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There are a range of models and structures that determine features of alcohol and other drug treatment. Despite some structures being long-established, less is known about how specific aspects of service delivery impact treatment-seeking for people who use alcohol and other drugs. This Australian qualitative study explored both people with lived experience of problematic alcohol and other drug use, and health care staff's experiences of service delivery.Thirty-nine semi-structured interviews with people with lived experience and staff from either alcohol and other drug specialist, or broader health-care services, explored experiences of service delivery processes and procedures. Transcripts were thematically analysed and guided by a broad interest in barriers to treatment-seeking.Within alcohol and other drug specialist services (i) time spent on wait lists; and (ii) poor implementation of assessment processes were identified barriers to treatment-seeking and engagement. Within broader health-care services (i) organisational expectations around behaviour and engagement; (ii) alcohol and other drugs viewed as separate to service role; and (iii) limited opportunities to informally engage were identified barriers to treatment-seeking.Results suggest opportunities to engage and undertake needs-based care planning are yet to be fully realised, particularly at the intake and assessment stages of alcohol and other drug service delivery; with frequent reassessment resulting in people repeatedly recounting traumatic experiences, often to different people, only to be placed back on wait lists with no support. Within broader health-care services aspects of service delivery may perpetuate stigma that places such people outside the purview of health care.

Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. In this study, we evaluate a T-cell–specific PET agent, [18F]F-AraG, as an imaging biomarker predictive of response to checkpoint inhibitor therapy. We determined the specificity of the tracer for activated T cells in vitro and in a virally induced model of rhabdomyosarcoma. Of all immune cells tested, activated human CD8+ effector cells showed the highest accumulation of [18F]F-AraG. Isolation of lymphocytes from the rhabdomyosarcoma tumors showed that more than 80% of the intratumoral signal came from accumulation of [18F]F-AraG in immune cells, primarily CD8+ and CD4+. Longitudinal monitoring of MC38 tumor-bearing mice undergoing anti-PD-1 treatment revealed differences in signal between PD-1 and isotype antibody–treated mice early into treatment. The differences in [18F]F-AraG signal were also apparent between responders and nonresponders to anti-PD-1 therapy. Importantly, we found that the signal in the tumor-draining lymph nodes provides key information about response to anti-PD-1 therapy. Overall, [18F]F-AraG has potential to serve as a much needed immunomonitoring clinical tool for timely evaluation of immunotherapy.Significance:These findings reveal differences in T-cell activation between responders and nonresponders early into anti-PD-1 treatment, which may impact many facets of immuno-oncology, including patient selection, management, and development of novel combinatorial approaches.

FACS analyses, expression of transporters and kinases in immune cells, tumor growth.

Brief interventions (BIs) delivered in primary care can reduce harmful alcohol consumption. Yet, clinicians do not routinely offer BIs to reduce harmful alcohol use.We explored the perspectives of clinicians and patients about the use of alcohol BIs during consultations in Australian primary care.Semi-structured interviews and focus groups (face-to-face and virtual) were undertaken with 34 general practitioners, eight practice nurses and 17 patients. Field notes were made from audio-recordings and themes were identified using a descriptive qualitative approach with the field notes as the point of data analysis.Participants identified barriers within the consultation, practice setting and wider healthcare system plus across the community which reduce the delivery of BIs in primary care including: Australian drinking norms; inconsistent public health messaging around alcohol harm; primary care not recognized as a place to go for help; community stigma towards alcohol use; practice team culture towards preventive health, including systems for recording alcohol histories; limitations of clinical software and current patient resources.Multiple layers of the healthcare system influence the use of BIs in primary care. Identified facilitators for embedding BIs in primary care included: (i) raising community and clinician awareness of the health harms of alcohol, (ii) reinforcing a primary care culture that promotes prevention and, (iii) supportive resources to facilitate discussion about alcohol use and strategies to reduce intake. Alcohol BIs in primary care could be further supported by community public health messages about alcohol use.Alcohol is a major source of harm in the community and primary care (including family doctor and general practice settings) can play a role in reducing harmful alcohol use. When clinicians talk to their patients about alcohol use, research has shown they can reduce how much they drink each week. We spoke with general practitioners, nurses and patients in Australia to work out what is getting in the way of conversations about alcohol in primary care. We found that both clinicians and patients think we need to raise community awareness about the health harms of alcohol, that there are health system barriers, and there could be better resources to use in consultations. Low-income patients are particularly disadvantaged by financial costs associated with alcohol and counselling services when they seek help. To increase conversations about alcohol in primary care, it could be more helpful to target the broader community, the health system and primary care.

