Impact of coordinated care on adherence to antihypertensive medicines among adults experiencing polypharmacy in Australia.

BACKGROUND: Adherence to antihypertensives is key for blood pressure control. Most people with hypertension have several comorbidities and require multiple medicines, leading to complex care pathways. Strategies for coordinating medicine use can improve adherence, but cumulative benefits of multiple strategies are unknown. METHODS: Using dispensing claims for a 10% sample of eligible Australians, we identified adult users of antihypertensives during July 2018-June 2019 who experienced polypharmacy (≥5 unique medicines). We measured medicine use reflecting coordinated medicine management in 3 months before and including first observed dispensing, including: use of simple regimens for each cardiovascular medicine; prescriber continuity; and coordination of dispensings at the pharmacy. We measured adherence (proportion of days covered) to antihypertensive medicines in the following 12 months, and used logistic regression to assess independent associations and interactions of adherence with these measures of care. RESULTS: We identified 202 708 people, of which two-thirds (66.6%) had simple cardiovascular medicine regimens (one tablet per day for each medicine), two-thirds (63.3%) were prescribed >75% of medicines from the same prescriber, and two-thirds (65.5%) filled >50% of their medicine on the same day. One-third (28.4%) of people experienced all three measures of coordinated care. Although all measures were significantly associated with higher adherence, adherence was greatest among people experiencing all three measures (odds ratio = 1.63; 95% confidence interval: 1.55-1.72). This interaction was driven primarily by effects of prescriber continuity and dispensing coordination. CONCLUSIONS: Coordinating both prescribing and dispensing of medicines can improve adherence to antihypertensives, which supports strategies consolidating both prescribing and supply of patients' medicines.

Common pitfalls in the use of hypertonic sodium bicarbonate for cardiac toxic drug poisonings.

BACKGROUND: Hypertonic sodium bicarbonate is advocated for the treatment of sodium channel blocker poisoning, but its efficacy varies amongst different sodium channel blockers. This Commentary addresses common pitfalls and appropriate usage of hypertonic sodium bicarbonate therapy in cardiotoxic drug poisonings. SODIUM BICARBONATE WORKS SYNERGISTICALLY WITH HYPERVENTILATION: Serum alkalinization is best achieved by the synergistic effect of hypertonic sodium bicarbonate and hyperventilation (PCO2 ∼ 30-35 mmHg [0.47-0.6 kPa]). This reduces the dose of sodium bicarbonate required to achieve serum alkalinization (pH ∼ 7.45-7.55) and avoids adverse effects from excessive doses of hypertonic sodium bicarbonate. VARIABILITY IN RESPONSE TO SODIUM BICARBONATE TREATMENT: Tricyclic antidepressant poisoning responds well to sodium bicarbonate therapy, but many other sodium channel blockers may not. For instance, drugs that block the intercellular gap junctions, such as bupropion, do not respond well to alkalinization. For sodium channel blocker poisonings in which the expected response is unknown, a bolus of 1-2 mmol/kg sodium bicarbonate can be used to assess the response to alkalinization. SODIUM BICARBONATE CAN EXACERBATE TOXICITY FROM DRUGS ACTING ON MULTIPLE CARDIAC CHANNELS: Hypertonic sodium bicarbonate can cause electrolyte abnormalities such as hypokalaemia and hypocalcaemia, leading to QT interval prolongation and torsade de pointes in poisonings with drugs that have mixed sodium and potassium cardiac channel properties, such as hydroxychloroquine and flecainide. THE GOAL FOR HYPERTONIC SODIUM BICARBONATE IS TO ACHIEVE THE ALKALINIZATION TARGET (∼PH 7.5), NOT COMPLETE CORRECTION OF QRS COMPLEX PROLONGATION: Excessive doses of hypertonic sodium bicarbonate commonly occur if it is administered until the QRS complex duration is < 100 ms. A prolonged QRS complex duration is not specific for sodium channel blocker toxicity. Some sodium channel blockers do not respond, and even when there is a response, it takes a few hours for the QRS complex duration to return completely to normal. In addition, QRS complex prolongation can be due to a rate-dependent bundle branch block. So, no further doses should be given after achieving serum alkalinization (pH ∼ 7.45-7.55). MAXIMAL DOSING FOR HYPERTONIC SODIUM BICARBONATE: A further strategy to avoid overdosing patients with hypertonic sodium bicarbonate is to set maximum doses. Exceeding 6 mmol/kg is likely to cause hypernatremia, fluid overload, metabolic alkalosis, and cerebral oedema in many patients and potentially be lethal. RECOMMENDATION FOR THE USE OF HYPERTONIC SODIUM BICARBONATE IN SODIUM CHANNEL BLOCKER POISONING: We propose that hypertonic sodium bicarbonate therapy be used in patients with sodium channel blocker poisoning who have clinically significant toxicities such as seizures, shock (systolic blood pressure < 90 mmHg, mean arterial pressure <65 mmHg) or ventricular dysrhythmia. We recommend initial bolus dosing of hypertonic sodium bicarbonate of 1-2 mmol/kg, which can be repeated if the patient remains unstable, up to a maximum dose of 6 mmol/kg. This is recommended to be administered in conjunction with mechanical ventilation and hyperventilation to achieve serum alkalinization (PCO2∼30-35 mmHg [4-4.7 kPa]) and a pH of ∼7.45-7.55. With repeated bolus doses of hypertonic sodium bicarbonate, it is imperative to monitor and correct potassium and sodium abnormalities and observe changes in serum pH and on the electrocardiogram. CONCLUSIONS: Hypertonic sodium bicarbonate is an effective antidote for certain sodium channel blocker poisonings, such as tricyclic antidepressants, and when used in appropriate dosing, it works synergistically with hyperventilation to achieve serum alkalinization and to reduce sodium channel blockade. However, there are many pitfalls that can lead to excessive sodium bicarbonate therapy and severe adverse effects.

