Volume 182 Issue 7

Advantages to patients of a single anaesthetic for more than one operation are obvious; attracting generalist surgeons, training them and ensuring they have adequate credentials remain hurdles With the inexorable increase in specialised surgery, the concept of “general” surgeons, what they do, and what they represent, is difficult to categorise. Indeed, is there a need for a generalist surgeon when it seems that most areas of our bodies have a designated subspecialist? . . . credentialling, clinical governance and continuing professional development are of critical importance for the practising surgeon. In this issue of the Journal (page 337), Wilson, a general practitioner–surgeon makes a compelling case for the continuing existence of the general surgeon.1 He presents an affirmative argument through the details of his experience in performing multiple elective surgical procedures on individual patients. Most of the procedures were relatively minor, yet traversed a wide range of subspecialties. The complication rates were low, and there can be no doubt that the patients benefited from a single visit to an operating theatre to have multiple problems treated. Where can a trainee gain experience in many of the minor procedures described by Wilson? Emphasis in tertiary hospitals has traditionally been on major caseloads, yet a veritable gold-mine of minor operative cases are present in day-surgical units. With a little imagination and cross-specialty cooperation, a 6-month term exclusively in a day-surgical unit would provide a trainee with a solid grounding in minor operative surgery. Rotations through regional surgical centres, where general surgical operative lists continue to remain varied,2 would provide another significant learning opportunity for trainees. However, the role of the GP–surgeon in major population centres seems limited, especially in view of credentialling requirements imposed by health care authorities. The issues of credentialling, clinical governance and continuing professional development have been highlighted by the Royal Australasian College of Surgeons (RACS) as being of critical importance for the practising surgeon, and much effort has been invested in formulating policies to reflect this and, in turn, maintain a high standard in surgical care. Who is responsible for ensuring that practitioners who are not fellows of the RACS comply with accepted surgical guidelines? While Wilson describes himself as a “GP–surgeon”, he is a fellow of both the Royal Australasian and Edinburgh Colleges of Surgeons, a factor that would certainly ease the path of credentialling in his case. The ongoing need for GP proceduralists in rural regions is unquestionable, and the various support and training mechanisms have been described at length in the Journal.3 The RACS has clearly outlined the general surgical curriculum.4 It states, “trainees should gain sufficient experience in operative surgery to achieve competency in managing common surgical conditions and emergencies as outlined”, and subsequently lists a comprehensive range of surgical conditions. Currently, most advanced trainees seem to attain competency in a core group of the listed procedures and then move into subspecialty regions, rarely to venture outside their chosen field. The lack of young, qualified surgeons to serve the community in a range of generalist procedures will become magnified by the ageing and eventual retirement of a substantial proportion of the Australian surgical community.5 It is precisely this group of surgeons who, by virtue of previous training and experience, remain adept at a wide range of general surgical procedures. There appears to be an opportunity for senior surgeons, perhaps wishing to step back from on-call emergency work, to become “day surgery specialists” and impart invaluable knowledge and skill to junior colleagues. The concept of a general surgeon able to perform a range of procedures on a single patient under a single general anaesthetic is worthy. While there is no rigorous evidence to prove it, anecdotally, at least, there is a definite need for such individuals within the medical community. The importance of performing minor surgical procedures well needs to be re-emphasised, and while the major cases may have more “lustre” for trainees, it soon becomes apparent during surgical practice that much patient satisfaction can be derived from successfully curing ingrown toenails, carpal tunnel syndrome or anal fissure.

Martin H Bruening FRACS, FRCSEd, MS · Guy J Maddern FRACS, PhD, MD

Environmental strategies must be complemented by behavioural approaches to help children learn to use roads safely In Australia, pedestrian injury is the leading cause of death among 1–14-year-olds.1 In 2000, 38 child pedestrians in this age group died2 and about 1140 (29 per 100 000) were hospitalised, often with lengthy stays, because of injuries sustained when hit by a vehicle.1 These rates decrease with age and are lowest for 10–14-year-olds.1 The most recent comparison with other OECD countries shows that Australia has the 13th lowest pedestrian fatality rate for 0–14-year-olds,3 with slightly more pedestrian deaths among 0–5-year-olds than the median rate for all OECD nations (1.03 per 100 000 versus 0.89 per 100 000).4 The primary predictors of this child pedestrian trauma relate to the interaction between the characteristics of the child and the design and nature of the road environment to which the child is exposed. A Western Australian case–control study of child pedestrians aged 1–14 years identified four key environmental and behavioural factors that independently predicted the likelihood of child pedestrian injury.5 These comprised the volume of traffic encountered by the child, presence of visual obstructions, availability of footpaths on the child’s street of residence, and the child’s behaviour. Predictors also vary according to the age of the child. Whereas 1–2-year-olds are more likely to be hit by a reversing vehicle, the most common cause of pedestrian trauma in 3–9-year-olds is mid-block “dart-out” (entering the road between intersections and not seeing, or misjudging, a gap in traffic).6,7 Pedestrians aged under 10 years are particularly vulnerable because of their small physical size and underdeveloped abilities for dealing with traffic situations, both cognitive (attention focus, interpreting traffic signs) and perceptual (locating sounds, judging speed, peripheral vision).6 Given these limitations, children under the age of 10 do not have the ability to cross roads without adult help. Ten to 14-year-olds are also vulnerable, but more because of their failure to apply safe pedestrian skills than because of their lack of skills. Further, road trauma in this age group may also be associated with general delinquency and problem behaviour.8 Many of these predictors of pedestrian trauma can be prevented or modified and are therefore amenable to intervention.7 While debate continues about the merits of environmental (passive) versus behavioural (active) intervention strategies to reduce this road trauma, evidence suggests that all are necessary, and no single strategy is sufficient.6 A multifaceted approach that combines strategies targeting the behaviour of all road users (including education, training and publicity), the road environment and vehicle design have been found to be the most effective.3 Strategic approaches involving public health, education, health promotion, urban planning, engineering and motor vehicle design are required. Consequently, while efforts are needed to make the road environment safer for pedestrians by reducing the speed and volume of traffic to which they are exposed, it is also necessary for pedestrians (particularly children) to learn how to use these road environments safely. Yet research into behavioural approaches to pedestrian safety has lagged behind environmental research.9 Behavioural programs for children need to be developmentally appropriate and include modelling and training by an adult in a social context and road environments relevant to the child. Programs also need to be interactive and involve problem-solving with consistent and prompt feedback from a caring adult, rather than merely following rules.10 The use of didactic knowledge-only strategies (such as rote learning of rules) is inappropriate, as younger children are not able to generalise this learning to real roads.11 Roadside training and, to a lesser extent, realistic simulations appear to improve visual timing and gap selection, to increase the ability to identify safe and dangerous crossing locations, and to enhance learning of appropriate strategies for crossing at parked cars. Such training has produced positive results with children as young as 5 years.12,13 Several new approaches to children’s pedestrian safety education are being tested. These include programs targeting younger children and adults who care for children, and use of new technologies. Two Australian reviews recommend targeting 0–5-year-olds, arguing that, with good quality pedestrian safety training, young children could demonstrate a rudimentary conception of danger, which improves with age.14,15 Some Australian jurisdictions have developed curricula and materials based on these approaches, such as the Victorian “Starting Out Safely” program. Engaging parents and helping them recognise their important role in their children’s pedestrian safety has the potential to significantly enhance children’s safety on and near roads.14 Parents provide the best role models and one of the only means for children to receive the necessary personalised one-on-one training and to practise crossing real roads. Technologies that use interactive simulations (eg, visual reality computer) coupled with real road experience and “pretend” road practice (the “pretend” road is set up parallel to a real one) can enable children to practise their skills, receive consistent and instant feedback and repetition, and be introduced with careful control to the complexity of traffic.16 While reviews of the impact of behavioural and environmental programs on preventing road trauma in children have demonstrated mixed success, it is apparent that programs need to take a comprehensive preventive approach with modifications to the road environment, enforcement, engineering and education. While much still needs to be done to determine the optimal mix and “dose” of these approaches to reduce child pedestrian trauma, every effort must be made to keep children safe near traffic and roadways that are becoming increasingly busy and complex.

