Validation of ICD-10-AM Coding for Myocardial Infarction Subtype in Hospitalisation Data.

BACKGROUND: International Classification of Disease (ICD) codes are central for identifying myocardial infarction (MI) in administrative hospitalisation data, however validation of MI subtype codes is limited. We measured the sensitivity and specificity of ICD-10-AM (Australian Modification) codes for ST-elevation MI (STEMI) and non-STEMI (NSTEMI). METHODS: A sample of MI admissions was obtained from a dataset containing all MI hospitalisations in Western Australia (WA) for 2003, 2008 and 2013. Clinical data were collected from hospital medical records (n=799 patients). Cases were classified by ICD-10-AM codes for STEMI, NSTEMI and unspecified MI, and compared to clinical classification from review of available electrocardiographs (ECGs) and cardiac biomarkers (n=660). Sensitivity and specificity for ICD-10-AM coding versus clinical classification was measured, stratified by calendar year of discharge. RESULTS: The majority of classifiable cases had MI recorded in the principal diagnosis field (STEMI n=293, 84.2%; NSTEMI n=202, 74.3%; unspecified MI n=20, 50.0%). Overall sensitivity of the ICD-10-AM STEMI code was 86.3% (95% CI 81.7-90.0%) and was higher when restricted to MI as a principal versus secondary diagnosis (88.8% vs 66.7%). Comparable values for NSTEMI were 66.7% (95% CI 61.5-71.6%), and 68.8% vs 61.4% respectively. Between 2003 and 2013, sensitivity for both MI subtypes increased: 80.2-89.5% for STEMI, and 51.2-73.8% for NSTEMI. Specificity was high for NSTEMI throughout (88.2% 95% CI 84.1-91.6%), although improving over time for STEMI (68.1-76.4%). CONCLUSIONS: The sensitivity and specificity of ICD-10-AM codes for MI subtypes in hospitalisation data are generally high, particularly for principal diagnosis cases. However, the temporal improvement in sensitivity in coding of MI subtypes, particularly NSTEMI, may necessitate modification to trend studies using administrative hospitalisation data.

In Vivo Half-Life Extension of BMP1/TLL Metalloproteinase Inhibitors Using Small-Molecule Human Serum Albumin Binders.

Reducing the required frequence of drug dosing can improve the adherence of patients to chronic treatments. Hence, drugs with longer in vivo half-lives are highly desirable. One of the most promising approaches to extend the in vivo half-life of drugs is conjugation to human serum albumin (HSA). In this work, we describe the use of AlbuBinder 1, a small-molecule noncovalent HSA binder, to extend the in vivo half-life and pharmacology of small-molecule BMP1/TLL inhibitors in humanized mice (HSA KI/KI). A series of conjugates of AlbuBinder 1 with BMP1/TLL inhibitors were prepared. In particular, conjugate c showed good solubility and a half-life extension of >20-fold versus the parent molecule in the HSA KI/KI mice, reaching half-lives of >48 h with maintained maximal inhibition of plasma BMP1/TLL. The same conjugate showed a half-life of only 3 h in the wild-type mice, suggesting that the half-life extension was principally due to specific interactions with HSA. It is envisioned that conjugation to AlbuBinder 1 should be applicable to a wide range of small molecule or peptide drugs with short half-lives. In this context, AlbuBinders represent a viable alternative to existing half-life extension technologies.

Retrospective use of PBPK modelling to understand a clinical drug-drug interaction between dextromethorphan and GSK1034702.

1. In a clinical trial, a strong drug-drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI. 2. In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702. PBPK models were populated with the in vitro parameters and DDI simulations conducted and compared to the observed data from a clinical study with DM and GSK1034702. 3. GSK1034702 was a potent direct and metabolism-dependent inhibitor of human CYP2D6, with inhibition parameters of: IC50 = 1.6 µM, Kinact = 3.7 h-1 and KI = 0.8 µM. Incorporating these data into PBPK models predicted a DDI after repeat, but not single, 5 mg doses of GSK1034702. 4. The DDI observed with repeat administration of GSK1034702 (5 mg) can be attributed to metabolism-dependent inhibition of CYP2D6. Further, in vitro data were generated and several potential mechanisms proposed to explain the interaction observed following a single dose of GSK1034702.

