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Abstract Background There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. Methods This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18–65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. Discussion This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Abstract Objective To investigate the associations between low education and risk of mental disorders, substance use disorders and self‐harm in different age‐groups. Methods All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed‐up for these disorders in health care registers 2001–2016. Subjects were stratified into four age‐groups: 10–18, 19–27, 28–50, and 51–70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models. Results Low education increased the risk of substance use disorders and self‐harm in all age‐groups. Males aged 10–18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19–27 years had increased risks of anxiety and depression, and those aged 28–50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0–1.3) for bipolar disorder to 5.4 (95% CIs 5.1–5.7) for drug use disorder. Females aged 51–70 years had increased risks of schizophrenia and autism. Conclusion Low education is associated with risk of most mental disorders, substance use disorders and self‐harm in all age‐groups, but especially among those aged 28–50 years.

Introduction Low back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines.Methods and analysis This is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient–participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient–participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned.Ethics and dissemination The trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publications in journals, media and conference presentations.Trial registration number ACTRN12622001505796.

Abstract Objectives We aimed to develop a Service Capacity Index for Substance Use Disorders (SCI‐SUD) that would reflect the capacity of national health systems to provide treatment for alcohol and drug use disorders, in terms of the proportion of available service elements in a given country from a theoretical maximum. Methods Data were collected through the WHO Global Survey on Progress with Sustainable Development Goals (SDG) Health Target 3.5, conducted between December 2019 and July 2020 to produce the SCI‐SUD, based on 378 variables overall. Results The SCI‐SUD was directly derived for 145 countries. We used multiple imputation to produce comparable SCI‐SUD estimates for countries that did not submit data (40 countries) or had very high level of missingness (9 countries). The final SCI‐SUD demonstrates considerable consistency and internal stability and is strongly associated with the macro‐level economic, healthcare‐related and epidemiologic (such as prevalence rates) variables. Conclusion The presented methodology represents a step forward in monitoring the global situation in regard to the development of treatment systems for SU disorders, however, further work is warranted to improve the external validity of the measure (e.g., in‐depth data generation in countries) and ensure its feasibility for regular reporting (e.g., reducing the number of variables).

Abstract Background Chronic non-cancer pain (CNCP) is complex and often requires multimodal management comprising of both pharmacological and non-pharmacological treatments. To inform delivery of CNCP management, it is important to understand how current health services providing non-pharmacological treatments are accessed by exploring the experiences of people attempting to access services. In doing so, this study sought to explore the underlying drivers of service access barriers. Methods This study explored the experiences of Australians accessing services for CNCP using semi-structured telephone interviews undertaken between 01 October 2020 and 31 March 2021. Thematic analysis was guided by Levesque et al.’s 2013 conceptual framework of access to health care, with emerging themes mapped to five dimensions of accessibility and corresponding abilities of consumers: Approachability/Ability to perceive; Acceptability/Ability to seek; Availability and Accommodation/Ability to reach; Affordability/Ability to pay; and Appropriateness/Ability to engage. Results The 26 participants (aged 24–78 years, 22 female) reported accessing a range of services including general practitioners (GP), allied health services, and specialised pain clinics, for a variety of conditions. Three themes were mapped to accessibility dimensions (in brackets): ‘GP as guide or gatekeeper’ (Approachability); ‘Outside of my control’ (Availability and Accommodation; Affordability); and ‘Services aren’t always good enough’ (Appropriateness). A fourth identified theme illustrated how participants responded to encountering these barriers: ‘Leading my own pain management’. Participant experiences suggest problems with the translation of contemporary pain management principles into practice, including continued application of biomedical health models as opposed to the biopsychosocial model, and demonstrate systemic issues with service delivery, including a lack of benchmarking of specialised services. Conclusions The identified themes highlight several evidence-to-practice gaps in the delivery of health services for people with CNCP in Australia. To address these gaps, there is a need for improved clinician training, increased investment in specialised pain services, and development of clear primary care pathways for CNCP management for evidence-based multimodal pain management to be accessible and equitable.

Abstract Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.

Purpose The POPPY II cohort is an Australian state-based cohort linking data for a population of individuals prescribed opioid medicines, constructed to allow a robust examination of the long-term patterns and outcomes of prescription opioid use.Participants The cohort includes 3 569 433 adult New South Wales residents who initiated a subsidised prescription opioid medicine between 2003 and 2018, identified through pharmacy dispensing data (Australian Pharmaceutical Benefits Scheme) and linked to 10 national and state datasets and registries including rich sociodemographic and medical services data.Findings to date Of the 3.57 million individuals included in the cohort, 52.7% were female and 1 in 4 people were aged ≥65 years at the time of cohort entry. Approximately 6% had evidence of cancer in the year prior to cohort entry. In the 3 months prior to cohort entry, 26.9% used a non-opioid analgesic and 20.5% used a psychotropic medicine. Overall, 1 in 5 individuals were initiated on a strong opioid (20.9%). The most commonly initiated opioid was paracetamol/codeine (61.3%), followed by oxycodone (16.3%).Future plans The POPPY II cohort will be updated periodically, both extending the follow-up duration of the existing cohort, and including new individuals initiating opioids. The POPPY II cohort will allow a range of aspects of opioid utilisation to be studied, including long-term trajectories of opioid use, development of a data-informed method to assess time-varying opioid exposure, and a range of outcomes including mortality, transition to opioid dependence, suicide and falls. The duration of the study period will allow examination of population-level impacts of changes to opioid monitoring and access, while the size of the cohort will also allow examination of important subpopulations such as people with cancer, musculoskeletal conditions or opioid use disorder.

Abstract 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.

Abstract Background Treatment guidelines for generalized anxiety disorder (GAD) are based on a relatively small number of randomized controlled trials and do not consider patient-centered perceptions of treatment helpfulness. We investigated the prevalence and predictors of patient-reported treatment helpfulness for DSM-5 GAD and its two main treatment pathways: encounter-level treatment helpfulness and persistence in help-seeking after prior unhelpful treatment. Methods Data came from community epidemiologic surveys in 23 countries in the WHO World Mental Health surveys. DSM-5 GAD was assessed with the fully structured WHO Composite International Diagnostic Interview Version 3.0. Respondents with a history of GAD were asked whether they ever received treatment and, if so, whether they ever considered this treatment helpful. Number of professionals seen before obtaining helpful treatment was also assessed. Parallel survival models estimated probability and predictors of a given treatment being perceived as helpful and of persisting in help-seeking after prior unhelpful treatment. Results The overall prevalence rate of GAD was 4.5%, with lower prevalence in low/middle-income countries (2.8%) than high-income countries (5.3%); 34.6% of respondents with lifetime GAD reported ever obtaining treatment for their GAD, with lower proportions in low/middle-income countries (19.2%) than high-income countries (38.4%); 3) 70% of those who received treatment perceived the treatment to be helpful, with prevalence comparable in low/middle-income countries and high-income countries. Survival analysis suggested that virtually all patients would have obtained helpful treatment if they had persisted in help-seeking with up to 10 professionals. However, we estimated that only 29.7% of patients would have persisted that long. Obtaining helpful treatment at the person-level was associated with treatment type, comorbid panic/agoraphobia, and childhood adversities, but most of these predictors were important because they predicted persistence rather than encounter-level treatment helpfulness. Conclusions The majority of individuals with GAD do not receive treatment. Most of those who receive treatment regard it as helpful, but receiving helpful treatment typically requires persistence in help-seeking. Future research should focus on ensuring that helpfulness is included as part of the evaluation. Clinicians need to emphasize the importance of persistence to patients beginning treatment.

