Letters

To the Editor: I read with great interest the article by Byard et al,1 as well as the previous work by these authors on paramethoxyamphetamine (PMA)-related fatalities in South Australia.2 In 2001, I encountered a similar fatal "outbreak" in Belgium: six fatal cases, four of them in the Antwerp metropolitan area.3,4 Striking similarities between the Belgian and Australian fatalities include the clinical symptoms, the autopsy findings and the history of alleged "ecstasy" intake. Pure PMA tablets were found on a victim with an "xTc" logo pressed onto the surface of the tablets.3 I agree with Byard et al1 that the sudden "outbreaks" of death from PMA intoxication probably do not result from contamination during the synthesis of 3,4-methylene-dioxymethamphetamine (MDMA). In Belgium, there are strong indications that the resurgence of PMA resulted from a legal loophole. Early in 2001, PMA was encountered for the first time in the blood sample of a young girl who presented to an emergency department for alleged ecstasy intoxication. A few weeks later, the first fatal case was reported, and over a period of a few months five other fatal cases were seen. After the first two deaths, PMA captured a lot of media attention and even evoked some political disturbance. By the end of 2001, PMA and its precursor molecule, p-methoxyphenylacetone, were placed on the list of regulated and restricted substances (and hence the unauthorised possession of these products became a criminal offence). Afterwards, no more fatalities were reported. I therefore hypothesise that illicit amphetamine manufacturers were aware of the (temporary) legal vacuum in Belgian law before the deaths occurred and substituted PMA for MDMA because PMA precursors were easier to obtain and less strictly controlled by legislation. It has been suggested in the Australian illicit drug report 1994,5 as well as by Byard et al,1 that manufacturers of PMA may have been deliberately marketing it as another drug (eg, MDMA) or may have promoted it specifically as a drug to augment the effects of MDMA. If this is the case, there may be serious implications for criminal liability, as we now know that PMA intoxication has a significantly worse clinical outcome than MDMA intoxication (including a greater likelihood of QRS-interval prolongation, extreme hyperthermia, seizures and a significantly lower score on the Glasgow Coma Scale).6

Werner Jacobs

To the Editor: I read with interest the MJA supplement The student and junior doctor in distress — "our duty of care".1 It is encouraging to see the time, effort and research currently being devoted to the health and mental wellbeing of our colleagues. One aspect of the medical workforce that was not discussed is that of locum doctors, who, in metropolitan and rural New South Wales, are increasingly called upon to staff public hospitals. Under this system, a doctor registers with a locum agency, hospitals advise the agency (often multiple agencies) of the shifts they need filled, and the agency then sends to all the doctors on their books a list of shifts available. Doctors then choose which shift(s) they would like to work and the agencies supply their names to the hospitals. They are paid by the hospital — the current rate for all doctors, Post Graduate Year (PGY) 1 and upwards, being a minimum of $70–$80 an hour — and the agency receives a 10%–15% commission. In contrast, the base hourly rate for a full-time PGY 1 doctor is $23.11, with a loading of 75% on Sundays and 100% for any hours worked beyond a 10-hour shift. The only barrier to locum work is that a doctor is unable to have two rates of pay within the one Area Health Service. There is thus a strong incentive for full-time employees to refuse extra overtime work at their own hospital and do locum work at other hospitals. The number of shifts needing to be filled by hospitals increases as Junior Medical Officers choose this option. The current restrictions on access to provider numbers, rather than serving as an incentive to remain in the hospital system, have encouraged many junior doctors to seek locum work. It is also relevant that, as more graduate students come through the system, more doctors are older and have financial obligations. Many have had good incomes prior to studying medicine and wish to maximise their earnings once they graduate. Wilhelm2 and Mouret3 both observe that financial concerns are a major stressor for Junior Medical Officers. There are significant disadvantages for the locum doctor (eg, lack of ongoing education from patient follow-up, feedback about mistakes, mentor and peer support; inadequate supervision of "safe working hours") and for the healthcare system (eg, lack of continuity of care; locums' unfamiliarity with the hospital and its procedures; variable skill levels of locums; resentment by regular staff of pay rate discrepancies; cost). While there is no doubt a role for locum doctors within the healthcare system, there is no overall control of the situation. Locum agencies are businesses that exist to make money for their owners. The hospitals see themselves as paying top dollar for locum doctors and therefore see no obligation to provide training and counselling. The doctors are in the middle. To protect the doctors and also the hospitals, changes must be considered. Representatives of the NSW Medical Board, Postgraduate Medical Council and Area Health Services need to discuss this issue.

