'It's a fragile open door'-enhancing COVID-19 vaccination rates in people receiving treatment for substance use disorder.

BACKGROUND: People with substance use disorder are at high risk of harms from COVID-19 infection. Vaccine hesitancy is common in this population and compounds pre-existing barriers to accessing health care. A drug and alcohol service in Sydney, Australia introduced strategies to enhance COVID-19 vaccination in people receiving opioid agonist treatment (OAT). We report vaccination outcomes and staff experiences of this. METHODS: This mixed methods study (i) retrospectively evaluated vaccine uptake in people accessing OAT and (ii) explored perceptions of staff who delivered vaccination interventions through surveys and semi-structured interviews. RESULTS: Of the 984 patients receiving OAT on 9 December 2021, 90.9% had received the first COVID-19 vaccination and 86.7% the second. Australia wide vaccination rates on that date were 93.1% and 88.7% for first and second doses, respectively. Staff commented that having a deep knowledge, understanding and connection with the patient group drove implementation and success of vaccination interventions. This was further supported by staff engagement with the vaccination interventions, and communication and sharing information, both between staff and with patients. CONCLUSION: High rates of COVID-19 vaccination can be achieved in a vulnerable population. Engaged staff providing information and facilitating access to healthcare underpin this success.

Hepatitis C virus testing, liver disease assessment and treatment uptake among people who inject drugs pre- and post-universal access to direct-acting antiviral treatment in Australia: The LiveRLife study.

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct-acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole-blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre-DAA era to 38% in the DAA era. Significant liver fibrosis (F2-F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18-7.04) and attending a clinical follow-up with nurse (aOR, 3.19; 95% CI, 1.61-6.32) or physician (aOR, 11.83; 95% CI, 4.89-28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.

Prevalence and factors associated with polydrug use among clients seeking treatment for alcohol misuse.

INTRODUCTION: The aim of this paper was to examine the client and psychosocial characteristics associated with polydrug use in patients with alcohol misuse as their primary drug of concern (PDC) seeking treatment from substance use treatment centres. METHODS: Self-report surveys were undertaken with clients attending 1 of 34 community-based substance use treatment centres across Australia with alcohol as their PDC. Survey items included client's socio-demographic characteristics, level of alcohol dependence, use of other drugs including tobacco, health and wellbeing factors including health-related quality of life. The factors associated with polydrug use (alcohol use concurrent with at least one other drug) were examined. RESULTS: In a sample of 1130 clients seeking treatment primarily for alcohol problems, 71% reported also using another drug. The most frequently used drug was tobacco (50%) followed by cannabis (21%) and benzodiazepines (15%). Excluding tobacco use, 35% of participants reported polydrug use. Factors associated with any polydrug use were younger age, lower education levels, lower levels of mental health related quality of life and housing risk (i.e., risk of eviction or experienced homelessness in past 4 weeks). When tobacco was excluded, factors associated with polydrug use were age, lower physical and mental health-related quality of life, and housing risk. DISCUSSION AND CONCLUSIONS: Most adults seeking treatment for alcohol misuse as their PDC reported using another drug in addition to alcohol. Treatment services should be designed accordingly to maximise the likelihood of treatment engagement and success.

Correlates of treatment engagement and client outcomes: results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder.

INTRODUCTION AND AIMS: There is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes. METHOD: Bayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial. RESULTS: Among the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling. DISCUSSIONS AND CONCLUSIONS: These findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Mood, sleep and pain comorbidity outcomes in cannabis dependent patients: Findings from a nabiximols versus placebo randomised controlled trial.