Objectives Although opioid prescribing and harms have increased in Australia, there is a lack of population-level evidence about the drivers of long-term opioid use, dependence and other harms. This study aims to profile the POPPY II cohort, with respect to sociodemographic and clinical health characteristics and patterns of opioid initiation. Approach The POPPY II cohort includes adult residents (≥18 years) in NSW who were initiated on prescribed opioids subsidised through Australia’s Pharmaceutical Benefits Scheme for any period between 1st July 2003 and 31st December 2018. The cohort has been linked to nine other datasets containing information on socio-demographic and clinical characteristics, health service use, and adverse outcomes. Results There were 3,569,433 people in the cohort. One in four people were aged ≥65 years at the time of opioid initiation (26.8%) and half were female (52.7%). About 71% resided in a major city. Approximately 6% had evidence of being treated for cancer in the year prior to opioid initiation (5.8%). In the 3 months prior to cohort entry, 27% used an analgesic medicine and 21% used a psychotropic medicine. Less than a third initiated on a strong opioid (22.2%) and the most commonly initiated opioid was paracetamol/codeine (61.3%). Conclusion The POPPY II study is the largest post-marketing surveillance study of prescribed opioids in Australia, and one of the largest studies worldwide. Understanding the characteristics of the cohort will inform future work aimed at generating robust evidence of the long-terms patterns and outcomes of prescribed opioid use in the Australian community.

Background As dispensings for benzodiazepines and gabapentinoids have increased in recent years, risk of increased mortality has been identified, particularly when used with opioids. There is limited research examining use of these medicines among people with opioid dependence and whether mortality risk varies according to opioid agonist treatment (OAT) status. This study characterizes patterns of opioid analgesic utilization and concomitant use of benzodiazepines, gabapentinoids and OAT among people with opioid dependence initiating opioid analgesics. It also assesses mortality risk associated with exposure to these medicines. Methods Retrospective cohort study in New South Wales, Australia, including 28,891 people with documented opioid dependence initiating opioid analgesics between July 2003 and December 2018. Linked administrative records provided data on prescription dispensings, sociodemographics, clinical characteristics, OAT and mortality. Generalised estimating equation models estimated incidence rate ratios (IRR) comparing periods in and out of OAT for the number of opioid analgesic dispensings. Periods of concomitant use of opioid analgesics, benzodiazepines, gabapentinoids, and OAT were identified. Cox models assessed associations between concomitant medicines use with mortality risk. Results At the time of opioid analgesic initiation, 43.7% of the cohort were in OAT. The most commonly initiated opioid was codeine (67.8%). In the 90 days prior to the index opioid dispensing, benzodiazepines were more frequently dispensed than gabapentinoids, but rates varied over time. Between 2004 and 2018, benzodiazepine dispensings decreased (41.7% to 21.1%) while gabapentinoid dispensings increased (0.2% to 7.9%). Incidence of opioid analgesic dispensings was higher during periods out of OAT compared to in OAT (5.8 v. 2.3 per person-year; IRR 0.39, 95% CI 0.38, 0.41). Analyses investigating associations between medicine exposure and mortality are ongoing. Conclusion People with opioid dependence had high rates of recent benzodiazepine utilization and current OAT enrollment at the time of opioid analgesic initiation. OAT was associated with a significant reduction in opioid analgesic prescribing.

Objectives There are critical periods of mortality risk at onset and cessation of opioid agonist treatment. We aim to determine whether non-fatal overdose followed the same pattern as fatal overdose, comparing the first 4 weeks of treatment and treatment cessation and the remainder time off treatment, with the remainder treatment time, to determine intervention markers. Approach Retrospective cohort study of people with a history of opioid agonist treatment using linked New South Wales data. The incidence of non-fatal overdose hospitalization; emergency department presentation; and fatal overdose from national death records were compared. Rates were calculated using generalized estimating equations adjusting for demographics, year, and recent health and incarceration events. Results The rate of an emergency department drug overdose presentation was highest. It was more than three-fold the rate of opioid non-fatal overdose hospitalisation and 14 times higher than fatal opioid overdose. It was also twice the rate of non-opioid non-fatal overdose hospitalisation. Fatal overdose was lowest while in treatment. This differed from the measures of non-fatal overdose, the overdose rate was elevated in the first four weeks in treatment as well as the first four weeks post treatment. Conclusions Retention on opioid agonist treatment is protective against drug related overdose. There is elevated risk of non-fatal overdose at treatment initiation that is not evident for fatal overdose, however the first month of treatment cessation is a critical period for both non-fatal and fatal overdose. These findings emphasize the importance of treatment retention and interventions for polysubstance overdose at cessation.

Background Injecting-related bacterial and fungal infections are associated with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. Methods and findings Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants’ index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. Conclusions Following hospitalizations with injection drug use–associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder. Thomas Brothers and co-workers study health outcomes in people with injection drug use-associated infections receiving opioid agonist treatment. Author summary Why was this study done? Injecting-related bacterial and fungal infections are an increasingly common cause of pain, disability, and death among people who inject drugs (PWID). Treatment of injecting-related infections has tended to focus on antimicrobial therapy and/or surgery, without addressing underlying substance use-related needs. Opioid agonist treatment (OAT; including methadone and buprenorphine) has been associated with decreased risks of other injecting-related health harms (including HIV infection, hepatitis C virus infection, and overdose death) and may be associated with reduced risks of recurrence after injecting-related infections. What did the researchers do and find? We identified 8,943 people with opioid use disorder who were admitted to hospital with injecting-related infections in New South Wales, Australia, between 2001 and 2018. We found that use of OAT after hospital discharge was associated with both lower risks of death and of rehospitalization with injecting-related infections. Death and rehospitalization with injecting-related infections were common, even among study participants using OAT. What do these findings mean? OAT should be considered as part of a multicomponent treatment strategy for injecting-related infections, aiming to reduce death and reinfection.

Regulators and payers play a pivotal role in facilitating timely and affordable access to safe and efficacious medicines. They use evidence generated from randomised clinical trials (RCTs) to support decisions to register and subsidise medicines. However, at the time of registration and subsidy approval, regulators and payers face uncertainty about how RCT outcomes will translate to real-world clinical practice. In response to this situation, medicines policy agencies worldwide have endorsed the use of real-world data (RWD) to derive novel insights on the use and outcomes of prescribed medicines. Recent reforms around data availability and use in Australia are creating unparalleled data access and opportunities for Australian researchers to undertake large-scale research to generate evidence on the safety and effectiveness of medicines in the real world. Highlighting the critical importance of research in this area, Quality Use of Medicines and Medicine Safety was announced as Australia's 10th National Health Priority in 2019. The National Health and Medical Research Council, Medicines Intelligence Centre of Research Excellence (MI-CRE) has been formed to take advantage of the renewed focus on quality use of medicines and the changing data landscape in Australia. It will generate timely research supporting the evidentiary needs of Australian medicines regulators and payers by accelerating the development and translation of real-world evidence on medicines use and outcomes. MI-CRE is developing a coordinated approach to identify, triage and respond to priority questions where there are significant uncertainties about medicines use, (cost)-effectiveness, and/or safety and creating a data ecosystem that will streamline access to Australian data to enable researchers to generate robust evidence in a timely manner. This paper outlines how MI-CRE will partner with policy makers, clinicians, and consumer advocates to leverage real-world data to co-create real-world evidence, to improve quality use of medicines and reduce medicine-related harm.

