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Introduction: Self-poisoning is the most common form of hospitalised self-harm in young people and has been increasing over the last decade. The COVID-19 pandemic was associated with further increases in self-harm in adolescents. There are limited data on changes after pandemic restrictions ended. This study aimed to describe recent trends in self-poisoning in young people. Setting: Australia 2018–2023. Methods: A retrospective analysis of self-poisoning calls to Australia's poisons information centres. Intentional poisoning exposures in people aged 5–19 years were included in the main analysis. We also examined intentional poisonings in people aged 20 and over for comparison. We used interrupted time-series analysis to estimate the impact of COVID-19 (March 2020) and 're-opening' (December 2021), when many restrictions were lifted in Australia. We compared effects in the jurisdictions with most disruptions and lockdowns with other jurisdictions. Results: There were 201,755 self-poisonings documented, 64% female, with 19,946 children (aged 5–14, 9.9%) and 44,388 adolescents (aged 15–19, 22.0%). There was a steep increase in the rate of poisoning in female children and adolescents – with the annual increase being 1.361 (95% confidence interval = [1.074, 1.735]) and 1.154 (95% confidence interval = [1.049, 1.283]) times faster than pre-pandemic trends in these two groups between March 2020 and December 2021. Following relaxation of restrictions, there was a sudden drop and then slow decline in self-poisonings (despite rising COVID-19 infection rates). There was an overall 29.6% increase in intentional poisonings in young people over the study period. This is markedly more pronounced among young females (37.0%) vs males (11.2%). There were substantial jurisdictional variations, with larger increases in Victoria, Tasmania and the Australian Capital Territory. Conclusion: There has been a marked increase in child and adolescent female self-poisonings over the last 6 years, with increases strongly associated with COVID-19 pandemic restrictions but persisting after their removal. [ABSTRACT FROM AUTHOR]

Aims: To compare a low-dosing protocol to standard practice for methadone-buprenorphine transfers. Methods: We undertook a nonrandomized open-label clinical trial across 8 sites from NSW, Australia. Participants prescribed methadone wishing to transfer to buprenorphine could either choose or be randomized to a low-dose transfer or standard care transfer as per NSW health guidelines. The low-dose protocol started at 0.2 mg BD and increased to 16 mg on day 6, with flexible dosing thereafter. The primary outcome was continuation of buprenorphine 1 week post-transfer. Binary logistic regression was used to access the primary outcome with demographic differences between the groups included as covariates. Results: There were 117 participants who commenced the study, 101 in the low-dose arm and 16 in standard care. Mean methadone dose was 82 mg in the low-dose arm and 46 mg in standard care. The primary outcome was met by 81 participants in the low-dose arm (80%) and 13 participants in standard care (81%). There was no significant between-arm difference in the odds of the primary outcome (OR = 2.22; 95% CI: 0.45–10.91; P = 0.327). Four participants (4%) in the low-dose arm experienced precipitated withdrawal against 1 (6%) in standard care. Higher methadone dose decreased the odds of successful transfer by 20% (OR = 0.8 per 10 mg methadone; 95% CI: 0.7–0.99; P = 0.04). Withdrawal scores between the 2 arms were similar. Conclusions: We were unable to detect a difference between low dosing and standard care for methadone to buprenorphine transfers. Increasing methadone dose was a predictor of success; setting (ambulatory or inpatient) was not. [ABSTRACT FROM AUTHOR]

