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Opioid agonist treatment (OAT) clients frequently bear costs associated with their treatment, including dosing fees. This study aimed to explore the financial and social impact of dosing fees upon clients.Cross-sectional survey of people who use opioids regularly (N = 402) between December 2017 and March 2018, conducted in Australia. Dosing fees were calculated and expressed as percentage of income, by OAT type. Consequences and strategies for difficulties making payments were examined as proportions.A total of N = 360 participants had ever been in OAT and N = 245 participants currently engaged in OAT reported data on dosing fees, of them 53% (n = 129) reported paying dosing fees. Compared to clients with high levels of dosing supervision, those with moderate or low levels of supervision were more likely to pay dosing fees. The median 28-day dosing fee was AUD$110 (interquartile range AUD$80); median 28-day income was AUD$1520 (interquartile range AUD$700). For those who paid dosing fees, the fee comprised10% of total monthly income for 70% of participants; however, 23% of participants paid fees comprising 10% to 20%, and 7% of participants paid fees comprising 20% or more of monthly income. Among those that had ever been in OAT, 72% experienced difficulties in paying treatment costs; 36% left treatment earlier than intended and 25% had been excluded due to payment difficulties.Negative consequences of treatment costs to clients, particularly dosing fees, are evident. These costs impact treatment access and retention that may negatively impact clients' physical health, mental health and social wellbeing.

Introduction The Australian guidelines to reduce health risks from drinking alcohol were released in 2020 by the National Health and Medical Research Council. Based on the latest evidence, the guidelines provide advice on how to keep the risk of harm from alcohol low. They refer to an Australian standard drink (10 g ethanol). Recommendations •Guideline 1: To reduce the risk of harm from alcohol-related disease or injury, healthy men and women should drink no more than ten standard drinks a week and no more than four standard drinks on any one day. The less you drink, the lower your risk of harm from alcohol. •Guideline 2: To reduce the risk of injury and other harms to health, children and people under 18 years of age should not drink alcohol. •Guideline 3: To prevent harm from alcohol to their unborn child, women who are pregnant or planning a pregnancy should not drink alcohol. For women who are breastfeeding, not drinking alcohol is safest for their baby. Changes as result of the guideline The recommended limit for healthy adults changed from two standard drinks per day (effectively 14 per week) to ten per week. The new guideline states that the less you drink, the lower your risk of harm from alcohol. The recommended maximum on any one day remains four drinks (clarified from previously "per drinking occasion"). Guidance is clearer for pregnancy and breastfeeding, and for people aged less than 18 years, recommending not drinking.

Background and aims Not all people experiencing opioid dependence benefit from oral opioid agonist treatment. The aim of this study was to examine perceptions of (supervised) injectable opioid agonist treatment (iOAT) (described as ‘an opioid similar to heroin self‐injected at a clinic several times a day’) among people who regularly use opioids and determine how common iOAT eligibility criteria accord with interest in iOAT. Design Cross‐sectional survey Setting Sydney, Melbourne and Hobart, Australia. Participants A total of 344 people (63% male) who use opioids regularly and had ever injected opioids, interviewed December 2017–March 2018. The mean age of participants was 41.5 years [standard deviation (SD) = 8.5]. Measurements Primary outcome measures were interest in iOAT, factors associated with interest and the proportion of participants who would be eligible using common criteria from trials and guidelines. We examined willingness to travel for iOAT, medication preferences and perspectives on whom should receive iOAT. Findings Overall, 53% of participants (n = 182) believed that iOAT would be a good treatment option for them. Participants who believed that iOAT was a good treatment option for them were more likely to be male [adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) = 1.10–2.82], have used heroin in the past month (aOR = 6.03, 95% CI = 2.86–12.71), currently regularly inject opioids (aOR = 1.84, 95% CI = 1.16–2.91) and have met ICD‐10 criteria for opioid dependence (aOR = 3.46, 95% CI = 1.65–7.24). Those interested in iOAT had commenced more treatment episodes (aOR =1.06, 95% CI = 1.00–1.12). Among those interested in iOAT (n = 182), 26% (n = 48) met common eligibility criteria for iOAT. Conclusions Interest in injectable opioid agonist treatment does not appear to be universal among people who regularly use opioids. Among study participants who expressed interest in injectable opioid agonist treatment, most did not meet common eligibility criteria.

INTRODUCTION AND AIMS Quality of life (QOL) is a relevant and quantifiable outcome of drug dependence treatment. We assessed health-related QOL for people released from three centre-based compulsory treatment (CCT) centres in Vietnam, using the EQ-5D. The study aimed to examine the prognostic value of health-related QOL in relation to time to relapse to heroin use among the participants. DESIGN AND METHODS Two hundred and eight CCT participants with heroin dependence were interviewed at release, and at 3, 6 and 12 months post-release. Health-related QOL was measured with the EQ-5D. Kaplan-Meier survival models were fitted using Cox modelling to examine the rate, timing and prediction of the number of days to heroin relapse and to examine the predictability of the health-related QOL measures for days to relapse. Relapse was defined as first time of heroin use. RESULTS The study found a substantial relapse rate (85.6%) among participants within 12 months following release from CCT centres; the mean number of days to relapse was 57.7 (SD = 31.6). There was no statistically significant change over time in the mean values of health-related QOL (P = 0.11). While the total index score (across the five pre-specified EQ-5D domains) did not have a significant effect in predicting cumulative relapse, lower scores on the Visual Analogue Scale of the EQ-5D were significantly (P

