Editorials

Updated guidelines recommend improving access to specialised stroke units and thrombolytic therapy, and the rapid assessment of patients with transient ischaemic attacks for stroke risk Stroke, with its high incidence and serious consequences, is one of the foremost health challenges for Australia and globally. Although stroke rates appear to be decreasing,1 population ageing will intensify the impact of this disease and the need for effective prevention and management strategies.2 Stroke is a complex disease with a range of causes, manifestations, outcomes and treatment approaches, but is too common and costly to be left as the province of a single clinical discipline, neurology. As the therapeutic time window in which to rescue or “protect” the brain from ischaemic damage is extremely short, there is a need for good systems of communication and responsive, expert team care, both in the community and in hospitals, to ensure safe and effective delivery of interventions early after onset and in subsequent phases of acute stroke. Indeed, the single most important therapeutic advance in stroke medicine is arguably the recognition that well coordinated, multidisciplinary care in the form of stroke care units (SCUs) can significantly improve the chances of recovery from stroke. So how can we improve patient access to expert SCU care and therapies that provide the best opportunity for a favourable outcome? A popular approach to improving the quality of health care delivery is the development of clinical guidelines. A good example is the Clinical guidelines for acute stroke management,3 produced by the National Stroke Foundation in 2007. These guidelines update a document published in 2003 and are available from the Foundation’s website (http://www.strokefoundation.com.au). They aim to provide clinicians and patients with all the key information needed to make the best decisions about the benefits and risks of treatment, through the use of systematically developed statements, recommendations and algorithms based on supporting grades of evidence. In addition, the document may provide a degree of medicolegal protection for the treating clinician, and political leverage for developing services both locally and generally. So what can we learn from these stroke guidelines, developed with specific relevance to the local context? The guidelines followed the rigorous standards of development and production set down by the National Health and Medical Research Council (NHMRC) and cover a wide range of clinically relevant topics in a simple, accessible format. The multidisciplinary expert working group that developed the guidelines is to be commended for seeking a wide range of external advice and comment, for incorporating consumer values and preferences in a unique additional grading of the recommendations, and for making sensible judgements for nearly half of the 148 recommendations where high-level randomised evidence was lacking — not surprisingly, mainly in the areas of supportive care and early rehabilitation. A key recommendation emphasised in the updated guidelines is the need for rapid assessment and management by specialists of patients who present not only with established features of an acute stroke but also with a transient ischaemic attack (TIA). TIA has generally been considered more “benign” than stroke and akin to migraine, because of its brevity and reversibility. However, recent studies show that the risk of recurrent stroke early after a TIA is similar to the risk after mild ischaemic stroke: about 10% in the first week and 20% by 3 months.4,5 Thereafter, the annual risks of stroke and myocardial infarction are around 5% and 2%–3%, respectively.6 Given that 30%–40% of patients with ischaemic stroke have had a preceding TIA or minor stroke,7,8 and that evidence is accumulating of the benefits of early interventions such as antiplatelet therapy, blood pressure-lowering therapy and carotid endarterectomy, TIAs provide an important opportunity for stroke prevention.8,9 However, the diagnosis of true stroke-related “focal” TIA is often challenging as it generally relies on patients recalling symptoms from a time when they were possibly impaired. As outlined in the stroke guidelines, a simple measure — the ABCD2 tool (a 7-point score calculated from age, blood pressure, clinical features, duration of symptoms, and diabetes status [Box])10 — can help clinicians, including those in primary care, with patient triage. Those at “high” risk of subsequent stroke have the option of admission to hospital to expedite investigations and management, while those with “low” risk could be followed up quickly in specialist outpatient clinics, where available. Early assessment offers further benefits for patients, through establishing correct diagnoses for TIA-mimics, such as syncope, seizure, anxiety–hyperventilation and vestibular disturbance, allowing specific interventions and avoidance of unnecessary, costly and sometimes risky avenues of management. For all these reasons, and as suggested by Kehdi et al in this issue of the Journal,11 early in-hospital management of patients with TIA may improve outcomes. However, there are major implications for resources and service configuration if rapid expert neurological assessment is to be provided to patients who present to emergency departments with TIA as well as those with stroke. Importantly, the stroke guidelines also included cost-effectiveness analyses of the currently available, clinically proven interventions for prevention and treatment of stroke. Most noteworthy was the finding that substantial economic and health-related benefits could be derived from improved patient access to high-quality stroke services through a modest additional investment of resources. Given that a substantial proportion of the Australian population lives in rural or remote areas, where there are no SCUs or other specialty services, the guidelines recommend the creation of networks linking smaller regional and rural centres to larger centres with SCUs. Furthermore, as the availability of SCUs varies widely even in urban settings, the guidelines recommend that ambulances preferentially transfer patients with suspected stroke to hospitals with SCUs. This recommendation is controversial. Recent audits12 and experience indicate that not all SCUs are resourced appropriately to allow safe and effective use of the thrombolytic agent, recombinant tissue plasminogen activator (rtPA), in carefully selected patients who present within the first few hours after the onset of ischaemic stroke. Given that rtPA is proven to be cost-effective, a reorganisation of services to allow ambulances to route patients directly to “active rtPA SCUs” could allow many more people to benefit from this treatment. How can the recommendations in the stroke guidelines be implemented in the real, service-challenged world, where modifying the behaviour of clinicians and providers is difficult, and clinical settings are often not conducive to change? The transfer of evidence into clinical practice has, to date, been unpredictable and often slow and haphazard for many reasons, including poor knowledge, limited therapeutic expertise, lack of time and, in particular, economic restraints. The use of guidelines can better align clinical management with evidence-based practice, but this is difficult when expertise and services are non-existent or inappropriately resourced. There is limited empirical evidence to support any specific strategy for change over another, but current data suggest that change is possible through comprehensive approaches that target different levels and settings in the health care system.13 The stroke management guidelines are a positive step. Implementation strategies, including the development of policy at the highest, central level, are now needed. A key step would be for the federal government to mandate the recommendation of the National Service Improvement Framework that all people with acute stroke receive SCU or appropriate alternative care around the country.14 Implementation of such policies would provide the best opportunity to improve the outcomes for patients with stroke and the growing population at risk of this devastating illness. ABCD2 tool for assessment of patients with transient ischaemic attack10 A. Age ≥ 60 years = 1 point. B. Blood pressure ≥ 140/90 mmHg = 1 point. C. Clinical features: unilateral weakness = 2 points, speech impairment alone = 1 point. D. Duration > 60 minutes = 2 points, 10–59 minutes = 1 point. D. Diabetes = 1 point. Total. 0–3 = low risk of stroke, 4–7 = high risk of stroke.

