Volume 180 Issue 6

National water-recycling guidelines will address both health and environmental risks Separating drinking water from sewage may seem obvious now, but the idea that sewage could affect health was not understood until the 19th century. Dr John Snow (1813–1858) was one of the first to make the connection when investigating a cholera outbreak in London. He noted that most of the people who were sick had consumed water from a pump in Broad Street, Soho, that was contaminated by sewage. When the pump’s handle was removed, the spread of cholera dramatically stopped. But it was not until the early 1900s that adequate separation of water supplies from sewage routes was achieved (at least in developed countries), resulting in substantially fewer cases of waterborne disease. . . . water is used for gardens, toilets and laundry, where water of lesser quality would suffice. In Australia, in 2004, we are 6 years into another drought, and water shortages and increasing climate variability are behind efforts to reduce water consumption and find other, sustainable ways of utilising all available water. While current efforts concentrate on reducing per-capita water use through more efficient appliances and water restrictions, other, longer-term strategies are also needed. These pressures are leading the community to consider alternative sources of water for some household uses. At present, potable-quality water is supplied for all household purposes. But more than 50% of this water is used for gardens, toilets and laundry, where water of lesser quality would suffice. The domestic use of alternative water sources — rainwater, stormwater, greywater and sewage — has the potential to expose large populations to pathogens and chemical contaminants unless the water is appropriately treated and managed. These treatments can be complex, and, to further confound the issue, permissible applications vary by jurisdiction. There are also many gaps in the regulations for urban domestic uses. Reports of health outcomes from reusing water predominately concern sewage reuse. These studies focus on the health of wastewater workers,1 farm workers and surrounding communities.2 Many of the studies are poorly designed and examine reuse of untreated sewage,3 which means they are of limited relevance to Australia. Because of the paucity of relevant studies on the health effects of other water sources, water quality is used as a proxy health-risk measure. Furthermore, much of the information on urban use of alternative water sources is in literature that is not readily accessible and often not peer reviewed. Thus, there is a pressing need for more rigorous scientific evidence to inform regulation. Rainwater collected from roofs is mixed with debris (eg, leaves and animal droppings) from the roof or from the guttering, and possibly contaminated by dead insects, trapped animals and leaf litter in the tank itself. Additionally, heavy metals from roofing materials, airborne pollutants from traffic emissions and industrial exhaust, or agricultural chemicals can contaminate rainwater supplies.4 It is widely accepted that rainwater can safely be used for bathing, laundering and watering the garden,5 and only in situations where a treated reticulated water supply is not available is it endorsed as a primary source of drinking water. Rainwater is generally considered safe to drink for most members of the community if it is clear, has low odour and taste, and the tank and roof are well maintained.5 Stormwater is rain that drains into the stormwater system from roofs, roads, footpaths and other ground surfaces and is channelled, untreated, directly to local waterways. The water carries rubbish, animal faeces, motor oil, petrol, tyre rubber, soil and debris. Use of this water has been limited to date, partly because of its seasonal variability in volume and the need for large-scale storages. However, in New South Wales, it has been proposed that stormwater from local residences be redirected to irrigate local sports fields, wetlands6 and parks.7 Greywater is sourced from kitchen, laundry and bathroom drains but excludes toilet water. Some guidelines exclude wastewater from the kitchen, as it can contain higher levels of wastes.8 Greywater may contain urine and faeces from nappy washing and showering, in addition to kitchen scraps, soil, hair, detergents, cleaning products and fats and oils. Greywater contaminants can include substances such as boron and phosphates, and the water is often alkaline and saline.9 Treated greywater may potentially be used for toilet flushing, laundering and subsurface garden watering. However, reusing greywater for gardens can detrimentally alter the properties of soil and gradually kill plants sensitive to phosphorus, including Australian native flora. Sewage is water entering the sewerage system. It has all the contaminants of greywater, in addition to high concentrations of faecal material. This water can be reclaimed after rigorous treatment at a sewage treatment plant and piped to individual households, as part of a dual-reticulated water-supply system (additional to and separate from normal tap water), for uses such as toilet flushing, garden watering and washing of cars and outdoor surfaces. It may also be used for irrigating sports fields and public parks, as well as for fire control, sewerage flushing, dust suppression, topping up of ornamental ponds or irrigating agricultural crops. A number of such systems are currently in place across Australia and are the focus of long-term assessment.10-14 Some new urban developments are planning to incorporate alternative water sources, such as reclaimed sewage water at Rouse Hill in Sydney,10 but there are questions about the potential impact on public health, particularly if long-term regulation and governance issues are not adequately addressed. With the exception of good-quality rainwater, all of the above water types are unsuitable for drinking. However, if they are supplied to thousands of individual households, incidents of accidental ingestion are bound to occur. In addition, errors in plumbing installation may result in the non-potable water being “cross-connected” to potable water taps. Regulatory oversight, awareness by health professionals of the potential for waterborne diseases, and continuing surveillance programs will be required to monitor and minimise these risks. Recognising the need for better guidance for regulators and water suppliers, the Environment Protection and Heritage Council and the Natural Resource Management Ministerial Council have initiated the development of national guidelines for water recycling. These guidelines are intended to provide a unified approach across Australia, and will address both health and environmental risks, and be developed in collaboration with the National Health and Medical Research Council. In keeping with recent revisions to the Australian Drinking Water Guidelines,15 a risk-management approach will be adopted, emphasising the multiple-barrier principle and ongoing monitoring of the effectiveness of systems to protect public health.

Teresa Z Mitakakis PhD, BSc(Hons) · Martha I Sinclair PhD, BSc(Hons) · Karin Leder MB BS(Hons), FRACP, MPH

RCT evidence for rehabilitation is strengthened by an observational cohort study The study by Sundararajan et al1 (page 268) is a novel data linkage study and is best described as a cohort study. The study showed 35% lower mortality in patients with cardiovascular disease who had undergone cardiac rehabilitation when compared with patients who had not undergone cardiac rehabilitation. However, even the best cohort studies can give only limited inference on treatment effects. For example, observational studies suggested that women who used hormone replacement therapy (HRT) had a lower incidence of cardiovascular events than did non-users.2 However, not only did prospective randomised controlled trials (RCTs) fail to confirm the protective effect of HRT,3 they suggested that such treatment might actually cause cardiovascular disease.4 The apparent impressive protection of HRT suggested by observational databases may have been accounted for by socioeconomic differences between the users and non-users of HRT. Thus, RCTs have assumed the strongest evidence in suggesting a relationship between treatment and outcome. So why does the database linkage study by Sundararajan et al1 appeal at all? Perhaps it is because the evidence base for cardiac rehabilitation programs fails to convince all medical practitioners, despite “level 1” evidence existing from other studies.5 Even the best RCTs have intrinsic limitations. The first is that most trials exclude older, sicker patients with multiple comorbidities and those who might not cooperate with the trial protocol. This often results in a clinical trial of low-risk patients, which may miss a beneficial effect of treatment. The second limitation of RCTs, more common in single-centre studies, is publication bias. It is hard work to prepare a study for publication — even harder for a negative study than for a positive one. As a result, investigators are less likely to submit negative studies and journal editors are less likely to accept them for publication. Publication bias is likely to exist in most, if not all, areas of published research. So, what are the limitations of the evidence specifically regarding cardiac rehabilitation? The Cochrane Library review of exercise-based rehabilitation for coronary heart disease reviewed 51 RCTs of 8440 patients.5 Total cardiac mortality was reduced by 31% (random effects model odds ratio [OR], 0.69; 95% CI, 0.51–0.94) and 26% (random effects model OR, 0.74; 95% CI, 0.57–0.96) in the exercise-only and comprehensive cardiac rehabilitation groups, respectively. Neither intervention had any effect on the occurrence of non-fatal myocardial infarction. In other words, exercise that did not affect cardiac risk factors was as effective in reducing cardiac mortality as a comprehensive program that included exercise and successfully reduced cardiac risk factors. The reasons for this are unclear given the level 1 evidence supporting the proven effects of lowering blood pressure6 or serum cholesterol7 in reducing cardiac mortality. Furthermore, one has to be currently active to experience the benefit of physical activity or fitness — loss of activity and fitness means loss of the protection of exercise. So, medical practitioners can have reasonable doubts about the protective effects of a 6- or 8-week cardiac rehabilitation program on cardiac mortality years after the event, despite the Cochrane evidence. And this is why the data linkage article by Sundararajan et al appeals.1 The clinical trial data in the Cochrane review were derived from selected patients who had undergone exercise training for periods varying from a few weeks to several years. Sundararajan et al show that Australian patients with coronary heart disease who had undergone cardiac rehabilitation for 6–8 weeks had a better survival rate than did patients not undergoing cardiac rehabilitation. Although the study may be fraught with problems similar to those described for the HRT studies, it is pleasing to note how similar is the magnitude of protection from death associated with cardiac rehabilitation in this Australian series compared with that described in the Cochrane review. This observational study lends strong support to the trial information. Patients surviving an acute coronary syndrome should be referred for cardiac rehabilitation, as the experience may save their life. There is another nugget in the article by Sundararajan et al.1 Patients with acute coronary syndromes not undergoing coronary artery bypass surgery are very much less likely to undergo cardiac rehabilitation than patients who have received surgery. Percutaneous cardiac intervention is now performed twice as often as cardiac surgery. Such patients are often younger and fitter and return to work and their usual life within days of their procedures. Alternative models of rehabilitation are required for these patients who have not been physically deconditioned. These were recently discussed in this journal by Scott et al.8 One such model is the COACH Program, which has been validated by two RCTs.9,10 The COACH Program is a training program for patients with coronary heart disease, in which a healthcare professional coach trains patients to aggressively pursue the target levels for their particular coronary risk factors while working in partnership with their own doctors. The COACH Program has been shown to have a favourable effect on many coronary risk factors, including total and low-density lipoprotein cholesterol, arterial blood pressure, dietary saturated fat intake, body weight, and the performance of regular walking.8,9 If patients do not attend cardiac rehabilitation, then alternative strategies for achieving secondary prevention are required. The COACH Program is one such effective method. In summary, the evidence supporting cardiac rehabilitation is less than convincing, particularly when the rehabilitation is confined to the period after an acute cardiac illness. The data linkage study by Sundararajan et al adds support to the Australian practice of convalescent-phase cardiac rehabilitation.

