Volume 193 Issue 9

Passive surveillance cannot be relied on as the sole means of surveillance On 22 April 2010, use of seasonal trivalent influenza vaccine in children aged 5 years and under was suspended across Australia, pending an investigation into an apparent increase in reports of adverse events following immunisation (AEFI).1 This unprecedented halt to a national immunisation initiative followed Western Australia’s decision to place a moratorium on the use of this vaccine in young children after observing a spike in emergency department presentations for high fever and febrile convulsions after vaccination.2 A subsequent investigation by the Therapeutic Goods Administration indicated that febrile convulsions related to the vaccine were reported from all jurisdictions except the Northern Territory.2 The apparent rate of febrile convulsions following vaccination was 5–9 per 1000 doses administered, about 50 times higher than that reported following measles–mumps–rubella vaccination.2,3 A recent review, requested by the Minister for Health in WA, has highlighted significant deficiencies in AEFI surveillance.4 In Australia, the current mechanism for identifying AEFI nationally is passive surveillance. Passive surveillance relies on health providers and the public recognising and reporting suspected AEFI to state or federal health authorities. The constraints that are inherent to passive surveillance, including under-reporting and biased reporting, are compounded by the diverse approaches to surveillance that are employed throughout Australia, as illustrated by a fourfold difference in AEFI reporting rates per 100 000 population between jurisdictions.5,6 Adding to concerns about variable sensitivity across the state systems is the inevitable delay in collection, aggregation and analysis of AEFI reports forwarded to the national authority. A number of the issues evident during the response to the vaccine-associated reactions were recognised 5 years earlier during the National Vaccine Safety Workshop.7 A clear set of recommendations for improving adverse event surveillance was identified at the time, but many of the recommendations have not been adequately addressed. Robust postmarketing surveillance is vital for influenza vaccines because seasonal trivalent influenza vaccine does not require clinical trial data to demonstrate safety before release — it is assumed that safety is not altered by the annual change in the combination of vaccine strains. While past experience suggests that this is true, history also indicates that future vaccine scares are inevitable and we should plan accordingly.8 Trivalent influenza vaccine, in particular, highlights the need for postmarketing surveillance to be linked with the capacity for rapid review and response, because a large proportion of the vaccine is administered over a short period before the onset of the influenza season each year. The way forward is to establish a coordinated, uniform approach to AEFI reporting, coding, collation and analysis. A standing vaccine safety monitoring group which includes key stakeholders — representing the regulators, state and national immunisation programs and vaccine safety and epidemiology experts — needs to be urgently established. The inability of the existing surveillance systems to detect the early signal of an increased incidence of febrile convulsions, within 24 hours of receiving 2010 seasonal trivalent influenza vaccine, demonstrates that passive surveillance cannot be relied on as the sole means of surveillance. Complementary active surveillance systems which can methodically detect potential AEFI signals, quickly establish rates and establish causality should be developed. The Australian Childhood Immunisation Register is uniquely placed to contribute to vaccine safety surveillance through data linkage with hospital morbidity and emergency department datasets, as demonstrated by a recent study from South Australia.3 Sentinel surveillance in four tertiary care Australian paediatric hospitals has been shown to be an effective mechanism of surveillance for specific AEFI.9 Implementing active AEFI surveillance systems will require sustainable funding, but this will be a small fraction of the cost expended on vaccines and vaccine delivery and could be resourced by levying a surcharge per vaccine dose sold, similar to methods adopted elsewhere to support compensation for vaccine-associated injuries.10 Central to any system of vaccine safety monitoring are issues of governance; specifically, transparency in decision making. Other countries currently provide full disclosure and web access to de-identified AEFI reports and open access to the deliberations of expert committees.11,12 This engenders public trust in immunisation programs, and similar strategies should be considered in Australia. The vast majority of Australian parents, vaccine recipients and health care providers trust public health authorities to assess and monitor vaccine safety. This is critical to ensure that the benefits of vaccination outweigh any potential risks. In the aftermath of the 2010 seasonal trivalent influenza vaccine experience, maintaining the public’s trust requires that we get started on building the fully functional, standard-of-care AEFI surveillance system that Australia deserves. Vaccine safety should be an integral component of the National Immunisation Strategy, which should include strategies for comprehensive and complementary passive and active systems of surveillance.

Michael S Gold MB ChB, MD, FRACP · Paul Effler MD, MPH · Heath Kelly BSc, MB BS, MPH · Peter C Richmond MB BS, MRCP, FRACP · Jim P Buttery MB BS, FRACP, MSc

There is still room for improvement, both in decreasing delays in, and deciding who is eligible for, reperfusion therapy In patients with acute ST-segment-elevation myocardial infarction (STEMI), early coronary reperfusion — within 1 to 2 hours of symptom onset — by either thrombolysis or primary percutaneous coronary intervention (PCI) reduces the mortality rate by half. However, this benefit quickly dissipates with further delay in treatment.1 As “time is muscle”, it is the time from symptom onset to reperfusion (or total ischaemic time), rather than the mode of reperfusion, that is the critical determinant of outcome. Hence the imperative to minimise: (i) delay by patients in recognising symptoms as possible myocardial infarction (MI) and seeking medical help; (ii) delay in ambulances responding to calls; (iii) delays in diagnosing STEMI on first medical contact; and (iv) omissions or delays in administering the most appropriate means of reperfusion in eligible patients. In this issue of the Journal, Huynh and colleagues, using data from a prospective Australian registry, report on processes of care and outcomes of 755 patients presenting with suspected STEMI.2 There is good and bad news in this report. The good news is that the median time from symptom onset to first medical contact in this cohort was 105 minutes (1.75 hours) compared with 3.2 hours for patients with undifferentiated chest pain, reported in 2005.3 If the sample in the study by Huynh and colleagues2 is representative of most patients with MI, this suggests that public recognition of warning symptoms and the need to seek medical help urgently has improved over the past 15 years in response to public education campaigns that target individuals at high risk and behavioural barriers to action.4 Reperfusion reduced mortality at 12 months (adjusted for baseline risk as calculated using the Global Registry of Acute Coronary Events [GRACE] risk score) by 65% (and by 78% if administered in a timely fashion), similar to results noted in recent overseas observational studies that used similar risk-adjustment methods.5 Finally, there was no difference between metropolitan and rural patients in the time to presentation or the proportions of patients who received reperfusion therapy, or who received it in a timely manner, and the same applied to inhospital and 12-month mortality rates. This suggests the “city–bush” gap in coronary care noted in past studies6 is being closed, although more rural patients (74%) received thrombolysis, while more metropolitan patients (68%) received primary PCI. The bad news is that one in three patients did not receive any form of reperfusion — a figure common to other countries and which has proven resistant to change.7 Unfortunately, contraindications to either form of reperfusion in individual patients were not reported, but contraindications and patient refusal have been reported to account for no more than 10% of all patients with STEMI.8 This means just over one in five patients were likely to have been eligible for reperfusion therapy but failed to receive it. Factors associated with not receiving reperfusion therapy on regression analysis included a past history of diabetes or documented coronary stenoses on angiography, acute pulmonary oedema on presentation, left bundle branch block on electrocardiogram (ECG), and a non-cardiologist as the treating doctor. In other studies of patients eligible for reperfusion therapy, additional factors have included older age, admission to a facility not capable of performing PCI, increasing time to presentation, renal insufficiency, prior stroke or coronary artery bypass grafting, being female, and presentation without chest pain or with an equivocal ECG.5,7 Some of these associations reflect diagnostic uncertainty in patients with atypical clinical presentations and non-diagnostic ECGs or clinician concern about the risk of bleeding in older patients (especially underweight women) and those with renal failure or prior stroke. However, registry data show that in this patient group at relatively high risk, early reperfusion therapy compared with no reperfusion reduces inhospital mortality by 38%, with primary PCI being more effective than thrombolysis.9 Clinicians may need to recalibrate their perceptions of benefit and risk in groups of patients who have often been excluded from clinical trials. The other bad news is that among patients receiving reperfusion therapy in the study by Huynh and colleagues (61%, primary PCI; 37%, thrombolysis), only one in three received it within an optimal time frame.2 The median door-to-needle time (D2N) for thrombolysis was 43 minutes (versus a 30-minute standard) and door-to-balloon time (D2B) for primary PCI was 102 minutes (versus a 90-minute standard). These times are longer than those reported in contemporary cohorts in other developed countries, such as 33 minutes D2N and 83 minutes D2B in a Canadian cohort,5 and 30 minutes D2N and 86 minutes D2B in the GRACE international registry.10 Attention has recently shifted to reducing total system delay, defined as the time from first contact with the health care system (ie, ambulance) to initiation of reperfusion therapy, which now appears to be more strongly associated with mortality than patient delay in seeking care.11 In reducing system delay, the timing of PCI (immediate v delayed v rescue) and its relation to thrombolysis in patients presenting to non-PCI-capable hospitals becomes a pivotal issue. Current Australian and New Zealand guidelines state that fibrinolysis is preferred to primary PCI in patients presenting within 1 hour of symptom onset unless balloon insufflation can occur within 60 minutes after first medical contact (in most cases, this is patient pick-up by ambulance).12 In patients presenting between 1 and 3 hours after symptom onset, fibrinolysis is preferred unless primary PCI can occur within 90 minutes of first medical contact. Studies show that in patients with symptom onset of less than 3 hours and for whom transfer to PCI-capable hospitals would delay primary PCI for more than 90 minutes, the combination of early lysis and aggressive use of rescue PCI (in the third of patients with persistent ST-segment elevation, cardiogenic shock, severe heart failure or serious ventricular arrhythmias) confers comparable outcomes with that achieved with primary PCI.13 In this regard, prehospital thrombolysis undertaken by ambulance paramedics, combined with early PCI where appropriate, seems to be an underused strategy in reducing system delay.14 Another issue is the role of risk stratification in deciding who should receive which form of reperfusion. A treatment-risk paradox is often seen whereby eligible patients at high absolute risk of death or recurrent MI are less likely to receive reperfusion therapy (for reasons already mentioned) than those at lower risk9 and in whom treatment delays attenuate the absolute benefit of reperfusion to a greater degree. In considering transferring patients presenting within 6 hours of symptom onset for primary PCI, the higher the risk profile, the larger the reduction in mortality benefit with primary PCI compared with thrombolysis for each 10-minute increase in PCI-related time delay.15 Delays must be minimised in high-risk patients, rather than simply working to a 60-minute or 90-minute D2B rule. The equipoint between primary PCI and fibrinolysis (the PCI-related time delay at which primary PCI loses its superiority in terms of mortality benefit compared with fibrinolysis) may be as little as a D2B time of 40 minutes in a high-risk situation (such as a young patient presenting early with a large anterior infarction) versus 179 minutes in lower risk situations (such as an older patient presenting late with a non-anterior infarction).16 Several strategies have been shown in both Australian and overseas studies to be effective in reducing total ischaemic time (Box),17-19 and these need to become mainstream care. This will require a multifaceted approach involving educating both patients and doctors; coordinating ambulance, emergency department and cardiac catheterisation laboratory components of care; establishing integrated networks of non-PCI and PCI-capable hospitals with decision support and transfer processes that take patient risk and time to presentation into account; and ongoing data collection and feedback within clinical registries. Strategies for decreasing delays in reperfusion therapy Hospital-based strategy Potential tools Prehospital ECG and field assessment by paramedics Prehospital ECG policy Guidelines for field assessment with electronic transmission to, and verification of ECG diagnosis by, emergency department staff Prehospital thrombolysis for patients who are within 1 hour of symptom onset Training of paramedics in ECG diagnosis and administration of thrombolytic agents Transfer of PCI-eligible patients direct to a PCI-capable facility Pre-destination protocol for paramedics Rapid assessment and ECG on patients presenting to emergency departments with chest pain Dedicated chest pain cubicles in emergency departments with ECGs taken within 10 minutes of arrival Rapid management of diagnostically uncertain cases Formal order sets for suspected myocardial infarction in cases of initially non-diagnostic ECG Rapid initiation of thrombolysis in eligible patients Formal thrombolysis protocols that can be initiated by emergency department nurses or physicians without consulting the cardiology department Emergency department bypass of PCI-eligible patients with direct transfer to a catheterisation laboratory Prehospital (or first hospital) assessment policy Guidelines for direct activation of the catheterisation laboratory by emergency department staff without review or approval by cardiologists Single-call activation of the catheterisation laboratory team Alert system with single person as contact (senior registrar or consultant) Catheterisation team fully operational within 30 minutes of activation Staff policy and roster Performance of PCI 7 days a week, 24 hours per day Clearance of elective cases; maintained availability of ready-to-go equipment and staff Prompt data feedback Time-entry forms for door-to-needle and door-to-balloon times, and these times notified to all team members after each procedure Team-based approach Team training program; limited handovers with single team approach Regionalised “hub-and-spoke” hospital networks which expedite patient transfer to PCI-capable facility Triage and expedited transfer guidelines for referring and receiving hospitals PCI = percutaneous coronary intervention. ECG=electrocardiogram.