Craig S Anderson FRACP, PhD

Cervical cancer screening needs to take into account a partially vaccinated population and new technologies A national, well funded and organised program of screening using the conventional Pap smear has significantly reduced the incidence of and mortality from cervical cancer in Australia.1 While the program has been in place, there has been a great increase in knowledge of the pathogenesis of cervical cancer, with certain oncogenic subtypes of human papillomavirus (HPV) shown to be a necessary cause for development of this disease.2 In addition, a national program of vaccination against two of the 15 oncogenic viruses began in April 2007, and tests to detect HPV are now available. Furthermore, research showing that new technologies for screening cervical samples are superior to conventional cytology has also been published.3,4 How is the cervical screening program responding to the presence of a partially vaccinated population and these newly available tests? When the Pharmaceutical Benefits Advisory Committee assessed the value of funding HPV vaccination, it noted that the current cumulative lifetime risk of cervical cancer in Australia’s screened population is 0.78% — a substantial reduction from the estimated 2.4% risk in an unscreened population, reflecting the success of the screening program. With continued screening, this risk was predicted to further decrease to 0.38% following vaccination of 12-year-old girls, 0.43% for 14-year-old girls and 0.59% for 26-year-old women.5 The Committee further commented that there would be cost savings if vaccination were to completely replace cervical screening, but the cervical cancer lifetime risk would increase to 1.173%.5 The recommendation therefore is that screening must continue after vaccination. The screening interval and screening test for vaccinated women should be different to those for unvaccinated women and should be determined by population-based research over the next 5–10 years, as the vaccinated cohort reaches maturity. A national HPV vaccination register is being established, which will be critical for determining the appropriate screening regimen. HPV testing is already recommended and funded as a “test of cure” for follow-up of high-grade cervical disease after treatment. The Digene HPV test is used in Australia and detects any one of 13 high-risk HPV subtypes but does not identify the specific subtypes. Although some individual HPV subtyping assays are available, these are expensive and not widely used, and no serological tests for HPV are available in routine practice. Use of the HPV test is therefore limited but, given its importance, should its use be expanded for screening and management of cervical disease? There has been much discussion overseas about replacing cervical cytology tests with HPV testing for primary screening.6 Currently, there is no justification for this as HPV testing is highly sensitive but not specific. It has a limited role in women under the age of 30 years, as large studies have shown that about 25% of women in this age group test positive for the oncogenic viruses.7 The great majority of these women clear the virus naturally, usually via a cell-mediated immune response or, less often, through an antibody response. Such infected women may not show any sign of disease. It is when the virus persists that women are at greater risk of both high-grade cervical intraepithelial disease and invasive cancer. HPV testing is also not recommended before vaccination8 in women who request it but are already sexually active as the decision to proceed with vaccination will not be altered by the results of the test. HPV testing may have a greater role in the management of indeterminate abnormalities detected by cervical cytology tests. Data from large United States studies are fairly compelling in assigning a true risk of significant disease based on cervical cytology and HPV testing. The latter is more accurate than colposcopy in determining the significance of low-grade squamous intraepithelial lesions detected by cervical cytology. So-called “reflex” HPV testing in women with these findings is recommended in the US.9 Another major question for cervical cancer screening in the short term is whether image-guided liquid-based cytology samples should be used as the preferred screening test. The use of liquid-based cytology in this country has long been controversial.10 However, there is now good evidence that one of the techniques — the ThinPrep Imaging System (Hologic, Marlborough, Mass, USA) — is superior to conventional cytology.4 This technique decreases the number of unsatisfactory samples and detects more true abnormalities. There are also substantial laboratory efficiencies when using this technology, which could potentially overcome the chronic shortage of trained scientists. The increased sensitivity might allow the screening interval to be lengthened. This technique also provides a sample for HPV and other microbiological testing, and is ideal for a vaccinated population in which the number of screen-detected abnormalities will decrease. Although Australia has an enviable record in the control of cervical cancer, new knowledge and associated technologies should be incorporated into screening and management of cervical disease, as they offer real benefits. Both HPV testing and ThinPrep imaging are more expensive than conventional cytology, but they could be cost-effective if used appropriately in conjunction with a comprehensive review of the cervical screening program.

