Publications by authors named "Louisa Degenhardt"

539 Publications

Changes in illicit drug use and markets with the COVID-19 pandemic and associated restrictions: findings from the Ecstasy and Related Drugs Reporting System, 2016-20.

Addiction 2021 Jun 22. Epub 2021 Jun 22.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

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.
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http://dx.doi.org/10.1111/add.15620DOI Listing
June 2021

International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management.

Pain 2021 07;162(Suppl 1):S117-S124

Pain Research, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, United Kingdom.

Abstract: The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.
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http://dx.doi.org/10.1097/j.pain.0000000000002266DOI Listing
July 2021

Genome-wide association study of phenotypes measuring progression from first cocaine or opioid use to dependence reveals novel risk genes.

Explor Med 2021 28;2:60-73. Epub 2021 Feb 28.

Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA 02118, USA.

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 < 5 x 10 were identified, one (rs61835088 = 1.03 x 10) for cocaine in the combined EA-AA meta-analysis in the gene on chromosome 1, and two for opioids in the AA portion of the sample in intergenic regions of chromosomes 4 (rs4860439, = 1.37 x 10) and 9 (rs7032521, = 3.30 x 10). After meta-analysis with data from the replication cohorts, the signal at rs61835088 improved (HR = 0.87, = 3.71 x 10 and an intergenic SNP on chromosome 21 (rs2825295, HR = 1.14, = 2.57 x 10) 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.
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http://dx.doi.org/10.37349/emed.2021.00032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192073PMC
February 2021

Opportunities to enhance linkage to hepatitis C care among hospitalised people with recent drug dependence in New South Wales, Australia: A population-based linkage study.

Clin Infect Dis 2021 Jun 9. Epub 2021 Jun 9.

The Kirby Institute, UNSW Sydney, Sydney, Australia.

Background: People who inject drugs are at greater risk of hepatitis C virus (HCV) infection and hospitalisation, yet admissions are not utilised 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 hospitalised while eligible for direct-acting antiviral (DAA) therapy, and treatment uptake according to hospitalisation 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 hospitalisation.

Results: Among 57,467 people, 14,938 (26%) had evidence of recent drug dependence, 50% (n=7,506) of whom were hospitalised while DAA eligible. Incidence of selected cause-specific hospitalisation was highest for mental health-related (15.84 per 100 person-years [PY]), drug-related (15.20 per 100PY), and injection-related infectious disease (9.15 per 100PY) hospitalisations, and lowest for alcohol use disorder (4.58 per 100PY) and liver-related (3.13 per 100PY). 65% (n=4,898) of those hospitalised had been admitted >2 times and 46% (n=3,437) were hospitalised >7 days. By the end of 2018, DAA therapy was lowest for those hospitalised >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 hospitalisation-particularly mental health, drug, and alcohol admissions-presents an opportunity for engagement in HCV care.
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http://dx.doi.org/10.1093/cid/ciab526DOI Listing
June 2021

Alcohol use among young Australian adults in May-June 2020 during the COVID-19 pandemic: a prospective cohort study.

Addiction 2021 Jun 9. Epub 2021 Jun 9.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.1111/add.15599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212116PMC
June 2021

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

JAMA Psychiatry 2021 Jun 2. Epub 2021 Jun 2.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Sydney, Australia.

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.

Objective: To estimate the association of time receiving OAT with mortality.

Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.

Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included.

Data Extraction And Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses.

Main Outcomes And Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically.

Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56).

Conclusions And Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and insurance coverage remains low. Work to improve access globally may have important population-level benefits.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173472PMC
June 2021

Big data and predictive modelling for the opioid crisis: existing research and future potential.

Lancet Digit Health 2021 06;3(6):e397-e407

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.1016/S2589-7500(21)00058-3DOI Listing
June 2021

Public health impacts to date of the legalisation of medical and recreational cannabis use in the USA.

Neuropharmacology 2021 08 16;193:108610. Epub 2021 May 16.

National Drug and Alcohol Research Centre, University of New South Wales, 22-32 King St, Randwick, NSW, 2031, Australia.

