Letters

In reply: Much of the literature about evidence-based medicine (EBM) has focused on the science of generating evidence, or the technical process of critically appraising and interpreting evidence for individual patients. In our article1 we opted to discuss EBM as a social activity with inherent potential for multiple manifestations. To describe EBM as a social activity is to emphasise how its definition, interpretation and application, and the ethical implications of those factors, are dependent on societal values and priorities — be they explicit or implicit. Debate about what EBM means, or should mean, in the context of Australian policy and practice does not degrade or negate the clearly ethical practice of consulting the best available research when making clinical or policy decisions. We challenge the view of Parker et al that by identifying and discussing how the concepts or language associated with EBM could be misused or misappropriated we will somehow reduce the motivation of health professionals to find and apply the best treatments. Indeed, our proposition is quite the opposite. Few of today's readers of the MJA will be unfamiliar with the benefits of systematic reviews of the best available research in their clinical area, and few are likely to be dissuaded of that view by our article. Our exploration of the relationship between ethics and EBM does not "misinterpret" EBM, but, rather, purposefully describes scenarios or social consequences about which there may be ethical concerns. If we can articulate clearly what we do not want EBM to mean, and describe the processes and consequences that we would consider unethical, it can only strengthen the development of an ethical and acceptable notion of what we do want from evidence-based policy and practice.

Simon R Tomlinson

To the Editor: Chronic hepatitis C virus (HCV) infection affects almost 200 000 Australians.1 It is monitored clinically by serial liver function tests (LFTs) and HCV RNA detection by polymerase chain reaction (PCR). HCV RNA is a marker of chronic infection and levels reflect response to antiviral therapy. However, testing for the presence of HCV RNA is expensive and, under the current Medicare Benefits Schedule, is not available to people with HCV antibodies and abnormal LFTs unless they are undergoing antiviral therapy. Using an in-house PCR assay, it has been shown that abnormal LFTs largely predict the presence of HCV RNA.2 We aimed to confirm this finding using a more reproducible PCR assay (Roche Amplicor HCV test) and to further investigate the relationship between LFTs and HCV RNA. We studied 323 HCV antibody-positive patients seen at the Fairfield Infectious Diseases Hospital, Melbourne, between May 1995 and September 1996. The Victorian Infectious Diseases Reference Laboratory performed all PCR assays and LFTs on these patients. Approval for the use of de-identified data was obtained from the Ethics Committee of the Royal Melbourne Hospital Research Foundation. Normal serum alanine aminotransferase (ALT) levels from at least two tests over a period of at least six months were considered to demonstrate normal liver function. In order to determine improved predictors of the presence of HCV RNA, the proportion of patients who were HCV RNA-positive and had an initially normal ALT level and the proportion with a normal ALT level persisting over six months were examined for each 10-IU/mL subdivision within the normal ALT range (0–50 IU/mL). Of the 323 patients, 88% were aged between 20 and 49 years and 68% were men. At initial testing, 251 (78%) were HCV RNA-positive by PCR, 206 (64%) had an abnormal ALT result and 183 (57%) had both a positive PCR result and an abnormal ALT level. An abnormal ALT level predicted the detection of HCV RNA in 89% (183/206) of patients and in 82% (14/17) if an abnormal ALT result was found within six months of an initial normal result. Of the 117 patients with a normal initial ALT level, only 49 (42%) had a negative PCR result. However, an initial ALT level of ≤ 20 IU/mL was more likely to be associated with a negative PCR result than an initial normal ALT level > 20 IU/mL (78% v 23%, respectively; P < 0.001). The probability of a negative PCR result was highest if the initial ALT level was ≤ 20 IU/mL and remained normal for at least six months (see Box). We concluded that, while an abnormal ALT level in a patient with HCV antibody generally predicted the presence of HCV RNA, the absence of HCV RNA was best predicted by an initially low ALT level that remained within the normal range for at least six months. Proportion of patients with normal initial serum ALT level and persistently normal ALT level who were positive for HCV RNA by PCR, divided into 10-IU/mL subdivisions of the normal ALT range Initial ALT range (IU/mL) Number (%) PCR positive, all patients Number (%) PCR positive, patients with persistently normal ALT over six months ≤ 10 2/11 (18%) 2/3 (67%) 11–20 7/29 (24%) 0/11 (0) 21–30 18/30 (60%) 11/12 (92%) 31–40 23/27 (85%) 8/8 (100%) 41–50 18/20 (90%) 2/2 (100%) ALT = Alanine aminotransferase. HCV = Hepatitis C virus. PCR = Polymerase chain reaction.

Heath A Kelly · William J Maskill · William Sievert · D Scott Bowden

To the Editor: The letter "Prejudice against mental illness" in the 20 August issue of the Journal1 resonates with my own experiences when attempting to obtain income protection insurance. Many colleagues have a similar story. In 1994, I suffered an episode of major depression requiring hospitalisation. I was a first-year resident medical officer, had relocated to a different city, and had just moved out of home for the first time, at the age of 25. Subsequently, I have progressed well in my career, and will soon complete specialist training. I have dealt successfully with a number of substantial personal and career hurdles, including postgraduate examinations and training, difficult property transactions, engagement and subsequent break-up of the engagement, the death of a flatmate, and illness and personal difficulties within my family and close friends. I have invested considerable time and effort in cognitive–behavioural therapy, and changed many attitudes and behaviours contributing to the initial breakdown. Wary of the implications for insurance, I have been reluctant to have any contact with my psychiatrist. My last appointment was a courtesy visit two years ago, with another visit 12 months before that. I have continued to self-prescribe an antidepressant tablet in the belief that it is probably doing more good than harm. Without any reference to medical reports, an examination, or an appraisal of my achievements and performance, several experienced brokers have confirmed that my history prevents me from being able to obtain income protection insurance, even with an exclusion clause for mental health problems. The one insurer that will consider covering people with a history of depression, with such an exclusion clause, requires me to be off any treatment for 12 months. It is understandable that an income protection insurer would refuse cover for depression-related claims. However, I fail to see why I am denied the opportunity to purchase insurance against the myriad other accidents and illnesses that can befall anyone, irrespective of their history. It appears the underwriters' methods are based on actuarial data that are overly generalised, and undoubtedly many years out of date in terms of diagnosis and prognosis of mental illness. Ironically, private health insurers cannot refuse to cover any patient, regardless of pre-existing conditions. Such discrimination reflects endemic ignorance and prejudice about mental health and illness. It is time for a review of the criteria by which insurers may reject applications.

