471 results on '"Nicholas A Buckley"'
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2. 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.
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Natalie Thurtle, Katharine A Kirby, Jane Greig, Karla Bil, Paul I Dargan, Godwin N Ntadom, and Nicholas A Buckley
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Public aspects of medicine ,RA1-1270 - Abstract
Mother-to-child-transmission of lead via the placenta is known to result in congenital lead toxicity. Between 2010 and 2021, Médecins Sans Frontières and other stakeholders responded to a severe lead poisoning outbreak related to artisanal gold mining in Northern Nigeria. Extensive environmental remediation occurred following outbreak identification; source control efforts are ongoing within the community. We aimed to describe the prevalence of congenital lead poisoning in this cohort and analyse the association between neonatal blood lead concentration (BLC) and medium-term lead-related outcomes during the study period. Children enrolled in the lead poisoning programme between July 2010 and 25 January 2018 who had a screening BLC at ≤4 weeks of age were included. For time-to-event analysis, medium-term outcomes were classified as lead-related (death from lead encephalopathy, and/or met chelation threshold) and non-lead-related (non-lead-related death, on programme no chelation, exit from programme without chelation). Cox regression analysis and ROC analysis were performed. 1468 children were included. All-cause mortality 2.3%; geometric mean neonatal BLC 13.7 μg/dL; 'lead-related death or treatment' 19.3%. For every doubling in neonatal BLC, there was an almost 8-fold increase in adjusted hazard ratio (HR) for the composite lead-related outcome (p
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- 2023
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3. Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming.
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Eranga Sanjeewa Wijewickrama, Fahim Mohamed, Indika B Gawarammana, Zoltan H Endre, Nicholas A Buckley, and Geoffrey K Isbister
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundHump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites.MethodsWe conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming.ResultsThere were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points.ConclusionssCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.
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- 2021
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4. Case fatality of agricultural pesticides after self-poisoning in Sri Lanka: a prospective cohort study
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Nicholas A Buckley, ProfMD, Mohamed Fahim, PhD, Jacques Raubenheimer, PhD, Indika B Gawarammana, ProfPhD, Michael Eddleston, ProfPhD, Michael S Roberts, ProfPhD, and Andrew H Dawson, ProfFRCP
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Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Pesticide poisoning is among the most common means of suicide globally, but can be prevented with regulation of the most hazardous agents. We aimed to compare the lethality of pesticides ingested by our cohort, seek evidence on variation between human and regulatory animal toxicity, and establish change over time in the case fatality of individual pesticides in Sri Lanka. Methods: We examined the case fatality of agricultural pesticides in a prospective cohort in nine hospitals serving rural populations in Sri Lanka. We included all patients (>11 years) who had presented to a South Asian Clinical Toxicology Research Collaboration study hospital during the study period. Patients were enrolled by clinical research assistants and were regularly reviewed. Identification of the ingested pesticide was generally on the basis of history or positive identification of the container, supported by nested blood analysis. Findings: From March 31, 2002, to Dec 31, 2019, 34 902 patients (median age 29 years [IQR 21–40]; 23 060 [66·1%] male) presented with a possible or known pesticide self-poisoning. We identified 23 139 specific pesticides that were ingested. Poisoning was fatal in 2299 (6·6%) patients. Case fatality varied greatly from 0·0% (several substances) to 41·8% (paraquat). The three most toxic agents (ie, paraquat, dimethoate, and fenthion) were banned between 2008 and 2011. Since 2013, the five agents causing the most deaths (ie, profenofos, propanil, fenobucarb, carbosulfan, and quinalphos) had a case fatality of 7·2–8·6%. A steady decline was seen in overall case fatality of pesticide poisoning (10·5% for 2002–06 to 3·7% for 2013–19), largely attributable to pesticide bans. A modest fall in case fatality for non-banned pesticides was also seen. Interpretation: Declines seen in case fatalities of poisonings with non-banned pesticides suggest that medical management improved over time. The human data for acute toxicity of pesticides should drive hazard classifications and regulation. We believe that a global benchmark for registration of pesticides should include a less than 5% case fatality after self-poisoning, which could prevent many deaths and have a substantial effect on global suicide rates. Funding: The Wellcome Trust and the National Health and Medical Research Council of Australia. Translations: For the Sinhala and Tamil translations of the abstract see Supplementary Materials section.
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- 2021
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5. Risks of Squamous Cell Carcinoma of The Lip and Cutaneous Melanoma in Older Australians Using Hydrochlorothiazide (HTCZ)
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Benjamin Daniels, Sallie-Anne Pearson, Claire M Vajdic, Anton Pottegård, Nicholas A Buckley, and Helga Zoega
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Demography. Population. Vital events ,HB848-3697 - Abstract
Introduction HCTZ is first-line treatment for hypertension and among the most commonly used medicines in Australia. Recent evidence suggests increased risks of lip and skin cancers in association with HCTZ use. Objectives and Approach To determine the risk of SCC of the lip and melanoma among people prescribed HCTZ in Australia we conducted a case-control study nested within a cohort of Department of Veterans’ Affairs clients 65 years and older in 2004-2015. We identified incident cases of SCC of the lip (lip cancer) and of cutaneous melanoma (malignant melanoma), each matched by sex and age with up to 20 controls through risk-set sampling. We ascertained HCTZ use from dispensing data and classified use according to ever/never use and cumulative use. We estimated odds ratios (ORs) associating HCTZ use with lip cancer and malignant melanoma using conditional logistic regression, adjusting for predefined confounders obtained from dispensing and hospitalisation data. Results For lip cancer (45 cases) ever-use of HCTZ yielded an OR of 2.6 (95%CI: 1.4–5.0) and high HCTZ use (>25,000mg) an OR of 4.7 (1.61–13.7). For malignant melanoma (659 cases) ever-use of HCTZ resulted in an OR of 1.2 (1.0–1.5) and high HCTZ use in an OR of 1.2 (0.8–1.8). Conclusion / Implications Our study provides further evidence that the photosensitising properties of HCTZ may promote SCC carcinogenesis, and possibly melanoma, in susceptible sun-exposed tissues. Our findings are the first from the Australian population—already at elevated risk of developing skin cancer—and add to the growing body of data supporting the need for skin cancer prevention advice and behaviours, and potentially heightened surveillance, for individuals prescribed this medication.
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- 2020
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6. Australian Suicide Prevention using Health-Linked Data (ASHLi): Protocol for a population-based case series study
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Sallie-Anne Pearson, Rose Cairns, Nicholas A Buckley, Gregory Carter, Andrew Page, Andrea Schaffer, Kate M Chitty, Jennifer L Schumann, Nicole J Gonzaga, and Jacques E Raubenheimer
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Medicine - Abstract
Introduction In Australia, suicide is the leading cause of death for people aged 15–44 years. Health professionals deliver most of our key suicide prevention strategies via health services, but other efficacious population-level strategies include means restriction and public awareness campaigns. Currently, we have no population-level data allowing us to determine which individuals, in what parts of Australia, are likely to use our most promising interventions delivered by health services. The aims of this study are to describe: (1) health service utilisation rates in the year prior to death by suicide, and how this varies by individual case characteristics; (2) prescribed medicines use in the year prior to death by suicide, medicines used in suicide by poisoning and how this varies by individual case characteristics.Methods and analysis This is a population-based case series study of all suicide cases in Australia identified through the National Coronial Information System (NCIS) from 2013 to 2019. Cases will be linked to administrative claims data detailing health service use and medicines dispensed in the year before death. We will also obtain findings from the coronial enquiry, including toxicology. Descriptive statistics will be produced to characterise health service and prescribed medicine use and how utilisation varies by age, sex, method of death and socioeconomic status. We will explore the geographical variability of health service and medicine use, highlighting regions in Australia associated with more limited access.Ethics and dissemination This project involves the use of sensitive and confidential data. Data will be linked using a third-party privacy-preserving protocol meaning that investigators will not have access to identifiable information once the data have been linked. Statistical analyses will be carried out in a secure environment. This study has been approved by the following ethics committees: (1) the Justice Department Human Research Ethics Committee (REF: CF/17/23250), (2) the Western Australian Coroners Court (REF: EC 14/18 M0400), (3) the Australian Institute of Health and Welfare (REF: EO2017/4/366) and (4) NSW Population & Health Services Research Ethics Committee (REF: 2017/HRE1204). Findings will be published in peer-reviewed journals, presented at conferences and communicated to regulatory authorities, clinicians and policy-makers.
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- 2020
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7. Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers.
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Indira Ratnayake, Fahim Mohamed, Nicholas A Buckley, Indika B Gawarammana, Dhammika M Dissanayake, Umesh Chathuranga, Mahesh Munasinghe, Kalana Maduwage, Shaluka Jayamanne, Zoltan H Endre, and Geoffrey K Isbister
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundAcute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites.Methodology/principal findingsWe recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (Conclusions/significanceAKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.
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- 2019
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8. Prediction of organophosphorus insecticide-induced intermediate syndrome with stimulated concentric needle single fibre electromyography.
