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Abstract People with a history of injecting drug use are a priority for eliminating blood-borne viruses and sexually transmissible infections. Identifying them for disease surveillance in electronic medical records (EMRs) is challenged by sparsity of predictors. This study introduced a novel approach to phenotype people who have injected drugs using structured EMR data and interactive human-in-the-loop methods. We iteratively trained random forest classifiers removing important features and adding new positive labels each time. The initial model achieved 92.7% precision and 93.5% recall. Models maintained >90% precision and recall after nine iterations, revealing combinations of less obvious features influencing predictions. Applied to approximately 1.7 million patients, the final model identified 128,704 (7.7%) patients as potentially having injected drugs, beyond the 50,510 (2.9%) with known indicators of injecting drug use. This process produced explainable models that revealed otherwise hidden combinations of predictors, offering an adaptive approach to addressing the inherent challenge of inconsistently missing data in EMRs.

ABSTRACTBackground: In the aftermath of child trauma, post-traumatic stress (PTS) and depression symptoms often co-occur among trauma exposed children and their parents. Studies have used latent class analysis (LCA) to examine PTS and depression symptoms and identify homogeneous subgroups among trauma exposed children. However, little is known about subgroups or classes of PTS and depression reactions of parents of traumatised children.Objectives: (1) Determine PTS and depression symptom classes at 2–9 months post-trauma, and (2) to examine sociodemographic covariates among parents of trauma exposed children.Methods: Using harmonised individual participant data (n = 702) from eight studies (Australia, UK, US) included in the Prospective studies of Acute Child Trauma and Recovery Data Archive (PACT/R), we modelled these phenomena at the symptom level using LCA.Results: Our LCA yielded three solutions: ‘high internalizing symptom’ class (11%); ‘low PTS-high depression’ class (17%); and ‘low internalizing symptom’ class (72%). Parents of children in the ‘low PTS-high depression’ class were more likely to have children of older age and be part of an ethnic minority, compared to the ‘low internalizing symptoms’ class. Mothers were more likely to be in the ‘high internalizing symptom’ class compared to the ‘low internalizing symptoms’ class.Conclusions: These findings reveal a qualitative structure and relationship between depression and PTS symptoms that highlights the importance of assessing and targeting a broad range of internalising symptoms in post-trauma psychological treatment.

Background While people who experience incarceration have remarkably poor health profiles, undertaking research to inform evidence-based responses is complicated by difficulties of recruiting people in prison; high rates of socioeconomic marginalisation, study attrition; and legislative and financial barriers to linked data research. There are many advantages to pooling data from multiple studies involving people who experience incarceration, including greater statistical power and geographic and participant heterogeneity. However, there are also challenges that need to be addressed. Methods We combined four prospective cohort studies of adults released from prisons in four Australian states. Pre-release interviews, and validated screening assessments, were linked to primary care, medicine dispensing, hospital, alcohol and other drug treatment services, ambulatory mental health, ambulance, corrective services, and death records. Data were harmonised by team members reviewing variable definitions and categories within subject domains. Results The combined cohort consists of 4,232 adults, including 1,544 Indigenous people and 905 women, with a median age of 31 years. Data linkage will enable a median of 9.3 years of prospective follow-up after release from incarceration. Differences in data structures, coding systems between and within datasets, changes over time, and grouping of records belonging to the same event were also addressed. Conclusion This combined multi-site cohort study is an example of a complex, policy-oriented data linkage project. It was developed to underpin evidence-based, culturally appropriate interventions, health policy and service development for people who were incarcerated. This presentation will discuss the processes and pitfalls experienced while building a multi-sectoral, multi-jurisdictional data linkage project.

