Letters

To the Editor: One concern that medical practitioners and pharmacists have about patient counselling is the uncertainty about the amount of information which should be given to patients, especially regarding possible adverse reactions to medications.1 Studies have found that providing information on possible adverse reactions can affect patients' willingness to take the medication.1 Research in cognitive psychology provides clear evidence that the order in which information is presented has a significant influence on judgement. Information received first is likely to have a disproportionately large effect on judgement, the "primacy effect".2-4 Despite clear evidence supporting the "order effect" in diverse areas, research has not been undertaken to investigate whether the order effect is present in medication information. To test the hypothesis that differently ordered sequences of the same information about a drug can result in different judgements,5 804 subjects were presented with a short description of a fictitious medication. The descriptions were presented in one of two formats (Box): (A) positive–negative (therapeutic benefits followed by potential adverse reactions) or (B) negative–positive order (potential adverse reactions followed by therapeutic benefits). The surveys were randomly distributed to university students, mindful of the limitation of extrapolating the data to the general population. Subjects rated the medication (from very bad to very good) and the likelihood of taking the medication (from very unlikely to very likely) on seven-point Likert scales. For analysis, we used the independent sample t test, which is robust and therefore considered suitable for this analysis. Two descriptions of a fictitious medicine for treatment of diabetes A: Diabetic MedicationThis medication is effective; it lowers sugar levels. It makes one feel better and boosts energy. It may cause nausea and headache. B: Diabetic MedicationThis medication may cause headache and nausea. It boosts energy and makes one feel better. It is effective; it lowers sugar levels. Of the 804 completed questionnaires, 403 were in the positive–negative order and 401 were in the negative–positive order. Participants given the positive–negative description of the medication rated it more positively (mean, 4.43; SD, 1.02) than those given the negative–positive description (mean, 3.70; SD, 1.62) (P < 0.001). Similarly, participants reported a higher likelihood of taking the medication when information was presented in the positive–negative order (mean, 4.23; SD, 1.62) compared with the negative–positive order (mean, 3.54; SD, 1.66) (P < 0.001). We found that the order of presentation of medication information significantly affected judgement of the medication. Subjects rated the medication more favourably when positive information was presented first. These results suggest a potential benefit in presenting medication benefits before discussion of possible adverse effects. Such an approach might apply to medical practitioners and other healthcare professionals when counselling patients. It might also be a consideration in the format of written information, such as Consumer Medicine Information.

Abilio C de Almeida Neto BScPsychol(Hons), PhD · Timothy F Chen BPharm, DipHPharm · Joyce H L Chan BPharm(Hons)

To the Editor: The conclusion of Holland et al that horse-related injuries in children account for a considerable number of deaths and injury is unarguable.1 In New Zealand, hospitalisation rates for falls from horses and rugby injuries are comparable.2 Despite these disconcerting facts, the data on horse-riding injuries need to be put in a balanced perspective. The frequency of injuries in adult equestrian activity, Pony Club riding, occupational riding (including professional jockeys) and riding for leisure are quite different. Collective raw data are misleading. The freak accident of actor Christopher Reeve in 1995, with the resulting much-publicised quadriplegia, brought public attention worldwide to the question of acute spinal cord injury (ASCI) in horse riding and led to widespread parental concern about "spine safety" in this sport. Spinecare Foundation was subsequently involved in a review of 32 patients with ASCIs from horse riding admitted to the spinal cord injury units at Royal North Shore and Prince Henry hospitals, Sydney, for the years 1976 to 1996.3 Occupational and leisure riding accounted for 88% of injuries. ASCIs occurred in only two riders under the aegis of the Equestrian Federation of Australia — one while competing and the other while training. There were no injuries in children younger than 14 years of age in any form of riding. Most importantly, in the study period, there had been no ASCIs in Pony Club riders, of which there were 22 000 in New South Wales in 1996. Neither had there been an ASCI in those who participated in Riding for the Disabled. In the context of these comments, it is relevant to briefly revisit the contentious topic of Down syndrome children taking part in Riding for the Disabled and in sport generally. Since 1970 (from when accurate records are available), no child with Down syndrome in NSW has had an ASCI in any sport, let alone in a well-defined non-sporting accident. There is simply no case for the radiological screening of the cervical spine for atlanto-axial instability in asymptomatic children with Down syndrome before they undertake Riding for the Disabled. The indications for this examination have been set down.4 We hold that the public and the medical profession can continue to be reassured by this information. Certainly, a child wearing a lap seat belt or other poorly fitting restraint in the rear passenger compartment of a car is at infinitely greater risk for spinal cord injury than when astride a horse at Pony Club. Further, as Holland et al have documented,1 if he or she is wearing a protective helmet the chances of head injury would be reduced significantly. Safety in all potentially dangerous sports should be foremost in the minds of those who administer, supervise and participate in such games. As yet there are no hard data to support the wearing of body protectors to reduce the risk of ASCI, or other vertebral injuries, in horse riding. In reply: One of the reasons for publishing our data was to raise the level of awareness of both the frequency and severity of horse-related trauma in Australian children.1 This trauma appeared to be associated with a low level of compliance with basic safety measures, in particular the use of a Standards-approved riding helmet.1,2 We stated clearly in our article that the risk of injury needed to be viewed in the context of the important social and health benefits of horse-riding as a sporting and leisure activity.1 Taylor and Roe have commented on the perceived benefits of Riding for the Disabled, especially in children with Down syndrome. Certainly, the available data suggest that in this strictly supervised scenario horse riding would appear to be very safe.3 However, the evidence for therapeutic benefit would appear to be relatively weak, and the risks of this form of equestrianism cannot be compared with the more common interaction that might occur between a normal child and horse.4 The incidence of spinal cord injury in children fortunately appears low, at less than 2% of children admitted with all forms of traumatic injury.5 In this context, the use of spinal cord injury as a measure of the safety of a sport for children is flawed. While children may be at greater risk of injury when inappropriately restrained in a motor-vehicle accident, this fact in itself does not make horse-riding, or indeed any other high-risk sporting activity, safe. The use of appropriate safety devices and responsible adult supervision does.

