Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Bone targeting agents, but not radiation therapy, improves survival in patients with bone metastases from advanced urothelial carcinoma receiving pembrolizumab: results from the ARON-2 study.

The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.

Enhanced surveillance of notifications of hepatitis C to Queensland Health up to 19 years previously.

In this study we aimed to assess the utility of following up historical hepatitis C notifications for enhanced surveillance and linking cases to further testing and treatment. Queensland hepatitis C notifications from June 2018, 2013, 2008 and 2003 who were not incarcerated at the time of testing were followed up. The most recent identified clinicians for cases were contacted by telephone. When no information about a current clinician was available, the case was contacted via a letter or text message. Clinicians and cases were encouraged to pursue further testing and treatment and provide information about management. Following notification but prior to this study's follow-up, a majority of cases (309/532; 58%) had a negative polymerase chain reaction (PCR) test or underwent treatment.Clinician follow-up was successful in 21% of eligible cases, with the proportion decreasing with increasing time since notification. In conclusion, contacting clinicians to link notified cases to further testing and treatment may increase testing and treatment in a small proportion of cases notified up to nine years post-notification. From our experience, the follow-up of notifications before this time is unlikely to result in improved outcomes.

Using notifications data to increase hepatitis C testing and treatment rates in Queensland.

Australia's goal of eliminating hepatitis C by 2030 requires increases in uptake of and access to testing and treatment. As hepatitis C is a notifiable condition, health departments have access to information about people exposed to the hepatitis C virus (HCV), including the details of notifying clinicians who ordered their diagnostic pathology tests. Hepatitis C RNA testing confirms active infection that requires treatment, whereas a positive antibody test result only indicates prior exposure to the virus. We undertook a pilot project in Queensland to follow up hepatitis C notifications with clinicians, aiming to increase HCV-RNA testing and treatment uptake. For all individuals with a first-time hepatitis C notification in Queensland between 3 November 2020 and 28 May 2021, we sought information regarding hepatitis C RNA testing from laboratories, excluding those cases diagnosed in prisons. Cases who did not have RNA testing identified as part of or after their initial diagnostic tests were followed up via their notifying clinician. Interviews with selected clinicians were undertaken to improve our understanding of the follow-up process. There were 769 new hepatitis C notifications during our study period: 244 had no subsequent RNA test identified and were followed up for this study. Of these, 134 cases were lost to follow-up; 26 were already being effectively case managed; 22 reported previous treatment and no further risk; and 62 were eligible for HCV-RNA testing. Twenty-six cases subsequently started hepatitis C treatment. Thirty-four percent of notifications that required follow-up resulted from testing initially requested in hospital settings. Following up hepatitis C notifications can result in increased treatment rates; however, the process was resource-intensive and often failed to result in further contact between clinicians and patients. Our findings also highlight the importance of supporting better continuity of care between hospitals and community settings.

Sex Differences in Systemic and Coronary Arterial Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) predominantly affects females. Systemic and coronary arterial abnormalities are present in HFpEF and may contribute to HFpEF in females. We performed a cross-sectional study of 32 participants with HFpEF and 26 controls. Arterial hemodynamics were noninvasively assessed by combining arterial tonometry with echocardiography. Coronary microvascular function was assessed by rubidium-82 positron emission tomography as the myocardial flow reserve. Coronary vascular resistance (CVR) at rest and vasodilator stress were calculated using positron emission tomography. CVR reserve was calculated as stress - rest CVR. Multivariable linear regression assessed the associations of female sex with arterial hemodynamics in participants with and without HF, and the association of HF with arterial hemodynamics within each sex stratum. Demographics and left ventricular systolic and diastolic function were similar between males and females. Among those with HFpEF, females had a higher steady and pulsatile arterial load and more impaired (less negative) CVR reserve than males. Conversely, in controls, females had similar hemodynamics to males. We then divided the sample based on sex. Femaleswith HFpEF had a higher pulsatile arterial load and higher stress CVR than control females. Among males, arterial hemodynamics were similar, regardless of HFpEF status. The measures of early pulsatile arterial load were independently associated with higher E/e' and lower myocardial flow reserve in females only. In conclusion, despite similar left ventricular function between sexes, older females with HFpEF are characterized by additional systemic and coronary arterial hemodynamic abnormalities compared with males with HFpEF and similarly aged females without HFpEF.