V Michael Jelinek MD, FRACP, FACC

Can we solve a riddle by burying an illusion? Over the past 40 years, the prevalence of asthma appeared to rise inexorably in both the developed and the developing world. So the report by Robertson and colleagues in this issue of the Journal (page 273), showing a decline in reported symptoms in children since 1993,1 is to be warmly welcomed. It comes with supporting evidence, in the form of reduced hospital admissions for asthma in Victoria, but also with a catch. The prevalence of reported hay fever and eczema has increased over the same period. Why the prevalence of asthma increased and why it may now be stabilising or declining is baffling. Robertson et al suggest one possibility may be the increased use of daycare facilities. The “hygiene hypothesis” — the inverse relationship between microbial or infection exposure and allergic disease — was first suggested by Gerrard et al while studying allergic disease in the Metis Indian community in Canada.2 Strachan refined this observation from large UK cohorts, in which he found an inverse relation between the number of older siblings and the prevalence of hay fever, but not asthma.3 He emphasised that the link was through atopy to allergic disease. Several studies have subsequently shown reduced asthma prevalence in school-aged children with early daycare attendance. These children tend to show more early wheezing, but less asthma later on. The proposed explanation is that they contract more upper respiratory tract infections from close contact with children, and this leads them to have more early wheezing, but, in turn, protects them from later developing atopy and atopic disease. This explanation seems less likely in the study by Robertson et al, given that the prevalence of hay fever and eczema increased while asthma prevalence decreased. However, one would need to know the atopic status of the children to clarify the issue. The 26% reduction in current wheeze prevalence in Melbourne, while significant, is within the range found in Australia in phase 1 of the International Study of Asthma and Allergies in Childhood (ISAAC) study. For example, in the four Australian centres that took part, there was a 19% difference between the highest and lowest prevalence. For sleep disturbance and speech limitation, this was 40%.4 There is even greater variation in large cities. In Mumbai (Bombay), for example, reported current wheeze varied by more than 100% in different parts of the city. Large cities are not homogeneous, with large variations in many factors that may affect wheezing, such as housing conditions, smoking prevalence, diet and variable access to healthcare. Over time, with gentrification and changes in zoning, factors may vary even in the same narrow geographic location. Robertson et al also note that awareness of asthma in the community is a determinant of the prevalence of reported symptoms. The pool of individuals with a history of symptoms in any population will be larger than the proportion who report symptoms in a defined period. In a resurvey of 700 young adults, all of whom had 4 years previously responded positively to at least one of three asthma questions, only two-thirds reported symptoms. In the first survey, 28% had responded positively to all three questions, and in the second, 29%. However, only 60% were the same individuals.5 Just how large this pool is has recently been clarified, at least in New Zealand. In a 26-year follow-up of a birth cohort in Dunedin, 73% reported wheezing on at least one occasion and 51% on at least two.6 Given that there is likely to be some loss to recall, wheezing at some time between birth and adulthood appears virtually universal. Clearly, most of this wheezing is occasional, trivial, inconsequential, and a normal phenomenon. It is now easy to see how a change in diagnostic and hence societal emphasis on wheezing, as opposed to bronchitis, with attendant changes in treatment, can enhance recall for asthma in cross-sectional surveys. Perhaps this emphasis is now stabilising and the diagnostic label “asthma” is being applied slightly less frequently in Melbourne. The strengths of the ISAAC approach — simple questionnaires requiring minimal funding — allow large-scale international comparisons of children (in fact, this is the only way that such large population studies can be conducted), but interpreting relatively small changes over time in a very asthma-“savvy” environment like Australia is more difficult. Although the ISAAC approach clearly shows that reported asthma symptoms are far more frequent in Australia, New Zealand and the United Kingdom compared with, say, Albania or India (more than 10-fold), smaller differences over relatively short time intervals in individual countries are harder to interpret. In the past 30 years there have been many cross-sectional studies reporting an increase in the prevalence of asthma symptoms over time. In only two has this been accompanied by measures of airway hyperresponsiveness. In the first, in the United Kingdom, Burr et al showed that current asthma symptom reporting had doubled over a 15-year period, but exercise-induced fall in peak expiratory flow rate had not changed.7 In the second, Peat et al showed a doubling of current symptoms and airway hyperresponsiveness, predominantly among atopic children, suggesting an increase in asthma relating to greater allergen exposure.8 There is a real need for the measurement of objective markers over time in similar populations. The advent of easily obtainable markers of airway inflammation, such as exhaled nitric oxide or constituents of breath condensate, may allow population studies of airway inflammation to be quantified and tracked over time. Perhaps it is time to abandon our inconvenient population model of asthma as a disease, just as doctors did for essential hypertension in the 1950s.9 Nature provides no obvious support for asthma and we can neither define nor measure it accurately; indeed, it remains a mystery because it is largely an illusion. The late Geoffrey Rose (Professor of Epidemiology at the London School of Hygiene and Tropical Medicine) suggested that we should seek the answers to “disease” by exploring populations rather than atypical minorities.10 We need to consider applying this concept to airway inflammation. Now that appropriate tools are becoming available, we should measure airway inflammation and airway responses in large populations and explore the environmental and genetic factors that affect the airway at a population level. This might reveal that it is not just the upper end of the distribution of airway inflammation (which we arbitrarily and inconsistently call asthma) that varies by environment, and over time, but the whole distribution. In the meantime, Robertson and colleagues have shown that parent-reported asthma symptoms of young Melbourne children have declined in the past decade. This may or may not be an early signal for a real decline in asthma prevalence. What it does suggest is that asthma prevalence has not increased, which in itself is a welcome observation.

Julian Crane MB BS, FRCP, FRACP

Targets for the prevalence of smoking in 2010 are embarrassingly modest The Risk Factor Prevalence Survey conducted by the National Heart Foundation in Australian capital cities in 1989 revealed that, for the first time ever, there were more ex-smokers than current smokers among Australian adults of working age. This major landmark in public health went unnoticed, and, well over a decade later, has still not been achieved in Britain. How can it be that the cradle of epidemiology and the home of the British Doctors Study (and all that it has taught us about the harm done by smoking) is itself doing so poorly in tobacco control? The UK has undeniably made a huge contribution to the science behind effective tobacco control When a survey of over 9000 Londoners in 2002 revealed that 29% were smokers and 27% were ex-smokers, it comes as no surprise that one of the first comments regularly made by visitors from “Down Under” concerns the high ambient levels of tobacco smoke — from the halls of Heathrow onwards. Smoke-free policies are in place on London buses and the Underground, but there are still some smoking carriages on long-distance trains, and many shopping centres permit smoking. Waiting in a crowd for a commuter train at peak-hour is decidedly unpleasant for non-smokers, while pubs and restaurants can comply fully with the “Public Places Charter on Smoking” simply by displaying a sign saying “Smoking permitted throughout”. Despite the recommendation of the International Union Against Cancer (UICC) that tobacco control should combine legislation, education and cessation activities, the Blair Government has until very recently put all of its eggs in the “cessation” basket. Having nicotine replacement therapies and bupropion available on the National Health Service is undeniably important in removing economic barriers to effective aids to quitting smoking, and supporting this with publicly funded smoking-cessation clinics is unprecedented. However, the “ring-fence” around funding for these clinics is not necessarily permanent, and the overall approach remains decidedly unbalanced when judged against the UICC’s recommendation. The UK government has conspicuously failed to take a strong lead, either nationally or within Europe, in adopting the regulatory strategies on smoking and the tobacco industry that are now taken for granted in Australia and New Zealand. UK newspapers and billboards continued to carry advertisements for cigarettes until February 2003, a decade after they disappeared in Australia. Sophisticated, community-wide health promotion using prime-time electronic media, now an export industry for Australia, remains virtually unknown as a tobacco-control activity here, with embryonic campaigns only just beginning to emerge. Evidence that the major tobacco manufacturers are well aware of diversion of significant fractions of their outputs into smuggling operations has not prompted effective official action. Consequently, tax has not been paid on perhaps a third of cigarettes sold in London, significantly undermining the use of price as a disincentive to smoking. The minimum age at which children can purchase cigarettes is stuck at 16 years, and packets of 10, known to appeal especially to school-age smokers because of their low price and greater ease of concealment, are still on the market. Warnings on cigarette packets have been enlarged in size and range, but this is a small advance in an environment that, by standards now well established in Australia, remains otherwise remarkably permissive of smoking. The UK has undeniably made a huge contribution to the science behind effective tobacco control and, beginning with the first report on smoking from the Royal College of Physicians in 1962, has been a pioneer in collating and publishing authoritative, independent expert reviews of the accumulating epidemiological and clinical data as a stimulus to official public health action. It also gave the world the prototypic advocacy organisation Action on Smoking and Health (ASH). Seen through “colonial” eyes, however, it doesn’t have the teeth that have regularly been bared by its Australian counterpart (ASH Australia), the Cancer Council of Victoria, or the Australian Council on Smoking and Health. Meanwhile, the UK Department of Health apparently feels no pressing need to adopt international best practice in tobacco control. A further consequence of the dearth of effective advocacy is the tolerant attitude of the media, up to and including the BBC. For example, the opinions of vested interests that the wider introduction of smoke-free policies would bring an end to commercial and civilised life as we know it are reported uncritically, and seemingly without any effort to find examples that disprove such assertions. Radio audiences are much more likely to be treated to an aside that smoke-free policies in bars in France have been an abject failure than to one that reminds listeners that active smoking accounts for 30% of avoidable cancers, or that passive smoking measurably increases the risk of lung cancer and heart attack, for example among non-smoking staff in bars. The coverage of smoking issues is truly meagre — it takes 4444 deaths from smoking to generate a newspaper story, but only 0.375 deaths from measles, 1.5 from variant Creutzfeldt–Jakob disease, and 22.5 from HIV/AIDS.1 It feels like a time-warp — the British media now are where the Australian media were a generation ago — which is what the overall figures for the prevalence of smoking show, too. But, it also demonstrates an interesting point — the apparent gullibility of the media here is not so much a case of “who pays the piper, calls the tune” (since advertisements for cigarettes have disappeared from newspapers), but the failure of government and health interests to generate and maintain vigorous discussion about the hazards of smoking, active and passive. While no less an expert than Professor Sir Richard Peto argues, with good foundation, that smoking-cessation activities will save lives much faster than waiting to create a whole new generation of non-smokers, this view has allowed the UK government to avoid facing up to the need for a comprehensive tobacco control policy. Its targets for the prevalence of smoking in 2010 are embarrassingly modest. They concentrate on short-term indicators for smoking-cessation services without a population focus, and these are likely to be reached simply as an extension of the background downwards trend of an absolute reduction of around 0.25% per annum. Meanwhile, Britons continue to die from smoking at the rate of one every 5 minutes. Roll on 1989!

