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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.

AIMS: Treatment of methamphetamine dependence requires monitoring of recent use or abstinence. Self-report is commonly used for routine monitoring, but the accuracy of self-report is not established. For the treating clinician, the key accuracy statistic is the negative predictive value (NPV). The study aim was to estimate the NPV of self-reported non-use of methamphetamine compared with an oral fluid reference standard. DESIGN, SETTING AND PARTICIPANTS: This study was a secondary (subgroup) analysis from a randomized controlled pharmacotherapy trial. Three Australian outpatient addiction services took part. Particpants were 139 people dependent on methamphetamine. MEASUREMENTS: Weekly oral fluid samples over 12 weeks to determine methamphetamine (and amphetamine) concentrations were used as the reference standard. Self-report of any methamphetamine use in the previous 7 days by the time-line follow-back method was the index test. Standard diagnostic accuracy statistics were calculated for all available paired episodes (n = 1134). Three NPV values were calculated: unadjusted NPV and NPV adjusted for clustering of observations through logistic regression and generalized estimating equation (GEE). We also calculated the NPVs for a range of prevalence rates of methamphetamine use, for the calculated levels of sensitivity and specificity. FINDINGS: Sensitivity was 96.4% [95% confidence interval (CI) = 95-97.5], specificity was 63.7% (95% CI = 57.3-69.8) and positive predictive value (PPV) was 90.8% (95% CI = 88.8-92.6). The unadjusted NPV was 82.7% (95% CI = 76.5-87.9), adjusted NPV by logistic regression 82.7% (95% CI = 73.9-91.5) and GEE 76.8% (95% CI = 66.8-86.8). At a methamphetamine use prevalence of 5%, the estimated NPV would be 99.7% (95% CI = 99.6-99.9) and at 95% prevalence, 48.2% (95% CI = 39.6-57.0). CONCLUSIONS: Self-report of no recent methamphetamine use appears to be sufficiently accurate to be clinically useful at the expected prevalence rates of metham

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

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

Background and aims: Prior to February 2018, codeine was available over-the-counter (OTC) in Australia as a pharmacist-only medicine (Schedule 3) in low-strength formulations when in combination with simple analgesics. In February 2018, The Advisory Committee on Medicines Scheduling (ACMS) upscheduled codeine-containing medicines (CCM) to Schedule 4 (prescription-only medicine). This study aimed to determine the impact of upscheduling on prescriptions, overdoses and deaths. Method(s): This study used interrupted time series analysis, a quasi-experimental design, to retrospectively evaluate the impact of upscheduling on overdose poisoning calls to the Victorian Poisons Information Centre (VPIC), Emergency Department (ED) presentations to Austin Health, and deaths reported to the Victorian Coroner from 1 January 2013-31 December 2019. Result(s): There was a significant reduction in the trend of high-strength codeine poisoning calls by 0.36 (P = 0.03, 95 % CI = [-0.69, -0.04]). Low-strength codeine poisoning calls to the VPIC reduced by 13.31 (P <0.001, 95 % CI = [-16.80, 9.82]]) calls in February 2018, followed by continued reduction of 0.12 calls per month. High-strength codeine overdose ED presentations reduced in the first quarter of 2018 by 3.72 presentations (P = 0.004, 95 % CI = [-6.13, -1.31]). Low-strength codeine overdose ED presentations after the first quarter of 2018 by 0.33 (P = 0.03, 95 % CI = [-0.63, -0.03]) presentations per month. Codeine-related deaths reduced by 7.19 (P < 0.001, 95 % CI = [-9.44, -4.94]) deaths in February 2018. Conclusion(s): Codeine upscheduling to prescription-only medicine has reduced codeine-related poisoning calls, overdoses and unnatural death in Victoria.Copyright © 2021 Elsevier B.V.

