Letters

To the Editor: We read with interest the recent editorial and articles on health technology assessment.1-4 We are pleased that the Journal highlighted this important policy process that attempts to ensure that technologies that improve health gain or health care are supported and those that do not contribute to an improved outcome are not supported. The description of HealthPACT in the editorial1 is not quite accurate in that HealthPACT is a subcommittee of the Medical Services Advisory Committee (MSAC). Its funding comes through MSAC with some supplementation from the Australian Health Ministers’ Advisory Committee. The techniques of early detection and horizon scanning have been developed, and the results of this work are available to the health community of Australia, be it jurisdictional, public, private or specialised. In particular, if promising health care technologies are identified through this process, they are referred to MSAC for a full health technology assessment, thus ensuring that appropriate technologies are identified as early as possible in the technology cycle and are assessed by MSAC for introduction into the health care system. This horizon-scanning activity does not currently involve drugs or vaccines, and the Australian health care system could benefit from this process, just as the National Institute for Health and Clinical Excellence in the United Kingdom and the Canadian Agency for Drugs and Technologies in Health undertake comprehensive horizon scanning. With respect to conflicts of interest, MSAC is very specific at all levels of its operation. At the commencement of every advisory panel and MSAC meeting, the Chair requests declaration of conflicts of interest. These are recorded in the minutes and appropriate decisions are made on the participation of the person declaring a conflict based on an assessment of the issue. This is formal and explicit, and is on the public record. It is important to state this, as the article by Petherick and colleagues implies that MSAC does not record conflicts of interest.4 In fact, MSAC places great importance on declaration of conflicts of interest.

Brendon J Kearney · Stephen L Blamey

To the Editor: I wish Professor Carr the very best in his attempt to eliminate the somewhat confusing term “Barrett’s oesophagus” from the literature.1 Changing well entrenched medical nomenclature is difficult, however. I tried to do this with “microscopic colitis” 10 years ago2 but was not successful. After all, I argued, we do not speak of “microscopic bronchitis” or “microscopic salpingitis” — so why should we have the term microscopic colitis? It is nonetheless pleasing to note that the definition of microscopic colitis has tightened up over the past 10 years,3 and I think this may be a more realistic aim for Professor Carr with the term Barrett’s oesophagus. Admittedly, the two entities are not perfectly analogous, as, unlike microscopic colitis, Barrett’s oesophagus is classically associated with abnormally coloured mucosa. However, in both entities, the endoscopist usually takes biopsies from endoscopically flat mucosa, specifically looking for the disease in question. I am not sure I can see myself in 10 years’ time looking down someone’s oesophagus and saying, “I think there may be some columnar metaplasia down there. I wonder if there is some intestinal metaplasia as well?” Maybe this would be a good conversation opener in the halls of the pathology department, but certainly not in the endoscopy suite! I think I will still be saying, “That looks like Barrett’s, but we will need to take biopsies to make sure”.

Andrew A Thomson

In reply: I thank Dr Thomson for his kind comments. I sympathise with his attempts to eliminate the term “microscopic colitis”1,2 and would happily join him in this campaign. I agree it is important to tighten up the definitions of ambiguous terms. For example, “indeterminate colitis” is another term that continues to be used in different ways, despite attempts to clarify its definition.3 However, in the case of Barrett’s oesophagus, there are precise definitions, but they are mutually exclusive. The British Society of Gastroenterology uses one definition (not requiring goblet cells), whereas other national bodies use another definition (requiring the demonstration of goblet cells histologically).4 Therefore, when an endoscopist says “That looks like Barrett’s”, he or she could be saying either that the mucosa appears glandular or that a pathologist will find goblet cells in it. The two are not the same and we should not confuse them. I believe we should not use “Barrett’s oesophagus” because it is defined differently by different people; confusion regarding the site of a particular biopsy can cause it to be applied inappropriately; and we have existing terminology that does the job. I accept that a few lone voices are not going to change well entrenched terminology. However, we can hope that the national and international bodies that construct guidelines in this area will take heed, accept the challenge and deal with the problem.

