bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II study of high dose epirubicin in combination with cyclophosphamide in patients with advanced breast cancer
Authors: Levi J. A. , Tattersall M. H. , Beith J. M. , Bell D. , Snyder R. D. , Wheeler H.
Published: March 2008

Abstract Background: Combination chemotherapy for metastatic breast cancer will palliate symptoms in the majority of patients but only a small percentage will have prolonged survival. Higher doses of doxorubicin lead to increased response rates in breast cancer and early studies have shown that epirubicin could be tolerated in higher doses with less relative toxicity than doxorubicin.

Aims: This study was initiated to assess the dose of epirubicin that could be tolerated by escalating its dose while maintaining a fixed dose of cyclophosphamide. Simultaneously tumour response rate, spectrum of toxicities, duration of response and overall survival in patients with metastatic breast cancer were assessed.

Methods: Patients with metastatic breast cancer commenced chemotherapy with a starting dose of epirubicin of 120 milligram per metre squared (mg/m2) and cyclophosphamide 600 mg/m2. The dose of epirubicin was to be escalated or reduced depending on toxicity.

Results: Forty female patients were entered into this study and three patients withdrew because of toxicity. Overall tumour response rate was 75% with 27.5% of patients obtaining a complete response. Median time to progressive disease was 35 weeks and median overall survival was 48 weeks, with median survival for complete responders being 103 weeks. Thirty‐one (77%) patients completed five or more courses of treatment. Haematological toxicity was the main side effect and 70% of patients required a dose reduction. No patients were eligible for a dose escalation. One patient died as a consequence of neutropenic sepsis. Four (10%) patients had treatment ceased because of decrease in left ventricular ejection fraction and one patient died as a consequence of heart failure. Four patients remain alive.

Conclusions: High dose epirubicin combined with cyclophosphamide is an effective treatment regimen for metastatic breast cancer obtaining higher overall response rates with increased percentage complete responses compared to conventional dose chemotherapy. Although toxicity was increased, high dose chemotherapy was well tolerated and mortality associated with treatment was not increased. No dose escalations of epirubicin were possible and a dose of 90mg/m2 of epirubicin would be the maximum dose when used in combination with cyclophosphamide. Further trials are required to determine the influence of this high dose therapy on survival duration and whether comparable benefits can be achieved with shorter durations of therapy. (Aust NZ J Med 1995; 25: 474–478.)
The accuracy of hospital records and death certificates for acute myocardial infarction
Authors: Boyle C. A. , Dobson A. J.
Published: March 2008

Background: In Australia information on the incidence of acute myocardial infarction (AMI) is available from routinely collected morbidity and mortality data. Given that these data are used for monitoring AMI it is important to assess their quality.

Aims: This paper examines the accuracy of the hospital records and death certificates.

Methods: Morbidity and mortality data were compared with the Newcastle heart disease register which is part of the WHO MONICA Project for 1986–1991 and sensitivity and positive predictive values calculated.

Results: For non‐fatal AMI the hospital diagnostic coding had sensitivity of 78.9% (95% confidence interval [CI] 77.1%‐80.7%), and positive predictive value of 65.6% (95% CI 63.7%‐67.4%). Sensitivity was higher for men than for women and decreased with increasing age. Sensitivity was higher in those with no history of either AMI or other ischaemic heart disease (IHD), higher in current smokers than ex‐smokers or never smokers, and lower in those with a self‐reported history of high blood pressure. Sensitivity also varied among hospitals. Positive predictive value varied only with hospital.

Both sensitivity and positive predictive value were high for death certificate data — 89.9% (95% CI 88.4%‐91.3%) and 96.0% (95% CI 95.1%‐97.0%), respectively.

Conclusions: Although the mortality data appear to be quite accurate, the hospital data alone are not accurate enough to be used to estimate rates or trends of heart attacks. Additional data are required in order to determine numbers of non‐fatal AMIs accurately. (Aust NZ J Med 1995; 25: 316–323.)
Directional coronary atherectomy for lesions of the proximal left anterior descending artery: initial clinical results, complications and histopathological findings
Authors: Sankardas M. A. , Cameron J. , McEniery P. , Garrahy P. , Aroney C. , Dare A. , Holt G. , Bett N.
Published: March 2008

Background: Directional coronary atherectomy is a percutaneous technique which extends the role of balloon angioplasty to bulky eccentric coronary lesions.

Aims: To report the early experience, clinical results, complications and histopathological findings of directional coronary atherectomy (DCA) in proximal left anterior descending artery (LAD) stenosis.

Methods: Study of 25 lesions in 24 patients on whom directional atherectomy was performed on the proximal LAD artery with the Simpson coronary atherectomy device.

Results: Twenty‐five procedures were performed on 24 patients with stenosis in the proximal LAD artery. There were 21 males and three females with a mean age of 56.5 years. Sixteen patients presented with stable angina and eight with unstable angina. Eight patients had previous myocardial infarction (MI). Angiographic success was obtained in 24 of 25 lesions (96%). The mean lesion length was 13.1 ± 3.7 mm and the mean LAD artery diameter was 3.6 ± 0.5 mm. Minimal luminal diameter improved from 0.9 ± 0.4 mm to 3.0 ± 0.5 mm and the percentage diameter stenosis reduced from 75 ± 12% to 16 ± 9%. Complications included acute occlusion in one patient, non‐Q MI in three patients, local vascular complications in one patient and side‐branch loss in one patient. Histology demonstrated fibrous cap of atherosclerotic plaque in 100%, media and internal elastic lamina in 28% and intimal hyperplasia in 100% of restenotic lesions and 27% of native lesions. Restenosis rates in angiographically restudied patients was 27%. The mean minimal luminal diameter at follow‐up was 2.3 ± 0.9 mm and the mean percentage diameter stenosis was 35 ±21%.

