All-cause mortality before and after DAA availability among people living with HIV and HCV: An international comparison between 2010 and 2019.

BACKGROUND: Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants. METHODS: We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability. RESULTS: Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm3 (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72-1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3-2.6] vs. 0.8/100 PY [95 % CI = 0.7-0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0-1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15-2.61]). CONCLUSION: Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era.

Is use of opioid agonist treatment associated with broader primary healthcare use among men with recent injecting drug use histories following release from prison? A prospective cohort study.

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.

Recruiting and retaining community-based participants in a COVID-19 longitudinal cohort and social networks study: lessons from Victoria, Australia.

BACKGROUND: Longitudinal studies are critical to informing evolving responses to COVID-19 but can be hampered by attrition bias, which undermines their reliability for guiding policy and practice. We describe recruitment and retention in the Optimise Study, a longitudinal cohort and social networks study that aimed to inform public health and policy responses to COVID-19. METHODS: Optimise recruited adults residing in Victoria, Australia September 01 2020-September 30 2021. High-frequency follow-up data collection included nominating social networks for study participation and completing a follow-up survey and four follow-up diaries each month, plus additional surveys if they tested positive for COVID-19 or were a close contact. This study compared number recruited to a-priori targets as of September 302,021, retention as of December 31 2021, comparing participants retained and not retained, and follow-up survey and diary completion October 2020-December 2021. Retained participants completed a follow-up survey or diary in each of the final three-months of their follow-up time. Attrition was defined by the number of participants not retained, divided by the number who completed a baseline survey by September 302,021. Survey completion was calculated as the proportion of follow-up surveys or diaries sent to participants that were completed between October 2020-December 2021. RESULTS: At September 302,021, 663 participants were recruited and at December 312,021, 563 were retained giving an overall attrition of 15% (n = 100/663). Among the 563 retained, survey completion was 90% (n = 19,354/21,524) for follow-up diaries and 89% (n = 4936/5560) for monthly follow-up surveys. Compared to participants not retained, those retained were older (t-test, p <  0.001), and more likely to be female (χ2, p = 0.001), and tertiary educated (χ2, p = 0.018). CONCLUSION: High levels of study retention and survey completion demonstrate a willingness to participate in a complex, longitudinal cohort study with high participant burden during a global pandemic. We believe comprehensive follow-up strategies, frequent dissemination of study findings to participants, and unique data collection systems have contributed to high levels of study retention.

Discontinuation of opioid agonist treatment following release from prison in a cohort of men who injected drugs prior to imprisonment in Victoria, Australia: A discrete-time survival analysis.

BACKGROUND: Retention in opioid agonist treatment (OAT) following release from prison is associated with improved outcomes, however factors associated with post-release OAT discontinuation in Australia are poorly understood. We examined post-release OAT discontinuation in a cohort of men who engaged in approximately monthly injecting drug use (IDU) prior to imprisonment in Victoria, Australia. METHODS: Longitudinal data were used to calculate incidence of first-event post-release OAT discontinuation among men released from prison receiving OAT, and single-event discrete-time survival methods were used to estimate associations with post-release OAT discontinuation. RESULTS: Among 110 participants, 55 OAT discontinuations were observed in the two years post-release, an overall crude incidence rate (IR) of 46 per 100 person-years (PY) (95 % confidence interval [95 %CI]: 36-60 per 100PY). Incidence was greatest between release from prison and first follow-up (IR: 84 per 100PY, 95 %CI: 62-116 per 100PY). Initiating OAT during index imprisonment (versus transitioning from community OAT; adjusted hazard rate [AHR]: 2.17, 95 %CI: 1.14-4.13) and identifying as Aboriginal and/or Torres Strait Islander (AHR: 4.95, 95 %CI: 2.00-12.25) were associated with an increased hazard of OAT discontinuation. CONCLUSION: In a cohort of men with recent histories of IDU released from prison receiving OAT, half reported OAT discontinuation within two years of release from prison, with incidence of discontinuation greatest soon after prison-release. Targeted support for men who initiate OAT during episodes of imprisonment and Aboriginal and/or Torres Strait Islander peoples is necessary to reduce incidence of OAT discontinuation among people at greatest risk of discontinuation.

High rates of resumption of injecting drug use following release from prison among men who injected drugs before imprisonment.