Objective: Early antivenom administration is essential for effective treatment. We investigated the delays in antivenom administration. Methods: We reviewed snakebites from the Australian Snakebite Project (2006–2021) given antivenom, presenting to hospital within 12 h. We extracted demographics, snake type, time of bite, hospital arrival, blood collection, antivenom treatment and hospital transfer. Results: There were 2,169 patients recruited to Australian Snakebite Project 1,132 patients received antivenom within 12 h of the bite, and 1,019 of these were envenomated: median age 41 years (IQR: 24–57 years); 738 (72%) males. A pressure bandage was applied in 950 (93%), a median of 15 min (IQR: 5–30 min) post-bite. Specific snakes were identified by venom assays in 855 patients (80%), including 328 brown snakes (32%), 173 tiger snakes (17%), 74 rough-scaled snakes (7%), 85 red-bellied black snakes (8%), 49 taipans (5%) and 26 death adders (3%). Seventy-seven patients (7%) received antivenom without envenomation. The median length of hospital stay was 41 h (IQR: 24–67 h). The median time to hospital was 60 min (IQR: 30–105 min), to first blood tests was 90 min (IQR: 59–154 min) and to antivenom was 235 min (IQR: 155–345 min). There was a median delay in blood tests of 20 min (IQR: 10–37 min) and a median delay to antivenom of 147 min (IQR: 84–249 min). Non-specific systemic symptoms occurred in 641 (63%) patients, which occurred a median of 24 min (IQR: 10–60 min) post-bite, which was at a median of 180 min (IQR: 106 to 275 min) prior to antivenom administration. Time to antivenom in the 314 transferred patients was similar to those not transferred. Time to antivenom was significantly shorter for 189 patients given antivenom prior to transfer, median 183 min (IQR: 110–270 min), compared to 130 patients given antivenom after transfer, median 363 min (IQR: 289–513 min; P <0.001). Discussion: Antivenom administration was delayed on average by 2.5 h after hospital presentation, despite three-quarters arriving in hospital within 3 h, the optimal time for antivenom administration. Patients requiring transfer received antivenom in a similar time, but earlier if administered prior to transfer, highlighting the possible benefits of pragmatic clinical decision-making prior to blood tests. Conclusion: We found the leading cause of delays to antivenom administration after patients arrive in hospital was waiting for blood results. Systemic symptoms occurred early in most cases and could be given greater weight in decisions about early antivenom. [ABSTRACT FROM AUTHOR]

Introduction: Naloxone is an effective antidote, but its short half-life means repeated doses, and infusions are often required. We investigated the effectiveness of adding intramuscular naloxone to titrated intravenous naloxone in opioid overdose in preventing recurrence of respiratory depression. Methods: This double-blinded randomised placebo-controlled trial was conducted in patients with suspected opioid poisoning and respiratory depression (respiratory rate <10 breaths/min or oxygen saturation <93%). Patients were randomised to receive either intramuscular naloxone 1,600 µg or saline placebo. All patients received titrated intravenous naloxone 100 µg and were managed on an opioid poisoning care pathway. The primary outcome was recurrence of respiratory depression within 4 h. Secondary outcomes were the proportion receiving naloxone infusions, number of naloxone boluses administered, reversal of respiratory depression at 10 min, and precipitation of opioid withdrawal (any symptom). Results: Recurrence of respiratory depression within 4 h was less common in 28/69 (41%) patients receiving intramuscular naloxone versus 48/67 (72%) patients receiving placebo (difference 31%, 95% CI: 13–46%; P < 0.001). Fewer naloxone infusions (5/69; 7% versus 25/67; 37%, difference 30%, 95% CI: 15 to 55%; P < 0.001) and fewer naloxone doses were administered (median 2, IQR: 1 to 5, versus median 5, IQR: 2 to 8; P = 0.001) in the intramuscular group. Reversal of respiratory depression at 10 min was similar between groups (51/69; 74% intramuscular naloxone versus 47/67; 70% placebo; P = 0.703). Opioid withdrawal occurred in 35/69 (51%) given intramuscular naloxone compared to 28/67 (42%) in the placebo group (difference 9%; 95% CI: −8 to 27%; P = 0.308). Discussion: The favourable pharmacokinetics of intramuscular naloxone, particularly its longer duration of activity, likely explains the improved effectiveness with lower recurrence of respiratory depression. Conclusion: The addition of intramuscular naloxone 1,600 µg to titrated intravenous naloxone prolonged effective reversal of respiratory depression, with fewer naloxone doses and infusions given, and no significant difference in patients developing withdrawal. [ABSTRACT FROM AUTHOR]