Aims To examine perceptions of extended‐release (XR) buprenorphine injections among people who regularly use opioids in Australia. Design Cross‐sectional survey prior to implementation. XR‐buprenorphine was registered in Australia in November 2018. Setting Sydney, Melbourne and Hobart. Participants A total of 402 people who regularly use opioids interviewed December 2017 to March 2018. Measurements Primary outcome concerned the proportion of participants who believed XR‐buprenorphine would be a good treatment option for them, preferred weekly versus monthly injections and perceived advantages/disadvantages of XR‐buprenorphine. Independent variables concerned the demographic characteristics and features of current opioid agonist treatment (OAT; medication‐type, dose, prescriber/dosing setting, unsupervised doses, out‐of‐pocket expenses and travel distance). Findings Sixty‐eight per cent [95% confidence interval (CI) = 63–73%] believed XR‐buprenorphine was a good treatment option for them. They were more likely to report being younger [26–35 versus > 55 years; odds ratio (OR) = 3.16, 95% CI = 1.12–8.89; P = 0.029], being female (OR = 1.67, 95% CI = 1.04–2.69; P = 0.034)

Background and Aims: There is limited evidence on the relationship between retention in opioid agonist treatment for opioid dependence and characteristics of treatment prescribers. This study estimated retention in buprenorphine and methadone treatment and its relationship with person, treatment, and prescriber characteristics. Design: Retrospective longitudinal study.Setting: New South Wales, Australia.Participants: People entering the opioid agonist treatment program for the first time between August 2001 and December 2015.Measurements: Time in opioid agonist treatment (primary outcome) was modelled using a generalised estimating equation model to estimate associations with person, treatment, and prescriber characteristics. Findings: The impact of medication type on opioid agonist treatment retention reduced over time; risk of leaving treatment when on buprenorphine compared with methadone was higher among those that entered treatment earlier (e.g. 2001-2003: OR 1.59, 95% CI 1.44-1.74) and lowest among those that entered most recently (2013-2015: OR 1.24, 95% CI 1.12-1.37). In adjusted analyses, risk of leaving was reduced among people whose prescriber had longer tenure of prescribing (e.g. 3 versus 8 years: OR 0.94, 95% CI 0.93-0.95) compared with prescribers with shorter tenure. Aboriginal and Torres Strait Islander people, being of younger age, past-year psychosis disorder, and having been convicted of more criminal charges in the year prior to treatment entry were associated with increased risk of leaving treatment. Conclusion: In New South Wales, Australia, retention in buprenorphine treatment for opioid dependence, compared with methadone, has improved over time since its introduction in 2001. Opioid agonist treatment (OAT) retention is affected not only by characteristics of the person and his or her treatment, but also of the prescriber, with those of longer prescribing tenure associated with increased retention of people in OAT.

Background Disadvantage and transgenerational trauma contribute to Aboriginal and Torres Strait Islander (Indigenous) Australians being more likely to experience adverse health consequences from alcohol and other drug use than non-Indigenous peoples. Addressing these health inequities requires local monitoring of alcohol and other drug use. While culturally appropriate methods for measuring drinking patterns among Indigenous Australians have been established, no similar methods are available for measuring other drug use patterns (amount and frequency of consumption). This paper describes a protocol for creating and validating a tablet-based survey for alcohol and other drugs (“The Drug Survey App”). Methods The Drug Survey App will be co-designed with stakeholders including Indigenous Australian health professionals, addiction specialists, community leaders, and researchers. The App will allow participants to describe their drug use flexibly with an interactive, visual interface. The validity of estimated consumption patterns, and risk assessments will be tested against those made in clinical interviews conducted by Indigenous Australian health professionals. We will then trial the App as a population survey tool by using the App to determine the prevalence of substance use in two Indigenous communities. Discussion The App could empower Indigenous Australian communities to conduct independent research that informs local prevention and treatment efforts.