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Chanika Alahakoon, Tharaka L Dassanayake, Indika B Gawarammana, E Michael Sedgwick, Vajira S Weerasinghe, Ahmed Abdalla, Michael S Roberts, and Nicholas A Buckley
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Medicine ,Science - Abstract
BACKGROUND:Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to over-activity of muscarinic and nicotinic cholinergic circuits. Intermediate syndrome (IMS) is mediated via prolonged nicotinic receptor stimulation at the neuromuscular junction and its onset is between 24-96 hours post ingestion. The aims of the present study were 1) to investigate whether neuromuscular junction dysfunction within the first 24 hours following exposure, quantified by jitter in single fibre electromyography (SfEMG), can predict IMS, and 2) to compare the changes in SfEMG jitter over the course of the illness among patients who developed IMS (IMS+) and those who did not (IMS-). METHODS AND FINDINGS:We conducted a prospective cohort study in a tertiary care hospital in Sri Lanka on 120 patients admitted between September 2014 and August 2016 following DSP by OP insecticides viz., profenofos 53, phenthoate 17, diazinon 13, chlorpyrifos 5, others 12, unknown 20. SfEMG was performed every second day during hospitalization. Exposure was confirmed based on the history and red blood cell AChE assays. IMS was diagnosed in patients who demonstrated at least three out of four of the standard IMS criteria: proximal muscle weakness, bulbar muscle weakness, neck muscle weakness, respiratory paralysis between 24-96 hours post ingestion. Respiratory failure requiring intubation occurred in 73 out of 120 patients; 64 of these were clinically diagnosed with IMS. Of the 120 patients, 96 had repeated SfEMG testing, 67 of them being tested within the first 24 hours. Prolonged jitter (>33.4μs) within the first 24 hours was associated with greatly increased risk of IMS (odds ratio = 8.9, 95% confidence intervals = 2.4-29.6, p = 0.0003; sensitivity 86%, specificity 58%). The differences in jitter between IMS+ and IMS- patients remained significant for 72 hours and increased jitter was observed in some patients for up to 216 hours. For intubated patients, the median time for jitter to normalize and median time to extubate were similar, and the two variables had a moderate positive correlation (r = 0.49, P = 0.001). CONCLUSIONS:Prolonged jitter recorded with SfEMG
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- 2018
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9. Diagnosis-based and external cause-based criteria to identify adverse drug reactions in hospital ICD-coded data: application to an Australia population-based study
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Wei Du, Sallie-Anne Pearson, Nicholas A Buckley, Cathy Day, and Emily Banks
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Prescribing ,Medicines ,Public aspects of medicine ,RA1-1270 - Abstract
Objectives: External cause International Classification of Diseases (ICD) codes are commonly used to ascertain adverse drug reactions (ADRs) related to hospitalisation. We quantified ascertainment of ADR-related hospitalisation using external cause codes and additional ICD-based hospital diagnosis codes. Methods: We reviewed the scientific literature to identify different ICD-based criteria for ADR-related hospitalisations, developed algorithms to capture ADRs based on candidate hospital ICD-10 diagnoses and external cause codes (Y40–Y59), and incorporated previously published causality ratings estimating the probability that a specific diagnosis was ADR related. We applied the algorithms to the NSW Admitted Patient Data Collection records of 45 and Up Study participants (2011–2013). Results: Of 493 442 hospitalisations among 267 153 study participants during 2011–2013, 18.8% (n = 92 953) had hospital diagnosis codes that were potentially ADR related; 1.1% (n = 5305) had high/very high–probability ADR-related diagnosis codes (causality ratings: A1 and A2); and 2.0% (n = 10 039) had ADR-related external cause codes. Overall, 2.2% (n = 11 082) of cases were classified as including an ADR-based hospitalisation on either external cause codes or high/very high–probability ADR-related diagnosis codes. Hence, adding high/very high–probability ADR-related hospitalisation codes to standard external cause codes alone (Y40–Y59) increased the number of hospitalisations classified as having an ADR-related diagnosis by 10.4%. Only 6.7% of cases with high-probability ADR-related mental symptoms were captured by external cause codes. Conclusion: Selective use of high-probability ADR-related hospital diagnosis codes in addition to external cause codes yielded a modest increase in hospitalised ADR incidence, which is of potential clinical significance. Clinically validated combinations of diagnosis codes could potentially further enhance capture.
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- 2017
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10. Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming.
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Anjana Silva, Christopher Johnston, Sanjaya Kuruppu, Daniela Kneisz, Kalana Maduwage, Oded Kleifeld, A Ian Smith, Sisira Siribaddana, Nicholas A Buckley, Wayne C Hodgson, and Geoffrey K Isbister
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BACKGROUND:Sri Lankan Russell's viper (Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell's vipers. This study aimed to investigate evidence of myotoxicity in Russell's viper envenoming, response to antivenom and the toxins responsible for myotoxicity. METHODOLOGY AND FINDINGS:Clinical features of myotoxicity were assessed in authenticated Russell's viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman's correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 μg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 μM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity. CONCLUSION:The study shows that myotoxicity in Sri Lankan Russell's viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties.
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- 2016
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11. Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka.
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Anjana Silva, Kalana Maduwage, Michael Sedgwick, Senaka Pilapitiya, Prasanna Weerawansa, Niroshana J Dahanayaka, Nicholas A Buckley, Christopher Johnston, Sisira Siribaddana, and Geoffrey K Isbister
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
OBJECTIVE:We aimed to investigate neurophysiological and clinical effects of common krait envenoming, including the time course and treatment response. METHODOLOGY:Patients with definite common krait (Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6 wk and 6-9 mth post-bite. PRINCIPAL FINDINGS:There were 33 patients enrolled (median age 35 y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20-32 h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5 h post-bite (2.8-7.2 h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7 h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12 h. sfEMG abnormalities gradually improved over 24 h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96 h post-bite (54-216 h). On discharge, median 8 days (4-12 days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6 wk post-bite. There were no clinical or neurophysiological abnormalities at 6-9 mth. CONCLUSIONS:Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis.
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- 2016
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12. Kinetic Estimation of GFR Improves Prediction of Dialysis and Recovery after Kidney Transplantation.
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Timothy J Pianta, Zoltan H Endre, John W Pickering, Nicholas A Buckley, and Philip W Peake
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Medicine ,Science - Abstract
BackgroundThe early prediction of delayed graft function (DGF) would facilitate patient management after kidney transplantation.MethodsIn a single-centre retrospective analysis, we investigated kinetic estimated GFR under non-steady-state conditions, KeGFR, in prediction of DGF. KeGFR(sCr) was calculated at 4h, 8h and 12h in 56 recipients of deceased donor kidneys from initial serum creatinine (sCr) concentrations, estimated creatinine production rate, volume of distribution, and the difference between consecutive sCr values. The utility of KeGFR(sCr) for DGF prediction was compared with, sCr, plasma cystatin C (pCysC), and KeGFR(pCysC) similarly derived from pCysC concentrations.ResultsAt 4h, the KeGFR(sCr) area under the receiver operator characteristic curve (AUC) for DGF prediction was 0.69 (95% CI: 0.56-0.83), while sCr was not useful (AUC 0.56, (CI: 0.41-0.72). Integrated discrimination improvement analysis showed that the KeGFR(sCr) improved a validated clinical prediction model at 4h, 8h, and 12h, increasing the AUC from 0.68 (0.52-0.83) to 0.88 (0.78-0.99) at 12h (p = 0.01). KeGFR(pCysC) also improved DGF prediction. In contrast, sCr provided no improvement at any time point.ConclusionsCalculation of KeGFR from sCr facilitates early prediction of DGF within 4 hours of renal transplantation.
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- 2015
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13. Population Pharmacokinetics of an Indian F(ab')2 Snake Antivenom in Patients with Russell's Viper (Daboia russelii) Bites.
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Geoffrey K Isbister, Kalana Maduwage, Ana Saiao, Nicholas A Buckley, Shaluka F Jayamanne, Shahmy Seyed, Fahim Mohamed, Umesh Chathuranga, Alexandre Mendes, Chandana Abeysinghe, Harindra Karunathilake, Indika Gawarammana, David G Lalloo, and H Janaka de Silva
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
There is limited information on antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell's viper bites.Patient data and serial blood samples were collected from patients with Russell's viper (Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab')2 snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance (CL), intercompartmental clearance (Q), central compartment volume (V) and peripheral compartment volume (VP). Between-subject-variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre-antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70 y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 L h(-1), V,2.2L, Q,0.178 L h(-1) and VP,8.33L. The median half-life of distribution was 4.6 h (10-90%iles:2.6-7.1 h) and half-life of elimination, 140 h (10th-90th percentilesx:95-223h).Indian F(ab')2 snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.
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- 2015
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14. Clinical effects and antivenom dosing in brown snake (Pseudonaja spp.) envenoming--Australian snakebite project (ASP-14).
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George E Allen, Simon G A Brown, Nicholas A Buckley, Margaret A O'Leary, Colin B Page, Bart J Currie, Julian White, Geoffrey K Isbister, and ASP Investigators
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Medicine ,Science - Abstract
BACKGROUND: Snakebite is a global health issue and treatment with antivenom continues to be problematic. Brown snakes (genus Pseudonaja) are the most medically important group of Australian snakes and there is controversy over the dose of brown snake antivenom. We aimed to investigate the clinical and laboratory features of definite brown snake (Pseudonaja spp.) envenoming, and determine the dose of antivenom required. METHODS AND FINDING: This was a prospective observational study of definite brown snake envenoming from the Australian Snakebite Project (ASP) based on snake identification or specific enzyme immunoassay for Pseudonaja venom. From January 2004 to January 2012 there were 149 definite brown snake bites [median age 42 y (2-81 y); 100 males]. Systemic envenoming occurred in 136 (88%) cases. All envenomed patients developed venom induced consumption coagulopathy (VICC), with complete VICC in 109 (80%) and partial VICC in 27 (20%). Systemic symptoms occurred in 61 (45%) and mild neurotoxicity in 2 (1%). Myotoxicity did not occur. Severe envenoming occurred in 51 patients (38%) and was characterised by collapse or hypotension (37), thrombotic microangiopathy (15), major haemorrhage (5), cardiac arrest (7) and death (6). The median peak venom concentration in 118 envenomed patients was 1.6 ng/mL (Range: 0.15-210 ng/mL). The median initial antivenom dose was 2 vials (Range: 1-40) in 128 patients receiving antivenom. There was no difference in INR recovery or clinical outcome between patients receiving one or more than one vial of antivenom. Free venom was not detected in 112/115 patients post-antivenom with only low concentrations (0.4 to 0.9 ng/ml) in three patients. CONCLUSIONS: Envenoming by brown snakes causes VICC and over a third of patients had serious complications including major haemorrhage, collapse and microangiopathy. The results of this study support accumulating evidence that giving more than one vial of antivenom is unnecessary in brown snake envenoming.
