Implementing simple algorithms to improve glucose and lipid management in people with diabetes and acute coronary syndrome.

AIM: Diabetes mellitus is associated with increased risk of adverse outcomes following acute coronary syndrome. Translating evidence-based recommendations into practice is necessary to improve outcomes. We evaluated whether implementing algorithms to guide inpatient care improved glycaemic control, and increased use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and lipid-lowering medication in a tertiary cardiac unit. METHOD: A 3-month audit (phase 1) was conducted to evaluate hyperglycaemia and dyslipidaemia management, and medication prescriptions. Consecutive people with diabetes admitted for acute coronary syndrome were prospectively identified. Target blood glucose level was defined as 5-10 mmol/l. A multidisciplinary committee designed and implemented decision-support algorithms plus education. A 3-month post-implementation audit (phase 2) was conducted. RESULTS: There were 104 people in phase 1 and 101 in phase 2, with similar characteristics [HbA1c 64 ± 20 mmol/mol vs. 61 ± 21 mmol/mol (8.0 ± 1.8% vs. 7.8 ± 1.9%]. Post implementation, the incidence of blood glucose levels > 10 mmol/l was lower [phase 1: 46.4% vs. phase 2: 31.8%, rate ratio (RR) = 0.77, 95% confidence intervals (CI) 0.60-0.98; P = 0.031], without a difference in blood glucose levels < 5mmol/l (phase 1: 4.9% vs. phase 2: 4.5%, RR = 1.20, 95% CI 0.70-2.08; P = 0.506). SGLT2 inhibitor prescriptions increased significantly (baseline to discharge: 12.5% to 15.4% vs. 7.9% to 24.8%; P = 0.007) but high-intensity statin prescriptions did not (baseline to discharge: 35.6% to 72.1% vs. 40.6% to 85.1%; P = 0.074). Prescription rates of non-statin lipid-lowering medications were not significantly increased. CONCLUSIONS: Implementing decision-support algorithms was associated with improved inpatient glycaemic control and increased use of cardioprotective therapies at discharge in people with diabetes and acute coronary syndrome.

Evaluation of long-term clinical and health service outcomes following coronary artery revascularisation in Western Australia (WACARP): a population-based cohort study protocol.

INTRODUCTION: Coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) are procedures commonly performed on patients with significant obstructive coronary artery disease to relieve symptoms of ischaemia, improve survival or both. Although the efficacy of both procedures at the individual level has been established, the impact of advances in coronary artery revascularisation procedures (CARP) on long-term outcomes and cost-effectiveness at the population level are yet to be assessed. Our aim is to evaluate a minimum of 6-year outcomes and costs for the total population of patients who had CARP in Western Australia (WA) in 2000-2005. METHODS AND ANALYSIS: This retrospective population cohort study will link clinical and administrative health data for a previously defined cohort including all patients in WA who had a CARP in the period 2000-2005. The cohort consists of 19,014 patients who had 21,175 procedures (15,429 PCI and 5746 CABG). We are now collecting a minimum of 6 years follow-up of morbidity and mortality data for the cohort using the WA Data Linkage System, clinical registries and hospital records, with 12 years follow-up for cases in the year 2000. Comparison of long-term outcomes for different CARP will be reported (PCI vs CABG; bare metal stents vs drug-eluting stents vs CABG). Cost-effectiveness analysis of CARP from the perspective of the healthcare sector will be performed using individual level cost data and average costs from Australian Refined Diagnosis Related Groups. ETHICS AND DISSEMINATION: This study has received ethics approval from the University of Western Australia, the Western Australian Department of Health and all participating hospitals. Being a large population cohort study, approval included a waiver of informed consent. All findings will be presented at local, national and international healthcare/academic conferences and published in peer-reviewed journals.

Synchronous x-ray and radio mode switches: a rapid global transformation of the pulsar magnetosphere.