INTRODUCTION The extant Alcohol's Harms to Others (AHTO) literature is largely comprised of reports from victims. We investigated AHTO from perpetrators' perspectives, including how harms were associated with individual characteristics, and alcohol quantities consumed during the perpetration incident. METHODS Participants (N = 2932) were 14-19 years old, recruited primarily through social media and screened as risky drinkers. They completed face-to-face (n = 594) or self-administered (n = 2338) surveys. They self-reported whether during their last risky drinking session (LRDS) they had perpetrated any verbal abuse, physical abuse or property damage. A multinomial logistic regression examined whether nine factors were associated with perpetrating zero, one or 2+ categories of AHTO. RESULTS Eleven percent (n = 323) reported perpetrating at least one form of AHTO (7.5% verbal, 1.9% physical and 4.6% property). Perpetration of AHTO at LRDS was uniquely associated with: younger age, male gender, experiences of childhood physical punishment, greater perpetration incident-specific drinking, concurrent illicit drug use, and less frequent use of safety strategies while drinking in the past 12 months. Controlling for the other variables, an increase of six Australian standard drinks (60 g of alcohol) increased the odds of perpetration by 15% [95% confidence interval (CI) adjusted odds ratio (AOR) 1.08, 1.23], and an increase of 15 Australian standard drinks increased the odds by 42% (95% CI AOR 1.20, 1.69). DISCUSSION AND CONCLUSIONS Individual characteristics, larger quantities of alcohol consumed, and a disinclination to practice harm reduction amplified risk of AHTO perpetration. This has implications for health promotion and risk prevention/reduction strategies.

Prescription drug monitoring programs (PDMP) are databases which collect prescribing and dispensing information for high-risk medicines, and are one approach to mitigate prescription opioid-related risks.To examine correlates of PDMP use under voluntary and mandatory conditions, among a representative sample of community pharmacists in Victoria, Australia.An online anonymous survey was conducted and collected data in relation to pharmacist and pharmacy characteristics, comfort in performing certain tasks, PDMP training and the frequency of PDMP use under voluntary and mandatory conditions. Multivariate logistic regression models were performed to determine the effect of each covariate on voluntary and mandatory PDMP use.In total, 265 pharmacists participated (response rate 47%). Under voluntary conditions, a quarter of pharmacists (24.9%) used the PDMP all the time, while half (51.7%) used the PDMP all of the time, once mandated. Pharmacies that stocked naloxone (OR: 1.96; 95% CI 1.11-3.45) and pharmacists that had attended formal PDMP training (OR: 1.78; 95% CI 1.05-3.05), were significantly associated with regular PDMP use under voluntary conditions. Under mandatory conditions, increased odds of PDMP use were associated with pharmacies that stocked naloxone (OR: 1.88; 95% CI 1.06-3.34). Pharmacists working in regional and rural areas had significantly lower odds (OR: 0.35; 95% CI 0.20-0.63) of always using the PDMP, as did pharmacists with 15 years' experience (OR: 0.24; 95% CI 0.11-0.51) once use was mandated.Given that PDMP utilisation was slower or less regular amongst pharmacists located in regional and rural areas, pharmacists with more years of experience and those not already supplying naloxone, targeted training aimed at these sub-populations may be beneficial.

Most clinical trials exploring various combinations of chemo- and immunotherapy rely on serial biopsy to provide information on immune response. The aim of this study was to assess the value of (18)F-arabinosyl guanine ((18)F-AraG) as a noninvasive tool that profiles tumors on the basis of the key player in adaptive antitumor response, CD8+ cells, and evaluates the immunomodulatory effects of chemotherapy. Methods: To evaluate the ability of (18)F-AraG to report on the presence of CD8+ cells within the tumor microenvironment, we imaged a panel of syngeneic tumor models (MC38, CT26, LLC, A9F1, 4T1, and B16F10) and correlated the signal intensity with the number of lymphocytes found in the tumors. The capacity of (18)F-AraG to detect immunomodulatory effects of chemotherapy was determined by longitudinal imaging of tumor-bearing mice (MC38 and A9F1) undergoing 2 types of chemotherapy: oxaliplatin/cyclophosphamide, shown to induce immunogenic cell death, and paclitaxel/carboplatin, reported to cause immunogenically silent tumor cell death. Results: In the tumor panel, (18)F-AraG revealed strikingly different uptake patterns resembling cancer-immune phenotypes observed in the clinic. A statistically significant correlation was found between the (18)F-AraG signal and the number of PD-1–positive CD8+ cells isolated from the tumors (r (2) = 0.528, P < 0.0001). In the MC38 model, paclitaxel/carboplatin did not result in an appreciable change in signal after therapy (1.69 ± 0.25 vs. 1.50 ± 0.33 percentage injected dose per gram), but oxaliplatin/cyclophosphamide treatment led to close to a 2.4-fold higher (18)F-AraG signal (1.20 ± 0.31 vs. 2.84 ± 0.93 percentage injected dose per gram). The statistically significant increase in signal after oxaliplatin/cyclophosphamide was also observed in the A9F1 model (0.95 ± 0.36 vs. 1.99 ± 0.54 percentage injected dose per gram). Conclusion: The ability of (18)F-AraG PET to assess the location and function of CD8+ cells, as well immune activity within tumors after immune priming therapy, warrants further investigation into its utility for patient selection, evaluation of optimal time to deliver immunotherapies, and assessment of combinatorial therapies.