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- 2012
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15. Delayed psychological morbidity associated with snakebite envenoming.
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Shehan S Williams, Chamara A Wijesinghe, Shaluka F Jayamanne, Nicholas A Buckley, Andrew H Dawson, David G Lalloo, and H Janaka de Silva
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
IntroductionThe psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied.ObjectivesTo assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims.MethodsThe study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming.ResultsPrevious snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; pConclusionsSnakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigation.
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- 2011
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16. Acute human lethal toxicity of agricultural pesticides: a prospective cohort study.
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Andrew H Dawson, Michael Eddleston, Lalith Senarathna, Fahim Mohamed, Indika Gawarammana, Steven J Bowe, Gamini Manuweera, and Nicholas A Buckley
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Medicine - Abstract
agricultural pesticide poisoning is a major public health problem in the developing world, killing at least 250,000-370,000 people each year. Targeted pesticide restrictions in Sri Lanka over the last 20 years have reduced pesticide deaths by 50% without decreasing agricultural output. However, regulatory decisions have thus far not been based on the human toxicity of formulated agricultural pesticides but on the surrogate of rat toxicity using pure unformulated pesticides. We aimed to determine the relative human toxicity of formulated agricultural pesticides to improve the effectiveness of regulatory policy.we examined the case fatality of different agricultural pesticides in a prospective cohort of patients presenting with pesticide self-poisoning to two clinical trial centers from April 2002 to November 2008. Identification of the pesticide ingested was based on history or positive identification of the container. A single pesticide was ingested by 9,302 patients. A specific pesticide was identified in 7,461 patients; 1,841 ingested an unknown pesticide. In a subset of 808 patients, the history of ingestion was confirmed by laboratory analysis in 95% of patients. There was a large variation in case fatality between pesticides-from 0% to 42%. This marked variation in lethality was observed for compounds within the same chemical and/or WHO toxicity classification of pesticides and for those used for similar agricultural indications.the human data provided toxicity rankings for some pesticides that contrasted strongly with the WHO toxicity classification based on rat toxicity. Basing regulation on human toxicity will make pesticide poisoning less hazardous, preventing hundreds of thousands of deaths globally without compromising agricultural needs. Ongoing monitoring of patterns of use and clinical toxicity for new pesticides is needed to identify highly toxic pesticides in a timely manner.
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- 2010
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17. The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka.
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Pradeepa Jayawardane, Andrew H Dawson, Vajira Weerasinghe, Lakshman Karalliedde, Nicholas A Buckley, and Nimal Senanayake
- Subjects
Medicine - Abstract
Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research.Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements.Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research.
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- 2008
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18. Improvement in survival after paraquat ingestion following introduction of a new formulation in Sri Lanka.
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Martin F Wilks, Ravindra Fernando, P L Ariyananda, Michael Eddleston, David J Berry, John A Tomenson, Nicholas A Buckley, Shaluka Jayamanne, David Gunnell, and Andrew Dawson
- Subjects
Medicine - Abstract
Pesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following its introduction into Sri Lanka.Clinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standard formulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%-17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the original formulation to 55% with INTEON, p < 0.001). Median survival time increased from 2.3 d (95% CI 1.2-3.4 d) with the standard formulation to 6.9 d (95% CI 3.3-10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5-3.4) to 1.5 d (IQR 0.5-5.5); p = 0.02.The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption.
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- 2008
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19. Does restricting pack size of paracetamol (acetaminophen) reduce suicides?
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Nicholas A Buckley and David Gunnell
- Subjects
Medicine - Published
- 2007
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20. Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose ( <scp>ATOM</scp> ‐7)
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Angela L. Chiew, Geoffrey K. Isbister, Paul Stathakis, Katherine Z. Isoardi, Colin Page, Kirsty Ress, Betty S.H. Chan, and Nicholas A. Buckley
- Subjects
Pharmacology ,Pharmacology (medical) - Published
- 2023
21. Dose ingested, vomiting, and outcome in patients ingesting a standard paraquat 20SL formulation
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Eileen Deuster, John A. Tomenson, Fahim Mohamed, Indika Gawarammana, Nicholas A. Buckley, Martin F. Wilks, and Michael Eddleston
- Subjects
PP796 ,paraquat ,emesis ,formulation ,General Medicine ,Toxicology ,mortality - Abstract
FAO specifications for liquid paraquat dichloride SL formulations require the use of an emetic agent to stimulate vomiting within 30 min of ingestion. To date, there is no high-quality evidence of efficacy, despite use of the PP796 emetic since 1979. We first examined the validity of patients' self-reported dose of paraquat ingested by examining the relationship with blood paraquat concentration and time to death for patients ingesting the standard paraquat SL formulation in a Sri Lankan cohort. As a secondary outcome, we assessed whether ingestion resulted in vomiting within 30 min and whether vomiting was associated with good outcome.Patients presenting with paraquat SL self-poisoning were prospectively studied in ten Sri Lankan hospitals in 2003-08. Data on reported dose ingested, incidence and timing of vomiting after ingestion, treatment received, plasma paraquat concentration, and outcome were collected prospectively on presentation to hospital. Time between ingestion and blood sampling was incorporated by covariate adjustment.441 patients were recruited to the case series, presenting a median (IQR) of 3.0 (1.5-8.1] h post ingestion. Outcome was known for 435 patients of whom 322 (74.0%) died within 42 days, a median of 1.3 (0.6-4.4) days post ingestion. Median reported dose ingested was 15 to30 mL. There was a highly significant linear trend between log plasma paraquat and reported dose ingested (Importantly, we found good agreement between reported dose ingested and plasma paraquat concentration, case fatality, and time to death, suggesting that the reported dose is a valid marker for the dose ingested. Vomiting occurred within 30 min for 68.5% of patients, exceeding the characteristics for a purported effective emetic in the FAO specifications. However, vomiting within 30 min was associated with approximately double the risk of death compared to those who did not vomit, larger paraquat ingestions, and higher blood paraquat concentrations. In addition, death occurred in many patients who did not vomit, and the proportion vomiting within 30 min only reached 82.1% for the highest ingested dose group. Overall, we found no evidence of benefit resulting from incorporation of the emetic, suggesting that the current FAO specification is not effective at preventing deaths after ingestion of the paraquat SL formulation.
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- 2022
22. Long-term use of proton-pump inhibitors: whole-of-population patterns in Australia 2013–2016
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Benjamin Daniels, Sallie-Anne Pearson, Nicholas A. Buckley, Claudia Bruno, and Helga Zoega
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background: Proton-pump inhibitors (PPIs) are among the most prescribed medicines worldwide and concern about their long-term use is growing. We used dispensing claims for every person in Australia dispensed publicly subsidized PPIs between 2013 and 2016 to determine the incidence and prevalence of PPI use and to examine the patterns and durations of PPI treatment among individuals continuing treatment beyond the guideline-recommended maximum 12 weeks. Methods: We estimated annual prevalence and incidence per 100 people and duration of treatment for every Australian dispensed publicly subsidized PPIs between 2013 and 2016. We examined patterns of PPI treatment in three patient subgroups using PPIs for more than 12 weeks duration; people receiving maintenance, long-term continuous or long-term intermittent treatment. We calculated the proportion in each subgroup stepping down from higher to lower PPI strengths, stepping up from lower to higher PPI strength and discontinuing treatment. Results: PPIs were dispensed to 4,388,586 people; 60% were women; median age at initiation was 52 years [interquartile range (IQR): 36–65]. Standard and high strength PPIs accounted for 95% of dispensings. Annual incidence and prevalence were 3.9/100 and 12.5/100, respectively, in 2016 and highest among individuals over 65 years (prevalence range: 33–43/100). Most people (67%) stopped treatment after one dispensing; while 25%, 6% and 10% continued on maintenance, long-term continuous and long-term intermittent treatment, respectively. Median duration of treatment in people continuing treatment was 501 days (IQR: 180–not reached) for maintenance treated individuals and ‘not reached’ for long-term treated individuals. We observed 35%, 20% and 47% of people stepping down from higher to lower treatment strengths on maintenance, long-term continuous and long-term intermittent treatment, respectively. Conclusions: Longer-term treatment with higher strength PPIs is common. Targeted regulation of PPI prescribing may improve the uptake of lower strength formulations and reduce both harms and costs associated with long-term PPI treatment.
