Editorials

Self-experimentation in Australia is alive and well Many advances in modern medicine owe a great deal to human experimentation. Indeed, much of biomedical research is irrelevant to mainstream medicine unless its clinical utility is established through human experimentation, for, as observed by the English essayist Alexander Pope, "the proper study of mankind is man."1 Today the circumstances and conduct of human experimentation are painstakingly policed by ethics committees, but even such strict surveillance cannot guarantee safety: "because experiments with humans are voyages into the unknown, an element of risk is always involved; the potential for death, injury, or illness can be reduced, but it can not be eliminated."2 It is this very uncertainty that presents a dilemma for researchers. Sir George Pickering, past Regius Professor of Medicine at Oxford, delineated this quandary: "The experimenter has one golden rule to guide him . . . Is he prepared to submit himself to the procedure? If he is, and if the experiment is actually carried out on him, then it is probably justifiable. If he is not, then [it] should not be done."2 In short, the researcher should be the guinea pig. Risk-laden stories of researchers being guinea pigs abound in medicine's heritage. They include that of John Hunter, the 18th-century English anatomist and surgeon, who allegedly inoculated himself with venereal pus. The symptoms of gonorrhoea and primary syphilis were soon apparent and during the last 15 years of his life he was plagued by a legacy of angina pectoris presumably due to tertiary syphilis.2,3 Other celebrated accounts include that of Werner Forssmann, who, in the 1920s, catheterised his heart with ureteric tubes. This risk-laden technique lay fallow until the 1940s, when Cournand and Richards in the United States refined and employed it in ground-breaking work in cardiorespiratory physiology. In 1956, all three were awarded the Nobel Prize in Medicine or Physiology.2 In the 1950s the enthusiasm for self-experimentation within the Department of Internal Medicine at Washington University, St Louis, earned it the name the "Kamikaze School of Medicine".2 Bill Harrington, a young researcher, courted death from cerebral haemorrhage with profound thrombocytopenia after being infused with plasma from a patient with idiopathic thrombocytopenic purpura (ITP).2 A fellow researcher, Tom Brittingham III, repeatedly injected himself with leukaemic white cells in an attempt to produce white-cell antibodies. He almost killed himself when he had an anaphylactoid reaction accompanied by profound hypotension and severe pulmonary oedema after being infused with plasma from a patient with aplastic anaemia.2 Nonetheless, these unsettling self-experiments established the immune basis of ITP and white-cell-associated transfusion reactions. Harrington's work inspired Jan Dausset of Paris to pursue research into the immunology of ITP and white cells, which culminated in his being awarded the 1980 Nobel Prize for demonstrating human leukocyte antigen (HLA; the transplantation antigen) in white cells.2 Australian researchers have also succumbed to the human guinea pig syndrome. In 1951, as the first wave of myxomatosis raced along the Murray River, its arrival in Mildura coincided with an outbreak of Murray Valley encephalitis in the surrounding district. The public was gripped by fear that the myxoma virus was responsible for the outbreak of encephalitis. This fear reached such heights that the chairman of Mildura Base Hospital challenged R G Casey, the Minister responsible for the Commonwealth Scientific and Industrial Research Organisation (CSIRO), and Sir Frank Macfarlane Burnet, Director of the Walter and Eliza Hall Institute (WEHI), to test the harmlessness of the myxoma virus on themselves! Spurred on by intense media pressure, Macfarlane Burnet, Frank Fenner (Professor of Microbiology at the John Curtin School of Medicine, but working at WEHI) and Ian Clunies Ross (Director of the CSIRO) inoculated themselves with enough myxoma virus to kill 100–1000 rabbits. All three suffered no harm, and in true political style this fact was made public by Casey through an announcement in Federal Parliament.4 The culture of the Kamikaze School of Medicine was further manifest when Australian clinical researchers performed radiolabelled platelet studies on themselves,5 or underwent unpleasant bone marrow aspirations to procure marrow cells for drug studies.6,7 Finally, the experiments of Barry Marshall, who ingested Helicobacter pylori,8 are now legend in medicine. His self-experiments eventually turned prevailing concepts of peptic ulcer causation and treatment on their head. Now, in the new millennium, the report in this issue of the Journal by Landmann and Prociv attests that self-experimentation in Australia is alive and well. In a series of self-experiments these investigators have shown that dog hookworm (Ancylostoma caninum) infection causing symptomatic eosinophilic enteritis is more likely to enter the body orally than percutaneously.9 What drives researchers to be their own guinea pigs? Lawrence Altman, in his delightful book Who goes first? The story of self-experimentation in medicine, proposes a number of motivating factors.2 These include reliability (researchers being more likely to adhere compulsively to the research protocol), dependability (for observations and detecting problems with design), a spirit of adventure, first-hand experience, self-protection, convenience (avoiding the frustrations of recruiting and being involved in the nuances of informed consent) and experience (when the experiments involve risk, the experience of the researcher is important and many will risk exposing themselves rather than others). However, self-experiments are subject to criticism.2 Potential problems include loss of objectivity, cumulative exposure to risks and comorbidities in the self-researcher (including self-experimentation suicide), but particularly the inherent limitations of a research design focusing on a single subject.10 Despite all this, researchers who enlist as guinea pigs will continue to grace medical research. Modern research is increasingly complex, with sophisticated designs and statistics, bewildering technology and the added burden of the close monitoring of projects by ethics committees. This impersonal and mechanistic culture is far removed from the humanistic and romantic spirit of adventure embodied in altruistic self-experimentation. As long as human research is informed by the premise that "because we were venturing into the unknown . . . a man is entitled to risk his own life. He is not entitled to risk somebody else's",2 researchers as guinea pigs will always be with us.

Martin B Van Der Weyden MD, FRACP, FRCPA

Australia must consider carefully the implications of developing a specialty of hospital medicine A hospitalist is a clinician who safely manages a patient's acute hospital course and who specialises in hospital medicine, free of any compelling priorities of ambulatory care.1,2 Hospitalists work only with inpatients, taking over care from primary care physicians after admission to hospital. They are site-defined specialists with skills in general internal medicine,3 who care for patients with a wide range of organ derangements, illnesses (and ages) within the specific location of an acute hospital. The hospitalist movement is most active in the United States, with adherents soon to be comparable in numbers to cardiologists.4 Many leading US hospitals now have active hospitalist programs,5 and, in this setting, the hospitalist is usually a specialist physician. About half are general physicians rather than single-system specialists; the others are often specialists in intensive care.6 The US movement is establishing its own credentials as well as its own areas of research and teaching.5 The major "driver" for this trend in the US was initially related to funding. Hospitalists represent a rationalisation of the medical workforce within an acute hospital, appealing to a cost-oriented, managed-care model. The evidence for the impact of hospitalists is so far unconvincing, although there is some evidence that patient length of stay is decreased when hospitalists manage care.5 The evidence for improved quality of care and patient satisfaction is equivocal.5 What possible advantages would the hospitalist bring for Australian medicine in the new century? Those in favour of the concept suggest that a physician with specific training in acute hospital medicine would be more appropriate than the existing system in Australia, whereby the patient's admitting physician is usually trained as a single-system specialist. This is because a hospitalist has skills and training in general medicine, particularly acute medicine on a background of chronic complex conditions. Not only do they consequently have a more holistic approach to patients with complex, chronic problems, but they are also specifically trained in caring for the seriously ill and resuscitation. This set of skills may be especially relevant in Australian hospitals, where there is evidence of an alarming incidence of potentially preventable deaths and serious complications.7,8 Hospitalists may bring extra skills and expertise in acute medicine and resuscitation as a way of addressing this problem. In the US model, hospitalists also have skills in the organisational aspects of the hospital stay, including communication with all other inpatient services required by the patient, as well as in discharge planning and end-of-life care. Hospitalists in the US are also involved in the acute medical aspects of surgical and obstetric inpatient management. How does the US hospitalist concept "fit in" with current Australian hospital medicine? From an Australian perspective, considering the concept of a hospitalist may assist us in focusing on the changing patient population in our hospitals and re-examining what the role of an acute hospital is exactly. The US concept of the hospitalist suggests that hospital medicine can now essentially be viewed as a general specialty, with system specialists consulted as required. This would seem to require a radical departure from the current Australian model. However, in Australia, it is already common for single-system specialists to hand over care to more general acute-care physicians in the emergency department and intensive care unit. The complexities of acute medicine now demand its own specialists with general training and experience, such as those who practise emergency and intensive care medicine. This is because understanding not only how each organ is affected in acute insults, but also how the affected organs interact with each other, is crucial to the practice of acute medicine. A similar generalist approach is now being demanded in specialties such as geriatrics and rehabilitation. Further, with the increasing comorbid complexity of patients in acute hospitals, management by multiple referral is often required, especially in large teaching hospitals, with a potential danger of there being no generalist to pull it all together. Australian rural hospitals and smaller metropolitan hospitals resisted the move that occurred in the latter part of the last century to increased physician specialisation, often more by default than choice. The US hospitalist model represents a trend back to this "general physicians" concept and using single-system specialists as they once used to be — referring a patient only when the generalist requires an opinion. Perhaps geriatricians in Australia would consider that this concept is already incorporated into their own model of care. Single-system specialists in America seemed willing to forgo control of hospital care because it was interfering more and more with their professional life.4 Increasingly, specialist physicians are practising ambulatory medicine in outpatient settings or performing specialised procedural skills, often in non-hospital settings. With this change in practice arose the very practical issue of the amount of time left to manage increasingly ill and complex patients in an acute hospital setting. Similarly, surgeons spend much of their day either in an operating theatre or an outpatient setting. However, in the US, just as important in allowing professionally non-threatening expansion of the hospitalist model were the relatively low fees that non-procedural hospital inpatient care attracted. Do we need to develop site-specific acute hospital specialists in Australia? Is there a call for a hospitalist in Australia, similar to the US model: one whose training and skill covers acute medicine and resuscitation medicine, chronic and multisystem problems, as well as aged care and end-of-life care — a coordinator of admission and discharge planning, a clinical governance coordinator and a communicator between all the service providers involved in patient care? The current system of clinician responsibility in Australian hospitals has evolved over many years. This evolutionary process has been influenced by many factors, including accountability of the individual clinician, the patient–doctor relationship and continuity of care. Changing this system by replacing existing hospital specialists with hospitalists would radically change the way we deliver healthcare and, at this stage, the advantage of the hospitalist, even in the US setting, is speculative. Potential benefits to patients and the cost of this change would need to be carefully evaluated in the Australian setting — in the same way we would evaluate the relative cost–benefit of a new drug or procedure. Just as importantly, a well-informed debate is needed about important issues raised by the hospitalist concept. These include the future role of acute hospitals, the population of patients who may be managed in such hospitals and their expected needs, and how to set the balance between ambulatory and hospital-based care. In addition, if single-system specialists continue to play a central role in this environment, we need to think about how they will maintain their skills across a broad range of ambulatory and acute hospital care.

