Volume 188 Issue 7

The main objectives of medical negligence law relate to substandard care — the direction the law will take when new treatment approaches come along is not always clear If two heads are better than one, then four should be much better, and six should be truly formidable. The axiom is especially likely to hold true when the problem at hand is multifaceted, and each head carries knowledge that is relevant, different, and complementary. Therein lies the allure of multidis-ciplinary care (MDC) teams in cancer care. An age has passed since any surgeon, radiologist, pathologist, radiation oncologist, medical oncologist, or general practitioner could legitimately claim to be working both in splendid isolation and safely. Consultation among clinicians is integral to modern medical care. But the physical meeting of so large and diverse a group of busy clinicians, together with their allied health colleagues, for purposes of devising treatment plans for individual patients is a relatively recent phenomenon. Twenty years ago, the notion would surely have been met with disbelief in many hospitals. Today, the growing complexity of cancer treatment, coupled with new knowledge about the promise of team-based management in health care,1,2 are quickly establishing MDC teams as a standard feature of high-quality cancer care. Evidence of the effect of MDC on quality of care is still emerging. Recent studies suggest that cancer patients managed through MDC teams may have better decisions made about their care,3 live longer,4 enjoy better quality of life during treatment,5 and receive services more efficiently.6 However, substantial gaps remain in understanding the impact of MDC.7-9 From a medicolegal perspective, the salient aspect of MDC is that it shifts aspects of clinical decision making away from single actors and toward groups. How will courts handle allegations of substandard decision making levelled at all members of the team, or the team itself? Will team members with second-hand know-ledge of the patient’s condition assume less responsibility for faulty plans than those directly involved in the patient’s care? What of members who opposed the care path chosen? And what obligations do hospitals have to ensure MDC teams are established and that they play a meaningful role in clinical decision making? The short answer to these questions is that we don’t know yet. The absence of negligence claims targeting MDC in Australian courts and Anglo-American jurisdictions abroad means that we must speculate (although it is surely just a matter of time before litigation on point materialises). A threshold question in any negligence claim is whether the wrongdoer owed a duty of care to the person wronged. In medical negligence claims, the defendant’s duty is rarely disputed. In fact, tort law textbooks present the patient–doctor relationship as a paradigmatic example of a dutiful relationship. Occasionally, however, the assumption is challenged. Telemedicine10 and supervision of trainees by senior doctors at a distance11 are two recent examples of circumstances that force close consideration of the contours of the patient–doctor relationship. In both situations, duties may be imposed, even when the defendant clinician works at a considerable remove from the injured patient. The wise course is for each member of an MDC team to assume that, by virtue of their involvement in a team meeting, they assume certain responsibilities to the patient. (Indeed, responsibilities arise in virtually any setting in which doctors turn their mind to a particular patient and give advice.) Fulfilling those responsibilities requires sound judgement and informed input, commensurate with what would be expected of a team member’s professional peers were one of them seated at the same table and presented with the same information. If the first step in a medicolegal analysis of MDC is to recognise that the team and its members may be exposed to liability for their activities, the second step is sober assessment of how large that exposure is, and what can be done to minimise it. In this vein, the article by Evans and colleagues in this issue of the Journal (→ Medicolegal implications of a multidisciplinary approach to cancer care: consensus recommendations from a national workshop)12 is a welcome addition to the literature. The authors outline consensus recommendations developed at a workshop of experts. Their suggestions are clear and useful, particularly the need for attention to MDC activities in the informed consent process and careful documentation of team membership and resolutions. To these, I would add a simple exhortation to participants in MDC team meetings. Speak up! Your professional responsibilities entail weighing in wherever your expertise is relevant. If information is insufficient to render an informed opinion, say so. Group consensus is helpful, and learned clinical colleagues acting in good faith will often arrive at it, but, as Sidhom and Poulsen point out, MDC meetings should not be regarded as a strictly democratic process in which majorities rule.13 Disgruntled wallflower is the wrong part to play in an MDC team. Standards of care in medical negligence law are fluid and progressive. Today’s cutting-edge treatment may become a routine and expected treatment in the future, as it diffuses through clinical practice and evidence of its efficacy mounts. A curious aspect of negligence law is that novel treatments or approaches to care tend to raise heightened liability risks in their innovation phase, but once they gain currency, the risk profile flips: failure not to employ them becomes the greater liability risk. Recognition of this legal reality brings special resonance to the investigation of the uptake of MDC approaches among breast surgeons by Marsh and colleagues in this issue of the Journal (→ National Breast Cancer Audit: the use of multidisciplinary care teams by breast surgeons in Australia and New Zealand).14 Standards of care are not defined purely by reference to the prevalence of particular practices in the medical community; nor are recommendations and guidelines from august professional bodies, such as the National Breast Cancer Centre, accepted as definitive proof as to whether a particular practice has become an accepted standard. On the other hand, both factors are highly relevant considerations in determining the applicable standard of care. In Australia today, at least in some settings, MDC has probably become the standard of care for treatment of some cancers, particularly breast cancer. For other cancers, it likely stands on the cusp of becoming so. Thus, Marsh and colleagues’ findings14 should grab the attention of administrators and practitioners working in hospitals that have not adopted MDC practices. Rural and private facilities appear particularly likely to be in this situation. Many rural and private hospitals will face barriers to MDC that their counterparts in urban and public settings do not, as the article’s authors point out.14 Standards of care can bend to accommodate unavoidable resource and manpower constraints. However, in institutions where an MDC approach is feasible but is not being pursued, hospital leaders should carefully review their position. It is conceivable that a claimant may allege that the appropriate approach for breast cancer treatment was not followed and that, had it been, the harm in question would not have occurred. Such accusations would be likely to fall particularly heavily on the institution itself for failing to organise for effective MDC. Success for the plaintiff in this type of claim will not be easy. The evidence that MDC systematically improves quality of cancer care remains quite thin,7-9 which makes proving that it would have done so in an individual case an uphill climb. Nonetheless, it is quite possible that litigation along these lines may be brought. In that event, defendant institutions will no doubt find the attendant publicity unsavoury, whatever the claim’s outcome. The law aims to promote high-quality care, not retard it. Legal doctrine is neither static nor vacuum-sealed. As practices change, and promising initiatives like MDC emerge, the law must evolve to accommodate them, without abandoning its commitment to holding providers accountable for substandard care. Timely scholarship, like the articles in this issue of the Journal,12,14 can help guide that evolution at the right pace and in the right direction.

David M Studdert LLB, ScD, MPH

The benefits are greater efficacy and faster onset of action; the price is increased risk of bleeding . . . The mainstay of antiplatelet therapy for patients with acute coronary syndromes (ACS), including those undergoing early percutaneous coronary intervention (PCI), is the combination of aspirin and clopidogrel.1-3 Aspirin inhibits platelet thromboxane A2 production and platelet activation, and reduces the relative risk of recurrent ischaemic events in patients at high risk of vascular events by about 22% (absolute risk reduction [ARR], about 2%) at the expense of an increase in the odds of major bleeding events by about 60% (absolute risk increase [ARI], about 0.5%).1 Clopidogrel inhibits ADP-induced platelet activation by blocking the platelet P2Y12 receptor. When added to aspirin therapy in patients with ACS, it reduces the risk of recurrent ischaemic events by a further 20% (ARR, about 2.1%) at the expense of an increase in major bleeding events by approximately 38% (ARI, about 1%).2,3 Clopidogrel has several potential limitations, however. First, the onset of action is delayed, with a “therapeutic” level of 50% inhibition of ADP-induced platelet aggregation, as measured by light transmission aggregometry (LTA), not being reached until 4–6 hours after a 300 mg loading dose, and 2 hours after a 600 mg dose. Second, there is a “ceiling” effect — even a 900 mg dose achieves only around 60% inhibition of ADP-induced platelet aggregation. Third, laboratory testing suggests that “therapeutic” platelet inhibition is not achieved in a substantial proportion of patients because of individual variability in platelet inhibition by clopidogrel.4 Finally, there is uncertainty about the clinical benefit with higher loading doses of clopidogrel of 600 mg or 900 mg compared with 300 mg.5,6 Prasugrel is a novel thienopyridine prodrug whose rate, magnitude and consistency of platelet ADP inhibition is greater than for clopidogrel. It achieves more than 50% inhibition of platelet aggregation (measured by LTA) within 1 hour of a 60 mg loading dose.7,8 The safety and effectiveness of prasugrel have been compared with standard-dose clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel — Thrombolysis in Myocardial Infarction (TRITON–TIMI 38).9 A total of 13 608 patients with moderate-to-high-risk ACS scheduled for PCI were randomly assigned to receive prasugrel (60 mg loading and 10 mg daily maintenance dose) or clopidogrel (300 mg loading and 75 mg daily maintenance dose) for 6 to 15 months. Aspirin 75–162 mg daily was recommended for all patients. After a median duration of 14.5 months, the primary efficacy outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke occurred in 12.1% of patients taking clopidogrel and 9.9% of those taking prasugrel (hazard ratio [HR], 0.81; 95% CI, 0.73–0.90). Stent thrombosis was also reduced (2.4% clopidogrel v 1.1% prasugrel; HR, 0.48; 95% CI, 0.36–0.64). However, the key safety endpoint of major bleeding not related to coronary artery bypass graft (CABG) was increased (1.8% clopidogrel v 2.4% prasugrel; HR, 1.32; 95% CI, 1.03–1.68). All major bleeding (including CABG-related) was increased (1.7% v 2.5%; HR, 1.31; 95% CI, 1.16–1.50), as was fatal bleeding (0.1% v 0.4%; HR, 4.19; 95% CI, 1.6–11.1). Overall mortality did not differ significantly between treatment groups. A post-hoc subgroup analysis identified less clinical efficacy and greater bleeding among patients with a history of stroke or transient ischaemic attack, older people (age > 75 years), and those with bodyweight less than 60 kg. It is likely that these results are externally valid. However, by design, the study drug was only given after the coronary anatomy had been defined by angiography. This does not reflect usual clinical practice where clopidogrel is given at the time of presentation with ACS. Because there is a delay in the onset of action of clopidogrel, the design was biased in favour of prasugrel. Also, the prescribed standard 300 mg loading dose of clopidogrel was lower than that now adopted by many clinicians following reports of an improved inhibition of platelet aggregation with higher loading doses of clopidogrel such as 600–900 mg in patients with PCI.6 These caveats aside, the data suggest that treating 1000 patients with ACS at moderate-to-high risk of vascular events with prasugrel (compared with clopidogrel at the standard approved dose) for a median duration of 14.5 months would prevent about 22 major vascular events and cause eight major haemorrhages, including three fatal bleeds. The implications for clinicians, should prasugrel gain regulatory approval, are that it may allow cardiologists to delay their decision to administer a P2Y12 inhibitor until after coronary angiography (thus avoiding the bleeding risk of clopidogrel in patients who need urgent CABG), and to use prasugrel instead of clopidogrel in the acute phase of ACS, possibly using clopidogrel for long-term maintenance therapy. The implications of these results for researchers are that it is important to determine whether the risk of long-term bleeding with prasugrel may be reduced, without compromising efficacy, by using lower doses and by avoiding its use in those with previous stroke or low bodyweight, and older people. A lower dose of prasugrel is presently being compared with clopidogrel in the TRILOGY study, involving 10 000 patients with ACS who are treated medically. Research is also needed to evaluate the potential for individualised antiplatelet therapy based on the results of point-of-care testing of platelet function and genetic polymorphisms. Meanwhile, large randomised trials are presently comparing: the efficacy and safety of a high loading dose and maintenance dose of clopidogrel (versus a low loading dose and maintenance dose); the oral reversible non-thienopyridine ADP receptor antagonist, AZD6140, with clopidogrel; and the parenteral reversible non-thienopyridine ADP receptor antagonist, cangrelor, with clopidogrel, all in patients with ACS treated with an early invasive strategy.

Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MB BS, FRACP, FRCPA · Paul E Langton MB BS, FRACP

Global environmental change is threatening the health and survival of humankind — are we doing enough to ensure the environmental and social bases for health? Global warming and resultant climate change pose serious risks to human health.1-3 However, global warming is only one of a nested series of threats to the health — and even survival — of humankind. With this in mind, is our current approach to both clinical and public health sufficient? Parallel threats to the health and wellbeing of humanity arise from a myriad of anthropogenic problems (Box). All such problems, acting synergistically, stress the ecological and social foundations upon which humanity relies for air to breathe, water to drink, food to eat, and disposal of waste, and without which there can be no civilisation and no economy. Taken together, they comprise what has been described as global environmental change (GEC).4 There are many drivers of GEC. Our complex society is heavily dependent on oil to function, even though the supply of easily recoverable oil has peaked or is about to peak.5 However, the fossil fuel bonanza over the past century and a half has enabled a human population explosion that, in turn, has been driving GEC. As populations expand and encroach into new areas, destroying natural habitats and putting animals and humans into close proximity, humans are being increasingly exposed to novel animal diseases. HIV and emerging diseases such as Ebola virus, severe acute respiratory syndrome and H5N1 avian influenza may be manifestations of this.6 The rising population, ecological stress, and neoliberal-driven economic disparity all contribute to political unrest and human violence,7,8 which drive further GEC. Consequently, humanity is facing a series of serious, unprecedented ecological and social changes caused by ourselves. Of these, it is global warming that, if not the most dangerous threat, is the fulcrum about which to coordinate analysis and action. To express concern about the survival of humankind is not being alarmist. Our understanding of the threats facing humanity has moved to a point where the full range of possibilities confronting us can be appreciated. Where we end up consequent to GEC in the next two centuries will be somewhere on a continuum that extends from the extinction of Homo sapiens, through collapse or patchy disintegration of complex industrialised society, to a sustainable industrial civilisation. Exactly where we find ourselves on this continuum depends on how quickly and effectively we act environmentally, economically and socially. Our survival also depends on our ability to control weapons of mass destruction, which are more likely to be used as the consequences of GEC generate conflict over access to ever scarcer resources. As health carers, we are involved on several levels. Individually, we are both part of the cause of GEC and recipients of its effects. As health care professionals, we will need to modify both our health systems and the way we practise to meet the challenge of new health problems, and to adapt to old health problems in new guises. As health professionals, we also have a duty of care to our patients to strongly advocate for action. Serendipitously, GEC also presents unique opportunities. GEC and economic inequity have related causes. Thus, a strategic approach would enable humanity to derive a set of solutions that will make the world both environmentally sustainable and more economically just,7 with flow-on benefits for health. Indeed, Jonathan Patz proposed that “global climate change could be the greatest public health opportunity we’ve had in over a century”.9 Changes needed to mitigate and adapt to GEC present specific health opportunities; for instance, less car use means more exercise. Howard Frumkin has explained how redesigning cities and rearranging traditional work practices can enhance exercise, build social capital, and make a healthier society.10 While beneficial, such changes are not in themselves sufficient. GEC is adversely affecting our society and will continue to do so. The medical community can no longer limit its focus to hospital waiting times, fee levels, workforce shortages, obesity and diabetes. These issues all become starkly irrelevant if the ecological and social systems on which we depend for both our survival and our capacity to deliver services, save lives and care for people stop working. We need a profound shift in our paradigm. The health care sector is not only responsible for delivering health care, but must also ensure the environmental and social bases for health itself. To meet this responsibility, we can act personally — buy a hybrid car, for instance. Individually, we can join and financially support organisations that are working for change: Doctors for the Environment Australia, the Medical Association for Prevention of War, the Australian Conservation Foundation, and others. But collectively, our academic colleges and professional associations must advocate strongly and clearly to government about the gravity of our predicament and the need for urgent, wide-ranging action. Humanity needs a new vision for health for the year 2100: to make sure we have an economically equitable society on an ecologically healthy planet. The stakes are high — we must not fail. The challenge I put to all of us and to our health and political leaders is to work together to make this vision a reality. Serious current environmental problems* Destruction/loss of natural resources natural habitat (ecosystem services) wild food sources biological diversity soil (erosion, salinity, fertility) Ceilings on natural resources (soft ceiling, raising the ceiling costs) energy (fossil fuel and alternatives) fresh water photosynthetic capacity of plants Harmful things made or moved around toxic chemicals alien species atmospheric gases (greenhouse gases → climate change, ozone destruction) Increasing human population actual numbers impact per capita on the environment (resource use and waste) * Derived from Diamond J. Chapter 16. In: Collapse: how societies choose to fail or survive. London: Allen Lane, 2005.

Peter W Tait MB BS, FRACGP

Objective: To explore the involvement of members of the Royal Australasian College of Surgeons (RACS) Section of Breast Surgery in Australia and New Zealand in multidisciplinary care (MDC) teams.Design and setting: Questionnaire sent to all full members of the RACS Section of Breast Surgery in December 2006.Participants: 239 of 262 active full members of the RACS Section of Breast Surgery (response rate, 91.2%).Main outcome measures: Surgeons’ use of, and the composition and functioning of, MDC teams in public and private practice, and in metropolitan, regional and rural settings.Results: 85% of responding surgeons reported participating in at least one fully established MDC team. Public-sector teams were operationally more consistent and functional than private teams, and rural teams were less well developed than those in metropolitan and regional centres. The six core disciplines recommended by the National Breast Cancer Centre appear to be well represented in most teams. Patients and their general practitioners were not considered to be part of the treatment team by surgeons.Conclusions: MDC is supported by most breast surgeons, but there are deficits in rural areas, and in the private sector relative to the public sector.

Claire J Marsh BHSc(Hons) · Margaret Boult BSc(Hons), GDIM · Jim X Wang PhD · Guy J Maddern PhD, FRACS · David M Roder PhD · James Kollias MB BS, FRACS

Objective: Minimal trauma fractures may be the first indication of osteoporosis. Our aim was to determine the proportion of patients who underwent bone density testing for osteoporosis of those with a minimal trauma wrist fracture treated in the emergency department (ED).Design: This observational retrospective cohort study used explicit medical record review and scripted telephone interviews.Setting: EDs of three metropolitan hospitals in Melbourne in 2006.Participants: Patients aged 50 years and over who were treated for wrist fracture due to minimal trauma. Data collected included demographic details, fracture details, causes of injury, any bone density testing and any osteoporosis-related medication change.Main outcome measure: The proportion of patients who underwent bone density testing in the follow-up period.Results: 131 patients were studied; 83% were female, and the median age was 71 years. No patient was referred by an ED or fracture clinic for bone density testing (95% CI, 0–3.5%). Telephone follow-up data were obtained from 91 patients. Of these, 28 reported having bone density testing after their fracture, of whom 14 (50%; 95% CI, 32%–67%) were found to have osteoporosis. Seven were treated with a bisphosphonate and one with a selective oestrogen-receptor modulator.Conclusion: Follow-up of patients suffering minimal trauma wrist fractures treated in the ED is poor. Systems to improve the identification and treatment of osteoporosis in this group are needed if future osteoporotic fractures and their consequences are to be avoided.

