Letters

Martin B Van Der Weyden Editor, The Medical Journal of Australia, Locked Bag 3030, Strawberry Hills, NSW 2012. medjaustATampco.com.au Comment: The distress conveyed by Maxwell and Kaye is the latest in a litany of concerns and complaints to the Journal over recent years about the workings of ethics committees.1 At the centre of the protests is the perceived tardiness and inefficiency of human research ethics committees (HRECs) in Australia.2,3 But the past decade has also seen reform. The National Health and Medical Research Council (NHMRC) has clarified the relationship between research and quality assurance and when quality assurance proposals require ethical scrutiny.4 Furthermore, the NHMRC’s National statement on ethical conduct in research involving humans is clear in its advice that HRECs must establish working procedures that include “timely consideration and review of research protocols”, and it also outlines procedures for expediting review of minimal-risk research.5 On multicentre research, the statement is also clear, stressing the need to minimise unnecessary duplication in review of such research, and calling for “prompt and efficient consideration of multi-centre research protocols” and adoption of “other administrative procedures to accelerate timely consideration and avoid unnecessary duplication”.5 With such clear enunciations, what could go wrong? But, as Maxwell and Kaye attest, things do go wrong. It seems that either the NHMRC recommendations have yet to be translated into reality or the “silo” mentality of HRECs is deeply ingrained. The time may well have arrived to consider performance indicators for HRECs, or even an accreditation process. After all, clinical research and quality assurance should not be at the mercy of inefficient HRECs.

Martin B Van Der Weyden

Gordon R W Davies Psychiatrist, 33 Smith St, Wollongong, NSW 2500. alienistATihug.com.au To the Editor: The recent article on obesity by Proietto and Baur in the Journal1 coincided with another by Campos in New Scientist,2 in which he criticised the conventional view of the risks of obesity and the norms usually accepted. Campos quoted evidence suggesting that, in fact, the group in the overweight range (body mass index [BMI], 25–30 kg/m2) are healthier than those with a BMI below 25 kg/m2. He also noted that between 1990 and 2002, despite a further increase in the prevalence of obesity in the United States, the incidence of type 2 diabetes hardly changed, while cardiovascular death rates fell. According to Campos, similar claims about the risks of obesity have been repeated over the past 50 years and relate more to cultural and political factors than to reliable scientific evidence. Clearly, this view is inconsistent with that articulated by Proietto and Baur. While Campos’ view obviously does not apply to the grossly obese, there is a strong suggestion that the overall evidence base is inconsistent. This may be because the assumption of a linear relationship between excess weight and illness is false. It is further likely that there is confounding of variables, with weight a proxy for lack of exercise. As Campos points out, large-scale observational studies are inevitably poorly controlled. If this is so, then it may well be more useful for the medical profession to emphasise exercise and lifestyle rather than weight loss. It may be much easier to obtain and reinforce behavioural change in these areas, and avoid the common feeling of hopelessness (“why bother”) expressed by people who find it hard to diet and to lose weight.

Gordon R W Davies

Ray C McHenry,* Richard W Gilhome,* Chris Hensman* * General Surgeon, Eastern Surgical, Suite 7529, Police Road, Mulgrave, VIC 3170. To the Editor: We take issue with the recommendations on treatment of morbid obesity in the otherwise excellent article on obesity management by Proietto and Baur.1 Like most non-surgical clinicians involved in the management of obesity, they fail to differentiate between the treatment of obesity (body mass index [BMI], 30–35 kg/m2) and morbid obesity (BMI > 35 kg/m2). The literature is crystal clear — non-surgical treatments are unsuccessful in achieving and maintaining weight loss in morbid obesity.2,3 We are unaware of any branch of medicine, other than morbid obesity management, where respected clinicians routinely recommend treatments (drugs, diet and lifestyle modification) which have been proven not to be effective. We challenge all clinicians to accept what the evidence clearly shows, that: the only known effective treatment for morbid obesity is surgery;2,3 and laparoscopic adjustable gastric banding is much safer than bypass/diversion surgery4 and just as effective; it is the treatment of choice for morbid obesity.

Ray C McHenry · Richard W Gilhome · Chris Hensman

Huy A Tran Director of Clinical Chemistry, John Hunter Hospital, Hunter Region Mail Centre, Locked Bag No 1, New Lambton Heights, NSW 2310. huy.tranAThunter.health.nsw.gov.au To the Editor: I read with interest the recent article on obesity in Australia by Proietto and Baur1 and would like to comment on the issue of proteinuria and measurement of insulin level in obese patients. Proteinuria in obesity, commonly referred to as obesity-related glomerulopathy, is a clinical syndrome with an estimated incidence of about 2% in obese subjects.2 With a fifth of the population being obese,1 the sheer number suspected to have this condition will create an enormous management and cost burden. Furthermore, the incidence of this condition appears to have increased disproportionately to the incidence of obesity.2 The syndrome of obesity-related glomerulopathy comprises the triad of morbid obesity, marked proteinuria without oedema, and normal serum albumin concentration. It can occur in any degree of obesity but is more common in the morbidly obese group (body mass index > 40 kg/m2; Class III obesity). It often presents as proteinuria on urinary dipstick testing, with marked proteinuria seen on confirmatory testing (up to 32 g/day).2 Other features of the nephrotic syndrome do not occur, and the cholesterol level is often lower than that in patients with nephrotic syndrome. However, glomerular filtration rate is raised, and glomerulosclerosis is seen on biopsy. The pathogenesis is unknown. Obesity-related glomerulopathy is a diagnosis of exclusion: secondary causes of proteinuria should be fully eliminated, including hypertensive renal disease and undetected type 2 diabetic renal disease. More often than not, biopsy will be required to guide management, with cost implications. Although the condition is said to be benign, in a small proportion of patients it progresses to end-stage renal failure requiring replacement therapy, further adding to the cost of management. Fortunately, the condition is readily reversible with weight loss, which is an important emphasis in management. 3 My second comment relates to the case of the overweight adolescent described by Proietto and Baur. In this patient, measurement of insulin level is not indicated.4 There is no standardised insulin immunoassay, the sample has to be collected and processed correctly to produce a valid result, and the result would not add to or alter the management of the condition. It is doubtful if normative data exist for adolescents, but the clinical picture suggests the insulin resistance syndrome. As the primary goal would be to detect disordered glucose metabolism, appropriate testing of glucose level is all that is required.

