A Placebo-Controlled Randomized Trial of Vigabatrin in the Management of Acute Alcohol Withdrawal.

OBJECTIVE: To undertake a double blinded randomised placebo-controlled trial to assess the efficacy of vigabatrin, a GABA-transaminase inhibitor, as a benzodiazepine sparing agent in the management of acute alcohol withdrawal syndrome in a residential setting. METHODS: We enrolled 120 patients with alcohol use disorder who were randomly assigned to either treatment with vigabatrin (2g/day for 4 days) or placebo. The primary outcome was defined as the number of participants in each treatment arm needing diazepam for withdrawal management. A secondary outcome prespecified was the total dose of diazepam received by participants in each treatment arm. Participants were recruited on admission to a residential withdrawal unit at St Vincent's Hospital Melbourne from December 2014 to April 2019. RESULTS: No significant difference was observed in the number of participants requiring benzodiazepines during their residential withdrawal stay with 44 participants (78.6%) in placebo arm requiring at least one dose of diazepam compared to 38 (66.7%) in vigabatrin arm (p = .156). An 18.1% difference was observed between the proportion of participants who received a total dose of >100mg of diazepam during their residential withdrawal stay in placebo arm (32.1%), compared to vigabatrin arm (14.0%, p = .022). There were higher rates of reported adverse events in placebo arm with nine (15.0%) participants reporting adverse events compared with two (3.3%) participants in vigabatrin arm (p = .027). CONCLUSION: Vigabatrin significantly reduced the number of participants requiring >100mg diazepam over the course of their alcohol withdrawal and was associated with a reduction in adverse effects when compared to placebo.

Alcohol use in the year following approach bias modification during inpatient withdrawal: secondary outcomes from a double-blind, multi-site randomized controlled trial.

BACKGROUND AND AIMS: Approach bias modification (ApBM) targeting alcohol approach bias has been previously shown to reduce likelihood of relapse during the first 2 weeks following inpatient withdrawal treatment (IWT). We tested whether ApBM's effects endure for a longer period by analysing alcohol use outcomes 3, 6 and 12 months post-discharge. DESIGN: A double-blind, sham-controlled randomized controlled trial. SETTING: Four IWT units in Melbourne, Australia. PARTICIPANTS: Three hundred alcohol IWT patients (173 men, 126 women, 1 non-binary; mean age 43.5 years) were recruited between 4 June 2017 and 14 July 2019. Follow-up data collection was completed on 22 September 2020. INTERVENTION AND CONTROL TRAINING: Four ApBM sessions were delivered during IWT. ApBM trained participants (n = 147) to avoid alcohol and approach non-alcohol beverage cues. Controls (n = 153) responded to the same stimuli, but without approach/avoidance training. MEASUREMENTS: Date of first lapse was recorded for non-abstinent participants to determine time to first lapse. Time-line follow-back interviews assessed past-month alcohol consumption at each follow-up, with participants reporting no alcohol consumption classified as abstinent. In analyses of past-month abstinence, non-abstinence was assumed in participants lost to follow-up. Number of past-month drinking days, standard drinks and heavy drinking days (five or more standard drinks for women or non-binary; six or more standard drinks for men) were calculated for non-abstinent participants at each follow-up. FINDINGS: ApBM significantly delayed time to first lapse [ApBM median: 53 days, 95% confidence interval (CI) = 21-61; controls = 12 days, 95% CI = 9-21, P = 0.045]. Past-month abstinence rates at 3-, 6- and 12-month follow-ups were 33/153 (21.6%), 30/153 (19.6%), and 24/153 (15.7%) in controls; and 51/147 (34.7%), 30/147 (20.4%) and 29/147 (19.7%) in the ApBM group, respectively. Past-month abstinence was significantly more likely in ApBM participants than controls at the 3-month follow-up [odds ratio (OR) = 1.93, 95% CI = 1.16-3.23, P = 0.012], but not at 6- or 12-month follow-ups (6-month OR = 1.05, 95% CI = 0.60-1.95, P = 0.862; 12-month OR = 1.32, 95% CI = 0.73-2.40, P = 0.360). No significant group differences were found for indices of alcohol consumption in non-abstinent participants. CONCLUSIONS: Approach bias modification for alcohol delivered during inpatient withdrawal treatment helps to prevent relapse, increasing rates of abstinence from alcohol for at least 3 months post-discharge.

Review of management priorities for invasive infections in people who inject drugs: highlighting the need for patient-centred multidisciplinary care.

There has been a global increase in the burden of invasive infections in people who inject drugs (PWID). It is essential that patient-centred multidisciplinary care is provided in the management of these infections to engage PWID in care and deliver evidence-based management and preventive strategies. The multidisciplinary team should include infectious diseases, addictions medicine (inclusive of alcohol and other drug services), surgery, psychiatry, pain specialists, pharmacy, nursing staff, social work and peer support workers (where available) to help address the comorbid conditions that may have contributed to the patient's presentation. PWID have a range of antimicrobial delivery options that can be tailored in a patient-centred manner and thus are not limited to prolonged hospital admissions to receive intravenous antimicrobials for invasive infections. These options include discharge with outpatient parenteral antimicrobial therapy, long-acting lipoglycopeptides (dalbavancin and oritavancin) and early oral antimicrobials. Open and respectful discussion with PWID including around harm reduction strategies may decrease the risk of repeat presentations with injecting-related harms.