The legality of cannabis use has been changing in a number of jurisdictions around the world. In the U.S., it has been legalised for medicinal and/or recreational uses in 34 jurisdictions and counting. This study leverages the decades-long experience of legalisation in the U.S. to provide an overview of the associated changes in public attitudes, cannabis markets and adverse health effects. We found a broad-based warming of public attitudes toward legalisation, potentially influenced by the increasingly positive portrayal of cannabis in media and declines in cannabis risk perceptions. Potency of cannabis products increased significantly while prices fell sharply. Although adults were less responsive to price changes than adolescents, adults who use cannabis regularly were sensitive to prices, with an estimated 10% price reduction leading to about 2.5% increase in the rate of use. Overall, past-year cannabis use has increased in adults since 2002, and adults over 26 years old who resided in states with medicinal cannabis laws were more likely to have used cannabis in the past 30 days, to have used daily, and to have higher rates of cannabis use disorders than adults who resided in states without legalised medicinal cannabis. Traffic fatalities involving cannabis temporarily increased in some states post-legalisation, and there were more presentations to medical services related to chronic regular cannabis use. There is suggestive evidence that adverse health consequences have increased among people who use cannabis regularly since legalisation. More robust research is needed to determine whether these effects of legalisation are temporary or long-term.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108610DOI Listing
August 2021

The effect of person, treatment and prescriber characteristics on retention in opioid agonist treatment: a 15-year retrospective cohort study.

Addiction 2021 May 12. Epub 2021 May 12.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, NSW, Australia.

Background And Aims: There is limited evidence on the relationship between retention in opioid agonist treatment for opioid dependence and characteristics of treatment prescribers. This study estimated retention in buprenorphine and methadone treatment and its relationship with person, treatment and prescriber characteristics.

Design: Retrospective longitudinal study.

Setting: New South Wales, Australia.

Participants: People entering the opioid agonist treatment programme for the first time between August 2001 and December 2015.

Measurements: Time in opioid agonist treatment (primary outcome) was modelled using a generalized estimating equation model to estimate associations with person, treatment and prescriber characteristics.

Findings: The impact of medication type on opioid agonist treatment retention reduced over time; the risk of leaving treatment when on buprenorphine compared with methadone was higher among those who entered treatment earlier [e.g. 2001-03: odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.45-1.75] and lowest among those who entered most recently (2013-15: OR = 1.23, 95% CI = 1.11-1.36). In adjusted analyses, risk of leaving was reduced among people whose prescriber had longer tenure of prescribing (e.g. 3 versus 8 years: OR = 0.94, 95% CI = 0.93-0.95) compared with prescribers with shorter tenure. Aboriginal and Torres Strait Islander people, being of younger age, past-year psychosis disorder and having been convicted of more criminal charges in the year prior to treatment entry were associated with increased risk of leaving treatment.

Conclusion: In New South Wales, Australia, retention in buprenorphine treatment for opioid dependence, compared with methadone, has improved over time since its introduction in 2001. Opioid agonist treatment retention is affected not only by characteristics of the person and his or her treatment, but also of the prescriber, with those of longer prescribing tenure associated with increased retention of people in opioid agonist treatment.
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http://dx.doi.org/10.1111/add.15514DOI Listing
May 2021

Pharmaceutical Opioid Use Patterns and Indicators of Extramedical Use and Harm in Adults With Chronic Noncancer Pain, 2012-2018.

JAMA Netw Open 2021 Apr 1;4(4):e213059. Epub 2021 Apr 1.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Importance: Despite concern about harms related to long-term prescribed opioid use among individuals with chronic noncancer pain (CNCP), no study has examined whether the same patients engage in a risky pattern of use consistently for the long term.

Objective: To examine the prevalence, incidence, persistence, and cessation of a range of opioid behaviors, indicators of extramedical use, and harm among individuals who are prescribed opioids.

Design, Setting, And Participants: This 5-year prospective cohort study in communities across Australia included 1514 adults who were prescribed opioids for CNCP. Data collection took place from August 2012 to December 2018, and data analysis took place from February to November 2020.

Exposure: Prescription opioid use.

Main Outcomes And Measures: High-dose opioid use (≥200 oral morphine equivalent [OME] mg/d); requesting an increase in opioid dose; requesting an early prescription renewal; tampering with opioid medication; diversion of medication to others; and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision opioid dependence. Cessation of opioid use was also assessed.