A cohort study: temporal trends in prevalence of antecedents, comorbidities and mortality in Aboriginal and non-Aboriginal Australians with first heart failure hospitalization, 2000-2009.

BACKGROUND/OBJECTIVES: Little is known about trends in risk factors and mortality for Aboriginal Australians with heart failure (HF). This population-based study evaluated trends in prevalence of risk factors, 30-day and 1-year all-cause mortality following first HF hospitalization among Aboriginal and non-Aboriginal Western Australians in the decade 2000-2009. METHODS: Linked-health data were used to identify patients (20-84 years), with a first-ever HF hospitalization. Trends in demographics, comorbidities, interventions and risk factors were evaluated. Logistic and Cox regression models were fitted to test and compare trends over time in 30-day and 1-year mortality. RESULTS: Of 17,379 HF patients, 1,013 (5.8%) were Aboriginal. Compared with 2000-2002, the prevalence (as history) of myocardial infarction and hypertension increased more markedly in 2006-2009 in Aboriginal (versus non-Aboriginal) patients, while diabetes and chronic kidney disease remained disproportionately higher in Aboriginal patients. Risk factor trends, including the Charlson comorbidity index, increased over time in younger Aboriginal patients. Risk-adjusted 30-day mortality did not change over the decade in either group. Risk-adjusted 1-year mortality (in 30-day survivors) was non-significantly higher in Aboriginal patients in 2006-2008 compared with 2000-2002 (hazard ratio (HR) 1.44; 95% CI 0.85-2.41; p-trend = 0.47) whereas it decreased in non-Aboriginal patients (HR 0.87; 95% CI 0.78-0.97; p-trend = 0.01). CONCLUSIONS: Between 2000 and 2009, the prevalence of HF antecedents increased and remained disproportionately higher in Aboriginal (versus non-Aboriginal) HF patients. Risk-adjusted 1-year mortality did not improve in Aboriginal patients over the period in contrast with non-Aboriginal patients. These findings highlight the need for better prevention and post-HF care in Aboriginal Australians.

Validation study of GRACE risk scores in indigenous and non-indigenous patients hospitalized with acute coronary syndrome.

BACKGROUND: Although cardiovascular disease is the major cause of premature death among Indigenous peoples in several advanced economies, no acute coronary syndrome (ACS) risk models have been validated in Indigenous populations. We tested the validity and calibration of three Global Registry of Acute Coronary Events (GRACE) scores among Aboriginal and non-Aboriginal Australians. METHODS: GRACE scores were calculated at admission or discharge using clinical data, with all-cause deaths obtained from data linkage. Scores for GRACE models were validated for; 1) in-hospital death, 2) death within 6 months from admission or 3) death within 6 months of discharge (this also for 1 and 5-years mortality). RESULTS: Aboriginal patient were younger (62 % aged <55 years versus 15 % non-Aboriginal) and their median GRACE scores lower than non-Aboriginal patients, as was crude mortality at 6 months from admission (6 % vs 10 %) and at 1 and 5 years. After age stratification, risk scores for Aboriginal patients were equivalent or higher, especially among those aged <55 years. There was a trend to more deaths after discharge among Aboriginal patients in each age group, suggesting an age-related under-estimation of risk. The c-statistics for the three GRACE models within both groups were between 0.75 and 0.79. CONCLUSIONS: We demonstrated for the first time that while the discriminatory capacity of GRACE risk scores among Indigenous Australians is good, the models may need re-calibrating to improve risk stratification in this and other Indigenous groups, where age of onset of coronary disease is much younger than among the original reference population.

Disparities experienced by Aboriginal compared to non-Aboriginal metropolitan Western Australians in receiving coronary angiography following acute ischaemic heart disease: the impact of age and comorbidities.

