Editorials

Patients with severe disease now have access to promising new drugs To have lived through a revolution, to have seen a new birth of science, a new dispensation of health . . . is not given to every generation. – William Osler (1913) Driven by evidence from well designed clinical trials, infliximab, a monoclonal antibody that targets tumour necrosis factor alpha (TNF-α), was recently listed on the Pharmaceutical Benefits Scheme (PBS) for treatment of ankylosing spondylitis.1 This is welcome news for patients with a disorder for which, until now, there have been few effective therapeutic options. Ankylosing spondylitis affects about 0.5%–1.0% of the population and typically begins between the ages of 15 and 40 years. It causes painful stiffness of the spine, progressive disability and loss of independence during the prime productive years. About 70% of patients go on to develop bony fusion of the spine, and the mortality rate for people with the condition is 1.5–4 times higher than that of the general population.2 To date, the treatment of ankylosing spondylitis has been unsatisfactory. Rheumatologists have combined physiotherapy and non-steroidal anti-inflammatory drugs, with the modest goal of relieving pain and stiffness, but such therapies do not alter the underlying disease process. Drugs that modify the disease process and prevent joint damage in rheumatoid arthritis (eg, corticosteroids, methotrexate and leflunomide) are of marginal benefit in ankylosing spondylitis. Randomised controlled trials have shown that sulfasalazine is of some benefit in ankylosing spondylitis, but only for peripheral joint involvement.3 Clearly, novel approaches for treating ankylosing spondylitis have been long overdue. Over the past decade, advances in basic medical research have seen the emergence of biological response modifiers that target critical mediators of the inflammatory response, such as TNF-α. Since August 2003, three biological agents that inhibit TNF-α have been listed on the PBS for severe rheumatoid arthritis: infliximab and adalimumab (monoclonal antibodies directed against TNF-α), and etanercept (a soluble receptor that acts as a “decoy receptor” for TNF-α). In 1995, it was recognised that TNF-α occurs in high concentrations in inflamed sacroiliac joints in patients with ankylosing spondylitis,4 thus identifying TNF-α as an important target for development of therapeutic agents. In the same year, international experts in ankylosing spondylitis established the Assessments in Ankylosing Spondylitis (ASAS) working group. This group included clinical epidemiologists, representatives of the pharmaceutical industry, and individuals with ankylosing spondylitis. The first goal of the ASAS group was to select and test the validity of a set of standardised clinical, serological and radiographic endpoints for clinical research and routine practice. Otherwise, rheumatologists were faced with the real possibility that new therapies would emerge from basic research but fail to find their rightful place in the treatment of patients with ankylosing spondylitis because the available tools to measure efficacy were too insensitive. By consensus, the following domains were selected to assess the efficacy of disease-controlling therapy: functional capacity, pain, spinal mobility, patient global assessment, spinal stiffness, peripheral joint swelling, erythrocyte sedimentation rate, spine and hip x-rays, fatigue and enthesitis (inflammation at sites of ligament, tendon or joint capsule insertion into bone).5 These endpoints are now used almost uniformly in studies of anti-TNF therapy in ankylosing spondylitis. Another outcome measure to emerge from the ASAS group was the “ASAS-20”, representing a 20% improvement in a composite score of efficacy.6 Recently, the group released a consensus statement for selection of appropriate candidates for treatment with anti-TNF therapy.7 This statement formed the basis of the current PBS restrictions on the use of infliximab in ankylosing spondylitis. Early data to emerge from uncontrolled studies of anti-TNF therapy in ankylosing spondylitis paved the way for randomised controlled trials. In a 3-month clinical trial, 18 of 34 patients (53%) treated with infliximab met the predefined response criterion, compared with 3 of 35 (9%) patients receiving placebo.8 There was significant improvement in almost all outcome measures, including quality-of-life and functional measures. These improvements persisted during an open-label extension study in which all participants were given infliximab for an additional 42 weeks.9 In the largest anti-TNF randomised controlled study to date, 277 patients with ankylosing spondylitis received either etanercept or placebo.10 At 24 weeks, 59% of the etanercept group and 28% of the placebo group met the ASAS-20 criteria for response. Although the mean disease duration among participants in the study was over 10 years, there were significant improvements in seemingly irreversible measures of spinal mobility. Anti-TNF therapy is not without risk. Importantly, most side effects of anti-TNF therapy did not emerge from randomised controlled trials but from post-marketing reports. Mild injection-site reactions occur in 10%–35% of patients using the subcutaneous formulations (etanercept and adalimumab), while infusion reactions can occur with the intravenous preparation (infliximab). The risk of reactivation of latent tuberculosis is well recognised. Thus, patients must be screened with a chest x-ray and Mantoux test before initiation of anti-TNF therapy. As TNF is important in preventing dissemination of intracellular organisms, anti-TNF therapy increases the risk of Aspergillus, Listeria and Cryptococcus infections, and live vaccinations are contraindicated. To date, post-marketing surveys have not shown an increase in risk of malignancy from anti-TNF therapy. There have been case reports of anti-TNF therapy being associated with autoimmune disorders, demyelination (optic neuritis and multiple sclerosis), exacerbation of cardiac failure, and abnormal liver function tests. However, the absolute risk of developing these complications after anti-TNF therapy is yet to be defined. In order to claim that anti-TNF therapy truly modifies the disease, researchers need to demonstrate that the treatment can slow down or prevent bony fusion and ankylosis. To date, this has not been achieved. A major limiting factor has been the requirement for study participants to demonstrate unequivocal radiographic evidence of sacroiliitis. As this is a late clinical feature of the disease, patients with early ankylosing spondylitis have been excluded from anti-TNF studies. Yet it is this cohort that is most likely to respond to anti-TNF therapy and in whom disease modification may be most readily apparent. Recently, a novel algorithm-based protocol for identifying patients with early ankylosing spondylitis in general practice recommended magnetic resonance imaging of sacroiliac joints for all people with inflammatory back pain and HLA-B27 positivity.11 Anti-TNF therapy has revolutionised the way in which we think about ankylosing spondylitis. By approving anti-TNF therapy for people with severe ankylosing spondylitis, the PBS has allowed clinical investigators in Australia to remain at the front line of this revolution.

Lionel Schachna MB BS, FRACP, PhD

An important Australian initiative that sets an international precedent We’ve got major problems at a really early age . . . to do these elderly health assessments, are they going to dig us up? We’re dead and buried by then. We might as well set up a clinic next to the cemetery.1 These poignant words were spoken by Dr Puggy Hunter, recipient of the Human Rights and Equal Opportunity Commission’s Human Rights Medal in 2001 and former Chair of the National Aboriginal Community Controlled Health Organisation (NACCHO), who passed away at the age of 50 years in 2001. He made these observations after the federal government’s launch of the Enhanced Primary Care Package in November 1999. Among other things, the package was designed to assist general practitioners to provide preventive care for Australians over the age of 75 years through Medicare Benefits Schedule rebates. For Aboriginal or Torres Strait Islander people the age limit was lowered to over 55 years.2 As 53% of Aboriginal men and 41% of Aboriginal women die before reaching the age of 50 years,3 representatives from NACCHO,4 general practice groups and the Australian Medical Association expressed concern that relatively few Aboriginal people would benefit from these rebates. Moreover, an evaluation in 2003 found that few Aboriginal and Torres Strait Islander people over 55 years had accessed the Enhanced Primary Care rebates.5 In this population, preventive health assessments are obviously needed earlier, given the occurrence of preventable chronic disease at younger ages and higher rates than in other Australians.6 Preventive healthcare can both reduce costs to the health sector and enhance health equity for Aboriginal peoples and Torres Strait Islanders, as most of the factors underpinning health disparities relate to social disadvantage (Box). For example, if renal disease is detected early, end-stage renal failure can be avoided and treatment will reduce mortality by 50%.12 However, during 1997–2002, Aboriginal and Torres Strait Islander Australians (compared with non-Indigenous Australians) were twice as likely to be referred late for dialysis treatment. (Late referral is defined as first attending a renal unit or being seen by a nephrologist less than 3 months before the initiation of dialysis.) In the intervening years, NACCHO has lobbied hard for the Medicare Benefits Schedule to make preventive health checks accessible to younger Aboriginal people.4 On 5 May 2004, the Federal Minister for Health launched a new Medicare Benefits Schedule rebate for an adult health check of Aboriginal and Torres Strait Islander people aged 15–54 years (Item 710).13 The challenge now is for GPs to make use of this rebate. Firstly, they need to understand what comprises an effective preventive health assessment for this population. In 2001, NACCHO led an alliance of eight non-government organisations — the Chronic Disease Alliance — to undertake a review of the evidence for preventive interventions, with the support of the Royal Australian College of General Practitioners and the Australian Government Department of Health and Ageing. The outcome — The national guide to a preventive health assessment in Aboriginal and Torres Strait Islander peoples — was completed in 2004,6 and a pilot study has been conducted with over 40 GPs. The guide lists a range of health problems and risk factors that are amenable to prevention, and supplements the “red book” of the Royal Australian College of General Practitioners.14 It takes into consideration the differing demographic and epidemiological factors that influence the development of disease in Aboriginal and Torres Strait Islander populations and was the basis for the descriptor for the new rebate. Secondly, changing practice to align with the evidence requires more than guidelines. Multifaceted strategies are needed, including decision-support systems, clinical audit, feedback, and support from opinion leaders.15 A health system that relies on free market provision of preventive healthcare can perpetuate inequity, as those who need the interventions are least able to afford and access the provisions. Proactive encouragement of preventive health assessments requires incentives and penalties, as well as removal of administrative and legislative barriers. Even with the rebate, implementing adult health checks in general practice may not be easy. According to 2001–02 data from the BEACH study (Bettering the Evaluation And Care of Health), at least 70% of GPs in Australia have, to their knowledge, not provided care for a single Aboriginal or Torres Strait Islander person in that period.8,9 Thus, changing practice to maximise the uptake of adult health checks for this population will require a range of supportive activities, such as: Distributing the guide to every GP; Promoting a suite of resources to assist GPs to better identify Aboriginal or Torres Strait Islander people and to improve cross-cultural communication;13 Developing ancillary resources such as case studies; Upskilling GPs using the expertise of Aboriginal community-controlled health services through coordinator positions established within NACCHO affiliates; Enhancing and supporting the role of Aboriginal health workers; Developing a communication strategy for the broader Aboriginal and Torres Strait Islander population to increase the demand for adult health checks;8,10 and Introducing clinical audit points for professional development. Bulk-billing for these assessments is critically important given the significant socioeconomic disparity between Aboriginal and Torres Strait Islander people and the broader Australian population.16 Mechanisms for improving access to medications under the Pharmaceutical Benefits Scheme for Aboriginals and Torres Strait Islanders are also required. This has been proposed by the Australian Pharmaceutical Advisory Council, NACCHO, the AMA and the Pharmacy Guild in a series of new reforms.17 2004 is the final year of the United Nations International Decade of the World’s Indigenous Peoples, and the development of this Medicare Benefits Schedule rebate removes a significant cost barrier from the delivery of preventive healthcare to Australian Indigenous people. The adult health check is an important Australian initiative that sets an international precedent. A total of 1977 services were claimed against Item 710 (Health Insurance Commission data18) from May to August 2004. This appears slower than the initial claim rate of elderly health assessment items (Enhanced Primary Care) for which an extensive implementation strategy was funded by the government. It is now time to finance an appropriate implementation strategy for the adult health check. General practice groups, including Divisions, should assist GPs to use the new adult health-check rebate for the identification and timely management of unrecognised health problems among Aboriginal and Torres Strait Islander Australians — the populations in which this is most urgently needed. Justification for a Medicare Benefits Schedule rebate for adult health checks for the Aboriginal and Torres Strait Islander population Aboriginal people and Torres Strait Islanders: have lower participation rates in preventive health programs (eg, cervical screening and breast cancer detection).7 have high rates of undetected risk factors and chronic disease.6 are referred late for end-stage disease, making treatment options more expensive (eg, if renal failure develops).6 are less likely to ask for preventive health assessments (significantly lower rates of requests for check-ups).8 have unequal access to Medicare (rate of use of the Medicare Benefits Schedule by Aboriginal people and Torres Strait Islanders is less than half that of other Australians, yet their overall health needs are about three times greater).9 General practitioners: miss opportunities for prevention (eg, significantly lower rates of vaccination by GPs in encounters with Aboriginal and Torres Strait Islander people10), leading to higher rates of hospital admissions for preventable diseases.11 find the preventive assessment process complex (comorbidity, sociocultural considerations).6 experience difficulties in delivering preventive healthcare to the Aboriginal and Torres Strait Islander population (inadequate remuneration for the time required, lack of knowledge of relevant health issues and inability to identify Indigenous Australians).6

Naomi R Mayers · Sophie Couzos MPH

Hypothermia is now standard care for some types of cardiac arrest Out-of-hospital cardiac arrest is a leading cause of unexpected death in the developed world, occurring in about 1 in 1500 adults each year.1 Successful recovery from out-of-hospital cardiac arrest depends on the rapid activation of the “chain of survival”: an immediate call to the ambulance service, bystander delivery of external cardiac massage and expired-air breathing, defibrillation and the provision of advanced life support by paramedics.2 Unfortunately, survival with good neurological outcome at hospital discharge is rare after out-of-hospital cardiac arrest. Studies in Perth and Melbourne show that less than 5% of these patients survive to hospital discharge.3,4 As the average response time of ambulances in most Australian cities is between 7 and 12 minutes, considerable neurological injury occurs during this prolonged period of cardiac arrest, even with bystander cardiopulmonary resuscitation. While paramedics may restore spontaneous circulation and transport some patients alive to an emergency department, most remain comatose because of the severe anoxic brain injury.4 To improve outcome, considerable emphasis has been placed on shortening the time between cardiac arrest and defibrillation. As decreasing ambulance response times towards 5 minutes would be prohibitively expensive, alternative approaches to earlier defibrillation have been proposed. These include fire-fighters co-responding with ambulance services to patients with suspected cardiac arrest,5 or installation of automatic defibrillators in public places.6 On the other hand, recent data from Canada have cast doubt on the effectiveness of paramedic advanced life-support programs, which did not improve survival rates when introduced.7 What therapies are available after arrival at the hospital? In most cases, no immediate cardiology intervention is required, and treatment has therefore been largely supportive until the neurological outcome could be determined. Common intensive care practice has been to defer neurological assessment for at least 3 days, to allow more accurate clinical assessment.8 Recently, an “old” therapy for anoxic brain injury — therapeutic hypothermia — has been re-introduced into clinical practice. In this issue of the Journal, Williamson and colleagues (page 500) describe the use of this therapy in a patient who was comatose after near-drowning.9 The use of mild therapeutic hypothermia after cardiac arrest was first described in the 1950s, but later abandoned without being formally tested in clinical trials.10 Interest in hypothermia was revived in the early 1990s when animal studies and preliminary clinical studies suggested benefit. Subsequently, two prospective, randomised, controlled clinical trials have been conducted.11,12 In a recent Australian trial, patients who remained comatose after resuscitation from out-of-hospital cardiac arrest were treated with either 12 hours of therapeutic hypothermia (33°C) or standard care.11 At hospital discharge, 49% of those treated with hypothermia were discharged home or to rehabilitation, compared with 24% of those treated with standard care. In a European study, 55% of patients treated with hypothermia (33°C for 24 hours) had a favourable outcome at 6 months, compared with 39% of those treated with standard care.12 Subsequently, the International Liaison Committee on Resuscitation (which includes the Australian Resuscitation Council) endorsed the use of therapeutic hypothermia for patients with anoxic brain injury after out-of-hospital cardiac arrest, particularly when the initial cardiac rhythm is ventricular fibrillation (Box).13 Therefore, this treatment should now be regarded as a standard of care for this condition. However, a number of issues require further consideration if therapeutic hypothermia is to be applied more widely. Firstly, uncertainty remains about the effectiveness of this therapy in patients with out-of-hospital cardiac arrest due to causes other than ventricular fibrillation. Patients with asystolic out-of-hospital cardiac arrest have a dismal prognosis,14 as do those with coma after near-drowning, hanging, or other causes of asphyxia. Clinical data on the effects of therapeutic hypothermia in these groups are lacking. The role that therapeutic hypothermia played in the recovery of the patient reported by Williamson and colleagues is uncertain. Secondly, a protocol needs to be established in the emergency department for the rapid induction of hypothermia in patients who are unconscious after out-of-hospital cardiac arrest. In most hospitals, this will require consensus to be reached between emergency physicians, intensive care physicians and cardiologists on the indications for the provision of this treatment. Finally, there are technical issues to be considered in the rapid induction of hypothermia. In previous studies, hypothermia was induced through surface cooling with ice packs and/or refrigerated air blankets.11,12 This approach is slow and logistically difficult in busy emergency departments. Other technologies for the rapid induction of hypothermia are therefore under investigation.10 Currently, we are exploring the use of a rapid intravenous infusion of large-volume (30 mL/kg), ice-cold crystalloid fluid to induce hypothermia. Preliminary data suggest that this is relatively simple, effective, inexpensive and not associated with pulmonary complications.15 As there is often a delay between resuscitation and emergency department initiation of hypothermia, cooling in the ambulance would be ideal. In a study supported by the National Heart Foundation, paramedics in Melbourne are now infusing large-volume (2000 mL), ice-cold crystalloid fluid, together with a muscle relaxant, immediately after out-of-hospital cardiac arrest to induce hypothermia as soon as possible after resuscitation. If this is confirmed as feasible, further studies are planned which will examine the use of therapeutic hypothermia after asystolic and asphyxial cardiac arrest. Recommendations on therapeutic hypothermia from the International Liaison Committee on Resuscitation In October 2002, the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation recommended: Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C–34°C for 12–24 hours when the initial rhythm was ventricular fibrillation. Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest. Preliminary data from clinical trials of perinatal asphyxia indicate that induced hypothermia is feasible and safe, but data on long-term neurological morbidity are not yet available. Until additional paediatric data become available, clinicians should tailor therapy for individual patients based on their assessment of the risks and benefits of hypothermia.