Anne-Maree Kelly MD, MClinEd, FACEM · Megan Clooney RN · Debra Kerr BN, MBL · Peter R Ebeling MD, FRACP

Objective: To determine the association between smoking in pregnant teenagers and baby birthweight.Design, setting and participants: A retrospective population-based study of women aged < 20 years who gave birth to liveborn singletons in Australia between January 2001 and December 2004. Data were drawn from the National Perinatal Data Collection.Main outcome measures: Maternal smoking, birthweight, low birthweight (LBW).Results: The prevalence of LBW in babies born to teenage smokers was 9.9%, compared with 6.0% in babies born to teenage non-smokers (odds ratio [OR], 1.72 [95% CI, 1.57–1.90]). On average, babies born to teenage smokers were 179.8 g lower in birthweight than babies born to teenage non-smokers (95% CI, 165.5 –194.1 g; t = 24.6, P < 0.001). Smoking, Indigenous status, Socio-Economic Indexes for Areas category and parity were independently associated with LBW (all ORs > 1.3; P < 0.001) after adjusting for maternal age group. Teenagers smoking > 10 cigarettes a day had babies with lower birthweight that those who smoked ≤ 10 cigarettes a day, demonstrating a dose–response relationship. The babies of teenage smokers who stopped smoking before 20 weeks’ gestation had birthweights similar to those of babies born to teenage non-smokers. One in 15 teenage smokers stopped smoking during pregnancy.Conclusion: Babies whose mothers smoked during pregnancy were more likely to have LBW than babies whose mothers did not smoke. Mothers who continue to smoke in the second half of pregnancy increase their baby’s risk of LBW. There is significant scope to improve the quitting rate, and health professionals need to target smoking cessation at all contacts with pregnant women who continue to smoke.

Denise L Chan · Elizabeth A Sullivan MB BS, MPH, MMed(Sexual Health)

Objective: To determine which aspects of open disclosure “work” for patients and health care staff, based on an evaluation of the National Open Disclosure Pilot.Design, setting and participants: Qualitative analysis of semi-structured and open-ended interviews conducted between March and October 2007 with 131 clinical staff and 23 patients and family members who had participated in one or more open disclosure meetings. 21 of 40 pilot hospital sites, in New South Wales, South Australia, Victoria and Queensland, were included in the evaluation. Participating health care staff comprised 49 doctors, 20 nurses, and 62 managerial and support staff. In-depth qualitative data analysis involved mapping of discursive themes and subthemes across the interview transcripts.Results: Interviewees broadly supported open disclosure; they expressed uncertainty about its deployment and consequences, and made detailed suggestions of ways to optimise the experience, including careful pre-planning, participation by senior medical staff, and attentiveness to consumers’ experience of the adverse event.Conclusion: Despite some uncertainties, the national evaluation indicates strong support for open disclosure from both health care staff and consumers, as well as a need to resource this new practice.

Rick A M Iedema BA, MA, PhD · Nadine A Mallock BHealthEcon, MHealthServMgt · Roslyn J Sorensen BSocWk, PhD · Elizabeth Manias RN, BPharm, PhD · Anthony G Tuckett PhD · Allison F Williams BAppSci(Nursing), MNursing, PhD · Bruce E Perrott MBA, PhD · Suzanne H Brownhill PhD · Donella A Piper BA, LLB(Grad)(Hons), LLM · Suyin Hor · Desley G Hegney RN, BA(Hons), PhD · Hermine B Scheeres PhD · Christine M Jorm MB BS, MD, PhD

Concerns about medicolegal implications of a multidisciplinary approach to cancer care may act as a barrier to the implementation of best practice approaches. While multidisciplinary meetings carry a low level of medicolegal risk, improved documentation and transparency in approach will assist in limiting liability for individual health professionals and health services. The medicolegal implications of a multidisciplinary approach are not affected by whether a health professional bills the patient for attendance at multidisciplinary meetings.

Alison C Evans BSc, PhD · Helen M Zorbas MB BS, FASBP · Megan A Keaney MB BS, MHA · Mark A Sidhom BEc, LLB, MB BS · Holly E Goodwin BAppSc, GradCertPH · Janice C Peterson BHSc, GradCertHSc

Injury is a leading cause of disability and death in Australia and is recognised as a national health priority area. The foundation of successful injury prevention is injury surveillance, and national policies and strategies developed over the past 20 years to reduce the burden of injury in Australia have included 22 recommendations on surveillance — only three of which have been completely implemented. Priorities for improving injury surveillance include: improving current injury mortality and morbidity data collection systems; filling the gaps in injury surveillance; maintaining vigilance over data quality; increasing the integration and accessibility of injury data; developing technical expertise in surveillance. Barriers to implementation of the current National Injury Prevention and Safety Promotion Plan include the lack of an implementation plan, performance management structure, appropriate national governance structure and resources — all of which could be overcome with government commitment.

Rebecca J Mitchell MA(Psych), MOHS · Rod J McClure PhD, FAFPHM · Ann M Williamson BSc(Hons), PhD · Kirsten McKenzie BSSc(Psych)(Hons), PhD

Patients with adrenal insufficiency (AI) require additional glucocorticoid doses during surgery or medical illness, but there is no universally accepted regimen for glucocorticoid supplementation therapy. The high doses and long duration of glucocorticoid coverage that have traditionally been used do not reflect the hypothalamic–pituitary–adrenal response to surgical stress and medical illness in normal people. While the optimal dose and duration of supplementation therapy have not been established, our recommendations are based on extrapolation from what constitutes a normal cortisol response to stress, on expert opinion derived from the medical literature, and on clinical experience. The recommended use of lower doses of glucocorticoids during surgical and medical stress should not de-emphasise the importance of additional supplementation during such events. Our recommendations do not replace clinical judgement, but their use will ensure that patients with AI are safely managed during illness or surgery without the risk of an adrenal crisis or excessive steroid dosing.

Caroline Jung MB BS, FRACP · Warrick J Inder MB ChB, MD, FRACP

There has been a call to include empathy as a selection criterion in medical training. Empathy is a complex construct currently assessed by self-rating and observational scales, which may be complicated by the subjectivity of such measurements. Neuroscientific research into disorders of empathy such as autism should be encouraged to help further refine the evolving construct of empathy. Empathy may be more common in females, and selection for higher empathy may discriminate against males unless sex-specific adjustments are included in selection criteria. Physician empathy may lead to greater patient satisfaction and confidence in physicians, but more evidence is needed to support links to physician competence. In contrast, academic performance and conscientiousness have been clearly linked to physician competence. Competence and empathy may be independent qualities developed by different aspects of medical training. Provision of better work conditions and environments for physicians may forestall erosion of empathy, reducing the need to predict and enhance its development. Empathy should be valued in medical students and doctors, but more research is needed into the nature, assessment, and correlates of empathy before its adoption as a selection criterion for medical students.

