Choosing wisely? Quantifying the extent of three low value psychotropic prescribing practices in Australia

Background: The global Choosing Wisely campaign has identified the following psychotropic prescribing as low-value (harmful or wasteful): (1) benzodiazepine use in the elderly, (2) antipsychotic use in dementia and (3) prescribing two or more antipsychotics concurrently. We aimed to quantify the extent of these prescribing practices in the Australian population. Methods: We applied indicators to dispensing claims of a 10% random sample of Australian Pharmaceutical Benefits Scheme beneficiaries to quantify annual rates of each low-value practice from 2013 to 2016. We also assessed patient factors and direct medicine costs (extrapolated to the entire Australian population) associated with each practice in 2016. Results: We observed little change in the rates of the three practices between 2013 and 2016. In 2016, 15.3% of people aged ≥65 years were prescribed a benzodiazepine, 0.5% were prescribed antipsychotics in the context of dementia and 0.2% of people aged ≥18 years received two or more antipsychotics concurrently. The likelihood of elderly people receiving benzodiazepines or antipsychotics in the context of dementia increased with age and the likelihood of receiving all three practices increased with comorbidity burden. In 2016, direct medicine costs to the government of all three practices combined, extrapolated to national figures, were > $21 million AUD. Conclusions: Our indicators suggest that the frequency of these three practices has not changed appreciably in recent years and that they incur significant costs. Worryingly, people with the greatest risk of harm from these prescribing practices are often the most likely to receive them

Trends in opioid utilisation in Australia, 2006-2015: Insights from multiple metrics

Purpose: Population-based observational studies have documented global increases in opioid analgesic use. Many studies have used a single population-adjusted metric (number of dispensings, defined daily doses [DDDs], or oral morphine equivalents [OMEs]). We combine these volume-based metrics with a measure of the number of persons dispensed opioids to gain insights into Australian trends in prescribed opioid use. Methods: We obtained records of prescribed opioid dispensings (2006-2015) subsidised under Australia's Pharmaceutical Benefits Scheme. We used dispensing claims to quantify annual changes in use according to 3 volume-based metrics: DDD/1000 pop/day, OME/1000 pop/day, and dispensings/1000 pop. We estimated the number of persons dispensed at least one opioid in a given year (persons)/1000 pop using data from a 10% random sample of Pharmaceutical Benefits Scheme-eligible Australians. Results: Total opioid use increased according to all metrics, especially OME/1000 pop/day (51% increase) and dispensings/1000 pop (44%). Weaker opioid use remained stable or declined; strong opioid use increased. The rate of persons accessing weaker opioids only decreased 31%, and there was a 238% increase in persons dispensed only strong opioids. Strong opioid use also increased according to dispensings/1000 pop (140%), OME/1000 pop/day (80%), and DDD/1000 pop/day (71% increase). Conclusions: Our results suggest that the increases in total opioid use between 2006 and 2015 were predominantly driven by a growing number of people treated with strong opioids at lower medicine strengths/doses. This method can be used with or without person-level data to provide insights into factors driving changes in medicine use over time

Activated prothrombin complex in the management of direct thrombin inhibitor-associated intracerebral haemorrhage.

Intracerebral haematoma expansion independently predicts poor functional outcome and mortality. Therefore, it is important to act quickly to arrest this expansion. Whilst a direct antidote to dabigatran remains in development, the use of factor VIII inhibitor bypassing activity may offer a practical strategy for arresting haemorrhage in individuals taking direct thrombin inhibitors.NRE is supported by a Research Training Fellowship from The Dunhill Medical Trust [grant number RTF44/0114].This is the author accepted manuscript. The final version is available from Oxford University Press at http://dx.doi.org/10.1093/qjmed/hcv219

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

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

Trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia (2003–2015)