Stephen A Bernard MD, FACEM, FJFICM

The justice system could go further in supporting the needs of those it detains after they are returned to the community Nearly 20 years ago, public attention was drawn to the previously hidden tragedy of deaths in prison and police custody. Initially, attention was focused on deaths of Indigenous people. However, it quickly became apparent that the death rate for all people held in custody was much higher than that for the general population. The result was a detailed investigation into the causes of the problem, in the form of the Royal Commission into Aboriginal Deaths in Custody.1 The Royal Commission made over 300 recommendations on penal policy, cell design, custody management regimens, treatment programs, services to Indigenous offenders and a host of other topics. In addition, the Deaths in Custody Monitoring Program was established at the Australian Institute of Criminology (AIC) to scrutinise and report on deaths in prison or police custody.2 In parallel with the acknowledged problem of deaths in custody, there is an equally significant tragedy in the form of high death rates among released prisoners3-5 and offenders in the community.6,7 In the decade after the Royal Commission (1990 to 1999), the AIC monitoring program recorded 628 deaths in police or prison custody. Over the same period, in Victoria alone, 820 men and women who had been released from prison died unnatural deaths.4 The study by Coffey and colleagues in this issue of the Journal (page 473) shows that the problem is not confined to adult offenders but affects juveniles as well.8 The high rate of unnatural deaths among offenders living in the community is a major public health issue, but what can we do to reduce these rates? One of the groups at greatest risk is injecting drug users — over half of the unnatural deaths examined in the earlier Victorian study were heroin related,4 and drug-related offences were an indicator of high mortality risk in the study by Coffey et al.8 Drug treatment and maintenance (methadone) programs lower the risk of death by overdose.9 However, many of those at greatest risk are profoundly alienated from society, and we need to find ways to engage them. For example, heroin-dependent Indo-Chinese offenders frequently face rejection by their families and community, and are isolated from the mainstream community as well. Female offenders often come from backgrounds of extensive sexual and physical abuse, their heroin dependency is often supported by prostitution,5 and any interventions need to take account of their responsibilities as parents.10 Treatment and maintenance programs need to be delivered in ways that meet the material, social and cultural needs of those at risk. Overdose risk can be dramatically lowered by behaviour changes, like not using drugs by yourself, being aware of variations in the purity of heroin, and not taking heroin in conjunction with alcohol or benzodiazepines. Again, the problem is partly that those at greatest risk are also the most difficult to communicate with, and tend to be unrealistic in judging risks to themselves. Peer-based education and information dissemination programs have shown they can transmit the key messages about risk reduction to this group (eg, how to avoid overdose and recognise its signs),9 but, again, a range of approaches tailored to the needs of specific groups at risk is required. Such approaches could include maximising the effectiveness of needle and syringe program workers by having them provide standardised, evidence-based messages and materials on safe injecting, overdose prevention and support options.9 The importance of heroin as a cause of unnatural death should not obscure the other dangers that offenders face. Individuals who have the combination of mental disorder and drug and alcohol misuse experience much higher risks of both overdose and suicide and can find it difficult to obtain the kind of treatment and support services that might alleviate their problems. Older offenders are at increased risk of a variety of general health problems, such as diabetes, cancer and liver disease, and there need to be programs that link at-risk offenders with healthcare and support services.11 People who are released from custody are at greatly increased risk, in part because their tolerance for heroin is reduced, and also because return to the community can be a time of great emotional stress. Prisoner release support programs like the Victorian Bridging the Gap program have shown that the period before release can be an important “window of opportunity” when offenders are motivated to plan for their release.12 A key feature of this program is intensive, outreach-based support, with the support agency helping the releasee to identify his or her specific needs and brokering access to material support, healthcare and social services. Releasees who participated in Bridging the Gap had improved outcomes as measured by accommodation stability and engagement in drug-treatment programs, and these in turn translated into lower rates of reoffending.12 Finally, we need to attend to an important lesson from the Royal Commission. Despite real improvements in custodial management, the number of deaths of Indigenous people in custody has continued to increase because there are now more Indigenous people in custody.2 The high rate of unnatural deaths among offenders is a public health problem that requires changes in the way that healthcare services are delivered to this vulnerable population. However, we also need to recognise that the justice system has a key role to play in ensuring that its goals of punishing offenders and preventing crime are properly balanced by a consideration of the health and support needs of the people who are the subjects of its interventions.

Stuart Ross

Despite well publicised claims of the therapeutic value of dietary supplements and other new treatments, the evidence for their effectiveness is modest The distinction between conventional and alternative medicine is often based on the presence or absence of scientific evidence. However, this evidence is expensive to gather, and often difficult to interpret and reduce to practical advice. Age-related macular degeneration (ARMD), the dominant and rapidly increasing cause of permanent visual loss in Australia, is an important case in point. Its prevalence rises from 0.7% in the 65–74-years age group to 5.4% at 75–84 years and 18.5% in people over 85.1 Definitive treatment does not yet exist. While we have some knowledge of risk factors, this knowledge is imperfect and has recently been muddied by well publicised claims (discussed below) that, although evidence-based, are preliminary and need to be interpreted with caution. The early signs of ARMD include hypo- or hyperpigmentation of the retina and large yellow drusen (> 63 μm) or soft drusen with indistinct margins.2 A few small hard drusen can be found in almost everyone over 50 years of age, and, in contrast to large or soft drusen, do not appear to progress with age.1 Loss of vision from ARMD occurs either as a result of choroidal neovascularisation with exudation and haemorrhage (the “wet” form) or by slow atrophy of the retinal-pigment epithelium and overlying receptors (the “dry” form). Wet ARMD is twice as common as the dry type and causes rapid vision loss. About 10% of patients with wet ARMD who present early with distorted vision and an eccentric neovascular lesion can be treated successfully with laser photocoagulation.3 However, the recurrence rate is over 60%, and further vision is then usually lost. Another small proportion of patients can be treated with photodynamic therapy (involving low-intensity red laser treatment after intravenous verteporfin infusion), but the functional benefit is usually modest.4 There is no treatment yet for the dry form of ARMD. Elderly people fear blindness and the loss of independence greatly, and the prevalence of ARMD is rising dramatically. It is no surprise that recent studies of possible risk factors have attracted a lot of public interest. People with an ARMD-affected first-degree relative have a 50% lifetime risk of experiencing advanced ARMD and vision loss, and tend to develop it earlier.5 Smoking is associated with a fourfold increase in the risk of ARMD and visual loss and, again, tends to promote earlier occurrence.6 Weaker associations have been found with obesity, hypertension, macro-vascular disease, raised cholesterol and fibrinogen levels, cumulative light exposure and cataract surgery. Dietary associations have also been found both with the signs of ARMD and with progression to vision loss.7-9 In a well conducted, prospective study, dietary fat intake was systematically analysed after correcting for other risk factors.9 Vegetable fat intake had the strongest relationship with ARMD progression, with a relative risk of 3.82 for the highest fat-intake quartile compared with the lowest quartile. Higher intakes of total fat and of saturated, monounsaturated, polyunsaturated and transunsaturated fats all raised the relative risk of ARMD progression about twofold. Weekly fish intake and eating nuts two to three times a week were mildly protective. The implication is that a large shift away from vegetable oils, margarine and fat-containing processed foods might reduce this epidemic of blindness in the elderly. Some of these measures conflict with conventional advice on controlling cardiovascular conditions and need further research.10 Definitive evidence for the effectiveness of certain interventions might be obtained by randomly assigning those in the top quartile of risk to receive either a diet with low vegetable fat, fish, nuts and fruit, or a normal diet. There is also evidence from a randomised controlled trial that high-dose dietary supplements of the antioxidants vitamin C, vitamin E, beta-carotene and zinc can reduce the risk of progression from large or soft drusen to advanced ARMD and visual loss by about 20% compared with controls over 6 years.11 However, high-dose zinc can cause gastric irritation or anaemia, and beta-carotene may possibly be associated with an increased risk of lung cancer among smokers. Uncontrolled studies suggest the antioxidants selenium, lutein and zeaxanthin, which localise in the normal macula, may also help. There are as yet no studies to show whether dietary supplements are protective in patients with only small drusen or in the 20% of patients who are at genetic risk. It is not yet known whether major dietary adjustment and/or introduction of dietary supplements for large numbers of elderly people will be justified in terms of preventing blindness. On present evidence, we should identify people at increased risk of ARMD (ie, those with a family history, large or soft drusen, or vision loss in one eye from ARMD), encourage them to stop smoking, and promote a diet that includes vegetables, fish and nuts and reduces fatty foods laced with vegetable oils. Antioxidant supplements should be recommended if a fresh diet is impractical and if retinal signs of progression are present. For people of advanced age with a lower risk of ARMD, we might compliment them on reaching seniority and note that, in the dietary supplement study mentioned above,11 only 1.3% of patients with small drusen experienced ARMD progression over a 6-year period. Retinal images showing age-related macular degeneration (ARMD) A. “Dry” ARMD. Large soft macular drusen, signifying a high risk of progressive visual loss. B. “Wet” ARMD. Arrowed area delineates advanced wet macular degeneration with subretinal exudation and neovascular scar tissue. These changes result in blindness.

Ian J Constable FRANZCO, FRACS, FRCS

There is yet no convincing evidence that testosterone therapy is safe or effective in counteracting any effects of ageing One of the most challenging and time-consuming aspects of medical practice is discussing with patients what they have gleaned from the Internet or popular lay publications. One topic of such discussion is the use of testosterone in male ageing, with public interest fuelled by persuasive publications like Maximising manhood,1 The testosterone revolution2 and Male menopause.3 Much of the information gained from these books may seem to be very convincing, but is, at best, “ahead of the evidence”. It is often difficult for doctors not to appear old-fashioned, ignorant or downright contrary when showing scepticism or advising caution in the face of such conviction. . . . beware when entrepreneurial business ventures overtake evidence-based medicine. In this issue of the Journal, Handelsman (page 419) has documented temporal and regional trends in testosterone prescribing in Australia.4 He has shown increases in prescribing corresponding to popular promotion of androgen therapy in ageing. This rise has been particularly marked in Western Australia, coincident with the opening in that state of entrepreneurial clinics aimed at the ageing-male market. There is no doubt that testosterone therapy benefits patients with documented hypogonadism associated with conditions such as Klinefelter’s syndrome and hypopituitarism. Current prescribing guidelines allow for this, regardless of age. However, for the use of testosterone in men of middle age and older with borderline low serum levels of testosterone, the evidence for both efficacy and safety is yet to be established. The original description of the efficacy of testosterone therapy for the vicissitudes of age has been shown to be no more than a powerful placebo effect.5 Nevertheless, it would seem that those who espouse testosterone therapy in this setting have identified an expanding market. The Australian population is ageing: 28% of men are over the age of 50 and 12% over the age of 65 years. It is projected that by 2021, 4.0 million Australians will be over the age of 65, an increase of 1.7 million from today’s estimate.6 Together with a documented fall in testosterone level with age, where it is estimated that 20% of men over the age of 60 will have a testosterone level below the reference range, this predicts a large population of men as potential customers for androgen therapy.7,8 Although most studies have shown a gradual decline in testosterone level with age, the clinical consequences of this are not known. Conditions such as muscular frailty, loss of bone mass, cognitive decline and erectile dysfunction are also age related, but whether testosterone deficiency has a causal role is not clear. More importantly, it has not yet been established that testosterone therapy has any role in correcting these conditions. It has been a widely held belief that androgen deficiency is a common and correctable cause of erectile dysfunction. However, in a cohort of 1455 men presenting with erectile dysfunction, we found that testosterone deficiency constituted a correctable cause in only 3%.9 All of those who responded to testosterone therapy for erectile dysfunction had a testosterone level < 7 nmol/L, well below the reference range of 11–37 nmol/L. The use of testosterone therapy in patients with normal or slightly depressed androgen levels seems to be of little benefit.10 A similar finding has been documented in the response of bone density to testosterone therapy. The largest and longest-term study in this setting examined testosterone treatment in 108 men aged over 65 years with a baseline testosterone level more than 1 standard deviation below the young adult mean (ie, < 16.5 nmol/L).11 Lumbar spine bone density rose significantly only in those with a baseline testosterone level below the reference range (ie, below 10 nmol/L). Another, smaller study has shown a significant increase in lumbar spine density with androgen therapy in men with a baseline testosterone level < 12.1 nmol/L.12 Muscle mass and strength decrease with age, and it is tempting to link this with the decline of testosterone. In hypogonadal men, testosterone therapy improves muscle strength. In men aged over 65 years, testosterone treatment leads to a fall in fat mass and a rise in lean body mass, together with a perception of increased strength. However, although a perception of improved muscle function was reported, no objective change in measured physical function, such as walking or stair climbing, knee flexion or in muscle strength as measured by dynamometer, was demonstrated.13,14 The safety of sex hormone therapy in menopausal women, used widely for the last 60 years, has recently been scrutinised and reassessed.15 Knowledge about the safety of sex hormone replacement in men is, by contrast, in its infancy. No studies have been conducted for long enough to identify the long term risks of androgen therapy in ageing. Because of lack of statistical power in studies, it is not known whether testosterone use will increase the incidence of androgen-dependent disease such as prostate cancer, although a sustained rise in prostate-specific antigen level has been observed.13 Two other side-effects of testosterone treatment have been identified in short term studies, namely an increase in obstructive sleep apnoea and increased haematocrit and polycythaemia, both of which may have implications for cardiovascular risk.13,16 Handelsman has documented the effect on testosterone prescribing of entrepreneurial clinics aimed at the ageing-male market.4 Daily, we see advertisements for similar commercial enterprises which deal in unregistered and/or unproven prescribing, including DHEA (dehydroepiandrosterone) or testosterone to men and women, progesterone cream, and lozenges of variable mixes of oestrogens, progestins and androgens. We should beware when entrepreneurial business ventures overtake evidence-based medicine. What is needed now regarding testosterone therapy in ageing are large, long-term, prospective, randomised, placebo-controlled studies to establish if there is, indeed, benefit for specific symptoms and to identify potential risks.17