Huy A Tran

Joseph Proietto,* Louise A Baur† * Endocrinologist, Department of Medicine, Repatriation Hospital, Heidelberg, VIC 3081; † Paediatrician, Children's Hospital at Westmead Clinical School, Sydney, NSW. j.proiettoATunimelb.edu.au In reply: We agree with McHenry and colleagues that, until very recently, surgery was the only effective treatment for morbid obesity. However, the development of effective pharmacotherapy that targets the underlying cause — increased hunger — may well change this situation, as evidenced by the effect of leptin treatment in leptin-deficient children.1 In the not-too-distant future, a medical alternative may be possible. The issue of the relative merits of surgery to insert a foreign body (gastric band) or permanently alter the anatomy of the gastrointestinal tract versus lifelong pharmacotherapy will need to be considered. However, economic as well as health issues may be important, and, as McHenry and colleagues suggest, may still favour surgery as the preferred therapy. We thank Davies for bringing to our attention Campos’ book The obesity myth, in which he claims that overweight individuals are in fact healthier than those of normal weight.2 While many of the book’s other claims can be challenged (such as the statements that the prevalence of type 2 diabetes is not rising in the United States, and that bald men have higher testosterone levels), the fact that there is no simple linear relationship between body mass index (BMI) and illness is correct. Sex, race and fat distribution can all influence the relationship. Moderately overweight women with gynoid (hip and thigh) fat are not at increased risk of illness.3 In contrast, South Asian people have an increased risk of developing diabetes at lower BMI values than people of European background. We agree with Davies that maintaining fitness through regular exercise is very important in minimising the health consequences of obesity. Tran raises the issue of whether it is useful to measure insulin levels in children. It is not unreasonable to assume that insulin levels are raised in most obese children, but this is not always the case. The National Health and Medical Research Council clinical practice guidelines for management of overweight and obesity in children and adolescents state that: “Fasting insulin and glucose should be considered in obese children or adolescents, particularly those with a family history of type 2 diabetes, those with acanthosis nigricans and those from certain ethnic backgrounds”.4 In the presence of insulin resistance, serum glucose level remains normal because of high insulin levels. Thus, glycaemia cannot be used to monitor improvement in insulin sensitivity.

Joseph Proietto · Louise A Baur

Richard X Davey Chemical Pathologist, Melbourne Health Shared Pathology Service, Western Hospital, Gordon Street, Footscray, VIC 3011. richard.daveyATwh.org.au To the Editor: In 1996, the Journal published my assessment of the scientific validity of a 1994 decision by the Australian Health Insurance Commission (HIC) to limit the Medicare rebate payment for assessment of thyroid function to thyroid-stimulating hormone level (TSH), except in certain more complex clinical conditions.1 For these, levels of TSH and of other indicators of thyroid function, such as thyroxine, are tested simultaneously and a rebate given for the group of tests. Although discussion concerning this diagnostic strategy persists,2 nearly a decade later it is appropriate to assess the outcome of this initiative. Publicly accessible HIC data3 on privately ordered, then publicly refunded, thyroid function tests in Australia for the fiscal years 1994–2002 were retrieved and are presented graphically (Box). Figure A shows the change in thyroid function test ordering sought by the HIC occurring in 1997 through to 2000 and probably now consolidating. Overall, before the initiative, there were 1.55 TSH tests ordered for each thyroid function group test, and in 2002 this increased to 2.65. The outcome in the elderly is similar, but the change is even more noticeable for thyroid testing in young women and men (with ratios of about 5 to 1 and 7 to 1, respectively). Clinicians have presumably come to accept the high negative predictive value of a normal TSH result for ruling out primary thyroid disease as both necessary and sufficient to finalise thyroid diagnoses in the young. By contrast, thyroid disorders are more common among the elderly, who thus more readily satisfy the HIC requirements for thyroid function group tests. The approximately fourfold increase in absolute terms in the number of single TSH tests performed over 9 years (from 2731 per 100 000 persons per annum in 1994 to 10 763 in 2002) can also be seen as vindicating the HIC’s decision to run with a “TSH first” testing protocol. The same pattern is seen in the age and sex groups illustrated (15–24 years and 75–84 years). The present speed, ease and relative economy of obtaining a TSH test, and the reliability, particularly at low TSH levels, of using this measure for thyroid disease case finding, make ordering a TSH test no longer an indulgence,4 but a clinical necessity. The national cost-of-living index for 30 June of each fiscal year5 was used to standardise the annual expenditure on thyroid function tests to 1994 dollar values, thus allowing comparison across the decade (Figure B). From 1995 to 2002, the HIC has contained annual expenditure to under $20 million for thyroid function group testing. This is both desirable and appropriate. That this has been sustained for 7 years in the face of increasing numbers of first-line TSH tests is both astonishing and commendable. Most of the increase in costs of TSH testing is probably explained by the acceptance of its use as a first-line test. Between the 1996 and 2001 censuses, the population grew from 17.9 to 18.8 million, and the proportion over 65 years also increased (from 12% to 12.5%). Both these trends are continuing,5 and both also explain some of the increase in ordering of TSH tests. It is unclear if any of this change is also due to testing moving from the totally public, hospital sector, not funded by the HIC, to the HIC-funded sector. Effect of changes to the Health Insurance Commission rebate for thyroid function testing A: Ratio of the number of single tests ordered (thyroid-stimulating hormone [TSH]) to the number of thyroid function group tests ordered (TSH and thyroid hormones). Data are tests per 100 000 persons per annum. B: Annual expenditure on thyroid function testing in Australia.

Richard X Davey

Jan R Stockigt Senior Endocrinologist, Alfred Hospital, Commercial Road, Prahran, VIC 3181. jrsATnetspace.net.au Comment: In his timely review of changing patterns of thyroid function testing, Davey suggests that Australian Health Insurance Commission (HIC) policy is responsible for the increased emphasis on a “TSH-first” strategy, with consequent containment of costs for other thyroid function tests. While this may in part be true, the trend towards initial TSH testing has been advocated worldwide1 following the development of TSH assays sufficiently sensitive to distinguish the typical suppressed TSH levels of thyrotoxicosis from normal levels. The developments documented by Davey are a consequence of technological development, perhaps enhanced by selective rebating as a result of HIC policy. It is unfortunate that current HIC policy is sometimes described as prohibiting more complete thyroid function testing, unless TSH level is abnormal. Rebate policy does not prohibit any line of testing and it is because the “TSH-first” approach has some serious, well-documented deficiencies.2 Measurement of levels of thyroid hormone in addition to TSH is clearly sanctioned in HIC regulations when TSH level alone can be misleading, for example in suspected pituitary dysfunction, or in monitoring the treatment of thyroid dysfunction. The adverse consequences, both human and financial, of relying on TSH measurement alone in such situations can be serious and may outweigh the savings achieved by restrictive testing. It must be noted again that a normal concentration of immunoreactive TSH has no predictive value in ruling out potentially life-threatening hypopituitarism,3 which may present with prominent hypothyroid features. The effective integration of clinical and laboratory investigation of potential thyroid dysfunction requires an active laboratory–clinical interface. There are over a dozen patterns of thyroid function — some trivial or inconvenient, some quite serious — that can be misdiagnosed or incorrectly managed if communication across this interface is inadequate.4 Effective communication requires relevant information from the clinician and a response to this information within the laboratory. It is a reality that current patterns of investigation in Australia frequently fall short of this ideal. If, as a result of automation and effective competition, the unit cost of assays can eventually be reduced in relation to the total cost of medical care, it may become appropriate to revert to a more complete panel of initial testing that integrates tropic hormone and target gland secretion, a strategy that remains the cornerstone of definitive endocrine investigation.

