The crux of the matter: did the ABC's Catalyst program change statin use in Australia?

This article argues that the ABC’s Catalyst program criticising statins affected people’s willingness to take these drugs. Abstract Objectives: To examine the impact of a two-part special edition of the Australian Broadcasting Corporation\u27s science journalism program Catalyst (titled Heart of the matter), aired in October 2013, that was critical of HMG-CoA reductase inhibitors (“statins”). Design, setting and participants: Population-based interrupted time-series analysis of a 10% sample of Australian long-term concessional beneficiaries who were dispensed statins under the Pharmaceutical Benefits Scheme (about 51% of all people who were dispensed a statin between 1 July 2009 and 30 June 2014); dispensing of proton pump inhibitors (PPIs) was used as a comparator. Main outcome measures: Change in weekly dispensings and discontinuation of use of statins and PPIs, adjusting for seasonal and long-term trends, overall and (for statins only) stratified by the use of cardiovascular and diabetes medicines. Results: In our sample, 191 833 people were dispensed an average of 26 946 statins weekly. Following the Catalyst program, there was a 2.60% (95% CI, 1.40%–3.77%; P < 0.001) reduction in statin dispensing, equivalent to 14 005 fewer dispensings Australia-wide every week. Dispensing decreased by 6.03% (95% CI, 3.73%–8.28%; P < 0.001) for people not dispensed other cardiovascular and diabetes medicines and 1.94% (0.42%–3.45%; P = 0.01) for those dispensed diabetes medicines. In the week the Catalyst program aired, there was a 28.8% (95% CI, 15.4%–43.7%; P < 0.001) increase in discontinuation of statin use, which decayed by 9% per week. An estimated 28 784 additional Australians ceased statin treatment. Discontinuation occurred regardless of the use of other cardiovascular and diabetes medicines. There were no significant changes in PPI use after the Catalyst program. Conclusions: Following airing of the Catalyst program, there was a temporary increase in discontinuation and a sustained decrease in overall statin dispensing. Up until 30 June 2014, there were 504 180 fewer dispensings of statins, and we estimate this to have affected 60 897 people

2-methyl-4-chlorophenoxyacetic acid and bromoxynil herbicide death.

CASE REPORT: We report a fatal case of a 37 year old gentleman who ingested a MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial examination, our patient declined dramatically over his 18 h admission with increasing CO2 production, hyperthermia and metabolic derangement to eventually die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA concentration was 83.9 μg/mL and bromoxynil concentration was 137 μg/mL. DISCUSSION: The patients' mechanism of death appeared to be uncoupling of oxidative phosphorylation, excess CO2 production and hyperthermia. There is limited knowledge on the acute toxicity of these herbicides, in particular bromoxynil, and this case highlights the relentless progression of severe toxicity in humans.The collaboration was supported by an NHMRC Program Grant (1055176). Geoff Isbister is supported by an NHMRC Senior Research Fellowship ID 1061041 and Mike Roberts is supported by an NHMRC Senior Principal Research Fellowship ID 1002611

Does Restricting Pack Size of Paracetamol (Acetaminophen) Reduce Suicides?

The authors discuss a new study that examined the change in deaths attributed to paracetamol poisoning in England and Wales in the six years before and after a legislated reduction in the maximum pack size

A decade of Australian methotrexate dosing errors

"OBJECTIVE: Accidental daily dosing of methotrexate can result in life-threatening toxicity. We investigated methotrexate dosing errors reported to the National Coronial Information System (NCIS), the Therapeutic Goods Administration Database of Adverse Event Notifications (TGA DAEN) and Australian Poisons Information Centres (PICs). DESIGN AND SETTING: A retrospective review of coronial cases in the NCIS (2000-2014), and of reports to the TGA DAEN (2004-2014) and Australian PICs (2004-2015). Cases were included if dosing errors were accidental, with evidence of daily dosing on at least 3 consecutive days. MAIN OUTCOME MEASURES: Events per year, dose, consecutive days of methotrexate administration, reasons for the error, clinical features. RESULTS: Twenty-two deaths linked with methotrexate were identified in the NCIS, including seven cases in which erroneous daily dosing was documented. Methotrexate medication error was listed in ten cases in the DAEN, including two deaths. Australian PIC databases contained 92 cases, with a worrying increase seen during 2014-2015. Reasons for the errors included patient misunderstanding and incorrect packaging of dosette packs by pharmacists. The recorded clinical effects of daily dosage were consistent with those previously reported for methotrexate toxicity. CONCLUSION: Dosing errors with methotrexate can be lethal and continue to occur despite a number of safety initiatives in the past decade. Further strategies to reduce these preventable harms need to be implemented and evaluated. Recent suggestions include further changes in packet size, mandatory weekly dosing labelling on packaging, improving education, and including alerts in prescribing and dispensing software."NHMRC Program Grant: 105517