Real-world effectiveness of pembrolizumab as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma: the ARON-2 study.

BACKGROUND: The advent of immune-checkpoint inhibitors has challenged previous treatment paradigms for advanced urothelial carcinoma (UC) in the post-platinum setting as well as in the first-line setting for cisplatin-ineligible patients. In this study, we investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC. METHODS: Data from patients aged ≥ 18 years with cisplatin-ineligible UC and receiving first-line pembrolizumab from January 1st 2017 to September 1st 2022 were collected. Cisplatin ineligibility was defined according to the Galsky criteria. Thirty-three Institutions from 18 countries were involved in the ARON-2 study. RESULTS: Our analysis included 162 patients. The median follow-up time was 18.9 months (95%CI 15.3-76.9). In the overall study population, the median OS was 15.8 months (95%CI 11.3-32.4). The median OS was significantly longer in males versus females while no statistically significant differences were observed between patients aged < 65y versus ≥ 65y and between smokers and non-smokers. According to Recist 1.1 criteria, 26 patients (16%) experienced CR, 32 (20%) PR, 39 (24%) SD and 55 (34%) PD. CONCLUSIONS: Our data confirm the role of pembrolizumab as first-line therapy for cisplatin-unfit patients. Further studies investigating the biological and immunological characteristics of UC patients are warranted in order to optimize the outcome of patients receiving immunotherapy in this setting.

Uptake of COVID-19 vaccination among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) may be at elevated risk of adverse outcomes from SARS-CoV-2 infection; however, data on COVID-19 vaccine uptake among PWID are scarce. This study aimed to determine COVID-19 vaccine uptake among PWID, identify factors associated with sub-optimal uptake, and compare uptake to the general population. METHODS: The Australian Needle Syringe Program Survey is an annual sentinel surveillance project, comprising a self-completed questionnaire and provision of a dried blood sample for HIV and HCV testing. In 2021, respondents provided information on their COVID-19 vaccination status. Multivariate logistic regression models identified correlates of vaccine uptake. RESULTS: Among 1166 respondents, 49% had been vaccinated and in most states and territories, vaccine uptake was significantly lower than among the general population. Independent predictors of vaccine uptake were longer duration of vaccine eligibility (AOR 3.42, 95% CI 2.65, 4.41); prior SARS-CoV-2 diagnostic testing (AOR 2.90, 95% CI 2.22, 3.79); injection of opioids (AOR 1.91, 95% CI 1.20, 3.05); and current opioid agonist therapy (AOR 1.70, 95% CI 1.23, 2.33). Women (AOR 0.70, 95% CI 0.54, 0.92) and those who reported daily or more frequent injection (AOR 0.75, 95% CI 0.57, 1.00) were significantly less likely to be vaccinated. CONCLUSIONS: In most Australian states and territories, uptake of COVID-19 vaccine among PWID lagged uptake among the general population. Increased efforts are required to ensure PWID have equitable access to vaccination. Vaccination programmes within harm reduction services and via outreach, coupled with increased support for peers to act as vaccine champions, are likely to reduce barriers and improve COVID-19 vaccine uptake in this population.

HIF activation enhances FcγRIIb expression on mononuclear phagocytes impeding tumor targeting antibody immunotherapy.