Abstract Background Primary needle and syringe programs (NSPs) have been integral for the prevention of blood-borne virus (BBV) transmission among people who inject drugs. Despite this, many people who inject drugs face barriers accessing these services, particularly after-hours when most services are closed. To our knowledge, the St Kilda NSP, in Melbourne, Victoria, is the only primary NSP providing 24/7 dedicated stand-alone face-to-face services for people who inject drugs in Australia. We conducted an evaluation of the St Kilda NSP to assess its role and effectiveness in meeting client needs. Methods Mixed research methods were used to conduct the evaluation. We analysed four quantitative data sets including the Victorian Needle and Syringe Program Information System data; NSP ‘snapshot’ survey data; and St Kilda NSP records of after-hours contacts and naloxone training events. Qualitative interviews were conducted with 20 purposively selected NSP clients, which were focused on individual needs, expectations and experiences accessing the service. Interviews were audio recorded and transcribed, and data were analysed thematically. A convergent research design was used to merge the five data sets. Results St Kilda NSP had 39,898 service contacts in 2018; 72% of contacts occurred outside business hours. Similarly, of 1,185,000 sterile needles and syringes dispatched, 71% were distributed outside business hours. Participants described valuing the after-hours service because drug use patterns did not always align with standard NSP opening hours and after-hours access afforded anonymity when collecting injecting equipment. Narratives highlighted several additional benefits of the 24/7 service, including: access to safer sex equipment; material support; naloxone training; referrals to specialist services; face-to-face emotional and social support from a non-judging worker; and for women involved in sex work in particular, being able to seek refuge when feeling unsafe on the streets. Conclusions Our study provides evidence of the social and health benefits (beyond that of preventing BBV transmission) that can be gained through the provision of 24/7 primary NSP services. Findings support the need for the establishment of after-hours primary NSPs in other areas of Australia where active street-based drug markets operate outside business hours and concentrated numbers of people who inject drugs live and spend time.

Abstract Background A precipitous decline in health status among people recently released from prison is common. In Victoria, Australia, opioid agonist treatment (OAT) in the community involves frequent contact with primary care, potentially facilitating broader use of primary healthcare services. Among a cohort of men who injected drugs regularly pre-imprisonment, we estimated differences in rates of primary healthcare use and medication dispensation between people who did and did not receive OAT post-release. Methods Data came from the Prison and Transition Health Cohort Study. Three-month post-release follow-up interviews were linked with primary care and medication dispensation records. Generalised linear models were fit with one exposure (OAT: none/partial/complete) for 13 outcomes relating to primary healthcare use, pathology testing, and medication dispensation, adjusted for other covariates. Coefficients were reported as adjusted incidence rate ratios (AIRR). Results Analyses included 255 participants. Compared to no OAT use, both partial and complete OAT use were associated with increased rates of standard (AIRR: 3.02, 95%CI: 1.88–4.86; AIRR: 3.66, 95%CI: 2.57–5.23), extended (AIRR: 2.56, 95%CI: 1.41–4.67; AIRR: 2.55, 95%CI: 1.60–4.07) and mental health-related (AIRR: 2.71, 95%CI: 1.42–5.20; AIRR: 2.27, 95%CI: 1.33–3.87) general practitioner (GP) consultations, total medication (AIRR: 1.88, 95%CI: 1.19–2.98; AIRR: 2.40, 95%CI: 1.71–3.37), benzodiazepine (AIRR: 4.99, 95%CI: 2.81–8.85; AIRR: 8.30, 95%CI: 5.28–13.04) and gabapentinoid (AIRR: 6.78, 95%CI: 3.34–13.77; AIRR: 4.34, 95%CI: 2.37–7.94) dispensations, respectively. Partial OAT use was also associated with increased after-hours GP consultations (AIRR: 4.61, 95%CI: 2.24–9.48) and complete OAT use? with increased pathology utilisation (e.g. haematological, chemical, microbiological or immunological tissue/sample testing; AIRR: 2.30, 95%CI: 1.52–3.48). Conclusion We observed higher rates of primary healthcare use and medication dispensation among people who reported partial and complete OAT use post-release. Findings suggest that access to OAT post-release may have a collateral benefit in supporting broader health service utilisation, underscoring the importance of retention in OAT after release from prison.

