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Pharmaceutical claims data are often used as the primary information source to define medicine exposure periods in pharmacoepidemiological studies. However, often critical information on directions for use and the intended duration of medicine supply are not available. In the absence of this information, alternative approaches are needed to support the assignment of exposure periods. This study summarises the key methods commonly used to estimate medicine exposure periods and dose from pharmaceutical claims data; and describes a method using individualised dispensing patterns to define time-dependent estimates of medicine exposure and dose. This method extends on important features of existing methods and also accounts for recent changes in an individual's medicine use. Specifically, this method constructs medicine exposure periods and estimates the dose used by considering characteristics from an individual's prior dispensings, accounting for the time between prior dispensings and the amount supplied at prior dispensings. Guidance on the practical applications of this method is also provided. Although developed primarily for application to databases, which do not contain duration of supply or dose information, use of this method may also facilitate investigations when such information is available and there is a need to consider individualised and/or changing dosing regimens. By shifting the reliance on prescribed duration and dose to determine exposure and dose estimates, individualised dispensing information is used to estimate patterns of exposure and dose for an individual. Reflecting real-world individualised use of medicines with complex and variable dosing regimens, this method offers a pragmatic approach that can be applied to all medicine classes.

Aims: This study examined the social, material and temporal effects of extended-release buprenorphine depot treatment (BUP-XR), among a group of participants commencing BUP-XR in Australia, and considered the situated potentials of these new opioid agonist treatment technologies. Methods: Using a longitudinal qualitative design, 36 participants (25 men, 11 women; mean age 44 years) were interviewed, with 32 followed-up, to generate accounts of BUP-XR experiences. Analysis was informed by sociological approaches which attend to the multiple effects of novel health interventions as they are put to use and made to work, with a focus on tracing change over time. Analysis: The shift from daily to monthly dosing altered how opioid agonist treatment was experienced, reconfigured participants’ relationship to treatment, and affected the temporal patterns of participants’ lives. Extending temporal relations released participants from short-term cycles of living and produced different forms of subjectivity, bringing about both transformation and loss. Monthly dosing, and a sense of normalcy characterized by absenting the routines and felt effects of drugs or treatment medications, potentiated a feeling of stability for many participants. For some, disrupting daily routines precipitated disconnection from treatment and social care relations. The transition from daily to monthly dosing required adaptation and new ways of engaging with treatment and care, with medication acting as a bridge to care without necessarily being the focal point. Conclusions: As BUP-XR treatment gains traction internationally, it will be important to attend to the multiple, and sometimes unexpected, effects this intervention makes in the social and material lives of clients. How choice, social connection, and care can be maintained to help secure BUP-XR’s longer-term impact, and how clients can be supported to adjust to what is felt to be a new normal, will be considerations in future treatment delivery.

Alcohol is a leading risk factor for death and disease in young people. We compare age-specific characteristics of young people who experience their first ('index') alcohol-related hospitalisation or emergency department (ED) presentation, and whether age at index predicts 12-month rates of readmission.We used a retrospective linked-data cohort of 10,300 people aged 12-20 years with an index alcohol-related hospital and/or ED record in New South Wales, Australia from 2005 to 2013. Age group (early adolescent [12-14 years], late adolescent [15-17 years], young adult [18-20 years]) and diagnosis fields were used in logistic regression analyses and to calculate incidence rates with adjustment for year of index event, sex, socioeconomic disadvantage and residence remoteness.People who experienced their index event in early adolescence (adjusted relative risk ratio [ARRR] 0.45 [95% confidence interval 0.39, 0.52]) or late adolescence (ARRR 0.82 [0.74, 0.90]) were less likely to be male compared to young adults. Early adolescents (ARRR 0.60 [0.51, 0.70]) and late adolescents (ARRR 0.84 [0.76, 0.93]) were less likely to have a hospitalisation index event. Early adolescents (adjusted incidence rate ratio 1.40 [1.15, 1.71]) and late adolescents (adjusted incidence rate ratio 1.16 [1.01, 1.34]) were more likely than young adults to have a subsequent 12-month non-poisoning injury ED presentation.We identified preventable hospital events in young people who have previously experienced an alcohol-related ED presentation or hospitalisation, with age-specific characteristics and outcomes that can be used to inform future health policy and service planning.