Thomas K F Taylor DPhil(Oxon), FRCS, FRACS · Justin P Roe MB BS, FRACS · Andrew J A Holland BSc, MB BS, FRACS, FRACS(Paed) · Gerard T Roy

To the Editor: In their case report entitled "Dangerous bodies", Nocera and colleagues described a case of poisoning with aluminium phosphide tablets,1 which generate the fumigant gas phosphine when exposed to moisture.2 The foul odour emanating from the patient alarmed hospital staff, leading to evacuation of the emergency department. After the patient died, they sealed his body in an impervious suit and bin. It was buried, without autopsy, using earth-moving equipment — it being considered too dangerous to do this by hand. The burial was filmed for television. The article sought to highlight risks to hospital staff from poisoned patients and indicated that phosphine gas emanating from this patient could be toxic before it was able to be smelt. Despite stated fears of extreme toxicity, no air samples were collected for analysis, and the sole symptom among staff was nausea (not unexpected given the smell). In parts of India, where wheat is commonly stored in the home before being ground into flour, aluminium phosphide tablets are widely available for household use to stem insect attack on the grain.3,4 Ingestion of these tablets is a common way to attempt suicide, with perhaps as many as 15 000 cases per year, two-thirds of which are fatal. The hospital in the city of Chandigarh, in northern India, treats about 50 cases per year. The breath of patients who have ingested aluminium phosphide has a characteristic garlic-like odour. Diagnosis is based on history and a positive result (blackening) on tests of the patient's breath with paper moistened with fresh silver nitrate solution. Hospital staff take no special precautions during resuscitation, and surviving patients are managed with routine supportive care. Autopsies are routine. No threat is perceived by hospital staff. Metal phosphides have been safely used by trained people in Australia for decades. They are Schedule 7 poisons and so require an expensive permit for purchase. Consequently, their use for suicide is rare. Nocera and colleagues understandably reacted with caution to an unusual situation. However, we consider that, in documenting their experience, they overstated the risk. Because of the legal and ethical issues involved in patient care in a situation of alleged risk, we consider that risk estimates should, when possible, be based on available evidence rather than theoretical possibilities. In general, apart from a few highly toxic, mainly anticholinesterase compounds that can be absorbed through the skin (eg, sarin and tabun), there are no known poisons that will seriously endanger hospital staff routinely caring for patients in an emergency department. Competing interests: The authors have no association with companies that manufacture or market aluminium phosphide, and had no financial support for preparation of this letter. In reply: In our article, we clearly stated that the emergency department was evacuated on the instructions of officers from the New South Wales Fire Brigades.1 The officers then placed the patient's body within a fire brigade hazardous materials encapsulated suit and, when that began to distend with phosphine gas emissions from the body, into a hazardous materials recovery bin. In contrast, Christophers and colleagues state that staff at the hospital in Chandigarh, India, take no special precautions in antemortem or postmortem care of patients who have taken aluminium phosphide tablets. I am disappointed that they provide no data on air sampling for phosphine gas during this care to justify this practice. Our case highlights the problems confronting emergency department staff with a critically ill patient and an unknown chemical hazard. In this case, the chemical hazard was not correctly identified for over 30 minutes. The risk cannot be estimated, as suggested by Christophers and colleagues, until the chemical agent and its vapour concentration are correctly identified. Retrospective determinations cannot be used to guide the immediate emergency department response, or to determine what personal protective equipment is needed by staff during the initial confusion of a hazardous materials incident. In addition to organophosphates, over 30 chemical agents have the potential to be used as chemical weapons. Furthermore, the toxicity profiles of many industrial chemicals are unknown or incomplete. We do not believe that any hospital or emergency department staff should be exposed to avoidable danger during antemortem or postmortem care of patients, or that healthcare institutions should be exempt from their statutory obligations under occupational health and safety legislation.

Allen J Christophers · Surjit Singh · David G Goddard · Antony Nocera FACEM, MSc (Emergency Planning and Disaster Management)

To the Editor: Your readers might be interested to examine the full story of Dorothy Reed's initial encounter with William Osler,1 and to learn that he later apologised for his initial negative reaction to her expressed intention to enter medical school, and gave her great support. She later said of him: "He was my friend and to me William Osler has always stood for the greatest personality and the soundest medical teaching possible at that time." Some of her unpublished memoirs are included in a book edited by Jill Ker Conway.2

Tony E Seymour

To the Editor: The South Pacific Underwater Medicine Society (SPUMS) recommends that, before starting scuba-diving activities, all candidates undertake a medical assessment by a doctor trained in diving medicine. SPUMS recommends a minimum age of 14 years for all entry-level scuba activities, as does Australian Standard 4005.1. This recommendation is based on the belief that younger children do not have the emotional maturity and confidence to safely manage underwater emergencies. Such emergencies, which may include running out of air, being separated from your buddy, being caught in a strong current, and equipment malfunction, can all result in panic.2,3 A diver who panics will typically make a rapid ascent to the surface, risking life-threatening pulmonary barotrauma and decompression illness.2 Commercial scuba diving instructor agencies are introducing a number of introductory activities for children as young as eight years. SPUMS urges caution in assessing young children as fit to dive. Medical practitioners making these assessments should clearly understand the nature of the activity to be undertaken, the equipment to be used and the nature of the environment in which the training is to occur. They should also understand the nature of the certification to be awarded. The presence of at least one legal guardian during this assessment is desirable to ensure that the risks are fully understood and to ensure the desire for the child to undertake the activity is not that of the parents alone. An individual may meet the criteria laid down in a standard or understand and accept the risks of an aquatic sport. However, it is not clear that a young child is mature enough to make this informed choice.4 Clearly, some 14-year-olds also lack sufficient maturity, and an experienced diving physician will advise them to delay their open-water certification course until greater maturity is demonstrated. Alternatively, some children younger than 14 years may be completely safe in undertaking a highly structured, one-on-one, supervised scuba experience in a swimming pool. However, it should be understood that trialling scuba equipment in a swimming pool has resulted in significant morbidity. SPUMS continues to recommend a minimum age of 14 years for all entry-level scuba activities involving open-water dives, and recommends caution in assessing younger children for all other scuba experiences.