Annabelle Farnsworth FRCPA, FIAC, DipCytopath(RCPA)

Determining risk is the first step in deciding on appropriate management Osteoporosis, most simply and elegantly defined as “too little bone in the bone”, is generally the result of progressive bone loss which, for all practical purposes, starts at menopause in women and at about the age of 50 years in men. Because women have a lower bone organ density than men and then lose bone more rapidly,1 and also because women live longer, osteoporotic fractures, particularly at the hip, affect more women than men in Western countries — there are 20 000 hip fractures per year in Australia, with women outnumbering men by a ratio of two to one. The immediate cost of osteoporosis in Australia has been estimated at nearly $2 billion per year, with a further $5–6 billion in indirect costs.2 Doctors are in a difficult position when it comes to managing osteoporosis and preventing fractures. As with most disorders, they need to know the risk of an event such as fracture before reaching a treatment decision. They know that bone mineral density (BMD), measured by dual energy x-ray absorptiometry (DXA), is a major determinant of fracture risk, and they may have read that the risk goes up by a factor of 1.5–2 for every standard deviation fall in BMD3 (which is actually incorrect, as shown below), but they have no means of converting this information into absolute numbers. This is partly because of long-standing confusion between odds and risk, exemplified by the fact that the relative risks quoted in the literature3 are generally odds ratios or hazard ratios. The difference between odds and risk, well understood by professional statisticians, is not well understood by most clinicians. If 30 women out of 100 develop a fracture over a given period, the fracture risk is 30/100 or 0.30, but the fracture odds are 30/70 or 0.43 — a very different figure. At low levels of risk, say below 0.10, the difference between odds and risk is very small (one in 10 is close to one to nine) and can legitimately be ignored. However, as the risk increases, or the period over which it is calculated is extended, odds rise in a multiplicative fashion with fall in BMD, but risk does not. Odds have no upper limit, whereas risk can never rise above unity or rise by a multiplicative factor. A recent article sought to dispel this confusion by explaining the difference between fracture odds and fracture risk by reference to published data.4 A follow-up article,5 based on a prospective study carried out in Perth,6 contained a graph representing true fracture risk as a function of age and BMD in women without prevalent fracture. For those who would like to calculate the 6-year risk, the formula is: Odds = 0.025 × 1.08age > 55 × 1.49 –ve T-score Risk is then derived from odds as: odds/(1 + odds) We now wish to make this graph more readily available to doctors in Australia by reproducing it (Box). In women with any symptomatic prevalent fracture after the age of 50 years, 5 years should be added to the patient’s age because, in the above study, the effect of prevalent fracture on fracture risk was equivalent to a 5-year increase in age.5 (This, incidentally, shows the fallacy of using fracture as a substitute for densitometry in the diagnosis of osteoporosis, as is increasingly happening in Australia). Moreover, as men and women experience fractures at about the same BMD,7 it is probably safe to use the same graph to calculate approximate fracture risk in men by adding one to the T-score. Needless to say, it is for the individual clinician, in consultation with the patient, to decide the level of risk at which any particular intervention is called for. An arguable policy is to use calcium supplementation (with vitamin D if indicated) to prevent bone loss in patients at low risk, and to reserve more expensive remedies for patients at high risk in whom osteoporosis is already established, especially as the pivotal studies for these remedies have been performed in patients with T-scores of − 2 or lower. We are aware that our fracture risks are somewhat higher than those derived from the Garvan Institute algorithm8 which are in turn higher than those from the World Health Organization algorithm,9 but the former appears to underestimate the effect of age, and the latter has already been criticised as being too low.10 Only time will show which model is nearest the truth. Six-year fracture risk in women aged over 50 years without prevalent fractures

B E Christopher Nordin MD, PhD, FRACP · Richard L Prince MD, ChB, FRACP · Graeme R R Tucker BSc