INTRODUCTION: Aboriginal Australians have a substantially higher frequency of ischaemic heart disease (IHD) events than their non-Aboriginal counterparts, together with a higher prevalence of comorbidities. The pattern of health service provision for IHD suggests inequitable delivery of important diagnostic procedures. Published data on disparities in IHD management among Aboriginal Australians are conflicting, and the role of comorbidities has not been adequately delineated. We compared the profiles of Aboriginal and non-Aboriginal patients in the metropolitan area undergoing emergency IHD admissions at Western Australian metropolitan hospitals, and investigated the determinants of receiving coronary angiography. METHODS: Person-linked administrative hospital and mortality records were used to identify 28-day survivors of IHD emergency admission events (n =20,816) commencing at metropolitan hospitals in 2005-09. The outcome measure was receipt of angiography. The Aboriginal to non-Aboriginal risk ratio (RR) was estimated from a multivariable Poisson log-linear regression model with allowance for multiple IHD events in individuals. The subgroup of myocardial infarction (MI) events was modelled separately. RESULTS: Compared with their non-Aboriginal counterparts, Aboriginal IHD patients were younger and more likely to have comorbidities. In the age- and sex-adjusted model, Aboriginal patients were less likely than others to receive angiography (RRIHD 0.77, 95% CI 0.72-0.83; RRMI 0.81, 95% CI 0.75-0.87) but in the full multivariable model this disparity was accounted for by comorbidities as well as IHD category and MI subtype, and private health insurance (RRIHD 0.95, 95% CI 0.89-1.01; RRMI 0.94, 95% CI 0.88-1.01). When stratified by age groups, this disparity was not significant in the 25-54 year age group (RRMI 0.95, 95% CI 0.88-1.02) but was significant in the 55-84 year age group (RRMI 0.88, 95% CI 0.77-0.99). CONCLUSIONS: The disproportionate under-management of older Aboriginal IHD patients is of particular concern. Regardless of age, the disparity between Aboriginal and non-Aboriginal Australians in receiving angiography for acute IHD in a metropolitan setting is mediated substantially by comorbidities. This constellation of health problems is a 'double-whammy' for Aboriginal people, predisposing them to IHD and also adversely impacting on their receipt of angiography. Further research should investigate how older age and comorbidities influence clinical decision making in this context.

Transfers to metropolitan hospitals and coronary angiography for rural Aboriginal and non-Aboriginal patients with acute ischaemic heart disease in Western Australia.

BACKGROUND: Aboriginal people have a disproportionately higher incidence rate of ischaemic heart disease (IHD) than non-Aboriginal people. The findings on Aboriginal disparity in receiving coronary artery procedures are inconclusive. We describe the profile and transfers of IHD patients admitted to rural hospitals as emergency admissions and investigate determinants of transfers and coronary angiography. METHODS: Person-linked hospital and mortality records were used to identify 28-day survivors of IHD events commencing at rural hospitals in Western Australia. Outcome measures were receipt of coronary angiography, transfer to a metropolitan hospital, and coronary angiography if transferred to a metropolitan hospital. RESULTS: Compared to non-Aboriginal patients, Aboriginal patients with IHD were more likely to be younger, have more co-morbidities, reside remotely, but less likely to have private insurance. After adjusting for demographic characteristics, Aboriginal people with MI were less likely to be transferred to a metropolitan hospital, and if transferred were less likely to receive coronary angiography. These disparities were not significant after adjusting for comorbidities and private insurance. In the full multivariate model age, comorbidities and private insurance were adversely associated with transfer to a metropolitan hospital and coronary angiography. CONCLUSION: Disparity in receiving coronary angiography following emergency admission for IHD to rural hospitals is mediated through the lower likelihood of being transferred to metropolitan hospitals where this procedure is performed. The likelihood of a transfer is increased if the patient has private insurance, however, rural Aboriginal people have a lower rate of private insurance than their non-Aboriginal counterparts. Health practitioners and policy makers can continue to claim that they treat Aboriginal and non-Aboriginal people alike based upon clinical indications, as private insurance is acting as a filter to reduce rural residents accessing interventional cardiology. If health practitioners and policy makers are truly committed to reducing health disparities, they must reflect upon the broader systems in which disparity is perpetuated and work towards a systems improvement.

