An analysis of the trends in the usage of Pharmaceutical Benefits Scheme-subsidised cancer drugs in Australia from 2012 to 2022.

PURPOSE: Cancer treatment remains a significant and escalating healthcare expense worldwide. Although annual reports on total cancer care costs are available, the potential impact of evolving treatment guidelines and the introduction of new drugs on future budgeting remains largely uncertain. The aim of this study was to examine the trends in the use of Pharmaceutical Benefits Scheme (PBS)-subsidised cancer drugs in Australia over the past decade. METHODS: PBS codes for all PBS-subsidised cancer drugs that were listed in government-endorsed treatment protocols were obtained and used to retrieve usage data. Their patterns of use, represented by the number of prescriptions (services) processed by Services Australia, were analysed for the period between 2012 and 2022. RESULTS: The overall prescribing of cancer drugs is outpacing Australia's population growth, primarily due to an ageing population and the accelerated rise in cancer diagnoses observed over the past decade. From 846 eviQ protocols, 141 cancer drugs were available on the PBS, of which kinase inhibitor (39 drugs) and monoclonal antibody drugs (24 drugs) had the highest increase in use during the study period; 16% and 23% respectively. Of the 8 drug classes, hormonal agents (20 drugs) were the most prescribed. CONCLUSION: The utilisation of PBS-listed cancer drugs is increasing faster than population growth, especially for high-cost monoclonal antibody and kinase inhibitor drugs, indicating continued pressure on government spending.

A Scoping Review of Pharmacogenomic Educational Interventions to Improve Knowledge and Confidence.

OBJECTIVES: Poor knowledge and confidence in pharmacogenomics are key barriers to implementation. Education of future health care professionals is required to enhance appropriate use of pharmacogenomics; however, the optimal education approach is unclear. This systematic scoping review evaluates pharmacogenomic educational interventions to improve knowledge and confidence. FINDINGS: A total of 24 studies were included. Most (90%) studies delivered pharmacogenomic education to pharmacy students and consisted of didactic lectures and workshops with case studies. To supplement case studies, self or class aggregated (52%, 12 of 23), mock (43%, 10 of 23) or faculty member provided (4%, 1 of 23) pharmacogenomic data were used in the case scenarios. All studies used quantitative methods, including student assessments and scaled surveys to assess the impact of the educational intervention on knowledge and/or confidence in pharmacogenomics. On average, the educational interventions improved knowledge acquisition by 21%, confidence in pharmacogenomic data interpretation by 37%, confidence in communication of pharmacogenomic information to patients by 41% and to health care professionals by 44%. Improvement in communication with other health care professionals was greater in students involved in interprofessional learning compared to self-pharmacogenomic testing. SUMMARY: The measures used to determine the effect of educational interventions on student knowledge and confidence varied. Innovative pedagogy, specifically interactive case-based learning and simulation such as interprofessional learning, enhances the knowledge and confidence of students in pharmacogenomics. Course-embedded self-pharmacogenomic testing may offer a supplementary, interactive component to case-based learning by using real-life reports as the foundation of knowledge and confidence acquisition.

Poisonings in Older People with Dementia: A Systematic Scoping Review and Meta-Analysis.

BACKGROUND: Older people with dementia are at a particularly high risk of poisonings and their subsequent harms. OBJECTIVE: This review aimed to describe the key agents, incidence, risk factors, and disposition of poisonings in people with dementia reported in the literature. METHODS: Medline, Embase, CINAHL, and PsycINFO databases were searched from 1 September 2001 to 1 September 2021. Terms for dementia, poisonings, and older adults formed the search concepts. Quantitative studies published in English, describing poisonings in older people with dementia, including Alzheimer's disease, were included. Two investigators independently assessed articles for eligibility and extracted relevant data. A meta-analysis of the incidence of poisonings in people with dementia across studies was performed. RESULTS: Of 4,579 articles, 18 were included for final synthesis. Nervous system medications were implicated in over half of all medicinal poisonings, with anti-dementia agents, benzodiazepines, and opioids the most common classes. The non-medicinal agents frequently associated with poisonings were personal care and household products. The yearly incidence of poisoning varied across definitions of poisoning from 3% for International Classification of Disease-defined poisonings to 43% for adverse drug event-defined poisonings. Several risk factors were identified, including multimorbidity, psychotropic medication use, and living in residential care. Where described, up to one in five poisonings resulted in hospitalisation and in death. CONCLUSIONS: Poisonings are common in people with dementia, involving commonly prescribed medications or easily accessible substances. Given the significant outcomes associated, further research is required to better understand these poisonings and improve public health strategies to reduce the occurrence of this preventable harm.