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- 2020
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23. The impact on poisonings of up‐scheduling of modified release paracetamol to Schedule 3 (pharmacist only medicine)
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Rose Cairns, Firouzeh Noghrehchi, and Nicholas A Buckley
- Subjects
General Medicine - Published
- 2023
24. Psychotropic and other medicine use at time of death by suicide: a population‐level analysis of linked dispensing and forensic toxicology data
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Kate M Chitty, Nicholas A Buckley, Jessy Lim, Zein Ali, Jennifer L Schumann, Rose Cairns, Benjamin Daniels, Sallie A Pearson, David B Preen, and Andrea L Schaffer
- Subjects
General Medicine - Published
- 2023
25. Opioid prescribing patterns among medical practitioners in New South Wales, Australia
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Andrea L. Schaffer, Natasa Gisev, Fiona M. Blyth, Nicholas A. Buckley, David Currow, Timothy A. Dobbins, Andrew Wilson, Louisa Degenhardt, and Sallie‐Anne Pearson
- Subjects
Health (social science) ,Medicine (miscellaneous) - Published
- 2023
26. Prescribing trend of tapentadol in a Sydney local health district
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Jennifer Mirabella, Deepa Ravi, Angela L. Chiew, Nicholas A. Buckley, and Betty S. Chan
- Subjects
Analgesics, Opioid ,Tapentadol ,Pharmacology ,Pain, Postoperative ,Morphine ,Phenols ,Delayed-Action Preparations ,Australia ,Humans ,Pharmacology (medical) ,Oxycodone ,Tramadol - Abstract
Tapentadol, an opioid with mu-opioid receptor agonism and noradrenaline reuptake inhibition, has been increasingly used in Australia since 2011. However, data on hospital prescribing trends and indications are scarce. This study aimed to investigate hospital prescribing trends of tapentadol, oxycodone and tramadol in a Sydney local health district (LHD) and the indications for tapentadol hospital prescriptions in an Australian tertiary hospital.We analysed 5-year patient dispensing for tapentadol, oxycodone and tramadol from four hospitals in a Sydney LHD with data expressed as oral morphine equivalents (OME). We also conducted a retrospective review of 140 and 54 patients prescribed tapentadol at a tertiary hospital's surgical and spinal units in 2020.Over 5 years in the Sydney LHD, there was a 19.5% reduction in total dispensing of these opioids from 1 225 210 to 986 477.5 OME milligrams. Decreases were specifically for oxycodone (-37.8% immediate-release, -65.2% sustained-release) and tramadol (-74.6% immediate-release, -70.1% sustained-release). Contrastingly, hospital prescriptions of tapentadol immediate-release increased by 223.2% between 2018-19 and 2020-21 while sustained-release increased by 17.9% from 2016-17 to 2020-21. By 2020-21, tapentadol overtook oxycodone to become the most prescribed opioid in the Sydney LHD (51.4%). At the hospital's surgical units, 137 (97.9%) patients were prescribed tapentadol for acute post-operative pain with the majority (54.0%) prescribed both immediate-release and sustained-release tapentadol, while 71.1% were prescribed for neuropathic pain in the spinal units.In a Sydney LHD, tapentadol prescriptions increased significantly to become the preferred opioid analgesic. At the hospital's surgical units, off-label prescriptions of tapentadol sustained-release for acute post-operative pain were observed.
- Published
- 2022
27. Delayed Acetaminophen Absorption Resulting in Acute Liver Failure
- Author
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Huiling Tan, Paul Stathakis, Benoj Varghese, Nicholas A. Buckley, and Angela L. Chiew
- Subjects
Critical Care and Intensive Care Medicine - Abstract
Introduction. Acetaminophen is a common medication involved in deliberate and accidental self-poisoning. The acetaminophen treatment nomogram is used to guide acetylcysteine treatment. It is rare to develop hepatotoxicity with an initial acetaminophen concentration below the nomogram line. We present a case of acetaminophen ingestion with an initial concentration below the nomogram line that developed hepatic failure, due to a delayed peak acetaminophen concentration secondary to coingesting medications that slow gastric emptying. Case Report. A 43-year-old (55 kg) female presented after ingesting an unknown quantity of acetaminophen, clonidine, and alcohol. Her acetaminophen level was 41 mg/L (256 μmol/L) at 4.5 h post-ingestion, well below the nomogram line, and ALT was 25 U/L. Hence, acetylcysteine was not commenced. She was intubated for decreased level of conscious. A repeat acetaminophen level 4 h later was 39 mg/L (242 μmol/L), still below the nomogram line. She was extubated 24 h later.At 38 h post-ingestion she developed abdominal pain, the repeat acetaminophen level was 85 mg/L (560 μmol/L), ALT was 489 U/L, and acetylcysteine was commenced. The patient developed hepatic failure with a peak ALT of 7009 U/L and INR of 7.5 but made a full recovery. It was discovered that she had ingested a combination acetaminophen product containing dextromethorphan and chlorphenamine. Acetaminophen metabolites were measured, including nontoxic glucuronide and sulfate conjugates and toxic cytochrome P450 (CYP) metabolites. The metabolite data demonstrated increasing CYP metabolites in occurrence with the delayed acetaminophen peak concentration. Discussion. Opioids and antimuscarinic agents are known to delay gastric emptying and clonidine may also have contributed. These coingested medications resulted in delayed acetaminophen absorption. This case highlights the issue of altered pharmacokinetics when patients coingest gut slowing agents.
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- 2022
28. Prescribed medicine use and extent of off‐label use according to age in a nationwide sample of Australian children
- Author
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Andrea L. Schaffer, Claudia Bruno, Nicholas A. Buckley, Rose Cairns, Melisa Litchfield, Simon Paget, Helga Zoega, Natasha Nassar, and Sallie‐Anne Pearson
- Subjects
Epidemiology ,Pediatrics, Perinatology and Child Health ,Australia ,Prevalence ,Humans ,Infant ,Off-Label Use ,Practice Patterns, Physicians' ,Child ,Anti-Bacterial Agents - Abstract
Medicine prescribing for children is impacted by a lack of paediatric-specific dosing, efficacy and safety data for many medicines.To estimate the prevalence of medicine use among children and the rate of 'off-label' prescribing according to age at dispensing.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).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 children1 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 children1 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%).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.
- Published
- 2022
29. The impact of tightened prescribing restrictions on proton pump inhibitor use in Australia: An evaluation using interrupted time series analysis
- Author
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Benjamin Daniels, Andrea Schaffer, Nicholas A. Buckley, Claudia Bruno, Min Jun, Sallie‐Anne Pearson, and Helga Zoega
- Subjects
Epidemiology ,Australia ,Humans ,Interrupted Time Series Analysis ,Nonprescription Drugs ,Proton Pump Inhibitors ,Pharmacology (medical) ,Practice Patterns, Physicians' ,Drug Prescriptions - Abstract
In May 2019, Australia's Pharmaceutical Benefits Scheme (PBS) tightened the prescribing restrictions for publicly subsidized high and standard strength proton-pump inhibitors (PPIs). We aimed to determine the impacts on PPI use in Australia.Population-based interrupted time series analysis of PBS dispensing claims for a 10% sample of PBS-eligible Australian residents from January 2017 to December 2020 and national prescription and over-the-counter sales to pharmacies from January 2017 to October 2020. We examined trends in monthly PPI dispensings, switches from higher to lower strength formulations, and volume (kg) dispensed and sold.From May 2019, we observed a small, immediate decrease (-7830 [95%CI: -8818 to -6842]) in standard strength PPI dispensings/month, which rebounded to exceed pre-intervention levels by December 2020. High strength dispensings decreased until the end of the study period to less than half their pre-intervention average/month; low strength dispensings/month increased until the end of the study period to more than double their pre-intervention average/month. We observed transient increases in switches to lower strength formulations post-intervention. The kilograms of PPIs sold/month followed a similar pattern to PBS kilograms dispensed/month with the exception of standard strength formulations where PBS dispensings decreased by -74 (95%CI: -93 to -55) but total sales remained unchanged (comprising PBS and private prescriptions, and over-the-counter sales).Tightened prescribing restrictions had an immediate and sustained impact on PPI use in Australia, with decreased high strength use and increased low strength use. Some patients likely switched to private market prescriptions for standard strength PPI, given the observed patterns in total volume sold/dispensed.