Konrad Jamrozik DPhil, FAFPHM, MFPH · David P Weller PhD, FRACGP, FAFPHM · Richard F Heller MD, FRCP, FRACP, FAFPHM

Objective: To describe the patterns of use of cardiac rehabilitation in Victoria and to assess whether the survival benefits predicted in clinical trials have been realised in the community. Design: Cohort study based on data linkage. Participants: All patients admitted for acute myocardial infarction (AMI), coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) in Victoria in 1998 (n = 12 821). Interventions: Attendance at one of 66 participating outpatient cardiac rehabilitation centres in Victoria. Main outcome measures: Rates of attendance at rehabilitation based on key factors such as diagnosis, age, sex, and comorbidity. Five-year survival for attendees compared with non-attendees. Results: Rates of participation in rehabilitation were 15% for AMI, 37% for CABG, and 14% for PTCA. Rehabilitation attendance rates dropped sharply after 70 years of age. Attendees had a 35% improvement in 5-year survival (hazard ratio for death associated with rehabilitation attendance, 0.65 [95% CI, 0.56–0.75]). Conclusions: Attendance rates at cardiac rehabilitation are suboptimal, even though attendance confers a clinically significant difference in 5-year survival. The elderly, women, and those with comorbid conditions may benefit measurably from increased rates of attendance.

Vijaya Sundararajan MD, MPH, FACP · Stephen Begg MPH · Ric Marshall PhD · Stephen J Bunker PhD · Helen McBurney PhD

Objective: To determine the change in prevalence of asthma, eczema and allergic rhinitis in Australian schoolchildren between 1993 and 2002.Design: Questionnaire based survey, using the protocol of the International Study of Asthma and Allergy in Childhood.Setting: Metropolitan Melbourne primary schools within a 20 km radius of the GPO in 1993 and 2002.Subjects: All children in school years 1 and 2 (ages 6 and 7) attending a random sample of 84 schools in 1993 and 63 schools in 2002.Main outcome measures: Parent-reported symptoms of atopic disease; treatment for asthma; country of birth.Results: There was a 26% reduction in the 12-month period prevalence of reported wheeze, from 27.2% in 1993 to 20.0% in 2002. The magnitude of reduction was similar for boys (27%) and girls (25%). The 12-month period prevalence of reported eczema increased from 11.1% in 1993 to 17.2% in 2002, and rhinitis increased from 9.7% to 12.7%. There were reductions in the proportion of children attending an emergency department for asthma in the previous year (3.6% to 2.3%), the proportion admitted to hospital (1.7% to 1.1%) and the proportion taking asthma medication (18.5% to 13.4%). Of those who reported frequent wheeze, there was an increase in the proportion taking regular inhaled steroids (34.5% to 40.9%).Conclusion: There has been a significant reduction in the prevalence of reported asthma in Melbourne schoolchildren, whereas the prevalence of eczema and allergic rhinitis has continued to increase.

Colin F Robertson MD, FRACP · Mary F Roberts BAppSci · Johanna H Kappers BNursSci

Objectives: (i) To evaluate the benefits and adverse effects of a Diabetes Day Care Program (DDCP); and (ii) to compare outcomes in two cohorts diagnosed before and after implementing the DDCP (“pre-DDCP” and “post-DDCP”).Design: Outcomes from the pre-DDCP cohort were compared with those of the post-DDCP cohort.Setting: The study was conducted from March 2001 to October 2002 at the Children’s Hospital at Westmead.Participants: The pre-DDCP cohort comprised all children newly diagnosed with type 1 diabetes from March 2000 to November 2000 (n = 49). The post-DDCP cohort were those diagnosed from November 2000 to August 2001 (n = 61).Main outcome measures: Length of stay, adverse events, insulin requirement and glycohaemoglobin (HbA1c) level over the first year after diagnosis were ascertained from medical records. Questionnaires to measure parents’ knowledge of diabetes, emotional adjustment to diabetes, and responsibility for and conflict over specific diabetes management tasks were completed by parents at 6-monthly intervals.Results: Median length of hospital stay decreased from 5.14 days (range, 2–10) to 1.70 days (range, 0–10) (P < 0.001). There were no differences between the two cohorts in insulin requirement at 12 months (pre-DDCP: 0.9 U/kg [95% CI, 0.8–1.0]; post-DDCP: 0.8 U/kg [95% CI, 0.7–0.9]; P = 0.22), HbA1c level at 12 months (pre-DDCP: 8.4% [95% CI, 8.0%–8.9%]; post-DDCP: 8.2% [95% CI, 7.9%–8.5%]; P = 0.37) and adverse events over the first year after diagnosis. Both groups reported similar scores for the parental questionnaires.Conclusions: Ambulatory stabilisation of children with type 1 diabetes provides similar metabolic outcomes for the child, and comparable levels of diabetes knowledge and similar psychosocial outcomes for the family, to inpatient stabilisation programs.

Shubha Srinivasan MB BS, FRACP · Maria E Craig FRACP, PhD · Linda Beeney PhD · Rachel Hayes MND · Nuala Harkin RSCN, APN · Geoffrey R Ambler FRACP, MD · Kim C Donaghue FRACP, PhD · Christopher T Cowell MB, FRACP

Even with new diagnostic modalities, autopsy remains an important tool for quality and safety assurance. A systematic review of reports from 1996 to 2002 found autopsies detected, on average, 23.5% of clinically missed diagnoses involving the principal or underlying cause of death, and 9% of errors that would or could have affected the patient’s outcome. We surveyed pathology laboratories and hospital administrators across Australia, and found a decline in the hospital autopsy rate from 21% (210/1000 deaths) in 1992–93 to 12% (118/1000 deaths) in 2002–03. This decrease is in adult autopsies (66% of all autopsies in 1992–93; 39% in 2002–03). Perinatal autopsies increased from 29% to 58% of all autopsies in this period, mainly due to more examinations of fetuses less than 20 weeks’ gestation. Factors contributing to this decline may include community attitudes, clinicians’ reluctance to request autopsy (partly because of administrative burdens in making the request), hospital concern about legal action if a misdiagnosis is detected, and funding priorities. Reversing this decline will require cooperative action at several levels of the healthcare system, and from government bodies.

The Royal College of Pathologists of Australasia Autopsy Working Party

QuestionWill implantation of defibrillators improve survival in patients with prior myocardial infarction and severely impaired left ventricular function? Trial detailsDesign: A prospective, randomised, non-blinded, multicentre, controlled trial of medical therapy versus implanted cardiac defibrillators (ICDs) in patients with severely impaired ventricular function resulting from prior myocardial infarction. Background: Patients with severely impaired left ventricular function are at high risk of sudden death from ventricular arrhythmias. The presence of spontaneous arrhythmias or arrhythmias induced at cardiac electrophysiological (EP) study identifies a high-risk group, but even in the absence of spontaneous or induced arrhythmias the risk of sudden death is considerable. The ICD is known to be effective in treating malignant ventricular arrhythmias. The MADIT-II trial was designed to evaluate the effect of an ICD on survival in patients with severe left ventricular dysfunction caused by previous infarction. Methods: 1232 patients from 76 sites were enrolled over 4 years. All had prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less, and were randomly assigned in a 3:2 ratio to receive a defibrillator (742 patients) or conventional medical therapy (490 patients). Spontaneous ventricular arrhythmias or EP testing were not required for entry into the trial. The primary endpoint was death from any cause. Results: The two treatment groups were similar at baseline with respect to clinical characteristics and medication use at the last follow-up. During a mean follow-up of 20 months, the mortality rate was 19.8% in the conventional therapy group and 14.2% in the ICD group. The hazard ratio for the risk of death from any cause in the defibrillator group compared with the conventional therapy group was 0.69 (95% CI, 0.51–0.93; P = 0.016). Subgroup analysis showed that defibrillator therapy improved survival regardless of age, sex, ejection fraction, New York Heart Association class or QRS interval. Conclusion: In patients with a prior myocardial infarction and advanced left ventricular impairment, prophylactic implantation of a defibrillator improves survival. CommentaryRationale for the trialFor several years, it has been routine clinical practice to implant ICDs in survivors of cardiac arrest or malignant ventricular arrhythmia. The prophylactic use of ICDs in high-risk patients who have not yet had a ventricular arrhythmia is more controversial. Patients with impaired left ventricular function are at high risk of malignant ventricular arrhythmias, but the implantation of a defibrillator is relatively expensive. There are large numbers of patients with impaired ventricular function, and to implant ICDs in all would place a considerable burden on the health budget. A possible solution is to identify those at highest risk using cardiac EP testing. The MADIT1 and MUSTT2 trials reported that ICDs improved survival in patients with coronary artery disease, reduced left ventricular function, non-sustained ventricular tachycardia, and inducible ventricular tachycardia at EP testing. Recent research, however, suggests that the EP study may be a relatively insensitive method of identifying those at highest risk.3 Moreover, it appears that the lower the left ventricular ejection fraction, the less sensitive the EP study becomes. The MADIT-II study was designed to investigate the potential survival benefit of ICDs in those without spontaneous arrhythmias and without performing EP testing.4 Trial methodsThe trial methods were relatively sound. The sample size (1232 patients from 76 sites in the United States and Europe) was adequate. Random allocation of patients resulted in well-matched treatment groups with similar baseline characteristics and similar medical therapy at last follow-up. Treating physicians were encouraged to prescribe effective drug therapy for heart failure and to minimise the use of conventional antiarrhythmics. Similar proportions in both groups received angiotensin-converting enzyme inhibitors, β-blockers and statins. Attendance rates at follow-up were 94% in the conventional therapy group and 97% in the defibrillator group. The trial was open label because blinding was not practical, but the primary end-point was unequivocal — death from any cause. However, a criticism is that mean follow-up was only 20 months, and this may impair assessment of cost-effectiveness. Another criticism is that when the trial commenced in 1997, a selection criterion was that patients have frequent spontaneous or repetitive ventricular premature contractions. This requirement was removed 6 months later, but only 23 of the 1232 patients were enrolled in those first 6 months. New informationThe trial showed that ICDs improve survival in patients with severely impaired left ventricular function caused by previous myocardial infarction, even in the absence of spontaneous arrhythmias or inducible arrhythmias at EP testing. A disturbing finding was that new or worsening heart failure requiring hospitalisation was more frequent in the ICD group. The cause of this is uncertain. One possible explanation is that the patients in the ICD group lived longer and therefore had more time to develop cardiac failure. Another is that the cardiac failure was caused by asynchronous ventricular contraction caused by ventricular pacing. The results of the recent DAVID5 trial tend to support the latter hypothesis. If this is indeed the case, the cardiac failure can probably be reduced by judicious programming of the pacing function of the ICD. Implications for clinical practiceThe routine use of ICDs in patients with an ejection fraction of 0.30 would have profound implications for healthcare spending. Routine use of ICDs for this indication would potentially increase the number of implants by a factor of between 10 and 30 per annum. Currently, about 950–1000 ICDs are implanted annually in Australia and New Zealand, at a total cost for hardware alone of about A$30 million (my estimates based on information obtained from device manufacturers). A 15-fold increase in the implantation rate would result in an increase in the annual cost for the hardware alone of about A$420 million. This is about twice the annual budget of a large Australian teaching hospital. This figure does not take into account the increase in hospital and professional fees. Moreover, it is uncertain that there are enough trained cardiac electrophysiologists to implant defibrillators in and follow up such a large number of patients. By comparison, Australian national spending on the lipid-lowering “statin” drugs in the 2001–2002 financial year was about A$670 million.6 Australian cardiologists have not yet embraced the findings of MADIT-II. This is probably because of the cost implications, preferring to wait until the findings are confirmed in other large trials. However, preliminary reports of the COMPANION7 trial appear to confirm the MADIT-II findings (the study populations of these two trials are not strictly comparable). The findings of another large trial of prophylactic ICD use, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), will soon be reported, and might shed additional light on this question. The true cost of implementing the MADIT-II findings awaits a detailed cost–benefit analysis. The cost of ICD hardware has been falling for several years, but it is difficult to predict the magnitude of future cost reductions. It may be possible to identify a low-risk cohort which will not benefit from ICD implantation, but the preliminary results are not encouraging. Recently, in the United States, the Centers for Medicare and Medicaid Services approved the use of ICDs in Medicare patients meeting the MADIT-II inclusion criteria and having a QRS duration of more than 120 ms. This decision was based, in part, on a subsequent analysis of the MADIT-II data, which showed that the benefit was greatest in this group of patients.8 The MADIT-II trial is likely to provoke vigorous debate over the best use of healthcare spending for some time to come.