Pulsars emit from low-frequency radio waves up to high-energy gamma-rays, generated anywhere from the stellar surface out to the edge of the magnetosphere. Detecting correlated mode changes across the electromagnetic spectrum is therefore key to understanding the physical relationship among the emission sites. Through simultaneous observations, we detected synchronous switching in the radio and x-ray emission properties of PSR B0943+10. When the pulsar is in a sustained radio-"bright" mode, the x-rays show only an unpulsed, nonthermal component. Conversely, when the pulsar is in a radio-"quiet" mode, the x-ray luminosity more than doubles and a 100% pulsed thermal component is observed along with the nonthermal component. This indicates rapid, global changes to the conditions in the magnetosphere, which challenge all proposed pulsar emission theories.

Impact of acute and chronic risk factors on use of evidence-based treatments in patients in Australia with acute coronary syndromes.

OBJECTIVE: To determine whether acute risk factors (ARF) and chronic risk factors (CRF) contribute differently to the use of evidence-based treatments (EBT) for patients with acute coronary syndromes (ACS). DESIGN: Data were collected through a prospective audit of patients with ACS. Management was analysed by the presence of acute myocardial risk factors and chronic comorbid risk factors at presentation. SETTING: 39 hospitals across Australia. PATIENTS: 2599 adults presenting with ACS. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Use of EBT, in-hospital and 12-month death, recurrent myocardial infarction and bleeding. RESULTS: The number of ARF and CRF at presentation predicted in-hospital and 12-month death, recurrent myocardial infarction and bleeding. Patients with higher numbers of ARF were more likely to receive EBT (aspirin at presentation, 81.1% for zero ARF to 85.7% for > or =3 ARF, p<0.001; angiography 45.9% to 67.5%, p<0.001; reperfusion for ST elevation 50% to 70%, p = 0.392; beta blocker at discharge 66.5% to 74.4%, p<0.001). Patients with higher numbers of CRF were less likely to receive EBT (aspirin at presentation 90.4% for zero CRF to 68.8% for > or =4 CRF, p<0.001; angiography 78.8% to 24.7%, p<0.001; reperfusion for ST elevation 73.4% to 30%; p<0.001, beta blocker at discharge 75.2% to 55.6%; p<0.001). In multivariate regression analysis, ARF and CRF were the strongest predictors of receiving or failing to receive EBT, respectively. CONCLUSIONS: Patients presenting with many ARF are more likely to receive EBT, while patients presenting with many CRF are less likely to receive them. This has important implications for future quality-improvement efforts.

Trends in coronary artery revascularisation procedures in Western Australia, 1980-2001.

OBJECTIVES: To describe trends in the use of coronary artery revascularisation procedures (CARPs) and to determine whether or when CARP rates will stabilise. SETTING: State of Western Australia. PATIENTS: All patients treated by coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1980 and 2001. DESIGN: Descriptive study. MAIN OUTCOME MEASURES: Age standardised rates of first and total CARPs, CABGs, and PCIs. RESULTS: Overall rates for both total and first CARPs among men and women rose steeply from 1980 to 1993, when they abruptly stabilised or actually started to decline. Rates in age groups under 65 years tended to rise earlier in the period and remained relatively flat, while rates for people over the age of 75 years started to rise later and were still increasing at the end of the study. CONCLUSIONS: Despite continuing increases in capacity to perform both CABG and PCI in Western Australia and evidence of continuing increases in the use of CARPs in the elderly population, rates appear to have stabilised for the first time since they were introduced.

Trends in two year risk of repeat revascularisation or death from cardiovascular disease after coronary artery bypass grafting or percutaneous coronary intervention in Western Australia, 1980-2001.