BACKGROUND: Mood, sleep and pain problems are common comorbidities among treatment-seeking cannabis-dependent patients. There is limited evidence suggesting treatment for cannabis dependence is associated with their improvement. This study explored the impact of cannabis dependence treatment on these comorbidities. METHODS: This is a secondary analysis from a 12-week double-blind placebo-controlled trial testing the efficacy of a cannabis agonist (nabiximols) against placebo in reducing illicit cannabis use in 128 cannabis-dependent participants. Outcome measurements including DASS-21 (Depression, Anxiety, and Stress subscales); Insomnia Severity Index (ISI); and Brief Pain Inventory (BPI), were performed at weeks 0, 4, 8, 12 and 24. Each was analysed as continuous outcomes and as binary cases based on validated clinical cut-offs. RESULTS: Among those whose DASS and ISI scores were in the moderate to severe range at baseline, after controlling for cannabis use, there was a gradual decrease in severity of symptoms over the course of the trial. BPI decreased significantly until week 12 and then rose again in the post-treatment period during weeks 12-24. Neither pharmacotherapy type (nabiximols vs placebo) nor number of counselling sessions contributed significant explanatory power to any of the models and were excluded from the final analyses for both continuous and categorical outcomes. CONCLUSIONS: Participants in this trial who qualified as cases at baseline had elevated comorbidity symptoms. There was no evidence that nabiximols treatment is a barrier to achieving reductions in the comorbid symptoms examined. Cannabis dependence treatment reduced illicit cannabis use and improved comorbidity symptoms, even when complete abstinence was not achieved.

COVID-19 Impact on Australian Patients with Substance Use Disorders: Emergency Department Admissions in Western Sydney before Vaccine Roll Out.

Background: In this study, we determined the impact of the COVID-19 pandemic on Western Sydney patients with substance use disorders (SUD) by comparing emergency department (ED) admission rates before and after the onset of the COVID-19 pandemic and before the rollout of COVID-19 vaccination. Methods: ED admission data for patients with SUD were retrieved from the local electronic medical record (eMR) on the hospital central database. ED data collected from 25 January to 25 July 2019 (before the COVID-19 pandemic) were compared with data from 25 January to 25 July 2020 (early pandemic). ED admission reasons were categorised based on the presenting complaints and ED diagnoses. Results: Despite an overall reduction in ED admissions during the early pandemic, compared to the pre-pandemic period, admissions for patients with SUD increased significantly (1.7% to 3.4%, p < 0.01). ED admission rates related to infection (0.05% to 0.12%, p < 0.01), local infection (0.02% to 0.05%, p < 0.01), trauma (0.06% to 0.12%, p < 0.01), alcohol (0.01% to 0.03%, p < 0.05), and other issues (0.06% to 0.10%, p < 0.05) increased significantly among Indigenous patients with SUD. ED admission rates related to drugs (0.12% to 0.39%, p < 0.01), infection (0.21% to 0.34%, p < 0.01), local infection (0.07% to 0.18%, p < 0.01), gastrointestinal (0.15% to 0.23%, p < 0.05), trauma (0.14% to 0.25%, p < 0.01), alcohol (0.36% to 0.74%, p < 0.01), and 'other' issues (0.47% to 0.91%, p < 0.01) increased significantly among non-Indigenous patients with SUD. Four cases of COVID-19 were reported among these patients. Conclusions: There was an increase in ED admissions for patients with SUD in the initial six months of the COVID-19 pandemic (before vaccine rollout), mainly for drugs, systemic infection, local infection, trauma, and alcohol-related reasons. Now that most people in New South Wales have been vaccinated against COVID-19, a further study is needed to quantify the effect of the pandemic on patients with SUD in the post-vaccine era.

Assessing the concurrent validity, inter-rater reliability and test-re-test reliability of the Australian Treatment Outcomes Profile (ATOP) in alcohol and opioid treatment populations.

BACKGROUND AND AIMS: The Australian Treatment Outcomes Profile (ATOP) is a brief instrument measuring recent substance use, risk profile and general health and wellbeing among clients attending alcohol and other drug (AoD) treatment services. This study evaluates the ATOP for concurrent validity, inter-rater and test-re-test reliability among alcohol and opioid treatment groups. DESIGN: For concurrent validity and inter-rater reliability, participants completed an ATOP with a clinician and an ATOP plus standardized questionnaires (time-line follow-back, Opiate Treatment Index, Kessler-10, 12-item Short Form Survey, World Health Organization Quality of Life-BREF, Personal Wellbeing Index) with a researcher within 3 days. For test-re-test reliability, participants completed two ATOPs with a researcher within a 3-day interval. SETTING: Outpatient AoD treatment centres in Australia. PARTICIPANTS: For testing concurrent validity and inter-rater reliability, 278 participants were recruited by advertisements in waiting-rooms or clinician invitation during 2016 to 2018. A further 94 participants were recruited to examine test-re-test reliability. MEASUREMENTS: Statistical tests used for concurrent validity and test-re-test reliability were Pearson's and Spearman's rank order correlations for continuous variables, and Cohen's κ for nominal variables. Inter-rater reliability was assessed using Krippendorf's α. FINDINGS: Most Australian Treatment Outcomes Profile items returned excellent or moderate validity and reliability. For the main substances used-alcohol, cannabis and benzodiazepines-concurrent validity, inter-rater reliability and test-re-test reliability all reached excellent or good agreement (0.72-0.96). Psychological health, physical health and quality of life showed fair to strong agreement with their comparator scales (0.47-0.85). CONCLUSIONS: The Australian Treatment Outcomes Profile is a validated and reliable instrument for assessing recent substance use and clinical risk, health and welfare among alcohol and opioid clients in alcohol and other drug treatment settings. Its ability to reliably measure complex constructs, such as psychological and physical health, against longer scales makes it suitable for integration into routine clinical care, enabling regular monitoring of patient outcomes and safety parameters.