Elizabeth Swinburn

To the Editor: It was most enlightening to read the articles on cosmetic surgery in the 17 June 2002 issue of the Journal. In particular, the Clinical Update by Castle et al on psychosocial wellbeing and cosmetic surgery1 is pertinent to everyday practice. The warning given that cosmetic specialists should be concerned about patients who have had numerous procedures, in particular patients who have previously sued physicians, is a poignant one. Psychological testing of patients who wish to have plastic and cosmetic surgery is not routine, and plastic or cosmetic surgeons cannot be expected to carry out such testing. Liaison with psychologists and psychiatrists can be conducted on a case-specific basis, but not routinely. The aim is to screen for body dysmorphic disorder, but this can be quite difficult, as the presentation is often obscure.2 In reality we live in a world where appearance is very important, and self-esteem is related to appearance. Age discrimination is a reality, and cosmetic surgery has been shown to improve a patient's psychosocial wellbeing.3 The issue of advertising of cosmetic surgery services is a vexed one, as is the issue of where cosmetic surgery should be performed. As it is usually not performed in public hospitals, it has been relegated to the private sector in Australia, and private hospital appointments that might include cosmetic surgery have been vigorously protected by special-interest craft groups in Australia. Misconceptions by the general medical community are rife, due to both the lack of exposure to cosmetic surgical procedures and the lack of information on the subject. The assistance of the general practitioner, together with a thorough patient history, is very valuable in determining whether cosmetic surgery is likely to have a positive psychosocial outcome. Unfortunately, the generally poor attitude of the Australian medical community towards cosmetic surgery has led to patients being afraid of a negative response when asking their GPs about cosmetic surgery. Often referrals are either not made or are made by an anonymous practitioner, which is not an ideal situation. Liaison with surgeons who have previously treated a patient is ideal, but cooperation in this area is not always forthcoming, as some surgeons fear litigation from former patients. With most cosmetic surgeons being shut out of the medical mainstream, access to potential patients comes through normal commercial means, such as advertising in the Yellow Pages and in magazines. It is to be hoped that in future there will be more contact between cosmetic surgeons and other medical practitioners so that the true benefits and risks of the procedures can be understood by the general medical community, who, in turn, can counsel their patients in a sympathetic manner as to whether cosmetic surgery is advisable.

Darryl J Hodgkinson

To the Editor: According to the article by Kennedy in the Journal,1 we failed to address the objections to the RARE SALAMI trial (the Royal North Shore and Ambulance Regional Study of a Stenting Strategy as an Alternative to Lytic/Medical Therapy in Acute Myocardial Infarction) in our account of the fate of this trial.2 Allegedly, we contravened standard advice regarding emergency cardiac care ("to attend the nearest hospital emergency department as quickly as possible").1 However, the standard advice is to call an ambulance,3 not to go to hospital by private transport. Kennedy also claimed that the trial would interfere with " . . . established therapeutic networks and ongoing therapeutic relationships, including relationships with hospitals".1 The reason we ignored such objections was that the wellbeing of networks seemed unimportant in comparison with the welfare of patients with life-threatening illness. The issue of the risk to patients of transport time and treatment delays with the new strategy was also raised,1 but Kennedy did not challenge the actual measured delays or other published evidence we referred to.2 These suggested that mortality was likely to be reduced with the RARE SALAMI strategy. Without reference to published data, he quoted the opinions of clinicians and a municipal council to support the opposite conclusion. The northern suburbs of Sydney are not so remote or exotic that opinion based on knowledge of the "local practicalities" he referred to1 would outweigh the evidence of published data. We argued that complexities of treatments, patients' condition and the pressure of time precluded fully informed consent.2 Allegedly, established guidelines were breached.1 However, the ethics committee, well aware of these, waived conventional informed consent after careful deliberation. A new area ethics committee, constituted subsequently,2 concurred with this decision. Now, in the light of new evidence, the RARE SALAMI trial, as originally proposed five years ago, can no longer be done. The recently presented DANAMI II study4 randomised 1129 patients to treatment with fibrinolysis at local hospitals or to transportation to angioplasty centres up to 153 km away. Transport was found to be safe, and angioplasty was associated with a 40% reduction in adverse outcomes. Field triage was not tested. However, we believe the results of the DANAMI II study now preclude randomisation of 50% of patients with suspected acute myocardial infarction presenting to the Ambulance Service (and eligible for the RARE SALAMI trial) to treatment at district hospitals. Ironically, in northern Sydney, status quo reigns and 100% of trial-eligible patients are taken to district hospitals and delays in achieving reperfusion persist! Thiemann, in a recent editorial, concluded that accrued evidence now favours treatment of patients with acute myocardial infarction in a few high-volume centralised angioplasty centres,5 and that field triage and direct transport to such centres holds great promise. He also deplored the lack of research into system changes and the economic self-interest that, he believed, had stymied change in the United States. Opposition to the RARE SALAMI trial was altruistic.6 However, it nevertheless stopped much needed research and hence may have compromised patients' rights to optimal care.

Helge H Rasmussen · Peter S Hansen · Gregory I C Nelson

In reply: Rasmussen, Hansen and Nelson have missed the entire thrust of my article.1 When an individual calls a health professional for help, we can assume he or she agrees to standard treatment, but not to be placed into an experiment. Failure to inform patients that they are being placed into an experiment is a denial of basic human rights. I outlined a mechanism by which it would be possible to conduct an experiment such as RARE SALAMI that would comply with the appropriate guidelines and avoid denial of informed consent. It is worth noting that failure to inform patients that they have been placed in a clinical experiment could also worsen our present medical indemnity crisis and lower the standing of medical research. It has been shown how institutional ethics committees can be subjected to local pressures.2 As a result, it is possible some may adopt pseudolegalistic interpretations of accepted guidelines and approve studies that would be rejected elsewhere. This is another reason why informed consent is so important. Without it some studies simply can't be done.