Ken Hillman FRCA, FJFICM

The US strain of West Nile virus could enter Australia, but we may be protected by the already present Kunjin virus Australia needs to consider the implications of the recent emergence and spread of West Nile virus in the United States, including the possibility of its spread to Australia. This development also raises questions about Kunjin virus, a subtype of West Nile virus, which already occurs widely in Australia. West Nile virus, a mosquito-borne flavivirus, was known to have a wide geographic range, extending from Africa through the Middle East to southern and eastern Europe and western Asia. The initial outbreak in New York city and adjacent counties in August 1999 resulted in 62 human infections and seven deaths of elderly patients.1,2 Genetic evidence suggests that the virus came from the Middle East. Over the next three years, it spread rapidly in the US, first in the north-east and then more widely, causing disease and deaths in humans, horses and birds.3 Birds, especially crows, were found to be responsible for both spread and maintenance of the virus in a natural cycle with culicine mosquitoes.3,4 By late November 2002, the virus had been detected in 43 states spanning the mainland US, with 3735 reported clinical cases and 215 deaths, almost all among the elderly.5 The virus had also spread to five provinces in Canada, with around 140 cases and two deaths. The speed of its spread was undoubtedly due to the presence of competent mosquito species and a large number of susceptible birds, and especially to a greatly increased propensity to spread in a virgin ecosystem. Before 1996, West Nile virus was known to cause high fever, chills, malaise, headache, backache, arthralgia, myalgia and retro-orbital pain, and, in about 50% of cases, a maculopapular rash,6 but neurological symptoms were uncommon. Since then, severe neurological illness, including encephalitis and meningitis, has been reported more frequently,6,7 together with an acute flaccid paralysis syndrome.6,8 Fatalities have generally been in the elderly. Although human acquisition is nearly always through the bite of an infected mosquito, unusual modes of transmission via organ transplantation,9 blood transfusion9,10 and possibly breastfeeding11 have recently been described in the US. West Nile virus is closely related antigenically and genetically to other members of the Japanese encephalitis serological group of flaviviruses, including Japanese encephalitis, Murray Valley encephalitis (MVE), and St Louis encephalitis viruses, and is almost identical genetically and immunologically to Kunjin virus.12 Kunjin virus, reclassified as a subtype of West Nile virus in 2000, is the most common flavivirus in Australia, occurring widely across northern Australia. Most infections with this virus are asymptomatic, but it causes occasional, mild febrile illness, similar to that traditionally described for West Nile virus, and rare cases of non-fatal encephalitis.13 It is closely related genetically to the West Nile strain in North America,1,2 both being members of West Nile lineage 1. However, unlike Kunjin virus, some recently isolated members of West Nile lineage 1 are known to cause fatal encephalitis in elderly patients,3,6,7 fatal disease in wild birds (in North America)3,14 and domestic geese (in Israel),15 and severe epizootics in horses, with significant mortality.7,13,14 In addition, recent experimental evidence has shown that the New York strain of West Nile virus is considerably more neuroinvasive than Kunjin virus.16 Could Kunjin virus mutate to be as virulent as recent West Nile strains seen in Europe and the US? Kunjin virus has been in our ecological system for many years without any apparent increase in virulence. Several mutations may be required to increase virulence substantially, and there seems little pressure to select for such mutations. Alternatively, could a more pathogenic strain of West Nile virus spread to Australia and, if it did, would it be able to establish itself in competition with Kunjin virus? West Nile virus has been isolated in Sarawak, Malaysia, and is endemic in western India; thus, it could conceivably spread slowly through the region. The virus is believed to have reached New York through carriage on an aircraft of an infected mosquito or an infected traveller with sufficient viraemia to infect a mosquito on arrival in the US. Similar mechanisms could allow its importation into Australia from the US, Europe or Africa. Although current disinsection procedures for aircraft are believed to minimise the first possibility, there is concern that an infected human traveller arriving in Australia might have sufficient viraemia to infect Australian mosquitoes. More information is urgently needed on viraemia levels during infection so that this risk can be properly assessed. Other routes of entry seem less likely. Although a horse infected with West Nile virus was recently imported into Australia from North America, viraemia levels in horses are believed to be insufficient to infect mosquitoes. Introduction of virus through migratory birds is doubtful because of the route and length of migration. Even if West Nile virus is introduced into Australia, it would have to compete with Kunjin virus for vertebrate hosts and vectors. Experience with other members of the Japanese encephalitis serogroup of flaviviruses suggests that they do not interfere with each other's ability to spread,12 despite the induction of cross-reacting antibodies. Thus, West Nile and Japanese encephalitis viruses coexist in western India, and MVE and Kunjin viruses coexist in Australia, while West Nile and St Louis encephalitis viruses appear to coexist in North America, and Japanese encephalitis and MVE viruses appear to coexist in Papua New Guinea. However, antibodies to Kunjin virus neutralise West Nile virus (and vice versa), and Kunjin virus is widely distributed over much of Australia, so it may prove more difficult for West Nile virus to find the susceptible vertebrate hosts it needs to become established or to spread rapidly. There is no treatment or vaccine available for West Nile infection, but people with prior exposure to Kunjin virus should be protected. Similarly, those exposed to other members of the Japanese encephalitis serological group, especially Japanese encephalitis and MVE viruses, may have limited protection against West Nile disease. The current Japanese encephalitis vaccine is unlikely to protect, although more research is needed to confirm this.17,18 Finally, could Japanese encephalitis virus spread in Australia as West Nile virus has done in the US? Japanese encephalitis virus has occurred in the Torres Strait of northern Australia nearly every year since 1995, and entered the Australian mainland in 1998.19,20 As Australia has the appropriate mosquitoes and avian and porcine vertebrate hosts for natural transmission cycles,20 it is likely that Japanese encephalitis virus will eventually become established here. However, the narrow range of bird species used by Japanese encephalitis virus as maintenance hosts (generally herons and egrets), the need for pigs as amplifier hosts, as well as the Australian ecosystem, climate and arid interior, would suggest that Japanese encephalitis virus is unlikely to match the spread of West Nile virus in North America. Migratory birds, wind-blown insects and rapid air transport of infected humans, animals and insects could all bring exotic pathogens into Australia. Identifying potential threats, maintaining aircraft disinsection and mosquito surveillance around major airports, as well as good internal surveillance, are important parts of the protection of human and animal health in this country.

John S Mackenzie BSc, PhD · Roy A Hall BSc, PhD · David W Smith FRCPA

Infectious diseases are still the dominating cause of death Papua New Guinea (PNG) has a population of about 5 million people, 85% of whom live in rural villages.1 Since becoming independent in 1975, PNG has experienced problems common to emerging nations of starting from a subsistence base and simultaneously seeking to achieve economic sustainability and nationhood as well as build systems of governance, defence, transport, communication, education and healthcare. Health system development has not kept pace with changing demands in PNG. Instead, primary health services have faltered, placing a heavier burden of disease on struggling secondary care facilities as opportunities for prevention and early treatment are lost because aidposts have closed or vaccination rates have fallen. Port Moresby, the capital and largest city, has a population of over 300 000. Port Moresby General Hospital (PMGH) is the country's major teaching and referral hospital, with 600 beds. Hospital-based studies of the causes of death and patterns of admissions to PMGH confirm that infections remain the major cause of adult hospitalisation and deaths in hospital, and that HIV/AIDS is now a leading cause of death in adult inpatients. Moreover, there has been no reduction since 1980 in the mortality rate of children under five years, and infectious diseases, predominantly pneumonia, are also the main cause of childhood deaths. Adults: Studies of medical records in the 1980s and again in the 1990s determined causes of death in adults admitted to medical wards and the intensive care unit at PMGH.2,3 The findings of these two studies are summarised in the Box. Malaria, tuberculosis, typhoid and pneumonia were the leading causes of death in patients in whom aetiology was determined. In addition, these same infections were suspected on clinical grounds to be the cause of death in more than half of those dying without confirmation of the cause. A further study in 2000 looking at reasons for medical admissions to PMGH (Dr G Tau, Chief Medical Officer, PMGH, personal communication) found infections remain the most common reason for admission, with tuberculosis being the most common (27%), followed by malaria (23%), pneumonia (15%), dysentery (12%), typhoid fever (8%), and HIV/AIDS (3%). According to statistics of the PNG Health Department, the reported national prevalences of tuberculosis, malaria, typhoid and other infections have not declined in the past three decades.1 Thus, the dramatic recent addition of HIV/AIDS has occurred against a background of no change in the high prevalences of other infectious diseases. As a result of cultural resistance, autopsy rates in PNG are very low, and, at the time of the two studies of causes of death,2,3 autopsy was performed in less than 3% of deaths. Needle autopsy, which, compared with full autopsy, is accurate in 77% of cases, appears to be an acceptable alternative for Papua New Guineans and could be applied to determine cause of death in the large numbers of patients who currently die from undiagnosed causes.4 In addition, better diagnostic facilities in microbiology laboratories would assist in diagnosing and treating infections earlier and more effectively. As economic prosperity increases, non-communicable diseases are becoming more apparent. New diagnostic facilities at PMGH — ultrasound, echocardiography and a private computed tomography facility — have markedly enhanced the ability to diagnose chronic, non-communicable diseases. Even allowing for this enhanced diagnostic capacity, the prevalence of these non-communicable diseases is increasing.1 Children: Reports on child health in rural areas of Papua New Guinea similarly indicate a dominance of infectious diseases. The major infectious diseases causing child mortality in PNG include pneumonia, measles, meningitis, malaria and neonatal sepsis. Between 1960 and 1980 the mortality rate for children under five years of age in PNG fell by an average of 3% per year, from 204 to 122 per 1000 livebirths. No improvement has occurred since then. By contrast, the mortality rate in this age group in East Asia and the Pacific region has fallen by 2.5% per year. The most optimistic figures for the current infant mortality rate, and the mortality rate in children under five years, puts the national rate at 77 per 1000 livebirths and 100 per 1000 livebirths, respectively; this represents no progress during the past decade. According to UNICEF, only four countries in the world have failed to improve the mortality rate among children under five years since 1980: Burma, Niger, Zambia, and PNG. The high child mortality rate is attributed to collapse of health service structure, law and order problems, closure of aidposts, deteriorating roads, and inadequate administrative assistance and support. Vaccine-preventable diseases, such as measles, whooping cough and Haemophilus influenzae infection, still kill children in PNG. Vaccination coverage is low and differs from province to province. According to figures in the National Health Plan, vaccination coverage averaged 64% for diphtheria–tetanus–pertussis and 60% for measles, while, in the Western Province, these proportions were only 30% and 27%, respectively.1 In a highlands province in 1997, coverage was about 33% for immunising doses of any vaccine.5,6 HIV/AIDS: The first case of AIDS in PNG was diagnosed in 1987. HIV in PNG is heterosexually transmitted and equal numbers of men and women are affected. Unprotected sex and a rising incidence of other sexually transmitted diseases and promiscuity have contributed to the rapid rise in cases of HIV/AIDS to epidemic levels. By the end of December 2001, 4700 cases had been reported.7 About A$200 million was committed to healthcare in the 2001 PNG National Budget, including $650 000 earmarked for HIV prevention and care. In addition, $20 million is being put into the National HIV/AIDS Support Project by AusAID. Some antiretroviral therapy is becoming available through UNAIDS. PNG faces the danger of following the experience of African nations, with the potential to lose half of its adult population to this disease. Investing in the future of the nation: PNG manifests the challenges facing many tropical nations where communicable disorders remain major causes of mortality and morbidity, but non-communicable diseases are becoming more apparent. This is in sharp contrast with Australia, where cancer, ischaemic heart disease and stroke are the leading causes of death (27.8%, 20.7% and 9.6%, respectively).8 In PNG, this background of infectious diseases is being overlaid by non-communicable diseases — hypertension, coronary artery disease and diabetes (Dr G Tau, personal communication).1 Declining health service efficiency has meant that HIV/AIDS has now taken hold, placing additional stress on an already skeletal system. The commitment of public resources to the control and alleviation of these problems needs to be seen as an investment in the future of the nation. Those responsible for the administration of healthcare may be encouraged from international experience that control of infectious diseases and lowering child mortality are achievable and worthwhile goals. Australian aid to PNG has been generous, with the estimated total aid to PNG for 2002–2003 being $351.4 million.9 Special attention should now be given to enhancing primary care services provided in the village aidposts and rural district health centres. At the same time, PNG requires continuing support from experienced clinicians and public health experts. It would be wise for Australian aid to support this and related workforce development. Australia has a special relationship with PNG. This should be used to work with PNG in the development and implementation of the PNG National Health Plan. Australian aid must be sensitive to the PNG political environment, and should not be provided without an explicit purpose or without clear accountability for its expenditure. In controlling the spread of HIV, tactics used in other countries to good effect, including the judicious and appropriate use of antiretroviral medications, need to be examined for their applicability in PNG. Admissions and deaths at Port Moresby General Hospital2,3 1984 study2 1994 study3 Total admissions 1242 2353 Deaths in hospital 120 (10%) 168 (7%) Preventable 7 0 Treatable 35 37 Ultimately fatal 31 71 Not determined 47 60 Number of deaths from confirmed infections 59/120 (49%) 80/168 (48%) Definitions Preventable: The cause of death is known and the illness is treatable or curable but the correct treatment was not given. Treatable: The cause of death is known and the illness is treatable or curable, but the patient died despite receiving the correct treatment. Ultimately fatal: The cause of death is known, but the illness is such that, despite treatment, it is ultimately fatal (eg, hepatoma). Not determined: The specific cause of death is unknown because the aetiological diagnosis could not be made.

Sirus Naraqi FRACP, FACP · Bairi Feling · Stephen R Leeder PhD FRACP

Health is one of our major industries, employing more than half a million people — 7.1% of the national work force.1 In the 1999–00 financial year its funding reached $55.7 billion, equivalent to 8.8% of Australia's GDP. The major costs are incurred by the hospital sector ($19.1 billion), medical services ($9.7 billion) and pharmaceuticals ($6.5 billion).2 Conventional wisdom would have it that such an extensive and expensive enterprise as ours is underpinned by a lively culture of research and development informing health policy. But is it? In October this year, the National Health and Medical Research Council (NHMRC) announced that, commencing in 2003, it would support 406 new research projects to the tune of $150 million.3 This welcome announcement was quickly followed by press releases from universities and research institutes proclaiming their success in attracting funds. However, not one of the 406 projects directly involves health policy research and development (R&D).3 Furthermore, of the 16 new NHMRC program grants — larger and longer-term multidisciplinary grants funded with an additional $118 million — only one (with funding of $6.8 million) specifically addresses health policy.4 In short, from 2003, less than three cents of every dollar the NHMRC is investing in new research has been earmarked for policy R&D in an industry that costs the nation nearly $56 billion. So, is health policy R&D in Australia a virtual desert? Before dismissing such a judgement as being too harsh, it might be helpful to revisit health policies that have had a major impact on our health system in the final quarter of the 20th century. Most will acknowledge that these include Medibank (1975) and its progeny, Medicare (1984);5 casemix funding (1993) that accelerated the drive for efficiency and effectiveness in the hospital sector;6,7 the evidence-based medicine movement (early 1990s)8 that, among other things, augmented the growth of evidence-based guidelines;9 and finally the development of an organisational structure for general practice — the Divisions (early 1990s).10 While not wishing to downplay the contributions of many Australians to these health policies, is it not significant that all but one were imported ideas? Medibank came from Canada,11 casemix funding from the United States,12 and evidence-based medicine from North America and the United Kingdom.8,13 Is it not intriguing that during this period of change, our own health bureaucracy apparently remained devoid of productive policy ideas? Why has Australian health policy been a net importer of ideas? Could it be that its culture has not fostered an environment for "think tanks", such as the Institute of Medicine and the Commonwealth Fund in the US, the King's Fund and the Nuffield Trust in the UK, or the Canadian Health Research Foundation, all of which regard health services research and policy as their primary concern? There can be no doubt that coping with the clinical dividends of biomedical and biotechnology research, along with changes in society's expectations, will require innovative approaches to the health system through R&D. This can best be fostered in an environment free of political patronage, that is permeable and receptive to ideas from academia, the health professions and bureaucracies, and the community itself. It will require capacity building, as recently recognised by the belated development of the Joint Health Services Research Program, a cooperative initiative of the NHMRC, the Commonwealth Department of Health and Ageing and the States.14 But, most importantly, it requires a flagship — an independent institute — for vision and leadership. Australia's health policy community recently published a collection of essays, Daring to dream: the future of Australian health care,15 which paid tribute to the many contributions of John Deeble to healthcare in this country. His legacy is wide-ranging, from Medibank and the Australian Health Institute (the progenitor of the Australian Institute of Health and Welfare) to his work in Indigenous health. The essays clearly show that the R&D desert of Australian health policy is dotted with oases. The dream, surely, is to consolidate this enterprise and other ventures, such as the Health Leaders' Network (www.hln.com.au), into a policy flagship. Is it dreaming too much to envisage a John Deeble Institute of Australian Health Policy? Australia is currently blessed with an array of internationally acclaimed medical research institutes. In light of this, the stark absence of an internationally recognised Australian institute for health policy is a damning national disgrace.