Jeffrey C L Looi MB BS

Treating clinicians need to make and own decisions about withholding futile treatment, instead of delegating them to patients’ families who are usually ill equipped to do so As a specialist physician for more than 20 years and, more recently, as a senior health manager, it has become apparent to me that staff at all levels across the hospital sector believe that they are actively treating a proportion of patients for whom such treatment is clearly futile. In providing this treatment, clinical leaders are on some level aware that they are doing a disservice to these patients, their families and the community, but seem ill equipped or unwilling to deal with the psychological, social and perceived legal challenges encountered in withholding futile treatment. Futile treatmentThe definition of futile treatment is complex and has been discussed in detail by others.1 One simple definition is treatment that gives no, or an extremely small, chance of meaningful prolongation of survival and, at best, can only briefly delay the inevitable death of the patient. It is helpful to use an example to illustrate: in my former clinical practice as a nephrologist, cases similar to that in the Box were becoming increasingly frequent. There are, of course, a variety of other clinical circumstances where treatment might not be strictly futile (in terms of prolonging survival) but in which complex quality-of-life issues are an important part of the decision-making process. For example, antibiotic treatment of curable pneumonia in a patient with advanced dementia who might then live some years would not be regarded as futile therapy but might still legitimately be questioned. In such situations, early consultation with patients, advanced care directives, and legal next-of-kin consent for incompetent patients are required. While there may be good arguments to not pursue active treatment in some of these cases, the context is quite different from that of futile treatment and requires a different approach to that proposed here. Futile treatment and the lawClinicians are under no moral or legal obligation to provide futile treatment2 and, indeed, I would contend that their obligation is to withhold treatment that keeps patients from their families and is invasive and unpleasant, in the absence of any likely survival benefit. Why, then, do clinicians pursue this course of action in the knowledge of its folly? Usually, when questioned, the response from clinicians in the common situation of an incompetent patient is: “Because the patient’s family or next of kin want us to do everything”. This is poor practice on two grounds: because futile treatment should not be continued even if apparently desired by the next of kin; and because, in my experience, most next of kin will accept a decision to withhold futile treatment, as long as they are not being asked (as is commonly the case) to personally make what they see as a life-ending decision. The legal situation is quite clear in all jurisdictions. Competent patients, or those holding authority to act on behalf of incompetent patients, cannot demand treatment that clinicians believe to be futile.2 This includes such treatment as cardiopulmonary resuscitation (CPR), dialysis, ventilation and, in some circumstances, even enteral or intravenous nutrition. It is quite surprising how little awareness of this legal situation there is among medical staff. Junior doctors often believe that consent of the next of kin is required to withhold CPR, when, in fact, even if the next of kin desires the patient to have CPR, they have no legal right to demand it if the treating clinicians consider it futile. Futile treatment and decision makingIn part, the current problem with clinical leadership in futile treatment relates to a misperception of the role of inclusiveness in decision making. Twenty-five years ago, medical leaders in hospitals were seen as decisive, but not in an inclusive way. Decisions would be made at the end of the bed, and the patient, his or her family, and the rest of the clinical team would, hopefully, be informed of the decision but not included in the decision-making process. Rightly, the educational and ethical framework has changed, such that it is now the norm to have multidisciplinary decision-making processes and to fully inform patients and their families about all aspects of care and clinical decisions. Unfortunately, some clinicians have interpreted this involvement of families in the clinical decision-making process for incompetent patients as a reason to delegate some of the clinical team’s decisions to the family, who, at the time, are ill equipped to deal with them. To illustrate this point, consider the case outlined in the Box. My approach to the family of this incompetent patient was to say that dialysis was not going to offer meaningful prolongation of survival and would be very unpleasant, and therefore that “the clinical team has decided not to offer this treatment and we will instead offer palliative care”. The more recent approach, with the misguided view of inclusive decision making, would be to give the family the gloomy prognosis but then leave them with the terrible question: “Do you want us to provide dialysis (which might be life-sustaining for a short period of time) or do you want us to not perform dialysis and instead provide palliative care?” In effect, the family hear this question as: “Do you want to make the decision to end the life of your loved one or do you want us to keep trying with a life-prolonging treatment?” While some spouses, children or other relatives may have sufficient psycho-emotional strength to deal appropriately with this scenario, many do not and will revert to the base position of “do everything, including dialysis”, in the mistaken belief that seeing their relative suffer and die despite treatment is better than living with the terrible responsibility of their (incorrect) belief that they consented to the death. Compare this with my approach, where the family are left with the view that the clinical team could do no more and decided that palliative care was best. In my experience, most families took comfort from this approach. A more common example is the decision to withhold CPR, which is usually made in the context of the treatment being considered futile for an incompetent patient. Modern practice would dictate, appropriately, that such a decision should not be made without full consultation with the family or next of kin. This is commonly misinterpreted by clinicians as a requirement for formal consent from the family to withhold CPR which, when asked for, is often refused for the same reason as given above. Few people are emotionally equipped to deal with a decision that they misinterpret to mean they let their relative die when his or her heart stopped. It is much better for them to know that the decision not to perform CPR was made and owned by the treating clinicians who have judged that they can do no more for the patient and that CPR would serve no purpose. Futile treatment and leadershipDiscussion with families about withholding futile treatment will always take considerable time, which must be allowed for, to ensure a full and complete picture is provided and their many inevitable questions can be answered. Families may request additional time to come to terms with a decision or even to gain another opinion on the prognosis and the futility of treatment. These requests should be granted, but with the understanding that it is the province of the clinicians to make these decisions. Very occasionally, some families will refuse to accept the clinical decision and will seek support from the legal system. Health services should support and welcome these rare legal challenges as an objective endorsement of actions to support the primary duty of care to the patient. There has not been a case where a court in Australia or the United Kingdom has overturned a carefully considered decision by a doctor to withhold treatment that is considered futile.3 While I have referred to clinicians and the clinical team, and strongly believe that treatment decisions are the province of the whole team, it is clear that the community looks to the (senior) medical practitioners for the security they need to accept decisions of great moment, such as withholding futile treatment. It is most important that the senior medical members of a hospital team be prepared to play a leadership role in these discussions and, based on their clinical experience, be prepared to make statements and communicate decisions in a way that inspires confidence in others. This leadership issue is therefore largely a problem of the medical profession. Indeed, junior medical staff and nursing and allied health staff in hospitals are often left with the consequences of poor or absent decision making by senior staff and will likely welcome the rebirth of leadership. Withholding futile care is not about saving money for the health system. The primary reason for clinicians to withhold futile care is to enable them to do their best by their patient. Certainly, some resources might be freed up, but only to be used by the many other patients with treatable conditions who are waiting for hospital care and may, indeed, cost more to treat. I strongly encourage medical leadership groups within and outside of health services to raise and debate this issue and call for a re-evaluation of the relevant parts of undergraduate and postgraduate medical education curricula. This is not an issue that requires legislative change or widespread community debate; it is merely implementing good practice in the best interests of patients and is within the existing power of medical clinicians to effect change today. An 88-year-old man is admitted with advanced renal failure for consideration of maintenance dialysis treatment. He is bed-bound, with longstanding type 2 diabetes, dementia, widespread macrovascular and microvascular disease, amputations, poor vision and advanced ischaemic cardiomyopathy. From clinical experience and registry data, nephrologists know that, while dialysis in the short term might provide some prolongation of life (perhaps weeks or months), it will be at the price of a long-term inpatient stay (probably until death), frequent vascular access surgery and a high risk of even earlier death from the complications of treatment. Maintenance dialysis treatment is therefore reasonably seen as futile in this clinical context.