- Published
- 2021
30. Epidemiology and renal injury following 2-methyl-4-chlorophenoxyacetic acid (MCPA) poisoning
- Author
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Thilini M. Wijerathna, Nicholas A. Buckley, Indika B. Gawarammana, Jacques Raubenheimer, Seyed Shahmy, Umesh Chathuranga, Chathura Palangasinghe, Fathima Shihana, and Fahim Mohamed
- Subjects
Adult ,Male ,Multidisciplinary ,Lipocalin-2 ,Creatinine ,Humans ,Female ,Prospective Studies ,2-Methyl-4-chlorophenoxyacetic Acid ,Acute Kidney Injury ,Cystatin C ,Kidney ,Biomarkers - Abstract
2-Methyl-4-chlorophenoxyacetic acid (MCPA) is a widely used chlorophenoxy herbicide. MCPA poisoning causes mitochondrial dysfunction, which can lead to kidney injury and death. The objective of this study is to describe the epidemiology, case fatality and extent of renal injury in a large cohort of MCPA self-poisonings. The study consists of two parts: (1) A report of epidemiological data and clinical outcomes in MCPA poisoned patients in Sri Lanka between 2002 and 2019; (2) Evaluation of acute kidney injury (AKI) using renal biomarkers in a subset from this cohort. Serum creatinine (sCr) and biomarkers were measured soon after hospitalization (2 [IQR 1–3] h) and at different time intervals. We measured serum biomarkers: sCr, cystatin C (sCysC), creatine kinase (CK), and urinary biomarkers: creatinine, kidney injury molecule-1 (KIM-1), clusterin, albumin, beta-2-microglobulin (β2M), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), trefoil factor 3 (TFF3) and cytochrome C (CytoC). Kidney Disease Improving Global Outcomes (KDIGO) criteria was used to define acute kidney injury (AKI). There were 1653 patients; 65% were male. The median time from ingestion to examination was 3:54 (IQR 2:19–6:57) h. The overall case-fatality rate was 5.3%. Patients who died were older (42 [IQR 33.5–54] vs 27 [IQR 20–37] for survivors). The median estimated amount of MCPA ingested by patients who died was also greater (88 [IQR 34–200] vs. 30 [IQR 15–63] ml in survivors). Moderate to severe AKI (AKI2/3) was uncommon (6/59 patients in the biomarker study had KDIGO stage 2 or 3). Most patients in AKI2/3 group with increased sCr were older (median age 35 years [IQR 27–41]) compared to No AKI (23 years (19–29) years) or AKI1 (26 years (21–40) years) group who had no or mild increase in sCr. These patients had no pre-existing kidney diseases. In these patients, serum creatinine (maximum medium concentration; 1.12 [IQR 0.93–1.67] mg/dl) and CK (maximum medium concentration; 284 [IQR 94–428] U/l) were increased but sCysC (maximum medium concentration; 0.79 [IQR 0.68–0.81] mg/l) remained in the normal range within 72 h. All urinary biomarkers performed poorly in diagnosing AKI (area under the receiver operating characteristic curve
- Published
- 2022
31. Trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia (2003–2015)
- Author
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Sallie-Anne Pearson, Nicholas A. Buckley, Emily A Karanges, Alex Trussell, Rose Cairns, Melisa Litchfield, Adam Todd, Shafkat Rahman, and Natasa Gisev
- Subjects
Adult ,Male ,medicine.medical_specialty ,Health (social science) ,Population ,Medicine (miscellaneous) ,Fentanyl ,Risk Factors ,Humans ,Medicine ,Medical prescription ,education ,Aged ,Retrospective Studies ,Transdermal ,Aged, 80 and over ,Fentanyl overdose ,education.field_of_study ,business.industry ,medicine.disease ,Confidence interval ,Analgesics, Opioid ,Substance abuse ,Opiate Overdose ,Opioid ,Emergency medicine ,Female ,Drug Overdose ,business ,medicine.drug - Abstract
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
- Published
- 2021
32. Optimising alkalinisation and its effect on QRS narrowing in tricyclic antidepressant poisoning
- Author
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Geoffrey K. Isbister, Rose Cairns, Katherine Z Isoardi, Therese M. Becker, Nicholas A. Buckley, Betty S. Chan, Jared A Brown, Angela L. Chiew, and Kieran Pai
- Subjects
Pharmacology ,Mechanical ventilation ,medicine.drug_class ,business.industry ,Tricyclic antidepressant poisoning ,Poisoning ,medicine.medical_treatment ,Australia ,Tricyclic antidepressant ,Arrhythmias, Cardiac ,Antidepressive Agents, Tricyclic ,Electrocardiography ,QRS complex ,Anesthesia ,Toxicity ,Hyperventilation ,medicine ,Breathing ,Humans ,Pharmacology (medical) ,Dual therapy ,medicine.symptom ,business ,Retrospective Studies - Abstract
The objectives are to determine the effect of NaHCO 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. This was a retrospective review of TCA poisonings from three Australian toxicology units and a poisons information centre (Jan 2013-Jan 2019). We included patients with TCA toxicity who ingested>10mg/kg or had clinically significant toxicities consistent with TCA poisoning, and analysed patients' clinical, electrocardiogram and biochemical data. Of 210 patients, 84 received NaHCO and ventilation (dual therapy), 12 NaHCO , 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(1.5g vs.1.3g,p A combination of NaHCO and mechanical ventilation was most effective in achieving serum alkalinisation and was associated with a more rapid narrowing of the QRS interval. We would advise the maximal dose of NaHCO should be
- Published
- 2021
33. Circulating intestinal fatty acid binding protein and intestinal toxicity in Russell’s viper envenomation
- Author
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Varan Perananthan, Fahim Mohamed, Indika Gawarammana, Andrew H. Dawson, Nicholas A. Buckley, and Thilini Wijerathna
- Subjects
medicine.medical_specialty ,Abdominal pain ,VIPeR ,Snake Bites ,Viper Venoms ,macromolecular substances ,Fatty Acid-Binding Proteins ,Toxicology ,Gastroenterology ,Internal medicine ,medicine ,Coagulopathy ,Animals ,Humans ,Russell's Viper ,Envenomation ,business.industry ,Neurotoxicity ,General Medicine ,Blood Coagulation Disorders ,medicine.disease ,Intestinal toxicity ,Intestinal Fatty Acid-Binding Protein ,medicine.symptom ,business - Abstract
Abdominal pain is known to be an early clinical predictor of severe systemic Russell's viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain is unknown, but we postulated it might be due to intestinal microvascular endothelial gut damage. Gut-toxicity can be detected using the novel biomarker Intestinal Fatty Acid Binding Protein (IFABP). We also wanted to explore the mechanisms and consequences of this toxicity by measuring procalcitonin as a specific marker of sepsis triggered by bacterial endotoxin, and serum cystatin-C (CysC) as a measure of acute kidney injury. We hypothesised that severe gut-injury might lead to gut-barrier failure, translocation of gastrointestinal microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake-bite severity, including acute kidney injury that was previously attributed to direct venom effects.Serial plasma samples previously collected from 16 RV envenomations with abdominal pain, 15 RV envenomations without abdominal pain and 25 healthy controls were assayed for IFABP. A subgroup of these RV envenomations were assayed for procalcitonin (The median peak IFABP for RV envenomations was much higher than healthy controls [3703.0 pg/mL (IQR 2250.1-13702.0 pg/mL) vs. 270.1 pg/mL (IQR 153.5-558.0 pg/mL) (IFABP is significantly elevated indicating enterocyte damage occurs in RV envenomation. IFABP correlated with markers of sepsis (procalcitonin) and acute kidney injury (serum CysC) suggesting that enterocyte damage resulting in translocation of microbial associated molecular patterns (MAMPs) contributes to RV envenomation associated SIRS and sepsis.
- Published
- 2021
34. Trajectories of pregabalin use and their association with longitudinal changes in opioid and benzodiazepine use
- Author
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Nicholas A. Buckley, Andrea L Schaffer, Sallie-Anne Pearson, and Jonathan Brett
- Subjects
Male ,medicine.drug_class ,Pregabalin ,Benzodiazepines ,medicine ,Outpatient setting ,Humans ,Benzodiazepine ,business.industry ,Australia ,Middle Aged ,Opioid-Related Disorders ,Confidence interval ,Discontinuation ,Analgesics, Opioid ,Clinical trial ,Anesthesiology and Pain Medicine ,Neurology ,Opioid ,Anesthesia ,Concomitant ,Female ,Neurology (clinical) ,business ,medicine.drug - Abstract
Concomitant use of pregabalin with opioids and/or benzodiazepines is common, despite the increased risks. However, clinical trials suggest pregabalin can have an opioid-sparing effect when treating acute postoperative pain. We explored how opioid and benzodiazepine use changed over time in people initiating pregabalin, using dispensing claims data for a 10% sample of Australians (2013-19). Among 142,776 people initiating pregabalin (median age = 61 years, 57% female), we used group-based trajectory modelling to identify 6 pregabalin dose trajectories in the first year postinitiation. Two trajectories involved discontinuation: after one dispensing (49%), and after 6 months of treatment (14%). Four trajectories involved persistent use with variable estimated median daily doses of 39 mg (16%), 127 mg (14%), 276 mg (5%), and 541 mg (2%). We quantified opioid and benzodiazepine use in the year before and after pregabalin initiation using generalised linear models. Over the study period, 71% were dispensed opioids and 34% benzodiazepines, with people on the highest pregabalin dose having highest rates of use. Opioid use increased postpregabalin initiation. Among people using both opioids and pregabalin, the geometric mean daily dose in oral morphine equivalents increased after pregabalin initiation in all trajectories, ranging from +5.9% (99% confidence interval 4.8%-7.0%) to +39.8% (99% confidence interval 38.3%-41.5%) in people on the highest daily pregabalin dose. Among people using both pregabalin and benzodiazepines, the dose remained constant over time for people in all trajectories. Notwithstanding its reputation as opioid-sparing, in this outpatient setting, we observed that people using opioids tended to use higher opioid daily doses after pregabalin initiation, especially those on high pregabalin doses.
- Published
- 2021
35. Alcohol‐related suicide across Australia: a geospatial analysis
- Author
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Andrew Page, Peter Malouf, Jennifer L. Schumann, Nicholas A. Buckley, Tristan Hurzeler, Firouzeh Noghrehchi, and Kate M. Chitty
- Subjects
Acute effects ,medicine.medical_specialty ,Geospatial analysis ,Alcohol Drinking ,030309 nutrition & dietetics ,Distribution (economics) ,computer.software_genre ,Disease cluster ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Environmental health ,medicine ,Cluster Analysis ,Humans ,030212 general & internal medicine ,Risk factor ,Socioeconomic status ,suicide ,0303 health sciences ,Spatial Analysis ,acute alcohol use ,business.industry ,alcohol ,Public health ,Public Health, Environmental and Occupational Health ,Age Factors ,Australia ,Time of death ,Geography ,Cross-Sectional Studies ,alcohol‐related suicide ,Public aspects of medicine ,RA1-1270 ,business ,computer - Abstract
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.