Results: Of the 1514 participants, 672 (44.39%) were men, the mean (SD) age was 58 (19) years, and 737 (48.68%) were unemployed. At each annual interview, approximately 1 in 8 people (10.98% [95% CI, 10.33%-11.63%] to 14.73% [95% CI, 13.98%-15.48%] at any given interview) were taking more than 200 OME mg/d; comparatively more had requested an increased dosage in the previous 3 months (8.46% [95% CI, 7.89%-9.03%] to 23.77% [95% CI, 22.82%-24.73%]); and fewer asked for an early prescription renewal (4.61% [95% CI, 4.19%-5.03%] to 13.97% [95% CI, 13.24%-14.70%]). In any given interview, between 3.06% (95% CI, 2.72%-3.40%) and 7.86% (95% CI, 7.31%-8.41%) of respondents reported tampering and between 0.47% (95% CI, 0.33%-0.60%) and 1.39% (95% CI, 1.16%-1.62%) reported diversion to others. Between 8.28% (95% CI, 7.71%-8.84%) and 13.06% (95% CI, 12.35%-13.77%) met criteria for opioid dependence at each interview. Opioid cessation increased across interviews, from year 1 (9.15% [95% CI, 8.55%-9.74%]) to year 5 (20.02% [19.14%-20.89%]). There was considerable incidence and cessation in all behaviors from 1 interview to the next: most who engaged in any of these behaviors only did so at only 1 interview. For pharmaceutical opioid dependence, between 55.26% (95% CI, 53.81%-56.71%) and 64.44% (95% CI, 62.87%-66.00%) of cases in 1 interview did not meet dependence criteria in the following interview.

Conclusions And Relevance: These findings suggest considerable fluidity in opioid use, extramedical behaviors, and opioid dependence among people with CNCP. This reinforces the need for reassessment of the effectiveness and safety of prescription opioid use over time.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035647PMC
April 2021

Pharmaceutical Opioid Use Patterns and Indicators of Extramedical Use and Harm in Adults With Chronic Noncancer Pain, 2012-2018.

JAMA Netw Open 2021 Apr 1;4(4):e213059. Epub 2021 Apr 1.

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Importance: Despite concern about harms related to long-term prescribed opioid use among individuals with chronic noncancer pain (CNCP), no study has examined whether the same patients engage in a risky pattern of use consistently for the long term.

Objective: To examine the prevalence, incidence, persistence, and cessation of a range of opioid behaviors, indicators of extramedical use, and harm among individuals who are prescribed opioids.

Design, Setting, And Participants: This 5-year prospective cohort study in communities across Australia included 1514 adults who were prescribed opioids for CNCP. Data collection took place from August 2012 to December 2018, and data analysis took place from February to November 2020.

Exposure: Prescription opioid use.

Main Outcomes And Measures: High-dose opioid use (≥200 oral morphine equivalent [OME] mg/d); requesting an increase in opioid dose; requesting an early prescription renewal; tampering with opioid medication; diversion of medication to others; and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision opioid dependence. Cessation of opioid use was also assessed.

Results: Of the 1514 participants, 672 (44.39%) were men, the mean (SD) age was 58 (19) years, and 737 (48.68%) were unemployed. At each annual interview, approximately 1 in 8 people (10.98% [95% CI, 10.33%-11.63%] to 14.73% [95% CI, 13.98%-15.48%] at any given interview) were taking more than 200 OME mg/d; comparatively more had requested an increased dosage in the previous 3 months (8.46% [95% CI, 7.89%-9.03%] to 23.77% [95% CI, 22.82%-24.73%]); and fewer asked for an early prescription renewal (4.61% [95% CI, 4.19%-5.03%] to 13.97% [95% CI, 13.24%-14.70%]). In any given interview, between 3.06% (95% CI, 2.72%-3.40%) and 7.86% (95% CI, 7.31%-8.41%) of respondents reported tampering and between 0.47% (95% CI, 0.33%-0.60%) and 1.39% (95% CI, 1.16%-1.62%) reported diversion to others. Between 8.28% (95% CI, 7.71%-8.84%) and 13.06% (95% CI, 12.35%-13.77%) met criteria for opioid dependence at each interview. Opioid cessation increased across interviews, from year 1 (9.15% [95% CI, 8.55%-9.74%]) to year 5 (20.02% [19.14%-20.89%]). There was considerable incidence and cessation in all behaviors from 1 interview to the next: most who engaged in any of these behaviors only did so at only 1 interview. For pharmaceutical opioid dependence, between 55.26% (95% CI, 53.81%-56.71%) and 64.44% (95% CI, 62.87%-66.00%) of cases in 1 interview did not meet dependence criteria in the following interview.