Bruce P Wilson FRACP · Mark A McGuire PhD, FRACP

Clinical trials represent a major investment by investigators, sponsors and participants, and it is reasonable to attempt to gain the maximum information from them. Practitioners and regulatory agencies are keen to know whether there are subgroups of trial participants who are more (or less) likely to be helped (or harmed) by the intervention under investigation, and a recent survey of trials published over 3 months in four leading journals found that 70% included subgroup analyses.1,2 Furthermore, regulatory guidance documents (such as the Committee for Proprietary Medicinal Products September 2002 document Points to consider on multiplicity issues in clinical trials3) strongly encourage appropriate subgroup analyses. The results of subgroup analyses can also drive changes in practice guidelines. For example, the United States National Institutes of Health issued a clinical alert following the unexpected finding in the BARI (Bypass Angioplasty Revascularisation Investigation) trial that mortality after angioplasty in patients with diabetes was nearly double that after bypass-graft surgery (P = 0.003).4 Meaningful information from subgroup analyses within a randomised trial is restricted by multiplicity of testing and low statistical power. There is therefore a tension between our wish to identify heterogeneity in the responses of trial participants to trial interventions and our technical capacity for doing so. Surveys on the adequacy of the reporting of clinical trials consistently find the reporting of subgroup analysis to be characterised by poor practice.2,5-7 Item 18 of the CONSORT checklist (Box 1) deals with the multiplicity issues that arise in subgroup analysis.8 Problems in subgroup analysisThe problem of multiple testingStatistical investigation of large numbers of subgroups inevitably shows significant interactions with the effectiveness of the trial intervention. By definition, testing at the 5% level of significance will erroneously report a statistically significant difference between subgroup categories in about 5% of the tests performed (so-called false-positive results). Trials with multiple comparisons to assess the comparability of randomised groups at baseline confirm this prediction.1,9 In subgroup analysis, where a plethora of factors (eg, sex, age, race, centre, smoking status, stage of disease, and coexistent disorders) may influence outcome, the risk of false-positive results is high.10 Overly enthusiastic analysis of subgroups can reveal statistically significant differences in outcome between subgroups even where neither arm of the study receives any intervention.11 In some cases, such as in the ISIS-2 study, which found a slight adverse impact of aspirin therapy on patients born under the star signs Gemini and Libra, and that aspirin helped after the first, but not subsequent, infarctions,12 the results of the subgroup analysis may be dismissed as contrary to current understanding of biological mechanisms. In other cases, such as the BARI trial,4 whether the finding was valid could only be established by additional studies.13,14 The problem of statistical powerMost studies enrol just enough participants to ensure that the primary hypothesis can be adequately tested. Therefore, statistical tests on subgroups will have only power to detect substantially larger effects on the same endpoint. Loss of compliance, together with adjustments for multiple testing, will exacerbate this lack of power.6 In consequence, when tested separately, many of the subgroups will fail to show the statistically significant treatment effect that was shown in the main population; at the same time, genuine differences in response to treatment (so-called heterogeneity) between study subpopulations may also go undetected. Can the problems be overcome?Despite subgroup analyses generally lacking statistical power, when used repeatedly to look for differences across many factors (eg, sex, age, smoking status, blood pressure) they have a proclivity to detect spurious effects. We are thus forced to reconcile our wish to find genuine differences between subgroups with the need to minimise the risk of accepting and publishing false positives.2,6 One solution to this dilemma is to accept that the results of subgroup analysis are hypotheses. Guidelines such as those given in Box 2 are intended to help readers identify which hypotheses are strong and which are weak. However, even among experts, opinions range from only accepting pre-specified subgroup analyses supported by a very strong a priori biological rationale15 to a more liberal view in which subgroup analyses, if properly carried out and carefully interpreted, are permitted to play a role in assisting doctors and their patients to choose between treatment options.16 Trial designAre the subgroups appropriately defined?Subgroups based on characteristics measured after randomisation, such as compliance, should be avoided, as allocation to the subgroup may be influenced by the intervention. Similarly, it is preferable to use the intention-to-treat population, as reasons for withdrawal may not be balanced between treatment arms. For example, adverse drug events may be a more important reason for withdrawals from an active treatment arm, whereas lack of efficacy may be more important in a placebo-controlled arm.17 Were the subgroup analyses planned before commencement of the study?In general, subgroup analyses should be defined a priori and purposely on the basis of known biological mechanisms or in response to findings in previous studies. Ideally, the choice of the subgroups and the expected direction of the subgroup difference should be justified in the trial protocol. Where a particular subgroup analysis is of great interest, adequate power to show the results can be designed into the trial, for example by using an expanded endpoint for the subgroup analysis. At the other extreme, subgroup analyses that are decided on once the dataset has been examined should be treated with scepticism. Intermediate between these two extremes are cases, such as occurred in the BARI trial, in which the subgroup analysis, although not originally planned, was decided on during the course of the trial in response to findings in other studies (with the investigators remaining blinded to the interim results of BARI).4 ReportingThe study report should include all the information required to assess the validity of subgroup analyses reported. In particular, the number of subgroup analyses should be declared, as this will enable readers to assess whether the issue of multiple testing is being dealt with. Analyses planned a priori, and the rationale for choosing them, should be clearly stated. Summary data, including event numbers and denominators for all the subgroup analyses, even the uninteresting ones, should be included, as this will facilitate future meta-analyses of the data and help prevent publication bias.18 The impact of multiple tests on the chance of declaring as statistically significant at least one false-positive result is shown in Box 3. Statistical analysisSome investigators avoid the issue of multiplicity of testing by tabulating the observed outcomes for the subgroups of interest without undertaking any formal statistical analysis. The data become available for meta-analysis,18 but there is the disadvantage that the investigator may fail to detect and draw attention to an important heterogeneity in the population. The statistical methods used should be appropriate for the hypothesis being tested. The common practice of performing subgroup-specific tests of treatment effect is flawed in that it is testing the wrong hypothesis.19 The hypothesis that should be tested is whether the treatment effect in a subgroup is significantly different from that in the overall population.19 Testing for a statistically significant treatment effect in a subgroup is hindered by a small sample size. The appropriate tests to use when analysing heterogeneity of responses among subgroups are interaction tests,2,10 for which worked examples are available.19,20 One study found that these were used in only 43% of 35 trials which reported subgroup analyses in their sample.2 Finally, the article should state whether the statistical tests used included adjustments for multiplicity. InterpretationBecause subgroup analyses have less power to detect a therapeutic effect than the main study, the trial report, especially in the Abstract or Conclusions, should emphasise the overall result. Given the risks of false-positive findings when multiple subgroup analyses are performed, it is not surprising if a subgroup-specific test shows a significant (P < 0.05) or suggestive (P = 0.05 to P = 0.10) effect of treatment, even when the trial failed to do so overall.2,7 Investigators are often tempted to highlight a particular subgroup analysis.2,7 For example, in one trial the suggestion that a psychosocial nursing intervention following myocardial infarction was harmful for women (P = 0.064), but not men (P = 0.94), was highlighted, even though the intervention did not affect survival in the overall population21 (and a test for interaction was not significant2). A number of arguments may be used to support the validity of a claimed subgroup effect (see, for example, the BARI trial4 and Rathore et al22): replication in another independent study; the presence of a dose–response relationship; reproducibilty of the observation in independent samples within the study, such as within individual sites; and the availability of a biological explanation. Of these, the first is the strongest evidence. For example, even though the BARI study found no difference in survival following bypass surgery or angioplasty in the overall population, the validity of the subgroup findings was supported by other studies.4 On the other hand, the report by Rathore et al that digoxin use is associated with a significantly increased risk of death among women (P < 0.014)22 is weakened by the fact that it was a post-hoc analysis which was motivated by “biological suspicion” rather than by suggestive findings in earlier trials. Biological justifications for the findings of a posteriori (exploratory) analyses, on the other hand, carry little weight6,23 — the reports that diabetes is more common in boys born in October,24 and that lung cancer is more common in people born in March,25 included (in)credible biological explanations after the findings had been revealed. The strategies for overcoming some of these difficulties in interpreting subgroup analyses will be explored in a forthcoming article in this series. 1: CONSORT checklist of items to include when reporting a trial8 Selection and topic Item no. Descriptor Ancillary analyses 18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating those pre-specified and those exploratory. 2: Checklist for subgroup analyses Design Are the subgroups based on pre-randomisation characteristics? What is the impact of patient misallocation on the subgroup analysis? Is the intention-to-treat population being used in the subgroup analysis? Were the subgroups planned a priori? Were they planned in response to existing trial or biological data? Was the expected direction of the subgroup effect stated a priori? Was the trial designed to have adequate power for the proposed subgroup analysis? Reporting Is the total number of subgroup analyses undertaken declared? Are relevant summary data, including event numbers and denominators, tabulated? Are analyses decided on a priori clearly distinguished from those decided on a posteriori? Statistical analysis Are the statistical tests appropriate for the underlying hypotheses? Are tests for heterogeneity (ie, interaction) statistically significant? Are there appropriate adjustments for multiple testing? Interpretation Is appropriate emphasis being placed on the primary outcome of the study? Is the validity of the findings of the subgroup analysis discussed in the light of current biological knowledge and the findings from similar trials? 3: Probability of at least one significant result at the 5% significance level given no true differences Number of tests Probability 1 0.05 2 0.10 3 0.14 5 0.23 10 0.40 20 0.64