Has there been an increase in nitrous oxide use and associated harms in Australia? An analysis of triangulated data sources, 2003-2020.

BACKGROUND: There is growing concern, globally, regarding use of nitrous oxide (N2O) for intoxication purposes. This paper aims to examine trends in: (i) past six month N2O use among a sample of people who use regularly use ecstasy and/or other illicit stimulants (2003-2020); (ii) volume of N2O-related Google searches and social media posts (2009-2020); and (iii) N2O-related calls to Poisons Information Centres (PIC) (2004-2020). METHODS: Data were obtained from annual interviews with sentinel samples of Australians aged ≥16 years who used ecstasy and/or other illicit stimulants ≥monthly and resided in a capital city (∼800 each year); Google search activity; social media posts; and exposure calls to four PIC. RESULTS: Among samples of people who regularly use ecstasy and/or other illicit stimulants, past six-month N2O use increased 10% each year from 2009 to 2020, with the sharpest increase observed between 2015 and 2018 (25.4% p/year; 95% CI: 14.6-37.1). Frequency and quantity of N2O use remained stable and low. Google search probabilities increased by 1.8% each month from January 2009 and December 2019 (95% CI: 1.5-2.2), with the sharpest increase observed between July 2016 to December 2017 (6.0% p/month; 95% CI: 4.4-7.5). Social media posts increased 2.0% per month from January 2009 and December 2019 (95% CI: 1.1-3.0), with the sharpest increase observed between March and October 2017 (19.2% p/month; 95% CI: 1.7-39.7). The number of N2O-related calls to Australian PIC increased sixfold between 2016 (16) and 2020 (111). CONCLUSIONS: Triangulation of various data sources indicate significant shifts in N2O use and harms in Australia. This includes increases in use, Google searches and social media posts, although these have plateaued in recent years, coupled with increased rates of harm. These findings correspond with evidence of a global increase in N2O use and harm, highlighting the need for education of both people who use N2O and health professionals.

Substances Detected During Coroner Postmortem Toxicology Analyses in Poisoning- and Nonpoisoning-Related Suicides.

Importance: Determining the association between drug use and suicide is complicated but can help to inform targeted suicide prevention strategies. Objective: To examine the substances prevalent in poisoning- and nonpoisoning-related suicides in Australia. Design, Setting, and Participants: This was a multiple-year, cross-sectional study of suicides from July 2013 to October 2019 in Australia with toxicology data available in a national coronial database. The cause of death was classified as poisoning related if any type of poisoning was determined by the coroner to contribute to the cause of death. Prevalence ratios (PRs) were calculated to compare substance detection in poisoning- vs nonpoisoning-related suicides. Data were analyzed from October 2021 to April 2023. Exposures: All substances detected in decedents at the time of death according to toxicology reports were recorded. Main Outcome(s) and Measure(s): The most common individual substances and substance classes were identified. From these, blood concentrations of substances of interest were analyzed, and the most commonly occurring combinations of substance classes were listed. Results: Toxicology was performed on 13 664 suicide decedents (median [IQR] age, 44 [31-57] years; 10 350 male [76%]). From these, 3397 (25%) were poisoning-related suicides (median [IQR] age, 50 [38-63] years; 2124 male [63%]). The remainder were classified as nonpoisoning-related suicides (median [IQR] age, 42 [29-55] years; 8226 male [80%]). PRs for common medicine classes being detected in poisoning-related suicides compared with nonpoisoning-related suicides were as follows: antidepressants (PR, 1.63; 95% CI, 1.54-1.73), benzodiazepines (PR, 2.01; 95% CI, 1.90-2.13), nonopioid analgesics/anti-inflammatory drugs (PR, 1.88; 95% CI, 1.78-2.00), and opioids (PR, 2.72; 95% CI, 2.58-2.87). Alcohol (as ethanol ≥0.03 g/100 mL) was almost equally prevalent in poisoning- and nonpoisoning-related deaths (PR, 1.07; 95% CI, 1.01-1.14), whereas amphetamines (PR, 0.68; 95% CI, 0.61-0.77) and cannabinoids (PR, 0.67; 95% CI, 0.60-0.74) were detected more often in nonpoisoning-related suicides. Combinations of multiple sedative agents in poisoning-related suicides were common. Conclusions and Relevance: Both poisoning- and nonpoisoning-related suicide deaths featured a high prevalence of psychotropic medicines or potential intoxication, which suggests the association of suicide with poor mental health and substance misuse. Findings suggest that substances with a high involvement in poisoning-related suicides should be prescribed cautiously, including antidepressants that are toxic in overdose, sedatives, opioids, and potentially lethal combinations.

Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease.

INTRODUCTION: Paracetamol is one of the most used medicines worldwide and is the most common important poisoning in high-income countries. In overdose, paracetamol causes dose-dependent hepatotoxicity. Acetylcysteine is an effective antidote, however despite its use hepatotoxicity and many deaths still occur. AREAS COVERED: This review summarizes paracetamol overdose and toxicity (including mechanisms, risk factors, risk assessment, and treatment). In addition, we summarize the epidemiology of paracetamol overdose worldwide. A literature search on PubMed for poisoning epidemiology and mortality from 1 January 2017 to 26 October 2022 was performed to estimate rates of paracetamol overdose, liver injury, and deaths worldwide. EXPERT OPINION: Paracetamol is widely available and yet is substantially more toxic than other analgesics available without prescription. Where data were available, we estimate that paracetamol is involved in 6% of poisonings, 56% of severe acute liver injury and acute liver failure, and 7% of drug-induced liver injury. These estimates are limited by lack of available data from many countries, particularly in Asia, South America, and Africa. Harm reduction from paracetamol is possible through better identification of high-risk overdoses, and better treatment regimens. Large overdoses and those involving modified-release paracetamol are high-risk and can be targeted through legislative change.

Melatonin use in children and adolescents: A scoping review of caregiver perspectives.

Despite melatonin's popularity as a pediatric sleep-aid, little has been investigated around caregivers' understanding and perception of melatonin use for their dependent. This scoping review analyzes the current literature on pediatric melatonin use, to understand how caregivers' perceptions around melatonin are shaped by their illness/medication-related beliefs, treatment experience and preferences. A literature search was conducted across Embase, Medline, PsycINFO, PubMed and Scopus, generating 184 results for screening against the inclusion criteria. Nineteen studies were retrieved, comprising of 1561 children and adolescents, aged 8.7 ± 2.3 years (range: 0-44 years), conducted primarily in the United States of America (n = 6), Canada (n = 3) and the Netherlands (n = 3). Studies were evaluated for their study design and caregiver-centered outcomes, encompassing: 1) illness/treatment-related beliefs, 2) treatment satisfaction/effectiveness, 3) treatment preference/acceptability, and 4) impact of child's sleep disturbance on caregivers' quality-of-life. Sleep disturbances necessitating melatonin use occurred alongside congenital/neurodevelopmental comorbidities in 18 studies (95%). Melatonin was commonly associated with "naturalness" and "safety". Concepts of treatment satisfaction versus effectiveness were minimally differentiated within included studies. Caregivers preferred concurrent use of melatonin and behavioral interventions for management of their dependents' sleep. Improved sleep in the dependent generally led to better quality-of-life for caregivers and their family.

The impact of cannabis legalization and decriminalization on acute poisoning: A systematic review.

