Volume 183 Issue 3

We know what to do, but doing it is the challenge In 1992, the late Fred Hollows warned of the catastrophic effects that HIV would have in remote Indigenous communities. His trademark candour caused considerable stir, and a number of important initiatives were implemented, such as the Tri-state HIV/STI Project in Central Australia and the National Indigenous Australians’ Sexual Health Strategy. However, it would be hard to argue that HIV is widely believed to be a priority in Indigenous health 13 years later. Health-seeking behaviour based on the presence of genital symptoms or awareness of risk is limited in many Indigenous communities . . . Until now, the prevalence of HIV in the Indigenous community has been considered similar to that in the non-Indigenous community.1 In this issue of the Journal (page 124), Wright et al present evidence of a higher rate of HIV among Indigenous people in Western Australia than in the non-Indigenous population.2 They report that, while the rate of HIV notifications in the non-Indigenous population declined between 1985 and 2002, it increased in the Indigenous population. The difference in risk for Indigenous women was striking — 39% of all female HIV notifications in WA since 1994 have been for Indigenous women, giving an Indigenous : non-Indigenous age-standardised rate ratio of 18. In contrast, the rate ratio for Indigenous males was 2. Wright et al also confirmed the marked differentials in risk of other sexually transmitted infections (STIs) in the Indigenous population — with Indigenous : non-Indigenous age-standardised rate ratios of 242 for syphilis, 77 for gonorrhoea and 16 for chlamydia. The data in this study are likely to predominantly reflect the situation in rural and remote regions of WA, and the authors acknowledge the difficulties of interpreting surveillance data. Nevertheless, the findings demand attention. Health-seeking behaviour based on the presence of genital symptoms or awareness of risk is limited in many Indigenous communities: the concept of “sexual health” is a construct usually confined to well-resourced urban populations. Few Indigenous children in remote areas complete high school and, as a result, there are few reliable means of informing young people about health risks. Although many Aboriginal Health Services have instituted local programs of distribution, condom use appears to be uncommon,3 and there is anecdotal evidence of an increase in injection drug use in remote areas. In settings of social disruption and dislocation, such as among individuals who congregate on the fringes of major urban areas, sex is often exchanged for favours, alcohol and other substances. Not surprisingly, reinforcement and maintenance of health messages and wide implementation of interventions are difficult to achieve in these settings. It is not entirely clear why the prevalence of HIV has remained low in remote Aboriginal Australia; however, this might be explained by the structure of local sexual networks. In simple terms, the sexual network identifies who is having sex with whom, how often and where. Individuals in a sexual network operate in a social space, not necessarily a geographic space. Because of the sensitivity surrounding this issue, there has been very little published on the complex sociocultural factors that determine the structure of Indigenous sexual networks in remote Australia. It is known that Indigenous people living in remote areas may travel extensively across the country, but are likely to choose partners they already know and who share the same background. This has been termed “assortative” partnering, and has been observed in other populations.4 The absence of HIV from a network protects all its members — it is only when an HIV-infected individual enters the network that transmission occurs. Such individuals may have travelled to large urban areas and contracted HIV through injection drug use or homosexual contact. As a result, a substantial proportion of the members of the sexual network will become infected, although in small communities the absolute numbers will remain low. This implies that control of HIV in the Indigenous population will require multiple small interventions that target individual sexual networks, as well as reflecting the local sociocultural conditions. In the 1990s, the rates of curable STIs (chlamydia, gonorrhoea and trichomoniasis) were found to be many times higher in the Indigenous population in the Northern Territory, compared with the non-Indigenous population. However, the rate of a non-curable, viral STI (human papillomavirus) was higher in the non-Indigenous than in the Indigenous population. This suggested that a major reason for the disparity in rates is the limited access to and use of clinical services in remote areas, rather than differences in average rates of partner change.5 Health professionals who have worked in remote health settings know how hard it is to do more than simply react to the patients who walk through the clinic doors with an acute problem. Maintaining population health programs, such as immunisation, health promotion and risk factor modification, is always difficult in these settings, and these programs are first to suffer when a medical crisis occurs. The opportunity costs of a local HIV epidemic are considerable: HIV does not just affect the individual who is infected — sexual partners are also at risk, and transmission can occur antenatally and during breastfeeding. Ongoing risk behaviour after a diagnosis of HIV is documented, driven by psychiatric and substance abuse-related factors. The medical system is compelled to react to the presence of HIV infection in a particular community. In one remote community, this required an increase in the staff of the local public health unit from three to eight, and other programs fell by the wayside (unpublished data). This migration of resources may be one of the major costs of an HIV epidemic in remote Indigenous Australia. Evidence from Africa suggests that STI control early in an HIV epidemic may be effective in limiting the spread of HIV,6 but this strategy is less useful once the HIV epidemic is established. Good STI control requires a coordinated program that addresses health promotion, diagnostic and screening services, rapid access to appropriate treatment and locally appropriate contact tracing. This is not easy, nor cheap, but it is possible — as seen with a successful program in Central Australia.7 Others have also implemented relatively effective programs.8 Primary care providers can use a new Medicare rebate item (item 710) to screen for STIs in Indigenous people as part of a broader preventive health assessment. The new National Aboriginal and Torres Strait Islander Sexual Health and Blood Borne Virus Strategy, to be announced later in the year, will provide a useful review of existing programs, and recommendations for specific action. HIV testing is central to HIV control: it determines the extent of the epidemic and helps plan local interventions. Antenatal screening and antiviral treatment of an HIV-infected mother can almost eliminate the risk of transmission of HIV to the neonate; appropriately timed therapy has obvious benefits for the individual in terms of morbidity and mortality, and successful treatment reduces the viral load and decreases the risk of transmitting HIV through sexual contact. There is no need to reinvent guidelines for testing in Indigenous settings — they already exist. Sustainable implementation is the challenge that faces primary care providers. The data from Wright et al provide a compelling reason for meeting this challenge now.

Francis J Bowden FRACP, MD

Estimating glomerular filtration rate using a simplified formula will lead to a vast increase in detection of chronic kidney disease in Australia In patients with chronic kidney disease (CKD), the degree of reduction in the glomerular filtration rate (GFR) is closely linked to the development of complications of CKD, and GFR is the best index for classifying the severity of the disease. In 2002, a US working party produced a five-stage classification of CKD, with guidelines for management according to stage, based largely upon GFR (Box).1 The classification is logical and simple and has enjoyed worldwide endorsement. However, one problem has impeded widespread usage of the classification — most clinicians do not measure or calculate GFR. Why estimate GFR?The gold standard for measurement of GFR is kidney clearance of inulin, but this method is a research tool and not practical for clinical practice. GFR may be accurately measured by determining the clearance rate of exogenous radioisotopes, such as radiolabelled Cr51-EDTA. Alternatively, the measurement of 24-hour creatinine clearance provides a reasonable, though less accurate, approximation. Both methods are inconvenient, time-consuming and costly. Serum creatinine concentration is widely used as a surrogate marker of GFR, but is crude and insensitive. For example, among the nationally representative AusDiab cohort of 11 247 Australian adults, 1.1% had elevated serum creatinine levels whereas 11.2% had a calculated GFR < 60mL/min.2 Because of these anomalies, much effort has been directed at deriving formulas that use serum creatinine level together with other clinical variables, such as age, sex and weight, to yield an accurate estimated GFR (eGFR). The abbreviated MDRD (Modification of Diet in Renal Disease) formula for deriving eGFR has been extensively validated in US populations and is endorsed for the classification of CKD.1 The inputs required for the (predominantly white) Australian population are serum creatinine level, age and sex (the performance of the formula is less satisfactory among people of Chinese origin,3 and thus possibly others of Asian ethnicity, and is untested among Indigenous Australians). Thus, all data required for calculating eGFR using the abbreviated MDRD formula are currently provided on the typical pathology request form, making automated reporting of eGFR potentially feasible. The growing burden of CKDThe burden of CKD has long been underappreciated. Stage 5 CKD (end-stage kidney disease [ESKD]), which requires dialysis or transplantation to prevent death from kidney failure, provides the most obvious burden of CKD, as dialysis and transplantation are highly visible and enormously costly health problems. Earlier stages of CKD are more prevalent and may be even more costly than ESKD. Projections based on data from the AusDiab survey suggest that 1.4 million Australian adults (11.4% of the non-institutionalised population) had CKD stages 3–5 in 2000.2 Of these, 11 660 (< 1%) were living on dialysis or a functioning kidney transplant.4 For the 99% with CKD who were not receiving dialysis or had not had a transplant, two major consequences have become apparent: increased risk of developing ESKD and increased cardiovascular risk compared with the normal population. Both of these risks are associated with a progressive increase in mortality rate through successive stages of CKD, as was demonstrated in a longitudinal study of subjects in a large health maintenance organisation in the United States (figures represent 5-year mortality rates): no CKD, 10.2% ± 0.5%; stage 2, 19.5% ± 1.9%; stage 3, 24.3% ± 0.8%; stage 4, 45.7% ± 3.5%.5 Indeed, overwhelming evidence now shows that CKD is an independent risk factor for cardiovascular disease and should be added to the list of “traditional” risk factors.6 The need to identify CKDIdentifying cases of CKD may help to prevent ESKD and the attending increase in cardiovascular morbidity and mortality. There is clear evidence that intervention may slow the rate of decline in GFR for people with CKD, particularly if identified at an early stage. Blood pressure control, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for patients with proteinuric nephropathies, blood sugar control and regular clinical follow-up are all proven to be of benefit.7 Reduction in the cardiovascular burden associated with CKD through aggressive management of traditional and non-traditional (eg, elevated calcium phosphate product) cardiovascular risk factors appears likely to be effective, although definitive studies are awaited. CKD is generally asymptomatic. Subject awareness at all stages other than stage 5 is almost non-existent, and clinician awareness is similarly low.8 Thus, detecting CKD requires GFR measurement or estimation. In this issue of the Journal (page 138), a working group representing the peak bodies of Australian nephrology, pathology and biochemistry plus Kidney Health Australia has proposed that eGFR be automatically calculated whenever a serum creatinine measurement is requested through any pathology service in Australia. The eGFR will be reported whenever the value is < 60 mL/min, enabling classification of the patient within CKD stages 3–5. Values above 60 mL/min will not be reported, because of inaccuracies in eGFR in that range and because the complications of CKD are mainly seen at GFR < 60 mL/min. The program will include a comprehensive, ongoing strategy for quality control of laboratory serum creatinine measurements, as this is critical to the accuracy of eGFR, and a major education campaign designed to provide clinicians with guidance on interpreting eGFR and managing CKD. This initiative may prove to be incredibly important if Australia is to limit the current escalation in the burden of CKD. One crucial aspect will be to determine whether automated reporting of eGFR and early detection of CKD result in better health outcomes for the general population, by formally assessing the impact on the health system and individuals before and after the recommended change in eGFR reporting. As with any bold undertaking, there are certain risks and limitations. Firstly, an enormous number of patients will be identified, particularly among elderly Australians. The AusDiab study suggests the majority of patients with stage 3 CKD will be elderly women.2 The natural history of CKD in older people is poorly understood, as is the difference between the impact of normal ageing versus disease on GFR. The potential for increased costs to the health care system through an increase in tests, prescriptions and referrals to nephrologists may be significant, and the potential benefits are uncertain. The increase in workload for nephrologists, in particular, may be unsustainable. Education of clinicians will be crucial here, as will further research into the natural history of CKD in older people. Secondly, although eGFR is well validated for adult whites, caution will be required in applying eGFR to other patient groups such as Indigenous Australians and people of Asian origin.3 Finally, clinicians must not fall into the trap of interpreting an eGFR of > 60mL/min as indicative of healthy kidney function. While GFR is the best overall measure of kidney function and therefore the dominant determinant of the stage of CKD, for people at risk of kidney disease, testing for other markers of kidney damage — such as hypertension, haematuria, abnormal structure and, most importantly, albuminuria/proteinuria — must not be forgotten. K/DOQI classification of chronic kidney disease1 CKD stage Definition Prevalence in Australian adults2 1 Kidney damage (albuminuria, haematuria or abnormal kidney imaging), eGFR > 90 mL/min 0.9% (n = 112 000) 2 Kidney damage, eGFR 60–90 mL/min 2.0% (n = 250 000) 3 Moderate kidney failure, GFR 30–59 mL/min 10.9% (n = 1 400 000) 4 Severe kidney failure, GFR 15–29 mL/min 0.3% (n = 40 000) 5 End stage kidney disease requiring dialysis or transplant, GFR < 15mL/min 0.1% (n = 13 000) CKD = chronic kidney disease. eGFR = estimated glomerular filtration rate. K/DOQI = Kidney Disease Outcomes Quality Initiative.