Bronwyn GA Stuckey BA, FRACP

Many maternal deaths in Australia are still preventable The recently released report Maternal deaths in Australia 1997–1999 is the twelfth in a series of triennial reports, spanning over 35 years.1 The maternal mortality ratio (MMR) for this triennium was 8.2 per 100 000 confinements — one of the lowest national MMRs in the world. The MMR of a country reflects, in part, the overall health of women, the quality of the maternity services, and women’s access to those services. For comparison, the MMR per 100 000 confinements for the United Kingdom over this period was 11.4 and for the United States (for the year 2000), 17.0; Sweden had the lowest rate (2.0).2,3 There are huge differences in MMRs between developed and developing countries, with about 99% of global maternal mortality occurring in Africa, Asia and Latin America. The World Health Organization estimated that, in the year 2000, the MMR for Sierra Leone was 2000 per 100 000, or one death for every 50 confinements, compared with Australia’s one death for every 8500.3 While it is easy to see the magnitude and urgency of the problem of maternal mortality in developing countries, what, if anything, can be learned from analysing the rare maternal deaths in countries such as Australia? The answer lies in the fact that mortality represents the “tip of the iceberg” of severe morbidity; for every case of mortality directly or indirectly caused by pregnancy or its management, there are probably 50 women who experience a life-threatening complication but survive with varying degrees of short- and long-term sequelae. Improvements in obstetric care, which result from considering maternal mortality, can therefore be expected to apply to a broad population of childbearing women and their infants.4 Australia has witnessed a one-third reduction in the MMR over the past 30 years, from 12.7 per 100 000 confinements in 1973–1975 to 8.2 per 100 000 in 1997–1999. Higher rates of maternal mortality are seen for older women and for Indigenous women (Box). The highest risk of death was among women aged 40 years and older, who form an increasing proportion of the childbearing population, and who are more likely to use assisted reproduction techniques for conception, with higher multiple pregnancy rates. The inequity seen in all-cause mortality among Aboriginal and Torres Strait Islander women is reflected in the higher MMR for this population, who, in this triennium, represented about 3% of confinements, but 8% of deaths. There were no deaths in the triennium from terminations of pregnancy. If estimates are correct that over 80 000 termination procedures are performed in Australia annually, then these procedures carry exceptionally low risks of serious perioperative complications. Several conditions warrant special mention. Obstetric haemorrhage is still the major direct cause of maternal mortality (deaths directly caused by complications of pregnancy or its management). A recent report from Victoria supports the clinical impression of an increasing incidence of emergency hysterectomy for severe obstetric haemorrhage, possibly related to the increasing proportion of women embarking on pregnancy after one or more caesarean sections, with an increased risk of the more severe forms of abnormal placental implantation — placenta praevia, accreta and percreta.5 This is another change in the characteristics of the obstetric population which warrants close observation through systematic and comprehensive maternal mortality analysis. The Australian and UK reports encourage maternity institutions to rehearse the management of simulated cases of obstetric haemorrhage, which is happening in some, but not all, Australian institutions. Amniotic fluid embolism was responsible for seven deaths in Australia in the 1997–1999 triennium. Although small numbers are open to overinterpretation, it is noted that, in five of these cases, labour was induced. There is community and clinical concern about adverse consequences of induction of labour, especially when undertaken for non-clinical indications. We reiterate the need for maternity units (of all sizes) to have disaster plans for the immediate management of the rare and unpredictable cases of amniotic fluid embolism, which usually present with acute syncope and haemorrhage. Thromboembolism and severe hypertension continue to be major contributors to maternal mortality, with six deaths in each category. Some of these deaths were considered preventable, and, with the trend towards more obesity, higher caesarean rates and women delaying childbirth into their 40s, awareness of the indications for perioperative thromboprophylaxis is increasingly important. Adherence to clinical practice guidelines for severe hypertensive disorders, including earlier specialist referral, would have prevented at least some of the six deaths from hypertensive disorders. Deaths related to cardiac disease and psychiatric illness dominate the category of indirect maternal deaths (deaths in which the pregnancy was complicated by pre-existing disease). Eight deaths due to psychiatric causes mirrored what has been found in the UK, where increasing numbers of maternal deaths are reportedly due to psychiatric conditions. Clinicians and the community need to be reminded about not ignoring or dismissing symptoms of depression, especially suicidal intent, during and following pregnancy.2 There is an emerging group of women at risk of maternal death — those who have had surgery for major congenital heart disease as infants or children, and who are now attaining reproductive age. These women are at risk of severe cardiac complications during and after pregnancy, and require sophisticated and multidisciplinary management. Despite a very low risk of death associated with pregnancy, no-one should claim that, in a country like Australia, mere survival rates could serve as an indicator of the quality of maternity services. However, because of the implications for the broader population of women experiencing pregnancy and childbirth, maternal mortality warrants continuing systematic ascertainment, and high-level investigation and reporting, with reasonable timeliness, so that recommendations are relevant to current practice. Key findings of Maternal deaths in Australia 1997–19991 The 1997–1999 maternal mortality ratio (MMR) was 8.2 deaths per 100 000 confinements, compared with 9.1 per 100 000 in 1994–1996. There were 90 maternal deaths: 34 direct, 28 indirect, and 28 incidental deaths. The main causes of death were obstetric haemorrhage (8 deaths), psychiatric disease (8 deaths), amniotic fluid embolism (7 deaths), and cardiac disease (7 deaths). The highest risk of death was seen in women aged 40 years and older (MMR, 23.2 deaths per 100 000 confinements, compared with 4.0 deaths per 100 000 confinements for those aged 20–24 years). The MMR for Aboriginal and Torres Strait Islander women remains three times higher than the MMR for non-Indigenous women.

James F King MPH, FRANZCOG, FRCSC · Emma K Slaytor MPH, BMedSci(Hons) · Elizabeth A Sullivan MPH, MMed, FAFPHM

Establishing a causal link between HPV and certain head and neck cancers would have implications for prognosis, prevention and therapy More than half a million cases of squamous cell carcinoma (SCC) of head and neck mucosa are diagnosed each year, making it the eighth most common malignancy globally.1 The highest incidence has been observed in developed countries like Australia, where there were 853 new cases in 2001, accounting for 3.8% of all cancers in men and 1.9% of all cancers in women.2 Tobacco and alcohol consumption are accepted as the two major risk factors for head and neck cancer,3 and micronutrient deficiencies, genetic factors and poor oral hygiene are also suspected of playing a role.4 Over recent years, both epidemiological and experimental evidence has implicated oncogenic human papillomavirus (HPV) in the development of a subset of head and neck cancers.5-7 This evidence has been strongly supported by a recent large case–control study coordinated by the International Agency for Research on Cancer (IARC).8 The study, involving centres in nine countries (including the Royal Prince Alfred Hospital in Sydney), concluded that HPV plays an aetiological role in many oropharyngeal cancers and possibly in a small group of cancers of the oral cavity. In all studies, the association has been strongest in the tonsil, where HPV DNA positivity rates frequently exceed 50%. HPV type 16, predominant in cervical cancers, is overwhelmingly the most common type.8-10 The critical issue now is to confirm that the association of HPV with these cancers is causal, as is clearly the case with cervical cancer. This may have implications for prognosis, treatment and prevention. Both the mutagens in tobacco smoke and alcohol and the HPV oncogenes E6 and E7 are known to disrupt the two major pathways controlling the cell cycle — those involving the tumour suppressors p53 and pRb (the retinoblastoma protein). Experimental evidence supporting a causal role has come from reports that the HPV genome is found localised to only the primary tumour cells and their metastases, at similar copy numbers to those reported in other HPV-associated malignancies, including those of the cervix.9,10 Demonstration (by reverse transcription/polymerase chain reaction assays) that E6 and E7 are active in the cancer cell has also been of key importance in establishing an aetiological role.7 Integration of HPV DNA into the host chromosome, which frequently heralds malignant conversion in cervical lesions, has also been observed, although there are indications that the proportion of head and neck cancers carrying the virus in non-integrated form in the cell nucleus may be higher than in the cervix.10 Seroreactivity against the viral capsid proteins and oncogenes has also been associated with an increased risk of cancer.8 Molecular analyses of p53 and of cellular proteins in the pRb pathway (including cyclin D1, a positive regulator, and p16, a negative regulator of the cell cycle) have suggested that HPV-positive head and neck cancers are a biologically distinct group. HPV-positive cancers are generally characterised by loss of expression of pRb and cyclin D1 and overexpression of p16 following inactivation of pRb by the viral E7 oncoprotein.6,11 In contrast, HPV-negative tumours consistently show overexpression of pRb and cyclin D1 and loss of p16. Mutations in the p53 gene appear to be much more common in HPV-negative cancers than in HPV-positive cancers. In HPV-positive cancers, p53 inactivation is achieved by interaction with the viral oncoprotein E6. Nonetheless, HPV and p53 mutations appear to coexist in at least a proportion of head and neck cancers. The recent IARC study,8 like other, smaller surveys, shows that HPV-positive head and neck cancers are more common in patients who do not smoke or chew tobacco,8,12 but HPV infection and tobacco consumption together are associated with an increased risk (whether the effect is additive or synergistic is not known). Several studies have reported a clustering of HPV-positive cancers in younger age groups,13 but the association with age remains controversial. HPV has statistical associations with a history of multiple sexual partners, the practice of giving oral sex and a history of genital warts, suggesting sexual transmission, although conclusive data are lacking.8,12 A lower rate of oral exposure to HPV because of cultural or social attitudes relating to sexual practices (notably orogenital contact) may help explain the lack of HPV DNA in a recent small series of tonsillar cancers from Chinese patients.14 What are the practical implications of an aetiological role for HPV in head and neck cancer in the clinical setting? The prognosis for head and neck cancer has not improved appreciably over the past two decades, despite a better understanding of the biology of invasive tumours, advances in surgery and the increased use of combined-modality treatment. Clinical staging is the primary guide to treatment modality, but provides a limited guide to outcome. There have been general expectations that genetic analysis is “the way of the future” in terms of identifying markers for prevention, therapy and prognosis. Attempts to find prognostic cellular markers in head and neck cancers have been disappointing, but including HPV status as a variable in the data analysis may yield more rewarding results. There are real prospects that HPV itself may provide a new generation of prognostic markers. Surveys have consistently linked HPV-positive cancers with a more favourable clinical outcome than HPV-negative cancers. The risk of recurrence or death from the disease associated with HPV status is independent of established prognostic factors, including tumour stage and lymph-node metastasis.6,10,11 The apparently better prognosis for patients with HPV-positive cancers may reflect the inability of the viral E6 protein to fully inactivate p53 and/or the adverse effect of radiation and other toxic agents on the ability of E6 to interfere with p53 and other host proteins, so that the cancers are more susceptible to therapy. Screening of head and neck cancers for HPV 16 and/or raised p16 as a marker of HPV-related transformation (Box) may identify a new group of patients (those with HPV-negative tumours) who would benefit from closer-than-usual follow-up or additional therapy. However, large-scale prospective studies will be needed to establish the cost-effectiveness of this approach. Internationally, HPV DNA testing is gaining acceptance as an adjunct to cytology in cervical cancer screening programs. Early diagnosis is still the best predictor of good outcome in head and neck cancer. The possible public health benefits of cytological screening and/or detection of HPV DNA in cells collected from the oral cavity by dentists or general practitioners await evaluation. Such studies will need to include details of how and when specimens are taken and cost–benefit analyses. Both in Australia and overseas, clinical trials are under way to test HPV vaccines (developed from viral capsids generated in the laboratory) for prevention of cervical cancer. The demonstrated efficacy of an HPV 16 vaccine in preventing persistent infection in the female genital tract15 has raised expectations that such vaccines may eventually reduce the incidence of head and neck cancer. However, the potential of vaccine programs designed for the genital tract to reduce the incidence of HPV infection in the head and neck is still to be evaluated. Specific randomised controlled trials to address the prevention of persistent oral HPV infections may need to be considered. Therapeutic vaccines based on the viral oncogenes E6 and E7 remain at the experimental stage, but may eventually prove a valuable addition to surgical, radiation and chemotherapeutic approaches to managing advanced disease. Upregulation of p16 as a marker of HPV-mediated transformation in tonsillar cancer cells Strong, diffuse staining for p16 is shown in a high proportion of tumour cells (arrow). A close-up view of tumour cells (inset, x 400) shows staining throughout the nucleus and cytoplasm. Glossary Viral oncogenes. DNA sequences in the viral genome that code for a protein capable of setting the cell on a course to malignant transformation. Tumour suppressors. Classes of proteins that protect the cell against malignant transformation (eg, by monitoring the integrity of the cell or by preventing unscheduled cell cycling).

Barbara R Rose PhD, MASM, BSc · Christopher J O’Brien FRACS · Wei Li MMed, MM

Promoting psychological wellness in doctors requires tailored interventions Doctors’ health and wellbeing seems to be attracting increasing international attention by the medical profession. 1,2 Is this because doctors’ health is worse than it used to be? Is medicine becoming too overwhelming for its practitioners? Does health promotion targeted at the profession work? And what is the profession doing about the health of its members? Unhealthy doctors cannot be expected to deliver high-quality healthcare Doctors are physically healthier than the average person in the community,3 even though they do not always follow their own healthcare advice (see Kay et al, page 368). 4-7 At the same time, they have significant psychological vulnerabilities,8 and are more likely than the average person to suffer from one or more of “the three D’s” — drugs, drink and depression (including suicide). Whether this is predominantly due to the stress of the job or to pre-existing personality traits has long been debated (see Riley, page 350). 9 The relatively small proportion of doctors who experience mental illness or substance misuse are described as being impaired. Many of them ultimately come to the attention of state medical boards, usually through referral by concerned colleagues. The New South Wales Medical Board has established an Impaired Registrants Panel, whose members work with impaired doctors and medical students to decide on how they can continue to work or study while the public interest is being protected (see Wilhelm and Reid, page 372). Troubled doctors are a larger group who are significantly affected by stress, although their disability may not be such that they cannot practise. Screening Australian doctors for anxiety and depression using the General Health Questionnaire has revealed a high level of stress among general practitioners;10 similarly, in New Zealand, severe stress symptoms are much higher among GPs than in the general population. 11 This troubled group is at risk of becoming impaired in due course. The most visible group are the dissatisfied doctors. They complain about “the system” and its demands, and contemplate leaving the profession. 12 Nevertheless, they are able to function quite well and do not have a “health problem” in the strictly medical sense. Whether they can be said to have “hypo-wellbeingness” is an interesting philosophical question. Whatever one’s viewpoint, these doctors may be at risk of “burnout”. Strategies aimed at promoting health and wellbeing among doctors must firstly consider which of these three groups is being addressed, and then tailor the intervention accordingly. The impaired doctor needs an early intervention and rehabilitation program; the troubled doctor needs a preventive approach to stress, plus an easily accessible referral pathway;13 and the dissatisfied doctor needs social support together with reform of “the system” so that known deficiencies (eg, workforce shortages, excessive paperwork, low remuneration levels) are adequately addressed. What has been done in Australia to reach these groups of doctors? Most states have the equivalent of a doctors’ health advisory service (DHAS), which often has little funding and depends on considerable goodwill by a panel of treating doctors. However, in May 2004, the DHAS network formed an Australasian doctors’ health planning and reference group, which may help to coordinate and refocus efforts in this area. Since 1999, there have also been national doctors’ health conferences every 2 years. To try to provide a more sustainable service in Victoria, the Australian Medical Association (Victoria) and the Medical Practitioners Board set up the Victorian Doctors’ Health Program in 2001. The aim of the Program is to provide confidential medical services to doctors, as well as referrals to specialists, such as psychiatrists, if required (see Warhaft, page 376). However, Australia is some way short of the US model of Physician Recovery Networks, which, although having no statutory role, intervene in situations where doctors are considered at risk (see Brown and Schneidman, page 390). Several specialist colleges have established their own support services for members who are experiencing difficulties. For example, the Australian and New Zealand College of Anaesthetists has been particularly active in supporting colleagues, especially in the area of substance misuse. Similarly, the Royal Australian and New Zealand College of Psychiatrists has assisted its impaired practitioners to obtain help through colleague support panels. Divisions of General Practice have taken up various wellbeing programs covering areas such as stress management techniques, improving skills in the business aspects of running a medical practice, and providing opportunities for social support through peer networking. 14 Unfortunately, the causal links between the impaired, the troubled and the dissatisfied are not very clear, and this has implications for the type of preventive programs being pursued. For example, do the various “docs-4-docs” programs run by Divisions of General Practice (with the aim of supporting GPs to better withstand the stresses of their profession) do anything to prevent impairment?15 This seems unlikely, as doctors with psychological problems are less likely to engage in the relatively open forums that the Divisions organise. The challenge has also been taken up by several Australian universities, which have developed “personal and professional development” programs to deal with self-care for health professionals. 16 An innovative way of promoting psychological health has been introduced at Monash University, where first-year medical students undertake a single-semester subject that teaches “mindfulness”-based stress management techniques that they can practise on themselves. 17 Similar courses are also being offered at postgraduate level. We need a better understanding of which programs work best for which groups of doctors. In the meanwhile, we can use liberal doses of common sense to guide us on what is worthwhile. Useful approaches are likely to include the provision of well advertised but confidential referral pathways for medical students and doctors who need help, the enhancement of a “no blame” culture that accepts and supports those who are starting to falter (see Hayhow, page 365), and attention to solving defects within the healthcare system. Unhealthy doctors cannot be expected to deliver high-quality healthcare. The increased attention to this issue in recent years is timely for doctors, their families and their patients.

