Volume 177 Issue 7

Probably in the short term, but results of ongoing trials are needed to determine longer-term safety Oestrogens play an important role in the development of breast cancer. This is most evident in postmenopausal women: circulating levels of endogenous oestradiol are higher in those who develop breast cancer,1 while use of hormone replacement therapy (HRT) increases breast cancer risk.2 Recent results from the Women's Health Initiative randomised trial showed a 26% excess rate of breast cancer development in women who took combined continuous equine oestrogens and medroxyprogesterone acetate for a mean of 5.2 years compared with placebo.3 This finding is consistent with results of earlier epidemiological studies that suggest breast cancer incidence is increased more by combined preparations than by oestrogen alone.2 Further evidence that oestrogen is important in breast cancer development comes from a study of over 9300 postmenopausal women with early breast cancer.4 This found that anastrozole (an aromatase inhibitor that dramatically reduces oestrogen production) significantly reduced the rate of new contralateral breast cancers compared with tamoxifen (hazard ratio, 0.42; 95% CI, 0.22–0.79; P = 0.005).4 Despite the increased incidence of breast cancer in women who use HRT, most studies have shown either no effect on mortality or a decrease.5 The reason appears to be that breast cancers that develop in HRT users are smaller and clinically less advanced, with a lower rate of node positivity, better differentiation and more favourable histological type, than cancers that develop in women not using HRT.2 Menopausal symptoms are reported by two-thirds of postmenopausal women with breast cancer.6 Can HRT be safely used by these women, or does it have the same impact on breast cancer recurrence as it appears to have on breast cancer development? A number of publications have addressed this issue. One systematic review documented 11 studies involving 214 women who took HRT after a diagnosis of breast cancer, and found that the risk of breast cancer recurrence was lower in HRT users (relative risk [RR], 0.64 (95% CI, 0.36–1.15) than in control women who did not use HRT.5 Durna and colleagues report similar findings in this issue of the Journal (page 347).7 They found significantly lower rates of recurrence (RR, 0.62; 95% CI, 0.43–0.87) and death from breast cancer (RR, 0.40; 95% CI, 0.22–0.72) in women who used HRT compared with non-users.7 These are important data and are also consistent with those of a recently published United States case–control study of 174 women who chose to use HRT after breast cancer diagnosis and matched non-users.8 These three studies reported a consistent reduction in recurrence and death from breast cancer in breast-cancer survivors who used HRT to treat menopausal symptoms, but all had potential confounding factors.5,7,8 All studies to date have been observational and are thus subject to a variety of biases. In the Australian study, women who used HRT after treatment of breast cancer had smaller tumours and fewer involved nodes compared with non-users, and were more likely to have used HRT before diagnosis.7 Although the final model adjusted for a number of prognostic factors, these did not include tumour grade, concurrent use of tamoxifen or oestrogen-receptor status. Concurrent tamoxifen is a particular confounding factor, as it was prescribed for almost 60% of women who used HRT, and would have limited the effects of oestrogen on normal and malignant breast epithelium.9 Duration of HRT use after a diagnosis of breast cancer was short in all three studies — a median of only 1.75 years in the Australian study. Surprisingly, in both the Australian7 and American8 studies there appeared to be a lower rate of breast cancer recurrence in patients taking progestogen alone, vaginal oestrogen alone, or a combination of the two. It is difficult to believe that the small amounts of oestrogen absorbed from vaginal preparations could have a positive influence on breast cancer recurrence and survival. This suggests that other characteristics of women who use HRT, whether vaginal or oral, may influence outcome. Socioeconomic status is an independent predictor of breast cancer recurrence and survival: women with more education and higher socioeconomic class have a lower recurrence rate and better survival.10 Hot flushes are more commonly reported by educated women,6 and these women are more likely to take HRT. Thus, socioeconomic factors could conceivably be part of the reason for the better outcome of women with breast cancer who take HRT. What other possible reasons are there to explain why HRT use by women with breast cancer might improve survival? Most of the oestrogens used in HRT preparations are conjugated, a form that does not occur naturally in humans. They are termed "impeded oestrogens", as they interfere with the effect of more powerful, naturally occurring oestrogens, such as oestradiol, and their biological effect on breast cancer cells is unclear. In the pharmacological doses used, they are likely to have direct anti-oestrogenic effects and may also downregulate the oestrogen receptor. The progestogens used in combined HRT preparations may also have anti-oestrogenic effects and are weak aromatase inhibitors. This may be relevant in postmenopausal women, as much of the oestrogen present within their breast cancers is produced locally from androgens by aromatase.11 How should women with breast cancer who develop menopausal symptoms be treated? For vaginal dryness, water-based lubricating gels and vaginal moisturisers significantly improve symptoms. If these measures fail, then locally delivered oestrogens are effective.12 For systemic symptoms, such as hot flushes, evening primrose oil, soya and black cohosh are rarely effective, but low-dose megestrol acetate and the antidepressants venlafaxine and fluoxetine were shown to have benefits in randomised trials in breast-cancer survivors.12,13 More recently, isoflavones from red clover were shown to reduce hot flush symptoms in postmenopausal women,14 although there have been no studies in breast-cancer survivors. When these remedies fail, then HRT can be given in the knowledge that current data do not show any detriment in terms of recurrence or survival. Effective agents for osteoporosis in women with breast cancer include bisphosphonates, tamoxifen, raloxifene, diet and exercise.12 Ongoing randomised trials of HRT in breast-cancer survivors will determine whether longer-term HRT is safe. These trials will evaluate whether the increased incidence of breast cancer and reduced sensitivity of mammography in women using HRT2 are important issues in women with breast cancer. Even if these trials show HRT to be safe, the problem in future will be how to treat menopausal symptoms in women taking one of the new aromatase inhibitors, which are already replacing tamoxifen in postmenopausal women with hormone-responsive breast cancer.4 It makes no sense to give these women oestrogen. Ongoing studies are investigating the role of a variety of agents, including tibolone (a synthetic corticosteroid with oestrogenic, androgenic and progestational activity).

J Michael Dixon

Conference presentations are preliminary findings which should be interpreted with caution by the media, health professionals and the public When organisers began planning the XXIXth International Congress of Ophthalmology, held in Sydney earlier this year, an early consideration was how to promote media coverage of the conference, with the aim of raising public awareness of the specialty of ophthalmology and eye health more generally. A company which specialises in media relations for medical conferences was retained to work with the conference scientific program committee to develop a media strategy. As a result of the press releases issued, there were more than 520 news reports in print, broadcast and online media in Australia and overseas, including substantial stories in major media outlets. This is not an unusual scenario. Australian journalists are often approached to run stories arising out of conferences. In Europe and North America, where there is a larger market for such stories and a more established tradition of specialist medical and scientific reporting, media management of medical and scientific conferences is even bigger business. Such media management can have advantages for conference organisers, sponsors, participants, the media and the public: Conference organisers may wish to encourage media coverage as a way of promoting greater awareness of their profession or of particular health issues, and prefer to guide the media agenda so they are not left on the back foot, responding ad hoc to journalists' demands. Presenters may welcome media coverage to promote awareness of their work or professional interests. Corporate interests, conference funders and sponsors, and institutions such as universities, hospitals and research centres, often actively encourage such publicity. Indeed, both corporate and non-corporate interests have paid the expenses of Australian journalists to attend health and medical conferences, with the aim of promoting coverage. The media, driven by the community's thirst for health and medical news, finds conferences newsworthy on several grounds. Often they provide the first airing of research not yet formally published, and the timeliness of the presentation provides an additional "news hook". Also, conferences often provide a rare opportunity to make contact with and interview leading experts from around the world. Conference reports can contribute to public good, by alerting policy makers, researchers, health professionals and the general public to important new developments. However, there can be a downside. As recently noted, media coverage of new research often does not reflect an evidence-based assessment of its significance; for example, the media is less likely to report randomised trials, relative to observational studies.1 This illustrates the priorities which drive news gathering; one of the media's main criteria for story selection, particularly in health, is whether the story is likely to interest its audiences. Study methodology is far less likely to influence story selection. As well, most journalists and news managers have not been trained in understanding the relative merits of different types of scientific evidence. Other difficulties include the particular circumstances of conferences making it difficult for the media to scrutinise the validity of research findings or researchers' claims, and, as the results have usually not been published, difficulty in obtaining informed comments from other sources. The practical constraints of covering a conference and meeting deadlines may also encourage the media to rely on a single source. Journalists often have to rely on what presenters say about their findings without having access to the data or other information useful in assessing such comments. They may cover conferences without actually attending the presentation itself, and so not have the benefit of comments or criticism from an informed audience. Further, the conference presentation may vary from what journalists are told in an interview. The media may cover research findings in advance of their presentation — this adds to their newsworthiness in the media competition to be first. But it also amplifies all the problems mentioned above, as illustrated in a recent conference preview in The Bulletin.2 The article was based on several interviews and an abstract released in advance of the conference. By the time the study findings were actually presented, they had been revised because of further analysis. Even if conferences have a legitimate scientific objective, they may not follow a sound scientific review process. Just because a paper has been accepted for presentation does not mean it will have scientific merit, although it may still end up on the front pages of the newspapers. A recent report of media coverage of scientific meetings in the United States raised similar concerns, finding that many of the presentations covered by the media were not subsequently published in journals, raising questions about their scientific merit.3 The report concluded that press coverage of scientific meetings often did not make it clear that these were preliminary findings of uncertain validity. As a consequence, patients may experience undue hope or anxiety or may seek unproved, useless or even dangerous interventions. The authors urged conference organisers to be cautious in their promotions; researchers to emphasise the limitations of their work when being interviewed; and the media to emphasise the preliminary nature of conference presentations. Many in the media might counter that they are not in the business of health education or promotion. But if the media's role includes providing independent, critical and balanced news coverage, journalists and news managers should be careful to apply the same standards of scrutiny to conference presentations as to other sources of news. Finally, the media's audiences — whether the general public or health professionals — should approach news reports of conference proceedings, and indeed all sources of health and medical information, with a sensible caution.