Martin B Van Der Weyden MD, FRACP, FRCPA

A dream becoming a reality The Cochrane Library is now available free to all Australians who have Internet access. At the 3rd Annual Meeting for Australasian Contributors to the Cochrane Collaboration, held in Melbourne in October this year, the Federal Minister for Health and Ageing announced this important milestone — universal access to high-quality health information. Just as ready access to "clean" drinking water has come to be seen as a public health milestone of the 19th century, so, in the future, ready access to "clean" health information might well be dubbed as a major public health achievement of this century. The United Kingdom and Ireland, as well as several other countries in Europe, also have free access and the Library is also available free to developing countries. Such access will have a direct impact on satisfying clinicians' daily information needs, and an indirect impact on their practices through the information accessed by patients, consumer organisations, policymakers, and others. So where will this lead us? To understand some of the implications requires an understanding of both the history and the future of the Cochrane Collaboration.1 In 1979, a challenge came from the UK epidemiologist Archie Cochrane, who stated: "It is surely a great criticism of our profession that we have not organised a critical summary, by speciality or subspeciality, adapted periodically, of all relevant randomised controlled trials."2 Meeting Cochrane's challenge required two important steps: (i) assembling all controlled trials in one database, and (ii) completing and maintaining systematic reviews of these trials. The first step corresponds to the Cochrane Central Register of Controlled Trials, which now includes over 350 000 trials, and the second to the Cochrane Database of Systematic Reviews, which currently contains 1456 complete Cochrane reviews, and the protocols for 1101 planned reviews. How did the Cochrane Library come to be? In Cochrane's 1979 article1 he challenged the medical profession in general, but singled out obstetrics as the specialty most in need of an evidence base from controlled trials. When Iain Chalmers (who had worked in obstetrics) became Director of the UK National Perinatal Epidemiology Unit in 1978, he initiated a classified bibliography of randomised trials of interventions in pregnancy, childbirth and early infancy, using both electronic searches and manual searches of over 60 journals. This bibliography provided the raw material for an international collaboration to prepare systematic reviews, which were eventually published in 1989 in a seminal, two-volume, 1500-page book entitled Effective care in pregnancy and childbirth.3 The book concluded with a chapter summarising which interventions (of the 283 assessed) were supported by reasonably strong research evidence (100 were deemed effective, 36 promising, 86 of unknown benefit and 61 so unlikely to be useful that they should be abandoned). Importantly, not only was a paperback summary prepared for women published concurrently, but also a six-monthly electronic update of the systematic reviews — the Oxford Database of Perinatal Trials. This "pilot" project was well received. In 1992, the UK National Health Service provided crucial support for Chalmers to work with others to extend the process to other areas of healthcare. Recognising that the work could not be done by a single group or country, the international Cochrane Collaboration was founded in 1993 at the first Cochrane Colloquium, held in Oxford. Two years later the Cochrane Database of Systematic Reviews was launched, and the late Chris Silagy, inaugural Director of the Australasian Cochrane Centre, became the first elected Chair of the Steering Group, guiding the growth of reviews prepared by members of 49 Collaborative Review Groups, which, collectively, are responsible for covering most health problems. At the 1995 Cochrane Colloquium, David Sackett described the Cochrane Collaboration as a plane that took off while it was still being built. In 2002, the Collaboration is flying at a respectable altitude. But what still needs to be done for Cochrane's dream to become a reality? One sobering fact is that less than 10% of more than 350 000 published controlled trials have been synthesised within Cochrane reviews. To complete the journey will require three things: Review efforts will need to be sustained and extended by appropriate support and training in systematic reviewing. The science of research synthesis will need to develop an academic capacity and infrastructure equivalent to those of other fields of specialised medical endeavour. To maximise clinical relevance and uptake, the Library interface and reviews have to become more attuned to the needs of users and the users need to be more sophisticated in applying evidence. Reviewers will need to have access to all trials, not just those published in electronically indexed journals. Registration of all trials at inception is necessary, and is becoming a reality (see the meta-register at www.controlled-trials.com). Finally, we need to recognise that the Cochrane Library synthesises only intervention studies. At the 1996 Cochrane Colloquium, Hilda Bastian, chair of the Cochrane Consumer Network, suggested "people often ask if we can afford to extend the Collaboration beyond the RCT; we also need to consider whether we can afford not to do so". We will also need more systematic use of non-randomised study data on harms or treatments, and equivalent collaborations for systematic reviews of the accuracy of diagnostic tests, the natural history and prognosis of disease, and other types of clinical questions (see, for example, a description of Bayes Library of Diagnostic Studies and Reviews: <www.bice.ch/engl/content_e/bayes_library.htm>). In brief, although the announcement of free access to the Cochrane Library is an important and welcome milestone, much work remains to be done to make best use of the presently available results of clinical research relevant to the wellbeing of users of health services. Sceptics might ask what evidence there is that ready access to such databases will make a difference. Free access might be seen as an ethical obligation — in return for the public's participation and direct or indirect funding of research. However, adequate evaluation is also essential to both assess the impact and to guide improvements. The National Institute of Clinical Studies (<www.nicsl.com.au/>), which brokered the free Cochrane Library access, will also undertake an evaluation that will include process measures, such as who is accessing what, and a more detailed study of the difficulties and needs of end-users. However, we should recognise that information access is a necessary, but not sufficient, condition to bridge the gap between research and practice. It may be far from enough. Hence, more detailed evaluation might be planned to explore factors such as the impact of clinicians' skills in using evidence, attitudes to applying evidence, structural barriers to using proven interventions, and problems in matching evidence to individual patients' needs that limit any potential benefits of free access.

Paul P Glasziou PhD, FRACGP

When asked about features of women's health services that would best meet their needs, specific groups of Aboriginal and Torres Strait Islander women, despite their diversity, have given very similar responses.1-3 They want women's healthcare that takes a holistic rather than a narrow "single-disease" or biomedical approach; services that are accessible, flexible and supportive; and providers they can trust, who are respectful and who can communicate well. For many Aboriginal and Torres Strait Islander women, having access to a female provider is critical to their acceptance of women's healthcare services. The higher cervical cancer incidence and mortality for Aboriginal and Torres Strait Islander women compared with other women, and the available evidence about screening effectiveness, provide a strong imperative for healthcare providers and funders to listen carefully and respond to what women say they want.4 The article by Coory and colleagues in this issue of the Journal (page 544) quantifies and compares women's participation in cervical screening by analysing data from the Queensland Health Pap Smear Registry.5 Participation for women living in rural and remote Aboriginal and Torres Strait Islander communities in Queensland was generally lower than for women living in other areas. Proportions of women in these communities who had had a Pap smear over a two-year period ranged from 19% to 63%. These results suggest women's needs for women's health services are being better met in some communities than others. In interpreting their analysis, Coory et al used residence in a community where most people were Aboriginal and/or Torres Strait Islander as a proxy for Indigenous status. We believe this is a resourceful and reasonably valid way around Indigenous status not being identified on the Pap smear register. However, one limitation is that we can learn nothing about Aboriginal and Torres Strait Islander women living in other localities (ie, the majority of Aboriginal and Torres Strait Islander women in both Queensland and Australia more generally). It is important that the needs of these women are not neglected because of the lack of quantitative data with which to measure them. We commend the researchers for acknowledging the sensitivities of identifying data from individual Aboriginal and Torres Strait Islander communities in their research. However, rather than only obtaining permission to do so from a government department, we believe consulting directly with members of the communities concerned at an early stage of the project may have been beneficial. Although such a practice is uncommon in this type of research, and may be challenging and more time-consuming, it may also create or strengthen trust, links and understanding, which could be useful when implementing and evaluating subsequent interventions. Coory et al suggest that the higher cervical screening participation rates in some communities are an indication of what is achievable, and express support for a strategy of strengthening primary health care. We agree with these conclusions, but disagree that an intervention study where communities are randomised would be an ideal next step. Although randomised-community intervention trials have been implemented in other settings,6 for Aboriginal and Torres Strait Islander communities the barriers to delivery of women's health services are likely to be highly location-specific and the means to overcome them not amenable to random allocation. We believe any available resources would be better spent on (i) exploring in more detail the factors contributing to high and low levels of participation, and (ii) responding actively to identified issues in communities with lower levels of participation. Barriers to Aboriginal and Torres Strait Islander women accessing women's cancer screening services, and ways of responding to them, have been reviewed — most recently in the context of considering how to support the roles of general practitioners.1,4 We would like to highlight the need to also support the roles of Aboriginal Health Workers (AHWs). Because of their key role in providing primary health care for Aboriginal and Torres Strait Islander people, the need for improved clarity, recognition and support of AHW roles has been identified as a national priority.7 We have worked with many female AHWs who have had personal experience of the impact of cervical cancer on Aboriginal and Torres Strait Islander women and their communities, and are keen to be involved in women's health education and promotion activities. Some AHWs also want to provide women's clinical care, including taking Pap smears. Some of the specific areas needing attention are the provision of better training for AHWs in women's health, and issues of accreditation, legal cover and quality assurance for those wanting to take Pap smears. Finally, we urge caution about evaluating cervical screening programs solely on the basis of participation rates. Recent commentaries have begun to question a primary aim for screening programs of maximising participation, arguing that this may lead to the positive effects of screening being overstated, and the limitations and possible negative effects of screening and its sequelae being ignored or downplayed.8,9 These commentators acknowledge that providing more balanced information about screening may have a negative impact on participation rates, but stress the importance of individuals being informed about screening and being able to choose for themselves whether or not to participate.8 Qualitative research conducted with women in one rural Aboriginal community with high rates of participation in cervical screening found that many of the women had little understanding of cervical screening or its implications.10 For programs successful in terms of participation, questions may remain about the extent to which women are making an informed choice about screening. In many localities, providers' attempts to consistently give adequate information to Aboriginal and Torres Strait Islander women can be constrained by many factors, including lack of time, and language and cultural differences. These barriers, combined with a high level of concern about cervical cancer and evaluation criteria based mainly on participation rates, may lead to an emphasis on persuading women to have a Pap smear rather than on providing information and an opportunity for informed choice. We strongly advocate that evaluators of cervical screening programs take into account not only participation rates, but also Aboriginal and Torres Strait Islander women's views about available health services and their understanding of screening-related issues.