Conclusion: From this initial study, we conclude that DCA is an effective and safe procedure for the treatment of large proximal LAD lesions. DCA provides a large luminal diameter and a ‘smoother’ angiographic appearance compared to coronary angioplasty. Acute complication rates are low and restenosis rates were comparable with percutaneous transluminal coronary balloon angioplasty.
Alpha‐1‐antitrypsin PLowell: a normally functioning variant present in low concentration
Authors: Cook L. , Burdon J. , Brenton S. , Janus E. D. , Knight K.
Published: March 2008

Background: Alpha‐1‐antitrypsin deficiency is associated with a high risk for the development of emphysema, particularly for phenotype Pi ZZ, which is both deficient and an abnormal inhibitor of the powerful proteolytic enzyme, human neutrophil elastase. The rare variant PLowell is also expressed at abnormally low levels, but its anti‐elastase activity has not been described.

Aim: To study the anti‐elastase activity of alpha‐1‐antitrypsin PLowdl and compare it to the common M, S and Z proteins.

Method: Alpha‐1‐antitrypsin from a female patient aged 75 years with the rare genotype PLoweU NullBcllingham was studied for its ability to inhibit human neutrophil elastase in a time dependent manner.

Results: PLoweii has near normal function as an inhibitor of human neutrophil elastase with an association rate constant of 7.4 X 106 M'V1 at 25 °C, similar to that of M and S.

Conclusion: Alpha‐1‐antitrypsin PL is associated with a severe deficiency of alpha‐1‐antitrypsin similar to Z, but unlike that protein it has near normal function as an anti‐elastase.
Immune surveillance and autoantigen recognition in the central nervous system
Authors: Sedgwick JONATHAN D.
Published: March 2008

The central nervous system (CNS) is considered to be a severely disadvantaged site for the elicitation of immune responses. First, there is no specialised lymphatic drainage. Second, both glia and neuronal cells normally do not express appreciable levels of major histocompatibility complex molecules. Third, the vasculature of the CNS is, at least in most places, lined by endothelial cells that have tight junctions and form a barrier (the blood‐brain barrier) against most molecules and cells present in the circulation. Fourth, the cells most important in the initiation of immune responses, the leucocyte dendritic cell, are not present. Nevertheless, the existence of inflammatory diseases of this tissue, occurring naturally as in multiple sclerosis or in animals after peripheral immunisation with CNS autoantigens, indicates that the immune system can access and recognise antigens in this site. How this is achieved has become clearer in recent years and primarily seems to involve extravasation of activated but not resting T cells across the blood‐brain barrier, and recognition of antigen on macrophage‐like perivascular cells, rather than cells within the CNS parenchyme such as astrocytes or microglia. The processes involved in immunological patrolling of the CNS and development of autoimmune inflammatory disease are reviewed.
Cytotoxic lymphocyte‐mediated immunotherapy
Authors: Smyth MARK J. , Kershaw MICHAEL H.
Published: March 2008

Cytotoxic CD8+ T cells and NK cells play a role in the elimination of some viruses, graft rejection, antitumour responses, immuno regulation and some autoimmune diseases. The central importance of these cells in each of these immune responses and the therapeutic potential they offer, when effectively targeted, has justified continued interest in their Junction. Molecular biology has dominated the recent study of cytotoxic lymphocyte function, allowing the characterisation of recognition structures on cytotoxic lymphocytes, the definition of two distinct mechanisms of cytotoxicity and the determination of their relevance in vivo. Biological and genetic experimental approaches which exploit the targeted cytolytic activity of lymphocytes are now being developed for immunotherapy. A greater knowledge of the biology of cytotoxic lymphocytes when adoptively transferred, the development of engineered monoclonal antibodies and the characterisation of novel endogenous tumour cell antigens, has us on the brink of using these cells to greater therapeutic advantage. This article reviews ongoing efforts to characterise the mechanism of action of cytotoxic lymphocytes and outlines the progression of approaches designed to enhance the anti‐tumour activity of these cells.
Understanding the pathogenesis of type 2 diabetes: can we get off the metabolic merry‐go‐rounds?
Authors: Proietto JOSEPH , Rosella GENNARO , Andrikopoulos SOFIANOS , Thorburn ANNE
Published: March 2008