A Brief History of Ebolavirus Disease: Paving the Way Forward by Learning from the Previous Outbreaks.

In this review, Ebolavirus Disease (EVD) outbreaks have been comprehensively reviewed from their beginning until now. It chronologically discusses how each outbreak was tackled, national and international actions taken, diagnostic methods applied, the infection control procedures put in place, and the lessons learnt from each epidemic for the control of subsequent epidemics. Data for this review were obtained from literature published between 1967 and 2016 in key medical databases, the official websites of various governmental organisations, international public health agencies, and regulatory bodies. Despite major developments in the field of EVD, there has been little progress in its specific therapy or prevention. Historically, individuals who recovered from EVD acted as a source of fresh frozen plasma (containing IgG) that has been used to treat other acutely ill patients, however this therapeutic modality has limitations due to the risk of transmission of blood-borne infections. With the use of advanced and efficient purification methods the incidence of unwanted side effects following immune serum therapy has currently been greatly reduced. Creation of a safe plasma pool that covers immunoglobulins against all strains of EVD is now a research priority. Recommendations on how future EVD outbreaks can be better managed have been discussed.

Validation of the Australian Treatment Outcomes Profile for use in clients with cannabis dependence.

INTRODUCTION AND AIMS: The Australian Treatment Outcomes Profile (ATOP) was developed as a clinical tool for monitoring the substance use, health and wellbeing of clients in alcohol and other drug treatment. This is the first psychometric validation of the ATOP in a cannabis-dependent treatment population. DESIGN AND METHODS: A total of 128 individuals with cannabis dependence enrolled in an outpatient randomised controlled trial were administered the ATOP and gold-standard health and wellbeing questionnaires once by clinicians and once by researchers at baseline. Concurrent validity was assessed by testing ATOP Psychological Health, Physical Health and Quality of Life questions against concurrently administered gold-standard questionnaires: the Short Form 36 Health Survey (SF-36), the 21-item Depression, Anxiety and Stress Scale (DASS-21) and the Sheehan Disability Scale (SDS). Interrater reliability was tested by comparing clinician-administered ATOP items at the medical screening interview to the same ATOP items administered by researchers at baseline. RESULTS: ATOP Psychological Health showed moderate to strong correlations with SF-36 Mental Components, SF-36 Mental Health and DASS-21 scores (r = 0.40-0.52) and ATOP Physical Health with SF-36 Physical Components and SF-36 General Health scores (r = 0.36-0.67). The ATOP Quality of Life scale showed moderate agreement with the SDS and six-dimensional health state short form scales (r = 0.38-0.40). ATOP substance use, employment, education and child care items showed good to excellent interrater reliability (Krippendorff's α = 0.62-0.81), and tobacco use, Psychological Health, Physical Health and Quality of Life showed fair to moderate interrater reliability (Krippendorff's α = 0.42-0.53). DISCUSSION AND CONCLUSIONS: The ATOP appears to be valid and reliable when tested in a population with cannabis-dependence, justifying its widespread use in clinical settings.

Cannabis use in patients 3 months after ceasing nabiximols for the treatment of cannabis dependence: Results from a placebo-controlled randomised trial.