Jennifer M Hunt MB BS MPH FAFPHM Public Health · Lynore K Geia BN, RM, MPH

Glaucoma is the most common neurodegenerative disease of the optic nerve, with a prevalence of about 3%.1 This means that about 150 000 Australians, about 75% of whom are aged over 70, have glaucoma. This number will double over the next 30 years as our population ages.2 After macular degeneration, glaucoma is the second most common cause of irreversible blindness in our community,3 and the commonest cause of preventable blindness. The basis for the most common form of glaucoma is multifactorial. Genetic linkage analysis has isolated several putative genes for open-angle glaucoma, but these account for only a small percentage of cases. Risk factors for open-angle glaucoma identified in Australian cross-sectional analyses include age and intraocular pressure, family history of glaucoma,4 myopia, systemic hypertension and diabetes.5 In glaucoma there is a relatively slow loss of retinal ganglion-cell axons. Early loss is usually in the mid-peripheral visual field. The disease becomes symptomatic at a relatively late stage when central vision is affected and the visual acuity declines, or extensive loss of peripheral vision leads to problems with mobility. However, because progression of the visual field loss is relatively slow, glaucoma is responsible for a relatively small number of the new cases of visual acuity impairment detected annually.6 Underpinning the treatment of glaucoma is a reduction in intraocular pressure. Recent reports7,8 provide evidence for setting a target intraocular pressure level for each patient, depending on the assessed risk of progressive visual damage, such as extent and rate of prior damage, proximity of the visual damage to the point of fixation (most sensitive central vision), likely number of years of life remaining for the patient, family history, and the level of intraocular pressure at which damage has occurred. Usually, topical drug therapy is used first. Newer drugs such as prostaglandin F2α agonists (latanoprost, travoprost), prostamides (bimatoprost), topical carbonic anhydrase inhibitors (dorzolamide, brinzolamide), β-blockers (timolol, laevobunolol, betaxolol) and α2-agonists (brimonidine, apraclonidine) have tended to replace pilocarpine and adrenalin-related compounds. Since drugs are absorbed directly from the nasal mucosa into the venous circulation with hepatic by-pass, topical agents mimic intravenous drugs — their safety margin can be widened by simple eyelid closure and digital occlusion of the tear duct for at least two minutes after instillation. Non-compliance and difficulties with instillation techniques remain major challenges for the long-term treatment of this incurable and asymptomatic condition. Failure to achieve target intraocular pressures by medical means usually leads to laser procedures. Laser trabeculoplasty techniques offer a 75% chance of helpful intraocular pressure reduction, with a 50% chance of continuing benefit for up to five years. Lasers are also used to achieve peripheral iridectomies for angle-closure glaucoma, and to inhibit aqueous inflow by ciliary-body destruction in blind, painful eyes. If medical and laser treatments fail, incisional surgery is performed to create an alternative pathway for the aqueous humor onto the scleral surface. Augmented with antifibrotic agents (5-fluorouracil, mitomycin-C), a long-term success rate of up to 90% can be achieved. For patients with exaggerated healing responses (glaucoma secondary to uveitis or rubeosis), intraocular pressure reduction can be achieved with plastic tubes draining into plastic reservoirs (there are three types of implants — Molteno [Molteno Ophthalmic, Dunedin], Baerveldt [Pharmacia, Kalamazoo, Mich, USA], and Ahmed [New World Medical, Rancho Cucamonga, Calif, USA]). Beyond intraocular pressure reduction lies the hope of neuroprotection — an attempt to prevent initiation or progression of intracellular processes resulting in retinal ganglion-cell apoptosis (induced cell suicide). A large international multicentre prospective randomised clinical trial of the NMDA [N-methyl-d-aspartate]-receptor antagonist memantine is under way, with results expected in 2006. Our conventional approach of looking for visual field defects, or for their progression, with white-on-white automated perimetry is still the main method of monitoring for glaucoma stability, but a large proportion of the nerve fibres can be lost before an initial defect is seen. (In white-on-white automated perimetry, a white light target is projected into a white background bowl — the patient responds when the light is just seen and its intensity is varied until the threshold for seeing has been crossed, which determines the sensitivity of the retina at that point.) There are now several new techniques for the detection of glaucoma which are specifically designed to detect change at earlier stages of the disease. Psychophysical tests are available which target smaller subpopulations of ganglion cells, such as frequency-doubled perimetry, and short-wavelength automated perimetry (blue target/yellow background). Multifocal objective perimetry, recently developed at the Save Sight Institute,9 records a multifocal visual evoked potential and removes the need for patients' subjective responses. Optic disc and nerve fibre imaging techniques using scanning laser ophthalmoscopes (eg, Heidelberg retina tomograph [HRT, Heidelberg Engineering, Heidelberg, Germany]; GDx Access [Laser Diagnostic Technologies, Jackson, Fl, USA]) or optical coherence tomography can provide objective measures of structural change. Glaucoma blindness is largely preventable. While the visual damage is not reversible, it can usually be arrested. To achieve this, early diagnosis of this otherwise progressive, asymptomatic process is essential. Ninety per cent of the Australian population visits a general practitioner annually, yet 50% of patients with glaucoma identified in population surveys are undiagnosed and untreated.3 Clinically, the first changes occur at the optic disc and it is vital that clinicians look for the characteristic sign of optic disc cupping. Every GP should view a patient's optic disc with an ophthalmoscope from time to time, especially if one or more risk factors are present. Anyone with significant optic disc cupping, or asymmetry between the optic discs of the two eyes, should be referred for investigation.

Ivan Goldberg FRANZCO, FRACS · Stuart L Graham FRANZCO, FRACS · Paul R Healey FRANZCO, BMedSc, MMed

Patients undergoing surgery need good advice not only about whether a particular elective procedure is truly necessary and likely to be of benefit, but also about the nature and chances of an adverse outcome from the surgery itself. Those with heart failure, coronary artery disease, diabetes or emphysema are more likely to suffer serious complications or death after major surgery. Epidural anaesthesia and analgesia may be a preferable technique in such patients,1 as epidural block can attenuate the neurohumoral stress response to surgery,2 potentially improving postoperative cardiorespiratory function and reducing complications. Many small randomised controlled trials (RCTs) have supported this conjecture, but, because most serious complications after anaesthesia and surgery are rare, none has had sufficient power to demonstrate whether epidural block significantly improves postoperative outcome. A solution to this problem is to combine the results of all available trials in a meta-analysis. Applying this approach to data from 141 RCTs involving 9559 patients, Rodgers et al showed that the use of epidural or spinal block (with or without general anaesthesia) resulted in a significant 30% reduction in mortality after surgery.3 Outcomes causing major morbidity (major morbidity endpoints) such as thromboembolism and pneumonia were also reduced. Another recent systematic review found that epidural block reduces postoperative myocardial infarction.4 Although these findings are supportive, they were based exclusively on small RCTs, and meta-analyses sometimes give conflicting results when compared with large RCTs.5 In 1984, Yusuf et al explained how large, simple randomised trials can reliably detect moderate effects on important but uncommon outcomes such as death or major morbidity after surgery.6 Two of us are part of an Australian group that has recently published the results of a large multicentre RCT of epidural block in 888 high-risk patients undergoing major abdominal surgery (the MASTER trial).7 Patients were randomly allocated to receive general anaesthesia with or without epidural block. The epidural block was established before the commencement of surgery (epidural anaesthesia) and epidural analgesia was continued for three days after surgery. All other care was left to the discretion of the anaesthetist and surgical team: most patients were managed in general surgical wards after surgery, although some required high-dependency or intensive care. Thus, our trial was a test of effectiveness in routine practice and its results can be generalised. There was no significant difference in mortality at 30 days or in overall morbidity — 57% of epidural and 61% of control group patients had at least one morbidity endpoint (sepsis, respiratory failure, myocardial infarction, heart failure, renal failure, gastrointestinal [bleeding or need for parenteral nutrition], hepatitis, or haematological [anaemia, leukopenia, or thrombocytopenia]) or died (P = 0.30). Mortality at 30 days was low in both groups (epidural, 5.1%; control, 4.3%). Of the eight morbidity endpoints studied, only one, respiratory failure, occurred less frequently in patients managed with epidural block (epidural, 23%; control, 30%; P = 0.03). Another large RCT published recently showed similar results.8 Thus, there is no evidence that epidural block improves outcome in most patients undergoing major abdominal surgery with general anaesthesia, other than for respiratory complications. Nevertheless, in the MASTER trial, pain scores over the first three days after surgery were significantly lower in the epidural group. This difference occurred despite most participants in the control group receiving multimodal analgesia.1 This demonstrates some benefit from epidural block: a reduction in pain may assist deep breathing and coughing after surgery, and this may help prevent atelectasis and pneumonia. The MASTER trial, and other recent data,3,8 provide some evidence to support this conjecture. What are the risks of epidural block? One should take into account the risk of an epidural haematoma when an epidural or spinal needle is placed, particularly in a patient receiving anticoagulation therapy (eg, perioperative thromboprophylaxis). The risk of epidural haematoma or abscess is very low, with estimates varying widely from about 1 : 1700 to 1 : 200 000.9,10 Concern regarding damage to the spinal cord (leading to paraplegia) or nerves must be weighed up against the benefits of improved postoperative analgesia. Evidence-based practice is dependent on good quality research, and the best evidence comes from large trials.6 The MASTER trial provides reliable information for doctors and their patients on which to base their decisions regarding the best methods of anaesthesia and analgesia after surgery. Epidural block seems to provide additional benefit for patients at increased risk of postoperative respiratory complications. When considering use of epidural block, doctors and patients also need to weigh up the benefits of improved pain relief against the (rare) risk of paraplegia and other nerve injury. Our experience has been that some patients will choose postoperative epidural analgesia after being given this information.

Paul S Myles MPH, MD, FCARCSI, FANZCA · Ian Power FRCA, MD, FFPMANZCA, FANZCA · Konrad Jamrozik DPhil, FAFPHM, MFPHM

It’s time to adopt a cost-effective approach Hypertensive disorders in pregnancy, and particularly pre-eclampsia, remain major causes of maternal and perinatal mortality,1,2 accounting for 15% of maternal deaths and 4% of perinatal deaths. Therefore, a key aim of modern antenatal care is the timely detection and management of pre-eclampsia.1,2 A traditional belief is that this is best achieved by regular, and increasingly frequent, antenatal visits, allowing for both blood pressure measurement and dipstick urinalysis to detect new-onset proteinuria. This strategy underpins the schedule of antenatal care that is still most commonly followed in Australia; namely, monthly visits until 28 weeks of pregnancy, fortnightly visits until 36 weeks and weekly visits thereafter.3 However, it has been apparent for some time that the frequency of visits could be safely reduced without adversely affecting outcomes,4 a notion now confirmed by randomised controlled trials both in the developed and developing world.5 Similarly, it has long been recognised that dipstick urinalysis performs poorly in the detection of proteinuria,1 requiring confirmation by either a formal 24-hour urine collection or a spot urine protein/creatinine ratio.2 However, the accuracy of a dipstick reading is significantly improved if it is read with an automated device rather than visually,6 offering the possibility that routine automated testing for proteinuria may have a place in the detection of pre-eclampsia. In this issue of the Journal, the study by Murray and her colleagues (page 477) explores this possibility.7 The authors prospectively evaluated automated dipstick urinalysis in the diagnosis of pre-eclampsia in almost 1000 unselected women. In a quarter of the women who developed pre-eclampsia proteinuria arose before hypertension. From this, the authors concluded that if the initial screening urinalysis is negative then routine urinalysis thereafter is unnecessary in women with no high-risk factors for pre-eclampsia. These findings and conclusions should encourage providers of antenatal care to reflect on their own practice and to consider whether routine urinalysis is justified, thereby facilitating the provision of the most cost-effective care. The report by Murray et al should also stimulate us to reflect on the cost-effectiveness of the other tests routinely undertaken during antenatal care. It is of concern that there is considerable variation in routine antenatal testing in our hospitals, and that practice is often at odds with available evidence.8 These inconsistencies are not only indicative of inequalities in care, but also suggest wastage of precious and limited resources. Standardisation of antenatal care across Australia, through the development of clinical practice guidelines, might reasonably be expected to reduce this wastage. In the United Kingdom, the National Institute of Clinical Excellence has commissioned the development of such guidelines with 43 recognised stakeholders and a projected completion date by September 2003 (www.nice.org.uk). In Australia, through a project funded by the Victorian Department of Human Services, the three largest public hospital providers of maternity services in Victoria have already developed consensus guidelines on antenatal care. These encompass the delivery of antenatal care, including guidelines for most of the routine tests undertaken in pregnancy.8 These guidelines provide an evidence-based foundation for the rational delivery of antenatal care in these three hospitals. However, they offer far more. The guidelines could be used as a catalyst for the development of national guidelines for antenatal care. An important component of any such development, and one missing from the Three Centres Consensus Guidelines, must be a thorough cost-effectiveness analysis of the various tests and interventions recommended. A cost-effectiveness analysis is important because much of the evidence for the various antenatal testing is imported from overseas and may not be readily applicable to Australia. For example, a recent cost appraisal of screening methods for Down's syndrome in the United Kingdom costed a first-trimester ultrasound examination at about £4 ($12),9 a fraction of the Medicare cost in Australia ($60–$70). In addition, the prevalence of the various infections, such as syphilis and HIV, varies in different regions of Australia, and consequently the currently recommended strategies for screening may need to be modified on a regional basis.10 Such analyses are critical components of the further development of evidence guidelines, but, frustratingly, there has been little support at a national level for the funding necessary for their development and implementation. This is despite an estimate that between $75 million and $100 million is spent annually on antenatal screening in Australia.11