Jan R Stockigt

Peter J Gilbar,* Christine V Carrington† *† Co-Chair, Committee of Specialty Practice in Oncology, The Society of Hospital Pharmacists of Australia, Suite 3, 27-33 Raglan Street, South Melbourne, VIC 3205. peter_gilbarAThealth.qld.gov.au To the Editor: The national media recently highlighted the tragic consequences of the inadvertent spinal administration of the antineoplastic drug vincristine. The 7.30 Report (ABC Television) detailed the case of a young man erroneously administered vincristine intrathecally instead of, as intended, intravenously, resulting in progressive neurotoxicity, paralysis and death.1 Since the first report in 1968 of unintentional intrathecal administration of vincristine,2 many, invariably fatal, cases have been described. These have involved a combination of human and system errors affecting the medical, nursing and pharmacy professions. On behalf of the Society of Hospital Pharmacists of Australia, we recommend the following strategies to reduce the opportunity for error: Only specifically trained and designated oncology staff should prepare, dispense and administer cytotoxic medication. Intrathecal chemotherapy should only be administered during normal working hours, and in an area where no other cytotoxic drugs are given or stored. Medical staff must use a formal checking procedure, involving an oncology-trained nurse, to ensure the right drug is given at the right dose, by the right route, to the right patient. Intrathecal drugs must be packaged separately and clearly labelled both on the syringe and outer container “For intrathecal use”. Specifically designated containers should be used for transportation of intrathecal drugs from the pharmacy and for storage on the ward. Intrathecal doses should be delivered separately and preferably administered after drugs to be given by other routes have been supplied to the ward and administered. Vincristine should be prepared in a small-volume intravenous bag rather than a syringe.3 For adults, prepare vincristine in an intravenous bag in 50 mL of sodium chloride 0.9% and administer it as a short intravenous bolus over 5–10 minutes. Smaller volumes and a slower administration rate are suggested for children. While this method has been criticised as potentially increasing the risk of extravasation injury, this has not been reported as a problem. Vincristine should be clearly labelled both on the intravenous bag and outer container “For intravenous use only — fatal if given by other routes”. Negative labels, such as “Not for intrathecal use”, must never be used. Many hospitals currently use syringes for vincristine and increase the diluent volume in the syringe as a deterrent to intrathecal administration; however, fatalities have occurred after the administration of vincristine supplied in 10 mL4 and 20 mL5 syringes. The safest method of eliminating the potential for spinal instillation of vincristine remains the abolition of the syringe as a means of administration.

Peter J Gilbar · Christine V Carrington

Nat Lenzo Head, Department of Nuclear Medicine, Royal Perth Hospital, Wellington Street, Perth WA 6000, and Co-ordinator, WA PET/Cyclotron Service, Sir Charles Gairdner Hospital, Nedlands, WA 6009 nat.lenzoAThealth.wa.gov.au To the Editor: I read with interest the article by Ware et al1 and the response from Davies.2 Let me first commend Ware and his colleagues on an excellent piece of investigative journalism. For the readers’ information, there are about 200 operational positron emission tomography (PET) scanners in the United States, and the United Kingdom has recently committed to 50–60 PET scanners within the next 5–10 years.3 This is based on the vast amount of published evidence with respect to the benefit of PET for the diagnosis, staging and monitoring of a range of malignancies and other disorders. Despite more than 15 000 publications3 and the fact that some countries reimburse for many indications not covered in Australia (eg, breast cancer restaging, dementia assessment), our authorities request “Australian data” before allowing expansion of the Medicare benefit for PET in Australia. The issuing of only eight Medicare licences (ie, about 1 per 2.5 million population) also impedes access to what may be the most important imaging development of the past 20 years. What was not mentioned by Ware et al is the grossly inadequate amount paid for PET services under the Medicare Benefits Scheme in Australia. Currently, the reimbursement for a fluorodeoxyglucose PET scan in the US is about US$2000/scan. In Australia, the Medicare Benefits Scheme pays about $900. This makes our reimbursement one of the cheapest in the world. So cheap that it makes no economic sense for private entities to provide PET services in this country (note: isotope cost, about $350/patient; cost of PET set-up, $2.5–5 million). So the Commonwealth has no need to worry — it already has done much to slow the growth of clinical PET in Australia. Before Davies replies that we need “Australian data”, cost-effectiveness data, etc, before allowing new technology expansion, I ask: are Australian data so much better than those from our colleagues overseas? And what is the level of evidence for much of what we currently do and get paid for in clinical practice? For example, what is the rationale behind the reimbursement, without limit, of regular computed tomography scanning in the follow-up of patients with treated lymphoma? I direct readers to the articles by Guppy et al4 and Dryver et al5 to see what little benefit there is in this practice. Of course, these are British and Canadian studies, so surely they cannot be taken seriously.

Nat Lenzo

Robert E Ware,* Hilton W Francis,† Kenneth E Read‡ * Nuclear Medicine Physician, 49 Augusta Road, Lenah Valley, TAS 7008; † Rheumatologist, Hobart; ‡ Barrister, Malthouse Chambers, Hobart. robwareATtrump.net.au To the Editor: In light of our article examining the Australian Government’s review of positron emission tomography (PET),1 it is interesting to note that the accompanying official response is attributed to the Department of Health and Ageing (DOHA).2 When asked to clarify its role in the review of PET, DOHA had previously persuaded the Commonwealth Ombudsman that it had contributed only secretarial support to the process. With no accountability for policy decisions or the review itself, is it any wonder that DOHA’s response does not address the hard evidence that the politicians are “misusing” evidence-based medicine. The comment that “one of the concerns that has been raised about the PET reviews is that the government did not follow the views of individuals who were involved in the process” does not relate to our text. We are aware that individual opinion is considered very low-level evidence. Our argument is that the supporting committee made a decision that PET was safe, clinically effective and potentially cost-effective on the basis of the evidence it reviewed. The Medical Services Advisory Committee (MSAC) itself did not review any evidence, so, by changing the decision of its supporting committee, MSAC’s own opinion was substituted without any sound scientific basis. Therefore, the decision at a ministerial and government level to restrict Medicare funding for PET is purely a political decision, and must not be misrepresented as “evidence-based”. Indeed, the evidence suggests that the policy decision to restrict Medicare funding for PET prejudiced the objective analysis of the evidence by MSAC. The suggestion that “the government is funding the collection of data by service providers to improve the evidence base related to the use of PET in a wider range of indications” is misleading. To improve the level of evidence for PET would require, in the words of the permanent medical adviser to MSAC, “very large randomised trials, which are probably not feasible”. The current data collection is not a randomised trial. For many of the indications being examined, the validity of the PET findings and consequent management changes will not be assessed. There is no plan to evaluate cost-effectiveness. Therefore, the process is not going to improve the level of evidence for subsequent decision-making. Perhaps this is the outcome envisaged for 2006! The problem with the PET review was a fundamental disregard for the promised standards. The ongoing problem is that MSAC is not an appropriately legislated body (unlike the Pharmaceutical Benefits Advisory Committee). MSAC is secretive and its process and decision-making are difficult and costly to penetrate. Unless the structure, process and accountability of MSAC are changed, history is likely to repeat itself. The official response to our article only serves to heighten our concerns.