Ian A Scott FRACP, MHA, MEd

Objective: To describe the contemporary management and outcomes of patients presenting with ST-segment-elevation myocardial infarction (STEMI) in Australia.Design, participants and setting: Observational analysis of data for patients who presented with suspected STEMI and enrolled in the Australian Acute Coronary Syndrome Prospective Audit from 1 November 2005 to 31 July 2007.Main outcome measures: Factors associated with use of reperfusion therapy and timely use of reperfusion therapy, and the effects of reperfusion on mortality.Results: In total, 755 patients had suspected STEMI. Median time to presentation was 105 minutes (IQR, 60–235 minutes). Reperfusion therapy was used in 66.9% of patients (505/755), and timely reperfusion therapy in 23.1% (174/755). Thombolysis was administered in 39.2% of those who received reperfusion therapy (198/505), while 60.8% (307/505) received primary percutaneous intervention. Cardiac arrest (OR, 2.83; P = 0.001) and treatment under the auspices of a cardiology unit (OR, 2.14; P = 0.02) were associated with use of reperfusion therapy. A normal electrocardiogram on presentation (OR, 0.42; P = 0.01), left bundle branch block (OR, 0.18; P = 0.001), acute pulmonary oedema (OR, 0.34; P < 0.01), history of diabetes (OR, 0.54; P < 0.01), and previous lesion on angiogram of > 50% (OR, 0.51; P = 0.001) were associated with not using reperfusion. Inhospital mortality was 4.0% (30/755), mortality at 30 days was 4.8% (36/755), and mortality at 1 year was 7.8% (59/755). Receiving reperfusion therapy of any kind was associated with decreased 12-month mortality (hazard ratio [HR], 0.44; 95% CI, 0.25–0.78; P < 0.01). Timely reperfusion was associated with a reduction in mortality of 78% (HR, 0.22; P = 0.04). There were no significant differences in early and late mortality in rural patients compared with metropolitan patients (P = 0.66).Conclusion: Timely reperfusion, not the modality of reperfusion, was associated with significant outcome benefits. Australian use of timely or any reperfusion remains poor and incomplete.

Luan T Huynh MB BS, FRACP · Jamie M Rankin MB BS, FRACP · Phil Tideman FRACP · David B Brieger MB BS, PhD, FRACP · Matthew Erickson BM BS, FRACP · Andrew J Markwick MB BS · Carolyn Astley RB, BN · David J Kelaher BPharm, MSc · Derek P B Chew MB BS, MPH, FRACP

Objective: To use neonatal thyroid-stimulating hormone (TSH) concentration data to measure the iodine status of the population of the Australian state of Victoria.Design, participants and setting: Retrospective analysis of the results of 368 552 neonatal heel-prick blood tests for TSH concentration in Victoria in the years 2001–2006.Main outcome measures: Iodine deficiency as indicated by a mean percentage of neonatal TSH concentrations > 5 mIU/L of over 3% in accordance with World Health Organization, United Nations Children’s Fund and International Council for the Control of Iodine Deficiency Disorder criteria; comparison of findings for the nine Department of Human Services health regions in Victoria.Results: The mean percentage of neonatal TSH concentrations > 5 mIU/L ranged from 4.07% in 2001 to 9.65% in 2006, and this increase was statistically significant (P < 0.001). The populations of all nine Victorian health regions showed increasing iodine deficiency over the study period. Metropolitan populations had higher iodine deficiency than non-metropolitan populations, and this difference was also statistically significant (P < 0.05). These results are consistent with urinary iodine excretion research in Victoria.Conclusions: The high percentage of elevated TSH concentrations among newborns is of concern and requires ongoing monitoring. Neonatal TSH assay is part of routine screening in Australia, and thus offers an effective and economical method of monitoring population iodine status.

Ashequr Rahman MB BS, MSc, MPH · Gayle S Savige PhD · Nicholas J Deacon PhD · Ivan Francis BSc, GradDipCompSci · Janice E Chesters PhD

Objective: To understand self-injury and its correlates in the Australian population.Design, participants and setting: Cross-sectional survey, using computer-assisted telephone interview, of a representative sample of 12 006 Australians from randomly selected households.Main outcome measures: Data on demographics, self-injury, psychiatric morbidity, substance use, suicidality, disclosure and help-seeking.Results: In the 4 weeks before the survey, 1.1% of the sample self-injured. For females, self-injury peaked in 15–24-year-olds; for males, it peaked in 10–19-year-olds. The youngest self-injurers were nine boys and three girls in the 10–14-year age group, and the oldest were one female and one male in the 75–84-year age group. Mean age of onset was 17 years, but the oldest age of onset was 44 years for males and 60 years for females. No statistically significant differences existed between those who did and did not self-injure on sex, socioeconomic status or Indigenous status. Most common self-injury method was cutting; most common motivation was to manage emotions. Frequency of self-injury during the 4-week period ranged from 1 to 50 instances (mean, 7). Self-injurers were significantly more psychologically distressed, and also more likely to use substances. Adults who self-injured were more likely to have received a psychiatric diagnosis. Self-injurers were more likely to have experienced recent suicidal ideation (OR, 11.56; 95% CI, 8.14–16.41), and have ever attempted suicide (OR, 8.51; 95% CI, 5.70–12.69). Most respondents told someone about their self-injury but fewer than half sought help.Conclusion: The prevalence of self-injury in Australia in the 4 weeks before the survey was substantial and self-injury may begin at older ages than previously reported. Self-injurers are more likely to have mental health problems and are at higher risk of suicidal thoughts and behaviour than non-self-injurers, and many self-injurers do not seek help.

Graham Martin MD, FRANZCP, DPM · Sarah V Swannell BPsych(Hons), GradCertBiostat · Philip L Hazell MB ChB, PhD, FRANZCP · James E Harrison MB BS, MPH, FAFPHM · Anne W Taylor BA, MPH, PhD

Objective: To determine whether changes in 24-hour average background ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and particulates < 10 μm (PM10) increase the risk of hospital emergency department (ED) presentations for asthma among children.Design, setting and subjects: A time-stratified case-crossover method was used to analyse data of 603 children and young adults aged 0–19 years who were resident in a south-west metropolitan area of Perth, Western Australia, and who had presented with asthma at any public ED within Perth between 1 January 2002 and 31 December 2006. Effect sizes were assessed in relation to age group, sex and season of exposure. City-wide background air pollution was estimated from air monitoring network data.Main outcome measures: ED presentation with asthma.Results: Patients 0–4 years with 1-day lagged exposure to NO2 and CO showed the most significant risk of ED presentation for asthma. An interquartile range (IQR) increase in NO2 resulted in an odds ratio (OR) of 1.70 (95% CI, 1.08–2.69). An IQR increase in CO resulted in an OR of 1.40 (95% CI, 1.06–1.84).Conclusions: The effect sizes observed in this study were higher than those of past studies, and indicated that children aged 0–4 years were the most vulnerable to the effects of air pollution. The period of exposure most clinically relevant is the day before ED presentation.

Gavin Pereira MAppStats, BCM, GCResCom · Angus Cook MB ChB, PhD · Annemarie J B M De Vos PhD, MPH, RN · C D’Arcy J Holman MB BS, MPH, PhD

Objectives: To compare the clinical outcomes and mortality rates of Aboriginal and Torres Strait Islander people of Kimberley origin receiving haemodialysis (HD) treatment with other subsets of Aboriginal and Torres Strait Islander HD patients (Northern Territory, Western Australia excluding the Kimberley region, the rest of Australia) and Australian non-Indigenous HD patients.Design, participants and setting: Retrospective identification of Aboriginal and Torres Strait Islander patients of Kimberley origin and analysis of secondary data from the Australia and New Zealand Dialysis and Transplant Registry; this group was compared with other Australian patients receiving HD treatment from 1 January 2003 to 31 December 2007.Main outcome measures: Clinical outcome measures; comorbid conditions; death rates per 100 patient-years, unadjusted and adjusted (for age, sex, comorbid conditions, late referral to nephrologist treatment).Results: Seventy per cent of HD treatments for Aboriginal and Torres Strait Islander patients of Kimberley origin was provided in the Kimberley. They had comparable adjusted mortality rates to non-Indigenous Australian patients (adjusted mortality rate ratio, 0.80; 95% CI, 0.51–1.23).Conclusions: This is the first report showing similar mortality rates for Aboriginal and Torres Strait Islander people exclusively from a remote area of Australia and non-Indigenous Australians receiving HD treatment. HD treatment delivered closer to home can be safe and effective in remote areas.

