Acute arsenic exposure secondary to deliberate self-poisoning with sheep dip.

A 53-year-old male patient presented to a regional hospital Emergency Department approximately 2 h post an intentional ingestion of Coopers Instant Wetting Powder Sheep Dip (66% arsenic trioxide, 23% sulphur and 0.42% rotenone), mixed in 600 mL water, as a suicide attempt. On arrival to the Emergency Department, the patient had nausea, vomiting and diarrhoea. Seven hours post ingestion, hypotension developed (BP 90/60 mmHg) and intravenous fluids were commenced. He later developed QTc prolongation. He was treated with 2,3-Dimercapto-1-propanesulfonic acid (DMPS) and N-acetylcysteine and improved without development of neurology. Further investigation of NAC efficacy in humans in the setting of acute arsenic poisoning is required and the optimal duration of treatment and dosing needs to be established. This case highlights an uncommon poisoning which presented to the Emergency Department, the acute symptoms of arsenic toxicity and considerations for management.

Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication.

INTRODUCTION: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. METHODS: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. RESULTS: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. CONCLUSION: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.

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.

Co-exposure to gamma-hydroxybutyrate is associated with attenuated neuropsychiatric and stimulant effects of metamfetamine.

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.

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.

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.

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 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.

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.

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.

Diagnostic stability in very young children with autism spectrum disorders.

Autism Spectrum Disorders (ASD) diagnosis in very young children may be delayed due to doubts about validity. In this study, 77 children received a diagnostic and developmental evaluation between 16 and 35 months and also between 42 and 82 months. Diagnoses based on clinical judgment, Childhood Autism Rating Scale, and the Autism Diagnostic Observation Schedule were stable over time. Diagnoses made using the Autism Diagnostic Interview were slightly less stable. According to clinical judgment, 15 children (19%) moved off the autism spectrum by the second evaluation; none moved onto the spectrum. Results indicate diagnostic stability at acceptable levels for diagnoses made at age 2. Movement off the spectrum may reflect true improvement based on maturation, intervention, or over-diagnosis at age 2.

The modified checklist for autism in toddlers: a follow-up study investigating the early detection of autism spectrum disorders.

Autism spectrum disorders (ASD) often go undetected in toddlers. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to screen 3,793 children aged 16-30 months from low- and high-risk sources; screen positive cases were diagnostically evaluated. Rescreening was performed on 1,416 children aged 42-54 months. Time 1 Positive Predictive Value (PPV) was .36 for the initial screening and .74 for the screening plus follow-up telephone interview; values were similar for Time2 PPV. When separating referral sources, PPV was low for the low-risk sample but acceptable with the followup telephone interview. Children with ASD from the low-risk and high-risk samples were highly similar. Results indicate that the M-CHAT continues to be a promising instrument for the early detection of ASD.

Anomalous Lattice Dynamics in AgC4N3: Insights From Inelastic Neutron Scattering and Density Functional Calculations.

We have performed temperature dependent inelastic neutron scattering measurements to study the anharmonicity of phonon spectra of AgC4N3. The analysis and interpretation of the experimental spectra is done using ab-initio lattice dynamics calculations. The calculated phonon spectrum over the entire Brillouin zone is used to derive linear thermal expansion coefficients. The effect of van der Waals interaction on structure stability has been investigated using advanced density functional methods. The calculated isothermal equation of states implies a negative linear compressibility along the c-axis of the crystal, which also leads to a negative thermal expansion along this direction. The role of elastic properties inducing the observed anomalous lattice behavior is discussed.

Predictors of optimal outcome in toddlers diagnosed with autism spectrum disorders.

A diagnosis of autism spectrum disorder (ASD) is usually taken to be permanent. In this study, 13 two-year-old children with ASD lost the diagnosis by age 4, at which time they scored within the normal range on standardized measures of cognitive and adaptive functioning. No differences were found in symptom severity, socialization, or communication between children who lost the ASD diagnosis and children who did not, but children with PDD-NOS were significantly more likely than those with full autistic disorder to move off the spectrum. The clearest distinguishing factor was motor skills at age 2. Results support the idea that some toddlers with ASD can lose their diagnosis and suggest that this is difficult to predict.

Differentiating between autism spectrum disorders and other developmental disabilities in children who failed a screening instrument for ASD.

This study compared behavioral presentation of toddlers with autistic spectrum disorders (ASD) and toddlers with global developmental delay (DD) or developmental language disorder (DLD) who display some characteristics of ASD using the diagnostic algorithm items from the Autism Diagnostic Observation Schedule, Generic (ADOS), the Childhood Autism Rating Scale (CARS), and Modified Checklist for Autism in Toddlers (M-CHAT). To date, 195 children have failed the M-CHAT and have been diagnosed with ASD, DD or DLD. Children with ASD had prominent and consistent impairments in socialization skills, especially joint attention skills and were more impaired in some aspects of communication, play, and sensory processing. Children with ASD and children with DD/DLD shared common features, but certain behavioral markers differentiated the two groups.

Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (SπNo or SoNπ, respectively), relative to detection when signal and noise are in identical phase at each ear (SoNo). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: SoNo, SπNo, and SoNπ. BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the SπNo condition relative to SoNo and SoNπ conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., SoNo amplitude-SπNo amplitude) were significantly predictive of behavioral SπNo BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

Negative area compressibility in silver(I) tricyanomethanide.

The molecular framework Ag(tcm) (tcm(-) = tricyanomethanide) expands continuously in two orthogonal directions under hydrostatic compression. The first of its kind, this negative area compressibility behaviour arises from the flattening of honeycomb-like layers during rapid pressure-driven collapse of the interlayer separation.