The aetiology of non‐insulin‐dependent diabetes mellitus (NIDDM) is not known. The concordance of NIDDM in identical twins and differences in the prevalence rate of NIDDM between different racial groups suggest a genetic cause. Hyperglycaemia in established diabetes is caused by a combination of hepatic insulin resistance, impaired peripheral (muscle and fat) glucose uptake and a defect in glucose‐mediated insulin secretion. However, it is not known if these defects are all inherited or if one can cause the others. This uncertainty is due to the fact that hyperglycaemia per se can cause defects in insulin action and insulin secretion that resemble those found in NIDDM. Furthermore the elevated free fatty acid (FFA) levels found when NIDDM is associated with obesity are known to cause both peripheral and hepatic insulin resistance. Recently we have demonstrated the mechanism by which elevated FFA levels can cause hepatic insulin resistance. However, we also have evidence that the converse holds in that genetically engineered hepatic insulin resistance in a transgenic rat model leads to obesity. Thus an understanding of the pathogenesis of NIDDM is complicated by the fact that hyperglycaemia and obesity can be both causes and consequences of insulin resistance. To overcome these difficulties, studies in young, euglycaemic diabetes‐prone subjects have been conducted. Results suggest that there may be different causes for NIDDM in different racial groups.
Primary hyperaldosteronism: A missed diagnosis in ‘essential hypertensives’?
Authors: Brown M. A. , Cramp H. A. , Zammit V. C. , Whitworth J. A.
Published: March 2008

Background: It has been recognised recently that primary hyperaldosteronism may be more common than previously thought, the frequency of diagnosis being improved by screening using a plasma aldosterone concentration to renin activity ratio.

Aims: To determine the frequency of primary hyperaldosteronism, screening with both plasma aldosterone to renin concentration (PRC) and activity (PRA) ratios, in normokalaemic subjects previously diagnosed as having essential hypertension.

Methods: Plasma potassium, aldosterone and PRCs and PRA and blood pressure (BP) were measured in 74 hypertensive subjects previously diagnosed by one physician as having essential hypertension. A normal range for plasma aldosterone/renin ratios was determined in 147 control subjects.

Hypertensive subjects with elevated aldosterone/renin ratios were further assessed for primary hyperaldosteronism using saline loading and fludrocortisone suppression. Those in whom plasma aldosterone concentration exceeded 140 pmol/L after suppression tests underwent adrenal vein sampling for measurement of aldosterone and Cortisol concentrations as well as adrenal CT scanning to diagnose the cause of primary hyperaldosteronism. The main outcome measures were a diagnosis of aldosterone producing adenoma or bilateral adrenal hyperplasia based upon adrenal vein sampling.

Results: Four subjects (5%) had an elevated plasma aldosterone to renin ratio using PRC and six (8%) using PRA. Two subjects (2.7%) in this selected population had primary hyperaldosteronism, both of whom had BP > 160/110 mmHg at the time of testing.

Conclusions: The frequency of normokalaemic primary hyperaldosteronism appears to be greater than previously thought, though the true incidence in the general population of hypertensive subjects remains unknown. The sensitivity of diagnosis (but not specificity) may be improved by measurement of the plasma aldosterone/renin ratio and PRC is at least as adequate as PRA for this process.
G‐CSF stimulated donor granulocyte collections for prophylaxis and therapy of neutropenic sepsis
Authors: Grigg A. , Vecchi L. , Bardy P. , Szer J.
Published: March 2008

Background: The administration of granulocyte colony‐stimulating factor (G‐CSF) increases the granulocyte count in normal donors and enables the collection of large numbers of mature myeloid cells by leukapheresis. This has potential value in the treatment of sepsis unresponsive to antibiotics in patients with severe neutropenia.

Aim: To evaluate the tolerability of granulocyte collections in normal donors receiving G‐CSF, the optimal method of collection and the clinical factors influencing the efficacy of granulocyte infusions.

Methods: Analysis of the outcome of 55 granulocyte collections from 26 donors for progressive bacterial or fungal sepsis in neutropenic patients (n‐8) or as prophylaxis in patients with recent fungal infections undergoing allogeneic bone marrow transplantation (BMT) (n=3).

Results: G‐CSF was well tolerated in most donors. Fatigue occurred commonly after the second collection. The median WCC per 200–220 mL bag was 351X1097L. Collections were optimised with the use of a sedimenting agent (dextran) and a deepened interface setting on the cell separator. There was only a weak correlation between the number of granulocytes infused and the increment in the patient, but levels were usually maintained 0.5X 1097L for the next 24 hours. The infusions were successful in three septic patients without multi‐organ dysfunction and prophylactically, in two patients with localised fungal infections undergoing MBT The infusions were not beneficial in patients with septicaemia and established organ dysfunction or with extensive pulmonary aspergillosis.

Conclusions: G‐CSF mobilised granulocyte collections are feasible and the preliminary evidence suggests that the infusion of these cells may be useful early in the prophylaxis or treatment of severe neutropenic sepsis.
Sotalol proarrhythmia: a report of five cases and an audit of the use of sotalol in a teaching hospital
Authors: Basta M. N. , Leitch J. W. , Fletcher P. J.
Published: March 2008

Abstract Background: Polymorphic ventricular tachycardia is an uncommon complication of sotalol use.

Aims: The aims of this study were: (1) to report five cases of sotalol proarrhythmia and (2) to audit the use of sotalol in a teaching hospital population.

Methods: Five patients with sotalol proarrhythmia (defined as new ventricular arrhythmias associated with sotalol administration) were identified over an 18 month period. Sotalol use for patients admitted to the John Hunter Hospital was audited over a six month period with 85 patients (55 males) identified from die pharmacy database. Medical records were reviewed and the details of treatment including sotalol dose and indication determined. Creatinine clearance was estimated by the Cockcroft and Gault regression equation.