Michael C Kennedy

To the Editor: I thought it most appropriate that you juxtaposed the articles by Kilmartin et al1 and Fitzgerald2 in your General Practice issue (15 July). Missing from each article is a key aspect from the patient's point of view. As a patient, I value, above all else, continuity of care by my general practitioner. In this age of increasing sessional work (by both female and male doctors) and of increasing employment of doctors on a sessional basis by corporations, this feature of general practice is threatened. As a former GP, I am increasingly being asked to comment by lawyers (for both plaintiffs and defendants) on cases where patients have fallen through the cracks that are an inevitable aspect of sessional care. Patients are being seriously harmed because of poor communication and poor or no handover between sessional doctors. What is most disturbing is the absence of failsafe mechanisms to ensure that communication, both verbal and, more importantly, written, between the sessional GPs in a practice comes as close as possible to providing the continuity of care offered by the now nearly obsolete five- or six-day-a-week and after-hours family doctor.

Peter C Arnold

To the Editor: I offer the following additions to the growing list of favourite books with a medical flavour.1,2 The house of God, by pseudo-intern Samuel Shem, is an irreverent, bawdy, cult classic ("Catch-22 with stethoscopes"). I was particularly intrigued by the "laws of the house of God", including "placement comes first" and "if you don't take a temperature, you can't find a fever." The woman who walked into doors, by Dubliner Roddy Doyle, is a heartrending narrative of emotional and physical abuse of a woman by her partner, and of neglect by her health professionals. "A nurse . . . She'd seen me before . . . I waited to be asked. Ask me. Ask me. Ask me. I'd tell them everything. Look at the burn. Ask me about it. Ask. No. . . Her boyfriend was waiting." "The doctor never looked at me. He studied part of me but he never saw all of me." Another is The plague, by French novelist Albert Camus and translated by Stuart Gilbert. " 'Please, doctor, what is it?' 'It might be — almost anything. There's nothing definite as yet.' . . . On returning to his flat [Dr Bernard] Rieux rang his colleague Richard, one of the leading practitioners in the town. "'No,' Richard said, 'I can't say I've noticed anything exceptional.' 'No cases of fever with local inflammation?' 'Wait a bit! I have two cases with inflamed glands.' 'Abnormally so?' 'Well,' Richard said, 'that depends on what you mean by "normal".' "

C Ross Philpot

To the Editor: In their recent article, Makdissi and Brukner stated that resumption of play should follow the "30/30" rule.1 In the article, the authors cited three references, each of which relates to position statements rather than to any scientific reference that "blue skies and lack of rainfall are not adequate reason to breach the 30 minute return to play rule".2-4 Unless there are reasonable scientific explanations why lightning should strike someone in the presence of blue skies, I would think that this policy needs some reconsideration. It seems logical that if a storm is moving away, the skies should become blue, and the time between lightning and thunder should increase. I would have thought that if there was a weather watcher around, he or she could monitor the situation, and ascertain that the storm was moving away, and this would allow for earlier resumption of sport. Can you imagine a weather watcher preventing play in an AFL game, or even a minor suburban game of football, because of the threat of lightning if the skies were indeed blue? If I am to take this recommendation to my local football club, I would like to see evidence that this has some credible scientific backing.

David Vivian

In reply: The "30/30" rule is a simple and easy-to-remember rule designed to reduce the probability of lightning strikes. Two important studies over recent years have led to its development. First, in 1993, Holle et al analysed the number of casualties relative to flash rates during thunderstorms and found that most casualties occur at the beginning and end of storms.1 They concluded that individuals typically wait too long to seek safe shelter and often resume too soon. Secondly, in 1999, Lopez and Holle examined the distribution of successive flashes for large numbers of different types of storms, and found that, although most were separated by less than 8 km, a significant number of successive flashes occurred up to 13 km apart.2 This was noted to be more likely with larger, more complex storms. Given that lightning can strike kilometres forwards or backwards from the storm front, being within 10 km of lightning activity (as estimated by a "flash-to-bang" count of 30 seconds) reflects a risk that the next flash might conceivably be at the observer's location, irrespective of whether there are blue skies overhead. This is why blue sky alone is not enough reason to break the 30/30 rule.

Michael Makdissi

To the Editor: I enjoyed reading Makdissi and Brukner's "Recommendations for lightning protection in sport",1 but I feel that in addressing an audience of renowned golf hacks the authors have made a glaring omission. It is well known in golfing circles that the first rule of lightning self-protection on the golf course is to always carry a 1-iron in the bag and in appropriate conditions to reach for it — because not even God can hit a 1-iron!