IntroductionEach year, an estimated two million Australians commence opioids, with 50 000 developing longer-term (persistent) opioid use. An estimated 3%–10% of opioid-naïve patients prescribed opioids following surgery develop persistent opioid use. This study will compare rates of persistent opioid use between two commonly used postoperative opioids, oxycodone and tapentadol, to understand if initial postoperative opioid type is important in determining longer-term outcomes.Methods and analysisA retrospective data linkage study that analyses administrative data from hospital and community pharmacies. Data will be obtained from at least four pharmacies that service large hospitals with comparable supplies of oxycodone and tapentadol. The study will include at least 6000 patients who have been dispensed a supply of oxycodone or tapentadol to take home following their discharge from a surgical ward. The primary outcome measure will be persistent opioid use at 3 months postdischarge for opioid naïve people who receive either immediate release tapentadol or immediate release oxycodone. Hierarchical logistic regression models will be used to predict persistent opioid use, controlling for covariates including comorbidities.Ethics and disseminationEthics approval has been obtained through the Monash University Human Research Ethics Committee (29977). We will present project findings in a peer-reviewed journal article, in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data statement.

Introduction and aims Alcohol and other drug (AOD) treatment seekers who smoke tobacco are more likely to die of tobacco-related causes than those attributable to their primary drug of concern (PDOC), yet smoking cessation is frequently overlooked in the context of AOD treatment settings. We explored rates of AOD treatment success among participants who quit or continued smoking 12 months after initiating AOD treatment. Design and methods Secondary analysis of data from a prospective multisite naturalistic outcome study of 559 smokers recruited from 21 publicly funded specialist AOD services as part of the Patient Pathways National Project. Results Only 7.1% of participants successfully quit smoking at 12-month follow-up; however, doing so was associated with a 30% increase in treatment success (i.e. reliable reductions in use of their PDOC) (χ2 = 8.74, P = 0.003) and a 21% reduction in the severity of PDOC dependence (χ2 = 4.559, P = 0.033). Furthermore, those who did not nominate tobacco as a drug of concern reported demographic characteristics indicative of greater social disadvantage. Discussion and conclusions Despite low overall rates of smoking cessation, our findings suggest clients who do successfully quit have a greater likelihood of achieving reductions in PDOC use and dependence severity. These results reinforce efforts to promote more comprehensive, routine provision of smoking cessation care (i.e. counselling and nicotine replacement therapy). AOD treatment presents a crucial opportunity to deliver smoking cessation care to all clients who smoke, particularly those who are unconcerned about their use, as this group may stand to benefit most.

Objectives To characterise the community pharmacy supply of naloxone by supply type - individual prescription, prescriber bag, and non-dispensed (supplied over the counter or expired) - during 2014-2018; to examine whether the 2016 rescheduling of naloxone as an over-the-counter drug influenced non-dispensed naloxone supply volume. Design, setting Analysis of monthly naloxone prescriptions (Pharmaceutical Benefits Scheme) and sales data (IQVIA), 2014-2018, for Australia and by state and territory; time series analysis of non-dispensed naloxone supply to assess effect of rescheduling on naloxone supply. Major outcomes Total naloxone supply to community pharmacies; prescribed and non-dispensed naloxone supply. Results During 2014-2018, 372 351 400 μg units of naloxone were sold to community pharmacies: non-dispensed naloxone accounted for 205 866.5 units (55.3%), prescriber bags for 155 841 units (41.8%), and individual prescriptions for 10 643.5 units (2.9%). Population-adjusted national naloxone sales to community pharmacies increased between 2014 and 2018 (per year: incidence rate ratio [IRR], 1.15; 95% CI, 1.09-2.22). This increase was primarily attributable to increased volumes of prescriber bag naloxone (IRR, 1.63; 95% CI, 1.50-1.78) and, to a lesser extent, increased individual prescription supply (IRR, 2.04; 95% CI, 1.85-2.26). Non-dispensed naloxone supply volume was unchanged at the national level (IRR, 0.93; 95% CI, 0.85-1.01); changes in non-dispensed supply immediately following rescheduling and subsequently were not statistically significant in time series analyses for most jurisdictions. Conclusions Total naloxone supply to community pharmacies in Australia increased between 2014 and 2018, but rescheduling that enabled over-the-counter access did not significantly influence the volume of non-dispensed naloxone.