Results: The audit indicated that sotalol was prescribed predominantly for management of atrial arrhythmias (80%). Paroxysmal atrial fibrillation was the most common indication (71%). Although female patients were older (72±13 vs 62+15 years, p<0.001) and had a lower creatinine clearance (55±24 vs 82±32 mg/minute, p<0.001) than male patients, they were prescribed similar doses of sotalol (206±112 vs 193±93 mg/day). The ratio of sotalol dose to creatinine clearance was higher in female patients (4.0±2.6 vs 2.16±1.5, P<0.01). The five patients with proarrhythmia (torsades de pointes in four patients and polymorphic ventricular tachycardia in one patient) were all female. Daily sotalol dose (odds ratio for each 160 mg tablet 4.9 [95% confidence interval 1.5–16] and female gender (p<0.01) were significant risk factors for proarrhythmia'.

Conclusion: Sotalol dose was not appropriately adjusted for creatinine clearance which is age and gender dependent. Female patients have an increased risk of proarrhydimia and should receive lower doses of sotalol.
Streptococcus pneumoniae carriage and penicillin/ ceftriaxone resistance in hospitalised children in Darwin
Authors: Skull S. A. , Leach A. J. , Currie B. J.
Published: March 2008

Background: The prevalence of resistant Streptococcus pneumoniae (SP) is increasing worldwide. Pneumococcal prevalence and susceptibility patterns are not known for children in the Top End of the Northern Territory.

Aims: To determine the prevalence of nasopharyngeal carriage of pneumococci in children hospitalised in Darwin, and the extent of penicillin and ceftriaxone resistance in these isolates.

Methods: Nasopharyngeal swabs were collected on admission from 85 children who had not received antimicrobials for their admission illness. Antimicrobial resistance was determined following selective culture for SP isolates. Minimal inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined using the E‐test method.

Results: The overall prevalence of nasopharyngeal SP carriage was 44%. Carriage occurred more often in Aboriginal children from rural areas (56%) than in urban children (24%) (OR 3.94, 95% CI 1.35 ‐ 11.78, p<0.01). Thirty per cent of isolates were penicillin resistant, 35% were ceftriaxone resistant, and 49% were resistant to at least one of these. One isolate showed high‐level resistance to both antimicrobials; all other resistant isolates were of intermediate‐level resistance. For the same isolate, MICs for ceftriaxone were more often higher than those for penicillin. Five isolates had intermediate resistance to ceftriaxone whilst remaining sensitive to penicillin.

Conclusions: The prevalence of pneumococcal resistance to penicillin and ceftriaxone in hospitalised children in Darwin is much higher than previously reported in Australia. This has implications for future antimicrobial management and highlights the need for regular regional surveillance of SP resistance. The development of conjugate pneumococcal vaccines for children under two years is a priority.
Changes in job aspirations during physician training in Australia
Authors: Kanagarajah S. , Page J. H. , Heller R. F.
Published: March 2008

Background: There is uncertainty regarding the effects of physician training on planned practice features of Australian physician trainees, for example plans for urban or rural, full‐time or part‐time and academic/research or purely clinical practice. These plans may differ between male and female trainees and between generalists and sub‐specialists.

Aim: To examine the changes in anticipated practice patterns over the course of advanced physician training.

Methods: Longitudinal study of doctors in Australia who passed the Part I clinical examination of the Royal Australasian College of Physicians in 1991, 1992 and 1993, followed annually up until 1995. Changes in future practice plans regarding full‐ or part‐time work, rural or urban practice and pure clinical work or a mixture with research were examined among generalist and specialist trainees and among men and women. Statistical analysis included the calculation of chi square for trend statistics and intraclass correlation coefficients.

Results: At least one follow‐up questionnaire was received from 80% of the 334 original respondents. The majority had been able to obtain their training job of choice. By the time of last follow‐up, around 80% planned to practise in a capital city, indicating a shift during training from those who initially stated no preference. There was also a shift towards combining research with clinical practice and among women wishing to practise part‐time only. Generalists were more likely to wish to practise outside a capital city than specialists.

Conclusions: The training programme should be revised so that careers in rural and provincial centres are encouraged and so that it is sensitive to the needs for physicians to develop research capacity. Training and career opportunities should allow all candidates (particularly women) wishing part‐time employment to achieve their full career potential.
Adult asthma and gastro‐oesophageal reflux: the effects of omeprazole therapy on asthma
Authors: Teichtahl H. , Kronborg I. J. , Yeomans N. D. , Robinson P.
Published: March 2008

Background: Approximately 40–60% of patients with asthma have gastro‐oesophageal reflux (GOR) and it has been postulated that this may worsen asthma severity.

Aims: To investigate the effect of the potent gastric acid inhibitor omeprazole 40 mg orally daily on peak expiratory flow rate (PEFR), asthma symptoms and histamine bronchial responsiveness in adult patients with both asthma and GOR.

Methods: This was a double blind, randomised, placebo controlled, crossover study. Upper gastrointestinal endoscopy, 24 hour oesophageal pH measurements, spirometry and histamine bronchoprovocation test (HIT) were performed prior to entry. Phase 1:2 week placebo run‐in period, with baseline recording of PEFR, asthma and GOR symptoms, and use of inhaled p2‐agonist. Phase 2: patients randomised to receive either placebo or omeprazole 40 mg/d for four weeks. Phase 3: placebo for two weeks. Phase 4: patients crossed over to opposite treatment from that of phase 2. Spirometry, and diary cards were assessed at beginning and end of phases 2 and 4. HIT was performed at the end of phase 2 and at the beginning and end of phase 4.