Michael Gullquist

To the Editor: We write to alert policy makers and clinicians to the challenge presented by rising cannabis use in north-east Arnhem Land, in the Northern Territory, given that many current cannabis users were previously petrol sniffers. In the past five years, there has been a rise in cannabis use and evidence of expansion of supply links in the Miwatj region.1 There are concerns that rising cannabis use is associated with social effects: increased family violence, drug–alcohol psychosis, self-harm and suicide, and community disruption. Policy makers seeking to foster initiatives to minimise harmful outcomes must develop general policies that can have local effects in a varied Northern Territory population. NT police have targeted cannabis in remote communities. A Substance Abuse Select Committee and Illicit Drugs Task Force, each with Indigenous representation, will report to the NT government during 2002. We recently began collecting baseline data to allow us to evaluate the effects on patterns of use of cannabis (and related harm) of community-wide interventions. These interventions will be similar to those implemented for petrol sniffing,2 but with a focus on improved availability of appropriate drug education. We have selected a random sample of about a third of the residents (aged 13–34 years) from two communities. From this sample, current cannabis users (at least weekly) and past petrol sniffers have been identified by using health worker consensus classification, supported by data from review of the health clinic chart and self-report, if available. These data for 145 males and 141 females are presented in the Figure. Among males aged 20–34 years, 74% are current cannabis users and, of these, 60% are former petrol sniffers. To date, 57 cannabis users have agreed to interview (34 males and 23 females) and, of these, 38 met DSM-IV criteria for cannabis dependence.3 A particular health concern is that persistent cannabis use may compound any residual cognitive impairment from petrol sniffing. Current cannabis users among people aged 13–34 years in northeast Arnhem Land Results for samples from two remote communities in the Miwatj region, assessed by using health worker consensus classification, self-report data, and supporting data from health clinic chart review.

Alan R Clough · Sheree Cairney · Paul Maruff · Robert Parker

To the Editor: In Australia, an estimated 11 000 people become infected with hepatitis C virus (HCV) each year.1 Most are injecting drug users. The Early Hepatitis C Intervention Project was a collaboration between the STD Services Surveillance Unit, Drug and Alcohol Resource Unit and Infectious Diseases Unit at the Royal Adelaide Hospital, Adelaide, South Australia. Its objectives were to manage people who had seroconverted in the preceding 12 months and to provide standard treatments for drug use and dependence. Services included information and education on HCV, referral, counselling, psychosocial support and three-monthly clinical evaluation. The project was approved by the Ethics Committee of the Royal Adelaide Hospital and funded by the Department of Human Services for 18 months. The attendance rate was low. Of 88 people with HCV seroconversion who were identified as eligible for enrolment by the Surveillance Unit (from the mandatory notification scheme), 57 agreed to further contact by mail or telephone, and 12 attended for risk assessment. Of these, eight enrolled in the project (10% of those eligible). Despite demographic variation within the group, similarities included difficulties with accommodation, finances, mental health and social integration. Seven of the eight participants had injecting drug use as the risk factor for HCV infection. Most participants also used alcohol and cannabis. During the program, half decreased their risk-taking behaviour: four reduced injecting drug use, and four reduced alcohol use, reaching low risk levels. Characteristics of participants at their last interview are summarised in the Box. Two participants are maintaining regular contact with the Drug and Alcohol Resource Unit. Despite encouragement, few of the target group engaged in the program. We do not know why so few people who agreed to attend a first appointment failed to do so. We did not have their permission or the resources to contact them again. Maintaining contact with participants also proved challenging, and was in part unsuccessful because of complex, multifaceted social issues aside from HCV infection (Box). These included unstable accommodation, use of health services only when in crisis, mental health problems, financial difficulties, polydrug use and continued risk-taking behaviours despite harm-reduction information. In conclusion, the Australian epidemic of HCV infection, driven by injecting drug use, is likely to continue unless a new approach to harm minimisation is developed. Such an approach will recognise that comorbidities and social dislocation influence risk of infection. Unless treatment programs address coexisting problems, it will be futile to offer definitive treatment for HCV infection.2 Within the limited objectives and resources of this project, we were unable to support these people comprehensively. We believe that a "one-stop shop" that includes active and intensive case management by a flexible, multidisciplinary team and deals with social, economic and mental health issues may be a more effective approach to the care of people with recent HCV infection. Characteristics of participants in the Early Hepatitis C Intervention Project at last interview Place of residence Current mental illness* Attendances Age, sex Employ-ment Polydrug use At 5 nominated appointments Total† IDU change‡ Persistent viraemia‡ 19, F No Yes NFA Yes 3 6 Reduced IDU Yes 21, F Part-time Yes NFA Yes 3 5 Reduced IDU No 21, M No Yes NFA Yes 3 4 No IDU at enrolment Yes 24, M Voluntary No Rental Yes 1 1 Denied IDU ever Yes 30, M Casual Yes NFA No 2 4 No IDU Yes 36, M No Yes Parents Yes 1 4 Unknown Yes 38, M Full-time Yes NFA Yes 2 3 Reduced IDU No 43, M Full-time No Rental Unknown 1 1 Unknown No IDU = injecting drug use. NFA = no fixed abode. * Mainly depression, anxiety and personality disorder. † Includes self-initiated visits. ‡ Determined by polymerase chain reaction.