Julia V Marley PgDipSc, PgDipPolSt, PhD · Hannah K Dent BSc(Hons) · Maree Wearne BNur, CertNephN, CertMid · Cherelle Fitzclarence BMed(Hons), MPHandTM, FRACGP · Carmel Nelson MPHandTM, FACRRM, FRACGP · Karen Siu BN, PGDIPNsg, NephrologyCert · Kevin Warr MB BS, FRACP · David Atkinson MB BS, MPH

The Australian Government has committed to reducing Indigenous disadvantage, including closing the life-expectancy gap within a generation, and to halving the gap in mortality rates for children under 5 years of age within a decade. Sixty per cent of the health gap between Indigenous and non-Indigenous Australians is attributable to the health of Indigenous people living in non-remote areas of Australia. We conducted a brief review of recent Australian original research publications on the health of the 53% of Indigenous people who live in urban areas, and found that data are sparse; there were only 63 studies in the past 5 years (11% of all articles about Indigenous health during this period). Although Indigenous Australians living in remote areas experience greater health disparity, the government will not achieve its aims without paying due attention to the non-remote-living population. More research is required, and particularly research that actually tests the impact of policies and programs.

Sandra J Eades BMed, PhD · Bronwen Taylor BTech, MSc · Sandra Bailey LLB · Anna B Williamson BPsych(Hons), PhD · Jonathan C Craig MB ChB, FRACP, PHD · Sally Redman BA(Hons), PhD

Iron deficiency anaemia (IDA) remains prevalent in Australia and worldwide, especially among high-risk groups. IDA may be effectively diagnosed in most cases by full blood examination and serum ferritin level. Serum iron levels should not be used to diagnose iron deficiency. Although iron deficiency may be due to physiological demands in growing children, adolescents and pregnant women, the underlying cause(s) should be sought. Patients without a clear physiological explanation for iron deficiency (especially men and postmenopausal women) should be evaluated by gastroscopy/colonoscopy to exclude a source of gastrointestinal bleeding, particularly a malignant lesion. Patients with IDA should be assessed for coeliac disease. Oral iron therapy, in appropriate doses and for a sufficient duration, is an effective first-line strategy for most patients. In selected patients for whom intravenous (IV) iron therapy is indicated, current formulations can be safely administered in outpatient treatment centres and are relatively inexpensive. Red cell transfusion is inappropriate therapy for IDA unless an immediate increase in oxygen delivery is required, such as when the patient is experiencing end-organ compromise (eg, angina pectoris or cardiac failure), or IDA is complicated by serious, acute ongoing bleeding. Consensus methods for administration of available IV iron products are needed to improve the utilisation of these formulations in Australia and reduce inappropriate transfusion. New-generation IV products, supported by high-quality evidence of safety and efficacy, may facilitate rapid administration of higher doses of iron, and may make it easier to integrate IV iron replacement into routine care.

Sant-Rayn S Pasricha MB BS, MPH · Stephen C Flecknoe-Brown MB BS, FRACP, FRCPA · Katrina J Allen MB BS, FRACP, PhD · Peter R Gibson MD, FRACP · Lawrence P McMahon MD, BS, FRACP · John K Olynyk MB BS, MD, FRACP · Simon D Roger MD, FRACP · Helen F Savoia MB BS, FRCPA · Ramdas Tampi MB ChB, FRACP, FRCPA · Amanda R Thomson MB BS, FRACP, FRCPA · Erica M Wood MB BS, FRACP, FRCPA · Kathryn L Robinson MB BS, FRACP, FRCPA

Unsettled behaviour in the first few months of life is a common clinical problem, with the associated risks of postnatal depression, premature cessation of breastfeeding, long-term psychological disturbance, and child abuse. Parents of new babies complain of difficulty accessing appropriate care and receiving conflicting advice. Although organic disturbance is implicated in only 5% of cases, gastro-oesophageal reflux disease, food allergies and lactose intolerance are often mistakenly diagnosed in unsettled babies. There is no evidence that acid-suppressive medications help in treating unsettled behaviour and, until the hypothesis that proton-pump inhibitors may predispose to food allergies has been properly investigated, treatment with acid-suppressive medications should be avoided in this population. Although unsettled behaviour in infants is commonly a transient neurodevelopmental phenomenon that peaks at 6 weeks of age, failure to diagnose other correctable problems, including breastfeeding difficulty and cows milk allergy, risks entrenching anxiety and disrupted mother–infant interactions in the long term. In the current climate of health system reform, the design and evaluation of an integrated, evidence-based, multidisciplinary primary care approach to management of unsettled babies and their mothers is a priority.

Pamela S Douglas MB BS, FRACGP · Harriet Hiscock MB BS, FRACP, MD

Objective: We reviewed resources for researchers interested in privacy issues surrounding secondary use of health data for research. These included applicable privacy regulations and available information on privacy perception in Australia. The review is timely because the current Australian Population Health Research Network infrastructure investments are likely to attract new researchers to the field.Data sources: We used Australian federal, state and territory regulations and programs, polls and surveys, public speeches and academic literature, and some international resources.Data synthesis: We identify four themes (de-identification, consent, bias and participation) emerging as areas of concern from the review, and discuss issues relevant to these themes. We provide arguments that excessive privacy regulation has a negative effect on public health research.Conclusions: There is little evidence of privacy complaints or breaches in health research, but significant concerns about consent and de-identification appear to persist in the community. New researchers need to take account of privacy regulation and may wish to take account of privacy perception when designing study and consent processes.

