Implementation of time-limited parenteral hydromorphone in people with treatment-resistant injecting opioid use disorder: a protocol for a single-site, uncontrolled, open-label study to assess feasibility, safety and cost.

INTRODUCTION: Supervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of time-limited SIOT using injectable hydromorphone delivered in an existing Australian public opioid treatment programme, with secondary outcomes of safety, cost, changes in drug use and other health outcomes. If feasible, the goal is to scale up the intervention to be more widely available in Australia. METHODS AND ANALYSIS: Between 20 and 30 participants will be offered two times per day hydromorphone to inject under direct observation, in addition to their current opioid agonist treatment (OAT), for up to 2 years. At the end of 2 years of supervised hydromorphone treatment, participants will be continued on standard OAT only. Informed consent will be obtained from all participants included in the study. This is a single-site, uncontrolled, open-label study where quantitative and qualitative interview data will be collected at baseline, 12 months and lastly at 3 months following their final hydromorphone dose. The main outcome measures are feasibility, as assessed by recruitment, retention and participation in treatment, and acceptability to participants, clinic staff and other stakeholders assessed by qualitative interviews. Secondary outcome measures of safety, as assessed by adverse events, and cost will also be assessed, as well as a range of other drug and health outcomes. ETHICS AND DISSEMINATION: This study received ethical approval from the St Vincent's Hospital Human Research Ethics Committee (2019/ETH00418). This will be the first study of time-limited SIOT in the Australian setting. All results will be submitted to peer-reviewed journals, scientific conferences and local practice meetings. A preliminary report on outcomes will also be presented to local health policy makers. A consumer and community forum will also be held to feedback results to a broader audience. TRIAL REGISTRATION NUMBER: ACTRN12621001729819.

Factors associated with experiencing stigma, discrimination, and negative health care treatment among people who inject drugs.

INTRODUCTION: Stigma has negative consequences for the health of people who inject drugs and people living with hepatitis C virus (HCV). This study evaluated factors associated with stigma related to injecting drug use (IDU) or HCV and those associated with being treated negatively by health workers. METHODS: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire including IDU- and HCV-related stigma, and negative treatment by health workers. Logistic regression was used to identify factors associated with experiencing stigma and negative treatment in a cross-sectional sample. RESULTS: Of 1,211 participants, 31% were women, 64% had injected drugs in the previous month, and 65% had been diagnosed with HCV. IDU-related stigma was reported by 57% of participants and was associated with being a woman, higher than Year 10 education, homelessness, opioid agonist treatment, recent injecting, overdose history, hospitalisation for drug use, and unknown HCV status. HCV-related stigma was reported by 34% of participants diagnosed with HCV and was associated with being a woman, homelessness, receptive needle/syringe sharing, arrest for drug use/possession, and recent HCV testing. Negative treatment from health workers was reported by 45% of participants and was associated with being a woman, receptive needle/syringe sharing, hospitalisation for drug use, and arrest for drug use/possession. DISCUSSION AND CONCLUSIONS: Results highlight important intersections and disparities in stigmatising experiences among people who inject drugs. Considering these intersections can assist health services provide more inclusive care.

Pilot study with randomised control of dual site theta burst transcranial magnetic stimulation (TMS) for methamphetamine use disorder: a protocol for the TARTAN study.

BACKGROUND: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. METHODS: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). DISCUSSION: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.

A qualitative study of using nicotine products for smoking cessation after discharge from residential drug and alcohol treatment in Australia.