Brendan F Murphy MB BS, PhD, FRACP

Clinical record A 51-year-old woman of European ancestry presented in 2006 with a 2-month history of lethargy, nausea and arthralgia, and 2 weeks of jaundice. Her past history included gastric bypass surgery for obesity at the age of 40 years, and laminectomy. She had been taking a commercial preparation of black cohosh (20 mg per day) intermittently for 3 years, with titration according to her menopausal symptoms. This preparation was available over the counter. It contained 20 mg of black cohosh root extract per tablet, and the manufacturer recommended a dose of 20 mg twice daily. Two months before symptom onset, the patient increased the dose to the manufacturer’s recommended dose because of worsening menopausal symptoms. The patient was not taking any other medications, including other herbal preparations, paracetamol, or non-steroidal anti-inflammatory drugs. She had no personal or family history of liver disease. She was an ex-smoker, with no history of illicit drug use, significant alcohol consumption, recent travel, tattoos, transfusions or sick contacts. Physical examination revealed jaundice and mild ascites, but no evidence of hepatic encephalopathy or stigmata of chronic liver disease. Results of laboratory studies were consistent with acute hepatitis. Serum albumin concentration was 36 g/L (reference range [RR], 31–44 g/L); elevations were noted in serum concentrations of aspartate aminotransferase (AST) (1327 U/L; RR, < 40 U/L), alanine aminotransferase (ALT) (1230 U/L; RR, < 50 U/L), alkaline phosphatase (ALP) (191 U/L; RR, 30–110 U/L), γ-glutamyltransferase (GGT) (523 U/L; RR, < 40 U/L), and bilirubin (106 μmol/L; RR, < 20 μmol/L). The international normalised ratio (INR) was 1.8 (RR, 1.0–1.2), serum creatinine concentration was 58 μmol/L (RR, 45–90 μmol/L) and MELD (Model for End-Stage Liver Disease) score was 16 (a score > 15 indicates that prognosis at 1 year will be improved by transplantation). Extensive investigations to exclude other causes of acute liver failure gave negative results, including serological tests for hepatitis A, B, and C; cytomegalovirus IgM; Epstein–Barr virus IgG and IgM; antinuclear antibody; anti-liver/kidney microsomal antibodies; antimitochondrial antibody; anti-smooth muscle antibody, α-1 antitrypsin; ceruloplasmin; and fasting iron studies. Abdominal computed tomography 1 month after presentation showed moderate ascites and a shrunken irregular liver contour, with a liver volume of 720 mL. Prominent vessels around the lesser curvature of the stomach suggested portal hypertension with collateral vessel formation. Doppler ultrasound examination a month later confirmed a small liver with coarse heterogeneous echotexture, and a macronodular surface. The portal vein was patent. A liver biopsy 6 weeks after presentation showed massive hepatocellular necrosis with preserved bile ducts, collapsed parenchyma, and no recognisable residual hepatocytes (Figures, A and B). There were extensive mononuclear inflammatory infiltrates with few neutrophils. Perls staining was negative for iron. A diagnosis was made of acute liver injury secondary to black cohosh ingestion. Over the subsequent weeks, the patient’s jaundice worsened, and her serum bilirubin level continued to rise. Frusemide was given to manage developing moderate ascites. Sixty-two days after presentation, the patient developed asterixis (“hepatic flap”), indicating encephalopathy and liver failure. She was diagnosed with subfulminant liver failure suitable for liver transplantation and was listed urgently for transplant. Liver function tests showed a serum albumin concentration of 30 g/L and elevated serum concentrations of AST (202 U/L), ALT (73 U/L), ALP (191 U/L), GGT (64 U/L) and bilirubin (728 μmol/L). The INR was 1.8. Her renal function rapidly deteriorated, with serum creatinine concentration rising to 255 μmol/L. The MELD score reached 37. A liver became available 5 days after the patient was listed, and a successful orthotopic liver transplantation was performed. Her postoperative course was uneventful. The explanted liver weighed 744 g and was distorted by multiple nodules of varying size, from 5 mm to 50 mm (Figure, C). Microscopically, there were areas of extensive submassive necrosis, capsule distortion, collapse of the hepatic parenchyma, and mononuclear inflammatory infiltrates around the portal tracts. Cholestasis was prominent. Nodular regeneration with portal–portal linkage was also evident in some areas, as seen in the pretransplant biopsy. Black cohosh is a herbal remedy used around the world for relief of menopausal symptoms. In Australia, over 200 listed medicines containing black cohosh are available without prescription.1 However, in the past decade, seven case reports of hepatotoxicity associated with black cohosh have been published.1-7 To our knowledge, our patient is the eighth reported case, and the sixth to require liver transplantation. Lessons from practice Black cohosh is a herbal remedy used by millions of women worldwide for the relief of menopausal symptoms. Emerging evidence of severe hepatotoxicity potentially linked with the use of black cohosh has raised concerns regarding its safety profile. The community needs to be educated about potential risks of alternative and herbal medications such as black cohosh, and further regulations are required to monitor the safety of these preparations. Black cohosh (Cimicifuga racemosa, also known as Actaea racemosa) is a perennial plant native to North America. The World Health Organization recognises its use for “treatment of climacteric symptoms such as hot flushes, profuse sweating, sleeping disorders and nervous irritability”.8 The American College of Obstetricians and Gynecologists stated that it may be helpful in the short term (6 months or less) for women with vasomotor symptoms of menopause.9 Although the exact mechanism of action is unknown, the primary active constituent of the black cohosh root is the terpene glycoside fraction, and the rhizome contains biologically active substances, including alkaloids, flavonoids, and tannins. However, despite the growing literature on the efficacy of black cohosh for menopausal symptoms, definite conclusions cannot be drawn because of the methodological shortcomings of available studies, such as lack of blinding, lack of long-term follow-up, and variations in product and dosage.10-12 Two safety reviews have found black cohosh extract to be well tolerated and adverse events to be rare when it is taken for up to 6 months.13,14 However, the seven case reports of hepatotoxicity potentially associated with black cohosh use in the past decade raise concern. Currently, there is no known biologically plausible mechanism to explain this hepatotoxicity, which is likely to be multifactorial. The plant contains both potentially hepatoprotective (triterpene glycosides) and hepatotoxic (salicylates, alkaloids) elements. Extracts and constituents of the rhizome have been shown to induce apoptosis and cell cycle arrest in human breast cancer cells,15,16 while extracts of the related plants Cimicifuga foetida and Cimicifuga dahurica inhibited proliferation of rat and mouse hepatocytes.17 The most likely cause of our patient’s liver failure was her use of black cohosh, although it has been recognised that 10% of patients receiving liver transplantation have idiopathic subfulminant liver failure.18 Our patient’s history of obesity treated with gastric bypass surgery 11 years before is unlikely to have contributed to the liver failure as she had shown no abnormalities of liver function previously, and no features of steatohepatitis were seen in the pretransplant liver biopsy specimens. Our case is also notable as the patient had used black cohosh intermittently at half the manufacturer’s recommended dose for 3 years, and at the manufacturer’s recommended dose (20 mg twice a day) for only 2 months before symptom onset. There is a widespread belief in the community that “natural” plant substances are safe, effective and free of side effects. Various regulatory bodies now recognise the association between black cohosh use and hepatotoxicity, and many recommend warning labels. The Therapeutic Goods Administration (TGA) was the first in the world to announce, in February 2006, that medicines containing black cohosh must include the label: “Warning: black cohosh may harm the liver in some individuals. Use under the supervision of a healthcare professional”.19 In November 2007, the TGA revised the warning to: “In very rare cases, black cohosh has been associated with liver failure. If you experience yellowing of the skin or eyes, dark urine, nausea, vomiting, unusual tiredness, weakness, stomach or abdominal pain, and/or loss of appetite, stop using this product and see your doctor”.20 Randomised controlled trials will provide more definitive information on the safety of black cohosh and its efficacy for alleviating menopausal symptoms. Animal models may provide useful information about the cause of idiosyncratic liver damage. The public needs to be educated about the potential risks of alternative and herbal medications, and further regulations are required to monitor the use and safety of these preparations. Currently, there are no agreed guidelines for monitoring liver function in patients taking black cohosh. We recommend that liver function be checked before and during use of black cohosh.

Elizabeth C-Y Chow MD · Marcus Teo MB BS · John A Ring MB BS, PhD · John W Chen MB BS

Re: “Implementing and sustaining transformational change in health care: lessons learnt about clinical process redesign”, by Katherine M McGrath, Denise M Bennett, David I Ben-Tovim, Steven C Boyages, Nigel J Lyons and Tony J O’Connell, in the Supplement to the 17 March issue of the Journal, “Health services under siege: the case for clinical process redesign” (Med J Aust 2008; 188: S32-S35). Box 5, shown here, was accidentally omitted from the article. 5 Example of the continuous improvement element of sustainability in process redesign at Flinders Medical Centre Within general medicine at Flinders Medical Centre, the junior doctors, consultants, department head and the redesign team meet every 2 weeks over lunch to review performance in regard to the redesign work, and to identify problems and improvement opportunities. This meeting is also an ideal mechanism for identifying, on a regular basis, the internal system problems that this group of clinicians face every day.

Katherine M McGrath · Denise M Bennett · David I Ben-Tovim · Steven C Boyages · Nigel J Lyons · Tony J O’Connell

Re: “Respiratory syncytial virus infections in children in Alice Springs Hospital”, the letter to the Editor by Apakasimaka Dede, David Isaacs, Paul J Torzillo, John Wakerman, Rob Roseby, Rose Fahy, George Clothier, Andrew White and Paula Kitto, in the 18 February issue of the Journal (Med J Aust 2008; 188: 261). A processing error caused the ninth and final author, Paula Kitto, BSc, BM BS, General Practice Registrar at the Centre for Remote Health, Alice Springs, NT, to be omitted from the authors’ byline. The web version of the article was corrected on 10 March 2008.

Apakasimaka Dede · David Isaacs · Paul J Torzillo · John Wakerman · Rob Roseby · Rose Fahy · George Clothier · Andrew White · Paula Kitto

Re: “The national inpatient medication chart: critical audit of design and performance at a tertiary hospital”, the research article by J Alasdair Millar, Robyn C Silla, Glenda E Lee and Ann Berwick, in the 21 January issue of the Journal (Med J Aust 2008; 188: 95-99). The caption for Box 5 suggested that the difference in colour between the two medication charts could be seen. In fact, the Box was printed on a black and white page. The colour version of the figure is shown below. The web version of the article was shown in colour and required no correction. 5 Prescriptions for oxycodone in the PRN section of the national inpatient medication chart (top) and in the combined prescription panel in the Royal Perth Hospital chart MR246 (bottom) Successive doses are written horizontally in the national inpatient medication chart (NIMC) — a novel design feature — but vertically in MR246 (and all other pre-existing charts). Thus, each column represents a specific dose in the NIMC but a specific date in the displaced charts. The NIMC grid is cramped but entries consume more chart space, and time-related changes in the requirements for the drug are obscured, whereas in MR246 this is apparent by inspection. Note also alternate day shading in the MR246, which aids visual inspection, and the buff colour, which allows easy identification in case records. PRN = pro re nata (as needed).

J Alasdair Millar · Robyn C Silla · Glenda E Lee · Ann Berwick

A 14-year-old boy was admitted with a 2-week history of increasing breathlessness and fatigue. He had a pulse rate of 130 beats/min and blood pressure of 100/66 mmHg with 16 mm paradox. Jugular venous pressure was raised 10 cm above the sternal angle, and heart sounds were faint. He had been diagnosed with refractory iron-deficiency anaemia in early childhood, for which he had been receiving blood transfusions. He denied any history of epistaxis, haemoptysis, malaena, haematuria or overt bleeding from any other site. On examination, the patient had multiple, blue-black, papular and nodular, compressible, non-pulsatile, vascular skin lesions, ranging in size from a few millimetres to 1–2 cm, distributed over the trunk and limbs, including the soles of the feet, perineal region (Figure A) and lips. A chest x-ray showed an enlarged cardiac silhouette suggestive of pericardial effusion (Figure B). This was confirmed by transthoracic echocardiography. Therapeutic pericardiocentesis showed haemopericardium. Blue rubber bleb naevus syndrome (Bean syndrome) is diagnosed in the presence of distinctive venous malformations on the skin, in the gastrointestinal tract and, less often, in other organs, leading to occult or overt gastrointestinal bleeding and chronic anaemia.1-3

Pankaj Malhotra · Madhav C Menon · Subramaniyan S Anand · Arshjyot Narula · Subhash Varma

Failure to atone. The true story of a jungle surgeon in Vietnam. Allen Hassan. Sacramento: Failure to Atone Press, 2006 (272 pp). ISBN 978 0 9776049 0 6. Dr Hassan’s background is remarkable. He was a United States Marine Sergeant who qualified in veterinary medicine before becoming a doctor and serving two terms as a civilian in Vietnam, later completing a degree in law. From this unique perspective he presents disturbing insights and images of the Vietnam War. His clinical volunteer work was in the battered province of Quang Tri in mid 1968, and the experience completely altered Hassan’s life. The core of the book is a harrowing episode — the massacre of 40 infants, all shot in the head, apparently by his own Marine Corps — and his efforts to get to the truth behind this tragedy. Several of the 774 doctors despatched by the American Medical Association’s Volunteer Physicians for Vietnam have contributed stories from their own tours of duty. Also acknowledged is the work of civilian teams from other countries, including Australia and New Zealand, and there is praise for the US medical corpsmen who, of necessity, undertook major clinical responsibilities. Surgical triumphs and disasters, atrocities on both sides and the despair of embittered servicemen are all recounted, but it is the bigger picture that haunts Hassan’s conscience: the courage and dignity of the Vietnamese people; the death and destruction wrought by futile bombardment of innocent civilians; the failure of aid programs to concentrate more on preventive medicine, public health and training; and guilt that his country is making the same mistakes in Iraq. The book is well bound, with an arresting full-colour dust jacket. Within, unfortunately, the photographs are mediocre and the text poorly edited, uneven and repetitious. Nevertheless, it should be read, not least for such accounts as the mutilated soldiers kept in Vietnam to avoid lowering morale back home, and sinister activities by the CIA. Scarcely believable, but sadly convincing.