Robyn M Walker MB BS, DPHM

To the Editor: Some of the principles underlying evidence-based medicine (EBM)* might have been around far longer than we tend to believe. Here is a fragment of one of the 8777 brief suttas (discourses) collected in the Anguttara-nikaya, or "Collection of the gradual sayings", one of the oldest Buddhist texts. The Buddha preaches to the Kalamas people: Yes, Kalamas, you may well doubt, you may well waver. In a doubtful matter wavering does arise. Now look you, Kalamas. Be ye not misled by report or tradition or hearsay. Be not misled by proficiency in the collections [citing the authority of religious texts], nor by mere logic or inference, nor after considering the reasons, nor after reflection on and approval of some theory, nor because it fits becoming, nor out of respect for a recluse (who holds it) . . . But if at any time ye know of yourselves: these things are profitable, they are blameless, they are praised by the intelligent; these things, when performed and undertaken, conduce to profit and happiness — then, Kalamas, do ye, having undertaken them, abide therein.1 This sutta shows the importance of mistrusting unquestioned tradition, even before the days of odds ratios, cost-effectiveness ratios or confidence intervals. Perhaps the lesson for innovative modern supporters of EBM2 would be to concentrate on higher ideals like "profit" (in the sense of beneficence or prosperity) and "happiness" as the really significant outcomes we should be aiming at. * The decision to send this note to the Journal is, of course, evidence-based. The Medical Journal of Australia (MJA) is second only to the BMJ in publishing the largest number of references indexed under the MeSH term "evidence-based medicine" in English-language journals. On a proportional basis, the MJA is at the top of the list: since November 1996 it has published 125 "EBM" articles out of a total of 2553, while the BMJ has published 248 "EBM" articles out of 14966 (OR, 3.06; 95% CI, 2.44–3.83). Could it be that MJA readers are three times more interested in EBM-related topics than BMJ readers?

Diego Rosselli MD EdM MSc

To the Editor: I wish to commend the Journal for publishing the article by Cunningham1 and the analysis of her findings in the accompanying editorial.2 Both articles stress the need for improved communication between Indigenous patients and hospital staff. The Kimberley Interpreting Service provides accredited Aboriginal language interpreters for six Kimberley languages, and is involved in training other interpreter candidates. We have been operating since November 2000 and are currently looking for funding to continue offering our service into the future. To date, we have been working primarily in the legal sector and are quite perplexed as to why we do not receive bookings from the health services. In 2002, the Kimberley Interpreting Service is targeting the health sector through a number of strategies, including the production of a promotional poster for use in hospitals and clinics, articles in medical publications, and face-to-face meetings with health professionals. I encourage your readers to find out more about our service and to pass the message on to colleagues. We can be contacted at kisATwn.com.au, or please visit our website at http://members.westnet.com.au/mirima/

Tea C Dietterich

To the Editor: Warfarin is frequently used in the same population that is at risk of age-related macular degeneration (ARMD), the commonest cause of blindness in the elderly. A recent report has suggested that warfarin may cause severe intraocular haemorrhage and loss of vision in the minority of patients who have the neovascular form of ARMD.1 We have also seen this occur in patients taking warfarin. There are methodological imperfections in the report, and the association is certainly not proven. Nevertheless, it would seem prudent to exercise some caution in the use of warfarin in patients who are or may be at risk. Our preliminary recommendations (pending a prospective study) are: If a patient has only one functioning eye (for whatever reason), an ophthalmologist's opinion should be sought as to the risk of neovascular ARMD in the seeing eye before or soon after commencing warfarin therapy. Low-risk patients are easily identified and warfarin use in these patients should have no visual sequelae. In patients considered at high risk of neovascular ARMD, the use of warfarin may carry a (currently unquantifiable) risk of visual loss. Alternatives to warfarin should be considered, and the possible risks of taking, or not taking, warfarin should be discussed with the patient. If a patient has two seeing eyes, the risk of bilateral visual loss from warfarin must be exceedingly small, and indeed there have not even been anecdotal reports of such an event. Warfarin can be used in such patients without regard to ocular status. Ophthalmologists should ask all patients they examine whether they take warfarin and should communicate to the treating doctor the presence or absence of factors that put this patient at high risk of neovascular ARMD.

Lionel M Kowal FRANZCO · C Alex Harper FRANZCO

To the Editor: I wish to report a case of quinine-induced disseminated intravascular coagulation (DIC) and haemolytic–uraemic syndrome (HUS). A 78-year-old woman presented with nausea, vomiting, diarrhoea, fever and confusion three hours after taking 150 mg of quinine for leg cramps. Five months earlier she had been admitted overnight for similar symptoms after quinine ingestion, her symptoms resolving over 12 hours without sequelae. Before this she had ingested quinine infrequently for the preceding five years without complication. Her past history included hypertension, hypercholesterolaemia and glaucoma; medications were simvastatin, lisinopril and latanoprost eye drops. On presentation her temperature was 40ºC, blood pressure was 150/90 mmHg; physical examination was otherwise unremarkable. Initial investigations showed serum creatinine concentration, 0.11 mmol/L (reference range, 0.05–0.10 mmol/L); platelet count, 124 × 109/L (reference range, 150–400 × 109/L); prothrombin time, 21.2 seconds (reference range, 11s–16s); activated partial thromboplastin time, 66.3 seconds (reference range, 25s–42s); fibrinogen concentration, 2.1 g/L (reference range, 1.5–4.0 g/L); and D-dimer level, > 4.0 mg/L (reference range, < 0.35 mg/L). No haemolysis was present on the initial blood film. The patient rapidly developed oliguric renal failure, progressive coagulopathy and thrombocytopenia. There was no focus of infection, and blood, urine and faecal cultures were negative. Urine microscopy showed 3 × 106 leukocytes per litre (reference range, < 10 × 106/L), 270 × 106 erythrocytes per litre (reference range, < 10 × 106/L) and granular casts. Her urine output improved following infusions of saline, dopamine and high dose frusemide, but renal function continued to deteriorate. The coagulopathy had resolved by 48 hours after taking the quinine, but thrombocytopenia and renal function continued to worsen, with a platelet count of 18 × 109/L and a serum creatinine concentration of 0.58 mmol/L, evidence of haemolysis with fragmentation of red blood cells, elevated concentrations of lactate dehydrogenase (2450 U/L; reference range, 110–250 U/L) and bilirubin (32 µmol/L; reference range, < 20 µmol/L), and low haptoglobin concentration (< 0.06 g/L; reference range, 0.3–2.15 g/L), consistent with haemolytic–uraemic syndrome. The patient was treated with four cycles of plasma exchange with 3 L volumes, corticosteroids and two cycles of haemodialysis over 11 days. Renal function gradually improved, although the serum creatinine concentration remained elevated at 0.17 mmol/L two months later. The most common adverse reaction to quinine is thrombocytopenia. Six cases of DIC and 10 cases of HUS following quinine ingestion have been previously reported.1-5 This is the first report of both DIC and HUS occurring together after exposure to quinine. Many of the case reports describe multiple presentations before quinine was identified as the precipitant. It is important that prescribers are aware of this rare but serious reaction which may occur following exposure to quinine, and that a history of ingestion is sought in anyone presenting with otherwise unexplained DIC or HUS.