INTRODUCTION: Tobacco smoking is highly prevalent among alcohol and other drugs (AOD) service clients and, despite interest in quitting, abstinence is rarely sustained. Nicotine products may assist after discharge from residential treatment services, but little is known about client receptivity to them. This study examined AOD withdrawal service clients' experiences of two types of nicotine products for smoking cessation post-discharge, combination nicotine replacement therapy (cNRT) and nicotine vaping products (NVP). METHODS: We held semi-structured telephone interviews with 31 Australian AOD service clients in a clinical trial of a 12-week smoking cessation intervention using Quitline support plus cNRT or NVP delivered post-discharge from a smoke-free residential service. We asked about health and social factors, nicotine cravings, Quitline experience, and barriers and facilitators to cNRT or NVP, then thematically analysed data. RESULTS: cNRT and NVP were described by participants as feasible and acceptable for smoking cessation. For most participants, cost limited cNRT access post study, as did difficulty navigating NVP prescription access. Quitline support was valued, but not consistently used, with participants noting low assistance with NVP-facilitated cessation. Participants considered both cessation methods acceptable and socially supported, and sought information on decreasing nicotine use via NVP. DISCUSSION AND CONCLUSIONS: AOD service clients highly valued receiving cNRT or NVP with behavioural support for smoking reduction or abstinence. Both interventions were acceptable to service clients. Findings suggest a potential need to examine both whether NVP use should be permitted in this context, and guidance on the individual suitability of cNRT or NVP.

96-week retention in treatment with extended-release subcutaneous buprenorphine depot injections among people with opioid dependence: Extended follow-up after a single-arm trial.

BACKGROUND: The most recent formulation of buprenorphine treatment is extended-release depot injections (BUP-XR) that are administered subcutaneously by health care professionals. This study aimed to observe treatment outcomes of BUP-XR delivered in standard practice during a 96-week follow-up period in a community setting. METHODS: This study is an extension of the CoLAB study, a prospective single-arm, multicentre, open label trial (N=100, 7 sites in Australia) among people with opioid dependence who received monthly injections of BUP-XR to evaluate the retention in treatment. Participants were followed for 96 weeks, comprising 48 weeks of the CoLAB study followed by a 48-week extension. RESULTS: Of 100 participants at baseline, 47 were retained on BUP-XR at 96 weeks. The median time retained on monthly depot was 90 weeks. Heroin use (adjusted OR=0.19, P=0.012) in the month prior to baseline was associated with lower odds of retention on BUP-XR. Older age at first opioid use (adjusted OR= 1.08, P=0.009) and longer duration in OAT at baseline (adjusted OR= 1.12, P=0.001) were associated with increased retention. Prevalence of past four-weeks opioid use was estimated at 4% at 96 weeks of treatment (prevalence 0.04, 95%CI: 0.00-0.11) compared to 15% at baseline. Quality of life and medication treatment satisfaction improved over time for those retained in treatment. CONCLUSION: This is one of the few studies to describe long term (96 week) retention in treatment with BUP-XR in a community setting. It displayed retention rates with 47% of participants completing 96 weeks of treatment with BUP-XR. Patient reported outcomes suggest improvements in client wellbeing. FUNDING: Indivior.

A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Participant experiences in a pilot study for methamphetamine withdrawal treatment: Implications for retention.

INTRODUCTION: There is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal. METHODS: Thematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital. RESULTS: Participants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants' subsequent decision to remain enrolled in the trial. DISCUSSION: The experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials.

Measuring Objective and Subjective Sleep during Lisdexamfetamine Treatment of Acute Methamphetamine Withdrawal: A Feasibility Study.

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.

How I manage severe bacterial infections in people who inject drugs.