David I Cook MD, FRACP · Val J Gebski BA, MStat · Anthony C Keech MScEpid, FRACP

Compassion for those with hepatitis C and accurate information about preventing its transmission will also benefit the wider community My GP’s rooms were the last place I would have expected to feel like a leper because I was sick, but that’s my story, and unfortunately it’s a fairly common one among people living with hepatitis C (HCV).1 Discrimination against people who are HCV-positive is not confined to healthcare settings, but this is where it is most often reported,2 partly because it’s the context in which affected people are most likely to disclose their condition. Discrimination also rears its ugly head at home, in social situations, at work, school, in the media and when we attempt to access services, such as insurance. It even clings to people beyond death, with families of people with HCV sometimes being refused viewings of their loved ones’ bodies, even though this is inconsistent with public health regulations. Several Australian government reports and a growing body of social research identify hepatitis C-related discrimination as an epidemic in its own right,3 and show that stigmatisation has detrimental effects on people’s health and quality of life,1 as well as significant social and economic costs.4 When the NSW Anti-Discrimination Board announced its world-first enquiry into hepatitis C-related discrimination in 2001, I decided to make a submission about my experience of being diagnosed with HCV. The Hepatitis C Council of NSW knew my story and that, as a journalist, I would be comfortable dealing with my colleagues, so I was asked if I would talk to the media to raise awareness of the enquiry and the issues it was investigating. Although there are an estimated 225 000 people in Australia with hepatitis C,5 many fear the consequences of disclosure in their daily lives, so very few are prepared to publicly identify themselves as HCV-positive. Since agreeing to talk to the media, I have been invited to tell my story many times. It is always rewarding work, because, as HIV/AIDS-positive speakers throughout the world have demonstrated,6 presenting a personal experience of living with an infection like HCV not only educates audiences about the disease and prevention strategies, but also challenges negative stereotypes that result in discrimination. I was diagnosed in March 2000 by the GP I had consulted for 7 years. She was used to me complaining of extreme tiredness, for which she diagnosed “some sort of virus” and recommended a few days off work. However, in January 2000, I felt as if I had aged 60 years in a couple of months. Vomiting after lunch was becoming routine. I had three weeks off work, but it made little difference to how I felt. I went back to the doctor in March to request a hepatitis C test because I had met a woman who was HCV-positive. She had described the debilitating symptoms that had forced her to give up her career as a medical practitioner, and I identified with them all, so I knew I had to be tested. Back in 1985, before hepatitis C got its name and before there was a test for it, I took heroin for a few months. When I sought help, my drug use was treated in a non-judgemental way by my family, a fabulous GP and a psychiatrist. I received excellent care and emerged with my self-respect intact and my body in good shape. Or so I had thought for 15 years. In 2000, my doctor’s response to my request for an HCV test was “you wouldn’t have that”. My subsequent admission of injecting drug use all those years ago was met with silence, but she ordered the test. When I went back for the results it seemed that she didn’t want to know about me or my illness, despite the fact that I was very sick. She offered almost no information at all about the virus, explaining that she “just doesn’t see it” in her surgery, and handed me a brochure produced in 1991, which said there was little in the way of treatment, that the prognosis was not good, and that the highest risk group was homosexual men. All of this was simply untrue in 2000, but I did not know that then. I felt that my GP’s diagnosis was not that I had a serious liver disease, but an untreatable moral malady. If I had been one of the many people who are diagnosed before they experience any symptoms, I would have left her rooms, not told a soul and tried to forget all about it. I didn’t go home filled with righteous indignation and contempt for my doctor that day. I was consumed with self-loathing — I felt like a piece of human debris, unclean and totally unworthy. But the gods were smiling on me. It was 27 March 2000 — the day the New South Wales Health Department launched the world’s first hepatitis C mass media public awareness campaign. On the news, doctors were talking about treatment and there was some discussion about discrimination. I rang the Hepatitis C Council of NSW helpline the next day and received accurate information, support, and referral to my local liver clinic. I was on the road to recovery, but the shame I felt about my positive status was hard to overcome. After my experience with my GP, I was wary of people finding out about my illness. Sometimes I still am. In the past four years I’ve met lots of people with hepatitis C, and many of them express shame and fear because they have had such negative experiences when they disclosed their HCV status. There were people in my treatment support group who expressed the medieval notion that their illness was direct punishment for their “sins” and that they deserved to suffer and to be treated poorly because they had injected drugs in the past. The NSW Anti-Discrimination Board enquiry into hepatitis C-related discrimination in 2001 found two reasons for discrimination.2 It heard evidence of many cases of stigmatisation as a result of ignorance about the virus and how it is transmitted, but it was the close association between injecting drug use and HCV infection that was found to be the main reason why people with hepatitis C were treated in a discriminatory manner. Its report, C-change, says much more needs to be done to educate the general community, and especially healthcare workers, about what hepatitis C is, how it is contracted and who contracts it. This requires the political will to change things, but is not an insurmountable problem. However, the enquiry found that the perception of people with hepatitis C as being “somehow deviant and automatically engaged in illegal or criminal behaviour” is far more difficult to tackle.2 It is acceptable to vilify very few groups within society these days, but people seem to feel it is quite reasonable to denigrate injecting drug users because their behaviour is illegal and highly stigmatised. In his introduction to the NSW Anti-Discrimination Board report, former president Chris Puplick comments: “Were this nexus to be severed, either by means of legislative change or by changes in perceptions, attitudes and responses, then most of the problems identified in the C-change report would be more easily resolved”.2 There is little hope of this vision being realised in the short term. I believe the Australian Government’s proposed Disability Discrimination Amendment Bill7-9 aims to overturn a Federal Court decision in 2000 that found addiction to a prohibited drug could be regarded as a disability.10 If the bill becomes law, illicit drug users (and their families) could, in some circumstances, face legalised and institutionalised discrimination. Healthcare workers have voiced concerns that such an amendment may result in the increased spread of bloodborne viruses, such as hepatitis C, and limit access to drug treatment programs.7 The illegal status of injecting drug use already results in negative health outcomes for many people with hepatitis C, especially if they are current injecting drug users.11 Quite simply, many do not attempt to seek medical treatment unless they absolutely have to, and, when they do, they sometimes report receiving very shoddy treatment. The Disability Discrimination Amendment Bill and the Federal Government’s rejection of evidence-based recommendations, such as harm minimisation, for combating the HCV epidemic stand in stark contrast to Australia’s highly successful response to HIV/AIDS. This response depended to a large extent on legislative action by Australian governments, in particular the repeal of laws that made homosexuality illegal and discrimination acceptable. A recent study has found that discrimination against people who are already vulnerable because they are ill can be “a profoundly negative experience”.11 This is so not only for the person with hepatitis C, but for the wider community as well, because access to information about preventing transmission is compromised when people are afraid of dealing with healthcare services.11 Around 40% of the relatively small number of people who undergo treatment become free of the virus.12 I consider myself extremely fortunate to count myself as one of them. The side effects of treatment12 were extremely difficult during my 48 weeks of therapy, but it was worth it. I have been free of the virus since 2001, and feel better than I have for many years. It’s wonderful to have a happy ending to share when I talk publicly about living with hepatitis C, but I hope the audience understands that it was not just the medicine that made me better. Love, understanding and compassion are great healers that many with hepatitis C just don’t experience.