AIMS: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD. DESIGN: A prediction model was developed for DSM-IV AD onset by age 25 years using an ensemble machine-learning algorithm known as 'Super Learner'. Shapley additive explanations (SHAP) assessed variable importance. SETTING AND PARTICIPANTS: Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys. MEASUREMENTS: The primary outcome to be predicted was onset of life-time DSM-IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview. FINDINGS: AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74-0.81] higher than any individual candidate risk model (0.73-0.77) and an area under the precision-recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders. CONCLUSIONS: A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models. ispartof: Addiction vol:118 issue:5 pages:954-966 ispartof: location:England status: published

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

We examined depression and anxiety prior to and during COVID-19 restrictions in Australian gay and bisexual men (GBM). In an online cohort, a COVID-19-focused survey was conducted in April 2020. During 2019 and in April 2020, 664 GBM completed the Patient Health Questionnaire (PHQ-9, measuring depression) and Generalized Anxiety Disorder Assessment (GAD-7, measuring anxiety). Increased depression and anxiety were defined as a ≥ 5 point increase on the respective scales. Mean PHQ-9 and GAD-7 scores increased between 2019 and 2020 (PHQ-9: from 5.11 in 2019 to 6.55 in 2020; GAD-7: from 3.80 in 2019 to 4.95 in 2020). The proportion of participants with moderate-severe depression (PHQ-9 ≥ 10) increased from 18.8% (n = 125) to 25.5% (n = 169), while the proportion of participants with moderate-severe anxiety (GAD-7 ≥ 10) increased from 12.7% (n = 84) to 17.3% (n = 115). Almost one-quarter of participants (n = 158, 23.8%) had increased depression; in these men, mean PHQ-9 increased from 2.49 in 2019 to 11.65 in 2020 (p n = 137) had increased anxiety; among these men, mean GAD-7 increased from 2.05 in 2019 to 10.22 in 2020 (p

Background Dual protection refers to the simultaneous prevention of sexually transmissible infection (STI) and unintended pregnancies. Optimal contraception and STI prevention strategies sometimes fail to align. Methods Using data from a large nationally representative population-based survey, we analysed the contraception and STI prevention behaviours at the last vaginal intercourse among 2420 heterosexually active women aged 16–34 years who had participated in the Second Australian Study of Health and Relationships, 2012–13. Results At their last vaginal intercourse, most women (95%) used contraception and half (49%) used condoms, either as a sole multipurpose method or in conjunction with another type of contraception. Condom use was highest (72%) among women whose most recent partner was a casual or occasional partner, followed by women with a regular partner (59%) and women with a cohabiting regular partner (40%). One-third of the women (34%) used condoms as a sole method, and 14% used oral contraceptives together with a condom. Few women used implants or intrauterine devices (8%) and, among them, very few women also used condoms (

Background and Hypothesis Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs. Study Design We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African ancestry; 42% female; 74% meeting lifetime criteria for an AUD). Study Results Cannabis use disorder (CUD) was prevalent in this analytic sample (70%), with 40% classified as mild, 25% as moderate, and 35% as severe. Polygenic risk for schizophrenia was positively associated with cannabis-related paranoia, feeling depressed or anhedonia, social withdrawal, and cognitive difficulties, even when controlling for duration of daily cannabis use, CUD, and age at first cannabis use. The schizophrenia PRS was most robustly associated with cannabis-related cognitive difficulties (β = 0.22, SE = 0.04, P = 5.2e−7). In an independent replication sample (N = 1446), associations between the schizophrenia PRS and cannabis-related experiences were in the expected direction and not statistically different in magnitude from those in the COGA sample. Conclusions Among individuals who regularly use cannabis, genetic liability for schizophrenia—even in those without clinical features—may increase the likelihood of reporting unusual experiences related to cannabis use.