Opioid use and harms associated with a sustained-release tapentadol formulation: a postmarketing study protocol

Introduction It has been argued that tapentadol may pharmacologically have lower abuse potential than other pharmaceutical opioids currently available. However, there has been no comprehensive triangulation of data regarding use and harms associated with this formulation. A sustained-release formulation (SRF) of tapentadol (Palexia) was released in Australia in 2011 and listed for public subsidy in 2013. We summarise here the methods of a postmarketing study which will measure postintroduction: (1) population level availability, (2) extramedical use and diversion, (3) attractiveness for extramedical use and (4) associated harms, of tapentadol compared against other pharmaceutical opioids. Methods and analysis We evaluated key sources on pharmaceutical use and harms in Australia. This review indicateddata from four sources that disaggregate pharmaceutical opioid formulations and capture tapentadol SRF could be triangulated. These data sources comprised: (1) national pharmaceutical opioid community sales data from 2011 to 2017, (2) national pharmaceutical opioid poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3) number of vendors on online marketplaces listing pharmaceutical opioids for sale and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms from interviews with people who regularly inject drugs in Australia. Ethics and dissemination Ethics approval is not required for use of pharmaceutical sales data. Ethics approval has been obtained for use of national pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace data and interview data from people who inject drugs (HC12086). Key findings will be published mid-2018 in a peer-reviewed academic journal, and presented at various conferences and professional meetings.This work was supported by investigator-initiated untied educational funding from Seqirus Pty Ltd (the marketer of tapentadol SRF in Australia) granted to AP, BL, MF, RC, and LD. BL, AP and LD are supported by NHMRC research fellowships (#1073858, #1109366 and #1041472). The National Drug and Alcohol Research Centre at UNSW Australia is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund

Discontinuities and disruptions in drug dosage guidelines for the paediatric population

AIMSThis study investigates paediatric drug dosage guidelines withthe aim of investigating their agreement with body surface area(BSA) scaling principles.METHODSA total of 454 drug dosage guidelines listed in the AMH-CDC 2015 were examined. Data extracted included the administration,frequency and dose per age bracket from 0 to 18 years. Drug treatments were categorized as follows: (1) The same dose rec-ommendation in milligrams per kilogram (mg kg 1) for all age/weights; (2) Change in the mg kg 1dosing according toage/weight; (3) Change in dose in mg according to age/weight; (4) Change from mg kg 1dosing to a dose in mg according toage/weight; (5) The same recommendation for all age/weight groups in mg; or (6) BSA dosing. Example drugs were selected toillustrate dose progression across ages.RESULTSMost drug treatments (63%) have the same mg kg 1dose for all age/weight groups, 14% are dosed in mg kg 1across all ageswith dose changes according to age/weight, 13% were dosed in mg across all ages with dose changes, 10% switched frommg kg 1to a set dose in mg, 4.2% have the same dose in mg for all age and weight groups and 2.2% are dosed according to BSA.CONCLUSIONSPaediatric dosage guidelines are based on weight-based formulas, available dosing formulations and prior patterns of use. Sub-stantial variation from doses predicted by BSA scaling are common, as are large shifts in recommended doses at age thresholds.Further research is required to determine if better outcomes could be achieved by adopting biologically based scaling of paedi-atric doses.NHMR