Murine Oatp1a/1b uptake transporters control rosuvastatin systemic exposure without affecting its apparent liver exposure.

Organic anion-transporting polypeptides (OATPs) mediate the liver uptake and hence plasma clearance of a broad range of drugs. For rosuvastatin, a cholesterol-lowering drug and OATP1A/1B substrate, the liver represents both its main therapeutic target and its primary clearance organ. Here we studied the impact of Oatp1a/1b uptake transporters on the pharmacokinetics of rosuvastatin using wild-type and Oatp1a/1b-null mice. After oral administration (15 mg/kg), intestinal absorption of rosuvastatin was not impaired in Oatp1a/1b-null mice, but systemic exposure (area under the curve) was 8-fold higher in these mice compared with wild-type. Although liver exposure was comparable between the two mouse strains (despite the increased blood exposure), the liver-to-blood ratios were markedly decreased (>10-fold) in the absence of Oatp1a/1b transporters. After intravenous administration (5 mg/kg), systemic exposure was 3-fold higher in Oatp1a/1b-null mice than in the wild-type mice. Liver, small intestinal, and kidney exposure were slightly, but not significantly, increased in Oatp1a/1b-null mice. The biliary excretion of rosuvastatin was very fast, with 60% of the dose eliminated within 15 minutes after intravenous administration, and also not significantly altered in Oatp1a/1b-null mice. Rosuvastatin renal clearance, although still minor, was increased ∼15-fold in Oatp1a/1b-null males, suggesting a role of Oatp1a1 in the renal reabsorption of rosuvastatin. Absence of Oatp1a/1b uptake transporters increases the systemic exposure of rosuvastatin by reducing its hepatic extraction ratio. However, liver concentrations are not significantly affected, most likely due to the compensatory activity of high-capacity, low-affinity alternative uptake transporters at higher systemic rosuvastatin levels and the absence of efficient alternative rosuvastatin clearance mechanisms.

Use and long-term outcomes of implantable cardioverter-defibrillators, 1990 to 2009.

BACKGROUND: Automated implantable cardioverter-defibrillators (ICDs) have become standard therapy for patients at high risk for sudden cardiac death. Linked data allow examination of trends in use and long-term survival after ICD implantation in an adult population. METHODS: Linked state-wide person-based data on hospital admissions and deaths from 1980 to 2009 were used to identify incident cases of ICD implantation. Population rates were calculated using census data. Kaplan-Meier techniques were used to describe cumulative survival. Cox regression models were used to determine the factors associated with the outcomes. RESULTS: Between 1988 and 2009, 1593 devices were implanted in patients in Western Australia, rising from 2 in 1988 to 245 in 2009; standardized population rates rose from 0.8 in 100000 in 1995 to 14.9 in 100000 in 2009. Mean age rose from 52.6 (SD 11.6) to 64.1 (11.4) years. Ventricular tachycardia (23%), cardiomyopathy (18%), and heart failure (16%) were the most frequent principal diagnoses. Ischemic heart disease was present in 49% of patients. Five-year cumulative survival was 0.74 (SE 0.01), and at 10 years, 0.53 (SE 0.03); median survival was 11.3 years. Readmission within a year, older age, heart failure, device complications, and chronic ischemic heart disease were associated with poorer survival. CONCLUSIONS: Implantable cardioverter-defibrillator use in adults at risk for sudden cardiac death has grown rapidly. Readmission within 12 months of discharge is associated with worse medium and long-term mortality. Survival for most patients younger than 65 years exceeds 10 years and 5 years for those aged ≥75 years.

Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential.