BACKGROUND: Injecting drug use is a risk factor for severe bacterial infection, but there is limited high-quality evidence to guide clinicians providing care to people who inject drugs. Management can be complicated by mistrust, stigma, and competing patient priorities. OBJECTIVES: To review the management of severe infections in people who inject drugs, using an illustrative clinical scenario of complicated Staphylococcus aureus bloodstream infection. SOURCES: The discussion is based on recent literature searches of relevant topics. Very few randomized clinical trials have focussed specifically on the management of severe bacterial infections among people who inject drugs. Most recommendations are, therefore, based on observational studies, extrapolation from other patient groups, and the experience and opinions of the authors. CONTENT: We discuss evidence and options regarding the following management issues for severe bacterial infections among people who inject drugs: initial management of sepsis; indications for surgical management; assessment and management of substance dependence; approaches to antibiotic administration following clinical stability; opportunistic health promotion; and secondary prevention of bacterial infections. Throughout, we highlight the importance of harm reduction and strategies to optimize patient engagement in care through a patient-centred approach. IMPLICATIONS: We advocate for a multi-disciplinary trauma-informed approach to the management of severe bacterial infection among people who inject drugs. We emphasize the need for pragmatic trials to inform management guidelines, including those that are co-designed with the community. In particular, research is needed to establish the comparative effectiveness, safety, and cost-effectiveness of inpatient intravenous antibiotics vs. early oral antibiotic switch, outpatient parenteral therapy, and long-acting lipoglycopeptide antibiotics in this scenario.

Is post-traumatic stress disorder a risk factor for development of opioid use disorder among individuals with chronic non-cancer pain? A systematic review.

Introduction: There is emerging evidence that posttraumatic-stress disorder may have mediating effects in development of chronic-non-cancer-pain and opioid-use-disorder independently, but its impact on the development of opioid-use-disorder in people with chronic-non-cancer pain is still unclear. Objectives: (i) Estimate the risk of opioid-use-disorder among individuals with chronic-non-cancer-pain and posttraumatic-stress disorder, relative to those with chronic-non-cancer-pain only, and (ii) identify potential correlates of opioid-use-disorder among people with chronic-non-cancer-pain and posttraumatic-stress disorder. Methods: This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Longitudinal, epidemiological, cohort, follow-up, retrospective, prospective and cross-sectional studies reporting measures of variance on the likelihood of developing opioid-use-disorder with posttraumatic-stress disorder among individuals with chronic-non-cancer-pain were identified from six-electronic databases (Medline, Embase, Evidence-based Medicine reviews, PsycINFO, Scopus and Web of Science) until December 2022. Results: Three out of the four studies, which met the selection criteria for this analysis reported statistically significant positive association between risk of developing opioid-use-disorder with posttraumatic-stress disorder among chronic-non-cancer-pain cohort (unadjusted Relative-Risk range: 1.51-5.27) but this association was not evident in the fourth study (adjusted Relative-Risk: 0.96; statistically non-significant), when adjusted for sociodemographic variables. The increased risk was noted particularly with females and chronic musculoskeletal pain conditions. Conclusions: Posttraumatic-stress disorder can increase the risk of development of opioid-use-disorder among people with chronic-non-cancer-pain and a better understanding of this relationship will help to predict and prevent the development of opioid-use-disorder and may also help in reducing the disability and burden associated with chronic-non-cancer-pain. Perspective: This review quantifies the risk of developing opioid-use-disorder in the context of posttraumatic-stress disorder among individuals with chronic-non-cancer-pain. Awareness and subsequent practice change will reduce the increasing global burden associated with the chronic-non-cancer-pain.

Understanding the research capacity of alcohol and other drugs services in New South Wales, Australia.