Conclusions And Relevance: These findings suggest considerable fluidity in opioid use, extramedical behaviors, and opioid dependence among people with CNCP. This reinforces the need for reassessment of the effectiveness and safety of prescription opioid use over time.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035647PMC
April 2021

Trends in treatment episodes for methamphetamine smoking and injecting in Australia, 2003-2019.

Drug Alcohol Rev 2021 Feb 28. Epub 2021 Feb 28.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

Introduction: We examined trends in Australian treatment episodes for smoking and injecting methamphetamine from 2003 to 2019.

Methods: Data from the Alcohol and Other Drug Treatment National Minimum Data Set, where amphetamines were the principal drug of concern, were analysed from 2003 to 2019. Rates were calculated per 100 000 population aged 10-100 years. Joinpoint software was used to identify changepoints and estimate the annual percentage change (APC) in the rate of treatment episodes. Treatment episode characteristics were compared for smoking versus injecting in 2019.

Results: The rate of treatment episodes for methamphetamine increased from 77 to 262 per 100 000 population between 2003 and 2019 (average APC 8%, P < 0.001), this being due to treatment episodes for smoking methamphetamine (average APC 32%, P < 0.001) with no significant increase in treatment episodes for injecting methamphetamine (average APC 3%). Treatment episodes for smoking increased sharply from 2003 to 2008 (APC 72%, P < 0.001) and again from 2010 to 2016 (APC 46%, P < 0.001), this upward trend being attenuated between 2016 and 2019 (APC 7%, P = 0.012). Treatment episodes for methamphetamine smoking (cf. injecting) involved younger clients (median age 30 vs. 35 years, P < 0.001) who were more likely to receive assessment or case management only (37% vs. 29%, P < 0.001).

Discussion And Conclusions: Increased methamphetamine treatment episodes in Australia since 2003 are due mostly to smoking the drug, this occurring among younger cohort who receive less substantive treatment than clients who inject methamphetamine.
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http://dx.doi.org/10.1111/dar.13258DOI Listing
February 2021

Trends in treatment episodes for methamphetamine smoking and injecting in Australia, 2003-2019.

Drug Alcohol Rev 2021 Feb 28. Epub 2021 Feb 28.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

Introduction: We examined trends in Australian treatment episodes for smoking and injecting methamphetamine from 2003 to 2019.

Methods: Data from the Alcohol and Other Drug Treatment National Minimum Data Set, where amphetamines were the principal drug of concern, were analysed from 2003 to 2019. Rates were calculated per 100 000 population aged 10-100 years. Joinpoint software was used to identify changepoints and estimate the annual percentage change (APC) in the rate of treatment episodes. Treatment episode characteristics were compared for smoking versus injecting in 2019.

Results: The rate of treatment episodes for methamphetamine increased from 77 to 262 per 100 000 population between 2003 and 2019 (average APC 8%, P < 0.001), this being due to treatment episodes for smoking methamphetamine (average APC 32%, P < 0.001) with no significant increase in treatment episodes for injecting methamphetamine (average APC 3%). Treatment episodes for smoking increased sharply from 2003 to 2008 (APC 72%, P < 0.001) and again from 2010 to 2016 (APC 46%, P < 0.001), this upward trend being attenuated between 2016 and 2019 (APC 7%, P = 0.012). Treatment episodes for methamphetamine smoking (cf. injecting) involved younger clients (median age 30 vs. 35 years, P < 0.001) who were more likely to receive assessment or case management only (37% vs. 29%, P < 0.001).

Discussion And Conclusions: Increased methamphetamine treatment episodes in Australia since 2003 are due mostly to smoking the drug, this occurring among younger cohort who receive less substantive treatment than clients who inject methamphetamine.
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http://dx.doi.org/10.1111/dar.13258DOI Listing
February 2021

Variations in Long-term Opioid Therapy Definitions: A Systematic Review of Observational Studies Using Routinely Collected Data (2000-2019).

Br J Clin Pharmacol 2021 Feb 24. Epub 2021 Feb 24.

Centre for Big Data Research in Health, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.1111/bcp.14798DOI Listing
February 2021

Trends in cocaine use, markets and harms in Australia, 2003-2019.