Globally, hepatitis B virus (HBV) is a leading cause of liver disease. People who inject drugs (PWID) are at greater risk than the general population of contracting HBV. This risk could depend on societal factors in different countries. We investigated the associations between country-level chronic HBV prevalence in PWID with national indicators of development and prevalence of HIV and hepatitis C virus (HCV).We used global systematic review data on chronic HBV prevalence (hepatitis B surface antigen-positive) among PWID and country-level sociodemographic characteristics from online databases. National random-effects meta-analysis estimates of HBV prevalence were the outcome in linear regression models testing for associations with country-level characteristics.The study included 131,710 PWID from 304 estimates in 55 countries: the pooled HBV prevalence among PWID in the countries analysed was 4.5% (95% CI 3.9-5.1), the highest regional pooled prevalence was in East and Southeast Asia (17.6% [13.3-22.3]), and the lowest was in Western Europe (1.7% [1.4-2.1]). In multivariable models, no indicators of development were associated with HBV prevalence, but there was evidence of positive associations between HBV prevalence in the general population and among PWID, and evidence of HIV and HCV prevalence in PWID being associated with HBV prevalence in PWID: multivariable coefficients 0.03 (95% CI 0.01-0.04); p 0.001, and 0.01 (95% CI 0.00-0.03); p = 0.01, respectively.HBV prevalence among PWID was associated with HIV and HCV prevalence among PWID and background HBV prevalence in the general population, highlighting the need for improving harm reduction in PWID and implementation of HBV vaccination, especially where HBV is endemic.

Aims: To describe (i) self-reported changes in drug use and (ii) trends in price, perceived availability, and perceived purity of illicit drugs, among people who regularly use ecstasy/ 3,4-methylenedioxymethamphetamine (MDMA) and other illicit stimulants in Australia following COVID-19 and associated restrictions. Design: Annual interviews with cross-sectional sentinel samples conducted face-to-face in 2016-19 and via video conferencing or telephone in 2020. Data were collected via an interviewer-administered structured questionnaire. Setting: Australian capital cities. Participants: Australians aged 16 years or older who used ecstasy/MDMA and other illicit stimulants on a monthly or more frequent basis and resided in a capital city, recruited via social media and word-of-mouth (n ~ 800 each year). Measurements: Key outcome measures were self-reported illicit drug market indicators (price, purity and availability) and, in 2020 only, perceived change in drug use (including alcohol and tobacco) since March 2020 and reasons for this change. Findings: For most drugs, participants reported either no change or a reduction in their use since COVID-19 restrictions were introduced. Ecstasy/MDMA was the drug most frequently cited as reduced in use (n = 552, 70% of those reporting recent use), mainly due to reduced opportunities for socialization. While market indicators were largely stable across most drugs, the odds of perceiving MDMA capsules as 'high' in purity decreased compared with 2016-19 [adjusted odds ratio (aOR) = 0.72, 95% confidence interval (CI) = 0.53-0.99], as did perceiving them as 'easy' to obtain (aOR = 0.42, CI = 0.26-0.67). The odds of perceiving cocaine and methamphetamine crystal as 'easy' to obtain also decreased (aOR = 0.67, CI = 0.46-0.96 and aOR = 0.12, CI = 0.04-0.41, respectively). Conclusions: After COVID-19-related restrictions were introduced in Australia, use of ecstasy/MDMA, related stimulants and other licit and illicit drugs mainly appeared to remain stable or decrease, primarily due to impediments to socialization.