Results: Twenty patients (eight female and 12 male) completed the study. The evening but not morning PEFR (% predicted) were significantly higher on omeprazole vs placebo (82 ± 4% SEM vs 79 ± 4% SEM; p<0.05). No significant differences were found in FEVj, FVC, histamine bronchial responsiveness and diurnal variation of PEFR between placebo and omeprazole treatments. Similarly, there were no significant differences during placebo and omeprazole periods in day time wheeze, cough, breathlessness, p2‐agonist use or night time wheeze and breathlessness. Day and night heartburn symptoms were significantly better on omeprazole vs placebo (p<0.05).

Conclusions: Omeprazole 40 mg daily improved evening PEFR in asthma patients with GOR. However, asthma symptoms, inhaled β2‐agonist use and histamine bronchial responsiveness did not change.
Perhexiline improves symptomatic status in elderly patients with severe aortic stenosis
Authors: Unger S. A. , Robinson M. A. , Horowitz J. D.
Published: March 2008

Abstract Background: The prognosis of severe symptomatic aortic stenosis is poor without aortic valve replacement, with no previous reports of beneficial effects of any medical treatment on either symptoms or outcome. However, this condition is increasingly a disease of the elderly and cardiothoracic surgery is associated with significant mortality and morbidity in this group.

Aims: We postulated that perhexiline, a novel anti‐ischaemic agent with an oxygen‐sparing metabolic effect in the myocardium (via inhibition of carnitine palmitoyltransferase‐1) and no adverse haemodynamic effects, may improve symptomatic status in elderly patients with severe aortic stenosis. We report here our initial experience with perhexiline treatment in such patients.

Methods: Elderly patients with symptomatic severe aortic stenosis, who were deemed unsuitable for aortic valve replacement, were treated with perhexiline, the drug dosage titrated according to steady state plasma perhexiline concentrations. NYHA functional class was determined prior to and three months following commencement of perhexiline, and changes were analysed using McNemar's test.

Results: Fifteen patients, age range 73–87, were followed for up to 30 months (median 18 months). Symptomatic status improved in 13 of the 15 patients over the first three months of perhexiline therapy (p<0.01), five patients becoming asymptomatic. Twelve month actuarial survival was 80% (95% CI=57, 100). Perhexiline was well tolerated, with no withdrawals due to toxicity or deteriorating clinical status.

Conclusion: Therapy with perhexiline was associated with a marked improvement in clinical status in this group of elderly patients with severe aortic stenosis.
Transfusion transmitted Yersinia enterocolitica infection in New Zealand
Authors: Theakston E. P. , Baker B. W. , Morris A. J. , Woodfield D. G. , Streat S. J.
Published: March 2008

Abstract Aims: To update and summarise cases of transfusion‐transmitted Yersinia enterocolitica infection in New Zealand and to evaluate critically suggested methods to reduce this rare but frequently fatal complication of blood transfusion.

Methods: Case reports of four recent transfusion‐transmitted Y enterocolitica infections in New Zealand are given and previous reports reviewed. Literature review and evaluation of proposed methods to decrease the incidence of transfusing yersinia contaminated blood.

Results: There have been eight cases of transfusion‐transmitted Y enterocolitica infection in New Zealand in the past five years. Four of the five deaths have been directly caused by the transfusion. This gives a transfusion incidence rate of one:65,000 and a fatality rate of one: 104,000 units transfused. This fatality rate is more than 80 times higher than that reported in the United States.

Conclusions: Why the incidence of transfusion‐transmitted yersinia is so high is not clear, since we do not store blood as long as many other countries, particularly the United States. In Auckland, however, the cases came at a time when the number of yersinia isolates from the community is reported to be rising.

Many suggestions for the prevention of this problem have been put forward reflecting the fact that there is as yet no perfect solution. Those which are easy to implement and cheap to perform are largely already in place and investigation is continuing into the other alternatives.
Time delay in the treatment of acute myocardial infarction (AMI): a comparison of primary percutaneous transluminal coronary angioplasty (PTCA) with thrombolysis
Authors: Hitchcock T. , Kidd H. M. , Taylor R.
Published: March 2008

Abstract Background: If primary percutaneous transluminal coronary angioplasty (PTCA) cannot be performed within times comparable to thrombolysis, the possible advantages of that management may be offset by the logistic difficulties associated with its delivery.

Aim: To measure and compare the time delay involved in administration of thrombolysis and primary PTCA over a one year period and examine causes for delay greater than 60 minutes.

Method: Prospective data collection on all patients treated with primary PTCA or thrombolysis. A quality improvement process was applied.

Results: Eighty‐five patients were treated with thrombolysis with a delay of 39±8 (SD) minutes, 12 patients being treated more than 60 minutes after presentation. Primary PTCA was used in 79 patients with a delay of 48±12 (SD) minutes, 21 patients being treated after more than 60 minutes. Time delays in the two management groups were significantly different (p=0.03) but that in primary PTCA during routine hours was not significantly different from that in thrombolysis treated patients (p=0.07). Causes for revascularisation delay greater than 60 minutes from presentation are discussed.