Name and address withheld

To the Editor: The recent creation of the National Institute for Clinical Studies (NICS) is an exciting new opportunity for bridging the gap between evidence and practice.1 In carrying out this task, NICS will be directed by the members of its Board. Balanced stakeholder representation on the Board is required for NICS to produce optimal results. At present the Board consists of nine members, of whom eight are medical practitioners. The importance of doctors in the process and implementation of quality improvement initiatives is indisputable. However, other healthcare professionals also play a central role in achieving quality health outcomes for patients.2 Board membership more representative of its stakeholders would provide NICS with a broader range of perspectives, which could only be seen as beneficial. Given the current debate surrounding ethics and evidence-based healthcare, the values and expectations of healthcare consumers also need to be taken into account.3 One of the definitions of quality in healthcare is "consistently meeting or exceeding informed customers' opinion".4 It is crucial that the consumer's voice be heard in matters relating to healthcare research and in the implementation of quality initiatives. As the relevance and acceptability of quality initiatives undertaken by NICS will have an impact on health outcomes for consumers, it is important that such initiatives take into account the preferences of consumers. For this reason, we believe it is imperative that NICS include a consumer on its Board. An example of successful integration of a wide range of stakeholders onto a board is the Federal Government-funded National Health Priority Action Council, with representation from State/Territory, Indigenous and consumer groups and a balanced gender mix. We hope that NICS has strategies in place to enhance stakeholder representation on its Board, as this may be a factor in determining whether or not NICS becomes another forgettable acronym.

Louise V Hall

In reply: The Board of the National Institute of Clinical Studies (NICS) agrees strongly with Hall and Lauder that closing the gap between evidence and practice involves input from consumers. We also agree that the Board of Directors should seek to incorporate input from consumers in its strategic and operational activities. Of equal concern to the Board is ensuring the input of other stakeholder groups also currently not reflected in the composition of Board membership. For example, nursing and allied health professions comprise about 80% of the healthcare workforce and have shown strong leadership in relation to evidence-based practice. We are keen to see such groups actively involved in all aspects of the Institute's work. As a Federal Government-owned company, the selection and appointment process for Board members is the responsibility of government and our constitution does not allow the Board to change its own membership. However, the Board is seeking input from both consumers and other key stakeholder groups, both through its initial consultation processes and through establishment of Board advisory groups specifically focused on consumer issues and nursing and allied health. These groups will provide direct and valued input into the strategic and operational activities of the NICS. Our first round of consultation, with over 300 organisations, highlighted a number of areas where there are currently major gaps between evidence and practice, such as cardiac failure, various forms of cancer treatment, prevention of deep vein thrombosis in hospitalised patients, prevention of bedsores, and prescribing of psychotropic drugs for children. We are now examining ways in which the NICS might usefully help in some of these areas to identify barriers and possible solutions that can be rolled out across the healthcare system and sustained. The success of the NICS in achieving this will depend on the willingness of all stakeholders (including health professionals, consumers and managers) to work together in a constructive way.

Louise V Hall BPhty · Allison E Lauder BSc(Nut), MND · Chris A Silagy

To the Editor: I am concerned that several statements in the article on cyclooxygenase-2 (COX-2) inhibition by Cleland and colleagues1 do not accurately reflect the clinical data. The authors postulate a prothrombotic tendency of celecoxib on the basis of the CLASS study (comparing celecoxib with ibuprofen or diclofenac)2 and four case reports. The authors concede that celecoxib has no effect on the rate of myocardial infarction (MI) in the CLASS study (a conclusion also reached by the United States Food and Drug Administration [FDA] review of CLASS3), which would seem to contradict their hypothesis that celecoxib is prothrombotic. Cleland and colleagues speculate that the differences between the CLASS study and the VIGOR study (which compared rofecoxib with naproxen)4 may be explained by low-dose aspirin use in CLASS and failure to use aspirin in 4% of patients in VIGOR with "CV [cardiovacular] risk factors". This speculation is unfounded. In the CLASS study patients in all treatment groups who used aspirin had higher MI rates than non-aspirin users, and presumably this higher rate would have been observed in VIGOR if aspirin users had been enrolled. This higher rate is probably because aspirin use serves as a marker for increased CV risk. In patients in CLASS similar to the 4% with "CV risk factors" in VIGOR, MI rates were similar in the celecoxib and non-steroidal anti-inflammatory drug (NSAID) groups (data on file, Pharmacia) and numerically much lower than in the VIGOR study subgroup. On the basis of these two flawed arguments, Cleland and colleagues apparently extrapolate the high rate of MI seen with the use of rofecoxib to celecoxib and suggest that high MI rates are a "class" effect. This proposal is scientifically unsound and is not supported by other clinical data, including over 12 000 patients in the celecoxib registration program (data on file, Pharmacia). No celecoxib study has shown an increased risk of MI compared with traditional NSAIDs. The authors correctly assert there is "little clinical evidence from community use to suggest that selective COX-2 inhibition has serious unwanted effects other than those seen with standard NSAIDs", but imply there are few community data. In fact, community use of celecoxib in Australia (at least 1.5 million patients exposed) and worldwide (more than 20 million) has been extensive, and with this degree of exposure one would expect significant adverse event patterns to emerge. Reference to the Adverse Drug Reactions Advisory Committee and FDA database does not indicate a prothrombotic tendency of celecoxib. Further, we at Pharmacia do not consider that the four case studies presented by Cleland et al provide strong support for a prothrombotic tendency for celecoxib, especially as all patients described had diseases with high risk for thrombosis. On the basis of a large body of controlled trial data (including CLASS) and extensive community exposure, the evidence does not show any more thrombosis with celecoxib than with NSAIDs. Results of the CLASS and VIGOR studies clearly differ. It is clinically unjustified and scientifically unsound to suggest that rates of MI seen with rofecoxib can be ascribed to celecoxib and described as a "class effect".

Christopher G Fenn

In reply: The response from the Medical Director of Pharmacia to our article highlights some problems for all clinicians and independent scientists seeking to evaluate the balance of risks and benefits of pharmaceuticals and to validate the marketing messages of pharmaceutical companies. On the one hand, we lack the time and statistical resources to trawl through all data related to all trials with a test drug. On the other, our efforts to evaluate data are confounded by the publication and reporting biases associated with company-sponsored studies. In this regard, it is notable that the definitive results of CLASS1 have not been published, although the Food and Drug Administration (FDA) review of the data is available through an FDA website,2 as indicated by Fenn. While this document places data in the public domain, its location is neither within the pathway of MEDLINE search engines, nor is it known to the general body of clinicians. As reported in the FDA presentation, CLASS was a very large, double-blind safety study of at least six months' treatment that failed to achieve its primary endpoint of reduced complicated upper gastrointestinal events with celecoxib relative to the comparator, non-steroidal anti-inflammatory drugs (NSAIDs). While an interim analysis at six months was published, with extrapolation of event rates to 12 months,3 failure to publish the final results has withheld important results from wider scrutiny. In essence, the FDA document shows no overall long-term safety advantage of celecoxib over standard NSAIDs.2 The FDA analysis4 of the VIGOR study5 also shows no overall safety advantage for rofecoxib compared with NSAID, with fewer complicated upper gastrointestinal events being offset by a highly statistically significant (P = 0.0016) increase in serious thrombotic cardiovascular events. Collectively, these FDA analyses invalidate the promotion of selective cyclooxygenase-2 (COX-2) inhibitors as a safe alternative to NSAIDs, notwithstanding encouraging results from short-term trials. Further, although an increase in serious cardiovascular events was not seen in the CLASS study, its design was not optimal for detecting increased cardiovascular risk, and it is unlikely that CLASS was sufficiently powered to detect the degree of increased risk seen with rofecoxib in VIGOR. As explained in our article,6 unbalanced prothrombotic eicosanoid production associated with selective COX-2 inhibition (ie, a class effect) appears the most likely explanation for the increased cardiovascular events seen in VIGOR. Finally, we wish to reassert that, for effective postmarketing surveillance, it is essential that prescribers be adequately informed about safety concerns associated with new drugs, particularly when they involve events that are common and not usually seen as unwanted drug effects.