Marshall Barr

Heart failure and palliative care: a team approach. Miriam Johnson, Richard Lehman, editors. Oxford: Radcliffe Publishing, 2006 (x + 150 pp). ISBN 978 1 85775 643 2. At first glance, this appeared to be another of the “palliative care for another subspecialty” works that have been appearing over the past few years. The amount of new and truly specialty-specific material in these can be limited, and one can only suppose that they are sometimes driven as much by publisher catalogue agendas as by real need. This is not the case with this short and well written book from the United Kingdom. The editors are a palliative care physician and a general practitioner who have developed an interest in this subpopulation of patients, for whom palliative and supportive care needs have hitherto tended to be largely ignored. They are modest about their aims, and write clearly with what appears to be comprehensive referencing to the small but growing literature on caring for patients who have end-stage heart failure. The syndrome of advanced heart failure is explained, with very readable accounts of epidemiology, pathophysiology and treatment. There is much reference to the work of one of the contributors, Scott Murray, and his coworkers in primary care at the University of Edinburgh, who have published on comparative needs of patients with heart failure and lung cancer. They highlight the fact that decision making and prognostication are, in general, harder in heart failure, which tends to run a more protracted and unpredictable course than many cancers. Murray has proposed a simple but radical alternative to attempts at precise prognosis as a guide to care planning, by asking: “Would I be surprised if my patient were to die within the next 12 months?” If the answer is “no”, then it is time to start thinking about the deployment of supportive and palliative care.1 The work is certainly UK-centric, however, for Australian readers this is still a good summary of the issues and the literature, together with some useful experience of setting up services in selected UK centres. The heart content would be of no interest to a cardiologist, just as most of the palliative care content would not be news to specialists in that discipline, but each discipline can learn about the other, and generalists will probably find some benefit in both.

Michael A Ashby

To the Editor: Recently, we treated a patient with fatal paramethoxyamphetamine (PMA) poisoning. We believe this is the first PMA poisoning to be reported in the Australian Capital Territory. PMA (street name, “death”) was first reported in the early 1970s during the emergence of recreational use of 3,4-methylenedioxymethamphetamine (MDMA [“ecstasy”]).1,2 Hyperthermia, coma and seizures are features of MDMA and PMA poisoning, but they are more severe with PMA ingestion; features of hypoglycaemia, hyperkalaemia and QRS interval prolongation are suggestive of PMA poisoning.3 Our patient was a 20-year-old man who was conveyed to the emergency department by ambulance after presumed MDMA ingestion. On presentation, he was unconscious (Glasgow Coma Score, 4/15) and had the following signs: temperature, 42.8°C; heart rate, 90 beats/min; QRS interval, 160 ms (reference range [RR], < 100 ms); blood pressure, 171/148 mmHg; oxygen saturation, 76% (RR, 95%–100%); and respiratory rate, 40 breaths/min. After intubation, external cardiac compressions and multiple DC shocks were required to restore circulation. The initial serum potassium level was 8.9 mmol/L (RR, 3.2–5.0 mmol/L). Hypoxaemia persisted, and a chest x-ray showed extensive bilateral airspace consolidation. The patient’s associates alleged that he habitually used equine clenbuterol and ovine androgen preparations in addition to ecstasy. The subsequent days were notable for resistant shock, rhabdomyolysis, cardiomyolysis and severe coagulopathy refractory to therapy. Oliguric renal failure necessitated extracorporeal blood purification. Hepatic failure and hypoglycaemia were pronounced. The most extreme biochemical derangements recorded in this case are listed in the Box. Five days after admission, the patient’s pupils were sluggishly reactive. Oculocephalic and oculocaloric reflexes were present but abnormal, while gag and cough reflexes were absent. A cerebral computed tomography scan showed extensive cerebral oedema. By Day 8, the patient had fixed pupils and worsening haemodynamic instability. He died 10 days after ingestion of PMA. The patient’s antemortem blood concentration of PMA was 2.3 mg/L — 2.0 mg/L above the typical fatal threshold of 0.3 mg/L previously reported.2-4 MDMA, methylenedioxyamphetamine (MDA) and methylecgonine were also detected at low levels. Since 2005, the Pharmacy Guild of Australia has instituted its “Pseudo Watch” program to reduce diversion of pseudoephedrine to illicit methamphetamine manufacture by a combination of retail restrictions and recording details of purchasers judged genuine. Supporting legislation varies by state.5 However, PMA is made from the readily available and unmonitored precursor, anethole. Further, PMA has a slower onset of action than MDMA, leading to the possibility of additional doses being ingested while awaiting effects. We believe medical practitioners should consider PMA poisoning in cases of severe reactions to ecstasy, especially those in which hypoglycaemia and hyperkalaemia are present. A “market” shift in drug use towards the more lethal PMA because of reduced availability of pseudoephedrine would be a cause for concern. Laboratory markers of multisystem organ dysfunction in a case of PMA poisoning Biochemical marker Extreme value (peak or nadir) Reference range Creatine kinase (U/L) 58 358 20–200 Troponin I (U/L) 85.83 < 0.06 Bilirubin (μmol/L) 412 2–20 ALT (U/L) 3961 < 55 Ammonia (μmol/L) 219 10–50 Platelet count (× 109/L) 18 150–400 ALT = alanine aminotransferase. PMA = paramethoxyamphetamine.

Paul G Lamberth · Geoff K A Ding · Liisa A Nurmi

To the Editor: The recent editorial by Waxman1 implies that early streaming of students during medical school training is to become the norm for admission to the Royal Australasian College of Surgeons’ Surgical Education and Training (SET) program. We would like to draw attention to the disturbing nature of this development for medical students and junior doctors alike. Waxman described the imperative for students to now decide upon a career in surgery “usually as undergraduate medical students”.1 He stated that some universities have proposed early streaming of students into specific surgical modules in later years of their medical programs. While early streaming may appear to be the answer to the growing conflict between the time constraints of undergraduate medical programs and the expanding body of medical knowledge, there are a number of significant pitfalls to this approach that are yet to be explored. First, early streaming may jeopardise the quality of the generalist education offered at medical schools. International experience from McGill University in Canada, which implemented an early-streaming program in the late 1970s, supports this notion.2 The cohorts from McGill’s early-streaming program had poorer overall performance than their predecessors in the non-streamed program on the Medical Council of Canada’s national licensing examination, which was attributed in part to their reduced opportunity for generalist training. Second, the notion that well resourced university surgical departments could provide an early-streaming package for undergraduate students that “[gives] their students an advantage and an almost guaranteed pathway into SET”1 creates gross inequity in access to surgical training. This system would disproportionately disadvantage students from both graduate-entry programs, which have a shorter course duration, and newer universities, which lack the resources to provide advanced surgical training modules. Third, the program disadvantages students who have not formed firm career intentions by the later years of their medical program. With data from the United Kingdom showing that more than a quarter of junior doctors change their career intentions in the 3 years after graduation,3,4 a significant proportion of medical graduates will gain no appreciable benefit from early streaming, and may in fact be disadvantaged by it. We strongly discourage the introduction of early-streaming programs in medical schools. All schools should graduate “pluripotent” undifferentiated doctors with a strong generalist background.

