Diagnostic Overshadowing of Chronic Hepatitis C in People With Mental Health Conditions Who Inject Drugs: A Scoping Review.

Diagnostic overshadowing refers to a phenomenon whereby people with mental health conditions encounter inadequate or delayed medical attention and misdiagnosis. This occurs when physical symptoms are mistakenly attributed to their mental health condition. This paper presents a scoping review focusing on direct causes and background factors of diagnostic overshadowing in the context of hepatitis C infection in people who inject drugs and have concurrent mental health conditions. Despite significant strides in hepatitis C treatment with direct-acting antiviral drugs, the complex interplay of mental health conditions and physical symptoms necessitates a nuanced approach for accurate diagnosis and effective screening. This review was conducted using Joanna Briggs Institute's methodology for scoping reviews. The databases searched included Medline, Embase, PsycInfo, Global Health, CINAHL and Scopus. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The search strategies identified 1995 records. Overall, 166 studies were excluded. Forty-two (42) studies met the inclusion criteria. Three (n = 3) studies represented direct causes, and 39 (n = 39) with background factors related to diagnostic overshadowing. Studies highlighted six key themes encompassing diagnostic overshadowing, with communication barriers, stigma and knowledge deficiencies being the most prominent. Recognising and addressing diagnostic overshadowing in chronic hepatitis C will lead to increased screening, diagnosis and timely administration of life-saving antiviral therapy, resulting in profound enhancements in well-being and health outcomes. Moreover, this proactive approach will play a pivotal role in advancing the global effort towards eliminating hepatitis C by 2030.

A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial.

BACKGROUND: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. METHODS: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. DISCUSSION: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

The reflections of health service providers on implementing contingency management for methamphetamine use disorder in Australia.

INTRODUCTION: Contingency management (CM) is the most effective treatment for reducing methamphetamine use. We sought to understand why CM has not been taken up to manage methamphetamine use disorder in Australia. METHODS: Six focus groups (4-8 participants per group) were conducted with health workers from agencies in Australia that provided drug-related health care to people who use methamphetamine. These agencies had no previous experience delivering CM for substance use. The potential acceptability and feasibility of implementing CM in their services were discussed. RESULTS: Participants felt that it would be beneficial to have an evidence-based treatment for methamphetamine use disorder. This sentiment was offset by concerns that CM conflicted with a client-centred harm-reduction approach and that it dictated the goal of treatment as abstinence. It was also perceived as potentially coercive and seen to reify the power imbalance in the therapeutic relationship and therefore potentially reinforce stigma. There was also concern about the public's perception and the political acceptability of CM, who would fund CM, and the inequity of providing incentives only to clients with a methamphetamine use disorder. Some concerns could be ameliorated if the goals and structure of CM could be tailored to a client's needs. DISCUSSION AND CONCLUSIONS: Many healthcare workers were keen to offer CM as an effective treatment option for people with methamphetamine use disorder, but CM would need to be sufficiently flexible to allow it to be tailored to client needs and implemented in a way that did not adversely impact the therapeutic relationship.

Factors associated with experiencing stigma, discrimination, and negative health care treatment among people who inject drugs.

INTRODUCTION: Stigma has negative consequences for the health of people who inject drugs and people living with hepatitis C virus (HCV). This study evaluated factors associated with stigma related to injecting drug use (IDU) or HCV and those associated with being treated negatively by health workers. METHODS: ETHOS Engage is an observational cohort study of people who inject drugs attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire including IDU- and HCV-related stigma, and negative treatment by health workers. Logistic regression was used to identify factors associated with experiencing stigma and negative treatment in a cross-sectional sample. RESULTS: Of 1,211 participants, 31% were women, 64% had injected drugs in the previous month, and 65% had been diagnosed with HCV. IDU-related stigma was reported by 57% of participants and was associated with being a woman, higher than Year 10 education, homelessness, opioid agonist treatment, recent injecting, overdose history, hospitalisation for drug use, and unknown HCV status. HCV-related stigma was reported by 34% of participants diagnosed with HCV and was associated with being a woman, homelessness, receptive needle/syringe sharing, arrest for drug use/possession, and recent HCV testing. Negative treatment from health workers was reported by 45% of participants and was associated with being a woman, receptive needle/syringe sharing, hospitalisation for drug use, and arrest for drug use/possession. DISCUSSION AND CONCLUSIONS: Results highlight important intersections and disparities in stigmatising experiences among people who inject drugs. Considering these intersections can assist health services provide more inclusive care.

Measuring Objective and Subjective Sleep during Lisdexamfetamine Treatment of Acute Methamphetamine Withdrawal: A Feasibility Study.

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.

Participant experiences in a pilot study for methamphetamine withdrawal treatment: Implications for retention.

INTRODUCTION: There is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal. METHODS: Thematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital. RESULTS: Participants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants' subsequent decision to remain enrolled in the trial. DISCUSSION: The experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials.

Perspectives and sentiments on contingency management from people who use methamphetamine.

INTRODUCTION: Contingency management (CM) is currently the most efficacious treatment for methamphetamine use, yet it is rarely available in routine care. We examined the viewpoints of people who use methamphetamine on CM as a potential treatment for methamphetamine use disorder. METHODS: Semi-structured qualitative interviews with 30 Australians aged 18 years or older who had used methamphetamine at least weekly in the past 6 months. RESULTS: Participants reported overall positive attitudes towards CM as a potential treatment option for methamphetamine use disorder. However, there was need for greater flexibility in meeting participant treatment goals (e.g., reduced use or complete abstinence), with particular concern about the viability of initiating abstinence, both in terms of the sufficiency of the initial financial incentive and managing withdrawal symptoms. There was strong interest in the use of digital technologies to provide remote CM, particularly around the convenience and flexibility this offered. Despite this, participants remained keen to access adjunctive treatment and support services but stressed that engagement with these additional services should not be mandatory. Marketing of CM will need to address preconceptions about drug-testing used in abstinence-based CM being punitive (especially urine testing) and its connotations with criminal justice interventions. DISCUSSION AND CONCLUSION: Positive attitudes towards CM bode well for potential uptake should CM be made available in routine clinical practice. However, there is a need to adapt CM to ensure it is feasible and attractive to people who are seeking treatment for methamphetamine use disorder.