Prescription drug monitoring programs (PDMP) are electronic databases that track the prescribing and dispensing of high-risk medicines such as opioids. They have the ability to provide clinicians with alerts, which identify medication-related risks, and are used to help inform decisions to supply. This study aimed to determine to what extent patient, pharmacist, and medication related characteristics and PDMP alerts influence decisions to dispense opioids and take other action, using a randomised controlled factorial design.Pharmacists completed an online factorial experiment, comprising six randomly generated vignettes, describing a hypothetical pharmacy patient. Pharmacists ranked the likelihood of dispensing an opioid prescription and indicated other actions, if any, they would make. Mixed-effects linear and logistical models were used to examine the association between the vignette (patient, medication and alerts), and pharmacist characteristics and the likelihood to dispense and take other actions.241 pharmacists were included in the analysis (n = 1353 vignettes). The PDMP alert for high dose and multiple prescriber episodes were significant predicators of reduced likelihood to dispense, with a respective 2.73- and 4.1-unit decrease in likelihood to dispense (p 0.001). Alerts had the strongest association with other actions such as contacting the prescriber, talking to the patient and recommending naloxone, though patient and medication characteristics including age, opioid dose, benzodiazepine use and co-morbidity were also associated with increased odds of engaging in some actions.PDMP alerts were the most significant predictor of reduced likelihood to dispense and were associated with the greatest odds of taking other actions. Well-established risk factors such as high dose and high-risk drug combinations, in the absence of PDMP alerts, were associated with some actions, though to a lesser degree than PDMP alerts. These findings have significant policy implications and suggest PDMP alerts are a greater driver of decisions to dispense opioids and take other actions, compared with other known clinical risk factors.

BACKGROUND AND AIM: The current phase of the North American 'opioid crisis' is characterised by illicit fentanyl use; however, the presence of illicit fentanyl in Australia is unknown. This study aimed to monitor unintentional fentanyl consumption in Australia. DESIGN: Rapid Urine Drug Screens (UDS) paired with surveys conducted within Supervised Injecting Facilities (SIFs), and confirmatory laboratory testing. SETTING: Sydney and Melbourne, Australia PARTICIPANTS: Clients who used heroin within the past 2 days (n=911 tests, 2017-2021). Participants were demographically similar to the overall client base (median age 43, 72% male). MEASUREMENTS: UDS were conducted using BTNX Rapid Response™ fentanyl urine strip tests with cross-reactivity to numerous fentanyl analogues. Positive urine samples were analysed using liquid chromatography coupled with tandem mass spectrometry. Surveys covered past 3 day drug use and lifetime report of fentanyl in heroin. FINDINGS: Two percent of participants reported intentional use of fentanyl, mostly through fentanyl patches. Of the 911 rapid UDS conducted, 17 (1.9%) yielded positive results. Eight of these (all from Melbourne) were not explained by survey-reported fentanyl use in the past 3 days. Of these 8 unexplained positives, confirmatory laboratory analysis was conducted on 6, with 4 deemed to be false positives, and 2 confirmed for the presence of fentanyl. This represents the first confirmation of unintended use of fentanyl type substances in this population. CONCLUSION: There is limited evidence of unintentional fentanyl use among people in Sydney and Melbourne, Australia who regularly inject heroin, suggesting that, currently, there is very little illicit fentanyl in Australian drug markets accessed by Supervised Injecting Facilities attendees. This study demonstrates the feasibility of quick onsite testing to cost-effectively screen large samples for fentanyl; however, the high false positive rate emphasises the need for confirmation of positive tests through advanced analytical techniques.

Background Opioid prescribing, for chronic non-cancer pain, has increased substantially in the past two decades and is associated with significant harms. Various public health approaches have been adopted to address these harms including the implementation of prescription drug monitoring programs (PDMPs). This systematic review aims to identify how PDMP use influences healthcare providers’ clinical decision-making. Methods Six databases were searched for literature up until April 2021. Empirical studies were included, with no restrictions placed on year, location, language or study design. Thematic analysis of the identified articles was conducted and where possible, meta-analyses were conducted using a random effect model in Stata. Results Forty-one articles related to 39 studies were included. All studies were conducted in the United States, published between 2005 and 2021 and most (n = 28) related to one state-level PDMP. PDMP utilisation influenced healthcare providers’ clinical decision-making across seven broad themes: (i) the supply of controlled substances, (ii) refusal to prescribe or treat, (iii) risk mitigation strategies, (iv) communication, (v) education and counselling, (vi) referrals and care coordination and (vii) stigma. Conclusions PDMP use influenced healthcare providers’ clinical decision-making, resulting in both intended and unintended outcomes for patients. PDMPs are a public health initiative designed to reduce harms associated with increased opioid prescribing, yet their use is associated with multiple unintended outcomes. Targeted research is needed to understand the impact of healthcare providers' clinical decision-making after PDMP utilisation, and the clinical outcomes for patients identified through these tools.