Andrew P Morton MB BS, FRACP

To the Editor: In 1998, the Australasian Diabetes in Pregnancy Society (ADIPS) published management guidelines for gestational diabetes mellitus (GDM).1 Recently, the American College of Obstetricians and Gynecologists (ACOG) published its clinical management guidelines for GDM.2 The Table shows there are few differences from the ADIPS guidelines. At this stage, ADIPS does not consider existing evidence warrants revision of its guidelines. ADIPS will retain its existing criteria for the diagnosis of GDM based on a 75 g oral glucose tolerance test (OGTT) pending publication of the Hyperglycaemia and Adverse Pregnancy Outcome Study.3 The results of this international prospective study of 25 000 pregnant women should be available in June 2004. A second publication, the draft National evidence-based guidelines for the management of Type 2 diabetes mellitus,4 does not include GDM, but initially recommended that "women with previous GDM should be retested every three years for undiagnosed Type 2 diabetes". This periodicity was selected to retest for undiagnosed disease when the cumulative risk of developing diabetes had reached 5%. The time interval was selected on the basis of European studies. In contrast, the ADIPS guidelines recommended testing every 1–2 years, but gave no reason for this, apart from the high risk of progression to diabetes among women of certain ethnic backgrounds who had had past GDM (as high as 47% over five years in Latino women5). A further, unstated reason for the 1–2-yearly testing was the major concern that fetal exposure to undiagnosed diabetes in any subsequent pregnancies could result in malformations. The following has now been inserted into the draft Type 2 guidelines: 4 "The guideline conclusion to retest women with previous GDM every 3 years represents minimum criteria. More frequent retesting may be appropriate depending on clinical circumstances, especially during the child bearing years." ADIPS supports this amendment fully and has revised its own guidelines in relation to maternal follow-up after GDM as follows: All women with previous GDM to be offered testing for diabetes with a 75 g OGTT 6–8 weeks after delivery; Repeat testing should be performed every 1–2 years among women with normal glucose tolerance and the potential for further pregnancies; If pregnancy is not possible, follow-up testing should be performed every 3 years, with more frequent retesting depending on clinical circumstances (eg, ethnicity, past history of insulin treatment in pregnancy, recurrent episodes of GDM). Differences between management guidelines for gestational diabetes mellitus (GDM) from the Australasian Diabetes in Pregnancy Society (ADIPS, 1998) and the American College of Obstetricians and Gynecologists (ACOG, 2001) [Table corrected on 27 August 2002.] ADIPS ACOG Universal versus selective screening by blood test Universal unless low GDM incidence or resources limited No recommendation. States that "many physicians elect to screen all pregnant patients as a practical matter" Differences in definition of low risk for GDM Age < 30 years, obesity, family history of diabetes Age < 25 years, body mass index < 25 kg/m2. No known diabetes in first-degree relative Oral glucose tolerance test used 75 g, 2-hour, 2-point blood sampling 100 g, 3-hour, 4-point blood sampling Criteria for diagnosis of GDM Plasma glucose level: Fasting, ≥ 5.5 mmol/L and/or 2-hour, ≥ 8.0 mmol/L Plasma glucose level: Fasting, ≥ 5.3 mmol/L; 1-hour, ≥ 10.0 mmol/L 2-hour, ≥ 8.6 mmol/L; 3-hour, ≥ 7.8 mmol/L; (2 or more time points need to elevated) Insulin therapy commenced after medical–nutrition therapy Plasma glucose level: Fasting, ≥ 5.5 mmol/L and/or 1-hour postprandial, ≥ 8.0 mmol/L and/or 2-hour postprandial, ≥7.0 mmol/L Plasma glucose level: Fasting, ≥ 5.3 mmol/L and/or 1-hour postprandial, ≥ 7.2–7.8 mmol/L and/or 2-hour postprandial, ≥ 6.7 mmol/L

on behalf of the Australasian Diabetes in Pregnancy Society

To the Editor: While we enjoyed reading Sewell's article summarising advances in paediatrics, there was no mention of developments in general paediatric surgery.1 About a third of all patients admitted to a paediatric hospital have surgical conditions. Viable advances would thus have significant implications for many children and their families. Prevention: Although vaccination against infectious diseases remains vital, the greatest killer of children in Australia is trauma.2 Detailed analysis of patterns of injury morbidity and mortality enable recommendations for prevention to be made. Legislation to reduce the risk of scalding was enacted in 1999 in NSW to regulate the temperature of hot water in new homes. Similar measures, in addition to educating families and their local doctors, have been proposed to prevent driveway and horse-related trauma in children.3,4 Overseas data confirm that such interventions may be effective in helping to reduce Australia's present mortality rate from injury of 9.5 per 100 000 children in 1991–1995 to Sweden's rate of 5.2 per 100 000.5 Diagnosis: Laser Doppler imaging of paediatric burns will enable the surgeon to determine the requirement for operative intervention within 48 hours of the burn, expediting treatment and reducing costs.6 In conjunction with the use of cultured keratinocytes, the risk of subsequent scarring should be minimised.7 Antenatal diagnosis of hydronephrosis and hydroureter has assisted in our understanding of the natural history of urological disease in childhood, helping refine the indications for surgical intervention.8 Intervention: The safety of early surgical intervention in childhood is now well established. Many common conditions such as hypospadias are now optimally treated before the child's first birthday, requiring earlier referral.9 Minimally invasive surgery has now evolved into a useful additional technique in children, in conjunction with the development of appropriate indications, suitable instruments and specialist surgical skills.10 While brevity may be an editorial necessity, paediatric surgery encompasses many areas. Although our selection represents a personal choice, advances require active involvement and consultation with colleagues across all specialties.

Andrew J A Holland · Daniel T Cass · John Pitkin

In reply: The points made by three senior surgeons at The Children's Hospital at Westmead Hospital, emphasising important areas of progress in general paediatric surgery, are valid and point to the wide range of advancing activities in paediatric care. Given the difficulty of covering all areas in a brief article, I am pleased that the Letters to the Editor section of the Journal provides another opportunity to broaden the discussion.