Norman J Carr

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

To the Editor: Panton–Valentine leukocidin (PVL) is a potent necrotising toxin, which, although produced by less than 5% of all Staphylococcus aureus strains, is strongly associated with pathogenic isolates that cause recurrent furunculosis and severe necrotising pneumonia.1 The virulence of PVL-positive community-associated methicillin-resistant S. aureus (CA-MRSA) causing necrotising pneumonia was recently highlighted in the Journal.2 Conversely, PVL produced by methicillin-sensitive S. aureus (MSSA) is uncommon.1 Here, we describe a case of fulminant necrotising pneumonia caused by PVL-positive MSSA, which, to our knowledge, is the first reported case in Australia. A previously well 33-year-old man presented to the emergency department with a 48-hour history of pleuritic chest pain, fever and productive cough. On presentation, the patient was hypotensive, and in acute renal failure and hypoxemic respiratory failure (type I). Chest x-ray showed bilateral widespread air space consolidation. Despite treatment with intravenous fluid resuscitation and early broad-spectrum antibiotics (ceftriaxone, azithromycin, vancomycin and co-trimoxazole), the patient’s condition rapidly deteriorated, requiring intubation and inotropic support. Multiple blood and sputum cultures isolated MSSA. Bronchoscopy revealed widespread airway haemorrhage. A trans-oesophageal echocardiogram excluded endocarditis. Progressive leukopenia developed. Septic shock and respiratory failure worsened, despite treatment with flucloxacillin as well as maximal inotropic and ventilatory support. The patient died 72 hours after presentation from fulminant pneumonia. Polymerase chain reaction testing subsequently identified the PVL gene in the isolated MSSA. Rising rates of CA-MRSA causing recurrent furunculosis and severe necrotising pneumonia have been reported worldwide.3 Necrotising pneumonia often affects children and young adults,1 and, despite current treatments, mortality rates are over 50%.4 Our patient exhibited two major factors predictive of increased lethality: leukopenia and airway bleeding.4 PVL has been well described in CA-MRSA; it is present in at least 96% of the two predominant strains in south-east Australia.3 There is some evidence that PVL is the major pathogenic factor of CA-MRSA, although this remains controversial.5 The precise pathogenesis of PVL has not yet been discovered; however, a severe inflammatory response secondary to PVL’s cytolytic effects on polymorphonuclear leukocytes, as well as the induction of other bacterial virulence factors, are possibilities.1 Therapies directed against the PVL toxin, including antibiotics such as clindamycin that target the bacterial ribosome, or intravenous immunoglobulin, have been suggested but have little supportive data.2,3,6,7 In contrast to CA-MRSA, the PVL gene is found much less frequently in MSSA, being present in only 2% of isolates in one French study.1 Specific Australian prevalence data are lacking, but PVL-positive MSSA isolates have similar potential to cause severe invasive disease.1,6 Most cases of severe necrotising staphylococcal pneumonia and recurrent furunculosis are caused by CA-MRSA, and empirical therapy for these conditions should cover this organism. This case involving MSSA highlights the role that PVL may play in the pathogenicity of these conditions, and shows that the development of novel therapeutics directed at PVL may be of value.

Ada S-Z Cheung · Craig A Aboltins · John R Daffy · Peter A Stanley

To the Editor: Predicting research quality on the basis of past research publications is clearly imprecise, as noted by Nicol et al in their recent article on National Health and Medical Research Council (NHMRC) grant applications.1 They note that assessor ratings of applicants’ “track records” correspond poorly with the bibliometric data for authors, and that there is vast variability between discipline panels. For immunology, the correlation between track record scores and journal impact or citations was high, at over 0.7. For public health, the correlation was actually negative. The authors consider some possible reasons for the wide discrepancies, such as poor coverage of public health publications in the journals captured by Institute for Scientific Information citation indexes. Nevertheless, they are at a loss to explain why the variation is quite so great, and conclude by suggesting that the time is right for an automated approach to assessing quality. We need to consider the implications of this suggestion carefully. Track record within NHMRC project grants is assessed relative to opportunity, with regard to factors such as legitimate career interruptions, administrative and teaching load, and typical publication rates for the field in question. In the fellowship or program grants schemes, there appears to be less emphasis on relativity, which may explain some of the closer correspondence between actual and expected citation rates. We need to be clear that the use of an “automated” system that uses surrogate measures of research quality will disadvantage individuals who experience a period of illness, take maternity leave, change their research area, or carry a period of heavy administrative or teaching load, as well as those who publish books, book chapters or government publications. It will also disadvantage teams in which feasibility requires fieldwork collaborators whose applied work does not readily translate into peer-reviewed journal publications. For instance, much public health research is based in the community or takes advantage of data collections in the public health system. Collaborators working in this context often have relatively limited opportunities for peer-reviewed publication. Nevertheless, their active collaboration is often critical for achieving a feasible research plan. Also disadvantaged would be teams with a new or junior investigator, particularly if the new team member was the first named investigator. On the other hand, a move to an automated system of quality assessment would further advantage grant applicants who work in research-dedicated institutes, those engaged in basic research, and those who do not require external collaboration. Given these reservations, I suggest further investigation, by discipline, of what makes a “good” track record, before recommending a single assessment formula.