Peter Schattner MD, MMed, FRACGP · Sandra Davidson BA, Grad Dip Behav Studies Hlth Care · Nathan Serry MB BS, FRANZP

We need a national tobacco act to regulate all aspects of tobacco manufacturing and marketing “Fire safe” cigarettes are those which self-extinguish when they are not being smoked, as opposed to regular cigarettes which continue to burn. For nearly two decades there has been opposition from the tobacco industry to proposals for legislation that would mandate fire-safe, or “reduced ignition propensity”, cigarettes. And this is despite the fact that smoking is the leading cause of residential and total fire deaths in at least eight countries, including Australia.1 The good news is that two jurisdictions in North America have now legislated to require all cigarettes to pass a “fire-safe” standard. Around 14 people in Australia die from cigarette-caused fires annually, and infants are over-represented in these deaths . . . The evidence that cigarettes cause fires is extensive. Data from the Australasian Fire Authorities Council (Mr C Donnelly, Director Corporate Strategy, New South Wales Fire Brigades, on behalf of the Australasian Fire Authorities Council, personal communication 5 February 2004) show that, annually, at least 4574 fires are caused directly by cigarettes and smokers’ materials around Australia (excluding the Northern Territory and South Australia, for which no data were available). In addition, an unknown proportion of another 78 894 fires of indeterminate origin could be associated with smoking. Determining the exact ignition source of a fire is often difficult because the evidence is generally destroyed. Cigarette butts are easily destroyed in fires, and conclusions about their role in causing fires are therefore deduced from a combination of evidence about the location and ignition point of fires (eg, beds, furniture, roadsides) and the elimination of other possible causes. The costs of cigarette-caused fires in terms of lives lost and property damaged are high. Around 14 people in Australia die from cigarette-caused fires annually,2 and infants are over-represented in these deaths, often dying in household fires resulting from cigarettes igniting bedding or furniture.3 In 1998–99, smoking-related fires throughout Australia cost some $52.1 million in tangible costs — health costs, private property damage and fire service costs — plus an estimated $28.5 million in intangible costs (such as the value of lives lost in such fires). This estimate is highly conservative, as it excludes valuations of public property damage, such as national parks, loss of animals, and of amenity while bushland regenerates.4 In Australia, particular focus has fallen on the role of discarded cigarettes as one cause of our infamous bushfires. Conservatively, it is estimated that about 7% of bushfires are caused by discarded cigarettes,5 and all states and territories now have laws for prosecuting people who discard lighted butts. A recent study has confirmed the ability of cigarettes to ignite bush litter. In outdoor conditions, with wind speed about 40 km/h, grassy fuel moisture content about 12% of oven dry weight, and humidity 14%, cigarette butts caused three ignitions in 75 trials (4%). If 1000 smouldering butts were discarded in comparable conditions, 40 fires might result.6 The same 2003 study examined butt discard rates on median strips next to two traffic lights on two of Sydney’s major arterial roads. Everyone’s daily experience of seeing people discarding glowing butts hardly needed confirmation, and the study found 426 discarded butts in a 3-week period.6 Education, fines, and talkback radio vilification of butt-throwers would thus appear to have minimal impact on this practice. Australian fire investigators report that hundreds of fire officers are often unnecessarily exposed to physical and psychological harm from cigarette-caused fires. Fire-cause investigators and other fire industry leaders unanimously support the introduction of regulations to reduce the fire risk of cigarettes.7 Tobacco companies commonly add burn accelerants, such as sodium and potassium citrate, to cigarette paper.8 However, in the United States, tobacco companies have patented many reduced ignition propensity cigarettes,9 and their own market research has shown them to be acceptable to smokers.10 To date only one such brand has been released (Philip Morris’s Merit, which is available in the USA and New Zealand). A recent comparative study of self-extinguishment showed that all regular manufactured cigarettes, 73% of Merit cigarettes, but no hand-rolled cigarettes (wrapped in virtually citrate-free paper), burnt full length.11 The hand-rolled cigarettes were wrapped in a brand of cigarette paper containing only trace levels of impregnated citrate. The elimination of citrate and other burning agents in cigarette paper thus appears to be a simple and effective means of dramatically reducing the ignition propensity of cigarettes. Now, after decades of advocacy from paediatricians, trauma physicians and fire authorities, both the state of New York and Canada have passed legislation on “fire-safe” cigarettes. From July this year, all cigarettes sold in the state of New York must pass a performance standard requiring that no more than 25% of cigarettes tested shall exhibit full-length burns on a bed of filter paper specified in the test method.12 (Merit would thus fail the New York standard.) Canada’s similar legislation was passed in March 2004, to take effect from October 2005.13 It would appear ethically inconceivable that the tobacco industry, knowing that it can produce products that will greatly reduce the potential to cause fires, should refuse to release them onto the market. Why, then, does it continue to do this, given the potential for saving lives, property and the likely public relations benefits to that beleaguered industry that would almost certainly follow? Evidence from internal tobacco company documents shows that the industry’s principal concerns appear to be legal — they are concerned about litigation relating to people burnt in fires caused by cigarettes that the industry could have made less combustive. As a 1983 British American Tobacco document stated: In view, however, of their recent decision taken by the Tobacco Institute not to work actively in the development of self-extinguishing cigarettes (for product liability reasons) it will be necessary for B&W management to define its wishes . . . [emphasis added].14 A major impediment to regulating fire-safe cigarettes in Australia is that the constituents of tobacco products are totally unregulated.15 Their ingredients and “quality” are not controlled by any food, pharmaceutical or poisons legislation, allowing the industry to avoid the sort of regulatory standards that could require cigarettes with reduced ignition propensity to conform to a standard. Instead, the industry enters into self-regulatory agreements with government, such as the current arrangement to list additives on industry websites. This agreement allows local manufacturers to avoid listing any ingredients they do not wish to reveal by designating them as generic “processing aids” or declaring them commercial-in-confidence.15 This regulatory “no-man’s land” should be replaced by a national tobacco act,16 which would allow complete regulation of all aspects of tobacco manufacturing and marketing. Such regulation, in mandating reduced ignition propensity cigarettes, would save lives, millions of dollars in damage and contribute to bushfire reduction. In the event that a national tobacco act was opposed by one or both of the major political parties, interim cigarette reduced ignition propensity regulations should be introduced, in line with those introduced in the Canadian and New York State jurisdictions.

Simon Chapman PhD · Antony Balmain

Altruism and trust lie at the heart of research on human subjects. Altruistic individuals volunteer for research because they trust that their participation will contribute to improved health for others and that researchers will minimise risks to participants. In return for the altruism and trust that make clinical research possible, the research enterprise has an obligation to conduct research ethically and to report it honestly. Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavourably on a research sponsor’s product. Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence available for clinical decision-making. Researchers (and journal editors) are generally most enthusiastic about the publication of trials that show either a large effect of a new treatment (positive trials) or equivalence of two approaches to treatment (non-inferiority trials). Researchers (and journals) typically are less excited about trials that show that a new treatment is inferior to standard treatment (negative trials) and even less interested in trials that are neither clearly positive nor clearly negative, since inconclusive trials will not in themselves change practice. Irrespective of their scientific interest, trial results that place financial interests at risk are particularly likely to remain unpublished and hidden from public view. The interests of the sponsor or authors notwithstanding, anyone should be able to learn of any trial’s existence and its important characteristics. The case against selective reporting is particularly compelling for research that tests interventions that could enter mainstream clinical practice. Rather than a single trial, it is usually a body of evidence, consisting of many studies, that changes medical practice. When research sponsors or investigators conceal the presence of selected trials, these studies cannot influence the thinking of patients, clinicians, other researchers, and experts who write practice guidelines or decide on insurance-coverage policy. If all trials are registered in a public repository at their inception, every trial’s existence is part of the public record and the many stakeholders in clinical research can explore the full range of clinical evidence. We are far from this ideal at present, since trial registration is largely voluntary, registry data sets and public access to them varies, and registries contain only a small proportion of trials. In this editorial, published simultaneously in all member journals, the International Committee of Medical Journal Editors (ICMJE) proposes comprehensive trials registration as a solution to the problem of selective awareness and announces that all eleven ICMJE member journals will adopt a trials-registration policy to promote this goal. The ICMJE member journals will require, as a condition of consideration for publication, registration in a public trials registry. Trials must register at or before the onset of patient enrolment. This policy applies to any clinical trial starting enrolment after 1 July 2005. For trials that began enrolment before this date, the ICMJE member journals will require registration by 13 September 2005 before considering the trial for publication. We speak only for ourselves, but we encourage editors of other biomedical journals to adopt similar policies. For this purpose, the ICMJE defines a clinical trial as any research project that prospectively assigns human subjects to intervention or comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Studies designed for other purposes, such as to study pharmacokinetics or major toxicity (eg, phase I trials), would be exempt. The ICMJE does not advocate one particular registry, but its member journals will require authors to register their trial in a registry that meets several criteria. The registry must be accessible to the public at no charge. It must be open to all prospective registrants and managed by a not-for-profit organisation. There must be a mechanism to ensure the validity of the registration data, and the registry should be electronically searchable. An acceptable registry must include at minimum the following information: a unique identifying number, a statement of the intervention (or interventions) and comparison (or comparisons) studied, a statement of the study hypothesis, definitions of the primary and secondary outcome measures, eligibility criteria, key trial dates (registration date, anticipated or actual start date, anticipated or actual date of last follow-up, planned or actual date of closure to data entry, and date trial data considered complete), target number of subjects, funding source, and contact information for the principal investigator. To our knowledge, at present, only www.clinicaltrials.gov, sponsored by the United States National Library of Medicine, meets these requirements; there may be other registries, now or in the future, that meet all these requirements. Registration is only part of the means to an end; that end is full transparency with respect to performance and reporting of clinical trials. Research sponsors may argue that public registration of clinical trials will result in unnecessary bureaucratic delays and destroy their competitive edge by allowing competitors full access to their research plans. We argue that enhanced public confidence in the research enterprise will compensate for the costs of full disclosure. Patients who volunteer to participate in clinical trials deserve to know that their contribution to improving human health will be available to inform healthcare decisions. The knowledge made possible by their collective altruism must be accessible to everyone. Required trial registration will advance this goal.

Catherine De Angelis MD · Jeffrey M Drazen MD · Frank A Frizelle MB ChB · Charlotte Haug MD · John Hoey MD · Richard Horton · Sheldon Kotzin · Christine Laine MD, MPH · Ana Marusic MD, PhD · A J P M Overbeke MD, PhD · Torben V Schroeder MD, DMSc · Hal C Sox MD · Martin B Van Der Weyden MD, FRACP, FRCPA

The benefits of whole-body CT screening need to be carefully weighed against the risks Whole-body computed tomography (CT) screening is currently marketed to asymptomatic individuals as a form of proactive and preventive healthcare. Commonly, the chest, abdomen and pelvis are scanned, but the head and neck are also included in the “five-region” scans offered by some commercial companies. In the United States, it has been estimated that, over the past 3 years, 15 million whole-body scans have been performed in about 400 centres.1 In Australia, clinics in Brisbane and Sydney are offering whole-body CT screening. Despite the growth in demand for whole-body scans, there is no evidence that they are effective in detecting serious, treatable disease without undue cost or undesirable effects. The value of many applications of imaging technology for diagnosing and monitoring disease and planning treatment is accepted. But sceptics of whole-body screening note the lack of evidence of benefit, the likelihood of clinically unimportant findings that may result in possibly needless further investigations, and the risks of radiation. There have been no published studies of the safety or efficacy of whole-body screening. In Australia, we identified only one ongoing study: researchers at the University of New South Wales are currently assessing 1500 people who have had whole-body CT scans, measuring significant pathological findings and their eventual outcomes (Fred Ehrlich, Professor of Public Health and Community Medicine, University of NSW, personal communication). The prevalence of findings on whole-body CT is high. In a recent conference presentation, it was reported that, of 1200 whole-body CT scans, 87% showed at least one finding, and nearly a third of patients were advised to undergo further testing or follow-up.2 In a study using CT to screen for lung cancer,3 700 ancillary findings (not related to lung cancer) were noted in about 1520 screened individuals. Most were false-positive results, and the follow-up adversely affected the patients’ quality of life and resulted in unnecessary diagnostic and interventional procedures.3 It has been estimated that, in healthy people, about 80% of abnormalities detected on CT screening studies may not be life-threatening;4 however, this estimate requires confirmation. Follow-up of non-significant findings has health, psychosocial and cost implications. In Australia, Medicare and private health insurance agencies do not cover the costs of a whole-body scan (currently over $800), but may reimburse follow-up diagnostic evaluations. What are the risks of whole-body screening? The radiation exposure has been estimated to be somewhere between 1 and 24 mSv per CT scan.5,6 However, owing to technical and anatomical factors, the dose can vary by a factor of 10 or more between patients.6 A 10 mSv radiation exposure is associated with an increased risk of fatal cancer of about 1 in 2000 (this can be compared with a lifetime risk of about 1 in 5).6 If screening were undertaken in Australia at 3-year intervals, the risk of radiation-related death would be an estimated 0.4%, 0.3% and 0.1% for men starting screening at 40, 50 and 60 years, respectively, and 0.6%, 0.4% and 0.2% for their female counterparts.7 Compared with 10 other types of x-ray, CT scans are responsible for the largest number of radiation-induced cancers per year in nine cancer sites examined.8 In Australia, the Radiation Advisory Council and the NSW Environment Protection Authority concluded in 2003 that whole-body screening by CT is inappropriate for the general diagnosis of healthy individuals. Similarly, the Royal Australian and New Zealand College of Radiologists and the Radiation Health and Safety Advisory Council have each published statements indicating that there is insufficient scientific evidence to support whole-body CT screening in asymptomatic patients with no family history suggesting disease.9,10 In the United States, several professional groups, including the American College of Radiology and the American Association of Physicists in Medicine, do not recommend whole-body CT screening for asymptomatic healthy individuals.11,12 In New South Wales, it has been illegal since 2003 to perform a whole-body CT scan without a written request from an independent medical practitioner. The radiation dose and health risks involved must be fully explained, individuals under the age of 50 must be told that they are more at risk of developing cancer as a result of the procedure, and written and informed consent must be obtained before the scan can be performed.13 Breaches of these new regulations may attract fines of up to $27 500 for individuals, $165 000 for corporations and/or a maximum of two years’ imprisonment.13 This approach disallows self-referral. We made enquiries to medical defence providers and professional organisations regarding the referral of asymptomatic patients for whole-body CT screening. One medical indemnity provider indicated that, in the event of an untoward incident, members would not be indemnified if they practised whole-body CT screening for asymptomatic patients or referred patients using particular referral formats supplied by commercial CT screening companies. We suggest that practitioners check with their own indemnity provider regarding their coverage under these circumstances. The key question is whether whole-body CT screening will lead to detection of unsuspected diseases, resulting in earlier treatment and improved outcomes, or simply reveal abnormalities for which follow-up and treatment will result in no overall gain. This question can only be answered with well designed studies. In the interim, the community interest in whole-body CT screening is growing, and GPs, especially, may be put in a difficult position by patients requesting a referral for a whole-body scan. Some Internet sources of information on whole-body CT screening are listed in the Box. Consumers and medical practitioners need to be wary of the many claims that are made in support of whole-body CT screening for early disease. Guidelines — based on the current evidence of benefits and risks of whole-body CT screening, assessed by reputable professional and consumer bodies — would be valuable to assist the decisions of both medical practitioners and consumers and to provide a better basis for informed consent. In conclusion, the current evidence suggests that patients should be advised that there is no proven benefit, and indeed possible detriment, from undertaking whole-body CT screening. Internet sources of information on whole-body computed tomography Australian professional and government organisations Royal Australian and New Zealand College of Radiologists www.ranzcr.edu.au/open/policies/diagnostic_imaging/pol2_2.htm Radiation Health and Safety Advisory Council www.arpansa.gov.au/pubs/rhsac/st1_aug02.pdf NSW Environment Protection Authority www.epa.nsw.gov.au/radiation/ctbodyscans.htm NSW Health www.ppc.health.nsw.gov.au/news/2002/September/26-09-02ct.htm www.health.nsw.gov.au/news/2003/June/08-06-03ct.htm www.chs.health.nsw.gov.au/pubs/factsheet/pdf/body_scan_fs.pdf International professional organisations US Food and Drug Administration wwwfda.gov/cdrh/ct American College of Radiology www.acr.org/departments/pub_rel/press_releases/total-bodyCT.html Health Physics Society hps.org/documents/CTPosStm.pdf Other sources of information your patients may be using Life Span Medical Imaging www.lifespanmedical.com.au Total Health Screening www.totalhealthscreening.com.au Health Imaging CT www.openmrimgt.com/healthscreen/index.htm Be Well Body Scan www.bewellbodyscan.com Full Body Scanning www.fullbodyscanning.com/sanfrancisco/full-body-scan.jsp The Oprah Winfrey Show www.oprah.com/tows/pastshows/tows_2000/tows_past_20001002_b.jhtml www.oprah.com/tows/pastshows/tows_2000/tows_past_20001002_c.jhtml

Cleola Anderiesz PhD, BSc · J Mark Elwood MD, DSc · Brian R McAvoy MD, FRACGP, FRCP · Lizbeth M Kenny MB BS, FRANZCR