Scientific evidence and the relationship between the medical profession, politics and the public are dynamic and inter-related In 1848, Rudolf Virchow asserted that “medicine is a social science, and politics nothing but medicine on a grand scale”.1 Regarded by many to be the father of modern pathology, Virchow saw clear responsibilities for doctors to engage with the broader social concerns that cause illness and harm. A century and a half later, human health faces threats ranging in scale from terrorism and climate change to the consequences of violence, substance misuse, poverty and environmental hazards that we deal with every day in our emergency departments and our clinics. On a handful of issues, such as smoking, health care professionals have been instrumental in changing public policy. But, with many ongoing social ills, is civic action a duty of modern clinicians? Following the September 11 terrorist attacks in the United States, the world’s leading medical journals expressed opposing views on this question. The editors of the New England Journal of Medicine implored doctors not to react directly to terrorism, but instead to treat injured patients, continue with medical research and ensure that the medical community is prepared for future terrorist attacks.2 In response, the Lancet’s Richard Horton argued that anyone working in the health professions is concerned with prevention as well as healing, that medicine cannot escape politics, and to reduce the burden of harm caused by violence, doctors must address how the political determines the clinical.3 Putting aside legitimate practical concerns — after all, few doctors think they have the time or skills to be effective political agents — the real question is whether or not we should nurture interest in addressing the health of communities among health care professionals, arming them with appropriate skills and promoting opportunities for engagement. If we examine the dual historical trajectories of scientific medicine and the place of professionals in society, we realise that this is not just a question of individual political or moral persuasion. Instead, it is one that depends on prevailing culture and circumstances of the time. In the 19th century, for example, doctors found professional distinction difficult to attain, largely because the scientific basis of medical practice was rudimentary and their treatments were often harmful. Public health activism was one way in which doctors could achieve status and authority. While not all doctors embraced it, public health was at least deemed to be complementary to the work of medicine.4 This changed rapidly early in the 20th century as scientific and clinical evidence evolved, and, in mastering this body of evidence, doctors became valuable to the public.5 Based on new understanding of bacteriology, germ theory and specific disease-based treatments, the biomedical model of disease triumphed. The new medical schools focused on diseases more than on people or populations, and on cures rather than on the social, behavioural and environmental forces that maintain health or produce disease. Unlike efforts to change social conditions, which were seen to be tainted by politics, advocacy and social diversity, the reductionism, objectivity and certainty of the biomedical model had great appeal. By the 1950s, the income, professional status and authority of doctors far exceeded that of public health professionals, and deep antipathies had evolved between them. In the most recent 50 years, this relationship has become less polarised, due especially to three scientific and sociological developments. The first was the birth of modern epidemiology and multivariate analysis. They demonstrated that most major illnesses were not random occurrences and that peoples’ overall health status was not only a consequence of the care they received. We now know that they are influenced by a range of social factors, including income and social status, social support networks, education and literacy, employment and working conditions, and social and physical environments.6,7 Second, business and government replaced the individual as the principal purchasers of health care, and have been increasingly interested in research that reveals disparities in health status, unequal access to treatment and variable quality of care. Managers and policymakers have challenged the view that entrenched health problems can be solved simply by more doctors, more medicines or faster discharge times. Third, fuelled by the repercussions of high-profile cases such as the Bristol Royal Infirmary8 and Bundaberg Hospital9 cases, cynicism grew about the medical profession’s ability to put aside its own interests and to self-regulate standards of performance. In light of such developments, it is no accident that doctors have been concerned with issues of professionalism. In February 2002, a transatlantic team of physicians published a Charter of Medical Professionalism, which was a bold restatement of the responsibilities of doctors as professionals — a sort of modern Hippocratic Oath.10,11 From July 2003, the American Council of Graduate Medical Education and the American Board of Medical Specialties required that all American medical and specialist training programs teach and assess “professionalism” as a core competency. The concept of professionalism rapidly gained traction, and the Charter provided a road map. It offered three fundamental principles: primacy of patient welfare, patient autonomy and social justice. The first two were uncontroversial. Social justice, however, with its implied responsibilities for public roles that redress social inequalities, was greeted with some ambivalence and much confusion, and needed clarification. With colleagues at Harvard I developed a conceptual and operational model based on our qualitative research with a range of professionals, academics, consumers and social commentators.12 Finding the label “social justice” generally unhelpful, we preferred the term “public roles”, which we defined as advocacy for and participation in improving the aspects of communities that affect the health of individual patients. We justified doctors’ public roles on the premise that doctors and the public expect discipline-based expertise to encompass all aspects of diagnosis, prevention and treatment; patients expect the medical profession to do what it can to promote their health; and doctors can be effective advocates for societal change through changes in legislation, advertising, public awareness and so on. We set reasonable limits on these obligations, based on the strength of evidence and the feasibility of doctor-promoted change. We identified three strategies for action by busy clinicians: community participation, individual political involvement, and collective advocacy through professional organisations. We made the case that individuals could choose activities — small or large — that suit their own situation and disposition. In the US the model generated considerable debate, became required reading for many medical training programs, and has been used in a variety of policy documents. In a survey of 1662 American doctors in six specialties, over 90% rated each of community participation, political involvement and collective advocacy as important roles, although fewer than half reported being involved in such activities in the previous 3 years.13 Dr John Furler and his team from the University of Melbourne Department of General Practice then explored the usefulness of the model for the Royal Australian College of General Practitioners’ policy on health inequalities. They conducted 80 interviews and two focus groups with a range of internal and external stakeholders.14 To some degree, Australian responses echoed the ambivalence to the concept of social justice observed in the US — public roles were supported when expressed within a familiar framework centred on care and compassion, but contested when expressed as matters of justice and fairness, particularly if any personal sacrifice was perceived. Their findings highlighted the tensions between the dual responsibilities of professional bodies to the public and to their members, and the importance of leadership from professional organisations in promoting public engagement. So what can we conclude? First, that both scientific evidence and the relationship between the medical profession, politics and the public are dynamic and inter-related. Second, most doctors now seem to accept that their expertise should include knowledge about social determinants of illness and access to care and that, even when they are not personally involved, it is important that the profession provides a responsible expert voice on such determinants in public debate. Third, public roles are most likely to gain traction among doctors when conceptualised as issues of care and compassion rather than as actions of justice and redistribution. Clinicians want their expertise put to good use in the public sphere in a way that complements rather than detracts from their core responsibility of being expert in the traditional doctor–patient relationship, and the rewards reaped from it. Fourth, a double challenge lies ahead because, while contemporary professional standing may partly depend on public engagement, the effectiveness of such engagement depends, in turn, on how convinced the public is that the profession has its own house in order.15 And finally, conceptual clarity, realistic expectations and good role models are needed if clinicians are to engage effectively with important public concerns. Teaching about social determinants of health alone is insufficient. To use this information and be effective political agents, future health care professionals will need skills in advocacy and public participation. Virchow led an extraordinarily civic-oriented life, as a participant in the 1848 Berlin uprisings and later as a Berlin city counsellor, cofounder of the German Progressive Radical Party, and member of parliament. With public-spiritedness and the right tools, modern health care professionals could be both active clinicians and evidence-based advocates on important health-related matters in their communities. Virchow would be pleased — medicine would once again be a social science.