The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose

OBJECTIVE: The aim of the present study was to examine the relationship between serious arrhythmias in patients with psychotropic drug overdose and electrocardiography (ECG) findings that have been suggested previously to predict this complication. METHODS: Thirty-nine patients with serious arrhythmias (ventricular tachycardia, supraventricular tachycardia or cardiac arrest) after tricyclic antidepressant overdose or thioridazine overdose were compared with 117 controls with clinically significant overdose matched to each case for the drug ingested. These patients with psychotropic drug overdose had presented for treatment to the Department of Clinical Toxicology, Newcastle and to the Princess Alexandra Hospital, Brisbane. The heart rate, the QRS width, the QTc and QT intervals, the QT dispersion, and the R wave and R/S ratios in aVR on the initial ECGs were compared in cases and controls. RESULTS: The cases had taken dothiepin (16 patients), doxepin (six patients), thioridazine (five patients), amitriptyline (five patients), nortriptyline (three patients), imipramine (one patient) and a combination of dothiepin and thioridazine (three patients). In 20 of the 39 patients with arrhythmias, the arrhythmia had been a presumed ventricular tachycardia. Of the other 19 patients, 15 patients had a supraventricular tachycardia, two patients had cardiac arrests (one asystole, one without ECG monitoring) and two patients had insufficient data recorded to make classification of the arrhythmias possible. The QRS was ≥ 100 ms in 82% of cases but also in 76% of controls. QRS ≥ 160 ms had a sensitivity of only 13% and occurred in 2% of controls. QRS > 120 ms, QTc > 500 and the R/S ratio in aVR appeared to have a stronger association with the occurrence of arrhythmia: QRS > 120 ms (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.46–8.68), QTc > 500 (OR, 3.07; 95% CI, 1.33–7.07), and R/S ratio in aVR > 0.7 (OR, 16; 95% CI, 3.47–74). Excluding thioridazine overdoses and performing the analysis for tricyclic antidepressant overdoses alone gave increased odds ratios for QRS > 120 ms (OR, 4.83; 95% CI, 1.73–13.5) and QTc > 500 (OR, 4.5; 95% CI, 1.56–13) but had little effect on that for the R/S ratio in aVR > 0.7 (OR, 14.5; 95% CI, 3.10–68). CONCLUSION: ECG measurements were generally weakly related to the occurrence of arrhythmia and should not be used as the sole criteria for risk assessment in tricyclic antidepressant overdose. The frequently recommended practice of using either QRS ≥ 100 ms or QRS ≥ 160 ms to predict arrhythmias is not supported by our study. R/S ratio in aVR > 0.7 was most strongly related to arrhythmia but had estimated positive and negative predictive values of only 41% and 95%, respectively. The use of these specific predictors in other drug overdoses is not recommended without specific studies

Policymaking ‘under the radar': a case study of pesticide regulation to prevent intentional poisoning in Sri Lanka

Background Suicide in Sri Lanka is a major public health problem and in 1995 the country had one of the highest rates of suicide worldwide. Since then reductions in overall suicide rates have been largely attributed to efforts to regulate a range of pesticides. The evolution, context, events and implementation of the key policy decisions around regulation are examined. Methods This study was undertaken as part of a broader analysis of policy in two parts—an explanatory case study and stakeholder analysis. This article describes the explanatory case study that included an historical narrative and in-depth interviews. Results A timeline and chronology of policy actions and influence were derived from interview and document data. Fourteen key informants were interviewed and four distinct policy phases were identified. The early stages of pesticide regulation were dominated by political and economic considerations and strongly influenced by external factors. The second phase was marked by a period of local institution building, the engagement of local stakeholders, and expanded links between health and agriculture. During the third phase the problem of self-poisoning dominated the policy agenda and closer links between stakeholders, evidence and policymaking developed. The fourth and most recent phase was characterized by strong local capacity for policymaking, informed by evidence, developed in collaboration with a powerful network of stakeholders, including international researchers. Conclusions The policy response to extremely high rates of suicide from intentional poisoning with pesticides shows a unique and successful example of policymaking to prevent suicide. It also highlights policy action taking place ‘under the radar', thus avoiding policy inertia often associated with reforms in lower and middle income countrie

Alcohol-related suicide across Australia : a geospatial analysis

Background: The acute effects of alcohol consumption are a major risk factor for suicide. Positive blood alcohol concentrations are present in almost one-third of all suicides at time of death. These suicides are defined as alcohol-related suicides. This cross-sectional study examines the geospatial distribution/clustering of high proportions of alcohol-related suicides and reports on socioeconomic and demographic risk factors. Methods: National Coronial Information System (NCIS) data were used to calculate proportions of suicides with alcohol present at the time of death for each level 3 statistical areas (SA3) in Australia. A density analysis and hotspot cluster analysis were used to visualise and establish statistically significant clustering of areas with higher (hotspots) and lower (coldspots) proportions. Subsequently, socioeconomic and demographic risk factors for alcohol use and suicide were reported on for hot and cold spots. Results: Significant clustering of areas with higher proportions of alcohol-related suicide occurred in northern Western Australia, the Northern Territory and Queensland, as well as inland New South Wales and inland Queensland. Clustering of SA3s with significantly lower proportions occurred in major city and inner regional Sydney and Melbourne. Conclusion and implications for public health: Results from this study identify areas in which prevention strategies should target alcohol use and can be used to inform prevention strategy design. Additionally, hotspots and coldspots identified in this study can be used for further analysis to better understand contextual risk factors for alcohol-related suicide