It all depends on which studies you emphasise Four years ago in the Journal we posed the question of whether active and passive exposure to cigarette smoke could cause breast cancer. We concluded, at the time, that biological plausibility had been established, but that the epidemiological evidence was inconclusive.1 This was consistent with a 1997 report2 of the California Environmental Protection Agency (Cal/EPA), which found that the link between environmental tobacco smoke (ETS) and breast cancer was inconclusive. However, in a recent draft review of the health effects of ETS,3 the Cal/EPA stated that the evidence for a causal association between ETS and breast cancer is now conclusive. Its latest report was based on a systematic review of 15 studies, 11 of which had been published since the 1997 report. Is this new conclusion justified? Until the 1990s, most case–control and cohort studies examining the association between cigarette smoke exposure and breast cancer focused on active smoking. These studies did not adequately ascertain the whole-of-life ETS exposure of the participants.1,4,5 Notably, childhood exposure was usually ignored.6 This is of particular relevance, as chemical carcinogenesis studies of breast cancer in experimental animals, and other studies on the development of the mammalian breast, indicate that breast ductal cells would be most susceptible to chemical carcinogenesis during puberty and first pregnancy.5 Thus, it is possible that childhood, adolescent and adult exposure to cigarette smoke up until the delivery of a woman’s first child is a crucial component of lifetime exposure. If an association with ETS did exist, case–control and cohort studies on active smoking and breast cancer could have underestimated the effects by inadequate assessment of ETS exposure.1,4-6 The conclusion of the Cal/EPA report on ETS and breast cancer3 is based on a systematic review that gives prominence to the recent studies in which several sources of ETS exposure have been ascertained and to the clear dose–risk relationships seen in some studies. The meta-analysis used in the Cal/EPA’s review yielded a relative risk of 1.40 (95% CI, 1.17–1.68) — a significantly increased risk. However, a closer look at the studies reviewed in the latest Cal/EPA report raises some questions about its conclusion. Of the 15 studies in the review, five were cohort studies, of which none showed a statistically significant increase in breast cancer risk with ETS exposure. Several of these cohort studies had a very limited assessment of ETS — for example, defining exposure as simply being married to a smoker. However, one of the five cohort studies, which prospectively assessed childhood, adult and occupational ETS among US nurses,7 also showed no association. Moreover, another major cohort study8 published since the Cal/EPA review supports the conclusion of the US nurses’ study in regard to ETS. In this report of a 5-year follow-up of a cohort of 116 564 Californian teachers, 1150 new cases of invasive breast cancer were diagnosed among the 76 189 never-smoking women who provided data on ETS.8 The study aimed to ascertain total lifetime ETS exposure, although the published analysis is limited to household exposure throughout life. No significant association between ETS exposure and breast cancer was found for any age range of exposure or by menopausal status. However, a significant association was found between active smoking and breast cancer. The relative risks of acquiring breast cancer after ETS exposure in childhood, adulthood, or both childhood and adulthood, were 0.92, 0.93 and 0.93, respectively. Adding this new study to the Cal/EPA’s meta-analysis, the overall relative risk, based on the six cohort studies, is 1.01 (95% CI, 0.92–1.12) — that is, there is no significant effect. The strong association between ETS exposure and breast cancer emphasised in the Cal/EPA report3 is based on five case–control studies regarded as “unlikely to have missed important ETS exposures”. The summary odds ratio for these studies was 1.92 (95% CI, 1.54–2.39). The association was stronger in premenopausal women (summary odds ratio, 2.20; 95% CI, 1.70–2.85). However, if a true association exists, it is difficult to see why the two high-quality US cohort studies of nurses and teachers7,8 showed no association. In both studies, data on ETS exposure were collected before the diagnosis of breast cancer, thus avoiding recall bias, and both groups are likely to have given reasonably complete and valid information, including data on childhood exposures. Other research results add to the complexity of the issue. A 2002 systematic review, based largely on the same case–control studies as the Cal/EPA review,3 concluded that the strength of the association with breast cancer is similar for passive as for active smoking9 — a conclusion that others find implausible.7 One possible explanation for this seeming paradox could be that the association is linked mainly or exclusively to ETS exposure in childhood or early adolescence, as has also been suggested for active smoking, perhaps through hormonal mechanisms as well as the direct effects of carcinogens.10 The fact that p53-gene mutations in breast tumours are increased in smokers compared with non-smokers or ex-smokers suggests a genotoxic effect of smoking on breast tissue.11 Further complexities related to genotype may emerge: one case–control study12 showed that the association between passive smoking and breast cancer was stronger in rapid acetylators (ie, women who, owing to their specific NAT2 genotype, more rapidly metabolise carcinogenic compounds, such as aromative amines, in tobacco smoke). However, with regard to active smoking, slow acetylators were more at risk.12 Although many genotypes have been reported to affect the association between active or passive smoking and breast cancer,13 the results are inconsistent and do not explain the variable epidemiological results. Is a causal association between ETS exposure and breast cancer now certain, as the Cal/EPA draft report proposes? The jury would be wise to stay out on this one. If the emphasis is put on cohort studies, there appears to be no association between ETS exposure and breast cancer. If the emphasis is put on case–control studies with more detailed information on ETS exposure — but the possibility of recall bias — there appears to be an increased risk, especially in premenopausal women. An analysis focusing on childhood and adolescent ETS exposure may be the key to solving the current confusion. Such an analysis could be based on a pooled analysis of available studies with access to the original data, or on further assessment and follow-up of the ongoing cohort studies. In the interim, it is prudent to accept the possibility of an association, while also accepting the limitations of the available evidence. The International Agency for Research on Cancer has just released a major report on smoking, in which it states that the evidence does not support a causal link between either active or passive smoking and breast cancer.14 However, the report confirms a causal link between ETS and lung cancer, which, in itself, justifies efforts to restrict ETS.

J Mark Elwood MD, DSc · Robert C Burton MD, PhD

High-quality primary evidence from an Australian and New Zealand study provides a definitive answer The 1998 report of a meta-analysis by the Cochrane Injuries Group Albumin Reviewers presented an important public health issue and questioned the practices of many doctors in Australian intensive care units (ICUs).1 Using data from 24 studies involving 1419 patients, the meta-analysis reported that the administration of albumin-containing fluids to critically ill patients increased the absolute risk of death by 6%, suggesting one extra death for every 17 patients given albumin. The authors recommended that albumin should not be administered to critically ill patients outside the context of rigorously conducted, randomised trials. A subsequent meta-analysis did not resolve the issue of albumin’s safety in the critically ill.2,3 Due to its ready availability, albumin has been widely used in Australian ICUs. Even after the publication of the Cochrane review, half of all patients in surveyed ICUs in Australia received albumin during their ICU stay (R Bellomo, S Finfer, unpublished data). Extrapolating these results would mean that 50 000 patients received albumin in Australian ICUs each year and, if the Cochrane meta-analysis was correct, this would result in an additional 3000 deaths annually. Thus, the issue of albumin’s safety was of particular importance in Australia. The recent publication of the SAFE (Saline versus Albumin Fluid Evaluation) study in the New England Journal of Medicine4 not only brings certainty to the issue of albumin’s safety in a heterogeneous population of adult ICU patients, it also marks the coming of age of clinical research in Australian and New Zealand ICUs. The SAFE Study, a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian Red Cross Blood Service, and The George Institute for International Health, was a double-blind, randomised controlled trial of albumin versus saline for fluid resuscitation involving 6997 patients. Conducted in 14 ICUs in Australia and two in New Zealand, it was funded by the National Health and Medical Research Council and the Health Research Council of New Zealand, and by direct grants from the Australian federal, state and territory governments, the two New Zealand hospitals and CSL Ltd. Internationally, the SAFE Study is the largest randomised controlled trial conducted in intensive care or transfusion medicine to date. An accompanying editorial acknowledged that the SAFE Study heralded a new era in critical care marked by the large, simple randomised trial.5 The design of the study reflected the SAFE collaborators’ desire to conduct a definitive trial that would answer an important clinical question and provide results that would be widely applicable in ICUs around the world. As a result, the trial sought to include as many adult patients admitted to participating ICUs as possible by using broad, simple inclusion criteria and few exclusion criteria. The main inclusion criterion was that the treating clinician believed that fluid administration was indicated for the treatment of intravascular volume depletion. The primary outcome measure was all-cause mortality 28 days after randomisation. The only broad patient groups excluded were those admitted to the ICU after liver transplantation, burns or cardiac surgery. The study enrolled 6997 patients in 69 weeks, an average recruitment rate of 101 patients per week. The rapid recruitment rate was made possible by the commitment of the clinical staff in the participating ICUs, the provision for delayed consent, and web-based randomisation and fluid distribution. The blinded study design was possible as both study fluids were manufactured by CSL Ltd and packaged in specially designed blinding materials6 before distribution by the Australian Red Cross Blood Service, New Zealand Blood Service and participating centres’ blood banks. What did the study find? The primary outcome was available for 99.1% of the 6997 patients randomised; of these, 726 assigned albumin (20.9%) and 729 assigned saline (21.1%) had died by Day 28. The relative risk of death for patients assigned albumin compared with patients assigned saline was 0.99 (95% CI, 0.91–1.09; P = 0.87). There were no differences in secondary outcomes, with patients assigned albumin and saline having similar incidences of new organ failure, similar durations of mechanical ventilation and renal replacement therapies, and similar ICU and hospital lengths of stay. Key findings of the study are shown in the Box. The study identified six predefined subgroups: patients with and without trauma, with and without severe sepsis, and with and without acute respiratory distress syndrome (ARDS). As a previous meta-analysis had suggested that trauma patients resuscitated with colloid solutions had higher mortality than those resuscitated with crystalloid solutions,7 trauma was a stratification variable in the study. Patients with severe sepsis and ARDS were identified at baseline to determine whether the increased capillary permeability to albumin seen in those conditions8,9 resulted in a treatment effect that differed from that seen in the study patients without those conditions. Within the predefined subgroups there was limited evidence of a treatment effect favouring saline in patients with trauma, and favouring albumin in patients with severe sepsis. The possibly detrimental effect of albumin in patients with trauma was limited to patients with evidence of traumatic brain injury, namely those patients admitted to the ICU as a result of trauma who had a documented unsedated Glasgow Coma Scale score less than 14 and evidence of brain injury on cerebral computed tomography. The investigators cautioned readers that such subgroup differences frequently occur by chance, and the accompanying editorial advised cautious interpretation of the subgroup findings.5 Thus, the study demonstrated that, in this heterogeneous population of adult ICU patients, albumin can be considered safe, without demonstrating any clear efficacy advantage over saline. The SAFE Study achieved its goal of providing a definitive answer to an important clinical question. The result is widely applicable in those ICUs around the world where purified albumin is available. In addition, the study has demonstrated that investigators in Australian and New Zealand ICUs are capable of conducting large-scale collaborative trials on modest budgets and in a realistic timeframe. The SAFE Study has been described as a landmark study that heralds a new era in critical care.5 We hope that it will be only the first of many such studies. Key findings of the SAFE Study4 6997 patients were randomised to receive either albumin (3497) or saline (3500). The primary outcome (alive or dead at 28 days) was available for 6933 patients (99.1%). No significant difference was seen between the albumin and saline groups in: 28-day all-cause mortality (20.9% v 21.1%; P = 0.87) days in the intensive care unit (6.5 [SD, 6.6] v 6.2 [SD, 6.2]; P = 0.44) days in hospital (15.3 [SD, 9.6] v 15.6 [SD, 9.6]; P = 0.30) days of mechanical ventilation (4.5 [SD, 6.1] v 4.3 [SD, 5.7]; P = 0.74) days of renal replacement therapy (0.5 [SD, 2.3] v 0.4 [SD, 2.0; P = 0.41)

Simon R Finfer FRCA, FRCP, FJFICM · Neil W Boyce FRACP, PhD · Robyn N Norton PhD, MPH

One function of such services is to help clinicians ask the “right” questions The article by Gill and colleagues in this issue of the Journal (page 204)1 raises the issue of the ethics of clinical ethics services and, secondarily, their potential legal liability. Expressly or by implication, the article points to many difficulties and pitfalls of such services, and certainly raises more questions than it answers. But, in doing so, it reflects a necessary and valid function of ethics services: to help those who should make the decisions ask as many of the “right” (ie, ethically relevant) questions as possible. It is not the function of ethics services to make those decisions. The authors make some important points. Variability in decisions or failure to reach consensus does not mean ethics consultations are pointless — it is as important to highlight moral differences as to resolve them. When conducted well, clinical ethics services can be a valuable hospital resource and a powerful, critical voice contributing to ethical practice. “Doing ethics” is an exercise of power, and power must be exercised ethically. But simply a desire to do good is not sufficient to ensure that. Our goal of doing good can blind us to the harm that is also unavoidably inflicted, and sometimes that infliction is unethical. Doing ethics is a matter of both substance and process. Questions that help to provide insights about process ethics include: Who should decide? On what basis? Using which procedures? For what purposes? One of my “process” concerns about the Acute Clinical Ethics Service (ACES) described by Gill et al is that the ACES team does not necessarily include a person trained in applied or practical ethics and, moreover, that the authors do not recognise the need for doing so. I also have substantive or principle-based ethical concerns. For example, their “organisational principles” do not make it clear that, when values conflict, the basic ethical and legal presumption governing decision-making is that the patient’s values should take priority, and therefore that contravening them must be fully justified. Rather, these principles instruct the ACES to consider “the facts of the case and the values and preferences of all stakeholders”. Most ethical issues involve a conflict of values, which means values must be prioritised when not all can be honoured. Justifying the breaches of values that result is the essence of doing ethics. An important function of a clinical ethics service is to provide such justification or to comment on that provided by others. This allows the clinical ethics service to fulfil its advisory role in individual cases, to establish precedents that can guide future decisions and to serve a teaching function within the healthcare institution as a whole. However, my purpose here is to address the broader ethical issues underlying an ethics service rather than the ethical issues raised by the cases presented by Gill et al, with whose analysis and conclusions I do not necessarily agree. Committee decisions, as compared with individual ones, can spread the responsibility. A committee can make a decision that no one person — in particular, no committee member — acting alone would make. In all the cases described by Gill et al, the issue was that of shortening life (by either withholding treatment or aborting a fetus), and the physicians doing that were morally reassured by the ACES’s involvement. Might that have allowed the “caring team” to implement decisions that their moral intuitions were indicating were unethical? While these decisions may have been ethical, we must always be aware that we ignore such intuitions at our ethical peril. Could the ACES be legally liable for its advice?A clinical ethics service could be held legally liable if it failed to act as a reasonably competent committee. In a Quebec Superior Court case,2 the court held the ethics committee of a McGill teaching hospital liable for negligence in its review of the informed consent forms for a research protocol. The very remote risk of death was not disclosed. A subject in the research trial died from an anaphylactic shock reaction to the injection of a dye. If the membership of an ethics service or committee is not reasonably constituted, it could give rise to a claim based on systems negligence for failure to establish a reasonably safe system for ethics review. Not having a trained ethicist as part of a service or committee, or at least available for ad-hoc consultation, raises this issue, although that absence may be able to be justified. Moreover, an ethics committee and a “single ethics expert” are not mutually exclusive alternatives, as often both are needed. Ethics services or committees may have an obligation to report unethical and illegal actions. If they do not intervene at all, there may be no liability, but, having intervened, they may be liable for failure to take reasonable care when it is clear that that failure could result in harm to others. Patient consentThe basic presumption concerning patients’ medical records is that they are subject to strict duties of privacy and confidentiality. Therefore, obtaining informed consent from the patient (or the legal representative of an incompetent patient) to consult the ethics committee is necessary. Acting without such consent would need to be justified. As presently drafted, the organisational principles outlined by Gill and colleagues could cause some confusion as to whether these rules apply. Once again, it should be made clear that, in situations in which values conflict, the basic presumption is that the patient’s values should take priority. Characteristics of the members of the ethics consultation teamThe relationship between an ethics consultation team and the hospital administration raises the issue of conflict of interest in those people who are both members of the ethics service and part of the hospital organisation. If their obligations or goals as members of a clinical ethics service could conflict with their duties as people holding hospital appointments, then there is such a conflict, whether or not in the particular circumstance a conflict arises in practice. Strong ethical sensitivity is required to identify and deal with such conflicts. An assumption that people of good intention acting in good faith are competent ethics committee members — in particular, that they are, by virtue of those characteristics, sufficiently educated in ethics — is not valid. A recent US Institute of Medicine report3 has recommended that substantial resources be devoted to such education. Schools of ethicsGill and colleagues mention various schools of ethics that “may assist with the resolution of ethical conflicts”. These schools can be looked at as different “lenses” through which one can view a situation that raises ethical dilemmas. When all reflect back the same response, one can be reasonably certain that acting in that way is ethical. But when conflicting responses show up, difficulties arise. These difficulties usually reflect an irresolvable conflict of values. In such cases, it is very important to give the reasons (ie, justification) for giving priority to one value or set of values and thereby contravening another value or set of values. Indeed, providing such justification is the essence of “doing ethics”. ConclusionThe article by Gill and colleagues raises some very important issues, and the cases they describe may raise substantial controversy in relation to healthcare ethics services. Certainly, if North American experience holds true in Australia, many doctors may feel, at least initially, that their professional autonomy is threatened by an ethics committee or even an ethicist. Many nurses, however, will see ethics committees and ethicists as empowering them to challenge doctors’ decisions that they believe are unethical. Junior members of the medical profession, especially students and residents, and a few of its leaders, will be the first to accept the benefits of properly constructed ethics consultation services and to promote their integration into the healthcare setting. As ethics services become more familiar, more people will recognise both their benefits and (as we should always keep in mind) their dangers. Like democracy, ethics committees and ethics consultations are not a perfect system, but they are better than the alternative of having no ethics consultation process at all.