A Case Study of Pain Management at End-of-Life for a Patient on High-Dose Buprenorphine.

In Australia, high-dose sublingual buprenorphine and long-acting injectable buprenorphine are available. High-dose buprenorphine is used predominantly in the setting of opioid use disorder and has a role in chronic pain. Palliative care specialists are increasingly involved in pain management and end-of-life care for patients on these medications, yet there is a lack of education and training about high-dose buprenorphine for palliative care specialists. We describe our experience caring for John (fictional name), a gentleman with chronic pain and a new high-grade post-transplant lymphoproliferative disorder prescribed high-dose buprenorphine. We share the challenges and experience in caring for John as he deteriorated into the terminal phase and died of his illness. We include potential management options and the rationale for our decision to rotate John from high-dose sublingual buprenorphine to subcutaneous oxycodone. We conclude with practice implications and suggestions for improved patient care and clinician experience, including increased collaboration between palliative medicine, acute pain, and addiction medicine services, increased education and training for palliative care specialists about high-dose buprenorphine, and ultimately the development of consensus high-dose buprenorphine to oral morphine equivalence guidelines.

Screening for risky drinkers among hospitalised inpatients using the AUDIT: A feasibility, point prevalence and data linkage study.

INTRODUCTION: Risky drinking frequently remains undiagnosed or untreated, including in hospitalised inpatients. Using the Alcohol Use Disorders Identification Test (AUDIT), we assessed the feasibility of screening for risky drinking and whether screening results aligned with alcohol-attributable diagnoses in an inpatient population. METHODS: We conducted a cross-sectional survey across a tertiary health service in Melbourne, Australia. Researchers collected demographics, AUDIT scores and acceptability from all eligible adult inpatients available on day of survey. Main outcomes were prevalence of risky drinking (AUDIT ≥8), mean AUDIT score and patient acceptability. Identification of risky drinking by the abbreviated 'AUDIT-C' or discharge diagnoses (extracted by data-linkage with medical records) was compared. RESULTS: Of 473 eligible inpatients, 61% (n = 289) participated, 22% (n = 103) were unavailable and 17% (n = 81) declined. Median age was 64 years (IQR = 48, 76); 54% (n = 157) were male. Mean AUDIT score was 4.4 (SD = 5.5). Risky drinking prevalence was 20% (n = 57), 2% (n = 7) had scores suggestive of dependence (AUDIT ≥20, a subset of risky drinkers). Odds of risky drinking were reduced in females (OR 0.19, 95% CI 0.09, 0.41; P < 0.001) and participants ≥70 years (OR 0.22, 95% CI 0.07, 0.71; P = 0.01). Alcohol-attributable diagnoses did not consistently align with risky drinking, with half of inpatients with wholly attributable diagnoses classified as low risk. Most inpatients considered screening acceptable (89%, n = 256). DISCUSSION AND CONCLUSIONS: Pre-admission risky drinking was evident in one-fifth of hospital inpatients, but alcohol-attributable diagnoses were unreliable proxy measures of risky drinking. Screening in-patients with the AUDIT was acceptable to inpatients and can be feasibly implemented in an Australian tertiary hospital setting.

Effect of Cognitive Bias Modification on Early Relapse Among Adults Undergoing Inpatient Alcohol Withdrawal Treatment: A Randomized Clinical Trial.

Importance: More than half of patients with alcohol use disorder who receive inpatient withdrawal treatment relapse within weeks of discharge, hampering subsequent uptake and effectiveness of psychological and pharmacologic interventions. Cognitive bias modification (CBM) improves outcomes after alcohol rehabilitation, but the efficacy of delivering CBM during withdrawal treatment has not yet been established. Objective: To test the hypothesis that CBM would increase the likelihood of abstaining from alcohol during the 2 weeks following discharge from inpatient withdrawal treatment. Design, Setting, and Participants: In a randomized clinical trial, 950 patients in 4 inpatient withdrawal units in Melbourne, Australia, were screened for eligibility between June 4, 2017, and July 14, 2019, to receive CBM or sham treatment. Patients with moderate or severe alcohol use disorder aged 18 to 65 years who had no neurologic illness or traumatic brain injury were eligible. Two-week follow-up, conducted by researchers blinded to the participant's condition, was the primary end point. Both per-protocol and intention-to-treat analysis were conducted. Interventions: Randomized to 4 consecutive daily sessions of CBM designed to reduce alcohol approach bias or sham training not designed to modify approach bias. Main Outcomes and Measures: Primary outcome was abstinence assessed using a timeline followback interview. Participants were classified as abstinent (no alcohol use in the first 14 days following discharge) or relapsed (any alcohol use during the first 14 days following discharge or lost to follow-up). Results: Of the 950 patients screened for eligibility, 338 did not meet inclusion criteria, 108 were discharged before being approached, and 192 refused. Of the 312 patients who consented (referred sample), 12 withdrew before being randomized. In the final population of 300 randomized patients (CBM, n = 147; sham, n = 153), 248 completed the intervention and 272 completed the follow-up. Of the 300 participants (173 [57.7%] men; mean [SD] age, 43.47 [10.43] years), 7 patients (3 controls, 4 CBM) withdrew after finding the training uncomfortable. Abstinence rates were 42.5% (95% CI, 34.3%-50.6%) in controls and 54.4% (95% CI, 46.0%-62.8%) in CBM participants, yielding an 11.9% (95% CI, 0.04%-23.8%; P = .04) difference in abstinence rates. In a per-protocol analysis including only those who completed 4 sessions of training and the follow-up, the difference in abstinence rate between groups was 17.0% (95% CI, 3.8%-30.2%; P = .008). Conclusions and Relevance: The findings of this clinical trial support the efficacy of CBM for treatment of alcohol use disorder. Being safe and easy to implement, requiring only a computer and joystick, and needing no specialist staff/training, CBM could be routinely offered as an adjunctive intervention during withdrawal treatment to optimize outcomes. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617001241325.