Background Opioid agonist treatment (OAT) is an effective intervention for opioid dependence. Extended-release buprenorphine injections (BUP-XR) may have additional potential benefits over sublingual buprenorphine. This single-arm trial evaluated outcomes among people receiving 48 weeks of BUP-XR in diverse community healthcare settings in Australia, permitting examination of outcomes when BUP-XR is delivered in standard practice. Methods Participants were recruited from a network of specialist public drug treatment services, primary care and some private practices in three states. Following a minimum 7 days on 8–32 mg of sublingual buprenorphine (±naloxone), participants received monthly subcutaneous BUP-XR injections administered by a healthcare practitioner and completed monthly research interviews. The primary endpoint was retention in treatment at 48 weeks. Findings Participants (n = 100) were 28% women, mean age 44 years with a long history of OAT (median 5.8 years); heroin was the most common opioid of concern (58%). Treatment retention at 24 and 48 weeks was 86% and 75%, respectively. Participants with past-month injecting drug use (OR 0.23; 95%CI: 0.09–0.61) or heroin use (OR 0.23; 95%CI: 0.08–0.65) at baseline had lower odds of being retained in treatment to 48 weeks. Reductions in multiple forms of extra-medical drug use were observed. Improvements in quality of life, participation in employment, and treatment satisfaction measures were also observed. Interpretation This real-world implementation study of BUP-XR demonstrated high retention and treatment satisfaction. This study provides important additional data on the uptake and experience of clients, with relevance for policy makers, health service planners, administrators, and practitioners. Funding Indivior. Trial registration ClinicalTrials.gov Identifier: NCT03809143

Summary We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

Psychoactive substances – chemical compounds which can alter a person’s mood, thoughts, and behaviors may be liable to misuse and cause addiction. Internationally, many strategies have been implemented in order to limit the supply and demand of illegal substances, with a wide variation at the country level. Thailand is an upper-middle income country in Southeast Asia. Since 2015, Thai authorities and policymakers have instituted many changes to the legal controls on illegal drugs. The aim of this review was to summarise the history of drug control and regulation in Thailand, focusing on opioids (including Kratom), methamphetamines and cannabis, and the outcome of recent strategies. Recent measures towards decriminalising substance use disorders are also discussed.

INTRODUCTION This study aimed to gather a range of opinions, including those of affected people (consumers, concerned others) to identify clinical research priorities for methamphetamine and emerging drugs of concern in Australia, to guide the work of the National Centre for Clinical Research on Emerging Drugs (NCCRED). METHODS A priority setting study was conducted (February-March 2019) in four phases: online stakeholder survey, thematic analysis of responses, rapid literature review, expert panel ranking of priorities against predetermined criteria. RESULTS Forty-seven respondents completed the survey, including people identifying as one or more of: researcher (53%, n = 25), clinician (45%; n = 21), family/friend/caregiver of someone who uses methamphetamine/emerging drugs (15%, n = 7) and consumer of methamphetamine/emerging drugs (13%, n = 6). Expert panel, evidence-informed top-ranked clinical research priorities for methamphetamine were: strategies to overcome barriers to intervention uptake, pilot medication trials for adults seeking treatment, and communication strategies regarding evidence-based treatments. For emerging drugs of concern, top-ranked priorities were: piloting community-located drug checking, feasibility of social media/other opportunities to alert consumers of emerging risks, GHB overdose and withdrawal management, and impacts of an early warning information system on reducing harms. DISCUSSION AND CONCLUSIONS We demonstrate feasibility of a structured, collaborative clinical research priority setting process. Results have informed the establishment of NCCRED; using the identified priorities to guide seed funding, fellowships/scholarships and research programs. Broader uptake of this methodology by policymakers/research funders would assist to embed areas of concern identified by affected communities and other stakeholders in research prioritisation.

Approximately 29.5 million people, or 0.6% of the global adult population, have a drug use disorder (United Nations Office on Drugs and Crime (UNODC), World Drug Report (ISBN: 978–92–1-148291-1, eISBN: 978–92–1-060623-3, United Nations publication, Sales No. E.17.XI.6), 2017). People who use illicit drugs often do not disclose their drug use due to the illegality and stigma associated with that use. The opportunistic nature of brief interventions for illicit drug use makes therapeutic engagement critical to effectiveness. In many settings time will be limited so that brief interventions also need to be efficient.

Background To quantify the extent to which methamphetamine use is associated with increases in crime net of any premorbid risk of criminality among people who use the drug. Methods Four one-month data panels from 469 participants dependent on methamphetamine were drawn from the MATES cohort (N = 501). Odds ratios for within-person effects were extracted from a random intercept logistic regression model for crime during periods of methamphetamine use compared to no use. Effects were adjusted for time-varying measures of age, other substance use, and socio-economic disadvantage (income, unemployment and unstable accommodation). Involvement in crime (property crime, drug dealing, fraud, violent crime) and days of methamphetamine in the past month were assessed using the Opiate Treatment Index. Results Crime was more likely during months when participants used methamphetamine compared to when they did not (OR 13.2 95% CI 8.5–20.6; AOR 4.7 95% CI 2.8–8.0), this reflecting more property crime (OR 10.6 95% CI 6.3–18.0; AOR 5.5 95% CI 2.8–10.8), violent crime (OR 8.2 95% CI 4.2–15.9; AOR 3.4 95% CI 1.5–8.0), fraud (OR 3.4, 95% CI 2.0–5.8; AOR 1.7 95% CI 0.8–3.3) and dealing drugs (OR 18.2 95% CI 10.2–32.5; AOR 5.9 95% CI 3.0–11.9), although the adjusted relationship for fraud was not significant. Effects were dose related. Conclusions The use of methamphetamine was associated with significant increases in crime beyond premorbid risk for criminality. Crime is a likely social consequence of methamphetamine use and efforts are needed to reduce this impact.