Melissa Sweet MA

Benefits depend on the patient’s absolute cardiovascular and bleeding risks The benefit of aspirin for patients with previous symptomatic atherothrombosis of the heart, brain and limb in the secondary prevention of recurrent serious vascular events is well established. However, the role of aspirin in the primary prevention of cardiovascular disease among people who have no symptoms of vascular disease is controversial.1 A recent summary of the evidence has prompted recommendations from the third US Preventive Services Task Force2,3 and the American Heart Association.4 The evidence is based on a systematic review of five randomised controlled clinical trials of the effectiveness and safety of long-term aspirin use (75–500 mg a day or every other day) over 3–7 years in over 50 000 individuals with no previous symptomatic cardiovascular disease.5-9 Most participants were middle-aged men, although there were more than 10 000 women included in two trials and substantial numbers of patients aged 70–80 years in four of the five trials. Among patients randomly allocated to receive aspirin, the rate of subsequent serious vascular events (non-fatal stroke, non-fatal myocardial infarction, or death due to vascular causes) was reduced significantly, from 4.8% (no aspirin) to 4.2% (aspirin) over about 56 months' follow-up. This is an odds reduction of 13% (95% CI, 5%–19%) and an annual risk reduction of about 0.1% (ie, one serious vascular event avoided per 1000 patients treated with aspirin for one year) (see Box). Most of the benefits of aspirin were due to a significant 28% (95% CI, 13%–40%) reduction in the odds of a coronary event (myocardial infarction or sudden death). There was no reduction in the occurrence of all stroke. However, aspirin was associated with a non-significant 40% (95% CI, −10% to 100%) increase in the odds of haemorrhagic stroke, which is consistent with the excess risk of haemorrhagic stroke seen in secondary prevention trials using aspirin.1 In absolute terms, this represents an excess risk of one haemorrhagic stroke per 10 000 patients treated with aspirin per year.10 Aspirin was also associated with a 70% (95% CI, 40%–110%) increase in the odds of major extracranial (mainly gastrointestinal) haemorrhage, which is an excess of 0.7 (95% CI, 0.4–0.9) major extracranial haemorrhages per 1000 patients treated with aspirin per year (see Box).10 The Preventive Services Task Force concluded that there is now good evidence that aspirin lowers the incidence of coronary heart disease (CHD) in adults who are at increased risk, and that it also increases the incidence of gastrointestinal bleeding.2 It considered that there was fair evidence that aspirin increases the risk of haemorrhagic stroke.2 The evidence was most reliable for men aged 40–75 years and less reliable for women and older men. The optimum dose of aspirin is not known, but dosages of 75–150 mg/day seem to be as effective as higher doses and are associated with a lower risk of adverse gastrointestinal effects. The American Heart Association recommends low-dose aspirin prophylaxis in people with a 10-year CHD risk of over 10% (ie, > 1% per year),4 whereas the Preventive Services Task Force recommends aspirin for people with a five-year CHD risk of over 3% (ie, > 0.6% per year).2,3 The latter is justifiable, in our view: for every 1000 patients with a 3% risk of a coronary event over five years, long-term aspirin therapy prevented 4–12 coronary events and caused 0–2 haemorrhagic strokes and 2–4 major gastrointestinal bleeding events. This represents a benefit-to-harm ratio of about 2.0 (see Box). The benefit-to-harm ratio of aspirin was most favourable among people at high risk of a future cardiovascular event and low risk of haemorrhagic complications. The implication for clinicians is that decisions to prescribe aspirin therapy for the primary prevention of cardiovascular events should be based on an assessment of the patient's absolute risk of a vascular event without aspirin, the absolute risk of a gastrointestinal or intracranial haemorrhage with aspirin, and the patient's preference. In addition, decisions about aspirin therapy should be reviewed at least every five years, or when new vascular risk factors are detected. Risk stratification should incorporate specific information about multiple risk factors, rather than simply counting the number of risk factors.11,12 Risk factors for cardiovascular disease include increasing age, being male, cigarette smoking, increasing blood pressure, increasing blood total cholesterol level, decreasing high-density lipoprotein cholesterol level, raised fasting blood glucose level (ie, diabetes mellitus), and a positive family history of cardiovascular disease (in younger adults).4,13 Risk factors for haemorrhagic complications of aspirin include increasing age, any bleeding diathesis, uncontrolled hypertension, and concomitant use of other nonsteroidal anti-inflammatory agents or anticoagulants. Enteric-coated or buffered preparations of aspirin do not clearly reduce adverse gastrointestinal effects. People at increased cardiovascular risk who may wish to consider long-term aspirin therapy (75–150 mg/day) are men over 40 years of age, postmenopausal women, and younger people with risk factors for cardiovascular disease (eg, hypertension, diabetes).4,13 However, there is still insufficient information to reliably identify the minority of individuals who will benefit and the minority who will be harmed by regular treatment with aspirin. Further information will soon be available from several studies: the Women's Health Study (comparing aspirin 100 mg taken every alternate day with placebo among 40 000 healthy postmenopausal women); the Aspirin in Asymptomatic Atherosclerosis trial (comparing low-dose aspirin with placebo in 3300 middle-aged participants with asymptomatic peripheral atherosclerosis, identified by an ankle brachial pressure index of ≤ 0.9); and the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance) trial (comparing aspirin with a clopidogrel/aspirin combination for preventing serious vascular events among about 15 000 people at high risk of cardiovascular disease who are currently taking aspirin). In the meantime, the challenge for clinicians is to translate the evidence into practice by ascertaining the absolute risk of subsequent serious vascular events for all people who may be at risk, and to prescribe long-term aspirin 75–150 mg/day, with long-term follow-up, for those with an absolute risk of CHD exceeding 3% over the next five years. The challenge for academic clinicians is to devise more valid "risk calculators" that incorporate the risk of serious cardiovascular events and the risk of adverse events, such as intracranial and gastrointestinal haemorrhage. Summary (based on five randomised controlled trials) of the effectiveness of long-term aspirin use in primary prevention of coronary events3 Absolute risk (%) Number of events avoided or caused (95% CI)* Outcomes Control Aspirin Odds ratio (95% CI) AR 1% AR 3% AR 5% Benefits (events avoided) All coronary events (non-fatal or fatal MI, or sudden death) 2.4% 1.9% 0.72 (0.60–0.87) 3 (1–4) 8 (4–12) 14 (6–20) Fatal coronary events 0.7% 0.6% 0.87 (0.70–1.09) All-cause mortality 3.5% 3.4% 0.93 (0.84–1.02) 1 (0–2) 2 (0–5) 4 (0–8) Non-fatal stroke, non-fatal MI, or death due to vascular causes 4.8% 4.2% 0.87 (0.81–0.95) 1 (0–2) 4 (2–6) 6 (2–10) No change All stroke 1.3% 1.4% 1.02 (0.85–1.23) NC NC NC Harms (events caused) Haemorrhagic stroke† 0.17% 0.22% 1.4 (0.9–2.0) 1 (0–2) 1 (0–2) 1 (0–2) Major gastrointestinal bleeding event‡ 0.5% 0.8% 1.7 (1.4–2.1) 3 (2–4) 3 (2–4) 3 (2–4) Benefit-to-harm ratio 0.75 2.0 3.5 MI = myocardial infarction. NC = no change. * Events per 1000 patients treated for five years with aspirin, compared with no aspirin, according to the patient's baseline absolute risk (AR) of coronary heart disease over the next five years. † Data from secondary prevention trials suggest that increases in haemorrhagic stroke may be offset by reduction in ischaemic stroke in patients at very high risk for cardiovascular disease (ie, > 10% risk over five years). ‡ Rates may be two to three times higher in people aged over 70 years.