Euan M Wallace · Jeremy J N Oats

The second round of trials may provide more answers The coordinated care trials were nothing if not ambitious! In 1994, the Council of Australian Government proposed that the organisation, funding and management of health and community services could be restructured into three streams: 1 a general stream for individuals needing either occasional or uncomplicated healthcare; an acute stream for patients needing specialised services for acute illness; and a coordinated stream for patients requiring a mix of healthcare services over an extended period. It was assumed that in the last stream patients would benefit by having their care managed and coordinated. Following a national tender process, nine trials of coordinated care were activated and funded by the Commonwealth (Box 1). A central premise of the trials was that better coordination of the care of people with chronic or complex needs would reduce hospitalisation, and the savings could cover the costs of coordination. The coordinated care trials were the largest and most ambitious experiment of a new method of organising healthcare services ever attempted in Australia. The trials ran for two years. Evaluation was undertaken both nationally and at the local level. Much of the trial documentation and evaluation reports are available on the Commonwealth Department of Health and Ageing's website.3 Despite this effort and expenditure, the outcomes were disappointing (Box 1). In general, the trials did not demonstrate improved health and well-being of the participants. A significant reduction in hospital admissions in the intervention compared with the control group was seen in only three of the trials, and for most trials an accrued operating deficit was found. Was this ambitious healthcare experiment a failure? It is hard to say because, unfortunately, the design of the trials made it difficult for them to achieve their stated objectives. The trials included the following design shortcomings. Each trial was funded for two years, but the first six months were devoted to recruitment and the last six months were a wind-down phase. Thus, in many trials, the actual intervention was for 12 months or less, a very short period in which to make an impact on complex illnesses. Difficulty in recruiting sufficient numbers of participants forced many trials to relax inclusion criteria, with the result that many individuals entered in the trial were inherently unable to benefit from coordinated care, since they were not sick enough, or had insufficiently complex problems to warrant care coordination.4,5 In many trials, the same intervention was applied to all participants regardless of the severity of their condition or ability to respond to the intervention. Interventions varied markedly between trials. The chosen measure of well-being, the SF-36, was not optimal to assess the types of intervention, especially over the relatively short trial periods. Despite these shortcomings, the trials provided a number of benefits. Fundholding allowed trials to fund strategies such as quit smoking interventions that otherwise would not have been possible.6 Because of the evaluation needs, many service organisations received major technology upgrading of information systems. The trials received the full cooperation of the Health Insurance Commission, enabling the use of Pharmaceutical Benefits Scheme and Medical Benefits Scheme (MBS) information for evaluation purposes. New enhanced primary care MBS schedule items were announced shortly before the publication of the final results. Finally, much of the qualitative evaluation showed that participants in the intervention groups appreciated the extra coordination of their care. The new round of coordinated care trials that has just commenced (Box 2) has taken on board much of what has been learnt from the first round. The trials are for three years rather than two, have better-targeted interventions, and outcome measures have been carefully selected for their sensitivity to the type of intervention. The possibility remains, however, that the essential premise that better coordination reduces hospitalisation is misguided. It may be that lack of coordination in a complex care system operates as a functioning rationing system, so that better care coordination reveals unmet needs rather than resolving them. Experience in the mental health field implies that this may be so.7,8 With an ageing population and increasing burden of chronic diseases, the government has given priority to increased service coordination, vertical integration and cost containment. The coordinated care trials are just one of several strategies aimed at achieving these objectives. It might well be that the objectives are mutually exclusive and that improved coordination comes at a cost. 1: First round of coordinated care trials General coordinated care trials Nine trials in six States and Territories were funded, involving 10 967 intervention and 5571 control participants. Trials were designed as either randomised (where individuals were assigned at random to the intervention or control group) or geographically controlled (where two matched regions were used, one receiving the intervention). The trials ran from June 1997 to December 1999. Only the SA HealthPlus trial based participant inclusion on specific diagnoses, which included respiratory disease, diabetes, cardiovascular disease, stroke and somatisation. Primary hypothesis Coordination of care of people with chronic or complex needs results in improved participant health and well-being within existing resources. Eligibility Varied by trial, based on one or more of age, complex care needs, or specific diagnosis. Intervention Varied by trial, based on different models of care coordination, care planning and funds pooling. Outcome measures SF-36 measured at baseline, 12 months and 24 months. Health and community service use and expenditure from the Health Insurance Commission and other sources. Results Intervention groups did not perform better than control groups for either SF-36 scales or reductions in hospitalisation, readmission, or length of stay for those hospitalised. Trials were unable to fund coordinated care out of savings from reduced hospitalisation. Aboriginal coordinated care trials Four trials among Aboriginals and Torres Strait Islanders involved 6600 participants. The trials were located in Katherine West (NT), the Tiwi Islands (NT), Wilcannia (NSW) and Perth/Bunbury (WA), and were conducted between 1997 and 1999. Primary aims related to community empowerment and capacity building. The National Evaluation Summary outlines the background, description, experiences and outcomes of the trials.2 The national evaluation found that all trials showed enhanced service access, progress in infrastructure development, and improved individual and community empowerment. Funds pooling was successful in providing greater flexibility in resource allocation. 2: Second round of coordinated care trials Six trials (three general, three Aboriginal community). Began in late 2002 to run for three years. General trials Northern Venture: Continuation of Care 21 first-round trial, Adelaide. Team Care II: Continuation of Team Care first-round trial, Brisbane. Coordinated Health Care: Continuation of North Eastern first-round trial, Victoria. Coordinated Health Care has included specific diagnoses (respiratory disease, heart failure and complex diabetes) as part of its inclusion criteria. Team Care II and Coordinated Health Care are randomised controlled trials with about 2000 intervention participants and 1000 control participants expected. Northern Venture is a prospective intervention cohort trial using matched population controls. It will have about 2000 participants. Objectives 1. To identify people who are most likely to benefit from coordinated care. 2. To identify processes and infrastructure for effective integration and coordination of care. 3. To enhance the health status, quality of life and functional status of participants, and reduce the burden on carers. Outcome measures A range of quality-of-life, functional status and health assessment tools, plus carer instruments measured at baseline and at regular intervals. Health and community service use and expenditure from HIC and other sources. Aboriginal trials South West Aboriginal Medical Service (SWAMS): Continuation of SWAMS first-round trial, WA. Sunrise: Katherine East, NT. Mid North Coast: NSW. Objectives of Aboriginal trials 1. To improve the health of communities. 2. To improve community understanding or control of health and related services. Intervention Different models of care coordination, care planning and funds pooling. Outcome measures Access to primary healthcare services Involvement in population health programs Preventable hospital admissions Length of stay in hospital Improved processes of care Involvement of individuals in decisions about care Social concerns Preventable mortality

Adrian J Esterman MSc, CStat · David I Ben-Tovim PhD, FRANZCP

Simple statements of risks and benefits may not reveal the complexity of human responses to research participation In this issue of the Journal, Scott and colleagues (page 507) report on a retrospective study of family members' experience of participation in a previous study following their child's diagnosis with Ewing's sarcoma.1 The research is important because it casts empirical light on an ethical issue often debated in human research ethics committee meetings: how does research affect those who participate in it? Ethics committees can be very cautious about granting approval for research into sensitive areas because of concern about the impact on research participants. People participate in research for many reasons. They may feel an obligation to their doctor, they may not think they have a choice in the matter, they may hope or believe they will benefit from the research, or they may just wish to help others.2-4 Regardless of the reasons research participants may have for participating, the National Health and Medical Research Council (NHMRC) guidelines5 make clear that the primary duty of members of ethics committees is to attend to the "dignity and wellbeing" of research participants. Ethics committees focus, above all, on the risk of harm or discomfort to participants and on the requirement that participants make a free and informed choice to participate in research. Committees need to bear in mind that In clinical research . . . the risks of participation must be balanced by the possibility of intended benefits to the participants. In other research involving humans . . . the absence of intended benefits to a participant should justly be balanced by the absence of all but minimal risk.2 However, the data from Scott et al suggest that balancing risks and benefits is not necessarily a straightforward matter. How research participants experience risks and benefits can be rather complex. First — at least for research into sensitive areas such as serious and life-threatening illness — participants may find it painful and distressing to recall past events or articulate complex emotions. However, doing so in a supportive environment may actually be beneficial. Scott et al indicate that the benefits gained by participants in their study came despite the pain of talking about distressing events. I would argue that the evidence in their article suggests that some benefits seemed to accrue to participants because they could talk about painful experiences. Ethics committees may be able to separate out the risks and benefits conceptually, but in people's experience of taking part in research, as in other areas of our lives, things are seldom so tidy. Furthermore, the qualitative data reported imply that an additional benefit to participants was the opportunity to learn more about Ewing's sarcoma. Research participants often ask questions — about their illness and its treatment, about the researcher's opinion of the medical care they are receiving, or about other treatment alternatives that may be available. Participating in research can provide extra contact with "experts", which may be of benefit to participants. The question arises, "Is it ethical to inform prospective research participants of such benefits?". Members of ethics committees may not be comfortable with answering "yes" to this question, because they are likely to be worried about the coercive effect of such information. They may also be concerned about other factors that come into play when the researchers' role is extended to include answering participants' questions. They may be apprehensive about the possible effects on the scientific integrity of the research itself; they may believe that research staff are not the best people to answer questions about the participant's condition; or they may be concerned about role confusion for researchers when they also provide advice.6 In addition to considering how researchers should respond to requests for information, it is important to consider why researchers are being placed in this position at all. It is an indictment of our healthcare system that patients may think they need to take part in research in order to have their needs for information and reassurance met. The study by Scott et al also raises the tricky question of the role of altruism in research participation. Nearly all of the study participants felt that their involvement would benefit others. Researchers may encourage such beliefs, often in the context of explaining that they can not guarantee that the research will benefit the participants themselves. The possibility of benefit to others is sometimes all that can be held out as an incentive for potential participants. Even here, however, things are not that simple. Feeling that others are helped by our involvement in research can be of benefit to us, as concern for our own interests and concern for others' interests are actually closely intertwined.7,8 Sometimes we act altruistically because we enjoy the feeling of being an altruistic person and the positive response it engenders in others. In a sense, our self-interested choices can be re-interpreted as altruistic, and vice versa. In Scott and colleagues' study, feeling that others might benefit from their involvement perhaps offered the participants a way to make sense of difficult and otherwise inexplicable events. Finally, the whole issue of risks, benefits and altruism is further complicated by questions about whose notions of risks, benefits and altruism are to count. Ethics committee members, research participants and researchers are all likely to offer different interpretations of these concepts in specific situations. For example, should ethics committees intervene if research participants choose to believe their involvement will help other people like them if, in fact, there is little evidence that this will occur? Can committee members or researchers accurately judge the risks and benefits of research for a participant, or should the emphasis be principally on facilitating choice? Human emotions and ethics are complicated, and simple statements of risks, benefits and altruistic intent are unlikely to reveal the complexity of the situation. What are ethics committees, researchers and participants (potential and actual) to make of all this? They should, at least, recognise that guidelines are only that, and can never substitute for careful and nuanced consideration of the meanings of terms such as "risk" and "benefit". The NHMRC's Commentary on the national statement on ethical conduct in research involving humans, released this year, provides something of a roadmap in this area.9 But committees will still need skills, knowledge, time and resources to consider these issues thoughtfully. While skills and knowledge may not be in doubt, we know that many committees lack the time and resources needed to do justice to these thorny issues.10

Annette J Braunack-Mayer BMedSci(Hons) PhD

A case of public policy confusion In recent years, there has been an increasing focus on the mental health of children and adolescents.1 This is part of the broader process of reform of Australian mental health services, which now emphasises mental health promotion, the development of preventive approaches, early detection of mental disorders and early treatment interventions.2 At the same time, there is now clearer recognition that, in a country as culturally and linguistically diverse as Australia, specific attention must be paid to the cultural dimensions of mental disorder and mental health service design and the specific needs of Indigenous people, immigrants and refugees.3 Major national mental health policy statements now recognise these issues, and funding for State-based transcultural mental health units and centres for the treatment and support of torture and trauma survivors is one aspect of implementing this policy. This is consistent with increased attention being paid to the mental health of immigrants and refugees internationally.4 Of the 6.1 million refugees worldwide for whom demographic data are available, 45.6% are aged under 18 years, although the proportion of children and adolescents varies considerably by region (eg, 56% of refugees in Africa, 23% of refugees in Europe).5 In 2001 there were 900 000 asylum applications pending worldwide.5 The article by McKelvey and colleagues6 in this issue of the Journal (page 413) is important for several reasons. Firstly, research data on the mental health of immigrant and refugee children and adolescents are scarce. The study contributes to knowledge about one of the largest immigrant/refugee communities in Australia in a way that cannot be achieved even by large-scale and expensive studies that aim to be representative of the Australian population.1,7 The recent national survey of 4500 children and adolescents "provides only very limited information about the mental health of children and adolescents living in non-English speaking families".1 Secondly, the authors carefully avoided methodological pitfalls commonly seen in cross-cultural mental health research. They used appropriate translation methods for the questionnaire, worked in partnership with community leaders and Vietnamese-speaking mental health professionals, and conducted research interviews in either English or Vietnamese, using bilingual research staff who were trained and supervised in interview administration. Such attention to appropriate cross-cultural research methods is essential to ensure the validity of information obtained. Thirdly, the study is important because of the finding that the prevalence of psychiatric disorders in Vietnamese children and adolescents was not significantly different from that found in a general Western Australian sample8 and in a national sample,1 despite the fact that many of these children and adolescents had been affected by the stresses of migration to a vastly different cultural environment and that many came from families who had lived through the traumas of war. The data of McKelvey and colleagues relate to Vietnamese refugees settling in Western Australia at one point in time. The same rigorous research process is highly desirable when comparing other refugee populations, especially those experiencing different traumas before migration or different experiences of settlement within Australia. A clinical challenge is to identify subgroups who have suffered, or are at risk of developing, adverse psychiatric consequences. In the study by McKelvey et al, the low rates of mental health problems identified by parents highlights but one of the difficulties that young people from migrant families have in accessing mental health services. There may be a range of explanations for the relatively low rate of mental disorders identified in the study. However, if corroborated by studies of other ethnic groups and research in other settings, these data may reflect a feature of Australian society that has been a considerable success. That is, our capacity to accept immigrants and refugees from all over the world; to integrate new arrivals into a generally harmonious and well-functioning multicultural society; to create the conditions necessary for refugees to recover from trauma; and to provide an environment that is conducive to normal development, especially in children and adolescents. Underpinning this success have been legal and policy frameworks for multiculturalism, extensive services that have supported the successful permanent settlement of immigrants and refugees, and the general goodwill shown by the Australian population to immigrants and refugees. Unfortunately, recent years have seen a substantial bipartisan policy shift in Australia's treatment of asylum seekers, particularly of people arriving unauthorised by boat.9 The policy of mandatory detention of unauthorised "boat people" is now the subject of heated debate. One component of the debate has been the question of whether prolonged detention has harmful effects on the mental health of detainees in general,10 and on the mental health and development of children and adolescents in particular.11 On this latter issue, the subject of an inquiry by the Human Rights and Equal Opportunity Commission, there is remarkable unanimity of medical opinion: prolonged detention is causing harm to the mental health and development of children and adolescents.12 Also of concern is the plight of refugees who have been granted temporary protection visas and live within the community. In comparison with refugees who have obtained permanent residency visas, these people have substantially restricted rights, including the preclusion of family reunion and limited access to social services, English-language training and other services. There is concern that such restrictions may contribute to mental health problems in this group.13,14 Children's emotional and social development may be adversely affected if they are living with parents who are functionally impaired because of depression, anxiety or other mental health problems relating to the stresses and uncertainties of being a temporary visa holder. Current immigration policy, in the form of prolonged detention of asylum seekers and the move to temporary visas for some, is resulting in harm to the mental health of already vulnerable children, adolescents and adults. The mental health impact of this aspect of immigration policy appears at odds with national mental health policy and with the successful settlement policies that still apply to authorised immigrants and some refugees. The study by McKelvey and colleagues6 shows that we can do very much better than this.