BACKGROUND AND AIMS: Many countries have recently legalized medicinal and recreational cannabis. With increasing use and access come the potential for harms. We aimed to examine the effect of cannabis legalization/decriminalization on acute poisoning. METHODS: A systematic review and meta-analysis registered with PROSPERO (CRD42022323437). We searched Embase, Medline, Scopus and Cochrane Central Register of Controlled Trials from inception to March 2022. No restrictions on language, age or geography were applied. Abstracts from three main clinical toxicology conferences were hand-searched. Included studies had to report on poisonings before and after changes in cannabis legislation, including legalization and decriminalization of medicinal and recreational cannabis. Where possible, relative risk (RR) of poisoning after legalization (versus before) was calculated and pooled. Risk of bias was assessed with ROBINS-I. RESULTS: Of the 1065 articles retrieved, 30 met inclusion criteria (including 10 conference abstracts). Studies used data from the United States, Canada and Thailand. Studies examined legalization of medicinal cannabis (n = 14) and decriminalization or legalization of recreational cannabis (n = 21). Common data sources included poisons centre records (n = 18) and hospital presentations/admissions (n = 15, individual studies could report multiple intervention types and multiple data sources). Most studies (n = 19) investigated paediatric poisoning. Most (n = 24) reported an increase in poisonings; however, the magnitude varied greatly. Twenty studies were included in quantitative analysis, with RRs ranging from 0.81 to 29.00. Our pooled estimate indicated an increase in poisoning after legalization [RR = 3.56, 95% confidence interval (CI) = 2.43-5.20], which was greater in studies that focused on paediatric patients (RR = 4.31, 95% CI = 2.30-8.07). CONCLUSIONS: Most studies on the effect of medicinal or recreational cannabis legalization/decriminalization on acute poisoning reported a rise in cannabis poisoning after legalization/decriminalization. Most evidence is from US legalization, despite legalization and decriminalization in many countries.

Clinical features of COVID-19 rapid antigen test exposures reported by an Australian poisons information centre: a prospective study.

INTRODUCTION: Coronavirus disease COVID-19 rapid antigen tests are a useful tool in detecting infection, and their use has increased in many countries since they became commercially available in late 2021. Some rapid antigen tests contain sodium azide, which can be toxic in small doses. This study aimed to describe the clinical characteristics of exposures to COVID-19 rapid antigen tests. METHODS: This is a prospective study conducted by the New South Wales Poisons Information Centre. From 22 January 2022 to 31 August 2022, rapid antigen test exposures were followed up to obtain outcome information. Data collected included: brand/ingredients, exposure route, demographics, symptoms, and disposition. RESULTS: We recorded 218 exposures in the seven-month study period. Complete follow-up information was available in 75% (n = 164). There were 53 exposures to sodium azide-containing products (35 with follow-up data) and 165 to non-sodium azide-containing products and unknown ingredient exposures (129 with follow-up data). Overall, unintentional exposures predominated (n = 182), and 151 were ingestions. The vast majority (>90%) did not develop symptoms, and all symptoms that developed were mild. Most cases (95%, n = 208) did not require referral to a healthcare facility. CONCLUSIONS: In this prospective series, few patients developed symptoms, regardless of the sodium azide content, likely due to low concentration and low volume within the test kits. However, ongoing toxicovigilance is warranted.

Psychotropic and other medicine use at time of death by suicide: a population-level analysis of linked dispensing and forensic toxicology data.