Graeme J Hankey MD FRCP FRACP · John W Eikelboom MSc FRACP FRCPA

Research papers should have a short section on how the results should be communicated to the public By all accounts, many of the half million Australian women who regularly take combined oestrogen and progestin hormone replacement therapy (HRT) were alarmed by the news on Wednesday, 10 July 2002, reporting that a United States study had shown HRT to increase the risk of breast cancer by 26%, as well as causing more vascular disease. Subsequently, numerous media reports, based on press releases from organisations such as the US National Institutes of Health (NIH)1 and the Cancer Council of New South Wales,2 continued to highlight the apparently large increases in risks caused by combined HRT and called for restrictions on the use of this treatment. General practitioners and cancer help-lines were inundated by enquiries from frightened women and reports of mass withdrawals from therapy soon followed. The source of this concern was the early termination of the NIH-funded Women's Health Initiative (WHI) trial comparing combined HRT and placebo among healthy postmenopausal women. The study was stopped after five years by an independent Safety and Data Monitoring Committee when a predetermined safety boundary for the risk of invasive breast cancer was crossed at an interim analysis. The report of the trial, published in JAMA,3 suggested that women allocated to combined HRT experienced increased risks of invasive breast cancer, coronary heart disease, stroke and venous thromboembolism, and decreased risks of colorectal cancer and hip fracture (Box 1). It was argued that, when all these outcomes were summed in a "global index", the adverse effects outweighed the benefits. However, treatment effects on only two of the outcomes — fractures and venous thromboembolism — met conventional criteria for statistical significance when appropriate (and prespecified) account was taken of the multiplicity of statistical tests performed. Even without adjustment for the dozens of statistical tests, the 95% confidence intervals for each of the other outcomes reportedly affected by combined HRT (including the global index) were consistent with a broad range of possible effects, including little or no effect. For example, any effect on the relative risk of invasive breast cancer appeared to lie somewhere in the range from no effect to an increase of about a half to two-thirds, whereas any effect on the absolute risk of the same outcome appeared to lie somewhere in the range from no excess cases to about 17 extra cases per 10 000 women per year. This very large degree of uncertainty about the true size (and arguably the existence) of most of the treatment effects reported is not reflected in any of the press releases we have seen, including that from JAMA,4 all of which report apparently precise estimates of the excess risks. However, the controversy that followed publicity about the results of the trial did not reflect concerns about the strength of the evidence, but rather dissatisfaction with the way in which the study outcomes were described. While the original report published in JAMA provided estimates of both relative-risk and absolute-risk differences, press releases from most sources focused on the relative increases in risk — in particular, the 26% increase in invasive breast cancer. That this increase in relative risk reflected a difference in incidence of eight cases per 10 000 women per year was much less emphasised. It was suggested by the economics editor of the Sydney Morning Herald that the reported 26% increase was likely to have been misinterpreted by many women as meaning that combined HRT conferred a one-in-four chance of developing invasive breast cancer.5 Others argued that the use of relative risks in press releases was a deliberate effort to dramatise results that would appear much less newsworthy if described in absolute terms. The same commentators suggested that press releases should focus instead on absolute treatment effects, as these are of most direct relevance to the advice provided by doctors and the decisions made by women. Are these criticisms justified? Certainly, there is little doubt that the way in which risk data are presented influences treatment preferences.6-9 In a recent randomised trial in which general practitioners were asked whether they would prescribe a preventive treatment that had negligible side effects, 91% of those given information about relative risks alone said they would do so, compared with 63% of those given information about absolute risks.6 Other studies suggest that the way in which risk information is presented to consumers can generate even greater divergence in preferences.7 Should we therefore abandon the use of relative risks entirely in interpreting the results of clinical trials? Almost certainly not — although a strong case can be made for not allowing relative risks to dominate press releases without appropriate reference to absolute risks. Arguably, each has a place in communications to doctors and patients, and neither should be relied upon exclusively, as both have strengths and weaknesses. For example, while relative risks are usually generalisable to a variety of different patient subgroups (since the proportional effects of treatments are often broadly similar in most major patient subgroups), absolute risks are not (since absolute effects are determined in large part by background disease risks, which can vary substantially). Conversely, relative-risk estimates do not provide sufficient information for assessing the ratio of benefit to harm, as this can only be calculated from estimates of absolute treatment effects. Given the obvious complexity of identifying and delivering the most appropriate message to consumers (whether doctors or patients), medical journals might well consider taking a more substantive role in overseeing the broader dissemination of information about the results of major randomised trials. At a recent seminar ("The HRT debate: how should the new evidence affect policy?") conducted by the Australian Health Policy Institute at the University of Sydney, it was suggested that research papers should have a short section on how the results should be communicated to the public (Sally Crossing, Chair, Breast Cancer Action Group NSW, personal communication). Journals could assume more responsibility in two ways. Firstly, by ensuring compliance with a checklist of essential statistical components to be included in press releases issued by journals (Box 2); and secondly, by publishing a section within the main journal article that summarises the key messages for consumers, with reference to the same checklist. Such a checklist should include requirements for information about absolute as well as relative treatment effects, and for information about the full range of possible effects consistent with the observed result. If journals were to adopt this policy, it would be less likely that consumers would be misled, unintentionally or otherwise, by information released through the press. One can only speculate as to whether providing such information after the termination of the WHI would have altered the subsequent 30% fall in sales of the most commonly prescribed HRT preparations in Australia.10 1: Main results of the Women's Health Initiative trial of oestrogen plus progestin in healthy postmenopausal women3 Outcome Hazard ratio* Adjusted 95% CI† Unadjusted 95% CI Cardiovascular disease 1.22 1.00–1.49 1.09–1.36 Coronary heart disease 1.29 0.85–1.97 1.02–1.63 Stroke 1.41 0.86–2.31 1.07–1.85 Venous thromboembolism 2.11 1.26–3.55 1.58–2.82 Cancer 1.03 0.86–1.22 0.90–1.17 Invasive breast 1.26 0.83–1.92 1.00–1.59 Endometrial 0.83 0.29–2.32 0.47–1.47 Colorectal 0.63 0.32–1.24 0.43–0.92 Fractures 0.76 0.63–0.92 0.69–0.85 Hip 0.66 0.33–1.33 0.45–0.98 Vertebral 0.66 0.32–1.34 0.44–0.98 Deaths from other causes 0.92 0.62–1.35 0.74–1.14 Total deaths 0.98 0.70–1.37 0.82–1.18 Global index‡ 1.15 0.95–1.39 1.03–1.28 * Hazard ratios from Cox regression analyses of outcome among 8506 women randomly allocated to oestrogen plus progestin and 8102 women allocated to placebo. † Adjusted using group sequential methods to correct for multiple analyses over time. ‡ First event for each participant from among the following: coronary heart disease, stroke, pulmonary embolism, breast cancer, endometrial cancer, colorectal cancer, hip fracture, and death from other causes. 2: Essential statistical components for medical journal press releases describing the results of randomised clinical trials A. Provide estimates of absolute treatment effect in addition to estimates of relative treatment effect Estimates of relative treatment effect should not be provided without accompanying information about absolute treatment effect (or, at least, absolute disease rates). If the rates observed in the trial are substantively different from absolute disease rates in major patient subgroups, the limited generalisability of the observed absolute treatment effects should be acknowledged. For example, among perimenopausal women beginning hormone replacement therapy (HRT), whose average age is 10–15 years younger than those recruited to the Women's Health Initiative (WHI), any absolute increase in invasive breast cancer incidence is likely to be less than that observed in WHI, as breast cancer rates are strongly age related. B. Describe the full range of possible effects consistent with the observed result Avoid inappropriate focus on point estimates of either relative or absolute effect when confidence intervals indicate a broad range of potential effects. For example, the WHI result for invasive breast cancer risk was reported in press releases as a 26% increase in relative risk (and, occasionally, as an absolute excess of 8 cases per 10 000 women per year). However, the observed result is consistent with no increase in risk, as well as with an increase in relative risk of half to two-thirds and an increase in absolute risk of up to about 17 cases per 10 000 women per year (based on unadjusted 95% confidence intervals).

Anushka Patel MB BS, MS, FRACP · Robyn Norton PhD, MPH · Stephen MacMahon PhD, FACC, FAHA

Objective: To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is associated with increased risk of recurrence and mortality.Design: Retrospective observational study.Participants and setting: Postmenopausal women diagnosed with breast cancer and treated by five Sydney doctors between 1964 and 1999.Outcome measures: Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from primary tumour were compared between women who used HRT for menopausal symptoms after diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour characteristics.Results: 1122 women were followed up for 0–36 years (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43–0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19–0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22–0.72). Continuous combined HRT was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12–0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10–0.73).Conclusion: HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.

Eva M Durna MBioeth · Leo R Leader MD, FRANZCOG · Peter Sjoblom PhD · John A Eden MD, FRANZCOG · Barry G Wren MD, FRANZCOG · Gillian Z Heller PhD

Objective: To describe the natural history of rheumatic manifestations of Ross River virus (RRV) disease.Design: Prospective longitudinal clinical review.Setting: North Queensland local government areas of Cairns, Douglas, Mareeba and Atherton during January to May 1998.Participants: General practice patients diagnosed with RRV disease on the basis of symptoms and a positive RRV IgM result.Main outcome measures: Rheumatic symptoms and signs assessed as soon as possible after disease onset and on two subsequent occasions (up to 6.5 months after onset).Results: 57 patients were recruited, 47 of whom were reviewed three times (at means of 1.1, 2.4 and 3.6 months after disease onset). Results are reported for these 47: 46 (98%) complained of joint pain at first review, with the ankles, wrists, fingers, knees and metacarpophalangeal joints (II–IV) most commonly involved. Prevalence of joint pain decreased progressively on second and third reviews, both overall (92% and 68% of patients, respectively), and in the five joints most commonly affected. The prevalence of other common rheumatic symptoms and signs, and use of non-steroidal anti-inflammatory drugs, also progressively declined over the three reviews.Conclusions: Earlier studies may have overestimated the prevalence and duration of symptoms in RRV disease. Progressive resolution over 3–6 months appears usual.