BackgroundAlcohol is a major source of harm in Australia that disproportionately affects low-income communities. Alcohol brief interventions (ABIs) combine an assessment of a person’s alcohol use with advice to reduce health risks. Despite their effectiveness, ABIs are not routinely performed by clinicians. This article presents a protocol for a feasibility trial of pragmatic implementation strategies and a new set of resources to support clinicians to complete ABIs in Australian general practices.AimTo explore the facilitators and barriers to increasing the uptake of ABIs in primary care, including acceptability, reach, adoption, fidelity, and sustainability.Design & settingA mixed-methods evaluation of the uptake of ABIs in general practice clinics serving low-income communities in Melbourne, Australia. The approach is informed by the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT).MethodThe implementation strategies and resources will be trialled in five general practices over 12 months. The primary outcome will be change in the proportion of adult patients with a complete alcohol history in their electronic medical records. Baseline data collection includes a practice survey to describe practice routines for ABIs and de-identified patient medical record data on completed alcohol histories (repeated at 3, 6, 9, and 12-months post-intervention). Survey and interview data will also be collected from clinicians, patients, and primary health network staff to assess acceptability and feasibility of the intervention.ConclusionThe study will explore how the implementation strategies and resources can improve alcohol screening and management among low-income patients in general practice.

Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. In this study, we evaluate a T-cell–specific PET agent, [18F]F-AraG, as an imaging biomarker predictive of response to checkpoint inhibitor therapy. We determined the specificity of the tracer for activated T cells in vitro and in a virally induced model of rhabdomyosarcoma. Of all immune cells tested, activated human CD8+ effector cells showed the highest accumulation of [18F]F-AraG. Isolation of lymphocytes from the rhabdomyosarcoma tumors showed that more than 80% of the intratumoral signal came from accumulation of [18F]F-AraG in immune cells, primarily CD8+ and CD4+. Longitudinal monitoring of MC38 tumor-bearing mice undergoing anti-PD-1 treatment revealed differences in signal between PD-1 and isotype antibody–treated mice early into treatment. The differences in [18F]F-AraG signal were also apparent between responders and nonresponders to anti-PD-1 therapy. Importantly, we found that the signal in the tumor-draining lymph nodes provides key information about response to anti-PD-1 therapy. Overall, [18F]F-AraG has potential to serve as a much needed immunomonitoring clinical tool for timely evaluation of immunotherapy. Significance: These findings reveal differences in T-cell activation between responders and nonresponders early into anti-PD-1 treatment, which may impact many facets of immuno-oncology, including patient selection, management, and development of novel combinatorial approaches.

BACKGROUND AND AIMS Pharmaceutical opioids are a significant contributor to the global 'opioid crisis', yet few studies have comprehensively distinguished between opioid types. We measured whether a range of common pharmaceutical opioids varied in their contribution to the rates and characteristics of harm in a population-wide indicator of non-fatal overdose. DESIGN Retrospective observational study of emergency department (ED) patient care records in the Victorian Emergency Minimum Data set (VEMD), July 2009 to June 2019. SETTING Victoria, Australia. CASES ED presentations for non-fatal overdose related to pharmaceutical opioid use (n = 5403), where the specific pharmaceutical opioid was documented. MEASUREMENTS We compared harms across the nine individual pharmaceutical opioids most commonly sold, and considered where multiple opioids contributed to the overdose. We calculated supply-adjusted rates of ED presentations using Poisson regression and used multinomial logistic regression to compare demographic and clinical characteristics of presentations among nine distinct pharmaceutical opioids and a 10th category where multiple opioids were documented for the presentation. FINDINGS There were wide differences, up to 27-fold, between supply-adjusted rates of overdose. When considering presentations with sole opioids, the highest supply-adjusted overdose rates [per 100 000 oral morphine equivalents (OME); 95% confidence interval (CI)] were for codeine (OME = 0.078, 95% CI = 0.073-0.08) and oxycodone (OME =0.029, 95% CI = 0.027-0.030) and the lowest were for tapentadol (OME = 0.004, 95% CI = 0.003-0.006) and fentanyl (OME = 0.003, 95% CI = 0.002-0.004). These rates appeared related to availability rather than opioid potency. Most (62%) poisonings involved females. Codeine, oxycodone and tramadol were associated with younger presentations (respectively, 59.5%, 41.7% and 49.8% of presentations were 12-34 years old), and intentional self-harm (respectively 65.2%, 50.6%, and 52.8% of presentations). Relative to morphine, fentanyl [ 0.32 relative risk ratio (RRR)] and methadone ( 0.58 RRR) presentations were less likely to be coded as self-harm. Relative to morphine-buprenorphine, codeine, oxycodone and tramadol presentations were significantly more likely to be associated with the less urgent triage categories (respectively 2.18, 1.80, 1.52, 1.65 RRR). CONCLUSIONS In Victoria, Australia, rates and characteristics of emergency department presentations for pharmaceutical opioids show distinct variations by opioid type.