Steven J Chadban PhD, FRACP · Francesco L Ierino PhD, FRACP

In the competition for official development assistance, health is losing out to governance and security Governance, law and justice were “big ticket” items in the 2005–06 Australian federal budget, reflecting the increasing focus on national security in Australia and elsewhere. Our current aid budget reflects this trend. Australian official development assistance (ODA) seeks “to advance Australia’s national interest by assisting developing countries to reduce poverty and achieve sustainable development”.1 According to AusAID, the agency responsible for the ODA program, poverty reduction remains central, reflecting Australia’s humanitarian values and its economic and security interests. The Australian Government has committed to a number of interrelated policy, program and partnership initiatives. In 2005–06, these initiatives seek to promote a closer partnership with Indonesia and engagement with fragile states, to stimulate broad-based economic growth, to strengthen efforts to promote better governance, to tackle transnational threats (notably HIV/AIDS), and to contribute to greater stability and security. A fair contribution?Australian contributions to ODA, now $2.49 billion a year, have been increasing over the past 5 years — a step in the right direction. Budget allocation has risen from 0.25% of gross national income (GNI) in 2001–02 to 0.28% in 2005–06. However, this gradual rise must be seen against the much larger decline over the past 30 years: in 1975–76, 0.45% of GNI was allocated to ODA, falling to 0.43% in 1985–86, 0.32% in 1995–96; and 0.28% in 2005–06.2 Current levels are well below the 0.42% committed, on average, in 2004 by nations belonging to the OECD (Organisation for Economic Co-operation and Development).3 This prompts questions about how Australia will achieve the ODA targets required to meet the United Nations’ Millenium Development Goals, to which we committed in 2000. If it is to do so, a timetable for achievement should be reiterated, with Australian ODA reaching 0.5% of GNI by 2009, nearly double the current level, and 0.7% by 2015.4,5 Without allocating considerably more resources, Australia will be substantially under target. Who benefits?Australia’s ODA is increasingly directed to near neighbours; around 42% is allocated to just three countries — Indonesia, Papua New Guinea and the Solomon Islands. The allocation to the whole continent of Africa, where poverty and conflict cut deepest,6 and where the impediments to achieving the Millenium Development Goals are greatest, stands at only 3% of Australia’s ODA. Support for other resource-constrained countries in South and East Asia is not much greater. Assistance to those in greatest need remains crucial if the benefits of greater equity, stability7 and control of infectious diseases,8 for example, are to be achieved. Attainment of the Millenium Development Goals needs better governance, but also increased and more effective aid for basic services in the poorest countries. One of the agreed indicators of effective aid targeting is the proportion going to countries classified as “Least Developed” by the UN’s Economic and Social Council. As little as 0.05% of Australia’s GNI goes to Least Developed Countries, one of the lowest rates of all OECD donors.9 A notable trend in Australia’s latest aid budget is the increased focus on governance, which now attracts 36% of ODA, squeezing out other commitments (Box). Almost half of this governance expenditure goes towards law and justice, with large tranches allocated to the Department of Defence and the Australian Federal Police for their activities overseas. This commitment to a “whole of government” approach has seen greater involvement of Australian experts with limited experience of developing countries, and inadvertently undermines the concentration of development expertise within AusAID itself. A healthy contribution?In 2005–06, Australia is devoting only 12% of ODA to health, substantially less than countries such as the United Kingdom (22%),10 and much the same proportion as in the past few years. Within this health allocation, an increasing share is devoted to multisectoral HIV/AIDS programs; their funding has increased from around $25 million in 2001–02 to around $70 million in 2005–06. While increased HIV/AIDS funding is necessary and welcome, commitment to non-HIV health-related expenditure has declined, in some cases markedly. Countries such as Laos, Cambodia and Vietnam no longer receive AusAID funds for health and, in the case of Laos, had primary health care funds cut precipitously. Health is significantly linked to poverty, but there are no short-cuts or easy solutions to re-establishing, reforming, and reshaping functional, efficient, and more equitable health systems. Basic health care requires sustained investment in human resources, infrastructure, community-level health promotion, and essential services for primary care, as well as attention to the social determinants of ill health. While supporting basic services is not the most glamorous issue, with neither the profile of HIV/AIDS nor the visibility of uniformed police and defence force personnel, these services remain the cornerstone to promoting health and to ensuring that communities can participate in, shape and control their own development. The Australian Council for International Development (ACFID), an independent association of Australian non-government overseas aid and development agencies, estimates that a fair Australian contribution to the global aid requirements for health would be around A$580 million, substantially above our current commitment of A$299 million.2 Keeping track of where ODA goesKeeping track of ODA is important. Otherwise, we cannot assess the range of activities underway and their outcomes. In recent years, the monitoring of ODA has been made more difficult because of the greater proportion devoted to governance and security, the control of funds by government departments other than AusAID, the failure to separate HIV/AIDS from general health sector reporting, and a reduction in detailed statistical presentation (eg, AusAID has not published a detailed listing of all funded projects since 2001). The level of funding allocated to Australian government departments exposes us to the criticism of “boomerang aid”. The ability to track and account for where funds have actually gone, the proportion tied to purchase of Australian products,11 and the share that goes into basic infrastructure and service delivery in the social sectors, or other forms of direct poverty reduction, should be enhanced. Aid effectiveness remains a key challenge.12-14 While there are no simple answers, numerous international organisations have made a commitment to promoting evidence-informed policy and allocating resources to learning lessons and reflecting on current practice, in partnership with academic and country-based experts.15 Australian commitment to this trend is to be encouraged. Will government follow the lead of a generous public?The response of the Australian community to the 2004 earthquake and tsunami in the Indian Ocean demonstrated popular concern for the needs of others. In fact, even before the tsunami, private contributions by Australians to aid and development were increasing by around 10% per year in real terms (from around $380 million in 2000 to $443 million in 2004, both figures in 2004–05 dollars [G Luke, Policy Adviser to Australian Council for International Development, personal communication, June 2005]), indicating strong interest and support for development cooperation. We need to tap into this public solidarity and ensure that ODA, despite its limitations, obtains more resources and attention. Increasing commitment to health and education will reinforce governance and security, but this is not why they should be supported. Health and education should attract funds because we care about other people,16 because we have a commitment to promoting human security in the region, and because we find it unacceptable that women die in childbirth because of lack of health services, that preventable diseases kill so many children before the age of 5, and that infectious and non-communicable diseases are decimating economies. Basic services require support, which cannot be provided within the existing aid envelope. The Australian Government White Paper on aid, currently being drafted and due in early 2006, is an opportunity to reinforce commitments to dramatically increase ODA and should place health firmly back on the agenda. The Australian public has demonstrated a willingness to contribute directly. Can we mobilise a matching political commitment? Australian official development assistance by sector* * From analyses of AusAID budgetary data (G Luke, Australian Council for International Development, personal communication). Funds not earmarked for a particular sector (either because they go to multisectoral initiatives, such as gender and environment, or to development banks and United Nations agencies) are excluded. †Expressed in 2004–05 Australian dollars.

Anthony B Zwi PhD, FAFPHM · Natalie J Grove BOccThy, MPH · Maria-Theresa Ho MHP, MD

Treatment has advanced, but a stigma still surrounds this disorder Epilepsy affects some 120 000 to 200 000 Australians. It is defined as a disorder with recurrent unprovoked seizures, but 4%–5% of the population may experience at least one seizure at some point in their lives.1 About half the people who develop epilepsy present in the first two decades of life. A second peak occurs in people older than 60 years. Pathophysiology and clinical geneticsFor 25 years, the classification of epilepsy syndromes has been embedded in the seizure type (partial or generalised onset) and the presence or absence of an underlying brain disorder (symptomatic or idiopathic),2 along with acceptance that there is a genetic basis with complex patterns of inheritance for idiopathic epilepsy. Indeed, in the past decade or so, examination of large pedigrees with multiple affected members has led to the discovery of several epilepsy genes. These gene defects most commonly disrupt the function of voltage-gated or neurotransmitter-gated ion channels, producing alterations in neuronal excitation within brain networks.3 These discoveries have enhanced our understanding of seizure pathophysiology, but they have also begun to cast doubt on the current classification of the epilepsies. The distinctions between partial and generalised and between idiopathic and symptomatic are difficult to support when individuals sharing gene defects present with very different epilepsies.4 Despite this, the known epilepsy genes do not yet explain the most common epilepsies, where gene combinations interacting with environmental or epigenetic factors are expected to provide the answers. NeuroimagingThere have been tremendous advances in neuroimaging technology. Magnetic resonance imaging (MRI) can demonstrate a variety of cerebral pathologies not reliably found with computed tomography (CT). These include hippocampal atrophy in mesial temporal lobe epilepsy, focal and diffuse malformations of cortical development, and vascular malformations and focal encephalomalacia. A CT brain scan is no longer an adequate investigation for epilepsy. The ability to measure volumes of specific brain structures and quantify signal change has opened new areas of neuroscience research in humans with epilepsy. Cross-sectional and, more recently, longitudinal studies of regional brain volumes have provided evidence of progressive brain damage with intractable focal seizures.5 Functional neuroimaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) are valuable in assessment for epilepsy surgery, but have contributed little to our understanding of the aetiology of epilepsy. The development of new PET and SPECT ligands and MRI spectroscopy holds the promise of advances using in vivo neurochemistry. Treatment and prognosisWith therapy, 60%–70% of people with epilepsy will have a good prognosis with complete control of seizures on the first medication tried. In the past 10–15 years we have seen the introduction of lamotrigine, vigabatrin, gabapentin, tiagabine, topiramate oxcarbamazepine and levetiracetam to the therapeutic armoury. These new antiepileptic drugs (AEDs) provide a greater range of options and differing side-effect profiles than existed with the older array of AEDs (barbiturates, phenytoin, carbamazepine and valproate).6 However, 20%–30% of patients will not respond completely to medication and there has been no major change in the proportion of children and adults whose seizures remain refractory to medication — even with the release of these new AEDs. There has been a growing awareness of the futility of years of different AED trials in individuals and AED polytherapy.7 The failure of two well-supervised medication trials in partial epilepsy should alert the physician of the need to consider options such as epilepsy surgery. A randomised, controlled trial of surgery for temporal-lobe epilepsy has shown 58% of the surgical candidates were seizure-free at one year, compared with 8% of medically treated patients.8 Surgery should not be seen as the last resort, but as a complement to medical treatment in refractory cases. Comorbidity of epilepsyDoctors have become very adept at counting seizures to determine the success of interventions. In the past decade, attempts have been made to assess the impact of epilepsy and its treatment upon a person’s quality of life. We are becoming more aware of the effects of the older AEDs on endocrine function and their teratogenic potential.9 Long-term AED use is associated with osteopenia, and vitamin D and calcium supplements are appropriate. More than 30% of patients with epilepsy may suffer depression. The depression is not simply the result of a chronic medical illness; it seems that the two disorders may share a common pathological substrate. Recognition and treatment of depression is important to the success of the treatment of the epilepsy itself.10 The futureIn the next decade or so, we can expect that genetic testing for particular epilepsies will complement and perhaps lessen our current dependence on clinical profiles and electroencephalography. It is conceivable such testing may aid us in selecting the most appropriate AED and predicting hypersensitivity side effects of AEDs. Currently, AEDs are administered to control seizures or the clinical expression of epilepsy, but we have no means to intervene to prevent epileptogenesis. Advances in our knowledge will certainly occur in the next decade. But without a greater understanding of epilepsy and seizures in the community, we will not lessen the stigma that still surrounds the disorder in schools and the work place. Epilepsy is a common disorder and deserves attention in public education programs.