AimsWe assessed how opioid agonist treatment (OAT) for opioid use disorder (OUD), specifically methadone andbuprenorphine, including buprenorphine-naloxone, is delivered in routine clinical practice, with a focus on factors thataffect access to and delivery of these services. The aims of this review were to summarize eligibility criteria for entry toOAT, doses in routine clinical practice, access to and eligibility for unsupervised dosing and urine drug screening practicesin OAT programs globally.Methods We completed searches of PubMed, Embase, and grey literature databases forcross-sectional or observational cohort studies of OAT using either methadone or buprenorphine. Dose data extracted fromeligible studies were compared with guidelines provided by WHO.Results We found 140 reports from 41 countries thatcontained data for at least one of the relevant indicators. A diagnosis of opioid dependence or opioid use disorder was themost common eligibility requirement for OAT (13 or 17 countries). Reported mean or median doses for methadoneranged from 16–131 mg whereas range for buprenorphine was 2.5–19 mg. Access to unsupervised dosing under someconditions was reported in 18 of 27 countries. Frequency of regular urine drug screenings (UDS) ranged from several timesa week to eight times per year (methadone) or as clinically indicated.ConclusionsOpioid agonist treatment practices,including doses prescribed, vary greatly both within and across countries. Of particular concern is the persistence of lowerdose prescribing practices, in which patients may be prescribed doses below those proven to yield significant clinicalbenefits

In Vietnam, like many countries in East and Southeast Asia, the government has invested heavily in center-based compulsory treatment (CCT) as the mainstay demand reduction strategy for illicit drug use. This approach has been criticised on human rights grounds. Meanwhile, community-based voluntary methadone maintenance treatment (MMT) has been implemented for nearly a decade with promising results. To date, there have been no comparative Vietnamese studies of these approaches.The study, involving 208 CCT participants and 384 MMT participants with heroin dependence, was a combined retrospective and prospective observational study conducted over three years between 2012 and 2014 (with data at five time-points). The primary outcome was: self-report heroin use (confirmed by urinalysis). The four secondary outcomes were: illegal behaviours, overdose, blood-borne virus (BBV) risk behaviours, and monthly drug expenditure. Mixed effects regression analyses, which took into account baseline differences between the groups, were used to analyse the data. This study is registered with ClinicalTrials.gov, number NCT03071315.The study found MMT was more strongly associated with four outcome measures compared to CCT (reduction in heroin use (β = 3.39, SE = 0.31, p .0001) (equivalent to an odds ratio of 29.67 (95% CI 21.76-40.45)), reduction in illegal behaviours (β = 0.94, SE = 0.39, p .0001), (equivalent to an odds ratio of 2.56 (95% CI 1.79-3.78)), reduction in BBV risk behaviours (β = 1.08, SE = 0.17, p .0001), (equivalent to an odds ratio of 2.94 (95% CI 2.48-3.49)), and reduction in monthly drug spending (β = -VND1,515,200 (equivalent to US$72.00), SE = VND452,900, p .0001)). The analyses did not support the hypothesis that MMT was associated with better outcomes pertaining to overdose (β = -0.27, SE = 0.30, p = .62), probably due to the infrequency of these self-reported events.Our observational study suggests that MMT is associated with greater reductions in heroin use, BBV risk behaviours, drug-related illegal behaviours, and monthly drug spending compared with CCT. In the context that the CCT approach has been criticized for human rights violations, this study provides evidence to support the scale up of MMT and the transition of CCT to voluntary community based treatment.

Aim To evaluate the feasibility of conducting a study of structured brief intervention (BI) for reducing problem alcohol use among individuals who experienced earthquake. Methods Following the Wenchuan earthquake, 1336 clients from 18 local hospitals were invited to complete the Alcohol Use Disorders Identification Test (AUDIT). Of those, 239 individuals (AUDIT score of greater than or equal to 7) were included in the study. The participants from intervention village hospitals who were assigned to the BI group (n = 118) received a structured BI lasting 15-30 min plus general health education. The participants from the control village hospitals were assigned to the control group (n = 121) only received general health education. Baseline and post-intervention assessments at 12 weeks were conducted using the AUDIT, Substance Abuse Knowledge Scale (SAKS), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS) and General Well-being Schedule. Results At 3 months follow-up, the BI group had reduced scores on AUDIT (F = 65.84; P < 0.001) and increased on SAKS (F = 44.45; P < 0.001), but the control group had increased scores on SAS (F = 10.76; P = 0.001) and SDS (F = 18.43; P < 0.001) compared with baseline. BI group showed more decreases for AUDIT scores (group × time effect, F = 34.8; P < 0.001), and had mores increases for SAKS scores (group × time effect, F = 15.7; P < 0.001) compared with control group. Conclusion The study demonstrated the feasibility of a study of BI in problem alcohol users who experienced traumatic events. Further research need to be done to test the effectiveness of BI over a longer period of time, and provide evidence in support of BI as an effective technique in China.