Michael J Davies

To the Editor: Abdulla and Ward’s excellent article on tako-tsubo cardiomyopathy (TTC)1 raises two important issues. The first issue is the diagnostic dilemma faced by emergency physicians and cardiologists in differentiating TTC from ST-elevation myocardial infarction (STEMI) in centres that lack coronary angiogram capabilities. In patients presenting with chest pain and ST elevation on electrocardiography, the diagnosis of TTC might be suspected on recognition of risk factors and the common psychological, physical and emotional stressors that precipitate TTC.1 Supporting evidence can be obtained by demonstration of basal hyperkinesis and apical or midventricular hypokinesis on transthoracic echocardiography. This modality is now available in many centres without coronary angiography. However, if the diagnosis is incorrectly made as STEMI rather than TTC, the patient runs the risk of unnecessary thrombolysis. Alternatively, after risk–benefit analysis, the clinicians may transfer the patient to a facility with coronary angiography to confirm TTC. The second issue is the therapeutic dilemma facing intensivists treating TTC-related shock with adrenergic inotropes. Although cardiogenic shock in TTC is uncommon, it can still occur (4.2%).2 As increased endogenous catecholamines are thought to be central to the pathophysiology of TTC,3 treating shock with inotropes puts the clinician in a quandary. Agents such as adrenaline, dobutamine, dopamine, milrinone and noradrenaline increase cyclic AMP within the myocardial cell, and are commonly used to restore blood pressure and cardiac output. However, in TTC, inotropes may theoretically delay resolution of the apical ballooning. A recent echocardiographic study showed no improvement in apical and midventricular akinesis with the use of low-dose dobutamine.4 Levosimendan is a calcium sensitiser that has been used successfully to stabilise shock secondary to TTC (with and without use of an intra-aortic balloon pump).5 Levosimendan is non-adrenergic and allows earlier introduction of β-blockers than would be possible with adrenergic inotropes. I agree that prospective trials are needed to guide management in this intriguing condition.

Laven Padayachee

In reply: I thank Padayachee for his interest in our review.1 We read Padayachee’s published case series of the use of levosimendan to help recovery of left ventricular dysfunction in tako-tsubo cardiomyopathy (TTC)2 after our review was published. I agree that levosimendan is the inotropic agent of choice in this situation, and this approach has been used successfully in my hospital on two occasions. This is, in fact, what we meant by “In our experience, β-blockade in conjunction with non-adrenergic inotropes can prevent this vicious cycle and allow the ventricle to recover (unpublished data)”. As Padayachee rightly points out, definitive evidence on this point would require a proper randomised trial, which would be very difficult to organise, given the low incidence of tako-tsubo cardiomyopathy and the small fraction of patients who develop cardiogenic shock requiring inotropic support. I think that it is probably better to simply state that levosimendan therapy works and makes scientific sense, so “just do it”. However, Padayachee also surmises that, if the patient has a typical wall-motion abnormality and a typical history, it might be possible to avoid unnecessary thrombolytic therapy in cases of TTC. Unfortunately, my understanding is that this is not the case. Occlusion of the left anterior descending artery (LAD) may result in the classic TTC wall-motion abnormality if the LAD extends far beyond the apex (usually with a non-dominant right coronary). As myocardial infarction can be precipitated by stressful events, and the evolution of electrocardiographic changes in TTC is similar to that seen with an anterior infarct after thrombolysis, there is still no clear way to discriminate between the two diagnoses apart from immediate coronary angiography. Whether computed tomography (CT) angiography can accurately discriminate remains to be seen — this might be useful in centres that have CT but not a cardiac catheterisation laboratory. Until then, I believe it is probably less harmful to give TTC patients thrombolysis than to withhold thrombolysis from patients with large anterior infarcts. Lastly, I invite Padayachee and other interested clinicians who frequently manage these patients to participate in an ongoing study of genetic predisposition to TTC for which we are currently enrolling participants.

