Adrian Dunlop

Assessment and treatment of hepatitis C virus infection among people who inject drugs in the opioid substitution setting: ETHOS study.

BACKGROUND Access to hepatitis C virus (HCV) treatment remains extremely limited among people who inject drugs (PWID). HCV assessment and treatment was evaluated through an innovative model for the provision of HCV care among PWID with chronic HCV infection. METHODS Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) was a prospective observational cohort. Recruitment was through 5 opioid substitution treatment (OST) clinics, 2 community health centers, and 1 Aboriginal community controlled health organization in New South Wales, Australia. RESULTS Among 387 enrolled participants, mean age was 41 years, 71% were male, and 15% were of Aboriginal ethnicity. Specialist assessment was undertaken in 191 (49%) participants, and 84 (22%) commenced interferon-based treatment. In adjusted analysis, HCV specialist assessment was associated with non-Aboriginal ethnicity (adjusted odds ratio [AOR], 4.02; 95% confidence interval [CI], 2.05-7.90), no recent benzodiazepine use (AOR, 2.06; 95% CI, 1.31-3.24), and non-1 HCV genotype (AOR, 2.13; 95% CI, 1.32-3.43). In adjusted analysis, HCV treatment was associated with non-Aboriginal ethnicity (AOR, 4.59; 95% CI, 1.49-14.12), living with the support of family and/or friends (AOR, 2.15; 95% CI, 1.25-3.71), never receiving OST (AOR, 4.40; 95% CI, 2.27-8.54), no recent methamphetamine use (AOR, 2.26; 95% CI, 1.12-4.57), and non-1 HCV genotype (AOR, 3.07; 95% CI, 1.67-5.64). CONCLUSIONS HCV treatment uptake was relatively high among this highly marginalized population of PWID. Potentially modifiable factors associated with treatment include drug use and social support.

Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal: A Randomized Clinical Trial

IMPORTANCE There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. OBJECTIVE To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. DESIGN, SETTING, AND PARTICIPANTS A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. INTERVENTIONS A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. MAIN OUTCOMES AND MEASURES Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. RESULTS Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). CONCLUSIONS AND RELEVANCE In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12611000398909.

A randomised controlled trial of sublingual buprenorphine-naloxone film versus tablets in the management of opioid dependence

BACKGROUND Buprenorphine-naloxone sublingual film was introduced in 2011 in Australia as an alternative to tablets. This study compared the two formulations on subjective dose effects and equivalence, trough plasma levels, adverse events, patient satisfaction, supervised dosing time, and impact upon treatment outcomes (substance use, psychosocial function). METHODS 92 buprenorphine-naloxone tablet patients were recruited to this outpatient multi-site double-blind double-dummy parallel group trial. Patients were randomised to either tablets or film, without dose changes, over a 31 day period. RESULTS No significant group differences were observed for subjective dose effects, trough plasma buprenorphine or norbuprenorphine levels, adverse events and treatment outcomes. Buprenorphine-naloxone film took significantly less time to dissolve than tablets (173±71 versus 242±141s, p=0.007, F=7.67). CONCLUSIONS The study demonstrated dose equivalence and comparable clinical outcomes between the buprenorphine-naloxone film and tablet preparations, whilst showing improved dispensing times and patient ratings of satisfaction with the film.

Treatment for hepatitis C virus infection among people who inject drugs attending opioid substitution treatment and community health clinics: The ETHOS Study