Leslie G Cleland · Michael J James

To the Editor: Chronic hepatitis C (HCV) infection affects more than 200 000 Australians.1 As the degree of hepatic fibrosis is the best predictor of morbidity, liver biopsy has a central role in management. Biopsy is also carried out to exclude additional pathology. However, because liver biopsy carries real risks and is expensive,2,3 debate exists as to whether liver biopsy should be performed routinely.3,4 Despite controversy surrounding the need to treat patients with minor histological changes,4 our impression is that many informed patients request treatment irrespective of liver histology. In Australia, liver biopsy is a prerequisite for antiviral therapy under the Pharmaceutical Benefits Scheme Highly Specialised Drugs Program (Box).5 To assess the impact of liver biopsy on management, we performed a retrospective study of patients with chronic HCV infection who underwent liver biopsy from March 1998 to December 2000. We identified 76 patients (51 men, 25 women), with a mean age of 29 years (range, 20–52 years). The biopsy was performed to stage and grade hepatitis C in all patients, and additionally to investigate a second pathology in seven patients. No alternative diagnoses were raised. Additional diagnoses (all suspected before biopsy) were confirmed in three patients and refuted in four patients. Biopsy findings were all consistent with chronic HCV infection, with some degree of fibrosis in 69 patients. There were five patients with histologically confirmed cirrhosis (including incomplete cirrhosis in three), and this was clinically evident in two patients. When S100 criteria at the time of biopsy were applied, after exclusions on clinical grounds, only one patient would have been ineligible for interferon monotherapy based on liver histology. Under current S100 criteria, nine patients would be ineligible for combination therapy, but all nine would remain eligible for monotherapy. Of our patients who attended follow-up and were HCV RNA positive, 62 of 64 patients received or are awaiting therapy. Our results confirm the finding that liver biopsy in patients with chronic HCV infection rarely identifies alternative diagnoses.3 These data reflect the fact that most chronic liver diseases can be diagnosed before biopsy. Biopsy remains an important tool for histological diagnosis of cirrhosis. However, as unexpected findings are uncommon and some patients will be treated irrespective of liver histology, there is an emerging argument not to perform liver biopsy routinely. This argument will strengthen if valid biochemical markers of fibrosis are confirmed.6 We believe each patient should be assessed individually, and treatment could be offered without biopsy to patients who: meet all criteria for treatment under current guidelines other than known liver histology; have no alternative or additional diagnoses after thorough work-up; strongly desire treatment regardless of histology, and there is sound indication for treatment (eg, extrahepatic symptoms, concerns of vertical or occupational transmission); have a high chance of sustained viral response (eg, favourable genotype); have no clinical, biochemical or haematological suggestion of cirrhosis; and with the physician, accept the implications of treatment without biopsy. An alternative strategy could be to consider a biopsy in patients who do not have a sustained virological response, to allow prognostication. Clearly, such changes would greatly affect biopsy practices in Australia. Section 1005 criteria for use of combination therapy with interferon alfa 2b and ribavirin Patients with chronic hepatitis C who satisfy the following criteria are eligible for interferon alfa 2b and ribavirin: On liver biopsy, are staged as METAVIR stage 2 or greater, or METAVIR stage 1 with grade A2 or A3 inflammation (except patients with coagulation disorders); Have abnormal alanine aminotransferase levels in conjunction with demonstration of viral infection (HCV RNA positive);* Do not have other liver disease;* Are not pregnant, not lactating, and are using two reliable methods of contraception;* Have no history of significant psychiatric illness; Would be likely to attend regularly for treatment and follow-up; and Take no more than seven standard alcoholic drinks a week. Genotype of virus should be assessed before treatment Treatment course is 24 weeks except: With Genotype 1 and patients with cirrhosis or bridging fibrosis (regardless of genotype), where treatment course is 48 weeks; and Treatment will be continued for 48 weeks only if HCV RNA qualitative assay is negative at 24 weeks. OR Patients who have relapsed after treatment with interferon 2a/2b monotherapy supplied as a Section 100 medication. This course is limited to 24 weeks. Section 1005 criteria for use of monotherapy with interferon alfa 2b Patients with chronic hepatitis C confirmed on liver biopsy (except patients with coagulation disorders) are eligible for interferon alfa 2b monotherapy if they satisfy the criteria marked with asterisks above. (When monotherapy fails, patients become eligible for combination therapy.) Treatment is to cease if plasma HCV RNA remains detectable by HCV RNA qualitative assay after 12 weeks of treatment. The course must be continuous and excludes retreatment of non-responders or patients who relapse.

Ian F Yusoff · Lindsay Mollison · Leanne Totten · John Olynyk

To the Editor: With the recognition that supplements of folate given early in pregnancy can reduce the incidence of neural tube defects,1,2 Australian manufacturers were allowed voluntary food fortification with folate from 1995, and these foods subsequently became available from August 1996. We assessed the impact of this fortification by comparing the results of assays of serum folate, a sensitive index of folate intake, before and after the introduction of folate-fortified foods. Data were available for serum folate samples assayed by the chemiluminescence method (Chiron Healthcare Pty Ltd, Scoresby, Victoria) at our laboratory in Melbourne. Quality assurance data indicated no analytical drift, and external proficiency testing yielded satisfactory results throughout the period under study. A total of 20 506 samples from women aged 14–45 years, the target group for supplementation, and 5528 samples from men of the same age group were assayed during 1993–2000. The results for the years 1993–1996, before fortification, where sample numbers were relatively small, were pooled. The results were analysed by Bhattacharya plot, eliminating the effect of outlier values,3 mindful of the limitations of extrapolating data derived from clinical material to the community. The mean values are shown in the Box. In both groups there was a small incremental rise in mean serum folate concentrations, and a fall in the prevalence of low values, after the introduction of fortification. The mean value of 14.0 nmol/L for women in 1993–1996 increased by about 19% to 16.7 nmol/L in 2000. The percentage of low values decreased from 8.5% to 4.1% over that period. Although it is possible that the increase in serum folate concentration reflects dietary education and use of folate supplements in women of reproductive age rather than food fortification specifically, parallel changes were also observed in men. In the United States, folate fortification of all enriched cereal grain products was mandated from January 1998. This led to a dramatic increase of 250% in mean folate levels in women aged 15–44 years,4 and an increase of 50% in the median values (uncorrected for outliers) for men, women and children of all ages submitted for clinical evaluation.5 By comparison, the increase in folate levels in Australia has been very small. We conclude that to obtain a significant increase in folate intake in the community by food fortification, a policy of mandatory rather than voluntary fortification is required. Serum folate concentrations in Victorian women and men aged 15–45 years before (1993–1996) and after (1997–2000) the introduction of voluntary food folate fortification Year 1993 to 1996 1997 1998 1999 2000 Women Number 3865 2989 4168 4385 5099 Mean folate concentration (nmol/L)* 14.0 14.5 15.3 16.4 16.7 95% confidence limits 6.7–28.3 5.0–38.6 5.7–38.1 5.7–41.0 5.6–45.5 % Low values† 8.5 7.1 5.7 4.3 4.1 Men Number 1077 849 1130 1117 1355 Mean folate concentration (nmol/L)* 14.0 14.9 15.7 16.5 16.2 95% confidence limits 6.4–28.7 4.7–31.0 5.5–35.6 6.2–41.6 5.9–42.1 % Low values† 7.9 8.1 6.5 4.1 5.1 * Derived from log normal distribution of community values by Bhattacharya method. † 8.0 nmol/L.