- Published
- 2021
36. The Association Between Problematic Use of Alcohol and Drugs and Repeat Self-Harm and Suicidal Ideation
- Author
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Kate M, Chitty, Rachael C, Cvejic, Teresa, Heintze, Preeyaporn, Srasuebkul, Kirsten, Morley, Andrew, Dawson, Gregory, Carter, Michael, Dinh, Nicholas A, Buckley, and Julian N, Trollor
- Published
- 2022
37. Role of age-sex as underlying risk factors for death in acute pesticide self-poisoning: a prospective cohort study
- Author
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Andrew H. Dawson, Jacques Raubenheimer, Nicholas A. Buckley, and Firouzeh Noghrehchi
- Subjects
Male ,medicine.medical_specialty ,Age effect ,Toxicology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Pesticides ,Prospective cohort study ,Sri Lanka ,business.industry ,Poisoning ,030208 emergency & critical care medicine ,General Medicine ,Pesticide ,3. Good health ,Hospitalization ,Increased risk ,Female ,Self poisoning ,business - Abstract
There is growing evidence in the literature that patients' age is associated with increased risk of death in acute pesticide poisoning. However, few studies have investigated whether the age effect differs between males and females. We aimed to examine the association between age-sex and risk of death in acute pesticide self-poisoning.A prospective cohort of deliberate pesticide-poisoned patients admitted to ten rural Sri Lankan hospitals between March 2002 and December 2019. The pesticide ingested was identified based on identification of container or history. A mixed effects logistic regression was fitted to investigate the effect of age-sex on death in acute pesticide self-poisoning adjusting for clinical symptoms on admission, measured by Glasgow Coma Scale and Poison Severity Score, and controlling for clustering among hospital sites.In total, 201 different pesticides were ingested by patients. 6,643 patients ingested an unknown pesticide. A single pesticide was co-ingested with alcohol by 4,603 patients. Of the 28,303 patients enrolled, 2,028 patients died, resulting in case fatality of 7.2% (95% CI 6.9-7.5). The effect of age on case fatality was stronger for males after 21 years of age. The odds of dying for each 5 years increase in age was 1.26 (95% CI 1.23-1.28) times higher for males versus 1.14 (95% CI 1.10-1.19) times higher for females. Missing data were handled by multiple imputation.Patient's age-sex are important risk factors for death in acute pesticide self-poisoning even after controlling for clinical effects. The age effect on the odds of dying was significantly different for males and females, with this effect being stronger for males. Given that patient's age and sex are very easy to collect on admission, our study highlights the need for incorporating these risk factors in policy and clinical decisions.
- Published
- 2021
38. Opioids and antidepressants: which combinations to avoid
- Author
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Varan Perananthan and Nicholas A. Buckley
- Subjects
Pharmacology (medical) - Published
- 2021
39. Urinary microRNAs as non-invasive biomarkers for toxic acute kidney injury in humans
- Author
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Indika Gawarammana, Devanshi Seth, Nicholas A. Buckley, Fathima Shihana, Fahim Mohamed, Geoffrey K. Isbister, Mugdha V. Joglekar, Wilson K. M. Wong, and Anandwardhan A. Hardikar
- Subjects
0301 basic medicine ,Paraquat ,medicine.medical_specialty ,Urinary system ,Science ,Glycine ,Viper Venoms ,Toxicology ,Gastroenterology ,Article ,Nephrotoxicity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,microRNA ,medicine ,Animals ,Humans ,Russell's Viper ,Kidney ,Multidisciplinary ,business.industry ,Oxalic Acid ,Non invasive biomarkers ,Acute kidney injury ,Reproducibility of Results ,Diagnostic markers ,Acute Kidney Injury ,medicine.disease ,Fold change ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cohort ,miRNAs ,Medicine ,business ,Biomarkers - Abstract
MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine samples from patients with Russell’s viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 samples in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell’s viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had > 17 fold change (p 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.
- Published
- 2021
40. Price mark-up on the street sales of prescription pharmaceuticals in Australia
- Author
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Jacques Raubenheimer, Nicholas A. Buckley, and Oluwaseun Egunsola
- Subjects
Health (social science) ,Price difference ,Drug prices ,Medicine (miscellaneous) ,Monetary economics ,Business ,Black market ,Medical prescription ,health care economics and organizations - Abstract
Background: This study aims to compare the price difference between the official price for pharmaceutical drugs and the price when sourced from the black market in Australia. Methods: Drug prices r...
- Published
- 2020
41. Urinary versus serum microRNAs in human oxalic acid poisoning: Contrasting signals and performance
- Author
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Devanshi Seth, Nicholas A. Buckley, Fathima Shihana, Anandwardhan A. Hardikar, Fahim Mohamed, and Mugdha V. Joglekar
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Urinary system ,Renal function ,Urine ,Kidney ,Kidney Function Tests ,Toxicology ,Gastroenterology ,Nephrotoxicity ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,microRNA ,medicine ,Humans ,Ingestion ,business.industry ,Oxalic Acid ,Acute kidney injury ,General Medicine ,Acute Kidney Injury ,medicine.disease ,Fold change ,MicroRNAs ,030104 developmental biology ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
MicroRNAs are key regulators of the normal kidney function and development, and altered in acute kidney injury (AKI). However, there is a lack of studies comparing serum and urine miRNA expression in toxic AKI in humans. We aimed to compare the global signature of urinary and serum microRNAs, with and without kidney injury, after human oxalic acid poisoning. We profiled urinary microRNAs in patients who ingested oxalic acid and developed no injury (No AKI n = 3), moderate injury (AKIN2 n = 3) or severe injury (AKIN3 n = 3) and healthy controls (n = 3). We validated a signature of 30 urinary microRNAs identified in the discovery profiling, in a second cohort of individuals exposed to oxalic acid (No AKI n = 15, AKIN2 n=11 & AKIN3 n= 18) and healthy controls (n=-27) and we compared the results with previously published serum data. Global profiling in toxic AKI patients showed a higher expression of urinary microRNAs and lower expression of serum microRNAs. Most urine microRNA in the validation cohort were significantly upregulated (25/30, fold change >2.8 and p < 0.05) in AKIN2/3 patients compared to No AKI. Four urinary microRNAs (miR-191, miR-19b, miR-20a and miR-30b) had good diagnostic performance (AUC greater than 0.8) to predict AKIN2/3 between 4-8 hours post ingestion. Poisoning irrespective of AKI led to significantly lower expression of many microRNAs in serum but relatively few changes in urinary miRNA expression. In conclusion, urinary microRNA signature provides a stronger measure of AKI in oxalic acid poisoning compared to serum microRNA. Kidney injury has the greatest impact on urinary microRNA, while poisoning itself was better reflected in serum miRNA. Plasma and urinary microRNAs signatures provide complementary information in toxic kidney injury.
- Published
- 2020
42. D-dimer testing for early detection of venom-induced consumption coagulopathy after snakebite in Australia (ASP-29)
- Author
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Geoffrey K Isbister, Tina Noutsos, Shane Jenkins, Katherine Z Isoardi, Jessamine Soderstrom, and Nicholas A Buckley
- Subjects
Elapid Venoms ,Fibrin Fibrinogen Degradation Products ,Antivenins ,Australia ,Humans ,Snake Bites ,General Medicine ,Prospective Studies ,Disseminated Intravascular Coagulation - Abstract
To assess the accuracy and marginal value of quantitative D-dimer testing for diagnosing venom-induced consumption coagulopathy (VICC) in people bitten by Australian snakes.Analysis of data for suspected and confirmed cases of snakebite collected prospectively by the Australian Snakebite Project, 2005-2019, from 200 hospitals across Australia.1363 patients for whom D-dimer was quantitatively assessed within 24 hours of suspected or confirmed snakebite.Diagnostic performance of quantitative D-dimer testing for detecting systemic envenoming with VICC (area under the receiver operating characteristic curve, AUC); optimal D-dimer cut-off value (maximum sum of sensitivity and specificity).D-dimer values exceeded 2.5 mg/L within three hours of the bite for 95% of patients who developed VICC, and were lower than 2.5 mg/L for 95% of non-envenomed patients up to six hours after snakebite. The AUC for diagnosing envenoming with VICC on the basis of quantitative D-dimer testing within six hours of snakebite was 0.97 (95% CI, 0.96-0.98; 944 patients). Diagnostic performance increased during the first three hours after snakebite; for quantitative D-dimer testing at 2-6 hours, the AUC was 0.99 (95% CI, 0.99-1.0); with a cut-off of 2.5 mg/L, sensitivity was 97.1% (95% CI, 95.0-98.3%) and specificity 99.0% (95% CI, 97.6-99.6%) for VICC. For 36 patients with normal international normalised ratio (INR) and activated partial thromboplastin time (aPTT) values 2-6 hours after snakebite, the AUC was 0.97 (95% CI, 0.93-1.0); with a cut-off of 1.4 mg/L, sensitivity was 94% (95% CI, 82-99%) and specificity 96% (95% CI, 94-97%). In all but one of 84 patients who developed VICC-related acute kidney injury, D-dimer values exceeded 4 mg/L within 24 hours of the bite.D-dimer concentrations assessed 2-6 hours after snakebite, with a cut-off value of 2.5 mg/L, could be useful for diagnosing envenoming with VICC.
- Published
- 2022
43. Angiotensin axis antagonists increase the incidence of haemodynamic instability in dihydropyridine calcium channel blocker poisoning
- Author
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Nicholas A. Buckley, Jessica J M Huang, Betty S. Chan, Jared A Brown, Angela L. Chiew, Katherine Z Isoardi, Geoffrey K. Isbister, and Rose Cairns
- Subjects
Adult ,Male ,Dihydropyridines ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,Angiotensin II Receptor Blockers ,Pharmacology ,Toxicology ,Angiotensin Receptor Antagonists ,03 medical and health sciences ,0302 clinical medicine ,Renin–angiotensin system ,medicine ,Humans ,030212 general & internal medicine ,Amlodipine ,Receptor ,Aged ,Retrospective Studies ,business.industry ,Incidence (epidemiology) ,Hemodynamics ,030208 emergency & critical care medicine ,General Medicine ,Middle Aged ,Calcium Channel Blockers ,Haemodynamic instability ,Toxicity ,Female ,business ,Dihydropyridine Calcium Channel Blocker ,medicine.drug - Abstract
Amlodipine, a dihydropyridine calcium channel blocker (CCB), is the leading cause of cardiovascular drug-related overdose deaths in the USA. In contrast, angiotensin-II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) cause minimal toxicity in overdose. ACEIs/ARBs are often combined with dihydropyridines in hypertension treatment. Co-ingested ARBs/ACEIs may significantly contribute to the toxicity of dihydropyridine, but this has not been investigated.To investigate the clinical outcomes from dihydropyridine overdoses with ARBs/ACEIs versus dihydropyridine overdoses alone.This was a retrospective study of patients reported to the New South Wales Poisons Information Centre (NSW PIC) and 3 toxicology units (Jan 2016 to Jun 2019) in Australia. Patients14 years who took an overdose of dihydropyridines (amlodipine, felodipine, lercanidipine, nifedipine) were included. Concurrent overdoses with non-dihydropyridine CCBs, alpha-blockers and beta-blockers were excluded. Patient demographics, drugs exposure details, serial vital signs, treatments and outcome were collected.There were 100 patients. 68 took mixed overdoses of dihydropyridines with ARBs/ACEIs and 32 took single overdoses of dihydropyridines without ARBs/ACEIs. The mixed group had lower median nadir mean arterial pressures (62 vs 75 mmHg,Combined overdoses of dihydropyridines with ARBs/ACEIs caused more significant hypotension and required more haemodynamic support than overdoses of dihydropyridines alone.