Aim: Substance use disorders (SUD) result in substantial morbidity and mortality worldwide. Opioids, and to a lesser extent cocaine, contribute to a large percentage of this health burden. Despite their high heritability, few genetic risk loci have been identified for either opioid or cocaine dependence (OD or CD, respectively). A genome-wide association study of OD and CD related phenotypes reflecting the time between first self-reported use of these substances and a first DSM-IV dependence diagnosis was conducted. Methods: Cox proportional hazards regression in a discovery sample of 6,188 African-Americans (AAs) and 6,835 European-Americans (EAs) participants in a genetic study of multiple substance dependence phenotypes were used to test for association between genetic variants and these outcomes. The top findings were tested for replication in two independent cohorts. Results: In the discovery sample, three independent regions containing variants associated with time to dependence at P < 5 × 10−8 were identified, one (rs61835088 = 1.03 × 10−8) for cocaine in the combined EA-AA meta-analysis in the gene FAM78B on chromosome 1, and two for opioids in the AA portion of the sample in intergenic regions of chromosomes 4 (rs4860439, P = 1.37 × 10−8) and 9 (rs7032521, P = 3.30 × 10−8). After meta-analysis with data from the replication cohorts, the signal at rs61835088 improved (HR = 0.87, P = 3.71 × 10−9 and an intergenic SNP on chromosome 21 (rs2825295, HR = 1.14, P = 2.57 × 10−8) that missed the significance threshold in the AA discovery sample became genome-wide significant (GWS) for CD. Conclusions: Although the two GWS variants are not in genes with obvious links to SUD biology and have modest effect sizes, they are statistically robust and show evidence for association in independent samples. These results may point to novel pathways contributing to disease progression and highlight the utility of related phenotypes to better understand the genetics of SUDs.

Summary: Background: A considerable proportion of people who inject drugs are unstably housed. Although unstable housing is associated with HIV and HCV infection among people who inject drugs, its contribution to transmission is unknown. We estimated the global and national proportions of incident HIV and HCV infections among people who inject drugs attributed to housing instability from 2020 to 2029. Methods: In this modelling study, we developed country-level models of unstable housing and HIV and HCV transmission among people who inject drugs in 58 countries globally, calibrated to country-specific data on the prevalences of HIV and HCV and unstable housing. Based on a recently published systematic review, unstably housed people who inject drugs were assumed to have a 39% (95% CI 6–84) increased risk of HIV transmission and a 64% (95% CI 43–89%) increased risk of HCV transmission. We used pooled country-level estimates from systematic reviews on HCV and HIV prevalence in people who inject drugs. Our models estimated the transmission population attributable fraction (tPAF) of unstable housing to HIV and HCV transmission among people who inject drugs, defined as the percentage of infections prevented from 2020 to 2029 if the additional risk due to unstable housing was removed. Findings: Our models were produced for 58 countries with sufficient data (accounting for >66% of the global people who inject drugs population). Globally, we project unstable housing contributes 7·9% (95% credibility interval [CrI] 2·3–15·7) of new HIV infections and 11·2% (7·7–15·5) of new HCV infections among people who inject drugs from 2020 to 2029. Country-level tPAFs were strongly associated with the prevalence of unstable housing. tPAFs were greater in high-income countries (HIV 17·2% [95% CrI 5·1–30·0]; HCV 19·4% [95% CrI 13·8–26·0]) than in low-income or middle-income countries (HIV 6·6% [95% CrI 1·8–13·1]; HCV 8·3% [95% CrI 5·5–11·7]). tPAFs for HIV and HCV were highest in Afghanistan, Czech Republic, India, USA, England, and Wales where unstable housing contributed more than 20% of new HIV and HCV infections. Interpretation: Unstable housing is an important modifiable risk factor for HIV and HCV transmission among people who inject drugs in many countries. The study emphasises the importance of implementing initiatives to mitigate these risks and reduce housing instability. Funding: National Institute for Health Research and National Institute of Allergy and Infectious Diseases and National Institute for Drug Abuse.

Background: The use of amphetamines is a global public health concern. We summarise global data on use of amphetamines and mental health outcomes. Methods: A systematic review and meta-analysis (CRD 42017081893). We searched Medline, EMBASE, PsycInfo for methamphetamine or amphetamine combined with psychosis, violence, suicidality, depression or anxiety. Included studies were human empirical cross-sectional surveys, case-control studies, cohort studies and randomised controlled trials that assessed the association between methamphetamine and one of the mental health outcomes. Random effects meta-analysis was used to pool results for any use of amphetamines and amphetamine use disorders. Findings: 149 studies were eligible and 59 were included in meta-analyses. There was significant heterogeneity in effects. Evidence came mostly from cross-sectional studies. Any use of amphetamines was associated with higher odds of psychosis (odds ratio [OR] = 2.0, 95%CI 1.3–3.3), violence (OR = 2.2, 95%CI 1.2–4.1; adjusted OR [AOR] = 1.4, 95%CI 0.8–2.4), suicidality OR = 4.4, 95%CI 2.4–8.2; AOR = 1.7, 95%CI 1.0–2.9) and depression (OR = 1.6, 95%CI 1.1–2.2; AOR = 1.3, 95%CI 1.2–1.4). Having an amphetamine use disorder was associated with higher odds of psychosis (OR = 3.0, 95%CI 1.9–4.8; AOR = 2.4, 95%CI 1.6–3.5), violence (OR = 6.2, 95%CI 3.1–12.3), and suicidality (OR = 2.3, 95%CI 1.8–2.9; AOR = 1.5, 95%CI 1.3–1.8). Interpretation: Methamphetamine use is an important risk factor for poor mental health. High quality population-level studies are needed to more accurately quantify this risk. Clinical responses to methamphetamine use need to address mental health harms. Keywords: Amphetamines, Anxiety, Depression, Mental health, Methamphetamine, Psychosis, Substance use, Suicidality, Violence

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018–September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

Summary: A need exists to accurately estimate overdose risk and improve understanding of how to deliver treatments and interventions in people with opioid use disorder in a way that reduces such risk. We consider opportunities for predictive analytics and routinely collected administrative data to evaluate how overdose could be reduced among people with opioid use disorder. Specifically, we summarise global trends in opioid use and overdoses; describe the use of big data in research into opioid overdose; consider the potential for predictive modelling, including machine learning, for prevention and monitoring of opioid overdoses; and outline the challenges and risks relating to the use of big data and machine learning in reducing harms that are related to opioid use. Future research for improving the coverage and provision of existing interventions, treatments, and resources for opioid use disorder requires collaboration of multiple agencies. Predictive modelling could transport the concept of stratified medicine to public health through novel methods, such as predictive modelling and emulated trials for evaluating diagnoses and prognoses of opioid use disorder, predicting treatment response, and providing targeted treatment recommendations.