OBJECTIVES: To determine the numbers and types of medicines dispensed around the time of death to people who die by suicide; to compare the medicines recently dispensed and those recorded in post mortem toxicology reports. DESIGN, SETTING, PARTICIPANTS: Analysis of linked National Coronial Information System (NCIS) and Pharmaceutical Benefits Scheme (PBS) data from the Australian Suicide Prevention using Health Linked Data (ASHLi) study, a population-based case series study of closed coronial cases for deaths of people in Australia aged ten years or more during 1 July 2013 - 10 October 2019 deemed by coroners to be the result of intentional self-harm. MAIN OUTCOME MEASURES: Proportions of people to whom medicines were dispensed around the time of death, by medicine group, class, and specific medicine; comparison of medicines recently dispensed and those detected by post mortem toxicology. RESULTS: Toxicology reports were available for 13 541 of 14 206 people who died by suicide (95.3%; 10 246 men, 75.7%); poisoning with medicines contributed to 1163 deaths (8.6%). At least one PBS-subsidised medicine had been dispensed around the time of death to 7998 people (59.1%). For three medicine classes, the proportions of people in whom the medicines were detected post mortem and their death was deemed medicine-related were larger for those without records of recent dispensing than for people for whom they had been dispensed around the time of death: antidepressants (17.7% v 12.0%), anxiolytics (16.3% v 14.8%), and sedatives/hypnotics (24.3% v 16.5%). At least one recently dispensed medicine not detected post mortem was identified for 6208 people (45.8%). CONCLUSIONS: A considerable proportion of people who died by suicide were not taking psychotropic medicines recently dispensed to them, suggesting non-adherence to pharmacotherapy, and a smaller than expected proportion were using antidepressants. Conversely, medicines that had not recently been dispensed were detected post mortem in many people for whom poisoning with medicines was a contributing factor, suggesting medicine stockpiling.

Hospital admissions for paracetamol poisoning declined following codeine re-scheduling in Australia.

BACKGROUND: Codeine was restricted to prescription only in Australia in 2018. This intervention aimed to reduce harms from codeine dependance and use, including toxicity from co-formulated paracetamol. We aimed to quantify the impact of this intervention on paracetamol poisoning hospital admissions in a national hospital admissions database. METHODS: We analyzed the number of paracetamol overdoses resulting in hospital admissions from the Australian Institute of Health and Welfare National Hospital Morbidity Database, January 2011 to June 2020. We used interrupted time series analysis to quantify the effect of codeine re-scheduling on the monthly number of paracetamol poisoning-related hospital admissions in Australia. We compared paracetamol poisonings with no opioid combinations, and poisonings with probable paracetamol-codeine combinations. RESULTS: There was an immediate and sustained decrease (level shift) in the number of paracetamol poisoning-related hospital admissions following codeine re-scheduling (RR=0.85; 95% CI 0.80-0.89). This reduction was due to the decrease in poisonings with likely paracetamol-codeine combinations (RR=0.62; 95% CI 0.57-0.67) while there was no change in other paracetamol poisonings (RR=0.91; 95% CI 0.96-1.01). CONCLUSION: Codeine re-scheduling in Australia appears to have reduced paracetamol poisoning-related hospital admissions.

Hospitalised poisonings in Australian children: a 10-year retrospective study.

INTRODUCTION: Paediatric poisoning is a major cause of childhood injury, and most poisonings are preventable. We aimed to describe hospitalisations resulting from poisoning and envenomation in Australian children, including demographics, cause of the exposure, hospital length of stay, rates of intensive care unit admission and in-hospital deaths. We also aimed to describe risk factors for increased length of stay and intensive care unit admission. METHODS: A retrospective analysis was performed of hospitalised poisoning and envenomation cases of children (<15 years) in Australia from 1 July 2009 to 30 June 2019. A nationwide hospital admissions database was used for this study. RESULTS: During the 10-year study period 33,438 children were admitted to hospital due to a pharmaceutical or non-pharmaceutical poisoning/envenomation; an average of 74.8 cases per 100,000 population per year. Approximately 10 children were admitted to hospital each day for poisoning. Over 70% of these cases were due to pharmaceuticals (n = 23,628), most frequently non-opioid analgesics, anti-pyretics and anti-rheumatics (n = 8759, 37.1% of pharmaceutical exposures). The most common non-pharmaceutical exposure was contact with venomous animals and toxic plants (n = 4578, 46.7% of non-pharmaceuticals). Intentional self-harm occurred in 7833 (23.4%) of cases. Intensive care unit admission was required in 519 cases (2.5% of the 20,739 cases where this information was available), while 200 (0.96% of 20,739) needed ventilator support. Ten children (0.03%) died. Older age, female sex, poisoning with pharmaceuticals and metropolitan hospital location were associated with increased length of stay. Older age and poisoning with pharmaceuticals were also associated with intensive care unit admission. CONCLUSION: Approximately 10 children were admitted to hospital with poisoning every day in Australia. Most poisonings were due to pharmaceuticals, particularly simple analgesics that are found in most Australian homes. Severe outcomes (intensive care unit admissions and deaths) were rare.