- Published
- 2020
44. The clinical toxicity of imidacloprid self-poisoning following the introduction of newer formulations
- Author
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Varan Perananthan, Nicholas A. Buckley, Andrew H. Dawson, Fahim Mohamed, Seyed Shahmy, and Indika Gawarammana
- Subjects
Male ,Insecticides ,Administration, Oral ,Pharmacology ,Toxicology ,Neonicotinoids ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Imidacloprid ,parasitic diseases ,Humans ,Medicine ,Prospective Studies ,030212 general & internal medicine ,Sri Lanka ,Low toxicity ,business.industry ,030208 emergency & critical care medicine ,General Medicine ,Middle Aged ,Nitro Compounds ,Respiration, Artificial ,Cns toxicity ,chemistry ,Toxicity ,Self poisoning ,Respiratory Insufficiency ,business - Abstract
Self-poisoning with imidacloprid has been previously shown to have low toxicity in humans. Since 2007 newer formulations of Imidacloprid with unknown solvents have been introduced and the potential clinical consequences of these products have not been described.Clinical and demographic data were prospectively collected from admissions following oral ingestion of imidacloprid from seven hospitals in Sri Lanka. Data was collected from 2002 to 2007 in an already published study. We compared this data on poisonings collected from 2010 to 2016 following the introduction of new formulations of imidacloprid.From 2002-2007, there were 56 patients with ingestion to imidacloprid compared to 67 patients post 2010 The median time to presentation prior to 2007 was 4 h (IQR 2.3-6.0 hrs) and post 2010 was only 2.0 hr (IQR 1.5 to 3.1 hrs). The median amount ingested was 15 ml (IQR 10.0-50.0mls) prior to 2007 and 27.5mls (IQR 5.0-71.8mls) post 2010. In both studies most patients developed non-specific symptoms including nausea, vomiting, epigastric pain and headache. However, prior to 2007 only 1.9% of the cohort required mechanical ventilation due to respiratory failure and there were no reported deaths. In contrast, post 2010; deaths occurred in 3.0% of the cohort and 6.0% required mechanical ventilation for respiratory failure. The cause of mortality was due to one case of cardiorespiratory failure and the other due to a prolonged admission complicated with lobar pneumonia leading to decompensated liver failure on the background of undiagnosed liver cirrhosis.Although acute exposure to imidacloprid is usually associated with mild non-specific symptoms, since the introduction of new formulations of imidacloprid, the toxic profile has changed with reported cases of death as well as an increase in cases requiring mechanical ventilation. The change in toxicity could be due to the solvents used in the newer formulations but also due to higher dose of imidacloprid described in our latter cohort. Further research into these solvents needs to be done and continued toxicovigilance is required.
- Published
- 2020
45. Reporting of alcohol as a contributor to death in Australian national suicide statistics and its relationship to post‐mortem alcohol concentrations
- Author
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Nicholas A. Buckley, Jennifer L. Schumann, Lauren L. Moran, Tristan Hurzeler, Kate M. Chitty, and Daniel G. Chong
- Subjects
medicine.medical_specialty ,Population ,030508 substance abuse ,Medicine (miscellaneous) ,Alcohol ,Odds ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Outcome variable ,Cause of Death ,Blood alcohol ,Epidemiology ,Statistics ,medicine ,Humans ,030212 general & internal medicine ,education ,Cause of death ,education.field_of_study ,Ethanol ,business.industry ,Australia ,Suicide ,Psychiatry and Mental health ,chemistry ,Blood Alcohol Content ,Code assignment ,Autopsy ,0305 other medical science ,business - Abstract
Aim To describe the assignment of International Classification of Disease (ICD)-10 alcohol codes as underlying or contributory causes of death by the Australian Bureau of Statistics during mortality coding for suicides according to the blood alcohol concentration (BAC) detected at autopsy. Design Population-based case-series descriptive analysis. Setting and participants Data for all alcohol-related (Alc+) suicide deaths (aged 15+) in Australia from 2010-2015 (n = 3132) from the National Coronial Information System. Measurements Alc+ suicides were categorised as those with a post-mortem BAC ≥0.05 g/100 mL. The outcome variable was whether the case was assigned an ICD-10 alcohol code (F10.0-F10.9, R78.0, T51, X45 and/or X65). We estimated OR for the assignment of codes in Alc+ suicides using BAC as the key predictor. We also examined several covariates that have been implicated in the risk of Alc+ suicides. Findings An ICD-10 alcohol code was assigned during the mortality coding process in 47.6% (n = 1491) of Alc+ suicides. Higher BAC was associated with higher odds of having a code assigned; cases with a BAC over 0.20 g/100 mL over were twice as likely to have an alcohol code assigned (adjusted OR [AOR] = 2.06, 95% CI = 1.59, 2.67) compared with cases with a BAC of 0.050-0.075 g/100 mL. Compared with New South Wales, higher likelihood of code assignment was found in Northern Territory (AOR = 3.85, 95% CI = 2.32, 6.63) and Western Australia (AOR = 2.89, 95% CI = 2.27, 3.68). Compared with 15-24 year olds, 25-44 (AOR = 0.79, 95% CI = 0.63, 0.99) and 65-84 year olds (AOR = 0.63, 95% CI = 0.43, 0.93) were less likely to have a code assigned. Conclusions An ICD-10 alcohol code was not assigned as an underlying or contributory cause of death in over half of suicides in Australia (2010-2015) with a BAC ≥0.05 g/100 mL. The higher the BAC detected at autopsy, the more likely cases were to be assigned an alcohol code during the mortality coding process.
- Published
- 2020
46. Subacute and chronic neuropsychological sequalae of acute organophosphate pesticide self-poisoning: a prospective cohort study from Sri Lanka
- Author
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Vajira S. Weerasinghe, Indika Gawarammana, Nicholas A. Buckley, and Tharaka L. Dassanayake
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Erythrocytes ,Context (language use) ,Neuropsychological Tests ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,Cognition ,Organophosphate Poisoning ,0302 clinical medicine ,Epidemiology ,Reaction Time ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,business.industry ,Organophosphate ,Neuropsychology ,030208 emergency & critical care medicine ,General Medicine ,Middle Aged ,Pesticide ,chemistry ,Acute Disease ,Acetylcholinesterase ,Female ,Sri lanka ,business ,Neurocognitive - Abstract
Some epidemiological evidence implicates acute organophosphate (OP) pesticide poisoning in long-term neurocognitive deficits. However, no study has prospectively followed up poisoned patients long-term from the time of intoxication. We aimed to determine whether clinically significant acute OP self-poisoning leads to subacute and chronic neurocognitive deficits, in a prospective follow up study.Employing Mini Mental State Examination, Digit Span and Cambridge Neuropsychological Test Automated Battery (CANTAB), we compared multiple cognitive functions in 222 patients hospitalized with acute OP pesticide self-poisoning with a control group of 52 patients hospitalized with paracetamol overdose, at three time points: on discharge following clinical recovery, 6 weeks and 6 months post-ingestion. Intergroup comparisons at each time point were done in multiple regression models, adjusting for sex, age, education and psychiatric comorbidities. OP within-group analysis was done to determine a dose-response relationship.After adjusting for covariates, the OP poisoned group had significantly poorer working memory (Digit Span) and episodic memory (CANTAB Paired Associates Learning); impaired spatial planning (CANTAB Stocking of Cambridge); and slower response speed in the sustained attention task (CANTAB Rapid Visual Information Processing), in the post-discharge assessment. Only working memory and episodic memory measures were impaired in the OP group at 6 weeks, whereas no significant intergroup differences were observed at 6 months. The OP subgroup who had complete red cell acetylcholinesterase inhibition on admission had poorer episodic memory when tested post-discharge than those who had partial inhibition, but no significant subgroup differences were observed at 6 weeks or 6 months.Acute OP pesticide poisoning may cause neuropsychological impairment that outlasts the cholinergic phase on a subacute time scale; but does not cause measurable chronic neuropsychological deficits.