Background Take home naloxone (THN) programs have been rapidly upscaled in response to increasing opioid-related mortality. One often cited concern is that naloxone provision could be associated with increased opioid use, due to the availability of naloxone to reverse opioid overdose. We conducted a systematic review to determine whether THN provision is associated with changes in substance use by participants enrolled in THN programs. Methods We conducted a systematic review of the literature to assess changes in heroin or other substance use by people who use opioids following THN provision. Results Seven studies with 2578 participants were included. Of the seven studies, there were two quasi-experimental studies and five cohort studies. Based on the Joanna Briggs Institute quality assessment, four studies were of moderate quality and three studies were of high quality. Of the five studies that reported on the primary outcome of heroin use, no study found evidence of increased heroin use across the study population. Five studies reported on other substance use (benzodiazepines, alcohol, cocaine, amphetamine, cannabis, prescription opioids), none of which found evidence of an increase in other substance use associated with THN provision. Four studies reported on changes in overdose frequency following THN provision: three studies reporting no change, and one study of people prescribed opioids finding a reduction in opioid-related emergency department attendances for participants who received naloxone. Conclusion We found no evidence that THN provision was associated with increased opioid use or overdose. Concerns that THN supply may lead to increased substance use were not supported by data from reviewed studies.

Background and aims In Australia, oxycodone has been associated with increasing rates of harm over time, despite reduced use, reformulation to a tamper-resistant form and in contrast to most prescription opioids. We explored characteristics of oxycodone-related ambulance attendances to understand whether presentation characteristics could explain increasing oxycodone harm. Design Retrospective study of coded ambulance patient care records related to extramedical oxycodone use, January 2013 to September 2018. Setting Victoria, Australia. Cases A total of 2788 oxycodone-related ambulance attendances. Measurements Primary outcomes were temporal changes in characteristics of oxycodone presentations over time (from 2013 to 2018) and following reformulation. Covariates include demographic characteristics, presentation severity, mental health, substance use and poisoning intent. Findings Average age was 41.3 (± 16.4) years with females comprising 56.4% of attendances (n = 2788). The proportion of females in oxycodone-related attendances increased over time [an average increase in the odds ratios of 5% per year (OR) = 1.05, 95% confidence interval (CI) = 1.01-1.10]. Other temporal trends included a reduced likelihood of naloxone administration (OR = 0.92, 95% CI = 0.85-1.00), heroin involvement (OR = 0.81, 95% CI = 0.66-0.99), comorbid mental health symptoms (OR = 0.87, 95% CI = 0.82-0.92) and unknown intent poisoning (OR = 0.91, 95% CI = 0.85-0.96); and a greater risk of alcohol involvement (OR = 1.06, 95% CI = 1.01-1.11), non-opioid extramedical pharmaceutical use (OR = 1.05, 95% CI = 1.01-1.10), comorbid suicidal thoughts or behaviours (OR = 1.10, 95% CI = 1.05-1.15) and past history of psychiatric issues (OR = 1.22, 95% CI = 1.16-1.27). Interrupted time-series analysis showed that reformulation was associated with an immediate effect on sex, severity, accidental poisoning and unknown intent poisoning, although these were not sustained over time. Alcohol involvement in the attendance (OR = 1.43, 95% CI = 1.17-1.74, i.e. an average increase in the odds of 43% per year), Glasgow Coma Scale (OR = 1.28, 95%CI 1.04 - 1.57), a previous history of psychiatric issues (OR = 0.80, 95% CI = 0.70-0.92, i.e. an average decrease in the odds of 20% per year, heroin involvement (OR = 0.22, 95% CI = 0.05 - 0.98) and illicit drug use (OR = 0.45, 95% CI = 0.23 - 0.87) showed statistically significant relative changes following the reformulation. Conclusions The characteristics of oxycodone presentations in Australian ambulances attendances appear to be changing over time, including more female presentations; increasing alcohol use, extramedical use of non-opioid pharmaceuticals and suicidal thoughts or behaviours and decreasing heroin and illicit drug involvement.

Background Selgantolimod is a novel oral, selective Toll-like receptor 8 (TLR8) agonist in development for the treatment of chronic hepatitis B (CHB). TLR8 is an endosomal innate immune receptor and a target for treatment of viral infections. This first-in-human study investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selgantolimod in healthy volunteers. Methods Of 71 subjects enrolled, 59 received a single dose of selgantolimod (0.5, 1.5, 3 or 5 mg) or placebo, and 12 were evaluated for food effect. Safety, PK and PD activity by induction of cytokines, chemokines and acute phase proteins were assessed. PK/PD analyses were conducted. Results Single doses of 0.5–5 mg were generally safe. No serious adverse events (AEs) or AEs leading to discontinuation were reported, and most were Grade 1 in severity. Selgantolimod displayed rapid absorption and dose-proportional PK and PD activity. Food had minimal effect on PK but resulted in diminished PD activity. In PK/PD analyses, near-saturation of induction for most evaluated biomarkers occurred at the 5-mg dose. Conclusions Single doses of up to 5 mg selgantolimod were safe and induced dose-dependent PD responses. These data support evaluation of selgantolimod in combination with other agents in future clinical studies of CHB. Australian New Zealand Clinical Trials Registration: ACTRN12616001646437.