Donna S Cross EdD · Margaret R Hall PhD

Early experience confirms that riluzole improves survival and is well tolerated The recently established Australian Motor Neurone Disease Registry estimates that 1200 Australians are living with motor neurone disease (MND), and 370 new patients are diagnosed each year. Most patients die within 3 years of diagnosis. Aetiological mechanisms implicated in the development of MND have been linked to the glutamatergic neurotransmitter system, with excessive activation of glutamate receptors at the synaptic cleft now believed to trigger destruction of motor neurones.1 This “excitotoxicity” theory of MND gave rise to the development of new therapeutic approaches and, ultimately, clinical trials involving riluzole. This drug was initially thought to act solely as an inhibitor of glutamate release, although subsequent postulated effects include indirect antagonism of glutamate receptors and inactivation of neuronal voltage-gated sodium ion channels. Regardless of the precise mode of action, two large trials in the 1990s established the efficacy of riluzole in the treatment of MND.2,3 A double-blind, placebo-controlled study undertaken in 155 patients with MND showed a significant prolongation of survival and an improvement in functional outcome measures for those treated with 50 mg of oral riluzole twice daily.2 A larger, dose-ranging study undertaken in 959 patients confirmed the beneficial effect of riluzole on survival, being in the order of 3–6 months.3 In the original study,2 the therapeutic effect of riluzole was more prominent in patients with bulbar-onset MND, while the second study found no significant differences in the responses of bulbar- and limb-onset groups.3 Subsequent retrospective analyses suggest a survival benefit even longer than 6 months in both patient groups, but these data have been confounded by recent general improvements in the care of MND patients, particularly the use of percutaneous endoscopic gastrostomy for nutritional support and non-invasive ventilation for respiratory insufficiency, in the setting of a multidisciplinary approach to care.4 Riluzole remains the only medication to slow the progression of a neurodegenerative disease, leading to an increased survival for patients with MND.5 In some countries including Australia, riluzole’s manufacturer had difficulty gaining a listing for the medication on pharmaceutical benefits schemes, in part due to issues related to “quality of life”, despite trial data documenting improvement in patient longevity.2,3 Quality of life is a nebulous measure and the findings using quality-of-life scales in MND clinical trials have proved inconsistent to date.6 After dissecting arguments related to quality-of-life issues, and with intense lobbying by the MND community — patients, clinicians and care groups — riluzole was finally listed by the Australian Pharmaceutical Benefits Scheme (PBS) in June 2003 (see Box for criteria). Linked to the original riluzole trials were studies conducted to establish the safety profile of riluzole in MND patients, including the Riluzole Early Access Program run here in Australia. The primary objective of these open-label, single-treatment studies was to enable patients with MND to receive riluzole therapy pending its commercial availability, health authority approval and, in the case of Australia, listing on the PBS. Through such a process, the safety profile of riluzole was expanded. These later studies established that riluzole was generally well tolerated by patients with MND. Adverse events were predominantly gastrointestinal, with nausea, weight loss and dysphagia being the most frequent,7 although it may be argued that the latter symptoms more likely reflect disease activity itself. Measurement of full blood count before initiation of therapy is suggested, as, rarely, blood dyscrasias may develop with riluzole. As riluzole is metabolised hepatically and significant hepatotoxicity occurs in about 0.2% of patients,7 testing liver function monthly for the first 3 months and then at 3 monthly intervals remains important. However, patients with MND can have or develop abnormal liver function for many reasons other than taking riluzole, including the use of alternative therapies, emphasising the need for baseline measurements before initiating riluzole therapy and withholding the drug if liver function is grossly abnormal (eg, liver enzymes elevated above five times normal). When should MND patients commence taking riluzole? Certainly, any patient with clinically probable or definite MND (based on a combination of upper and lower motor neurone abnormalities in two to three spinal regions) warrants consideration. It could be argued that, given suggestions that patients benefit most from therapeutic intervention in the early stages of MND, the earlier riluzole is started the better. It is inevitable that, by giving riluzole to patients in whom MND is suspected, a few patients in the “possible” and “probable” clinically diagnosed categories will receive this treatment for conditions other than MND, with the correct diagnosis only becoming apparent over time.8 However, given the putative neuroprotective properties of riluzole, this approach has no identifiable drawbacks. Giving riluzole to patients with advanced disease is problematic, and the current PBS guidelines for authority prescriptions of riluzole stipulate that the date of MND diagnosis (disease duration, ≤ 2 years) and the results of respiratory testing (forced vital capacity, ≥ 60%) must be supplied with the initial authority application. Obtaining adequate measures of vital capacity may be difficult in patients with bulbar onset, although the use of face masks in specialised respiratory units may circumvent this difficulty. Finally, patients must be aged ≤ 75 years to qualify for PBS subsidisation, primarily because there is limited information regarding the benefits of riluzole in the older age group.9 Questions remain about the benefits of riluzole on survival in patients with advanced MND, and whether the effect of riluzole on motor neurones diminishes over time. Certainly, there is no evidence to suggest that riluzole reverses motor neurone degeneration and, despite extensive counselling about what to expect, patients may have unrealistic expectations of riluzole therapy. My own experience in the trial setting was that when their deficits did not diminish, some patients ceased taking riluzole, believing it not to be beneficial. This reinforces the need for a detailed discussion between the treating physician and the patient with MND at the time of commencing riluzole. Patients need to understand the role of riluzole therapy; specifically, that it is not a cure, but that it has been established to slow the rate of deterioration in muscle function and thereby increase longevity and quality of life. Clearly, good communication skills and empathy are needed when conveying this information to the patient and their family. Pharmaceutical Benefits Scheme (PBS) criteria for riluzole authority (June 2003) Approved indication Treatment of motor neurone disease PBS indication for authority Initial treatment of motor neurone disease, as diagnosed by a neurologist, in patients aged 75 years or less, with disease duration of 2 years or less and who have at least 60% of predicted forced vital capacity within 2 months prior to commencing riluzole therapy and who: 1) are ambulatory, and a) have not undergone tracheostomy, and b) have not experienced respiratory failure; OR 2) are not ambulatory, and a) have not undergone tracheostomy, and b) have not experienced respiratory failure, and c) are either able to use upper limbs or able to swallow. The date of diagnosis and the results of spirometry (in terms of percentage of predicted forced vital capacity) must be supplied with the initial authority application.

Matthew C Kiernan PhD, FRACP

A major theme of the 2004 World Congress of Clinical Pharmacology and Therapeutics was worldwide equity of access to medicines The 8th World Congress of Clinical Pharmacology and Therapeutics was held in Brisbane in August 2004. There were 940 participants from 60 countries, with Japan, Germany, Korea, South Asia and the United Kingdom well represented. The Congress featured three themes: Medicines and Society; Therapeutic Horizons; and Drug Discovery, Development and Disposition. Our report focuses on the Medicines and Society theme, which was strongly emphasised at the 8th Congress, differentiating it from previous Congresses. The prominence of this theme was to encourage the participation of clinical pharmacologists from South Asia and the Pacific regions, where access to lifesaving medicines and confidence in their quality are matters of everyday importance. The Congress also sought to encourage clinical pharmacologists from the developed world to engage with the serious global inequities in access to medicines for the major infectious diseases in the developing world, such as tuberculosis, malaria and HIV/AIDs, as well as the emerging developed-world lifestyle disorders, notably cardiovascular disease. Equity of access to medicinesSeveral plenary lectures focused on access to medicines in developing countries. Suwit Wibulpolprasert (Senior Advisor on Health Economics, Ministry of Public Health, Thailand) gave an inspirational and challenging presentation Philanthropy for the few — equity of access for the many?, tackling the difficult issue of donated medicines. He exposed the increasing gap between rich and poor in both developed and developing countries, and the many interacting social, political and financial influences that conspire to take resources away from the people who most need medicines. He concluded with practical steps that clinical pharmacologists could take to alleviate problems of access to medicines, such as promoting the use of the World Health Organization (WHO) model list of essential drugs in their own countries.1 This theme was reinforced by Sri Suryawati (Head of the Department of Clinical Pharmacology, Gadjah Mada University, Yogyakarta, Indonesia) who challenged all clinical pharmacologists to become involved in achieving the three “As” of medicine use in their own countries: access, affordability and appropriate use. An important and contentious recent issue has been access to cheap, generic versions of fixed-dose combinations of antiretro-viral drugs to deal with the HIV epidemic in Africa. Lembit Rago (Director of the WHO Division of Quality and Safety of Drugs, Geneva, Switzerland) discussed the difficult progress towards international acceptance of WHO guidance regarding registration of these products. Attention was also given to the rapidly expanding complementary medicines sector. Charlie Xue (Program Leader, Division of Chinese Medicine, RMIT University, Melbourne, Vic) outlined the WHO’s perspective on traditional medicine, and provided examples of the role of complementary medicine as a mainstay of public health systems in South-East Asia and the Pacific regions. Chu Quoc Truong (Director of The National Hospital of Traditional Medicine, Hanoi, Vietnam) related that the Vietnamese government has formally integrated traditional medicine with Western conventional medicine, with apparent good effect, notably wide acceptance of both traditions, allowing selection of cost-effective options from each. Tony Smith (Emeritus Professor of Clinical Pharmacology, University of Newcastle, NSW) summed up the unfinished business for clinical pharmacology and world health. He reminded Congress participants that clinical pharmacology arose as a discipline largely in developed countries and continues to be vital to the stellar advances in drug discovery, providing guidance to early-phase human studies, interpretation of pharmacokinetic, clinical and adverse-effects profiles, and development of product information for virtually every significant new chemical entity entering clinical practice. However, many of the needs of developing countries remain unmet, partly because of the limited numbers of clinical pharmacologists. He highlighted the vital tasks of these “few”: political advocacy for appropriate drug use; elaboration and implementation of national medicines policies; and specific “bread and butter” tasks, such as the collaborative development of standard treatment guidelines and essential medicines lists, and the promotion of rational prescribing, especially through training programs in medical schools. All the plenary speakers uniformly encouraged the international umbrella organisation for clinical pharmacology, the International Union of Basic and Clinical Pharmacology (IUPHAR), to continue to become more proactive in these areas, particularly through strong collaborations with WHO and similar organisations. This paradigm shift was strongly endorsed at the IUPHAR council meeting held during the Congress. Proper use of medicinesAnother theme running strongly through the meeting, and prominent in the Medicines and Society stream, was the concept of QUM (quality use of medicines), which was developed in Australia in the early 1990s. The Congress was an important opportunity for Australia to showcase our progress in QUM, through the gathering of evidence about what actually works, followed by implementation of effective strategies through networks, products and services. The major sponsorship of the Congress by our own National Prescribing Service — itself a prominent outcome of the QUM movement — effectively emphasised the importance of the movement in Australia and its potential for other parts of the world. Tom MacDonald (Professor of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK) delivered an entertaining contribution with the important message that large returns in population health outcomes would accrue if we could better implement evidence-based guidelines and improve patients’ adherence to therapy. For the prevalent cardiovascular disorders, lowering blood pressure is the intervention with the best evidence. Despite its proven benefits, blood-pressure control is poor worldwide. There are good arguments to support a more aggressive approach to blood-pressure management and treatment of younger individuals, but long-term compliance is a problem. Drug safetyAn increasing concern echoed in the Congress is the safety of medicines in older people, who are likely to have multiple comorbidities and increasing exposure to multiple, potent medicines. The future conduct of pharmacovigilance for new drugs is being shaped by interesting therapeutic risk management initiatives across the world, some of which were presented in a lively symposium entitled Medication safety and pharmacovigilance. These initiatives seek to better identify, evaluate and minimise the impact of adverse reactions, and to communicate evolving safety risks throughout the life cycle of a drug. Susana Perez-Gutthann (Senior Director, Global Epidemiology, Safety and Risk Management, Pfizer Worldwide Development, Barcelona, Spain) emphasised the need for this process to be proactive. The techniques of pharmacoepidemiology and use of advanced information technology to “mine” large automated health databases have revolutionised pharmacovigilance. The problem of the “therapeutic orphan” status of children was examined in depth by speakers from Europe, the United States and Australia. Incentives to pharmaceutical companies to evaluate already marketed medicines in children, along with mandatory studies for new medicines in this age group (provided they are potentially useful) has been a successful strategy in the US since the mid-1990s and is now having a positive impact in Europe. A paediatric working party has advised Australian Health Ministers via their Advisory Council on steps to improve access to prescription drugs registered for use in children and the quality use of these medicines. However, the Congress heard that political pressure still needs to be maintained to overcome this problem for children in all countries. Advertising medicinesA symposium on the controversial topic of direct-to-consumer advertising of prescription pharmaceuticals drew great interest, as the situations in Canada, the US, Europe, Thailand, New Zealand and Australia were compared. This advertising is legal only in the US and New Zealand. There were two main themes: first, that regulation is difficult; and secondly, as presented most forcibly by Barbara Mintzes (Postdoctoral Fellow, Centre for Health Services and Policy Research, University of British Columbia, Vancouver, Canada), that there are many, and increasing, instances of advertisements that skirt the boundaries of existing laws and regulations in jurisdictions where this advertising is illegal. In developing countries, Krisantha Weerasuriya (Regional Adviser, Essential Drugs and Medicines Policy, WHO Regional Office for South-East Asia, New Delhi, India) pointed out that there is, in reality, often no distinction between supposed prescription and over-the-counter medicines in terms of access. It is very difficult to control direct-to-consumer advertising of so-called prescription drugs when prescription-only status is not upheld at law — the case in most countries in South-East Asia. However, in countries where direct-to-consumer advertising is currently illegal, there appears little appetite for its introduction because of concerns about quality use of advertised medicines, consumer demand leading to distortion beyond the “reasonable” need for medicines, and finally, morbidity and mortality from the adverse effects of medicines whose use was unnecessary. However, it was emphasised that there is continuous and considerable pressure from industry and advertising interests to reverse this attitude. We have concentrated on the theme Medicines and Society, not because the other core themes of the Congress were less important, but because the urgency of addressing inequities in access to essential medicines around the globe is overwhelming. We were delighted that there was strong support to build on this focus at the 9th World Conference of Clinical Pharmacology and Therapeutics, which will be held in Montreal, Canada, in 2008 (http://www.cpt2008.com/).