Andrew F Bleasel MB BS, PhD, FRACP

How to submit a manuscript using Editorial Manager Prepare your submission To submit your manuscript online, you will need: 1. An electronic manuscript file that contains no identifying information (no author names or addresses, no acknowledgements). 2. An abstract of your manuscript. All articles except Letters to the Editor, Obituaries and Book Reviews require an abstract of some kind (see <www.mja.com.au/public/information/instruc.html>). Even an editorial requires a one- or two- sentence descriptive abstract. 3. Details of your co-authors: name, qualifications, position, institution, email address. 4. A disclosure statement completed for all authors. Our disclosure form is available at <www.mja.com.au/ public/information/disclosure.doc>. 5. High-resolution copies of any figures or photographs in separate files (if your manuscript is illustrated). 6. A covering letter in support of your submission (not required for Letters to the Editor, Book Reviews or Obituaries) saved in a separate electronic file. Register with Editorial Manager Everybody needs a username and password to log in to the MJA’s Editorial Manager site. If you haven’t used Editorial Manager with the MJA before, you will need to register first. Go to <www.editorialmanager.com/mja/>, click on “Register”, and follow the steps. We have registered all MJA reviewers already. If you are a reviewer, you should have received your username and password in an email. Submit your article Go to <www.editorialmanager.com/mja/> and click on “Submit a manuscript”. There are several steps to making a submission. Each time you complete a step, the system saves your work. If your session is interrupted for any reason, you can come back and complete your submission at a later time. Problems? Call Kerrie Harding or Christine Hooper in the editorial office: +61 2 9562 6666. No internet access? Send your submission by post. We would appreciate receiving the manuscript on a disk as well as on paper, if that is possible. On 1 July 2005, the MJA began using an online manuscript submission and peer review system called Editorial Manager. Provided by Aries Systems in the US, Editorial Manager is used by many journals throughout the world (including Australian Health Review, American Heart Journal, Annals of Emergency Medicine, and Cell). Indeed, many MJA authors and reviewers have already used Editorial Manager or a similar system. Editorial Manager records manuscript submission and peer review in a database accessible via the world wide web. This administrative technique is very efficient. Authors enter their submissions directly into the database, receiving instant confirmation that their work has been received. Using Editorial Manager, authors are less likely to omit required information from their submission, and this reduces delays. Editorial Manager streamlines the communication between editors and potential reviewers, and makes it easy and quick for reviewers to receive a copy of the manuscript. The same streamlined method of communication is used to submit reviews, request manuscript revisions, and receive a final article. Journals using Editorial Manager commonly report that the administrative work and time taken to reach a decision on manuscripts are greatly reduced, and the number of manuscripts submitted rises. Editors, authors and reviewers can log in at any time to check the status of their manuscripts. Because Editorial Manager is a web-based system, it is available wherever and whenever there is an internet connection, not just in the office. This accessibility also makes it easier for authors and reviewers overseas to contribute to the MJA. So, we are expecting Editorial Manager to bring many benefits — benefits that should ultimately be expressed in better articles published more quickly in the MJA. We are also nervously prepared for the potential downside. New computer systems never appeal to everybody. The website provides plenty of written instructions, but we are also ready to spend time on the phone with new users answering their questions. We encourage all users of the system to give us feedback to guide future development of the system. And, although we are encouraging all authors to use Editorial Manager, no author will be discriminated against for not using the system. You can still post us a handwritten essay, if that is your modus operandi, and the editors (some with a thrill of nostalgic pleasure) will respond in like style. We do feel, however, that most authors will be much better served by the new system, and strongly urge them to take it up.

Craig M Bingham BA · Christine Hooper · Kerrie Harding

Objective: To compare trends and rates of HIV and sexually transmitted infections in Indigenous and non-Indigenous people of Western Australia.Design and setting: Analysis of WA notification data for chlamydia, gonorrhoea, and primary and secondary syphilis in 2002, and for HIV infections from 1983 to 2002.Main outcome measures: Rates of HIV and sexually transmitted infection by Indigenous status.Results: In 2002, there were 3046 notifications for chlamydia, 1380 for gonorrhoea and 64 for syphilis. When information on Indigenous status was available, Indigenous people accounted for 41% of chlamydia and 76% of gonorrhoea notifications, with Indigenous : non-Indigenous age-standardised rate ratios of 16 (95% CI, 14–17) and 77 (95% CI, 67–88), respectively. Indigenous people accounted for 90.6% of syphilis notifications (age-standardised Indigenous : non-Indigenous rate ratio, 242 [95% CI, 104–561]). From 1985 to 2002, HIV notification rates for non-Indigenous people in WA declined and rates for Indigenous people increased. From 1994 to 2002, there were 421 notifications of HIV infection in WA residents, 52 (12.4%) in Indigenous people and 369 (87.6%) in non-Indigenous people. Indigenous people accounted for 39% and 6.2% of all notifications in WA females and males, respectively. The Indigenous : non-Indigenous rate ratios were 18 (95% CI, 12–29) for females and 2 (95% CI, 1–3) for males.Conclusions: Indigenous Western Australians are at greater risk of HIV transmission than non-Indigenous people. Strategies to prevent further HIV infection in Indigenous Australians should include control of sexually transmitted infections.

Michael R Wright BSW, MAE(IH) · Carolien M Giele RN, BSc(Hons), MPH · Phyll R Dance BA, PhD · Sandra C Thompson FAFPHM, PhD

Objective: To reduce pethidine prescribing in hospital emergency departments (EDs).Design: Multi-centre drug use evaluation (DUE) process.Setting and participants: Emergency departments in 23 public hospitals (22 in New South Wales, 1 in Victoria) from 1 September 2002 to 31 August 2003. Participating hospitals included seven principal referral hospitals, six major non-teaching hospitals and 10 district or community hospitals. Data for comparison were collected from 12 non-participating hospitals.Interventions: Hospital coordinators at each participating hospital were provided with support to implement a range of prescribing interventions in their ED in each of three DUE cycles. Interventions included educational materials (guidelines, posters, prescribing reminders), audit and feedback, and small-group discussions. Three audits of pethidine prescribing were undertaken. Prescribing was compared with evidence-based guidelines and non-concordance identified.Main outcome measures: Number of dosage units of parenteral analgesics issued to the ED from each hospital’s pharmacy department was recorded monthly and aggregated in 3-month periods.Results: In the 12 months between the preintervention period and the equivalent post-intervention period, pethidine use decreased by 62% in project hospitals (4669 to 1793 units) and 56% in control hospitals (1476 to 648 units). Six months after project completion there was a significantly greater reduction from baseline in participating hospitals (71%; 4669 to 1348 units) compared with non-participating hospitals (64%; 1476 to 532 units; P < 0.001). There was a concurrent increase in use of both morphine and tramadol.Conclusion: There was a sustained reduction in pethidine use during the study period, which may indicate successful promotion of safer analgesic prescribing. It is not clear whether changes were a result of collaborative DUE methods or other factors.

Karen I Kaye BPharm, DHP · Susan A Welch BPharm · Sharon R Davis BPharm, DipNut · Linda V Graudins BPharm, DHP, FSHPA · Andis Graudins FACEM, PhD · Tai Rotem BSOCSCI · Richard O Day MD, FRACP

Objective: To identify changes in mental health literacy in regard to depression between 1998 and 2004.Design and setting: Face-to-face interviews with a random and representative sample of the South Australian population in 2004, compared with a similarly conducted survey in 1998 that used the same vignette, questions and methodology.Participants: 3015 randomly selected participants, aged 15 years and over.Main outcome measures: Responses to both open-ended and direct questions about symptoms and treatment options for depression.Results: The 3015 interviews conducted represented a response rate of 65.9%. Compared with 1998, in 2004 there was a significant increase in the proportion of people recognising depression in the vignette, acknowledging personal experience of depression, and perceiving professional assistance to be more helpful and less harmful. However, although more people nominated psychiatrists or psychologists as therapists of choice, the difference between 1998 and 2004 was not significant.Conclusions: There has been a significant increase in mental health literacy, at least as regards depression, in the South Australian community between 1998 and 2004. The lack of significant change in psychiatrists and/or psychologists being perceived as therapists of choice is of concern and suggests that community education about their expertise may be appropriate.

Robert D Goldney MD, FRANZCP, FRCPsych · Laura J Fisher BA(Hons) · Eleonora Dal Grande MPH · Anne W Taylor MPH

The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function. The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%. The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73m2). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to “automatically” generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73m2 be reported by laboratories as “> 60 mL/min/1.73m2”, rather than as a precise figure.