Lisa Waller BA

Clinical recordA 56-year-old woman presented to her general practitioner a fortnight after a trip to Bali. She had a 2-week history of profuse loose brown stools, lethargy, weakness, nausea and some dyspeptic symptoms. The diarrhoea had initially settled with loperamide, but then recurred. A faecal specimen was collected for microscopy, culture and testing for enteric viruses, all of which gave negative results. Routine blood tests showed mild iron deficiency with no anaemia. Serum levels of vitamin B12 and folate were in the reference ranges. Serological testing for Toxoplasma and Cytomegalovirus showed no evidence of recent infection. An initial course of metronidazole for presumed Giardia infection was unhelpful, and she was referred for further gastroenterological evaluation. At the time of review by the gastroenterologist, she had had persistent diarrhoea for nearly 4 weeks. Thyroid, respiratory, abdominal and cardiovascular examination gave unremarkable results. A faecal enzyme-linked immunoassay analysis for Giardia antigens gave negative results. Gastroscopy showed mild diffuse gastritis, and a rapid urease test for Helicobacter pylori was negative. The duodenum appeared normal, and small-bowel biopsy specimens were sent for disaccharidase testing and histopathological examination. No abnormalities were seen on colonoscopy. Faecal fluid was collected and sent in formalin for saline–acid fixation faecal testing. Examination of small-bowel biopsy specimens showed moderate villous blunting with increased intraepithelial and lamina propria lymphocytes and no evidence of dysplasia or malignancy, no granulomas or parasites. The report concluded that this appearance was very suggestive of coeliac disease. (Figure 1). However, examination of the faecal specimen in saline–acid fixative revealed oocytes of Cyclospora cayetanensis (Figure 2). 1: Small-bowel biopsy specimens taken before and after treatment with trimethoprim–sulfamethoxazole, showing moderate villous blunting before treatment (left) and normal architecture after treatment (right) (original magnification, x 50). 2: Oocysts of Cyclospora cayetanensis (left) and Cryptosporidium parvum (right), showing size difference (original magnification, x 1000). A diagnosis was made of small intestinal villous atrophy secondary to C. cayetanensis infection. The patient was treated with trimethoprim–sulfamethoxazole (800 mg/160 mg twice daily for 5 days). Her symptoms resolved within days. Serological tests and a repeat small-bowel biopsy were undertaken to exclude latent coeliac disease. Serological testing was negative for antigliadin and antiendomysial antibodies, and there was no evidence of residual villous atrophy in the biopsy specimen (Figure 1). The patient remained well on follow-up after completing the course of antibiotics. This case of protracted diarrhoea in an Australian traveller initially appeared consistent with coeliac disease. Further analysis revealed infection with Cyclospora cayetanensis, which was successfully treated with antibiotics. The increasing number of documented outbreaks of Cyclospora infection,1 and the need for special preparation of stool samples for their detection,2 highlight the importance of a high degree of suspicion in cases of traveller’s diarrhoea. C. cayetanensis is a protozoan which was first recognised as a human intestinal parasite in the early 1990s.3 In 1994, Butcher et al described the first case in an Australian traveller of explosive diarrhoea caused by a large acid-fast spherical organism that had only recently been classified as a member of the genus Cyclospora.4 Since then, reports of outbreaks of Cyclospora infection have increased,1 presumably due to greater awareness of this parasite. Outbreaks have been reported from many parts of the world, including North, Central and South America, Europe, South East Asia, India, South Africa, and the Caribbean Islands.5,6 The mode of transmission is thought to be faecal–oral, or via ingestion of contaminated water. The mechanism by which the protozoan causes villous atrophy is not well understood, but organisms have been found at the site of inflammatory changes. Like Cryptosporidium spp. (which are morphologically similar [Figure 2]), Cyclospora spp. cause nausea, profuse diarrhoea and weight loss, as well as profound fatigue. Abdominal pain and bloating can manifest as “indigestion” or “heartburn”. If untreated, symptoms last for 6 weeks to 3 months (longer in the immunocompromised), and can be mistaken for irritable-bowel syndrome. The treatment of choice is trimethoprim–sulfamethoxazole, with ongoing prophylaxis for patients with AIDS.7 Clinicians need to be aware that the histopathological appearance of the small intestine in C. cayetanensis infection is similar to that in coeliac disease. Other causes of small-intestine villous atrophy include viral enteritis, giardiasis, and cows’ milk allergy. Hence, diagnosis of coeliac disease should not be based purely on the finding of villous atrophy. Investigations that we used to test the diagnosis in this patient included a highly specific immunoassay for giardia antigens, as well as testing for antiendomysial and antigliadin antibodies to disprove coeliac disease definitively. However, the clinical history (particularly onset and duration of illness) needs to be considered before requesting these tests. In the setting of recent travel or a community outbreak, a high index of suspicion for infectious causes of villous blunting is warranted. Despite the increasing knowledge about the genus Cyclospora, many infections are missed, as the parasite can be difficult to detect in human faecal samples. Clinicians need to be aware that acid-fast staining is required, and that this requires preservation of the faecal specimen in formalin.3 It is also important to realise that Cyclospora oocysts are usually shed in low numbers, even when the patient is very ill. In addition, faecal specimens sent to pathology laboratories for examination for ova and parasites are commonly not examined for Cyclospora spp. Hence, Cyclospora testing must be specifically requested.2 Finally, laboratory investigators need to be aware that Cyclospora cysts are morphologically similar to cysts of Cryptosporidium parvum. The most obvious difference is size, as Cyclospora cysts are larger (8–10 μm) than Cryptosporidium cysts (4–6 μm) (Figure 2). It is important to differentiate the two, as Cyclospora infection can be treated with antibiotic therapy, whereas management of Cryptosporidium infection is largely supportive.5 Dialogue between the clinician and pathologist can help to avoid confounding diagnoses. Newer techniques, such as polymerase chain reaction (PCR) testing for parasite DNA, are currently being developed, but are expensive and may not be available in a routine laboratory. Lessons from practice Cyclospora cayetanensis was relatively recently recognised as an intestinal parasite that causes protracted diarrhoea. Beware of histological and clinical overlap with other conditions, including coeliac disease, cryptosporidiosis and irritable-bowel syndrome. Cyclospora organisms can be difficult to detect: faecal specimens need to be transported in a saline–acid fixative, and examination for Cyclospora needs to be specifically requested. Treatment is a 7–10-day course of trimethoprim–sulfamethoxazole.

Vidyut Pinge-Suttor BSc(Med), MB BS · Chris Douglas FRCPA(App) · Antony Wettstein FRACP

All women and men with a history of fragility fractures should be considered for treatment of osteoporosis to reduce their risk of future fracture. There is high-level evidence for the anti-fracture efficacy of treatment in women with osteoporosis, particularly if there is prevalent fracture; the evidence is less compelling for women with osteopenia, with or without a fracture, and for men. The rigorously investigated drugs reported to reduce vertebral fractures are the bisphosphonates alendronate and risedronate, the selective oestrogen-receptor modulator raloxifene, the anabolic agent parathyroid hormone and, most recently, strontium ranelate. Only the two bisphosphonates and hormone replacement therapy (HRT) have been reported to reduce hip fractures in community-dwelling women, and calcium plus vitamin D and hip protectors have been reported to reduce these fractures in elderly people in institutions. HRT is not recommended in women for fracture risk reduction alone. Evidence for the anti-fracture efficacy of calcitonin, fluoride, anabolic steroids and active vitamin D metabolites is insufficient to justify their use; lifestyle changes, while not shown to reduce fracture risk, may have a role in maintaining bone strength throughout life.

Ego Seeman BSc, FRACP, MD · John A Eisman FRACP, PhD

Kerry-Ann F O’Grady,* Terence M Nolan† * Senior Research Officer, Vaccine and Immunisation Research Group, Murdoch Children’s Research Institute, Flemington Road, Parkville, VIC 3052; † Head, School of Population Health, University of Melbourne, Melbourne, VIC. k.ogradyATunimelb.edu.au To the Editor: In Australia, personal and health information that identifies an individual cannot be used or disclosed for research without specific requirements being met.1 Even if these requirements are met, data custodians may still refuse access if their views are discordant with those of the relevant human research ethics committee (HREC). It is now evident that there are adverse consequences of this well-meaning legislation. Our research group conducts community-based vaccine trials. Recently, we attempted to use school enrolment lists to mail information to parents about a study. Despite approval from the Royal Children’s Hospital HREC, one major governing body of Victorian public schools rejected our proposal on privacy grounds, as did several independent schools. Only a small number of schools raised no privacy concerns at all. The main concern expressed was that the use of these registers for health research was not related to the primary purpose of collection, and families had not consented to this use. The net result was substantially reduced access to the population eligible for recruitment. We now have a situation in which the legislation may actually do more harm than good. This is an emerging issue here in Australia and overseas.2,3 Even more worrying are the findings of an Australian survey in which 61% of adults believed that even their de-identified health information should not be used for research purposes without their consent.4 Health research is dependent on access to population datasets to recruit participants, monitor health indicators, identify risk factors and inform interventions. Non-representative access threatens a study’s validity, resulting in poorly informed interventions, policy and funding decisions. The situation may now have progressed beyond reasonable trade-offs between the public good and individual privacy to the point where important research cannot be done at all, and the opportunity for advances in health are lost. Despite statutory guidelines,1,5 there are widespread differences in interpretation of the legislation, particularly regarding the terms “practicable” and “public good”. Amendment of the legislation in this respect is therefore urgently required, together with clauses which facilitate a researcher’s ability to inform the public of a particular project and enable individuals, not organisations, to decide whether they wish to participate. There needs to be greater effort in gaining public understanding of the legislation and its intent with respect to research. In addition, upfront declarations and “opt-out” clauses about the use of personal information for health research must also be included in the privacy statements that organisations are now legally required to provide to individuals at the point of data collection.

Kerry-Ann F O’Grady · Terence M Nolan

Paul Chadwick,* Beth Wilson† * Information Privacy Commissioner, † Health Services Commissioner, Office of the Victorian Privacy Commissioner, GPO Box 5057, Melbourne, VIC 3000. enquiriesATprivacy.vic.gov.au In reply: We are familiar with concerns such as those expressed by O’Grady and Nolan, and we are grateful for this opportunity to respond, so that readers can consider the views side by side. Privacy is not new. Ethical obligations of confidentiality in medical settings date back to Hipprocrates. New privacy legislation — Health Records Act 2001 (Vic); Information Privacy Act 2000 (Vic); Privacy Act 1988 (Cwlth) — clarifies these obligations and also sets a higher standard of accountability. (Other states and territories also have legislation or are contemplating it.) The new laws cover all sorts of personal information, but health information is especially delicate. Wrongly handled, it can lead to discrimination — not just embarrassment or loss of dignity. In Victoria, this was recognised by Parliament when it passed the Health Records Act as a separate piece of legislation to deal specifically with health information. The policy behind the privacy laws is aimed at promoting trust between health service providers and the public by reassuring them that their personal information will be respected, particularly in an electronic age in which information can be speedily transmitted far and wide. If surveys show the public to be wary about the use of their health information for research, it would seem to be in the best interests of the research community to embrace new standards rather than to seek to unravel or avoid them. Privacy legislation was drafted after extensive consultation, taking into account competing factors and the need to balance respect for privacy with other public interests, including research. Research is very important, and privacy is a cherished and longstanding value. Reputable research can coexist with the recent statutory expressions of privacy, just as reputable research has always coexisted with respect for privacy. Many data custodians perhaps do not yet realise that privacy laws rarely require an existing legitimate practice to cease completely, but rather may require the practice to be adapted to meet new standards. For example, for researchers seeking to recruit subjects for a study, the data custodian may disseminate the researchers’ initial letter rather than hand over lists of names and addresses to researchers. Once recipients opt in, direct consensual dealings with the researchers proceed as usual. Researchers can always use properly de-identified information, or they may use information with the consent of the subject. As with all new laws, the privacy laws will become better understood with time and experience. Some data custodians are understandably overcautious, while others have blamed privacy laws for preventing them from providing information in situations in which disclosure is permitted. Many adapt with ingenuity and effectiveness. Privacy Commissioners and the Health Services Commissioner are available to explain the laws. We, along with everyone with an interest in collecting and using the sensitive information of others, must recognise and consider the subtleties inherent in balanced privacy protection.

Paul Chadwick · Beth Wilson

Robert N Atkinson Orthopaedic Surgeon, 135 Hutt Street, Adelaide, SA 5000. wattle135ATozemail.com.au To the Editor: In response to Leeder,1 there is no community in this world that can provide free, at the point of contact, healthcare for all its citizens to the current limits of modern medical technology. This problem will in fact become greater as the technology increases and becomes more expensive. Within the available healthcare resources, there is some medical treatment that is essential and there is some that is quality-of-life treatment; where the two merge depends on one’s point of view. If you choose to play sport and injure your knee, the question of who should pay for the treatment arises. If you smoke or have any other lifestyle risk factors, how much should be funded by you, and how much by others? And, within a healthcare system where there is patient contribution, does this contribution empower and encourage individuals to adopt a healthy lifestyle? In essence, I believe the debate in healthcare should be about accessibility of limited resources. Who draws the line, how is the line drawn, and at what level is it drawn? Pouring money into the public health sector may well parallel the analogy of adding another lane to the motorway. We must be careful to share the responsibility of healthcare between the individual and the healthcare providers in an inclusive and not exclusive manner.