Background: The literature suggests patient characteristics and higher opioid doses and long-term duration are associated with problematic opioid behaviours but no one study has examined the role of all these factors simultaneously in a long-term prospective cohort study. Methods: Five-year, community-based, prospective cohort of people prescribed opioids for chronic non-cancer pain (CNCP). Logistic mixed effect models with multiple imputation were used to address missing data. Oral morphine equivalent (OME) mg per day was categorised as: 0 mg OME/day, 1–49 mg OME/day (reference), 50–89 mg OME/day, 90–199 mg OME/day and 200mg+ OME/day. Patient risk factors included: age, gender, substance use, mental health history and pain-related factors. Main outcomes included: Prescribed Opioids Difficulties Scale (PODS), Opioid-Related Behaviours In Treatment (ORBIT) scale, and ICD-10 opioid dependence. Multiple confounders for problematic opioid behaviours were assessed. Findings: Of 1,514 participants 44.4% were male (95%CI 41.9–46.9) and their mean age was 58 years (IQR 48–67). Participants had a mean duration of pain of 10 years (IQR 4.5–20.0) and had been taking strong opioids for a median of four years (IQR 1.0–10.0). At baseline, median OME/day was 73 (IQR 35–148). At 5-years, 85% were still taking strong opioids. PODS moderate-high scores reduced from 59.9% (95%CI 58.8–61.0) at baseline to 51.5% (95%CI 50.0–53.0) at 5-years. Around 9% met criteria for ICD-10 opioid dependence at each wave. In adjusted mixed effect models, the risk factors most consistently associated with problematic opioid use were: younger age, substance dependence, mental health histories and higher opioid doses. Interpretation: Both patient risk factors and opioid dose are associated with problematic opioid use behaviours.

Introduction Opioid agonist treatment is effective for opioid dependence and newer extended-release buprenorphine (BUP-XR) injections represent a significant development. The Community Long-Acting Buprenorphine (CoLAB) study aims to evaluate client outcomes among people with opioid dependence receiving 48 weeks of BUP-XR treatment, and examines the implementation of BUP-XR in diverse community healthcare settings in Australia.Methods and analysis The CoLAB study is a prospective single-arm, multicentre, open-label trial of monthly BUP-XR injections in people with opioid dependence. Participants are being recruited from a network of general practitioner and specialist drug treatment services located in the states of New South Wales, Victoria and South Australia in Australia. Following a minimum 7 days on 8–32 mg of sublingual buprenorphine (±naloxone), participants will receive monthly subcutaneous BUP-XR injections administered by a healthcare practitioner at intervals of 28 days (−2/+14 days). The primary endpoint is participant retention in treatment at 48 weeks after treatment initiation. Secondary endpoints will evaluate dosing schedule variations, craving, withdrawal, substance use, health and well-being, and client-reported treatment experience. Qualitative and costing substudies will examine implementation barriers and facilitators at the client and provider level.Ethics and dissemination The study has received ethics approval from the St Vincent’s Hospital Sydney Human Research Ethics Committee (Ref. HREC/18/SVH/221). The findings will be disseminated via publication in peer-reviewed journals, presentations at national and international scientific conferences, and in relevant community organisation publications and forums.Trial registration number NCT03809143Protocol identifier CoLAB1801, V.4.0 dated 01 August 2019

Introduction More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. Objectives To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. Methods We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. Results The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. Conclusions The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population. Key words Mortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort.

PURPOSE:To understand the characteristics of a minority of Australian gay and bisexual men (GBM) who, despite an increase in the number and availability of HIV risk reduction strategies, do not consistently use a strategy to protect themselves from HIV. METHODS:This analysis is based on data from 2,920 participants in a national, online, prospective observational cohort study. GBM who never or rarely used HIV risk reduction strategies (NRR) were compared with two groups using multivariate logistic regression: i) GBM using pre-exposure prophylaxis (PrEP) and ii) GBM frequently using risk reduction strategies (FRR) other than PrEP. RESULTS:Compared to PrEP users, NRR men were younger (p

IntroductionNo prospective studies have examined the prevalence, antecedents or concurrent characteristics associated with self-harm in non-treatment-seeking primary school-aged children.MethodsIn this cohort study from Melbourne, Australia we assessed 1239 children annually from age 8-9 years (wave 1) to 11-12 years (wave 4) on a range of health, social, educational and family measures. Past-year self-harm was assessed at wave 4. We estimated the prevalence of self-harm and used multivariable logistic regression to examine associations with concurrent and antecedent factors.Results28 participants (3% of the 1059 with self-harm data; 18 girls [3%], 10 boys [2%]) reported self-harm at age 11-12 years. Antecedent (waves 1-3) predictors of self-harm were: persistent symptoms of depression (sex-age-socioeconomic status adjusted odds ratio [aOR]: 7.8; 95% confidence intervals [CI] 2.6 to 24) or anxiety (aOR: 5.1; 95%CI 2.1 to 12), frequent bullying victimisation (aOR: 24.6; 95%CI 3.8 to 158), and recent alcohol consumption (aOR: 2.9; 95%CI 1.2 to 7.1). Concurrent (wave 4) associations with self-harm were: having few friends (aOR: 8.7; 95%CI 3.2 to 24), poor emotional control (aOR: 4.2; 95%CI 1.9 to 9.6), antisocial behaviour (theft-aOR: 3.1; 95%CI 1.2 to 7.9; carrying a weapon-aOR: 6.9; 95%CI 3.1 to 15), and being in mid-puberty (aOR: 6.5; 95%CI 1.5 to 28) or late/post-puberty (aOR: 14.4; 95%CI 2.9 to 70).ConclusionsThe focus of intervention efforts aimed at preventing and reducing adolescent self-harm should extend to primary school-aged children, with a focus on mental health and peer relationships during the pubertal transition.

Summary: Background: Globally, an estimated 15·6 million people inject drugs. We aimed to investigate global variation in the age profile of people who inject drugs (PWID), identify country-level factors associated with age of PWID, and assess the association between injecting drug use (IDU) in young people and rates of injecting and sexual risk behaviours at the country level. Methods: We derived data from a previously published global systematic review done in April, 2016 (and updated in June, 2017) on the percentage of young PWID, duration of IDU, average age of PWID, average age at IDU initiation, and the percentage of PWID reporting sexual and injecting risk behaviours. We also derived national development indicators from World Bank data. We estimated the percentage of young PWID for each country, using a random-effects meta-analysis (DerSimonian-Laird methodology) and generated pooled regional and global estimates for all indicators of IDU in young people. We used univariable and multivariable generalised linear models to test for associations between the age indicators and country urban population growth, youth unemployment percentage, the percentage of PWID who are female, the percentage of the general population aged 15–24 years, Gini coefficient, opioid substitution therapy coverage (per PWID per year), gross domestic product (GDP) per capita (US$1000), and sexual and injecting risk behaviours. Findings: In the original systematic review, data on age of PWID was reported in 741 studies across 93 countries. Globally, 25·3% (95% uncertainty interval [UI] 19·6–31·8) of PWID were aged 25 years or younger. The highest percentage of young PWID resided in eastern Europe (43·4%, 95% UI 39·4–47·4), and the lowest percentage resided in the Middle East and north Africa (6·9%, 5·1–8·8). At the country level, in multivariable analysis higher GDP was associated with longer median injecting duration (0·11 years per $1000 GDP increase, 95% CI 0·04–0·18; p=0·002), and older median age of PWID (0·13 years per $1000 increase, 0·06–0·20; p