- Published
- 2020
47. Potentially inappropriate benzodiazepine use in Australian adults: A population‐based study (2014–2017)
- Author
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Danni Zheng, Andrea L Schaffer, Nicholas A. Buckley, Sallie-Anne Pearson, Jonathan Brett, and Benjamin Daniels
- Subjects
Adult ,Male ,medicine.medical_specialty ,Health (social science) ,Adolescent ,Substance-Related Disorders ,medicine.drug_class ,Population ,Medicine (miscellaneous) ,Inappropriate Prescribing ,Logistic regression ,Cohort Studies ,Benzodiazepines ,Young Adult ,Humans ,Medicine ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,Benzodiazepine ,business.industry ,Australia ,Guideline ,Middle Aged ,Pharmacoepidemiology ,Population based study ,Population Surveillance ,Emergency medicine ,Cohort ,Female ,business ,Cohort study - Abstract
Inappropriate benzodiazepine use continues to cause substantial morbidity and mortality globally. We aimed to characterise the initiation of new benzodiazepine treatment episodes in Australia and identify correlates of potentially inappropriate benzodiazepine use.We conducted a population-based cohort study using dispensing claims from a 10% sample of Pharmaceutical Benefit Scheme eligible Australians (2014-2017). Our cohort comprised adults initiating a new benzodiazepine treatment; we defined potentially inappropriate use as ≥3 benzodiazepine dispensing over any continuous 90-day period in the year following initiation. We examined characteristics associated with potentially inappropriate benzodiazepine use using multivariable logistic regression.People initiating a new benzodiazepine treatment episode (n = 276 765) were more frequently female (59.1%) and 65 years of age (73.6%). In the 90 days prior to initiating benzodiazepine, people were commonly dispensed antidepressants (26.5%), opioid analgesics (17.6%) and antipsychotics (4.7%). In the first year after initiation, 20 938 (9.5%) people experienced 'potentially inappropriate use'. Having a greater initial quantity of benzodiazepine dispensed [odds ratio (OR), 1.10; 95% confidence interval (CI) 1.08-1.12 per 10 defined daily doses increase], dispensing of antipsychotics (OR 3.00, 95% CI 2.86-3.15) and 5 unique medicines (OR 2.54, 95% CI 2.44-2.64; vs. ≤5 unique medicines) in the 90 days prior to initiation were associated with potentially inappropriate benzodiazepine use.Approximately, 1 in 10 people who initiated benzodiazepines were using it beyond the guideline recommended period. We identified factors at the time of initiation associated with potentially inappropriate use; clinicians should consider these before prescribing benzodiazepines and initiate conversations about alternative therapy when necessary.
- Published
- 2020
48. Utilisation of teratogenic medicines before and during pregnancy in Australian women
- Author
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Nicholas A. Buckley, Alys Havard, Smriti Raichand, Sallie-Anne Pearson, and Helga Zoega
- Subjects
Adult ,medicine.medical_specialty ,Population ,Third trimester ,Risk Assessment ,03 medical and health sciences ,Fetus ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,030212 general & internal medicine ,education ,education.field_of_study ,030219 obstetrics & reproductive medicine ,High prevalence ,business.industry ,Obstetrics ,Australia ,Obstetrics and Gynecology ,Gestational age ,General Medicine ,medicine.disease ,Drug Utilization ,Teratology ,Teratogens ,In utero ,Female ,Pregnancy Trimesters ,New South Wales ,business - Abstract
BACKGROUND Given the potential hazards of teratogenic medicines, to a fetus exposed in utero, monitoring their use around pregnancy is imperative. AIM To measure utilisation of teratogenic medicines (Therapeutic Goods Administration's category D or X) in women who gave birth in New South Wales, Australia, during pregnancy and the 24 months prior. MATERIALS AND METHODS We used linked population-based datasets including dispensing and perinatal data for all deliveries in NSW between 2005 and 2012. We included pregnancies among concessional beneficiaries only, with complete ascertainment of dispensing claims. Pre-pregnancy and during-pregnancy periods were based on birth dates and gestational age. We determined prevalence of exposure using percent of pregnancies in which women had at least one dispensed teratogenic medicine in three-month time periods. RESULTS The study included 191 588 pregnancies (145 419 women). Prevalence of exposure to D/X medicines anytime during pregnancy was 2.0% (
- Published
- 2020
49. Changes in sales of analgesics to pharmacies after codeine was rescheduled as a prescription only medicine
- Author
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Rose Cairns, Natasa Gisev, Sallie-Anne Pearson, Jared A Brown, Andrea L Schaffer, and Nicholas A. Buckley
- Subjects
medicine.medical_specialty ,Prescription Drugs ,Analgesic ,Population ,Nonprescription Drugs ,Community Pharmacy Services ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030212 general & internal medicine ,Medical prescription ,Adverse effect ,education ,Pholcodine ,education.field_of_study ,Codeine ,business.industry ,Australia ,Commerce ,Interrupted Time Series Analysis ,General Medicine ,Dextromethorphan ,Dihydrocodeine ,Analgesics, Opioid ,Drug and Narcotic Control ,business ,medicine.drug - Abstract
Objective To investigate changes in sales to pharmacies of over-the-counter (OTC) and prescription analgesics, cold and flu products, and cough suppressants after the rescheduling of codeine as a prescription only medicine in February 2018. Design Interrupted time series analysis of sales to pharmacies. Setting Pharmaceutical sales to community pharmacies in Australia, March 2015 - March 2019. The period January 2017 (month after rescheduling was announced) to January 2018 (month before rescheduling was implemented) was excluded from the time series analysis. Main outcome measures Monthly pack and tablet sales per 10 000 population of OTC and prescription analgesics, cold and flu products, and cough suppressants. Results During 2016, 7586 packs and 248 127 tablets of OTC codeine per 10 000 population were sold to pharmacies; in the 14 months after rescheduling, a small level increase in monthly prescription codeine sales was evident (2247 tablets/capsules per 10 000 population; 95% CI, 1231-3264 per 10 000 population). Monthly OTC analgesic sales increased by 258 (95% CI, 151-365) packs per 10 000 population and 37 856 (95% CI, 26 143-49 569) tablet/capsules per 10 000 population. Monthly sales of single ingredient paracetamol (41 415 [95% CI, 31 374-51 456] tablets/capsules per 10 000 population), ibuprofen (1392 [95% CI 916-1868] tablets/capsules per 10 000 population), paracetamol/ibuprofen (1618 tablets [95% CI, 1567-1669] tablets/capsules per 10 000 population), and other paracetamol combinations (233 [95% CI, 112-353] tablets/capsules per 10 000 population) all increased, but not those of prescription analgesic products not containing codeine. Rises for OTC cold/flu products containing the opioid derivative dextromethorphan were small; sales of OTC cough suppressants containing opioid derivatives (dextromethorphan, pholcodine, dihydrocodeine) did not change. Conclusions The rescheduling of codeine was followed by increased sales to pharmacies of paracetamol, ibuprofen, and paracetamol combination products. While these products carry no risk of dependence, their inappropriate use is also associated with harms that warrant adverse event monitoring.
- Published
- 2020
50. Early acetaminophen-protein adducts predict hepatotoxicity following overdose (ATOM-5)
- Author
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Nicholas A. Buckley, Betty S. Chan, Laura P. James, Kylie McArdle, Angela L. Chiew, John W. Pickering, and Geoffrey K. Isbister
- Subjects
Adult ,Male ,medicine.medical_specialty ,acetaminophen overdose ,Adolescent ,NAPQI ,Metabolite ,digestive system ,Gastroenterology ,Acetylcysteine ,Young Adult ,chemistry.chemical_compound ,Interquartile range ,Internal medicine ,Benzoquinones ,medicine ,Humans ,Prospective Studies ,Acetaminophen ,Liver injury ,Hepatology ,business.industry ,organic chemicals ,digestive, oral, and skin physiology ,Australia ,Alanine Transaminase ,Analgesics, Non-Narcotic ,Middle Aged ,medicine.disease ,digestive system diseases ,stomatognathic diseases ,Treatment Outcome ,Liver ,chemistry ,Toxicity ,Administration, Intravenous ,Female ,Imines ,Chemical and Drug Induced Liver Injury ,Drug Overdose ,business ,Biomarkers ,medicine.drug - Abstract
Acetaminophen-protein adducts are specific biomarkers of toxic acetaminophen (paracetamol) metabolite exposure. In patients with hepatotoxicity (alanine aminotransferase [ALT]1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen. Our aim was to characterise acetaminophen-protein adduct concentrations in patients following acetaminophen overdose and determine if they predict toxicity.We performed a multicentre prospective observational study, recruiting patients 14 years of age or older with acetaminophen overdose regardless of intent or formulation. Three serum samples were obtained within the first 24 h of presentation and analysed for acetaminophen-protein adducts. Acetaminophen-protein adduct concentrations were compared to ALT and other indicators of toxicity.Of the 240 patients who participated, 204 (85%) presented following acute ingestions, with a median ingested dose of 20 g (IQR 10-40), and 228 (95%) were treated with intravenous acetylcysteine at a median time of 6 h (IQR 3.5-10.5) post-ingestion. Thirty-six (15%) patients developed hepatotoxicity, of whom 22 had an ALT ≤1,000 U/L at the time of initial acetaminophen-protein adduct measurement. Those who developed hepatotoxicity had a higher initial acetaminophen-protein adduct concentration compared to those who did not, 1.63 nmol/ml (IQR 0.76-2.02, n = 22) vs. 0.26 nmol/ml (IQR 0.15-0.41; n = 204; p0.0001), respectively. The AUROC for hepatotoxicity was 0.98 (95% CI 0.96-1.00; n = 226; p0.0001) with acetaminophen-protein adduct concentration and 0.89 (95% CI 0.82-0.96; n = 219; p0.0001) with ALT. An acetaminophen-protein adduct concentration of 0.58 nmol/ml was 100% sensitive and 91% specific for identifying patients with an initial ALT ≤1,000 U/L who would develop hepatotoxicity. Adding acetaminophen-protein adduct concentrations to risk prediction models improved prediction of hepatotoxicity to a level similar to that obtained by more complex models.Acetaminophen-protein adduct concentration on presentation predicted which patients with acetaminophen overdose subsequently developed hepatotoxicity, regardless of time of ingestion. An adduct threshold of 0.58 nmol/L was required for optimal prediction.Acetaminophen poisoning is one of the most common causes of liver injury. This study examined a new biomarker of acetaminophen toxicity, which measures the amount of toxic metabolite exposure called acetaminophen-protein adduct. We found that those who developed liver injury had a higher initial level of acetaminophen-protein adducts than those who did not.Australian Toxicology Monitoring (ATOM) Study-Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.
- Published
- 2020
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