Abstract Background There are significant challenges associated with studies of people released from custodial settings, including loss to follow-up in the community. Interpretation of findings with consideration of differences between those followed up and those not followed up is critical in the development of evidence-informed policies and practices. We describe attrition bias in the Prison and Transition Health (PATH) prospective cohort study, and strategies employed to minimise attrition. Methods PATH involves 400 men with a history of injecting drug use recruited from three prisons in Victoria, Australia. Four interviews were conducted: one pre-release (‘baseline’) and three interviews at approximately 3, 12, and 24 months post-release (‘follow-up’). We assessed differences in baseline characteristics between those retained and not retained in the study, reporting mean differences and 95% confidence intervals (95% CIs). Results Most participants (85%) completed at least one follow-up interview and 162 (42%) completed all three follow-up interviews. Retained participants were younger than those lost to follow-up (mean diff − 3.1 years, 95% CI -5.3, − 0.9). There were no other statistically significant differences observed in baseline characteristics. Conclusion The high proportion of participants retained in the PATH cohort study via comprehensive follow-up procedures, coupled with extensive record linkage to a range of administrative datasets, is a considerable strength of the study. Our findings highlight how strategic and comprehensive follow-up procedures, frequent contact with participants and secondary contacts, and established working relationships with the relevant government departments can improve study retention and potentially minimise attrition bias.

Background: Patients with diabetes mellitus (DM) have worse outcomes following percutaneous coronary intervention than nondiabetic patients. The novel Supreme DES is a biodegradable polymer sirolimus-eluting stent designed to synchronize early drug delivery, limiting the potential for long-term inflammatory response. The purpose of this study was to evaluate the safety and efficacy of the Supreme DES in patients with DM. Methods: This is a prespecified analysis of the diabetic subgroup from the PIONEER III randomized (2:1), controlled trial, comparing the Supreme DES with a durable polymer everolimus-eluting stent (DP-EES). The primary safety and efficacy composite endpoint was target lesion failure at 1 year, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Results: The PIONEER III trial randomized 1629 patients, of which 494 (30.3%) had DM with 331 (398 lesions) randomly assigned to Supreme DES and 163 (208 lesions) to DP-EES. Among patients with DM, target lesion failure at 1 year was 6.1% (20/331) with Supreme DES vs 3.7% (6/163) with DP-EES (hazard ratio = 1.65; 95% confidence interval = 0.66-4.10, P = .28). The composite of cardiac death or target vessel myocardial infarction was 3.3% (11/331) with Supreme DES and 3.7% (6/163) with DP-EES (hazard ratio = 0.90; 95% confidence interval = 0.33-2.44, P = .83). There were no significant differences in other secondary endpoints. Conclusions: This prespecified substudy of the PIONEER III trial demonstrated the relative safety and efficacy of the novel Supreme DES when compared with commercially available DP-EES in diabetics at 1 year. Longer term follow-up will be required to ensure continued safety and efficacy of the Supreme DES.

Background: The Supreme healing-targeted drug-eluting stent (DES) is designed to promote endothelial healing to reduce stent-related adverse events. This may be particularly relevant among complex lesions that have a higher rate of adverse events. We sought to compare 1-year outcomes of percutaneous coronary intervention in complex lesions between the Supreme DES and contemporary durable-polymer, everolimus-eluting stents (DP-EES). Methods: PIONEER III was a multicenter, prospective, single-blind clinical trial, randomizing 1629 patients with either an acute or chronic coronary syndrome in a 2:1 ratio to the Supreme DES or DP-EES. Complex lesions (American College of Cardiology/American Heart Association type B2/C) were found in 1137 patients. Outcomes were also compared for specific parameters of lesion complexity: severe calcification, long length (>20 ​mm), and severe tortuosity. The primary end point was target lesion failure at 1 ​year. Results: At 1 ​year, there was no difference in target lesion failure between the Supreme DES and DP-EES: (5.7% vs 5.6%; hazard ratio 1.00, 95% confidence interval 0.59-1.68, P = .99). Similarly, there were no differences in the secondary end points of lesion success (99.7% vs 99.4%, P = .41), device success (97.0% vs 98.5%, P = .14), target vessel failure (6.5% vs 7.4%, P = .50), major adverse cardiac events (7.8% vs 8.5%, P = .64), or stent thrombosis (0.7% vs 1.1%, P = .48). A trend was observed toward a higher rate of target lesion revascularization with the Supreme DES (2.5% vs 0.9%, P = .06). Conclusions: This study suggests that the Supreme DES is as effective and safe at 1 ​year compared with the standard DP-EES across a broad spectrum of lesion complexity.