Russell L Gruen MB BS, PhD, FRACS

To decrease overall mortality, we need to focus on maximising appropriate medical therapies Increasing attention is being given to assessing and improving the quality of care of patients presenting with acute coronary syndromes (ACS).1,2 In this issue of the Journal, Chew and colleagues report on the use and survival impact of early invasive management (coronary angiography and revascularisation) in 3393 patients with ACS enrolled in the Australian prospective ACACIA (Acute Coronary Syndrome Prospective Audit) registry.3 They used propensity-adjusted regression modelling to quantify effects of invasive care independently of other confounders such as patient characteristics, contraindications to invasive care and use of pharmacological treatments. While rates of invasive care appeared near to optimal (90%) in patients with ST-segment-elevation myocardial infarction (STEMI), rates were purported to be less optimal in those with non-STEMI (71%) and unstable angina (45%). The study is unique in showing a 47% reduction in all-cause death at 1 year as a result of early invasive care, a finding used to argue for a greater use of this approach across the spectrum of ACS. The magnitude of this treatment effect is at odds with systematic reviews of randomised trials which report that survival benefits are restricted to patients with STEMI undergoing primary angioplasty, with relative risk reduction of death (compared with thrombolysis) no more than 32%.4 Such patients represented just over a fifth of the patients evaluated in ACACIA. In contrast, contemporary trials of routine invasive care versus medical therapy in patients with non-ST-segment elevation ACS (NSTEACS), who comprised three-quarters of the cohort, show no conclusive mortality benefit, although reinfarction and anginal burden are significantly reduced.5 Separate analyses for patients with STEMI versus those with NSTEACS were not reported, which brings into question the validity of implying that greater use of an invasive strategy among all patients with ACS would translate into proportionately more survival benefit. The authors argue that their cohort included many high-risk patients who tend to be excluded from trials, and among whom they infer a survival benefit was achieved. Several issues warrant consideration. Can observational studies validly show treatment benefits not seen in randomised trials? How replicable are these effects? If such an effect is real, would the number of lives saved from optimising invasive care exceed that achieved from optimising other forms of care, thus serving as a quality improvement priority? If so, what might be the most effective optimisation strategies? Even the best observational design can be biased by prognostically important baseline differences among patients, often because of unobserved or unreported treatment selection biases. Chew et al did their best to minimise such bias by estimating the likelihood (or propensity) of patients to receive invasive care on the basis of patient characteristics ascertained before such treatment was given. The association between invasive care and 12-month mortality was then assessed with regression modelling that adjusted for variables known or thought highly likely to influence mortality, including medical therapies such as statins and angiotensin-converting enzyme (ACE) inhibitors — although antiplatelet agents and β-blockers were notably absent. This association was then further adjusted after inserting the propensity score as a continuous variable. Unfortunately, methodological concerns persist for several reasons. First, the literature is replete with high-profile examples of well performed observational studies (eg, hormone replacement therapy and cardiovascular mortality, β-carotene and cancer prevention) suggesting favourable treatment effects that were later dismissed or reversed in large, pragmatic randomised trials. Second, different observational studies, which have included analytical methods other than propensity scoring, give very different results. An American study showed that early coronary angiography for acute myocardial infarction (AMI) was associated with a 50% reduction in mortality at 7 years using propensity analysis (designed to control for overt bias), but this fell to a 16% decrease when instrumental variable analysis was used (designed to control for hidden bias as well).6 A propensity-adjusted analysis of French patients with STEMI presenting to interventional versus non-interventional hospitals (the former highly correlated with higher rates of invasive care) revealed only a 24% decrease in mortality at 1 year.7 Third, the most appropriate design for observational studies remains unclear, with some arguing propensity scoring is no better than traditional multivariate regression adjustment.8 Fourth, as propensity analysis cannot adjust for unmeasured characteristics, sensitivity analyses are recommended to gauge effects of potential confounders which, for invasive care in ACS, may include patients’ socioeconomic status.9 Finally, trials of invasive care may actually overestimate treatment effects achievable in routine practice given the expertise, logistical support and rapid institution required for the optimal results available in high-volume research centres. With regard to prioritising efforts at improving quality of care, the use of early invasive care in patients with STEMI in the study by Chew et al was in accordance with trials and guidelines. In contrast, within the total cohort, there was considerable underuse of key drugs at discharge and at 12 months, respectively: β-blockers, 68% and 57%; aspirin, 87% and 74%; statins, 82% and 72%; ACE inhibitors or angiotensin receptor antagonists, 67% and 64%. This underuse was most pronounced in patients not receiving invasive care and, by association, not admitted to a metropolitan centre. Of all AMI-related deaths that are prevented by therapeutic interventions, both acutely and as secondary prevention, medical treatments account for 80% of these (35% acutely, 45% secondarily) compared with only 6% for early invasive management.10 If all indicated drugs are prescribed to eligible patients, risk-adjusted mortality at 6 months is reduced by 90% compared with patients who receive none of these drugs.11 Routine use of more costly invasive care is not associated with population survival benefit beyond that seen with optimal medical management.12 Thus, if decreasing overall mortality is the aim, a focus on maximising administration of appropriate medical therapies across all hospitals should take precedence over extending invasive care to all or most patients with ACS, especially as there are low-cost interventions that can increase rates of prescribing at discharge up to 90%.13 This is not to say the delivery of timely invasive intervention, particularly to patients presenting to non-interventional hospitals, is unimportant given its mortality benefit in STEMI4 and morbidity reduction in high-risk NSTEACS.5 There are actionable strategies for improving region-wide access to intervention14 and reducing door-to-balloon times15 for patients with acute STEMI, and these deserve consideration in Australian settings. Risk stratification methods for identifying patients with NSTEACS who are most in need of referral to interventional centres16 require universal implementation. More globally, quality improvement strategies — comprising use of opinion leaders and educational outreach, guideline-based decision support tools, regular audit and feedback, and clinical process redesign — have been validated in the management of patients with ACS,17 and innovative, multidisciplinary programs that integrate multiple strategies need to be maintained. What is critical is the continuance of well designed prospective registries like ACACIA, which provide standardised and representative data that allow us to monitor the quality of care and the effects of whatever actions we may take towards improving it.

