A risk-based approach to community illicit drug toxicosurveillance: operationalisation of the Emerging Drugs Network of Australia - Victoria (EDNAV) project.

INTRODUCTION: The Emerging Drugs Network of Australia - Victoria (EDNAV) project is a newly established toxicosurveillance network that collates clinical and toxicological data from patients presenting to emergency departments with illicit drug related toxicity in a centralised clinical registry. Data are obtained from a network of sixteen public hospital emergency departments across Victoria, Australia (13 metropolitan and three regional). Comprehensive toxicological analysis of a purposive sample of 22 patients is conducted each week, with reporting of results to key alcohol and other drug stakeholders. This paper describes the overarching framework and risk-based approach developed within Victoria to assess drug intelligence from EDNAV toxicosurveillance. METHODS: Risk management principles from other spheres of public health surveillance and healthcare clinical governance have been adapted to the EDNAV framework with the aim of facilitating a consistent and evidence-based approach to assessing weekly drug intelligence. The EDNAV Risk Register was reviewed over the first two years of EDNAV project operation (September 2020 - August 2022), with examples of eight risk assessments detailed to demonstrate the process from signal detection to public health intervention. RESULTS: A total of 1112 patient presentations were documented in the EDNAV Clinical Registry, with 95 signals of concern entered into the EDNAV Risk Register over the two-year study period. The eight examples examined in further detail included suspected drug adulteration (novel opioid adulterated heroin, para-methoxymethamphetamine adulterated 3,4-methylenedioxymethamphetamine (MDMA)), drug substitution (25B-NBOH sold as lysergic acid diethylamide, five benzodiazepine-type new psychoactive substances in a single tablet, protonitazene sold as ketamine), new drug detection (N,N-dimethylpentylone), contamination (unreported acetylfentanyl) and a fatality subsequent to MDMA use. A total of four public Drug Alerts were issued over this period. CONCLUSIONS: Continued toxicosurveillance efforts are paramount to characterising the changing landscape of illicit drug use. This work demonstrates a functional model for risk assessment of illicit drug toxicosurveillance, underpinned by analytical confirmation and evidence-based decision-making.

Characteristics and time course of benzodiazepine-type new psychoactive substance detections in Australia: results from the Emerging Drugs Network of Australia - Victoria project 2020-2022.

INTRODUCTION: The emergence of benzodiazepine-type new psychoactive substances (NPSs) are a growing international public health concern, with increasing detections in drug seizures and clinical and coronial casework. This study describes the patterns and nature of benzodiazepine-type NPS detections extracted from the Emerging Drugs Network of Australia - Victoria (EDNAV) project, to better characterise benzodiazepine-type NPS exposures within an Australian context. METHODS: EDNAV is a state-wide illicit drug toxicosurveillance project collecting data from patients presenting to an emergency department with illicit drug-related toxicity. Patient blood samples were screened for illicit, pharmaceutical and NPSs utilising liquid chromatography-tandem mass spectrometry. Demographic, clinical, and analytical data was extracted from the centralised registry for cases with an analytical confirmation of a benzodiazepine-type NPS(s) between September 2020-August 2022. RESULTS: A benzodiazepine-type NPS was detected in 16.5 % of the EDNAV cohort (n = 183/1112). Benzodiazepine-type NPS positive patients were predominately male (69.4 %, n = 127), with a median age of 24 (range 16-68) years. Twelve different benzodiazepine-type NPSs were detected over the two-year period, most commonly clonazolam (n = 82, 44.8 %), etizolam (n = 62, 33.9 %), clobromazolam (n = 43, 23.5 %), flualprazolam (n = 42, 23.0 %), and phenazepam (n = 31, 16.9 %). Two or more benzodiazepine-type NPSs were detected in 47.0 % of benzodiazepine-type NPS positive patients. No patient referenced the use of a benzodiazepine-type NPS by name or reported the possibility of heterogenous product content. CONCLUSION: Non-prescription benzodiazepine use may be an emerging concern in Australia, particularly amongst young males. The large variety of benzodiazepine-type NPS combinations suggest that consumers may not be aware of product heterogeneity upon purchase or use. Continued monitoring efforts are paramount to inform harm reduction opportunities.

Non-fatal intoxications involving the novel benzodiazepine clonazolam: case series from the Emerging Drugs Network of Australia - Victoria project.

INTRODUCTION: Clonazolam is an unregistered novel benzodiazepine which emerged in global illicit drug markets in 2014. We describe the clinical features of four cases of non-fatal clonazolam mono-intoxications from patients presenting to emergency departments in Australia. CASES: Four patients aged between 16 and 19 years presented to hospital with a sedative toxidrome (Glasgow Coma Scale range 8-13) and elevated heart rate (median heart rate 100 beats per minute, range 92-105) following reported benzodiazepine exposure. Three patients reported the use of a large quantity (7-20 tablets) of Xanax®, a brand of alprazolam not commercially available in Australia. Two patients required nasopharyngeal airway insertion following the development of airway obstruction. The median time to return of a normal conscious state (Glasgow Coma Scale 15) was 23 h (range 5-30 h). Clonazolam (range 0.2-2.1 µg/L) and its main metabolite 8-aminoclonazolam (range 5.9-19.1 µg/L) were the only substances detected by liquid chromatography-tandem mass spectrometry in blood samples of all patients. CONCLUSION: Clonazolam intoxication resulted in sedation with mild sinus tachycardia. Three patients who reported multiple tablet exposures experienced prolonged sedation, and two of these patients developed airway obstruction. In this series, clonazolam was unknowingly ingested through possible illicit substitution within an unregulated counterfeit benzodiazepine product.