AIMS: To investigate whether, over the 21 year period 1980-2001, there had been a reduction in the risk of repeat revascularisation or death from cardiovascular disease in the cohort of all patients who were treated by coronary revascularisation in Western Australia. SETTING: State of Western Australia. PATIENTS: All patients treated by coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1980 and 2001. DESIGN: Cohort study. MAIN OUTCOME MEASURES: Risk of repeat coronary artery revascularisation procedures (CARP) and risk of death from cardiovascular disease after first CARP. RESULTS: After a CABG procedure, the two year risk of repeat revascularisation remained low (less than 2%) across the period 1980-2001. For PCI, however, this risk declined significantly from 33.6% in 1985-9 to 12.4% in 2000-1. The risk of death from cardiovascular disease after a CARP declined by about 50% between 1985 and 2001. CONCLUSIONS: Outcomes such as the risk of repeat revascularisation and the risk of death from cardiovascular disease have improved significantly for patients who underwent CARPs across the period 1980-2001. This has occurred despite an increasing trend in first CARP rates among older people and those with a recent history of myocardial infarction.

Fetal or infant death in twin pregnancy: neurodevelopmental consequence for the survivor.

AIM: To determine the neurodevelopmental morbidity in the surviving twin after fetal or infant death of the co-twin. METHODS: Twin pregnancies with an antepartum or infant death delivered between 1981 and 1992 were identified from the Northern Perinatal Mortality Survey. Information on the neurodevelopmental morbidity of infant survivors of a deceased co-twin was obtained by a questionnaire sent to the community paediatrician or general practitioner. RESULTS: A total of 111 children who survived infancy after the fetal death of the co-twin (group 1) and 142 from liveborn twin pairs in which one twin died in infancy (group 2) were traced. Responses were received from 97 (87%) and 130 (92%) respectively. In group 1, the cerebral palsy prevalence was 93 (95% confidence interval (CI) 43 to 169) per 1000 infant survivors; it was more common in like-sex pairs (8/70) with a prevalence of 114 (95% CI 51 to 213) compared with 45 (95% CI 1 to 228) per 1000 infant survivors in unlike-sex pairs (1/22). The overall prevalence of neurodevelopmental morbidity (including developmental delay) was 175 (95% CI 106 to 266) per 1000. In group 2, the cerebral palsy prevalence was 154 (95% CI 84 to 223) per 1000 infant survivors in like-sex (16/104) and 77 (95% CI 9 to 251) in unlike-sex (2/26) survivors; the overall prevalence of neurodevelopmental morbidity was 246 (95% CI 172 to 320) per 1000. CONCLUSIONS: The risk of cerebral palsy is increased in the surviving twin after a fetal or infant co-twin death compared with the general twin population. Like-sex twins are at greater risk than unlike-sex. The probable cause, in addition to the consequences of prematurity, is twin-twin transfusion problems associated with monochorionicity.

Investigation of the epidemiology and prenatal diagnosis of holoprosencephaly in the North of England.

OBJECTIVE: This study was undertaken to provide epidemiologic data on the prevalence of holoprosencephaly and to assess the sensitivity of routine ultrasonographic screening in a low-risk population. STUDY DESIGN: A population-based register of congenital abnormalities was used to identify reported cases of holoprosencephaly between 1985 and 1998. Sources included fetal losses, termination for fetal anomaly, stillbirths, and live births. Prenatal diagnoses and pregnancy outcomes were determined. RESULTS: Sixty-eight cases of holoprosencephaly were found among 531,686 births. The total prevalence (including pregnancy terminations) was 1.2 cases/10,000 registered births, and the birth prevalence (affected live births and stillbirths at >24 weeks' gestation) was 0.49 cases/10,000 births. Prenatal diagnosis was achieved in 71% of cases, rising to 86% during the second half of the study period; the mean gestational age at diagnosis was 19.8 weeks' gestation. Chromosomal abnormalities (75% of which were trisomy 13) were present in 38% of cases in which a karyotype was established. All those with aneuploidy (80% diagnosed prenatally) had other nonfacial anomalies; additional anomalies were also common in the euploid group (61% diagnosed prenatally), with 90% having facial abnormalities and 70% having other abnormalities. CONCLUSION: The prevalence of holoprosencephaly in second-trimester pregnancies was about 1 in 8000. Prenatal detection reached 86% with a routine anomaly scanning program. The etiology could usually be determined, which has important implications for recurrence risks.