PURPOSE: To apply physiologically-based pharmacokinetic (PBPK) modeling to investigate the consequences of reduction in activity of hepatic and intestinal uptake and efflux transporters by cyclosporine and its metabolite AM1. METHODS: Inhibitory potencies of cyclosporine and AM1 against OATP1B1, OATP1B3 and OATP2B1 were investigated in HEK293 cells +/- pre-incubation. Cyclosporine PBPK model implemented in Matlab was used to assess interaction potential (+/- metabolite) against different processes (uptake, efflux and metabolism) in liver and intestine and to predict quantitatively drug-drug interaction with repaglinide. RESULTS: Cyclosporine and AM1 were potent inhibitors of OATP1B1 and OATP1B3, IC(50) ranging from 0.019-0.093 µM following pre-incubation. Cyclosporine PBPK model predicted the highest interaction potential against liver uptake transporters, with a maximal reduction of >70% in OATP1B1 activity; the effect on hepatic efflux and metabolism was minimal. In contrast, 80-97% of intestinal P-gp and CYP3A4 activity was reduced due to the 50-fold higher cyclosporine enterocytic concentrations relative to unbound hepatic inlet. The inclusion of AM1 resulted in a minor increase in the predicted maximal reduction of OATP1B1/1B3 activity. Good predictability of cyclosporine-repaglinide DDI and the impact of dose staggering are illustrated. CONCLUSIONS: This study highlights the application of PBPK modeling for quantitative prediction of transporter-mediated DDIs with concomitant consideration of P450 inhibition.

Impact of the introduction of drug eluting stents on clinical outcomes in patients undergoing percutaneous and surgical coronary artery revascularisation procedures in Western Australia.

BACKGROUND: Increasing rates of percutaneous coronary intervention (PCI) and decreasing rates of coronary artery bypass graft (CABG) surgery followed the introduction of drug eluting stents in Western Australia in 2002. We assessed the impact of these changes on one-year outcomes for the total population of patients undergoing coronary artery revascularisation procedures (CARP) in Western Australia between 2000-2004. METHODS: Clinical and linked administrative data (inpatient admissions and death) were merged for all patients who had their first CARP with stent or CABG in Western Australia between 2000-2004. The clinical data were collected from all hospitals in Western Australia where CARP procedures are performed. We calculated the unadjusted (Kaplan-Meier) and adjusted (Cox) risks for one-year death (all-cause), death (all-cause) or admission for myocardial infarction (MI), target vessel revascularisation (TVR) and the composite outcome of death/MI/TVR (major adverse cardiac events, MACE). RESULTS: Over the study period, there were 14,118 index CARPs. The use of drug eluting stents increased from 0% to 95.8% of PCI procedures, and PCI procedures increased from 61.1% to 74.4% of all CARPS. There were no temporal changes in adjusted one-year mortality or death/MI. Overall, adjusted one-year MACE fell from 11.3% in 2000 to 8.5% in 2004 (p<0.0001) due to a significant reduction in TVR in the PCI group. CONCLUSION: The introduction of drug eluting stents and resulting changes in coronary revascularisation strategies were not associated with changes in the one-year risk of major clinical endpoints (death or death/MI), but were associated with a significant reduction in the risk of MACE, driven entirely by a reduction in TVR after PCI. This real world study supports the effectiveness of drug eluting stents in reducing repeat procedures in the total CARP population without increasing the risk of death or MI.

Voting with their feet--predictors of discharge against medical advice in Aboriginal and non-Aboriginal ischaemic heart disease inpatients in Western Australia: an analytic study using data linkage.