Robert E Ware · Hilton W Francis · Kenneth E Read

Joshua P Hanson,* Carmel T Taylor,† Ann R Richards,‡ Ina L Smith,§ Craig S Boutlis¶ *Registrar, ¶ Physician, Cairns Base Hospital, PO Box 902, Cairns, QLD 4870; † Scientist, § Research and Development Coordinator, Public Health Virology, Queensland Health Scientific Services; ‡ Public Health Nurse, Tropical Public Health Unit, Cairns, QLD. joshua_hansonAThealth.qld.gov.au To the Editor: The Japanese encephalitis flavivirus is the most common cause of encephalitis in Asia. Death occurs in 25% of clinical cases, and permanent neurological deficits occur in up to 50% of survivors.1 Infection is transmitted from amplifying hosts (primarily waterbirds and pigs) by Culex mosquitoes. Although the virus has been isolated in the Western Province of Papua New Guinea,2 and clinical cases have been described in the Western Province and suspected in the Milne Bay region,3 to our knowledge cases have not been reported from around Port Moresby. In January 2004, a 66-year-old man of European background was evacuated to our hospital with a 7-day history of fever and confusion. On examination, he had generalised upper motor neurone signs and a Glasgow coma score fluctuating between 6 and 10. Computed tomography and magnetic resonance imaging showed multiple non-specific white-matter lesions bilaterally. An electroencephalogram (EEG) demonstrated diffuse slowing in the delta to theta range in both hemispheres, with preserved response to painful stimulation. Lumbar puncture showed clear cerebrospinal fluid (CSF), with a leukocyte count of 65 × 106 cells/L (81% mononuclear) (reference range [RR], < 5 × 106 cells/L), normal erythrocyte count, raised protein level of 0.79 g/L (RR, 150–500 mg/L); glucose level of 4.3 mmol/L (RR, 2.8–4.0 mmol/L) and negative bacterial and fungal cultures. The CSF was also negative for cryptococcal antigen and by polymerase chain reaction (PCR) testing for enterovirus and herpes simplex, Japanese encephalitis, Murray Valley encephalitis and Kunjin viruses. Serological tests were negative for syphilis and human immunodeficiency virus infection. Paired sera from Days 2 and 19 of admission were tested in parallel against a panel of flaviviruses using a haemagglutination inhibition assay.4 This showed fourfold rises in antibody titre against dengue virus serotypes 1, 3 and 4, and Japanese encephalitis, Murray Valley encephalitis, Kunjin, Alfuy and Kokobera viruses, and twofold rises in titre against dengue virus serotype 2 and Stratford virus. Overall, these results were diagnostic of recent flavivirus infection but were non-specific. IgM antibody responses to the same flaviviruses were measured in sera and CSF using an in-house enzyme-linked immunosorbent assay (ELISA), with strongest reactivity demonstrated to Japanese encephalitis virus (Box). The patient had lived in Papua New Guinea since 1970, predominantly on a church-run farm at Bootless Bay, about 20 km from Port Moresby. He had not travelled outside this region in the month before his illness, and had no history of Japanese encephalitis vaccination or of dengue fever. The farm was situated about 150 metres from a piggery. The patient had no direct contact with this piggery. His accommodation was poorly screened against mosquitoes. After 3 weeks of primarily supportive intensive care, the patient was discharged to a general ward. His neurological recovery was slow. After 5 months, he was able to walk with assistance and required a tracheostomy to protect his airway. He was judged likely to experience permanent neurological deficits. The clinical, epidemiological, radiological, EEG and serological features of this case strongly support a diagnosis of Japanese encephalitis. Japanese encephalitis virus is difficult to detect in CSF by isolation or PCR because of neutralising antibodies and the limited duration of viraemia, which may have accounted for the negative PCR result in this case, despite the use of a highly sensitive method.5 This case highlights the desirability of further defining the epidemiology of Japanese encephalitis in the Port Moresby region, as well as reconsidering the current recommendation to vaccinate Australians only if they intend travelling to the Western Province of Papua New Guinea.1 IgM antibody levels, measured against a panel of flaviviruses by enzyme-linked immunosorbent assay (ELISA) JE = Japanese encephalitis. MVE = Murray Valley encephalitis. * IgM levels were measured as the P/N (positive/negative) ratio (ratio of the absorbance of the test sample to the absorbance of a negative control sample tested against the same antigen).

Joshua P Hanson · Carmel T Taylor · Ann R Richards · Ina L Smith · Craig S Boutlis

To the Editor: The Australian Technical Advisory Group on Immunisation (ATAGI) is responsible for maintaining and updating the Australian immunisation handbook, on behalf of the National Health and Medical Research Council (NHMRC).1 At its 25th meeting, in April 2004, ATAGI discussed data (then unpublished) presented by Hanson and colleagues on evidence for the spread of Japanese encephalitis virus beyond the Western Province of Papua New Guinea to the Port Moresby region.2 ATAGI believes it is probable the virus has spread to other parts of Papua New Guinea. The current (8th) edition of The Australian immunisation handbook states on page 179: “Current understanding of the ecology of the JE [Japanese encephalitis] virus elsewhere in Papua New Guinea is fragmentary and unsubstantiated. Therefore no definitive recommendations about JE vaccination for travellers to other parts of Papua New Guinea can be made at the current time.” ATAGI agreed that the evidence provided by Hanson and colleagues was compelling, and sufficient to warrant expanding the current recommendation for Japanese encephalitis vaccination. ATAGI is proposing the recommendation be changed to include travellers staying more than one month in all parts of Papua New Guinea, not just those planning to stay in the Western Province. A public consultation process to change this recommendation is being conducted as part of the requirements of the NHMRC Act 1992. A public consultation paper is available from the Immunise Australia Program website (www.immunise.health.gov.au). Submissions close on 17 September and can be directed to Ms Letitia Toms, Assistant Director, Immunisation Section, Department of Health and Ageing, MDP 14, GPO Box 9848, Canberra, ACT 2601 (letitia.tomsAThealth.gov.au).

on behalf of the Australian Technical Advisory Group on Immunisation (ATAGI)