Robert N Atkinson

Elizabeth Harris,* Sarah J Simpson,† Rosemary Aldrich,‡ Jenny Stewart Williams§ * Director, † Program Manager, Centre for Health Equity Training Research & Evaluation (CHETRE), University of NSW, LMB 7103, Liverpool BC, NSW 1871. ‡ Conjoint Academic, School of Medical Practice and Population Health, § Research Officer, Newcastle Institute of Public Health; University of Newcastle, Newcastle, NSW. elizabeth.harrisATswsahs.nsw.gov.au To the Editor: Leeder rightly points out that increased funding of the healthcare system does not necessarily result in improved equity within the health system or better health outcomes for the population.1 This challenges us to develop ways of systematically examining how current healthcare practices either increase or decrease equity. The following two Australian initiatives illustrate how we might work to achieve equity in health — that is, provide opportunities for all Australians to achieve their full health potential.2 Clinical practice guidelines (CPGs) are one mechanism frequently used to facilitate improvements in the quality of clinical practice and healthcare. However, the evidence on which CPGs are based often excludes, or does not consider, the needs of relatively disadvantaged populations.3-5 Recognising this gap, the Health Advisory Committee of Australia’s National Health and Medical Research Council published a handbook for developers of guidelines about ways to access, review and collate evidence of the effect of socioeconomic position on health, and apply that evidence when developing CPGs.5,6 At the policy level, Health Impact Assessment (HIA) is gaining increasing recognition as a tool for assessing the potential effects of a policy or program on health. Health Impact Assessment that systematically addresses equity may also offer a way of incorporating equity concerns into the decision-making process. However, HIA is a comparatively new field, and decision makers are not usually trained in assessing the impact of policy decisions on equity. Through the Public Health Education and Research Program, the Australian Government has commissioned the development of an HIA framework to assist decision makers in systematically identifying potential health equity impacts of policies. This equity-focused HIA framework is currently being tested (through case studies in Australia and New Zealand) to assess whether and where it adds value to the decision-making processes. These two examples illustrate practical ways in which decisions by practitioners and policy makers can routinely incorporate equity issues in the Australian healthcare system. Ongoing investment and commitment is required to evaluate whether such initiatives make a real difference in achieving equity in health.

Elizabeth Harris · Sarah J Simpson · Rosemary Aldrich · Jenny Stewart Williams

James Tibballs,* Sharon Kinney† * Associate Director, Intensive Care Unit, Royal Children’s Hospital, Flemington Road, Parkville, Melbourne, VIC 3052; † Lecturer, School of Nursing, University of Melbourne, Melbourne, VIC. james.tibballsATrch.org.au To the Editor: The introduction of a medical emergency team (MET) at the Austin Hospital significantly reduced cardiac arrest and deaths, and reduced time spent by survivors of cardiac arrest in the intensive care unit (ICU) and in hospital.1 We note that the evaluation of the MET was preceded by a 12-month period of education and a 2-month “run-in” period before the effects of the MET were analysed. We would be interested to know the incidence of death and cardiac arrest, and the duration of ICU and hospital admission in survivors of cardiac arrest during these two periods. Another MET service also claimed substantial benefits in patient outcomes,2 but was criticised on the basis that the results may have been due to better education of ward staff in recognising the antecedent signs of cardiac arrest and/or the creation of more “do-not-resuscitate” orders.3 While the latter criticism cannot be levelled at the study by Bellomo et al, no attempt is made to separate out the effects of the lengthy education period and the operation of the MET. This is a pity, because it would have been a relatively simple matter to do so without detracting from the obvious benefit of the service. Why was a 2-month “run-in” period between education and operation of the MET allowed before analysis of results? Was this a post-hoc decision or were there foreseeable difficulties during the introduction of the MET? Did patient outcomes change during these two periods compared with the period before the MET?

James Tibballs · Sharon Kinney

Rinaldo Bellomo Director, Department of Intensive Care, Austin and Repatriation Hospital, Studley Road, Heidelberg, VIC 3084. Rinaldo. BELLOMOATarmc.org.au In reply: Tibballs and Kinney raise important questions about our trial of a medical emergency team (MET).1 My colleagues and I are, in fact, currently studying these issues. Preliminary (not fully double-checked) data show that during the education period there were 69 cardiac arrests — an average of 23 cardiac arrests per 4-month block. This is a clear reduction from the 63 recorded during the 4-month control period and similar to the 22 cardiac arrests reported during the 4-month MET period. These 69 cardiac arrests led to a total of 227 intensive care unit bed-days or a 75 bed-day average for each 4-month block, about 50% of the number recorded during the control period, but more than twice as many as during the MET period. These patients remained in hospital for a total of 986 hospital bed-days or 328 days per 4-month block, close to an 80% reduction compared with our control period, and twice as many as the number achieved during the MET period. Unfortunately, although we are pursuing mortality data, we won’t be able to provide them for another 6 months because of a changeover in the computer system at our hospital. Tibballs and Kinney are invited to contact me directly by mid-2004. The 2-month run-in period was chosen prospectively, as we expected that the uptake of the MET (a major change of culture) might be slow and require time and encouragement. We were wrong: the MET was taken up with zest and enthusiasm. The histogram (Box 4) in our article1 shows no cardiac arrests during the run-in period, not because they were not recorded, but because there were literally none for 2 months in a row! Obviously, there were also no post-cardiac-arrest bed-days. Again, mortality figures for this period should be available by mid-2004. As we stated in the Discussion of our article, the educational program associated with the MET may indeed have been partly responsible for the findings. We were careful at all times to say that introducing the MET was effective, not the MET per se (see Conclusion).1 We are not aware of any prospective studies testing the effectiveness of introducing a hospital-wide education program aimed at increasing awareness of the significance of physiological instability. Our findings support a powerfully beneficial role of education, but only represent a post-hoc analysis and require validation in other settings and institutions. The role of education was prospectively and separately investigated in the recently completed multicentre cluster-randomisation MERIT study (Medical Early Response Intervention and Therapy). Its results should be available in the second half of this year.

Rinaldo Bellomo

Timothy H J Florin Director of Gastroenterology, Department of Medicine, University of Queensland, Mater Health Services’ Adult Hospital, South Brisbane, QLD 4101. t.florinATuq.edu.au To the Editor: In their article on adoption of celecoxib and rofecoxib by Australian general practitioners, Kerr et al noted that “the increase in COX-2 [cyclooxygenase-2] prescribing coincided with a period of energetic marketing to the medical profession, which promoted the message that the new C2SNs [COX-2-selective non-steroidal anti-inflammatory drugs] were ‘safer’ than traditional NSAIDs [non-steroidal anti-inflammatory drugs].”1 The implication is that the decision of Australian GPs to prescribe these new drugs may have been less than independent or rationally informed. The reason for prescribing C2SNs is that, like traditional NSAIDs, they relieve arthritic pain and so promote mobility, although, unlike traditional NSAIDs, they do not inhibit cyclooxygenase-1. While the power of advertising is undeniable, the simple message about C2SNs is that there is an approximate 50% reduction in clinically significant gastrointestinal (GI) complications compared with traditional NSAIDs.2 There are over a dozen articles to support the better GI side-effect profile of C2SNs. Most data support a non-cumulative, reversible, but constant, risk of peptic and other, more distal GI bleeds, or perforation, with the coefficient of risk being significantly greater for NSAIDs.3 Although the data from the CLASS study did suggest that the higher GI morbidity of NSAIDs seemed to diminish with time,4 that of celecoxib remained at a constantly lower rate.5 This is clinically important for all our patients, and especially for our ageing population with their comorbid conditions and polypharmacy. I suggest that it is for this single reason that many doctors have been quick to take up C2SNs for their patients. The better GI safety enfranchised patients who previously could not take NSAIDs safely, and could explain why the overall anti-inflammatory market increased by 20%.1 However, no one suggests that the C2SNs are free of non-GI side-effects. To the best of my knowledge, COX-2-specific NSAIDs have not been promoted as being free of non-GI side-effects or better than COX-1-specific NSAIDs in this regard. While agreeing with the last sentence of Dowden’s editorial that “new is not always better”,3 the opposite — that “new is sometimes better” — is also true. Thus, we persuaded the accountants in our hospital, who rightly participate in the determination of which drugs are available on its formulary, to accept one of the COX-2 drugs because of its better GI complication profile. While this will not reduce its pharmacy budget, it is anticipated to reduce overall hospital costs in this area,5 which should allow a reapportionment of its budget to other areas of need. Of course, the hospital is watching carefully for any unforeseen “serious adverse effects which sometimes only emerge after marketing”.3

Timothy H J Florin

Stephen J Kerr,* Andrea Mant,† Fiona E Horn,‡ Kevin McGeechan,§ Geoffrey P Sayer¶ * Decision Support Coordinator, National Prescribing Service, PO Box 1147, Strawberry Hills, NSW 2012; † Area Advisor, Quality Use of Medicines, South East Health, Sydney Hospital, Sydney, NSW; ‡ Research Analyst, § Senior Research Analyst, ¶ General Manager — Research, Health Communication Network, St Leonards, NSW. skerrATnps.org.au In reply: The advantage of the COX-2-selective NSAIDs (C2SNs) is the reduction in clinically significant gastrointestinal complications compared with conventional NSAIDs, but, as Florin agrees, other toxicities, including the risk of renal failure and heart failure, are similar for C2SNs and the older drugs.1 We speculated that doctors may have been more aware of the differences between the new and the conventional anti-inflammatories rather than the similarities: between 4.7% and 7.9% of patients in our study cohorts were treated with a combination of drugs which placed the patient at risk of renal complications. Florin points out that there is an approximate 50% reduction in clinically significant gastrointestinal (GI) complications with C2SNs compared with conventional NSAIDs. If, in a population, the annual incidence of serious GI complications with NSAID use is around 1.4%,2 then the absolute risk reduction is 0.7%. This means that about 140 patients would need to be treated with a C2SN for one year to prevent one serious GI complication. Messages conveyed in this way may be more pertinent to clinical decision making than a statement about relative risk reduction. Florin also notes the problems with elderly patients who often take multiple medications, and are probably at increased risk of upper-GI events with NSAIDs. Our data demonstrated very high prescribing rates in patients who were not elderly. Over 20% of patients in our cohorts were aged less than 50 years, and over 50% were aged less than 65 years. Furthermore, between 34.5% and 61.3% had no pain medication prescribed in the 12 months before the first C2SN prescription, suggesting that C2SNs may have been used as a first-line pain medication in these patients. Quality use of medicines advocates prescribing which is safe, judicious, effective and cost-effective. Recent pharmacoeconomic studies suggest the cost-effectiveness may only be realised when prescribing of C2SNs is confined to patients who are at high risk of GI complications.3,4