Background: Parents are the main supplier of alcohol to children but it is not known whether mothers and fathers equally contribute to the supply of alcohol to their female and male children as these children transition to adulthood. Objectives: i) to determine whether the gender of the parent is associated with the gender of the adolescent offspring when alcohol is supplied and ii) whether the gender of the parent supplying is associated with gender differences in adolescent binge drinking and alcohol related harms. Methods: Longitudinal cohort of 1,927 (males = 1052) Australian adolescents (mean age 12.9 years), recruited in 2010/11 from schools in Australia and surveyed annually for six years. We assessed the association between adolescent and parent gender related to subsequent adolescent drinking, binge drinking (>4 standard drinks), and alcohol-related harms. Results: At mean age of 12.9 years about one in ten children report parental supply of alcohol which increases to about four in ten children by 17.8 years. Mothers consistently more often supply their daughters with alcohol than their sons, [Wave 5 OR 1.77 (1.53,2.05)], while mothers less often supply sons than their daughters, [Wave 5 OR 0.82 (0.71,0.95)]. Mothers’ supply of alcohol to daughters predicts substantially increased odds of daughters binge drinking, [OR 1.67 (1.10,2.53)] and experiencing alcohol related harms, [OR 1.65 (1.10,2.48)]. Conclusion: There is a need to involve both mothers and fathers and to equally target female and male children in programs to reduce the harmful consequences of parental supply of alcohol to their children.

Aims: To estimate change in young people's alcohol consumption during COVID-19 restrictions in Australia in early-mid 2020, and test whether those changes were consistent by gender and level of consumption prior to the pandemic. Design: Prospective longitudinal cohort. Setting: Secondary schools in New South Wales, Tasmania and Western Australia. Participants: Subsample of a cohort (n = 443) recruited in the first year of secondary school in 2010-11. Analysis data included three waves collected in September 2017-July 2018, September 2018-May 2019 and August 2019-January 2020), and in May-June 2020. Measurements: The primary predictors were time, gender and level of consumption prior to the pandemic. Outcome variables, analysed by mixed-effects models, included frequency and typical quantity of alcohol consumption, binge drinking, peak consumption, alcohol-related harm and drinking contexts. Findings: Overall consumption (frequency × quantity) during the restrictions declined by 17% [incidence rate ratio (IRR) = 0.83; 95% confidence interval (CI) = 0.73, 0.95] compared to February 2020, and there was a 35% decline in the rate of alcohol-related harms in the same period (IRR = 0.66; 95% CI = 0.54, 0.79). Changes in alcohol consumption were largely consistent by gender. Conclusions: From a survey of secondary school students in Australia, there is evidence for a reduction in overall consumption and related harms during the COVID-19 restrictions.

Background People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalization, yet admissions are not utilized for HCV treatment initiation. We aimed to assess the extent to which people with HCV notification, including those with evidence of recent drug dependence, are hospitalized while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalization in the DAA era. Methods We conducted a longitudinal, population-based cohort study of people living with HCV in the DAA era (March 2016–December 2018) through analysis of linked databases in New South Wales, Australia. Kaplan-Meier estimates were used to report HCV treatment uptake by frequency, length, and cause-specific hospitalization. Results Among 57 467 people, 14 938 (26%) had evidence of recent drug dependence, 50% (n = 7506) of whom were hospitalized while DAA eligible. Incidence of selected cause-specific hospitalization was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100 PY), and injection-related infectious disease (9.15 per 100 PY) hospitalizations, and lowest for alcohol use disorder (4.58 per 100 PY) and liver-related (3.13 per 100 PY). In total, 65% (n = 4898) of those who were hospitalized had been admitted ≥2 times, and 46% (n = 3437) were hospitalized ≥7 days. By the end of 2018, DAA therapy was lowest for those hospitalized ≥2 times, for ≥7 days, and those whose first admission was for injection-related infectious disease, mental health disorders, and drug-related complications. Conclusions Among people who have evidence of recent drug dependence, frequent hospitalization—particularly mental health, drug, and alcohol admissions—presents an opportunity for engagement in HCV care.

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.