The impact of tightened prescribing restrictions for PBS-subsidised opioid medicines and the introduction of half-pack sizes, Australia, 2020-21: an interrupted time series analysis.

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.

Correction: Neonatal blood lead concentration predicts medium term lead-related outcomes in children ≤5 years old with congenital lead poisoning: A retrospective cohort study in Northern Nigeria.

[This corrects the article DOI: 10.1371/journal.pgph.0001644.].

Quality use of publicly subsidised tapentadol in Australia: a population-based analysis.

BACKGROUND: Sustained-release (SR) tapentadol was listed on Australia's Pharmaceutical Benefits Scheme (PBS) in 2014 for chronic severe pain requiring long-term opioid treatment. Dispensings have increased since listing despite declining trends in other PBS-listed opioids. Preferential prescribing of SR opioids may increase the risk of dependence and accidental overdose, particularly when used to treat acute pain. AIMS: To explore the quality use of publicly subsidised tapentadol in Australia. METHODS: We examined annual initiation rates and patterns of use of tapentadol (SR) in the dispensing records of a 10% random sample of PBS-eligible Australians (2014-2021). We used national tapentadol sales data to assess the proportion of sales attributable to the PBS. RESULTS: Tapentadol initiation increased from 2014, peaking at 7.5/1000 adult population in 2019 before declining to 5.3/1000 in 2021. We identified 63 766 new users between 2014 and 2020, of whom 92.8% discontinued in the first year following initiation, 58.0% had only a single dispensing and 34.3% had no other opioids dispensed in the 3 months before or after initiation. 27.8% of new users were dispensed tapentadol on the same day as potentially interacting medicines. There was a sustained drop in the proportion of sales attributable to the PBS from June 2020 onwards, from an average of 69.1%, to 63.9% of pack sales. CONCLUSIONS: Patterns of use suggest tapentadol (SR) is generally used for short duration. Although most tapentadol sold in Australia is subsidised, there is evidence of a shift towards private sales.