Changes in medication regimen complexity index following medication-related hospital admissions: A retrospective single-centre study.

BACKGROUND: Medication-related hospitalisations present an opportunity for de-prescribing and simplification of medication regimens. The Medication Regimen Complexity Index (MRCI) is a tool for measuring the complexity of medication regimens. OBJECTIVES: To evaluate whether MRCI changes following medication-related hospitalisations, and to evaluate the relationship between MRCI, length of stay (LOS) in hospital, and patient characteristics. METHODS: A retrospective medical record review of patients admitted to a tertiary referral hospital in Australia for medication-related problems, January 2019 to August 2020. MRCI was calculated using pre-admission medication lists and discharge medication lists. RESULTS: There were 125 patients who met inclusion criteria. The median (IQR) age was 64.0 years (45.0-75.0) and 46.4% were female. Median MRCI decreased by 2.0 following hospitalisation: from median (IQR) 17.0 (7.0-34.5) on admission vs 15.0 (3.0-29.0) on discharge (p < 0.001). Admission MRCI predicted LOS ≥2 days (OR 1.03, 95%CI 1.00-1.05, p = 0.022). Allergic reaction-related hospitalisations were associated with lower admission MRCI. CONCLUSIONS: There was a decrease in MRCI following medication-related hospitalisation. Targeted medication reviews for high-risk patients (e.g., those with medication-related hospitalisations) could further reduce the burden of medication complexity following discharge from hospital and possibly prevent readmissions.

Poisonings with ADHD medication in children under the age of 5 years in Australia: a retrospective study, 2004-2019.

OBJECTIVE: To describe the temporal relationships in attention-deficit hyperactivity disorder (ADHD) medication poisoning exposures in children; describe patient demographics, medications involved, poisoning exposure reasons and disposition. DESIGN: A population-based, retrospective cohort study of calls to Australia's largest Poisons Information Centre. Poisoning exposure counts and dispensing-adjusted rates were modelled with Poisson, quasi-Poisson and negative binomial regression where appropriate. SETTING: Calls to the New South Wales Poisons Information Centre and dispensings on the Pharmaceutical Benefits Scheme. PATIENTS: Children under the age of 5 years. RESULTS: There were 1175 poisoning exposures to ADHD psychostimulants, 2004-2019; averaging 73 per year. Accidental poisonings accounted for 94% of cases. Methylphenidate was most frequently implicated (63%). Thirty-four per cent of cases were referred to hospital and a further 21% of calls were made by hospital staff. Poisoning exposure counts for all ADHD psychostimulants increased by 2.7% (95% CI=0.42% to 4.9%) per year; however, this differed by agent. Methylphenidate poisoning exposures increased by 5.2% per year (95% CI=4.3% to 6.1%), lisdexamfetamine increased by 62% per year (95% CI=48% to 76%), while dexamphetamine poisoning exposures decreased by 5.5% per year (95% CI=-9.5% to -1.4%). These trends are reflected in the number of dispensings; however, dispensings increased at a faster rate than exposures. When poisoning exposures were expressed as dispensing-adjusted rates, there was a 16% decrease (95% CI=-20% to -13%) per year. CONCLUSIONS: ADHD medication use has increased, associated with an increased number of paediatric poisoning exposures. However, poisoning exposures per dispensed prescription has decreased. The majority of cases required hospitalisation, indicating the need for further poisoning prevention strategies.

Prescribed medicine use and extent of off-label use according to age in a nationwide sample of Australian children.