There have been few large-scale nationally representative studies on the prevalence of substance use among doctors. In addition, the association of different medical specialties with the use of different substances requires further research.To investigate how the use of alcohol, tobacco and illicit drugs varied between junior doctors enrolled in different specialty training programmes.A secondary analysis was conducted on a national survey of 12 252 Australian doctors. The population of interest was junior doctors currently enrolled in a specialty training programme, termed vocational trainees (VT; n = 1890; 15.4% of the overall sample). Self-report prevalence of current alcohol, tobacco and illicit drug use were assessed and hazardous alcohol use was assessed using the Alcohol Use Disorders Identification Test. Logistic regression was used to examine the association between specialty and substance use, adjusting for demographic characteristics when required.One in six VT reported hazardous levels of alcohol use (n = 268; 17.3%). After adjusting for confounders, the association between the prevalence of alcohol use and the specialties of emergency medicine/intensive care unit (odds ratio (OR) 2.15; 95% confidence interval (CI) 1.40-3.32; P 0.001), anaesthetics (OR 2.53; 95% CI 1.35-4.76; P = 0.004) and obstetrics/gynaecology (OR 1.89; 95% CI 1.19-3.02; P = 0.007) remained significant. No significant associations were found between tobacco use/illicit drug use/hazardous alcohol use and medical specialty.While rates of substance use and hazardous alcohol use in VT are similar, if not lower, than the general population, it poses a concern that there are higher rates of alcohol use in certain medical specialties.

Childhood trauma and mental disorders increase the risk of opioid dependence. We aimed to examine whether childhood trauma and mental disorders are associated with opioid agonist treatment (OAT) engagement, contact with the criminal justice system, and mortality among people with opioid dependence.This observational study linked survey data from 1482 people receiving OAT in Sydney, Australia (2004-2008) to administrative data on OAT, crime, and mortality through 2017. We used survey data to assess childhood trauma, depression, panic disorder, post-traumatic stress disorder (PTSD), borderline personality disorder, anti-social personality disorder (ASPD), and comorbid substance dependence. We used discrete-time analysis to examine time from opioid dependence onset to OAT entry and mortality. Poisson regressions were used to analyze time receiving OAT and number of charges.Participants with extensive childhood trauma histories and ASPD were less likely to enter OAT and those with depression were more likely to enter OAT in any given year after opioid dependence onset. Panic disorder, PTSD, and borderline personality disorder were associated with less time in OAT. Extensive histories of childhood trauma, PTSD, ASPD, and comorbid substance dependence increased risk of charges for any offence. There were no significant associations between the exposure variables and mortality.Our findings suggest that childhood trauma and mental disorders increase the risk of adverse treatment and social outcomes among people with opioid dependence. Interventions that aim to reduce harm among people with opioid dependence may consider the effect of childhood trauma and mental disorders on OAT engagement and crime.

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.

Background and Objectives: Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in diagnostic criteria and in the overall study design. The aim of this study was to systematically review and, where appropriate, meta-analyse estimates related to the pairwise comorbidity between mood disorders and substance-related disorders, after sorting these estimates by various study designs. Methods: We searched PubMed (MEDLINE), Embase, CINAHL and Web of Science for publications between 1980 and 2017 regardless of geographical location and language. We meta-analysed estimates from original articles in 4 broadly defined mood and 35 substance-related disorders. Results: After multiple eligibility steps, we included 120 studies for quantitative analysis. In general, regardless of variations in diagnosis type, temporal order or use of adjustments, there was substantial comorbidity between mood and substance-related disorders. We found a sixfold elevated risk between broadly defined mood disorder and drug dependence (odds ratio = 5.7) and fivefold risk between depression and cannabis dependence (odds ratio = 4.9) while the highest pooled estimate, based on period prevalence risk, was found between broadly defined dysthymic disorder and drug dependence (odds ratio = 11.3). Based on 56 separate meta-analyses, all pooled odds ratios were above 1, and 46 were significantly greater than 1 (i.e. the 95% confidence intervals did not include 1). Conclusion: This review found robust and consistent evidence of an increased risk of comorbidity between many combinations of mood and substance-related disorders. We also identified a number of under-researched mood and substance-related disorders, suitable for future scrutiny. This review reinforces the need for clinicians to remain vigilant in order to promptly identify and treat these common types of comorbidity.