Richard O Day MD, FRACP · Donald J Birkett FRACP, DPhil · John Miners PhD · David A Henry FRCP · Gillian M Shenfield PhD, FRACP, FRCP · J Paul Seale PhD, FRACP

Objective: To identify variation in the rates of use of key evidence-based therapies and in clinical outcomes among patients hospitalised with acute coronary syndromes (ACS).Design: Retrospective analysis of data on care processes and clinical outcomes of representative patient samples recorded by the Queensland Health Cardiac Collaborative registry.Setting: 18 public hospitals (3 tertiary, 15 non-tertiary) in Queensland, August 2001 to December 2003.Study population: 2156 patients who died or were discharged after troponin-positive ACS.Main outcome measures: Comparison of proportions of highly eligible patients receiving indicated care and in-hospital mortality between subgroups categorised by age, sex, comorbidities (diabetes, renal failure, chronic obstructive pulmonary disease and mental disorder), type of admitting hospital (tertiary or non-tertiary), and cardiologist involvement (transfer or non-transfer to cardiology unit).Results: Patients aged ≥ 65 years were less likely than younger patients to receive heparin (79% v 87%), β-blockers (79% v 87%), lipid-lowering agents (78% v 87%), coronary angiography (51% v 66%), and referral to cardiac rehabilitation (17% v 33%). Patients with diabetes were less likely than others to receive coronary angiography (50% v 63%), while those with moderate to severe renal failure were less likely to receive thrombolysis (52% v 84%), heparin (71% v 83%), β-blockers (69% v 84%), lipid-lowering agents (61% v 84%), in-hospital cardiac counselling (46% v 64%) and referral to cardiac rehabilitation (9% v 25%). Patients admitted to tertiary hospitals were more likely than those admitted to non-tertiary hospitals to receive coronary angiography (85% v 55%) and referral to cardiac rehabilitation (36% v 21%). Risk-adjusted mortality was highest in patients with moderate to severe renal failure (15% v 3%) and older patients (6% v 2%).Conclusions: Variations exist in the provision of indicated care to patients with ACS according to age, diabetic status, renal function and type of admitting hospital. Excess mortality in elderly patients and in those with advanced renal disease may be partially attributable to failure to use key therapies.

Ian A Scott FRACP, MHA, MEd · Mark A Jones BSc(Hons) · Andy B Duke · Irene C Darwin BSpThy, GradCertManagement · Kathy H Harvey GradCertManagement

Objectives: To determine population-based rates and outcomes of hypertensive disorders in pregnancy.Design: Cross-sectional study using linked population databases.Setting and participants: All women, and their babies, discharged from hospital following birth in New South Wales, between 1 January 2000 and 31 December 2002.Main outcome measures: Rates of hypertensive disorders in pregnancy, maternal and infant morbidity and mortality, and level of hospital care for the birth admission.Results: 250 173 women and their 255 931 infants were included in the study. Overall, 24 517 women (9.8%) had a hypertensive disorder in pregnancy, including 1411 (0.6%) with chronic hypertension, 10 379 (4.2%) with pre-eclampsia, 731 (0.3%) with chronic hypertension with superimposed pre-eclampsia, and 10 864 (4.3%) with gestational hypertension. Women with, and infants exposed to, hypertension were more likely to suffer death or major morbidity than those without hypertension. Infants of mothers with hypertension were more likely to be to born preterm and small for gestational age. Just over half the women with major morbidity or mortality delivered in hospitals with a high level of medical care. In contrast, most infants with major morbidity or mortality were delivered in hospitals with neonatal intensive care units.Conclusions: Hypertension is a common complication of pregnancy, and adverse outcomes are increased among hypertensive women and their babies. Clinicians appear to be better at identifying and seeking an appropriate level of care for pregnancies where the infant is at risk of a poor outcome than when the mother is at risk. More specific antenatal indicators of poor maternal outcome would help guide the referral of hypertensive women to higher levels of care.

Christine L Roberts MB BS, DrPH · Jane B Ford BA(Hons), PhD · David J Henderson-Smart FRACP, PhD · Charles S Algert BSc, MPH · Jonathan M Morris FRANZCOG, PhD

Objectives: To report the incidence of multispecialty surgical conditions in patients presenting to a procedural general practice.Design and setting: A more than 18-year survey (1 August 1983 – 31 January 2002) of the surgical records of a general practitioner–surgeon in an urban general practice.Participants: 211 patients each with multiple, elective, surgical problems (mostly non-major) treated at one operation.Results: The 211 patients represented 9.03% of the practitioner’s elective, non-referred, general practice surgical workload. Two separate procedures were performed at one surgical episode for 155 patients (73.5%), three separate procedures for 53 patients (25.1%), and four separate procedures for three patients (1.4%). Having all surgical conditions treated in a single episode resulted in considerable savings in time, convenience and expense for both the patient and the health care system.Conclusion: There appears to be a place, at least in our major cities, for an appropriately trained and recognised general surgeon, to service patients with more than one minor condition requiring surgery.