Ian A Scott FRACP, MHA, MEd

Long (or short) QT syndrome is life-threatening, not as rare as once thought, and treatable if diagnosed “The fault dear Brutus is not in our stars, but in ourselves”. Through the lens of molecular medicine we are now beginning to see those faults more clearly. We can now increasingly understand why some apparently healthy children and young adults die without warning. The long-QT syndrome is foremost among responsible causes, and is known to be the consequence of mutations in genes encoding ion channel function.1 Originally an esoteric condition of great rarity, its prevalence is now estimated as one in 2000.2 Life depends on the continuous sequence of depolarisation and repolarisation in our heart cells. The QT interval is the time from the onset of depolarisation (the q wave) to the end of repolarisation (completion of the T wave) and is best measured over several R-R intervals in leads II or V5. It is not a value physicians ordinarily pay much attention to when they read an electrocardiogram (ECG; Box). Nor is it always easy to measure. Exactly where the T wave merges with the isoelectric baseline is subject to individual interpretation and hence error.3 It also varies with heart rate, requiring normalisation for comparison, and is longer in women than men. But it is important. The long-QT syndrome is essentially an autosomal dominant condition in which sudden death is commonly linked to situations of increased adrenergic activity, such as exercise and emotion, but also occurs at rest and during sleep.4 Seizures are common and easily lead to misdiagnosis. Although mutations in at least 10 genes have been found, long-QT syndromes 1 (LQT1), 2 (LQT2) and 3 (LQT3) constitute 95% of genotyped cases. LQT1 and LQT2 involve decreased function and hence diminished current flow in the slow and fast repolarising potassium currents, IKs and IKr, respectively, while LQT3 involves an increase in slow sodium current during the plateau phase of the action potential. The net effect is prolongation of the action potential and, most importantly, an increased dispersion of recovery times in different myocardial cells. This increased dispersion allows re-entry to occur with potentially fatal ventricular tachycardia and fibrillation, which manifests clinically as fainting and sudden death. LQT1 is the most common type, and events are typically triggered by exercise, including swimming, and emotion.5 The child found unconscious at the bottom of the swimming pool may well have LQT1.6 Events may occur with exercise or at rest in LQT2 and also, characteristically, with loud noises such as being awakened by a telephone call.7 LQT3 has been linked to death during sleep or inactivity, with a lower likelihood of events, but increased mortality. What are the implications for physicans and general practitioners? Fainting is common, most often vasovagally mediated, and benign. How do we decide otherwise? The key is to be mindful of possible long-QT syndrome when checking the history; fainting or a seizure during exercise, or when upset or angry, and premature death (including drownings or accidents) in family members should ring alarm bells and trigger detailed exploration of the family history, close scrutiny of ECGs and appropriate referral. In such settings, a corrected QT (QTc) interval > 0.45 seconds in males and > 0.47 seconds in females makes the diagnosis virtually certain. With diagnosis comes the dual responsibility of triaging individual patient risk and screening the wider family. The most important factor determining individual risk is the length of the QT interval — long intervals (QTc ≥ 0.5 seconds) equal high risk.8 Knowledge of the genotype is also predictive. β-Blockers are generally first-line treatment, although in genotyped individuals, evidence is lacking for a protective action in LQT3. Modifying risk by avoidance of competitive sport and QT-prolonging drugs (see http://www.qtdrugs.org) is important. Implantable defibrillators are appropriate in high-risk patients, but decisions about prophylactic implantation in intermediate-risk patients must balance the reduction in probability of sudden death against the not inconsiderable morbidity of life-long device therapy in young people. As well as personal history and ECG, family screening should include genetic testing if it is available. When a functionally important mutation is uncovered, testing of family members will disclose up to a third of individuals whose QT intervals are normal, and yet who carry the mutation.9 However, a genotypic diagnosis is possible in only two-thirds of clinically certain cases. Continuing research may diminish this gap. The establishment of registries, such as presently exist in New Zealand (http://www.cidg.org), facilitates surveillance of widely dispersed families and aids ongoing research. While the risks of QT prolongation are now well established, attention has recently been drawn to excessively short QT intervals. In a small number of families identified to date, a QTc interval of < 340 milliseconds has been also associated with a family history of sudden death.10 The first two syndromes described (short-QT syndromes 1 and 2), show a gain of channel function for IKr and IKs, the mirror opposite of the corresponding LQT2 and LQT1 with loss of function in those same channels. Although five short-QT syndromes have been recognised already, it nonetheless seems unlikely that they will rival the long-QT syndrome in prevalence. In conclusion, cardiac repolarisation is a complex interplay of ionic currents precariously maintaining stability. Dramatic progress has been made over the past 50 years in recognising, deciphering and predicting the clinical risk of the long-QT syndrome. Yet this knowledge counts for little if we fail to identify and protect at-risk individuals. Perhaps you will take a closer look at the QT interval in your next patient presenting with “just” another fainting attack. Electrocardiogram showing a markedly prolonged QT interval. The long ST segment is suggestive of long-QT syndrome 3.