Michael R Ward

To the Editor: It is a worthy aspiration for Australia to become the world’s healthiest country, but it will take revolutionary leadership to prevent and manage the effects of obesity that will reverse the previous gains in reducing heart disease.1 In addition, we have to overcome the adverse impact on the health of young people caused by fundamental changes in Australia, highlighted by Eckersley.2 He also identifies medical practitioners as a potential obstacle in that we are overfocused, with government approval, “on an individual, biomedical, disease-centred approach to health at the expense of a more social, preventative model”. He also calls for an increase from the current investment in prevention and public health programs, 1% of health expenditure — but that will only occur if his more radical suggestion is adopted: that governments change their focus from wealth to health creation. It was Japan that embraced this concept, with a health creation policy developed in 1978. It led to a law ensuring that at least 5% of their compulsory health insurance expenditure is allocated to preventive activities. If we are going to achieve Ring and O’Brien’s vision, we are going to have to do more than adopt Japan’s healthy diet. Other keys to their success are: good antenatal care; reinforcement of high breastfeeding rates by provision of small incentive payments; routine home visits to women during pregnancy and during the postpartum period by maternal and child health care workers; and all parents having their own maternal child health record. While these and other measures have probably contributed to Japan having the lowest infant mortality in the world, these interventions are also likely to have influenced their longevity by preventing the Barker hypothesis from being applied. This hypothesis, or developmental origins theory, was derived from observations of infants who are small at birth being at higher risk of increased blood pressure and other adverse cardiovascular endpoints later in life.3 It is interventions during the early years that have evidence of high returns on investment — whereas attempts to influence adult behaviour are difficult, and can fail.4,5

Bret Hart

In reply: Our paper demonstrates the considerable potential for improving Australia’s already competitive international mortality ranking by focusing on several selected conditions and inequalities in their distribution among Australians.1 Hart recognises the aspirational nature of the paper and proposes several challenges and opportunities to improve the health of the mothers, babies and young children of Australia. We agree. As shown by our evidence, Australia’s performance on mortality in infancy and early childhood is less than stellar. We acknowledge that our ranking on some childhood risk factors, such as obesity (which can confer lifelong health disadvantage and may affect future mortality), may well be similar or even worse. A critique of these was beyond the scope of our paper, as we confined our analysis to measures of past mortality. There is ample evidence of effective interventions for infants, children, adolescents, adults and older people, and for various population groups. The interventions include preventive or clinical services — as the Journal’s own repository of guidelines shows.2 We contend that rather than being alternatives, childhood and adulthood interventions are complementary (as are biomedical and social interventions), and we have to advance simultaneously on many fronts. Australia has accelerated to be among the world’s leaders on mortality and life expectancy, but, as Hart presages, this will not remain the case merely through a continuation of current trends. It may take a revolution, but we can at least be clear about how we compare in these areas and what we need to achieve.

Ian T Ring · John F O’Brien

To the Editor: In their report of a child with peanut allergy who developed sunflower seed allergy, Hsu and Katelaris caution against marketing claims of “safe alternatives” in allergic children.1 Their report also raises practical issues for those advising the parents of a child with food allergy: what is the risk of a new allergy developing; should a child with peanut or tree nut allergy avoid similar foods as well; and will food avoidance prevent new allergy from developing? The natural history of peanut and tree nut allergy is for polysensitisation to develop over time. One study demonstrated that, in children younger than 2 years with peanut or tree nut allergy, 19% were sensitised and 2% were clinically reactive to more than one nut.2 By the age of 14 years, the percentages had risen to 72% and 47%, respectively. This has led to people with peanut or tree nut allergy being advised to avoid all nuts and seeds.2 Strategies commonly advised to reduce the risk of allergy developing are to avoid food allergens and to delay the introduction of allergenic foods until the age of 2 years, but evidence to support their effectiveness is limited,3 particularly for preventing food allergy.4 While studies in infants at high risk of allergic disease have reported an increased risk of eczema with early introduction of solids (before the age of 3–4 months),3 and a protective effect against asthma and eczema with the avoidance of environmental and food allergens in the first 6 months of life,4 a recent systematic review found “no strong evidence to support the association between early solid feeding and the development of persistent asthma, persistent food allergy, allergic rhinitis, or animal dander”.5 Furthermore, there is currently no evidence that avoidance strategies applied beyond 6 months of age are effective for allergy prevention, and provisional evidence that such strategies might actually promote sensitisation and food allergy rather than tolerance.6 So how should we advise patients? The peanut and tree nut avoidance strategies advised will be largely dictated by: choking hazards in infants; the risks of cross-contamination in commercially prepared foods; and the potential for confusion in young children (and caregivers) trying to differentiate one “nut” product from another. Regarding the risk of developing new food allergy, we should advise patients that: new allergies may develop with time; this risk is unpredictable; we have little evidence to recommend avoidance beyond the age of 6 months as an effective preventive strategy; and parents should not be optimistic (given the current state of knowledge) that such strategies will prevent new sensitisation once food allergy has developed.