Review article: Rapid review of the emergency department-initiated buprenorphine for opioid use disorder.

Opioid-related harms have been increasing in Australia over the last 5 years. Patients with opioid use disorder are over-represented in ED presentations. Opioid agonist treatment is the most effective community-based treatment. Buprenorphine is considered the safest of these treatments to use in the ED setting. This rapid review investigated the effectiveness of initiating buprenorphine in the ED setting. Medline, Embase, Emcare, PSYCinfo, CINAHL and Cochrane Central Register of Controlled Trials databases were searched. Randomised and non-randomised studies published in peer-reviewed journals that involved the initiation of buprenorphine in the ED setting were considered eligible. The search revealed 350 articles of which 11 were included in the review; three articles representing two randomised controlled trials (RCTs) and eight observational studies. Data were extracted from included papers and risk of bias assessed on the RCTs. One well-conducted RCT showed that buprenorphine initiated in the ED does improve treatment engagement up to 2 months after an ED visit. Eight observational studies, one with a comparator group reported positive results for this intervention. There is strong evidence that clinicians should consider commencing buprenorphine in the ED for patients with opioid use disorder when combined with a direct and supported referral or 'warm handover' to community care. Further implementation studies and investigation of long-acting injectable buprenorphine treatment are required.

Driving change: A partnership study protocol using shared emergency department data to reduce alcohol-related harm.

BACKGROUND: Sharing anonymised ED data with community agencies to reduce alcohol-related injury and assaults has been found effective in the UK. This protocol document outlines the design of an Australian multi-site trial using shared, anonymised ED data to reduce alcohol-related harm. DESIGN AND METHOD: Nine hospitals will participate in a 36 month stepped-wedge cluster randomised trial. After a 9 month baseline period, EDs will be randomised in five groups, clustered on geographic proximity, to commence the intervention at 3 monthly intervals. 'Last-drinks' data regarding alcohol use in the preceding 12 h, typical alcohol consumption amount, and location of alcohol purchase and consumption, are to be prospectively collected by ED triage nurses and clinicians at all nine EDs as a part of standard clinical process. Brief information flyers will be delivered to all ED patients who self-report risky alcohol consumption. Public Health Interventions to be conducted are: (i) information sharing with venues (via letter), and (ii) with police and other community agencies, and (iii) the option for public release of 'Top 5' venue lists. OUTCOMES: Primary outcomes will be: (i) the number and proportion of ED attendances among patients reporting recent alcohol use; and (ii) the number and proportion of ED attendances during high-alcohol hours (Friday and Saturday nights, 20.00-06.00 hours) assigned an injury diagnosis. Process measures will assess logistical and feasibility concerns, and clinical impacts of implementing this systems-change model in an Australian context. An economic cost-benefit analysis will evaluate the economic impact, or return on investment.

Managing attention deficit hyperactivity disorder in adults using illicit psychostimulants: A systematic review.

CONTEXT: Attention deficit hyperactivity disorder and stimulant use disorder commonly co-exist, and appropriate treatments have not been well established. OBJECTIVE: To provide guidance for treatment of co-existing attention deficit hyperactivity disorder and stimulant use disorder. DATA SOURCES: A systematic review of published English articles using MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane, utilising consistent search terms. STUDY SELECTION: Randomised controlled trials, comparing any treatment arm with a control group, for participants meeting Diagnostic and Statistical Manual of Mental Disorders or equivalent criteria for both attention deficit hyperactivity disorder and stimulant use disorder. RESULTS: Eight trials were identified for inclusion in this review. Four of eight studies showed improvement in attention deficit hyperactivity disorder outcome measures compared with placebo. Two of six studies that reported substance use outcomes showed improvement in treatment arms compared with placebo. Studies to show effect tended to be those with the highest treatment dosage. CONCLUSION: Evidence for the efficacy of treatment of patients with comorbid stimulant use disorder and attention deficit hyperactivity disorder is limited. Promising outcomes need replication in further studies utilising higher treatment dosage.