The Australasian Creatinine Consensus Working Group

Chronic fatigue syndrome (CFS) describes a disorder comprising chronic debilitating fatigue that cannot be explained by any known chronic medical or psychological condition.1 To date, the only therapies that have consistently ameliorated symptoms in this disorder are cognitive behavioural therapy and graded exercise.2-5 This article describes a graded exercise program based on the exercise prescription used in our recent randomised controlled trial.5 This program has since been successfully implemented in a clinical practice. It includes the concept of pacing and is aimed at non-bed-bound, sedentary patients with CFS, as well as those already undertaking minimal aerobic exercise (ie, no more than three sessions per week of 20 minutes’ duration). Engaging the patientEngaging patients with CFS in an exercise program can be difficult, as many fear that exercise will exacerbate their symptoms. Patients should therefore be informed that all studies that used an exercise intervention in CFS reported improved physiological and psychological function,2-5 and that the protocol described here was not associated with any major relapse.5 Importantly, this exercise protocol is based on individual capabilities and is increased only if the patient is coping. A structured exercise protocol may also help prevent CFS patients overdoing physical activity and consequently exacerbating symptoms on days that they feel comparatively better. Patients should also be informed that exercise has been associated with improvement in physical function, fatigue and mood disorder in other chronic illnesses, such as cancer,6 cardiac heart failure,7 and in particular multiple sclerosis8 and fibromyalgia,9 which are both associated with debilitating fatigue, and in which exercise was once considered contraindicated. Finally, aerobic exercise can halt further deconditioning, which would typically further reduce physical capacity and worsen psychological symptoms.10 Preparing for the program Before beginning any exercise program, patients should be screened by a medical doctor. Patients should also be informed that the exercise sessions are in addition to their normal activities, and that some initial aches and pains are usual when beginning exercise for the first time. Patients should purchase or hire a heart rate monitor, as this will assist in keeping heart rate (beats per minute, [bpm]) constant during exercise sessions. Alternatively, heart rate can be determined by assessing pulse rate. Patients should also be taught how to determine their ratings of perceived exertion (RPE) using the Borg scale11 (Box 1). Patients must record their RPE on completion of each exercise session and then average these values each fortnight. The averaged RPE value forms the basis for determining the duration of future exercise sessions. An exercise diary is also important (Box 2). This allows patients to monitor progress over time and also assists in linking poor performance with a possible emotional or physiological event. The exercise program Exercise should be attempted once every second day and should be in a form that uses the major muscles of the body, such as walking, jogging, swimming or cycling. The duration of each exercise session during the first fortnight should be negotiated with the patient, and may range from 1 to 10 minutes, depending on individual physical capabilities. For those already exercising, the duration should be one that the individual is currently coping with consistently. The intensity of the exercise should represent a pace that the individual can perform comfortably. Importantly, this intensity should be determined on a day when symptom severity is typical, rather than either better or worse than usual. The average peak heart rate when exercising at a comfortable pace on a typical day should be recorded, with this intensity representing the patient’s target heart rate (±3 bpm) for future sessions. The “warm-up” time that it takes for heart rate to reach this target is included in the overall exercise duration. Program monitoring and modification Patients should contact their doctor the day after their first exercise session to discuss how they coped with the session. If the patient feels that the initial session was too easy (ie, an overall RPE score of 9 or lower), a slight increase in duration could be considered. Conversely, if the RPE score was greater than 14, then the duration of subsequent sessions for that fortnight should be reduced to a time period that elicits an RPE score of 11–14. It is important that the patient be eased gently into the exercise program. At the end of each fortnight, patients should contact their doctor to determine the next fortnight’s exercise prescription. If patients coped with the exercise regimen, did not experience a major relapse, and reported averaged fortnightly RPE values of 14 or less, then the exercise duration for the following fortnight should be increased by 2–5 minutes. If the average RPE score was 15 or higher, then the exercise duration should be reduced to a time period that elicits an averaged fortnightly RPE score of 11–14. The same procedure and recommendations for the first fortnight apply to the next and subsequent fortnights, in that individual target heart rate is kept constant, and RPE scores are recorded after each exercise session and averaged at the end of each fortnight. Importantly, many CFS sufferers describe fluctuations in their symptoms and capabilities. However, on days that patients feel comparatively well, they must adhere to their current exercise regimen and must not perform any extra exercise above this level. This rule also applies to normal everyday physical tasks, such as housework and gardening. In addition, on days when symptoms are worse, patients should either shorten the session to a time they consider manageable or, if feeling particularly unwell, abandon the session altogether. They should always endeavour to commence the exercise program again when symptoms subside to a tolerable level. When recommencing exercise, the pace should be comfortable, while the duration should be reduced to a time that the individual feels is manageable and elicits an RPE score of 11–14. Patients should then continue at this modified duration for a fortnight and increase this time period for the subsequent fortnight only if the averaged fortnightly RPE score was 14 or lower. Finally, if the duration of exercise reaches 30 minutes, patients could consider increasing the intensity of sections of the exercise session. An example of this would be where the first minute of every 10 minute section of the session is performed at a higher intensity (RPE, 15–16). The number of higher intensity minutes can be marginally increased each fortnight if averaged fortnightly RPE scores fall within the guidelines described earlier. 1 Borg’s Ratings of Perceived Exertion Scale* Perceived exertion Rating 6 Very, very light 7 8 Very light 9 10 Fairly light 11 12 Somewhat hard 13 14 Hard 15 16 Very hard 17 18 Very, very hard 19 20 * Borg G. Psychophysical bases of perceived exertion. Medicine and Science in Sports and Exercise 1982; 14 (5): 378.11 2 Extract from an exercise diary Date & time of exercise: Friday 12 Feb, 10.00 am Exercise duration: 6 mins Average peak heart rate intensity (comfortable pace): 125 bpm Rating of perceived exertion (RPE) at the end of the exercise session: 14 General comments: Struggled with the exercise today, felt very tired — but did not sleep well last night.

Karen E Wallman PhD · Alan R Morton DipPE, MSc, EdD · Carmel Goodman MD · Robert Grove PhD

Macrophagic myofasciitis is characterised by sheets of macrophages in striated muscle, a few lymphocytes and inconspicuous muscle fibre damage. It is due to aluminium contained in vaccines, and is localised to the inoculation site. We report the first Australian case, detected incidentally when investigating a raised serum creatine kinase level. Clinical record During investigations for gastroesophageal reflux, a 32-year-old man was noted to have intermittently raised serum creatine kinase levels: 78 U/L in April 2003, 484 U/L in July 2003 and 8846 U/L in August 2003 (reference range, < 196 U/L), with normal troponin levels. He had no neuromuscular symptoms and played sport regularly. A previous serum creatine kinase level of 2000 U/L had been recorded in April 2000, when he had multiple pulmonary emboli after an overseas trip. He had been given inactivated hepatitis A (Havrix) and poliomyelitis vaccines intramuscularly in March 2000, and a booster inoculation for hepatitis A in February 2001. He was taking allopurinol for renal calculi and omeprazole for reflux. His father had died from motor neurone disease and a brother had fasciculations. The patient had no evidence of muscle weakness or wasting, no fasciculations, and the remainder of his neurological examination, as well as needle electromyography, was normal. Muscle biopsy The interstitial connective tissue of the deltoid muscle contained a dense infiltrate of large macrophages (Figure A). Electron microscopy showed spiculated structures within these macrophages (Figure B). When an electron beam hits a sample it releases x-rays of wavelength specific to the elements in the sample. Using this principle, an EDAX x-ray detector revealed an aluminium peak (Kα, 1.48 keV) from the aggregates. A: Deltoid muscle biopsy. Densely packed macrophages with abundant cytoplasm (arrowhead) were seen between muscle fibres (M), together with a few peripheral lymphocytes (thin arrow). No muscle fibre necrosis, regeneration, multinucleate giant cells, Michaelis–Guttmann bodies (found in malakoplakia) or granulomas were present. The macrophages stained positively with acid phosphatase and CD68. The lymphoid population showed a mixture of T and B lymphocytes. Stains for acid-fast bacilli were negative. (Haematoxylin and eosin. Bar = 50 m.) B: Electron micrograph showing electron-dense, randomly orientated, fine spiculated structures (asterisks) within a macrophage (M) (200 nm resin sections on nickel grids examined in a Philips CM120 electron microscope. Osmium and uranyl acetate. Bar = 1 µm.) Macrophagic myofasciitis is characterised by the presence of sheets of macrophages in striated muscle, a few lymphocytes and inconspicuous muscle fibre damage. It is due to the persistence of vaccine-derived aluminium in the muscle at the injection site and the myofasciitis is localised to the injection site. Since macrophagic myofasciitis was first described in 1993,1 more than 200 cases have been identified in France, with only a few cases reported from other countries.2 This is the first case of macrophagic myofasciitis reported in Australia. Aluminium is used as an adjuvant in diphtheria – tetanus –pertus sis, some Haemophilus influenzae type b, pneumococcal, hepatitis A and B, anthrax and rabies vaccines, as well as in tetanus toxoid.3 For example, each millilitre of Havrix contains 0.5 mg of aluminium, as aluminium hydroxide. The mechanism of macrophagic myofasciitis is thought to be secondary to an ongoing local immune reaction to the long-term persistence of this aluminium in the muscle.4 Macrophagic myofasciitis commonly occurs in adulthood, although the age ranges between 1 and 70 years.5,6 The clinical picture is variable, and includes nonspecific symptoms such as myalgia, arthralgia, muscle tenderness, muscle weakness, fever and fatigue. A few patients show raised serum creatine kinase levels and myopathic electromyography.6,7 Neurological manifestations resembling multiple sclerosis have been reported in some patients,8 and rarely it is associated with other diseases such as inclusion body myositis.9 Co-existent autoimmune diseases have been recorded in some patients with macrophagic myofasciitis.10 Steroids, analgesics and antibiotics have been used in attempts to treat this condition.10 Our patient did not have any neuromuscular symptoms and the muscle biopsy was performed because of his raised serum creatine kinase level. There was no correlation between macrophagic myofasciitis and the clinical signs and symptoms in this patient, who was asymptomatic. Therefore, we consider this histological finding to be incidental in a patient with a “CKopathy”. Recently, a genetic predisposition to macrophagic myofasciitis has been suggested to account for the disparity between the low prevalence of this disorder and the widespread use of aluminium-containing vaccines, as well as the variable incidence of this condition in different populations.5 The diagnosis of macrophagic myofasciitis is important to bear in mind, as other diagnoses such as sarcoidosis, connective tissue disease, tuberculosis, Whipple’s disease and malakoplakia may be entertained. The patient could then be subjected to needless further investigations and undue anxiety. We hope this report will help increase awareness of this condition, and predict that more Australian cases will come to light in future deltoid muscle biopsies.

Meena Shingde MB BS, MD · Roger Pamphlett MD, FRACP, FRCPath · James Hughes FRACP · Ross Boadle Dip(MT), MAIMS · Edward J Wills MD, FRCPA

Vietnam veterans reported a high prevalence of health problems among their partners and children in a 1998 survey. Data about the effect of our veterans’ war service on the health of their families are quite limited. These data are mainly from the Vietnam and Gulf Wars; cover veterans, partners and children independently; and largely focus on the individuals’ medical conditions and risk factors. Australia should develop a broad research strategy that uses a wider definition of health, looks at veterans’ families as a whole, and does so from a range of perspectives, including sociological, life-course and trans-generation perspectives. Preventive research should be emphasised, especially into enhancing resilience of veterans’ families. The use and usefulness of current services should be evaluated, including whether they need to be more family-inclusive.