I Harry Minas FRANZCP · Susan M Sawyer MD FRACP

The most direct way to reduce percutaneous injuries is to make devices safer In this issue of the Journal, Whitby and McLaws (page 418) provide a thorough epidemiological account of occupational exposure to bloodborne pathogens by hollow-bore needles in one hospital.1 More studies such as theirs are needed in Australia, where there has been relatively little attention focused on this issue, as indicated by the few references to studies by Australian investigators cited in their article. As an American I find this surprising, because many successful prevention programs introduced in Australia have earned the admiration of public health professionals in other countries. Three examples come to mind: laws requiring seatbelt use and advanced passenger protection in motor vehicles; progressive HIV prevention programs; and programs to prevent ultraviolet light exposure and skin cancer. I am among the admirers of Australia's strong prevention record. In light of these progressive programs, how might one explain the relative neglect in Australia of such a serious occupational risk as bloodborne pathogen exposure? Some answers may be extrapolated from the United States, where I have observed a culture of self-sacrifice among healthcare professionals that compels them to place self-interest at the bottom of their priority scale. I have also seen administrators make healthcare worker safety a low priority when protective measures for their employees require a financial commitment. Finally, resistance to new prevention policies for healthcare workers is likely to be strongest where there is a lack of surveillance data. This is the "no data, no problem" syndrome. In Australia, an awareness of the significance of the problem of exposure to bloodborne pathogens is necessary before a national commitment can be made to its solution. Percutaneous injuries are the most frequent type of injury sustained by healthcare workers, and the most life-threatening.2 This remains true despite important advances, including the availability of the hepatitis B vaccine and post-exposure chemoprophylaxis for HIV-exposed healthcare workers.3,4 Therefore, I am convinced that the only choice is to accept the responsibility of caring for our caregivers — in Australia and elsewhere. The first step towards overcoming neglect is documenting the problem. The report by Whitby and McLaws provides a fine example, on a small scale. With reported annual percutaneous injury rates of 4–15 injuries per 100 full-time-equivalent staff,1 and device-specific injury rates occurring usually in the range of 1–20 injuries per 100 000 devices used,5 the participation of numerous institutions and a long term commitment are required to maintain a database that can guide and sustain large-scale prevention programs.6,7 Active surveillance programs support strong policy initiatives, as has been seen in the US, where surveillance data have supported new regulations, guidelines and advisories issued by our government agencies, as well as state and national legislation.8,9 Widespread surveillance should become a national goal for Australia. There is a global network of countries in Europe, Asia and South America with advanced surveillance programs eager for collaborative exchange. Surveillance data reveal the causes of bloodborne pathogen exposures and they lead to conclusions that are difficult to ignore. Surveillance data from the International Health Care Worker Safety Center, University of Virginia, from 1996 to 2000 (84 hospitals, 23 243 injuries) show that 98.5% of percutaneous injuries sustained by healthcare workers were caused by sharp medical devices (exceptions include injuries from windshield glass, teeth, fingernails and bone fragments). Therefore, the most direct route to preventing percutaneous injuries is to make injurious devices safer to handle. I find it incredible that the debate still persists whether educational programs or safer devices should be the preferred method of protecting healthcare workers. If you asked a soldier dispatched to the frontlines of battle whether he would prefer a protective shield or an educational poster, there would be no need for discussion. Let us move quickly to get protective devices into the hands of healthcare workers, while providing the best educational methods to support the use of safer technology. The lack of data on the effectiveness of safety devices is often raised as a barrier to their adoption. Although there are several studies demonstrating the efficacy of safety-engineered needle devices, there nevertheless remains a need for further well-designed clinical trials as new and safer technology comes into the market place.10-11 But where data are lacking on potentially life-saving technology there should also be a responsibility to collect those data, rather than merely rejecting the technology by reason of their absence. But we should also not dismiss the use of common sense in weighing the potential safety impact of many safer devices: intravenous infusion systems with needleless access ports and needleless line connections cannot cause needlestick injuries (as long as one does not override the system and use needles with them); plastic capillary tubes and vacuum tubes all but eliminate the possibility of lacerations; blunt-tipped suture needles do not cause needlestick injuries. Not every device category requires a clinical trial to prove a reduction of injuries, especially if that device eliminates a needle or sharp item. Another area of time-consuming debate is whether safety devices are cost-effective. We now have a law in the US, the first in the world, requiring healthcare employers to provide safety-engineered devices for the prevention of percutaneous injuries, without consideration of their financial impact on individual healthcare facilities.9 Whitby and McLaws say that "such a situation should not be allowed to occur in Australia". Perhaps they need not worry about the potential cost burden in Australia. As the first customers of this new technology, US healthcare institutions, which comprise the largest medical device market in the world, are bearing the brunt of the cost burden. The new law has caused medical device companies to shift into high-volume production of safety-engineered devices. Economies of scale are already bringing prices down, as is the intense competition to gain market share in this new product area. These benefits will no doubt spill over to other countries. But I would hope for the sake of its healthcare workers, and in keeping with its strong tradition in the field of prevention, that Australia's response would be more active than simply waiting to see what washes up on shore.

Janine C Jagger MPH, PhD

The benefits of statin therapy do not come without financial cost The aim of the recently reported Heart Protection Study1 in the United Kingdom, with over 20 000 participants aged 40–80 years, was to establish whether statin therapy is of benefit to people who are at high risk of cardiovascular disease (CVD) but have average-to-low levels of total cholesterol and LDL-cholesterol. High-risk patients (defined as those having previous coronary heart disease, diabetes, stroke, or peripheral vascular disease) were treated with simvastatin (40 mg daily), antioxidant vitamins (20 mg beta-carotene, 250 mg vitamin C and 600 mg vitamin E daily) or placebo in a 2 × 2 factorial design. Among patients allocated to the antioxidant arm of the trial, there was no change in incidence of any prespecified endpoints, and there were small but significant increases in blood levels of LDL-cholesterol and triglycerides, which have the potential to increase CVD risk with long-term antioxidant use.2 High-dose antioxidant therapy is therefore not recommended.3 Reductions in cardiovascular events (including myocardial infarction, stroke and either coronary or peripheral arterial revascularisation) occurred with simvastatin therapy in women, elderly people, and people with previous cerebrovascular disease, peripheral artery disease, renal impairment or diabetes (see Box). Translating the results of the HPS into clinical practice, patients with an absolute overall CVD risk of more than 17% over five years (the lowest rate occurring in any subgroup of the HPS treated with placebo) should receive high-dose statin therapy, equivalent to 40 mg/day simvastatin, independent of baseline levels of total cholesterol; and other cardioprotective therapy, such as β-blockers and aspirin. Overall CVD risk can be estimated with the National Prescribing Service charts,4 which refer to CVD rather than coronary heart disease risk — a strategy flowing from the HPS outcomes.1,4 These charts, based on the Framingham study, provide only an approximation of absolute risk, but serve as a useful guide. Examples of patients with five-year CVD risk above 17% include most men over 60 years who smoke and have diabetes, and a 60-year-old non-smoking, non-diabetic man with blood pressure of 160/95 mmHg and a total cholesterol/HDL-cholesterol ratio of 6: 1.4 Benefits are likely to occur after 12 months of statin therapy, with greater benefits occurring the longer therapy is continued. Allowing for non-compliance, the HPS showed that about a third of major CVD events are likely to be prevented by statin therapy over five years. In the HPS, 23% of patients in the simvastatin group were smokers, 22% were being treated with antihypertensive agents, 20% with β-blockers, 25% with angiotensin-converting enzyme inhibitors (ACE inhibitors) and 21% with aspirin. Relative risk reductions in CVD incidence of up to 80% may be expected when statins are combined with standard cardioprotective agents (aspirin, β-blockers and ACE inhibitors) and stopping smoking.3 Given that CVD reduction in the HPS was independent of baseline cholesterol levels, it has been suggested that lipid levels need not be measured before commencing statin therapy in high-risk patients.3 However, fasting levels of triglycerides and HDL-cholesterol should be measured after 1–2 months, as therapy may need to be modified if these lipids are inadequately controlled by statin therapy alone. For example, gemfibrozil therapy may be considered for patients with low HDL-cholesterol levels.5 The HPS included about 6000 individuals with diabetes — the largest number in any statin trial reported to date. The CVD event rate for placebo-treated diabetics without coronary heart disease was 18.6%, compared with 22.5% for non-diabetics with coronary heart disease. Thus, the HPS confirms diabetes as a "coronary-equivalent" risk disorder for CVD.6 However, risk of CVD may vary from low to very high, depending on age and other risk factors, so it is still necessary to determine the global risk of CVD for an individual with diabetes when assessing the need to treat with a statin.4 Subjects at highest risk of CVD in the HPS had slightly elevated baseline serum creatinine levels (> 200 μmol/L), although only results of univariate analysis have been provided. The HPS confirms the high CVD risk in patients with impaired renal function and also supports the need for treatment of their dyslipidaemia.7 Caution is required in giving statin therapy to patients with more severe renal impairment, as they are at increased risk of myopathy.8 In the HPS, the safety profiles for statin and placebo therapy were similar. This finding may partly be a consequence of the exclusion of patients who showed adverse reactions to simvastatin during a 4–6-week run-in period leading up to the trial. However, only 32% of 63 603 screened patients were allocated to receive simvastatin in the study, so the low adverse event rate in the study may not necessarily apply to an unselected population. Of particular importance with regard to safety was the low incidence of myopathy (defined as serum creatine kinase levels exceeding 10 times the upper limit of normal), which occurred in only 11 simvastatin-treated patients and six placebo-treated patients. These results are reassuring, but muscle symptoms and creatine kinase levels should still be monitored periodically, and withdrawal of statin therapy should be considered if myalgia occurs or creatine kinase levels rise to more than three times the upper limit of normal.9 There were no apparent safety concerns in patients with low baseline LDL-cholesterol levels (< 3 mmol/L), in whom average LDL-cholesterol levels during the trial were 1.8 mmol/L in the simvastatin-treated group and 2.7 mmol/L in the group receiving placebo. The association between low levels of total cholesterol and increased cerebral haemorrhage found in a study by Iso et al10 was not borne out by the HPS. The safety and efficacy of treatment with 40 mg/day of simvastatin demonstrated by the HPS will probably result in a higher average dose being used in Australia, where the current average dose is 25 mg/day (Glen Godresse, Specialist/Hospital Product Manager, Merck Sharp and Dohme Australia Pty Ltd, personal communication). The benefits of statin therapy do not come without financial cost, although the long-term savings as a result of statin therapy are very likely to outweigh that cost.11 As CVD remains the single most important cause of mortality in Australia, consideration should be given to extending the availability of statins under the Pharmaceutical Benefits Scheme to include patients shown in the HPS to benefit from therapy: diabetics, women over 40 years, elderly people, and those with peripheral vascular disease, renal disease and low-to-average cholesterol levels, if their estimated global CVD risk exceeds 17% over five years.4 Absolute risk reductions and numbers needed to treat to prevent one cardiovascular event1 Event ARR (%)* NNT† All-cause mortality 1.8% 56 Mortality due to CHD 1.5% 83 Non-fatal myocardial infarction 2.1% 48 Coronary revascularisation 2.6% 38 Ischaemic stroke 1.2% 83 MVE without baseline CHD 4.7% 21 MVE with baseline CHD 5.7% 18 MVE with baseline creatinine > 200μmol/L 9.0% 11 MVE in patient aged < 65 years 5.2% 19 MVE in patient aged ≥ 70 years 5.1% 20 CHD = coronary heart disease. MVE = major vascular event (includes CHD, stroke, revascularisation). * Absolute risk reduction (%), simvastatin therapy v placebo. † Number needed to treat with simvastatin 40 mg/day to prevent one event over 5.3 years.