David Harley PhD, FAFPHM · David Bossingham FRCP, FRACP · David M Purdie MMedSc, PhD · Nirmala Pandeya BSc, MMedSc · Adrian C Sleigh MD, MPH, FRCP

Objective: To describe the natural history, treatment and cost of Ross River virus-induced epidemic polyarthritis (RRV disease).Design: Questionnaire-based longitudinal prospective study.Participants and setting: Patients in the greater Brisbane area, Queensland, diagnosed with RRV disease by their general practitioners based on clinical symptoms and paired serological tests between November 1997 and April 1999.Main outcome measures: Scores on two validated quality-of-life questionnaires (Clinical Health Assessment Questionnaire and Medical Outcomes Study Short Form 36) were obtained soon after diagnosis and one, two, three, six and 12 months thereafter. Scores were compared between patients diagnosed with RRV disease alone and those with RRV disease plus other conditions.Results: 67 patients were enrolled. Most patients with RRV disease alone had severe acute symptoms, but followed a consistent path to recovery within three to six months. Other conditions, often chronic rheumatic diseases or depression, were identified in half the cohort; their quality-of-life scores suggested stable chronic illness between six and 12 months after diagnosis. Non-steroidal anti-inflammatory drugs (NSAIDs) were taken by 58% of patients (average use, 7.6 weeks; range, 2–22 weeks). Time off work averaged 1.9 days, and direct cost to the community was estimated as $A1018 per patient.Conclusions: Symptom duration and frequency of long-term symptoms may have been overestimated by previous studies of RRV disease. Disease persisting six to 12 months after RRV diagnosis was largely attributable to other conditions, highlighting the need to seek other diagnoses in RRV patients with persistent symptoms.

Andrea D Mylonas BA, RN · Allison M Brown RN, Grad Cert CDM · Tracy L Carthew RN, BN · David M Purdie MMedSc, PhD · Nirmala Pandeya GradDipAppSc, MMedSc · Louisa G Collins BEc, MPH · Andreas Suhrbier MA, PhD · Barry McGrath MB BS, PhD · Elizabeth J Reymond FRACGP, PhD · Philip C Vecchio FRACP, MBA · Ian D Gardner PhD, FACTM · Ferdinandus J de Looze MB BS, MSc

The Irukandji syndrome was named in 1952.1 It is the set of severe systemic symptoms that occur some 30 minutes after some jellyfish stings.2,3 The only species so far identified as causing the syndrome is Carukia barnesi, a small carybdeid box jellyfish occurring in the Cairns area (latitude, 16o44'S; longitude, 145o40'E), north Queensland.3 The bell of this tiny jellyfish is just 12 mm in diameter in mature specimens. The original description of the Irukandji syndrome is (paraphrased): the severe systemic symptoms developing 30 minutes or so after a mild skin sting from Carukia barnesi. Severe low back pain; excruciating muscle cramps in all four limbs, the abdomen and chest; sweating, anxiety, restlessness, nausea, vomiting, headache and palpitations occur.2,3 Since this original description, based on stings occurring around Cairns in north Queensland, life-threatening hypertension,3 pulmonary oedema and toxic global heart dilatation4 have been added as further complications of the syndrome. These symptoms were described after Irukandji syndrome resulted from stings occurring in the Whitsunday Islands, and later in the tropical Great Barrier Reef region.5 Recent research now suggests this syndrome is caused by at least five or six small carybdeids similar to C. barnesi and two larger carybdeid jellyfish species (bell diameter about 60–70 mm at maturity; L-A Gershwin, PhD student, University of California, Berkeley, 1999; and J Seymour, Senior Lecturer, James Cook University 2000–2002; personal communications), with the difference in severity of symptoms probably varying with the species. We describe the first recorded death from Irukandji syndrome in an overseas tourist on Hamilton Island in the Whitsunday Islands, Queensland (20o20'S, 148o56'E), in January 2002. This case was followed by another death of a 44-year-old tourist from the US in April 2002 from Irukandji syndrome on the outer Great Barrier Reef, off Port Douglas, about 1300 kilometres north of the first fatality.6 Both deaths occurred from intracerebral haemorrhage after severe hypertension caused by envenomation by a jellyfish. Clinical recordOn 30 January 2002, at about 1115 hours, a 58-year-old tourist from the UK was stung on the face and chest soon after entering shallow water at a beach on Hamilton Island. He did not see the creature, but said to his wife "something has got me", and they left the water. Over about 20 minutes he became distressed, with generalised muscular cramping pains, sweating, anxiety and nausea. He presented to the resort doctor, who noted he had hypertension (260/160 mmHg) and tachycardia (pulse, 142 beats per minute) and he was given 100 mg pethidine, 15 mg morphine, 10 mg metoclopramide, 25 mg promethazine and 5 mg diazepam, all intramuscularly, at 1150 hours. At 1200 hours his condition suddenly deteriorated and he became unresponsive, with stertorous breathing. A provisional diagnosis of cerebrovascular accident (CVA) was made. His past medical history included an aortic valve replacement in 1995 for aortic stenosis (he was taking 8 mg warfarin daily, and had had an international normalised ratio [INR] of 5.0 a week earlier). Intravenous access was obtained, an airway inserted with oxygen supplementation, electrocardiographic monitoring begun, and urgent transfer to a mainland hospital requested. A doctor and nurse flight team arrived at 1400 hours to find the patient unconscious with fixed dilated pupils and a blood pressure of 180/64 mmHg. The patient was sweating, salivating profusely, had a mild epistaxis, stertorous breathing and erythematous flushing of the face, neck and anterior chest. He was given 2.5 mg midazolam and 100 mg suxamethonium intravenously, and intubated; sedation was maintained with midazolam, morphine and vecuronium, and he was given 1 mg aliquots of phentolamine in an attempt to control his blood pressure, although this remained between 210/134 mmHg and 170/110 mmHg during the flight. He arrived at Mackay Base Hospital at 1620 hours. No attempt was made to sample nematocysts, as no sting site was clearly delineated, although skin flushing and intermittent diaphoresis (of the face and upper body; noted in helicopter, but not specified in notes) were noted and remained throughout the night. A chest radiograph showed cardiomegaly and unfolding of the aorta. Initial electrocardiography showed atrial fibrillation and right bundle branch block. Computed tomography scan, showing extensive intracerebral haemorrhage Computed tomography of the brain showed an 8 × 5 × 7 cm haemorrhage centred on the basal ganglia, 1 cm midline shift and right lateral ventricle effacement with subarachnoid extension filling the third and fourth ventricles, a small haemorrhage in the cerebral peduncles and the left caudate nucleus, with blood surrounding the brainstem at the foramen magnum (Box). The haemorrhage was not considered surgically salvageable by the neurosurgeon. On admission, his INR was 4.9 (recommended range, 2.0–3.5), and he was given 5 mg vitamin K and four units of fresh frozen plasma. Glyceryltrinitrate infusion was started at 1 μg per minute and increased to 20 μg per minute to maintain diastolic BP at < 90 mmHg. His troponin-T level was 0.27 μg/L (normal range, < 0.005 μg/L) and white blood cell count was 17.6 × 109/L (normal range, 4.5–10.5 × 109/L). Results of liver function tests were normal, although the aspartate aminotransferase level increased to 51 U/L (normal range, < 40 U/L) by 0630 hours the next morning. Bilateral lung crepitations were noted at 0250 hours. A chest x-ray showed peribronchial cuffing consistent with early pulmonary oedema: 40 mg frusemide was given intravenously. The patient's pupils remained fixed and dilated, and brain death was confirmed at 1710 hours on 31 January. A postmortem examination was not performed. DiscussionStings causing the delayed effects of the Irukandji syndrome are well known in the Whitsunday area, with almost every patient developing hypertension and a rise in cardiac troponin levels,7 as seen in our patient. Some develop delayed toxic cardiac dilatation and heart failure; a few develop painful neurasthenic burning pain in both lower limbs or in the jaw, priapism or acute angioneurotic oedema within minutes of the initial sting, often accompanied by an audible wheeze.7 Stings from the outer Great Barrier Reef in the Cairns region have also caused severe hypertension and heart failure.5 The second death from intracranial haemorrhage after jellyfish envenomation occurred in this northern reef area and was attributed to hypertension of an Irukandji syndrome.6 Hypertension can be life-threatening, with the highest readings being some 280/180 mmHg.7 Our patient's high INR probably placed him at much higher risk of a cerebrovascular accident. Similar deaths may have occurred in the past, with the relationship to Irukandji syndrome not being recognised. There is currently no first aid treatment for carybdeid jellyfish stings, although immediate vinegar dousing is advised to prevent further envenomation from inactivated stinging cells present on the skin.7,8 Blood pressure must be monitored after envenomation and hypertension treated with 5 mg phentolamine given intravenously (although in this case the aliquots were smaller because high ambient temperature and humidity with profuse sweating caused clinical dehydration). Most cases of envenomation by jellyfish causing Irukandji syndrome occur some distance from medical care, with helicopter or medical response often too late to treat the early pain and hypertension. As intravenous nitrates are effective in reducing hypertension, sublingual nitroglycerine spray may help control blood pressure until skilled medical aid is available. Research on venom from Carukia barnesi caught in the Cairns region shows it acts as a presynaptic neuronal sodium channel agonist, strongly stimulating noradrenalin release, and causing many clinical features of the Irukandji syndrome.9 Venom studies on carybdeid jellyfish are urgently needed to develop preventive strategies and effective treatments for Irukandji syndrome, including an antivenom.