Drug Alcohol Rev 2021 Feb 24. Epub 2021 Feb 24.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

Introduction: This paper aims to describe cocaine use, markets and harms in Australia from 2003 to 2019.

Methods: Outcome indicators comprised prevalence of use from triennial household surveys; patterns of use from annual surveys of sentinel samples who use stimulants; and cocaine-related seizures, arrests, hospitalisations, deaths and treatment episodes. Bayesian autoregressive time-series analyses were conducted to estimate trend over time: Model 1, no change; Model 2, constant rate of change; and Model 3, change over time differing in rate after one change point.

Results: Past-year population prevalence of use increased over time. The percentage reporting recent use in sentinel samples increased by 6.1% (95% credible interval [CrI ] 1.2%,16.9%; Model 3) per year from around 2017 (48%) until the end of the series (2019: 67%). There was a constant annual increase in number of seizures (count ratio: 1.1, CrI 1.1,1.2) and arrests (1.2, CrI 1.1,1.2), and percentage reporting cocaine as easy to obtain in the sentinel samples (percent increase 1.2%, CrI 0.5%,1.8%; Model 2). Cocaine-related hospitalisation rate increased from 5.1 to 15.6 per 100 000 people from around 2011-2012 to 2017-2018: an annual increase of 1.3 per 100 000 people (CrI 0.8,1.8; Model 3). While the death rate was low (0.23 cocaine-related deaths per 100 000 people in 2018; Model 2), treatment episodes increased from 3.2 to 5.9 per 100 000 people from around 2016-2017 to 2017-2018: an annual increase of 2.9 per 100 000 people (CrI 1.6,3.7; Model 3).

Discussion And Conclusions: Cocaine use, availability and harm have increased, concentrated in recent years, and accompanied by increased treatment engagement.
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http://dx.doi.org/10.1111/dar.13252DOI Listing
February 2021

The Lancet Public Health Commission on gambling.

Lancet Public Health 2021 01;6(1):e2-e3

Harvard University, Cambridge, MA, USA.

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http://dx.doi.org/10.1016/S2468-2667(20)30289-9DOI Listing
January 2021

Prevalence of childhood maltreatment among people with opioid use disorder: A systematic review and meta-analysis.

Drug Alcohol Depend 2021 02 20;219:108459. Epub 2020 Dec 20.

National Drug and Alcohol Research Centre, UNSW Sydney, 22-32 King Street, Randwick, NSW, 2031, Australia.

Background: Experience of childhood maltreatment (CM) is a risk factor for opioid use disorder (OUD). CM is also associated with comorbid mental disorders and poor treatment outcomes among people with OUD. To our knowledge, this is the first systematic review and meta-analysis to estimate the prevalence of CM among people with OUD.

Methods: We searched MEDLINE, EMBASE, and PsycINFO to identify observational studies that evaluated CM among people with OUD from January 1990 to June 2020. Prevalence of each CM type, sample characteristics, and methodological factors were extracted from each eligible study. Random-effects meta-analyses were used to pool prevalence estimates. Stratified meta-analyses were used to assess heterogeneity.

Results: Of the 6,438 publications identified, 113 studies reported quantitative CM data among people with OUD and 62 studies (k = 62; N = 21,871) were included in primary analyses. Among people with OUD, the estimated prevalence of sexual abuse was 41% (95% CI 36-47%; k = 38) among women and 16% (95% CI 12-20%; k = 25) among men. Among all people with OUD, prevalence estimates were 38% (95% CI 33-44%; k = 48) for physical abuse, 43% (95% CI 38-49%; k = 31) for emotional abuse, 38% (95% CI 30-46%; k = 17) for physical neglect, and 42% (95% CI 32-51%; k = 17) for emotional neglect. Sex, history of injecting drug use, recruitment methods, and method of assessing CM were associated with substantial heterogeneity.

Conclusions: People with OUD frequently report the experience of CM, supporting the need for trauma-informed interventions among this population. Future research should consider the impact of CM on OUD presentations and when assessment is appropriate, use of validated instruments.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855829PMC
February 2021

Clinical correlates and outcomes associated with pregabalin use among people prescribed opioids for chronic non-cancer pain: A five-year prospective cohort study.

Br J Clin Pharmacol 2021 Aug 26;87(8):3092-3104. Epub 2021 Jan 26.

National Drug and Alcohol Research Centre, UNSW, Sydney, Australia.