AIMS: To estimate incidence of post-release injecting drug use (IDU) among men who injected drugs before imprisonment and determine factors associated with post-release IDU frequency. DESIGN, SETTING, PARTICIPANTS: Prospective cohort study of men reporting monthly IDU before a period of sentenced imprisonment in Victoria, Australia, recruited between September 2014 and May 2016 (n = 195). MEASUREMENTS: Any post-release IDU and IDU frequency was measured via self-report at 3-month follow-up interview. IDU frequency, measured over the preceding month, was categorised as no IDU, irregular IDU (1-4 days IDU) and regular IDU (≥5 days IDU). Incidence of any IDU was calculated at 3 months post-release. Factors associated with IDU frequency were estimated using ordinal logistic regression. FINDINGS: Most (83%) participants reported post-release IDU (265 per 100 person-years, 95% CI, 227-309); with half (48%) reporting regular IDU, 23% irregular IDU and 29% no IDU in the month preceding follow-up. Poorer psychological well-being at follow-up (General Health Questionnaire [GHQ-12] score; adjusted odds ratio [AOR], 1.18; 95% CI, 1.07-1.29) and post-release unemployment (AOR, 4.57; 95% CI, 1.67-12.49) were associated with increased IDU frequency. Retention in opioid agonist treatment (AOR, 0.49; 95% CI, 0.24-0.98) was associated with reduced IDU frequency. Non-linear (inverted-u) associations between IDU frequency and age (age: AOR, 1.51; 95% CI, 1.17-1.96; age-squared: AOR, 0.99; 95% CI, 0.99-0.99) and pre-imprisonment IDU frequency (pre-imprisonment IDU frequency: AOR, 1.36; 95% CI, 1.15-1.61; pre-imprisonment IDU frequency-squared: AOR, 0.99; 95% CI, 0.99-0.99) were found, with odds peaking at age 39 and 19 days IDU, respectively. Longer baseline sentence length was associated with reduced odds of irregular and regular IDU (AOR, 0.99; 95% CI, 0.99-0.99). CONCLUSION: Among Australian men who inject drugs before imprisonment, resumption of injecting drug use after release from prison appears to be common, with imprisonment seeming to have little impact on reducing injecting drug use behaviour.

Criminal Justice Involvement after Release from Prison following Exposure to Community Mental Health Services among People Who Use Illicit Drugs and Have Mental Illness: a Systematic Review.

Illicit drug use and mental illness are common among people in prison and are associated with higher rates of reoffending and reimprisonment. We conducted a systematic review, searching MEDLINE, Embase, and PsycINFO to January 10, 2022, for studies reporting criminal justice involvement following exposure to community mental health services among people released from jail or prison who use illicit drugs and have mental illness. Our search identified 6954 studies; 13 were eligible for inclusion in this review. Studies were separated into three broad categories based on community mental health service type. Eleven of 13 studies reported a reduction in criminal justice involvement among participants exposed to community mental health services compared to a comparison group. Findings indicate a need to expand and improve integration and referral mechanisms linking people to community mental health services after jail or prison release, alongside a need for tailored programs for individuals with complex illicit drug use and mental health morbidities.

Psychiatric well-being among men leaving prison reporting a history of injecting drug use: A longitudinal analysis.

BACKGROUND: Community reintegration from prison is typically stressful, with several health and social outcomes impacting psychiatric well-being during this time, often exacerbated among individuals with histories of drug use. Longitudinal data was used to assess change in psychiatric well-being over 2 years following release from prison among men who reported a recent history of injecting drug use. METHODS: Data for this study come from the Prison and Transition Health cohort study of 400 men recruited in prison prior to release and followed up over three time points. Psychiatric well-being was assessed using the 12-item General Health Questionnaire. We calculated change in individual General Health Questionnaire scores between interviews and identified covariates associated with General Health Questionnaire score using linear mixed-effects regression. RESULTS: Data from 690 follow-up interviews among 326 participants were included in analyses. There was considerable variation in individuals' General Health Questionnaire scores. Moving accommodation frequently and frequent illicit drug injections were associated with an increase in General Health Questionnaire score (i.e. decline in psychiatric well-being). Two or more prior adult imprisonment episodes, social supports and past month primary healthcare attendance were associated with a decrease in General Health Questionnaire score. CONCLUSION: Our findings identify health, social and structural influences on psychiatric well-being after release from prison that can inform re-entry programmes to support community reintegration.

COVID-19 vaccine acceptability among people in Australia who inject drugs: Implications for vaccine rollout.

INTRODUCTION: Vaccine acceptability is a key determinant of vaccination uptake. Despite being at risk of adverse outcomes from coronavirus-19 disease (COVID-19), COVID-19 vaccine acceptability among people who inject drugs is unknown. We surveyed people who inject drugs in Melbourne, Australia to assess potential uptake of COVID-19 vaccines prior to distribution. METHODS: Cross-sectional study, comprising interviewer-administered structured telephone interviews completed from 30 November to 22 December 2020 in Melbourne, Australia. Participants were people aged 18 years or older who injected drugs at least monthly in the past 6 months and had resided in Melbourne in the past 12 months recruited via needle-syringe programs and word-of-mouth. MEASUREMENTS: COVID-19 hypothetical vaccine acceptability, participants' demographic, drug use and drug treatment characteristics. RESULTS: Fifty-eight percent (57/99) of the sample reported that they would definitely or probably be vaccinated for COVID-19, with the remainder indicating that they would not (22%) or were undecided (20%). Among those who indicated that they would definitely or probably not be vaccinated or were undecided (n = 42), safety concerns were most often cited as a reason for not wanting to be vaccinated. DISCUSSION AND CONCLUSIONS: Although a majority of sampled people who inject drugs indicated that they would definitely or probably be vaccinated, efforts to reduce hesitancy and allay COVID-19 vaccine safety concerns will be necessary to optimise vaccine uptake among this population.