Co-morbidity data in outcomes research: are clinical data derived from administrative databases a reliable alternative to chart review?

Evaluation of co-morbidity data is essential in health outcomes research. Co-morbidity data derived from administrative databases has been criticized for lacking the accuracy required for clinical research. We compared co-morbidity data derived from a Canadian provincial hospitalization database with chart review in 817 adults treated with a percutaneous coronary intervention at a single tertiary care hospital between 1994 and 1995. While the administrative database tended to under-estimate the prevalence of some co-morbid conditions, the agreement between chart review and administrative data was good to very good for most conditions. Asymptomatic conditions were noted to have lower levels of agreement. Multivariate risk models for all-cause mortality constructed from both data sources were almost identical, suggesting minimal misclassification. The results indicate that clinical data abstracted from most Canadian hospitalization databases can provide reliable information regarding baseline co-morbid conditions believed to influence survival in a population undergoing percutaneous coronary interventions.

A preliminary examination of cryotherapy and secondary injury in skeletal muscle.

PURPOSE: The purpose of this study was to document the presence of secondary injury in skeletal muscle, to quantify it, and to determine whether it is altered by acute cryotherapy. METHODS: Crush injuries to the triceps surae of 19 adult male Sprague-Dawley rats were either treated continuously with ice for 5 h (N = 10) or received no ice treatment (N = 9). After treatment, tissues were assayed for the reduction of triphenyltetrazolium chloride (TTC) to triphenylformazan (formazan red). TTC reduction is indicative of oxidative function and serves as an indicator of cellular damage. RESULTS: A significantly lower TTC reduction rate was seen in both cold-treated injured tissue (6.59 +/- 1.01 microg x mg(-1) x h(-1)) and nontreated injured tissue (4.48 +/- 0.79 microg x mg(-1) x h(-1)) compared with uninjured controls (ice group = 7.94 +/- 1.49 microg x mg(-1) x h(-1), no-ice group = 6.62 +/- 0.75 microg x mg(-1) x h(-1)). These data indicate that crushing of muscle tissue produces injury measurable with the TTC reduction assay. Additionally, in crush-injured tissues, a significantly lower TTC reduction rate was seen in untreated tissues (4.48 +/- 0.79 microg x mg(-1) x h(-1)) compared with ice treated tissues (6.59 +/- 1.01 microg x mg(-1) x h(-1)), indicating that cryotherapy reduces the magnitude of secondary injury. CONCLUSIONS: From these data, it can be concluded that secondary injury occurs after primary crush injury and that secondary injury is retarded by acute treatment with 5 h of continuous cryotherapy.

Improved clinical outcome after widespread use of coronary-artery stenting in Canada.

BACKGROUND: The introduction and refinement of coronary-artery stenting dramatically changed the practice of percutaneous coronary revascularization in the mid-1990s. We analyzed one-year follow-up data for all percutaneous coronary interventions performed in a large, unselected population in Canada to determine whether the use of coronary stenting has been associated with improved outcomes. METHODS: Prospectively collected data on all percutaneous coronary interventions performed on residents of British Columbia, Canada, between April 1994 and June 1997 were linked to province-wide health care data bases to provide the date of the following end points: subsequent target-vessel revascularization, myocardial infarction, and death. Baseline characteristics and procedural variables were identified and Kaplan-Meier survival curves were generated for 9594 procedures divided into seven groups, one for each sequential half-year period. RESULTS: The overall burden of coexisting illnesses remained stable throughout the study period. A large increase in the rate of coronary stenting (from 14.2 percent in the period from April to June 1994 to 58.7 percent in the period from January to June 1997) was associated with a significant reduction in the rate of adverse cardiac events at one year (from 28.8 percent to 22.8.percent; adjusted relative risk, 0.79; 95 percent confidence interval, 0.69 to 0.90; P<0.001). This reduction in adverse events was exclusively due to a large reduction in subsequent target-vessel revascularization (from 24.4 percent to 17.0 percent; adjusted relative risk, 0.72; 95 percent confidence interval, 0.62 to 0.83; P<0.001) without significant changes in the overall rates of myocardial infarction (5.4 percent, P=0.28) or death (3.9 percent, P=0.65). CONCLUSIONS: The need for target-vessel revascularization during one year of follow-up decreased after percutaneous coronary intervention during the mid-1990s. The reduction was coincident with the introduction and subsequent widespread use of coronary stenting.