Peter J Fenner MD, FRCGP · John C Hadok MB BS, DA(UK), Dip IMC, FIMC, RCS(Ed), FACRRM

In contrast to curative therapies, preventive therapies are administered to largely healthy individuals over long periods. The risk–benefit and cost–benefit ratios are more likely to be unfavourable, making treatment decisions difficult. Drug trials provide insufficient information for treatment decisions, as they are conducted on highly selected populations over short durations, estimate only relative benefits of treatment and offer little information on risks and costs. Epidemiological modelling is a method of combining evidence from observational epidemiology and clinical trials to assist in clinical and health policy decision-making. It can estimate absolute benefits, risks and costs of long-term preventive strategies, and thus allow their precise targeting to individuals for whom they are safest and most cost-effective. Epidemiological modelling also allows explicit information about risks and benefits of therapy to be presented to patients, facilitating informed decision-making.

Danny Liew BMedSc, MB BS · John J McNeil FRACP, PhD · Anna Peeters BSc, PhD · Stephen S Lim BA, BSc · Theo Vos MD, MSc

The United States will invest nearly US$70 billion (US$260 per capita) on medical research this year, more than half of which will be sponsored by the biopharmaceutical industry. This investment has been shown to provide major gains in basic, disease-oriented and patient-oriented research. It also provides a huge economic return on investment — whether measured in terms of jobs created, health costs saved, or the dollar value of lives saved. Australia, whose investment in medical research is less than 10% that of the United States, should increase its national commitment.

Leon E Rosenberg MD

At the end of May this year the Rheumatology Associations of Australia and New Zealand hosted a combined scientific conference in Christchurch, New Zealand. Notable among the presentations was a retrospective observational study on the association between gastrointestinal (GIT) bleeding and the use of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or cyclo-oxygenase II (COX-II) inhibitors (Box 1). The essential finding of the study was that among 20 patients with bleeding related to peptic ulcer or oesophagitis, six were taking low-dose aspirin, four were taking COX-II inhibitors and one an NSAID. The researchers concluded "that aspirin is still more commonly associated with GIT bleeding than conventional NSAIDs and COX-II inhibitors". One week later, the headline "Doctors warn: just one tablet of aspirin a day may be enough to do you serious harm" appeared on page one of the respected morning broadsheet the Sydney Morning Herald. The accompanying story, reprinted in Box 2, related that a "world first study" from the Prince of Wales Hospital in Sydney "found that: where any drug was implicated in [GIT] haemorrhage, low-dose aspirin was consistently the likeliest culprit — ahead of anti-inflammatory drugs which are more often blamed for the condition. All 120 patients eventually recovered but many had to have transfusion, adrenaline shots or surgery." The chairman of rheumatology at the Prince of Wales Hospital was quoted as saying that "It is of some considerable concern that aspirin, even at 100 mg a day, is likely to be associated with gastrointestinal hemorrhage", adding, "When patients are admitted vomiting and passing blood, it's pretty dramatic". Such a blood, guts and fear story proved irresistible to the media. Before the day was out television news and radio commentators carried the story with such graphic gusto as "new research shows that even small doses of aspirin can cause potentially fatal stomach bleeding", or "a daily dose of aspirin to thin the blood to avoid heart disease or stroke may be deadly, causing ulcer bleeding". On the day, the story was carried by at least 20 media outlets, including most of the prime-time television evening news broadcasts in eastern Australia (information gathered by Media Monitors Australia). The process of transferring information from the researchers to the newspaper had transformed a conference poster of a retrospective observational study of only 20 patients into sensational medical news! This breaking of "a world first study" undoubtedly caused disquiet and despair in the community, as people with heart or cerebrovascular disease were faced with the decision as to whether they should continue taking aspirin to prevent a heart attack or stroke, or stop taking it to prevent a "fatal" stomach bleed. This is an impossible choice in the absence of vital information, such as the absolute risk of GIT bleeding and the benefit-to-harm ratio for low-dose aspirin. Their doctors were also impotent, as they were not privy to information on which the news story was based. Because of the implications of such a sensational story, the Journal sought to put the report into context, approaching both a cardiologist and the story's creators for comment (see the letters following this article). In response to this request, the medical researchers raised the philosophical question of when a scientific fact becomes established and accepted as fact, and whether this process requires the blessing of peer review. The journalists stressed their responsibility to report medical matters and pointed out that journalistic judgement takes precedence over scientific or evidential rigour. It should be no surprise that the research on which this medical news was based has yet to appear in the scientific literature. Does this matter? The timing of wide dissemination of medical research outcomes to other researchers, clinicians and the public remains a contentious issue.1-4 Journalists want to be the first to break important medical news, and their editors know that there is an insatiable public appetite for health matters, more so if dressed up as "miraculous cures" or "dire threats".5 Researchers also want to be first in reporting new findings, as this is critical for their research funding, professional advancement and peer approval. Most do this through respected peer-reviewed journals. Despite these similar aspirations, there exists an inherent tension between the two cultures: "Media constraints of time, brevity and simplicity preclude careful documentation, nuance positions and precautionary qualifications that scientists feel are necessary to present their work."2 And at the centre of this tension is what the participants perceive science to be. Frank Davidoff, the emeritus editor of the Annals of Internal Medicine, argues that science does not exist until it is published.6 All that takes place before publication is part of the doing of science: the critique of ideas, methods, data and hypotheses, either informally through conversations in cafes and corridors, or more formally from the podiums of clinical or scientific meetings. The science becomes established when it has stood up to the scrutiny of peer review and the quality filters of the editorial process and is "in print ".6 Being in print in the press is not science, it is story telling. Furthermore, press coverage before publication may well do the community a disservice, as the imprimatur of the press conveys a sense that the information is valued, accurate and widely accepted. But the softness of prepublication information is highlighted by the fact that almost half of the abstracts of scientific or clinical meetings are not published,7 and a quarter of meeting abstracts that receive prominent press coverage share the same fate.8 One feature of medical reporting is sensationalism.5,9-11 This phenomenon has been attributed to "miscommunication" arising from the different cultures and styles of science and journalism.10 However, at times both parties may benefit from sensational stories.11 The reporter has a front-page story, and the researchers (and their institutions) bask in the publicity. But, more importantly, sensationalism may occur because no one is responsible or accountable "for the results of transactions between reporters and researchers in the way that an editor is responsible for the peer review process and content of a scientific journal . . . In the wake of a sensationalised medical story, the involved parties can always point the finger at each other".11 This lack of accountability has prompted a call for a watchdog to spotlight both good and bad medical stories.11 Robotham and Whitehead stress that "a basic tenet of journalistic ethics is that journalists should be independent" (see the letters following this article). But with independence comes responsibility and accountability, and this applies on both sides of the fence: both to reporters and researchers and their respective institutions. In the absence of such accountability the public will continue to be bombarded by the touting of "miracle cures" — which, on closer inspection, are years away or apply only to rats; or the proclaiming of "dire threats" to health, which, on closer scrutiny, are tentative at best and are usually followed by a dissenting story and the inevitable backflip. Subjecting the public to a roller coaster ride of excitement and disappointment or anxiety and anger will eventually engender cynicism for medical research and its reporting, and this would be a shame. After all, the aim of both parties is to publish and report medical science for the good of all. 1: The impact of cyclo-oxygenase II (COX-II) inhibitors on gastrointestinal (GIT) bleeding Background: Our previous study demonstrated that aspirin is a more commonly associated risk factor for GIT bleeding than both conventional NSAIDs and COX-II inhibitors. This study reports the impact of COX-II inhibitors on GIT bleeding in a third time period (2001) following the listing of a second COX-II inhibitor (rofecoxib). Method: Medical records of patients admitted to Prince of Wales Hospital, Sydney, with GIT bleeding or those requiring a gastroscopy during the period of 1 March to 31 August 2001 were reviewed. Results: 31 out of 321 patients have met the criteria. Of these 20 had bleeding related to peptic ulcer disease or reflux oesophagitis. Of this group, four were on a COX-II inhibitor, six were taking low dose aspirin (100–150 mg/d) and one was on a conventional NSAID. One patient was on clopidogrel only and another on warfarin only. Two patients were on prednisolone. Only two patients had a previous history of peptic ulcer disease. Overall in both studies of the three time periods, 35% were on aspirin, 20% on NSAID's and 11% were on COX-II inhibitors. A very small percentage were on warfarin, clopidogrel or prednisolone, and the remainder were not on any medications known to be associated with increased risk of GIT bleeding. Conclusion: Our most recent data confirms our previous study that aspirin is still more commonly associated with GIT bleeding than conventional NSAID's and COX-II inhibitors. J Bertouch, L Lee, H P McNeill, T Bolin Prince of Wales Hospital, Australia 2: Doctors warn: just one tablet of aspirin a day may be enough to do you serious harm Even very low doses of aspirin designed to prevent stroke and heart attack can cause life-threatening stomach bleeding, says a Sydney study that challenges the widespread use of the blood-thinning therapy. The world-first study looked at all patients admitted to Prince of Wales Hospital with gastrointestinal bleeding during three six-month periods between 1999 and 2001. It found that where any drug was implicated, low-dose aspirin was consistently the likeliest culprit — ahead of anti-inflammatory drugs, which are more often blamed for the condition. All 120 patients eventually recovered, but many had to have transfusions, adrenaline shots or surgery to stem the bleeding. The hospital's chairman of rheumatology, Jim Bertouch, said the results indicated the preventive aspirin doses most commonly used in Australia — a single daily tablet of 100–150 milligrams — may be too high. He suggested that doses of 75 mg, already used in Britain, might be more appropriate. Low-dose aspirin was implicated in up to a third of the gut hemorrhages diagnosed during the study, Dr Bertouch said. By contrast, arthritis medications, previously maligned as likely to cause stomach bleeding, caused fewer bleeds, about a quarter of the total. But the new COX-2 inhibitor arthritis drugs, which include the popular Celebrex — heavily promoted as safer for the stomach than older anti-inflammatories — were still involved in one in eight hemorrhages. The rest of the bleeds were either not linked with any drugs, or with a range of other drugs. "It is of some considerable concern that aspirin, even at 100 mg a day, is likely to be associated with gastrointestinal hemorrhage", said Dr Bertouch, who presented the research at a rheumatology conference in New Zealand last month. "When patients are admitted vomiting and passing blood, it's pretty dramatic". Terry Bolin, chairman of the Prince of Wales Hospital's Gastrointestinal and Liver Unit and a co-author of the study, said "We've known for years that aspirin was a risk but we were unaware that the really low dose aspirin had the same risk." Doctors should check whether patients were carriers of H. pylori bacteria that precede stomach ulcers, because this further increased bleeding risk from aspirin and other drugs, Associate Professor Bolin said. Associate Professor Con Aroney, a spokesman for the National Heart Foundation, said the benefits of aspirin outweighed the risks for people with a history of coronary heart disease or stroke. But daily aspirin was not recommended to prevent heart disease in healthy people. Julie Robotham Medical Writer, Sydney Morning Herald (June 7, 2002: 1)