Hedley G Peach PhD, FFPH

Clinical record 1 Area of necrosis on right shin 2 Areas of necrosis at graft site A 50-year-old woman was referred for surgical consultation after accidental self-inoculation with Gudair ovine Johne’s disease (OJD) sheep vaccine 18 days earlier. The automatic vaccination syringe had been hanging from her neck by a plastic delivery tube connected to the vaccine pack when a sheep had bumped the syringe. This resulted in a needle-stick injury to her right shin. Within hours, the area became red, and 3 days later she consulted her general practitioner. Tetanus toxoid was administered, and she commenced a course of dicloxacillin. The inflammation failed to resolve and had progressed to a 2 cm-diameter area of skin necrosis by the time of presentation (Box 1). The necrotic skin and subcutaneous fat were then debrided. Despite careful wound packing, a tender nodule developed in the overhanging edge of the ulcer. On Day 15 after presentation, soft granulation tissue extending down to the deep fascia and the overhanging skin were debrided. A week later, a split skin graft was applied. Although the graft was successful when seen about 7 weeks after initial presentation, two red, tender areas had appeared about 5 mm from the edge of the graft. Within a further 9 days, the inferolateral area had proceeded to necrosis. At the patient’s request, further surgery was delayed until 2 months later (Box 2), when two necrotic areas and associated granulation tissue (arrows A and B) were curetted. No obviously oily material was detected (mineral oil is a component of the vaccine). The uppermost red tender area (arrow C), had settled, but subsequently flared up and discharged a little serous fluid. All three areas of necrosis had finally healed when the patient was seen 6 weeks later, and there was no evidence of inguinal lymphadenopathy, although the patient reported continuing fatigue and nausea. During the course of treatment of the leg, she developed recurrent urinary tract infections due to Proteus mirabilis. Histopathological observations on all occasions showed necrosis with adjacent marked oedema and granulation tissue, with polymorphs and occasional acid-fast bacilli (at the time of the first and second operation) but no microcavities suggestive of oil implantation. No stains are available to help differentiate human oil from mineral oil. No pathogens were cultured. For the past year, the patient has been free of systemic symptoms and her leg remains healed. Ovine Johne’s disease (OJD) is a chronic wasting disease of sheep caused by the “S” strain of Mycobacterium avium subsp. paratuberculosis. It has spread widely through Australian sheep flocks, causing significant economic loss since it was first detected in New South Wales in 1980. A national vaccination program to control OJD is currently in progress using Gudair vaccine (CZ Veterinaria, Porriño, Spain),1 which is distributed by Pfizer Animal Health. (The Gudair vaccine has been available in Australia since late 1999 for experimental use in about 50 approved flocks. This research work led to registration of the product in April 2002.) Vaccination of sheep against OJD is now widespread in Australia: over 7 million vaccinations have been performed — primarily in the central and southern tablelands and south-west slopes of New South Wales, across Victoria and on Kangaroo Island (SA), and to a lesser extent in the northern tablelands and western areas of NSW, mainland South Australia, Tasmania and Western Australia. Each 1 mL dose of Gudair contains killed (heat-inactivated) Mycobacterium paratuberculosis organisms and mineral oil, with thiomersal as a preservative. The oil forms a depot at the injection site to act as a potent adjuvant, stimulating a cell-mediated immune response to the mycobacteria. In humans, accidental injection or exposure of the skin surface or mucous membrane may cause a severe local reaction and, uncommonly, a systemic reaction. Despite education of vaccinators, there have recently been seven documented cases of accidental self-inoculation in Australia resulting in prolonged morbidity.2,3 Wider use of the vaccine has increased the risk of self-inoculation injuries. There is a need to improve safety for farmers during vaccination and to bring the potential for serious complications of self-inoculation to the attention of doctors in rural areas. Accidental self-injection may occur because of inadequate animal restraint, poor inoculation technique or carelessness, facilitated by hanging the automatic vaccinating syringe from the neck (Box 3) or shoulder.3 Although self-inoculation in this patient did not appear to penetrate the deep fascia, there was nonetheless severe long-term morbidity. The volume of injected material that is sufficient to cause necrosis is unknown. It is postulated that the adjuvant mineral oil combined with killed mycobacterial cell-wall components is responsible for provoking the necrotic response.3 This explains why antibiotics do not prevent necrosis and why surgical debridement of the inflammatory vaccine material is the preferred therapeutic approach. Mycobacterial cell-wall antigens have been traditionally added to oil-emulsion adjuvants (Freund’s complete adjuvant) to enhance the efficacy of experimental vaccines in stimulating cell-mediated immune responses. Such oil-based adjuvants, although generally considered too reactive for routine use in human vaccines, are considered acceptable for use in animals. Research in heavily OJD-infected Australian merino sheep flocks has shown that OJD vaccine injection-site lesions are common, but usually cause minimal untoward sequelae when administered subcutaneously at the recommended site (ie, high on the neck behind the ear).4 Necrosis similar to that seen in human case reports is usually only observed in a small proportion of vaccinated sheep. The vaccine product label clearly states that users should seek medical attention immediately if accidental self-administration occurs. Further information is contained in a fact sheet provided to farmers that emphasises the importance of avoiding exposure to the vaccine and outlines the procedure to follow if exposure occurs.5 A more detailed fact sheet prepared for medical practitioners, based on reports in the medical and veterinary literature,6,7 outlines a graded medical and surgical approach to intervention after clinical assessment of the patient’s condition.8 Box 4 presents a summary of our recommendations for treatment of accidental self-inoculation with OJD vaccine. These are based on the manufacturer’s recommendations, together with preliminary evidence from the case described here and a series of six similar cases.3 Accidental self-inoculation with Gudair vaccine has major occupational health and safety implications, and it is essential that medical practitioners be aware of the emerging use of oil-based OJD vaccine in the sheep industry and the potential seriousness of accidental self-inoculation. Further information is available from the Poisons Information Centre (tel: 13 11 26) or Pfizer Animal Health Veterinary Services (tel: 1800 814 883). Lessons from practice Accidental injection of the skin or exposure of the skin surface or a mucous membrane to an oil-based animal vaccine may cause a severe local, or occasionally systemic, reaction. Redness after exposure to vaccine material may indicate a granulomatous reaction with associated necrosis, rather than infection. Necrosis or apparent abscess requires early surgery to remove necrotic tissue and any remnants of the vaccine material. Despite debridement, prolonged morbidity may occur. 3 Administration of sheep vaccine for ovine Johne’s disease Note vaccine and syringe slung from neck. ◆ 4 Recommended treatment following accidental self-inoculation with ovine Johne’s disease vaccine Category 1 injury (superficial skin exposure). Simply wash the contaminated area. If vaccine material is splashed onto mucosal surfaces (eg, eyes), there is greater risk of a local adverse reaction, and topical corticosteroids should be considered. Category 2 injury (simple needle-stick injuries without injection). Treat symptomatically (eg, wash skin, ensure appropriate tetanus cover, prescribe topical corticosteroids and oral antibiotics to prevent opportunistic infection). Category 3 injury (injection of vaccine material). Acute pain and inflammation are usually evident within 24 hours. Perform early surgery and drainage to remove the oil-based vaccine material before it spreads or elicits a severe granulomatous reaction. Category 4 injury (lesion that has progressed to necrosis or granulomatous ulceration). Perform surgical debridement to remove any residual vaccine material. Skin grafting may ultimately be required.

Graeme D Richardson MB BS, FRACS, FRCS · Ian I Links BVSc, DipBact · Peter A Windsor BVSc, PhD

Although children in Australia generally have good health, some alarming indicators of poor health and wellbeing exist, which are related to major socioeconomic discrepancies. The pathways connecting socioeconomic disadvantage to child health outcomes are complex and poorly understood. Reducing social disadvantage requires strategies beyond the health arena, involving political, moral, cultural and economic initiatives. Developing “social capital” — cohesion in communities, a sense of belonging and involvement in community affairs — may be a key strategy in improving health indicators. Overseas studies of early intervention and home visiting programs in early childhood have shown improvements in child health and development outcomes. Similar programs have been introduced in Australia and face considerable challenges in their widespread roll-out and evaluation. Health professionals need to develop practical ways to interact with community programs and thus improve social capital.

Karen J Zwi FRACP, MRCP, MSc · Richard L Henry MD, FRACP

To the Editor: One of the great privileges in practising obstetric medicine is to support a couple through a successful confinement when they have previously been advised against attempting pregnancy because of pre-existing maternal disease. However, in some cases, pregnancy carries a substantial risk of morbidity and mortality to both the mother and infant. Indeed, many maternal deaths in Australia are still preventable,1 and underlying cardiac disease is an important cause.2 Recently, I was consulted for preconception counselling by a young woman with dilated cardiomyopathy. Based on the limited evidence in the literature, her risk of dying as a result of pregnancy would be greater than 25%.3 Similarly, I was recently involved in the care of a young woman with Eisenmenger syndrome who elected to terminate her pregnancy due to the 50% mortality associated with pregnancy with this condition.4 Pregnancy in young women with moderate renal failure carries a significant risk of permanent decline in renal function, along with a high risk of intrauterine growth retardation and prematurity for the baby.5 Organ transplantation offers the best hope for women in this situation, as pregnancy outcomes are excellent after solid organ transplantation (with the exception of lung transplantation). However, many women have organ dysfunction severe enough to compromise pregnancy outcome, but not to warrant transplantation.6 Pregnancy in the presence of maternal disease may also pose a substantial cost to the community. A 2001 study in the United Kingdom estimated the mean cost of pregnancy care for five mothers with severe cardiac disease to be £23 000, not including the cost of neonatal care.7 One mother and one baby died. Options for couples with pre-existing maternal disease are limited. In Queensland, they are excluded from adopting a child because they are not infertile and because of the mother’s medical condition. Altruistic surrogacy would allow them to have a child that is genetically their own without risking the mother’s and infant’s health. However, legislation on surrogacy varies significantly between Australian jurisdictions (Box),8 and, in Queensland, all surrogacy arrangements — both commercial and altruistic — are illegal. Thus, my patient with dilated cardiomyopathy faces prosecution if she were to attempt surrogacy anywhere in Australia while a Queensland resident, whereas it would be freely available to her if she moved 80 km south and became a New South Wales resident. I believe altruistic surrogacy should be available for women in whom underlying medical conditions result in a significant risk of morbidity or mortality associated with pregnancy. Legislation on surrogacy arrangements in Australia* Queensland: The Surrogate Parenthood Act 1988 (Qld) makes all arrangements relating to surrogacy illegal in Queensland, imposing criminal penalties on all parties involved in both altruistic and commercial surrogacy arrangements. Tasmania: The Surrogacy Contracts Act 1993 (Tas) makes it an offence to make or receive a payment or to publish any advertisement in relation to a surrogacy contract. All surrogacy contracts are void and unenforceable. South Australia: The Family Relationships Act 1975 (SA) makes it an offence to enter into a surrogacy contract for valuable consideration, and contracts are illegal and void. Australian Capital Territory: The Parentage Act 2004 (ACT) does not prohibit non-commercial surrogacy, provided no advertising or intermediaries are involved, and payments to cover expenses are allowed. Victoria: The Infertility Treatment Act 1995 (Vic) prohibits commercial surrogacy, and has complex criteria regarding eligibility of surrogate mothers. * New South Wales, Western Australia and the Northern Territory do not have surrogacy legislation.

Adam P Morton

Comment: Morton feels that women for whom pregnancy poses a substantial risk should be offered altruistic surrogacy, so that they can still have a child that is genetically their own. The suggestion is commendable but opens a hornets’ nest. First, “genetic ownership” is a bit of a fiction at best, given that the only item genetically owned by the mother is an egg with 23 chromosomes and some cytoplasm. Admittedly, Morton refers to couples rather than to women, but few are the men who have incontrovertible evidence of any genetic stake in their alleged offspring,1 and, given the rate with which partnerships change, thousands willingly care for children in whom they know they have no genetic stake at all. After implantation of the fertilised embryo, the carrier of the pregnancy owns whatever there is to be owned, irrespective of where some of the genes came from. At birth, genetic ownership changes again, and the child becomes its own “genetic owner”. So, how much “genetic ownership” of a child can there be? Second, who would qualify for altruistic surrogacy? It seems reasonable that women with Eisenmenger syndrome should not embark on a pregnancy given the high mortality associated with it. But how do we know that collecting ova and all it entails, and the subsequent years caring for a baby/toddler/child/teenager, would not be an even greater challenge to the woman’s health than pregnancy? Third, where will these surrogates come from (especially for women without sisters or other suitable family volunteers), and how do we ensure that they will be happy to hand back the child to its “genetic owners”? How will we protect these altruistic women in subsequent years against potential law suits for alleged failures in duty of care to the child that they carried (for example, by exposure to toxins during the pregnancy)? Fourth, is there not a far easier and more logical solution to this problem, provided that egg collection does not endanger the woman’s health? Why not preserve the woman and her partner’s frozen embryos until the woman’s medical condition is sufficiently stable to both sustain a pregnancy and care for the child that hopefully results from it? If the woman’s health cannot be restored sufficiently to achieve this, these couples could then show some altruism of their own by donating the embryos to infertile couples who desperately want a child irrespective of whether they can claim “genetic ownership”. Thus far, there is little evidence that altruistic donation and genetic ownership are even half way to meeting each other.2 However, Morton should be commended for drawing attention to a national problem in women’s health. The disparities and discrepancies between the Australian states and territories in almost anything that relates to reproduction2-5 is an utter disgrace. Reproductive health should be equitable among all Australians.

Marc J N C Keirse

To the Editor: Osteonecrosis of the jaw, recently reported in patients treated with bisphosphonates, may be analogous to the historic occupational disease “phossy jaw”.1,2 Phossy jaw was osteonecrosis of the jaw caused by exposure to white phosphorus during the manufacture of matches. “Lucifer” strike-anywhere matches were first produced in 1833. They were made by dipping the match ends into a mixture containing white phosphorus.3 Workers were exposed to fumes from the white phosphorus during mixing and spreading of the dip material, and dipping, drying and boxing of the matches.3,4 The first case series, comprising 22 cases, was reported in Vienna in 1845.5 About 11% of those exposed developed the disease.5 The average period from first exposure to diagnosis was 5 years.4,5 Occasionally, this period was as short as a few months.5 The mandible and maxilla could be affected, the mandible in 60% of cases (Box).3 Dental decay was considered a prerequisite, and preventive measures included dental surveillance and treatment within the factories.4 In that pre-antibiotic era, phossy jaw was fatal in about 20% of cases, usually because of septicaemia or meningitis.5 Donald Hunter, British doyen of occupational medicine, commented: “It was the most distressing of all the occupational diseases because it was very painful and was accompanied by a foul fetid discharge that made its victims almost unendurable to others. It was obstinate and chronic, the treatment was agonising and the final result was a distressing disfigurement. It was this disfiguring effect plain to every observer that made phosphorus poisoning so notorious and led to determined efforts for its abolition in every civilised land.”5 In 1906, several European countries banned the manufacture and importation of white phosphorus matches at the Berne Convention.4,5 A safe substitute, sesquisulfide, had been discovered by a French chemist and successfully used for manufacture of strike-anywhere matches in 1898.4,6 In the United States, John Andrews published a report in 1910 of 150 cases of phossy jaw from 15 of 16 match factories then in operation.4,6 The Diamond Match Company, which held the American patent rights for sesquisulfide, waived their rights, thereby allowing the entire US match industry to use this alternative.6 Congress then passed the Esch law, which imposed a prohibitive tax on white phosphorus matches and banned their import and export.4,6 Eventually safety matches were developed that used amorphous red phosphorus, which did not have the toxic properties of white phosphorus.5 Phosphorus necrosis of the jaw A Deformity resulting from excision of entire lower jaw in a case of phosphorus necrosis. (Case of Dr John P. Andrews, The Occupational Diseases, W Gilman Thompson, D Appleton & Co, New York, 1914). B Phosphorus necrosis of entire lower jaw excised by Mr McCarthy in 1884 (London Hospital Medical College Museum).