Introduction: Fentanyl-related overdose is an ongoing concern among countries with high prescription opioid utilisation. This study examines trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia between 2003 and 2015, overall, and by age/sex. Methods: This was a retrospective nationwide study of prescription dispensings and coronial records. Transdermal fentanyl utilisation was examined using Pharmaceutical Benefits Scheme dispensing records. Details of fatal fentanyl overdoses were extracted from the National Coronial Information System. Results: Transdermal fentanyl utilisation increased 5.1-fold between 2003 and 2015, from 0.28 to 1.39 mg/1000 population/day and was consistently higher among females and adults aged ≥85 years. The utilisation of higher strength patches (75 and 100 mcg/h) was more common among males aged 25–44 years. A total of 291 fatal fentanyl overdoses were recorded, increasing from no recorded deaths in 2003 to 2.23 deaths/1 000 000 population in 2015. Rates were higher among males (increasing from 0 to 3.72 deaths/1 000 000 population) and for adults aged 25–44 years (increasing from 0 to 5.34 deaths/1 000 000 population). The number of deaths/kg fentanyl dispensed was highest among males aged <25 years (45.45, 95% confidence interval 21.80–83.59). Most deaths (70.1%) involved the intravenous administration of fentanyl from transdermal patches. Discussion and Conclusions: Rates of transdermal fentanyl utilisation and fatal fentanyl overdose across Australia increased between 2003 and 2015. Although transdermal fentanyl utilisation was consistently greater among females and older adults, rates of fatal fentanyl overdose were highest among younger males. Interventions to reduce extramedical use among this high-risk population group are necessary to minimise fentanyl-related harms

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Salbutamol in acute organophosphorus insecticide poisoning - a pilotdose-response phase II study

Treatment of acute organophosphorus (OP) insecticide poisoning is difficult, with many patients dying despite best care. Pre-clinical studies have shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or reducing bronchoconstriction. In this small pilot dose-response study, we aimed to explore whether addition of nebulized salbutamol to standard care might improve resuscitation.We performed a single-blind phase II study comparing the effect of two different doses of nebulized salbutamol versus saline placebo, in addition to standard treatment. Primary outcome was oxygen saturations over the first 60 min of resuscitation; secondary outcomes included heart rate, incidence of dysrhythmias, time to 'atropinization', atropine dose required, and mortality.Seventy-five patients were randomized to receive 5 mg (Salb5, n = 25) or 2.5mg (Salb2.5, n = 25) of salbutamol, or saline placebo (NoSalb, n = 25), by nebulizer. Oxygen saturations did not differ between groups over the first 60 min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to 1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p = .9898). Heart rate was also similar across the three arms. Median time to full atropinization, and atropine dose required, were the same for all three arms (NoSalb 15.0 [10-16] min and 12.6 [8.0-13.4] mg, Salb2.5 15.0 [10-16] min and 12.6 [9.3-16.8] mg, and Salb5 15.0 [10-20] min and 12.6 [10.7-20.6] mg; p = .4805 and p = .1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5 groups and two (8%) in the NoSalb group.This pilot study, within the limitations of its small size and variation between patients, found no apparent evidence that administration of nebulized salbutamol improved resuscitation of patients with acute OP insecticide self-poisoning. The data obtained provides a basis to design further studies to ultimately test the role of salbutamol in OP insecticide poisoning

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods:Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours

The sinus tarsi approach in displaced intra-articular calcaneal fractures: a systematic review

Purpose: Although open reduction and internal fixation is currently considered the gold standard in surgical treatment of displaced intra-articular calcaneal fractures, various different approaches exist including the limited lateral approach. The aim of this systematic review was to combine the results of studies using the sinus tarsi approach, which is the most frequently applied limited lateral approach. Method: A literature search in the electronic databases of the Cochrane Library and Pubmed Medline, between January 1st 2000 to December 1st 2010, was conducted to identify studies in which the sinus tarsi approach or a modified sinus tarsi approach was utilized for the treatment of displaced intra-articular calcaneal fractures. The methodological quality of the included studies was assessed using the Coleman methodology score. Results: A total of eight case series reporting on 256 patients with 271 calcaneal fractures was identified. Overall good to excellent outcome was reached in three-quarters of all patients. An average complication rate of minor wound complications of 4.1% was reported and major wound complications in 0.7%. The need for a secondary subtalar arthrodesis occurred at an average rate of 4.3%. The average Coleman methodology score was 56.8 (range 39-72) points. Conclusion: The results, i.e. functional outcome and complication rates, of the sinus tarsi approach compare similarly or favourably to the extended lateral approach. Therefore, in the process of tailoring the best treatment modality to the right patient and the right fracture type, the sinus tarsi approach might be a valuable asset