AIMS To estimate adherence and response to therapy for chronic hepatitis C virus (HCV) infection among people with a history of injecting drug use. A secondary aim was to identify predictors of HCV treatment response. DESIGN Prospective cohort recruited between 2009 and 2012. Participants were treated with peg-interferon alfa-2a/ribavirin for 24 (genotypes 2/3, G2/3) or 48 weeks (genotype 1, G1). SETTING Six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community-controlled health organization providing drug treatment services in New South Wales, Australia. PARTICIPANTS Among 415 people with a history of injecting drug use and chronic HCV assessed by a nurse, 101 were assessed for treatment outcomes (21% female). MEASUREMENTS Study outcomes were treatment adherence and sustained virological response (SVR, undetectable HCV RNA >24 weeks post-treatment). FINDINGS Among 101 treated, 37% (n = 37) had recently injected drugs (past 6 months) and 62% (n = 63) were receiving OST. Adherence ≥ 80% was 86% (n = 87). SVR was 74% (75 of 101), with no difference observed by sex (males: 76%, females: 67%, P = 0.662). In adjusted analysis, age < 35 (versus ≥ 45 years) [adjusted odds ratio (aOR) = 5.06, 95% confidence interval (CI) = 1.47, 17.40] and on-treatment adherence ≥ 80% independently predicted SVR (aOR = 19.41, 95% CI = 3.61, 104.26]. Recent injecting drug use at baseline was not associated with SVR. CONCLUSIONS People with a history of injecting drug use and chronic hepatitis C virus attending opioid substitution treatment and community health clinics can achieve adherence and responses to interferon-based therapy similar to other populations, despite injecting drugs at baseline. Younger age and adherence are predictive of improved response to hepatitis C virus therapy.

Addressing dependent amphetamine use: A place for prescription

Amphetamines are among the most widely used of illicit drugs in Australia, and evidence documenting the occurrence of amphetamine-related harms, particularly among chronic regular users, is increasing, A review of contemporary Australian treatment approaches suggests that conventional modalities are unlikely to address the needs of a large proportion of dependent amphetamine users. This has prompted clinicians in Australia and the United Kingdom to commence treatment programmes incorporating substitution therapy. Despite the positive impressions of clinicians involved in these programmes, further research is required to establish the role and efficacy of such treatment approaches. Issues to be addressed in the establishment of a controlled study are examined.

Changes in cigarette and alcohol use during cannabis abstinence

OBJECTIVE Cannabis causes lower mortality and morbidity than alcohol and tobacco so it is clinically important if quitting cannabis is associated with substitution with these substances. This study tests if cannabis is substituted with alcohol and/or tobacco during cannabis abstinence, and factors predicting such substitution. METHOD A secondary analysis of a prospective community based study quantified cannabis, alcohol and tobacco use with Timeline Follow-back during a two-week voluntary cannabis abstinence and at one-month follow-up in non-treatment seeking cannabis users (n=45). Cannabis use was verified by urine THC-COOH levels. RESULTS Alcohol use increased by 8 standard units (SU; d=0.48)/week and cigarette use by 14 cigarettes/week (d=0.29) during cannabis abstinence. Those using less of each substance at baseline had greater increases during cannabis abstinence (alcohol P<0.0001, tobacco P=0.01). There was a decrease in alcohol (-4.8 SU, d=-0.29) and tobacco (-13 cigarettes/week, d=-0.26) use at follow-up, when most participants (87%, n=39) had resumed cannabis use. Increased cigarette use was predicted by cannabis withdrawal related sleep difficulty (insomnia) (P=0.05), restlessness (P=0.03) and physical symptoms (P=0.02). Neither alcohol nor cigarette use increased significantly in those (13.3%, n=6) who remained abstinent from cannabis through to follow-up. CONCLUSIONS Abstaining from cannabis was associated with increases in alcohol and tobacco use that decreased with resumption of cannabis use; however there were no increases in individuals who remained abstinent from cannabis at one-month follow-up. Tobacco use did not increase in those experiencing milder cannabis withdrawal symptoms. Research on substitution in treatment seekers during outpatient cannabis abstinence is needed.

Assessment and delivery of treatment for hepatitis C virus infection in an opioid substitution treatment clinic with integrated peer-based support in Newcastle, Australia