Jack Metz · Ken A Sikaris · Ellen L Maxwell · Mark D Levin

To the Editor: In late 1998, a clinical audit in the Thoracic Division of the Prince Charles Hospital found the autopsy rate was 7% of all patients who died in the Division (excluding Palliative Care) for the 12 months to September 1998. Following discussions and acknowledgement of the importance of hospital autopsy as a clinical audit tool, the Division's policy to consider an autopsy in all patients who died was reinforced. Registrars were educated in seeking approval and in counselling relatives. As a result of these interventions and ongoing audit, a decision in relation to autopsy is now recorded in more than 90% of charts following a patient's death, compared with 40% initially. The autopsy rate progressively increased, and, from March 2000 to January 2001, it was 35%, five times the baseline rate, and the refusal rate was 11% (Box). The rate of limited autopsies (generally only excluding the brain) increased from 20% to 50%. However, from early 2001, coinciding with the ongoing negative Australian press coverage related to aspects of autopsies, there has been a marked decrease in relatives' agreement to allow autopsy and extent of autopsy. The refusal rate for autopsy increased to 30% for the four months to May 2001, and was 25% to September 2001. The autopsy rate fell dramatically to 27% and 13% for the same periods. Nine of the 10 autopsies were limited, usually to a single organ or body cavity. Data from death certificates are vital for education, research and public health purposes.1,2 Autopsies remain the only way to audit the accuracy of death certificates. A review found that the rate of clinical diagnostic inaccuracy for major findings at autopsy is about a third, and this rate has not changed since 1912.3 This unavoidable baseline of diagnostic error4 does not necessarily indicate incompetence or malpractice. It is essential that the public understand that medicine is not an exact science, that we do misdiagnose conditions, and that identification of these "errors" is of value to relatives, to future patients and to society. Legislative changes are being proposed in Australia that will make obtaining consent for autopsies more complex and potentially distressing for relatives. Education of medical staff and the general public must accompany these changes if they are not to be the final "nail in the coffin" of the hospital autopsy and remove an important facet of continuing improvement of medical practice. Autopsy rates in the Thoracic Division of the Prince Charles Hospital

Helen E Ward · Belinda E Clarke · Paul V Zimmerman · Michael I Cleary

To the Editor: The National Health and Medical Research Council has launched new Australian alcohol guidelines1 to help reduce alcohol-caused deaths in Australia, estimated to have been 3290 in 1997.2 Male drinkers are advised to drink no more than an average of 40 g alcohol per day and females no more than an average of 20 g of alcohol per day to prevent chronic health problems (eg, alcoholic liver cirrhosis). Furthermore, it is recommended that, provided there are no other situational or individual risk factors (such as driving or being pregnant), men drink no more than 60 g on any day and women no more than 40 g to prevent acute conditions associated with bouts of intoxication (eg, alcohol-related injuries). Volumes of alcohol intake reported at each NHMRC risk level by 10 030 respondents to the 1998 National Drug Strategy Household (NDSH) survey were calculated.3 The data were weighted for age and sex. Volumes of alcohol reported to have been consumed at different risk levels were summed for all subjects and expressed as percentages of the total reported consumption of the sample. It was found that 39% of total consumption was categorised as being drunk by people who exceeded low-risk limits for chronic harm (36% for men, 45% for women). It was found that 51% of total consumption occurred on days when the drinker exceeded low-risk limits for acute harm (53% for men and 47% for women). Drinking that was risky for either acute or chronic harm was found to comprise 67% of total consumption (see Table). For young men aged 18–24 years this figure was 93% of all alcohol consumed. These estimates are conservative, as the level of drinking reported in the 1998 NDSH survey is consistent with an adult per capita consumption of only 46.5% of that estimated by the Australian Bureau of Statistics for that year on the basis of import, export and production data.3 The high proportion of all alcohol consumed that places drinkers at risk of serious harm helps explain why per capita alcohol consumption correlates so closely with levels of suicide, road death, homicide, liver cirrhosis and other causes of death.4 It follows that policies which reduce the total consumption of alcohol in Australia will reduce the associated health and economic costs by reducing levels of risky drinking. Further, policies which successfully reduce high-risk drinking will also reduce total population consumption of alcohol. Percentage of alcohol consumed at risk levels for acute and/or chronic harm, as specified in the new Australian alcohol guidelines,1 by age and sex (n = 10 030, weighted data) Age (years) Females (%) Males (%) Total (%) 14–17 71.3 77.4 75.1 18–24 82.3 92.9 89.9 25–39 68.1 66.4 66.9 40–64 67.7 62.0 63.6 65 + 46.5 39.5 41.4 All ages 68.4 66.5 67.0

Tim R Stockwell · Penny Heale · Tanya N Chikritzhs · Paul Dietze · Paul Catalano

To the Editor: From 1 February to 30 June 2001, 277 602 prescriptions for the smoking cessation drug bupropion hydrochloride (Zyban, GlaxoSmithKline) were processed. The Health Insurance Commission approved 343 737 prescriptions for bupropion between 1 February and 30 June.1 Comparing this figure with the 277 602 processed scripts, some 66 135 (19.2%) scripts went unfilled. One reason for this may have been extensive publicity given to reports of deaths and numerous adverse reactions following bupropion use. The website of the Australian Drug Reactions Advisory Committee (ADRAC) reports that, as at 22 June, there had been 18 reports of deaths in patients aged from 30 years to 69 years who were using or who had recently stopped using bupropion.2 ADRAC summarised intelligence on these deaths thus: ... there were a variety of reported causes of death and not a single consistent mode of death. In addition to being smokers, several patients had other existing risk factors for unexpected death such as alcohol abuse, diabetes or cardiomyopathy. Eleven of the 18 patients had an alternative explanation for death that was at least as plausible as a possible effect of bupropion. In four reports, the available information was very limited and it was not possible to assess the cause of death. Further information is being sought on three cases to aid assessment of the cause of death.2 Smokers are at 3.1 times greater risk of dying (from any cause) than non-smokers and twice as likely to die from coronary disease and stroke.3 People with depression are three times as likely to be daily smokers4 and have double the suicide rate of non-smokers.5 In Australia, sudden coronary fatalities occur at a rate of about 450 per million people aged under 65,6 perhaps at a rate of 355 per million in non-smokers and about double that in smokers. In three months (the period of recommended bupropion use), one would expect 180 deaths per million smoker-users. Thus, among 277 602 Australian smokers, 50 might die during any given three-month period without any added risk from bupropion. This estimate helps to place the 18 fatalities reported to ADRAC in context. The 277 602 scripts represent about 9.5% of Australia's 2.9 million regular smokers. These people, their families and doctors deserve to have their anxieties about the risks of using bupropion addressed. We would urge the government to commission urgently a case–control study of morbidity and mortality among smokers and their relationships to use or non-use of bupropion.

