonist therapy (OAT) is the first-line treatment for opioid use disorder. However, there is growing concern regarding the increasing methamphetamine use among those on OAT, as well as the impact of such use may have on OAT retention and outcomes. We sought to identify the predictors of crystal methamphetamine initiation or re-initiation among people on OAT, in order to facilitate the development of effective preventive strategies. METHODS: We employed multivariable generalized estimating equations to identify the predictors of crystal methamphetamine use initiation or re-initiation among those who were on OAT within two prospective cohorts in Vancouver, Canada between 2005 and 2020. RESULTS: Of the 1281 participants receiving OAT, the median age was 43 years, and 59.2 % were male at baseline. During study follow-up, 564 (44.0 %) initiated or re-initiated crystal methamphetamine use while receiving OAT. In a multivariable model, a higher crystal methamphetamine use initiation or re-initiation rate was positively associated with younger age, unstable housing, unprotected sex, history of crystal methamphetamine use, as well as recent cocaine, prescription opioid, and unregulated opioid use (all p < 0.05). CONCLUSIONS: We identified high and increasing rates of crystal methamphetamine use initiation or re-initiation among our sample of people on OAT. Intervention strategies including housing program referral, sexual risk reduction, and integrated treatment approaches targeting polysubstance use are urgently needed to reduce the risks associated with methamphetamine use as well as the co-use of methamphetamine and opioids.

Development of a Highly Efficient Long-Acting Cocaine Hydrolase Entity to Accelerate Cocaine Metabolism.

It is particularly challenging to develop a truly effective pharmacotherapy for cocaine use disorder (CUD) treatment. Accelerating cocaine metabolism via hydrolysis at cocaine benzoyl ester using an efficient cocaine hydrolase (CocH) is known as a promising pharmacotherapeutic approach to CUD treatment. Preclinical and clinical studies on our first CocH (CocH1), in its human serum albumin-fused form known as TV-1380, have demonstrated the promise of a general concept of CocH-based pharmacotherapy for CUD treatment. However, the biological half-life of TV-1380 (t1/2 = 8 h in rats, associated with t1/2 = 43-77 h in humans) is not long enough for practical treatment of cocaine dependence, which requires enzyme injection for no more than once weekly. Through protein fusion of a human butyrylcholinesterase mutant (denoted as CocH5) with a mutant (denoted as Fc(M6)) of Fc from human IgG1, we have designed, prepared, and tested a new fusion protein (denoted as CocH5-Fc(M6)) for its pharmacokinetic profile and in vivo catalytic activity against (-)-cocaine. CocH5-Fc(M6) represents the currently most efficient long-acting cocaine hydrolase with both the highest catalytic activity against (-)-cocaine and the longest elimination half-life (t1/2 = 229 ± 5 h) in rats. As a result, even at a single modest dose of 3 mg/kg, CocH5-Fc(M6) can significantly and effectively accelerate the metabolism of cocaine in rats for at least 60 days. In addition, ∼70 nM CocH5-Fc(M6) in plasma was able to completely block the toxicity and physiological effects induced by intraperitoneal injection of a lethal dose of cocaine (60 mg/kg).

El auge y la caída del mito de la epinefrina en la mano / The Rise and Fall of the Epinephrine Myth in the Hand

La posibilidad de operar a los pacientes con afecciones de la mano bajo anestesia local con la lidocaína y la epinefrina usando la técnica WALANT provocó una revolución en la cirugía de la mano, que facilitó la vida de los pacientes y disminuyó los costos de los servicios hospitalarios. Es necesario que los cirujanos conozcan la técnica y la historia de esta técnica. El objetivo fue identificar los orígenes del auge y la caída del mito y del dogma de la prohibición de la adrenalina en los bloqueos anestésicos de los dedos. Se realizó un análisis crítico de los principales textos de los artículos y los libros sobre el uso de la epinefrina en la anestesia de los dedos. La creación del mito de prohibir el uso de la epinefrina en los bloqueos anestésicos de los dedos se produjo debido a la mala interpretación de los informes de los casos de necrosis ocurridos que, en realidad, no fueron causados por la epinefrina. Ese mito influyó en la aparición de un dogma. La historia del uso de la epinefrina en los bloqueos de los dedos anestésicos demuestra que las interpretaciones superficiales y erróneas de las complicaciones clínicas publicadas como informes de casos pueden generar mitos y dogmas. Solo la ciencia puede prevenir y destruir tales mitos y dogmas médicos(AU)

The possibility of operating patients with hand conditions under local anesthesia, with lidocaine and epinephrine, using WALANT technique caused a revolution in hand surgery, which made life easier for patients and lowered the costs of hospital services. Surgeons need to be aware of the possibilities and history of WALANT technique. The objective was to identify the origins of the rise and fall of the myth and dogma of the prohibition of adrenaline in anesthetic finger blocks. A critical analysis of the main texts of the articles and books on the use of epinephrine in finger anesthesia was carried out. The conception of the myth of banning the use of epinephrine in anesthetic finger blocks occurred due to misinterpretation of reports of necrosis occurring, which were not actually caused by epinephrine. That myth influenced the appearance of a dogma. The history of the use of epinephrine in anesthetic finger blocks demonstrates that superficial and misleading interpretations of clinical complications published as case reports can breed myth and dogma. Only science can prevent and destroy such medical myths and dogmas(AU)