Immune parameters are elevated in psychosis, but it is unclear whether alterations are homogenous across patients or heterogeneity exists, consistent with the hypothesis that immune alterations are specific to a subgroup of patients. To address this, we examine whether antipsychotic-naïve first-episode psychosis patients exhibit greater variability in blood cytokines, C-reactive protein, and white cell counts compared with controls, and if group mean differences persist after adjusting for skewed data and potential confounds. Databases were searched for studies reporting levels of peripheral immune parameters. Means and variances were extracted and analyzed using multivariate meta-analysis of mean and variability of differences. Outcomes were (1) variability in patients relative to controls, indexed by variability ratio (VR) and coefficient of variation ratio (CVR); (2) mean differences indexed by Hedges g; (3) Modal distribution of raw immune parameter data using Hartigan's unimodality dip test. Thirty-five studies reporting on 1263 patients and 1470 controls were included. Variability of interleukin-6 (IL6) (VR = 0.19), tumor necrosis factor-α (TNFα) (VR = 0.36), interleukin-1β (VR = 0.35), interleukin-4 (VR = 0.55), and interleukin-8 (VR = 0.28) was reduced in patients. Results persisted for IL6 and IL8 after mean-scaling. Ninety-four percent and one hundred percent of raw data were unimodally distributed in psychosis and controls, respectively. Mean levels of IL6 (g = 0.62), TNFα (g = 0.56), interferon-γ (IFNγ) (g = 0.32), transforming growth factor-β (g = 0.53), and interleukin-17 (IL17) (g = 0.48) were elevated in psychosis. Sensitivity analyses indicated this is unlikely explained by confounders for IL6, IFNγ, and IL17. These findings show elevated cytokines in psychosis after accounting for confounds, and that the hypothesis of an immune subgroup is not supported by the variability or modal distribution.

Context and PurposeMeasurement‐based care (MBC) is an evidence‐based health‐care practice in which indicators of disease are tracked to inform clinical actions, provide feedback to patients and improve outcomes. The current opioid crisis in multiple countries provides a pressing rationale for adopting a basic MBC approach for opioid use disorder (OUD) using DSM‐5 to increase treatment retention and effectiveness.ProposalTo stimulate debate, we propose a basic MBC approach using the 11 symptoms of OUD (DSM‐5) to inform the delivery of medications for opioid use disorder (MOUD; including methadone, buprenorphine and naltrexone) and their evaluation in office‐based primary care and specialist clinics. Key features of a basic MBC approach for OUD using DSM‐5 are described, with an illustration of how clinical actions are guided and outcomes communicated. For core treatment tasks, we propose that craving and drug use response to MOUD should be assessed after 2 weeks, and OUD remission status should be evaluated at 3, 6 and 12 months (and exit from MOUD treatment) and beyond. Each of the 11 DSM‐5 symptoms of OUD should be discussed with the patient to develop a case formulation and guide selection of adjunctive psychological interventions, supplemented with information on substance use, and optionally extended with information from other clinical instruments. A patient‐reported outcome measure should be recorded and discussed at each remission assessment.ConclusionsMBC can be used to tailor and adapt MOUD treatment to increase engagement, retention and effectiveness. MBC practice principles can help promote patient‐centred care in OUD, personalized addiction therapeutics and facilitate communication of outcomes.

In Vietnam, two dominant approaches for heroin treatment are center-based compulsory rehabilitation (CCT), funded by the Vietnamese government and community-based voluntary methadone maintenance treatment (MMT), funded primarily by international donors. Recent reduction in international funding requires more efficient allocation of government funding for public health programs. A cost-effectiveness analysis comparing two approaches provides a useful source of evidence to inform the government about funding reallocation.The study was a combined retrospective and prospective, non-randomized cohort comparison over three years of CCT and MMT in Vietnam, conducted between 2012 and 2014, involving 208 CCT participants and 384 MMT participants with heroin dependence. The primary end-point was drug-free days over three years. Total costs, including both program and participant personal costs were measured and cost-effectiveness compared. Mixed effects regression analyses were used to analyze effectiveness data and non-parametric bootstrapping method was used to compare cost-effectiveness.Over three years, MMT costed on average VND85.73 million (US$4108) less than CCT (95% CI: -VND76.88 million, -VND94.59 million). On average, a MMT participant had 344.20 more drug-free days compared to a CCT participant (p0.001). The incremental cost-effectiveness ratio for MMT was -VND0.25 million (US$11.99) (95% CI: -VND0.34 million, -VND0.19 million) per drug-free day suggesting MMT is the more cost effective alternative.Compared to CCT, MMT is both less expensive and more effective in achieving drug-free days. If the government of Vietnam invests in MMT instead of CCT, it is potentially a cost-saving strategy for reducing illicit drug use among heroin dependent individuals.