On- and off-label utilisation of antipsychotics in Australia (2000-2021): Retrospective analysis of two medication datasets.

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.

Intestinal injury in paracetamol overdose (ATOM-8).

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.

Measurement of an intestinal biomarker during poisonings from select toxicants and toxins.

INTRODUCTION: Intestinal toxicity can occur following ingestion of various drugs, chemicals, and toxins. Intestinal fatty acid binding protein is a cytosolic protein specific to intestinal epithelial cells released into the systemic circulation following intestinal injury. Understanding intestinal toxicity in poisoning has the potential to explain mechanisms of toxicity and gastrointestinal symptoms. METHODS: Plasma samples were retrospectively analysed for intestinal fatty acid binding protein in 25 healthy controls and in those poisoned with Gloriosa superba (n = 18), Thevetia peruviana (n = 26), organophosphates (in various solvents) (n = 17), paracetamol (n = 14), glyphosate (n = 20), 2-methyl-4-chlorophenoxyacetic acid (n = 18) and propanil (n = 19). RESULTS: Median peak plasma intestinal fatty acid binding protein concentrations were significantly higher in patients poisoned with Gloriosa superba (2,994.1 µg/L; interquartile range 600.0-5,158.2, P < 0.001), Thevetia peruviana (1,292.5 µg/L; interquartile range 760.3 - 2,076.2; P < 0.001), glyphosate (1,803.6 µg/L; interquartile range 225.7-8,927.7; P < 0.001), 2-methyl-4-chlorophenoxyacetic acid (1,236.2 µg/L; interquartile range 192.6 - 1,709.7; P = 0.010), paracetamol (1,066.5 µg/L; interquartile range 512.9 - 1,336.9; P = 0.035), and organophosphate poisoning (729.8 µg/L; interquartile range 431.5 - 1,588.2; P = 0.046) than in healthy controls (221.6 µg/L; interquartile range 134.8 - 460.1). Median intestinal fatty acid binding protein was not statistically significantly increased compared to controls after propanil poisoning (630.0 µg/L; interquartile range 23.5 - 1,390.3; P = 0.423). CONCLUSIONS: Our pilot study describes intestinal injury assessed by elevated plasma intestinal fatty acid binding protein concentrations following the ingestion of several poisons. This serves as a foundation for further exploration into enterocyte damage in toxicology.

Five healthcare trajectories in the year before suicide and what they tell us about opportunities for prevention: a population-level case series study.

Background: Suicide prevention requires a shift from relying on an at-risk individual to engage with the healthcare system. Understanding patterns of healthcare engagement by people who have died by suicide may provide alternative directions for suicide prevention. Methods: This is a population-based case-series study of all suicide decedents (n = 3895) in New South Wales (NSW), Australia (2013-2019), with linked coronial, health services and medicine dispensing data. Healthcare trajectories were identified using a k-means longitudinal 3d analysis, based on the number and type of healthcare contacts in the year before death. Characteristics of each trajectory were described. Findings: Five trajectories of healthcare utilisation were identified: (A) none or low (n = 2598, 66.7%), (B) moderate, predominantly for physical health (n = 601, 15.4%), (C) moderate, with high mental health medicine use (n = 397, 10.2%), (D) high, predominantly for physical health (n = 206, 5.3%) and E) high, predominantly for mental health (n = 93, 2.4%). Given that most decedents belonged to Trajectory A this suggests a great need for suicide preventive interventions delivered in the community, workplace, schools or online. Trajectories B and D might benefit from opioid dispensing limits and access to psychological pain management. Trajectory C had high mental health medicine use, indicating that the time that medicines are prescribed or dispensed are important touchpoints. Trajectory E had high mental health service predominantly delivered by psychiatrists and community mental health, but limited psychologist use. Interpretation: Although most suicide decedents made at least one healthcare contact in the year before death, contact frequency was overall very low. Given the characteristics of this group, useful access points for such intervention could be delivered through schools and workplaces, with a focus on alcohol and drug intervention alongide suicide awareness. Funding: Australia's National Health and Medical Research Council.