Conclusions: With appropriate facilities and organisation, patients with acute myocardial infarction presenting within normal working hours can be treated with primary PTCA without compromising their care due to time delay. Many patients managed with primary revascularisation by thrombolysis or primary PTCA with a delay of more than 60 minutes have identifiable clinically appropriate delays.
Sublingual nifedipine in human pregnancy
Authors: Gallery E. D. M. , Gyory A. Z.
Published: March 2008

Abstract Background: Nifedipine is widely used for acute lowering of blood pressure in obstetric hypertensive emergencies. It has not been approved for this indication or widely assessed.

Aims: To examine retrospectively the efficacy of nifedipine over a 12 month period in a high risk obstetric service.

Methods: Chart review of all patients admitted to hospital in the antenatal period with moderate to severe hypertension. Description of their management, usage of nifedipine, and pregnancy outcome.

Results: Sublingual nifedipine resulted in significant lowering of blood pressure without hypotension. Pregnancy outcome was satisfactory in all patients.

Conclusions: Sublingual nifedipine was effective, easy to administer, and without serious complications in this retrospective study.
Early management and outcome of acute stroke in Auckland
Authors: Anderson N. E. , Bonita R. , Broad J. B.
Published: March 2008

Abstract Background: Studies of acute stroke management in stroke units and tertiary referral hospitals may not accurately reflect practice within the population. Reliable information on the management of stroke within a population is sparse.

Aims: To compare clinical practice in acute stroke management in Auckland with guidelines for the management and treatment of stroke in other countries; to provide a baseline measure against which future changes in management can be evaluated.

Methods: All new stroke events in Auckland residents in 12 months were traced through multiple case finding sources. For each patient, a record of investigations and treatment during the first week of hospital admission was kept.

Results: One thousand eight hundred and three stroke events (including subarachnoid haemorrhages) occurred in 1761 patients in one year. Twenty‐seven per cent of all events were managed outside hospital and 73% of the stroke events were treated in an acute hospital. Of the 1242 stroke events admitted to an acute hospital in the first week, only 6% were managed on the neurology and neurosurgery ward, 83% were managed by a general physician or geriatrician and 42% had computed tomography (CT). Of 376 validated ischaemic strokes, 44% were treated with aspirin and 12% with intravenous heparin. Of die 690 unspecified strokes (no CT or autopsy), 38% received aspirin and 0.5% heparin. The 28 day in‐hospital case fatality for all stroke events admitted to an acute hospital during the first week was 25%.

Conclusions: In Auckland, management of acute stroke differed from clinical guidelines in the high proportion of patients managed in the community, the low rate of neurological consultation, and the low frequency of CT scanning. Despite these deficiencies in management, the 28 day hospital case fatality in Auckland was similar to other comparable studies which had a high proportion of cases evaluated by a neurologist and CT.
Implementation of guidelines for No‐CPR orders by a general medicine unit in a teaching hospital
Authors: Lowe J. , Kerridge I.
Published: March 2008

Background: No‐cardiopulmonary resuscitation (CPR) orders are frequently used to limit the use of cardiopulmonary resuscitation in patients who die in hospital. International research has consistently highlighted major deficiencies in the formulation, documentation and communication of such orders. There has been little Australian research into No‐CPR orders and the impact of clinical guidelines.

Aims: This audit aimed to examine compliance with published guidelines for No‐CPR orders previously developed by the hospital Clinical Ethics Committee.

Methods: The notes of all patients who died while under the care of the General Medicine Unit during June‐December 1994 were reviewed to evaluate the use of No‐CPR orders. Adherence to hospital No‐CPR guidelines was evaluated as well as the principal diagnosis, age, level of care and competence of patients to state their wishes.

Results: A No‐CPR order was documented in 61% (n=40) of the 66 patients who died during this period. Of these patients 80% were judged to be incompetent and were unable to be involved in decisions not to resuscitate. There was substantial compliance with the guidelines, with the exception of documenting involvement of nursing staff.

Conclusions: No‐CPR orders are frequently implemented as a result of failure to respond to curative therapy and do not represent abandonment of the patient. Although this study demonstrates the value of No‐CPR guidelines and the audit process, the findings raise fundamental issues regarding the involvement of nursing staff, and of patients, that need to be further addressed.
Inappropriate sinus tachycardia (1ST): management by radiofrequency modification of sinus node
Authors: Jayaprakash S. , Sparks P. B. , Vohra J.
Published: March 2008

Background: Inappropriate sinus tachycardia (IST) is a rare form of supraventricular arrhythmia. It can cause disabling symptoms and may be refractory to medical treatment. In symptomatic drug refractory patients, sinus node excision or total ablation of the sinus node with permanent pacemaker implantation was the only therapeutic option. Recently, radiofrequency (RF) modification of the sinus node has been reported to be an effective treatment for this condition.

Aim: To present our experience with sinus node modification using RF energy in the management of 1ST

Methods: Between 1989> to 1996 three patients (two females and one male), aged 28–36 years were diagnosed with symptomatic IST All had failed multiple drugs and hence underwent sinus node modification using RF. In the first two patients, the site of RF application was guided by anatomical landmarks using fluoroscopy to localise the presumed most superior portion of the crista terminalis and also the earliest site of atrial activation. In fhe third patient, a 20 pole electrode catheter was used to map the crista terminalis and guide the ablation. Success was defined by 20–30% reduction in the heart rate with normal atrial activation sequence after ablation.