Martin B Van Der Weyden MD, FRACP, FRCPA

To the Editor: The front-page article in the Sydney Morning Herald on 7 June this year1 highlights the problem of premature media coverage of a scientific presentation,2 potentially causing distress and confusion. Without being subjected to full peer-review and unavailable for analysis in its full published form, such data should not be presented to the public as scientific fact, and should not be sensationalised so as to encourage patients and doctors to change management. A small single-centre observational study is regarded as Level 4 evidence and cannot be used to recommend a change in management. At most, such data might be considered hypothesis-generating and used as the basis for a properly conducted clinical trial. In a meta-analysis of 70 000 "high risk" patients, antiplatelet therapy, mainly with aspirin, reduced rates of stroke, myocardial infarction and vascular death by 25%.3 Aspirin also reduced by almost half the rate of graft occlusion after coronary bypass surgery.4 The press article has confused such patients and may lead to their discontinuing life-saving therapy. It cites Bertouch as stating that 75 mg of aspirin "might be more appropriate". There are no data, either from the Prince of Wales study or any other, to support the contention that 75 mg of aspirin causes less bleeding than 100 mg or 150 mg. The press release describes the research as a "world-first study", and Dr Bolin is cited as stating that "we were unaware that really low-dose aspirin had the same risk". However, as early as 1991, the Swedish Aspirin Low-Dose Trial showed that even 75 mg of aspirin produced more bleeding than placebo (P = 0.04).5 As a result of the Sydney Morning Herald article, patients are asking their doctors to make a judgement on ceasing their aspirin therapy, which might prove fatal, or reducing the dose from 100 or 150 mg to 75 mg, which is not supported by evidence and is not even a dose available in Australia. At a time when it is difficult enough to convince patients to take medication which is of proven benefit, both the press and the research community have a responsibility to the public to avoid recommendations which are not evidence-based and which detract from our efforts to reduce the mortality from Australia's biggest killer — cardiovascular disease.

Constantine N Aroney MD, FRACP

In reply: Aroney's letter raises a number of important issues. The first of these is the question of whether a scientific fact requires the blessing of peer review to become established as such. The corollary of this is whether or not all peer-reviewed facts are necessarily true. The answer to both questions is probably no. The second issue is how to control a media report, irrespective of whether it is based on a peer-reviewed study. The issue which concerns Aroney is an abstract presentation of the association of gastrointestinal bleeding with aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase II (COX-II) inhibitors, the conclusion of which was that, while the last two might be important in their own right, concurrent use of aspirin, even in a small dose, was more closely associated with bleeding risk, particularly if there was a past history of peptic ulceration.1 A "meta-analysis" of the media reports, which included both television and radio in addition to the quoted report in the Sydney Morning Herald,2 would have made it clear that the theme of the interviews reaffirmed the relative safety of aspirin in the vast majority of individuals, and highlighted the risk of aspirin use concurrently with NSAIDs and COX-II inhibitors, particularly when there is a history of past ulceration. The fact that the SMH report focused on one aspect of the study was counterbalanced by the others. We do not know how journalistic reporting is controlled. A primary question is whether or not aspirin is an effective agent for the prevention of cardiovascular disease beyond the management of acute myocardial infarction. More recent literature than that quoted by Aroney is now questioning the overall cardioprotective value of aspirin.3 This showed that aspirin given as prophylaxis against cardiovascular disease increased the risk of sudden death in every secondary prevention study and left the overall rate of myocardial infarction unchanged.4 Aspirin consistently failed to reduce overall mortality in every study of long-term prophylaxis after myocardial infarction, and in all but one after stroke.3 Furthermore, Cleland and colleagues have argued that a series of meta-analyses, which most people have accepted as proof of the efficacy of aspirin, are of doubtful validity.4 They questioned whether it is appropriate for the medical community to invest so much time and effort in prescribing aspirin and dealing with the adverse consequences of its long-term ingestion to the neglect of other, better proven and apparently more effective therapies such as angiotensin-converting enzyme inhibitors, β-blockers, and statins. At the very least, it can be said that there is controversy in the cardiovascular literature about the benefits of aspirin. Just as important is the issue of the safety of long-term aspirin use for cardioprotection. A recent multidisciplinary expert statement on NSAIDs concluded that, on current evidence, prophylactic use of aspirin should be reserved for patients with established vascular disease, because in other patients bleeding risks may outweigh cardiovascular benefit.5 A Danish study showed that 100–150 mg of aspirin daily increased the risk of haematemesis by a factor of 2.6, with no difference in the risk between enteric and non-coated product; when combined with an NSAID the risk was increased by a factor of 5.6.6 The authors concluded that the bleeding risk may offset some of the benefits of aspirin. It is no longer appropriate to simply "bury" the adverse gastrointestinal effects of low-dose aspirin in the NSAID side-effect "basket".7 It is apparent to us that dogma should not be so enshrined that it prevents the discussion of issues that might helpfully modify that dogma.

Terry D Bolin · James V Bertouch MD

In reply: The letter from Aroney displays some basic misunderstandings of the role of the media in reporting medical issues. Aroney states that "the press [has] a responsibility . . . to avoid recommendations which are not evidence-based and which detract from our efforts to reduce mortality from . . . cardiovascular disease." A press article does not itself make recommendations when it reports the recommendations of others — an essential distinction. In addition, the press has no responsibility to follow the agenda of the medical profession and its slavish insistence on the dogma of evidence-based medicine. The press owes doctors no more favours than it owes any other sector of the community. The role of the press is to raise and debate issues of public interest in a manner that is balanced and responsible. The news report about aspirin did all of this.1 We agree that publication in a peer-reviewed journal may add scientific credibility to research findings and that this may sometimes make them more newsworthy. But our responsibility is to report medical matters of interest to the community, which means we are not limited to peer-reviewed findings. Any substantial fact, observation or opinion relating to medical practice is fair game for a newspaper's attention. After the findings of Bertouch and colleagues were presented at a conference,2 they entered the public domain, as did their later comments made to us directly. It was entirely proper to report them. The fact that the gastrointestinal bleeding study was conducted by two heads of department at a major Sydney teaching hospital was instrumental to our decision to position and headline the report prominently. These individuals are respected experts in their fields, and they expressed to us serious concern about the degree to which aspirin was implicated in gut haemorrhage. It was that concern which led us to focus on the aspirin findings within the broader study. The news process is always selective and there is no obligation to give equal emphasis to all findings. The magnitude of follow-up by other media confirms the inherent public interest in the topic. It has previously been suggested that medical journalists are behaving irresponsibly when they step outside the strictures of peer review.3,4 Yet it is a basic tenet of journalistic ethics that journalists should be independent.5 Why, then, would we subscribe to the doctrine of evidence-based medicine, with all its flaws? We, and the community, have every right to be sceptical of the tyranny of peer review when the pharmaceutical industry manifestly uses financial muscle to influence what is studied and what is published.6 Even the Medical Journal of Australia accepts anecdotal findings when it can persuade itself the public interest is involved, recently publishing an eyewitness account of conditions inside an immigration detention centre7 and defending this on the basis that "our readership is sophisticated enough to interpret the content of such articles."8 Sydney Morning Herald readers are also sophisticated. On what basis should they have been denied this pertinent information about a widely used medicine — that doctor still knows best?