Abstract Background This study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia. Methods Notifications 1993-2012 were linked to cause-specific mortality records 1993-2013. Results Among 57,929 and 92,474 people with a HBV and HCV notification, 4.8% and 10.0% died since 1997. In early 2010s, 28% and 33% of HBV and HCV deaths were liver-related, 28% and 17% were cancer-related (excluding liver cancer), and 5% and 15% were drug-related, respectively. During 2002-2012, annual HBV-related liver death numbers were relatively stable (53 to 68), while HCV-related liver death numbers increased considerably (111 to 284). Age-standardised HBV-related liver mortality rates declined from 0.2 to 0.1 per 100 person-years (PY) (P

Abstract We provide a systematic review and meta‐analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]: 0.2 95% confidence interval [CI]: [−0.66, 1.06] P = 0.65), appetite (SMD: 0.81 95% CI: [−1.14, 2.75]; P = 0.42), nausea/vomiting (SMD: 0.21 [−0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [−0.01, 0.16]; P = 0.07), or sleep problems (SMD: −0.09 95% CI: [−0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [−0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [−0.02; 0.08]; P = 0.23) or poor mental health (RD: −0.01 [−0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer‐associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.

Abstract Background Injecting drug use is associated with considerable morbidity and mortality. Estimates of the size of the population of people who inject drugs are critical to inform service planning and estimate disease burden due to injecting drug use. We aimed to estimate the size of the population of people who inject drugs in Australia. Methods We applied a multiplier method which used benchmark data (number of people in opioid substitution therapy (OST) on a snapshot day in 2014) and multiplied it by a factor derived from the prevalence of current OST among people who inject drugs participating in the Australian Needle and Syringe Program Survey in 2014. Estimates of the total population of people who inject drugs were calculated in each state and territory and summed to produce a national estimate. We used the sex and age group distribution seen in datasets relating to people who inject drugs to derive sex- and age-stratified estimates, and calculated prevalence per 1000 population. Results Between 68,000 and 118,000 people aged 15–64 years inject drugs in Australia. The population prevalence of injecting drug use was 6.0 (lower and upper uncertainty intervals of 4.3 and 7.6) per 1000 people aged 15–64 years. Injecting drug use was more common among men than women, and most common among those aged 35–44 years. Comparison of expected drug-related deaths based on these estimates to actual deaths suggest that these figures may be underestimates. Conclusions These are the first indirect prevalence estimates of injecting drug use in Australia in over a decade. This work has identified that there are limited data available to inform estimates of this population. These estimates can be used as a basis for further work estimating injecting drug use in Australia.

Abstract Background The Australian Longitudinal Study on Male Health (Ten to Men) was established in 2011 to build the evidence base on male health to inform policy and program development. Methods Ten to Men is a national longitudinal study with a stratified multi-stage cluster random sample design and oversampling in rural and regional areas. Household recruitment was conducted from October 2013 to July 2014. Males who were aged 10 to 55 years residing in private dwellings were eligible to participate. Data were collected via self-completion paper questionnaires (participants aged 15 to 55) and by computer-assisted personal interview (boys aged 10 to 14). Household and proxy health data for boys were collected from a parent via a self-completion paper-based questionnaire. Questions covered socio-demographics, health status, mental health and wellbeing, health behaviours, social determinants, and health knowledge and service use. Results A cohort of 15,988 males aged between 10 and 55 years was recruited representing a response fraction of 35 %. Conclusion Ten to Men is a unique resource for investigating male health and wellbeing. Wave 1 data are available for approved research projects.

Summary: Background: Evidence on the effectiveness of opioid agonist treatment (OAT) in reducing crime is mixed. We aimed to assess the effect of OAT on crime in terms of delaying time to first charge and reducing overall charge rates, as well as the relationship between OAT retention and overall charge rates. Methods: We did a retrospective cohort study of opioid-dependent people who entered OAT for the first time between Jan 1, 2004, and Dec 30, 2010, in New South Wales (NSW), Australia. We used three linked NSW and national administrative datasets. Data on OAT were obtained from the Pharmaceutical Drugs of Addiction System, data on charges were obtained from the Reoffending Database, and data on mortality were obtained from the National Death Index. The cohort was followed up until Dec 31, 2011. Time-dependent OAT exposure was modelled using Cox proportional hazards models (time to first charge) and Andersen-Gill intensity models (total charge-days). Retention in OAT was modelled using two features of treatment engagement, number of OAT episodes and proportion of follow-up time in OAT (presented in quartile groupings: lowest, low-mid, low-high, highest) using zero-inflated negative binomial regression (total charges). All models were adjusted for sociodemographic, criminographic, and treatment-related variables. Findings: 10 744 new OAT entrants were included in the study. 5751 (53·5%) people were charged with an offence. In adjusted analyses, OAT was associated with an initial benefit in delaying the time to first charge (hazard ratio 0·43, 95% CI 0·33–0·55) and reducing total charge-days (0·39, 95% CI 0·30–0·52); however, these protective effects reduced over time. Total charge rates were higher as the number of OAT episodes increased (incident rate ratio [IRR] 1·13, 95% CI 1·11–1·15), and when relatively lower proportions of time were spent in OAT (IRR among the lowest three quartiles ranged from 1·11 [95% CI 1·02–1·21] to 1·22 [95% CI 1·12–1·33]). Interpretation: OAT was associated with a reduction in overall charge rates and was more protective as treatment engagement increased. Maximising treatment retention is crucial to achieving long-term health and social benefits of OAT. Funding: Australian National Health and Medical Research Council, Australian Institute of Criminology, National Institute on Drug Abuse, Australian Government Department of Health, UNSW Sydney.

Abstract. Pain is an experience that affects many people worldwide and is associated with higher mortality and lower quality of life. Cannabinoid, cannabis, and cannabis-based medicines (CBMs) are thought to reduce pain, but a proliferation of different products has led to variability in trials, creating a challenge when determining the assessment of efficacy in systematic reviews. We will conduct 2 systematic reviews commissioned by the International Association for the Study of Pain Task Force on the use of cannabinoids, cannabis, and CBMs for pain management: first, an overview review of systematic reviews to summarise the evidence base and second, a systematic review of randomised controlled trials of cannabinoids, cannabis, and CBMs. In these reviews we will determine the harm and benefit of CBM from the current literature and will interpret the findings in light of the quality of evidence and reviews included. We will search online databases and registries in any language for systematic reviews and randomised controlled trials. We will include studies that evaluate any cannabinoid or CBM vs any control for people with acute and chronic pain. Our primary outcomes for both reviews are the number of participants achieving (1) a 30% and (2) 50% reduction in pain intensity, (3) moderate improvement, and (4) substantial improvement. A number of secondary outcome measures will also be included. We will assess risk of bias and quality of evidence. We will analyse data using fixed and random effect models, with separate comparators for cannabis and CBMs. Prospero ID (CRD42019124710; CRD42019124714).