Simon C Chapman · Konrad Jamrozik

To the Editor: I read with interest the article by Hender and colleagues recently published in the Journal.1 I agree with the authors' conclusion that there is presently insufficient evidence to suggest the widespread use of endoluminal treatment for carotid artery disease. However, there are a number of problems with the authors' interpretation of our recent article comparing the outcome of surgical and endoluminal treatment of symptomatic carotid stenosis.2 Firstly, the figures in the Box are completely misleading. The percentages of adverse outcome quoted for patients undergoing endoluminal treatment are those that were found for cases receiving endarterectomy, while the figures quoted for endarterectomy are the findings for endoluminal treatment. [A correction of this error was published in the 3/17 December 2001 issue of the Journal, page 672.] Hence, any reader simply looking at the Box would be left with the false conclusion that the outcome of endoluminal treatment is superior. Secondly, the authors refer to our article2 as a "meta-analysis". In our article we went to some trouble to explain that a meta-analysis was not possible, as only one small randomised trial had been published at that time. Instead, we had to use reports from single centres and we discussed the difficulties of comparing the results when patients had not been randomised. Thirdly, the results of the CAVATAS trial were published in June 2001.3 A surprising finding was that the perioperative stroke rate (defined as a neurological deficit lasting seven days or more) for patients undergoing either carotid angioplasty (with or without stenting) or conventional endarterectomy was the same (around 10%). In fact, the disabling stroke rate of around 6% after either endovascular treatment or endarterectomy was three times higher than that found in the North American randomised trial of endarterectomy.4 Finally, the authors refer to our patients undergoing carotid stenting, whereas the majority of the patients referred to in fact received angioplasty alone.

Jonathan Golledge

To the Editor: As a geriatrician in the subacute sector with hospital medical officers (HMOs) rotating from a major teaching hospital, I am acutely aware of the cost to all concerned of inappropriate diagnostic testing. Discussion stimulated by Stuart et al1 and the editorial by Hammett and Harris2 may help elevate this issue into its rightful arena — quality care and clinical accountability. Donabedian,3 in looking at the assessment of quality care, describes "elements in the performance of practitioners", with technical performance defined as "knowledge and judgement used in arriving at the appropriate strategies of care". I believe that both these quality elements are deficient and that it is the responsibility of the senior clinicians to provide the necessary leadership in ensuring their acquisition. While I agree with Hammett and Harris that there are systems failures and that, as an example, improved feedback of results (particularly given changing HMO work practices and shorter length of patient stays) will provide some of the answers, there appears little doubt that a significant knowledge deficit exists among junior doctors regarding the use and interpretation of common tests and how often they should be ordered. The unfortunate fact is that we have known about these issues for many years and have yet to develop a sustained response. At our hospital we have attempted to modify the use of diagnostic tests by HMOs during their geriatrics rotation, with tutorials from biochemists and haematologists which are reinforced during consultant ward rounds and meetings. This is, however, doomed to failure unless the process is continued by all other clinicians who supervise HMOs. Emanuel and Emanuel4 define accountability in a number of domains. The least controversial of these, I suggest, is professional competence. It is incumbent on us as senior clinicians to "invoke, affirm and enforce professional standards",4 being accountable for the practices of those HMOs under our supervision. Appropriate use and understanding of diagnostic testing will reduce unnecessary patient discomfort while also reducing costs. As any geriatrician will tell you, additional years without insight simply provide grey hair, not improved clinical practice.

Michael J Murray

Letters The mystery of GP research output? MJA 2001; 175: 667 To the Editor: Askew et al ask why there is not more general practice research.1I think they would have come close to the answer had their analysis of publication rates by workforce sector included the relative rates of government salaried employment. The proportions of each group in salaried work are approximately: General practitioners, 18% (of whom only 2% are government employees); Physicians, 56%; Surgeons, 26%; and Public health physicians, 90%.2 While the Primary Health Care Research, Evaluation and Development (PHC-RED) program is a laudable and exciting strategy, it is hard to imagine that it will achieve much change in the rate of general practice research until research activity becomes part of the formal "job description" for a large proportion of GPs, as it is for many of our specialist colleagues. Of course, the incursion of corporatisation into Australian general practice will introduce important issues in regard to the amount of research undertaken and the nature of the research performed, as it has for Australian universities. As yet, PHC-RED has not developed a view as to how it might handle such influences. Phillip Gray General Practitioner, Central Queanbeyan Medical Centre, Focal Point Arcade, 25 Monaro Street, Queanbeyan, NSW 2620. gray.qbnATeffect.net.au Askew DA, Glasziou PP, Del Mar CB. Research output of Australian general practice: a comparison with medicine, surgery and public health. Med J Aust 2001; 175: 77-80. Medical masterfile [database]. Sydney: Australasian Medical Publishing Company, 2001.

Phillip Gray

Letters Australian general practice at a fork in the road: which way forward? MJA 2001; 175: 667 To the Editor: There are a number of deceptions current in the debate over doctors in Australia. Unfortunately, some of these are expressed in your editorial of 16 July 2001.1You fail to acknowledge there are two classes of doctors, as has been the case in Australia for decades — consultants (the princes), doing very well, and general practitioners (the paupers), struggling to survive. You comment that there is "a new phenomenon . . . dispirited doctors". In Australia, consultants are certainly not dispirited (they have never had it so good). However, there are dispirited GPs, who are grouping together in corporations to solve their economic and social problems. Where, Dr Van Der Weyden, have you been hiding? All of a sudden you would have us believe there is a fork in the road for GPs. In reality, there is no fork — just the steady downhill journey that has gone on for years. Instead of supporting and fighting for an increase in the insulting rates of rebate paid to GPs, you are critical of the very reasons GPs are entering the corporate structure. The statement in your editorial that received the greatest hoots of laughter from my fellow GPs was the classic remark "second, there is the challenge of general practice research and education, which has received little attention in the corporatisation debate". Research has never received attention in general practice, and was certainly not a concern before the move to corporatisation. As you yourself have stated, GPs received a mere 1.6% of the National Health and Medical Research Council's research projects over the years 1996 to 2000. Certainly, such lack of funding has stifled what should have been a rich and flourishing research culture, but what has been done about it? Percy S Rodgers General Practitioner, 2/133 Wilson Street, Brunswick, VIC 3056 Van Der Weyden MB. Australian general practice at a fork in the road: which way forward? [editorial]. Med J Aust 2001; 175: 62-63.