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.

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.

Community-based alcohol education intervention (THEATRE) study to reduce harmful effects of alcohol in rural Sri Lanka: design and adaptation of a mixed-methods stepped wedge cluster randomised control trial.

INTRODUCTION: Alcohol consumption is a leading cause of mortality, morbidity and adverse social sequelae in Sri Lanka. Effective community-based, culturally adapted or context-specific interventions are required to minimise these harms. We designed a mixed-methods stepped wedge cluster randomised control trial of a complex alcohol intervention. This paper describes the initial trial protocol and subsequent modifications following COVID-19. METHODS AND ANALYSIS: We aimed to recruit 20 villages (approximately n=4000) in rural Sri Lanka. The proposed intervention consisted of health screening clinics, alcohol brief intervention, participatory drama, film, and public health promotion materials to be delivered over 12 weeks.Following disruptions to the trial resulting from the Easter bombings in 2019, COVID-19 and a national financial crisis, we adapted the study in two main ways. First, the interventions were reconfigured for hybrid delivery. Second, a rolling pre-post study evaluating changes in alcohol use, mental health, social capital and financial stress as the primary outcome and implementation and ex-ante economic analysis as secondary outcomes. ETHICS AND DISSEMINATION: The original study and amendments have been reviewed and granted ethical approval by Rajarata University of Sri Lanka (ERC/2018/21-July 2018 and February 2022) and the University of Sydney (2019/006). Findings will be disseminated locally in collaboration with the community and stakeholders.The new hybrid approach may be more adaptable, scalable and generalisable than the planned intervention. The changes will allow a closer assessment of individual interventions while enabling the evaluation of this discontinuous event through a naturalistic trial design. This may assist other researchers facing similar disruptions to community-based studies. TRIAL REGISTRATION: The trial is registered with the Sri Lanka Clinical Trials Registry; https://slctr.lk/trials/slctr-2018-037.

Patterns of suboptimal antipsychotic use and misuse in Australia: What can routinely collected data tell us?

AIMS: There are increasing concerns about harms related to suboptimal antipsychotic use. Here we describe recent population-based trends in antipsychotic use and harms in Australia and identify population groups exhibiting patterns of use likely to contribute to these harms. METHODS: Using population-based data from the Australian Pharmaceutical Benefits Scheme (2015-2020), poisoning calls to the New South Wales (NSW) Poisons Information Centre (2015-2020) and poisoning deaths in all coronial records (2005-2018) in Australia, we measured trends in the prevalence of antipsychotic use and related deaths and poisonings. We applied latent class analyses to identify patterns of antipsychotic use that may contribute to harms. RESULTS: Quetiapine and olanzapine had the highest prevalence of use between 2015 and 2020. Noteworthy trends included increases of 9.1% and 30.8% in quetiapine use and poisonings, while olanzapine use decreased by 4.5% but poisonings increased by 32.7%. Quetiapine and olanzapine poisonings and related deaths had the highest rates of co-ingestion of opioids, benzodiazepines and pregabalin compared to other antipsychotics. We identified six distinct population groups using antipsychotics: (i) ongoing high-dose use with sedatives (8%), (ii) ongoing use (42%), (iii) ongoing use with analgesics and sedatives (11%), (iv) long-term low-dose use (9%), (v) sporadic use (20%) and (vi) sporadic use with analgesics (10%). CONCLUSION: Ongoing potentially suboptimal antipsychotic use and associated harms highlight the need to monitor such patterns of use, for example through prescription monitoring systems.

Persistence and Adherence to Cardiovascular Medicines in Australia.