Abstract. Introduction:. With the increasing availability of cannabis and cannabinoids and their potential utility for pain treatment, there is a growing need to evaluate the risk-benefit considerations of cannabinoids for the management of pain. As part of the IASP Cannabis and Cannabinoids Task Force, this protocol describes a planned overview of systematic reviews summarizing the risks of harm with cannabinoids that are relevant to patients receiving pain treatment. Methods:. This overview will involve literature searches of several databases and a defined search strategy that will target systematic reviews or meta-analyses of cannabinoids where harms are the primary focus. Data extraction will include various features of the cannabinoid(s) and the harm(s) being studied as well as other methodological features of each included systematic review. Methodological quality of each included review will be assessed using AMSTAR-2 as well as compliance with the PRISMA harms checklist. Prospero registration pending. Discussion:. The broad overview of reviews defined by this protocol is expected to synthesize available good quality evidence of harms that will help inform risk-benefit considerations about the use of cannabinoids for pain management.

The burden of mental, neurological, and substance use (MNS) disorders increased by 41% between 1990 and 2010 and now accounts for one in every 10 lost years of health globally. This sobering statistic does not take into account the substantial excess mortality associated with these disorders or the social and economic consequences of MNS disorders on affected persons, their caregivers, and society. A wide variety of effective interventions, including drugs, psychological treatments, and social interventions, can prevent and treat MNS disorders. At the population-level platform of service delivery, best practices include legislative measures to restrict access to means of self-harm or suicide and to reduce the availability of and demand for alcohol. At the community-level platform, best practices include life-skills training in schools to build social and emotional competencies. At the health-care-level platform, we identify three delivery channels. Two of these delivery channels are especially relevant from a public health perspective: self-management (eg, web-based psychological therapy for depression and anxiety disorders) and primary care and community outreach (eg, non-specialist health worker delivering psychological and pharmacological management of selected disorders). The third delivery channel, hospital care, which includes specialist services for MNS disorders and first-level hospitals providing other types of services (such as general medicine, HIV, or paediatric care), play an important part for a smaller proportion of cases with severe, refractory, or emergency presentations and for the integration of mental health care in other health-care channels, respectively. The costs of providing a significantly scaled up package of specified cost-effective interventions for prioritised MNS disorders in low-income and lower-middle-income countries is estimated at US$3-4 per head of population per year. Since a substantial proportion of MNS disorders run a chronic and disabling course and adversely affect household welfare, intervention costs should largely be met by government through increased resource allocation and financial protection measures (rather than leaving households to pay out-of-pocket). Moreover, a policy of moving towards universal public finance can also be expected to lead to a far more equitable allocation of public health resources across income groups. Despite this evidence, less than 1% of development assistance for health and government spending on health in low-income and middle-income countries is allocated to the care of people with these disorders. Achieving the health gains associated with prioritised interventions will require not just financial resources, but committed and sustained efforts to address a range of other barriers (such as paucity of human resources, weak governance, and stigma). Ultimately, the goal is to massively increase opportunities for people with MNS disorders to access services without the prospect of discrimination or impoverishment and with the hope of attaining optimal health and social outcomes.

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

Summary: Background: Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods: The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01–1·29, for less frequent cannabis use; and 1·17, 1·03–1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09–1·35; and 1·14, 1·03–1·26), lower pain self-efficacy scores (0·97, 0·96–1·00; and 0·98, 0·96–1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03–1·12; and 1·10, 1·06–1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. Funding: National Health and Medical Research Council and the Australian Government.

Summary: Background: Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15–64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. Methods: Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. Findings: We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15–64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2–23·7 million) PWID aged 15–64 years globally, with 3·2 million (1·6–5·1 million) women and 12·5 million (7·5–18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5–31·5) of PWID in North America and 33·4% (31·0–35·6) in Australasia, compared with 3·1% (2·1–4·1) in south Asia. Globally, we estimate that 17·8% (10·8–24·8) of PWID are living with HIV, 52·3% (42·4–62·1) are HCV-antibody positive, and 9·1% (5·1–13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6–88·9) of PWID mainly inject opioids and 33·0% (24·3–42·0) mainly inject stimulants. We estimate that 27·9% (20·9–36·8) of PWID globally are younger than 25 years, 21·7% (15·8–27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5–65·2) had a history of incarceration. Interpretation: We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. Funding: Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.

Summary: Background: People who inject drugs (PWID) are a key population affected by the global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention interventions for PWID include needle and syringe programmes (NSP), opioid substitution therapy (OST), HIV counselling and testing, HIV antiretroviral therapy (ART), and condom distribution programmes. We aimed to produce country-level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART, and condom programmes for PWID. Methods: We completed searches of peer-reviewed (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and disseminated data requests via social media and targeted emails to international experts. Programme and survey data on each of the named interventions were collected. Programme data were used to derive country-level estimates of the coverage of interventions in accordance with indicators defined by WHO, UNAIDS, and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST, and HIV testing coverage were also calculated. The protocol was registered on PROSPERO, number CRD42017056558. Findings: In 2017, of 179 countries with evidence of injecting drug use, some level of NSP services were available in 93 countries, and there were 86 countries with evidence of OST implementation. Data to estimate NSP coverage were available for 57 countries, and for 60 countries to estimate OST coverage. Coverage varied widely between countries, but was most often low according to WHO indicators (200 needle-syringes distributed per PWID and >40 OST recipients per 100 PWID). Interpretation: Coverage of HIV and HCV prevention interventions for PWID remains poor and is likely to be insufficient to effectively prevent HIV and HCV transmission. Scaling up of interventions for PWID remains a crucial priority for halting the HIV and HCV epidemics. Funding: Open Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on Drugs and Crime, Australian National Drug and Alcohol Research Centre, University of New South Wales Sydney.

Background: Although post-traumatic stress disorder (PTSD) onset-persistence is thought to vary significantly by trauma type, most epidemiological surveys are incapable of assessing this because they evaluate lifetime PTSD only for traumas nominated by respondents as their ‘worst.’ Objective: To review research on associations of trauma type with PTSD in the WHO World Mental Health (WMH) surveys, a series of epidemiological surveys that obtained representative data on trauma-specific PTSD. Method: WMH Surveys in 24 countries (n = 68,894) assessed 29 lifetime traumas and evaluated PTSD twice for each respondent: once for the ‘worst’ lifetime trauma and separately for a randomly-selected trauma with weighting to adjust for individual differences in trauma exposures. PTSD onset-persistence was evaluated with the WHO Composite International Diagnostic Interview. Results: In total, 70.4% of respondents experienced lifetime traumas, with exposure averaging 3.2 traumas per capita. Substantial between-trauma differences were found in PTSD onset but less in persistence. Traumas involving interpersonal violence had highest risk. Burden of PTSD, determined by multiplying trauma prevalence by trauma-specific PTSD risk and persistence, was 77.7 person-years/100 respondents. The trauma types with highest proportions of this burden were rape (13.1%), other sexual assault (15.1%), being stalked (9.8%), and unexpected death of a loved one (11.6%). The first three of these four represent relatively uncommon traumas with high PTSD risk and the last a very common trauma with low PTSD risk. The broad category of intimate partner sexual violence accounted for nearly 42.7% of all person-years with PTSD. Prior trauma history predicted both future trauma exposure and future PTSD risk. Conclusions: Trauma exposure is common throughout the world, unequally distributed, and differential across trauma types with respect to PTSD risk. Although a substantial minority of PTSD cases remits within months after onset, mean symptom duration is considerably longer than previously recognized.

