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INTRODUCTION: The administration of illicit drugs by injection is associated with considerable harm, including an increased risk of overdose. The chemical analysis of used syringes can enhance knowledge on injecting drug consumption beyond traditional data sources (self-report surveys). This additional information may be useful during significant global events like the COVID-19 pandemic. This study aimed to examine a snapshot of the drugs injected at the Medically Supervised Injecting Centre (MSIC) in Sydney, Australia, in 2019-2020. METHODS: Used syringes were collected from MSIC across three periods throughout 2019 and 2020 (February 2019, March-April 2020 and June-September 2020). Drug residues were extracted from used syringes using methanol before detection by gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. The chemical analysis results were compared to self-report data obtained from MSIC clients. RESULTS: Heroin (46-53%), methamphetamine (24-34%) and pharmaceutical opioids (15-27%) were the most common drug residues detected. The chemically detected drugs had declining coherence with the drugs self-reported by MSIC clients across the time periods examined. DISCUSSION AND CONCLUSIONS: There was no significant change in the drugs injected (heroin, methamphetamine and pharmaceutical opioids) across the three periods collected throughout varying COVID-19 lockdown restrictions. Changes in the frequency of other drugs injected and discrepancies between chemical analysis and self-report were potentially related to regulatory changes, degradation or misinformed sales. Routine chemical analysis of used syringes has provided an alternative information source to promote awareness of current drug trends and aid harm reduction.

BACKGROUND: Australia is yet to see widespread fentanyl-contaminated heroin, despite the established presence of fentanyl in other countries. International mortality trends alongside a local cluster of fentanyl-related deaths prompted interest in developing methods to monitor for fentanyl and other potentially harmful novel psychoactive substances (NPS) in Australia. METHODS: We tested novel methods to monitor for fentanyl and other NPS. From 2017-2021, clients from supervised injecting facilities (SIFs) in Melbourne and Sydney, Australia, contributed urine screens (UDS) with BTNX Rapid Response™ fentanyl test strips (FTS) paired with surveys, and injecting equipment associated with opioid overdoses for laboratory analysis. A single site piloted drug checking using FTS with laboratory confirmation. Two workshops were conducted with SIF staff, content experts and people with lived experience to determine how results can inform practices within SIFs. RESULTS: Of the 911 UDS with FTS conducted, less than 1% (n=8) yielded positive results that were not explained by self-reported pharmaceutical fentanyl use, with two laboratory confirmed fentanyl positive results. Injecting equipment from 59 overdoses was tested and neither fentanyl nor other NPS were identified. Drug checking with FTS (n=34) indicated the presence of fentanyl on three tests. Two specimens were subsequently sent for laboratory testing and classified as false positives as the presence of fentanyl was not confirmed. Workshop participants (n=21) felt routine monitoring with FTS currently had limited value. A process for using pre-defined signals to trigger surveillance was developed. CONCLUSION: The high false positive rates with FTS, relative to the small number of positive results and potential for them to undermine confidence in FTS emphasised the need for confirmatory testing. The role of routine surveillance was unclear within the current low-fentanyl context, however, a process was developed to upscal

BACKGROUND AND AIM: The current phase of the North American 'opioid crisis' is characterised by illicit fentanyl use; however, the presence of illicit fentanyl in Australia is unknown. This study aimed to monitor unintentional fentanyl consumption in Australia. DESIGN: Rapid Urine Drug Screens (UDS) paired with surveys conducted within Supervised Injecting Facilities (SIFs), and confirmatory laboratory testing. SETTING: Sydney and Melbourne, Australia PARTICIPANTS: Clients who used heroin within the past 2 days (n=911 tests, 2017-2021). Participants were demographically similar to the overall client base (median age 43, 72% male). MEASUREMENTS: UDS were conducted using BTNX Rapid Response™ fentanyl urine strip tests with cross-reactivity to numerous fentanyl analogues. Positive urine samples were analysed using liquid chromatography coupled with tandem mass spectrometry. Surveys covered past 3 day drug use and lifetime report of fentanyl in heroin. FINDINGS: Two percent of participants reported intentional use of fentanyl, mostly through fentanyl patches. Of the 911 rapid UDS conducted, 17 (1.9%) yielded positive results. Eight of these (all from Melbourne) were not explained by survey-reported fentanyl use in the past 3 days. Of these 8 unexplained positives, confirmatory laboratory analysis was conducted on 6, with 4 deemed to be false positives, and 2 confirmed for the presence of fentanyl. This represents the first confirmation of unintended use of fentanyl type substances in this population. CONCLUSION: There is limited evidence of unintentional fentanyl use among people in Sydney and Melbourne, Australia who regularly inject heroin, suggesting that, currently, there is very little illicit fentanyl in Australian drug markets accessed by Supervised Injecting Facilities attendees. This study demonstrates the feasibility of quick onsite testing to cost-effectively screen large samples for fentanyl; however, the high false positive rate emphasises the need for conf

