Analytically confirmed illicit and novel psychoactive drug use in Western Australian emergency departments: initial results from the Emerging Drugs Network of Australia (EDNA).

INTRODUCTION: The burden of acute illicit drug use in Australia is largely unknown. Establishing a prospective drug surveillance system in emergency departments using analytical confirmation may facilitate the early identification of emerging drugs. We describe demographic data and acute toxicity patterns, stratified by analytical confirmation of illicit drugs and novel psychoactive substances, to emergency departments in Western Australia. METHODS: Patients presenting with severe and/or unusual clinical features consistent with recreational drug toxicity were identified across five Western Australian emergency departments participating in the Emerging Drugs Network of Australia between April 2020 and December 2021. Demographic and toxicology patterns in patients with and without analytically confirmed illicit drugs/novel psychoactive substances from blood samples were collected during the emergency department presentation. RESULTS: The cohort included 434 severe and/or unusual toxicology presentations; median age 33 years (first and third quartiles 25-40 years), 268 (61.8%) males. Any substance (illicit, novel psychoactive substance, pharmaceutical) was detected in 405 (93.3%) presentations. Illicit drugs/novel psychoactive substances were detected in 257 (59.2%) presentations, including 73 (28.3%) with more than one confirmed illicit drug/novel psychoactive substance. Frequent illicit drugs identified were metamfetamine (n = 201, 77.9%) and gamma-hydroxybutyrate (n = 30, 11.6%). Forty-eight novel psychoactive substances were detected within 43 (16.7%) presentations. Novel benzodiazepines were most frequently detected (n = 29, 60.4%). Frequent pharmaceuticals detected included diazepam (n = 100, 26.1%) and clonazepam (n = 40, 10.4%). One hundred and fifty-five (35.7%) presentations were discharged home and 56 (12.9%) were admitted to intensive care. Presentations with detected illicit drugs/novel psychoactive substances had a lower median intensive care length of stay compared to presentations without detected illicit drugs/novel psychoactive substances (32.6 h versus 50.8 h respectively, P < 0.001). CONCLUSIONS: Integration of clinical and analytic data in patients with severe and/or unusual toxicology presentations via the Emerging Drugs Network of Australia provides insight into illicit drug/novel psychoactive substance use responsible for acute harm across Western Australian emergency departments.

Illicit drugs in the emergency department: Can we determine on clinical grounds if patients are intoxicated? Results from the Western Australian Illicit Substance Evaluation (WISE) study.

INTRODUCTION: Presentations related to illicit drugs are a feature of emergency department practice. Clinicians may form a belief that a patient is intoxicated with illicit drugs based on patient self-report, clinical features on presentation and the local prevalence of illicit drug use. But evidence of the accuracy of this assessment is lacking. The Western Australian Illicit Substance Evaluation (WISE) study enrolled patients believed by their treating clinician to be intoxicated with illicit drugs, and this analysis aims to evaluate the validity of this belief. METHODS: A blood sample was taken on patient arrival and details of patient history, examination and interventions were collected by clinical and research staff. Toxicological examination of biological samples used liquid chromatography-mass spectrometry techniques including Quadrupole Time of Flight screening and Triple Quadrupole targeted analyses. RESULTS: Of 632 study presentations, 518 had illicit drugs detected representing a positive predictive value of 0.82 (95% confidence interval 78.7, 84.9). Those with illicit drugs detected were significantly less likely to arrive by police transport (p = 0.010) or to have used alcohol (p < 0.001). They were significantly more likely to report illicit drug use (p < 0.001) and a much smaller proportion were admitted to a psychiatric ward (3.5% vs. 19.3%, p < 0.0001). Heart rate and systolic blood pressure were significantly higher in the illicit drug group (p = 0.004 and p = 0.003). DISCUSSION AND CONCLUSIONS: In this study, the positive predictive value of clinicians determining if their patient had taken illicit drugs was 0.82. Contemporaneous biochemical analysis in the clinical setting would increase this accuracy and inform patient care.

The Emerging Drugs Network of Australia: A toxicosurveillance system of illicit and emerging drugs in the emergency department.