Jillian R Sewell

To the Editor: Both the American Diabetes Association (ADA)1 and the World Health Organization (WHO)2 have lowered the fasting plasma glucose (FPG) level for the diagnosis of diabetes from 7.8 mmol/L to 7.0 mmol/L. The Australian Diabetes Society (ADS) has also adopted the lower level.3 However, these organisations differ in the procedure for diagnosis they recommend. The recent article by Hilton and colleagues4 compared these procedures, with particular attention to including an oral glucose tolerance test (OGTT). We, on the other hand, have investigated the impact of lowering the diagnostic FPG level to 7.0 mmol/L. Data were obtained by the Geelong Osteoporosis Study from an age-stratified sample of women randomly selected from electoral rolls for the Barwon Statistical Division5 and adjusted to match the national age profile. Venous FPG level was determined after an overnight fast, together with blood pressure (BP, seated) and anthropometric measurements, in 944 women aged 20–91 years (mean age, 47.5 years; SD, 17.8 years). History of diabetes was ascertained by questionnaire. The prevalence of self-reported diabetes and diabetes defined by an FPG level of 7.0 mmol/L or higher was 4.3% (95% CI, 3.0%–5.6%; 41 women), whereas using an FPG level of 7.8 mmol/L or higher gave a prevalence of 3.8% (95% CI, 2.6%–5.0%; 36 women). With the lower cut-off level, 29% of women (12) were unaware of their diabetes, compared with 19% (7) using the higher FPG level cut-off point. Characteristics of those identified using the lower cut-off FPG level are shown in the Table. After age-matching all patients with diabetes with control participants, diabetes was significantly associated with obesity (body mass index, > 30; odds ratio [OR], 4.2; 95% CI, 1.5–11.6) and central body fat distribution (waist/hip ratio, > 0.8; OR, 8.0; 95% CI, 2.3–25.9); and non-significantly associated with higher blood pressure (systolic, > 140 mmHg; diastolic, > 85 mmHg; OR, 2.0; 95% CI, 0.8–4.9). The new criterion for diagnosing diabetes identifies a subgroup of the population with a high proportion of obesity and android habitus, with a tendency to higher blood pressure. The recommendation of lowering the diagnostic FPG level increases the prevalence of diabetes by an apparently small proportion, but would diagnose diabetes in an additional 34 000 women in Australia. Characteristics (mean ± SD) of diabetic women (FPG ≥ 7.0 mmol/L) and controls (FPG < 7.0 mmol/L). Characteristic Diabetics (n = 41) Controls (n = 903) P* Age (years) 65.1 ± 11.1 46.7 ± 17.7 < 0.0001 Weight (kg) 74.5 ± 16.2 68.6 ± 14.4 0.03 Height (cm) 158.6 ± 5.6 161.9 ± 6.5 0.0007 BMI (kg/m2) 29.6 ± 6.1 26.2 ± 5.3 0.001 Waist/hip ratio 0.88 ± 0.06 0.80 ± 0.07 < 0.0001 Systolic BP (mmHg) 139 ± 21 121 ± 21 < 0.0001 Diastolic BP (mmHg) 83 ± 16 76 ± 12 0.007 * t test. FPG = fasting plasma glucose; BMI = body mass index; BP = blood pressure.

Julie A Pasco PhD · Mark A Kotowicz MB BS, FRACP · Margaret J Henry PhD · Geoffrey C Nicholson PhD, FRACP, FRCP

To the Editor: The recent letter by McElduff and Hitchman1 has some very practical implications. They were able to show that pregnant women having a glucose challenge test (GCT) in the afternoon were nearly twice as likely to have a positive result as women tested in the morning, so that more women tested in the afternoon were diagnosed with gestational diabetes mellitus (GDM). If the function of the GCT is to aid in the diagnosis of GDM, then either all women should be tested in the afternoon or the glucose "cut-point" for the morning test should be reduced. But does the GCT now have any relevance? In the United States, where testing for GDM often still involves a three-hour glucose tolerance test (GTT) using a 100 g glucose load and four blood samples, the GCT was introduced to reduce the number of women who had to have this long and, because of the higher dose of glucose, relatively unpleasant procedure. In Australia, where a two-hour, 75 g GTT is used (requiring two blood samples), it is not as important to offer a simpler initial test. With the use of an initial GCT, about a quarter of women will need to have a GTT for confirmation, and the definitive diagnosis of GDM will be delayed. Further, the GCT is not specific and some women who may have GDM will not have a GTT. In addition, there will inevitably be some women who are GCT-positive, some of whom will have GDM, who do not return for the definitive GTT. Thus, while a GCT may be convenient for a busy hospital clinic with space limitations, it may not necessarily be in the best interests of the patient. Whether a GCT is ultimately helpful or possibly a hindrance requires further evaluation.

Robert G Moses MD

To the Editor: We conducted a joinpoint analysis of death certificate data on prostate cancer from the Australian Bureau of Statistics. Between 1979 and 1994, mortality rates increased by 2.1% per year (95% CI, 1.6% to 2.5%). However, between 1994 and 1999, mortality decreased by 4.2% per year (95% CI, – 5.8% to – 2.4%). The total decrease in mortality rates for the five years to 1999 (the most recent year for which data were available) was 22.6% (95% CI, – 32.9% to – 12.7%). Joinpoint analysis is a statistical method that measures changing trends over time. It chooses the best-fitting points (called joinpoints) at which the rate of increase or decrease changes significantly.1 We did not look at the data and then choose 1994 as the start of the decreasing trend in prostate cancer mortality. The significant decrease since 1994 (and the consistent increase between 1979 and 1994) were identified by the joinpoint analysis. Whether early diagnosis and treatment of prostate cancer subsequent to screening with prostate-specific antigen (PSA) tests can save lives is still an open question that is best answered by randomised-controlled, long term trials. Nevertheless, it is important that we try to understand the recent decrease in population-based mortality. The mortality decline started in 1995, about five years after PSA testing became widely available in Australia. The use of PSA testing increased dramatically, reaching a peak in most States in 1994 and 1995.2 In 1996, the Australian Health Technology Advisory Committee reviewed the evidence and recommended against screening.3 Since then, the number of PSA tests has decreased.2 Recent mortality declines have also been observed in the United States and the United Kingdom following increases in the use of PSA testing. The mortality decline in the US has been greater than that in the UK, coinciding with more PSA testing in the US than the UK.4 At least three questions arise from these observations: Is it plausible that the decrease could be due to some factor other than PSA testing, such as better treatment? How do we explain these results to men who want to make an informed choice about whether to be tested? Is this type of evidence strong enough to warrant a change in the current recommendations on PSA testing?