INTRODUCTION AND AIMS: Previous studies suggest cannabinoid agonist treatment is effective in reducing cannabis use in dependent treatment seekers, however few studies have reported on post-treatment outcomes. We examine cannabis use outcomes 12 weeks after cessation of treatment from a randomised placebo-controlled trial of nabiximols for the treatment of cannabis dependence. METHOD: 128 participants received either nabiximols (n = 61) or placebo (n = 67) for 12 weeks, in combination with psychosocial interventions. Self-reported number of days of cannabis use in the previous 28 days was measured at baseline, 4, 8, and 12 weeks (end of treatment) and again at 24 weeks (3 months after treatment ceased). Urinalysis was used to confirm self-report data at Week 24 interview. RESULTS: A factorial mixed-effects model for repeated measures regression revealed that the nabiximols group used cannabis on 6.8 fewer days in the previous 28 days at week 12 (end of treatment) than the placebo group (p = 0.002, CI: 2.1,11.4), and 6.7 fewer days in the previous 28 days at the week-24 follow-up than the placebo group (p = 0.006, CI: 1.4,12.1). A significantly higher proportion of the nabiximols group (14/61; 23 %) than the placebo group (6/67; 9%) reported abstinence from cannabis in the previous 28 days at the week-24 research interview OR=3.0, CI: 1.1, 9.1; p=0.035, NNT=8, CI: 4, 71). DISCUSSIONS AND CONCLUSIONS: The benefits of treatment incorporating nabiximols with psychosocial interventions in reducing cannabis use appears to persist for up to 3 months after the cessation of treatment. A stepped care model of treatment is proposed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au.

Designing, implementing and evaluating the overdose response with take-home naloxone model of care: An evaluation of client outcomes and perspectives.

INTRODUCTION AND DESIGNS: Take-home naloxone (THN) interventions are an effective response to preventing overdose deaths, however uptake across Australia remains limited. This project designed, implemented and evaluated a model of care targeting opioid users attending alcohol and other drug (AOD) treatment, needle and syringe programs (NSP) and related health services targeting people who inject drugs. DESIGN AND METHODS: Service providers, consumers and regulators collaboratively designed a THN brief intervention (ORTHN, Overdose Response with Take-Home Naloxone) involving client education and supply of naloxone in pre-filled syringes, delivered by nursing, allied health and NSP workers. ORTHN interventions were implemented in over 15 services across New South Wales, Australia. The evaluation included client knowledge, attitudes, substance use and overdose experiences immediately before and 3 months after ORTHN intervention in a subsample of participants. RESULTS: Six hundred and sixteen interventions were delivered, with 145 participants recruited to the research subsample, of whom 95 completed the three-month follow up. Overdose-related attitudes amongst participants improved following ORTHN, with no evidence of increased substance use or failure to implement other 'first responses' (e.g. calling an ambulance). Nine participants (10%) reversed an overdose using THN in the follow-up period. Participants identified a willingness to access THN from a range of services. While a minority (16%) indicated they were unwilling to pay for THN, the median price that participants were willing to pay was $AUD20 (IQR $10.40). DISCUSSION AND CONCLUSIONS: The ORTHN model of care for THN appears an effective way to disseminate THN to people who use opioids attending AOD, NSP and related health-care settings.