A Michael Donoghue

Peter W Holmes,* David Armstrong,† Nicholas Freezer‡ * Deputy Director, Adult Respiratory Medicine, † Director, Paediatric Cystic Fibrosis Unit, ‡ Director, Adult and Paediatric Respiratory Medicine, Department of Respiratory and Sleep Medicine, Monash Medical Centre, Locked Bag 29, Clayton, VIC 3168. peter.holmesATsouthernhealth.org.au To the Editor: We congratulate Lam et al1 for identifying the major problems in transferring adolescents from the Royal Children’s Hospital, Melbourne, to adult care. The article and the accompanying editorial2 address a difficult problem relating to the transfer of adolescent patients from a stand-alone paediatric hospital to adult services. Lam et al conclude that there needs to be a change of attitude among adult physicians, and recommend the provision of additional resources to enhance the smooth transition to adult care. As long as paediatric services remain geographically separated from their adult counterparts in stand-alone hospitals, these problems will continue, regardless of any increase in resources. In New South Wales, tertiary paediatric services have now been incorporated onto the same campus as tertiary adult hospitals in shared-site arrangements. This facilitates the transition process, as adult physicians are more closely linked to their paediatric colleagues via shared clinical and research infrastructures. Such close cooperation allows paediatric and adult physicians to share their care during transition and provides the adult physicians with full access to the patients’ medical records and radiology, microbiology, laboratory and pulmonary function data. At Monash Medical Centre, we have taken this further by totally incorporating our adult and paediatric services into one single Department of Respiratory and Sleep Medicine. This arrangement allows an integrated approach to childhood, adolescent and adult care. The combination of services generates trust between all members of staff (an issue raised in the editorial2) and gives adult physicians a greater understanding of the needs of adolescents with complex health problems. One solution to the difficult problem of transition to adult care is to phase out stand-alone paediatric services with their own costly management infrastructure. A shared campus arrangement allows greater integration of the full range of tertiary paediatric and adult services and offers many advantages in providing a seamless transition to adult care.

Peter W Holmes · David Armstrong · Nicholas Freezer

Robert D Henderson,* Pamela A McCombe* * Neurologist, Royal Brisbane and Women’s Hospital, Herston Road, Herston, QLD 4029. Robert_HendersonAThealth.qld.gov.au To the Editor: We read with interest the recent article by Kiernan.1 Many patients with motor neurone disease (MND) are also taking complementary therapies, with the potential for drug interaction with riluzole. A recent patient highlighted this. A man in his 50s with progressive MND commenced riluzole at the time of diagnosis. Initial liver function tests performed after starting the drug gave normal results. Eight months later, with disease progression, he began taking low-dose naltrexone 50 mg dissolved in 50 mL of water, of which he took 4 mL a day. Three months later, he began to feel nauseous, with debilitating lethargy, and developed jaundice. Liver function tests showed: alanine aminotransferase level, 3030 U/L; and asparate aminotransferase level, 2074 U/L. On stopping taking both drugs, his symptoms resolved and the liver function test results gradually became normal. No other contributing cause for the hepatotoxicity was found. From the temporal profile, the hepatotoxicity in our patient was possibly due to the combination of riluzole and naltrexone, although either drug alone could be implicated, or there may have been another mechanism. Riluzole is predominantly metabolised by cytochrome P450 enzymes (CYP1A2), but there is considerable patient variability, and the hepatotoxicity mechanism is largely unknown2 (see also MIMS Online: http://www.mims.hcn.net.au). In recent months, low-dose naltrexone has become popular with patients who have MND, although there are no published data of efficacy. Hepatotoxicity caused by naltrexone is dose-dependent and uncommon.3 Naltrexone is metabolised by glucuronidation in the liver to an active metabolite, but a direct interaction with riluzole through cytochrome P450 enzymes appears unlikely.4 There have been no clinical studies to evaluate interactions with other drugs of either riluzole or naltrexone (apart from opiates).3 This case highlighted for us that patients may be taking other therapies for MND, and that clinicians should be aware of the possibility of serious drug interactions when riluzole is prescribed.

Robert D Henderson · Pamela A McCombe

In reply: Henderson and McCombe describe a patient to highlight an issue raised in a recent editorial:1 that patients with motor neurone disease (MND) may develop abnormal liver function tests for reasons other than riluzole therapy. In their patient, riluzole was prescribed for a year and liver function test results remained stable. Deterioration in liver function coincided with the introduction of naltrexone. Ultimately, riluzole, an established MND therapy, had to be ceased. Naltrexone is an authority medication, prescribed in the setting of alcohol or opioid dependence. MEDLINE searches failed to find any study or indication for naltrexone in the treatment of MND. An internet search, however, revealed a number of personal anecdotes, with a curiously Australian emphasis, suggesting an immuno-modulatory role for naltrexone in MND. A few further clicks of the mouse and the naltrexone ordering site with costings appeared. Patients with incurable diseases commonly seek “alternative” treatments2 at great personal financial cost, calculated at thousands of dollars per patient with MND.3 Often there is insufficient, or, as with naltrexone, no evidence that these treatments are effective.4 Most patients with MND will consider alternative therapy, irrespective of their educational background5 or understanding of disease pathophysiology. How each physician approaches the use of complementary and alternative therapies by their patients may develop into an important issue in the therapeutic relationship. Certainly, being aware of the possibility may prove critical. In the patient described by Henderson and McCombe, an unfortunate outcome of irreversible liver failure in a patient with NMD was averted through conventional monitoring of liver function.

Matthew C Kiernan

To the Editor: Forder et al conveyed that trials without allocation concealment have the potential to mislead.1 However, it is not true in any meaningful sense that “Without exception, allocation concealment is achievable in all randomised clinical trials. In contrast, it is not always possible to blind people to study treatments received.” Rather, “Masking may be defined as either the process (researchers not revealing treatment codes until the database is locked) or the result (complete ignorance of all trial participants as to which patients received which treatments). A masking claim indicates only the former . . . If masking is possible only some of the time, then clearly reference is being made to the result, and not the process. To be fair, then, one would have to ask if the result of allocation concealment is always possible . . . only the process of allocation concealment, but not its result, can be ensured.”2 Forder et al also state that certain methods (including sealed envelopes) are considered to be adequate concealment methods. Sadly, this is true, but only if the emphasis is on the word “considered”, because sealed envelopes are both imperfect at preventing direct observation of future allocations and useless at preventing the prediction of future allocations, even without direct observation. Because the extent of prediction depends on the specific restrictions used on the randomisation,3 allocation concealment is not even a binary phenomenon, and so to truly assess allocation concealment in a given trial, one must ask how much prediction is possible in that trial. Allocation concealment is perfect if no observation or prediction is possible, and only partially effective if some prediction is possible. Many trials use randomised blocks, and smaller block sizes tend to allow for substantial prediction.3-5 So, while methods aimed only at preventing the direct observations of future allocations may be considered to be adequate, it is clear that in reality they are not. That the authors failed to use this opportunity to set the record straight indicates their implicit agreement with the incorrect statement that methods aimed only at preventing the direct observations of future allocations are not only considered adequate, but actually are adequate. Pretending that allocation concealment is binary, and hence that it suffices to use methods aimed only at preventing the direct observations of future allocations, represents ignorance that may be bliss, but certainly is not harmless.

Vance W Berger

To the Editor: In their article on controlled trials, Forder et al1 described the trial by Karlowski et al on vitamin C and the common cold2 as an example of how patients’ or investigators’ preconceptions about the value of the treatment may affect a trial’s results. However, their presentation of this trial is misleading in two respects. Firstly, the Karlowski et al trial was reanalysed and the “placebo-effect explanation” of the original authors was shown to be erroneous.3 For example, their subgroup analysis of “blinded” and “non-blinded” participants excluded 42% of all episodes of colds, even though the subgroups were presented as complementary; numerous further problems are detailed elsewhere.3 Thus, the trial by Karlowski and colleagues cannot be seen as an example of the placebo effect in action. The concept of large and omnipresent placebo effects can be traced back to an early article by Beecher, who chose “15 illustrative studies” covering such conditions as, “severe postoperative wound pain, cough, headache, seasickness, etc.”4 Beecher calculated that the “average placebo-effect” was 35.2% (SE, ± 2.2%). However, these studies did not use a control group. The comparison was “before–after”, which is affected by the regression to the mean phenomenon as most of these conditions are self-limiting. Thus, Beecher’s studies did not measure the “effect” of placebo. A recent meta-analysis of 114 trials comparing a placebo group with a no-treatment group found no evidence of placebo effect on binary outcomes, and only a rather small effect on pain, thus disproving Beecher’s notion of great and universal placebo-effects.5 This empirical evidence was disregarded by Forder and colleagues. Although there are reasons to use placebo whenever practicable, the bias caused by the absence of a placebo control should not be exaggerated, and the “placebo effect” should also not be misused to support investigators’ own preconceptions.3 Secondly, the trial by Karlowski et al was focused on the effect of vitamin C on the common cold,2 and thus the “placebo effect explanation” in this particularly influential trial is crucial to the biological question. A recent meta-analysis of 55 placebo-controlled trials found that regular vitamin C supplementation had no effect on the incidence of colds in the general population (relative risk [RR], 0.98; 95% CI, 0.95–1.00), but reduced the incidence of colds in people exposed to substantial physical or cold stress (RR, 0.50; 95% CI, 0.38–0.66).6 Also, regular vitamin C intake reduced the duration of colds in adults by 8% (95% CI, 3%–13%) and in children by 13.5% (95% CI, 5%–21%). Although further studies are needed to evaluate the practical significance of these findings, it is evident that the interpretation by Karlowski and colleagues that the effect of vitamin C on the common cold may be explained by the break in the double blind2 is false and should not be reiterated.