Michael Coory MB BS, PhD · Peter Baade BSc, PhD

Comment: Using joinpoint analysis, Coory and Bade have identified a significant trend towards lower mortality rates from prostate cancer since 1994, and relate this chronologically to the increased use of prostate-specific antigen (PSA) testing in Australia. The authors raise three reasonable questions regarding this finding: Is it plausible that the decrease could be due to some factor other than PSA testing, such as better treatment? Ecological data such as those presented by Coory and Baade are subject to the pitfalls of ecological fallacy and confounding.1 Ecological fallacy exists when there is an apparent association (eg, more men in the population screened, fewer men in the population dying), but there is no association at an individual level. Confounding would occur when there are other factors that account for the outcome, or distort the relationship between PSA testing and mortality. Treatment is one such factor, but changes in diet and other factors could also play a role (eg, lycopene from tomato-based foods2). How do we explain these results to men who want to make an informed choice about whether to be tested? If these data were presented to men, then it would have to be explained that the data do not provide evidence of the benefits of screening and that many other factors could explain the relationship. Further, men need to be informed of the risks of false negative and false positive results associated with screening, and the risks of complications associated with treatment. It is important to assist men to make a balanced decision. Interestingly, studies in which men have been involved in such informed decisions show that information can reduce the probability that men will choose to be screened.3,4 Is this type of evidence strong enough to warrant a change in the current recommendations on PSA testing? Ecological associations generate hypotheses that are worthy of further investigation. Randomised controlled trial evidence at best, or case–control studies at least, would be required to provide evidence of the benefit of screening using PSA. Some such studies are currently in progress, including the prostate, lung, colorectal and ovarian cancer screening trial of the National Cancer Institute,5 and the European Screening Study for prostate cancer.6 Those in favour of PSA testing argue that it is the only means of diagnosing prostate cancer at an early and potentially curable stage.7 Against this is the argument that many prostate cancers are not clinically significant, as they are slow growing and will not spread, and there is a danger of diagnosis and treatment adding substantially to men's psychological and physical morbidity without benefits in terms of survival or quality of life.8 In the absence of evidence from randomised controlled trials or case–control studies, screening for prostate cancer using PSA testing remains controversial.9

Julie B Byles

To the Editor: A previously well 21-month-old boy presented with burns on his right thigh. His mother had been making popcorn in a domestic popcorn machine while holding the baby about a metre from the machine to watch it churning out the popcorn through a chute into a bowl. Soon after the corn started to pop, the baby screamed, pointing to his right thigh. The mother immediately removed his nappy and found an unpopped corn kernel lodged between the nappy and the thigh. General examination revealed two 4 mm burns on the child's right thigh (Figure). Kenacomb cream (Bristol-Myers Squibb) was applied four times daily, and the lesions healed after five days, leaving two depigmented scars. Burns to the right thigh caused by a popcorn maker. Although popcorn machines are gaining increasing popularity there are few reports of injury. One report describes corneal burns in three adults caused by steam from microwave popcorn.1 We believe that this is the first reported case of paediatric injury, highlighting the potential hazards of hot-air popcorn machines. Corn's ability to pop lies in the fact that the kernels contain a small amount of water (14% of weight) stored in a circle of soft starch inside the hard outer casing.2 When heated to about 232ºC,3 the water expands, creating pressure within, until eventually the casing gives way. The kernels explode and pop, allowing the water to escape as steam, turning the kernels inside out. It is likely that the temperature of kernels that do not pop (known to popcorn connoisseurs as "old maids")2 can reach as high as 200ºC. Because of their increased density compared with popped kernels, old maids can, as occurred in our case, be thrown further than popped kernels. It is also worrisome that some popcorn machines are designed so that they can be used by children.4 The information booklet that accompanies the popcorn machine in this case does state "close supervision is necessary when this appliance is being used by or near children", and has a warning that as "some hot unpopped corn may be thrown from the machine during the popping process be sure to place the [machine] facing away from you or do not stand directly in front of the machine whilst it is in operation". The mother of the child in our case did not note the warning in the instruction booklet. She was not standing directly in front of the machine. Further, she was of the impression that the fluffy popped corns are not hot. With the increased use of popcorn machines, consumers must be aware of the potential dangers of injuries, especially to young children. Our case emphasises the importance of keeping children at a safe distance while preparing hot food, including apparently harmless, fluffy popcorn.

T H H Guan Koh MA, MB BChir, FRCPCH, FRACP

To the Editor: The report by Mangion et al1 draws attention to a serious risk in the environment. The general public has been increasingly protected against the risk of harm from domestic products by a combination of legal liability actions and government regulation. Thus, the continuing availability to the general public of hydrofluoric acid (HF) in concentrations that are hazardous is something of an anachronism. While we applaud Mangion and colleagues for raising the issue of HF burns, we feel that their article is deficient in failing to mention a number of important points. Topical calcium gluconate has been shown to be more effective in treating HF burns if the preparation contains dimethyl sulfoxide (DMSO).2 There is a great risk of blindness with ocular exposure to HF. Slow local injection with 10% calcium gluconate using fine needles, titrating its effect against the patient's pain, is a well described technique. This is another treatment option that could have been tried. Nail removal, described by Mangion et al as an "extreme measure", is, unfortunately, often required. It is less likely to be required with the application of DMSO/calcium gluconate solution and retrograde ischaemic intravenous injection of calcium. Local excision of contaminated tissue may be required after exposure to concentrated solutions. Management should be a team effort from the first moment, involving an intensivist/toxicologist and surgeon, as burns surgeons are trained in the care of HF exposure, and surgery is often needed. The availability, packaging, and labelling of preparations containing HF have recently been changed. Since 1 December 2001 it has no longer been possible for the general public to purchase any HF preparation stronger than 1%. All preparations now carry prominent labelling drawing attention to the risk of blindness if even dilute solutions of HF get into the eyes. Containers are now less easy to open by children. These changes have been introduced by the National Drugs and Poisoning Committee of the Therapeutic Goods Administration as a result of an independent review and lobbying by the Australian and New Zealand Burn Association (ANZBA). The ANZBA guidelines for referral to a specialised burns unit include chemical burns. The peculiar challenge posed by HF burns emphasises the need for the guidelines to be more widely disseminated. Currently, the New South Wales Department of Health has adopted the guidelines, so this policy is official throughout New South Wales.