Tarney J Spencer,* Ben Clark† * Ophthalmology Registrar, † Ophthalmologist, Geelong Hospital, Ryrie St, Geelong, VIC 3228. drtarnAThotmail.com To the Editor: We are concerned about the recent number of patients presenting to our hospital after accidentally applying superglue to their eyes. Of the four cases in February and March 2004, two arose from patients mistaking cosmetic nail adhesive for their regular ocular lubricant, and applying it to the inferior ocular fornices, creating a tarsorrhaphy. Superglues are cyanoacrylate derivatives. Those used domestically are lower-alkyl derivatives than those designed for medical use and have higher tissue toxicity. The two patients who mistook nail glue for ocular lubricant both required surgical separation of the upper and lower eyelids, and both had significant corneal abrasions, periocular dermatitis and temporary loss of lashes as a result of the reparative surgery. Both were treated with chloromycetin ointment until the abrasions had healed. We examined the bottles containing the nail adhesives. They were remarkably similar to many ocular lubricant bottles, with no significant difference in size, colour or feel (Box). As both products are often kept together in a cosmetics area of the bathroom, accidental ocular application can occur. Similar cases have been reported in other countries over the past 20 years.1-3 The risk of accidental ocular (or potentially aural) application could be reduced by changes to bottles containing superglue, including: childproof cap to prevent conventional opening of the bottle; colour coding of the bottles; different bottle shape; and distinctive odour and/or colouring of the glue. Superglue and eye lubricant bottles Examples of bottles of synthetic nail adhesive (two on left) and eye lubricant (two on right), showing similar appearance and feel.

Tarney J Spencer · Ben Clark

Jeremy J N Oats,* H David McIntyre† (on behalf of the Australasian Diabetes in Pregnancy Society, in conjunction with the Women’s Health Committee of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists) * Clinical Director, Department of Women’s Services, Royal Women’s Hospital, Carlton, VIC; † Director, Department of Endocrinology, Mater Health Services, South Brisbane, QLD. jeremy.oatsATrwh.org.au To the Editor: Consensus guidelines for the management of gestational diabetes mellitus (GDM) were prepared by the Australasian Diabetes in Pregnancy Society in 1997–1998 and subsequently published in the Journal.1 Since that time, there have been two minor revisions to these guidelines. The first, in relation to the recommended frequency of follow-up testing of women identified as having GDM, was detailed in a letter to the Editor in 2002.2 The second concerns the timing of delivery of women with GDM. At the request of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the original recommendation that “continuation of the pregnancy in uncomplicated GDM to 10 days beyond term is acceptable provided that indications from fetal monitoring are reassuring” has been modified by replacing “10 days beyond term” with “full term” to bring this into line with current practice. The initial guidelines were arrived at by consensus of Australasian practitioners involved in the care of women with GDM. The Australasian Diabetes in Pregnancy Society recognised, both at the time and subsequently, that the level of evidence available to guide clinical decision-making fell well short of that necessary for a definitive statement on the timing of delivery. It is noteworthy that no international consensus exists concerning the optimal timing of delivery in pregnancies complicated by GDM. The American Diabetes Association, in its Clinical Practice Guidelines, recommends delivery “during the 38th week . . . unless obstetric considerations dictate otherwise”.3 The European Association of Perinatal Medicine does not make a recommendation, instead stating that “the optimal time of delivery and need to induce labour are still controversial.”4 There is currently a paucity of quality evidence on which to confidently base recommendations. We hope that current studies, such as the Australian Carbohydrate Intolerance in Pregnancy Study and the Hyperglycemia and Adverse Pregnancy Outcome Study,5 will provide this evidence.

Jeremy J N Oats · H David McIntyre

T C K Brown Former Director of Anaesthesia, Royal Children's Hospital, Flemington Road, Parkville, VIC 3052. tckbrownATnetspace.net.au To the Editor: The epidemic of recreational use of γ-hydroxybutyrate (GHB; also known as γ-OH) is a cause for concern, as it is a basal anaesthetic agent (ie, it renders the patient unconscious, with analgesic supplementation required for surgery). It is not surprising that people taking too much of it are becoming unconscious.1 GHB was introduced in France as a basal anaesthetic agent by Laborit about 1960. It has a slow onset of action (up to 10 minutes when given intravenously, thought to be due to conversion to an active metabolite, γ-butyrolactone).2 It causes bradycardia, sometimes requiring atropine administration to maintain cardiac output, and raises blood pressure. Respiration is slow and deep, so that alveolar ventilation is not reduced. Trials of GHB as an anaesthetic were conducted in Melbourne by Dr William Cole and myself in the late 1960s,3-5 and it was used for microlaryngeal surgery for several years. Its major problems were prolonged sleep (1–3 hours after 40–100 mg/kg in children) and a high incidence of postoperative vomiting, adding the danger of aspiration in unconscious patients. GHB was also tried as an anaesthetic in Dunedin, New Zealand, where it was found that the sleep time could be reduced by intravenous administration of physostigmine.6 The fact that this drug is a basal anaesthetic needs to be more widely publicised.

T C K Brown

Geoffrey M Forbes,*† Matthew J Zimmerman, † Brendan J Collins,† John T Edwards† * Head, † Gastroenterologist, Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, WA. geoff.forbesAThealth.wa.gov.au To the Editor: The editorial by Viiala and Olynyk on screening flexible sigmoidoscopy (FS)1 is a welcome reminder that there are alternative colorectal neoplasia (CRN) screening strategies to the Australian National Health and Medical Research Council’s preferred option of annual faecal occult blood testing. The availability of tests for CRN screening raises the issue of whether screening tests should be dictated by government or professional bodies, or requested by the consumer. FS and colonoscopy remain potential alternatives to faecal occult blood testing in Australia, as reflected by US screening guidelines2 and recent local data.1,3 However, it is unreasonable for Viiala and Olynyk to compare the risks of screening FS (generally diagnostic only) in average-risk subjects (perforation rate, 1/50 000) with the risks of colonoscopy (both diagnostic and therapeutic) in Western Australian tertiary hospital outpatients with symptoms or other risk factors for CRN (perforation rate 1/1000). Firstly, it is important to recognise that the perforation risk associated with screening FS comes not just from the diagnostic screening test (1/50 000), but also from follow-up colonoscopy and subsequent polypectomy in patients with distal adenomas seen on FS. Secondly, in the WA tertiary hospital cohort,4 the estimated perforation rate for diagnostic colonoscopy is about 1/2800 (and about 1/420 for colonoscopy accompanied by polypectomy). Asymptomatic subjects having screening colonoscopy are likely to have a lower risk than patients with symptoms or other significant comorbidities having investigative colonoscopy. Recent data from colonoscopic screening programs (which include subjects having polypectomy) have shown an overall perforation rate of less than 1/3000.5 Medical practitioners arranging colonoscopy, and people having this procedure, should be informed about the risks involved and, importantly, be aware that these risks are likely to vary according to the setting in which colonoscopy is performed.

