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N-acetyl cysteine for the treatment of alcohol use disorder: study protocol for a multi-site, double-blind randomised controlled trial (NAC-AUD study)

Por: Morley · K. · Arunogiri · S. · Connor · J. P. · Clark · P. J. · Chatterton · M. L. · Baillie · A. · Slade · T. · Berk · M. · Lubman · D. · Haber · P. S.
Introduction

Current treatments for alcohol use disorders (AUD) have limited efficacy. A previous 28-day pilot trial of N-acetyl cysteine (NAC) vs placebo found NAC to be feasible and safe, with evidence of improvement on some measures of alcohol consumption. Thus, the primary aim of the NAC-AUD study is to examine the therapeutic and cost-effectiveness of NAC vs placebo in improving treatment outcomes for AUD. We will also examine the (i) effect of NAC vs placebo on mood, markers of liver injury, cognition and hangover symptoms; and (ii) predictors of any response.

Methods and analysis

This double-blind trial will randomise participants with AUD to a 12-week regimen of either NAC (2400 mg/day) or placebo. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol (PEth). Secondary alcohol-related outcomes will include standard drinks per drinking day (SDDD) per week and absence of any HDDs. Other secondary outcomes will include markers of liver injury, depression, anxiety, craving, hangover symptoms, cognition and blood oxidative stress markers. We will also examine the cost-efficacy of NAC vs placebo.

Ethics and dissemination

Ethics approval for the study has been granted by The Sydney Local Health District Ethics Review Committee (X21-0342& HREC2021/ETH11614). There are no restrictions on publication from the sponsor or other parties.

Trial registration number

NCT05408247.

Interpractice variability in antibiotic prescribing for acute respiratory tract infections: a cross-sectional study of Australian early-career general practitioners

Por: Turner · A. · van Driel · M. L. · Mitchell · B. · Holliday · E. · Davis · J. · Tapley · A. · Davey · A. · Ralston · A. · Dizon · J. · Baillie · E. · Fielding · A. · Mulquiney · K. · Clarke · L. · Spike · N. · Magin · P.
Objectives

Frequency of general practitioners’ (GPs’) antibiotic prescribing for acute, self-limiting respiratory tract infections (aRTIs) is high. The practice environment and culture influence the clinical behaviour, including prescribing behaviour, of GP specialist vocational trainees (registrars). We aimed to assess inter-practice variability in registrars’ antibiotic prescribing.

Design

This was a cross-sectional analysis from the Registrar Clinical Encounters in Training (ReCEnT) cohort study, from 2010 to 2020.

Setting

ReCEnT documents registrars’ clinical experiences and behaviours. Before 2016, 5 of 17 Australian training regions participated in ReCEnT. From 2016, three of nine regions (~40% of Australian registrars) participated.

Participants

3210 registrars (response rate 91.8%) from 1286 training practices contributed to the analysis.

Outcome measures

The outcomes were prescription of an antibiotic for new diagnoses of (1) all aRTIs and (2) acute bronchitis diagnoses specifically. Prescribing percentages were calculated at the training practice level. Intraclass correlation coefficients (ICCs) were used to measure the ratio of interpractice variation to total variance. Median ORs (MORs) were also estimated to quantify interpractice variability.

Results

Practice-level antibiotic prescribing percentages ranged from 0% to 100% for both aRTIs and acute bronchitis diagnoses in the primary analysis. ICCs for aRTI prescribing were 0.08 (unadjusted) and 0.02 (adjusted). For acute bronchitis, ICCs were 0.10 (unadjusted) and 0.05 (adjusted). MORs were 1.66 (unadjusted) and 1.32 (adjusted) for aRTIs. MORs for acute bronchitis were 1.80 (unadjusted) and 1.53 (adjusted). This indicates a marked variation in the odds of a patient receiving antibiotics for an aRTI if randomly attending different practices.

Conclusions

There was considerable interpractice variation in registrars’ antibiotic prescribing frequencies. Further research is required to examine the factors accounting for this variation and to develop practice-level interventions to reduce antibiotic prescribing in high-prescribing practices.

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