To the Editor: The recent article by Johnston et al is an important contribution to the small but growing body of literature on the health effects of particulate matter (PM) pollution derived from bush or forest fire.1 The authors studied an important wood smoke PM exposure in Australia and showed consistent associations between higher concentrations of PM and emergency department presentations for asthma. Most research on the effects of PM has focused on motor-vehicle-derived PM pollution.2,3 However, Johnston et al do not appear to have accounted for serial correlation in their data. Measurements connected in time, such as repeated measurements of the same population, are likely to be correlated and not independent.4 Further, school holidays have been shown to influence hospital admission rates.5 The major Northern Territory school holidays in June and July are in the middle of the study period. Johnston et al adjusted for some important confounders in their analysis (acute respiratory infections and weekdays/weekends).1 However, in time-series data, especially those dealing with asthma, serial correlation, as well as other potentially important confounders such as school holidays and temperature and humidity, should also be assessed. It may be that, even after appropriate adjustments for serial correlation and potential confounders, the rate ratios found by Johnston et al may not alter appreciably. However, it would have been useful for the investigators to have at least discussed any effects that controlling for serial correlation and other potential confounders might have had on their findings.

Bin B Jalaludin · Guy B Marks · Geoffrey G Morgan

In reply: Jalaludin and colleagues query the potential effects that serial correlation and confounding by school holiday time periods may have had on our finding of an association between particulates derived from bushfire smoke and asthma presentations.1 As previously discussed by Schwartz, time series analyses are important to control for serial correlations, particularly those due to the effects of seasonality and weather fluctuations.2 Our study did not cover a number of seasons. It was conducted during one tropical dry season, a period characterised by remarkably stable day-to-day weather conditions.3 For this reason, we believe that the effects of any autocorrelation would have been negligible. It is of interest that the development of statistical methods for analysing time series of count data during the 1990s, and analysis of large studies of particulate pollution using these methods, did not have an important effect on the conclusions reached by earlier studies.4 There is evidence that hospital admissions for asthma fall during school holidays.5 Anecdotal reports of more regional fires suggest that, if anything, particulate concentrations over Darwin might increase at these times. A reanalysis of our data including school holiday periods as a potential confounding factor did not appreciably alter our results in either the continuous (revised incidence rate ratio [IRR],1.26; 95% CI, 1.12–1.41, compared with original IRR, 1.20; 95% CI, 1.09–1.34) or categorical analysis (see Table). Asthma presentations and exposure levels of PM10* (μg/m3) Rate ratio for asthma presentations (95% CI) Same-day PM10 category (μg/m3) Original analysis† Revised analysis‡ < 10 1.0 1.0 10–< 20 0.90 (0.60–1.35) 0.84 (0.43–1.63) 20–< 30 1.11 (0.74–1.69) 1.13 (0.58–2.18) 30–< 40 1.18 (0.72–1.97) 1.21 (0.58–2.50) ≥ 40 2.38 (1.46–3.90) 2.47 (1.21–5.01) * Particles of 10 microns or less in aerodynamic diameter per cubic metre. † Adjusted for influenza-like illness and weekday. ‡ Adjusted for influenza-like illness, weekday and school holiday periods.

Fay H Johnston · Anne Kavanagh · David MJS Bowman · Randall K Scott

To the Editor: The editorial by Steven and Shanahan on work-related stress1 indicated that claiming Medicare benefits for a workers compensation injury is specifically precluded. It also identified a need for guaranteed certainty of cost reimbursement for treatment. Medicare benefits are payable for professional services that are wholly covered by workers compensation, unless there is a reimbursment arrangement with the insurer.2 The patient may be bulk billed or given a private account. The recovery of any benefits paid once a settlement or judgement is made does not involve the practitioner. It is not claiming the benefit which is precluded, but keeping it if an outcome favourable to the plaintiff ensues. My understanding is that unsuccessful claims are rebatable under Medicare for clinically relevant medical services. The medicolegal expenses incurred, for example for reports, do not qualify, as they are not medically necessary. The fees are a private matter, as are any treatment charges in excess of the Medicare rebate. Herein lies the uncertainty.

Raymond L Carroll

In reply: What Carroll says is correct, but Section 3.6 of the general explanatory notes of the Medicare benefits schedule book also states that "The only exception to this is where a person has entered into a reimbursement arrangement with a compensation insurer. In such cases a Medicare benefit is not payable".1 While it may be arguable as to what actually constitutes a reimbursement arrangement, the situation is further clarified by Section 13.2.1 of the same schedule, which states: "Medicare benefits are not payable in respect of a professional service in the following circumstance: (b) where the medical expenses for the services are in relation to a compensable injury or illness for which the patient's insurer or compensation payer has accepted liability. However, if medical expenses relate to a compensable injury or illness and the insurer or compensation payer is disputing liability, Medicare benefits are payable until liability is accepted".