Objective The aims were to determine: (i) quantity and frequency of same-day use of opioids with benzodiazepines and/or alcohol amongst people who regularly tamper with pharmaceutical opioids; and (ii) socio-demographic, mental health, harms and treatment profile associated with same-day use of high doses. Method The cohort (n = 437) completed a retrospective 7-day diary detailing opioid, benzodiazepine, and alcohol intake. Oral morphine equivalent (OME) units and diazepam equivalent units (DEU) were calculated, with >200 mg OME, >40 mg DEU and >4 standard alcoholic drinks (each 10 g alcohol) considered a “high dose”. Results One-half (47%) exclusively consumed opioids without benzodiazepines/alcohol; 26% had days of opioid use with and without benzodiazepines/alcohol; and 26% always used opioids and benzodiazepines/alcohol. Same-day use of opioids with benzodiazepines/alcohol typically occurred on 1–3 days in the past week. Six in ten (61%) participants reported high dose opioid use on at least one day; one in five (20%) reported high dose opioid and high dose benzodiazepine/alcohol use on at least one day. The latter group were more likely to use prescribed opioid substitution therapy, often alongside diverted pharmaceutical opioids. Socio-demographic and clinical profiles did not vary according to high dose opioid, alcohol and benzodiazepine use, and there was no association with harms. Conclusions Same-day use of opioids with benzodiazepines/alcohol, and high dose combinations, are common amongst people who tamper with pharmaceutical opioids. Assessment of concomitant benzodiazepine/alcohol use during opioid therapy, implementation of real-time prescription monitoring systems, and research to clarify upper safe limits for polydrug depressant use, are potential implications.

This study examined correlates of transient versus persistent psychotic symptoms among people dependent on methamphetamine. A longitudinal prospective cohort study of dependent methamphetamine users who did not meet DSM-IV criteria for lifetime schizophrenia or mania. Four non-contiguous one-month observation periods were used to identify participants who had a) no psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient psychotic symptoms, n=85); and, (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent psychotic symptoms, n=37). Psychotic symptoms were defined as a score of 4 or greater on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content. Relative no psychotic symptoms, both transient and persistent psychotic symptoms were associated with childhood conduct disorder and comorbid anxiety disorders. Earlier onset methamphetamine use and being male were more specifically related to transient psychotic symptoms, while a family history of a primary psychotic disorder and comorbid major depression were specifically related to persistent psychotic symptoms. We conclude that there are overlapping but also distinct clinical correlates of transient versus persistent psychotic symptoms, suggesting potentially heterogeneous etiological pathways underpinning the psychotic phenomena seen amongst people who use methamphetamine.

Background To examine, among a cohort of opioid dependent people with a history of opioid agonist treatment (OAT), the frequency and incidence rates of non-fatal overdose (NFOD) hospital separations over time, by age and sex. Methods Retrospective cohort study of people with a history of OAT using state-wide linked New South Wales (NSW) data. The incidence of NFOD hospital separations involving an opioid, sedative, stimulant or alcohol was defined according to the singular or combination of poisoning/toxic effect using ICD-10-AM codes. Crude incidence rates were calculated by gender, age group and calendar year. Results There were 31.8 (31.3–32.3) NFOD per 1,000 person-years (PY). Opioid NFOD incidence was higher in women than men: incidence rate ratio (IRR) 1.11 per 1,000PY; 95 %CI: [1.06–1.17]; women had higher sedative NFOD rates than men, IRR 1.27 per 1,000PY [1.21–1.34]. Participants ≤25 years, 26-30yrs, and 31-35yrs had higher incidence of opioid NFOD compared to 46+yrs, with IRRs of: 1.45 per 1,000PY; [1.32–1.59]; 1.20 per 1,000PY; [1.11–1.30] and 1.22 per 1,000PY; [1.13–1.32], respectively. Between 2006-7 and 2016-17, the cohort accounted for 19 % of NSW opioid NFOD episodes, 12 % of sedative, 14 % of stimulant and 5 % of acute alcohol-related NFOD. Conclusions Hospital stays due to NFOD are a relatively frequent occurrence among opioid-dependent people. There are clear differences in rates and substances involved by sex, age and over time. Evidence-based interventions that prevent overdose among people who are opioid dependent need to be delivered to scale, including widespread community provision of naloxone.

7547 Background: Allogeneic Stem Cell Transplant (alloSCT) continues to be the optimal consolidation strategy for many patients with AML; cytogenetic and molecular abnormalities are known predictors of post-transplant outcomes. There is increasing evidence that Molecular Minimal Residual Disease (MMRD) following induction has important prognostic implications and its value in the prediction of post-transplant relapse continues to be elucidated. We aim to evaluate the impact of genetics and pre-transplant MMRD on clinical outcomes following alloSCT. Methods: We retrospectively evaluated eighty-nine patients, ≥18 years with a diagnosis of AML in complete morphologic remission (i.e. < 5% BM blasts by morphologic assessment) who received alloSCT between 01/2012-05/2018 at the University of Miami and for whom cytogenetic and comprehensive molecular data was available prior to transplantation. Patients were stratified into favorable, intermediate and poor-risk categories based on 2017 ELN criteria. MMRD was defined as persistent leukemia-specific mutations prior to transplantation (i.e. NPM1, FLT3, CEBPA, IDH1-2, RUNX1 and TP53). Persistence of DTA mutations (DNMT3A, TET2 and ASXL1) was not considered MMRD, patients with unavailable cytogenetic/molecular data at diagnosis were excluded. Results: Seventy-four (83%) patients were transplanted in CR1, myeloablative conditioning was used in 72% of patients. Two-year OS and LFS were 69.4% and 78.2%, respectively. Stratification by ELN criteria resulted in prognostic separation for patients transplanted in CR1: 2-year OS for favorable (87%), intermediate (68%) and adverse risk (51%) patients (p = 0.0417). The presence of MMRD was the strongest predictor of post-transplant outcomes for the whole cohort with 2-year OS and LFS of 29.4% and 37.1% (HR 5.45 [95%CI 2.43-12.3] p = 0.0001; HR 12.4 [95%CI: 3.76 to 39.8] p = 0.0001); respectively. Subgroup analysis confirmed that MMRD was associated with significantly inferior LFS for IM/favorable and adverse risk patients (HR: 6.76 [95% CI 1.12 to 40.9], p = 0.038). Conclusions: Pre-transplant MMRD was the most important prognostic factor for relapse and survival in our cohort of AML patients undergoing alloSCT. Correlation of MMRD with other transplant variables such as conditioning intensity, MRD status by MFC and the impact of pre-emptive/therapeutic strategies in high-risk patients continues to be explored.