Harri Hemilä

Peta M Forder,* Val J Gebski,† Anthony C Keech‡ * Statistician, † Principal Research Fellow, ‡ Deputy Director, NHMRC Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450. enquiryATctc.usyd.edu.au In reply: Allocation concealment refers to ignorance of future treatment assignment before randomisation whereas masking or blinding is most commonly used to refer to the concealment of treatment assignment after randomisation.1 There are two criteria for successful concealment of allocation: (i) physical concealment of the process of random assignment to treatment, and (ii) concealment of any pattern of consecutive assignments. Successful concealment of the process must prevent unauthorised access to randomisation lists, envelopes or algorithms; the best way is to use a centralised or remote service for randomisation, whereby an independent party other than the clinician or investigator accesses a secure sequence list or a secure computer system to generate the next allocation.2,3 Successful concealment of the pattern of random assignments prevents investigators from predicting a future treatment assignment on the basis of pattern recognition of allocations to date. Identifying a pattern of previous allocations can occur in open-label trials, in which all parties are aware of allocated treatments after randomisation, or if the blinding of patients and investigators has been compromised. The likely success of concealing the allocation process can reasonably be judged by its description in most trial reports (usually found in the Methods section). However, it is usually more difficult to assess the likelihood that investigators could have predicted future allocations. Unsuccessful concealment of treatment assignment after randomisation (masking or blinding) should be detailed in the trial report. In circumstances where the blinding has been substantially compromised, exploring the results of treatment separately among participants who were unblinded and those who remained blinded, should be considered, although these are no longer randomised comparisons. In the study by Karlowski et al,4 the placebo did not match the active treatment in taste, which alerted the investigators to the likely occurrence of significant unblinding within the study. To their credit, the investigators sought to quantify the extent of unblinding by means of a questionnaire at study close-out, and reported their findings by results of these responses. The particular grouping of responses, however, has been the subject of some discussion,5,6 and while the interpretation of a possible placebo effect has been challenged, it has not necessarily been disproven. (The absence of a placebo effect could be proven only if information concerning perceived benefits of vitamin C related more to cold frequency than cold symptoms. Biologically, it is far more plausible for a placebo effect to result in fewer cold symptoms reported than fewer colds reported.) This trial highlights the impact of compromised blinding in the reporting of trial results, emphasising the importance of maintaining adequate blinding for reliable and unbiased trial results. Good quality reporting of trials, in accordance with the CONSORT statement,7 includes describing the processes in enough detail to assure readers that any pattern of randomisation is not predictable. Authors should report issues relating to allocation concealment, blinding (where appropriate) and randomisation sufficiently to convey the message that these essential trial principles were successfully achieved.8

Peta M Forder · Val J Gebski · Anthony C Keech

H Patrick McNeil,* Michael C Grimm† * Associate Dean (Medical Education), South Western Sydney Clinical School, † Associate Professor of Medicine, St George Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2052. p.mcneilATunsw.edu.au To the Editor: We read with interest the article by Koczwara and colleagues proposing a national exit examination for all Australian medical school graduates.1 It is refreshing to see interest in educational outcomes, a distinctly different trend from earlier reforms that shifted curricular focus from content to the learning process, exemplified by problem-based learning (PBL). Although the early process-focused programs were based on sound pedagogy current at their time, their educational outcomes have been relatively disappointing, with marginal or no demonstrable improvements in knowledge structures, clinical skills, or generic capabilities such as self-direction.2 Rather than an indictment of PBL, the results may reflect what was missing in those programs: explicit focus on educational outcomes, alignment of assessments with outcomes, and attention to the learning environment. There is widespread agreement on the outcomes desired by medical schools. They include teamwork, effective communication, critical evaluation and reflective practice, as well as more traditional outcomes.3 Unfortunately, assessment methods have been slow to match curricular reforms, as these outcomes require new approaches, such as group and assignment work, peer assessment and portfolio examination, which are only now emerging in Australia.4 A national exit examination for Australian graduates is unlikely to adequately measure this range of outcomes. While Koczwara and colleagues recognise that a national examination “might need to include a clinical component” and “would necessarily entail the explicit statement of professional values and expectations”, they support a multiple-choice question examination, suggesting such performance “can correlate well with clinical skills and future performance in multiple disciplines”.1 While this might “complement rather than replace” other medical school assessments, the message sent by its failure to address personal and professional attributes would be invidious. In recognition of the limitations of multiple-choice questions, national examinations in North America now include a clinical component.5 This has major resource implications and, like all high-stakes assessments, uses relatively reliable, but much less valid measures — standardised or simulated clinical encounters. This is at odds with current initiatives in medical schools, which are moving to clinical assessments with higher face validity, such as the mini-CEX (mini-clinical examination exercise).6 It would be near impossible to adequately measure generic outcomes, such as teamwork, communication and reflection, in a single national examination. Koczwara et al recognise that insufficient attention has been paid to ensuring that achievement of educational outcomes is embedded in reform of medical curricula. Their solution is overly simple for a highly complex set of issues.

H Patrick McNeil · Michael C Grimm

Christopher Lawson-Smith Surgeon, and Surgical Examiner, Australian Medical Council, 1/10 McCourt Street, Leederville, WA 6007. lawsmithATbigpond.net.au To the Editor: Foreign medical graduates sitting for the Australian Medical Council (AMC) examinations are expected to achieve a standard comparable to that of Australian medical students. If we do not measure the level of knowledge and problem-solving ability nationally, there is no reasonable basis for presuming that the AMC examination is fair. A uniform examination-based assessment should be passed by all potential medical practitioners before registration in Australia. I would be in favour of a national exit examination.1

Christopher Lawson-Smith

To the Editor: The recent article by Koczwara and colleagues proposing a national exit examination for medical students1 prompted me to recall a 1970 trial of a national examination in surgery.2 Seven of the then eight medical schools participated. Interstate differences were wide for some questions; separate analyses of the 15 teaching hospitals showed variation to be even wider within a university than between universities. Do local differences still undermine the validity of a national examination? It is still uncertain what is actually tested by questions on paper. Context-free, standardised questions and answers assume clinical teaching and practice are standardised. However, clinical teachers writing examination items know well that many colleagues choose the “wrong” answer. Consensus may be imposed on those who differ. Teachers then forget their disparity, but expect candidates to choose only one “true” answer! Clinical performance is interactive, multifaceted, situation-specific and value-laden. Complex judgement and decision-making cannot be measured by ticking predetermined boxes. Clinical experts develop personal subsets of specific evidence, and seek different data for diagnosis and management. But separate, context-free tasks, as in an objective structured clinical examination (OSCE), naively assume they do not.3 OSCE even standardises scoring; examiners become recorders rather than assessors. Reductionist standardisation reflects a pseudoscientific attempt to apply objectivity, consistency and precision to complex human interactions around incomplete evidence and uncertainty, approximations, judgements, trade-offs and locally-determined decisions.4 Internal consistency of measuring instruments does not confer external validity in real world clinical practice. The inexorable growth of medical knowledge and technological opportunities continuously expands “what every doctor should know”. Medical learning today embraces a mix of science-based, problem-based and work-based learning experiences, with community-based experiences5 increasingly included. In their recent article, Koczwara and colleagues identified gaps in oncology education,2 a field ranging from molecular processes to euthanasia. Is oncology managed and taught consistently across different medical schools and hospitals across Australia? Which facets would you test in a national exit examination?6 Clinical performance today includes patient/person management, case management, health system management and self-management. Clinicians can judge student performance consistently. However, formal clinical examinations lack the range of cases and open-ended time that allow examiners to observe all the patient-care skills espoused by today’s curricula.7 Assessment of performance in case management and procedural skills within hospital practice can be conducted simpy by paired examiners.8

Ken Cox

In reply: We appreciate the insightful responses to our proposal.1 Lawson-Smith alludes to one of the most significant justifications for a national examination — fairness. One cannot expect foreign medical graduates to attain a standard comparable with that of Australian graduates if we do not measure this standard. We propose that we owe fairness not only to foreign graduates coming to Australia, but also to Australian medical students who have a right to confidently expect an education that will lead to similar knowledge, skills and attitudes, irrespective of which university they choose. And finally, we owe fairness to society, which would also expect the same standards of graduates irrespective of where they come from. Unless we consider what are acceptable standards, we operate within an environment where standards of outcome differ from place to place and as we do not measure outcomes uniformly, we do not know how they differ nor have a system to address potential deficiencies. McNeil and Grimm point out that medical education has focused less on outcomes and more on process, and raise concerns that assessment methods lag in the sophistication necessary to assess outcomes. We wonder whether the reason for this lack of sophistication lies in the relative lack of interest in this field, and also in the lack of agreement on what constitutes acceptable outcomes. The process of outcome assessment is indeed complex, and the first step is national consensus on appropriate outcomes to be uniformly achieved. McNeil and Grimm also point out that some of the desirable outcomes, such as teamwork, effective communication, critical evaluation and reflective practice, may be harder to test than medical knowledge. While this is certainly the case, reliable assessment methods do exist, such as the Moral Judgment Interview2 and Rest’s Defining Issues test.3 The mini-CEX (mini-clinical examination exercise) that McNeil and Grimm refer to, allows testing of judgement, professionalism, communication, organisation and efficiency.4 Cox questions whether a written examination can test the complex judgement and decision-making process that is better tested in the clinical setting by experienced clinicians. We propose that the national examination is not meant to replace clinician-based assessments and ongoing learning and feedback. Furthermore, a national examination does not need to be conducted only in the written form. Specialty exams already conducted nationally incorporate a clinical element and are conducted in multiple locations. The main objective of a national examination is to ensure the comparison of outcomes against agreed acceptable national standards. This objective should not impose specific limitations on the structure of the examination. Cox warns of the risk of “reductionist standardisation” and asks whether oncology is taught consistently across different medical schools in Australia. We acknowledge that uncertainty is ever present in medical decision-making, but remain hopeful that there exist core knowledge, skills and attitudes that patients can expect and that can provide a foundation for national standards. Oncology is not taught consistently across different medical schools in Australia today. While its mode of delivery may differ, we propose that its outcomes should not. And we hope that agreement on national outcome standards and a national process of assessment of these outcomes will be a first step in achieving that objective.

Bogda Koczwara

A 20-year old woman presented with a history of frequent epistaxis (from 10 years of age) and bleeding from the tongue (from 8 years of age). She also reported breathlessness on exertion, along with cyanosis and bulbous deformity of the fingers since 4 years of age. There was no history of bleeding from any other site or of a similar illness in the family. On examination, the patient had cyanosis and clubbing (Box 1), and a lumpy tongue (Box 2) suggestive of tongue telangiectasia. A chest x-ray showed left mid-zone opacity (Box 3), which was confirmed to be a pulmonary arteriovenous malformation (AVM) on spiral computed tomographic angiography (Box 4). Transcutaneous embolotherapy produced a marked improvement in her symptoms. The patient is currently asymptomatic and undergoing regular follow-up. The patient has hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu disease), an autosomal dominant disorder related to mutations on chromosomes 9 and 12. Clinical diagnosis is based on the findings of epistaxis, telangiectasia, visceral AVMs and family history. Fulfilling three of these criteria indicates a definite diagnosis; two, a possible case. In our patient, the presence of three of the four manifestations confirmed the diagnosis. Pulmonary AVMs are found in 14%–30% of patients with this disease.1 A family history of the disease may not be present in all cases, owing to de-novo germline mutations. As these occur more frequently in later cell divisions during gametogenesis, siblings are rarely affected. 1 Cyanosis and clubbing in a patient with Osler–Weber–Rendu disease 2 Tongue telangiectasia as a manifestation of the disease 3 Chest x-ray showing left mid-zone opacity (arrow) 4 Spiral computed tomographic angiogram This confirmed the presence of a pulmonary arteriovenous malformation (small arrow) with a large feeding vessel (large arrow).