Julie Robotham BA(Oxon) · Robert Whitehead

This issue of the Journal launches a series of articles on rehabilitation medicine aimed at general practitioners and other doctors who have not specialised in this field. We, and our co-authors, hope to demonstrate that rehabilitation is a dynamic and critical component of the therapeutic continuum, and one that is essential if patients are to regain good quality of life after serious illness or injury. Rehabilitation has been defined by the World Health Organization (WHO) as "a process aimed at enabling persons with disabilities to reach and maintain their optimal . . . functional levels . . . ."1 However, this definition will require some revision, as, in May 2001, WHO adopted the International Classification of Functioning, Disability and Health.2 The new classification has modified the concept of disability to recognise that personal and environmental factors directly influence the experience of people with disability, and the term "handicap" has been dropped because of its negative connotations. With the new terminology, rehabilitation is seen as a coordinated process that enhances "activity" and "participation" (Box 1). Rehabilitation medicine was recognised as a principal specialty in Australia in 1978 and as a Faculty of the Royal Australasian College of Physicians in 1991. The early development of the specialty was largely in response to the need to manage disabilities resulting from wars, and occupational and road trauma. There has traditionally been a focus on physical medicine, but increasingly rehabilitation is acknowledging the patient's social context.3 Topics for this MJA Practice Essentials – Rehabilitation Medicine series have been selected partly on the basis of the prevalence of the impairment or condition, and partly because of the impact they have on individuals. Stroke, musculoskeletal injuries, brain injury and rehabilitation in the context of older people will be examined, beginning with "Rehabilitation and older people" on page 387. There are many reasons why rehabilitation is of such importance in the new millennium. Firstly, populations are ageing rapidly, and the incidence and prevalence of common disabling conditions (such as stroke and fractured femur) increase markedly in older people (Box 2).4 Secondly, curative and perioperative medicine has greatly improved in recent years. Frail elderly people undergo major surgery, and trauma victims who in previous years would have died now survive. However, this may be at the cost of significant impairment and disability. Finally, the past few decades have seen the development of new chronically disabling conditions such as AIDS. These changes have had an enormous impact on the medical workforce, as a substantial cadre of highly qualified, committed medical specialists is needed to work in the rehabilitation field (the number of such specialists currently falls far short of agreed standards5), while other doctors need to be educated to refer appropriately and manage disability within their field of practice. The rehabilitation medicine physician is part of an interdisciplinary team the members of which have complementary roles. Allied health professionals and nurses are essential members of this team, whose input is determined by the patient's specific rehabilitation goals. Where does the general practitioner fit into these highly specialised areas? The GP's role in rehabilitation is primary care of people with disability, tertiary prevention of disability, coordination of maintenance care, and identification of situations requiring involvement of specialist rehabilitation services. There are also substantial opportunities for GPs to assist in the primary prevention of disability related to musculoskeletal injuries, particularly those occurring in the context of compensable road trauma or work injury. Additionally, patients will benefit if GPs have direct interaction with specialised rehabilitation services operating in inpatient or ambulatory care settings or in patients' homes. Effective interaction may be encouraged by the use of case conferencing and care planning, using the structure of the Enhanced Primary Care initiative.6 Finally, it is no longer sufficient to adopt a particular therapeutic approach because it "feels right"; an evidence base is just as important in rehabilitation medicine as it is in any other specialised field. Despite the relatively low use of expensive technology or drugs in rehabilitation, the high staff-to-patient ratio makes it an expensive commodity, and if we are to persuade private and public purchasers to commit to rehabilitation we need to provide data to support its value.7 Although rehabilitation is a relatively new research field, the last few years have seen a great increase in high quality publications, including systematic reviews from the Cochrane Collaboration,8,9 and clinical practice guidelines.10 Each article in this MJA series will review the research that backs up the aspects discussed, or point to the need for research where only consensus recommendations are available. Evidence-based recommendations will be graded according to the system of the National Health and Medical Research Council (Box 3).11 The rehabilitation paradigm differs from the curative one in many ways. It is an individualised, patient-oriented activity focused on disability rather than disease. Rehabilitation moves from impairment towards helping the patient find "ability" in the presence of obvious disability. 1: Definition of terms from the International Classification of Functioning, Disability and Health (ICF)2 In the context of health: Impairments are problems in body function or structure such as significant deviation or loss. Activity is the execution of a task or action by an individual. Participation is the involvement in a life situation. Activity limitations are difficulties an individual may have executing activities. Participation restrictions are problems an individual may experience in involvement in life situations. Environmental factors make up the physical, social and attitudinal environment in which people live and conduct their lives. 2: Increase in prevalence of disability in the Australian population with age (data for 1998) Reproduced from Australian Bureau of Statistics: Disability rates by age and sex, 1998.4 In this survey, disability was defined as a limitation, restriction or impairment which lasted, or was likely to last, for at least 6 months, and restrict everyday activities. 3: Level-of-evidence codes Evidence-based recommendations in the Rehabilitation series are graded according to the National Health and Medical Research Council system11 for assessing the level of evidence. E1 Level I: Evidence obtained from a systematic review of all relevant randomised controlled trials. E2 Level II: Evidence obtained from at least one properly designed randomised controlled trial. E31 Level III-1: Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method). E32 Level III-2: Evidence obtained from comparative studies with concurrent controls and allocation not randomised (cohort studies), case–control studies, or interrupted time series with a parallel control group. E33 Level III-3: Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group. E4 Level IV: Evidence obtained from case-series, either post-test, or pre-test and post-test.

Peter B Disler · Ian D Cameron · Stephen F Wilson

Older people make up the majority of participants in general rehabilitation programs. Stroke and hip fracture are the major diagnostic groups. Most older people with significant disability of recent onset have the potential to benefit from rehabilitation. Assessing an older person's premorbid functional and cognitive status, which are strong determinants of rehabilitation outcome, is an important component of management. The major goals of rehabilitation for older people are mobility and self-care without the assistance of another person. Evidence suggests that rehabilitation for older people involving a coordinated multidisciplinary team of health professionals (including nurses and doctors) is effective. Contemporary rehabilitation practice is not confined to traditional inpatient rehabilitation units; it also occurs in the community and other non-hospital settings, and involves general practitioners.

Ian D Cameron PhD, FAFRM(RACP) · Susan E Kurrle, MB BS, DipGerMed

To the Editor: The possible impact of the Internet revolution has been much discussed.1-3 In two surveys, conducted in 1999 and 2001, we surveyed oncology patients from two teaching hospitals in central Sydney to explore the experience and impact of Internet use among Australian oncology patients. In November 1999, a questionnaire was mailed to 240 eligible patients selected from 617 sequential registrations to the oncology units. Eligible patients were those who were alive, competent, had cancer, were of known address and whose attending medical officer was participating. In the second survey, to obtain a more representative sample, we invited all oncology patients visiting the outpatient clinics over a three-month period (September to December 2001) to participate. We received completed questionnaires from 142 patients (response rate, 59%) in 1999 and from 153 patients (number of refusals unknown) in 2001. Of these, 33% (47/142) in 1999 and 46% (70/153) in 2001 had accessed the Internet for information relating to their illness, either personally or through family and friends. In both surveys, most users accessed the Internet from home, the information sought was mainly in relation to treatment, and the most-visited Internet sites were those of cancer centres. Patient perceptions of the impact of Internet-acquired information on their experience of cancer are summarised in the Box. Most patients viewed its impact as positive. The advantages of using the Internet reported by patients included its speed, convenience, privacy, currency, diversity of viewpoints, and usefulness as a support tool. Many reported that they had sought corroboration of Internet information with information from other sources, especially their doctor. Problems identified with the Internet were its impersonal nature, time costs, overabundance of information, and concerns about the discovery of inappropriate, inaccurate or distressing information. Most respondents emphasised that they were able to recognise these limitations, but, notwithstanding, considered the Internet a valuable resource. For example, one respondent wrote: "I felt my capacity to cope with the illness and treatment greatly improved because I learned enough from the Internet to challenge my oncologist and thereby learn to trust him and his advice." Despite concerns expressed by many doctors, these oncology patients assessed impacts as either positive or neutral in overall influence. Increasing Internet use by patients and their families should not be viewed as a problem, but as an opportunity for patients and their treatment teams to work together, ensuring that patients have up-to-date information about their illness and its treatment and are aware that they are not alone in the fight against cancer. Perceived influence of Internet-acquired information among oncology patients in 1999 and 2001 Better No change Worse Question not answered 1999 survey (n = 47) Relationship with doctor 12 (26%) 30 (64%) 0 5 (11%) Discussions with doctor 20 (43%) 22 (47%) 0 5 (11%) Treatment decisions 22 (47%) 19 (40%) 1 (2%) 5 (11%) Coping with illness 26 (55%) 15 (32%) 1 (2%) 5 (11%) 2001 survey (n = 70) Relationship with doctor 24 (34%) 34 (49%) 2 (3%) 10 (14%) Discussions with doctor 42 (60%) 18 (26%) 1 (1%) 9 (13%) Treatment decisions 37 (53%) 25 (36%) 0 8 (11%) Coping with illness 32 (46%) 31 (44%) 1 (1%) 6 (9%)