BACKGROUND: Discharge Against Medical Advice (DAMA) from hospital is associated with adverse outcomes and is considered an indicator of the responsiveness of hospitals to the needs of Aboriginal and Torres Strait Islander Australians, the indigenous people of Australia. We investigated demographic and clinical factors that predict DAMA in patients experiencing their first-ever inpatient admission for ischaemic heart disease (IHD). The study focuses particularly on the differences in the risk of DAMA in Aboriginal and non-Aboriginal patients while also investigating other factors in their own right. METHODS: A cross-sectional analytical study was undertaken using linked hospital and mortality data with complete coverage of Western Australia. Participants included all first-ever IHD inpatients (aged 25-79 years) admitted between 2005 and 2009, selected after a 15-year clearance period and who were discharged alive. The main outcome measure was DAMA as reflected in the hospital record.Multiple logistic regression was used to determine disparities in DAMA between Aboriginal and non-Aboriginal patients, adjusting for a range of demographic and clinical factors, including comorbidity based on 5-year hospitalization history. A series of additional models were run on subgroups of the cohort to refine the analysis. Ethics approval was granted by the WA Human Research and the WA Aboriginal Health Ethics Committees. RESULTS: Aboriginal patients comprised 4.3% of the cohort of 37,304 IHD patients and 23% of the 224 DAMAs. Emergency admission (OR=5.9, 95% CI 2.9-12.2), alcohol admission history (alcohol-related OR=2.9, 95% CI 2.0-4.2) and Aboriginality (OR 2.3, 95% CI 1.5-3.5) were the strongest predictors of DAMA in the multivariate model. Patients living in rural areas while attending non-metropolitan hospitals had a 50% higher risk of DAMA than those living and hospitalised in metropolitan areas. There was consistency in the ORs for Aboriginality in the different multivariate models using restricted sub-cohorts and different Aboriginal identifiers. Sex, IHD diagnosis type and co-morbidity scores imparted different risks in Aboriginal versus non-Aboriginal patients. CONCLUSIONS: Understanding the risks and reasons for DAMA is important for health system policy and proactive management of those at risk of DAMA. Improving care to prevent DAMA should target unplanned admissions, rural hospitals and young men, Aboriginal people and those with alcohol and mental health comorbidities.

Reducing rip current drowning: An improved residual based lightweight deep architecture for rip detection.

Rip Currents are contributing around 25 fatal drownings each year in Australia. Previous research has indicated that most of beachgoers cannot correctly identify a rip current, leaving them at risk of experiencing a drowning incident. Automated detection of rip currents could help to reduce drownings and assist lifeguards in supervision planning; however, varying beach conditions have made this challenging. This work presents the effectiveness of an improved lightweight framework for detecting rip currents: RipDet+1, aided with residual mapping to boost the generalization performance. We have used Yolo-V3 architecture to build RipDet+ framework and utilize pretrained weight by fully exploiting the detection training set from some base classes which in result quickly adapt the detection prediction to the available rip data. Extensive experiments are reported which show the effectiveness of RipDet+ architecture in achieving a detection accuracy of 98.55%, which is significantly greater compared to other state-of-the-art methods for Rip currents detection.

Understanding the interplay of drug transporters involved in the disposition of rosuvastatin in the isolated perfused rat liver using a physiologically-based pharmacokinetic model.

The role of hepatic uptake (Oatp1a1 and Oatp1b4) and efflux (Bcrp and Mrp2) transporters in the disposition of rosuvastatin were investigated using the isolated perfused rat liver (IPRL). A simple physiologically-based pharmacokinetic model was developed to quantitatively determine the interplay between the individual transporters. Uptake and elimination of rosuvastatin in the IPRL was rapid and extensive. In the presence of rifamycin (an equipotent inhibitor of both Oatp1a1 and Oatp1a4) the perfusate clearance of rosuvastatin was reduced, but rifampicin (a potent inhibitor of Oatp1a4) had no effect upon the perfusate clearance. This might indicate a limited role for Oatp1a4, but it is possible that Oatp1a1 (or other uptake transporters) may have redundancy in their affinity for rosuvastatin. In the presence of GF120918 (a potent inhibitor of Bcrp) and in the Wistar TR- rat (a naturally occurring mutant not expressing Mrp2) the biliary clearance was reduced and virtually abolished in the TR- pre-incubated GF120918. Bcrp and Mrp2 appear to represent the primary efflux mechanisms for rosuvastatin in the rat. Rosuvastatin disposition in the IPRL is mediated in part by Oatp1a1 and efflux is almost entirely by Mrp2 and Bcrp. Other uptake processes may be involved.

Complex impact of remoteness on the incidence of myocardial infarction in Aboriginal and non-Aboriginal people in Western Australia.