Abstract Objective: To estimate service demand (willingness to seek or use services) for respite care among informal, primary carers of people with a psychological disability and to describe their characteristics. Methods: Analysis of data from the household component of the 2009 Survey of Disability Ageing and Carers (n=64,213 persons). Results: In Australia in 2009, 1.0% of people aged 15 years or over (177,900 persons) provided informal, primary care to a co‐resident with a psychological disability. One‐quarter (27.2%) of these carers reported service demand for respite care, of whom one‐third had used respite services in the past three months and four‐fifths had an unmet need for any or more respite care. A significantly greater percentages of carers with service demand for respite care spent 40 or more hours per week on caregiving, provided care to a person with profound activity restrictions and reported unmet support needs, compared to carers without service demand. Lack of suitable, available respite care models was a barrier to utilisation. Conclusions: Findings confirm significant service demand for, and under‐utilisation of, respite care among mental health carers. Implications: Increased coverage of respite services, more flexible service delivery models matched to carers’ needs and better integration with other support services are indicated.

Abstract Objective: To examine the validity and impact of record linkage using name code compared to full name records. Methods: A registry of 45,419 opioid substitution clients (1985–2007) was linked with national population‐based death and cancer registries using registrant's name, date of birth, sex, state, postcode and date of death. Records were linked using full name and then using the first two letters of the given and surname (2×2 name code). Sensitivity and specificity were computed and regression analysis used to identify factors related to linkage accuracy. Standardised mortality ratios (SMR) and standardised cancer incidence ratios (SIR) were estimated. Results: The sensitivity and specificity of name code compared to full name linkage were 65.31% and 99.91% for death records and 76.81% and 99.89% for cancer records. Registrants' age and sex and accuracy of the registries were associated with risk of false linkages. Death and cancer risks (SMR 6.98, 95%CI 6.77–7.19; SIR 1.16, 95%CI 1.08–1.24) were significantly under‐estimated using name code linkage (SMR 4.39, 95%CI 4.23–4.56; SIR 0.92, 95%CI 0.85–0.99). Conclusion: Record linkage using 2×2 name code has low sensitivity but high specificity, resulting in conservative estimates of death and cancer risk. This may translate to meaningful differences in outcomes.

Abstract Objective: To examine the association between self‐reported lifetime diagnosis of mental disorder and health‐related outcomes in prisoners during the first six months after release. Methods: We interviewed 1,324 adult prisoners in Queensland, Australia, within six weeks of expected release and one, three and six months post‐release. Outcomes of interest included health service access, housing, employment, substance use and criminal activity. We used multivariate logistic regression to investigate the association between self‐reported, lifetime diagnosis of mental disorder and these health‐related outcomes post‐release, adjusting for pre‐existing disadvantage. Results: 43.4% of participants reported a lifetime diagnosis of mental disorder. This group had increased crude odds of poor outcomes across all evaluated domains. After adjusting for pre‐existing disadvantage, significantly increased odds of poor outcomes persisted in the substance use, mental health, crime and health service access domains. Conclusions: People with a history of mental disorder experience particularly poor outcomes following release from prison that are not fully explained by pre‐existing disadvantage. Implications: Evidence‐based transitional programs for prisoners with a history of mental disorder should be provided at a level commensurate with need.

The Eastern Mediterranean Region (EMR) is witnessing an increase in chronic disorders, including mental illness. With ongoing unrest, this is expected to rise. This is the first study to quantify the burden of mental disorders in the EMR. We used data from the Global Burden of Disease study (GBD) 2013. DALYs (disability-adjusted life years) allow assessment of both premature mortality (years of life lost-YLLs) and nonfatal outcomes (years lived with disability-YLDs). DALYs are computed by adding YLLs and YLDs for each age-sex-country group. In 2013, mental disorders contributed to 5.6% of the total disease burden in the EMR (1894 DALYS/100,000 population): 2519 DALYS/100,000 (2590/100,000 males, 2426/100,000 females) in high-income countries, 1884 DALYS/100,000 (1618/100,000 males, 2157/100,000 females) in middle-income countries, 1607 DALYS/100,000 (1500/100,000 males, 1717/100,000 females) in low-income countries. Females had a greater proportion of burden due to mental disorders than did males of equivalent ages, except for those under 15 years of age. The highest proportion of DALYs occurred in the 25-49 age group, with a peak in the 35-39 years age group (5344 DALYs/100,000). The burden of mental disorders in EMR increased from 1726 DALYs/100,000 in 1990 to 1912 DALYs/100,000 in 2013 (10.8% increase). Within the mental disorders group in EMR, depressive disorders accounted for most DALYs, followed by anxiety disorders. Among EMR countries, Palestine had the largest burden of mental disorders. Nearly all EMR countries had a higher mental disorder burden compared to the global level. Our findings call for EMR ministries of health to increase provision of mental health services and to address the stigma of mental illness. Moreover, our results showing the accelerating burden of mental health are alarming as the region is seeing an increased level of instability. Indeed, mental health problems, if not properly addressed, will lead to an increased burden of diseases in the region.

Abstract Objective: There are few data about the incarceration of opioid‐dependent people involving large representative cohorts. We aimed to determine the prevalence and duration of incarceration in a large cohort of opioid‐dependent people in Australia using data linkage methods, and estimate the costs associated with their incarceration. Method: Retrospective linkage study of all entrants to opioid substitution therapy (OST) for the treatment of opioid dependence in NSW, 1985–2010, with data on incarceration, 2000–2012. The number and duration of incarcerations were calculated. The average daily cost of incarceration was applied to days of incarceration in the cohort. Results: Among 47,196 opioid‐dependent people, 37% (43% of men and 24% of women) had at least one episode of incarceration lasting one or more days. Men had a median of three (ranging between 1–47) incarcerations, and women, two (1–35). Indigenous men spent 23% of follow‐up time incarcerated, compared with 8% for non‐Indigenous men; similarly, Indigenous women spent a substantially greater proportion of time incarcerated than non‐Indigenous women (8% vs. 2%). Costs of incarceration of this cohort between 2000 and 2012 totalled nearly AUD$3 billion. Conclusions: This is the first study to examine incarceration of opioid‐dependent people across an entire population of such users. Our findings suggest that a substantial minority of opioid‐dependent people experience incarceration, usually on multiple occasions and at significant cost. Treatment for opioid dependence, inside and outside prisons, may help reduce incarceration of this cohort.