Hugh C O Martin · Michael J Muller

To the Editor: A recent editorial in the Journal attempted to define a role for angiotensin II receptor (AIIR) antagonists in patients with type 2 diabetes.1 This was in the light of recent trial evidence that these agents reduce progression to renal failure in patients with type 2 diabetes and diabetic renal disease. Unfortunately, the guidelines provided were somewhat confusing and fragmented. I believe that a simpler treatment guide can be constructed, particularly when it is emphasised that the aim in diabetes is to use agents that prevent not only renal failure but also cardiovascular events. Substantial evidence already supports a role for the angiotensin-converting enzyme (ACE) inhibitor ramipril in treatment of diabetes. The HOPE study included 3577 people with diabetes and another risk factor for cardiovascular disease who were randomised to either placebo or ramipril (10 mg) for 4.5 years.2 This group had a mean baseline blood pressure of 142/80 mmHg and no clinical proteinuria. Ramipril lowered the risk of the combined primary outcome of myocardial infarction, stroke and cardiovascular death by 25% (P ≤ 0.001), and this effect was independent of blood-pressure lowering. Furthermore, ramipril reduced progression to overt nephropathy by 22%, with a reduction evident in patients with or without proteinuria.2 This protective effect of ramipril on renal function is consistent with previous evidence that ACE inhibitors slow progression of chronic renal failure in diabetes,3,4 and that ramipril slows progression of chronic renal failure in non-diabetic nephropathy.5 Whether other ACE inhibitors have the same effect as ramipril on cardiovascular events, and what doses obtain such an effect, remains speculative. Similarly, while there is now evidence that AIIR antagonists also have renal-protective effects, there is no definitive evidence that they protect against cardiovascular events. In view of this, and in the absence of comparative trials, ramipril (and not other ACE inhibitors or AIIR antagonists) is currently the first choice for treatment for diabetic patients with hypertension, with normotension and microalbuminuria, or with hypertension and micro- or macroalbuminuria. As most patients with diabetes and hypertension require multiple agents to achieve a target blood pressure less than 130/80 mmHg, additional therapy with a β-blocker, diuretic or calcium-channel blocker is often necessary. The significance of the newly available trial data is that AIIR antagonists provide an alternative to ramipril for reducing progression to chronic renal failure in patients with diabetic nephropathy who cannot tolerate ACE inhibitors because of the side effect of cough.

Roger E Peverill PhD, FRACP

In reply: Peverill raises the question of how to integrate the new data on renal protection by angiotensin II receptor (AIIR) antagonists with existing data on cardiovascular protection by angiotensin-converting enzyme (ACE) inhibitors in patients with type 2 diabetes. An AIIR antagonist would be favoured for renal protection for a diabetic patient with hypertension and evidence of early or overt nephropathy. With regard to patients with microalbuminuria, the HOPE and MICRO-HOPE studies showed that therapy with the ACE inhibitor ramipril (10 mg/day) was associated with a 24% relative risk reduction for the development of overt nephropathy over 4.5 years.1 In contrast, treatment of similar patients with the AIIR antagonist irbesartan (300 mg/day) for 2.6 years resulted in a 70% risk reduction for the development of overt nephropathy.2 Use of an AIIR antagonist in patients with overt nephropathy has also been shown to slow progression to end-stage renal failure.3,4 As the HOPE and MICRO-HOPE studies specifically excluded such patients, evidence supporting use of an ACE inhibitor in this context is lacking. An ACE inhibitor could be used if a diabetic patient has microalbuminuria and a history of coronary heart disease or additional risk factors for cardiovascular disease, especially if normotensive. However, almost all patients with microalbuminuria require antihypertensive therapy as well as therapy to protect target organs. The relative importance of blood-pressure-lowering versus non-lowering effects of antihypertensive therapy on reducing risk of cardiovascular disease remains uncertain.5 Furthermore, a recent meta-analysis of cardiovascular protection in 62 605 patients with hypertension (including the HOPE and United Kingdom Prospective Diabetes studies) did not find that ACE inhibitors affected cardiovascular prognosis beyond their antihypertensive effects.6 Finally, it is important to note that neither ACE inhibitors nor AIIR antagonists provide total protection from cardiovascular and renal events, and that further improvements are needed for both microvascular and macrovascular protection in patients with type 2 diabetes.

George Jerums · Mark E Cooper · Richard E Gilbert · Robert C Atkins

To the Editor: The review by Brodaty and colleagues1 on drug treatment of Alzheimer's disease provides a good, concise and balanced overview. However, Pfizer takes issue with some of the referenced safety data. In Box 3 of that article (Profiles of cholinesterase inhibitors), in reference to adverse effects of donepezil (Aricept, Pfizer), it is stated that "At 10 mg/day, nausea (17% of patients), diarrhoea (17%) and vomiting (10%) may occur.49" Reference 49 at this point appears to be an incorrect citation. The figures of 17%, 17% and 10% for nausea, diarrhoea and vomiting, respectively, appear to have been taken from an article by Rogers and Friedhoff.2 It is important to note that this was a non-comparative, open-label extension study, and these incidences of gastrointestinal adverse events are inconsistent with data presented in the Australian Product Information for donepezil,3 which quote rates of nausea, diarrhoea and vomiting of 11%, 10% and 5%, respectively. These incidences are derived from a patient cohort of 1102 patents who participated in appropriately designed comparative (active and placebo) pre-registration studies of donepezil. These data have recently been confirmed in a one-year, randomised, placebo-controlled study of donepezil in patients with mild to moderate Alzheimer's disease.4 Incidences of 11.3%, 7.0% and less than 5% for nausea, diarrhoea and vomiting, respectively, are quoted in that study. We contend that, while the citation referenced by Brodaty et al was incorrect, the figures quoted for the gastrointestinal safety incidences for donepezil are also inconsistent with the Product Information and current published data.