BACKGROUND: Medicine prescribing for children is impacted by a lack of paediatric-specific dosing, efficacy and safety data for many medicines. OBJECTIVES: To estimate the prevalence of medicine use among children and the rate of 'off-label' prescribing according to age at dispensing. METHODS: We used population-wide primarily outpatient dispensing claims data for 15% of Australian children (0-17 years), 2013-2017 (n = 840,190). We estimated prescribed medicine use and 'off-label' medicine use according to the child's age (<1 year, 1-5 years, 6-11 years, 12-17 years) defined as medicines without age-appropriate dose recommendations in regulator-approved product information. Within off-label medicines, we also identified medicines with and without age-specific dose recommendations in a national prescribing guide, the Australian Medicines Handbook Children's Dosing Companion (AMH CDC). RESULTS: The overall dispensing rate was 2.0 dispensings per child per year. The medicines with the highest average yearly prevalence were systemic antibiotics (435.3 per 1000 children), greatest in children 1-5 years (546.9 per 1000). Other common medicine classes were systemic corticosteroids (92.7 per 1000), respiratory medicines (91.2 per 1000), acid-suppressing medicines in children <1 year (47.2 per 1000), antidepressants in children 12-17 years (40.3 per 1000) and psychostimulants in children 6-11 years (27.0 per 1000). We identified 12.2% of dispensings as off-label based on age, but 66.3% of these had age-specific dosing recommendations in the AMH CDC. Among children <1 year, off-label dispensings were commonly acid-suppressing medicines (35.5%) and topical hydrocortisone (33.1%); in children 6-11 years, off-label prescribing of clonidine (16.0%) and risperidone (13.1%) was common. Off-label dispensings were more likely to be prescribed by a specialist (21.7%) than on-label dispensings (7.5%). CONCLUSIONS: Prescribed medicine use is common in children, with off-label dispensings for medicines without paediatric-specific dosing guidelines concentrated in classes such as acid-suppressing medicines and psychotropics. Our findings highlight a need for better evidence to support best-practice prescribing.

Optimising alkalinisation and its effect on QRS narrowing in tricyclic antidepressant poisoning.

AIMS: The objectives were to determine the effect of NaHCO3 and/or mechanical ventilation on the biochemical profile and serum alkalinisation in tricyclic antidepressant (TCA) poisoning and investigate the impact of effective alkalinisation therapy on the QRS interval in TCA poisoning. METHODS: This was a retrospective review of TCA poisonings from three Australian toxicology units and a poisons information centre (Jan 2013 to Jan 2019). We included patients with TCA toxicity who ingested>10 mg/kg or had clinically significant toxicities consistent with TCA poisoning, and analysed patients' clinical, electrocardiogram and biochemical data. RESULTS: Of 210 patients, 84 received NaHCO3 and ventilation (dual therapy), 12 NaHCO3 , 46 ventilation and 68 supportive care treatment. When compared with single/supportive groups, patients who received dual therapy had taken a significantly higher median dose of TCA (1.5 g vs1.3 g, P < .001), a longer median maximum QRS interval (124 ms, interquartile ranges [IQR] 108-138 vs106 ms, IQR 98-115, P < .001) and were more likely to have seizures (14% vs3%, P = .006) and arrhythmias (17% vs1%, P < .001). The dual therapy group demonstrated greater increases in serum pH (median 0.11, IQR 0.04-0.17) compared to the single/supportive therapy group (median 0.03, IQR -0.01-0.09, p < .001). A greater proportion of patients reached the target pH 7.45-7.55 in the dual therapy group (59%) compared to the single/supportive therapy group (10%) (P < .001). For each 100 mmol bolus of NaHCO3 given, the median increase in serum sodium was 2.5 mmol/L (IQR 1.5-4.0). QRS narrowing occurred twice as quickly in the dual therapy vs single/supportive therapy group. CONCLUSIONS: A combination of NaHCO3 and mechanical ventilation was most effective in achieving serum alkalinisation and was associated with a more rapid narrowing of the QRS interval. We advise that the maximal dose of NaHCO3 should be <400 mmol (6 mmol/kg).