Ian D Steven · Michael Shanahan

To the Editor: In an article in the 1 April issue of the Journal,1 Sturm et al reported on a GP-based stroke audit ("ASAP") and stated that "the information obtained is likely to be representative of most Australian general practice environments". Without further information, we cannot be as confident. First, their sampling strategy was unconventional. Of all registered GPs from five Australian States and one Territory who were initially approached in May 2000, only 10.2% (n = 1850) of eligible GPs expressed interest in participating in the study. From each of 22 "geographical regions", up to 18 GPs were recruited, initially by random sampling and then by replacement, to obtain a sample of 396 GPs, of whom 321 (81%) provided data. No GP data by State and Territory or "geographical region" were provided to allow readers to judge the possibility of sampling bias. Unpublished data from our own GP survey about stroke issues in New South Wales raise this possibility. We conducted a postal survey of 490 randomly selected GPs from November 2000 to February 2001 (response rate, 60%). None of the 296 participating GPs stated they were enrolled in a stroke clinical audit. Second, although patients were clustered within GPs, no intracluster correlations (ICCs) were reported. Outcomes (eg, disease morbidity and risk factors) for patients recruited from general practices tend to be correlated at the GP level.2 ICCs quantify the extent to which individuals within clusters (such as a GP's practice) are similar to each other relative to individuals from other clusters. Conventional formulas for calculating confidence intervals assume that the ICC is zero (ie, no clustering). Yet, where correlation within clusters does exist (ie, ICC > 0), the effective sample size is reduced and the associated CIs are inevitably wider. For any given ICC greater than zero, larger cluster sizes also further reduce the effective sample size. Applying appropriate formulas,3 we calculated effective sample sizes for risk factors in the ASAP study, assuming three different magnitudes of ICCs, ranging from relatively modest (0.015) through more substantive (0.1) (see Box). Given the large denominator of the ASAP study, our methodological concern may be only minor in terms of the width of the CIs reported, but the reader is unable to judge whether or not this is the case, as no ICCs were reported. As sample-size calculations for future interventional studies would be informed by publication of ICCs,4 we encourage such reporting in future. Third, we believe the authors' quantitative findings would have been most useful if they had been age-adjusted in line with Australian community norms. Effective sample size, assuming three different magnitudes of intracluster correlation (ICC) Risk factor Actual n Effective n if ICC = 0.015 Effective n if ICC = 0.05 Effective n if ICC = 0.1 Total Hypertension 14 280 8643 4499 2670 Hypercholesterolaemia 12 516 7973 4317 2608 Smoking 14 297 8649 4500 2670 Diabetes 13 767 8455 4449 2653 Atrial fibrillation 14 194 8611 4490 2667 Stroke/transient ischaemic attacks 14 321 8657 4502 2671

Sandy Middleton · Neil J Donnelly · Jeanette E Ward

In reply: We thank Middleton et al for their interest in our article. As 96% of questionnaires in our ASAP study1 were completed by September 2000, their study (as yet unpublished) and ours were not concurrent. Statistically, based on the information given by Middleton et al, we would expect 5.5 GPs (296 x 333/18066) to be involved in both studies. Chance, or because direct involvement in the ASAP study had finished months earlier, may explain why none of the doctors in the survey by Middleton et al stated that they were involved in a stroke audit. In answer to the claim that "no GP data by State and Territory" were provided, we did in fact indicate in our article how many GPs from each State and Territory participated. Intracluster correlations (ICCs)2 for each risk factor in our study are shown in the Box. ICCs have a greater effect on sample size than on CIs, because CI width is inversely proportional to the square root of the sample size. The large sample size of ASAP means that the study has acceptable precision, even after allowing for ICCs. Overall estimates for risk factors were provided for the population of people consulting GPs, which is the relevant population. We would not necessarily expect the same distribution of risk factors in people not attending GPs. Age- and sex-specific risk-factor prevalences, shown in Box 3 of our article,1 can be used to calculate age- and sex-standardised rates for any desired population. We are confident that the information obtained in our study is likely to be representative of most Australian general practice environments. Intracluster correlations (ICCs) for stroke risk factors in the ASAP stroke audit1* Risk factor All Men Women Current smoker 0.07 0.09 0.08 Hyper-cholesterolaemia 0.06 0.06 0.07 Hypertension 0.06 0.05 0.07 Diabetes 0.04 0.05 0.07 Past TIA/stroke 0.018 0.024 0.013 Atrial fibrillation 0.016 0.017 0.023 TIA = transient ischaemic attack. * Calculated using the analysis of variance (ANOVA) method.2

Jonathan W Sturm · Stephen M Davis · John G O'Sullivan · Miriam E Vedadhaghi · Geoffrey A Donnan

To the Editor: Reactions to insect bites are unpleasant and can be dangerous.1 Kumar2 commented that people who react to mosquito bites with local itching and inflammation appeared less likely to develop malaria than those with no reaction. In a later personal communication, he gave me unpublished data showing an inverse linear relationship between the severity of the reaction to mosquito bites and the incidence of clinical malaria. Ross River virus infection is endemic in all Australian states. A specific serological test is available to confirm suspicious clinical illnesses. Some people have serological signs of past infection without any history of clinical disease. With Kumar's findings in mind, I asked people with a past history of clinical Ross River virus infection, proven by serology, whether they reacted to mosquito bites. All seven asked said that they had had no reaction. Their main complaint was the noise made by predatory mosquitoes. I then asked patients who were in the same age range and general social class, who lived in the same area and were attending clinics with other diseases, whether they had had any clinical illness diagnosed as Ross River virus infection. Of the 18 asked, none had had the clinical disease or serological tests for the disease. All 18 had moderate to severe reactions and itching with mosquito bites. The Box shows these results Fisher's exact test gives the probability of this finding as 0.0000003. These observations have not explored all aspects of the problem, so this level of probability may be optimistic, but, even so, it makes pointless any further informal collection of data. These findings justify a formal epidemiological study, including antibody titres. It should include those who react to mosquito bites and those who do not, and those with and without a past history of the clinical illness. This informal study suggests that reactions to mosquito bites protect against Ross River virus infection, and parallels Kumar's findings in malaria. There may be behavioural and biological explanations for this finding. People who itch with mosquito bites may take greater precautions to avoid them. Conversely, people who do not itch may spend more time outdoors and be more likely to be bitten. Biologically, reactions to bites may be examples of a generalised protective effect of local reactions against insect-borne diseases. The inflammatory reaction with itching may be a factor in defence against infection3 by limiting or destroying injected parasites and viruses locally or through a more vigorous generalised response that prevents disease or limits infection to a subclinical level. Investigation of local inflammatory response might provide clues to effective prevention and treatment. Reactions to mosquito bites among people with and without evidence of Ross River virus (RRV) disease No reaction Moderate to severe reaction Past RRV disease 7 0 No past RRV disease 0 18