Christine M O'Keefe PhD, MBA, BSc(Hons) · Chris J Connolly LLB

Liver abscess due to Klebsiella pneumoniae infection has been widely reported in Asia, but rarely reported in Australia until now. We describe four previously well Asian-born patients who presented across Australia with community-acquired K. pneumoniae liver abscesses. With prompt recognition, appropriate antibiotics and early drainage, outcome is significantly improved, although vigilance for metastatic complications is essential. Clinical recordsDuring 2008 and 2009, four patients (two men, two women) presented around Australia with community-acquired Klebsiella pneumoniae liver abscesses (KPLAs). All four patients were previously well and did not have diabetes. Patients 1, 2 and 3 were Australian residents who were born in Asia and had recently visited there; Patient 4 was visiting from China. All patients presented to hospital after several days of gastrointestinal and other symptoms. Liver abscess was shown on computed tomography scans, and K. pneumoniae infection was diagnosed following culture of abscess fluid or blood. Patients were treated with appropriate antibiotics and pigtail catheters for drainage; Patients 3 and 4 required surgical treatment. Patients 1, 2 and 3 were well at follow-up; Patient 4 returned to China and was lost to follow-up. Patient 3 suffered a recurrence about 10 months after her first presentation, but this was too remote to be clearly attributable to her short course of antibiotics (only 10 days). Box 1 summarises the clinical and microbiological details of the four patients. DiscussionA community-acquired Klebsiella pneumoniae primary invasive liver abscess syndrome has been recognised in Asia for more than 20 years, with almost 1000 reported presentations published by 2008; it has been reported less frequently in other regions.1 K. pneumoniae infection accounted for over 80% of primary liver abscesses reported from Taiwan in the 1990s.2 Increasingly, cases have been seen outside Asia, primarily among patients of Asian ethnicity, including in the United States.1,3 It has only rarely been reported in Australia until now.4,5 Of interest are an absence of prior hepatobiliary disease, an association with diabetes, and a risk of metastatic spread.6 Community-acquired KPLA has been associated with severe metastatic complications, including endophthalmitis. The reasons for the changing epidemiology away from Escherichia coli as the leading cause of pyogenic liver abscess are unclear, although selective pressure for Klebsiella through widespread amoxicillin use, to which it is almost universally resistant, has been postulated.7 A genetic predisposition is possible, given the disease is seen almost exclusively in patients of Asian ethnicity, even outside Asia, and very rarely in those of Caucasian origin.8,9 K. pneumoniae is frequently found as part of normal faecal flora, and spread to the liver is thought to occur from the intestines via the portal system.1 Ordinarily, any bacteria reaching the liver would then be phagocytosed and killed, and failure of this defence is presumed to lead to the formation of liver abscesses.1 Diabetes was present in about 50%–70% of patients reported from Taiwan,6 presumably conferring susceptibility by impairing neutrophil-mediated defence,10 and this also appears to be a risk factor for metastatic complications.6 It is interesting to note that none of the patients in our small sample had diabetes. Bacterial virulence is also of major importance, as the condition often affects previously healthy individuals. The presence of capsular polysaccharides of K. pneumoniae serotype K1 or K2 has been strongly associated with virulence through resistance to phagocytosis;10,11 our patients were all infected with one of these two serotypes. Commonly, K. pneumoniae strains causing liver abscess are hypermucoviscous, as defined by an unusual, highly mucoid colony appearance on culture, a feature strongly associated with the K1 or K2 serotype.11 This stickiness is the basis of the “string test”, which can be performed easily in the laboratory. The string test is a quick, useful investigation in this setting (Box 3).7 A colony that stretches more than 5 mm using a standard inoculation loop tests positive for hypermucovisosity.3 The geographical distribution of KPLA may be explained by the finding that K. pneumoniae isolates from Taiwan were far more likely to have a hypermucoviscous phenotype and to belong to K1 or K2 serotypes than those in other countries except South Africa, where invasive disease is also seen.12 Indeed, of the many K. pneumoniae capsular serotypes isolated from patients in an Australian tertiary hospital inpatient setting, K1 and K2 accounted for only 10 of 293 (3.5%) presentations.13 All our patients had recently been in Asia, which raises the possibility of exposure to these virulent strains of the organism. However, case reports from the US have involved emigrants from Vietnam and Korea who had not travelled home for some years.1 A third-generation cephalosporin such as ceftriaxone is usually an effective treatment, with good penetration of vitreous fluid and cerebrospinal fluid, allowing it to reach metastatic lesions in these locations.12 In the case of endophthalmitis, systemic antibiotics should be combined with intravitreal injections. Treatment is required until clinical state, biochemistry and radiology indicate resolution, often requiring antibiotics for 4 to 6 weeks. Another mainstay of therapy is computed tomography- or ultrasound-guided percutaneous abscess drainage. Surgical drainage may be necessary when percutaneous techniques have failed, as was seen in our Patients 3 and 4. Metastatic spread not uncommonly complicates KPLA; reports from Taiwan estimate the frequency of this at between 3.5% and 20%.12,14 Endophthalmitis, lung abscesses and meningitis are the more common complications. Ophthalmological and other organ review is therefore indicated when KPLA is diagnosed. Visual recovery in patients with endophthalmitis is often poor; a high index of suspicion and early intervention before visual changes are noted may improve outcome. Response to antibiotics and drainage is generally good. In contrast with patients with underlying biliary tract disease, long-term recurrence rates in patients with spontaneously occurring liver abscess appear to be low.15 Given the emerging global trend of K. pneumoniae liver abscesses, Australian clinicians should be mindful of this condition, particularly, but not exclusively, in patients of Asian origin with abdominal infection or whose cultures reveal this organism. In this setting, a hypermucoviscous isolate of K. pneumoniae may belong to serotype K1 or K2, and be associated with metastatic infection, particularly endophthalmitis, lung abscess and meningitis. 1 Clinical and microbiological details of four patients with community-acquired Klebsiella pneumoniae liver abscesses Patient 1 Patient 2 Patient 3 Patient 4 Year, state of presentation 2008, Victoria 2008, Victoria March 2008, Western Australia; Jan 2009, South Australia 2009, Northern Territory Demographics M; 33 y; Filipino-born; Victorian resident for 2 y F; 52 y; Malaysian-born; long-term Victorian resident F; 67 y; Malaysian-born; long-term SA resident M; 52 y; Chinese cargo ship sailor, passing through the NT Recent travel/contacts Lived with Filipino friends. Trip to Middle East via India 1 month prior Trip to Malaysia 6 weeks prior Trip to Malaysia between presentations Visiting from China Features on presentation 2 days of vomiting, myalgias, fevers and rigors; hypotension, mild epigastric tenderness, RUQ tenderness Several days of aches, rigors, diarrhoea; hypotensive, febrile 2008: 3 days of epigastric pain, low-grade fevers; 2009: 5 days of malaise, vomiting, RUQ pain 5 days of fever, jaundice, RUQ pain Notable investigations First abdominal U/S normal; CT of abdomen: 5 cm septate liver lesion (Box 2) Abdominal U/S: 9 cm multiloculated liver abscess; confirmed on CT of abdomen 2008: CT of abdomen: 3 cm liver lesion, near-resolved after 2 months; 2009: CT of abdomen: 6 cm liver abscess, progressed to 7.5 cm with central necrosis 1 week later CT abdomen: 8 cm multiloculated lesion Microbiology K. pneumoniae cultured on three sets of BC and abscess fluid; string test positive (Box 3) Resistant to ampicillin; sensitive to amoxicillin/clavulanic acid, ciprofloxacin, gentamicin K. pneumoniae BC and abscess fluid Resistant to ampicillin; sensitive to amoxicillin/clavulanic acid, ciprofloxacin, gentamicin 2008 and 2009: K. pneumoniae BC Resistant to ampicillin; sensitive to amoxicillin/clavulanic acid, cephazolin, ceftriaxone, gentamicin K. pneumoniae abscess fluid Resistant to ampicillin; sensitive to amoxicillin/clavulanic acid, cephazolin, ceftriaxone, gentamicin Serotype K1 K1 2008: isolate not serotyped; 2009: K2 K2 Drain/surgery Pigtail catheter Pigtail catheter 2008: no drainage; 2009: pigtail catheter then laparotomy for ongoing sepsis, with drainage of abscess and cholecystectomy Pigtail catheter, then laparotomy and chest drain Antibiotics Rationalised to ceftriaxone for 2 weeks; discharged on oral amoxicillin/clavulanic acid for 2 months Rationalised to ceftriaxone for 1 month; discharged on oral cotrimoxazole for 11 weeks (rash with ciprofloxacin) 2008: 1 week ceftriaxone then 5 days of amoxicillin/clavulanic acid; 2009: 3 weeks ceftriaxone then 1 week amoxicillin/clavulanic acid Initially timentin for 2 weeks; discharged on oral ciprofloxacin for at least 1 month Complications Brief acute renal impairment (creatinine to 180 μmol/L); 24 hours of septic shock requiring ICU 24 hours of septic shock requiring ICU 2009: 48 hours of septic shock requiring ICU Rupture through liver capsule and subphrenic collection and empyema, requiring laparotomy and chest drain BC = blood culture. CT = computed tomography. ICU = intensive care unit. RUQ = right upper quadrant. U/S = ultrasound. 2 Abdominal computed tomography scan showing a 5 cm abscess (arrow) in the right lobe of the liver in Patient 1 3 String test of a Klebsiella pneumoniae isolate demonstrating hypermucoviscosity Photo: Adam Jenney

James R Anstey MB BS · Timothy N Fazio · David L Gordon FRACP, FRCPA, PhD · Geoff Hogg BM BS, FRACP, FRCPA · Adam W Jenney MB BS, FRACP, PhD · Matthias Maiwald MD, FRCPA, D(ABMM) · Jonathan J Wilksch BSc(Hons)

Clinical record A 78-year-old woman who was previously very active and in good health presented to hospital feeling unwell and with an extensive rash, involving both upper limbs (C3–T1 dermatomes), consistent with herpes zoster. Three weeks later, extensive diffuse left upper limb neuropathic pain developed over her C5–C7 dermatomes. The following week, her condition worsened to include progressive severe paresis of the left upper limb; weakness in the right hand; bilateral lower limb weakness; patchy areas of paraesthesia affecting many areas of the upper limbs, trunk and proximal lower limbs; severe constipation; and urinary retention, which required insertion of an indwelling catheter. She was bedbound and needed assistance with all self-care activities. About 10 days after the onset of weakness, a neurologist diagnosed a cervical myelopathy and recommended magnetic resonance imaging of the spine. This revealed an area of inflammation at C2–C4 involving the full thickness of the spinal cord at that level, consistent with transverse myelitis (Figure). She was diagnosed with herpes zoster myelitis. Sagittal T2-weighted magnetic resonance image with gadolinium enhancement showing an ovoid hyperintense lesion in the upper cervical spinal cord (arrow). About 6 weeks after her initial presentation, the patient was transferred to another acute hospital for further assessment. Detailed examination revealed asymmetric tetraparesis; upper limbs (left greater than right) were affected more than the lower limbs. On manual muscle testing she had muscle strength in her limbs as follows: 0/5 in the proximal and 1/5 in the distal left upper extremity, 4/5 in the right upper extremity and 2/5 in both lower limbs, with partial loss of sensation from her C4 to L3 dermatomes. Laboratory findings for full blood cell count, urea and electrolytes were unremarkable except for mild hyponatraemia and mild derangement of liver enzymes. Because of the severity of the herpes zoster infection, the patient was tested for underlying immunocompromise. She was found to have a κ monoclonal gammopathy of undetermined significance (12.0 g/L IgG; reference range [RR], 7.0–16.0 g/L) and borderline low values of immunoglobulins IgA (0.40 g/L; RR, 0.7–4.0 g/L) and IgM (0.31 g/L; RR, 0.4–3.0 g/L). It was thought that all of these immune abnormalities were of questionable significance. Treatment was initiated with intravenous methylprednisolone (1 g/day for 6 days) and intravenous (300 mg three times a day for 6 days) then oral (800 mg five times a day for 2 weeks) aciclovir. During the course of this treatment, gradual improvement in power of all four limbs became evident. She was subsequently admitted to a spinal rehabilitation unit and discharged 8 weeks later with evidence of ongoing neurological and functional improvement. Her hospital stay was complicated by severe postherpetic neuralgia, which was eventually controlled with gabapentin (400 mg three times a day). She recovered bladder function but needed aperients to achieve controlled faecal continence. At discharge, neurological examination revealed persisting asymmetric tetraparesis. She had 4/5 upper extremity muscle strength in C7–T1 myotomes on the left, 4/5 in L2 and L3 myotomes in both lower limbs and her remaining myotomes were of normal power. She was able to walk with a four-wheel frame or a single-point stick for 10–20 m and was independent for many activities of daily living. At follow-up 9 months after her initial presentation, her condition was still improving gradually. She had weaned off the gabapentin with no residual postherpetic neuralgia. She was able to walk short distances unaided and had regained full independence with most of her self-care using aids. Herpes zoster is associated with several neurological complications, including postherpetic neuralgia, aseptic meningitis, meningoencephalitis, transverse myelitis, peripheral nerve palsies, cranial nerve palsies and granulomatous cerebral angiitis.1 These complications are particularly prevalent among older people and patients with immunodeficiency. A causative relationship with herpes zoster in many of these syndromes is probably more common than suspected owing to difficulties in diagnosis and lack of awareness among clinicians. However, to our knowledge, there are no published reports of any known association between the neurological complications of herpes zoster, including myelitis, and postherpetic neuralgia. Transverse myelitis is a focal inflammatory disorder of the spinal cord. It results in sensory, motor and autonomic dysfunction 2 Onset may be acute, developing over a few hours or several days, or subacute, developing over 1 to 2 weeks. The critical factor is an abnormal immune response to infection, rather than the direct effect of an infectious agent.3 Transverse myelitis may be an isolated entity or may occur with a background of viral diseases, vaccinations, systemic lupus erythematosus, vasculitis, multiple sclerosis, heroin misuse or trauma.3 About 25%–40% of cases of transverse myelitis are caused by viral infections with herpes viruses or poliovirus.2 A recent publication provides useful additional information about transverse myelitis.4 Lessons from practice Herpes zoster myelitis is rare in the context of normal immunity; it is more common among patients with immunocompromise. Clinicians should be aware of the close temporal relationship between skin rash and the onset of myelitis so that appropriate investigations and treatment can be instigated. Magnetic resonance imaging of the spine should be performed to aid diagnosis. Although early treatment of herpes zoster myelitis is preferable, delayed treatment may also be worthwhile. Transverse myelitis following herpes zoster or herpes zoster myelitis (HZM) is rare, and typically occurs in hosts who are immunocompromised. Its onset is usually acute, occurring shortly after the appearance of the rash, with the development of sensory, motor and autonomic dysfunction.5 No diagnostic test is completely accurate, as the virus cannot usually be isolated from blood or cerebrospinal fluid in HZM.5 In most cases, diagnosis of HZM is clinical and based on detection of typical vesicular lesions in dermatomal distribution in association with clinical features of transverse myelitis. Suggested treatment involves high doses of corticosteroids and aciclovir.5 The prognosis ranges from spontaneous recovery to ascending neurological progression and death.6 The frequency of transverse myelitis during or after varicella infection is reported to be 0.3%.7 Devinsky and colleagues analysed their findings in 13 immunocompromised patients with HZM.8 The pathogenesis of HZM is unclear, but it may be due to direct viral invasion, which was demonstrated in one autopsy case.9 Diagnosing HZM can be challenging. The importance of a careful clinical assessment to establish the likelihood of this diagnosis and the level of the spinal cord damage, in combination with confirmatory magnetic resonance imaging (MRI)7cannot be overstated. MRI not only provides information about the site but also the extent of spinal cord involvement, and excludes other possible diagnoses. In our patient, HZM was diagnosed based on the temporal relationship of myelopathy to the rash and MRI findings. Although the area of the spinal cord that was involved on the MRI scan was less extensive than that affected by the herpetic rash, we do not see this as clinically inconsistent. There are no proven treatment regimens for HZM, but there is anecdotal evidence for treatment of HZM with high doses of aciclovir and corticosteroids.5,10 It appears that antiviral treatment was not provided early to our patient because it was not initially recognised that the rash was due to herpes zoster. Once HZM was diagnosed, this treatment was provided. Despite the delay of 3 weeks following the onset of rash, improvement appeared consistent with a clinical response to this therapy. Although early treatment of herpes zoster with antivirals is crucial to prevent the development of postherpetic neuralgia, there is little evidence that such treatment reduces the risk of HZM. To date, no evidence has emerged regarding the protective efficacy of the new live, attenuated herpes zoster vaccine (Zostavax) against HZM. Trials assessing the impact of antivirals or the herpes zoster vaccine on risk of HZM would require very large numbers of participants, given the rarity of this complication. Nevertheless, the vaccine has proven to be efficacious in reducing the incidence of and morbidity associated with herpes zoster and postherpetic neuralgia in older adults.11 It has been noted in a previous case report that, following the diagnosis of HZM, even delayed treatment with oral antivirals may prevent neurological progression.12 Our case provides support for this assertion.