Ritesh Agarwal MD, DM · Ashutosh N Aggarwal MD, DM · Dheeraj Gupta MD, DM

Medical complications during pregnancy. 6th ed. Gerard N Burrow, Thomas P Duffy, Joshua Copel (editors). Philadelphia, Penn: Elsevier Saunders, 2004 (xiv + 565 pp). ISBN 0 7216 0435 8. Over the last 50 years maternal mortality reports have shown a rearrangement of the causes such that, in more developed countries, maternal medical disorders are now the dominant contributors. The statistics for severe obstetric morbidity demonstrate the same predominance of “medical” afflictions. This has occurred partly because of dramatic improvements in the management of obstetric conditions, but also because the pregnant population is ageing, and many more women with medical problems now chance pregnancy. It is no longer surprising when a 40-year-old obese smoker with type 2 diabetes, hypertension, ischaemic heart disease and renal impairment presents late in the first trimester for antenatal care! The complexities in the management of such patients — medical, pharmacological, obstetric, laboratory and psychological — comprise the subject matter of this worthwhile text. It is directed at physicians, obstetricians and general practitioners and covers amply the full range of medical problems seen in pregnancy. In a large multi-authored text, editorial oversight is important to maintain uniformity of style and distribution of priorities. There has been some laxity here, with idiosyncratic chapter length, detail in coverage and placement of topics. The chapter on pulmonary disease is more than three times the length of that covering renal disease. This does not reflect clinical reality. Eclampsia is dealt with in the neurology chapter rather than with pre-eclampsia, and cholestasis of pregnancy is detailed correctly in the liver chapter, but also at length in the dermatology chapter. A detailed scientific treatise on the immunology of pregnancy has no practical utility, and need not appear in this clinical text, and the impassioned coverage of smoking in pregnancy appears in the “Pulmonary” rather than “Substance Abuse” chapter. However, the full gamut of medical disturbances that are seen in pregnancy is well covered. Appropriately sandwiched between “Genetics” and “Emergency management” is a discourse on “Ethical issues in obstetrics”. Though interesting, it has no specific relevance to the book. A chapter dealing specifically with implications for the infant of maternal medical disease would have been more useful. Most physicians see few pregnant women and most obstetricians left internal medicine years ago. This text will be helpful for practitioners in either field who find themselves in unfamiliar territory. Barry N J WaltersObstetric Physician King Edward Memorial Hospital and Royal Perth Hospital, WA

Barry N J Walters

Communication for doctors. How to improve patient care and minimize legal risks. David Woods, editor. Oxford: Radcliffe Publishing, 2004 (xi + 125pp). ISBN 1 85775 895 1 This is a multi-authored book, and I thought it interesting that only five of the 12 authors are doctors. However, the non-doctor authors seem to have a good feel for the absolute importance of communication in the realm of medicine. The book is divided into 66 short “chapters”, each of one to three pages. All the chapters deal, almost exclusively, with communication — all the way from patient–doctor communication to the importance of the office receptionist communicating with the patient, and how to handle yourself with the media. It’s easy reading. The titles of each of the chapters tell almost the whole story, for example: “Hippocrates was right: treat people, not their disease” and “How non-verbal communication can give patients a sense of connectedness”. Other chapters include: “Thirty ways to make your practice more ‘patient-friendly’”, “Answering questions patients don’t ask”, “Making sure your language doesn’t mystify patients”, “Elevator etiquette: when is communication too effective?”, “Let’s hear it for sounder listening skills!” and “Strategies for not appearing rushed”. Most of us doctors learn the importance of communication through experience but I do think that if you can pick up a titbit here and a shortcut there, each of these can save you time while improving the quality of medicine you practice. You can never know too much about how to handle complaints from a patient or how to deal with an angry patient, and there are a couple of good chapters on these problems, which all doctors face. The final eight chapters deal with minimising legal risks, and when living in a litigious society, you can’t know enough about how to avoid any pitfalls. There are some “pearls” in every chapter of the book, and as I was reading, I did think that the reader could learn a lot in a short time by just leafing through the pages if these pearls were highlighted in some way within or at the end of each chapter. Even though I have a special interest in patient–doctor communication, I found this book to be helpful, with some aspects I haven’t previously considered. The book would be of especial value to course directors in academic medical centres in gathering ideas for sessions on improving communication. Edward C Rosenow IIIEmeritus Professor of Medicine Mayo Clinic College of Medicine, USA

Bernard Amos, former Director General of Health in New South Wales and founding General Superintendent of Westmead Hospital, died on 9 May 2005. Bernie was born in Townsville on 5 April 1935. He attended secondary school at “Shore” (Sydney Church of England Grammar School) in North Sydney. He became a formidable athlete, representing his school at the top level in cricket (his first love), rugby and athletics. He entered medicine at the University of Sydney in 1953, and began a long relationship with Royal North Shore Hospital (RNSH) as a student in 1956. Initially, he wanted to become a surgeon, but an accident with a blood-transfusion needle damaged a nerve in one hand, and, with characteristic insouciance and competence, he changed direction and completed training as a physician. He moved progressively through the ranks at RNSH, completing his residencies and registrar training and obtaining his Fellowship of the Royal Australasian College of Physicians in 1971. He became Clinical Superintendent at RNSH, and Director of Medical Services in 1964, while continuing to practise as a physician. Although his subsequent career was strongly identified with health administration, he remained a clinician at heart, with a keen understanding of the difficulties and frustrations of the clinical life. A critical moment of his professional life came in 1972, when he joined the Project Committee for the proposed Westmead Hospital. Bernie clearly saw the proposed hospital’s role in providing medical services in Greater Sydney and in New South Wales. Westmead had unobtrusively become the demographic centre of Sydney’s population, and there was a need for high-level teaching hospital services for the Western metropolitan population. His subsequent career took him further into the public domain. He became Chief Executive Officer of the Cumberland Area Health Service in 1986, and then of the Western Sydney Area Health Service in 1988. His public career reached its zenith with his appointment as Director General of the NSW Department of Health in 1989, an appointment he held until 1993. In recognition of his public service, he was made a Member of the Order of Australia in 1988 and an Officer of the Order of Australia in 1994. After his retirement in 1993, he continued to consult on health services and became Professorial Fellow in the Department of Public Health and Nutrition at the University of Wollongong. He was Chair of the Johnson & Johnson Medical Education Foundation and of the Institute of Psychiatry, and Deputy Chair of the Centenary Institute at Royal Prince Alfred Hospital. He had been President of the Medical Board of New South Wales from 1984 to 1989, and returned as a member of the Medical Board from 1993 to 1998. Bernie married Helen Harbison in 1960. Bernie’s public success was balanced by a profound devotion to Helen and their four children. He took great pride in his children’s achievements and loved spending time with his grandchildren. Bernie died of complex malignancy just a few weeks after his 70th birthday. In his largeness, his wisdom, his generosity, his restrained vigour, he seemed unfit for death. We offer his family our deepest sympathy, and our gratitude for sharing him with us and with the Australian community. Miles Little (With much help from the Amos family, Peter Castaldi and other friends)

Miles Little

Re: “Recognition of depression and psychosis by young Australians and their beliefs about treatment”, by Annemarie Wright, Meredith G Harris, John H Wiggers, Anthony F Jorm, Sue M Cotton, Susy M Harrigan, Rosalind E Hurworth and Patrick D McGorry, in the 4 July print issue of the Journal (Med J Aust 2005; 183: 18-23). There was an error in Box 3 (page 20) under the heading “Rural region A” “Proportion of population”. The population number given as n = 69 786 should have been n = 41 618. The html and pdf versions of the article published online were correct.

Annemarie Wright · Meredith G Harris · John H Wiggers · Anthony F Jorm · Sue M Cotton · Susy M Harrigan · Rosalind E Hurworth · Patrick D McGorry

Re: “Adult domiciliary oxygen therapy. Position statement of the Thoracic Society of Australia and New Zealand”, by Christine F McDonald, Alan J Crockett and Iven H Young, in the 20 June issue of the Journal (Med J Aust 2005; 182: 621-626). In the section on “Nocturnal oxygen therapy”, the hypoxaemia selection criterion for the study by Chaouat et al (reference 19) on page 623 (column 1) should read “Pao2 56–69 mmHg (7.4–9.2 kPa)” rather than “Pao2 56–59 mmHg (7.4–7.8 kPa)”. The html and pdf versions of the article published online were corrected on 28 June.

Christine F McDonald · Alan J Crockett · Iven H Young

ABCD of TIAs A simple ABCD score, devised and tested by UK researchers, can reliably predict which patients with a transient ischaemic attack (TIA) are most likely to have a stroke within the next 7 days. Patients with a TIA are scored up to a maximum of 6 points depending on: Age (≥ 60 years = 1); Blood pressure (systolic > 140 mmHg or diastolic ≥ 90 mmHg, or both = 1); Clinical picture (unilateral weakness = 2, speech disturbance without weakness = 1, other = 0); and, Duration of symptoms (≥ 60 min = 2, 10{59 min = 1, < 10 min = 0). The higher the ABCD score, the more likely the risk of a stroke within the next 7 days. Patients with a score of 6 have about a 30% risk of early stroke — the researchers say these patients need not only emergency investigation and treatment but also immediate admission to hospital, rather than referral to outpatient services. Lancet 2005; 366: 29-36 Soybean suggestion Soybean protein may have a role in preventing and treating hypertension, say US and Chinese researchers. 1 They conducted a randomised controlled trial in 302 people from three Chinese communities with pre-hypertension or stage 1 hypertension (systolic BP, 130 mmHg to 159 mmHg; diastolic BP, 80 mmHg to 99 mmHg). Subjects were randomised to receive a daily cookie, which contained either 40 g soybean protein or 40 g of complex carbohydrate, for 12 weeks. After 12 weeks, systolic and diastolic BPs had fallen by 4.3 mmHg and 2.8 mmHg, re-spectively, in the soybean protein group. However, both the researchers and editorialists expressed some concern that an increased soy protein intake may be linked to bladder cancer. The editorialists wondered whether an increased mixed vegetable protein intake might produce the same effect on blood pressure as soybean protein.2 1. Ann Intern Med 2005; 143: 1-9 2. Ann Intern Med 2005; 143: 74-75 Friends forever Friends, rather than family, may help the elderly to live longer, according to findings from the Australian Longitudinal Study of Aging. The study followed 1477 people aged 70 years or older for a decade. Those participants with a more extensive network of friends (whom they contacted face-to-face or by phone) had a lower risk of dying during the 10 years of follow-up than other participants. However, social networks made up of children and other relatives did not affect the subsequent survival of participants. J Epidemiol Community Health 2005; 59: 574-579 Trojan dog? “Pet therapy” dogs can acquire and therefore spread methicillin-resistant Staphylococcus aureus (MRSA), suggest UK authors. They reported that an 11-year-old border collie acquired MRSA in a district hospital after visiting care-of-the-elderly wards. Swabs from the asymptomatic dog’s nose, scalp and interdigital folds of the paws had been taken before and after visiting the wards. Only the post-visit swabs grew MRSA. The authors proposed a set of guidelines for preventing the spread of MRSA from pet therapy dogs, including hand disinfection by patients and staff members before and after touching dogs, and pet bathing after visiting. Further, cats should be banned from all clinical areas because of additional risks from the transmission of gastrointestinal tract diseases. J Hosp Infect 2005; 60: 186-188 Seek and treat Treating gestational diabetes — carbohydrate intolerance beginning or first recognised during pregnancy — reduces serious perinatal morbidity, according to the Australian Carbohydrate Intolerance Study in Pregnant Women Trial Group. The Group randomly assigned 1000 women between 24 and 34 weeks’ gestation who had gestational diabetes to receive either dietary advice, blood glucose monitoring and (as required) insulin therapy or routine care. Only 1% of the infants of women in the intervention arm experienced a serious perinatal complication (defined as death, shoulder dystocia, bone fracture and nerve palsy) compared with 4% of infants born to women in the control arm. Women in the intervention arm were more likely to have their labour induced and their infants were more likely to be admitted to a neonatal nursery, however, the caesarean delivery rate was similar in both groups of women. N Engl J Med 2005; 352: 2477-2486 Playstation thumb A young researcher has suggested that “playstation thumb” is a common condition among school-aged children.1,2 Karim, a 7th grade student, surveyed 120 students aged 9 to 13 years at his school in Durban, South Africa.2 In regular players, 8 of 28 boys and 7 of 17 girls suffered symptoms of “playstation thumb”, including pain and blisters of the thumbs. Children who played the games more had more symptoms, especially if they played for more than 3 hours per day. Karim conducted this survey as a project for his school’s Science Day. 1. Lancet 2004; 363: 1080 2. S Afr Med J 2005; 95: 412 Dr Ann Gregory, MJA