Timothy J Smith · Carly M Fox · Michael A Bonning

To the Editor: The editorial by Waxman1 on the Royal Australasian College of Surgeons’ new Surgical Education and Training (SET) program contains some factual errors that have led to anxiety among potential applicants. We wish to give the formal position of the College and to correct any misunderstandings. The SET program2 is evolutionary, builds on the strengths of the previously available program, and is based on an educationally sound framework and group of principles. Registering an interest in training with the College does not in itself confer an advantage but will enable those registered to receive up-to-date information and College publications. The College website also provides up-to-date, relevant information for potential applicants. Completion of the Australian and New Zealand Surgical Skills Education and Training (ASSET) course is not compulsory before selection into SET, but it must be completed by the end of the first 2 years of the SET program. The College and the specialist surgical associations and societies involved in the delivery of the SET program will rely on robust workplace-based assessment to monitor trainees’ progress and provide career advice. New in-training assessment tools are necessary to achieve this, and their implementation requires support, including courses for surgeons who undertake this vital work. Those contemplating a career in surgery will not have to decide on their career choices at an earlier stage than previously. In the previous program, graduates could apply during their internship but now must wait until their second year after graduation. The College is committed to a broad-based period of preparation for surgical training but does not wish to deny the opportunity to those in their second year after graduation who are certain of their career aspirations. Applications will also be accepted from those who delay their career decisions for whatever reason. Streaming medical students for vocational careers is an attractive educational philosophy, provided it does not interfere with the generalist experience required for all graduates. Furthermore, streaming is predicated on the medical colleges recognising this prior learning in their programs. Until this is resolved, the question of its implementation remains some way off. The current practice of undertaking electives in an area of interest is strongly supported. The College is committed to working with the universities for a more integrated approach across the continuum of learning and seeks to build on the meaningful and collaborative partnerships already established. The key interface is the practising surgeon in an academic position who understands the requirements of the College and the university, as well as the needs of the community. Selection into surgical training is through a national merit-based process. The curriculum vitae (CV) and its components of academic achievement, other accomplishments and clinical experience will each be scored and given appropriate weighting. The lower percentage overall for CVs (15%–25%) takes into account that many candidates will apply very early in their careers.2 While we laud the suggestion of university surgery departments providing a package for potential trainees, “giving their students an advantage and an almost guaranteed pathway into SET”1 does not necessarily follow, given the competitive nature of selection.

John P Collins · Ian D Civil

To the Editor: The revised recommendations of the Australasian Creatinine Consensus Working Group1 are improved with the recognition of an age-related reduction in glomerular filtration rate (GFR), but don’t deal with a number of other significant problems associated with an estimated GFR (eGFR). When a plasma creatinine measurement is requested, an eGFR is commonly provided, increasing the sensitivity but reducing the specificity of diagnosis of kidney disease. The eGFR remains a substantially flawed estimate of GFR. It is associated with significant predictive error (up to 30% of individual eGFRs differ by more than 30% from the measured GFR at 60–90 mL/min)2 and with substantial false positive and false negative outcomes. The flaws in the eGFR are, firstly, the limitations of creatinine clearance rate as a measure of GFR, and secondly (and more importantly), the use of age, sex and race as surrogates for muscle mass (the determining factor in creatinine production and, together with creatinine clearance, plasma creatinine level). Age, sex and race are imperfect predictors of muscle mass, and this leads to underestimation of GFR in people who are fit and well muscled and overestimation in those who are wasted and disabled. While reporting eGFR values represents a worthwhile advance on using plasma creatinine levels to detect kidney disease, it could be considered, at best, the “least bad” readily available measure of GFR. When no better test is readily available, how should we handle a suboptimal measure of GFR? Educating the medical profession about the limitations of eGFR is important, but, based on personal experience and anecdotal evidence, I believe that using conventional methods of informing doctors has not been uniformly effective. Providing “just in time” information support is likely to assist this process. Thus, I support the recommendation that laboratories routinely report eGFRs, but suggest that, when they do so, they add a product warning along the following lines: The eGFR is calculated assuming a normal muscle mass for age, sex and race. It will underestimate GFR in well muscled individuals and overestimate GFR in patients with muscle wasting. A creatinine clearance test or formal GFR measurement may be helpful in patients whose muscle mass differs from the average for their age and sex. Proteinuria and haematuria are other useful indicators of kidney disease. In patients over 70 years of age, an additional product warning, consistent with the Australasian Creatinine Consensus Working Group’s revised recommendations,1 could be as follows: GFR declines with age, and, in patients over 70 years of age, an eGFR of 45–59 mL/min/1.73m2, if stable over time and unaccompanied by proteinuria or haematuria, is unlikely to have specific renal prognostic or therapeutic implications.

William R Adam

To the Editor: The revised recommendations for the use of the estimated glomerular filration rate (eGFR) in the clinical setting use the Modification of Diet in Renal Disease (MDRD) formula to adjust drug dosing in people with renal impairment (Recommendation 6).1 Although the utility of the MDRD-based eGFR as a screening tool to identify people with chronic kidney disease represents an important clinical opportunity, we, and others,2,3 remain concerned about this recommendation. Certainly, adjusting the dose of renally excreted medicines based on a patient’s serum creatinine concentration alone is not appropriate. Accordingly, many drug monographs provide explicit dosing recommendations based on the estimated creatinine clearance (calculated using the Cockcroft–Gault formula) as a rational basis for dose adjustment using sound pharmacological principles. This assumes a significant correlation between the estimated creatinine clearance and the actual clearance of a drug (or metabolite). But such a correlation has not been established for the MDRD formula. Indeed, an empirical study comparing the use of the Cockcroft–Gault formula to the MDRD formula in 1067 elderly patients found that the MDRD formula significantly overestimated renal function and would, if used, lead to significantly higher doses of two drugs in question (enoxaparin and gentamicin) being administered.2 This highlights the need for further research to rigorously characterise the relationship between MDRD estimates of renal function and drug clearance before this formula can be recommended to guide dose adjustment in the clinical setting. Recommendation 6, that the MDRD-based eGFR should be used for dosing after considering body size,1 requires further clinical information about the patient — the same information needed to use the Cockcroft–Gault formula. Even limiting Recommendation 6 to drugs that are not “critical-dose drugs”1 is confusing. Many drugs would be considered critical-dose drugs when used in frail older people with some degree of renal impairment. We reaffirm the statement, from the 2008 Australian medicines handbook, that “there is no evidence that [automatically reported eGFR] is suitable for adjusting drug doses in people with renal impairment”.4

on behalf of the Editorial Advisory Board, Australian medicines handbook

In reply: We agree with Adam’s points that: The estimated glomerular filtration rate (eGFR) represents a worthwhile advance on the plasma creatinine level for detecting kidney disease, and is currently the best readily available measure of GFR; Educating the medical profession on the limitations of eGFR is important; and Further refinements of eGFR accuracy are highly desirable. Since the advent of automated laboratory reporting of eGFR, there has been a concerted effort by the Kidney Check Australia Taskforce to educate medical professionals and other clinicians about the strengths and limitations of eGFR and about how best to approach the patient with a significantly reduced eGFR. Education has been via printed office materials, accredited workshops, medical journal articles, online education, and decision-support systems embedded in medical software. Adding statements to laboratory reports has also been considered by the Australasian Creatinine Consensus Working Group, and some laboratories do provide explanatory eGFR statements. However, many have not embarked on this because of the difficulty of providing adequately informative explanatory remarks in very limited space. Individual laboratories balance the need for such supporting information against the space requirements on reports and the diminishing effect of excessive repetition. Given that routine reports are already complex, often containing over 20 result items, and that many millions of reports with serum creatinine results are produced annually in Australia, the value of any repetitive comment needs careful consideration. The response of clinicians to the introduction of automatic reporting of eGFR together with the linked educational campaign has been strongly positive, with outcomes that have included easier identification of chronic kidney disease, better decision making for affected patients, and more appropriate referral patterns, both in Australia and overseas. Nevertheless, we agree with Adam that eGFR is only an approximation of actual GFR and is subject to error. There are ongoing attempts to further improve the accuracy and clinical utility of eGFR through such ventures as the universal standardisation of creatinine calibration (which has already taken place in Australia and New Zealand) and the Chronic Kidney Disease Epidemiology Collaboration.1 McLachlan, on behalf of the Editorial Advisory Board of the Australian medicines handbook, reaffirms the Board’s position that eGFR is not appropriate for use in dosage calculations. However, for the reasons stated in the consensus document,2 we remain convinced that eGFR is a useful tool for most drug dosing decisions. We note with interest the recent change in the position taken by the British National Formulary (BNF 54) to one of support for the Modification of Diet in Renal Disease (MDRD)-based eGFR1 being used in place of creatinine clearance rate “for most drugs and for most patients of average build and height”3 — a stance similar to ours. In particular, we re-emphasise that eGFR, because of its ready availability, increases the rate of identification of renal failure. We agree with McLachlan that prescribers should continue to follow specific published recommendations for drugs such as enoxaparin and gentamicin (these are good examples of “critical-dose drugs” in the hospital setting). We note additionally that there is increasing acceptance of the eGFR in the drug literature. In the case of enoxaparin, the MDRD equation for eGFR has been used to assess the effect of renal function on bleeding in elderly patients4 and has been found to provide the best relationship with enoxaparin clearance in this setting.5 The eGFR is now an established feature of pathology reports in Australia, and we believe it is important to integrate this information into routine practice for drug dosing decisions. We therefore offer to work with the authors of the Australian medicines handbook and other interested parties to develop guidelines for drug dosing decisions using all available information.