Raymond E Wilson MB BS(Hons), FRACS, FRCS

1 Tsunami damage in Kandholhudoo on the Raa atoll Photograph: Andrew Robertson. Mention “the Maldives” and everyone immediately conjures up images of unspoiled coral islands, holiday resorts, spectacular diving sites and great surf. The Maldives (from the Sanskrit “mala-dvipa”, meaning “garland of islands”)1 is all that and more, from the bustling capital city of Malé to the 200 serene inhabited islands where the traditional occupations of fishing and boat building continue as they have for centuries. When the earthquake and subsequent tsunami struck Aceh on 26 December 2004, most Australians were contemplating the public holidays ahead of them. The tsunami, travelling at speeds of up to 800 kilometres per hour, struck countries around the Bay of Bengal and across the Indian Ocean. Tremors were felt in the Maldives at about 06:25 local time, and the tsunamis hit the Maldive atolls between 09:00 and 09:30. As the 1–4-metre waves struck the islands, 82 people died, 200 people were severely injured and a further 1100 required treatment. Twenty-six people remain missing. An estimated 2167 households (15 000 people or almost 5% of the population) were displaced from their homes,2 as over half the inhabited islands sustained damage (Box 1). The Australian responseLike many on Boxing Day, we had missed the early reports of the evolving disaster in Asia. However, we were soon thrust into its midst by the early morning news on 27 December 2004, and by an urgent teleconference of the Australian Health Disaster Management Policy Committee, as we considered what medical support might be needed. This Committee, chaired by the Commonwealth Department of Health and Ageing, and with State, Defence Force and Emergency Management Australia representation, played a key role in advising the Australian Government on what response could be mounted quickly. By early on 28 December, it became obvious that we needed to send civilian medical teams into the tsunami-affected areas. While the Australian Defence Force had prime responsibility for deploying medical teams into areas affected by both the 1998 Aitape (Papua New Guinea) tsunami and 2002 Bali bombing,3,4 Australia has not often deployed civilian medical teams into disaster areas. Most states and territories base their internal disaster relief medical teams around major hospitals; this is a practice which has been questioned since the 1997 Thredbo disaster.5 However, as the Western Australian State Health Coordinator in times of disaster, I knew we could put a medical team together at short notice. For the first teams, we relied on advice from Chief Health Officers and Directors of Medical Services within Australia as to who might be appropriate, available within hours and experienced in providing health care in developing countries. While effective, personal preparations were ad hoc, the initial choice of team members has since been debated, and issues such as in-country operating funds, team expenditure and telephone costs are still being resolved. 2 Destruction on Vilufushi in the Thaa atoll Photograph: Gavin Coppinger. Our key problems were time and distance, particularly as teams comprising members from different states were all leaving from Sydney (28 in two teams to Aceh and one team of 17 to the Maldives).2 For once, the “red-eye” overnight flight for those travelling from Perth to Sydney was to our advantage, enabling us to get the team to Sydney rapidly. The logistics of assembling a team, equipping it (for medical work and to live in the field), reassembling it when its role changed from surgical care to public health, and deploying it in it the 24 hours after arrival, was challenging. The team bound for the Maldives included a team leader (Andy Robertson), three general practitioners (Mark Adamski, Vince Duffy, and Grahaeme Hatfield), two public health physicians (Krishna Hort and Danny Csutoros), three emergency physicians (Colin Myers, Michael Novy and Peter Roberts), an infectious diseases physician (Dominic Dwyer), an anaesthetist (Gavin Coppinger), three nurses (Muriel Leclercq, Jeff Williams and William Kerr), a paramedic (Greg Gibson), an environmental health officer (Paul Miller) and a logistics officer (Chris Sykes). With great assistance from the NSW Ambulance Counter Disaster Unit, Westmead Hospital, Queensland Health, the NSW Fire Brigade and Emergency Management Australia, this team, along with tonnes of cargo, deployed on a loaned QANTAS 747 early on 30 December 2004, and arrived in Malé that evening. During this flight, it became clear that a doctor was required to accompany 70 injured Australians from Colombo back to Sydney, and emergency physician Peter Roberts readily volunteered. 3 Members of one of our small teams being conveyed in a small fishing boat (dhoni) Photograph: Colin Myers. In the MaldivesThe significant number of dead and injured had been well managed in the central Indira Gandhi Memorial Hospital in Malé and in regional hospitals and island medical centres.6 Having survived the initial onslaught, the Maldivians were now concerned about subsequent epidemics and other public health issues (including food and water supply), as well as primary care; our team, with its public health and infectious diseases physicians, environmental health officer and GPs had been structured with that in mind. The damage to the affected islands and the bravery of the people was noteworthy. Many reported the tsunami hitting from both sides of their island, leaving them with nowhere to run. There was a strong sense of community among the Maldivians, who banded together in this time of devastation. Maldivians pride themselves on cleanliness, and many went to neighbouring islands to help clean up. On islands such as Vilufushi and Madifushi, where near total destruction reigned and rubble lay everywhere (Box 2), “Where do you start?” was the question in everybody’s mind. The enthusiasm of the Maldivian people meant the teams were universally well received and the communities were keen to work with the teams to address local issues. Health care delivery across 200 islands was never going to be easy (Box 3). Moving personnel, equipment and resources and patients was a challenge, as virtually all transport meant traversing water. The teams used everything from small fishing boats (dhonis), Coastguard landing craft, hospital boats and ocean-going ships to seaplanes and Indian Airforce transports. 4 Reviewing patients at a clinic in Madifushi, Thaa atoll Photograph: Vince Duffy. It was critical to work closely with Maldivian Ministry of Health staff to “value add” to their efforts. This meant working in small teams with local staff throughout the Gaafu Alifu, Thaa and Raa atolls, south and north of Malé.6 Several islands had not seen medical staff since the tsunami and many were running short of pharmaceuticals — we were able to provide both (Box 4). There was a range of public health issues that needed addressing, from discouraging the use of chlorine on dead fish and animals, with resultant shortages of chlorine for the wells (Box 5), to monitoring the populations for outbreaks of dengue, scrub typhus and diarrhoeal diseases. Public health team members worked closely with the Ministry of Health’s Water and Sanitation division to implement strategies for accommodation, children’s health, water and sanitation, solid waste management and asbestos disposal. Strategies included acquiring bedding for islanders evacuated to other islands and arranging the supply of fruit and vegetables, especially for children, where local crops had been destroyed. There were also continuing problems with tsunami-related injuries. Many people on the worst affected islands had been swept out to sea, and presented with chest infections in resultant “near drowning” syndromes. Infected wounds, abrasions and crush injuries were also evident. Outbreaks of gastroenteritis and respiratory disease were fortunately uncommon, and exacerbation of locally endemic infectious diseases (including dengue and scrub typhus) had not occurred. Anxiety and depression, as the islanders struggled to come to terms with the destruction, were common. In giving health support, it was important not to become a burden on the local government. There were unfortunate cases of well-intentioned, but misguided, attempts by other international medical teams to take over the local health system or provide services that weren’t needed (eg, trauma surgery), and this placed further strain on Ministry of Health staff. 5 Damage to wells in Viligili, Gaafu Alifu atoll Photograph: Michael Novy. Courtesy of WA Health Department. ConclusionThe health response by the Maldives government was one of the few success stories after the tsunami. This rested on a well-organised, pre-existing infrastructure encompassing effective inter-island transport and island-based health care centres. Many issues remained, however, including profound anxiety about further waves; loss of the breadfruit, guava and other fruit trees following salt water contamination; contamination of drinking water; future withdrawal of foreign health care personnel; and concern that the Maldives may be forgotten in its recovery phase by both tourists and charities. Australia’s health response was rapid, effective and appropriate, but we did learn some lessons (Box 6). In the future, our response could be improved with the establishment of pre-selected state-based Disaster Medical Assistance Teams.7 Teams that later went to Aceh were state-based, and had the benefit of enough time to select, prepare and equip their personnel before deployment. The multi-jurisdictional nature of the earlier teams, however, captured the spirit of the Australian desire to assist all those affected by the tsunami. 6 Lessons learnt for team deployment Health intelligence Accurate health information needs to be provided to the teams before deployment. Team selection Military, developing country and/or rural and remote medical experience and disaster medicine training is useful. Team member flexibility is critical, especially being able to improvise and adapt to constantly changing circumstances. Interpreters, or team members who speak the local language, are highly desirable. Equipment National modular checklists of both self-sufficiency and medical stores need to be further developed, incorporating sections on primary care, paediatrics, chronic care and public health (including vaccines). There is a need for team-identifying clothing, principally vests and headwear. Communications A clear command and control structure is essential. Satellite phones with international coverage, and international roaming mobile phones are critical. Logistics Funding, insurance and indemnity issues should be resolved before deployment, including cash advances (US dollars were widely accepted) and credit cards. Guidelines on what will be funded on deployment (eg, mobile phone use, purchase of clothing) are necessary. Transport Agreements with commercial airline companies to rapidly deploy team members should be explored further.

Andrew G Robertson CSC, FAFPHM, FRACMA · Dominic E Dwyer MD, FRACP, FRCPA · Muriel G Leclercq BSc(Nursing)

Morbid obesity (defined as having a body mass index [BMI] > 40 kg/m2, or BMI > 35 kg/m2 with obesity-related comorbidities) is a medical disorder associated with increased morbidity and mortality. Management guidelines published by the National Health and Medical Research Council and by similar US and UK bodies have recommended surgery as the most effective treatment available for selected patients with morbid obesity. A recent meta-analysis of obesity surgery has documented its safety and effectiveness in resolving some of the major medical comorbidities that occur in obese patients. To date, no intervention other than surgery has proven either effective or cost-effective in treating severe obesity and its associated medical conditions. Targeting patients with metabolic complications of obesity (eg, type 2 diabetes) could lead to substantial cost savings for the public health system. Currently, Medicare pays for privately insured patients to undergo obesity surgery, while uninsured patients are denied access to surgery in public hospitals. This raises significant equity issues that should be addressed.

Michael L Talbot MB ChB, FRACS · John O Jorgensen MB BS, FRACS · Ken W Loi MB BS, FRACS