The Prison and Transition Health (PATH) cohort study: Prevalence of health, social, and crime characteristics after release from prison for men reporting a history of injecting drug use in Victoria, Australia.

BACKGROUND: People who inject drugs are overrepresented in prison and have diverse and complex health needs. However, outcomes after release from prison are poorly understood, limiting effective interventions supporting community reintegration. We describe the prevalence of socio-demographics, physical and mental health, alcohol and other drug use, and crime characteristics of men with histories of injecting drug use after their release from prison in Victoria, Australia. METHODS: Data come from the Prison and Transition Health (PATH) prospective cohort study. Interviews were undertaken approximately three, 12, and 24 months after release from their index prison episode and were completed in the community, or in prison for those reimprisoned during the study. We present cross-sectional descriptive statistics for each follow-up wave of the PATH study. RESULTS: Among 400 men recruited into PATH, 85 % (n = 336) completed at least one follow-up interview; 162 (42 %) completed all three interviews. Participants reported social disadvantage and health inequity, including high rates of unemployment, homelessness, and physical and mental health morbidities at each follow-up time point. Rapid return to illicit substance use was common, as was overdose (ranging 9 %-13 %), receptive syringe sharing (ranging 20 %-29 %), involvement in crime-related activities (ranging 49 %-58 %), and reimprisonment (ranging 22 %-50 %) over the duration of follow-up. CONCLUSION: Men in this study experienced substantial health and social challenges across a 24-month prospective follow-up period. Improved understanding of characteristics and experiences of this group after release from prison can inform more coordinated and continued care between prison and the community.

Ketamine Use Among People Who Regularly Use Ecstasy and Other Illicit Stimulants in Australia: Trends and Characteristics of Use, 2009-2019.

OBJECTIVE: Ketamine is a dissociative anesthetic used in medical practice, used recreationally since the mid-1960s. This study describes trends in ketamine use in sentinel cross-sectional samples of Australians who regularly use illicit stimulants, along with characteristics of consumers. METHOD: Data on trends in recent ketamine use (i.e., use in past 6 months) were drawn from annual interviews (approximately 800/year) with cross-sectional samples of people recruited from Australian state capitals from 2009 to 2019 as part of the Ecstasy and Related Drugs Reporting System (EDRS) study. Characteristics of those reporting recent use were examined in the 2019 EDRS data set (n = 728) using logistic regression. RESULTS: Recent ketamine use increased between 2009 and 2019 (10% to 41%, respectively, p < .001), primarily driven by use among participants recruited in Melbourne (21% to 84%, p < .001) and Sydney (19% to 68%, p < .001). However, frequency of use remained low. In 2019, consumer characteristics associated with use included being born outside of Australia and residing in Sydney or Melbourne (compared with Canberra). CONCLUSIONS: Among EDRS participants in Australia, we observed an increase in recent ketamine use between 2009 and 2019, although indicators of potential problematic use remained low. The increase in recent ketamine use was largely driven by increases in Melbourne and Sydney. Further research on drivers of use in these cities is required to effectively inform harm-reduction strategies.

Lifetime prevalence and correlates of self-harm and suicide attempts among male prisoners with histories of injecting drug use.

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.

Small-Format Drug Conjugates: A Viable Alternative to ADCs for Solid Tumours?

Antibody-Drug Conjugates (ADCs) have been through multiple cycles of technological innovation since the concept was first practically demonstrated ~40 years ago. Current technology is focusing on large, whole immunoglobulin formats (of which there are approaching 100 in clinical development), many with site-specifically conjugated payloads numbering 2 or 4. Despite the success of trastuzumab-emtansine in breast cancer, ADCs have generally failed to have an impact in solid tumours, leading many to explore alternative, smaller formats which have better penetrating properties as well as more rapid pharmacokinetics (PK). This review describes research and development progress over the last ~10 years obtained from the primary literature or conferences covering over a dozen different smaller format-drug conjugates from 80 kDa to around 1 kDa in total size. In general, these agents are potent in vitro, particularly more recent ones incorporating ultra-potent payloads such as auristatins or maytansinoids, but this potency profile changes when testing in vivo due to the more rapid clearance. Strategies to manipulate the PK properties, whilst retaining the more effective tumour penetrating properties could at last make small-format drug conjugates viable alternative therapeutics to the more established ADCs.