INTRODUCTION: Sciatica is a lower spine condition characterised by radiating leg pain below the knee. It may be accompanied by motor and sensory loss in the distribution of a spinal nerve. There are few effective treatments for sciatica. Orally administered glucocorticoids have shown some promise, however, any beneficial effects need to be confirmed and weighed against drug safety and cost-effectiveness, in a high-quality, definitive trial. METHODS AND ANALYSIS: The Oral Steroids In Sciatica (OASIS) trial is a randomised, placebo-controlled, double-blind trial that will evaluate a tapering regimen of oral prednisolone in 200 participants with acute sciatica. Participants will be recruited on presentation to general practice, specialist outpatient clinics or hospital emergency departments and randomised to receive orally administered prednisolone 50 mg per day, up to 3 days then tapering to cessation over 10 days, or placebo, for a maximum of 13 days, in addition to guideline advice. Participants will be followed for 1 year. The primary endpoint will be leg pain intensity at 2 weeks. Secondary outcomes will include back pain intensity, disability, time to recovery, quality of life and treatment success rate. Adverse events will be assessed and a cost-effectiveness analysis will be conducted. ETHICS AND DISSEMINATION: Ethical approval has been granted from the Human Research Ethics Committee, The University of Sydney. Trial results will be disseminated by publications and conference presentations and via the media. TRIAL REGISTRATION NUMBER: ACTRN12619001716156.

The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network was formed to build capacity and infrastructure for high-quality musculoskeletal clinical trials in our region. The purpose of this paper is to describe the steps taken in its formation to help others interested in establishing similar networks. In particular, we describe the steps taken to form the collaboration and our progress in achieving our vision and mission. Our aim is to focus on trials of highest importance and quality to provide definitive answers to the most pressing questions in our field.

Providing information about substances injected can reduce the negative impact of illicit drug consumption and support people who inject drugs to make informed decisions. In Australia, information about drugs injected relies largely on periodic self-report surveys. For the first time, the analysis of the residual content of used injecting equipment was conducted in a supervised injecting facility (SIF) located in Sydney, Australia. The aim was to gain a better understanding of the substances injected by clients through: (1) chemical analyses of the content of used syringes; (2) comparison of these results with clients' self-reported drug use; and (3) assessing the usefulness of analysing other injecting equipment to detect substances used. During one week in February 2019, syringes and other injecting equipment were collected at the Sydney SIF. Their residual content was analysed by gas-chromatography/mass-spectrometry. Heroin was the most commonly detected substance (present in 51% of syringes), followed by methamphetamine (22%) and oxycodone (10%). In addition to the main psychoactive substance, cutting agents reported in the literature were also detected in used syringes. The main psychoactive substance identified by laboratory analysis reliably corresponded with users' self-reported drug type. Analytical confirmation of substances injected allows for the provision of better targeted harm reduction messaging based on timely and objective data. The approach used is amenable to clients and feasible in the Australian SIF context. Upscaling and wider implementation could be done through Needle and Syringe Programs, and would support the early detection of harmful substances entering drug markets and better inform harm reduction strategies.

© Author(s) (or their employer(s)) 2019. Introduction: Central lumbar spinal stenosis (LSS) is a common cause of pain, reduced function and quality of life in older adults. Current management of LSS includes surgery to decompress the spinal canal and alleviate symptoms. However, evidence supporting surgical decompression derives from unblinded randomised trials with high cross-over rates or cohort studies showing modest benefits. This protocol describes the design of the SUrgery for Spinal Stenosis (SUcceSS) trial-the first randomised placebo-controlled trial of decompressive surgery for symptomatic LSS. Methods and analysis: SUcceSS will be a prospectively registered, randomised placebo-controlled trial of decompressive spinal surgery. 160 eligible participants (80 participants/group) with symptomatic LSS will be randomised to either surgical spinal decompression or placebo surgical intervention. The placebo surgical intervention is identical to surgical decompression in all other ways with the exception of the removal of any bone or ligament. All participants and assessors will be blinded to treatment allocation. Outcomes will be assessed at baseline and at 3, 6, 12 and 24 months. The coprimary outcomes will be function measured with the Oswestry Disability Index and the proportion of participants who have meaningfully improved their walking capacity at 3 months postrandomisation. Secondary outcomes include back pain intensity, lower limb pain intensity, disability, quality of life, anxiety and depression, neurogenic claudication score, perceived recovery, treatment satisfaction, adverse events, reoperation rate and rehospitalisation rate. Those who decline to be randomised will be invited to participate in a parallel observational cohort. Data analysis will be blinded and by intention to treat. A trial-based cost-effectiveness analysis will determine the potential incremental cost per quality-adjusted life year gained. Ethics and dissemination: Ethics approval ha