Margaret A Somerville AM, FRSC, LLD

Should we do it, is it worthwhile, and who should decide? In the Western world, the number of people living beyond 80 years is increasing. In the United States, it is expected that 43% of the population will reach the age of 80.1 In Australia, men and women who reach 80 years may expect a further 7 and 10 years of life, respectively, the majority being disability free.2 Cardiac surgery in Australia has entered its fifth decade, and is now commonly performed (18 000 cases/year). The total cost (including salaries, equipment, building depreciation, etc) of having coronary artery bypass grafting (CABG) (which constitutes 75% of all cardiac surgery) at Western Australian teaching hospitals is about $12 000 per case (WA Department of Health, 1994, unpublished data). Over the past decade, the proportion of cardiac surgery patients aged 80 years or more has risen from negligible to 7% in selected centres.2-4 Surgical outcomes are encouraging: a 2002–03 report from six Victorian public hospitals revealed mortality rates of 2%–4% for elective CABG and 10%–12% for aortic valve replacement.4 However, follow-up assessment by direct patient contact has not been universal — commonly, outcome analyses rely solely on physicians’ perceptions.2 In a series of 64 octogenarians having cardiac surgery over a 5-year period at three Australian hospitals, our research group prospectively assessed outcomes and directly spoke to patients at several time intervals.2 The need for surgery was compelling — all had class III/IV symptoms of angina and/or dyspnoea. The total in-hospital mortality was 6.3% (nil in those having elective surgery and 10.5% in those requiring urgent surgery). The incidence of significant complications was low (perioperative myocardial infarction, 1.6%; stroke, 1.6%). At a mean follow-up time of 2.8 years, 44 patients were still alive, 42 (95%) were free of cardiovascular symptoms, and 42 remained independent, with a significantly improved quality of life. Kaplan–Meier actuarial survival for hospital survivors at 4 years was 74%. Interestingly, 8 patients (18%) had remarried and 8 had commenced on sildenafil. Not surprisingly, 43 (98%) of the patients said they would recommend cardiac surgery. Despite these favourable outcomes, one in five of the study participants had been originally advised by their general practitioner and/or physician not to proceed with surgery because of their age. Discrimination based on age alone is not uncommon.1,5 Performing surgery in these octogenarians was on a needs basis — other patients on waiting lists were not disadvantaged. If people over a certain age are to be barred access to healthcare, it is for society to debate and for governments to legislate. In Australia, Katrina Bramstedt (a bioethicist at the Department of Community Medicine and General Practice, Monash University) has cogently argued that age discrimination is common. Yet there is no ethical justification for denying cardiac surgery to octogenarians,5,6 particularly as empirical evidence validates the potential benefit of this treatment.5 It has been stated that “survival is not the most important outcome in the elderly”.7 Not so. Of the 102 patients on whom we have now operated, all wished to continue to live independently. So what have we learnt? Firstly, that surgery can be safely performed in octogenarians. The best people to make the decision whether to operate are the surgeon and the cardiologist, working in conjunction with one another. Secondly, that the success of surgery is critically dependent on the quality of anaesthesia and postoperative intensive care. There must be ongoing clinical governance so that expected outcomes match actual results.8 Not only are more and more octogenarians choosing to have cardiac surgery, but the chances of a good outcome are improving. Advances in surgical techniques in recent years mean that the risks of cardiac surgery, for all patients but especially those over 80 years, have been substantially reduced. The availability of “off-pump” technology (ie, doing coronary artery anastomoses without the use of cardiopulmonary bypass [CPB]), including mechanical aortocoronary anastomotic devices, allows CABG to be done not only without CPB, but also without manipulating the aorta, thus reducing atheroembolic risk.9 Furthermore, the duration of CPB and global myocardial ischaemia can be minimised by combining off-pump techniques with CPB (eg, valve replacement with CABG). Also, selective use of ventricular fibrillation (rather than cardioplegic arrest) when repairing a mitral valve avoids global myocardial ischaemia. Surgeons have several options for the technical performance of these operations. While there may be no surgical consensus on the optimal technique for a given patient, in my view a “one shoe fits all” surgical approach may prove hazardous. It is important to prepare the patient optimally before surgery. This includes universal carotid screening and judicious use of prophylactic carotid endarterectomy, together with preoperative optimisation of renal function and maintenance of perioperative enforced diuresis.10 Although none of these innovations has been tested in randomised controlled trials, myocardial, cerebrovascular and renal complication rates are now low. A critical factor determining surgical outcomes is whether the patient is in need of urgent surgery (ie, surgery required as a hospital inpatient because the patient cannot be satisfactorily stabilised with medical treatment).2-4 Delays in referring symptomatic patients are invariably associated with rapid clinical deterioration and poor results. The role of percutaneous coronary intervention (PCI) versus surgery for coronary artery disease requires comment. Neither surgery nor PCI is benign.11 For comparable patients of any age in experienced hands, the risks of inducing death, myocardial infarction, stroke or neurocognitive deficits are the same with either approach.12,13 With surgery, the failure rate is lower and there is less need for repeat interventions. However, surgery requires a sternotomy and graft harvest incisions on the leg. A number of clinical factors are associated with increased risk of PCI failure (eg, left main coronary artery or multivessel disease, diabetes).14 Before PCI is undertaken, it is essential that the cardiologist and the surgeon carefully assess which procedure is optimal for a particular patient. If PCI fails, performing emergency surgery (ie, within 24 hours of hospital admission) is associated with markedly increased risks, particularly in octogenarians. Which octogenarians should be offered cardiac surgery? Many, if not the majority, should be readily identifiable as unsuitable because of advanced comorbidities. However, the 20% of patients in our series who were advised not to proceed with surgery had no clear features distinguishing them from the 80% advised to proceed. It is impossible to provide unambiguous criteria for refusing surgery. Nor am I suggesting that all octogenarians be offered this treatment. What I am advocating is that age alone must not be a barrier to accessing cardiac surgery. We can be heartened that careful evaluation allows us to pick the right patients and that these patients are achieving acceptable outcomes. Patients should be offered a choice. Those who have had cardiac surgery believe it is worthwhile and are very grateful.2

John MP Alvarez FRACS

More accurate food labelling would assist consumers and the food industry alike “We . . . can . . . not be held responsible for its content or any side-effects resulting from exposure to same. Your statutory rights are not affected. May contain traces of nuts” [website disclaimer].1 Conceived as a warning for allergic consumers, born and nurtured as a statement to dissuade potential litigation, the phrase “May contain traces of . . .” now threatens to become immortal as it enters the lexicon as a proxy for a blanket disclaimer. This situation developed as a response to the problem of hidden food allergens. Immediate hypersensitivity to certain foods, with the potential for anaphylaxis and death, affects about 6% of children and 2% of adults.2 Characterised by sudden allergic symptoms on ingestion and confirmed by positive skin and/or radioallergosorbent tests, inadvertent ingestion of a food allergen may require self-injection with adrenaline using an EpiPen (self-injectable adrenaline device) and/or medical resuscitation. Food allergy causes about 25% of anaphylactic deaths in the United Kingdom.3 There is also the distressing scenario of administering and/or witnessing emergency treatment that affects everyone, including parents, friends, carers and schools. “Hidden” allergens are hidden in the sense of being unrecognisable, such as egg in a pudding. In December 2002, Food Standards Australia New Zealand introduced changes to the Food Standards Code, making it mandatory that common food allergens and products derived from those allergens be labelled on packaged foods.4 Foods that are not labelled must have ingredient information available at the consumer’s request. Food allergens that must be declared include egg, milk, peanut, tree nuts, sesame, crustaceans, fish, soy, and cereals containing gluten. There are rare sensitivities for which mandatory labelling does not apply, including anaphylaxis to certain spices5 or fruits.6 In this issue of the Journal, the article by Smith et al7 (page 219) describes the first reported Australian cases of anaphylaxis to lupin, and the authors submit that foods containing lupins, used increasingly in manufactured food products, should be subject to mandatory labelling. Follow-up strategies after anaphylaxis include assessment in a specialist clinic, immunological and food analysis, provision of an EpiPen (now listed under the Pharmaceutical Benefits Scheme), practice with an EpiPen trainer, a written anaphylaxis action plan, a personal allergen identification medallion, access to useful websites (Box), and involvement of carers and schools. Education of children as well as their carers is crucial so that teenagers can walk away from childhood with skills to help keep them safe. There are simple principles to emphasise: Always carry an EpiPen Always read food labels Ask questions about food preparation (be aware of the risk of cross-contamination) No label/no eat No EpiPen/no eat Tell friends about a serious food allergy Tell friends if feeling unwell, especially after eating. How are we to interpret the disclaimer “May contain traces of . . .”? “May contain” means the allergen is stored or processed close to the food product, and/or added to other food lines, but not purposely included in the product. We don’t know the chances of accidental contamination, which may be measurable if the same production line is used, but remote if the allergen is restricted to a separate building. The word “traces” implies extremely small amounts, but defining the allergenic potential of foods, and thus obtaining a threshold dose that triggers reactions in the majority of sensitised subjects, has proved difficult.8 While people with allergies welcomed the 2002 changes to the Food Standards Code, their diet is now more restricted because of the proliferation of these “may contain” precautionary statements. Manufacturers argue that the risks associated with cross-contamination of food ingredients “from paddock to plate”, despite good manufacturing practice, have led to the many variations of “may contain” warnings. This has reduced the already limited food choices of consumers with allergies and has led to a rise in unnecessary avoidance of many foods that may in fact be safe. Since January 2003, Australia has had more than 50 food recalls for undeclared allergens.9 While many of the recalls have involved imported products, an alarming number have related to Australian-made foods recalled as a result of consumer complaints or government testing. How can we improve the current situation? Recently published Australian guidelines recommend that allergen minimisation, rather than banning certain foods, is the appropriate strategy in schools.10 If a school “thinks” it has banned an allergen, a level of complacency may develop among teachers and childcare workers. But if one focuses on allergen minimisation, then it follows that foods that have peanut, for example, in the ingredient list should be left for consumption at home and not sold in the school canteen, but foods that are labelled “May contain traces of . . .” can be allowed at school for the non-allergic school population. We must be alert to newly recognised hidden food allergens, such as the lupins identified by Smith et al.7 Consensus protocols are being developed to determine threshold doses of food allergens,11 and, in time, these may serve as a guide to more accurate labelling. Food manufacturers, food scientists, health professionals and consumer organisations must work towards reducing the number of precautionary statements. The Australian Food and Grocery Council now facilitates an Allergen Working Group, which draws together relevant stakeholders to focus on the needs of consumers with allergies. As Australia imports and exports both food ingredients and packaged foods, steps toward uniform regulations will assist consumers and the food industry alike. In time, with a cooperative approach, we may even find a smarter way of saying “May contain traces of . . .”. Useful websites for information about food allergy Anaphylaxis Australia Inc (www.allergyfacts.org.au) Australasian Society of Clinical Immunology and Allergy (www.allergy.org.au) Food Allergy and Anaphylaxis Network (www.foodallergy.org) Food Allergy and Anaphylaxis Alliance (www.foodallergyalliance.org)

Maria Said RN · John M Weiner MBBS,FRACP, FRCPA

A small number of Australian babies continue to acquire HIV infection unnecessarily The World Health Organization estimates that each year worldwide about 700 000 children are infected with HIV.1 Most of these infections occur through mother-to-child transmission in resource-poor settings, predominantly in Africa and Asia. Mother-to-child transmission rates of 30% continue to occur, despite the fact that this form of transmission is almost entirely preventable with antiretroviral therapy and formula feeding. The barriers to implementation of prevention strategies include restricted access to antenatal testing, cost and limited availability of antiretroviral therapy, poor workforce resources, and political obstacles, such as have occurred in South Africa.2 . . . the concerns about cost-effectiveness have largely been resolved . . . The outlook for babies born to HIV-positive mothers in high-income settings has improved dramatically. Most pregnant women with HIV infection in Western Europe or North America can expect an infection risk for their infant of less than 2%.3,4 This ability to interrupt perinatal transmission of HIV is, of course, only possible if the mother’s status is known. From 1998 to 2002, 103 pregnant Australian women were aware of their HIV-positive status. None of their infants was infected. During the same period, HIV was diagnosed in eight of the 15 infants born to mothers who became aware of their status only after giving birth.5 Overall, almost half the women in Australia with HIV infection known to have completed a pregnancy were unaware of their status before the birth of their baby.6 With this ignorance, no interventions can be offered. Despite the ready availability of prevention strategies, it appears that a small number of Australian babies continue to acquire HIV infection unnecessarily. The solution to this calamity is to prevent HIV infection in women and, when it does occur, to identify it before or during pregnancy. Unfortunately, national policies on antenatal screening are flawed. The Australian National Council on AIDS and Related Diseases recommends that “[pregnant] women found to be at higher risk of HIV . . . should be encouraged to undergo HIV antibody screening”, but does not explain the term “higher”.7 HIV antibody testing is now recommended for all pregnant women in the Northern Territory, New South Wales and Queensland, but the national guidelines continue to be followed in South Australia, Western Australia and Victoria. However, the facts show that existing practice fails to identify a number of preventable cases of mother-to-child transmission.8 The policy of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists is that HIV testing of pregnant women is the standard of care.9 Between 1995 and 1999, surveys indicated that rates of antenatal testing in Australia increased from 20%10 to 33%,11 and a recent survey suggests that the rate continues to increase slowly.12 Routine testing has been opposed on several grounds. There are quite reasonable concerns that routine testing might result in a degree of coercion and the conduct of testing without proper pre- and post-test counselling. Clearly, any recommendation to offer testing to all pregnant women would need to be accompanied by systematic strengthening of counselling and consent procedures. However, the strongest argument against routine antenatal testing has been that, given the low prevalence of diagnosed HIV infection in women, it is unlikely to be cost-effective. Our recent report challenges this position.13 We evaluated the cost-effectiveness of universal antenatal testing. We assumed that society would pay $39 000 per life-year gained, about twice the national average per-capita income. This value has been shown to result in efficient resource allocation.14 This is less than the cost per life-year gained for other screening programs currently under way in Australia, and is the valuation of a life-year gain used implicitly by the Australian Pharmaceutical Benefits Advisory Committee.15 The costs of universal testing — about $1.8 million — are offset by economic benefits for a prevalence of undiagnosed HIV of 0.0044%, or 1 in 23 000. The true prevalence is unknown, but available data suggest it is of this order. The major costs taken into account in our model were the training and time required for counselling about testing, and the pathology costs. The major benefit is that a young life might be extended by 60 or 70 healthy years. Many women in Australia with HIV infection were born overseas and are less likely to have comprehensive health insurance than those born here. Their access to antenatal care is thus limited. It is possible that women with undiagnosed HIV infection are currently over-represented among those missing the testing currently being done. If there were to be a uniform national approach to HIV testing, then education of the public, providers and clinic populations could be expected to improve the consent process. In the United States and Europe, anonymous HIV serological surveys among women giving birth in the 1980s gave way to recommendations for routine testing. Such surveillance of women giving birth has been seen as politically difficult in Australia.16 Given that concerns about cost-effectiveness have largely been resolved, the time has now come for public health and political courage to make it national policy that HIV testing be recommended for all women receiving antenatal care.

John B Ziegler FRACP, MD · Nicholas Graves PhD

A more efficient system of governance is needed to safeguard individual privacy while allowing registries to operate for the public good The recent controversy about cancer registries and patient privacy in the United Kingdom highlights the need for more debate about the governance of medical registries.1 For 40 years, identified data from UK patients with cancer have been transmitted to cancer registries without the patients’ express knowledge or consent. Although many benefits have flowed from analysis of these data, societal conventions have now changed, and questions are being asked in the UK and other countries, including Australia, about the privacy issues involved in the governance of medical registries in particular2-4 and medical research in general.5,6 Medical registries were traditionally established by public health authorities to monitor trends in the incidence of conditions such as infectious diseases and cancer. However, registries have become increasingly important in monitoring outcomes after the implementation of disease-prevention and treatment programs. They are now vital to quality-improvement programs that assess the safety of new drugs and procedures, identify best clinical practice and compare healthcare systems. For example, the Australian Orthopaedic Association National Joint Replacement Register currently monitors the use and survivorship of artificial hip- and knee-replacement prostheses,7 while the Victorian State Trauma Registry (VSTR) was established largely to monitor the effects of changes to the state trauma system.8 For registries to be effective, they must include all eligible participants so as to avoid biases that would affect the applicability and generalisability of results, and they must collect patient-specific data so as to adjust outcomes for risk and management factors. Further, in the absence of a unique national identification number, registries require name-based identification if participants are to be contacted for follow-up, or if registry data are to be validated against those held in other databases. The need for identified data raises consent and privacy issues. Registries must be established and governed in compliance with both federal and state legislation on privacy. Current requirements of this legislation have necessitated the development of consent procedures that maintain the effectiveness of medical registries, while informing patients and protecting their personal medical information. However, obtaining patient consent before participation in broad-based registries is often impractical and results in poor enrolment rates.,4 A more practical approach is to inform participants of their registration but to allow them to opt out of the registry. This approach resulted in the loss of fewer than 0.5% of eligible participants from the VSTR (unpublished data). This both complies with privacy legislation and achieves enrolment levels sufficient to maintain the scientific integrity of registries. Privacy legislation also sets down the circumstances under which privacy principles may be waived. For example, a human research ethics committee (HREC) may determine that the public benefit in allowing access to identified data substantially outweighs individuals’ right to privacy. However, as broad-based registries collect identified data from many sources, they are currently required to seek approval from many individual HRECs. This process is both time consuming and expensive. Further, many local HRECs have insufficient resources or expertise to evaluate the scientific merit of epidemiological research or to interpret privacy legislation,4,8,9 and consequently may reject legitimate research proposals. Registries could be established by legislation that overrides privacy provisions, but this approach lacks flexibility. A more workable system is required for establishing and governing medical registries that both safeguards individual privacy and allows the registries to continue to provide the foundations for quality-improvement programs and epidemiological research. No general guidelines for establishing and governing registries have been published, either in Australia or overseas. However, the National Health and Medical Research Council (NHMRC) has produced guidelines for genetic registers,10 which complement the National Privacy Principles11 with respect to the collection, use and disclosure of sensitive information, data quality and security, and the use of unique identifiers. After further development by the NHMRC in conjunction with federal and state privacy commissions, this model might be applied to other medical registries. We also propose that the NHMRC acts as an accrediting authority for institutions maintaining medical registries. This would ensure that the institutions comply with privacy legislation, maintain independence from the agencies that directly manage participating patients’ healthcare, and have the personnel, facilities and funding to maintain the registry and achieve its purpose. Institutions could be encouraged to seek accreditation by linking it to ongoing funding for registries. Further, a centralised HREC with scientific, ethical and legal expertise might be better able than local HRECs to ensure that registries can achieve their public health aims while maintaining patient privacy. Such a centralised committee should include patient advocates, as well as experts in epidemiology, ethics and privacy law. It could also provide guidance to local HRECs, if current legislation requires that they make their own determination, to avoid unnecessary duplication of review processes. Good registry governance involves developing a structure that includes stakeholders in management of institutions that analyse personal medical information; has a management independent of the institutions that provide healthcare; provides a research environment that maximises scientific benefit to patients and the wider community; and receives adequate funding to ensure continuity of data collection and quality assurance. We hope that developing processes to ensure good registry governance will allay public concerns about privacy and allow registries to continue to underpin programs of healthcare quality improvement and epidemiological research.