BACKGROUND: Hypoxia is a hallmark of the tumor microenvironment (TME) and in addition to altering metabolism in cancer cells, it transforms tumor-associated stromal cells. Within the tumor stromal cell compartment, tumor-associated macrophages (TAMs) provide potent pro-tumoral support. However, TAMs can also be harnessed to destroy tumor cells by monoclonal antibody (mAb) immunotherapy, through antibody dependent cellular phagocytosis (ADCP). This is mediated via antibody-binding activating Fc gamma receptors (FcγR) and impaired by the single inhibitory FcγR, FcγRIIb. METHODS: We applied a multi-OMIC approach coupled with in vitro functional assays and murine tumor models to assess the effects of hypoxia inducible factor (HIF) activation on mAb mediated depletion of human and murine cancer cells. For mechanistic assessments, siRNA-mediated gene silencing, Western blotting and chromatin immune precipitation were utilized to assess the impact of identified regulators on FCGR2B gene transcription. RESULTS: We report that TAMs are FcγRIIbbright relative to healthy tissue counterparts and under hypoxic conditions, mononuclear phagocytes markedly upregulate FcγRIIb. This enhanced FcγRIIb expression is transcriptionally driven through HIFs and Activator protein 1 (AP-1). Importantly, this phenotype reduces the ability of macrophages to eliminate anti-CD20 monoclonal antibody (mAb) opsonized human chronic lymphocytic leukemia cells in vitro and EL4 lymphoma cells in vivo in human FcγRIIb+/+ transgenic mice. Furthermore, post-HIF activation, mAb mediated blockade of FcγRIIb can partially restore phagocytic function in human monocytes. CONCLUSION: Our findings provide a detailed molecular and cellular basis for hypoxia driven resistance to antitumor mAb immunotherapy, unveiling a hitherto unexplored aspect of the TME. These findings provide a mechanistic rationale for the modulation of FcγRIIb expression or its blockade as a promising strategy to enhance approved and novel mAb immunotherapies.

Injecting drug use opportunities and reasons for choosing not to inject: A population-based study of Australian young adults who use stimulants.

INTRODUCTION: Understanding reasons for choosing not to inject drugs, among those who have never injected before, may be helpful for reducing transitions to injecting drug use. This study examines opportunities to inject and reasons for never injecting in young adults who used stimulants. METHODS: Data are from a population-based study of young adults who used ecstasy and methamphetamine (n = 313), recruited in Queensland, Australia in 2008/2009. At the follow-up, participants who had never injected (n = 293) completed a 13-item instrument on reasons for never injecting. We conducted a principal components analysis to identify types of reasons (scored 0-100) and multivariate regression to predict endorsement of these reasons. RESULTS: Approximately one-in-five of all participants ever had an opportunity to inject and there was no gender difference in the propensity to accept an opportunity. Four types of reasons, labelled risk perception, subjective effects, social environment and aversion, were identified. Male gender was associated with lower endorsement of risk perception (ß = -7.94; 95% confidence interval [CI] -13.37, -2.51) and social environment (ß = -7.35; 95% CI -13.15, -1.54). Having friends who injected was associated with lower endorsement of the social environment (ß = -8.88; 95% CI -14.83, -2.94), and higher endorsement of aversion (ß = 7.67; 95% CI 1.44, 13.89). DISCUSSION AND CONCLUSIONS: Our findings suggest that injecting drug use opportunities are common among young adults engaged in recreational drug use, with males and females equally likely to accept an opportunity. A strong aversion to injecting and a hedonic preference for non-injecting drug use may reduce the likelihood of accepting these opportunities.

Cardiac Sympathetic Positron Emission Tomography Imaging with Meta-[18F]Fluorobenzylguanidine is Sensitive to Uptake-1 in Rats.