INTRODUCTION: Enhancing health system research capacity can support improved quality care. This study assessed the research capacity of public local health district (LHD) and non-government organisation (NGO) alcohol and other drug (AOD) services, at the organisational, team and individual level. Research barriers and motivators were also examined. METHODS: Staff from LHD and NGO AOD treatment services in New South Wales completed an online survey using the Research Capacity and Culture (RCC) tool. Overall median research capacity scores are presented for the RCC subscales (organisational, team and individual). Comparisons were conducted by service type (LHD/NGO), geographical location (metropolitan/rural) and affiliation with a research network (yes/no). Qualitative questions explored barriers and motivators to research at individual and team levels. RESULTS: Of 242 participants, 55% were LHD-based and 45% NGO-based. Overall RCC scores indicated moderate research capacity at all levels. Organisational capacity (Med = 6.50, interquartile range [IQR] = 3.50) scored significantly higher than the team (Med = 5.00, IQR = 6.00) and individual level (Med = 5.00, IQR = 4.25). No differences in RCC scores existed between NGOs and LHDs. Metropolitan AOD services scored higher research capacity at the organisational level (Med = 7.00, IQR = 3.00) than rural services (Med = 5.00, IQR = 5.00). LHDs affiliated with a research network scored significantly higher at the organisational, team and individual level than non-affiliated LHD services. Key research barriers were inadequate time and funding. Motivators included skill development and problem-identification requiring change. DISCUSSIONS AND CONCLUSIONS: AOD services in New South Wales have moderate research capacity. Identified barriers and motivators can be used to target responses that enhance capacity and improve treatment outcomes.

Tobacco treatment incorporating contingency management, nicotine replacement therapy, and behavioral counseling for pregnant women who use substances: a feasibility trial.

Introduction: Most pregnant women with substance use problems smoke, and few will quit during their pregnancy. Tobacco treatment is often overlooked, with the focus usually placed on other substance use. Additionally, few targeted effective treatments for this group exist. To address this, the feasibility of an intensive tobacco treatment incorporating contingency management (CM) that featured non-face-to-face delivery was examined. Methods: A single-arm pre-post design feasibility trial was conducted in three antenatal services that support women who use substances in metropolitan Australia. Participants were over the age of 15, had <33-week gestation, and smoked tobacco daily. They received financial incentives for daily carbon monoxide-verified smoking abstinence or reduction through an internet-based CM programme, nicotine replacement therapy (NRT) posted to women and partners or household members who smoked and telephone-delivered behavioral counseling from study enrolment to birth. Results: Of the 101 referrals, 46 women (46%) consented. The mean (SD) age was 31(±6) years, and the gestation period was 22(±6) weeks. Nineteen (41%) of those enrolled were retained for 12-week postpartum. Of 46 women, 32 (70%) utilized CM; 32 (70%) used NRT for ≥2 weeks; 23 (50%) attended ≥1 counseling session; and 15 (22%) received NRT for partners/household members. Fifteen (33%) were verified abstinent from tobacco at delivery after a median (IQR) period of abstinence of 65(36-128) days. All non-smokers at birth utilized NRT and financial incentives, and 9/15 (60%) utilized counseling. Four (9%) were abstinent at 12-week postpartum. Median cigarettes smoked/day reduced from baseline to delivery (10(6-20) to 1(0-6) p =< 0.001). Women who quit smoking had more education (72% vs. 33% p =< 0.02), completed more CO samples (median (IQR) 101(59-157) vs. 2(0-20) p =< 0.001), and received more incentives (median (IQR) $909($225-$1980) vs. $34($3-$64) p =< 0.001). Intervention acceptability was rated favorably by participants (9 items rated 0-10 with scores >5 considered favorable). Discussion: This study demonstrated the feasibility and acceptability of a consumer-informed, non-face-to-face intensive tobacco treatment, highlighting the potential of remotely delivered technology-based CM to reduce the health impact of tobacco smoking in high-priority populations. The intervention demonstrates scale-up potential. Future studies should extend treatment into the postpartum period, utilizing new technologies to enhance CM delivery and improve counseling provision and partner support. Clinical trial registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374196, ACTRN1261800056224.

Substance use, socio-demographic characteristics, and self-rated health of people seeking alcohol and other drug treatment in New South Wales: baseline findings from a cohort study.

OBJECTIVE: To investigate the demographic characteristics, substance use, and self-rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. DESIGN: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. SETTING, PARTICIPANTS: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 - 30 June 2019. MAIN OUTCOME MEASURES: Socio-demographic characteristics, and substance use and self-rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. RESULTS: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine-type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20-39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine-type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53-82%, by principal drug of concern group) and reported poor psychological health (47-59%), poor physical health (32-44%), or poor quality of life (43-52%). CONCLUSIONS: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person-centred care.