Owen D Williamson GradDipClinEpi, FRACS · Peter A Cameron MD, FACEM · John J McNeil PhD, FRACP

GPs are inadequately reinforced and poorly funded — and don’t mention the paperwork “To tell you the truth, I thought of all the damned paperwork this was going to mean in the morning,” said United States General Walter Bedell Smith, recalling the signing of the armistice that ended World War II (New York Times, 8 May 1965). He might have been describing a typical afternoon in general practice. I timed myself one day: a fifth of the 2 hours seeing seven patients had been spent in skirmishes with paperwork. Soldiers fight, surgeons operate, and physicians treat — but GPs? We practise consultatio interruptus (courtesy M Van Der Weyden, MJA Editor). Illustrator: Futcher. First appeared in Australian Doctor, 2002. Paperwork is an occupational hazard for GPs. One GP counted a barrage of 1574 individual communications monthly.1 In cold cash terms, the Productivity Commission found that GPs’ administrative costs from government programs in 2001–02 were an estimated 5% of GPs’ total income in the base case (ie, $13 100 annually for a GP working at least one day a week).2 Putative financial incentives for GPs to provide quality care, such as vocational registration, the Practice Incentives Program (PIP), and Enhanced Primary Care (EPC) Medicare items, accounted for over three-quarters of these costs. The report also acknowledged the stress and frustration experienced by GPs in filling out forms and complying with government programs. In response to the Commission’s report, a GP Red Tape Taskforce has emerged.3 This cross-government group includes staff from the senior ranks of the departments of Health and Ageing and Veterans’ Affairs, Centrelink and the Health Insurance Commission. After consulting GPs, GP groups, consumers and other stakeholders, a draft of possible responses was released in October last year. These included streamlining the government’s information requirements, enhancing GP use of information technology, simplifying programs such as PIP, and minimising administrative costs.3 Discussions with GP groups since then have focused mostly on reworking PIP and EPC items. Predictably, actual reform is yet to materialise. Furthermore, within a year of the Taskforce becoming operational, the government announced its Medicare Plus package, which included tying allied healthcare services access to the EPC program.4 While laudable in its intent, it promised yet another salvo of red tape for GPs. Countermeasures raised since by GP groups will diminish this,5 but it remains an inherently flawed initiative. This war on paper is allied to major themes in the 2004 MJA General Practice issue: general practice funding and workforce pressures. Are fragmented government payments in a fee-for-service system really the way to go? Data furnished by Britt et al (page 100) have implications for current negotiations on restructuring Medicare items. We also asked our Dutch (Van Weel, page 110), British (Weller and Maynard, page 109), Canadian (Martin and Hogg, page 111), American (Green, page 113) and New Zealand (Malcolm, page 106) colleagues to tell us how they fared with funding. The only constant in their replies is that of change, and change can be difficult. Nor is it often well evaluated, say Van Weel and Del Mar (page 98), marshalling the evidence for various payment systems. It is also clear that most of the countries featured in this issue favour deploying capitation (lump sum payment per patient on the GP’s “list”) to pay their GPs. As for workforce pressures, they’re unlikely to improve in the near future (Charles et al, page 85). Some rural communities continue to favour doctors more than other healthcare services (Smith et al, page 91). So find out how a few rural GPs successfully outflanked their workforce problems (Joyner et al, page 96). This issue doesn’t neglect clinical problems — for example: why we shouldn’t panic about avian influenza (Isaacs et al, page 62); what we learnt in the aftermath of Implanon (Wenck and Johnston, page 117; Nisselle, page 64); who should eat which fish (Bambrick and Kjellström, page 61); what dilemmas GPs face in diagnosing and treating heart failure (Phillips et al, page 78); where the luxury of on-site psychologists seemed to benefit patients (Vines et al, page 74); how chronically ill patients like their GPs and their practices (Infante et al, page 74); how GPs can realistically tackle respiratory disease (Beilby et al, page 67) and childhood obesity (Wake and McCallum, page 82). In this issue, we have attempted to enter the fray of real general practice. The campaign against red tape aims to free GPs for what most of us really want to work at — patient care. The battle against red tape is part of the healthcare war.

Mabel Chew MB BS(Hons), FRACGP, FAChPM

Risks to the fetus make it imperative that revised guidelines for fish consumption are clear and reach those most likely to be affected Headlines such as “Mercury warning for children, pregnant women” and “Danger of too much fish” appeared in March throughout Australian newspapers. The media blitz was triggered by the release of revised advice from Food Standards Australia New Zealand (FSANZ) on health risks associated with consuming fish with high methylmercury (MeHg) content (Box).1 The warnings come after a Food and Agriculture Organisation of the United Nations/World Health Organization Expert Committee halved the “provisional tolerable weekly intake” of MeHg in pregnancy from 3.3 µg to 1.6 µg per kilogram bodyweight to protect fetal development.2 Fetal neurotoxicity of MeHg was discovered in the 1960s in Japan. It was named “fetal Minamata disease” after 25 cases of cerebral palsy were found in newborns whose mothers had high levels of MeHg exposure from eating fish contaminated by industrial pollution,3 while the expected number of cases in that population was less than one. Subsequent cohort studies following children from birth to 14 years in New Zealand4 and in the Faeroe Islands5 reported associations between maternal MeHg exposure from fish consumed during pregnancy and deficits in psychological performance or in neurophysiological testing. One prospective study in the Seychelles did not find such effects.6 The Minamata case and subsequent studies indicate that there may be a shift to the left in IQ distribution as a result of excessive MeHg exposure from fish, even at levels too low to produce overt mental retardation. However, a robust debate is continuing about the toxic level of exposure and the “safety margin” required to protect the fetus. The potential risk to children in Australia needs to be carefully considered. The new advice from FSANZ is welcome, as some commonly consumed ocean fish (such as shark) often have natural MeHg concentrations sufficient to cause high weekly exposures. Interestingly, no recommendation was made for tuna. Although canned tuna is usually sourced from smaller, younger fish and is relatively low in mercury, some tuna (albacore, bluefin) has higher concentrations. The United States Environmental Protection Agency advises vulnerable groups against consuming any fish with high mercury content.7 Fish is well established as a “healthy” food. Evidence for cardiovascular benefits from regular fish consumption emerged in the 1990s, as low rates of cardiovascular disease were found in populations with high levels of fish consumption. A number of studies indicate that omega-3 fatty acids reduce cardiovascular risk by improving lipid profiles, inhibiting atherosclerotic plaque, improving arrhythmia, improving vascular function, and reducing damage from ischaemia.8 Curiously, one study reported that high levels of MeHg exposure from fish increased the incidence of myocardial infarction.9 We are therefore faced with the difficult public health challenge of avoiding the health risks from MeHg intake in fish in vulnerable groups while taking advantage of the health benefits of fish consumption. The National Heart Foundation recommends fish be consumed at least twice a week, consistent with advice from FSANZ for most kinds of fish, but this is two to four times the latest recommendations for consumption of fish containing high levels of mercury. While some species of fish have high levels of MeHg, others, such as salmon and hake, have relatively low levels. Expecting consumers to change their understanding that “fish is good” to “some fish are good, sometimes”, and “some fish are not so good, sometimes” introduces a level of complexity into consumer health education that has rarely been seen. Parallels might be drawn with fats and oils, with important shifts in understandings from “all fats are bad” to “some fats are good”, or with alcohol consumption, where some patterns of moderate drinking might be more beneficial to health than abstinence.10 Patterns of fish consumption are highly variable, so ensuring advice reaches those most at risk is essential. For example, shark is frequently unintentional “by-catch”, often used in cheaper meals such as fish and chips and fishcakes, which are consumed fairly regularly by some groups. People more likely to rely on these products may also be less aware of, and less able to respond to, the health advice from FSANZ. While some relatively expensive fish are also high in mercury (swordfish, orange roughy), these are perhaps less likely to form a regular part of the diet. Mercury has a half-life of about 9 weeks, so that women who stop all consumption of fish on becoming pregnant may still be exposing their fetuses to high levels of mercury well into pregnancy. Therefore, we suggest that all healthcare professionals make women of child-bearing age aware of the revised FSANZ recommendations and the potential risks to the developing fetus associated with even moderate consumption of some types of fish during pregnancy. Standards of fish nomenclature should also be developed and enforced to reduce confusion and to ensure consumers are getting what they expect. Further, epidemiological research on actual levels of exposure and the efficacy of the FSANZ health advice is much needed. Revised Australian recommendations for fish consumption* One serve per week (no other fish that week)* One serve per fortnight (no other fish that fortnight)* Two or three serves per week Pregnant women, women intending to become pregnant, and children (up to 6 years) Orange roughy (sea perch), catfish OR Shark (flake), billfish (swordfish, broadbill, marlin) OR Any fish or seafood not listed to the left Rest of population Shark (flake), billfish (swordfish, broadbill, marlin) OR OR Any fish or seafood not listed to the left * Serving size = 150 g for adults and older children, 75 g for children aged up to 6 years.1

Hilary J Bambrick PhD · Tord E Kjellström MEng (Stockholm), MedDr (Stockholm)

To focus solely on reducing error may inadvertently reduce the quality of care In this issue of the Journal, Wenck and Johnston (page 117) describe the response of a medical indemnity insurer to the potential for claims associated with the contraceptive implant Implanon (Organon).1 The article stimulates reflection on whether the recent increased emphasis on risk management has been at the expense of quality assurance. The “quality movement” began in Australia over 30 years ago. The 1970s and 1980s saw the development of hospital accreditation through the Australian Council of Hospital Standards (now the Australian Council of Health Care Standards [ACHS], www.achs.org.au) and drove the system of credentialling medical staff in hospitals and delineating their clinical privileges that has become the norm. Accreditation of general practices resulted largely from the Australian government’s decision in the late 1990s to tie various government general-practice payments to accreditation. The “safety movement” developed more recently, catalysed in part in Australia by the 1995 report in this Journal of the Quality in Australian Health Care Study,2 and internationally by the report of the Bristol Inquiry3 and the US Institute of Medicine’s article To err is human.4 However, the increased momentum of the safety movement brings with it the risk that “risk management” (avoiding error) will overshadow “quality assurance” (enhancing quality). Further, Wenck and Johnston’s report raises the question of whether the prudential risk management outlined simply imposed financial disincentives to the continued use of Implanon, and increased funding for potential future claims. Or did it stimulate reduced error — clinical risk management? Recently, concern at the escalating cost of public liability insurance in general, and medical indemnity insurance in particular, has stimulated: A wave of tort law reform across Australia. An early reform that directly affected medical accident compensation, and hence medical indemnity costs, was the New South Wales Health Care Liability Act (2001). Reform of the medical indemnity industry. This culminated in Federal Parliament passing the Medical Indemnity (Prudential Supervision and Products Standards) Act (2003) and a number of subsequent bills. Over $300 million in federal subsidies for medical indemnity insurance premiums (the “Premium Support Scheme”) and medical negligence claims (the “High Claims” and “Exceptional Claims” schemes). Over $300 million in federal funding for the UMP (United Medical Protection) Support Scheme, which replaced the IBNRs (“Incurred but not reported” liabilities) Levy Scheme announced in 2002; the Commonwealth will now directly subsidise three-quarters of the IBNRs of doctors who were members of UMP at 30 June 2000. Now that medical indemnity is not directly provided by the medical defence organisations (MDOs), but by the subsidiary insurance companies they registered (“captive” insurers), the quid pro quo demanded by Government for the $600 million “rescue” injection of subsidies was: that the parent MDO or its subsidiary medical indemnity insurer provide enhanced programs of clinical risk management for their clients and that those clients participate in the programs offered, and that the medical indemnity insurers practise much higher standards of prudential risk management than did their MDO parents in the past. (Prudential risk management refers to how insurers set premiums and manage their reserves and business risk to ensure they remain solvent and able to meet liabilities as and when they arise.) In this process, the two meanings of the phrase “risk management” — the prudential risk management of the insurer, and the clinical/medicolegal risk-management services they offer those who are insured — became blurred. The article by Wenck and Johnston highlights the similarities and differences between these two forms of risk management. Prudential risk management can have perverse effects on clinical practice. For example, from around 1990, the MDOs moved away from “mutual” subscriptions (all doctors paid the same) to “differential” subscriptions (higher-risk disciplines paid higher rates). One result was that general practitioner and specialist obstetricians who practised low-volume obstetrics found a powerful reason to cease midwifery: the extra cost of obstetric indemnity far exceeded the income they derived from obstetric work. There were other factors as well, but the number of doctors for whose obstetric services rebates were claimed through Medicare dropped by 29% between 1989 and 1995.5 The sudden spate of claims arising from the use of the implantable contraceptive Implanon saw the MDOs respond in different ways. Prudentially, they needed to ensure that Implanon claims were properly funded. Clinically, they wanted to reduce the number of such claims by encouraging safe use. Some MDOs chose to maintain the status quo — perhaps relying on media reports either to deter doctors from using Implanon or to ensure they reviewed their clinical techniques. Other MDOs, such as MDA National and UMP, moved coverage for matters arising from Implanon use into the more costly “procedural general practice” category of insurance. The latter approach would predictably lead to most non-procedural GPs stopping use of Implanon in their clinical practice. Who would pay up to $10 000 more per year for insurance to cover a procedure they might perform 20–30 times a year for a fee of less than $30 per service? A third approach was adopted by the Medical Defence Association of Victoria (MDAV) in July 2003,6 demonstrating that risk management by an MDO can be vigorous without perversely affecting clinical services. GPs who used Implanon were advised that they might be asked to pay an excess of $5000 if they were unable to demonstrate adequate training and technique should an Implanon claim be brought against them. There was no fixed economic deterrent to using Implanon, but there was an incentive to “risk manage” clinically to avoid the $5000 excess. After monitoring claims in the ensuing period, MDAV announced in May 2004 that the excess would no longer be applied.7 Similarly, United Medical Protection announced on 21 May 2004 that Implanon insertion would revert to being covered in the non-procedural general practice category of insurance, but with ongoing conditions. To quote from UMP’s media release: It will be a condition of cover that members agree to adhere to risk management guidelines based upon the RACGP’s [Royal Australian College of General Practitioners’] guidelines . . . Members using Implanon will be required to undergo a training session in patient selection and counseling and Implanon insertion and removal techniques arranged by the manufacturer Organon. In addition, members will need to perform the first six insertions under the supervision of a medical practitioner experienced in Implanon insertion.8 MDA National had earlier announced, on 25 February 2004, that, with effect from the insurance year commencing 1 July 2004, Implanon cover would be available again in the non-procedural category — subject to adherence to risk-management guidelines.9 Some MDOs now offer premium discounts to members who satisfy specified standards for risk management in their practices or attend risk-management educational seminars and similar activities. I recently reviewed well over a thousand of the applications for MDAV’s RISQ (Risk Identification for Sustaining Quality) program. Some applicants supported the program strongly, saying the application process stimulated a major review of their practice’s policies. Others thought the discount was not worth the time required to complete the application. In my opinion, this latter group missed the point. The premium discount is a relatively minor immediate incentive when compared with the ameliorative effect that effective risk management may have on claims frequency, and hence the potential impact on their future premiums. Further, one member made another, poignant point: I know this is a very worthwhile exercise, but it’s had the effect of making me view every patient as a potential plaintiff. While his comment strikes an empathic chord, he also missed the point. Medical practice requires quality assurance and risk management. It also requires organisational governance — management of personnel, financial efficiency, systems efficiency, and so on — as much as clinical governance. All the various components of practice governance need to be managed. Focusing on any one component to the detriment of the others leads to a mismanaged practice. It is not a choice between risk management or quality assurance, we need both — less error is part of better quality. Saxe’s poem about the blind men and the elephant is apposite.10 Six blind men argue vigorously about the nature of the beast of which each is holding one part — the tusk, the trunk, an ear, a leg, and so on. The poem concludes: So oft in theologic wars, The disputants, I ween, Rail on in utter ignorance Of what each other mean, And prate about an Elephant Not one of them has seen! The elephant is clinical governance (continuous quality improvement). It has many parts. All must be subject to equal focus.