William Lam MB ChB, PhD

In reply: We thank Lam for pointing out an error in the referencing in Box 3 of our article1 regarding the figures for adverse events for donepezil. The correct reference was number 48 in our list, not 49, and was to Rogers, Farlow, Doody et al,2 not to Rogers and Friedhoff,3 as suggested by Lam. The other references in Box 3 were given as 20, 21, 23 and 48, but should have been listed as 19, 20, 21 and 47, respectively. Secondly, issue is taken with the rates of 17%, 17% and 10% for nausea, diarrhoea and vomiting, respectively, in people taking donepezil. We agree with the overall tenor of this letter that rates of side effects are generally lower in everyday practice. The figures we quoted for adverse events are higher than the 11%, 10% and 5% cited in the Australian Product Information for donepezil,4 as the article by Rogers and colleagues2 refers to rates of adverse events experienced by those on the 10 mg dose, after a forced titration after only one week on 5 mg. We presented data for adverse events at the 10 mg dose, as this was the dose recommended for donepezil given the findings of greater benefit on the higher dose. The Australian Product Information does not indicate whether the rates of adverse events refer to the 5 mg or 10 mg dose. Usual clinical practice, which is to start with 5 mg daily and increase to 10 mg after 4–6 weeks, results in fewer adverse events. The figures of 11.3% for nausea, 7% for diarrhoea and less than 5% for vomiting presented in the Nordic study,5 in which over 80% of patients were taking 10 mg of donepezil daily, with a more flexible titration schedule, appear to be more realistic.

Henry Brodaty AO, MB BS(SYD), MD(NSW), FRACP, FRANZCP · Jane R Hecker MB BS(Hons), FRACP · John A Snowdon MPhil, MD, FRCPsych, FRACP, FRANZCP · David J Ames BA, MD, FRCPsych, FRANZCP

To the Editor: I read with interest the recent article by Olynyk's group at Fremantle on the prevalence of coeliac disease in rural Western Australia.1 It is now increasingly realised that coeliac disease is underdiagnosed in adults because it may be clinically silent — but not necessarily asymptomatic. The symptoms, however, may be non-specific and not those traditionally associated with coeliac disease. In a recently reported small study from suburban Melbourne,2 I demonstrated that about 5% of patients (5/97) undergoing gastroscopy had coeliac disease based on small-bowel biopsy results. In only one of the patients was the disease suspected clinically. I have used these figures to argue the case for routine duodenal biopsy at the time of gastroscopy, regardless of the indication. It is important to note that in my study none of the patients presenting with diarrhoea, and only one of six with anaemia, had coeliac disease — so that restricting biopsy to this group would have missed most patients with coeliac disease. Timely diagnosis is important, as symptoms may be alleviated, presymptomatic nutritional deficiencies corrected, and the risk of cancer reduced by instituting a gluten-free diet. People presenting for gastroscopy represent a high-yield group for histological screening for coeliac disease in Australia.

Jeremy Ryan FRACP

In reply: We agree with Ryan that coeliac disease is common in the Australian community, with a prevalence of 1 in 250.1 Furthermore, all individuals positive for antiendomysial antibody who undergo small-bowel biopsy have typical features of coeliac disease.1 Clearly, there is a need to increase awareness relating to coeliac disease and determine appropriate screening strategies for our population. Ryan suggests that patients presenting for upper gastrointestinal endoscopy represent a group in whom a high diagnostic yield of coeliac disease is expected. However, clinical expression of the disease is variable.1 In this setting, we believe that it is important to determine the cost-effectiveness of the various screening strategies before introducing broad-based screening.3 There is no doubt that treatment of symptomatic patients who present with coeliac disease is appropriate, but there are limited data on outcomes for asymptomatic patients who are discovered in population-based screening programs. As we stated in our article, we recommend screening by serology and small-bowel biopsy if the clinical suspicion is high or the patient is in a high-risk group.

John K Olynyk BMedSc, MD, FRACP · Digby J E Cullen MB BS, FRACP · Guy Vautier BM, MRCP · Judith A Collett MB ChB, FRACP · Dominic F Mallon MB BS, FRACP · Chris J Hovell MRCP, DM

To the Editor: We are writing in response to the editorial of Ben-Tovim et al.1 Although we agree that more research into treatment efficacy in eating disorders is needed, we believe that the study to which reference is made2 is seriously flawed. The study should not be presumed to provide evidence about the effect of treatment on outcome, particularly as the majority of patients studied received no treatment. The high death rate (3/95 [3.2%] among patients with anorexia nervosa and 2/37 [5.4%] among patients with "eating disorders not otherwise specified") in such mildly ill patients (few of whom would have warranted hospitalisation on the basis of their weight) approximates that of seriously emaciated patients in longer-term studies of treatment outcome3,4 and could more properly be said to illustrate the results of having no treatment or inadequate treatment. Exactly what constituted specialised treatment is never actually described in the original article,2 in which "extended inpatient treatment" is defined as treatment lasting more than two weeks and "extended outpatient treatment" as three or more visits. Thus, the so-called "resource intensive treatment" the authors refer to would not necessarily represent even adequate management of these conditions. In our own 6–10-year outcome study5,6 cited by the authors, 61 emaciated patients with anorexia nervosa received, on average, 11 weeks of inpatient treatment consisting of nutritional rehabilitation and psychotherapy. Only one patient died (of suicide) and, of the patients fully assessed, 41/50 (82%) had a good or intermediate outcome. The degree of weight restoration achieved by the end of treatment correlated with the degree of osteoporosis 10 years later.7 In other studies, duration of illness and early intervention have been shown to significantly influence outcome.4 This contrasts with the findings of Ben-Tovim et al,2 which may have been skewed by an unusual level of chronicity in the study group. A recent study of 69 patients with eating disorders treated in our own multidisciplinary program showed that, on 12–18-month follow-up, 48/69 (70%) had improved and 34/69 (49%) no longer had an eating disorder diagnosis. Mean levels of all but one of the major behavioural and psychological features rated by the EEE-C (Eating and Exercise Examination by Computer) instrument8 were significantly reduced. The advice given by Ben-Tovim and colleagues to the parents of the hypothetical 15-year-old girl with anorexia nervosa is regrettably nihilistic and, if based on their Lancet study,2 not founded on sound or generalisable evidence. Parents should be referred to a program for which good outcomes have been demonstrated, treatment accords with published guidelines, the clinicians are suitably experienced, and in which early intervention is the aim.4

Janice D Russell MD FRACP FRANZCP · Suzanne F Abraham PhD