Background and aims: Prior to February 2018, codeine was available over-the-counter (OTC) in Australia as a pharmacist-only medicine (Schedule 3) in low-strength formulations when in combination with simple analgesics. In February 2018, The Advisory Committee on Medicines Scheduling (ACMS) upscheduled codeine-containing medicines (CCM) to Schedule 4 (prescription-only medicine). This study aimed to determine the impact of upscheduling on prescriptions, overdoses and deaths. Method(s): This study used interrupted time series analysis, a quasi-experimental design, to retrospectively evaluate the impact of upscheduling on overdose poisoning calls to the Victorian Poisons Information Centre (VPIC), Emergency Department (ED) presentations to Austin Health, and deaths reported to the Victorian Coroner from 1 January 2013-31 December 2019. Result(s): There was a significant reduction in the trend of high-strength codeine poisoning calls by 0.36 (P = 0.03, 95 % CI = [-0.69, -0.04]). Low-strength codeine poisoning calls to the VPIC reduced by 13.31 (P <0.001, 95 % CI = [-16.80, 9.82]]) calls in February 2018, followed by continued reduction of 0.12 calls per month. High-strength codeine overdose ED presentations reduced in the first quarter of 2018 by 3.72 presentations (P = 0.004, 95 % CI = [-6.13, -1.31]). Low-strength codeine overdose ED presentations after the first quarter of 2018 by 0.33 (P = 0.03, 95 % CI = [-0.63, -0.03]) presentations per month. Codeine-related deaths reduced by 7.19 (P < 0.001, 95 % CI = [-9.44, -4.94]) deaths in February 2018. Conclusion(s): Codeine upscheduling to prescription-only medicine has reduced codeine-related poisoning calls, overdoses and unnatural death in Victoria.Copyright © 2021 Elsevier B.V.

Objective: Varenicline is a partial agonist of alpha-4 beta-2 nicotinic receptors used to treat nicotine withdrawal. It is renally eliminated, with an elimination half-life of 24-hours (range 10-54). In overdose, vomiting, hypertension, tachycardia and tachypnoea are seen. Phentermine is a sympathomimetic amine anorectic agent. Phentermine overdose results in central and peripheral adrenergic stimulation with cardiovascular and central nervous system toxicity. To date, there are no published cases reporting serum drug concentrations in patients surviving varenicline overdose. We report a case of varenicline and phentermine overdose confirmed by high performance liquid chromatography-mass spectrometry (HPLC-MS) blood analysis. Case report: A 13-year-old female presented to the emergency department 13 hours after ingesting her mother's varenicline (15 x 1 mg) and phentermine (15 x 30 mg). She began vomiting within 30 minutes of ingestion and this continued every 15-30 minutes throughout the night. On arrival, she complained of light-headedness, palpitations, anxiety and bilateral leg weakness. Initial observations were: pulse 125 bpm, sinus tachycardia, BP 123/72 mmHg, respiratory rate 24/min, saturation 97% (room air), temperature 36.7degreeC. On examination, pupils were 4 mm, equal and reactive, and she had sweaty palms. There was no clonus or tremor. She was able to stand unaided but complained of subjective left-sided weakness. There was no focal weakness on objective neurological testing. Serum electrolytes, acid-base and renal function were normal. Symptoms resolved rapidly. She was observed for 22 hours and discharged well the next day. Serum concentrations of phentermine and varenicline were assayed by HPLC-MS at 13, 17 and 22 hours post-ingestion. Phentermine concentrations were 0.16 mg/L, 0.23 mg/L and 0.16 mg/L (therapeutic range 0.18-0.51). Varenicline concentrations were 4.2 ng/mL at 13-hours and 3.5 ng/mL 22-hours post-ingestion with calculated eliminati

Objective: Varenicline is a partial agonist of alpha-4 beta-2 nicotinic receptors used to treat nicotine withdrawal. It is renally eliminated, with an elimination half-life of 24-hours (range 10-54). In overdose, vomiting, hypertension, tachycardia and tachypnoea are seen. Phentermine is a sympathomimetic amine anorectic agent. Phentermine overdose results in central and peripheral adrenergic stimulation with cardiovascular and central nervous system toxicity. To date, there are no published cases reporting serum drug concentrations in patients surviving varenicline overdose. We report a case of varenicline and phentermine overdose confirmed by high performance liquid chromatography-mass spectrometry (HPLC-MS) blood analysis. Case report: A 13-year-old female presented to the emergency department 13 hours after ingesting her mother's varenicline (15 x 1 mg) and phentermine (15 x 30 mg). She began vomiting within 30 minutes of ingestion and this continued every 15-30 minutes throughout the night. On arrival, she complained of light-headedness, palpitations, anxiety and bilateral leg weakness. Initial observations were: pulse 125 bpm, sinus tachycardia, BP 123/72 mmHg, respiratory rate 24/min, saturation 97% (room air), temperature 36.7degreeC. On examination, pupils were 4 mm, equal and reactive, and she had sweaty palms. There was no clonus or tremor. She was able to stand unaided but complained of subjective left-sided weakness. There was no focal weakness on objective neurological testing. Serum electrolytes, acid-base and renal function were normal. Symptoms resolved rapidly. She was observed for 22 hours and discharged well the next day. Serum concentrations of phentermine and varenicline were assayed by HPLC-MS at 13, 17 and 22 hours post-ingestion. Phentermine concentrations were 0.16 mg/L, 0.23 mg/L and 0.16 mg/L (therapeutic range 0.18-0.51). Varenicline concentrations were 4.2 ng/mL at 13-hours and 3.5 ng/mL 22-hours post-ingestion with calculated eliminati