Alan E Dugdale

To the Editor: We write to express our concern at the publication of the recent supplement "Essential role of fats throughout the lifecycle", adorned by the sponsor's logo.1 It was an interesting counterpoint to an accompanying article in the main journal regarding the need for industry–academia collaborations to "strike a balance".2 While the issue of relationships between industry and doctors is complex, and few of us are truly independent, the publication of such a branded document is disquieting. Directed sponsorship, beyond mere advertising, undermines the credibility of such supplements and the Journal itself, regardless of the authors' expertise, objectivity and the importance of the topic. Unfortunately, we are left with the taste that this is a spread designed to butter us up.

Alex A Padiglione · Catherine E Marshall · Tony M Korman

In reply: "Oh what a feeling" to receive a congratulatory letter! But the euphoria was short lived, as, on closer inspection, congratulations turned to castigation. The offending event was the Journal's publication of an industry-supported supplement,1 and its practice of branding supplements with the logos of their sponsoring bodies. Although sponsorship by government agencies or non-profit health organisations rarely provokes comment, industry sponsorship is another matter. As industry support for research and other health-related activities will inevitably increase in the future, we at the Journal are pleased that Padiglione and colleagues have aired their anxiety. Irrespective of the source of sponsorship, the Journal's policy governing the publication of supplements follows the recommendations of the International Committee of Medical Journal Editors.2 These include that: the journal's editor must take full responsibility for policies, practices and content of supplements, must approve the appointment of the editors of supplements, and must retain the authority to reject articles; and the source of funding should be clearly stated and prominently located in supplements, preferably on each page. To these principles the Journal has added its own requirements.3 These include the need for peer review and that editors of and contributors to supplements declare competing interests and compensations. These were clearly identified on the title page of the offending publication.1 For our readers, the Journal is the bread and its supplements the butter. One can always refuse to taste the butter. But, for those who hanker after a little fat, we aim to ensure, through churning by external peer review and transparent sponsorship of the product, that "butter is better".

Martin B Van Der Weyden

To the Editor: Linezolid is the first of a new class of oxazolidinone antibacterials which was first registered in Australia in September 2001. It represents an important advance in the treatment of infections caused by some enterococci resistant to vancomycin and staphylococci resistant to methicillin.1 In clinical trials, the most commonly reported drug-related adverse events which led to discontinuation of linezolid therapy were headache, diarrhoea, nausea and vomiting.2 We describe a patient who developed peripheral and optic neuropathy while being treated with linezolid. A 76-year-old man was hospitalised in November 2000 for the third revision of a left total hip joint prosthesis. This was complicated by infection with methicillin-resistant Staphylococcus aureus (MRSA) isolated from hip joint washout. The organism was sensitive to vancomycin, teicoplanin, rifampicin and fusidic acid, and resistant to ciprofloxacin. Vancomycin therapy was commenced, but had to be replaced by rifampicin and fusidic acid when the patient developed fever (40°C), rigors, rash and eosinophilia. However, the patient developed severe, generalised pruritus. Therapy with rifampicin and fusidic acid was ceased and oral linezolid (600 mg twice daily) was given. Linezolid was initially well tolerated. However, about six months after starting treatment with the antibiotic, the patient presented to his general practitioner with numbness of his hands, feet and legs below the knee, intermittent sharp pain in both feet and blurred vision. He was hospitalised and linezolid therapy ceased. On admission, peripheral sensory loss in a glove-and-stocking distribution was noted. Nerve-conduction studies showed severe sensory-motor axonal neuropathy, more severe in the lower limbs than the upper limbs. Formal visual field testing showed patchy field damage, suggestive of drug-induced toxicity. The patient declined further ophthalmological review. Five months after he stopped taking linezolid, he reported subjective resolution of visual impairment, but the peripheral neuropathy persists. The patient's alcohol intake had been negligible. Ongoing medications include digoxin, irbesartan, frusemide, omeprazole, piroxicam and diazepam. We are not aware of any published articles describing peripheral or optic neuropathy associated with linezolid therapy. This information was not included in the original product information, but has been added to the revised version under the heading "Post-marketing surveillance".3 Up to June 2002 there had been only 13 reports of adverse reactions to linezolid to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). Four of these, including our report, describe peripheral neuropathy and involve adult males who had received 1.2 g of linezolid daily for six to nine months. No patient's neuropathy had resolved at the time of reporting. Moreover, linezolid was the sole suspected drug in all four reports. It is important to note that the maximum duration of treatment with linezolid in clinical trials has been 28 days. Reports of neuropathy received by the manufacturer have primarily involved patients treated for longer than 28 days.3 Our report highlights the importance of postmarketing surveillance and reporting of adverse drug reactions, especially when a drug is used outside original indications or duration.