Mimi Tang · Raymond J Mullins

To the Editor: The case reports presented by Gunja et al1 are a serious concern from many perspectives. The health authorities should be commended for their rapid risk assessment and alerting the community, which led to the immediate withdrawal and recall of the toy beads from the marketplace. However, the question needs to be asked: Could this situation have been prevented, and if so, how? There are many toys in Australia that potentially pose risks to children. These can include physical dangers, such as the size of toys, with risk of choking, to toxicological dangers, as we have seen with Bindeez toy beads (containing 1,4-butanediol), and psychological and social concerns, such as the effects of sexually provocative toys on young girls and “aggressive” toys (which may encourage violence) on young boys. More research is required to test the psychological influence of such toys on children. The evidence should be used in the development of guidelines for safer toys. At present, toy manufacturers in Australia must adhere to the Australian Toy Standard (AS/NZ 8124), established by Standards Australia.2 Toys are monitored and regulated mostly by the state governments. While the manufacturers are expected to adhere to these standards, they are in fact voluntary standards and self-regulated, and many toys can enter and be sold in Australia without meeting these standards. When a consumer or state government inspector is concerned about the safety of a toy, or if it violates the regulation, they may contact one of the state offices of fair trading, which have the power to remove the toy from the marketplace. This is essentially a post-hoc auditing system and plays an important role in safety, but action is essentially taken after a problem is detected, such as is the case with the Bindeez toys. In view of potential concerns, I believe what we need in Australia are stronger regulations and guidelines that we can provide to manufacturers to help produce safer toys. Our efforts should be towards preventing any potential harm by strengthening existing regulations, establishing consistent national and international standards for all imported toys, providing more resources for the verification and testing procedures and more expertise and wider consumer input into the safety and suitability of the types of toys permissible in Australia. We have a duty to protect and safeguard our children from both psychological and physical dangers.

Vicki Kotsirilos

To the Editor: Australia, like many other nations, is experiencing an epidemic of overweight and obesity. The most recent National Health Survey reported that 62% of men and 45% of women were overweight or obese.1 Among numerous associated concerns is the cost burden of obesity-related illnesses on individuals, the community and the health system. Among the 45–54-years age group (the stage at which osteoarthritis becomes a significant health problem), we calculated the population attributable risk (PAR) for osteoarthritis associated with obesity to be 25% for men and 22% for women, using a relative risk (RR) of 2.4 and obesity estimates of 23.3% for men and 20.1% for women. In terms of major health sequelae of the epidemic, this is second only to obesity-related type 2 diabetes (RR, 3.2; PAR, 34% for men, 31% for women). Some obese patients will have multiple obesity-related comorbidities. In 2005 in Australia, 2551 national hospital separations among people aged 45–54 years were for obesity-related osteoarthritis.2 Using data from the three most recent National Health Surveys, we projected the likely prevalence of obesity among 45–54-year-old Australians in 20251,3,4 and then estimated future hospital separations and direct health system expenditure, using costing information supplied by the Australian Institute of Health and Welfare.2 We project that in 2025, if Australians born between 1971 and 1980 maintain their current rate of weight gain, the proportion of obese 45–54-year olds will rise to 38.8% of men and 32.2% of women. The estimated number of hospital separations for obesity-related osteoarthritis will increase to 4216. The direct health system cost (in current dollars) will rise to $44.4 million, from an estimated $25.5 million in 2005. The 45–54-year-old population comprises a considerable proportion of the workforce, and obesity-related illness impacts on absenteeism5 as well as individuals’ and families’ quality of life. As the current generation of young adults ages, a trend toward increasing illness arising from high levels of obesity is likely, unless health and government policy initiatives to prevent weight gain are given higher priority.