Geoffrey M Forbes · Matthew J Zimmerman · Brendan J Collins · John T Edwards

Darryl J Hodgkinson Director, Cosmetic and Restorative Surgery Clinic, Double Bay Day Surgery, 20 Manning Road, Double Bay, Sydney, NSW 2028. dr_hodgkinsonATbigpond.com To the Editor: I would like to congratulate Peters et al on their strong stance against elective surgery in patients who smoke.1 The plastic surgery community became aware in the last two decades of the problems of healing in smokers. When patients claimed that they gave up cigarette smoking before surgery, we often found that the serum cotinine levels on testing were elevated, indicating that they had not given up smoking. Patients who are smokers and who develop a healing complication, in breast reduction, mastopexy, abdominoplasty or a facelift, often attribute the complication to the surgical technique rather than their own habit. Many of these patients have gone on to litigate successfully. Voracious plaintiff lawyers attribute only a small amount of blame to the patient whose smoking has, in fact, contributed significantly to their complication. In our plastic surgery practice, we have a non-smoking policy, and my malpractice insurer will not cover me for patients on whom I operate and who develop a complication associated with smoking. Hence, all patients who are smokers who wish to have elective surgery are referred to a smoking-cessation program and have to have given up smoking for at least 2 to 4 weeks before surgery. I prefer not to operate on smokers at all, as serum cotinine tests often confirm that their cessation attempt has been incomplete. In the United States, where patients pay for their own health insurance, their premiums are adjusted for lifestyle. In Virginia, in the 1990s, a “Healthy Virginian policy” existed where premiums were reduced for non-smokers. My suggestion would be that the Medicare levy also be either reduced for individuals who do not smoke or increased for those who do.

Darryl J Hodgkinson

Nicholas A Tonti-Filippini Medical Ethicist, 15 Alburnum Crescent, Lower Templestowe, VIC 3107. ntf-dslATkeypoint.com.au To the Editor: Some time ago, I was approached by a general practitioner who had been trying for more than 12 months to arrange surgery for a patient who was suffering from intermittent claudication. The indications for surgery seemed compelling. The man was in great pain and disabled by the condition. The vascular unit at a major metropolitan hospital refused to operate on him while he remained a smoker. The man had been an alcoholic, but had managed to beat that addiction and had been “dry” for the entire 12 months. With the patient’s permission, and at the request of the GP, I contacted the surgeon. The surgeon explained to me that his refusal to provide elective surgery was on the grounds that the patient smoked, which would increase recovery time and the risk of complications. After discussion of the ethical and legal situation, an early appointment for surgery was arranged with the patient. Peters and colleagues, authors of a recent editorial on smoking cessation and elective surgery,1 would do well to attend to the terms of the Commonwealth Disability Discrimination Act 1992. It is unlawful for a person who provides services, or makes facilities available, to discriminate against another person on the grounds of the other person’s disability. It seems legitimate to consider the effects of smoking on success rates as part of deciding whether elective surgery is likely to be safe and effective for an individual patient. However, the editorial suggests that patients be denied surgery, such as joint reconstruction, as a resource-allocation decision, even if the surgery would be in their interests. It is important that smoking is recognised as an addiction. Some groups, such as the mentally ill, are particularly prone to it. A study by the Harvard medical school found that people with mental illness are twice as likely to be smokers, and nearly 45% of all smokers in the United States are people with a “mental disorder”.2 To the extent that it is an addiction, smoking needs to be considered as a medical condition in much the same way as alcoholism is referred to as a medical condition. A doctor who did not provide a needed treatment to a smoker on the grounds that the patient was a smoker would be in violation of that person’s fundamental human right to healthcare and his or her right not to be discriminated against because of a disability. In fact, the doctor would be in breach not only of the Hippocratic oath, but of the Australian Medical Association’s Code of Ethics 2004,3 which states “. . . refrain from denying treatment to your patient because of a judgement based on discrimination”.

Nicholas A Tonti-Filippini

Matthew J Peters,* Lucy C Morgan,† Laurence Gluch‡ *Head, Department of Thoracic Medicine, †Thoracic Physician, ‡ Surgeon, Department of Breast and Endocrine Surgery, Concord Repatriation General Hospital, Hospital Road, Concord, NSW 2137. matthew.petersATcs.nsw.gov.au In reply: The rigid way in which Hodgkinson has addressed risk reduction in plastic surgery seems reasonable, as long as there is open disclosure and access to smoking-cessation services is assured. It is an unfortunate fact that our healthcare system cannot provide everyone with what they want, or need, in a clinically appropriate timeframe. Resources are finite. In his own case example, and without considering the legal or ethical basis of his intervention, once Tonti-Filippini arranged for a patient at high risk of complications to have surgery, someone else was immediately prevented from having hospital care that was necessary for them. If complications developed, extending hospital stay, more than one patient might have been adversely affected. Let me extend Tonti-Filippini’s case a little and imagine that a similar patient with peripheral vascular disease who was moved further down the vascular surgery waiting list as a result of the smoker’s surgery being expedited was an ex-smoker who had taken advice and ceased smoking to reduce risks and improve the surgical outcome. Then, in the period of surgical delay, the affected leg became acutely ischaemic and amputation (rather than vascular reconstruction) was required. Are there not ethical implications that follow? Reading more deeply into the Australian Medical Association’s Code of Ethics, one finds that we should work to increase standards and the quality of and access to medical services in the community, and make available our special knowledge and skills to assist those responsible for allocating healthcare resources. These are important obligations. Most smokers are addicted, and this is a medical problem that needs to be consistently identified and addressed; the issue of smokers with mental illness was highlighted in the editorial. If a clinical decision is made not to perform surgery in the context of continued smoking, it is not made because the person is a smoker, or because they have an addiction, but because the ongoing smoking has major, adverse consequences that we are unwise to ignore. The distinction is subtle but important.

