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BACKGROUND: Co-use of stimulants and opioids is often deliberate. However, the possibility remains that some people are unintentionally consuming fentanyl. To advance understanding of overdose risk, we examined the rate of concordance between self-reported fentanyl use and corresponding urine toxicology screen results. METHODS: Between August 2022-August 2023, 411 participants (adults who reported any non-medical drug use in the past three months) in Nevada and New Mexico completed a cross-sectional survey, of whom 64% (n = 270; the analytical sample) also completed a urine toxicology screen, which detects fentanyl use in the past three days. Positive predictive value, negative predictive value, sensitivity, and specificity were calculated using self-reported past three-day fentanyl use (yes/no) and urine toxicology screen results for the presence of fentanyl (positive/negative). RESULTS: Of the 270 participants who provided a urine sample, 268 are included in the descriptive statistics (two with inconclusive urine toxicology screen results were excluded). Of the 268 participants, 146 (54.5%) had a fentanyl-positive urine toxicology screen result, 122 (45.5%) had a fentanyl-negative urine toxicology screen result, 137 (51.1%) reported past three-day fentanyl use, and 130 (48.5%) reported no past three-day fentanyl use. Only 6.9% of those with a fentanyl-positive urine toxicology screen did not report recent fentanyl use. The sensitivity of self-reported fentanyl use was 93%, specificity was 97%, positive predictive value was 97%, and negative predictive value was 92%. DISCUSSION: The rate of unanticipated exposure to fentanyl (that is, positive urine screen and negative self-report) in this sample was low, at 6.9%. This runs counter to the national narrative that there is widespread unknown contamination of fentanyl in the drug supply. CONCLUSION: Future research is needed to further explore how people who use multiple substances interpret their overdose risk and what harm reduction methods they employ.