Olivia L W Ong MB BS, BMedSci · Andrew C Churchyard PhD, MB BS, FRACP · Peter W New MB BS, MClinEpi, FAFRM(RACP)

To the Editor: I thank Brieger and colleagues and Thompson for their comments on my article.1 Brieger et al2 refer to the United Kingdom National Institute for Health and Clinical Excellence Guideline Development Group that analysed the non-ST-elevation myocardial infarction (NSTEMI) trials to show an inverse relationship between rates of intervention and clinical outcomes.3 This is a post-hoc analysis and is therefore hypothesis generating rather than proof of concept; further, its results are confounded by the fact that intervention rates have increased in recent years, while medical treatment — particularly with clopidogrel and statins — has also improved. Brieger et al then contend that the Variations in the Application of Cardiac Care in Australia study4 provides justification for an interventional approach. This study demonstrated that patients treated in hospitals without percutaneous coronary intervention (PCI) facilities fare worse than patients at hospitals with PCI. The likely reason for this is that these patients are less likely to receive cardiac rehabilitation, aspirin, statins, β-blockers and timely thrombolysis. With respect to ST-elevation myocardial infarction (STEMI), Brieger and colleagues suggest that the evidence is even stronger because of CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction).5 In this study, patients treated medically were administered half-dose reteplase and full-dose abciximab. This treatment is not currently recommended and the study therefore has no relevance to the current debate. Brieger et al state that I erroneously cited TRANSFER-AMI (Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction)6 as evidence against a strategy of routine urgent transfer. This is the largest contemporary trial that compares urgent transfer with routine selective transfer after thrombolysis in hospitals without PCI facilities. The trial is thus the most relevant to our discussion. The fact that clinicians chose to transfer 89% of patients for PCI after a mean time of 23 hours in the selective management group does not negate the lack of significant benefits of routine urgent transfer after thrombolysis. I agree that TRANSFER-AMI is limited by the high rate of intervention. The problem remains, however, that the guidelines mandate transfer of all STEMI patients and fail to provide evidence to justify it. In the first paragraph of his editorial, Thompson7 cites the American College of Cardiology/American Heart Association guidelines8 as evidence for early coronary intervention. However, these guidelines state that “in initially stabilized UA [unstable angina]/NSTEMI patients, an initial conservative (selective invasive) strategy may be considered as a treatment option”.8 This statement is not in the Australian guidelines. Thompson acknowledges that the ICTUS (Invasive versus Conservative Treatment in Unstable Coronary Syndromes) trial9 provides up-to-date medical treatment, but notes the lower mortality rates compared with patients in the ACACIA (Acute Coronary Syndrome Prospective Audit) registry.10 He therefore concludes that these patients were not high risk. Yet one of the entry criteria for the ICTUS trial was an elevated troponin level, which is defined as high risk in the Australian guidelines. I drew attention to the fact that the Australian guidelines seem to be over-inclusive in their definition of high risk. The lower mortality rate in the ICTUS study and in other routine-versus-selective-PCI trials in NSTEMI presumably reflects exclusion of patients who are older, have other comorbidities such as renal impairment, or whose conditions are clinically unstable. Physicians treating patients such as those entered in the ICTUS trial — with electrocardiogram changes and a raised troponin level without other comorbidities or shock — should have the option to manage these patients with a selective invasive approach. Thompson states “the conclusion that conservative management alone will remove the need to open a blocked artery is hardly justified based on the ICTUS study results, which comprise just over 10% of the evidence base”. I had included two meta-analyses of all of trials of routine intervention as the cornerstone of my argument and pointed out that they had not shown a reduction in mortality. The ICTUS trial confirmed the conclusions drawn from those trials and is the only trial in which medical treatment was adequate. Thompson stated that I suggested that modern medical management could render invasive treatment irrelevant. This statement was not in my article. In summary, nothing in the rebuttal by Brieger et al or Thompson’s editorial provided any real evidence to justify an expensive, invasive policy requiring routine urgent (as opposed to selective) transfer of all patients with ST-elevation acute coronary syndromes or NSTEMI for PCI, nor for the establishment of more PCI units throughout regional Australia.

Brett H Forge

In reply: We thank Forge for his continued and welcome contribution to this debate. He is critical of our reference to the National Institute for Health and Clinical Excellence (NICE) guidelines, which show an inverse relationship between rates of intervention and clinical outcomes. The NICE analysis is supported by others,1 and we stand by our argument that if studies with greater differences in the randomisation arms show a greater treatment effect, the strength of the evidence supporting the intervention is enhanced. Dismissing this type of analysis on scientific grounds is disingenuous and contrary to National Health and Medical Research Council recommendations regarding the assessment and application of scientific evidence.2 Data supporting the role of invasive therapy in management of acute coronary syndromes (ACS) continue to evolve. A recently published patient-level meta-analysis of three studies, comprising 5-year outcomes of 5467 patients, showed a significant reduction in myocardial infarction (hazard ratio [HR], 0.77; 95% CI, 0.65–0.90), with consistent trends towards reduction in cardiovascular death (HR, 0.83; 95% CI, 0.68–1.01) and all death (HR, 0.90; 95% CI, 0.77–1.05).3 This meta-analysis showed the largest absolute benefit among the highest-risk patients assessed by a global risk score, supporting evidence that risk stratification should involve more comprehensive clinical evaluation than that provided by a single biomarker.4 It is true that these studies have not shown a reduction in mortality. This is most likely to be an issue of power. Based on the number of patients studied in randomised trials so far, the power needed to detect a 10% difference in mortality between treatment strategies is only 27%.1 Regarding TRANSFER-AMI (Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction), Forge now agrees that there are limitations associated with the high transfer rates in the conservative arm, which are greater than those seen in contemporary Australian practice. When the conservative arm receives better-than-standard practice, the direct effect is a bias of the outcome towards the null, limiting the quantification of absolute benefit associated with routine urgent transfer. Forge dismisses CARESS-in-AMI (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction) because of the management strategy in the conservative arm. The main limitation of this study is its small size; in an earlier study of 16 588 patients, combination half-dose reteplase and full-dose abciximab treatment had comparable mortality to full-dose reteplase alone.5 Finally, we would like to re-emphasise that National Heart Foundation of Australia (NHFA)/Cardiac Society of Australia and New Zealand (CSANZ) ACS guidelines are not prescriptive. They are designed to provide guidance to individual clinical practice, not to mandate one form of practice. Adherence to guidelines has been demonstrated to improve outcomes when instituted as part of a coordinated quality improvement strategy across a health care system. In addition to provision of optimal medical therapy and risk factor modification, approaches to ACS that incorporate timely access to revascularisation have made a significant contribution to this improvement in outcomes.

David B Brieger · Derek Chew · Constantine Aroney · Phil Aylward · Darren Walters · Anne-Maree Kelly · Andrew Boyden

In reply: Forge quotes the recommendation from the United States guidelines to consider conservative treatment after initial stabilisation of non-ST-elevation myocardial infarction.1 This may not the best option for patients in Australian regional hospital conditions. This pathway delivers less optimal outcomes1,2 and should only be considered if a seamless switch to an invasive approach can be made. The primary recommendation from the US guidelines for patients whose conditions are initially stabilised is that “an early invasive strategy . . . is indicated”.1 The benefit of an early invasive approach has been confirmed in the most recent meta-analysis comparing routine with selective invasive approaches.2 Over 5 years, the routine invasive approach achieved a relative reduction in deaths or myocardial infarctions of 19%, and an absolute reduction of 11.1% among highest-risk patients, 3.8% among intermediate-risk patients and 2% among lowest-risk patients. The results of the ICTUS (Invasive versus Conservative Treatment in Unstable Coronary Syndromes) trial3 showed no heterogeneity from the results of the other trials. Identifying patients at risk of complications and most likely to benefit from early intervention remains an ongoing challenge. Increasing experience has confirmed the value of an elevated troponin level as a predictor of increased risk, but also the need to apply some wisdom in interpreting it, with even more challenges with high-sensitivity troponin assays becoming available.4 For patients presenting to a regional hospital with non-ST-elevation acute coronary syndromes, the available evidence favours careful risk stratification and early transfer to an invasive facility for high-risk patients.