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: Pregabalin use was common, but for most people use was not associated with clinically meaningful improvements in pain or functioning.
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http://dx.doi.org/10.1111/bcp.14715DOI Listing
August 2021

Retention of opioid agonist treatment prescribers across New South Wales, Australia, 2001-2018: Implications for treatment systems and potential impact on client outcomes.

Drug Alcohol Depend 2021 02 19;219:108464. Epub 2020 Dec 19.

National Drug and Alcohol Research Centre, University of NSW, Sydney NSW 2052, Australia. Electronic address:

Background: There has been much research on the efficacy and effectiveness of opioid agonist treatment (OAT), but less on its implementation and sustainability. A challenge internationally has been recruiting and retaining prescribers. This paper aims to characterise the prescribers in terms of OAT prescribing behaviours.

Methods: Retrospective cohort study in New South Wales, Australia. Participants were 2199 OAT prescribers between 1 st August 2001-19th September 2018.We examined trends in initiation and cessation of OAT prescribers. Adjusted hazard ratios were calculated to estimate prescriber retention, adjusting for year of initiation, practice type, client load and treatment prescribed.

Results: The rate of prescribers ceasing OAT prescribing has been increasing over time: a prescriber who initiated between 2016-2017 had over four times the risk of cessation compared with one who initiated before 2001, AHR: 4.77; [3.67-6.21]. The highest prescriber cessation rate was in prescribers who had prescribed for shorter time periods. The annual percentage of prescribers who ceased prescribing among those who prescribed for ≤5 years increased from 3% in 2001 to 20 % in 2017. By 2017 more prescribers were discontinuing prescribing than new prescribers were starting. Approximately 87 % (n = 25,167) of OAT clients were under the care of 20 % of OAT prescribers (n = 202); half had been prescribing OAT for 17+ years.

Conclusions: OAT prescribing is increasingly concentrated in a small group of mature prescribers, and new prescribers are not being retained. There is a need to identify and respond to the reasons that contribute to newer prescribers to cease prescribing and put in place strategies to increase retention and broaden the base of doctors involved in such prescribing.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855715PMC
February 2021

Risk factors for indicators of opioid-related harms amongst people living with chronic non-cancer pain: Findings from a 5-year prospective cohort study.

EClinicalMedicine 2020 Nov 16;28:100592. Epub 2020 Oct 16.

National Drug and Alcohol Research Centre, UNSW, Sydney, Australia.

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.
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http://dx.doi.org/10.1016/j.eclinm.2020.100592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700907PMC
November 2020

Self-harm in primary school-aged children: Prospective cohort study.

PLoS One 2020 30;15(11):e0242802. Epub 2020 Nov 30.

Centre for Adolescent Health, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Introduction: No prospective studies have examined the prevalence, antecedents or concurrent characteristics associated with self-harm in non-treatment-seeking primary school-aged children.

Methods: In 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.

Results: 28 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).

Conclusions: The 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242802PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703962PMC
January 2021

The next wave? Mental health comorbidities and patients with substance use disorders in under-resourced and rural areas.

J Subst Abuse Treat 2021 02 4;121:108189. Epub 2020 Nov 4.

Injury Control Research Center, West Virginia University, United States of America; Center of Excellence for Suicide Prevention, Department of Veterans Affairs, United States of America; Department of Behavioral Medicine and Psychiatry, West Virginia University, United States of America.

The rapid spread of the coronavirus disease (COVID-19) has impacted the lives of millions around the globe. The COVID-19 pandemic has caused increasing concern among treatment professionals about mental health and risky substance use, especially among those who are struggling with a substance use disorder (SUD). The pandemic's impact on those with an SUD may be heightened in vulnerable communities, such as those living in under-resourced and rural areas. Despite policies loosening restrictions on treatment requirements, unintended mental health consequences may arise among this population. We discuss challenges that under-resourced areas face and propose strategies that may improve outcomes for those seeking treatment for SUDs in these areas.
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http://dx.doi.org/10.1016/j.jsat.2020.108189DOI Listing
February 2021

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta-analysis.

Addiction 2021 Jul 3;116(7):1664-1676. Epub 2021 Feb 3.

Health Protection Research Unit, Population Health Sciences, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol, BS8 2PS, UK.

Background And Aim: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID.

Methods: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models.

Results: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95.