© Australian Council for Educational Research 2019. Self-regulation and executive functioning impairments are common in children with fetal alcohol spectrum disorder. Given the high rates of fetal alcohol spectrum disorder identified amongst children living in the remote Fitzroy Valley region of Western Australia, the Alert Program® was identified as a culturally safe intervention for use in local primary schools. Researchers collaborated with Aboriginal Elders, community members, and staff from a Fitzroy Valley primary school to trial the Alert Program®. Teachers were trained to deliver eight Alert Program® lessons to children in class. Self-regulation and executive functioning were measured using teacher and parent/caregiver questionnaires three times. Data were analyzed using repeated-measures ANOVA. Teacher-led delivery of the Alert Program® was feasible in a region with high fetal alcohol spectrum disorder rates. As measured by teacher and parent/caregiver ratings, this curriculum may improve the self-regulation and executive functioning of children for some outcomes and provide sustained effects for some children. This community partnered pilot research, evaluated a school-based program to reduce the behavioral impact of fetal alcohol spectrum disorder, and informed design of a larger trial across eight Aboriginal community schools.

[This corrects the article DOI: 10.1371/journal.pone.0192783.].

Background & aims Prophylactic injections of factor VIII reduce the incidence of bleeds and slow the development of joint damage in people with hemophilia. The aim of this study was to identify optimal person-specific prophylaxis regimens for children with hemophilia A. Methods Analytic and numerical methods were used to identify prophylaxis regimens which maximize the time for which plasma factor VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII concentrations, and minimize risk of bleeds. Results It was demonstrated analytically that, for any injection schedule, the regimen that maximizes the lowest factor VIII concentration involves sharing doses between injections so that all of the trough concentrations in a prophylaxis cycle are equal. Numerical methods were used to identify optimal prophylaxis schedules and explore the trade-offs between efficacy and acceptability of different prophylaxis regimens. The prophylaxis regimen which minimizes risk of bleeds depends on the person’s pattern of physical activity and may differ greatly from prophylaxis regimens that optimize pharmacokinetic parameters. Prophylaxis regimens which minimize risk of bleeds also differ from prophylaxis regimens that are typically prescribed. Predictions about which regimen is optimal are sensitive to estimates of the effects on risk of bleeds of factor VIII concentration and physical activity. Conclusion The methods described here can be used to identify optimal, person-specific prophylaxis regimens for children with hemophilia A.

Introduction and Aims: North America has witnessed a dramatic rise in fatal opioid overdoses due to the unwitting consumption of non-pharmaceutical fentanyl and its analogues. While some of the drivers of this crisis—including profitability and access to high-potency opioids through internet sources—also apply in Australia, to our knowledge, there have been no ongoing surveillance studies of local populations. Therefore, this pilot study aimed to detect unintentional fentanyl consumption among people who inject heroin through instant urine screening, and determine the feasibility and acceptability of voluntary urinalysis of clients at the Medically Supervised Injecting Centre, Kings Cross, Sydney. Design and Methods: Brief surveys and urine drug screens were conducted with 67 participants in Wave 1 (October 2017) and 51 participants in Wave 2 (March 2018). Urine samples were tested with BTNX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/mL norfentanyl. These strips also cross-react to numerous fentanyl analogues. Results: There were no cases where positive urine tests suggested unwitting fentanyl use detected in this study. Discussion and Conclusions: These negative findings contrast sharply with similar Canadian studies. While no cases of fentanyl-laced heroin use have been detected so far, we have demonstrated that this surveillance design is low-cost, feasible and scalable approach to monitoring the considerable public-health threat of undetected fentanyl and its analogues in Australia. Further validation of cross-reactivity of test strips would strengthen this method.