Percy S Rogers

Letter Australian general practice at a fork in the road: which way forward? (In reply) MJA 2001; 175: 667 In reply: Despite Rogers' views to the contrary, disillusionment and disenchantment are pan-profession phenomena. Like general practitioners, consultants are unhappy with the deteriorating hospital conditions and working environment1 that are their lot. Further, I am not moved by Rogers' worn view of the profession as "them" (specialists) and "us" (GPs). Most modern GPs consider general practice a specialty. To qualify as a specialty, a branch of medicine needs to have a unique body of knowledge and techniques which are sustained and expanded by its members. Unfortunately, general practice lags behind other specialties in these requirements.2,3 It is depressing that the call for general practice to develop and enhance its educational and research programs occasioned "the greatest hoots of laughter" from Rogers and his fellow GPs. This destructive ethos persists in general practice, to its own detriment. In my editorial,4 I suggested that the trend to corporatisation in general practice presents an opportunity to address the lack of time, lack of critical mass and lack of recognition that are barriers to effective research in this field.5 If GP corporatisation simply replicates the current culture and barriers to research on a larger scale, what is the gain? Rogers' question "what has been done about it [research]?" reflects a passive approach — "important, but not my problem", "someone should do it, but not me". Unless research and education become the business of every GP, general practice as a specialty is in danger of disintegrating into multiple craft groups, not necesarily medically based. Such a development is certainly not a cause for hoots of laughter. Martin B Van Der Weyden Editor, The Medical Journal of Australia, Private Bag 901, North Sydney, NSW 2059. Perkins RJ, Petrie KJ, Alley PG, et al. Health service reform: the perceptions of medical specialists in Australia (NSW), the United Kingdom and New Zealand. Med J Aust 1977; 167: 201-204. Van Der Weyden MB. Promoting an evidence base for general practice [editorial]. Med J Aust 1999; 171: 60-61. McAvoy B. General practice research. Aust Fam Physician 2001; 30: 175-176. Van Der Weyden MB. Australian general practice at a fork in the road: which way forward? [editorial]. Med J Aust 2001; 175: 62-63. Kljakovic M. Flourishing research in academic general practice. NZ Fam Physician 1998; 25: 35-40. Make a comment

Martin Van Der Weyden

Letter Economy class syndrome: a forgotten lesson MJA 2001; 175: 669-670 To the Editor: The editorial by Gallus and Baker,1 and subsequent correspondence which speculated about prolonged calf pressure contributing to causing deep vein thrombosis,2 reminded me of an undergraduate lecture in 1948 about pulmonary embolism in people who slept in deck chairs in London air raid shelters during World War II. This lecture was given by Simpson, then a lecturer in forensic medicine (and later a respected authority in this specialty), who reported a significant increase in deaths from pulmonary embolism (to 24) in September and October 1940, soon after serious night air-attacks on London began.3 This compared with only four in September and October 1939. Twenty-one of these 24 deaths occurred in, or soon after leaving, air raid shelters. The pople who died were mostly elderly, obese and often had varicosities of the leg veins. A typical case was that of an overweight, 60-year-old woman who complained of numb legs and swollen ankles after sitting for 10 hours in a deck chair — she dropped dead in the street while walking home, eight minutes after leaving the shelter. Autopsy showed multiple small pulmonary embolisms and small tags of very fresh antemortem clot in the tibial veins. Simpson concluded that the process was mainly mechanical (calf compression causing obstruction, stasis, oedema and thrombosis), as sleeping in deck chairs causes compression of calf veins against the front edge of the chair for many hours. He proposed that people in air raid shelters should therefore be given provision for lying down. Indeed, by the time his letter was published, in December 1940, he noted that the number of cases of fatal pulmonary embolism were already decreasing, coinciding with the provision of bunks in the shelters. Stasis remains the precipitating factor in Virchow's triad of thrombus formation (abnormal blood flow [stasis], endothelial injury and hypercoagulability). Venous flow rate while lying down slows to half on standing and a third on sitting,4 even before calf compression is added. In 1940, civil authorities acknowledged the cause of an excess of cases of fatal pulmonary embolism and preventive measures were implemented, with documented success within two months. In 1954, Homans reported venous thromboembolism "probably due to sitting travel" by air and car.5 In 1988, calf pressure in cramped seating was blamed by the originators of the popular but restrictive term "economy class syndrome".6 In the 1990s, and in relation to the 2000 Olympic Games, a host of cases of flight-related pulmonary embolism were reported.1 But, in 2001, it seems the evidence for a causative effect must still be considered "circumstantial".1 Lloyd K Morgan Retired General Practitioner, PO Box 150, Lorne, VIC 3232 Gallus AS, Baker RI. Economy class syndrome [editorial]. Med J Aust 2001; 174: 264-265. Slonim L. Economy class syndrome Med J Aust 2001; 175: 176 Simpson K. Shelter deaths from pulmonary embolism. Lancet 1940; 2: 744. Ferrari E, Chevallier T, Chapelier A, Baudouy M. Travel as a risk factor for thromboembolic disease: a case-control study. Chest 1999; 115: 440-444. Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med 1954; 250: 148-149. Cruickshank JM, Gorlin R, Jannett B. Economy class syndrome. Lancet 1988; 2: 497-498. Make a comment

Lloyd K Morgan

Letter Taenia solium and neurocysticercosis MJA 2001; 175: 670-671 To the Editor: A 37-year-old Australian-born white woman presented on Christmas eve with a focal seizure with secondary generalisation. This had developed on a background of bifrontal headaches for which she had been taking ibuprofen. She was in otherwise good health, with no previous history of seizures, head injury or meningitis. On examination there were no focal neurological signs. Fundoscopy findings were normal. Computed tomography (CT) of the brain showed a small contrast-enhancing lesion, radiologically suggestive of a brain tumour. Therapy with phenytoin and dexamethasone was started, and she was referred for neurosurgical assessment. A magnetic resonance imaging (MRI) scan showed an 8 x 12 mm-enhancing nodule in the right posterior frontal cortex with surrounding oedema (Figure). She underwent excisional biopsy of the lesion, and histopathological examination showed a cysticercus cyst, the encysted larval form of Taenia solium, associated with an intense surrounding inflammatory reaction. Further questioning of the patient revealed that she was a frequent visitor to South-East Asia, where this organism is endemic in some areas.1,2 She remains well and seizure-free at follow-up. T. solium (pork tapeworm) is associated with two distinct infective states in humans: asymptomatic intestinal infection by an adult tapeworm, and cysticercosis, which is associated with clinical disease. Ingestion of eggs in contaminated food or water by an intermediate host, typically pigs but sometimes humans, leads to the development of cysticercosis, as seen in our patient. Humans acquire intestinal infection with the adult tapeworm by ingesting encysted larvae (cysticerci) in undercooked meat.1-3 Epilepsy is the most common presentation.1,2,4 The findings of cysticerci outside the central nervous system (such as in the posterior chamber of the eye, palpable within subcutaneous tissues, or as calcified nodules on plain x-rays) and the detection of anticysticercal antibodies in plasma or cerebrospinal fluid may assist in diagnosis of neurocysticercosis, and subsequently prevent unnecessary neurosurgery. However, patients with a single cerebral lesion or those with only calcified lesions are commonly seronegative.1-3 Stool examination for tapeworm eggs is insensitive, but may identify patients with intestinal infection.2 Whether treatment with praziquantel or albendazole improves long term outcome remains controversial.2,5 In cases of encephalitis, subarachnoid, spinal or ocular involvement, symptoms may worsen secondary to an inflammatory reaction around degenerating cysts. Co-administration of corticosteroids ameliorates some of this effect. Surgical treatment is reserved for patients with hydrocephalus.1-3 Neurocysticercosis is uncommon in Australia.5 Our case reminds us of the risks of infective diseases posed to travellers and migrants. It also highlights the importance of considering infective causes such as cysticerci, bacterial abscesses, toxoplasmosis and cryptococcomas in the differential diagnosis of space-occupying lesions seen on central nervous system imaging. Anthony T Zimmermann,* William S Jeffries † * General Medicine Advanced Trainee, Repatriation General Hospital, Daws Road, Daw Park, SA, 5041 † General Physician, Lyell McEwin Hospital, Elizabeth, SA atzimmATausdoctors.net Garcia HH, Del Brutto OH. Taenia solium cysticercosis. Infect Dis Clin North Am 2000; 14: 97-119. Garg RK. Neurocysticercosis. Postgrad Med J 1998; 74: 321-326. Pluschke M, Bennett G. Orbital cysticercosis. Aust N Z J Ophthalmol 1998; 26: 333-336. White AC Jr. Neurocysticercosis: a major cause of neurological disease worldwide. Clin Infect Dis 1997; 24: 101-115. Hellard ME, Street AC, Johnson PDR, et al. Detection of an aberrant motile larval form in the brain of a patient with neurocysticercosis. Clin Infect Dis 1998; 27: 391-393. Make a comment Magnetic resonance imaging (MRI) scan of the patient's brain MRI scan: axial section, T1-weighted image with intravenous contrast. Lesion clearly visible. Back to text