Background The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. Methods and Results Using national dispensing claims for a 10% random sample of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60-day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one-fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins; 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one-third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. Conclusions Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence.

Opioid prescribing patterns among medical practitioners in New South Wales, Australia.

INTRODUCTION: Prescriber behaviour is important for understanding opioid use patterns. We described variations in practitioner-level opioid prescribing in New South Wales, Australia (2013-2018). METHODS: We quantified opioid prescribing patterns among medical practitioners using population-level dispensing claims data, and used partitioning around medoids to identify clusters of practitioners who prescribe opioids based on prescribing patterns and patient characteristics identified from linked dispensing claims, hospitalisations and mortality data. RESULTS: The number of opioid prescribers ranged from 20,179 in 2013 to 23,408 in 2018. The top 1% of practitioners prescribed 15% of all oral morphine equivalent (OME) milligrams dispensed annually, with a median of 1382 OME grams (interquartile range [IQR], 1234-1654) per practitioner; the bottom 50% prescribed 1% of OMEs dispensed, with a median of 0.9 OME grams (IQR 0.2-2.6). Based on 63.6% of practitioners with ≥10 patients filling opioid prescriptions in 2018, we identified four distinct practitioner clusters. The largest cluster prescribed multiple analgesic medicines for older patients (23.7% of practitioners) accounted for 76.7% of all OMEs dispensed and comprised 93.0% of the top 1% of practitioners by opioid volume dispensed. The cluster prescribing analgesics for younger patients with high rates of surgery (18.7% of practitioners) prescribed only 1.6% of OMEs. The remaining two clusters comprised 21.2% of prescribers and 20.9% of OMEs dispensed. DISCUSSION AND CONCLUSION: We observed substantial variation in opioid prescribing among practitioners, clustered around four general patterns. We did not assess appropriateness but some prescribing patterns are concerning. Our findings provide insights for targeted interventions to curb potentially harmful practices.

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.

A Comparison of Inertial Measurement Units and Overnight Videography to Assess Sleep Biomechanics.

PURPOSE: The assessment of sleep biomechanics (comprising movement and position during sleep) is of interest in a wide variety of clinical and research settings. However, there is no standard method by which sleep biomechanics are measured. This study aimed to (1) compare the intra- and inter-rater reliability of the current clinical standard, manually coded overnight videography, and (2) compare sleep position recorded using overnight videography to sleep position recorded using the XSENS DOT wearable sensor platform. METHODS: Ten healthy adult volunteers slept for one night with XSENS DOT units in situ (on their chest, pelvis, and left and right thighs), with three infrared video cameras recording concurrently. Ten clips per participant were edited from the video. Sleeping position in each clip was coded by six experienced allied health professionals using the novel Body Orientation During Sleep (BODS) Framework, comprising 12 sections in a 360-degree circle. Intra-rater reliability was assessed by calculating the differences between the BODS ratings from repeated clips and the percentage who were rated with a maximum of one section of the XSENS DOT value; the same methodology was used to establish the level of agreement between the XSENS DOT and allied health professional ratings of overnight videography. Bennett's S-Score was used to assess inter-rater reliability. RESULTS: High intra-rater reliability (90% of ratings with maximum difference of one section) and moderate inter-rater reliability (Bennett's S-Score 0.466 to 0.632) were demonstrated in the BODS ratings. The raters demonstrated high levels of agreement overall with the XSENS DOT platform, with 90% of ratings from allied health raters being within the range of at least 1 section of the BODS (as compared to the corresponding XSENS DOT produced rating). CONCLUSIONS: The current clinical standard for assessing sleep biomechanics, manually rated overnight videography (as rated using the BODS Framework) demonstrated acceptable intra- and inter-rater reliability. Further, the XSENS DOT platform demonstrated satisfactory levels of agreement as compared to the current clinical standard, providing confidence for its use in future studies of sleep biomechanics.

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.