on behalf of the Australasian Creatinine Consensus Working Group

To the Editor: I read with interest the article by Morton et al, summarising their impressive results of lung transplantation in adolescents treated in an adult hospital.1 The authors state they “do not have an exclusion policy for patients suitable for LTx [lung transplantation] based on age or size criteria alone”, and refer small or very young children to overseas units. The accompanying editorial by Snell et al comments that a paediatric transplant unit would have too low a caseload (four to eight transplants per year) to ensure they deliver good results.2 I agree that large-volume units are desirable, yet of the 158 centres reporting adult lung transplantation to the International Society for Heart and Lung Transplantation, 59% averaged fewer than 10 lung transplants a year.3 While a Surgical Fellow at St Louis Children’s Hospital, Mo, USA (1996–97), I was part of the surgical team undertaking a transplantation operation on a 13-month-old ventilator-dependent infant referred from Sydney. He had an uncomplicated postoperative course, leading to early hospital discharge and early return to Australia. Over the ensuing 5 years, while I was in touch with the family, they travelled regularly to St Louis for follow-up, as local expertise in managing young lung transplant recipients was lacking. Referring families to overseas units may be a good, albeit extremely expensive, short-term solution, yet developing local expertise in the follow-up of these patients has to be part of this package, to ensure optimal management, referrals and dialogue with overseas transplantation centres. Such local expertise could provide the backbone of a future paediatric lung transplantation unit, preventing unnecessary deaths in this population. Although paediatric lung transplantation is challenging, results for isolated operations in children are similar to those in older age groups,3 so the “perception that the risk of undertaking LTx in children and adolescents does not warrant the reward”2 needs to be challenged. From 1990 to 2002, 190 children received transplants at St Louis Children’s Hospital (45% of them younger than 10 years), 30 of whom underwent living-related lung transplantation (generally reserved for patients too ill to wait for cadaveric lung transplants); although they were a higher-risk group, their survival statistics exceeded those of adult lung transplant patients.4 After all, a low case workload does not stop any of the four paediatric cardiac surgery units in this country from offering arterial switch operations. A local paediatric lung transplant follow-up service, perhaps attached to an adult unit, would be instrumental in optimising paediatric lung transplantation outcomes and could inform the debate on the pros and cons of setting up local paediatric lung transplantation services.

Monica C Robotin

In reply: We were interested to read about Robotin’s insights gained from her experience at St Louis Children’s Hospital, which has one of the largest and most successful paediatric lung transplantation units in the world. We agree that development of local expertise in paediatric lung transplantation would be a cost-efficient means of offering optimum care to young Australians. Because the experience in lung transplants at St Vincent’s Hospital, Sydney, has grown, we would like to provide this service for younger recipients, but our centre lacks specific expertise and facilities for ongoing paediatric care. A dedicated paediatric ward with experienced nursing staff in a family-friendly environment is essential to meet world’s best practice in this area. There are many complications of the underlying conditions that might benefit from paediatric specialty expertise. Our experience emphasises that a close working relationship with the patient and his or her family is crucial, and that distance from the location of care delivery and ease of access to the primary treating team are important factors. Given the tyranny of distance, a single Australian centre would be inefficient. However, analysis of outcomes in adult centres shows superior results with increasing transplantation volume, so the concept of small stand-alone centres is not supported by evidence.2 Logistics dictate that linking paediatric services to existing adult services in Australia should improve long-term outcomes. Our data show that performing adolescent lung transplantation in a centre with proven expertise in adult procedures produces excellent results. We advocate provision of adequate funding and resources in all Australian transplantation centres to achieve optimum service delivery in paediatric lung transplantation.

Judith M Morton · Allan R Glanville

In reply: We thank Robotin for her positive comments. We agree that the current successful lung transplantation outcomes for adolescents in Australia should be able to be extended to the whole paediatric population in due course.,2 The appropriate timing of the operation and peritransplantation management of young children with advanced lung diseases requires further consideration and debate.3 This should involve the existing lung transplantation services and specific committed paediatric institutions. However, we disagree that a very low caseload, with procedures performed in a number of institutions, is acceptable. On the basis of cost, training, staffing and political support, it is appropriate to concentrate the expertise. A solid case can be made for a national approach, supported by the Australian Government, with Nationally Funded Centre status. In time, this would provide solid paediatric expertise and access to lung transplantation, either in Australia, or even overseas, as appropriate, during the early evolution of such a program. The objective would be improved survival in children with severe lung disease while minimising the disruption and cost associated with young Australians and their families travelling internationally for lung transplantation care.

Gregory I Snell · Glen P Westall · Trevor J Williams

To the Editor: Applying for medical school in Australia is not an easy process. Prospective applicants must choose from 19 medical schools and multiple course options, navigate admissions processes and tests, and develop some understanding of the pathway towards full registration and vocational training. Despite this complexity, there is a paucity of information that provides a bird’s eye view of the Australian medical school admissions process. There is no single source of information that comprehensively maps the options available to those wishing to embark on a career in medicine. Existing references are often outdated1 or do not accurately identify all medical courses.2 To fill this information gap, the Australian Medical Students’ Association (AMSA) launched its inaugural Medical School Guide in 2007. The guide paves the way for informing prospective medical students about the challenges of studying medicine and the diversity of medical courses on offer in Australia. The guide contains two sections: “Essential Information” includes details about the categories of entry, admissions tests, support schemes and vocational training pathways; and “The Medical Schools” contains information about individual universities, including location, entry requirements and procedures, and contact details. AMSA produced the guide in conjunction with Medical Deans Australia New Zealand (MDANZ) and the Australian Medical Association. Information on individual courses was supplied by the universities, via MDANZ, to ensure accuracy. All but one medical school submitted enrolment information for publishing. The Medical School Guide was launched on the AMSA website (at http://www.amsa.org.au/medschoolguide.pdf), and promotional letters were sent to relevant stakeholder groups. In the 110 days immediately after its release, there were 37 555 hits on the webpage, with more than 3500 downloads of the guide. In 2008, AMSA hopes to attract the financial and in-kind support required to publish and distribute a hardcopy version of the Medical School Guide. AMSA also hopes to further develop the guide to include information for prospective international students about visa requirements and opportunities to enter the Australian health workforce. In a dynamic environment where numbers of medical students and schools are on the rise, there is a convincing case for a comprehensive, user-friendly guide to medical school admissions. The AMSA Medical School Guide aims to do this, and its effectiveness will require rigorous evaluation in years to come.

James M Hillis · Robert D Mitchell

The final truth The declining rate of non-forensic autop-sies has resulted in a loss of important knowledge for clinicians and pathologists, according to Canadian and US researchers. In their review, the authors found that errors in diagnosis which may have resulted in a change in therapy (class 1 errors) are missed in approximately 10% of cases. They also discovered that the expected prevalence of missed cases among non-autopsied patients significantly reduced the rate of antemortem detection of three serious illnesses: aortic dissection, pulmonary embolism, and active tuberculosis. Declining expertise, a lack of resources, and a reluctance to order post-mortem examinations all contribute to the problem. The authors suggest an alternate approach based on the establishment of regional government-funded autopsy centres which would allow proper pathologist training and resuscitate the dying art of the autopsy. N Engl J Med 2008; 358: 873-875 The eyes have it The relationship between fasting plasma glucose (FPG) and diabetic retinopathy has been questioned and clarified by a group of Australian and international researchers. In a large population-based study involving over 11 000 participants, the prevalence of retinopathy ranged from 9.6% to 15.8%. Retinopathy was diagnosed from multiple clinical photographs, and plasma glucose levels measured via fasting blood samples. Researchers found that there was inconsistent evidence for a glycaemic threshold for retinopathy, with data appearing to suggest a continuous relationship. Of particular concern was the finding that the commonly used FPG cut-off for diabetes of 7.0 mmol/L had a sensitivity of less than 40% for the detection of retinopathy. Lancet 2008; 371: 736-743 Down time for teens The results of a US randomised controlled trial suggest that adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression may benefit from a change to another antidepressant combined with cognitive behaviour therapy (CBT). A group of 334 teenagers with a diagnosis of major depressive disorder who had not responded to a 2-month trial of an SSRI were enrolled in the trial. Participants were randomly assigned to four groups receiving either: a different SSRI, a different SSRI plus CBT, a change to venlafaxine, or venlafaxine plus CBT. Therapy was continued for 12 weeks. CBT plus a switch to either medication showed the highest response rate, but those on venlafaxine had a greater incidence of side effects including an increase in diastolic blood pressure and the occurrence of skin problems. JAMA 2008; 299: 901-913 Depressed doctors — who pays? Hospital residents working in paediatrics have high rates of depression and “burnout” which may affect their prescribing ability, US researchers have found. In a prospective cohort study involving 123 residents in three paediatric residency programs, the prevalence of depression and burnout was assessed using validated rating scales. The rate of medication prescribing errors per month for each resident was also determined. In total, 20% of the participating doctors met the criteria for depression and 74% for burnout. Depressed residents were found to make over 6 times as many medication errors as non-depressed residents. The rates of errors per month did not differ for the residents suffering burnout. The authors call for screening of residents for signs and symptoms of depression, and warn that the alarming results of their study indicate a need to improve the mental health of trainees in the medical field. BMJ Online, 7 Feb 2008 Variable LFTs create confusion Liver function tests can show considerable variability in the same asymptomatic individual over time, resulting in unnecessary further investigations and patient anxiety, according to the results of a large population study. The US NHANES (National Health and Nutrition Examination Survey) included over 1800 participants in a reliability study aimed at characterising the magnitude of intra-individual variability of liver function test results. Tests included levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase and γ-glutamyltransferase. A significant percentage of results that were initially elevated were normal on a second examination (a mean of 17.5 days later), including 38% for bilirubin and 36% for AST. The analysis took into account possible confounders such as alcohol consumption, hepatitis, or use of medications known to be hepatotoxic. The authors suggest that clinicians need to be aware of the high variability of these tests and consider retesting asymptomatic individuals before proceeding to other, more expensive investigations. Ann Intern Med 2008; 148: 348-352

Tanya Grassi