Clinical record A 53-year-old woman with a 10-year history of coeliac disease controlled by a gluten-free diet presented with a 6-month history of dramatic weight loss and pyrexia. Physical examination showed wasting and peripheral oedema. Plasma albumin level was 23 g/L (normal, 34–48 g/L). Computed tomography of head, neck, chest, abdomen and pelvis, gallium and positron emission tomography scans, liver biopsy and bone marrow biopsy were normal. The serum lactate dehydrogenase (LDH) level was 466 U/L (normal, 110–230 U/L), raising the possibility of occult malignancy, especially enteropathy-associated T-cell lymphoma (EATL). Endoscopic duodenal biopsy revealed mild increase in intraepithelial lymphocytes, crypt hyperplasia and villous abnormality in keeping with coeliac disease. Molecular clonality studies of the lymphoid cells in the duodenal biopsy yielded a monoclonal band of T-cell receptor (TCR) γ gene rearrangement in two separate series of biopsies taken 6 weeks apart. Refractory sprue was diagnosed, and the patient received sequential trials of prednisolone, cyclosporin A and infliximab without benefit. High dose cyclophosphamide (2 g/m2) was administered 3 months later for presumed EATL. This resulted in immediate resolution of the fever and improved weight gain. The patient subsequently complained of paraesthesiae in her feet. Neurological examination was normal. Nerve conduction studies suggested an early axonal sensory peripheral neuropathy. Vitamin B12, folate, vitamin A-tocopherol, red blood cell transaminase and transketolase studies, vasculitic screen, glycated haemoglobin, syphilis serology and thyroid function tests were normal. Paraprotein was not detected in serum electrophoresis. Magnetic resonance imaging (MRI) of the brain showed non-specific patchy periventricular areas of high signal not suggestive of the suspected lymphoma. Her systemic symptoms of fever, sweats and weight loss responded to two further doses of cyclophosphamide (1 g/m2), despite worsening neurological symptoms. After 3 months, the patient relapsed with recurrence of pyrexia, and the serum LDH level progressively rose to 838 U/L. Neuropathy progressed to the point where she could not walk. Reflexes were lost, with a glove-and-stocking pattern of sensorimotor disturbance. A repeated nerve conduction study confirmed severe axonal sensorimotor peripheral neuropathy affecting both upper and lower limbs. Cerebrospinal fluid was normal, and there were no malignant cells. Repeated investigations, including brain MRI and upper gastrointestinal endoscopy, did not reveal any further evidence of malignancy. A right sural nerve biopsy showed severe loss of myelinated nerve fibres, and many of the surviving fibres showed varying stages of axonal degeneration (Box 1) associated with a sparse, patchy endoneurial mononuclear cell infiltrate in some fascicles and prominent endoneurial fibrosis on trichrome stain. The CD45RB immunostain showed increased numbers of immunopositive endoneurial lymphoid cells that showed immunopositivity with the T-cell markers CD3 (Box 2) and CD5. The CD68 immunostain showed increased endoneurial macrophages, and ultrastructural assessment confirmed macrophage phagocytosis of degenerate myelinated fibres. CD20 immunostain was negative. The Congo red stain for amyloid was negative. A TCRγ clonality study of the nerve biopsy showed a monoclonal band identical to the previous band detected in the duodenal biopsies, confirming infiltration of the nerve by T-cell lymphoma (Box 3). Subsequent treatment with cyclophosphamide, doxorubicin and dexamethasone was complicated by Enterococcus faecalis septicaemia and florid disseminated intravascular coagulation, leading to the patient’s death. Coeliac disease is associated with an increased risk of malignancy.1 Most of these tumours are T-cell lymphomas, in contrast to the common sporadic B-cell lymphomas that usually occur in the gastrointestinal tract. Enteropathy-associated T-cell lymphoma (EATL) often presents as refractory sprue. The risk of EATL usually decreases to a low level after adhering to a gluten-free diet for 5 years. Common symptoms of presentation include diarrhoea, abdominal pain and weight loss. Patients may also present with acute bleeding, perforation or obstruction.2 Our patient presented with weight loss, pyrexia and, subsequently, neuropathy. Clinical deterioration despite compliance with a gluten-free diet should raise suspicion of EATL. Conversely, as coeliac disease may be undiagnosed at the time of presentation of the intestinal lymphoma, patients with T-cell lymphoma or a gut primary localisation should be tested for coeliac disease. Endoscopy with biopsy is usually the test of choice. Laparotomy is performed in some instances, especially when patients present with an acute abdomen. Our case illustrates a number of interesting features. First, a definitive diagnosis of EATL may be elusive, and persistence in obtaining histological confirmation is warranted. The elevated serum lactate dehydrogenase (LDH) level raised the possibility of an underlying malignancy. Second, in patients with refractory sprue, a clonal TCRγ rearrangement often precedes the onset of overt T-cell lymphoma, which constitutes an early or cryptic form of EATL.3-5 The difficulty is distinguishing antigen-dependent T cells from neoplastic T cells. Management decisions may have to be based on DNA clonality studies alone. Finally, although central nervous system involvement has been reported,6,7 to our knowledge this is the first reported case of peripheral nerve involvement in EATL. Clinical evidence of peripheral neuropathy is observed in 0.1% to 8% of patients with malignant lymphomas,8 and neurotoxic chemotherapeutic agents are frequently presumed to be the cause. Peripheral nerve involvement in T-cell lymphomas is very uncommon.8-10 It is also interesting that the infiltrative neuropathy progressed relentlessly despite an initial good response of systemic symptoms to cyclophosphamide. Both refractory sprue and EATL carry a very poor prognosis, with a 5-year survival rate of 11%. This is related to the unresponsive malabsorption in cryptic EATL, which is often diagnosed late. Associated malabsorption and malnutrition make tolerance of chemotherapy difficult, and treatment-related complications such as gastrointestinal bleeding and perforation also worsen prognosis.2 Favourable outcomes with multi-drug therapy generally occur in patients who have minimal gastrointestinal symptoms before the diagnosis of lymphoma and can tolerate therapy. Chemotherapy should be considered for all patients and should constitute drugs active in intermediate- and high-grade lymphoma. A variety of regimens, including CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone), have been used. The optimal cytotoxic regimen is unclear, as data are limited to uncontrolled retrospective case series. The role of salvage treatments and high-dose chemotherapy at relapse also remains to be investigated.2 Earlier diagnosis and development of more effective treatments are required to improve the outcome for these patients. Lessons from practice Coeliac disease is associated with an increased risk of malignancy, especially intestinal lymphoma or enteropathy-associated T-cell lymphoma (EATL). EATL often presents as refractory sprue, but definitive diagnosis may be difficult and requires T-cell clonality studies. Earlier diagnosis and development of more effective treatments are warranted to improve the poor outcome in these patients. 1 Nerve fibres in varying stages of axonal degeneration Longitudinal section. Transverse section. 2 Positive CD3 immunostaining of lymphocytes 3 Polyacrylamide gel electrophoresis of T-cell receptors Lane 1, positive control; lane 2, negative control; lane 3, normal (polyclonal) control; lanes 4 and 5, duodenal biopsy, 12 Apr 2002; lanes 6 and 7, duodenal biopsy, 19 Jul 2002; lanes 8 and 9, nerve tissue, 9 Oct 2002.

Yoon-Sim Yap MBBS · Adrian Cummins FRACP, MD, PhD · Jennifer Hardingham BSc, PhD · Sunil Dabadghao MD, MBBS · John Norman MBBS, FRACP · Peter Blumbergs MBBS, FRACP, FRCPA

Clinical record A 35-year-old pregnant woman (gravida 4, para 3) presented in February 2004 at 35 weeks’ gestation with a 1-day history of vomiting, abdominal pain and drowsiness. She had no significant past medical history, was not taking any prescription medication, and had had an uncomplicated pregnancy up to that time. Her level of consciousness subsequently deteriorated, and she became responsive only to painful stimuli. She had a blood pressure of 190/110 mmHg, abdominal tenderness and generalised oedema. Urinalysis was positive for protein and leukocytes. Blood biochemical levels included creatinine 0.19 mmol/L (reference range [RR], 0.05–0.09 mmol/L); urea 9.2 mmol/L (RR, 2.5–8.3 mmol/L); ionised calcium 2.64 mmol/L (RR, 1.12–1.3 mmol/L); bicarbonate 32 mmol/L (RR, 22–28 mmol/L); amylase 2397 IU/L (RR, < 160 IU/L); lipase 1364 IU/L (RR, < 60 IU/L); urate 0.65 mmol/L (RR, 0.2–0.47 mmol/L); and phosphate 0.58 mmol/L (RR, 0.8–1.5 mmol/L). Abdominal ultrasound excluded acute cholecystitis. A fetal cardiotocograph showed reduced variability in fetal heart rate. Pre-eclampsia was diagnosed, and the woman underwent an urgent caesarean section 3 hours after presentation. The pre-eclampsia was managed with magnesium sulfate infusion, intravenous hydralazine and metoprolol. A 2574 g boy was delivered (Apgar score 3 at 1 minute, 9 at 10 minutes). Initially, he had a blood pH of 7.37 and serum calcium level of 4.12 mmol/L (RR, 2.1–2.6 mmol/L). Within 1 week he had made a full recovery from respiratory distress, jaundice and sepsis. Neonatal hypocalcaemia did not occur. Subsequently, a computed tomography (CT) scan of the woman’s abdomen confirmed acute pancreatitis, with an oedematous pancreas and fluid in the paracolic gutter (Box 1). Her serum parathyroid hormone (PTH) level on Day 2 was suppressed (0.66 pmol/L; RR, 1.3–6.8 pmol/L), with PTH-related protein undetectable (< 1 pmol/L). On Day 7, her serum 25-hydroxy-vitamin D level was inappropriately high (120 nmol/L; RR, 25–108 nmol/L). (On later questioning, she said she had not taken vitamin D supplements.) The level of 1,25-dihydroxyvitamin D was not measured. The serum level of angiotensin-converting enzyme was normal. The patient’s hypercalcaemia was managed by intravenous administration of saline, followed by frusemide and pamidronate 90 mg. Over the next few days, her condition improved and her blood pressure and renal function normalised. The hypercalcaemia resolved quickly — to the extent that, by Day 8, she had developed symptomatic hypocalcaemia requiring oral supplementation with calcium carbonate and calcitriol (Box 2). When her delirium had resolved, she reported a 1-month history of severe heartburn, for which she had self-medicated with antacids, taking up to 10 Rennie tablets a day (an over-the-counter [OTC] preparation containing calcium carbonate 680 mg and magnesium carbonate 80 mg per tablet) (10 tablets contain about 3 g elemental calcium). She had also been drinking up to three glasses of milk a day. In light of this history, milk-alkali syndrome was diagnosed, and the pancreatitis was attributed to hypercalcaemia. By Day 16, the pancreatitis had resolved and the calcium level normalised. She was discharged home without medication and has remained well. Milk-alkali syndrome — the triad of hypercalcaemia, metabolic alkalosis and renal insufficiency1 — is associated with ingesting large amounts of calcium and absorbable alkali. Before the advent of modern treatment for peptic ulcer disease (with H2-receptor antagonists, proton-pump inhibitors and antimicrobial therapy), excessive calcium intake related to over-the-counter (OTC) antacid preparations commonly caused hypercalcaemia. In recent years, there has been a resurgence of milk-alkali syndrome. In a series of 100 patients admitted with hypercalcaemia between 1990 and 1993, it was reported as the third most common cause (12%) of hospital admissions for hypercalcaemia after primary hyperparathyroidism and hypercalcaemia of malignancy.2 Reasons for this include the recent emphasis on calcium therapy for osteoporosis, ready availability of OTC calcium preparations, and the use of calcium carbonate rather than aluminium (as a phosphate binder) in patients with advanced chronic kidney disease. Oral calcium carbonate is now the predominant source of calcium and alkali associated with the development of milk-alkali syndrome (with or without milk intake). The amount of calcium carbonate required to be ingested per day to cause milk-alkali syndrome is reported to vary from as low as 4 g to as high as 60 g.3,4 Thus, there appears to be no direct link between the amount of calcium ingested and development of the syndrome, although reports are few.2 After as little as 1 week of treatment with calcium carbonate, patients can present with symptoms of hypercalcaemia, severe metabolic alkalosis and acute renal failure.5 Three previous cases of milk-alkali syndrome complicating pregnancy have been reported,6-8 one with associated pancreatitis. In our case, the pancreatitis resolved quickly as the calcium level fell. The parathyroid hormone (PTH) concentration was appropriately suppressed in response to the hypercalcaemia. The subsequent hypocalcaemia resulted from cessation of the high calcium ingestion together with suppression of PTH. This was compounded by the concurrent administration of pamidronate and, possibly, by calcium sequestration and fat saponification associated with the pancreatitis. Although we have attributed the pancreatitis to hypercalcaemia, it should be noted that the causal association between hypercalcaemia and pancreatitis is disputed. In a Mayo Clinic series of 1153 patients with hyperparathyroidism, the incidence of pancreatitis (1.5%) was similar to that in the general population.9 Pregnancy itself has also been independently associated with pancreatitis.10 The diagnosis of milk-alkali syndrome depends on a history of ingestion of excess calcium and absorbable alkali with exclusion of other causes of hypercalcaemia. Only a minority of exposed patients appear to develop the syndrome. Kapsner et al reported that, of 297 cardiac transplant patients receiving large doses of calcium carbonate as prophylaxis for osteoporosis, 65 patients developed hypercalcaemia but only three had milk-alkali syndrome.11 Susceptibility appears to depend upon variables such as pre-existing renal disease and concurrent medications (eg, thiazide diuretics and vitamin D supplements). Management of the syndrome includes removal of the precipitating (dietary) cause, together with rehydration. In pregnancy, additional complications may involve the fetus (suppression of fetal parathyroid function, neonatal hypocalcaemia and tetany). Our patient had experienced a fairly typical pregnancy, heartburn being a common symptom in pregnant women. An OTC preparation that she took to relieve the heartburn caused life-threatening biochemical derangements, and other pregnant women are potentially susceptible to such a course of events. A diagnosis of milk-alkali syndrome may be missed unless a detailed history is obtained, and information about OTC preparations is essential in all patients presenting with hypercalcaemia. As H2-receptor antagonists and proton-pump inhibitors are not often prescribed in pregnancy for gastro-oesophageal reflux symptoms, many women rely on OTC heartburn relief medication. It is therefore important to educate pregnant patients about OTC calcium carbonate-containing antacids. A limit of 1.2–1.5 g per day of elemental calcium (3.0–3.75 g calcium carbonate) appears safe.2 This equates roughly to six Rennie tablets, five Quick-Eze tablets, 150 mL Mylanta Plus suspension or 230 mL Gaviscon liquid. Interestingly, Gaviscon tablets and all other preparations (liquid or tablets) of Mylanta (except Mylanta Rolltabs) contain no calcium. Appropriate warning labels on all OTC calcium-containing preparations would help prevent further cases of this type. Lessons from practice Gastro-oesophageal reflux (“heartburn”) in pregnancy is common. Excessive use of over-the-counter (OTC) calcium-containing antacids to relieve this condition can lead to milk-alkali syndrome. Pregnant women need to be educated about the potential risks of milk-alkali syndrome. All patients presenting with hypercalcaemia should be asked about their use of OTC medications. A daily dose of six Rennie or five Quick-Eze tablets appears safe; alternatively, one of the many non-calcium containing antacids can be recommended. 1 Abdominal computed tomography scan at Day 2 The scan shows an oedematous pancreas (arrow) and fluid in the left paracolic gutter (arrowhead). 2 Serum calcium and albumin levels during the patient’s hospital stay