Conclusions: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.
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http://dx.doi.org/10.1111/add.15316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248165PMC
July 2021

Risk of discharge against medical advice among hospital inpatients with a history of opioid agonist therapy in New South Wales, Australia: A cohort study and nested crossover-cohort analysis.

Drug Alcohol Depend 2020 12 12;217:108343. Epub 2020 Oct 12.

National Drug and Alcohol Research Centre, 22-32 King St, Randwick NSW 2031, Australia.

Background: People who use illicit opioids have high rates of hospital admission. We aimed to measure the risk of discharge against medical advice among inpatients with a history of opioid agonist therapy (OAT), and test whether OAT is associated with lower risk of discharge against medical advice.

Methods: We conducted a cohort study of patients admitted to hospital in an emergency between 1 August 2001 and 30 April 2018 in New South Wales, Australia. All patients had a previous episode of OAT in the community. The main outcome was discharge against medical advice, and the main exposure was whether patients had an active OAT permit at the time of admission.

Results: 14,035/116,957 admissions (12 %) ended in discharge against medical advice. Admissions during periods of OAT had 0.79 (0.76-0.83; p < 0.001) times the risk of discharge against medical advice, corresponding to an absolute risk reduction of 3.0 percentage points. Risk of discharge against medical advice was higher among patients who were younger, male, identified as Aboriginal and/or Torres Strait Islander, and those admitted for accidents, drug-related reasons, or injecting-related injuries (such as cutaneous abscesses). In a subsample of 7793 patients included in a crossover-cohort analysis, OAT was associated with 0.84 (95 % CI 0.76-0.93; p < 0.001) times the risk of discharge against medical advice.

Conclusions: Among patients with a history of OAT, one in eight emergency hospital admissions ends in discharge against medical advice. OAT enrolment at the time of admission is associated with a reduction of this risk.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736124PMC
December 2020

Hospitalisations for non-fatal overdose among people with a history of opioid dependence in New South Wales, Australia, 2001-2018: Findings from the OATS retrospective cohort study.

Drug Alcohol Depend 2021 01 18;218:108354. Epub 2020 Oct 18.

National Drug and Alcohol Research Centre, University of NSW, Sydney, NSW, 2052, Australia. Electronic address:

Background: To examine, among a cohort of opioid dependent people with a history of opioid agonist treatment (OAT), the frequency and incidence rates of non-fatal overdose (NFOD) hospital separations over time, by age and sex.

Methods: Retrospective cohort study of people with a history of OAT using state-wide linked New South Wales (NSW) data. The incidence of NFOD hospital separations involving an opioid, sedative, stimulant or alcohol was defined according to the singular or combination of poisoning/toxic effect using ICD-10-AM codes. Crude incidence rates were calculated by gender, age group and calendar year.

Results: There were 31.8 (31.3-32.3) NFOD per 1,000 person-years (PY). Opioid NFOD incidence was higher in women than men: incidence rate ratio (IRR) 1.11 per 1,000PY; 95 %CI: [1.06-1.17]; women had higher sedative NFOD rates than men, IRR 1.27 per 1,000PY [1.21-1.34]. Participants ≤25 years, 26-30yrs, and 31-35yrs had higher incidence of opioid NFOD compared to 46+yrs, with IRRs of: 1.45 per 1,000PY; [1.32-1.59]; 1.20 per 1,000PY; [1.11-1.30] and 1.22 per 1,000PY; [1.13-1.32], respectively. Between 2006-7 and 2016-17, the cohort accounted for 19 % of NSW opioid NFOD episodes, 12 % of sedative, 14 % of stimulant and 5 % of acute alcohol-related NFOD.

Conclusions: Hospital stays due to NFOD are a relatively frequent occurrence among opioid-dependent people. There are clear differences in rates and substances involved by sex, age and over time. Evidence-based interventions that prevent overdose among people who are opioid dependent need to be delivered to scale, including widespread community provision of naloxone.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108354DOI Listing
January 2021

A large-scale genome-wide association study meta-analysis of cannabis use disorder.

Lancet Psychiatry 2020 12 20;7(12):1032-1045. Epub 2020 Oct 20.

Stanford University Graduate School of Education, Stanford University, Stanford, CA, USA.