Abstract Background Rodent models are invaluable for studying biological processes in the context of whole organisms. The reproducibility of such research is based on an assumption of metabolic similarity between experimental animals, controlled for by breeding and housing strategies that minimise genetic and environmental variation. Here, we set out to demonstrate the effect of experimental uraemia on the rat urinary metabolome and gut microbiome but found instead that the effect of vendor shipment batch was larger in both areas than that of uraemia. Results Twenty four Wistar rats obtained from the same commercial supplier in two separate shipment batches underwent either subtotal nephrectomy or sham procedures. All animals undergoing subtotal nephrectomy developed an expected uraemic phenotype. The urinary metabolome was studied using 1H-NMR spectroscopy and found to vary significantly between animals from different batches, with substantial differences in concentrations of a broad range of substances including lactate, acetate, glucose, amino acids, amines and benzoate derivatives. In animals from one batch, there was a complete absence of the microbiome-associated urinary metabolite hippurate, which was present in significant concentrations in animals from the other batch. These differences were so prominent that we would have drawn quite different conclusions about the effect of uraemia on urinary phenotype depending on which batch of animals we had used. Corresponding differences were seen in the gut microbiota between animals in different batches when assessed by the sequencing of 16S rRNA gene amplicons, with higher alpha diversity and different distributions of Proteobacteria subtaxa and short-chain fatty acid producing bacteria in the second batch compared to the first. Whilst we also demonstrated differences in both the urinary metabolome and gut microbiota associated with uraemia, these effects were smaller in size than those associated with shipment batch. Conclusions These results challenge the assumption that experimental animals obtained from the same supplier are metabolically comparable, and provide metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. We discuss strategies for reducing such variability and the need for transparency in research publications about the supply of experimental animals.

OBJECTIVES/GOALS: The present study investigated contextual factors linking rural Black American mens experiences of racial discrimination to their COVID vaccine hesitancy. Specifically, we investigated two potential mediators of the link between racial discrimination and COVID vaccine hesitancy: (1) medical mistrust, and (2) COVID conspiratorial beliefs. METHODS/STUDY POPULATION: Hypotheses were tested using structural equation modeling with 7 waves of data from 504 Black American men participating in a longitudinal study of risk behavior and substance use during young adulthood. At baseline, mens mean age was ~20. Data were collected before and during the COVID pandemic. The COVID pandemic began after Wave 4 data had been collected. A series of 3 online surveys, at 3-month intervals, were conducted to examine acute COVID-related stressors and impacts. RESULTS/ANTICIPATED RESULTS: The dual mediation model fit the data as follows: χ2(7) = 19.00, p < .008; χ2/ df = 2.71; RMSEA = 0.06; CFI = 0.95; SRMR= 0.04. Results indicated that racial discrimination was directly associated with increases in COVID conspiratorial beliefs (B = .14, p

Abstract Background Histories of self-harm and suicide attempts are common among people in prison in Australia, and substance dependence is an established risk factor for these lifetime experiences. We describe the prevalence of self-reported history of non-suicidal self-injury (NSSI) and suicide attempts in a cohort of men with recent histories of injecting drug use (IDU) imprisoned in Victoria, Australia. Baseline interviews from the Prison and Transition Health (PATH) prospective cohort study were conducted in the weeks prior to release from prison among 400 incarcerated men who reported regular IDU in the six months prior to incarceration. Results Participants completed a researcher-administered structured questionnaire that collected information on sociodemographics, substance use patterns, and physical and mental health indicators. More than one third (37%) reported a history of NSSI and almost half of participants (47%) reported a history of suicide attempts. In multivariable Poisson regression models, a history of NSSI was associated with: being aged 30–39 years; moving accommodation three or more times in the year prior to current sentence; self-reporting a history of mental illness diagnosis; current poor psychiatric well-being; and self-reporting three or more previous drug overdoses. History of suicide attempts was significantly associated with: self-reporting a history of mental illness diagnosis; current poor psychiatric well-being; and self-reporting a history of 1–2 and > 3 drug overdoses. Conclusion We observed a disconcertingly high lifetime prevalence of non-suicidal self-injury and suicide attempts among incarcerated males with a history of recent regular injecting drug use. Significant associations with indicators of mental illness and drug related harms support the need to prioritise in-prison screening and early intervention to reduce the risk of future harms for this population.