Patient-reported helpfulness of treatment is an important indicator of quality in patient-centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post-traumatic stress disorder, bipolar disorder, or alcohol use disorder. Data came from 30 community epidemiological surveys - 17 in high-income countries (HICs) and 13 in low- and middle-income countries (LMICs) - carried out as part of the World Health Organization (WHO)'s World Mental Health (WMH) Surveys. Respondents were asked whether treatment of each disorder was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Across all surveys and diagnostic categories, 26.1% of patients (N=10,035) reported being helped by the very first professional they saw. Persisting to a second professional after a first unhelpful treatment brought the cumulative probability of receiving helpful treatment to 51.2%. If patients persisted with up through eight professionals, the cumulative probability rose to 90.6%. However, only an estimated 22.8% of patients would have persisted in seeing these many professionals after repeatedly receiving treatments they considered not helpful. Although the proportion of individuals with disorders who sought treatment was higher and they were more persistent in HICs than LMICs, proportional helpfulness among treated cases was no different between HICs and LMICs. A wide range of predictors of perceived treatment helpfulness were found, some of them consistent across diagnostic categories and others unique to specific disorders. These results provide novel information about patient evaluations of treatment across diagnoses and countries varying in income level, and suggest that a critical issue in improving the quality of care for mental disorders should be fostering persistence in professional help-seeking if earlier treatments are not helpful.

Summary Background Opioid agonist treatment (OAT) reduces many of the harms associated with opioid dependence. We use mathematical modelling to comprehensively evaluate the overall health benefits of OAT in people who inject drugs in Perry County (KY, USA), Kyiv (Ukraine), and Tehran (Iran). Methods We developed a dynamic model of HIV and hepatitis C virus (HCV) transmission, incarceration, and mortality through overdose, injury, suicide, disease-related and other causes. The model was calibrated to site-specific data using Bayesian methods. We evaluated preventable drug-related deaths (deaths due to HIV, HCV, overdose, suicide, or injury) averted over 2020–40 for four scenarios, added incrementally, compared with a scenario without OAT: existing OAT coverage (setting-dependent; community 4–11%; prison 0–40%); scaling up community OAT to 40% coverage; increasing average OAT duration from 4–14 months to 2 years; and scaling up prison-based OAT. Outcomes Drug-related harms contributed differentially to mortality across settings: overdose contributed 27–47% (range of median projections) of preventable drug-related deaths over 2020–40, suicide 6–17%, injury 3–17%, HIV 0–59%, and HCV 2–18%. Existing OAT coverage in Tehran (31%) could have a substantial effect, averting 13% of preventable drug-related deaths, but will have negligible effect (averting Interpretation OAT can substantially reduce drug-related harms, particularly in settings with HIV epidemics in people who inject drugs. Maximising these effects requires research and investment into achieving higher coverage and provision and longer retention of OAT in prisons and the community. Funding UK National Institute for Health Research, US National Institute on Drug Abuse.

Routinely collected data have been increasingly used to assess long-term opioid therapy (LTOT) patterns, with very little guidance on how to measure LTOT from these data sources. We conducted a systematic review of studies published between January 2000 and July 2019 to catalogue LTOT definitions, the rationale for definitions and LTOT rates in observational research using routinely collected data in nonsurgical settings. We screened 4056 abstracts, 210 full-text manuscripts and included 128 studies, mostly from the United States (81%) and published between 2015 and 2019 (69%). We identified 78 definitions of LTOT, commonly operationalised as 90 days of use within a year (23%). Studies often used multiple criteria to derive definitions (60%), mostly based on measures of duration, such as supply days/days of use (66%), episode length (21%) or prescription fills within specified time periods (12%). Definitions were based on previous publications (63%), clinical judgment (16%) or empirical data (3%); 10% of studies applied more than one definition. LTOT definition was not provided with enough details for replication in 14 studies and 38 studies did not specify the opioids evaluated. Rates of LTOT within study populations ranged from 0.2% to 57% according to study design and definition used. We observed a substantial rise in the last 5 years in studies evaluating LTOT with large variability in the definitions used and poor reporting of the rationale and implementation of definitions. This variation impacts on research reproducibility, comparability of findings and the development of strategies aiming to curb therapy that is not guideline-recommended.