Results: The three patients described here had IST by clinical, electrocardiographic and electrophysiological criteria and were refractory to multiple antiarrhythmic drugs. The number of RF applications were 11, 15, and three applied at the site of earliest atrial activation for the control of heart rates. Patient 3 had a early recurrence at one month and underwent repeat sinus node modification (five RF applications). All three patients who underwent RF modification of the sinus node had a successful outcome. The procedure was uncomplicated and the patients remain asymptomatic during follow up (20, 12 and three months) with satisfactory control of heart rate, although one patient requires atenolol which was previously ineffective.

Conclusions: RF modification of the sinus node is feasible and effective for IST, and should be the treatment of choice in patients refractory to medical therapy.
The effect of treating people with reversible ischaemic attacks of the brain and eye on the incidence of stroke in Australia
Authors: Hankey G. J.
Published: March 2008

Background: Reversible ischaemic attacks of the brain or eye (RIA) are a risk factor for stroke. Strategies of stroke prevention include vascular risk factor control, antithrombotic therapy, and carotid surgery.

Aims: To determine the effectiveness, risks and costs of each stroke prevention strategy for patients with RIA and the Australian community, and the effect of treating people with RIA on the incidence of stroke in Australia.

Methods: Review of data from prospective community‐based studies to determine the prevalence of RIA, the incidence of stroke, and the proportion of stroke patients who report a RIA before their stroke; and data from randomised trials to determine the effectiveness, risks and costs of treatments for RIA.

Results: About 111,000 Australians have had a prior RIA. Each year, about 37,000 Australians suffer a stroke, of whom up to 8000 (22%) have had a prior (‘warning’) RIA. Targeting effective stroke prevention strategies to RIA patients with relevant treatable conditions may reduce the individual's stroke risk by two‐thirds (individual strategies) and possibly further (combination strategies). However, because the attributable risk of RIA for stroke is only about 22% (and may be less, given the role of other causal risk factors for stroke), strategies of stroke prevention in RIA patients can only reduce stroke incidence by up to 15% (from 22% to 7%).

Conclusions: The potential benefits of the ‘high risk’ approach to stroke prevention appear to be less than the ‘population’ approach, but both approaches are necessary and complementary. Indeed, the cost of implementing the ‘high risk’ approach may be less than the cost of the strokes prevented (255 million; i.e. 15% of 1.7 billion).
Evidence‐based cardiac practice
Authors: Silagy Chris
Published: March 2008

Increasing attention is being placed on using an evidence‐based approach within health care decision making. In order to apply this approach to a particular clinical scenario, the relevant clinical evidence must be available, accessible, accepted, applied, and audited. Cardiovascular medicine is a discipline in which a large body of evidence is available. The development of the Cochrane Library, as a source of systematic reviews concerning the effects of health care, will make this evidence more accessible. However, caution is required in interpreting systematic reviews, particularly when meta‐analytic techniques are used, to ensure that potential sources of bias in the identification and synthesis of the primary studies are minimised. A further challenge is to develop strategies to ensure the evidence is accepted and applied in clinical practice. Although there are no magic bullets to change behaviour of positions, there are a number of strategies which have been shown to influence change positively in clinical practice.
Evaluation of radiation dose and risk to the patient from coronary angiography
Authors: Harrison D. , Ricciardello M. , Collins L.
Published: March 2008

Background: Coronary angiography is a commonly performed diagnostic procedure with life saving benefits for the patient. However, because of its potential to deliver a high radiation dose, caution is warranted.

Aim: The purpose of this study was to determine the effective dose to an average patient from coronary angiography, to estimate the associated radiation risk in terms of fatal malignancy, and to examine ways effective dose may be reduced.

Method: The dose‐area product data from 210 examinations was used to determine the effective dose to the average patient by means of a commercially available software programme. Subsequently, the effective dose was used to estimate radiation risk based on die population averaged probability coefficients given in ICRP 60 and contrasted against age‐related risk coefficients from the NRPB. The components of effective dose and radiation risk were examined to identify the organs most at risk.

Results: The average effective dose was found to be 3.4±1.3 mSv. The risk of fatal malignancy was estimated as 170 per million cases, or around one in 6000. The average lung dose was 14.7 mSv, with the risk of fatal lung cancer estimated as 125 per million cases or one in 8000.

Conclusions: The average effective dose in this study was less than half that of most other studies. The lung was identified as the critical organ and the estimated risk of fatal cancer amounted to an increase of 0.017% above the normal incidence for the general population. The study affirmed that using a reduced cine frame rate, low dose pulsed fluoroscopy, added copper filtration and a conscious effort to reduce screening time can significantly reduce patient dose.
Transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of refractory ascites
Authors: Williams D. B. , Waugh R. , Selby W.
Published: March 2008

Background: The Transjugular Intrahepatic Portosystemic Shunt (TIPS) corrects portal hypertension and has proven to be effective in controlling variceal bleeding in patients with cirrhosis. Several reports have now appeared suggesting a possible role in patients with refractory ascites.