Warren M Smith MB BS, FRACP

Ethical issues are constantly changing as clinical research and practice push out the boundaries of what we know and do The beginnings of ethical and regulatory oversight of the human research enterprise are customarily traced to the Nuremberg Code, a set of principles and standards for medical experiments outlined by the Nuremberg war crimes tribunal in 1947 following revelations of the infamous Nazi experiments conducted during World War II.1 Ironically, Germany was the first Western country to officially require informed consent for non-therapeutic research. In 1900, the Prussian minister for religious, educational and medical affairs issued a directive after it came to light that Albert Neisser had injected syphilitic serum into prostitutes without their knowledge or consent;2 and in 1931, the Reich Minister of the Interior introduced Guidelines on innovative therapy and scientific experimentation following an inquiry into the Lübeck disaster, in which 75 infants died and 168 others developed tuberculosis after receiving a contaminated batch of oral BCG vaccine.3,4 In 1964, after more than a decade of drafting, the World Medical Association (WMA) issued the Declaration of Helsinki, elaborating on the basic principles in the Nuremberg Code.5 This was ratified in Australia the following year, and in 1966 the National Health and Medical Research Council (NHMRC) issued its first Statement on human experimentation.6 The requirement for ethical approval of NHMRC grant applications in 1973 and the addition of Supplementary Note 1 in 1976, defining the role and functioning of human research ethics committees (HRECs),6 marked the beginning of the current ethics oversight system in Australia. The devolution of responsibility for evaluation and approval of clinical trials from the Therapeutic Goods Administration (TGA) to local HRECs and the rapid growth of multicentre trials during the 1990s highlighted a number of weaknesses in the system, particularly the requirement for each HREC to give separate consideration to projects involving research in more than one institution.7 Recognising these issues, as well as the importance of applying ethical principles to all types of human research, the NHMRC released a significantly revised National statement on ethical conduct in research involving humans in 1999.8 Subsequently, concern that HRECs have become overburdened with management and regulatory functions that are primarily the responsibility of research institutions has generated discussion of the notion of “research governance”, defined as an organisational framework through which institutions are held accountable for maintaining standards of quality, safety, privacy, risk management and financial management of research, in addition to ensuring its ethical acceptability.9,10 Despite concerns about the risk of creating a massive new bureaucracy,11 the concept has been enthusiastically embraced12 and the 2007 revision of the NHMRC national statement has an entire section devoted to governance.13 The publication in this issue of the Journal of a survey of current knowledge of research governance by Babl and Sharwood14 is thus particularly timely (→ Research governance: current knowledge among clinical researchers). Researchers, students and clinicians were asked about their familiarity with “the essential national and international documents guiding GCRP” (good clinical research practice), namely the Declaration of Helsinki,5 the NHMRC national statement13 and Australian code for the responsible conduct of research.15 The results appear to show a worrying lack of familiarity with the content of some of these “key” documents, and Babl and Sharwood conclude that institutions are failing in their responsibility to provide adequate training for those engaged in research. Few would disagree that more resources should be devoted to training; however, the study probably overestimates the depth of ignorance. Babl and Sharwood seem unaware that formal guidelines for GCRP were originally published by the TGA in 1991 and superseded in 200016 by the Note for guidance on good clinical practice, a quality standard agreed to by the International Conference on Harmonization for the design, conduct, recording and reporting of clinical trials.17,18 While it is essential that principal investigators running clinical trials are familiar with its contents, it is of little relevance to students, researchers and clinicians not directly engaged in drug trials. As for the Declaration of Helsinki,5 this is no longer considered a key document. The sixth edition released in 2000 created a worldwide furore centred on two paragraphs, one concerning use of placebos in clinical trials, and the other asserting participants’ right of access to the best-proven treatment identified by the trial. Influential American and European regulatory bodies refused to accept the revisions, forcing the WMA to water down the offending paragraphs.19 As a consequence, the Declaration of Helsinki has declined in moral force and influence. Whereas in 1999, the NHMRC national statement listed it as a relevant publication,8 in the 2007 revision, it is relegated to a historical reference in the preamble.13 Also in this issue of the Journal, Ballantyne and Rogers report their survey of chairs of Australian HRECs on the fair inclusion of men and women in clinical research (→ Fair inclusion of men and women in Australian clinical research: views from ethics committee chairs ).20 They correctly point out that, historically, women have been excluded from clinical trials, resulting in inadequate data on safety and efficacy of marketed drugs, and their findings suggest a lack of awareness, concern and action on the part of HREC chairs. Following the thalidomide tragedy in the 1960s, there was major strengthening of the drug regulatory agencies in the United States, United Kingdom, Europe and Australia. At that time, in the absence of widespread use of effective means of contraception, there were justifiable ethical concerns about enrolling women of childbearing potential in clinical trials. Exclusion was commonplace until the late 1980s, when the increasingly powerful HIV/AIDS lobby pressured the US Food and Drug Administration into reviewing its drug approval policies.21 By 1990, the US National Institutes of Health (NIH) had introduced guidelines covering the inclusion of women in clinical trials, strengthened by legislation in 1993, and the most recent policy update in 2000 stated: “NIH experience has indicated that inclusion has been accomplished”.22 In Australia, a Women and Clinical Trials Working Party was established in 1995 to advise on changes to NHMRC guidelines,23 and its recommendations were incorporated into the 1999 National Statement,8 albeit in rather general terms. Ballantyne and Rogers are critical of this, believing that “HRECs require further instruction from the NHMRC about how to interpret and apply the generic principle of fair inclusion.” However, detailed instructions were, in fact, provided in the Human research ethics handbook, issued by the NHMRC in 2002.24 The fact that chairs of HRECs may not be aware of them probably indicates that unfair sex discrimination in clinical trials is no longer a significant issue. So, where to next in the field of human research ethics? Times have changed. With the increase in off-label prescribing in paediatric practice, our challenge now lies in ensuring that children are adequately represented in clinical trials — with responsibility shared by researchers, sponsors, HRECs and regulators. Human research ethics is a work in progress, and will remain so for the foreseeable future.