BACKGROUND Among people who inject drugs (PWID), the prevalence of hepatitis C virus (HCV) infection is high; however HCV treatment uptake remains low. New models of care are needed to address the growing burden of HCV-related disease in PWID and to understand the barriers to assessment and treatment of HCV. This study evaluated assessment and treatment for HCV infection among PWID attending an opioid substitution treatment (OST) clinic with an integrated peer support worker model. METHODS Clients with a history of IDU and chronic HCV infection, attending the Newcastle Pharmacotherapy Service, Newcastle Australia, were recruited as part of a multisite prospective observational study (the ETHOS Cohort). Additional chart review was conducted for clients not enrolled in the ETHOS Cohort. A peer support worker was introduced to complement and extend services offered by the clinical team. Client contacts and assessments with a nurse and/or peer worker were evaluated, including those who commenced HCV treatment. RESULTS A total of 1447 clients attended the OST service during February 2009 and June 2014. Of these, 378 (26%) were assessed by a nurse and 242 (17%) by a clinician. HCV treatment was commenced by 20 (5%) participants and 15 (75%) achieved a sustained virological response (SVR). During May 2009 and July 2011, 332 nurse contacts and 726 peer worker contacts were evaluated. The nurse-led contacts were related to HCV treatment (50%) and review of pathology tests (34%), whereas peer worker contacts included discussion about HCV treatment (75%), education, counselling and/or support (53%) and general discussion about HCV infection (59%). CONCLUSION These data demonstrate that peer support workers facilitate broader discussion about HCV treatment, education and/or support, allowing nurses to focus on HCV-related assessment and treatment. HCV treatment uptake was very low in this cohort, but SVR was high. The integration of peer support workers in treatment programs within OST clinics may address barriers to HCV care, but further studies are needed to assess their impact on assessment and treatment outcomes.

Harm reduction and drug users of Vietnamese ethnicity

P. Higgs, Research Officer, The Centre for Harm Reduction, Macfarlane Burnet Centre for Medical Research, PO Box 254 Fairfield 3078;L. Maher, Senior Lecturer, School of Medical Education, University of NSW Australia, Sydney 2052; J. Jordens, Research Officer, TheCentre for Harm Reduction, Macfarlane Burnet Centre for Medical Research, PO Box 254 Fairfield 3078; A. Dunlop, Senior MedicalOfficer, Turning Point Alcohol and Drug Centre, 54Ł62 Gertrude Street, Fitzroy 3065; P. Sargent, Research Assistant, School of MedicalEducation, University of NSW, Randwick 2052, Australia.Note from the Editor:

Cannabinoid replacement therapy (CRT): Nabiximols (Sativex) as a novel treatment for cannabis withdrawal.

Cannabis is a common recreational drug that is generally considered to have low addictive potential. However, an increasing number of cannabis users are seeking treatment for dependence on the drug. There is interest in using agonist (substitution) pharmacotherapies to treat cannabis dependence and here we outline a novel approach involving a buccal spray (nabiximols) that contains tetrahydrocannabinol (THC) and cannabidiol (CBD). We review recent research with nabiximols and highlight findings relevant to clinical practice.

Effect of treatment willingness on specialist assessment and treatment uptake for hepatitis C virus infection among people who use drugs: the ETHOS study.

Among people who inject drugs (PWID) with chronic HCV, the association between HCV treatment willingness and intent, and HCV specialist assessment and treatment were evaluated. The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort. Recruitment was through six opioid substitution treatment clinics, two community health centres and one Aboriginal community controlled health organisation in Australia. Analyses were performed using logistic regression. Among 415 participants (mean age 41 years, 71% male), 67% were ‘definitely willing’ to receive HCV treatment and 70% reported plans to initiate therapy 12 months postenrolment. Those definitely willing to receive HCV treatment were more likely to undergo specialist assessment (64% vs 32%, P < 0.001) and initiate therapy (36% vs 9%, P < 0.001), compared to those with lower treatment willingness. Those with early HCV treatment plans were more likely to undergo specialist assessment (65% vs 27%, P < 0.001) and initiate therapy (36% vs 5%, P < 0.001), compared to those without early plans. In adjusted analyses, HCV treatment willingness independently predicted specialist assessment (aOR 3.06, 95% CI 1.90, 4.94) and treatment uptake (aOR 4.33, 95% CI 2.14, 8.76). In adjusted analysis, having early HCV treatment plans independently predicted specialist assessment (aOR 4.38, 95% CI 2.63, 7.29) and treatment uptake (aOR 9.79, 95% CI 3.70, 25.93). HCV treatment willingness was high and predicted specialist assessment and treatment. Strategies for enhanced HCV care should be developed with an initial focus on people willing to receive treatment and to increase treatment willingness among those less willing.