For the drug testing of MDMA (3,4-methylenedioxymethamphetamine or 'ecstasy') and other drugs of abuse, urine is generally the matrix of choice. However, the main issue concerned with urine drug testing is the lack of sample integrity due to acts of urine adulteration. A novel approach in the fight against urine adulteration is researched in this article, involving the use of LC-MS/MS (liquid chromatography-tandem mass spectrometry) to study and identify stable reaction products between the chemical reaction of MDMA and hypochlorite. Samples were analysed on an X Bridge C 18 column ( 150mm x 4.6mm, 3.51-Jm, Waters). Chromatographic separation was achieved at a tlow rate of 0.3ml/min using gradient elution involving 2mM ammonium formate solution in Milli-Q water and acetonitrile as the mobile phases. Kinetic experiments were performed whereby 11-JL of urinary reaction mixture was injected every 30min of reaction. One major reaction product, N-chloroMDMA, was formed and found to be unstable at room temperature (20°C), possibly reverting back into MDMA. It is suggested that bleach may possibly be able to oxidise a low dosage of MDMA to below cutoff concentration values and thus, conceal MDMA use. However, more research is required.

Delta9 -tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis. It causes a decrease in motor function and concentration making it hazardous for an individual to drive whilst under the inftuence of this drug. Roadside testing procedures for cannabis are therefore necessary since it is the most widely used illicit drug in Australia and around the world and is commonly implicated in drug-driving offences.

B-Glucuronidase is on enzyme often employed to deconjugate B-glucuronides during urinary drug testing for benzodiozepines. It is commonly accepted that use of B-glucuronidase is a preferred method of hydrolysis over acid-catalyzed hydrolysis, which is known to induce benzodiozepine degradation and transformation. Very recently, we have reported that B-glucuronidase catalyzed hydrolysis is also a source of artefact production. We found that either oxazepam glucuronide present in patient urine or free oxazepam added in blank urine could be reduced to nordiozepom (desmethyldiozepom) during incubation with commercial B-glucuronidase enzymes. Formation of nordiozepom artefact was positively correlated with incubation temperature, incubation time, oxazepam concentration and enzyme concentration.

For the drug testing of MDMA (3,4-methylenedioxymethamphetamine or 'ecstasy') and other drugs of abuse, urine is generally the matrix of choice. However, the main issue concerned with urine drug testing is the lack of sample integrity due to acts of urine adulteration. A novel approach in the fight against urine adulteration is researched in this article, involving the use of LC-MS/MS (liquid chromatography-tandem mass spectrometry) to study and identify stable reaction products between the chemical reaction of MDMA and hypochlorite. Samples were analysed on an X Bridge C 18 column ( 150mm x 4.6mm, 3.51-Jm, Waters). Chromatographic separation was achieved at a tlow rate of 0.3ml/min using gradient elution involving 2mM ammonium formate solution in Milli-Q water and acetonitrile as the mobile phases. Kinetic experiments were performed whereby 11-JL of urinary reaction mixture was injected every 30min of reaction. One major reaction product, N-chloroMDMA, was formed and found to be unstable at room temperature (20°C), possibly reverting back into MDMA. It is suggested that bleach may possibly be able to oxidise a low dosage of MDMA to below cutoff concentration values and thus, conceal MDMA use. However, more research is required.

Delta9 -tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis. It causes a decrease in motor function and concentration making it hazardous for an individual to drive whilst under the inftuence of this drug. Roadside testing procedures for cannabis are therefore necessary since it is the most widely used illicit drug in Australia and around the world and is commonly implicated in drug-driving offences.

B-Glucuronidase is on enzyme often employed to deconjugate B-glucuronides during urinary drug testing for benzodiozepines. It is commonly accepted that use of B-glucuronidase is a preferred method of hydrolysis over acid-catalyzed hydrolysis, which is known to induce benzodiozepine degradation and transformation. Very recently, we have reported that B-glucuronidase catalyzed hydrolysis is also a source of artefact production. We found that either oxazepam glucuronide present in patient urine or free oxazepam added in blank urine could be reduced to nordiozepom (desmethyldiozepom) during incubation with commercial B-glucuronidase enzymes. Formation of nordiozepom artefact was positively correlated with incubation temperature, incubation time, oxazepam concentration and enzyme concentration.