ISSUE ADDRESSED: Underage drinkers most commonly source alcohol from older peers. However, few studies have examined older peers' supply-related beliefs and motivations. METHODS: A sample of 270 risky drinkers aged 18-19 years were interviewed in Australia where the legal purchase age is 18. They were asked about their provision to underage friends, awareness of secondary supply legislation (intended to prohibit such supply), and 24 psycho-legal beliefs around supply. RESULTS: Half (49%) provided alcohol to a 16-17 year-old friend to drink at a party they were both attending at least twice a year. Three-quarters reported provision was okay so long as the recipient(s) were in a safe environment, and 46% reported 'everyone gives alcohol to teenagers if they are in a safe environment'. There was significantly higher agreement that "my friends would think I was mean if I didn't give alcohol to a friend under the age of 18" (37%), compared to "my friends would think I was uncool if I didn't give alcohol to a friend under the age of 18" (26%). Two-thirds (69%) felt more responsible for an underage friend's safety if they provided the alcohol. A multivariate logistic regression revealed supply was more likely if the supplier: was aged 18 compared to 19 (95%CI OR: 1.57, 4.84), male (1.06, 3.27), of a higher SES quintile (1.08, 1.80), and believed alcohol supply to minors was morally acceptable (1.01, 1.33) and normal (1.04, 1.38). Knowledge of regulatory strategies (68%) designed to prevent supply to minors, and their perceived deterrent value did not significantly impact supply. CONCLUSIONS: Supply of alcohol to underage peers was perceived as morally and socially acceptable in a group of 18-19 year old risky drinkers. SO WHAT?: Opportunities include harm reduction initiatives that prioritise caring responsibilities towards friends, as opposed to relying on external enforcement measures alone.

Introduction and aims Despite growing concerns over the extramedical use of pharmaceutical opioids, few studies have focused on the contexts that shape this use or how it might lead to harm. There is also limited research examining how contexts might vary across different opioids, such as those with well-established abuse liabilities (e.g. oxycodone) and newer 'atypical' opioids (e.g. tapentadol). We aimed to address these gaps. Design and methods We analysed Australian paramedic case descriptions for tapentadol cases (n = 82) and a representative sample of oxycodone cases (n = 82) from a 6-year period (2013-2018). We used framework analysis to identify 'contexts' shaping extramedical use from cases where use of tapentadol or oxycodone was assessed to have significantly contributed to the attendances. Results Demographically, case descriptions from both drug types were broadly similar (approximately 55% female, 44% were 35-54 years old), as were the contextual factors. The most prevalent contexts common to both oxycodone and tapentadol cases were psychological distress, physical pain and social stressors. Suicidal intent was present across multiple contexts. Discussion and conclusions This study is one of the first to explore the contexts of extramedical pharmaceutical opioid use leading to acute harm. Our analysis found patients in complex, emergency situations, seeking rapid relief from physical pain, psychological distress, social issues and/or suicidal thoughts. These data highlight the complex needs of those experiencing harm from extramedical pharmaceutical opioid use, regardless of opioid type, and the importance of contextual factors shaping both use and subsequent harm.

OBJECTIVES: Exploration of experience of harms due to another person's drinking within a demographic particularly vulnerable to these consequences. Importance of study: Largest sampling of young Australian risky drinkers, who are underrepresented in general population surveys. The range of harms due to others' drinking reported here is more comprehensive than documented elsewhere. STUDY TYPE: Cross-sectional self-report survey. METHODS: Participants were 14-19 years old and screened as being within the riskiest-drinking 25% for their age cohort. The convenience sample of 3465 was recruited primarily by social media advertising. Face-to-face interviews were conducted in all eight Australian capital cities (n = 596), supplemented by online surveys (n = 2869). Past 12-month experience of 13 harms due to others' drinking was assessed by age, gender and perpetrator. RESULTS: Females were more likely to experience seven harms, mainly characterised by fear and harassment, including being harassed or bothered at a party or some other private setting (41% vs 34% of males, p < 0.001), being given unwanted sexual attention (71% vs 47%, p < 0.001) and being put in fear (33% vs 20%, p < 0.001). Males were more likely to experience three harms, characterised by aggression: being yelled at, criticised or verbally abused (38% vs 33% of females, p = 0.002), being pushed or shoved (42% vs 28%, p < 0.001) and being physically hurt (17% vs 11%, p < 0.001). Teenagers of a legal alcohol-purchase age were more likely to experience harassment in public settings (49% vs 32-34%, p < 0.001) and unwanted sexual attention (66% vs 51-59%, p < 0.001) compared with younger teenagers. Seven of the harms studied were more likely (p < 0.01) to be perpetrated by people the respondents knew, and five (those associated with fear and aggression) were more likely to be perpetrated by strangers. CONCLUSION: Young people who are risky drinkers commonly experience multiple harms from others' drinking. Many of these alcohol harms to others are reported here for the first time, as previous studies of adolescent drinking have focused almost exclusively on the harms young people have experienced from their own drinking. This refocusing on the harms caused by the drinking of others may prompt greater community concern and concomitant calls for better alcohol regulation.