Dysfunction of the cardiac sympathetic nervous system contributes to the development of cardiovascular diseases including ischemia, heart failure, and arrhythmias. Molecular imaging probes such as meta-[123I]iodobenzylguanidine have demonstrated the utility of assessing neuronal integrity by targeting norepinephrine transporter (NET, uptake-1). However, current radiotracers can report only on innervation due to suboptimal kinetics and lack sensitivity to NET in rodents, precluding mechanistic studies in these species. The objective of this work was to characterize myocardial sympathetic neuronal uptake mechanisms and kinetics of the positron emission tomography (PET) radiotracer meta-[18F]fluorobenzylguanidine ([18F]mFBG) in rats. Automated synthesis using spirocyclic iodonium(III) ylide radiofluorination produces [18F]mFBG in 24 ± 1% isolated radiochemical yield and 30-95 GBq/µmol molar activity. PET imaging in healthy rats delineated the left ventricle, with monoexponential washout kinetics (kmono = 0.027 ± 0.0026 min-1, Amono = 3.08 ± 0.33 SUV). Ex vivo biodistribution studies revealed tracer retention in the myocardium, while pharmacological treatment with selective NET inhibitor desipramine, nonselective neuronal and extraneuronal uptake-2 inhibitor phenoxybenzamine, and neuronal ablation with neurotoxin 6-hydroxydopamine reduced myocardial retention by 33, 76, and 36%, respectively. Clearance of [18F]mFBG from the myocardium was unaffected by treatment with uptake-1 and uptake-2 inhibitors following peak myocardial activity. These results suggest that myocardial distribution of [18F]mFBG in rats is dependent on both NET and extraneuronal transporters and that limited reuptake to the myocardium occurs. [18F]mFBG may therefore prove useful for imaging intraneuronal dysfunction in small animals.

Purebred-crossbred genetic parameters for reproductive traits in swine.

For swine breeding programs, testing and selection programs are usually within purebred (PB) populations located in nucleus units that are generally managed differently and tend to have a higher health level than the commercial herds in which the crossbred (CB) descendants of these nucleus animals are expected to perform. This approach assumes that PB animals selected in the nucleus herd will have CB progeny that have superior performance at the commercial level. There is clear evidence that this may not be the case for all traits of economic importance and, thus, including data collected at the commercial herd level may increase the accuracy of selection for commercial CB performance at the nucleus level. The goal for this study was to estimate genetic parameters for five maternal reproductive traits between two PB maternal nucleus populations (Landrace and Yorkshire) and their CB offspring: Total Number Born (TNB), Number Born Alive (NBA), Number Born Alive > 1 kg (NBA > 1 kg), Total Number Weaned (TNW), and Litter Weight at Weaning (LWW). Estimates were based on single-step GBLUP by analyzing any two combinations of a PB and the CB population, and by analyzing all three populations jointly. The genomic relationship matrix between the three populations was generated by using within-population allele frequencies for relationships within a population, and across-population allele frequencies for relationships of the CB with the PB animals. Utilization of metafounders for the two PB populations had no effect on parameter estimates, so the two PB populations were assumed to be genetically unrelated. Joint analysis of two (one PB plus CB) vs. three (both PB and CB) populations did not impact estimates of heritability, additive genetic variance, and genetic correlations. Heritabilities were generally similar between the PB and CB populations, except for LWW and TNW, for which PB populations had about four times larger estimates than CB. Purebred-crossbred genetic correlations (rpc) were larger for Landrace than for Yorkshire, except for NBA > 1 kg. These estimates of rpc indicate that there is potential to improve selection of PB animals for CB performance by including CB information for all traits in the Yorkshire population, but that noticeable additional gains may only occur for NBA > 1 kg and TNW in the Landrace population.

Relationship between FEV1 decline and mortality in patients with bronchiolitis obliterans syndrome-a systematic literature review.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is one of the most severe complications and the leading cause of late mortality and morbidity after lung transplantation (LT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). No approved treatment for BOS is available. This review aimed to systematically identify and summarise the findings regarding the relationship between FEV1 decline and mortality in patients who developed BOS following LT or allo-HSCT. METHODS: A systematic literature search was performed in the Medline, Embase and Cochrane reviews databases. Of the 501 potential studies identified 25 met inclusion criteria and were analysed. RESULTS: Overall, 13 studies reported a relationship between FEV1 and mortality, and 12 studies reported both mortality and FEV1 results but did not investigate the relationship between them. There was heterogeneity in the analyses, which investigated the relationship between FEV1 decline and mortality across the studies in terms of levels of lung functioning, comparison to a control group, treatment, and statistical methodology; nevertheless, a clear and consistent increase in the risk of death associated with FEV1 decrease was seen in the analysed studies. CONCLUSIONS: The systematic literature review identified studies and findings that support a relationship between FEV1 and mortality, with a decrease in FEV1 being statistically associated with increased risk of death. Knowing that lower FEV1 levels are associated with higher mortality rates may help assess the condition of a patient with BOS and monitor future treatment effectiveness. However, more evidence is needed to further investigate this relationship and to verify its clinical usefulness.