Margaret A Allman-Farinelli · Robert J Aitken · Lesley A King · Adrian E Bauman

To the Editor: I write in response to two articles published recently in the Journal.1,2 Both propose that substitution of doctors with paramedical professionals is reasonable. I disagree. I think it is imperative that before doctors decide to only see the “fun” patients, we had better be sure we want to surrender our status in the health care system. In the report by Oldmeadow and colleagues,1 as a result of workload constraints, the proposition is made to have physiotherapists run and manage an orthopaedic clinic. By the patient-to-doctor ratio in the study, the average load per week for each doctor was four new and five old patients in a 3-hour clinic. Perhaps readers will compare that load with their own. The study’s outcomes are a cause for concern. Recommendations for management and treatment by two physiotherapists were compared with those of an orthopaedic surgeon. If the surgeon’s opinion is deemed to be correct, then over 25% of the patients who attended these clinics would have been treated incorrectly. In addition, 13% of the physiotherapists’ assessments were not only wrong, but the management plans did not include referral to the surgeon. Remember, this was a highly artificial, simplified clinic treating a limited range of conditions. Consider what the error rate would be in an open clinic with no restrictions on the patients to be seen. In the same issue of the Journal, Smith and Baird proposed that radiographers are qualified in some way to read images.2 While radiographers are skilled technicians, in no way would their interpretive skill be equal to that of a general practitioner, radiologist, or consultant in any other specialty. We should not lower standards for the sole reason of speed of access. I would advocate focusing on consolidating the education of GPs, and so empower them as a group. GPs with special interests could equally act as the gatekeepers to clinics. It is unfair to foist the decisions on care, which are our duty, onto other professionals who are not as extensively trained as we. The job of a surgeon is not to operate on patients. It is rather to organise the care of patients who have a problem in the area of our specialty.

Jeffery M Peereboom

In reply: Peereboom appears to ignore reality. Recent news media1 gave an insight into the state of radiological services at some Sydney teaching hospitals. Thousands of images have never been seen by a radiologist. Yet, all of those images were seen by radiographers, who also saw the patients. I am frequently asked by doctors for my opinion about radiographs. At times, I volunteer my opinion to junior doctors and general practitoners. Thirty years of experience tells me that, if I don’t, they miss abnormalities, delaying treatment and decreasing the quality of care. Peereboom will have worked with radiographers capable of accurately interpreting radiographs. Today, many Australian radiography students have tertiary entrance scores in the 90s. Arguably, the only reason we cannot teach them to formally give their opinion on radiographs is because of a professional boundary drawn in the sand in the 1920s.2 However, the sand is shifting under the health care system. I have the greatest respect for radiologists’ knowledge, skills and intellectual capacity. However, an advanced practice role for radiographers is not just about respect. It is a human resource issue. Knowing that the current service model is antiquated, do we wish to limit the potential of both radiographers and radiologists in the future?

Tony N Smith

To the Editor: We read with interest the recent article by Oldmeadow and colleagues.1 Patients on waiting lists have long waits and poor quality of life,2 and we are currently piloting a similar model for assessment of patients referred for orthopaedic opinion for hip and knee arthroplasty.3 In keeping with other authors, the article by Oldmeadow and colleagues provides encouraging data to support role substitution. However, we suggest that important issues need to be addressed before wide-scale adoption and expansion of the model. More information is needed about the proportion of all referred patients eligible for the physiotherapist assessment, and the cost–benefit figures for “avoided” orthopaedic consultations. It is quite difficult to evaluate the outcomes given the exclusion criteria, which are common comorbidities in these settings. While the κ statistic implies concordance between two physiotherapists and one surgeon, the disagreement was still about one patient in four. Of course, this level of disagreement may also be found between surgeons. However, for a new health intervention, such discordance needs to be understood within an appropriate evaluation framework. What level of diagnostic error are consumers prepared to accept from any health care provider? The article reports five episodes of disagreement between the physiotherapists and the surgeon, where the need for surgery, medical treatment or further imaging was missed; this represents 13.2% of patient assessments (were there multiple missed opinions in individual cases?). The fact that a patient refused surgery is irrelevant if that decision was not identified a priori before surgical referral. Every consumer has the right to accept or reject recommendations about care based on the best available information about potential benefits and harms. An important role of specialist medical providers is that of diagnostician, particularly when there are multiple or complex conditions. Changes to the management of common musculoskeletal conditions should not reduce opportunities for expert input when required. Waiting times for many patients are clinically and ethically unacceptable and we agree new service delivery models are necessary. We suggest that: professional groups work together to develop agreed evidence-based protocols for triage, assessment, investigation and management of common musculoskeletal conditions; funding providers and health care organisations develop and evaluate new models of care, including their cost-effectiveness, and provide appropriate training and monitoring to ensure role redefinition is associated with maintenance of equal or better quality and safety of care; and a musculoskeletal clinical network be developed to support these objectives.

Caroline A Brand · Richard H Osborne · Ian P Wicks · Richard N de Steiger