Ian Hamilton-Craig PhD FRACP

A more proactive approach by GPs would help to ease the burden on family carers In Australia, up to 2.3 million people are involved in informal care of children, adults and older persons with disabling chronic and terminal conditions.1 Their role includes managing medications, therapies and medical emergencies; providing supervision and emotional support; and assisting with personal care, mobility and household tasks.1-3 While caring can provide considerable satisfaction and strengthen relationships, carers often feel exhausted, isolated and burdened by their responsibilities.1,3,4 In a recent survey of carers, 58% reported their physical health had been adversely affected, a third said they had sustained a physical injury, and over half reported depression, anxiety, high levels of stress and other impacts on their mental health.2 There have been many calls for general practitioners to be more proactive in addressing the support needs of carers,3-6 and carers have identified how this may be accomplished (see Box). A 1998 editorial on family carers in Australia3 called for strategies to raise health professionals' awareness about carers, to keep them abreast of programs available to carers, and to encourage them to be more proactive in helping carers to obtain support. Since then, there has been limited apparent progress in Australia (unlike Britain, where there has been considerable interest in the primary care team's designated responsibility for addressing carer needs7). Projects conducted through Divisions of General Practice to inform and educate doctors, to promote carer self-identification and discussion5-6 and to promote collaborative referral with regional carer respite services5 showed encouraging outcomes, but have failed to attract further funding from government. Carer associations have also acted by providing various resources. The GP information kit, Carer Checklist and Carers Profile assessment tools (trialled in New South Wales) are time-efficient and pave the way for discussion of carer issues.7,8 In Victoria, individual carers are encouraged to raise issues and to give their GPs a tailored service-provider kit, but this approach lacks systematic coverage. In South Australia, a GP working group is seeking to collaboratively explore various approaches, including GP education and involvement of practice managers. Government initiatives have focused on raising GPs' awareness of community services and referral pathways (eg, the Commonwealth CareLinks and Victorian Primary Care Partnership8). Supporting tools initiated by governments include service directories, consumer assessment and service coordination templates, referral mechanisms (both printed and Web-based) and consumer/carer charters. The full potential of information technology has not yet been harnessed. For example, including a "carer status" field in patient records would prompt early identification of care responsibilities. Software could also alert GPs to provide information or follow-up, and could even include (or electronically link to) carer fact sheets and resources, such as those produced by the national carer organisation Carers Australia. Even GPs committed to working with carers can face considerable barriers to implementing a proactive approach. The patient may not agree to the carer participating in the consultation, or the carer may be reluctant to discuss how he or she is managing, especially if the patient is present or the carer perceives the GP to be too "busy" or very medically focused.4,5,7,10 Either the patient or the carer may be reluctant to accept external assistance.5,6,10 The carer may forgo his or her own health checks or treatment plan because of the pressures of caregiving.2 Finally, in addition to lack of training, information and resources,5-7,11 GPs have to cope with increasing demands, time constraints and inadequate remuneration,5,7,9-11 problems that are often difficult to overcome. The Enhanced Primary Care (EPC) Medicare Benefits Schedule items provide an opportunity to focus on carers and partly address the issue of remuneration for GPs.12 With the patient's consent, carers can be formally included in care planning and case-conferencing activities. This enables GPs and other healthcare workers to hear carers' views on how well they and their patients are managing at home. GPs and carers can then jointly consider options for coordinated support. Where carer wellbeing is an issue, staff of regional carer respite services (or other workers assisting the carer) can usefully be involved.6 Health assessments, another EPC item, should also include screening for carer issues. However, GPs may still need to grapple with the thorny issues of consent, conflict and reluctance — interpersonal issues arising in the relationships between patients and carers and between patients/carers and their doctor. Much of the responsibility for monitoring patient records and maintaining information resources can be delegated to the practice manager or an allied health professional. For example, practice nurses have effectively undertaken health assessments13 and are well positioned to provide carer health education, service referral and coordination. A counsellor or carer-support worker attached to a general practice can assist with identifying carer needs and making referrals, as well as helping the carer to develop skills and to work through emotional or relationship issues.6 The Better Outcomes in Mental Health Initiative14 is relevant to assisting carers who are experiencing severe stress, anxiety or depression. The initiative provides incentive payments for mental health needs assessment, planning and review activities to doctors who register interest with their local Division of General Practice and receive training. We believe that including educational material on carer mental health issues in training packages would enhance this initiative. Given the absence of clear strategies and leadership on this issue over the past four years, the development of clinical practice guidelines and policy positions by governments and peak practitioner bodies is needed. The evolving Commonwealth-funded Primary Health Care Research Evaluation and Development Strategy15 provides an ideal opportunity to prioritise collaborative research in this area. The demonstration of the benefits to carers, those they care for, and the community generally, of an overtly aware and interventionist clinical approach is well overdue. What carers would like general practitioners to do6-8 Recognise their carer status and care responsibilities and include them in care planning and decision-making. Avoid assumptions about carer's capacity, confidence and willingness to provide home care. Provide plain-language information to the carer on the patient's condition, prognosis, treatment, care needs and management (including behaviour management). Provide information and referrals relevant to carers (eg, in-home and residential respite care options, counselling, peer support groups, financial entitlements, self-care and coping strategies). Give referrals to carer associations and state-wide condition-specific bodies as a starting point. Discuss and, where appropriate, assess the carer's own physical and psychosocial health needs. Engage other family members in understanding and sharing care responsibilities. Recognise grief and loss on cessation of caring.

Julie M Nankervis MSW MAPS · Peter J Waxman MB BS FRACGP · Denise A O'Hara MB BS MPH FAFPHM · Mary Burbidge MB BS

Trial evidence best informs real-world medicine when it is relevant to the clinical problem Controlled clinical trials provide the most reliable evidence of whether treatments are effective, particularly when the effects of treatment are moderate. Without such trials, ineffective treatments or, even worse, harmful interventions may be accepted in medical practice. Yet medical practice is often not based on clinical trial evidence, because the evidence is considered not relevant or does not exist. Real-world medicine must not only consider the effectiveness of specific treatments, but must do so in the context of patients who have multiple problems and who are often already receiving many different treatments in a setting different from that tested in the trial.1 Throughout the history of medicine, many treatments have been considered effective until well-controlled trials demonstrated otherwise.2 Some recent treatments based on observational data that have been discredited by randomised controlled trials include hormone replacement therapy to prevent coronary heart disease events,3 vitamin supplements to prevent lung cancer4 or cardiovascular disease events,5 and arthroscopic surgery for osteoarthritis of the knee.6 Although data from observational studies may be of value,7 these data may sometimes suggest a harmful outcome for treatments that are known, from controlled trials, to be effective, such as blood pressure treatment.7 Applying trial results to individual patientsAlthough clinical trial evidence for the introduction and use of new drugs is widely accepted, the "real-world" uptake is often erratic. For patients with coronary heart disease, the merits of statins, angiotensin-converting enzyme (ACE) inhibitors, β-blockers and aspirin are well recognised from clinical trial evidence, yet these treatments are still significantly underused.8 The gap between evidence and practice is even wider in other areas. Evidence is an essential part of good medical practice, but it is not the only information needed for clinical decision-making. Real-world medicine may ignore clinical trial evidence if it does not seem relevant to the clinical problem at hand or if the benefit is uncertain. A drug that shrinks a cancer is not necessarily useful unless it also improves the patient's quality of life or prolongs survival. A treatment that lowers blood pressure or cholesterol has value only if these outcomes are translated into meaningfully fewer cardiovascular events, without a penalty of increased adverse effects. Hence, evidence from trials is most applicable in practice when the design and the outcomes chosen are directly relevant to real patients, the trials are undertaken against a background of standard medical care, patients in trials are broadly representative of patients in the real world, and evidence from trials is integrated with individual patient characteristics for meaningful risk–benefit assessment. Absolute differences in risk (or numbers needed to treat) are recognised as most relevant to decision making; yet clinical trial results are often reported as changes in relative risk. For example, recent clinical trial results of breast cancer risk in women taking hormone replacement therapy appeared exaggerated if the increased risks were considered in relative rather than absolute terms. Treatment resulted in a 26% relative increase in breast cancer, which equated to an absolute increase of just 0.08% per year.3 Nevertheless, the relative treatment effect is of value if applied appropriately (by combining it with the individual's baseline risk), providing a better guide to the absolute effect of treatment in specific patient groups.1 ParticipationDespite the need for high-quality clinical trials, few patients participate in them, even in areas where trials are common. For example, less than 5% of eligible patients participate in most cancer trials9 and less than 10% in many cardiovascular trials.10 Low participation rates raise concerns that the results from trials apply only to select groups of patients. Scant participation is not necessarily a problem if patients are representative, but patients in trials are often narrowly selected because of the eligibility criteria, the setting, or the patients agreeing to participate. Strategies such as public access to ongoing trials through registers and more pragmatic trial designs are needed to maximise participation and ensure treatments are assessed in a variety of settings. The need for wider use of clinical trialsWhenever a new drug treatment is discovered that has the potential to help many patients, prevailing systems support well-controlled trials addressing effectiveness and safety. Systems to assess new technologies or interventions other than drugs are equally important, yet more challenging and much less developed. Also lacking are sufficient trials of new devices, health service management decisions, and trials in community or Third World settings. It has been suggested that clinical trials are too expensive, and funding outside the pharmaceutical industry is limited. A randomised clinical trial, evaluating a moderate treatment effect on important clinical outcomes, may cost from $1 million to more than $50 million. However, this cost needs to be put in the context of healthcare generally (more than $50 billion in Australia each year11) and the cost of not undertaking trials before deciding which treatments to support. The Australian government has recognised the importance of basing funding decisions for new health technologies (through the Pharmaceutical Benefits Advisory Committee and the Medicare Services Advisory Committee) on the best evidence of the effectiveness, safety and cost-effectiveness of each treatment. But funding more research on the cost-effectiveness of new technologies is also warranted. Specific clinical trials in this context may be much more cost-effective than using funds to introduce therapies on the basis of less reliable evidence.12 Consequently, a more proactive funding strategy for trials should be considered, extending the model proposed by Glasziou: 13 up to 1% of the national healthcare budget could be used to test new and existing health technologies for which there is inadequate evidence, but potentially large benefits or cost savings.14 One approach to monitor and implement some of these strategies is through the use of a comprehensive national trials register to aid the planning of new trials, ensure all trials are identified when evaluating trial evidence, and maximise participation of patients and doctors in ongoing trials.15 Many clinical trials already play a central role in everyday clinical practice. However, if we seriously address each of the above issues, health outcomes could be further improved through clinical trials assessing new health technologies and existing treatments in the real world of modern medicine. It is time for us to look at how to make this more of a reality.

R John Simes

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

J Michael Dixon

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

Melissa Sweet MA

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

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

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

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

The logic is simple, but the implementation difficult and the costs potentially astronomical. Simple, because the cause is usually ventricular fibrillation (VF), which, if corrected within one minute, leads to survival in well over 90% of patients.1 Implementation is difficult because of the 10% fall in survival for every minute that passes from onset of VF until a defibrillator can be used.1 Astronomical cost is anticipated if all people at high risk of VF were to be offered an implantable defibrillator,2 or if the conventional ambulance service were geared up to provide a response time of less than five minutes in metropolitan areas. Novel approaches are required, as the average Australian ambulance response to cardiac arrest is 8–10 minutes even in metropolitan areas, and the survival to discharge for VF is generally less than 10%. A new initiative is presented on page 305 of the Journal — Smith et al report the experience in Melbourne, where fire fighters have been trained to defibrillate, fire trucks are equipped with defibrillators, and a three-tier response (ambulance, intensive care ambulance, and fire vehicle) is made to 000 calls for suspected cardiac arrest.3 The Victorian Government and the Victorian Department of Health are to be complimented on trying a new approach, as are the emergency service officers who participated. But the results are disappointing, despite overall mean response time of 6.0 minutes and time to defibrillation of 8.8 minutes. Of 2942 events, 1331 patients were in cardiac arrest and considered for resuscitation, but just 155 were in VF. From these, there were 26 known survivors, of whom 10 received initial care from fire fighters and 16 from ambulance paramedics. Of the 10 initially treated by fire fighters, possibly half would not have survived with the later arrival of an ambulance. The low prevalence of VF (12% of all [155 of 1331]; 36% of presumed cardiac arrests [155 of 430]) contrasts with the 100% prevalence at the Melbourne Cricket Ground,4 suggesting that there was substantial delay in calling 000. In the Melbourne experience for three-tier response, costs were not estimated, but must include the wage margin negotiated with fire fighters, the cost of training and equipping vehicles, and any overtime worked. A rough estimate for a possible five lives saved among almost 3000 calls reported by Smith et al is more than $1 million. The question arises, is there a better way? In the United States, emergency medical services are usually provided by town or city fire departments. However, except in model cities like Seattle, response times are similar to or longer than those in Australia, and survival rates correspondingly bad. In Rochester, Minnesota (home of the Mayo Clinic), defibrillators are carried in police vehicles. As in Melbourne, these vehicles respond to an emergency (911) call and have reduced response time to five minutes, with overall survival boosted to more than 40%.5 This system has been tried in other US cities and rural areas, but without the same commitment or success. Regrettably, in most instances, the overall survival rate remains less than 10%, and could be worse in an environment where security is more intense and access more difficult. Is there another way to tackle this problem? Clearly, we can identify high-risk individuals and insert a pacemaker/defibrillator (as in US Vice President Dick Cheney), but at high cost, and with benefit to a small fraction1,2 of the more than 10 000 people who suffer cardiac arrest outside hospital each year in Australia. Most cardiac arrests are unexpected and occur in people with little or no apparent risk.1 A different way was first suggested by Frank Pantridge, who initiated the "coronary ambulance" concept. In 1968, he developed a small portable defibrillator, which he suggested be located like a fire extinguisher in buildings and public places.6 His idea fell flat, since the device could be used as a weapon, but has regained credibility with development of semi-automatic defibrillators that can only be activated if a person is in VF.7 These defibrillators were introduced into all ambulances in New South Wales in 1990, then into the Qantas aircraft fleet in 1991,8 then much more widely. The high survival rates for VF at the Melbourne Cricket Ground (71%),4 Chicago (O'Hare) Airport (75%)9 and Las Vegas casinos (53%)10 are attributable to very early use by first responders (St John volunteers, airport staff, passers-by, or security officers), who can initiate defibrillation well within the time it takes for conventional emergency services to arrive. What then is the current status of "public access defibrillation" — the fire extinguisher approach? The program has the blessing of the American Heart Association and the International Liaison Council on Resuscitation, which have been promoting it with increasing enthusiasm since 1990. In Australia, it has been promoted by St John Ambulance (the most experienced voluntary body), the Heart Foundation, and the Australian Resuscitation Council. In the US,7 state legislation has been introduced to permit early implementation, and federal legislation has been passed to provide defibrillators for isolated areas, and to require installation of defibrillators for "public access", with key staff trained, into all major federal buildings and into all passenger aircraft with one or more cabin attendants by mid-2004. In the United Kingdom,11 more than 800 defibrillators have been deployed in public places and another 3000 placements planned — and key staff trained — under a government initiative. Australia, regrettably, has fallen behind. The NSW Ambulance Service provided key advice in development of the original Laerdal semi-automatic defibrillator, while Qantas was the pioneer in the sky and set the benchmark for aircraft and airports in 1991. The National Health and Medical Research Council (NHMRC) has, to date, not seen cardiac arrest as a health priority, despite more than 10 000 lives lost yearly and a potentially high salvage rate. Currently, St John Ambulance Australia has a proposal before the federal government for a program with strong community links and has a belated chance to match or better what is happening in the US, the UK and elsewhere. The Melbourne experience reported in this issue may be disappointing, but it is an important step by the Victorian government, emergency services and medical personnel, who have already achieved recognition for other initiatives in pre-hospital care. We have new tools and we need to implement them to address the most common cause of sudden unexpected death in our community.