Identifying thresholds for clinically meaningful change among clients of drug and alcohol services using the Australian Treatment Outcomes Profile.

AIMS: The Austraian Treatment Outcomes Profile (ATOP) is a brief clinical outcomes tool used widely in the Australian alcohol and other drugs treatment sector to monitor clients' substance use, health, wellbeing and clinical risk factors. It has demonstrated reliability and validity, and has recommended clinical cut-offs for assessing single-occasion client-rated health scores. This study determined clinically meaningful change thresholds for ATOP substance use and health and wellbeing variables for use by clinicians in monitoring client progress, and for quality improvement and service evaluation. DESIGN, SETTING AND PARTICIPANTS: A framework for assessing clinically meaningful changes scores was developed by (1) calculating statistically reliable change thresholds using data-driven techniques with a reference sample of clinical ATOP data and (2) conducting a multi-disciplinary subject matter expert group to review the utility and validity of data-derived clinically meaningful change. The study was conducted within Outpatient Alcohol and Other Drug treatment services in New South Wales, Australia. The reference sample comprised 6100 ATOPs from clients at entry to public outpatient Alcohol and Other Drug treatment services; the subject matter expert group comprised 29 key stakeholders from the specialist alcohol and other drug treatment sector. MEASUREMENTS AND FINDINGS: We used the Reliable Change Index method to calculate clinically meaningful change thresholds for ATOP variables. For substance use variables, a change of 30% in days of use in the last 28 (minimum 4 days) was the threshold for clinically meaningful change for substance use; for health and wellbeing variables, a change of 2 or more points in psychological health, physical health or quality of life scores (measured on 0-10 scales) was the minimum clinically meaningful change. CONCLUSIONS: Clinically meaningful change thresholds have been proposed for Australian Treatment Outcomes Profile substance use and health and wellbeing items, based on statistical reliability and subject matter expert assessment. These will be used in the development of an outcomes metric for assessing change and assigning meaning in aggregated data for evaluation of services.

Cohort profile: POPPY II - a population-based cohort examining the patterns and outcomes of prescription opioid use in New South Wales, Australia.

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

All-cause and cause-specific mortality in individuals with an alcohol-related emergency or hospital inpatient presentation: A retrospective data linkage cohort study.

BACKGROUND AND AIMS: Alcohol consumption is a leading risk factor for premature mortality globally, but there are limited studies of broader cohorts of people presenting with alcohol-related problems outside of alcohol treatment services. We used linked health administrative data to estimate all-cause and cause-specific mortality among individuals who had an alcohol-related hospital inpatient or emergency department presentation. DESIGN: Observational study using data from the Data linkage Alcohol Cohort Study (DACS), a state-wide retrospective cohort of individuals with an alcohol-related hospital inpatient or emergency department presentation. SETTING: Hospital inpatient or emergency department presentation in New South Wales, Australia, between 2005 and 2014. PARTICIPANTS: Participants comprised 188 770 individuals aged 12 and above, 66% males, median age 39 years at index presentation. MEASUREMENTS: All-cause mortality was estimated up to 2015 and cause-specific mortality (by those attributable to alcohol and by specific cause of death groups) up to 2013 due to data availability. Age-specific and age-sex-specific crude mortality rates (CMRs) were estimated, and standardized mortality ratios (SMRs) were calculated using sex and age-specific deaths rates from the NSW population. FINDINGS: There were 188 770 individuals in the cohort (1 079 249 person-years of observation); 27 855 deaths were recorded (14.8% of the cohort), with a CMR of 25.8 [95% confidence interval (CI) = 25.5, 26.1] per 1000 person-years and SMR of 6.2 (95% CI = 5.4, 7.2). Mortality in the cohort was consistently higher than the general population in all adult age groups and in both sexes. The greatest excess mortality was from mental and behavioural disorders due to alcohol use (SMR = 46.7, 95% CI = 41.4, 52.7), liver cirrhosis (SMR = 39.0, 95% CI = 35.5, 42.9), viral hepatitis (SMR = 29.4, 95% CI = 24.6, 35.2), pancreatic diseases (SMR = 23.8, 95% CI = 17.9, 31.5) and liver cancer (SMR = 18.3, 95% CI = 14.8, 22.5). There were distinct differences between the sexes in causes of excess mortality (all causes fully attributable to alcohol female versus male risk ratio = 2.5 (95% CI = 2.0, 3.1). CONCLUSIONS: In New South Wales, Australia, people who came in contact with an emergency department or hospital for an alcohol-related presentation between 2005 and 2014 were at higher risk of mortality than the general New South Wales population during the same period.