OBJECTIVE: To determine the impact of remoteness on Aboriginal and non-Aboriginal myocardial infarction incidence rates in men and women of different ages. DESIGN: Descriptive study. SETTING: Western Australia. PARTICIPANTS: Incident cases of myocardial infarction in Western Australia from 2000-2004 identified from person-linked files of hospital and mortality records. Analysis was undertaken for Aboriginal and non-Aboriginal populations, separately and combined, by broad age group, sex and remoteness. MAIN OUTCOME MEASURE: Incidence of myocardial infarction. RESULTS: In the combined analysis, age-standardised incidence was significantly higher for men in very remote areas (rate ratio 1.31: 95% confidence interval (CI), 1.19-1.45) and in women in both regional (rate ratio 1.12: 95% CI, 1.01-1.20) and very remote (rate ratio 2.05: 95% CI, 1.75-2.41) areas. Aboriginal rates were substantially higher than non-Aboriginal rates in all substrata. Compared with metropolitan people, regional Aboriginal men and very remote non-Aboriginal men aged 25-54 years had significantly higher incidence rates. For the remaining rural strata, there was either no geographical disadvantage or inconclusive findings. CONCLUSIONS: Non-metropolitan disadvantage in myocardial infarction rates is confirmed in regional areas and women in very remote areas. This disadvantage is partly explained by the high rates in Aboriginal people. Non-metropolitan dwellers are not uniformly disadvantaged, reflecting the interplay of the many factors contributing to the complex relationship between myocardial infarction incidence and sex, age, Aboriginality and residence. Aboriginal Western Australians in all regions and young non-Aboriginal men living in very remote areas need to be targeted to reduce disparities in myocardial infarction.

Can we monitor heart attack in the troponin era? Evidence from a population-based cohort study.

BACKGROUND: Troponins (highly sensitive biomarkers of myocardial damage) increase counts of myocardial infarction (MI) in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain. METHODS: Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC) in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria) using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA) or traditional biomarkers only (MI-AHAck). RESULTS: Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHAck declined by 18%. CONCLUSIONS: Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHA ck are consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.

Erectile dysfunction as a predictor for subsequent atherosclerotic cardiovascular events: findings from a linked-data study.

INTRODUCTION: In spite of the mounting interest in the nexus between erectile dysfunction (ED) and cardiovascular (CV) diseases, there is little published information on the role of ED as a predictor for subsequent CV events. AIM: This study aimed to investigate the role of ED as a predictor for atherosclerotic CV events subsequent to the manifestation of ED. Method. The investigation involved the retrospective study of data on a cohort of men with ED linked to hospital morbidity data and death registrations. By using the linked data, the incidence rates of atherosclerotic CV events subsequent to the manifestation of ED were estimated in men with ED and no atherosclerotic CV disease reported prior to the manifestation of ED. The risk of subsequent atherosclerotic CV events in men with ED was assessed by comparing these incidence rates with those in the general male population. MAIN OUTCOME MEASURE: Standardized incidence rate ratio (SIRR), comparing the incidence of atherosclerotic CV events subsequent to the manifestation of ED in a cohort of 1,660 men with ED to the incidence in the general male population. RESULTS: On the basis of hospital admissions and death registrations, men with ED had a statistically significantly higher incidence of atherosclerotic CV events (SIRR 2.2; 95% confidence interval 1.9, 2.4). There were significantly increased incidence rate ratios in all age groups younger than 70 years, with a statistically highly significant downward trend with increase of age (P < 0.0001) across these age groups. Younger age at first manifestation of ED, cigarette smoking, presence of comorbidities and socioeconomic disadvantage were all associated with higher hazard ratios for subsequent atherosclerotic CV events. CONCLUSIONS: The findings show that ED is not only significantly associated with but is also strongly predictive of subsequent atherosclerotic CV events. This is even more striking when ED presents at a younger age.

Under-ascertainment of Aboriginality in records of cardiovascular disease in hospital morbidity and mortality data in Western Australia: a record linkage study.