Michael F O'Rourke MD, DSc

In this issue of the Journal, Loke and colleagues (page 291) present data from an analysis of 174 advertisements for pharmaceuticals appearing in six Australian medical publications.1 The findings are striking enough to be restated. Fewer than 8% of the advertisements contained quantitative data about the outcomes of therapy, and most of these framed the information in relative rather than absolute terms. Only 28% of the therapeutic claims in the advertisements conveyed clinical outcomes in any specific, substantive and unambiguous way. In the United States, pharmaceutical advertising is subject to the Federal Food, Drug, and Cosmetic Act,2 and Loke et al suggest that, in Australia, advertisements for drugs may be less informative than in the US. The pharmaceutical industry has long maintained that drug advertisements are an important vehicle for conveying important information about new drugs to prescribers. Is this how industry believes it should communicate with highly trained healthcare professionals? Should we really be surprised by the results of Loke et al, and, more importantly, should we be concerned? We know that the pharmaceutical industry spends enormous sums on promoting its products (about twice the amount spent on research and development),3 but most data on the effect of advertising on prescribing are unpublished, and have been gathered by advertising companies. The Association of Medical Publishers (AMP), a US-based organisation whose membership includes the publishers of nearly 200 biomedical journals, boasts "advertising in medical publications alone... can generate sales for both new and more-established products" [original emphasis].4 AMP reports a number of studies that have shown a significant increase in market share and retail sales as a result of medical journal advertising, which is reported to provide a return on investment (ROI) of about US$5.00 for every dollar spent, greater than detailing (ROI US$1.72) and direct-to-consumer advertising (ROI US$0.19).5 Most advertisements are for new and expensive drugs, so increased use due to promotion will contribute to the financial pressures on the Pharmaceutical Benefits Scheme (PBS). Does journal advertising also lead to inappropriate practices? Although there is a substantial body of research on the effects of pharmaceutical industry promotion generally, relatively little involves printed advertisements in medical journals. In a landmark study, Avorn and colleagues studied physicians' beliefs about the efficacy of two classes of drugs (propoxyphene analgesics and central/peripheral vasodilators) that were being heavily promoted as effective, despite evidence that they lacked any efficacy and offered no advantages over existing treatments.6 The authors found that, even though doctors reported paying little attention to drug advertisements, most doctors believed that these agents were effective. Do the results reported by Loke and colleagues have other implications? What is their relevance for the development of government policy? The Australian Competition and Consumer Commission (ACCC) is currently examining an application for reauthorisation of the Code of Conduct of the Australian Pharmaceutical Manufacturers' Association (now Medicines Australia). As part of the examination of the relationships between pharmaceutical industry participants, the ACCC is investigating claims in the media about some practices and whether they are in the best interests of the community (Lin Enright, Director, Public Relations, ACCC, personal communication). The ACCC should heed the results reported here. It is only two years since the review of direct-to-consumer advertising of pharmaceutical products in Australia.7 Although the review recommended against direct-to-consumer advertising, the subject is under continuing review, and some within the pharmaceutical industry are still pressing for change, maintaining that such a facility would enable them to provide important educational information about drugs to the public. Similar moves to relax laws relating to direct-to-consumer advertising are also occurring in Europe and Canada.8 The information reported by Loke et al on journal advertisements suggests that direct-to-consumer advertising is likely to be uninformative and promotional rather than educational in nature. Where should we look for guidance on appropriate standards for advertising pharmaceutical products? Medicines Australia polices a voluntary code of conduct that aims to set "standards of conduct for the activities of companies when engaged in the marketing of prescription products".9 This document places more emphasis on what not to do when promoting medicines, rather than offering guidance on how to provide balanced advice to clinicians about the efficacy and safety of medicines. Perhaps we should pay more attention to the advertising standards maintained in other industries. Generally, advertisements for technologically sophisticated products include prominent displays of their specifications, performance and selling price. Is it too much to ask that advertisements for modern drugs provide similar information? In an era of evidence-based medicine this should include data on the absolute effects of therapy, such as the response rates with and without treatment, and the number needed to treat, in order to avoid the ambiguities of relative measures such as the relative risk reduction. It would be best if this information related to comparisons with established therapies, not just placebo. Clinicians should also be told the dispensed price of the drug under the Pharmaceutical Benefits Scheme.

David A Newby BPharm, PhD · David A Henry MRCP, FRCP

In 1990, while the Royal Commission into Aboriginal Deaths in Custody was in progress, a group of Aboriginal women requested a meeting with the Federal Minister for Aboriginal Affairs so they could talk with him about issues of deep concern. They were granted 10 minutes. Two minutes into the meeting, as they told the Minister of the escalating incidence of violence within our communities, the Minister interrupted: "I know the problem. You tell me some solutions."1 Most Indigenous Australians regard research and researchers with cynicism and suspicion. We have good reason. We have been researched to death and beyond. Research does have an important role in helping find solutions. It can uncover what is happening and why. If designed and implemented appropriately, it can navigate a way forward and show what is, or is not, working. An accurate description, analysis and understanding of "problems" determines the actions of activists, workers in the field, policy-makers and service providers. Research therefore has a vital role to help inform both Indigenous peoples in their pursuit of appropriate services and non-Indigenous policy makers as we work together. In this issue of the Journal, Williams et al (page 300), reporting on assault-related admissions to hospital in Central Australia, conclude: ". . . assault-related admissions to hospital in the proportions we describe suggest a significant public health problem that requires attention."2 Their article is important, if only to strengthen the voices of Aboriginal women, who have been saying for some time that violence, in its many forms, is escalating at an alarming rate within our communities.3 But more is needed. Williams et al present their results from a reductionist research focus on morbidity and mortality. These parameters represent only the end-result of a vicious cycle of violence — a cycle that has had profound and lasting impacts on Indigenous families and communities across generations.4 No reference is made to the context, which embraces where, why and how such violence is occurring. A reference is made to "many resources . . . developed to assist healthcare workers, communities and individuals with alcohol and violence", but these are not discussed. Research into the health status of Indigenous peoples must begin to focus beyond statistical data. For research to have value and to be of benefit, we must try to find out if the strategies referred to are working or not, and why. Some researchers have observed that "there is abundant evidence that psychosocial factors have a profound impact on health", but that "little research to date has targeted the possible biopsychosocial pathways by which social, environmental and contextual conditions of living affect health".5 Indeed, the Australian Institute of Health and Welfare, while recognising the multiplicity of factors that might account for poor health status, relies predominantly on biomedical indicators of health.9 This fails to embrace the less easily measured aspects of community living and wellbeing, now deemed to be of prime importance by Indigenous peoples and public health researchers alike.7 The 1986 Ottawa Charter of Health Promotion outlines the fundamental conditions and resources for health: peace, shelter, education, food, income, a stable ecosystem, sustainable resources, social justice, and equity, which requires, among other things, equity in housing, education, income, and social power.8 Its principles resonate strongly with punyu. The word punyu, from the language of the Ngaringman of the Northern Territory, explains that concepts and functions of health or wellbeing must be considered from an interdisciplinary and multidisciplinary approach. Punyu encompasses person and country, and is associated with being strong, happy, knowledgeable, socially responsible (to "take a care"), beautiful, clean, and safe — both in the sense of being within the law/lore and in the sense of being cared for.9 Being well would therefore be an "achieved quality, developed through relationships of mutual care".10 We do not have peace in Indigenous communities, and all the other prerequisites listed here for health and wellbeing are also left wanting. The Ottawa Charter and the subsequent Sundsvall Statement bring into sharp focus the connectedness between human beings, their physical and social environments and their health and wellbeing. They emphasise that "Health is created and lived by people within the settings of their everyday life; where they learn, work, play and love. Health is created by caring for oneself and others, by being able to make decisions and have control over one's life circumstances and by ensuring that the society one lives in creates conditions that allow the attainment of health by all its members."11 This view echoes the same beliefs that underpin the quest for equality in health, which ensures all people have a right to be part of the process that impacts on their wellbeing at both personal and professional levels within the health service, education and research industries. As we reflect on this major public health problem, we must also consider our potential for doing things differently. There is an appealing reciprocity about the Indigenous punyu and the Western new public health movement, with its strong ecological framework. There exists an opportunity for strong partnerships between Indigenous and non-Indigenous healthcare professional educators and practitioners in shaping or reshaping the future education of healthcare professionals and meaningful health research, even research that focuses on violence. The Minister was right. We do need to focus on solutions. Some Indigenous Australians have argued for process evaluation research, looking at the application and outcomes of interventions and services within our communities. The search for solutions will have to involve greater discussion between Indigenous and non-Indigenous researchers in consideration of the more ecologically grounded interpretation of health promoted by Indigenous peoples, the Ottawa Charter and the Sundsvall Statement. We must develop ways of thinking about and engaging with problems, such as assault-related injuries, as we work together to find better tools for changing the wellbeing of Indigenous communities.

V Judy Atkinson BA, PhD · Jenny Graham DipOT, MSc(Ed), AFCHSE · Gloria Pettit BA, MA · Liz Lewis BA

Over the past 20 years, inhaled corticosteroids have become established as cornerstone therapy in the treatment of obstructive pulmonary disorders, ranging from asthma and chronic obstructive pulmonary disease to cystic fibrosis. The appropriate use of inhaled corticosteroids has transformed the management of asthma in children, improving the quality of life of children and their families, improving exercise tolerance, and reducing hospitalisation and mortality rates. Asthma mortality rates in Australia have fallen by more than 50% over the past 12 years, in parallel with our increased use of inhaled corticosteroids and the development of clinical guidelines.1 We have gained confidence in the safety of inhaled steroids at recommended doses, supported by national guidelines and extensive reviews.2 Local side effects, including oropharyngeal candidiasis and laryngeal dysfunction, can usually be controlled with the use of spacer devices. Further, at recommended doses, initial concerns about growth failure and impaired bone mineralisation have not been realised.2 In recent years, with the advent of more potent steroids and more efficient delivery systems, the relative doses commonly used have increased. There have been several reports of serious adverse events resulting from doses of inhaled corticosteroids in excess of those recommended. These include growth failure,3 and suppression of the hypothalamic–pituitary–adrenal axis4-6 — resulting in acute hypoglycaemia, altered consciousness and coma, convulsions7,8 and death.9 While the majority of these effects have been reported at higher doses, some have occurred at a dose within the recommended range, suggesting that individual susceptibility may also be important. These effects are more commonly associated with one potent inhaled corticosteroid, but this is probably a result of over-representation of that drug in the higher dosage range. Comparative studies would suggest that this is a class effect of inhaled corticosteroids.4 Are we overusing inhaled corticosteroids? New evidence-based National Asthma Council guidelines define the need for inhaled corticosteroids in asthma. They recommend an upper limit of 500 μg per day of fluticasone propionate (or equivalent) in children, and 1000 μg per day in adults with severe asthma. In support, a recent meta-analysis, examining the dose response to inhaled corticosteroids in adolescents and young adults, reported that 90% of the maximum benefit was achieved at a daily dose equivalent to 250 μg fluticasone propionate.10 Minimal further improvement resulted from increases up to 600 μg/day. The introduction of long-acting β-agonists at low doses of inhaled corticosteroids can achieve improved asthma control, avoiding the need for higher doses of inhaled corticosteroids. When asthma is not controlled by a dose of inhaled corticosteroids equivalent to 500 μg/day fluticasone propionate and long-acting β-agonists, consideration should be given to issues of adherence to the treatment regimen, inhaler technique or an alternative diagnosis. In the UK survey of adrenal crisis due to inhaled corticosteroids,9 three of the 28 children did not have asthma and, in five, asthma did not account for all the respiratory symptoms. Inhaled steroids have been shown to be ineffective in children with recurrent cough and those with episodic viral-associated wheeze. Clinicians should be alert to the clinical features of hypoadrenalism, particularly when precipitated at a time of metabolic stress, perhaps indicating adrenal crisis. Children taking excessive doses of inhaled corticosteroids (> 500 μg/day fluticasone propionate) should have their hypothalamic–pituitary–adrenal axis assessed, and their parents should be informed of the risks and the potential need for systemic corticosteroid cover during intercurrent illness and surgery. The National Asthma Council recommends the introduction of inhaled corticosteroids (alone or in combination) to gain control of symptoms. On clinical review, there should be a reduction (ie, back-titration) to an appropriate dose to optimise symptom control and reduce the likelihood of adverse effects. By comparison with their United States and European counterparts, Australian prescribers have used higher doses of inhaled corticosteroids, but there is now a clear incentive to reverse this trend. The availability of effective anti-inflammatory therapy, useful and well-publicised guidelines, as well as incentive payments to general practitioners for the treatment of moderate to severe asthma under the 3+ Visit Plan (http://www.health.gov.au/pq/asthma/3plusgp.htm), should pave the way for greater improvements in the management of asthma. The goal of asthma management is to achieve optimal control of asthma symptoms with the lowest effective medication dose, allowing children to enjoy a normal quality of life neither burdened by, nor at risk of, serious adverse events. Inhaled corticosteroids remain the cornerstone of asthma management. Responsible use of inhaled corticosteroids will reinforce confidence in the consumer, whereas irresponsible use will promote steroid phobia — a significant barrier to adherence.

John W Wilson PhD, FRACP · Colin F Robertson MD, FRACP