Background & Aims High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. Methods HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. Results 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24–2.36), recent incarceration (aOR 1.10; 95% CI 1.01–1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13–1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72–0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69–0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78–0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82–0.98), HBV coinfection (aOR 0.69; 95% CI 0.59–0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84–0.98). Conclusions These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. Lay summary To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.

Pregabalin has become widely used as an alternative to opioids in treating certain types of chronic non-cancer pain, but few studies have examined its clinical efficacy outside trials. We address this gap by examining the utilization, correlates and clinical outcomes of pregabalin use among an Australian community-based cohort of people prescribed opioids for chronic non-cancer pain. Through a five-year prospective cohort study (n = 1514) we examined associations between pregabalin use and pain severity and interference, mental health, opioid dose and past month use of ambulance and emergency department services. We used fixed-effects regression models to examine within-participant differences, and random-effects regression models to examine within and between participant differences in clinical outcomes. In an analysis of cases with complete data over five-years (n = 896), the prevalence of pregabalin use ranged from 16% at cohort entry to 29% at 36- and 48-months, and 46% reported pregabalin use at any time during the five years.. Pregabalin use was associated with greater pain severity and interference and greater use of high-risk opioid doses (>90 oral morphine equivalents/day). Pregabalin use was not associated with changes in mental health symptoms, ambulance, or emergency department attendance in the fixed or random effects models. Pregabalin use was common, but for most people use was not associated with clinically meaningful improvements in pain or functioning.

Background Mental disorders (MDs) are known risk factors for suicide. This systematic review updates the evidence base for this association and improves upon analytic approaches by incorporating study-level and methodological variables to account for measurement error in pooled suicide risk estimates. Methods A systematic review was conducted to review studies on MDs as risk factors for suicide. Relevant studies were searched using PubMed, Embase, PsychINFO, and existing reviews from 2010 to 19. Studies were eligible if they were longitudinal/case-control studies, representative of the general population, used diagnostic instruments, and quantified suicide risk. The outcome assessed was relative risks (RRs) for suicide due to MDs. A multi-level meta-regression approach was used to obtain pooled RRs adjusted for covariates and between-study effects. Findings We identified 20 eligible studies yielding 69 RRs. Disorder type, age, sex, use of psychological autopsy, study design, and adjustment for confounders were tested as predictors of pooled suicide risk. Overall, all disorders were significant predictors of suicide with predicted adjusted RRs ranging from 4·11 [2·09, 8·09] for dysthymia to 7·64 [4·3, 13·58] for major depressive disorder. Interpretation Our results indicate that MDs are important risk factors for suicide. This systematic review provides pooled RRs that have been adjusted for methodological sources of bias. Findings from our paper may inform suicide prevention strategies as part of national health agendas., Highlights • Mental disorders are important risk factors for suicide. • Differences in study methodology may contribute to over or underestimation of study-reported suicide risk. • It is important to analytically quantify sources of variation when synthesizing published evidence on suicide risk in a meta-regression framework.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Author(s): Chaillon, A; Bharat, C; Stone, J; Jones, N; Degenhardt, L; Larney, S; Farrell, M; Vickerman, P; Hickman, M; Martin, NK; Borquez, A | Abstract: BACKGROUND AND AIMS: The individual-level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established but there is less evidence on population-level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in community and prison on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation. DESIGN: Dynamic modeling. SETTING AND PARTICIPANTS: A cohort of 49,359 individuals who ever received OAT in NSW from 2001-2018. MEASUREMENTS: Receipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1-9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1-12 months ago. The model incorporated elevated mortality post-release from prison, and OAT impact on reducing mortality and incarceration. FINDINGS: Among the cohort, mortality was 0.9 per 100 person-years, OAT coverage and retention remained high (g50%, 1.74 years/episode). Over 2001-2020, we estimate OAT provision reduced overdose and other cause mortality among the cohort by 53% [95% credible interval: 49%-56%] and 27% [22%-30%], respectively. We estimate 1.2 deaths averted and 9.7 life-years gained per 100 person-years on OAT. Prison OAT with post-release OAT-linkage accounted for 12% [11%-13%] of all deaths averted by the OAT program, primarily through preventing deaths in the first month post-release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% [1%-2%] and 3% [2%-5%] of deaths, respectively. CONCLUSION: The community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population-level overdose and all-cause mortality in the past 20 years, partially due to high retention.