Michelle V Gordon MB BS(Hons) · P Shane Hamblin MB BS(Hons), FRACP · Lawrence P McMahon MD, BS, FRACP

Early diagnosis of language disorders and autism is important, and early intervention for autism and some language disorders makes a difference. Developmental surveillance of children to detect these disorders should be a routine part of medical practice. The persistence and pervasiveness of communication and socialising deficits differentiate children with autism from those with specific developmental language disorders. Hearing and vision assessment is essential in any communication disorder. Interventions, targeted to identified areas of need, should encompass communication enhancement, behavioural therapy, educational modification, parent education and family support. Pharmacological interventions have an important but discrete role in autism, but there are no magic bullets. It is important to remember that the normal childhood illnesses occur in children with developmental disorders. Parents should be directed to reliable websites on the Internet, and given information and books to read as well as phone numbers of relevant services (eg, autism associations). There is a need for increased government financial support for early intervention programs.

John Wray FRACP · Helen Knott BApplSc(S · Natalie Silove FRACP, MMed, FCP(SA)

A 58-year-old man of British descent presented in 2003 with chest pain, facial flushing and elevated jugular venous pressure but no leg oedema. He had been exposed to tuberculosis in childhood, had a strongly positive tuberculin test and had been followed up in the tuberculosis surveillance program with regular chest x-rays, but had never been diagnosed with tuberculosis. Chest x-ray on presentation showed calcified plaques and masses in the pericardium and mediastinum (Box 1). Computed tomography revealed extensive calcification of the pericardium (Box 2). Coronary angiography showed 70% stenosis in the left anterior descending artery. Cardiac catheterisation showed equalisation of diastolic pressures in all four chambers, with a positive square root sign (pattern of ventricular diastolic pressure characteristic of constrictive pericarditis). Pericardiectomy with left internal mammary bypass graft to the left anterior descending artery was performed. Severe constrictive pericarditis with a thick (up to 4 mm) layer of calcium plaque was found. Two large cystic masses within a thick calcified shell were present in the posterolateral aspect of the right side of the heart and the left posterior atrioventricular groove. Both contained creamy caseous material, which was drained (Box 3). Histopathological examination was consistent with chronic calcific pericarditis with no granuloma. Microbiological examination and culture did not show any organisms. The patient was treated with a 6-month regimen for Mycobacterium tuberculosis based on his known previous exposure to tuberculosis, strongly positive tuberculin test, and the operative and pathological findings. Corticosteroid therapy, which is sometimes recommended in the treatment of tuberculosis,1,2 was not considered as the patient did not have effusive pericarditis or active tuberculosis. At 12-month follow-up, he was fully active, without angina or shortness of breath. In Australia, the annual incidence of tuberculosis is 5–6 cases per 100 000.3,4 Tuberculous pericarditis is seen in 1%–2% of all cases of pulmonary tuberculosis.5 Extensive tuberculous pericarditis is rare in Anglo–Celtic populations. 1 Chest x-ray showing calcified mass along the diaphragmatic surface of heart (A) and calcified pericardium (B). 2 Pre-operative computed tomography scan showing large calcified masses (5 cm × 4 cm) in the left posterior atrioventricular groove (A) and right atrioventricular groove posterior to the tricuspid annulus (B), with calcification throughout. 3 Intraoperative photograph showing the opened large cystic mass posterior to the right atrioventricular groove, with caseous contents (arrow).

Shiromani Goyal M Ch · Kang-Teng Lim MB BS · Cheng-Hon Yap MB BS · Elizabeth W Ryan FRACP · Morteza Mohajeri FRACS

To the Editor: The disastrous events of Boxing Day, 2004 left hundreds of thousands dead, injured or homeless across large parts of Asia. Many aid teams dispatched to affected areas are grappling with the aftermath of this catastrophe. Here, I present one of many clinical observations of what we encountered in the field. It is a clinical anecdote, but one worth sharing, as it may guide future teams in similar situations. A 62-year-old woman was admitted to hospital with a history of vague ill-health for 12 months, and a subacute illness over the 4 weeks since immersion in the tsunami, with persistant cough, dyspnoea and weakness to the point of being largely bed-bound. She was cachectic, had a fever of 37.5°C and scattered crackles in both lower lung fields. Radiology facilities were not available and she was not producing sputum. She was treated empirically with antituberculous chemotherapy, as well as broad-spectrum antibiotics in the form of amoxycillin and ciprofloxacin orally, but her condition did not improve. X-ray facilities became available soon thereafter, and a chest x-ray showed changes more in keeping with a necrotising pneumonia than tuberculosis ( [a]). Her treatment was changed to intravenous meropenem (1 g every 8 hours) and her condition was slowly improving when we left. During our 2-week posting in Banda Aceh, we saw about 6–10 patients at three hospitals presenting about a month after their immersion, with fluctuating fever; chronic, non-productive cough; and radiological evidence of bilateral, asymmetric, necrotising pneumonia with cavitation. Some patients developed empyemas and pneumothoraces ( [b]). They failed to respond to broad-spectrum antibiotics including ampicillin/gentamicin/metronidazole and ticarcillin–clavulanate/cotrimoxazole. Burkholderia pseudomallei was cultured from the pleural fluid of two of these patients, and Nocardia sp. from the sputum of another. A notable feature of these patients was their subacute presentation weeks after immersion in the tsunami, the persistence of symptoms despite other broad spectrum antibiotic therapy, and the development of radiological and clinical manifestations of necrosis with pleural involvement. Many of our patients described the wave as being “black”. In view of the immersion in muddy water in a tropical environment, B. pseudomallei is likely to have been one of the causative organisms in many of these cases. However, it has not been possible to culture B. pseudomallei from all patients, and it is likely that their infections were polymicrobial given the circumstances of their injuries. A variety of bacterial organisms, as well as fungi, have been recognised in other such situations.1-3 When we were there, Fakinah hospital provided one of the few laboratory services in Banda Aceh, and the availability of these facilities were limited as they were focused on public health surveillance. Thus, collection of specimens for culture was not routine. Furthermore, when we arrived there were no nurses, no medical records and no medication or observation charts. While the situation improved rapidly during our stay, these limitations meant that recognition of emerging clinical patterns was important. Many of the antibiotics initially used for patients with immersion injuries were ineffective in this setting, and the use of carbapenems became our first-line, or early second-line, antibiotic in post-immersion respiratory infections in Banda Aceh. Chest x-rays of patients with subacute necrotising pneumonia (a) Bilateral consolidation with scarring and early cavitation in the lower lung fields (b) Bilateral necrotising pneumonia complicated by right pneumothorax

Anthony M Allworth

To the Editor: When discussing causes of childhood leukaemia, Ziegler et al stated, “Exposure to electromagnetic fields has been ruled out as playing any significant role”. 1 They cited one large study2 in support of this statement, but overlooked two independent pooled analyses that showed the opposite. Greenland et al analysed 12 studies involving 2656 patients and 7084 controls, 3 and Ahlbom et al analysed nine studies involving 3247 patients and 10 400 controls.4 Each analysis found an association with a doubling of risk of childhood leukaemia at levels of household exposure at and over 0.4 microtesla (4 milligauss). Confounders and sources of bias to explain these findings have been sought without success. Consequently, in 2002, the International Agency for Research on Cancer classified 50 and 60 Hz magnetic fields as a “possible carcinogen” (Group 2b)5 even though the mechanism of an effect is not clear. The role of magnetic fields in childhood leukaemia cannot be “ruled out”, given the substantial epidemiological evidence, the international classification of magnetic fields as a possible carcinogen, and the subtlety of gene–environment interactions. Moreover, although exposures to magnetic fields are low within most households, there is opportunity to easily prevent or treat the uncommon situations where household exposures exceed 0.4 microtesla by means of electrical engineering, household wiring and town planning.