'I just thought that was the best thing for me to do at this point': Exploring patient experiences with depot buprenorphine and their motivations to discontinue.

INTRODUCTION: Long-acting injectable depot buprenorphine is a recent addition to the suite of opioid agonist therapies (OAT) used to treat opioid use disorder (OUD). However, there has been little research that focuses on the lived experience of people receiving depot buprenorphine treatment and reasons for why people decide to discontinue. The aim of this study was to explore what it is like to receive depot buprenorphine and to understand the motivations behind why people discontinue. METHODS: Open-ended, semi-structured interviews were conducted between November 2021 and January 2022 with individuals who were either currently receiving depot buprenorphine or had discontinued or were in the process of discontinuing depot buprenorphine. Liberati, et al.'s (2022) adaptation of Dixon-Woods's (2006) candidacy framework was used to analyse the participant experiences. RESULTS: 40 participants (26 male, 13 female, 1 undisclosed; mean age 42 years) were interviewed about their experience with depot buprenorphine. At the time of the interview, 21 were currently receiving depot buprenorphine and 19 had discontinued this treatment or were in the process of discontinuing. Participants cited 4 key reasons why they decided to discontinue depot buprenorphine:1) feeling forced into the program, 2) experiencing negative side-effects, 3) finding the treatment ineffective, and 4) wanting to stop depot buprenorphine/OAT to use opioids again or feeling 'cured' and no longer in need of OAT. Participants were ultimately discussing issues related to clinician-patient power relations, agency and bodily autonomy, and the pursuit of well-being. CONCLUSION: Depot buprenorphine remains a promising treatment for OUD and offers potential to improve treatment adherence. Instances of restricted OAT choice and consumer concerns regarding a lack of agency must be addressed in order to enhance therapeutic relationships. Clinicians and other healthcare workers in this field also need greater access to information about depot buprenorphine to better address issues patients face during treatment. More research is required to understand patient and treatment choice given the options of these new treatment formulations.

Lisdexamfetamine for the treatment of acute methamphetamine withdrawal: A pilot feasibility and safety trial.

BACKGROUND: There is no effective treatment for methamphetamine withdrawal. This study aimed to determine the feasibility and safety of a tapering dose of lisdexamfetamine for the treatment of acute methamphetamine (MA) withdrawal. METHODS: Open-label, single-arm pilot study, in an inpatient drug and alcohol withdrawal unit assessing a tapering dose of oral lisdexamfetamine dimesylate commencing at 250 mg once daily, reducing by 50 mg per day to 50 mg on Day 5. Measures were assessed daily (days 0-7) with 21-day telephone follow-up. Feasibility was measured by the time taken to enrol the sample. Safety was the number of adverse events (AEs) by system organ class. Retention was the proportion to complete treatment. Other measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), the Amphetamine Withdrawal Questionnaire and craving (Visual Analogue Scale). RESULTS: Ten adults seeking inpatient treatment for MA withdrawal (9 male, median age 37.1 years [IQR 31.7-41.9]), diagnosed with MA use disorder were recruited. The trial was open for 126 days; enroling one participant every 12.6 days. Eight of ten participants completed treatment (Day 5). Two participants left treatment early. There were no treatment-related serious adverse events (SAEs). Forty-seven AEs were recorded, 17 (36%) of which were potentially causally related, all graded as mild severity. Acceptability of the study drug by TSQM was rated at 100% at treatment completion. Withdrawal severity and craving reduced through the admission. CONCLUSION: A tapering dose regimen of lisdexamfetamine was safe and feasible for the treatment of acute methamphetamine withdrawal in an inpatient setting.

Awareness of hepatitis C virus infection status among people who inject drugs in a setting of universal direct-acting antiviral therapy: The ETHOS Engage study.

BACKGROUND: Awareness of hepatitis C virus (HCV) infection status among people who inject drugs (PWID) can empower people with diagnosis, enable treatment uptake, and facilitate elimination. We aimed to evaluate awareness of HCV infection status among a large national cohort of PWID in an era of unrestricted HCV treatment. METHODS: ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participants completed a questionnaire containing self-reported HCV data (including infection status: never tested, tested/unknown, no current HCV infection [HCV RNA not detectable], current HCV infection [HCV RNA detectable]) and underwent point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Awareness was defined as concordant self-reported HCV status and test result. Awareness was assessed among all participants, those with current HCV infection, and participants who reported a lifetime history of HCV treatment. Logistic regression was used to assess factors associated with awareness in these three populations. RESULTS: Among 2,305 PWID, 65% (n=1,506) were aware of their HCV infection status (self-reported HCV status matched HCV point-of-care result). Awareness of infection status was higher among those who were not currently infected (70%, n=1,281/1,818) compared to those with current HCV infection (46%, n=225/487). After adjusting, those with current HCV infection were less likely to be aware of infection status (aOR: 0.40, 95%CI: 0.30, 0.45). Among those who reported a lifetime history of HCV treatment, 71% (n=592/829) were aware of their HCV infection status. CONCLUSION: Among a large cohort of PWID in Australia, awareness of HCV infection status is sub-optimal, with particularly concerning levels among those with active infection. Increased and simplified testing, post-test counselling, and post-treatment monitoring is warranted.