Peter L Thompson

To the Editor: Recent articles in the Journal by Forge1 and Thompson2 expressing contradictory opinions on the management of patients with non-ST-elevation acute coronary syndromes (NSTEACS) highlight the difficulties in formulating guidelines for this condition. Thompson argues that the routine invasive approach for patients with high-risk NSTEACS recommended by the National Heart Foundation of Australia (NHFA) guidelines is preferable to the selective invasive approach advocated by Forge. In arguing his case, Forge relies on the results of the ICTUS (Invasive versus Conservative Treatment in Unstable Coronary Syndromes) trial,3 which showed no advantage for the routine invasive approach. Unlike Forge, Thompson believes the ICTUS trial is of limited relevance. In part, he bases this contention on the fact that the 1-year mortality in the ICTUS study was 2.5% compared with 10.5% among Australian patients with non-ST elevation myocardial infarction, indicating that participants in the ICTUS trial were not high-risk patients. This part of his argument is flawed. All patients who entered the ICTUS trial had elevated troponin levels, which according to NHFA guidelines automatically places them in a high-risk category that requires routine angiography. A more likely explanation for the mortality differences is that patients in the ICTUS trial either received better care, or were more compliant with their medical treatment than their Australian counterparts. Thompson rightly argues that the ICTUS trial is but one study comprising “just over 10% of the evidence base” and that the totality of the data favours a routine invasive approach. Conversely, Forge contends that the ICTUS trial is the most contemporary of the studies and the one in which medical treatment most closely concurs with current best practice. Therefore, he argues, the results of this study should take precedence. Faced with these conflicting viewpoints, writers of guidelines have an onerous task, particularly when compliance with guidelines may be used by bureaucrats and administrators to judge physician performance. With respect to the NHFA guidelines for NSTEACS, a case can be made for more flexibility. For example, is it necessary to transfer all stable patients with NSTEACS and borderline troponin elevations from rural hospitals to metropolitan hospitals for angiography even when they may wait many days for such a transfer to occur? Ensuring that such patients receive, and are compliant with, optimal cardioprotective medications would be a greater gain. Guidelines are a valuable aid to clinical practice; they are not necessarily the overriding factor.

Richard W Harper

To the Editor: The recent discussion in the Journal on acute coronary syndromes is welcome. Forge1 questions the validity of the National Heart Foundation of Australia (NHFA) guidelines,2 which recommend universal routine early invasive management for patients with high-risk non-ST-elevation myocardial infarction (NSTEMI), interpreted by Forge as “virtually all patients with objective evidence of ischaemia”. As older patients usually have comorbidities, often major, the influence of NSTEMI on the clinical picture can be uncertain. Transfer from local surroundings and family support is a major decision. It is critical to establish which subgroups gain from early percutaneous coronary intervention, at present not clearly defined. The number needed to treat for substantial benefit is an essential guide to management policy. The logistics of transfer are complex, involving time and distance factors, availability of ambulances and cardiology beds — after acceptance by patient and relatives. Forge validly emphasises the potential loss of intensive cardiac care skills, staff morale and recruitment from the early transfer policy and large costs to the country hospitals from ambulance fees. It is irrefutable that general implementation of the NHFA guidelines would be a major budget item, involving specialised laboratory facilities with nursing, resident and interventional cardiologist availability, 24 hours a day, 7 days a week. Potentially, there are many competing medical financial needs, which a better targeted coronary intervention program could facilitate. Forge raises the issue of conflict of interest in relation to the development of the guidelines. Breiger and colleagues read this as an accusation that they had a pecuniary interest as authors.3 Their stated competing interests list membership of advisory boards, payment for presentations and expert testimony, receipt of research grants, and travel and accommodation expenses. This reflects their role as medical advisors to pharmaceutical and biotechnology companies. What is the aim of publishing competing interests except to provide a guide to significant potential bias affecting the validity of the presentation? Does the editorial staff have criteria for rejection of submissions for publication, or are readers left to make their own judgements? It is undoubted that a major expansion in expensive medical procedures would increase cardiologists’ income, but this is only one component of the program budget. The broader issue is that conflict of interest remains an integral part of personal and professional life, not easily controllable by governance.

John F Niall

To the Editor: We report the use of nebulised frusemide for the symptomatic treatment of end-stage congestive heart failure (CHF). An 84-year-old man with New York Heart Association class IV CHF was referred to the Community Heart Failure Team at St Vincent’s Hospital, Sydney, for ongoing management after a hospital admission for acute pulmonary oedema. His medical history included aortic stenosis, pulmonary hypertension, type 2 diabetes, chronic renal failure, atrial fibrillation, hypertension, chronic obstructive pulmonary disease (COPD) and hypercholesterolaemia. The patient’s medications were home oxygen via a concentrator at 2–4 L/minute; digoxin 62.5 μg three times a week; warfarin 5 mg daily; glyceryl trinitrate 25 mg daily (delivered via a patch); simvastatin 40 mg nightly; spironolactone 12.5 mg daily; frusemide 80 mg orally twice daily (flexible regimen); insulin/isophane (Protaphane; Novo Nordisk) variable dose twice daily; fluticasone 250 μg/salmeterol 50 μg (Seretide; GlaxoSmithKline) one dose twice daily; and omeprazole 20 mg daily. Previous trials of a β-blocker and angiotensin-converting enzyme inhibitor were not tolerated. Two days after the patient was discharged, a home visit by the clinical nurse consultant (CNC) found him with grossly oedematous legs, jugular venous pressure (JVP) elevated above his ears, and crepitations from the bases to the upper mid zones of his lungs. On Day 1 and 2 of CNC care at home, the patient received intravenous bolus doses of frusemide 80 mg, resulting in good diuresis. On Day 3, the CNC was unable to gain intravenous access and, after consulting the Community Heart Failure Team cardiologist and pharmacist, administered frusemide 80 mg via a nebuliser. The patient reported immediate improvement. Oxygen saturation increased from 88% to 97% on room air and his chest was clearer on auscultation. Increased diuresis occurred, with weight loss of 1 kg. Because the patient’s JVP and leg oedema were unchanged, the dose was repeated daily for 5 days until respite admission (for social reasons and intravenous frusemide administration). Nebulised frusemide had provided symptomatic relief from dyspnoea for about 5 hours with no adverse effects for the patient, but did not provide sufficient diuresis to reduce his fluid overload symptoms. Ultimately, a central catheter (“long line”) was inserted to enable the CNC to administer frusemide intravenously at the patient’s home. CHF-associated dyspnoea causes significant morbidity and distress for patients and carers. Nebulised frusemide has been used for relief of dyspnoea associated with asthma, COPD and malignancy.1 Its precise mechanism of action is unknown, but is believed to be through local lung rather than renal effects.1 Our searches of MEDLINE, EMBASE, CINAHL and the internet found no reports of the use of nebulised frusemide for dyspnoea resulting from pulmonary oedema or CHF. Patients with CHF receiving palliative care have limited options for diuresis when oral administration is ineffective and intravenous access is unavailable. The use of nebulised frusemide could have potential in this setting, but requires further research.

Kate A Towers · Kimberley A Bardsley · Peter S Macdonald

To the Editor: We report a case of ischaemic stroke in a 34-year-old man with severe vitamin C deficiency caused by poor nutrition. The patient was a lifelong non-smoker with no history of hypertension or hypercholesterolaemia, and no family history of stroke, although he had recently been diagnosed with type 2 diabetes mellitus. At presentation, neurological examination showed profound left-sided hemiparesis, with normal sensory examination and visual fields. Cardiovascular examination was normal, and there were no carotid bruits. The patient’s body mass index was 25.5 kg/m2. Magnetic resonance imaging of of his brain showed acute infarction in the right posterior corona radiata (Box, A). Coagulation and lipid profiles were normal. Glycosylated haemoglobin was 7.1%. Comprehensive testing for underlying thrombophilia, vasculitides and Fabry disease all returned negative results. Computed tomography angiography and carotid ultrasonography confirmed normal carotid and vertebral arteries. Transoesophageal echocardiography showed a structurally normal heart without a source of embolus. The patient had poor dentition, with calculus deposition, scorbutic gums and gingival inflammation (Box, B), and reported easy bruising in recent months. Suspecting a diagnosis of scurvy, we conducted a nutritional assessment of the patient. His diet consisted mainly of fast food, with negligible vegetable and fruit intake, and no vitamin supplementation. For the week before admission, we determined that his average vitamin C intake was 4 mg/day. This corresponded to a > 99% probability of inadequate intake when compared with the estimated average requirement of 30 mg/day for adults1 (z = − 4.33; P = 0.0015). Laboratory testing confirmed the presence of severe vitamin C deficiency (< 5 μmol/L; reference range, 40–100 µmol/L). The patient was admitted to a stroke unit, commenced on aspirin, ramipril and atorvastatin, and received dietary counselling. Vitamin C 1000 mg daily was prescribed for one month. Subsequent testing confirmed normalisation of his plasma vitamin C. Following inpatient rehabilitation, he regained motor function and returned to independent living. There is growing evidence that vitamin C deficiency is an important, but largely unrecognised, risk factor for modification in patients with cerebrovascular disease.2 Vitamin C is a water-soluble antioxidant that inhibits oxidation of low-density lipoprotein and protects against endothelial dysfunction. Primate models have confirmed that cerebral infarct size is inversely related to cerebral vitamin C content.3 Although scurvy is now relatively rare, subclinical vitamin C deficiency is not uncommon, being present in about 10% of the general population.4 Alcoholics, institutionalised and elderly people are particularly at risk. In this case, we hypothesise that an unhealthy diet resulted in deficiencies in antioxidants (including vitamin C), and that this contributed to stroke pathogenesis. The marked prematurity of disease onset may have resulted from effect modification of antioxidant deficiency on conventional atherosclerotic risk factors (such as diabetes). A cohort study previously observed the modifying effect of vitamin C deficiency on the association between stroke and hypertension.5 However, it is unlikely that a direct causal link will ever be established. Since malnutrition and unhealthy eating practices continue to be serious public health problems, we suggest attention to nutritional status should be incorporated into the new standard of stroke care. Perhaps a new adage should be considered: an orange a day keeps stroke away? A: Diffusion-weighted magnetic resonance image of the patient’s brain showing an acute infarction in the posterior limb of the right corona radiata. B: The patient’s mouth showing scorbutic gums consistent with scurvy.