Bruce Hocking

In reply: Hocking states that electromagnetic fields cannot be ruled out as a cause of childhood leukaemia. However, several large studies have all failed to find any association between childhood exposure to electromagnetic radiation and leukaemia.1-4 The two pooled meta-analyses Hocking refers to both found no increased incidence of leukaemia with exposure to electromagnetic fields of < 0.4 microtesla.5,6 Although there was an increased risk of leukaemia with exposure to ≥ 0.4 microtesla, 99.2% of children with leukaemia had not received such a high level of exposure. 5 In addition, both studies acknowledged the potential for selection bias. As such, for the overwhelming majority of children with leukaemia, exposure to electromagnetic fields does not play any significant causative role. Although we agree its effect cannot be ruled out for the remaining < 1% of patients, it should not be given undue epidemiological weight.

David S Ziegler · Luciano Dalla Pozza · Keith D Waters · Glenn M Marshall

To the Editor: The recent position statement by the Warfarin Reversal Consensus Group provides clear and concise guidelines for a number of clinical scenarios related to the use of warfarin. 1 Unfortunately, it makes the general statement about the periprocedural management of warfarin in patients with atrial fibrillation (AF), “clinical experience suggests that bridging therapy is not required” [page 496]. Clinicians caring for patients with large ischaemic stroke in these circumstances may beg to differ. Although studies of bridging therapy in patients with AF in the periprocedural period are lacking, there are data which suggest that there is a considerably higher risk of thromboembolism during this period than would be expected by simply calculating the risk for several days off anticoagulation therapy.2-4 My own study of such patients undergoing endoscopy found a stroke risk of up to 3% in those at high risk.2 Many of these strokes were severe. The prothrombotic periprocedural environment may be a factor here, although advanced age and vascular risk factors may also contribute. The outstanding risk factor, however, is a previous history of stroke,2 and this is also a major risk factor for perioperative stroke in patients without AF.5 I would suggest careful, individualised assessment of all patients, and judicious bridging therapy where possible for patients with AF who have a past history of stroke.

David J Blacker

To the Editor: The recent position statement from the Warfarin Reversal Consensus Group provides a comprehensive, coherent and practical approach to warfarin reversal management. 1 In reviewing the position statement, and with particular reference to the paragraph about modifiers of warfarin response, we noted that the contribution of cytochrome P450 2C9 (CYP2C9) genotype to the response to warfarin was not addressed. There is debate in the current literature about the clinical utility of evaluating CYP 2C9 genotype in patients already taking or about to start warfarin therapy. Nonetheless, a significant body of evidence supports the contribution of CYP2C9 genetic variants as modifiers of response to warfarin therapy. CYP2C9 is the enzyme principally involved in metabolising warfarin.2 Several studies have identified the presence of single nucleotide polymorphisms in the CYP2C9 gene resulting in the expression of two allelic variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) that are associated with reduced enzymatic activity, impaired metabolism of and increased sensitivity to standard warfarin doses.2,3 The allelic frequency of the mutant genotypes is in excess of 21% in the white population2 (they occur at reduced frequencies in African American populations and are rare in Asian populations4). The presence of allelic variants (CYP2C9*2 and CYP2C9*3) with reduced enzymatic activity is closely correlated with increased bleeding complications.2,3 Thus, there is potential for a considerable clinical impact given the large number of patients taking warfarin. We have identified an allelic frequency of CYP2C9*2 and CYP2C9*3 genotypes in an Australian population of patients attending an anticoagulant clinic comparable to that reported in the literature.2,3 We also identified international normalised ratios in excess of the target range in patients with the CYP2C9*2 or CYP2C9*3 genotype undergoing induction warfarin therapy with standard dosing regimens, relative to those who did not have these genotypes (personal, unpublished data, presented as: Cytochrome P450 CYP2C9 genotyping and warfarin induction therapy, presented at the 2004 Annual Scientific Meeting of the Haematology Society of Australia and New Zealand [Oct 17–20, Melbourne, Australia]). Recent reports suggest that CYP2C9 genotyping before inducing warfarin therapy may avert bleeding complications.5 However, CYP2C9 genotyping is currently only available within research institutes and larger corporations with research and development facilities and does not attract a Medicare rebate. While simple and inexpensive, genetic CYP2C9 screening has yet to be proven cost effective. However, genotyping may be of benefit in averting over-anticoagulation in certain clinical scenarios. These include commencing warfarin therapy in “high risk” elderly patients; those in whom low-dose, long-term, low-testing-frequency warfarin regimens are being contemplated; and in other “high risk” patients, such as those with conditions affecting warfarin metabolism, including liver disease, and in those taking medications known to interact with the hepatic metabolism of warfarin.

David J Blacker · Faye Gray · Keith Byron

To the Editor: The article by Baker et al was a timely review of managing anticoagulation therapy and balancing the risks of thrombosis and bleeding.1 However, in managing anticoagulation therapy before non-cardiac surgery in patients with mechanical cardiac valve prostheses, the suggested 5-day cessation of warfarin therapy, with only subcutaneous heparin cover, is not appropriate. I have had three patients with mechanical bileaflet mitral prostheses develop valve thrombosis while under this protocol, two with a fatal outcome. I have also had one patient with a mechanical bileaflet aortic valve develop a popliteal arterial embolus requiring thrombectomy, despite being treated according to the protocol. The consequences of valve thrombosis and thromboembolism far outweigh the lesser complications of increased bruising or bleeding associated with non-cardiac surgery. To avoid the potentially devastating complications of valve thromboembolism associated with the routine cessation of warfarin therapy 5 days before surgery, warfarin ought to be continued to maintain an INR (international normalised ratio) of around 2.0, supplemented with subcutaneous heparin. Alternatively, full intravenous heparinisation can be used while ceasing warfarin treatment, and continued postoperatively until the INR is restored to the therapeutic level. Warfarin should never be reversed with vitamin K, except in cases of life-threatening haemorrhage. Apropos of the therapeutic INR ranges generally recommended for mechanical cardiac valve replacements, the current generation of prostheses does not require the anticoagulation intensity of the older style prostheses.2,3 Lower intensity anticoagulation is sufficient to prevent thromboembolism at decreased risk of haemorrhagic complications.4 My personal practice for patients with bileaflet mechanical prostheses is to maintain an INR of 2.0–2.5 for aortic valves, and 2.5–3.0 for mitral valves. The higher intensity for mitral prostheses relates to potential increased thrombogenicity because of lower leaflet opening pressures, as well as the common association of left atrial dilatation and atrial fibrillation.

Serge Lubicz

To the Editor: A middle-aged woman with atrial fibrillation had her warfarin therapy stopped for 2 days before dental extraction. She had a catastrophic stroke and is now a plaintiff. I was asked if her medical management accorded with common practice. At the October 2004 Annual Conference of the Royal Australian College of General Practitioners, I conducted a straw poll of 20 experienced GPs, of whom 18 said they would stop warfarin for between 2 and 4 days before a dental extraction. Some of these GPs regarded a dental extraction as elective surgery and pointed me to authoritative (but slightly ambiguous) sources to back up their view. 1,2 However, a review of the medical and dental literature shows that this is an example of common practice lagging behind clinical evidence. The first controlled trial of dental extraction in patients on warfarin therapy was conducted in 1983.3 It showed that it was not necessary to cease warfarin prophylaxis for patients whose international normalised ratio (INR) was within the normal therapeutic range. Since then, two major literature reviews have confirmed these conclusions.4,5 A recent Australian review on warfarin reversal expresses a similar point of view.6 The incidence of a serious embolic complication from stopping therapy with warfarin is 1%, and this is three times more likely to occur than bleeding complications in patients whose warfarin therapy was continued.4 Furthermore, a stroke is a catastrophic event, while a bleeding tooth socket is simply messy and usually easily controlled. An authoritative review and position statement on warfarin therapy and dental procedures from the Australasian Society of Thrombosis and Haemostasis may be the catalyst required to align common practice with clinical evidence.