Genetic parameters and purebred-crossbred genetic correlations for growth, meat quality, and carcass traits in pigs.

Growth, meat quality, and carcass traits are of economic importance in swine breeding. Understanding their genetic basis in purebred (PB) and commercial crossbred (CB) pigs is necessary for a successful breeding program because, although the breeding goal is to improve CB performance, phenotype collection and selection are usually carried out in PB populations housed in biosecure nucleus herds. Thus, the selection is indirect, and the accuracy of selection depends on the genetic correlation between PB and CB performance (rpc). The objectives of this study were to 1) estimate genetic parameters for growth, meat quality, and carcass traits in a PB sire line and related commercial CB pigs and 2) estimate the corresponding genetic correlations between purebred and crossbred performance (rpc). Both objectives were investigated by using pedigree information only (PBLUP) and by combining pedigree and genomic information in a single-step genomic BLUP (ssGBLUP) procedure. Growth rate showed moderate estimates of heritability for both PB and CB based on PBLUP, while estimates were higher in CB based on ssGBLUP. Heritability estimates for meat quality traits were diverse and slightly different based on PB and CB data with both methods. Carcass traits had higher heritability estimates based on PB compared with CB data based on PBLUP and slightly higher estimates for CB data based on ssGBLUP. A wide range of estimates of genetic correlations were obtained among traits within the PB and CB data. In the PB population, estimates of heritabilities and genetic correlations were similar based on PBLUP and ssGBLUP for all traits, while based on the CB data, ssGBLUP resulted in different estimates of genetic parameters with lower SEs. With some exceptions, estimates of rpc were moderate to high. The SE on the rpc estimates was generally large when based on PBLUP due to limited sample size, especially for CBs. In contrast, estimates of rpc based on ssGBLUP were not only more precise but also more consistent among pairs of traits, considering their genetic correlations within the PB and CB data. The wide range of estimates of rpc (less than 0.70 for 7 out of 13 traits) indicates that the use of CB phenotypes recorded on commercial farms, along with genomic information, for selection in the PB population has potential to increase the genetic progress of CB performance.

Effects of additional electrical stimulation and pre-rigor conditioning temperature on the ageing potential of hot-boned bovine muscles.

OBJECTIVE: The aim of this study is to characterize the impact of additional electrical stimulation (AES) and various pre-rigor holding temperatures (for 3 h) on the ageing-potential of hot boned bovine M. longissimus lumborum (LL). METHODS: Paired LL loins from 12 bulls were hot-boned within 40 min of slaughter, immediate AES applied and subjected to various holding temperatures (5°C, 15°C, 25°C, and 35°C) for 3 h. RESULTS: AES did not accelerate the rate of rigor attainment, but the 3 h pre-rigor holding temperature did. Shear force values decreased as the pre-rigor holding temperatures increased. AES and holding for 3 h (at 25°C) resulted in higher water-holding capacity. CONCLUSION: Data confirmed that AES did not influence the various meat quality parameters in the present study, but pre-rigor holding temperature (25°C) alone or in combination with AES resulted in superior meat quality.

Effect of fast freezing then thaw-aging on meat quality attributes of lamb M. longissimus lumborum.