Nitric oxide-dependent endothelial function is unaffected by allopurinol in hypercholesterolaemic subjects.

1. Hypercholesterolaemia is associated with abnormal endothelium-related vasodilator function, possibly due to increased destruction .NO by superoxide anions (.O2-). Oxypurinol, a xanthine oxidase (XO) inhibitor with anti-oxidant properties and the active metabolite of the commonly used drug allopurinol, reduces .NO quenching in vitro and has been reported to acutely improve endothelial function in hypercholesterolaemic subjects. 2. The purpose of the present study was to determine whether oral allopurinol improves .NO dilator function in hypercholesterolaemic subjects. 3. A randomized double-blind, placebo-controlled cross-over design evaluated the effect of allopurinol (300 mg daily for 4 weeks) on forearm blood flow (FBF) responses to intrabrachial infusion of acetylcholine (ACh), sodium nitroprusside (SNP) and NG-monomethyl-L-arginine (L-NMMA) in nine hypercholesterolaemic subjects. 4. Endothelium-dependent vascular responses to ACh and L-NMMA were not significantly altered by allopurinol. The endothelium-independent vasodilator response to SNP was similarly unchanged. 5. These results indicate that allopurinol does not influence basal or stimulated activity of the .NO dilator system in hypercholesterolaemic subjects. If intracellular .O2- inactivation .NO is responsible for endothelial dysfunction in hypercholesterolaemia, the source may be other than XO dependent. However, generation of .O2- during the conversion of allopurinol to oxypurinol could offer an alternative, and probably more likely, explanation for the ineffectiveness of allopurinol in vivo.

Ground reaction forces and EMG activity with ankle bracing during inversion stress.

PURPOSE: The purpose of this investigation was to evaluate the effects of external ankle support on ground reaction forces and myoelectrical activity of selected lower extremity muscles during dynamic inversion stress. METHODS: Twenty-four healthy males performed five trials of a lateral dynamic movement at a rate between 80-90% of their maximal speed under three ankle brace conditions (no brace--control, Aircast Sport-Stirrup, Active Ankle). Ground reaction forces along the mediolateral axis and EMG activity of the peroneus longus, tibialis anterior, and medial gastrocnemius were simultaneously recorded during force plate contact. RESULTS: Ankle bracing did not affect peak impact force (P > 0.05), maximum loading force (P > 0.05), or peak propulsion force (P > 0.05) in the lateral direction compared with the control condition. Ankle bracing reduced the EMG activity of the peroneus longus during peak impact force compared with the control condition (P < 0.05), although no differences were noted between the two braces. Furthermore, peroneous longus activity during maximum loading force and peak propulsion remained unaffected (P < 0.05). Ankle bracing did not affect the EMG activity of the tibialis anterior and medial gastrocnemius at the point of peak impact force, maximum loading force (P > 0.05), and peak propulsion force (P > 0.05). CONCLUSIONS: These data suggest that ankle bracing may not affect the forces experienced at the foot and ankle, but helps reduce the strain placed on the peroneus longus during peak impact force. Furthermore, ankle bracing does not alter the function of the tibialis anterior and medial gastrocnemius during dynamic inversion stress.

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia.