Max Kamien

In reply: We thank Blacker for his constructive and helpful comments. Our recommendations on bridging therapy in patients with atrial fibrillation were for patients with chronic atrial fibrillation who had not previously had a thromboembolic event.1 We do agree with Blacker that extreme care needs to be exercised in patients with atrial fibrillation and a previous thromboembolism. These patients should be managed along the same lines as patients who are at relatively high risk of recurrent thromboembolism. We also wish to emphasise that it is extremely important to assess each individual patient carefully, and to use the consensus guidelines as guiding principles, and not apply them blindly. Dear and his colleagues correctly point out that there are several published studies that have confirmed increased warfarin sensitivity in allelic variants of the cytochrome P450 2C9 (CYP2C9) enzyme. Polymorphisms associated with reduced enzymatic activity have been reported to be associated with increased warfarin sensitivity. They suggest that determining the genotype of individuals before commencing warfarin therapy may be of benefit in reducing the incidence of over-anticoagulation in a select group of patients. We do not believe that this approach is currently practical or possible. From a practical point of view we recognise several reasons why patients become over-anticoagulated when treated with warfarin. In our article we discussed several important modifiers that contribute to an individual’s sensitivity to warfarin. While we agree that polymorphisms of the CYP2C9 gene on its own have been linked with increased sensitivity to warfarin, we are not aware of any studies showing a synergistic interaction of the polymorphism with other clinically recognised causes of increased warfarin sensitivity. Furthermore, we are not aware of any properly conducted studies that have attempted to address the clinical or economic viability of screening for CYP2C9 polymorphisms in patients for whom warfarin therapy is planned. Finally, the time required to obtain the results of this investigation would preclude its application in the routine management of patients who require warfarin therapy. The letter by Lubicz highlights the difficulties encountered in bridging anticoagulant therapy in patients with prosthetic valves. As pointed out in our article, the management of these patients is controversial and mostly anecdotal.1 We believe that the recommendations in our article are useful for most patients, but would like to emphasise the need to consult with the relevant experts in order to avoid bleeding or thrombosis. We would not recommend routine full therapeutic anticoagulation therapy with heparin immediately after surgery, or the combined use of warfarin at any international normalised ratio (INR) with subcutaneous heparin before surgery. Such approaches are more likely to cause confusion and predispose the patients to either bleeding or the risk of thrombosis. Patients with prosthetic valves require careful handling, and involving experts in their management is critical. Kamien’s comments are important and illustrate the difficulties in changing entrenched practices. We hope that our recommendations will go some way to improving the way we manage patients on warfarin therapy who are about to undergo surgery.

on behalf of the Warfarin Reversal Consensus Group

To the Editor: Incidents involving assaults on staff by medical equipment are uncommon, but have been reported in this Journal before. 1 We report another “attack”, involving an x-ray machine and an anaesthetist. A woman was scheduled for endoscopic retrograde cholangiopancreatography in the radiology suite. During induction of general anaesthesia, the patient’s foot moved against an x-ray table control knob (Box). This triggered slow, downward movement of an x-ray “C-arm”, which was positioned above the head of the unsuspecting anaesthetist. Tracheal intubation was rudely interrupted when the C-arm met the anaesthetist’s head and pushed it towards the patient’s face. However, the radiographer in attendance quickly reversed the movement just before the anaesthetist and patient collided. The radiology suite is often regarded as an unfriendly environment for anaesthetists.2 This incident reminds us that, in some cases, it may be frankly hostile! A patient’s foot activates a control knob on an x-ray table

Richard H Riley · Leigh J Coombs

Fast facts: Bipolar disorder. Guy Goodwin and Gary Sachs. Oxford: Health Press, 2004 (99pp). ISBN 1 903734 50 9. At first blush, a book from a series called Fast facts does not evoke enthusiasm — suggesting, rather, an uninspired commercial opportunism. However, this small volume is pleasingly pithy, erudite and accessible, as well as being helpfully informative. Goodwin and Sachs are eminent in the field of bipolar disorder, representing research groups from both sides of the Atlantic (Oxford and Harvard, respectively). The dominant style, however, is that quintessentially English amalgam of droll understatement and incisive intellectual directness. The authors are unabashed apologists for the scientific method in clinical medicine, while at the same time compassionate clinicians: “We believe that the medical model is useful in diagnosing bipolar disorder — indeed, we cannot see a viable or reliable alternative.” The richness of their clinical experience is apparent in their accounts of the condition, referring, for example, to the “mischievous state of elation” that characterises milder presentations of mania. When discussing the somewhat dry issue of aetiology, they engagingly describe the interplay of genetic vulnerability and life-event precipitants: “Triggers have the same relationship to the real causes of severe bipolar disorder as a spark has to gunpowder.” It is the sharp observations and commentary that make this volume distinctive. One striking instance is their discussion of the controversial issue of childhood bipolar disorder, which is being diagnosed at alarmingly high rates in the US: “It represents another of the ways in which practice in North America is different from that in most other parts of the world …. It is still possible for the sceptic to say that this is diagnosis inflation.” Bipolar disorder is a condition that is tentatively emerging from the shadows of shame, misunderstanding and fear. Thoughtful volumes such as this are a critical component of the process of destigmatisation. Philip B MitchellProfessor and Head, School of Psychiatry University of NSW, Sydney, NSW

Philip B Mitchell

Addictions and healing in Aboriginal country. Gregory Phillips. Canberra: Aboriginal Studies Press, 2003 (xix + 210 pp). ISBN 085575408. This is not the first book documenting the problems of addiction and healing in Aboriginal communities. It is, however, the first written by an Indigenous academic. It is also important because it puts forward a methodology for an Indigenous science that seeks to provide a theoretical and practical basis for Indigenous ways of knowing and working. The study is based on ethnographic research in an Indigenous community in north Queensland. Phillips first discusses his own role and responsibilities as an Indigenous academic working in an Aboriginal community. He articulates an Indigenous-defined methodological theory and culturally appropriate knowledge production, an issue that has received very little discussion in research among Indigenous Australians. Interweaving the voices of the community of “Big River” with a range of historical, anthropological and medical material, the experience of trauma and substance misuse is explored. Arising from these explanations, the author reflects on some of the ways the Big River community talk about addressing addiction problems. One fascinating chapter explores approaches to treating addictions among Native Canadians, where the author, together with a suicide prevention officer from Big River, made a number of visits to different communities and treatment programs. Through these experiences the author provides a provisional approach to the treatment of addictions, one that acknowledges the importance of culture and spirituality, but which also incorporates a number of other approaches, such as harm reduction, Alcoholics Anonymous and residential treatment. One criticism would be that the approaches to an Indigenous science outlined at the beginning are not clear in the following chapters. How would the Indigenous methodologies be replicated elsewhere? Do they rely on identification as an Indigenous person and in what ways can non-Indigenous academics and health professionals engage with this approach? In order for such important ways of knowing to be transferred elsewhere, it is important that such methodologies be clearly formulated. Nevertheless, this is an important book on a difficult subject, and one that successfully conveys the individual and social traumas of substance misuse and the ways communities are addressing them. Richard D ChenhallResearch Fellow Menzies School of Health Research, Darwin, NT

Richard D Chenhall

Biotech at the “bedside” A non-invasive, point-of-care proteomic assay may find a role in diagnosing bladder cancer as a useful adjunct to cystoscopy, according to US researchers.1 In a series of 1331 patients at increased risk for bladder cancer, they compared the performance of a nuclear matrix protein (NMP22) urinary assay with that of voided urine cytology, against a reference standard of cystoscopy with biopsy. The NMP22 assay was positive in 44 of 79 patients with cancer, whereas cytology test results were positive in only 12 of 76 patients. Further, the proteomic assay detected four cancers that were not visualised during initial endoscopy. This research paper is one of many enlightening articles in a JAMA theme issue on the medical applications of biotechnology,2 including molecular imaging and robotic surgery. There is also a discussion of intellectual property issues related to biotechnology research. 1. JAMA 2005; 293: 810-816 2. JAMA 2005; 293: 771-867 Theatre black-box With the advent of a Remote Analysis of Team Environments (RATE) tool, the days when the only long-standing records of an operation are the surgeon’s notes, the scrub nurse’s count sheet and the patient’s scar(s) may soon be over. Surgeons may like to keep an eye out for this "black-box" recorder, which can provide a permanent, synchronised, digital record of any operation. In a series of 10 laparoscopic cholecystectomies, the RATE tool was used to collect data from four cameras in the theatre (including laparoscopic images) and eight audio leads — time-stamping events of interest for later review. The record was also used to score the technical proficiency of the operating surgeons. J Am Coll Surg 2005; 200: 29-37 Mad dogs and Africans Death by rabies may be an unforeseen consequence of the HIV/AIDS pandemic in South Africa, according to a report in the South African Medical Journal. In AIDS-ravaged villages in KwaZulu-Natal province, on the east coast of South Africa, there appears to have been an "explosion" in the number of ownerless, feral dogs roaming the countryside. In 2004, feral dogs were implicated in the deaths of seven people in the province — five from rabies and two by mauling. A pilot research project is investigating the proposed link between AIDS and rabies; meanwhile, stray dogs are being culled and domestic dogs are being vaccinated. S Afr Med J 2005; 95: 78-79 Deadly air For every working day in the UK, two adults will die as a result of passive smoking in the workplace. And, in every week, one of these deaths will be in a hospitality industry employee — someone who has worked in a pub, bar, nightclub, hotel or restaurant. So estimates Jamrozik, an Australian Professor of evidence-based health care, using data held in national UK databases. The figures for death from passive smoking at home are even more dramatic — 2 700 deaths each year (approaching eight per day) for people aged 20 to 64 years, and 8 000 deaths each year among people aged 65 years or older. www.bmj.com Old but not out of it Healthy older women with breast cancer should be offered participation in new trials of chemotherapy because they are likely to derive a similar benefit to younger patients, according to authors writing for the international Cancer and Leukemia Group B. They reviewed data from four randomised trials that compared more aggressive with less aggressive chemotherapy regimens in 6 487 women with lymph node-positive breast cancer. Although only 8% of trial participants were aged 65 years or older, these women were just as likely to experience disease-free survival as younger women. Overall survival was worse for older patients, but this was because of death from causes other than breast cancer. Irrespective of age, disease-free survival in all women was longer with regimens containing more chemotherapy. JAMA 2005; 293: 1073-1081 Leukaemia vaccine Vaccine immunotherapy may supplement the beneficial effect of imatinib (Glivec) in chronic myeloid leukaemia (CML), say Italian researchers. They recruited 16 patients with CML and stable residual disease after treatment with imatinib or interferon alfa. After six subcutaneous vaccinations with a peptide vaccine (CMLVAX100) given at fortnightly intervals, seven of the patients achieved a complete cytogenetic remission. Further, there was a beneficial effect on cytogenetic response in all but one of the remaining patients. On the day before, and on the day of each vaccination, the researchers had also administered granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immune adjuvant. Lancet 2005; 365: 657-662 Dr Ann Gregory, MJA

Ann Gregory