Julia ML Brotherton · Stephen J Clarke · Susan Quine

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

Terry Spencer was born in Tenterfield, New South Wales, on 18 April 1917. He was brought up on a grazing property, where, because of isolation, education was difficult, but he was encouraged to read and absorb a wide range of information. He showed particular interest in mechanical matters, excelling in shooting with both rifle and pistol. After some years at Tenterfield Rural School and at "Shore" school in Sydney, Terry educated himself at home while working on the property, eventually passing his matriculation exams through the International Correspondence School at the age of 23. He enrolled in the Faculty of Science at the then New England University College, where he met his future wife, Margaret Cumpston. His studies were interrupted by the war. In 1940, he enlisted in the Air Force and trained as a radio and radar mechanic. Active war service contributed to the deafness that handicapped him in later life. When war ended, Terry was accepted as a medical student at the University of Sydney. After graduating in 1951, his first medical appointment was to Thursday Island, in the Torres Strait, where he took a special interest in diagnosis and treatment of tuberculosis in Indigenous people. It was there that his enduring interest in tropical medicine and insect-borne diseases began. In 1953, after gaining the Diploma of Tropical Medicine and Hygiene from the University of Sydney, he joined the Department of Health in Papua New Guinea. During his stay there (1953–1961), he became a specialist in the epidemiology and control of malaria. His expertise was recognised by his election as a Fellow of the Australasian College of Tropical Medicine in 1992. His other medical appointments included Visiting Medical Officer at the Prince Albert Memorial Hospital, in Tenterfield (1962–1974), and sole resident general practitioner in Werris Creek (1979–1987), a small town in northern New South Wales. Terry was a grazier, a malariologist, a great storyteller and a general practitioner with a wide range of abilities. Capable, conscientious and enthusiastic, with a quiet and friendly manner, whatever he undertook he carried out with integrity and to the best of his ability. He tackled all problems with courage and determination, not least his increasing helplessness in later years. He died on 15 February 2002. A loving and supportive husband and brother, Terry is survived by his wife Margaret and sister Anne.

Margaret Spencer OAM MSc PhD FACTM

Re "Thiazolidinediones and type 2 diabetes: new drugs for an old disease", the New Drugs, Old Drugs article by Trisha M O'Moore-Sullivan and Johannes B Prins in the 15 April issue of the Journal (Med J Aust 2002; 176: 381-386), in which an editing error resulted in the word "tryglyceride" replacing "total cholesterol". Thus, on page 383, the first sentence in the second dot point under the subheading "Both drugs increase HDL and LDL and decrease FFA levels; pioglitazone lowers triglyceride levels", the sentence should read "Rosiglitazone also tends to increase total cholesterol level and studies have reported variable effects on ratios of total cholesterol to high-density lipoprotein (HDL) and of LDL to HDL." The html and pdf versions of this article were corrected on Monday 30 September 2002.

Trisha M O'Moore-Sullivan MB BS, FRACP · Johannes B Prins MB BS, PhD, FRACP

Re the article "The contribution of airway structure to early childhood asthma", by McKay KO and Hogg JC, in the 16 September supplement to the Journal, Early childhood asthma: what we know and what we need to know (Med J Aust 2002; 177: S45-S47). The last two lines of the figure caption on page S46 were omitted. The full caption should read: "The vessels in the submucosa (a) are smaller than the vessels in the adventitia (c), and the vessels that pass through the muscle layer (b) connect them. These two sets of vessels are perfused in series, providing a basis for a difference in the nature of the inflammatory reaction in the submucosa and lumen compared with the peribronchiolar space." The html and pdf versions of the article were corrected on Monday 30 September 2002.

Karen O McKay LLB PhD · James C Hogg MD PhD

Slim chances In Other Journals image Childhood obesity has been back in the news again in Australia, with the advertisers of fattening foods taking some of the blame. A survey of households in the United States looked at another side of the equation: lack of exercise. Of 611 households, only 19% reported children walking and 6% cycling to school at least once a week during the preceding month. Barriers to such activity included distance (55%), traffic danger (40%), weather (24%) and dangers from crime (18%). The report concluded that care with siting new schools and road safety programs could address the first two of these issues. MMWR Morb Mortal Wkly Rep 2002; 51: 701-703 Temporal confounders Physical examination is a better predictor of giant-cell arteritis (GCA) than ultrasound, say Italian researchers. They examined 86 patients attending Reggio Emilia Hospital with a suspected diagnosis of GCA or polymyalgia rheumatica, comparing their findings with the findings on duplex ultrasonography and biopsy. Fifteen of the patients had GCA on biopsy. The ultrasound finding of a hypoechogenic halo around the lumen of the temporal artery (which has been associated with GCA) had a sensitivity of 40% and a specificity of 79% for GCA. Temporal artery abnormalities on examination (tenderness, or decreased or absent pulsation) had a sensitivity of 67% and a specificity of 99%. Ann Intern Med 2002; 137: 232-238 The hazards of protein Recent research in the United States proves that there’s still no such thing as a free lunch when it comes to dieting: the increasingly popular “low carbohydrate/high protein” approach may leave dieters subject to renal calculi and bone loss. Ten healthy volunteers were monitored while they consumed their usual diet for two weeks, then participated in the induction and maintenance phases of the Atkins diet (two weeks of severe carbohydrate restriction to < 20g/day followed by four weeks of less severe restriction). The diet led to a defacto doubling of protein and fat intake. Subjects lost weight, but showed significant increases in acid excretion and decreases in urine pH on the diet. They also developed hyperuricuria and hypercalciuria (which was not compensated for by an increase in intestinal calcium absorption, thus increasing the risk of stone formation and bone loss. Am J Kidney Dis 2002; 40: 265-274 Against the grain? Some may see it as un-Australian to legislate for mandatory fortification of foodstuffs, but the results of recent Canadian research make a strong case for adding folate to grain products to reduce the incidence of neural tube defects. Two separate studies looked at the rates of neural tube defects (NTDs) in two Provinces (1986-1999 in Ontario (1) and 1991-2001 in Nova Scotia (2)). Using data on livebirths, stillbirths and therapeutic abortions, as well as databases of congenital anomalies, they determined that the incidence of NTDs did not decrease after the recommendation for periconceptional folate supplementation was promulgated between 1993 and 1995, but that the rates did fall after folate fortification of flour and pasta was introduced in 1996-1998. In Nova Scotia the mean annual rate of NTDs was 2.55/1000 births during 1991–1994, 2.61/1000 births during 1995–1997 and 1.17/1000 births during 1998–2000 (RR 0.46, compared with 1991–1997). 1. CMAJ 2002; 167: 237-240 2. CMAJ 2002; 167: 241-245 The truth about cats and dogs The role played by household pets in the development of allergy remains unclear. Researchers in Detroit, USA(1), have reported that exposure to two or more cats or dogs in the first year of life reduces the overall subsequent risk of allergy. They followed a birth cohort of 474 children, correlating pet (dog and cat) exposure in the first year of life with atopy (defined as skinprick test positivity to one or more of six common aeroallergens) and seroatopy (any positive allergen-specific IgE test) at age six to seven. The prevalence of atopy was 33.6% in children with no pet exposure, 34.3% with exposure to one pet and 15.4% with exposure to two or more pets. Rates of seroatopy were similar. This gave an adjusted OR of 0.23 for atopy and 0.33 for seroatopy in children with two or more pets. The association appeared to be stronger in boys, but there were too few subjects in the study to fully evaluate this. Before rushing out to the pet shop you should know that studies on this topic have had conflicting results. Another group in the United States(2) studied only children with a parental history of allergy. Those whose mothers did not have asthma had a decreased risk of wheeze between the ages of one and five years if exposed to a cat (but not a dog) at age two to three months, and those with similar cat exposure whose mothers did have asthma had an increased risk of wheeze after age three. 1. JAMA 2002; 288: 963-972 2. Lancet 2002; 360: 781-782

Med J Aust 2002; 177 (7 Suppl).