Anthony T Zimmermann · William S Jeffries

Letter Eye exposure to squashed spiders MJA 2001; 175: 671 To the Editor: I read with great interest the letter from Isbister and Balit describing ocular reactions to squashed daddy longlegs spiders.1 As an arachnophile, I think it is a great pity that people go around squashing these harmless beasts that are very efficient at catching and eating real pests such as mosquitoes and flies. Living in a house that is well populated with daddy longlegs, I would like to enlighten readers on my own method of removing these harmless spiders from the house without harming either myself or the spider. This is the "open fist" method. The spider can be easily caught by placing the hand over and around the spider, leaving a small amount of space in the "open fist". It can then be removed from the house and released into the garden. I have used this method successfully on at least 20 occasions without suffering any bite or reaction. Long live daddy longlegs! John E Stuart Paediatrician, John Hunter Children's Hospital, Locked Bag 1, Hunter Mail Centre, NSW 2310. jstuartATdoh.health.nsw.gov.au Isbister GK, Balit C. Eye exposure to squashed spiders [letter]. Med J Aust 2001; 175: 391-392. Make a comment

John E Stuart

MJA 2001; 175: 672 To the Editor: In these days of increasing globalisation of medicine, it is refreshing to realise that there are some uniquely antipodean case scenarios. I wish to report two patients who presented to the emergency department with multiple injuries caused by a single kangaroo. Although there have been previous reports of kangaroos causing injury, this is usually in the passive capacity as an immovable obstruction to a moving vehicle.1 I do not believe there have been any reports of a single kangaroo causing injury to two people at the same time by actively inflicting injury, resulting in a need for hospital treatment. Patient 1: A 32-year-old man intervened in a fight between his dog and a grey kangaroo. The dog escaped, but the kangaroo then turned on the man, inflicting several deep abrasions to his chest, trunk and back, and a bite to his left forearm. X-rays revealed no underlying fractures, and the skin abrasions were treated conservatively. Prophylactic antibiotics and a tetanus booster were administered, and the patient was discharged. Patient 2: While driving past, a 50-year-old man saw the attack described above. He stopped to assist, and grabbed the tail of the kangaroo to distract its attention. The man was thrown to the ground, and sustained bruising to the right shoulder and upper arm. X-rays revealed no fracture, but the arm was immobilised in a sling for symptomatic relief of pain. The kangaroo escaped without injury. These two cases should serve as a warning that intervening in fights between animals poses the risk of injury, and that one kangaroo is easily capable of injuring two humans at the same time. Caution is required if approaching these animals in the wild. Alan E O'Connor Emergency Physician, Emergency Department, The Canberra Hospital, Yamba Drive, Woden, ACT 2606 Alan. O'ConnorATact.gov.au Whittle IR. Beware of boomerangs and kangaroos. Med J Aust 1980; 2: 347. Make a comment

Alan E O'Connor

Letter Improving the treatment of leg ulcers MJA 2001; 175: 670 To the Editor: The article by McMullin emphasises the importance of compression in the treatment of ulcers.1 External pressure equal to that inside the veins will collapse varicosities, which can easily be seen by standing in a swimming pool with water up to the chest. As one cannot spend one's life standing in a pool, it seemed to me that there should be some way of duplicating this in a more convenient form. After some experimentation, I have found a reasonably easy way is to use two sphygmomanometer cuffs, with the tubes connected by suitable plastic tubing, and containing enough water to about 3/4 fill one of the bladders. An insert is put in the canvas of one, to enable it to be worn around the waist (theoretically it should be at the height of the heart, but in practice there seems little difference if it is worn at waist height), and the other is wrapped around the ankle with the ulcer (see Box). The leg cuff is applied first, while still empty, over whatever dressing is preferred on the ulcer, and maybe a layer of cotton wool, as the cuff material can be rather coarse. Then the waist cuff is put on; this contains the water, which can be felt running down and expanding the lower cuff. The importance is that the pressure exerted will balance that in the veins, cannot exceed this, and will vary according to whether one is standing, sitting, or lying down, when water will run back into the upper cuff. As an ophthalmologist I don't get to treat many people with leg ulcers, but I have had vein problems myself for a number of years, with periodic small ulcers, none of which have ever grown to any size, and have healed in four weeks, most in rather less time, with the above management. Obviously, I don't claim it will cure everyone, but it does provide a more scientific pressure which is equal all round the leg, and balances the venous pressure at all times. In my case the pressure, when standing, works out at 66 mm Hg. Even if there is arterial insufficiency, the pressure is only that which is in the veins. No doubt, a purpose-made appliance which is easier to apply and covers a larger area could be produced. Graeme W Johnson Ophthalmologist, 4th Floor, 39 East Esplanade, Manly, NSW 2095. grapamATnsw.bigpond.net.au McMullin GM. Improving the treatment of leg ulcers. Med J Aust 2001; 175: 375-378. Make a comment Device for applying appropriate and even pressure in the management of leg ulcers A: The two connected sphygmomanometer cuffs, one extended to allow it to fit around the waist. B: The device as it is worn. Back to text