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INTRODUCTION: Acute metamfetamine toxicity is characterized by stimulant effects and neuropsychiatric disturbance, which is attenuated by gamma-aminobutyric acid type A receptor agonists including benzodiazepines. We utilized clinical registry data to examine the effect of co-exposure to a gamma-aminobutyric acid type B receptor agonist (gamma-hydroxybutyrate) in illicit drug cases with analytically confirmed exposure to metamfetamine. METHODS: The Emerging Drugs Network of Australia Victoria is an ethics board-approved prospective registry collecting clinical and analytical data (utilising blood samples) on emergency department illicit drug presentations. Comparison groups were defined by analytically confirmed exposure: lone metamfetamine, metamfetamine plus gamma-hydroxybutyrate, metamfetamine plus benzodiazepine, metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine. Cases with co-exposure to other stimulants or sedatives were excluded. RESULTS: Median metamfetamine blood concentrations were significantly greater in metamfetamine plus gamma-hydroxybutyrate (n = 153, median = 0.20 mg/L, interquartile range: 0.10-0.32 mg/L, 95 per cent confidence interval: 0.20-0.23 mg/L) and metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine (n = 160, median = 0.20 mg/L, interquartile range: 0.10-0.30 mg/L, 95 per cent confidence interval: 0.20-0.30 mg/L) positive groups compared to gamma-hydroxybutyrate negative groups including metamfetamine (n = 81, median = 0.10 mg/L, interquartile range: 0.05-0.21 mg/L, 95 per cent confidence interval: 0.09-0.18 mg/L) and metamfetamine plus benzodiazepine (n = 73, median = 0.10 mg/L, interquartile range: 0.06-0.20 mg/L, 95 per cent confidence interval: 0.09-0.20 mg/L) groups (P < 0.0004). Presenting heart rate in metamfetamine plus gamma-hydroxybutyrate cases (n = 153, median = 72 beats per minute, interquartile range: 63-86 beats per minute, 95 per cent confidence interval: 70-78 beats per minute) was significantly lower than metamfetamine plus benzodiazepine cases (n = 73, median = 84 beats per minute, interquartile range: 73-98 beats per minute, 95 per cent confidence interval: 80-90 beats per minute, P < 0.0001), and lone metamfetamine cases (n = 81, median = 110 beats per minute, interquartile range: 87-131 beats per minute, 95 per cent confidence interval: 93-120 beats per minute, P < 0.0001). Presenting temperature in metamfetamine plus gamma-hydroxybutyrate cases (median = 35.8 °C, interquartile range: 35.0-36.2 °C, 95 per cent confidence interval 35.6-35.9 °C) was significantly lower than metamfetamine plus benzodiazepine cases (median 36.2 °C, interquartile range 35.7-36.6 °C, 95 per cent confidence interval, 36.0-36.4 °C, P = 0.017), and lone metamfetamine cases (median = 36.5 °C, interquartile range: 35.8-37.1 °C, 95 per cent confidence interval: 36.2-36.7 °C, P < 0.0001). Median presenting systolic blood pressure was significantly (P ≤ 0.001) lower in benzodiazepine positive groups (metamfetamine plus benzodiazepine median = 120 mmHg, interquartile range: 109-132 mmHg, 95 per cent confidence interval: 116-124 mmHg and metamfetamine plus benzodiazepine plus gamma-hydroxybutyrate median = 124 mmHg, interquartile range: 110-137 mmHg, 95 per cent confidence interval: 120-129 mmHg). Incidence of sedation (Glasgow Coma Scale less than 9) was significantly greater in metamfetamine plus gamma-hydroxybutyrate cases (63 per cent) compared to metamfetamine plus benzodiazepine cases (27 per cent, P < 0.0001) and lone metamfetamine cases (15 per cent, P < 0.0001). Incidence of agitation was significantly lower in metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine cases (17 per cent, P < 0.0001) and metamfetamine plus gamma-hydroxybutyrate cases (34 per cent, P = 0.0004) compared to lone metamfetamine cases (58 per cent). DISCUSSION: Differences in gamma-aminobutyric acid type A and B receptor physiology may offer a gamma-aminobutyric acid type B agonist-facilitated alternative pharmacodynamic mechanism able to attenuate metamfetamine stimulant and neuropsychiatric toxicity. CONCLUSION: Metamfetamine intoxicated patients with analytically confirmed co-exposure to gamma-hydroxybutyrate had significantly reduced heart rate, body temperature and incidence of agitation compared to patients with lone metamfetamine exposure. Metamfetamine intoxicated patients with analytically confirmed co-exposure to a benzodiazepine had significantly reduced systolic blood pressure compared to patients with lone metamfetamine exposure. We hypothesize that gamma-aminobutyric acid type B receptor agonists may be beneficial in the management of acute metamfetamine toxicity.

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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.

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BACKGROUND: Gamma-hydroxybutyrate is a potent central nervous system depressant with a narrow recreational dose window and analytical detection time. We describe data relating to intoxicated patients presenting to emergency departments across metropolitan Adelaide who tested positive for gamma-hydroxybutyrate. This work was part of the Emergency Department Admission Blood Psychoactive Testing study. METHODS: Over a 15-month period, patients presenting to four metropolitan emergency departments with symptoms of drug intoxication were enrolled in the study. The methodology involved the collection of demographic and clinical data and a de-identified blood sample which underwent comprehensive toxicological analysis. Gamma-hydroxybutyrate was determined using an acid-catalysed cyclisation followed by liquid-liquid extraction and gas chromatography-mass spectrometry. Data relating to samples positive for gamma-hydroxybutyrate were examined. RESULTS AND DISCUSSION: A total of 1120 patients were enrolled between March 2019 and May 2020, 309 of whom were positive for gamma-hydroxybutyrate (27.6%). Of these, 256 (83%) were also positive for metamfetamine (methamphetamine). The most common clinical observation in gamma-hydroxybutyrate-positive patients was central nervous system depression (89%). There was a significant relationship between gamma-hydroxybutyrate status and sex; although males outnumbered females in absolute terms, a higher proportion of females (32%) tested positive for gamma-hydroxybutyrate than males (25%, P = 0.0155). Blood gamma-hydroxybutyrate concentrations ranged from 10 to 651 mg/L (0.096-6.2 mmol/L) and increasing gamma-hydroxybutyrate concentration correlated with severe toxicity. The presence of gamma-hydroxybutyrate had a significant impact on the patient discharge destination: the majority (69.2%) of gamma-hydroxybutyrate-positive patients were managed and discharged from the emergency department or their attached short stay wards. A significantly higher proportion of gamma-hydroxybutyrate-positive patients were admitted to the intensive care unit (28.2%) compared with gamma-hydroxybutyrate-negative patients (12.7%, chi-squared = 36.85, P <0 .001). Gamma-hydroxybutyrate positive cases accounted for 45.8% of all study-related intensive care unit admissions. CONCLUSIONS: Gamma-hydroxybutyrate is commonly detected in illicit drug-related emergency department presentations and is detected disproportionately in the patient cohort who require intensive care unit level care.