Introduction: Poisoning is a leading cause of morbidity and mortality that is increasing in many countries. Better data are needed to understand epidemiology and outcomes of poisoning. This work describes a new poisoning data linkage cohort in New South Wales, Australia (population approximately 8 million). Methods: This is a longitudinal health record linkage, 2011–2020, including data from: ambulance call-outs, emergency department presentations, hospital admissions, death registrations, the poisons centre, and four tertiary toxicology units. Individuals with poisoning, venomous animal/plant exposures, or adverse drug reaction events were included. Results: There were 845,217 linkable events relating to 400,642 ambulance, 688,484 emergency department, 682,013 admission, 40,456 toxicology, and 11,879 death records. There were 572,841 people with events; the median age at the time of first event was 57 years, and 51.9% were female. Events leading to patient admission were most commonly adverse drug reactions (n = 511,263), intentional poisonings (n = 68,646), unintentional poisonings (n = 54,840) and animal/plant exposures (n = 11,092). Demographics varied by cause: intentional poisoning (median age 33 years, 61.7% female); unintentional poisoning/animals/plants (median age 43 years, 45% female); and adverse drug reactions (median age 70 years, 54% female). Adolescent females had highest rates of intentional poisoning, while unintentional poisoning had a bimodal distribution, highest in children <5 years old and males aged 20 to 50 years. Substance use disorders were documented comorbidities for 44% of intentional poisoning, 29% of unintentional poisoning, and 13% of adverse drug reaction-related admissions; mood disorders were documented for 54%, 17% and 10% of these admissions, respectively. Discussion: Poisonings and hospitalised adverse drug reactions are common in New South Wales, affecting approximately 8% of the population in 10 years. This linkage improves understanding of poisoning risks and outcomes in Australia. Conclusions: This novel data linkage provides a unique opportunity to study poisoning across multiple settings for an individual over an extended period. [ABSTRACT FROM AUTHOR]

Introduction: Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning. Methods: We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed. Results: Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69–0.97) and 0.76 (95% CI 0.59–0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9). Discussion: The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning. Conclusions: Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients. [ABSTRACT FROM AUTHOR]

Antivenom is first line treatment for snake envenomation worldwide, despite few placebo controlled clinical trials demonstrating effectiveness. We aimed to investigate whether early antivenom in red-bellied black snake (Pseudechis porphyriacus) bites would prevent systemic myotoxicity. We undertook a multicentre randomized placebo-controlled trial of antivenom for red-bellied black snake bites with patients recruited from the Australian Snakebite Project (July 2014 to June 2020). In addition, we report all patients with red-bellied black snake bites during the same period, comparing the same outcomes. Patients over 2 years of age with definite red-bellied black snake bites and early systemic effects were randomized to receive 50 per cent glucose (placebo) or tiger snake antivenom within 6 hours post-bite, or in the cohort group received antivenom determined by the treating clinician. The primary outcome was the proportion of patients with myotoxicity (peak creatine kinase activity >1,000 U/L). Secondary outcomes were: area under the curve of total creatine kinase elevation over 48 hours, presence of venom post-antivenom, and adverse reactions. We analyzed both the randomized control trial patients and the combination of randomized control trial and cohort patients. Fifteen patients were recruited to the randomized controlled trial, and a cohort of 68 patients who were not randomized were included in the analysis. After treatment, two of seven patients given placebo had a peak creatine kinase activity >1,000 U/L versus none of the eight given antivenom (difference in favour of antivenom; 29 per cent; 95 per cent confidence interval:-18 per cent to +70 per cent; P = 0.2). The median area under the curve of total creatine kinase elevation over 48 hours in patients given placebo was 0 U/L*h (interquartile range: 0–124 U/L*h), which was not significantly different to those given antivenom: 197 U/L*h (interquartile range: 0–66,353 U/L*h; P = 0.26). Venom was not detected post-antivenom in six patients with measured venom concentrations given antivenom. Two patients given antivenom had immediate hypersensitivity reactions, one severe anaphylaxis, and another had serum sickness. Combining randomized and not randomized patients, three of 36 (8 per cent) administered antivenom less than 6 hours post-bite had a peak creatine kinase activity >1,000 U/L versus 17/47 (36 per cent) patients not receiving antivenom less than 6 hours post-bite (difference in favour of antivenom 29 per cent; 95 per cent confidence interval: 8 per cent to 44 per cent; P < 0.004). Overall, 13/36 (36 per cent) patients administered antivenom within 6 hours had hypersensitivity reactions, six severe anaphylaxis (17 per cent). We found that early antivenom was effective in red-bellied black snake bites, and only three patients need to be given antivenom within 6 hours to prevent myotoxicity in one (number needed to treat = 3). However, one in three patients administered antivenom developed a hypersensitivity reaction, and one in six had severe anaphylaxis. The major limitation of this study was the small number of patients recruited to the randomized controlled trial. Administration of antivenom in red-bellied black snake envenomation within 6 hours post-bite appeared to decrease the proportion of patients with myotoxicity, but a third of patients had adverse reactions. [ABSTRACT FROM AUTHOR]