Emily Y-J He · Louis W Wang · Matthew C Kiernan

To the Editor: Burger and colleagues reported the limitations of pre-August 2010 Pharmaceutical Benefits Scheme (PBS) criteria for subsidised anti-tumour necrosis factor-α (anti-TNF-α) treatment of perianal Crohn’s disease (CD).1 PBS-subsidised infliximab is now available for CD patients with a Crohn’s Disease Activity Index (CDAI) > 300 who have failed to achieve an adequate response to minimum doses of steroids and immunomodulators, and for patients with fistulising CD.2,4 In contrast with some Australian centres, our hospital has given infliximab to patients who fell outside these restrictions for indications for which clinical efficacy has been shown.1 We report on infliximab use and patient outcomes in patients with CD and ulcerative colitis (UC) since local PBS-subsidised use commenced in October 2008. Between October 2008 and February 2010, 57 patients at our hospital (44 with CD and 13 with UC) commenced infliximab treatment. Patients were assessed for remission status at 6–8 weeks after commencement of infliximab therapy (ie, after the induction course of three infusions). Twenty-four CD patients met PBS criteria. Of these, 12 achieved remission (CDAI < 150 [n = 8] or clinical remission on symptomatic grounds [n = 4]), eight showed clinical or endoscopic improvement justifying continued infliximab treatment, and four had no treatment response. Twenty CD patients did not meet PBS criteria. Of these, nine achieved remission (CDAI < 150 [n = 7] or clinical remission on symptomatic grounds [n = 2]), nine showed clinical or endoscopic improvement, and two had no treatment response. Reasons for not meeting PBS criteria were as follows: insufficient trial of prednisolone and an immunomodulator (10 patients, of whom 1 had no treatment response to infliximab); insufficient trial of an immunomodulator alone (7 patients, of whom 1 had no treatment response to infliximab); insufficient trial of prednisolone alone (2 patients); and CDAI < 300 (1 patient, who subsequently achieved clinical remission). Fourteen patients had perianal disease, of whom five did not meet PBS criteria. Of the 13 patients with UC, none were eligible for PBS-subsidised infliximab treatment. Six achieved, and remained in, clinical remission after a full infliximab induction course of three 5 mg/kg doses. Of the seven patients who did not, two initially responded but failed on reintroduction of treatment after an infliximab-free period. The other five had no response; three required colectomy. Our audit showed that less than half of patients receiving infliximab for inflammatory bowel disease fulfilled PBS guidelines for subsidised prescription, mostly because of relatively strict requirements for prior steroid and immunomodulator therapy, and the absence of UC as a listed indication. Furthermore, our CD patients who did not meet PBS criteria had similar treatment outcomes to those who did. Thus infliximab treatment can be of major benefit to patients with refractory disease whose only other treatment alternatives are experimental therapies or major surgery. Further revisions to PBS criteria for anti-TNF-α therapy, including relaxing restrictions for CD and providing access for patients with severe UC, are required.

Nicholas A Biehl · Janina Pawlik · Geoffrey M Forbes

To the Editor: I cannot argue with the push by Hickie and McGorry for services for young people from 12 to 25 years of age who suffer from “depression”.1 But I question their sequencing of treatments model that pervades the beyondblue draft clinical practice guidelines about which they editorialise. Their model presupposes a unitary entity of “major depression” that varies in severity, with milder conditions being treated by psychotherapy and more severe conditions being treated with antidepressant medication. Consider the following case to show how the guidelines get it wrong. A 16-year-old girl presents with her first episode of moderately severe major depression. She is treated as per the guidelines for depression with a selective serotonin reuptake inhibitor (SSRI) and rapidly develops a severe psychotic mania. She is certified to a psychiatric facility and requires a prolonged admission. For the next 2 years she remains chronically hypomanic, refusing to try better treatment. Eventually, following a severe depressive episode, her treatment is reorganised and her condition stabilises. However, the trauma and psychosocial damage from the hospitalisation and prolonged period of illness are significant. In the guidelines, bipolar disorder — arguably the only “biological” kind of depression in this age group — is separated from the body of recommendations for managing depression. The possibility that this episode of depression may be part of an as-yet-undeclared bipolar disorder needs to be thoroughly integrated into the understanding and management of “depression”.2 Features that would suggest possible bipolar disorder include psychomotor retardation and cognitive impairment,3 psychosis, reverse neurovegetative features (hyper-somnia or hyperphagia),4 a few manic symptoms mixed with depression5 (racing thoughts, distractibility, flight of ideas, increased energy or psychomotor agitation), or the depression not making sense psychologically. Past episodes of depression, brief hypomania, anti-depressant-induced hypomania, or a family history of bipolar disorder also need to be documented. Doctors should then routinely discuss with patients and families the possibility that bipolar disorder could be diagnosed, and warn that the patient may experience a manic switch. If the likelihood is high, as part of a proper process of informed consent, the patient should be offered concurrent lithium or antipsychotic medication. The patient and family can be assured that expert clinical observation over time will clarify the diagnosis and what treatment is appropriate. This approach not only involves the patient and family in decision making, giving knowledge and choices, but, importantly, incorporates the reality of diagnostic uncertainty.

Norman P Zimmerman

In reply: Zimmerman correctly highlights the intrinsic limitations of applying the current “evidence base” for managing severe depression in young people. In part, our critique of the new guidelines1 stems from our shared concern about their real utility in clinical practice. As we have outlined elsewhere, we do not favour a simple “sequencing of treatments” model or recognise a clear separation between early phases of severe unipolar or bipolar depression.2 The real difficulty for clinicians is that young people presenting with severe depression are not only at high risk of immediate harm, but may also be on the path to a range of different psychiatric (and neurobiological) outcomes, including bipolar disorder, psychotic disorders and comorbid alcohol and substance misuse.2,3 Unfortunately, there are no clear clinical, neuropsychological or biomedical predictors of the relative risks of developing these adverse outcomes.2,3 Consequently, we have recommended the development of a broader clinical trials network that recognises this complexity and seeks to develop a more relevant evidence base in the future.4 For now, we need to continue to develop clinical service initiatives that not only engage young people but can provide the longitudinal and more specialised care that may be required for those who develop more complex disorders.5

Ian B Hickie · Patrick D McGorry

To the Editor: In their recent letter, Colquhoun and Jenkins1 correctly note that the external jugular venous pressure is as reliable as the internal jugular venous pressure in estimating right atrial pressure. Furthermore, the external jugular vein is more readily visible and accessible for cannulation should accurate measurement be required. While routine clinical observation is important, direct invasive measurement of right atrial pressure may be required in patients who are critically ill or experiencing rapid fluid shifts, as when undergoing major surgery. Potential serious complications of central venous cannulation are a significant barrier to direct measurement, but it has been suggested that cannulation of a central vein may not be required to assess right ventricular filling pressures.2 Indeed, the early observations of direct measures of venous pressure by Berger3 and others in the 1930s were performed in peripheral veins. A more recent study by Amar et al2 showed a reliable correlation between peripheral venous pressure (PVP) and central venous pressure (CVP) in 150 patients without cardiac disease undergoing major non-cardiac surgery. PVP, measured in either the hand or forearm, was found to be 2–3 mmHg higher, on average, than CVP, with similar changes when fluid boluses were administered. Further studies have shown similar utility of PVP measurement in cardiac surgery,4 neurosurgery and paediatrics.5 The insertion of central venous catheters for pressure monitoring alone may not be warranted if connecting a pressure transducer to a simple cannula in a peripheral vein can attain the same information. Using peripheral venous pressure measurement, the risks of arterial puncture, pneumothorax and central venous catheter-related bloodstream infections can easily be avoided.

Stuart D Marshall

To the Editor: The article on home haemodialysis by Agar and colleagues describes a changing pattern of practice that has seen many patients enjoy the freedom of dialysing at night in their home environment.1 One consideration not mentioned is the need for appropriate vascular access. For a patient to engage in self-cannulation, a fistula needs to be created for ease of use. This requires a few imperatives in fistula design to be met. In my practice, an attempt is made to create an autogenous fistula for vascular access whenever possible. It is well documented that an autogenous arteriovenous fistula (AVF) is superior to prosthetic graft or catheter access in terms of access longevity and patient-related complications.2-4 In the past 11 years, I have found it necessary to create a new AVF with prosthetic material in no more than 1% of cases. For some patients, however, a fistula may be positioned where it is accessible to renal nursing staff but not for self-cannulation. This would make nocturnal home dialysis difficult and underpins the importance of surgical access design to facilitate it. For self-cannulating patients, great effort is made to create vascular access in the non-dominant arm, in the forearm rather than the upper arm, and with cephalic rather than basilic vein run-off. The cephalic vein lies on the upper outer aspect of the forearm with the limb in a neutral position, and a needle in it remains fairly secure when a patient is asleep. Guidelines on surgical placement of an AVF from the Society for Vascular Surgery, while not specifically prescriptive for patients wanting to self-cannulate, include the same recommendations.5 Use of a long saphenous vein loop fistula in the forearm, positioned appropriately, also provides ready access for a patient who may otherwise struggle with the dexterity required for venepuncture. A thigh loop is an alternative but less desirable option, as patients with chronic renal disease are likely to have lower-extremity occlusive disease, an increased incidence of groin infection, and a greater likelihood of vascular steal.5 I applaud efforts to facilitate nocturnal home dialysis, and enjoy the challenge of surgically creating vascular access to make this endeavour successful.

David N McClure

To the Editor: I applaud Leach and colleagues for their recent article examining lost opportunities with Australia’s health workforce.1 There are many lost opportunities in the area of rural health. National and international studies have documented that a health professional with rural origins is more likely to return to a rural area to work than a colleague who grew up in the city.2,3 My research over the past 4 years looks predominantly at primary school students and their parents, teachers and governesses who reside over 800 000 km2 of outback Australia and study by distance education. My research is mainly into primary school-aged students because it is generally agreed among career development theorists that students start to shape ideas about occupations long before they reach high school.4 The students I studied initially had little knowledge or interest in health careers (relevant educational activities were subsequently provided to the school community in 2008). I identified five main factors inhibiting their knowledge and interest in health careers: the severe chronic shortage of health professionals in rural and remote Australia (and therefore a shortage of positive health professional role models); the limited career pool of their parents (most of whom are involved in the agricultural industry); the isolation in which they live; the limited information about the health professions provided by the school (their window to the outside world, which did not make up for their environmental shortfall); and parental perceptions. Two factors influencing parental perceptions deserve mention: awareness of the unhealthy workloads and the high degree of burnout among rural medical practitioners (they didn’t want this for their children); and the negative images portrayed in the media (eg, reports about health workers’ pay). My research focused solely on developing an awareness of the health professions as possible career options for these students.5 However, other factors also prevent students who live in rural and remote Australia becoming health professionals: inequality of primary and secondary educational opportunities;6 falling access, participation, retention and success rates in tertiary education;7 and the financial, emotional, family and social costs of attending tertiary courses a long way from home.8 We are all aware of the hardships of urban-raised health professionals undertaking rural medical placements, but do we understand equally the hardships of rural and remote students studying in the city? If Australia is genuine about wishing to solve the rural health workforce crisis, students from rural and remote areas must be provided with real opportunities to become rural health professionals, because the evidence suggests that the long-term survival of rural health services may depend on the recruitment of rural students.