The objective of this study was to determine the effect of two different freezing rate then thaw-aging regimens on the quality attributes of lamb loins. The loins were randomly allocated to one of five different freezing/thawing/aging regimes: fast-(FF1A0) and slow-(SF1A0) frozen only; fast-(FF1A2) and slow-(SF1A2) frozen then thaw-aged for 14 days; aged for 14 days never frozen (A2). FF1A2 samples had a significantly higher water-holding capacity compared to the slow frozen regardless of further aging periods. FF1A2 samples had lower (p < 0.05) shear force values than A2 and higher (p < 0.05) water-holding capacity compared to the SF1A2. Fast freezing resulted in more intracellular cryo-damage, whereas slow freezing resulted in extracellular cryo-damage. FF1A0 and SF1A0 samples had lower (p < 0.05) myofibrillar proteins degradation. This study demonstrated that fast freezing then thaw-aging can result in an improved water-holding capacity and tenderness through the minimization of extracellular ice crystal formation, reduction in purge and drip losses, and improved proteolysis in thawed lamb.

Effects of electrical stimulation and pre-rigor conditioning temperature on aging potential of hot-boned beef M. longissimus lumborum.

The objective of this study was to create various pH/temp decline rates in hot-boned bull beef M. longissimus lumborum (LL) through a combination of electrical stimulation (ES) and pre-rigor holding temperature. The relationship between the pre-rigor interventions, the activities of µ-calpain and small heat shock proteins (sHSP), and the impacts on meat product quality were determined. Paired LL loins from 13 bulls were hot-boned within 40 min of slaughter, immediately ES and subjected to various holding temperatures (5, 15, 25, and 35°C) for 3 hr. The rate of muscle pH decline, sarcomere length, shear force, and proteolysis of muscle proteins were measured. ES-25°C had a longer sarcomere length compared to non-electrical stimulation samples. ES-25°C and ES-35°C samples had lower shear force values, higher µ-calpain activity and higher desmin, troponin-T, and sHSP degradation. The above findings suggest that pH/temp decline rates created in hot-boned muscle impacted muscle protein proteolysis by increasing the activity of proteases and degradation of sHSP.

Trends in methamphetamine and opioid use among clients of needle-syringe programs in Queensland, Australia: 2007-2015.

INTRODUCTION AND AIMS: Needle-syringe programs (NSP) are an underutilized source of data on drug injection trends; these data are essential for informing public health interventions. We examine trends in NSP service occasions from 2007-2015. DESIGN AND METHODS: Using standardised data from 26 NSP outlets through the Queensland NSP Minimum Data Set (QNSPMDS), trends in service occasions among clients intending to inject methamphetamine, heroin, opioid substitution therapy (OST) medications and other pharmaceutical opioids were assessed using multilevel mixed-effects negative binomial regression, adjusting for month, year, age and clustering by site. RESULTS: Over 1.5 million service occasions were recorded in 2007-2015. Methamphetamine was the main 'drug intended to inject' (33.7%), however cf. 2007, the incidence rate ratio decreased to 0.64 (95% CI: 0.62, 0.66) in 2009, remaining low until 2015. Among clients reporting methamphetamine injection, there was a shift in the form from base to the higher-potency crystal methamphetamine since 2012. Heroin injection (22.5% service occasions) initially increased (cf. 2007), followed by a decline to 0.77 (95% CI: 0.75, 0.79) in 2015. Significant and sustained increases in OST and other pharmaceutical opioids injection were observed throughout the study period, accounting for 7.2% and 19.8% of total visits, respectively. DISCUSSION AND CONCLUSIONS: The QNSPMDS provides unique, routinely collected, jurisdiction-wide and standardised data on the demographics of people who inject drugs, types of drugs injected and regional variations; these data are essential in informing policy, planning and program implementation. There remains significant opportunity to enhance engagement and linkage to care alongside needle-syringe provision.

Predictors of Aggressive Behavior While under the Influence of Illicit Drugs among Young Adult Methamphetamine Users.