Background and Aim: Paracetamol, a widely used medication, is known for its delayed hepatotoxicity in cases of overdose. However, the potential for intestinal toxicity resulting from very high paracetamol concentrations during absorption is not well explored. This study aims to investigate the presence of intestinal toxicity and its correlation with observations in early and late paracetamol toxicity. Methods: Serial samples of 30 patients with acute paracetamol overdose (> 10 g or 200 mg/kg) were prospectively tested. Markers of enterocyte damage, including plasma intestinal fatty acid binding protein (IFABP) and selected gut‐related microRNAs (miR‐21, miR‐122, miR‐194, and miR‐215), were analyzed. Sub‐analysis was performed on patients presenting with hyperlactatemia defined as a lactate greater than 2 mmol/L within 12 h post ingestion. Results: In paracetamol overdose patients, median plasma IFABP was significantly elevated compared with healthy controls (720 μg/L [interquartile range, IQR, 533–1644] vs 270 μg/L [IQR 153–558], P < 0.001). Four patients had early hyperlactatemia and had significantly higher median plasma IFABP compared with those without early hyperlactatemia (3028 μg/L [IQR 1399–3556] vs 574 μg/L [IQR 526–943], P = 0.007). Furthermore, two microRNAs (miR‐122 and miR‐215) were downregulated in early hyperlactatemia (P = 0.019 and P = 0.006, respectively). Plasma IFABP concentrations correlated with paracetamol concentration (Spearman's r = 0.55) and lactate (r = 0.60). Conclusions: Paracetamol overdose causes concentration‐related intestinal toxicity, and this is a possible explanation for the early hyperlactatemia syndrome. Intestinal toxicity has potential impacts on pharmacokinetics of other agents ingested and on the evolution of hepatotoxicity. Further studies are required to explore the mechanisms and prognostic implications of intestinal toxicity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half‐pack size item codes for IR formulations. Design, setting: Population‐based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS‐eligible residents and IQVIA national opioid medicine sales data (PBS‐subsidised and private prescriptions), 28 May 2018 – 6 June 2021. Main outcome measures: Mean amount of PBS‐subsidised opioid medicines dispensed per day and mean overall amount sold per day — each expressed as oral morphine equivalent milligrams (OME) — overall, by formulation type (IR, CR), and by specific formulation. Results: During the twelve months following the PBS changes, daily PBS‐subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, –106 146 to –56 984 OME) than the mean daily level for 2018–20, a decline of 3.8% after adjusting for the pre‐intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS‐subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half‐pack sizes comprised 8.4% of PBS‐subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. Conclusions: The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS‐subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions. [ABSTRACT FROM AUTHOR]

Objective: To determine antipsychotic utilisation patterns in Australian adults from 2005 to 2021, with a focus on on-label and off-label prescriptions. Methods: We examined antipsychotic dispensing trends in adults from 2005 to 2021 using a 10% sample of the Pharmaceutical Benefits Scheme (PBS) dataset, which contains patient-level information on medicines dispensed throughout Australia. The lack of diagnostic information in PBS was substituted by analysing BEACH (Bettering the Evaluation And Care of Health) dataset, a cross-sectional national survey from 2000 to 2016, consisting of data from general practitioner–patient encounters. Results: There were 5.6 million dispensings for 164,993 patients in PBS throughout this period; 69% patients had >1 dispensing, with a median of 6 per patient. Calculating the estimated period of exposure gave a total of 693,562 treatment episodes, with a median duration of 80 days. There were steady increases in both the incidence and prevalence of antipsychotic dispensings, mainly due to oral second-generation antipsychotics. The most commonly prescribed antipsychotics were quetiapine, olanzapine and risperidone, with a significant portion of patients receiving low-dose quetiapine without dose titration. Analysis of diagnostic indications from BEACH indicated that 27% of antipsychotic prescriptions were off-label for indications such as depression, dementia, anxiety and insomnia, at much lower prescribed daily dosages. Conclusion: The increasing prescribing and off-label use highlights concerns about chronic adverse effects caused by antipsychotics. The combined analysis of medication dispensings and the diagnostic indications for which they are prescribed is a novel approach and throws a spotlight on the need for additional monitoring of antipsychotics. [ABSTRACT FROM AUTHOR]