OBJECTIVE: The unprecedented rise in synthetic drugs, many containing unknown toxic agents, has made timely analytical diagnosis more difficult, and has reduced the confidence of clinicians providing ED management to this population of patients. This has also impacted the quality of evidence informing harm reduction responses. The Emerging Drugs Network of Australia (EDNA) brings together emergency physicians, toxicologists and forensic laboratories to establish a standardised ED toxicosurveillance system in Australia. METHODS: Blood analysis of intoxicated patients will be conducted by forensic laboratories to enable precise identification of the substances causing acute toxicity. This will be linked with clinical data collected at the time of ED presentation to enable analysis of the clinical effects and outcomes associated with different illicit and emerging drugs. Toxicological and clinical data collected across sentinel sites will align with a nationally endorsed minimum dataset. RESULTS: EDNA's collaborative network will establish a national system of surveillance and reporting of illicit and emerging drugs causing acute toxicity. Standardisation of data collection recorded in a national clinical registry will provide more robust data on epidemiology and associated harms. This will facilitate the translation of clinical and toxicological evidence into timely, appropriate harm reduction and policy. CONCLUSION: Our work represents a collaborative response to calls for more sophisticated data on emerging drug trends in Australia. EDNA will improve coordination between clinicians and analytical services by way of its standardised approach to surveillance and reporting.

An early warning system for emerging drugs of concern in the emergency department: Protocol for the Western Australian Illicit Substance Evaluation (WISE) study.

OBJECTIVE: An ever-increasing number of novel psychoactive substances are being detected worldwide. These emerging drugs have been demonstrated to cause toxicity in clusters, and deaths have been reported. We urgently need to learn more about their effects. We report the protocol for the Western Australian Illicit Substance Evaluation (WISE) study, a research project investigating illicit drug use in the ED. METHODS: Patients can be enrolled if the treating clinician strongly suspects they are currently intoxicated with a stimulant, hallucinogenic or cannabinoid drug; and an i.v. cannula or blood tests are required for routine clinical care. Patients are enrolled under a waiver of consent. A single additional blood tube is collected, de-identified and frozen on site. A temporary link between patient identification number and study identification number is retained for up to 10 business days post-hospital discharge to allow for clinical data collection, before this is destroyed and the patients become permanently de-identified. Samples are transported for external liquid chromatography-mass spectrometry analysis in batches once de-identified. RESULTS: The key outcome will be identification of any psychoactive drugs present in the blood sample, together with their respective concentration. This will be linked to the clinical effects, as well as being compared with the substance the patient believed they had taken. CONCLUSION: We consider the novel approach outlined forms a template for an early warning system for emerging drugs of concern, while also providing vital and comprehensive information on current drugs of abuse, their clinical effects and their impact on the health system.

ß-Methylphenylethylamines: common fragmentation pathways with amphetamines in electrospray ionization collision-induced dissociation.

ß-Methylphenylethylamines are positional isomers of amphetamines and have been discovered in sporting supplements. Although the fragmentation of the ß-methylphenylethylamine and N-methyl-ß-methylphenylethylamine in gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) systems is significantly different to their amphetamine and methylamphetamine isomers, under electrospray ionization commonly used in liquid chromatography-mass spectrometry (LC-MS) systems, the fragmentation of each of the isomeric pairs is almost identical. The similarities in fragmentation make it possible for the misidentification of the ß-methylphenylethylamines as the illicit amphetamines. It is proposed that the similarities are due to a fragmentation pathway involving a common phenonium ion intermediate. By careful control of fragmentation energies in liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems and/or close examination of the relative abundances of product ions formed by collision-induced dissociation (qualifier ratios), it is possible to distinguish the ß-methylphenylethylamines from the amphetamines, even if significant retention time separation is not achieved. In liquid chromatography-electrospray ionization-quadrupole time of flight (LC-ESI-QTOF) systems the mass spectra of the ß-methylphenylethylamines are identical to their amphetamine isomers. In such systems, retention time separation of the isomers is critical to avoid misidentification. During this study ß-methylphenylethylamine and N-methyl-ß-methylphenylethylamine have been identified in commercially available sporting supplements and oral fluid samples taken during the course of road-side drugs-in-drivers and workplace testing programmes. Copyright © 2015 John Wiley & Sons, Ltd.

Syntheses in enantiopure form of four diastereoisomeric naphthopyranquinones derived from aphid insect pigments.

The first syntheses are described of the four enantiopure naphthopyranquinones (1R,3R,4S)- and (1R,3R,4R)-3,4-dihydro-4,7,9-trihydroxy-1,3-dimethylnaphtho[2,3-c]pyranquinone (quinone A 1 and quinone A' 2) and their two C-3 epimers, the (1R,3S,4S)- and (1R,3S,4R)-diastereoisomers 5 and 6, using enantiopure lactate as the source of asymmetry. Key factors in these syntheses are the maintenance of stereochemical integrity throughout the sequences and intramolecular diastereoselective cyclisations of the titanium phenolates of phenolic lactaldehydes. For these cyclisations the differing degree of diastereoselectivity is explained as are the stereochemistries of the product 2-benzopyran-4,5-diols.