1. Vitamin E administration improves endothelial function in hypercholesterolaemic animals but, generally, has not been found to do so in man. The aim of this study was to determine whether vitamin E administration improves basal or stimulated function of the nitric oxide (NO) dilator system in patients with hypercholesterolaemia. 2. Seven subjects aged 47+/-3 (+/-S.E.M.) years with moderately elevated serum cholesterol concentrations (6.0+/-0.1 mmol/l) were given 4 weeks of placebo therapy followed by 500 i.u. of vitamin E twice daily for 4 weeks. Endothelium-dependent and -independent vasodilatation were assessed by intrabrachial infusion of acetylcholine and sodium nitroprusside, and forearm blood flow was measured by strain-gauge plethysmography. Basal NO function was assessed by infusion of NG-monomethyl-L-arginine. 3. Plasma alpha-tocopherol concentration was enhanced after administration of vitamin E (34.6+/-1.8 to 86.9+/-9.6 micromol/l; P<0.001). In addition, vitamin E administration significantly increased acetylcholine-mediated vasodilatation whether the results were expressed in terms of changes in absolute forearm blood flow (P<0. 01), forearm vascular resistance (P<0.05) or forearm blood flow ratios (P<0.001). Similarly, absolute forearm blood flow (P<0.05), forearm vascular resistance (P<0.01) and forearm blood flow ratio (P<0.01) responses to NG-monomethyl-L-arginine were augmented by vitamin E therapy. Sodium nitroprusside responses were unaltered. 4. These results indicate that 4 weeks therapy with 1000 i.u. of vitamin E daily improves basal and stimulated NO-related endothelial function in subjects with hypercholesterolaemia.

Modification of forearm resistance vessels by exercise training in young men.

The aim of this study was to determine whether a 4-wk handgrip training program would elicit changes in endothelium-dependent and endothelium-independent vasodilatation in resistance vessels of the human forearm. Minimum vascular resistance after a 10-min ischemic stimulus, an index of peak vasodilator capacity, was also determined. Forearm blood flow response to the endothelium-dependent vasodilator methacholine chloride did not change over the 4-wk-intervention period either in the group undertaking training (n = 11) or in control subjects (n = 6). Similarly, the response to sodium nitroprusside was not influenced by the handgrip training program. Peak vasodilator capacity of the trained forearms significantly increased, whereas no change was evident in the untrained limbs. These results suggest that 4 wk of forearm exercise training enhances peak vasodilator capacity of the vasculature without influencing stimulated activity of the nitric oxide dilator system.

Mechanism of stroke complicating cardiopulmonary bypass surgery.

BACKGROUND: Stroke is a devastating complication of cardiopulmonary bypass (CPB) surgery which occurs in 1 to 5% of cases. Strategies to reduce its incidence require a knowledge of the underlying pathology and aetiology. AIMS: To determine the incidence, pathology and aetiology of stroke complicating CPB. METHODS: Prospective review of clinical, operative and cranial CT scan findings in all cases of stroke complicating CPB procedures in our institution over an 18 month period. RESULTS: Twenty-one (1.6%, 95% CI 0.9-2.3%) cases of stroke were identified from 1336 CPB procedures. Cranial CT scan, performed in all but one patient, was normal in three patients or consistent with ischaemic stroke in 17 patients. There were no cases of haemorrhagic infarction or intracerebral haemorrhage. It was difficult to differentiate embolic and borderzone infarcts in two cases. After considering the clinical, operative and CT scan features together, 12 (57%, 95% CI 36-78%) of the cases were felt to be embolic in origin and nine (43%, 95% CI 22-64%) due to hypoperfusion in a borderzone. CONCLUSIONS: This study demonstrates that stroke remains an important complication of CPB procedures with an incidence in our series of 1.6%. The pathologic type of stroke is predominantly ischaemic in nature due to either cerebral embolism or borderzone infarction. Strategies for stroke prevention in patients undergoing CPB should be targeted primarily at these two mechanisms.