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CONTEXT: Cocaine and metamfetamine use and overdose deaths among United States adults have been increasing in recent years. We examined associations of medical outcomes with co-used opioids and other substances among cocaine, and metamfetamine exposures in people age ≥50 years (N = 9300) reported to the National Poison Data System, 2015-2021. METHODS: We first described increases in these exposures over time. We fitted generalized linear models for a Poisson distribution with a log link, one for cocaine exposures and the other for metamfetamine exposures, to examine associations of medical outcomes (major effects/death versus all others) with co-used other substances, controlling for exposure year and demographics. RESULTS: The number of exposures increased steadily during the seven years, but metamfetamine exposures increased more rapidly starting in 2018. One-fifth of cocaine and one-sixth of metamfetamine exposures suffered major effects/death. Co-use of prescription opioids (incident risk ratio = 2.00, 95% CI = 1.76-2.28 for cocaine; incident risk ratio = 1.62, 95% CI = 1.27-2.07 for metamfetamine), illicit fentanyl (incident risk ratio =1.88, 95% CI = 1.08-3.27 for cocaine; incident risk ratio = 2.05, 95% CI = 1.04-4.06 for metamfetamine), heroin (incident risk ratio =1.62, 95% CI = 1.37-1.90 for cocaine), or amfetamine (incident risk ratio =1.73, 95% CI = 1.28-2.33 for cocaine) was associated with a higher likelihood of major effects/death. DISCUSSION: Increases in the number of cocaine and metamfetamine exposures among older adults reported to poison centers are of concern, and so is the increased risk of major effects/death from polysubstance use, especially prescription and illicit opioids, among these illicit psychostimulant users. CONCLUSIONS: Healthcare provider screening of individuals at risk of cocaine and/or metamfetamine use and psychoeducation about the dangers of these substance use are needed.

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OBJECTIVE: Metamfetamine use can cause serious complications or death. We aimed to derive and internally validate a clinical prediction score to predict major effect or death in acute metamfetamine toxicity. METHODS: We performed secondary analysis of 1,225 consecutive cases reported from all local public emergency departments to the Hong Kong Poison Information Centre between 1 January 2010 and 31 December 2019. We split the entire dataset chronologically into derivation (first 70% of cases) and validation (the remaining 30% of cases) cohorts. Univariate analysis was conducted, followed by multivariable logistic regression in the derivation cohort to identify independent predictors of major effect or death. We developed a clinical prediction score based on the regression coefficients of the independent predictors in the regression model and compared its discriminatory performance with five existing early warning scores in the validation cohort. RESULTS: The MASCOT (Male, Age, Shock, Consciousness, Oxygen, Tachycardia) score was derived based on the six independent predictors: male gender (1 point), age (≥35 years, 1 point), shock (mean arterial pressure <65 mmHg, 3 points), consciousness (Glasgow Coma Scale <13, 2 points), need for supplemental oxygen (1 point), and tachycardia (pulse rate >120 beats/min, 1 point). The score ranges from 0-9, with a higher score indicating higher risk. The area under the receiver operating characteristic curve of the MASCOT score was 0.87 (95% CI 0.81-0.93) in the derivation cohort and 0.91 (95% CI 0.81-1.00) in the validation cohort, with a discriminatory performance comparable with existing scores. CONCLUSIONS: The MASCOT score enables quick risk stratification in acute metamfetamine toxicity. Further external validation is warranted before wider adoption.

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