Carmela E Corallo · Amalie E Paull

To the Editor: I read with interest the article on cervical screening by Dickinson.1 Cervical screening has been the most successful public health measure introduced for the prevention of cancer, and the Pap test has been highly effective in reducing cervical cancer mortality and morbidity. In New South Wales, between 1972 and 1999, the age-standardised incidence and mortality of cervical cancer fell by 49% and 66.6%, respectively.2 The overseas experience is similar, with the best screening programs reporting a 70% reduction in mortality rates, with slight annual mortality increases since 1986.3 That women continue to die from this potentially preventable disease emphasises the limitations of the current screening method and highlights the need for new directions. The conventional Pap test is "yesterday's tool for today's world", let alone tomorrow's! The Pap test is prone to errors at all levels, but, most importantly, at specimen collection and cytological interpretation. Consequently, relatively high numbers of false negative results are associated with the test. Further, the Pap test is only partially successful in predicting the biological behaviour of the cytological abnormality. As Dickinson states, minor abnormalities that come and go are unimportant, and can cause unnecessary alarm. These minor and transient abnormalities often lead to colposcopy, biopsy, surgical treatment and subsequent cytological and clinical or colposcopic follow-up, at a considerable cost to individual women, the screening program and taxpayers.4 Recent developments in cervical cytology and molecular biology have opened up new horizons.5 Liquid-based cytology, human papillomavirus (HPV) DNA testing and new molecular markers will help us to accurately select the patients who are likely to have biologically aggressive disease with a high probability of progression.4,5 With refinements, these new technologies will not only dramatically reduce the frequency of Pap test screening, but they may postpone the age for starting screening from 18 years to perhaps 25 or even 30 years. These new technologies come at a price. Liquid-based cytology costs about $30 and HPV DNA testing is about $90, and no Medicare rebates are currently available for these tests. The additional cost of these new technologies should be considered in the context of the cost of diagnosis, treatment and subsequent cytological and clinical follow-up of biologically insignificant disease. The money saved from improved patient selection for treatment and reduced frequency and late commencement of screening would allow more resources to be allocated to enrolling women (who are currently underscreened) and to funding these new technologies.

Ibrahim M Zardawi

To the Editor: Life expectancy in developed countries increased by an average of about 20 years during the 20th century. An editorial in the Journal by Rodger referred to mortality in populations having screening mammography.1 Data quoted indicated that there had been only slight changes in breast-cancer mortality in Australia up to 1996. Data for 1999 are available in the report of the Australian Bureau of Statistics Causes of death, published in December 2000.2 The standardised all-causes death rate per 100 000 for all persons in 1989 was 758.9 and in 1999 was 584.2, a reduction of 23.0%. For women, the standardised death rate attributable to breast cancer in 1989 was 27.2 and in 1999 was 22.1, a reduction of 18.75%. Recent decreases in breast cancer mortality of similar magnitude have also been observed in the United Kingdom and the United States.3 However, screening mammography could only be responsible for a small portion of these changes, because population screening has been in place for little more than a decade and the benefits of earlier detection and treatment would take more than five years to become evident. The causes of these dramatic reductions in death rates are not yet understood. Regarding the effect of population screening mammography on mortality rates, this is limited to breast-cancer-specific mortality and cannot be expected to translate into a reduction in overall mortality. In a recent overview of the situation in Sweden,4 breast-cancer-specific mortality in the screened group was 22% lower than in the non-screened group. However, the age-adjusted relative risk for total mortality was 1.00 (95% CI, 0.98–1.02). In other words, the mammographically screened population died less frequently from breast cancer, but nevertheless died at the same rate as the non-screened population (from other causes such as heart disease and other cancers). If we consider that, in the age group 40–79 years, breast cancer accounts for about 3% of total mortality, a reduction in breast cancer mortality of 25% would be 25% of 3%, or 0.75%. This change is so small that it would probably never be possible to show an effect of breast-cancer screening on overall population mortality. It is therefore realistic to regard the benefits of screening mammography as limited to early detection and treatment (possibly with improved quality of survival) and a reduction in breast-cancer-specific mortality.

In reply: I agree with Gough and welcome the more recent data showing up to an 18.75% reduction in breast cancer mortality in Australia in the 10 years from 1989. Obviously, this cannot be attributed solely to the now 10-year-old National Mammographic Screening Program, but it may result from a combination of the screening program, ad-hoc screening before the program, and the more rigorous use of adjuvant therapies based on the results of clinical trials. That breast screening is unlikely to have an impact on overall population mortality gives the lie to the conclusions of Olsen and Gøtzsche's overview,1 which are based only on overall mortality. Nevertheless, Gough and I agree that screening mammography is likely to deliver other benefits through detection of earlier-stage disease and a reduction in deaths from breast cancer.