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

IMPORTANCE: There are no effective medications for treating dependence on cannabis. OBJECTIVE: To examine the safety and efficacy of nabiximols in the treatment of patients with cannabis dependence. DESIGN, SETTING, AND PARTICIPANTS: This parallel double-blind randomized clinical trial comparing nabiximols with placebo in a 12-week, multisite outpatient study recruited participants from February 3, 2016, to June 14, 2017, at 4 outpatient specialist alcohol and drug treatment services in New South Wales, Australia. Participants had cannabis dependence (as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and were seeking treatment, were nonresponsive to prior treatment attempts, were 18 to 64 years of age, had no other substance use disorder, had no severe medical or psychiatric conditions, were not pregnant, were not mandated by a court to undergo treatment, and provided informed consent. Results for primary efficacy measures and all secondary outcomes were obtained using a modified intention-to-treat data set. INTERVENTIONS: Participants received 12-week treatment involving weekly clinical reviews, structured counseling, and flexible medication doses-up to 32 sprays daily (tetrahydrocannabinol, 86.4 mg, and cannabidiol, 80 mg), dispensed weekly. MAIN OUTCOMES AND MEASURES: Primary outcome was self-reported number of days using illicit cannabis during the 12-week period. Other outcomes included alternate cannabis use parameters (periods of abstinence, withdrawal, cravings, and problems), safety parameters (adverse events and aberrant medication use), health status, other substance use, and treatment retention. RESULTS: A total of 128 participants (30 women and 98 men; mean [SD] age, 35.0 [10.9] years) were randomized and received at least 1 dose of study medication. Participants had used a mean (SD) of 2.3 (2.1) g of cannabis on a mean (SD) of 25.7 (4.5) days in the past 28 days. Treatment retention was comparable for the 2 groups (placebo, 30 of 67 participants [44.8%]; nabiximols, 30 of 61 participants [49.2%]), and both groups used similar mean (SD) doses (placebo, 18.5 [9.5] sprays daily; nabiximols, 17.6 [9.5] sprays daily, equivalent to a mean [SD] of 47.5 [25.7] mg of tetrahydrocannabinol and 44.0 [23.8] mg of cannabidiol). For the primary end point, the placebo group reported significantly more days using cannabis during the 12 weeks (mean [SD], 53.1 [33.0] days) than the nabiximols group (mean [SD], 35.0 [32.4] days; estimated difference, 18.6 days; 95% CI, 3.5-33.7 days; P = .02). Both groups showed comparable improvements in health status, with no substantial changes in other substance use. Medication was well tolerated with few adverse events. CONCLUSIONS AND RELEVANCE: This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12616000103460.

Update on global epidemiology of viral hepatitis and preventive strategies.

Viral hepatitis is one of the major public health concerns around the world but until recently it has drawn little attention or funding from global health policymakers. Every year 1.4 million people die from viral hepatitis-related cirrhosis and liver cancer. However, the majority of the infected population are unaware of their condition. This population have significant obstacles to overcome such as lack of awareness, vulnerability, increased migration, disease stigma, discrimination, as well as poor health resources, conflict in policy development and program implementation. Despite implementing infection control measures over the last few decades eradication or significant disease reduction remains elusive. This study aims to present the current global prevalence status and examines potential elimination strategies. The information for this research were obtained through a systematic review, published scientific literatures, the official websites of various government organisations, international public health organisations and internationally recognised regulatory bodies over a period of 40 years between 1978 and 2018.

Ion transport blockers inhibit human rhinovirus 2 release.

Picornavirus replication causes leakage of cytoplasmic K+ and an influx of Na+ and Ca2+. In this study, we have explored the possibility that a blockade of Ca2+ and Na+ influx would reduce rhinovirus production and/or release. The Ca2+-channel blockers, verapamil and diltiazem, as well as the blocker of Na+/H+ exchange and the epithelial Na+ channel, EIPA, inhibited both virus production and release. The effect on virus release was more pronounced than the effect on production, thus raising the possibility that rhinovirus release may serve as a target for antiviral agents. Unexpectedly, our results also showed that the antiviral activity of the Ca2+-channel blockers was not due to the block of Ca2+ influx. Similarly, the antiviral activity of EIPA appeared to be unrelated to the blockade of cellular Na+/H+ exchanger or the epithelial Na+ channel. Potential alternative mechanisms of the antiviral activity of these compounds are discussed.

Characterisation of local immune responses induced by a novel nano-particle based carrier-adjuvant in sheep.

Most adjuvants require danger signals to promote immune responses against vaccine antigens. Our previous studies have characterised a powerful nano-particulate antigen delivery system, which by itself does not induce inflammation, and which further appears to induce substantial immune responses in mice and sheep without the requirement for added stimulators of toll like receptors or other pathogen recognition receptors. In the present study we dissect the nature of the early induction phase of the immune response stimulated by such a vaccine comprising 40 nm polystyrene nano-particles conjugated to the antigen. We analyse the kinetics of export from an individual draining lymph node from the sheep, of antibodies and cytokines as well as antigen responsive CD4 and CD8 T cells. Our results indicate that simple inert nano-bead based antigen delivery into the draining area of the lymph node is highly efficient at priming combined humoral and T cell antigen specific immunity without the need for added 'danger signals'. Furthermore this nano-bead adjuvant is a potent agent capable of promoting cross-priming for CD8 T cell induction in sheep. Interestingly, using nano-beads, similarly to what has been observed with natural pathogen based lymph node stimulation, a phase of CD4 T cell priming and export preceded CD8 T cell induction, suggesting the engagement of natural priming processes and kinetics.