Matthew J Peters · Lucy C Morgan · Laurence Gluch

B E Christopher Nordin,* Allan G Need† * Physician, Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA; † Head, Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, SA. christopher.nordinATimvs.sa.gov.au To the Editor: The article by Seeman and Eisman on treatment of osteoporosis1 not only neglects the pathogenesis and prevention of this condition, but also fails to appreciate the profound differences between the three main types of fragility fracture (peripheral non-hip, hip and spine). To say that adults lose bone with age because the “volume of bone resorbed is greater than the volume replaced” is a spectacular but common tautology which simply describes what would be expected from an external negative calcium balance. The common postmenopausal bone loss can generally be accounted for by the rise in calcium requirement due to a fall in calcium absorption and rise in obligatory calcium excretion.2-4 This can be corrected with hormones or compensated for with a calcium supplement, which is known to suppress bone resorption.5 In 20 trials of calcium therapy completed up to 1997, the loss of bone in 855 postmenopausal women treated with calcium was 0.3% per annum, compared with 1.0% per annum in 635 untreated control women (P < 0.001).6 In older women, this relative calcium deficiency is complicated by a decline in vitamin D status caused by reduced exposure to sunlight and progressive thinning of the skin. It has been known for 30 years that vitamin D deficiency is common in patients with hip fracture,7 for 20 years that this was also true in Australia,8 and for 12 years that vitamin D with calcium can reduce the hip fracture rate by 43% in 18 months in women in residential care.9 When it comes to established osteoporosis (the combination of low bone density with fracture), treatment needs to distinguish between the three main types of fracture referred to above. In hip fractures, surely the first priority must be to give adequate vitamin D and calcium. Most non-hip peripheral fractures occur in women with bone densities in the normal range,10 so the need for treatment is debatable unless bone turnover is very high. Vertebral fractures are a different matter. Unlike peripheral fractures, they do not “heal” in the usual sense — the deformity remains and often causes local pain and mechanical dysfunction. The recurrence rate is very high, because all the vertebrae have much the same bone density, and the osteoporotic collapse of one indicates that the others are ready to follow. This condition is notoriously difficult to manage and should almost be regarded as a medical emergency that requires full investigation — not least to exclude myeloma — and rapid, effective treatment. It is in the secondary prevention of these fractures that the remedies advocated by Seeman and Eisman probably have their main role and are most cost-effective. In fact, although the authors place great emphasis on prevalent fracture as a risk factor for further fracture, the reference they quote deals with prevalent vertebral fracture, not with prevalent non-hip peripheral fracture, where the evidence of benefit from bisphosphonates and raloxifene is very much weaker. We are arguing for much greater emphasis on the prevention of osteoporosis with adequate calcium after the menopause and adequate vitamin D in the elderly, and the use of appropriate investigation and selective treatment in the management of the condition when it is established.

B E Christopher Nordin · Allan G Need

Ego Seeman,* John A Eisman† * Professor of Medicine and Endocrinologist, Austin Hospital, Studley Road, Heidelberg, VIC 3084. † Professor of Medicine, and Director, Bone and Mineral Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, NSW. egosATunimelb.edu.au In reply: Our article concerned a discussion of evidence-based treatment for the prevention of osteoporotic fractures. Prevention of osteoporosis per se is important, but the approaches chosen must be evidence- based. Calcium supplementation may diminish, but not abolish, bone loss by reducing remodelling rate.1 Any association of a lifelong diet high in calcium appears to be with peak bone mass, not rates of bone loss,2 and may be attributable to differences in protein intake or physical activity. Despite opinion, meta-analysis of prospective, randomised, double-blind, placebo-controlled studies does not support a role for calcium supplementation in reducing fractures.3 Later rather than earlier intervention avoids needless exposure to treatment for large numbers of individuals at low absolute risk of fracture (ie, those who are unlikely to sustain a fracture even without treatment).4 Vitamin D is of course indicated in vitamin D deficiency. However, there is no evidence for anti-fracture efficacy of vitamin D in ambulant community dwellers.5

Ego Seeman · John A Eisman

John M N Hilton Associate Professor, Department of Pathology, University of Sydney; and Consultant in Forensic Medicine, PO Box 45, Katoomba, NSW 2780. kornhilATiinet.net.au To the Editor: Byard’s succinct dissertation on the Clark case1 omits one crucial aspect in redressing this miscarriage of justice. Without the vigorous and persistent efforts of a vocal and well directed support group, which included Mrs Clark’s legal team, their scientific and medical advisors, the Law Society of England, and her family, she would still be serving a life sentence in jail. An Australian example of the effectiveness of such a support group in combating injustice is afforded by the Lindy Chamberlain case.2 Historically, Sir Arthur Conan Doyle spearheaded the efforts — sustained over nearly 20 years — to exonerate Oscar Slater,3 an unfortunate German–Jewish immigrant to Glasgow who was condemned to death after a conviction for murder based largely on identification evidence given by one of the probable perpetrators. Slater was granted a reprieve from the death sentence at the last moment, only to serve some 17 years in a grim Scottish penitentiary. Less fortunate was Timothy Evans,4 who was convicted and hanged for murdering his wife and daughter on the evidence of one of London’s infamous mass murderers, John Christie. Evans was eventually pardoned — unfortunately, too late to save his life — largely thanks to a very active support group headed by the journalist Ludovic Kennedy. In contrast, those who lack such a support group are exemplified by Ziggy Pohl,5 who was convicted, despite rather than because of the evidence, of killing his wife in Queanbeyan, NSW. He served more than a decade in prison, only to have the true perpetrator confess after Pohl was released on parole. Byard highlights evidentiary shortcomings in one recent English case. How many other people have suffered the ignominy, distress and dire consequences of unjust convictions because they lacked the support of an individual or a group prepared to question the propriety of the conviction process?

John M N Hilton

Jessica H Ford,* Annette J Dobson† * Research Assistant, † Professor of Biostatistics, School of Population Health, University of Queensland, Herston Road, Herston, QLD 4006. A. DobsonATsph.uq.edu.au To the Editor: Helping pregnant women to stop smoking and not to resume after their baby is born is a key target for smoking prevention. Pregnancy (or trying to become pregnant) is a time when women are motivated to stop smoking for the sake of the baby and they are in contact with healthcare professionals who can help them do so. We have calculated the impact of smoking during pregnancy in terms of deaths, hospital separations and costs to the healthcare system, and estimated the extent to which these effects could be reduced through interventions initiated by healthcare professionals as part of routine clinical contact. We considered the following conditions: pre-eclampsia (which is less common among smokers), low birthweight (including hospital costs for the mother and the baby, and infant deaths), premature rupture of membrane, spontaneous abortion, ectopic pregnancy, placenta praevia (including infant death), and sudden infant death syndrome (SIDS). We used estimates of relative risks (RRs) for these conditions for women who smoke during pregnancy (or, for ectopic pregnancy, for women who might become pregnant) from meta-analyses.1-3 We obtained data on deaths,4 hospital separations,5 and costs to the healthcare system6 for 2001–02. The prevalence of smoking among pregnant women of all ages in New South Wales since 1994 has been in the range 17% to 22%.7 The prevalence of smoking among all women of child-bearing age in 2001 was about 28%.8 From these data, we calculated attributable fractions1,2,9 for average values (using point estimates for RRs and 20% for prevalence of smoking in pregnancy) and extreme values (using the 95% confidence limits for RRs and 17% and 22% for smoking prevalence). In summary, the average number of adverse events attributable to smoking each year in Australia are: infant deaths, 78 (extreme values, 66–87); hospital separations, 6890 (extreme values, 4130–9450); costs to the healthcare system, $23 million (extreme values, $16–$29 million). A Cochrane review of behavioural (not pharmacological) interventions for stopping smoking in pregnancy showed an absolute reduction of 6% (95% CI, 4%–8%).10 Thus, if the prevalence of smoking during pregnancy were reduced from 20% to 14%, we calculate that there would be 20 fewer infant deaths, 1600 fewer hospital separations, and a saving of $5 million to the Australian healthcare system per year. (Details of the calculations can be obtained from the authors.) These gains could be realised by increasing community awareness of the risks of smoking in pregnancy and helping health professionals to use smoking prevention strategies in their routine encounters with pregnant women.