BACKGROUND: Measuring the real burden of cardiovascular disease in Australian Aboriginals is complicated by under-identification of Aboriginality in administrative health data collections. Accurate data is essential to measure Australia's progress in its efforts to intervene to improve health outcomes of Australian Aboriginals. We estimated the under-ascertainment of Aboriginal status in linked morbidity and mortality databases in patients hospitalised with cardiovascular disease. METHODS: Persons with public hospital admissions for cardiovascular disease in Western Australia during 2000-2005 (and their 20-year admission history) or who subsequently died were identified from linkage data. The Aboriginal status flag in all records for a given individual was variously used to determine their ethnicity (index positive, and in all records both majority positive or ever positive) and stratified by region, age and gender. The index admission was the baseline comparator. RESULTS: Index cases comprised 62,692 individuals who shared a total of 778,714 hospital admissions over 20 years, of which 19,809 subsequently died. There were 3,060 (4.9%) persons identified as Aboriginal on index admission. An additional 83 (2.7%) Aboriginal cases were identified through death records, increasing to 3.7% when cases with a positive Aboriginal identifier in the majority (≥50%) of previous hospital admissions over twenty years were added and by 20.8% when those with a positive flag in any record over 20 years were incorporated. These results equated to underestimating Aboriginal status in unlinked index admission by 2.6%, 3.5% and 17.2%, respectively. Deaths classified as Aboriginal in official records would underestimate total Aboriginal deaths by 26.8% (95% Confidence Interval 24.1 to 29.6%). CONCLUSIONS: Combining Aboriginal determinations in morbidity and official death records increases ascertainment of unlinked cardiovascular morbidity in Western Australian Aboriginals. Under-identification of Aboriginal status is high in death records.

Using a Markov simulation model to assess the impact of changing trends in coronary heart disease incidence on requirements for coronary artery revascularization procedures in Western Australia.

BACKGROUND: The population incidence of coronary heart disease (CHD) has been declining in Australia and many other countries. This decline has been due to reduced population levels of risk factors for CHD and improved medical care for those at higher risk of CHD. However, there are signs that there may be a slowing down or even reversal in the decline of CHD incidence due to the 'obesity epidemic' and other factors and this will have implications for the requirements for surgical treatments for those with CHD. METHODS: Using a validated Markov simulation model applied to the population of Western Australia, different CHD incidence trend scenarios were developed to explore the effect of changing CHD incidence on requirements for coronary artery bypass graft (CABG) and percutaneous coronary interventions (PCI), together known as coronary artery revascularization procedures (CARPs). RESULTS: The most dominant component of CHD incidence is the risk of CHD hospital admission for those with no history of CHD and if this risk leveled off and the trends in all other risks continued unchanged, then the projected numbers of CABGs and PCIs are only minimally changed. Further, the changes in the projected numbers remained small even when this risk was increased by 20 percent (although it is an unlikely scenario). However, when the other CHD incidence components that had also been declining, namely, the risk of CABG and that of CHD death for those with no history of CHD, were also projected to level off as these were declining in 1998-2000 and the risk of PCI for those with no history of CHD (which was already increasing) was projected to further increase by 5 percent, it had a substantial effect on the projected numbers of CARPs. CONCLUSION: There needs to be dramatic changes to several CHD incidence components before it has a substantial impact on the projected requirements for CARPs. Continued monitoring of CHD incidence and also the mix of initial presentation of CHD incidence is required in order to understand changes to future CARP requirements.

PETN ignition experiments and models.

Ignition experiments from various sources, including our own laboratory, have been used to develop a simple ignition model for pentaerythritol tetranitrate (PETN). The experiments consist of differential thermal analysis, thermogravimetric analysis, differential scanning calorimetry, beaker tests, one-dimensional time to explosion tests, Sandia's instrumented thermal ignition tests (SITI), and thermal ignition of nonelectrical detonators. The model developed using this data consists of a one-step, first-order, pressure-independent mechanism used to predict pressure, temperature, and time to ignition for various configurations. The model was used to assess the state of the degraded PETN at the onset of ignition. We propose that cookoff violence for PETN can be correlated with the extent of reaction at the onset of ignition. This hypothesis was tested by evaluating metal deformation produced from detonators encased in copper as well as comparing postignition photos of the SITI experiments.