A comparison of the accuracy of mushroom identification applications using digital photographs.

OBJECTIVE: To compare the accuracy of three popular mushroom identification software applications in identifying mushrooms involved in exposures reported to the Victorian Poisons Information Centre and Royal Botanic Gardens Victoria. BACKGROUND: Over the past 10 years, an increasing number of software applications have been developed for use on smart phones and tablet devices to identify mushrooms. We have observed an increase in poisonings after incorrect identification of poisonous species as edible, using these applications. DESIGN: We compared the accuracy of three iPhone™ and Android™ mushroom identification applications: Picture Mushroom (Next Vision Limited©), Mushroom Identificator (Pierre Semedard©), and iNaturalist (iNaturalist, California Academy of Sciences©). Each app was tested independently by three researchers using digital photographs of 78 specimens sent to the Victorian Poisons Information Centre and Royal Botanic Gardens Victoria over a two-year period, 2020-2021. Mushroom identification was confirmed by an expert mycologist. For each app, individual and combined results were compared. RESULTS: Picture Mushroom was the most accurate of the three apps and correctly identified 49% (95% CI [0-100]) of specimens, compared with Mushroom Identificator (35% [15-56]) and iNaturalist (35% [0-76]). Picture Mushroom correctly identified 44% of poisonous mushrooms [0-95], compared with Mushroom Identificator (30% [1-58]) and iNaturalist (40% [0-84), but Mushroom Identificator identified more specimens of Amanita phalloides correctly (67%), compared to Picture Mushroom (60%) and iNaturalist (27%). Amanita phalloides was falsely identified, twice by Picture Mushroom and once by iNaturalist. CONCLUSIONS: Mushroom identification applications may be useful future tools to assist clinical toxicologists and the general public in the accurate identification of mushrooms species but, at present, are not reliable enough to exclude exposure to potentially poisonous mushrooms when used alone.

The Emerging Drugs Network of Australia - Victoria Clinical Registry: A state-wide illicit substance surveillance and alert network.

OBJECTIVES: With an increasingly dynamic global illicit drug market, including the emergence of novel psychoactive substances, many jurisdictions have moved to establish toxicosurveillance systems to enable timely detection of harmful substances in the community. This paper describes the methodology for the Emerging Drugs Network of Australia - Victoria (EDNAV) project, a clinical registry focused on the collection of high-quality clinical and analytical data from ED presentations involving illicit drug intoxications. Drug intelligence collected from the project is utilised by local health authorities with the aim to identify patterns of drug use and emerging drugs of concern. METHODS: The project involves 10 public hospital EDs in Victoria, Australia. Patients 16 years and over, presenting to a network ED with a suspected illicit drug-related toxicity and a requirement for venepuncture are eligible for inclusion in the study under a waiver of consent. Clinical and demographic parameters are documented by site-based clinicians and comprehensive toxicological analysis is conducted on patient blood samples via specialised forensic services. All data are then deidentified and compiled in a project specific database. RESULTS: Cases are discussed in weekly multidisciplinary team meetings, with a view to identify potentially harmful substances circulating in the community. High-risk signals are escalated to key stakeholders to produce timely and proportionate public health alerts with a focus on harm minimisation. CONCLUSIONS: The EDNAV project represents the first centralised system providing near real-time monitoring of community drug use in Victoria and is fundamental in facilitating evidence-based public health intervention.

From signal to alert: A cluster of exposures to counterfeit alprazolam tablets containing five novel benzodiazepines.

OBJECTIVE: To illustrate the toxicosurveillance role of the Emerging Drugs Network of Australia - Victoria (EDNAV) project in informing timely harm minimisation interventions. METHODS: Utilisation of an ethics approved clinical registry storing de-identified clinical and analytical data on Victorian ED illicit drug-related presentations. RESULTS: In April 2022, six adults presented to hospital with varying levels of sedation, following the use of counterfeit benzodiazepines. Comprehensive toxicological analysis identified five separate novel benzodiazepines within blood samples from each patient. A public 'Drug Alert' was subsequently issued, and local emergency physicians were notified. CONCLUSION: Toxicosurveillance projects, such as EDNAV, are critical to the continued monitoring and reporting of illicit substance use in the community.

A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department.

OBJECTIVE: To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED). BACKGROUND: Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared. DESIGN: We performed a prospective, randomized, double-blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18-65 years, who presented with migraine, were eligible for recruitment. Sixty-six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post-commencement of the study medicine infusion. RESULTS: Sixty-five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0-4.0) in the chlorpromazine arm versus 2.0 (1.0-4.0) in the prochlorperazine arm (median difference -0.5 (95% confidence interval, -1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277). CONCLUSIONS: Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.