Jessica H Ford · Annette J Dobson

Michael C Kennedy Research Associate, Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital, Darlinghurst, NSW 2010. drmkennATozemail.com.au To the Editor: Since the Sydney Olympics in 2000, many developments have occurred in drug use and the rules regulating drugs in sport. The most significant regulatory development is the acceptance by the Olympic Federation, and many other sports bodies, of the World Anti-Drug Agency’s World Anti-Doping Code.1 Caffeine and pseudoephedrine have been removed from the Prohibited List, and an in-competition monitoring program is under way to detect any changes in the patterns of use of caffeine, pseudoephedrine and other drugs not on the banned list. Had this code been used in 2000, the Romanian gymnast Andreea Raducan would have retained her gold medal, lost after she inadvertently used a cold preparation containing pseudoephedrine. Precise in-competition limits on blood and breath alcohol have been introduced in sports such as archery and modern pentathlon. β-Blocking agents and diuretics are completely banned in specific sports. A new category of “specified substances” now exists: . . . the prohibited list may identify specified substances which are particularly susceptible to unintentional anti-doping rule violations because of their general availability in medicinal products or which are less likely to be successfully abused as doping agents. These substances include cannabinoids, probenecid, glucocorticosteroids and ephedrine. Doctors treating athletes should advise them to inform their relevant sporting authority of drugs prescribed. If necessary, athletes can apply to the Australian Sports Drug Advisory Committee for a therapeutic use exemption for a banned substance. Notifiable substances can be documented on an Abbreviated Therapeutic Use Exemption form held by the national sporting body. There can be no doubt of the need for drug testing to ensure a level playing field. Drug use to enhance performance is unabated since the Sydney games, with scandals occurring around the world. The Bay Area Laboratory Corporation scandal, involving the anabolic steroid tetrahydrogestrinone, is the most prominent. This has ruined several sporting careers and led to criminal charges against company directors.2 Other anabolic steroids continue to be widely used, including nandrolone, which causes problems because of contamination of dietary supplements and some foods.3 One of the “holy grails” for drug cheats over the past 4 years has been to enhance oxygen transport and delivery. RSR13 (efaproxiral), an allosteric modifier of haemoglobin, is in clinical trial as a radiosensitising agent. It has been shown to increase Vo2max in dogs and hence has been of interest to endurance athletes. The manufacturer’s collaboration with the Olympic Analytical Laboratory of the University of California (Los Angeles) resulted in an analytical method now being available for detection of the drug in sport.4 Haemoglobin- and non-haemoglobin-based oxygen carriers are now available commercially. There are few scientific data about their use in sport, but it is likely they are misused by some athletes.5 Recombinant human erythropoietin is widely used in cycling and other endurance sports. A detection method developed from Australian research will limit its use, at least at the Olympic venue.6 Genetic manipulation is unlikely in 2004, but its potential is foreseen. This technology is also prohibited in the new code.1 Unfortunately, drugs will continue to be misused. The opportunity for Olympic winners to gain huge financial rewards will fuel their use.

Michael C Kennedy

Anton Y Peleg,* Wendy J Munckhof† * Infectious Diseases Registrar, Alfred Hospital, Prahran, VIC 3181; † Specialist in Infectious Diseases and Microbiology, Infection Management Service, Princess Alexandra Hospital, Brisbane, QLD. A. PelegATalfred.org.au To the Editor: Infection with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is emerging in many countries, including Australia.1 We report the first case of fatal necrotising pneumonia caused by CA-MRSA in Australia. A previously well 21-year-old Aboriginal man presented to the emergency department with fever and a productive cough. He had no known risk factors for sepsis (such as immunosuppression, diabetes, HIV infection, alcoholism, asplenia or recent influenza) and no history of hospitalisation in the previous 12 months. Chest x-ray revealed left mid-zone consolidation. He was prescribed amoxycillin–clavulanate and discharged. Two days later, the patient re-presented, with rigors, haemoptysis and agitation. Examination revealed a respiratory rate of 38 breaths per minute, oxygen saturation of 79% breathing room air, temperature of 38.7°C, sinus tachycardia (135 beats per minute), and a systolic blood pressure of 80 mmHg. Respiratory examination revealed diffuse coarse crepitations. No other source of infection was identified. The patient required intubation, mechanical ventilation and inotropic support. Sputum and blood samples were taken for culture, and empirical treatment was begun with intravenous ceftriaxone, erythromycin and a single dose of gentamicin and rifampicin. Initial investigations showed leukopenia (2.3 × 109/L; reference range [RR], 3.9–12.7 × 109/L), acute renal failure with a serum creatinine level of 0.18 mmol/L (RR, 0.06–0.11 mmol/L), and severe metabolic and respiratory acidosis (pH, 7.19; RR, 7.38–7.43). The following day, blood and sputum cultures showed gram-positive cocci resembling staphylococci, and intravenous flucloxacillin was added to the antibiotic regimen. Repeat chest x-ray revealed bilateral necrotising pneumonia. Despite resuscitation efforts, the patient died 48 hours after admission. Susceptibility testing of blood and sputum isolates subsequently confirmed MRSA. The isolate was sensitive to erythromycin, clindamycin, gentamicin, ciprofloxacin, tetracycline, vancomycin, rifampicin and fusidic acid. Methicillin resistance was confirmed by detection of the mecA gene by polymerase chain reaction (PCR). Further PCR testing of the isolate revealed the Panton–Valentine leukocidin (pvl) gene, an important virulence factor that has been associated with necrotising pneumonia2 and death,3 and is rarely found in methicillin-susceptible S. aureus or hospital-acquired MRSA isolates.1,2,5 Typing of the isolate by pulsed-field gel electrophoresis showed that it was the recently described “R” pulsotype of CA-MRSA, or “Queensland clone”.4 This clone was first noted in the white population in south-east Queensland in 2000, and is uncommon in Aboriginal people.4 Most CA-MRSA infection in Aboriginal people is caused by WA-MRSA, which may be less virulent than the Queensland clone of CAMRSA as it lacks the Panton–Valentine leukocidin.5 This is the first reported case of fatal necrotising pneumonia caused by CA-MRSA in Australia and illustrates the invasive nature of this infection. Thus far, CA-MRSA has predominantly caused skin and soft tissue infections, but the incidence of life-threatening sepsis is increasing. The first case of severe pneumonia caused by CA-MRSA in Australia was reported in early 2003.6 Fatal cases of necrotising pneumonia caused by CA-MRSA have also been described in the United States3 and France,7 and this presentation is becoming a particular feature of this organism. Clinicians should consider the possibility of CA-MRSA in any patient presenting to hospital with severe staphylococcal sepsis or pneumonia and should consider including parenteral vancomycin in the initial empirical therapy, particularly in geographic locations where CA-MRSA has been reported and in ethnic groups at increased risk.

Anton Y Peleg · Wendy J Munckhof