Paul Nisselle AM, FRACGP

We need evidence that can underpin fundamental change General practice and the rest of the primary care team, rather than specialist or hospital care, deliver the lion’s share (90%) of healthcare.1 They also provide the anticipatory care necessary for early and better management of the chronic diseases that characterise modern industrial societies. A strong, self-reliant primary care workforce increases quality as well as cost-effectiveness.2 Thus, the way a country remunerates its primary care workforce is vital. This is a good time to debate the options in Australia — a federal election year in which healthcare is likely to be a central issue. Changes to the administrative system can have enormous implications for primary care. So far, planned changes in Australia have been tentative, consisting of “add-on” improvements such as payments to general practitioners (GPs) in addition to the traditional fee-for-service arrangements. These include Practice Incentive Payments (PIPs), which pay GPs who can demonstrate using set protocols for managing some chronic diseases (eg, asthma, diabetes), and Service Incentive Payments (SIPs), which are specific payments for certain services such as mental health care and vaccination. The complexity of administering these programs has prompted complaints from GPs, and in response a Red Tape Task Force has been convened.3 Healthcare systems differ hugely from country to country, as we see from the articles that follow. Reimbursement is perhaps its most emotionally highly charged aspect and, however contentious an issue, some system has to be chosen. Strong primary-healthcare-led systems like those in the United Kingdom4 (page 109) and The Netherlands5 (page 110) use capitation systems as the basis of paying GPs: they contract to assume the obligation to provide care for a group of patients, and their financial rewards are independent of the actual service and care delivered. In the former Yugoslavia, with its socialist origins, remuneration took the form of a salary, accompanied by planning (and restriction in the number) of GPs. A more market-driven way of paying GPs is for GPs to “deliver” before payment (fee-for-service), and in competition with each other, as in Australia and the United States (page 113).6 Canada (page 111) has opted for a combination of methods,7 and New Zealand (page 106) is experimenting with a variety of interesting models in quick succession.8 Fee-for-serviceFinancial incentives have a direct influence on GPs’ behaviour. For example, in Belgium, 46% of GP–patient encounters are home visits,9 whereas in The Netherlands this is only a small proportion of GPs’ clinical activities. The population health status and infrastructures of the two countries hardly differ, so the difference can only be explained by incentives: under Belgian fee-for-service, a home visit is chargeable. It also strengthens patient satisfaction with the GP in a competitive environment. On the other hand, the Dutch GP receives a capitation fee irrespective of whether the patient is seen at home or at the practice (or not at all). One problem with fee-for-service payment is that the way GPs are funded is confounded by other innovations that Australia should be considering, such as patient registration. Although theoretically this could be separated from how doctors are paid (capitation, for example), nowhere does this occur. A second problem is that fee-for-service can be inflexible about who is remunerated. This has held back the proper utilisation of nursing in general practice in Australia simply because nearly all services in general practice are ineligible for a Medicare rebate if provided by nurses, even though for many services (eg, preventive10 or protocol-driven chronic care11) nurses may be better suited. A third problem is the need for a business mind with fee-for-service general practice. Many doctors want to practise unencumbered by a “small shopkeeper” role. One consequence was the evolution in the 1980s of “entrepreneurial practices” (those whose owners were more interested in making a profit than serving their communities). These offered greater flexibility for the increasing numbers of doctors who, wanting “just to practise medicine” and happy to abdicate their commercial role, flocked there. “Perverse incentives” reward some clinical activities better than more valuable ones.12 For example, a GP who delivers many short consultations will earn more than one who has fewer and longer consultations — even though longer consultations are associated with better attention to preventive healthcare and psychosocial problems.13 Attempts to address this by providing less reliance on fee-for-service (to the fury of the Australian Medical Association)14 with additional alternative payment systems (so-called blended payments) such as PIPs and SIPs — funded by what might have otherwise gone to increased fees — are probably only partly successful. It is too early to tell if the complexity of administering them is any better than the fee restrictions that arose to discourage entrepreneurial practices. Do we need more fundamental reforms of the GP system? What are the alternatives? CapitationCapitation payment and its associated patient registration (the “list”) feels like clinical freedom for many GPs in the UK and The Netherlands: the GP accepts an obligation to provide care for the patients on the list and do what is in their best interests. It has offered GPs a level platform to counter medicalisation, overdiagnosis, over-referral and spurious prescribing, without the tilt of having to please the patient (something usually miscalculated in any case15). But there are disadvantages. A capitation system can be a haven for laziness, because payment comes irrespective of the quantity (let alone the quality) of care. GP-initiated activities — like anticipatory (chronic disease management) and preventive care — are particularly sensitive to this. Perhaps this is the basis for the reforms currently under way in the UK NHS.16 Disciplinary hearings against GPs in the UK and The Netherlands are, to a large degree, occupied with GP failure to provide enough care — in particular, failure to visit patients in a (perceived) emergency at home. In Australia, the focus of disciplinary hearings is on overservicing. The issue for capitation systems is deciding what is enough care; for fee-for-service, deciding what is too much. The solutionBlended payments (a mixture of fee-for-service and payments for good practice) sound sensible (the best of both worlds), but there is little evidence17 to reassure us we might not get the worst of both: entrepreneurial GPs learning which mix of activities yields the highest earnings, and government reacting by over-regulating the system to avoid this. GPs are at the forefront of evidence-based patient care. It would be good if GPs’ financing systems were established by good evidence, but little exists regarding the effects on service of different payment systems (Box). Thus, we need to trial different systems, not simply enact the latest political ideology. The current flux in the Australian healthcare system is surely an ideal environment for such experiments. Possible alternatives would be payment systems that allow for patient registration, that include the option of salaries for doctors uninterested in running a business, and that encourage doctors to collect and analyse clinical data about the services they provide. There is no doubt that such trials would be hard to conduct politically,17 and perhaps randomised controlled trials would have to give way to the pragmatics of quasi-experiments. But we need changes to the system that are fundamental, rather than the lean-to sheds propping Australia’s current archaic system. The evidence base for different primary care payment systems The best evidence comes from a Cochrane review.18 This is in need of update (last search date was 1997). The review compared four payment systems (fee-for-service, salary, capitation, and mixed), and accepted studies that were randomised controlled trials (RCTs) or controlled before–after (CBA) studies if there were at least two measurements before and two after the intervention (nine studies were excluded for failing this test). Two RCTs (total of 98 doctors) and two CBAs (216 doctors) were included: all had potential biases in their methods. Compared with capitation, fee-for-service was associated with more services, tests and referrals to specialists, but fewer referrals to hospital. Compared with salaried payment, fee-for-service was associated with more services and more continuity of care, but less patient satisfaction with access to care. A more recent narrative review (conducted at an international conference on the subject) reached the same conclusions.19

Chris Van Weel PhD, FRCGP · Chris B Del Mar MD, FRACGP

On July 4, exactly 90 years ago, The Medical Journal of Australia began its life “as the official organ of the British Medical Association in Australia”. Its purpose was clear — “to record the progress of scientific medicine, and to assist in rendering the practice of medicine in all its branches of the greatest benefit to the people of Australia”.1 In that first issue, the president of the Victorian branch of the British Medical Association warmly welcomed the Journal, noting that it symbolised “the intimate union of all the branches of the British Medical Association in Australia”, and that it would “continue every week to indicate and advocate the common aims, interests, and ideals of the profession”. He closed by wishing that the Journal prospere, procede et regna2 — “proceed prosperously and reign”! This bridging between the readers and the profession is the stuff of the Journal. The following 90 years have seen the formation of the Australian Medical Association in 1962,3 and, with the advent of the AMA Gazette in 1968, the disappearance of Federal and Branch news in the Journal. In the late 1980s, after nearly 60 years of living the Australian dream of being an owner/occupier, the Journal’s publisher — the Australasian Medical Publishing Company (AMPCo) — sold its Sydney premises to finance the AMA’s move to Canberra. This was the culmination of the Journal’s Sturm und Drang decade, with the destabilising turnover of editors — six in all — and tensions caused by AMPCo’s financial difficulties. However, after 90 years, the Journal’s purpose remains clear — to “be the recognised forum for information and commentary on all aspects of health care in Australia” through “original peer-reviewed clinical research of the highest standard”, “high level continuing medical education”, and “commentary and informed debate on standards of clinical practice, ethics, social, legal and other issues related to health care in Australia”.4 In this 90th anniversary issue, Gregory (page 9) surveys the “clinical research of the highest standard” published by the Journal during this time.5 Its ongoing commitment to “commentary and informed debate on standards of clinical practice” is exemplified by the Quality in Australian Health Care Study6 and the study of adverse events in Australian general practice,7 both of which played a part in the lead-up to establishing the Australian Council for Safety and Quality in Health Care. The Journal’s role as a forum for “ethics, social, legal and other issues” is reflected in our reports on end-of-life decisions,8,9 the health of asylum seekers in detention,10,11 and in our commitment to Indigenous health.12 Finally, pragmatic links to the world of medical research and to specialist and general practice were pursued through networking and the Journal’s Content Review Committee. A cursory review of the Journal’s progress over the past 90 years will readily identify broad changes which have come to pass. There has been a noticeable decline in the number of clinical studies, case reports and the more leisurely reviews, with a concomitant increase in studies of healthcare interventions and health system performance, as well as those on adverse lifestyles, substance misuse, mental illness and, more recently, consumer concerns. With the rise of evidence-based medicine came a barrage of evidence-based guidelines and further delineation of levels of evidence. The design and reporting of research itself adopted more rigorous formats, such as controlled trials, systematic reviews and structured abstracts. Significantly, the number of authors per article continues to multiply,13 and the international trend now is for authorship to involve a team of doctors, other healthcare professionals and scientists. Correspondingly, the number of Journal editors has also increased as the number of submissions continues to rise.13 In 2003 we received a record 917 submissions, compared with 856 in 2001 and 741 in 1999. On the downside, the blurring of the boundaries between commerce and research has spawned a culture of suspicion, particularly for research supported by pharmaceutical companies.14 It is interesting to note that all Journal articles are now accompanied by an item noticeably absent a decade ago — the competing interests statement. The Journal’s policy of safeguarding the integrity of research by exploring potential conflicts of interest of contributors and reviewers is detailed by Chew.15 What does the future hold? Just as Gutenberg’s printing press saw the demise of the monastic monopoly of manuscript production, electronic technology has changed both the essence of publishing itself, and ease of access to the latest research. The Medical Journal of Australia, like most other medical journals, simultaneously releases the electronic (eMJA) with the print Journal, and uses rapid online publication for selected articles. Future electronic developments are also anticipated. There are those who promote the notion that peer review and editing are things of the past.16 They believe science should simply be posted on the Internet, thus letting the world judge its quality. However, an editor’s first responsibility is to the readers, and they have signalled that they are too busy to separate the wheat from the chaff.17 They prefer that to be the function of quality filters — the editors, peer reviewers and editorial staff who ensure the clarity, brevity and non-exclusive language of the final product. This bridging between the readers and the profession is the stuff of the Journal. Despite enthusiastic predictions of its demise,18 the printed Journal will live on for some time. There is something reassuring about knowing where a journal’s contents will be revealed, its portability from bed to breakfast table, and the feel of something physical, that binds readers to the paper Journal.19 In any event, whatever changes the future may bring, as long as the Journal continues to add value to its core content of original articles, editorials, reviews and informed debate on contemporaneous healthcare issues in Australia, The Medical Journal of Australia will most certainly prospere, procede et regna.

Martin B Van Der Weyden MD, FRACP, FRCPA

“If in doubt, disclose” — Committee on Publication Ethics1 Under full glare of the media spotlight in February this year, the editor of The Lancet, Richard Horton, partially retracted an article published 6 years before.2,3 This act was triggered by allegations of research misconduct in the study, taken to The Lancet by a Sunday Times journalist.4 The Lancet’s investigations5 and the events that ensued involved the article’s authors (doctors at London’s Royal Free and University College Medical School), the institution’s ethics committee, the General Medical Council, the British Parliament, and even the Prime Minister, Tony Blair. Why the fuss? In 1998, this research report implied a link between autism, bowel disease and the combined measles– mumps–rubella (MMR) vaccine.3 A storm of controversy erupted, and MMR vaccination rates in England fell from 92% of children reaching the age of two in 1996/97 to 82% in 2002/03.6 Confirmed cases of measles rose from 112 in 1996 to 442 in 2003. When the allegations of misconduct were probed this year, it was found that, at the time the article was submitted and published, its lead author and senior investigator, Dr Andrew Wakefield, had not disclosed that he had been commissioned by the Legal Aid Board (for the sum of £55,000) to determine if there was evidence to support legal action by parents of children allegedly harmed by the MMR vaccine. Some of these children were also in Wakefield’s Lancet study. This led to a partial retraction of the article by 10 of its original 13 authors, but not by Wakefield.7 Richard Horton remarked, “If we had known the conflict of interest Dr Wakefield had in this work I think that would have strongly affected the peer reviewers about [its] credibility . . . in my judgement, it would have been rejected”.2 The Medical Journal of Australia has not had such sensational experiences (yet!). Conflict of interest in publication was first raised in a position statement by the International Committee of Medical Journal Editors, published in 1993.8 Our first conflict of interest statement appeared in the late 1990s, but declaring conflict of interest was deemed by many then to be optional — an exercise in political correctness. So, except in extreme situations, does conflict of interest really matter? Unfortunately it does. It is a principle long enshrined in the conduct of scientific research.9 Moreover, we can no longer ignore the growing body of evidence that conflict of interest can bias research outcomes. Systematic reviews have shown that results of sponsored studies are more likely to favour the sponsor when it is a pharmaceutical company,10 and industry-sponsored studies are not only associated with pro-industry conclusions, but with restrictions on publication and data sharing.11 As more research is funded by non-academic sources, we cannot ignore the potential for bias to affect its outcomes.12 Neither can we ignore an increasingly educated, involved 21st-century Western society that is calling for greater accountability in health research. What conflict of interest is notConflict of interest is not always present, and may be potential rather than actual. Such dual interests are better termed “competing” rather than “conflicting” interests (eg, commitment to a patient’s welfare and to a research project). Having a conflict of interest is, in itself, not wrong, and may be unavoidable. Disclosing competing interests should not be seen as an admission of wrongdoing, but as promoting transparency in the public record. What conflict of interest is“Financial or personal relationships that inappropriately influence (bias) . . . actions [of an author (or the author’s institution), reviewer, or editor] . . . The potential for conflict of interest can exist whether or not an individual believes that the relationship affects his or her scientific judgment”.13 Anything, be it personal, financial, academic, religious, or political, “which, when revealed later, would make a reasonable reader feel misled or deceived”.1 Current MJA policyAuthorsAll authors are required to provide a disclosure statement (Box). Funding sources are to be acknowledged, together with any role they played in study design, data collection, data analysis, interpretation of the data, their reporting and publication. A study may not be published if its sponsor asserts the right to control publication.13 We publish competing interests statements for all research, viewpoint and review articles, and, where such interests are declared to exist, for editorials and letters to the Editor. ReviewersPeer review is a useful but imperfect tool that we can refine by seeking to clarify potential biases: We do not ask those from the same institution(s) as the author(s) to review an article. We now ask all reviewers to provide a disclosure statement similar to the one authors provide (Box). Reviewers who disclose competing interests are not necessarily disqualified. Their reviews will be carefully considered by the editors, bearing their potential biases in mind, and in conjunction with comments from other reviewers. EditorsEditors commission articles, assess submitted articles, and ultimately decide their fate. Thus, MJA editors with competing interests relating to an article will exclude themselves from taking primary responsibility for it. ConclusionOur aim is not to exclude anyone with a potential conflict of interest from publishing or reviewing — to do so would disqualify virtually everyone (including editors). Conflicts of interest may occasionally be too extreme to allow publication of the article or involvement of someone in the decision-making process. However, our ultimate goal in advocating disclosure is to promote transparency, reduce bias, and maintain public trust in what we publish. Let the reader to be the judge! MJA disclosure statement for authors and reviewers (A) Authors are asked to indicate Yes or No to questions about affiliations with manufacturers of products mentioned in the article or of competing products: Ownership of stock or stock options or other financial instruments of companies whose products are mentioned in the article or who manufacture competing products (does not include mutual fund ownership) Ongoing paid consultancy with company or a competitor (actual or within the last 2 years) Employment with company or competitor (actual or within the last 2 years) Honorarium or other compensation for writing the article or for participating in the development of the article Honorarium or other compensation for conducting research related to material contained in the article Speaker fees and/or educational grants Travel assistance to attend meetings. (B) Authors are asked to provide details where the answer to any of the above questions is “yes”. (C) Authors are asked to declare any other (non-financial) competing interests.

Mabel Chew MB BS(Hons), FRACGP, FAChPM