Aims: To examine the outcome of TIPS for the treatment of refractory ascites in patients with cirrhosis.

Methods: Fifteen patients underwent TIPS for ascites between April 1992 and December 1996. The clinical findings, response to treatment, complications, shunt patency and survival of these patients were analysed.

Results: TIPS was successfully placed in all patients. The mean period of follow‐up was 375 days (range: 14–1165 days). In eight patients (53%) there was a reduction in the degree of ascites after shunt insertion, with six patients (40%) having complete resolution. Age, Child‐Pugh class or portal pressure gradient, before or after the procedure, were not predictive of response. Of five patients with renal insufficiency (serum creatinine >130 umol/L), only one had improvement in ascites control. Six patients (40%) required shunt revision during follow‐up, either for acute thrombotic occlusion (two) or stent stenosis (four). New or worsening encephalopathy developed in ten patients (67%). Two patients (13%) died of liver failure within 30 days. Cumulative survival was 46% at one year and 18% at two years. Treatment response was associated with increased survival (ρ=0.02), with median survival of 658 days as compared with 71 days for treatment failure.

Conclusions: TIPS can be effective in the treatment of refractory ascites in patients with cirrhosis. Our experience suggests the benefit may be less for patients with advanced liver disease and renal impairment. Controlled trials are needed to compare TIPS with other treatment modalities such as large volume paracentesis or peritoneovenous shunting.
Prevalence and vascular associations with migraine in older Australians
Authors: Mitchell P. , Wang J. J. , Currie J. , Cumming R. G. , Smith W.
Published: March 2008

Background: Migraine is a common disorder with recently described vascular associations, yet there are few Australian population‐based data describing migraine prevalence.

Aims: To assess the prevalence and vascular associations with lifetime past history of typical migraine headache in a representative sample of older Australians.

Methods: The Blue Mountains Eye Study examined 3654 permanent residents aged 49 or older living in two postcode areas, west of Sydney (82.4% participation) during 1992–4. A structured interview was administered, including questions about past or present history of typical migraine. The diagnosis was consistent with International Headache Society criteria.

Results: A lifetime past history of typical migraine was given by 17% of participants, including 22% of women and 10% of men, a female:male ratio of 2.3:1. A marked trend for declining lifetime migraine frequency with increasing age was found for both sexes. Modest statistically significant associations were found with vascular disease history, after multivariate adjustment, which included vascular risk factors. These associations were stronger in men than in women. Among men, typical migraine was significantly associated with history of angina, odds ratio (OR) 2.0, acute myocardial infarction (OR 1.9) and stroke (OR 2.2). Among women, statistically significant associations were present only with history of myocardial infarct (OR 1.8).

Conclusions: These data indicate similar prevalence rates for lifetime typical migraine history in a representative sample of older Australians, compared to recent US and Canadian populations. Modest, statistically significant associations between typical migraine and past history of vascular disease were found, with the strongest associations found in men.
Prevalence and demographic determinants of metronidazole resistance by Helicobacter pylori in a large cosmopolitan cohort of Australian dyspeptic patients
Authors: Katelaris P. H. , Nguyen T. V. , Robertson G. J. , Bradbury R. , Ngu M. C.
Published: March 2008

Background: The pre‐treatment sensitivity of Helicobacter pylori to metronidazole is a key determinant of successful eradication therapy and should influence local choice of therapy. However, there are few data defining the prevalence of metronidazole resistance (MR) in Australia.

Aim: To determine prospectively the prevalence and demographic determinants of MR in H. pylori isolates from a large and cosmopolitan cohort of dyspeptic patients in Sydney.

Methods: Consecutive dyspeptic patients undergoing endoscopy had gastric biopsies for histology, urease test and culture. Metronidazole resistance was determined by E‐test after subculture. An MIC >8 μg/mL defined MR. Patient age, gender, birthplace and history of previous nitroimidazole use were recorded.

Results: In 732 patients, H. pylori was present in 46.4%. Culture was successful in 81% and subculture for MR in 88% of these. In 237 evaluable patients the overall MR rate was 59.1%. Five patients had had prior triple therapy for H. pylori (of which four of five had MR). Therefore, the primary MR rate in the study population was 58.6% (136/232). MR was more prevalent in younger patients (ρ=0.0002). The MR rate was 70.4% in patients 18–39 years, 66.7% in those aged 40–59 years and lowest (38.9%) in those 60 years or older (ρ=0.002). The MR rate was highest in patients born in Southeast Asia (72.8%, 59/81) and significantly higher than in Australian born (48.1%, 26/54), or Southern European (46.2%, 24/52) born patients (ρ=0.002). There was no gender difference. Logistic regression to determine the impact of each variable (birthplace, age and gender) on MR identified Southeast Asia birthplace as a factor associated with greater likelihood of harbouring an MR isolate (OR 1.88, ρ=0.02). Southern European born patients had the lowest risk of MR (OR 0.70, ρ=0.02) as did patients older than 60 years (OR 0.56, ρ=0.04). A definite history of prior metronidazole use was infrequent and not predictive of MR.

Conclusions: While a high rate of MR is not unexpected in patients born in developing countries, the high rate in Australian born patients is surprising and of concern. This may relate to the high local usage of nitroimidazoles as monotherapy and has important implications for the effectiveness of metronidazole containing triple therapies.