BackgroundDespite the goal set by WHO to eliminate hepatitis C virus (HCV) as a public health threat, uptake of HCV testing and treatment remains low. To achieve this target, evidence-based interventions are needed to address the barriers to care for people with, or at risk of, HCV infection. We aimed to assess the efficacy of interventions to improve HCV antibody testing, HCV RNA testing, linkage to HCV care, and treatment initiation.MethodsIn this systematic review and meta-analysis, we searched MEDLINE (PubMed), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, and PsycINFO without language restrictions for reports published between database inception and July 21, 2020, assessing the following primary outcomes: HCV antibody testing; HCV RNA testing; linkage to HCV care; and direct-acting antiviral treatment initiation. We also searched key conference abstracts. We included randomised and non-randomised studies assessing non-pharmaceutical interventions that included a comparator or control group. Studies were excluded if they enrolled only paediatric populations (aged FindingsOf 15 342 unique records identified, 142 were included, which reported on 148 unique studies (47 randomised controlled trials and 101 non-randomised studies). Medical chart reminders, provider education, and point-of-care antibody testing significantly improved at least three study outcomes compared with a comparator or control. Interventions that simplified HCV testing, including dried blood spot testing, point-of-care antibody testing, reflex RNA testing, and opt-out screening, significantly improved testing outcomes compared with a comparator or control. Enhanced patient and provider support through patient education, provider care coordination, and provider education also significantly improved testing outcomes compared with a comparator or control. Integrated care and patient navigation or care coordination significantly improved linkage to care and the uptake of direct-acting antiviral treatment compared with a comparator or control.InterpretationSeveral interventions to improve HCV care that address several key barriers to HCV care were identified. New models of HCV care must be designed and implemented to address the barriers faced by the population of interest. Further high-quality research, including rigorously designed randomised studies, is still needed in key populations.FundingNone.

We aimed to characterise opioid analgesic utilisation over a 16-year period among a cohort of people with a history of opioid dependence, comparing rates of use in and out of opioid agonist treatment (OAT).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, and OAT. Generalised estimating equation models estimated the incidence and adjusted incidence rate ratios (IRR) comparing periods in and out of OAT for the number of opioid analgesic dispensings (overall, for strong opioids, and the most commonly dispensed opioid types) and the amount dispensed in oral morphine equivalent milligrams (OME).At initiation, 43.7% of the cohort were enrolled in OAT. The most commonly initiated opioid was codeine (including combinations with paracetamol; 67.8%), and 49.6% of the cohort were dispensed a psychotropic medicine in the previous 90 days. Incidence of all opioid analgesic dispensings was higher during periods out of OAT compared to in OAT (5.8 v. 2.3 dispensings per person-year; IRR 0.39, 95% CI 0.38, 0.41), with findings similar when stratified by type. Being in OAT was associated with a lower OME amount dispensed compared to out of OAT (-57.7%, 95% CI-58.8, -56.7).People with opioid dependence had high rates of recent psychotropic medicine utilisation and current OAT enrolment at the time of opioid analgesic initiation. OAT was associated with a significant reduction in opioid analgesic dispensing.