INTRODUCTION AND AIMS Prescribed psychotropic medications contribute to overdose mortality among people with alcohol and other drug (AOD) disorders. We report on prescribed psychotropic medication use among AOD treatment service attendees, focusing on sedative drugs. DESIGN AND METHODS Prospective multi-site naturalistic outcome study in residential and outpatient AOD treatment facilities in Victoria and Western Australia. A convenience sample of 480 people (57% male; mean age 36.1) entering treatment were surveyed, of whom 313 (65%) were followed up by telephone interview after a median of 377 days. Participants' prescribed psychotropic medication use was ascertained by self-report at baseline and follow-up. RESULTS At baseline, 41% of participants reported prescribed sedative medication (benzodiazepine, zopiclone or zolpidem) use within the past month, including prescriptions to treat withdrawal symptoms. At follow-up, the cohort reported a reduced rate of past month prescribed sedative use (23%; P 0.99 for change from baseline). At baseline, 40% of participants were prescribed an antidepressant and 13% an antipsychotic medication, which remained similar at follow-up (45% and 13%, respectively). DISCUSSION AND CONCLUSIONS The high level of prescribed sedative drug use reported by people receiving AOD treatment is a serious public health concern given the increasing incidence of drug overdose deaths in Australia.

Background Alcohol marketing on social networking sites (SNS) is associated with alcohol use among young people. Alcohol companies adapt their online marketing content to specific national contexts and responses to such content differ by national settings. However, there exists very little academic work comparing the association between alcohol marketing on SNS and alcohol use among young people in different national settings and across different SNS. Therefore, we aimed to extend the limited existing work by investigating and comparing the association between self-reported exposure to alcohol marketing on three leading SNS (Facebook, YouTube, and Twitter) and alcohol use among young people in diverse national contexts (India and Australia). Methods Cross-sectional, self-report data were obtained from a convenience sample of 631 respondents (330 in India; 301 in Australia) aged 13–25 years via online surveys. Respondents answered questions on their drinking behaviors and involvement with alcohol marketing on SNS. Results Many respondents from both countries reported interacting with alcohol content online, predominantly on Facebook, followed by YouTube and then Twitter. The interaction was primarily in the forms of posting/liking/sharing/commenting on items posted on alcohol companies’ social media accounts, viewing the event page/attending the event advertised by an alcohol company via social media, and/or accessing an alcohol website. Multivariate analyses demonstrated significant associations between respondents’ interaction with alcohol content and drinking levels, with effects differing by SNS, demographic group, and country. For example, having friends who shared alcohol-related content was an important predictor of usual alcohol consumption for Indian respondents (p

Objectives: We investigated young people’s exposure to alcohol advertising, their intentions to consume and purchase alcohol products following the viewing of advertisements, and whether they perceived the actors in the advertisements as being under the age of 25 years. Methods: Face‐to‐face interviews were completed with 351 risky drinking 16–19‐year‐old Australians, with a sub‐sample (n=68) responding to a range of alcohol advertisements in an in‐depth interview. Results: Participants were exposed to alcohol advertisements from an average of seven specific contexts in the past 12 months, with younger adolescents more likely to recall TV and outdoor billboards (n=351). Positive perception of advertisements was associated with increased intention to use and to purchase advertised products (n=68). A liqueur advertisement actor was perceived by 94% as being under 25 years‐old, and almost 30% thought the advertisement was marketed at people younger than 18 years of age. Conclusions: Young people’s perceptions of alcohol advertising are not necessarily in line with expert/industry assessment; products are sometimes marketed in a way that is highly appealing to young people. Greater appeal was associated with increased intention to consume and to purchase products. Implications for public health: These results indicate deficiencies in the effectiveness of current advertising codes in regard to protecting the health and wellbeing of adolescents.

INTRODUCTION AND AIMS Breathalyser estimate of blood alcohol concentration (BAC) is widely used as an objective intoxication measure, but is not always practical in nightlife contexts. This study uses in situ data collected in nightlife environments to explore how four measures of intoxication are related so as to inform the development of a more practical and reliable method of differentiating intoxication for people working in the night-time economy. DESIGN AND METHODS Nightlife patron interviews were conducted in five Australian cities. Participants completed demographic questions and were asked about current session (past 12 h) alcohol use, and four different measures of intoxication were assessed: BAC, participant's self-reported intoxication (0-10), interviewer rating of the participant's intoxication (0-10) and interviewer-rated number of the participants' of physical signs of intoxication. RESULTS A total of 7028 patrons were surveyed and n = 5273 included in analysis. Mean age was 23.9 years (SD = 6.36); 61.5% were male. There was a significant difference in occurrence of all observable intoxication symptoms across differing levels of BAC (P