Susan M Gorton

To the Editor: In response to Hall and colleagues,1 the Royal Australasian College of Surgeons supports any measures that have been proven to successfully reduce death and injury in young drivers. Raising the minimum legal drinking age (MLDA) to 21 years has been shown to significantly decrease road crash deaths in the United States.1 The College agrees with these authors that there would be major political obstacles and very little public support in Australia to increasing the MLDA; however, should the politicians and the public see first hand the devastating effects of alcohol on young people that our surgeons see on an all-too-regular basis, the mindset might change significantly. Hall and colleagues state other ways that we can achieve further reductions in road crash deaths — extending the zero-tolerance laws for young drivers until age 22 years, as it is in Victoria, or until 25 years for even further reductions.1 The College certainly supports this, particularly as evidence is building that the physical maturation of the part of the human brain that assesses risk and controls impulsive behaviour is not complete until age 25 years in men.2-4 The Trauma Committee is most concerned about alcohol-related trauma and will explore this issue at the annual Trauma Committee workshop, during the College’s Trauma Week. The workshop, entitled “Alcohol and injury”, will be held at the College in Melbourne on 18 November 2010.

Daryl R Wall

Trevor Beard was born on 11 May 1920 in Gloucester, United Kingdom. He studied medicine and surgery at the University of Cambridge and worked as a Resident Medical Officer at St Bartholomew’s Hospital and the City of London Maternity Hospital. In 1951, he moved from the UK to Australia and began general practice at Campbell Town in Tasmania. During this time, he vigorously spearheaded a successful campaign to eliminate human hydatid disease in Tasmania — the first jurisdiction in the world to declare provisional eradication of hydatid disease. He was formally recognised for this work when he was made an Officer of the Order of the British Empire (OBE) in 1966. Trevor devoted his life to improving public health. In the 1970s, he joined the Department of Health in Canberra in a senior public health policy role, and in the early 1980s, he moved into cardiovascular research at Canberra’s Woden Valley Hospital. After his official retirement in 1986, Trevor returned to Tasmania in 1987 and took up an Honorary Research Fellowship at the Menzies Research Institute in Hobart. Right up to the end, he remained active in his research on hypertension and salt intake, and was involved in various research projects, including the first large community survey of sodium intake in Australia. He wrote a guide to adopting a low-salt diet,1 and went on to develop a related website (http://www.saltmatters.org). He passionately promoted the use of low-salt diets to prevent hypertension and vigorously lobbied many areas of the food industry and government, playing a pivotal role in persuading the government to lower the official sodium intake recommendations in Australia in 2005. At a local level, he advocated successfully for the Royal Hobart Hospital and Meals on Wheels to provide low-sodium meals. Trevor actively campaigned for the introduction into Australia of the UK’s “traffic light” food-labelling system (which uses colour-coding to designate low, medium and high levels of total fat, saturated fat, sugar and salt in foods). In 2010, at the age of 90, he set a challenge for Drysdale House in Hobart — training ground for future chefs in Tasmania — to reconcile gastronomy with health by providing monthly lunches that would meet low fat, sugar and salt requirements. In addition to his OBE, Trevor received many other honours. He was awarded a Winston Churchill Fellowship in 1966, the Johnston Medal from the Royal Society of Tasmania in 1987, honorary life membership of Nutrition Australia in 1997, and honorary Fellowship of the Royal Australian College of General Practitioners in 1995. He was declared Senior Australian of the Year 2006 for Tasmania. Trevor died on 2 September 2010 of acute myocardial infarction following a successful total knee replacement and is survived by his four children, Tony, Jane, Simon and Lily. One of the many privileges of working with Trevor was witnessing his passion for his work. He was a man of formidable intellect, tenacity, good humour and personal warmth. We have lost a truly remarkable colleague and friend.

Fiona A Horwood

Michael Rozalla was born in Simla, India, on 25 June 1920 and was schooled in Simla and Naini Tal, both situated in the foothills of the Himalayas. He obtained his degree in medicine in Calcutta in 1945, and then served as a medical officer during World War II on the North-West Frontier of India and in Burma. After his discharge in 1948, he worked in a number of hospitals in England and then applied to the British Overseas Civil Service and took up duties in the colony of Sarawak in 1950. In 1960, after a period in Brunei, Michael returned to Kuching, the capital of Sarawak, as Head of the Health Section of the Medical Department of Sarawak. In this capacity, he was instrumental in establishing a fully organised Health Division in the Sarawak Medical Services. Among his notable contributions to the service of public health was his drafting of the Malaria Eradication Scheme, the Tuberculosis Scheme, and the Public Health Ordinance of Sarawak. During his time in Sarawak, Michael was the recipient of several World Health Organization fellowships in the areas of cholera and malaria, and represented Sarawak at various international disease conferences. In 1964, Michael was promoted to Deputy Director of Medical Services of Sarawak and, in the normal course of events, would have been recommended for promotion to Director in 1967, had he not elected to stand down in the interests of “Malaysianisation” (the Malaysian Government policy of replacing expatriate officers with local people where possible). He was made an Officer of the Order of the British Empire in 1969 for his service in Sarawak and Brunei. Michael migrated to Australia in 1970 and, in due course, was proud to become an Australian citizen. He joined the New South Wales Department of Health and took up the position of Deputy Director of Health in Bathurst. When the Department of Health was restructured in 1974, he was appointed Deputy Regional Director of Health, which included the duties of Medical Officer of Health. During this time, he set up the Community Health Programme in the Central West Region. Although Michael officially retired in 1980, he accepted a request from the Department to resume work as a Senior Medical Officer on a part-time basis. He worked on hospital disaster programs and completed a handbook for government medical officers working in NSW. He also prepared a booklet entitled Notes on triage and emergency treatment, which was incorporated into the NSW Disaster Medical Response Plan. He retired from part-time duties in 1990. Michael died on 18 April 2010 from complications of chronic renal failure and cerebrovascular disease. He was a scholar and a gentleman, and is sorely missed by all who knew and cared for him. He is survived by his wife Thea, son David and daughter Teen.

Thea J Rozalla

Tracking falls at the races Last year in the MJA, the first national study of horse-racing injuries in Australia revealed that jockeys are at substantial risk of injury or death from falls.1 Now, Hitchens and colleagues report factors associated with falls of thoroughbred-racing jockeys riding in flat races.2 Among a wide range of identified factors, faster speeds and tighter racing contributed to an increase in the incidence of falls, as did the relative inexperience of riders and horses. Among suggestions for reducing falls was the further investigation of the specific skills that experienced jockeys employ when riding inexperienced horses. 1 MJA 2009; 190: 83-862 Occup Environ Med 2010; 67: 693-698 Vodka and the heart Just one vodka-drinking binge can cause reversible myocardial injury, according to German researchers. In a research letter, Zagrosek and colleagues reported that in a small group of young adults they conducted cardiac magnetic resonance imaging before and after a standardised (!) vodka-drinking binge. Although left ventricular volumes and systolic functions remained unchanged, there were other subtle signs of cardiac injury which resolved within 1 week. The researchers said the reversible injury is most likely due to an inflammatory reaction. They suggested that repeated exposure to excessive amounts of alcohol might prevent the myocardium from full recovery and lead to alcoholic cardiomyopathy by triggering chronic inflammation. JAMA 2010; 304: 1328-1330 Sabotage in the lab Although friends suggested she was paranoid, Heather Ames, a PhD student at the University of Michigan, was convinced that someone was “monkeying” with her experiments. Maher, Nature’s biology features editor, tells the tale of how a jealous postdoctoral colleague working in the same lab was eventually caught out (on camera) contaminating refrigerated media, and of the difficulties in obtaining adequate redress afterwards. Maher interviewed involved parties and others for this feature, reporting their stance. And, as he puts it, vindictive peer review, dishonest reference letters and withholding key aspects of protocols from colleagues or competitors could do just as much to derail a career or a research project as vandalising experiments. Nature 2010; 467: 516-518 Desperately seeking livers Waiting times and even deaths while on the liver transplant waiting list at the Australian National Liver Transplantation Unit, based in Sydney, are rising. Prakoso and colleagues1 reported a waiting time for adults of 23 days in 1985-1993 compared with a time of 120 days in 2001-2008; and a mortality of 23 adults in the earlier period compared with 122 in the later period. In a linked editorial,2 Chapman says the trend is due not only to increases in the prevalence of hepatitis C but also broadened indications — older patients have been accepted in recent years. It is also due to a drop in the number of donor livers; and now “marginal livers” — such as steatotic livers; livers with viral hepatitis and older donor livers — have been used in select patients. 1 Intern Med J 2010; 40: 619-625 2 Intern Med J 2010; 40: 609-610 Revisiting vertebroplasty Earlier this year in the MJA, Clark and colleagues reported their experience observing dramatic pain relief when patients with severe pain caused by osteoporotic vertebral fractures less than 6 weeks old were managed with vertebroplasty.1 Their opinion about the benefit of vertebroplasty in the acute clinical setting is supported by evidence, now published, from the VERTOS II (Vertebroplasty Versus Conservative Treatment in Acute Osteoporotic Vertebral Compression Fractures) trial.2 An open-label randomised trial involving more than 200 patients in the Netherlands and Belgium with acute osteoporotic vertebral compression fractures and persistent pain, VERTOS II, found that vertebroplasty resulted in greater pain relief than conservative treatment. The procedure was not only effective — the pain relief was immediate and sustained for at least one year — it was also safe. In a linked editorial,3 European experts commented that the VERTOS II findings contrasted with those of Kallmes and colleagues and Buchbinder and colleagues published in the New England Journal of Medicine last year, which did not show a significant difference between vertebroplasty and sham treatment. 1 MJA 2010; 192: 334-337 2 Lancet 2010; 376: 1085-1092 3 Lancet 2010; 376: 1031-1032

Ann T Gregory