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) 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). Cannabis use disorder and cannabis use were genetically correlated (r 0·50, p=1·50 × 10), 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.
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http://dx.doi.org/10.1016/S2215-0366(20)30339-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674631PMC
December 2020

Perceptions of injectable opioid agonist treatment (iOAT) among people who regularly use opioids in Australia: findings from a cross-sectional study in three Australian cities.

Addiction 2021 06 23;116(6):1482-1494. Epub 2020 Nov 23.

National Drug and Alcohol Research Centre, UNSW Sydney, Sydney, Australia.

Background And Aims: Not all people experiencing opioid dependence benefit from oral opioid agonist treatment. The aim of this study was to examine perceptions of (supervised) injectable opioid agonist treatment (iOAT) (described as 'an opioid similar to heroin self-injected at a clinic several times a day') among people who regularly use opioids and determine how common iOAT eligibility criteria accord with interest in iOAT.

Design: Cross-sectional survey SETTING: Sydney, Melbourne and Hobart, Australia PARTICIPANTS: A total of 344 people (63% male) who use opioids regularly and had ever injected opioids, interviewed December 2017-March 2018. The mean age of participants was 41.5 years [standard deviation (SD) = 8.5].

Measurements: Primary outcome measures were interest in iOAT, factors associated with interest and the proportion of participants who would be eligible using common criteria from trials and guidelines. We examined willingness to travel for iOAT, medication preferences and perspectives on whom should receive iOAT.

Findings: Overall, 53% of participants (n = 182) believed that iOAT would be a good treatment option for them. Participants who believed that iOAT was a good treatment option for them were more likely to be male [adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) = 1.10-2.82], have used heroin in the past month (aOR = 6.03, 95% CI = 2.86-12.71), currently regularly inject opioids (aOR = 1.84, 95% CI = 1.16-2.91) and have met ICD-10 criteria for opioid dependence (aOR = 3.46, 95% CI = 1.65-7.24). Those interested in iOAT had commenced more treatment episodes (aOR =1.06, 95% CI = 1.00-1.12). Among those interested in iOAT (n = 182), 26% (n = 48) met common eligibility criteria for iOAT.

Conclusions: Interest in injectable opioid agonist treatment does not appear to be universal among people who regularly use opioids. Among study participants who expressed interest in injectable opioid agonist treatment, most did not meet common eligibility criteria.
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http://dx.doi.org/10.1111/add.15297DOI Listing
June 2021

Substantial Decline in Use of HIV Preexposure Prophylaxis Following Introduction of COVID-19 Physical Distancing Restrictions in Australia: Results From a Prospective Observational Study of Gay and Bisexual Men.

J Acquir Immune Defic Syndr 2021 01;86(1):22-30

Kirby Institute, UNSW Sydney, Kensington, Australia.

Background: In response to the novel coronavirus disease (COVID-19) pandemic, Australia introduced public health and physical distancing restrictions in late March 2020. We investigated the impact of these restrictions on HIV preexposure prophylaxis (PrEP) use among Australian gay and bisexual men (GBM).

Methods: Participants in an ongoing online cohort study previously reported PrEP use from 2014 to 2019. In April 2020, 847 HIV-negative and untested participants completed questionnaires assessing changes in PrEP use as a result of COVID-19 public health measures. Binary logistic multiple regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) to compare changes in PrEP use behaviors.

Results: Among 847 men, mean age was 44.1 years (SD: 12.7). PrEP use rose from 4.9% in 2015 to 47.2% in 2020. Among those, 41.8% (n = 167) discontinued PrEP use during COVID-19 restrictions. Discontinuing PrEP during COVID-19 restrictions was independently associated with being less likely to have recently tested for HIV (aOR: 0.17; 95% CI: 0.09 to 0.34; P < 0.001) and less likely to report sex with casual partners (aOR: 0.28; 95% CI: 0.14 to 0.54; P < 0.001).

Conclusions: By April 2020, following the introduction of COVID-19 restrictions, GBM dramatically reduced PrEP use, coinciding with a reduction in sexual activity. Longer-term impacts of COVID-19 restrictions on sexual behaviors among GBM need to be monitored because they may foreshadow fluctuations in prevention coverage and risk of HIV infection. Our findings indicate a potential need for clear, targeted information about resumption of PrEP and on-demand optimal dosing regimens in response to ongoing changes in restrictions.
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http://dx.doi.org/10.1097/QAI.0000000000002514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727320PMC
January 2021
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