Stephen J Kerr · Andrea Mant · Fiona E Horn · Kevin McGeechan · Geoffrey P Sayer

John S Dowden Editor in Chief, Australian Prescriber, Suite 3/2 Phipps Close, Deakin, ACT 2600. jdowdenATnps.org.au In reply: The general practitioners’ decision to prescribe COX-2 inhibitors was rational, but the information underpinning their decision was less than independent. A big reduction in short-term relative risk can be persuasive, even if the absolute benefit is small. General practitioners deal with whole patients, so they consider the overall risks of treatment, and not just one adverse effect. While COX-2 inhibitors may have gastrointestinal advantages, they may have cardiovascular disadvantages. Treatments for chronic conditions should be based on long-term data. The observation that most of the ulcer complications in the second half of the CLASS study were in patients taking celecoxib is therefore important.1 Undoubtedly, some patients who could not take non-selective non-steroidal anti-inflammatory drugs (NSAIDs) were able to tolerate COX-2 inhibitors. However, Kerr et al found that up to 61% of patients given a COX-2 inhibitor had not previously been prescribed any analgesia.2 It seems unlikely that so many people suddenly required analgesia that only a COX-2 inhibitor could provide. The Pfizer-funded study by MacDonald et al shows that UK general practitioners tended to prescribe COX-2 inhibitors for patients at risk of gastrointestinal haemorrhage.3 This follows the advice of the National Institute of Clinical Excellence (NICE). However, NICE also recommended against the routine use of COX-2 inhibitors.4 A review by the Canadian Co-ordinating Office for Health Technology Assessment has also concluded that COX-2 inhibitors may have no significant safety advantage over diclofenac.5 Solomon et al conclude that the cost of adverse effects of NSAIDs in low-risk elderly patients is modest.6 However, there is no comparison with COX-2 inhibitors, so we do not know if they reduce this cost. Hospital accountants may be interested to know that researchers at the Mayo Clinic concluded that, in terms of averting gastrointestinal events, the most cost-effective analgesic is paracetamol.7

John S Dowden

Alan Rodger Director, and Professor of Clinical Oncology, Beatson Oncology Centre, Western Infirmary, Dumbarton Road, Glasgow, Scotland G11 6NT, UK. alan.rodgerATnorthglasgow.scot.nhs.uk To the Editor: In their amusing Postcard from the UK, Jamrozik, Heller and Weller1 paint a picture familiar to most of us in the National Health Service (NHS), but, as with most art, some licence has been permitted. Comparing the size of the UK NHS workforce with that of the Chinese army is unfair: there are, as they know, four different health services in the UK (England, Scotland, Wales and Northern Ireland), which function separately and distinctly. The NHS Jamrozik et al describe is much more the English model. In Scotland, targets for cancer care have been set, although they will not be applied for over a year yet. In the meantime, NHS Scotland has awarded the three Scottish regional cancer networks an extra £25 million (A$62.5 million) to improve and enhance agreed cancer services to assist them achieve the agreed targets on waiting times, etc. Another example of the difference between the Scottish and English NHS can be found in the detail of the new consultant contract. Scotland is offering its consultants a sabbatical and England does not. I am reliably informed by one of the negotiators that the seed of that idea was sown by me when I was recounting enthusiastically some of the better experiences of working in Australia’s own, if complex, national health service. Finally, those of us who laboured during the 1990s at the coal face of Victoria’s health service will not be unfamiliar with targets. Infringement of targets set for the upper levels of the waiting list (no one in Category 3 could ever expect treatment, so no target was set), and for 12-hour waits in the emergency department, carried huge financial penalties for the institution. The good old NHS is far from unique in its fondness for targets.

Alan Rodger

Re “Multicentre research: negotiating the ethics approval obstacle course” a letter to the editor by Lynne M Roberts, Lucy Bowyer, Caroline S Homer and Mark A Brown in the 2 February issue of the Journal (Med J Aust 2004; 180: 139). There was an error in the Box summarising the requirements for gaining ethics approval. The entry for “Time taken to gain approval” in the column headed “U” should read 4.5 months (not 42 months). The html and pdf versions of the article available online have been corrected.

Lynne M Roberts RN, CM · Lucy Bowyer MB BS, MRCOG, FRANZCOG · Caroline S Homer RN, RM, PhD · Mark A Brown MB BS, FRACP, MD

Using Botulinum toxins cosmetically. Jean Carruthers, Alastair Carruthers. London: Martin Dunitz, 2003 (v + 81 pp + CD-ROM). ISBN 1 84184 217 6. Botulinum toxin is mainly known in Australia as Botox, one of its popular trade names. It has become a household word, not so much for its use as an exciting drug in almost every field of medicine, but as a deadly poison that has been somehow transformed into a softener of facial expression lines. This book on its cosmetic uses is a timely work indeed. Jean and Alastair Carruthers are the mother and father of the aesthetic use of botulinum toxin. Jean, an ophthalmologist, and Alastair, a dermatologist, first noted the softening of expression lines in some patients being treated for oculospasm in the 1980s. From then on, through their relentless application of science and artistry, they have steered the course for the safe treatment of expression lines, initially of the upper face, and more recently those of the mid and lower face and neck. Botulinum toxin injected in doses used for cosmetic enhancement appears to be a very safe treatment without much risk to the patient’s general health. However, there may be local effects, and the emphasis of this book is very much "safety first" through optimal dosing and careful injection placement. This short text presents the most up-to-date factual information that I have seen, and the accompanying procedural CD-ROM is a most interesting and highly effective teaching aid. Even the most experienced injector will learn tips and tricks from this work. This book simply and succinctly acts as a step-by-step guide to the injector, but I feel it is being directed to those with some experience, rather than the complete novice — it should not substitute for mentoring and formal training. I would have liked to see the patients in the CD-ROM after their treatment, so the attempted outcomes and their subtleties could have been shown, but otherwise it is a wonderful instructional aid. Gregory J GoodmanDermatologistSkin and Cancer Foundation, Toorak, VIC

Gregory J Goodman

Heart biomarker B-type natriuretic peptide — a 32-amino-acid polypeptide hormone secreted by cardiac ventricles — continues to show promise as a biomarker for heart disease, not only as a diagnostic tool when evaluating shortness of breath but also as an early warning signal in asymptomatic patients.1-3 . . . in diagnosis The Swiss B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) Study — a randomised controlled trial of 452 patients with acute dyspnoea — found that adding a single rapid bedside assay of B-type natriuretic peptide while the patient was in the ED led to shorter hospital stays (median, 8 days v 11 days) and reduced treatment costs.2 In BASEL, the diagnosis of heart failure was considered unlikely if the peptide level was below 100 pg/mL and most likely if the level was more than 500 pg/mL; clinical judgement and further testing was recommended in patients with levels that fell between these values. . . . in prognosis Framingham Offspring Study investigators used a community-based cohort of over 3000 middle-aged persons without heart failure in determining that B-type natriuretic peptide levels above the 80th percentile are associated with an increased risk of heart failure, atrial fibrillation, stroke and death, but not coronary heart disease events.3 The 80th percentile level in this cohort was 20.0 pg/mL for men and 23.3 pg/mL for women. 1. N Engl J Med 2004; 350: 718-720 2. N Engl J Med 2004; 350: 647-654 3. N Engl J Med 2004; 350: 655-663 Antibiotics and breast cancer: what’s the link? Inappropriate use of antibiotics is likely to fall as the word spreads that systemic antibiotic use has been linked to breast cancer. In a case–control study involving more than 10 000 pre- and postmenopausal women in the US, the risk of breast cancer and death from breast cancer was greater with increasing cumulative days of antibiotic use and applied to all of the (most common) antibiotic classes studied. However, this study could not determine whether it is antibiotic use that causes cancer, or whether the study findings reflect other, underlying factors, such as indication for antibiotic use or overall weakened immune function. JAMA 2004; 291: 827-835 Straining at stool? Chronic constipation in patients with obstructed defecation may respond to biofeedback, according to Italian authors. In their clinical review, they said obstructed defecation, which occurs in about 7% of the adult population, usually results from a maladaptive, learned paradoxical contraction (or failed relaxation) of the puborectal muscle and external anal sphincter when straining at defecation. They say studies to date indicate that more than half of the patients with this condition treated with a variety of biofeedback techniques (including sensory training during simulated defecation, electromyography and manometry) have benefited. However, controlled studies are lacking in this area. BMJ 2004; 328: 393-396 "On" overnight: off form Even a relatively benign night duty roster leads to some resident medical officers slowing down and slipping up when performing reaction-time tasks, according to South African researchers. They asked 33 anaesthetics residents to complete a battery of four reaction-time tasks on the mornings before and after a night on duty. The residents' working conditions seemed reasonable: the night duty followed an off-duty study day; they slept an average of 1 hour 40 minutes overnight; and they worked an average of 60 hours a week. However, the morning after night duty test performance with respect to either speed or accuracy had dropped by more than 15% (corresponding to a blood alcohol level of 0.05%) in about half of the study subjects — and especially for the more complex tasks. Occup Environ Med 2004; 61: 167-170 Talking tanapox In the USA, there is currently great concern about biological warfare in general and poxvirus infection in particular, and any suspicious causative agent requires prompt, accurate reporting. Accordingly, US authors report that a college student was recently infected with the poxvirus tanapox while caring for orphaned chimpanzees in the Republic of Congo.1,2 The disease was diagnosed using electron microscopy and PCR testing of a tissue sample on her return to the States, but not before she had been managed in the Congo for a series of other presumed conditions such as malaria, abscess, and tick-borne illness. Tanapox is a zoonosis, characterised by a febrile prodrome and usually only one to two typical pock lesions on the extremities (Figure), which leads to self-limited disease with full recovery in immunocompetent humans. The disease is said to be extremely rare outside of Africa. 1. N Engl J Med 2004; 350: 361-366 2. N Engl J Med 2004; 350: 324-327 — Dr Ann Gregory, MJA

Ann Gregory

Med J Aust 2004; 180 (6 Suppl).