Background Cannabis is the most prevalent illicit drug in the world. Demand for treatment of cannabis use disorders is increasing. There are currently no pharmacotherapies approved for treatment of cannabis use disorders. Objectives To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or supportive care for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to 4 March 2014), MEDLINE (to week 3 February 2014), EMBASE (to 3 March 2014) and PsycINFO (to week 4 February 2014). We also searched reference lists of articles, electronic sources of ongoing trials and conference proceedings, and contacted selected researchers active in the area. Selection criteria Randomised and quasi-randomised controlled trials involving the use of medications to reduce the symptoms and signs of cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in participants diagnosed as cannabis dependent or who were likely to be dependent. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors assessed studies for inclusion and extracted data. All review authors confirmed the inclusion decisions and the overall process. Main results We included 14 randomised controlled trials involving 958 participants. For 10 studies the average age was 33 years; two studies targeted young people; and age data were not available for two studies. Approximately 80% of study participants were male. The studies were at low risk of selection, performance, detection and selective outcome reporting bias. Three studies were at risk of attrition bias. All studies involved comparison of active medication and placebo. The medications included preparations containing tetrahydrocannabinol (THC) (two studies), selective serotonin reuptake inhibitor (SSRI) antidepressants (two studies), mixed action antidepressants (three studies), anticonvulsants and mood stabilisers (three studies), an atypical antidepressant (two studies), an anxiolytic (one study), a norepinephrine reuptake inhibitor (one study) and a glutamatergic modulator (one study). One study examined more than one medication. Diversity in the medications and the outcomes reported limited the extent that analysis was possible. Insufficient data were available to assess the utility of most of the medications to promote cannabis abstinence at the end of treatment. There was moderate quality evidence that completion of treatment was more likely with preparations containing THC compared to placebo (RR 1.29, 95% CI 1.08 to 1.55; 2 studies, 207 participants, P = 0.006). There was some evidence that treatment with preparations containing THC was associated with reduced cannabis withdrawal symptoms and craving, but this latter outcome could not be quantified. For mixed action antidepressants compared with placebo (2 studies, 179 participants) there was very low quality evidence on the likelihood of abstinence from cannabis at the end of follow-up (RR 0.82, 95% CI 0.12 to 5.41), and moderate quality evidence on the likelihood of treatment completion (RR 0.93, 95% CI 0.71 to 1.21). For this same outcome there was very low quality evidence for the effects of SSRI antidepressants (RR 0.82, 95% CI 0.44 to 1.53; 2 studies, 122 participants), anticonvulsants and mood stabilisers (RR 0.78, 95% CI 0.42 to 1.46; 2 studies, 75 participants), and the atypical antidepressant, bupropion (RR 1.06, 95% CI 0.67 to 1.67; 2 studies, 92 participants). Available evidence on gabapentin (anticonvulsant) and N-acetylcysteine (glutamatergic modulator) was insufficient for quantitative estimates of their effectiveness, but these medications may be worth further investigation. Authors' conclusions There is incomplete evidence for all of the pharmacotherapies investigated, and for many of the outcomes the quality was downgraded due to small sample sizes, inconsistency and risk of attrition bias. The quantitative analyses that were possible, combined with general findings of the studies reviewed, indicate that SSRI antidepressants, mixed action antidepressants, atypical antidepressants (bupropion), anxiolytics (buspirone) and norepinephrine reuptake inhibitors (atomoxetine) are probably of little value in the treatment of cannabis dependence. Preparations containing THC are of potential value but, given the limited evidence, this application of THC preparations should be considered still experimental. Further studies should compare different preparations of THC, dose and duration of treatment, adjunct medications and therapies. The evidence base for the anticonvulsant gabapentin and the glutamatergic modulator N-acetylcysteine is weak, but these medications are also worth further investigation.