BACKGROUND: Prior research indicates that patterns of combined alcohol and methamphetamine use may be associated with experiencing subjective feelings of aggression or hostility during methamphetamine use episodes. OBJECTIVES: This study examines whether subjective effects of methamphetamine use (i.e., aggression or hostility and paranoia) are associated with aggressive behavior while under the influence of any illicit drugs, controlling for combined alcohol and methamphetamine use and a number of other potential predictors. METHODS: Data from a population-based sample of Australian young adult methamphetamine users (n = 101) collected in 2010 was analyzed. A prediction model of aggressive behavior under the influence of illicit drugs was developed using penalized maximum likelihood logistic regression. RESULTS: Over one-third (34.7%) of methamphetamine users had engaged in verbal and/or physical aggression under the influence of illicit drugs in the last 12 months. In the prediction model, recurrent feelings of aggression or hostility attributed to methamphetamine use (≥3 times in the last 12 months) were associated with aggressive behavior (adjusted odds ratio 4.95, 95% confidence interval 1.67, 14.69). This association was independent of methamphetamine-attributed paranoia, combined alcohol and methamphetamine use, methamphetamine, ecstasy, cocaine, and cannabis use patterns, heavy episodic drinking, gender, and age. No association was found for combined alcohol and methamphetamine use. CONCLUSIONS: These findings indicate a link between methamphetamine-related subjective feelings of aggression or hostility and self-reported aggressive behavior while under the influence of illicit drugs. This suggests that subjective feelings of aggression or hostility may distinguish those who are involved in aggression from other methamphetamine users.

Hepatitis C viral infection and imprisonment among Aboriginal and Torres Strait Islander and non-Indigenous people who inject drugs.

INTRODUCTION AND AIMS: An understanding of the relationship between hepatitis C viral (HCV) infection and contextual factors such as imprisonment may contribute to the development of targeted treatment and prevention programs. We examine the associations of imprisonment and drug dependence with lifetime exposure to HCV, and whether these associations differ for Aboriginal and Torres Strait Islander and non-Indigenous people who inject drugs. DESIGN AND METHODS: Respondent-driven sampling was used in major cities and 'peer recruitment' in regional towns of Queensland to obtain a community sample of people who injected drugs, which comprised 243 Indigenous and 227 non-Indigenous participants who had ever been tested for HCV. Data are cross-sectional. Two binary Poisson models were developed to examine associations for variables relating to imprisonment, Indigeneity and drug use history. RESULTS: Sharing needles and syringes in prison (adjusted risk ratio 1.25, 95% confidence interval 1.02-1.53) remained significantly associated with HCV infection after adjustment for Indigeneity, injecting drug use history and drug dependence. Opioid dependence and concurrent dependence on opioids and methamphetamine was also independently associated with HCV infection. DISCUSSION AND CONCLUSIONS: Sharing needles and syringes in prison is linked with HCV infection, for both Aboriginal and Torres Strait Islander and non-Indigenous people who inject drugs. Further development of treatment and prevention programs in prisons is required, with consideration of the role of opioid and methamphetamine dependence in HCV exposure.

Experiences of police contact among young adult recreational drug users: A qualitative study.

BACKGROUND: While young adults who engage in recreational drug use are at increased risk of contact with police, their experiences of police contact have been largely overlooked. METHOD: In-depth qualitative interviews were conducted with 70 young adult amphetamine-type stimulant (ATS; i.e., ecstasy [MDMA] and methamphetamine) users who had experienced intensive alcohol and other drug-related police contact (e.g., being arrested, charged, or raided by police). These interviews focused on perceptions of personal experiences of alcohol and other drug-related police contact and general perceptions of police and policing and were conducted as part of a larger longitudinal study of drug use among a population-based sample of young adults from South-East Queensland, Australia. RESULTS: ATS users' perceptions of their personal interactions with police and general perceptions of police and policing were influenced by a number of factors, including police behaviour, prior contact with police, friends and family members' contact with police, and perceptions of their own behaviour leading to their contact with police. While a majority of ATS users reported that their contact with police had either a neutral or negative impact on their general perceptions of police and policing, some ATS users reported that police contact had a positive impact. For 70% of ATS users, police contact was reported to have had an impact on their substance use behaviours, resulting in either modification of their substance use behaviours to avoid further police contact or reduction in their substance use. CONCLUSIONS: These findings suggest that police contact among young adult ATS users can impact on both perceptions of police and policing and substance use behaviours, emphasising the importance of the quality and nature of police contact and its potential role in harm reduction.