Abstract Background Take-home naloxone (THN) programmes are an evidence-based opioid overdose prevention initiative. Elevated opioid overdose risk following prison release means release from custody provides an ideal opportunity for THN initiatives. However, whether Australian prisoners would utilise such programmes is unknown. We examined the acceptability of THN in a cohort of male prisoners with histories of regular injecting drug use (IDU) in Victoria, Australia. Methods The sample comprised 380 men from the Prison and Transition Health (PATH) Cohort Study; all of whom reported regular IDU in the 6 months prior to incarceration. We asked four questions regarding THN during the pre-release baseline interview, including whether participants would be willing to participate in prison-based THN. We describe responses to these questions along with relationships between before- and during-incarceration factors and willingness to participate in THN training prior to release from prison. Results Most participants (81%) reported willingness to undertake THN training prior to release. Most were willing to resuscitate a friend using THN if they were trained (94%) and to be revived by a trained peer (91%) using THN. More than 10 years since first injection (adjusted odds ratio [AOR] 2.22, 95%CI 1.03–4.77), having witnessed an opioid overdose in the last 5 years (AOR 2.53, 95%CI 1.32–4.82), having ever received alcohol or other drug treatment in prison (AOR 2.41, 95%CI 1.14–5.07) and injecting drugs during the current prison sentence (AOR 4.45, 95%CI 1.73–11.43) were significantly associated with increased odds of willingness to participate in a prison THN programme. Not specifying whether they had injected during their prison sentence (AOR 0.37, 95%CI 0.18–0.77) was associated with decreased odds of willingness to participate in a prison THN training. Conclusion Our findings suggest that male prisoners in Victoria with a history of regular IDU are overwhelmingly willing to participate in THN training prior to release. Factors associated with willingness to participate in prison THN programmes offer insights to help support the implementation and uptake of THN programmes to reduce opioid-overdose deaths in the post-release period.

Abstract Background Dual substance dependence and psychiatric and psychological morbidities are overrepresented in prison populations and associated with reoffending. In the context of an increasing prison population in Australia, investigating the needs of vulnerable people in prison with a dual diagnosis can help inform in-prison screening and treatment and improve prison and community service integration and continuation of care. In this study we quantified psychiatric well-being in a sample of people in prison with a history of injecting drug use in Victoria, Australia, and identified factors associated with this outcome. Methods and Results Data for this paper come from baseline interviews undertaken in the weeks prior to release as part of a prospective cohort study of incarcerated men who reported regular injecting drug use prior to their current sentence. Eligible participants completed a researcher-administered structured questionnaire that canvassed a range of issues. Psychiatric well-being was assessed using the 12-item General Health Questionnaire (GHQ-12) and potential correlates were included based on a review of the literature. Of the 317 men included for analyses, 139 were classified as experiencing current poor psychiatric well-being. In the multivariate model using modified logistic regression, history of suicide attempt (aOR = 1.36, 95%CI 1.03–1.78), two or more medical conditions (aOR = 1.87, 95%CI 1.30–2.67) and use of crystal methamphetamine in the week prior to their current sentence (aOR = 1.52, 95%CI 1.05–2.22) were statistically significantly associated with current poor psychiatric well-being. Conclusions Comprehensively addressing the health-related needs for this vulnerable population will require a multidisciplinary approach and enhancing opportunities to screen and triage people in prison for mental health and other potential co-occurring health issues will provide opportunities to better address individual health needs and reoffending risk.