IntroductionNorth America is amid an opioid use epidemic. Opioid agonist treatment (OAT) effectively reduces extramedical opioid use and related harms. As with all pharmacological treatments, there are risks associated with OAT, including fatal overdose. There is a need to better understand risk for adverse outcomes during and after OAT, and for innovative approaches to identifying people at greatest risk of adverse outcomes. The Opioid Agonist Treatment and Safety study aims to address these questions so as to inform the expansion of OAT in the USA.Methods and analysisThis is a retrospective cohort study using linked, routinely collected health data for all people seeking OAT in New South Wales, Australia, between 2001 and 2017. Linked data include hospitalisation, emergency department presentation, mental health diagnoses, incarceration and mortality. We will use standard regression techniques to model the magnitude and risk factors for adverse outcomes (eg, mortality, unplanned hospitalisation and emergency department presentation, and unplanned treatment cessation) during and after OAT, and machine learning approaches to develop a risk-prediction model.Ethics and disseminationThis study has been approved by the Population and Health Services Research Ethics Committee (2018HRE0205). Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data statement.

Aims: This review provides an up-to-date curated source of information on alcohol, tobacco and illicit drug use and their associated mortality and burden of disease. Limitations in the data are also discussed, including how these can be addressed in the future. Methods: Online data sources were identified through expert review. Data were obtained mainly from the World Health Organization, United Nations Office on Drugs and Crime and Institute for Health Metrics and Evaluation. Results: In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8, 0.77, 0.37 and 0.35% for past-year cannabis, amphetamine, opioid and cocaine use, respectively. European regions had the highest prevalence of heavy episodic alcohol use and daily tobacco use. The age-standardized prevalence of alcohol dependence was 843.2 per 100 000 people; for cannabis, opioids, amphetamines and cocaine dependence it was 259.3, 220.4, 86.0 and 52.5 per 100 000 people, respectively. High-income North America region had among the highest rates of cannabis, opioid and cocaine dependence. Attributable disability-adjusted life-years (DALYs) were highest for tobacco smoking (170.9 million DALYs), followed by alcohol (85.0 million) and illicit drugs (27.8 million). Substance-attributable mortality rates were highest for tobacco smoking (110.7 deaths per 100 000 people), followed by alcohol and illicit drugs (33.0 and 6.9 deaths per 100 000 people, respectively). Attributable age-standardized mortality rates and DALYs for alcohol and illicit drugs were highest in eastern Europe; attributable age-standardized tobacco mortality rates and DALYs were highest in Oceania. Conclusions: In 2015 alcohol use and tobacco smoking use between them cost the human population more than a quarter of a billion disability-adjusted life years, with illicit drugs costing further tens of millions. Europeans suffered proportionately more, but in absolute terms the mortality rate was greatest in low- and middle-income countries with large populations and where the quality of data was more limited. Better standardized and rigorous methods for data collection, collation and reporting are needed to assess more accurately the geographical and temporal trends in substance use and its disease burden.

Supplemental Digital Content is available in the text, Introduction and Aims: Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50 mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine. Design and Methods: A multisite prospective cohort study. Participants were patients who transferred from methadone to buprenorphine-naloxone at 1 of 4 specialist addiction centers in Australia and New Zealand. Clinicians were trained in the guidelines, and medical records were reviewed to examine process (eg, transfer setting, doses, and guideline adherence) and safety (precipitated withdrawal) measures. Participants completed research interviews before and after transfer—assessing changes in substance use, health outcomes, and side effects. Results: In all, 33 participants underwent transfer, 9 from low methadone doses (50 mg). The majority of high-dose transfers occurred in inpatient settings. There was reasonable guideline adherence, and no complications identified in the low and medium-dose transfers. Three high-dose transfers (20%) experienced precipitated withdrawal, and 7/33 participants (21%) returned to methadone within 1 week of attempted transfer. Discussions and Conclusions: Transfer is feasible in outpatient settings for those transferring from methadone doses below 50 mg; however, inpatient settings and specialist supervision is recommended for higher-dose transfers. The Australian clinical guidelines appear safe and feasible, although further research is required to optimize high-dose transfer procedures.

This study explored the experience and self-reported changes in health behaviours of people in a primary healthcare setting who received a brief intervention (BI) for illicit drugs linked to the Alcohol Smoking Substance Involvement Screening Test (ASSIST). Eighty-two participants from a sexual health clinic in Adelaide, South Australia, who were involved in a randomised controlled trial investigating the effectiveness of an ASSIST-linked BI delivered at baseline, were re-interviewed 3 months later and were administered a semi-structured questionnaire designed to elicit participant perspectives on the BI. Overall, participants’ comments were positive, with 78% reporting that the BI had some influence on their drug-taking behaviour; 72% reporting they had attempted to reduce drug use. Their comments highlighted several ways in which the BI helped them become ‘aware’ of the potential risks of using, the risks of continued substance use, the benefits of stopping or cutting down substance use and the strategies they used to change their behaviour. A smaller proportion of participants reported that the BI had no influence. These results indicate the ASSIST-linked BI is a brief, simple-to-administer intervention that provides participants with an opportunity to voluntarily and successfully enter into an intentional process of change.