Abstract Background: In Australia about half of the people who inject drugs (PWID) are hepatitis C (HCV) antibody positive (anti‐HCV+). The prevalence among opioid substitution treatment (OST) clients specifically is unclear, despite OST clinics being a potential setting for HCV care. This study aimed to report the prevalence of HCV among a large sample of NSW OST clients, understand whether HCV testing is translating into knowledge of status, and identify the correlates of inaccurate self‐reporting of HCV status. Methods: Participants completed an interview that included self‐reported HCV status. Participants also provided a blood sample that was tested for HCV IgG antibodies, and for viral load using a quantitative real‐time reverse‐transcriptase polymerase chain reaction. Valid interviews and viable blood sample were provided by 1,484 participants. Logistic regression modelling was used to identify independent predictors of knowledge of HCV antibody status. Results: Overall, 84% of participants were anti‐HCV+. Of these, 65% were RNA+. Four per cent of anti‐HCV negative participants were RNA+. One‐quarter of anti‐HCV+ participants did not know their status or reported it incorrectly, compared with 14.5% of anti‐HCV negative participants. Conclusion: The prevalence of HCV in this sample was higher than that found among other samples of people who inject drugs, suggesting the need for greater prevention efforts with OST clients. Anti‐HCV+ individuals are less accurate at reporting their HCV status than those who are anti‐HCV‐. Inaccurate knowledge is associated with different variables for anti‐HCV+ vs. anti‐HCV‐ individuals. There are opportunities to improve knowledge of HCV status and to therefore improve health outcomes and reduce transmission among this at‐risk population.

OBJECTIVE: To systematically review cohort studies of mortality among people who inject drugs, examine mortality rates and causes of death in this group, and identify participant- and study-level variables associated with a higher risk of death. METHODS: Tailored search strings were used to search EMBASE, Medline and PsycINFO. The grey literature was identified through online grey literature databases. Experts were consulted to obtain additional studies and data. Random effects meta-analyses were performed to estimate pooled crude mortality rates (CMRs) and standardized mortality ratios (SMRs). FINDINGS: Sixty-seven cohorts of people who inject drugs were identified, 14 of them from low- and middle-income countries. The pooled CMR was 2.35 deaths per 100 person-years (95% confidence interval, CI: 2.12-2.58). SMRs were reported for 32 cohorts; the pooled SMR was 14.68 (95% CI: 13.01-16.35). Comparison of CMRs and the calculation of CMR ratios revealed mortality to be higher in low- and middle-income country cohorts, males and people who injected drugs that were positive for human immunodeficiency virus (HIV). It was also higher during off-treatment periods. Drug overdose and acquired immunodeficiency syndrome (AIDS) were the primary causes of death across cohorts. CONCLUSION: Compared with the general population, people who inject drugs have an elevated risk of death, although mortality rates vary across different settings. Any comprehensive approach to improving health outcomes in this group must include efforts to reduce HIV infection as well as other causes of death, particularly drug overdose.

BACKGROUND:The Global Burden of Disease Study 2010 (GBD 2010), estimated that a substantial proportion of the world's disease burden came from mental, neurological and substance use disorders. In this paper, we used GBD 2010 data to investigate time, year, region and age specific trends in burden due to mental, neurological and substance use disorders. METHOD:For each disorder, prevalence data were assembled from systematic literature reviews. DisMod-MR, a Bayesian meta-regression tool, was used to model prevalence by country, region, age, sex and year. Prevalence data were combined with disability weights derived from survey data to estimate years lived with disability (YLDs). Years lost to premature mortality (YLLs) were estimated by multiplying deaths occurring as a result of a given disorder by the reference standard life expectancy at the age death occurred. Disability-adjusted life years (DALYs) were computed as the sum of YLDs and YLLs. RESULTS:In 2010, mental, neurological and substance use disorders accounted for 10.4% of global DALYs, 2.3% of global YLLs and, 28.5% of global YLDs, making them the leading cause of YLDs. Mental disorders accounted for the largest proportion of DALYs (56.7%), followed by neurological disorders (28.6%) and substance use disorders (14.7%). DALYs peaked in early adulthood for mental and substance use disorders but were more consistent across age for neurological disorders. Females accounted for more DALYs in all mental and neurological disorders, except for mental disorders occurring in childhood, schizophrenia, substance use disorders, Parkinson's disease and epilepsy where males accounted for more DALYs. Overall DALYs were highest in Eastern Europe/Central Asia and lowest in East Asia/the Pacific. CONCLUSION:Mental, neurological and substance use disorders contribute to a significant proportion of disease burden. Health systems can respond by implementing established, cost effective interventions, or by supporting the research necessary to develop better prevention and treatment options.

BackgroundThe Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010's mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders.MethodsRelative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty).ResultsMental and substance use disorders were responsible for 22.5 million (14.8-29.8 million) of the 36.2 million (26.5-44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%-60.8%)) and anorexia nervosa the lowest (0.2% (0.02%-0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20-30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%-8.6%) to 8.3% (7.1%-9.6%) of global DALYs, and would have changed the global ranking from 5th to 3rd leading cause of burden.ConclusionsCapturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.

The world is undergoing a rapid health transition, with an ageing population and disease burden increasingly defined by disability. In Sub-Saharan Africa the next 40 years are predicted to see reduced mortality, signalling a surge in the impact of chronic diseases. We modelled these epidemiological changes and associated mental health workforce requirements. Years lived with a disability (YLD) predictions for mental and substance use disorders for each decade from 2010 to 2050 for four Sub-Saharan African regions were calculated using Global Burden of Disease 2010 study (GBD 2010) data and UN population forecasts. Predicted mental health workforce requirements for 2010 and 2050, by region and for selected countries, were modelled using GBD 2010 prevalence estimates and recommended packages of care and staffing ratios for low- and middle-income countries, and compared to current staffing from the WHO Mental Health Atlas. Significant population growth and ageing will result in an estimated 130% increase in the burden of mental and substance use disorders in Sub-Saharan Africa by 2050, to 45 million YLDs. As a result, the required mental health workforce will increase by 216,600 full time equivalent staff from 2010 to 2050, and far more compared to the existing workforce. The growth in mental and substance use disorders by 2050 is likely to significantly affect health and productivity in Sub-Saharan Africa. To reduce this burden, packages of care for key mental disorders should be provided through increasing the mental health workforce towards targets outlined in this paper. This requires a shift from current practice in most African countries, involving substantial investment in the training of primary care practitioners, supported by district based mental health specialist teams using a task sharing model that mobilises local community resources, with the expansion of inpatient psychiatric units based in district and regional general hospitals.

BackgroundPopulation-based studies provide the understanding of health-need required for effective public health policy and service-planning. Mental disorders are an important but, until recently, neglected agenda in global health. This paper reviews the coverage and limitations in global epidemiological data for mental disorders and suggests strategies to strengthen the data.MethodsSystematic reviews were conducted for population-based epidemiological studies in mental disorders to inform new estimates for the global burden of disease study. Estimates of population coverage were calculated, adjusted for study parameters (age, gender and sampling frames) to quantify regional coverage.ResultsOf the 77,000 data sources identified, fewer than 1% could be used for deriving national estimates of prevalence, incidence, remission, and mortality in mental disorders. The two major limitations were (1) highly variable regional coverage, and (2) important methodological issues that prevented synthesis across studies, including the use of varying case definitions, the selection of samples not allowing generalization, lack of standardized indicators, and incomplete reporting. North America and Australasia had the most complete prevalence data for mental disorders while coverage was highly variable across Europe, Latin America, and Asia Pacific, and poor in other regions of Asia and Africa. Nationally-representative data for incidence, remission, and mortality were sparse across most of the world.DiscussionRecent calls to action for global mental health were predicated on the high prevalence and disability of mental disorders. However, the global picture of disorders is inadequate for planning. Global data coverage is not commensurate with other important health problems, and for most of the world's population, mental disorders are invisible and remain a low priority.