Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, non-invasive 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 non-responders 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.

BackgroundPeople seeking treatment for substance use disorders often have additional health and social issues. Although individuals presenting with alcohol as the primary drug of concern (PDOC) account for nearly half of all treatment episodes to the Australian alcohol and other drug (AOD) service system, previous treatment cohort studies have focused only on the profile of Australian heroin or methamphetamine users. While studies overseas indicate that clients seeking treatment primarily for their drinking are less likely to experience social and economic marginalisation than those seeking treatment primarily for illicit or pharmaceutical drug use, very little research has directly compared individuals presenting with alcohol as the PDOC to those primarily presenting with other drugs as their PDOC.MethodsSeven hundred and ninety-six participants were recruited at entry to specialist AOD treatment in Victoria and Western Australia, and completed measures of demographic and social factors, substance use, quality of life, service use, and criminal justice involvement. We compared those with alcohol as their PDOC to those with other drugs as their PDOC using Pearson chi-square and Mann–Whitney U tests.ResultsRates of social disadvantage, poor quality of life, high severity of substance dependence, and past-year AOD, mental health, acute health, and social service use were high in all groups. However, participants with alcohol as the PDOC were older; more likely to have an educational qualification; less likely to report criminal justice involvement, housing/homelessness service use, tobacco smoking, or problems with multiple substances; and reported better environmental quality of life; but were more likely to have used ambulance services, than those with other drugs as their PDOC.ConclusionsWhile those seeking treatment primarily for alcohol problems appear less likely to suffer some forms of social and economic disadvantage or to use multiple substances than those with a primary drug problem, they experience similarly high levels of substance dependence severity and mental health and AOD service use. These findings reinforce the need for AOD services to integrate or coordinate care with programs that address the many complexities clients frequently present with, while also acknowledging differences between those seeking treatment for alcohol versus other drug problems.

Background and Aims

The use of alcohol and other drugs at this celebratory event appears to be reflective of the greater than usual number of drinking hours that are available to participants. The use of safety strategies can be successful in mitigating some of the most common drug-related harms.

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Summary Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use (‘persistence’). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience (‘opioid‐naive’ having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed‐effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid‐naive and 27.24% opioid‐experienced patients met the criteria for persistence. For opioid‐naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69–0.94) for opioid‐naive patients and 0.81 (0.71–0.93) for opioid‐experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

Background and aims Despite increases in opioid prescribing and related morbidity and mortality, few studies have comprehensively documented harms across opioid types. We examined a population-wide indicator of extramedical pharmaceutical opioid-related harm to determine if the supply-adjusted rates of ambulance presentations, the severity of presentations or other attendance characteristics differed by opioid type. Design Retrospective observational study of coded ambulance patient care records related to extramedical pharmaceutical opioid use, Setting Australia Cases Primary analyses used Victorian data (n = 9823), with available data from other Australian jurisdictions (n = 4338) used to determine generalizability. Measurements We calculated supply-adjusted rates of attendances using Poisson regression, and used multinomial logistic regression to compare demographic, presentation severity, mental health, substance use and other characteristics of attendances associated with seven pharmaceutical opioids.Findings In Victoria, the highest rates of attendance [per 100 000 oral morphine equivalent mg (OME)] were for codeine (0.273/100 000) and oxycodone (0.113/100 000). The lowest rates were for fentanyl (0.019/100 000) and tapentadol (0.005/100 000). Oxycodone-naloxone rates (0.031/100 000) were lower than for oxycodone as a single ingredient (0.113/100 000). Fentanyl-related attendances were associated with the most severe characteristics, most likely to be an accidental overdose, most likely to have naloxone administered and least likely to be transferred to hospital. In contrast, codeine-related attendances were more likely to involve suicidal thoughts/behaviours, younger females and be transported to hospital. Supply-adjusted attendance rates for individual opioids were stable over time. Victorian states were broadly consistent with non-Victorian states. Conclusions In Australia, rates and characteristics of opioid-related harm vary by opioid type. Supply-adjusted ambulance attendance rates appear to be both stable over time and unaffected by large changes in supply.