Health and correctional staff acceptability of depot buprenorphine in NSW prisons.

BACKGROUND: Provision of opioid agonist treatment (OAT) in custodial settings is resource-intensive and may be associated with diversion, non-medical use, and violence. A clinical trial of a new OAT, depot buprenorphine (the UNLOC-T study), provided the opportunity to obtain health and correctional staff perspectives regarding this treatment prior to widespread roll-out. METHODS: Sixteen focus groups with 52 participants were conducted, including 44 health staff (nurses, nurse practitioners, doctors, and operational staff) and eight correctional staff. RESULTS: Key challenges to providing OAT identified as potentially being addressed by depot buprenorphine included 1) patient access, 2) OAT program capacity, 3) treatment administration procedures, 4) medication diversion and other safety issues and, 5) impact on other service delivery. CONCLUSIONS: The introduction of depot buprenorphine into correctional settings was considered to have the potential to increase safety for patients, improve staff / patient relations and advance patient health outcomes via expanded treatment coverage and efficiencies gained through enhanced health service delivery. Support was almost universal from both correctional and health staff participating in this study. These findings build on emerging research regarding the positive impact of more flexible OAT programs and could be used to engage support for the implementation of depot buprenorphine from staff in other secure settings.

Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs.

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.

Health and social characteristics of clients reporting amphetamine type substance use at entry to public alcohol and other drug services in New South Wales, Australia, 2016-2019.

INTRODUCTION: Amphetamine type substances (ATS) are commonly used by Australian alcohol and other drug service entrants. We describe demographic characteristics, patterns of ATS and other substance use, health and social conditions among clients entering New South Wales (NSW) public alcohol and other drug services. METHODS: Retrospective cohort of 13,864 records across six health districts (2016-2019) for clients seeking substance use treatment. These districts service approximately 44% of the NSW population aged 15 years and over. Multivariate analysis was conducted on a subsample for whom full data were available (N = 9981). Data included NSW Minimum Data Set for drug and alcohol treatment services and Australian Treatment Outcomes Profile items. RESULTS: Over the preceding 4 weeks, 77% (n = 10,610) of clients (N = 13,864) reported no recent ATS use, 15% (n = 2109) reported 'low frequency' (1-12 days) and 8% (n = 1145) 'high frequency' (13-28 days) use. ATS use was most common among people attending for ATS or opioids as primary drug of concern. A multinomial regression (N = 9981) identified that clients reporting recent arrest (aOR 1.74, 95% CI 1.36, 2.24), higher cannabis use frequency (aOR 1.01, 95% CI 1.00, 1.02), lower opioid use frequency (aOR 0.98, 95% CI 0.97, 0.99) and poorer quality of life (aOR 0.91, 95% CI 0.86, 0.97) were more likely to report 'high frequency' rather than 'low frequency' ATS use. DISCUSSION AND CONCLUSIONS: People who use ATS experience health and social issues that may require targeted responses. These should be integrated across all services, not only for clients with ATS as principal drug of concern.