Graeme W Johnson

Letters What a louse! MJA 2000; 173: 603

Paul Prociv

Letter A possible case of intestinal myiasis due to Eristalis tenax MJA 2000; 173: 652 To the Editor: A 42-year-old woman living in rural South Australia presented with a history of passing actively swimming "fish-like creatures" with her stool. There were no other symptoms (apart from a sense of revulsion). Specimens brought in by the patient were cylindrical larvae about 2.5 cm long with a "tail". Based on the characteristic morphology, they were identified by our local pathologist as "rat-tailed maggots", or larvae of the introduced drone fly (Eristalis tenax). The patient saw one to three of the larvae on about five occasions over a 2-week period, whereupon they spontaneously ceased to occur. She remained asymptomatic. There was nothing to suggest that the patient had a low standard of hygiene. The specimen, apparently passed with stool, was identified as a "rat-tailed maggot", or larva of the introduced drone fly (Eristalis tenax). Infestation of live humans or vertebrate animals with larvae of Diptera (fly) species is known as myiasis -- for part of their life cycle, the larvae feed on dead or living tissue or the ingested food of the host.1 Pseudomyiasis is the term used for deposition of maggots on faeces immediately after they are passed. Recognition of dead larvae in stool also comes into this category, as host infestation has not been established. A few patients with intestinal myiasis with drone fly larvae have been described previously, with the mode of infestation presumed to be consumption of water or food contaminated with fly larvae or eggs.2,3,5 Life stages of Eristalis tenax: (a) larva; (b) pupa; and (c) adult fly. The rat-tailed maggot usually breeds in drains, sewage pools, and other stagnant water. Although the larvae live on decaying organic matter, they must breathe air. For this, the breathing tube (the tail) is extended or contracted depending on the depth of the liquid in which they are feeding. Our patient had a septic toilet system. It is possible that the maggots could have bred in the tank and travelled upstream to the toilet bowl. The tank, however, was 10 metres away and appeared normal when opened and inspected, and no other family members noted the maggots in their stool. Doubts have been expressed about the theory that accidentally ingested fly larvae could survive in the environment of the gastrointestinal tract. Zumpt proposed an alternative kind of intestinal myiasis due to Eristalis tenax called "rectal myiasis".1 Flies, attracted to faeces, may deposit their eggs or larvae near or into the anus, and the larvae then penetrate further into the rectum. The larvae may then feed on faeces at this site, as long as the breathing tube reaches towards the anus. Although our patient had no symptoms, anal pruritus or discomfort has been described in other reports.4,5 Phillip B Whish-Wilson General practitioner PO Box 1118 Mount Barker, SA 5251 Zumpt F. The problem of intestinal myiasis in humans. S Afr Med J 1963; 37: 305-307. Lakshminarayana CS, Kanchana MV, Janakavalli R, Mallika M. Intestinal myiasis due to Eristalis tenax. J Indian Med Assoc 1975; 65: 234-235. Aguilera A, Cid A, Regueiro JM, et al. Intestinal myiasis caused by Eristalis tenax (letter). J Clin Microbiol 1999; 37: 3082. Hall MC. A note regarding myiasis, especially that due to syrphid larvae. Arch Intern Med 1918; 21: 309-312. Cookson HA, Oldroyd H. Intestinal infestation by larvae of a drone fly. Lancet 1937; 2: 804.

Phillip B Whish-Wilson

Letters Chromomycosis MJA 2000; 173: 656 To the Editor: A 38-year-old man presented with a hyperkeratotic, crusting lesion on his right knee which had been present for 17 years and had not responded to treatment (Box 1). The lesion developed in 1983 after he knelt on wood chips while cutting wood in scrub country to the west of Mackay in Queensland. The lesion had slowly increased in size and persisted despite various attempts at therapy. When it was about 1 cm in diameter, local excision was offered, but, as the surgeon was not able to guarantee the lesion would not recur, excision was not performed. In January 1996 a biopsy was taken. The report read "pseudoepitheliomatous hyperplasia" of the epidermis. In the dermis there was a "granulomatous inflammatory reaction in which there were collections of pigmented yeast bodies". The histological diagnosis was chromomycosis (chromoblastomycosis) (Box 2). Chromomycosis organisms are round, thick-walled brown cells, 5-12 mm in diameter, usually occurring in dermal microabscesses. After one month's culture, Cladophialophora carrionii (also known as Cladosporium carrionii) was isolated. By 1999, when the patient presented, he had been treated sequentially, without success, with ketoconazole (200 mg daily for six months), fluorocytosine (dose unknown) and terbinafine (250 mg daily). In October 1999, he was given itraconazole 100 mg daily. This dose was increased to 100 mg twice daily in November 1999 and was continued until May 2000, by which time the total dose of itraconazole administered was 54 g. (The patient was 179 cm tall and weighed 114 kg.) The drug has been well tolerated, with no abnormality of blood film or liver function. There has been a slow but steady healing of the knee lesion (Box 3). Chromomycosis (chromoblastomycosis) is a chronic mycotic infection of the cutaneous and subcutaneous tissues. It is diagnosed by the presence in the tissue of phaeoid (Greek phaeios, "dusky") muriform cells and by isolation and identification of the pathogenic fungus. The muriform cells represent an intermediate vegetative fungal form arrested between yeast and hyphal development. The dusky colour of these muriform cells results from a melanin pigment.1 The lesions produced by the infection are nodulo-verrucous. The fungal genera that can cause this infection (Cladophialophora, Fonsecaea, Phialophora, Rhinocladiella) live as saprophytes in soil and in decaying wood and vegetation. Infection is caused by inoculation, but the injury may be so minor as to go unnoticed and may have occurred years before the slow-growing lesion is noticed. It occurs most commonly on the feet or legs, but, in Australia, the upper limbs are more commonly involved. Cladophialophora carrionii infection is a common cause of chromoblastomycosis and, although the infection can be contracted from many environments, it is particularly prevalent in arid and semi-arid areas, most often in tropical and subtropical zones. It has been reported from North, Central and South America, Cuba, Jamaica, Martinique and many other countries, including India, South Africa, and Madagascar, as well as Australia and Northern Europe. It has occurred as an imported infection in the United Kingdom.2 Chromoblastomycosis is frustratingly difficult to treat, but it is becoming increasingly evident that itraconazole is the treatment of choice, at least for infections with Cladophialophora spp., partly because itraconazole accumulates in the skin and subcutaneous tissues owing to its lipophilicity.3 In adults the dose of itraconazole is 200 mg or more per day for as long as required (the dose is continued for a period two to three times longer than that required to obtain negative culture results).4 George R Crowe Plenary Physician, Pioneer Valley Private Hospital PO Box 8877, Mount Pleasant, QLD 4740 Michael Martin Pathologist, Central Queensland Pathology Laboratory Mackay, QLD Acknowledgements: Dr Brian Reid, Dermatologist, Townsville; Dr Andrew O'Neill, Mackay; Mr John Atkinson, Librarian, Mackay Base Hospital; and Ann James, Janssen-Cilag Australia. Guerrant RL, Walker DH, Weller PF. Tropical infectious diseases: priciples, pathogens and practice. London: Churchill Livingstone, 1999: 621-623. Champion RH, Burton JL, Ebling FJG. Textbook of dermatology. 5th ed. Oxford: Blackwell Scientific Publications, 1992: 1205-1206. Strickland GT. Hunter's tropical medicine. 8th ed. Philadephia: WB Saunders, 1999: 573. Borelli D. A clinical trial of itraconazole in the treatment of deep mycoses and leishmaniasis. Rev Infect Dis 1987; 9 Suppl 1: S57-S63. 1: The lesion The lesion on the knee when the patient presented in 1999. The lesion first developed in 1983 after the patient knelt on wood chips. Back to text 2: Chromomycosis organisms Photomicrograph (haematoxylin-eosin, original magnification x400) of skin biopsy in 1996, showing two Cladophialophora spores in a microabscess (arrow). Back to text 3: Healing after 17 years Treatment with itraconazole in late 1999 resulted in steady healing of the lesion. Back to text