OBJECTIVES:The causes of the large and persistent Black-White disparity in preterm birth (PTB) are unknown. It is biologically plausible that chronic stress across a woman's life course could be a contributor. Prior research suggests that chronic worry about experiencing racial discrimination could affect PTB through neuroendocrine, vascular, or immune mechanisms involved in both responses to stress and the initiation of labor. This study aimed to examine the role of chronic worry about racial discrimination in Black-White disparities in PTB. METHODS:The data source was cross-sectional California statewide-representative surveys of 2,201 Black and 8,122 White, non-Latino, U.S.-born postpartum women with singleton live births during 2011-2014. Chronic worry about racial discrimination (chronic worry) was defined as responses of "very often" or "somewhat often" (vs. "not very often" or "never") to the question: "Overall during your life until now, how often have you worried that you might be treated or viewed unfairly because of your race or ethnic group?" Prevalence ratios (PRs) with 95% Confidence Intervals (CI) were calculated from sequential logistic regression models, before and after adjustment for multiple social/demographic, behavioral, and medical factors, to estimate the magnitude of: (a) PTB risks associated with chronic worry among Black women and among White women; and (b) Black-White disparities in PTB, before and after adjustment for chronic worry. RESULTS:Among Black and White women respectively, 36.9 (95% CI 32.9-40.9) % and 5.5 (95% CI 4.5-6.5) % reported chronic worry about racial discrimination; rates were highest among Black women of higher income and education levels. Chronic worry was significantly associated with PTB among Black women before (PR 1.73, 95% CI 1.12-2.67) and after (PR 2.00, 95% CI 1.33-3.01) adjustment for covariates. The unadjusted Black-White disparity in PTB (PR 1.59, 95%CI 1.21-2.09) appeared attenuated and became non-significant after adjustment for chronic worry (PR 1.30, 95% CI 0.93-1.81); it appeared further attenuated after adding the covariates (PR 1.17, 95% CI 0.85-1.63). CONCLUSIONS:Chronic worry about racial discrimination may play an important role in Black-White disparities in PTB and may help explain the puzzling and repeatedly observed greater PTB disparities among more socioeconomically-advantaged women. Although the single measure of experiences of racial discrimination used in this study precluded examination of the role of other experiences of racial discrimination, such as overt incidents, it is likely that our findings reflect an association between one or more experiences of racial discrimination and PTB. Further research should examine a range of experiences of racial discrimination, including not only chronic worry but other psychological and emotional states and both subtle and overt incidents as well. These dramatic results from a large statewide-representative study add to a growing-but not widely known-literature linking racism-related stress with physical health in general, and shed light on the links between racism-related stress and PTB specifically. Without being causally definitive, this study's findings should stimulate further research and heighten awareness of the potential role of unmeasured social variables, such as diverse experiences of racial discrimination, in racial disparities in health.

Viruses are catalysts of biogeochemical cycling, architects of microbial community structure, and terminators of phytoplankton blooms. Viral lysis of diatoms, a key group of eukaryotic phytoplankton, has the potential to impact carbon export and marine food webs. However, the impact of viruses on diatom abundance and community composition is unknown. Diatom-virus dynamics were explored by sampling every month at 2 coastal and estuarine locations in Washington state, USA resulting in 41 new isolates of the pennate diatom Pseudo-nitzschia and 20 environmental virus samples. We conducted a total of 820 pair-wise crosses of the Pseudo-nitzschia isolates and viral communities. Viral communities infected Pseudo-nitzschia isolates in 8% of the crosses overall and 16% of crosses when the host and viral communities were isolated from the same sample. Isolates ranged in their permissivity to infection with some isolates not infected by any viral samples and others infected by up to 10 viral communities. Isolates that were infected by the most viral communities also had the highest maximum observed viral titers (as high as 16000 infectious units ml-1). Titers of the viral communities were host dependent, as titers for one viral sample on 8 different hosts spanned 4 orders of magnitude. Sequencing of the Pseudo-nitzschia Internal Transcribed Spacer 1 (ITS1) of the revealed multiple subgroups of hosts with 100% ITS1 identity that were infected by different viral communities. Indeed, we repeatedly isolated groups of isolates with identical ITS1 sequences from the same water sample that displayed different viral infection phenotypes. The interactions between Pseudo-nitzschia and the viral communities highlight the diversity of diatoms and emphasize the complexity and variability of diatom-virus dynamics in the ocean.