Robert H Loblay PhD, FRACP

Patients’ simple vital signs are a highly reliable predictor of life-threatening clinical events At a time when hospital staff are becoming increasingly dependent on new technologies, the review by Cretikos et al1 entitled “Respiratory rate: the neglected vital sign” is refreshing. It is a timely reminder that understanding, documenting and acting on changes in patients’ simple vital signs are of fundamental importance to clinical outcomes. An abnormal respiratory rate (high or low) is known to be a highly reliable predictor of life-threatening clinical events. However, daily documentation of this simple number in many hospitals is remarkably poor. More controversial is the question of how best to develop systems that use changes in vital signs to trigger clinicians to respond rapidly and effectively. In recent years, many Australian hospitals have embraced medical emergency teams (METs) as the answer.2 METs enable rapid, skilled medical responses to changes in patients’ vital signs, aiming to intervene and reverse patients’ downhill slides towards intensive care unit (ICU) admission, cardiac arrest, or death. Call criteria for the MET (changes in respiratory rate, pulse rate, blood pressure, and coma score) have been carefully researched and are highly predictive of adverse events. METs are resource-intensive and are usually comprised of an intensive care registrar, a medical registrar and skilled nursing staff. They provide resuscitation skills at short notice in busy hospitals, where the primary medical teams may be busy, inexperienced, under-resourced or slow to respond. Australian studies based on single centres with historical controls,3,4 and on a single-centre before-and-after study,5 have reported that the introduction of METs was associated with reductions in key adverse events. Although before-and-after studies cannot separate the effect of an intervention from other factors that may have changed over time, studies like these were used to justify the enthusiasm and funding needed for the Medical Early Response Intervention and Therapy (MERIT) study investigators, with the Australian and New Zealand Intensive Care Society’s Clinical Trials Group, to conduct the world’s first large multicentre randomised controlled trial of MET introduction versus usual care.6 In clinical trial terms, the results of the MERIT study were clearly negative. There was no difference between intervention and control hospitals for either a composite endpoint (incorporating cardiac arrest, unexpected death or unexpected ICU admission) or for the same key study outcomes analysed separately. Adverse events decreased in both the intervention and control hospitals during the study period (as they had also done in the previous single-centre studies3-5), suggesting that factors other than the introduction of METs were improving key endpoints in both intervention and control hospitals during the study period. The MERIT study also found that introducing METs markedly increased the number of calls to hospital emergency teams and increased the early designation of suitable patients with “do not resuscitate” (DNR) orders. Total hospital deaths (unexpected plus expected [DNR] deaths) were marginally higher in MET hospitals than in non-MET hospitals during the study period. The MERIT study was remarkable in that it involved 23 Australian hospitals and over 36 000 patients, used a vigorous education process, and changed established systems in 12 hospitals.6 In order to account for its negative findings, the study has been criticised for inadequate power, for inadequate calling of the MET in the MET centres, and for a Hawthorn effect likely in the unblinded study design. It has also been said that changes after MET introduction may take longer to mature than was allowed for in the study design. These criticisms have validity, but it is also highly likely that the results of the unique MERIT trial were essentially correct. METs do not provide a single solution to the complex problem of clinician management of clinical instability in hospital patients. However, they do enhance appropriate designation of patients with resuscitation status, and they do encourage education, documentation and attention to patients’ key vital signs. Supporting this view is the recent experience of a hospital in Victoria that has focused, for the past 10 years, on using the MET system to improve management of clinically unstable ward patients.7 Cardiac arrest rates fell before and after the introduction of a formal and informal education process and a MET in this hospital, but then continued to decrease annually for each of the following 5 years (to extremely low rates). This was despite the fact that the MET was unchanged over the 10-year period. It appeared that the most important parts of a MET system are not the MET at all, but rather the audit, educational programs and DNR designations associated with it. The article by Cretikos et al and the MERIT trial results inform us that understanding, education, documentation, rapid clinical response to abnormal vital signs, and early designation of patients with an appropriate resuscitation status really do matter. To improve our hospitals we need mechanisms for simple, real-time communication of abnormal vital signs to hospital clinicians, so that timely management can occur across all acute hospital beds. Communication systems that do this, and also report, audit, and provide staff education and training, exist now, and may enable improved clinical management of unstable in-hospital patients. METs are a simplistic “bandaid” response to a complex problem in our hospitals. They are not the best response. Instead we need better education, focused on those critical vital signs. We need earlier appropriate DNR designation, and we need to test real-time emergency information systems. The evidence is that patient outcomes can be improved.

D James Cooper MD, FRACP, FJFICM · Michael D Buist MD, FRACP, FJFICM

What will it take to break the funding drought in Australia? Donations to health and medical research have recently made headlines, with mining magnate Clive Palmer pledging $100 million to medical research and Indigenous needs.1 While this amount is an Australian record, it is somewhat eclipsed by “gigaphilanthropists” Bill and Melinda Gates’s multibillion dollar inputs to research and health delivery. The prefix “gigas” is Latin for “giant” and it is worth asking: Where are the giants of Australian giving? As Daniel Petre (an Australian philanthropist and former Microsoft vice-president) recently slammed the lack of generosity of richer Aussies,2 it is timely to consider where health and medical donation stands in Australia. How do we compare with other nations and what is the forecast for the future? Australia is blessed with superb philanthropists — just not enough of them. To borrow from poet Dorothea Mackellar,3 the comparison is in the order of “droughts and flooding rains”, particularly when pitted against the philanthropy-rich landscape in the United States. US philanthropy is a veritable flood. Since the mid 1990s, 2% of the US gross domestic product has been given to charities;4 the percentage in Australia is less than half of this — a relative drought.5 More recently, the prescribed private fund — a new style of private foundation akin to the US family foundation — has burgeoned in Australia, with some 610 formed since this tax-effective structure was instigated in 2001. Many of these were established by people far from the wealth apex. Still, when it comes to health and medical research, as prominent medical research leader and former Chief Medical Officer Professor Judith Whitworth points out, “Australian philanthropic funding — both corporate and private — lags way behind”.6 Australian health and medical research non-profit organisations (eg, the Royal Children’s Hospital Foundation, the Leukaemia Foundation) attract one in seven of all individual donation dollars.5 So the area is popular, ranking second to religious institutions. However, it is not even a close second, as it is a case of many donors but small dollars.5 While three in five donating Australians support health and medical research, the average gift is comparatively low: just $77 per annum (pa) compared with $529 pa to religion, $234 pa to international aid, and $220 pa to arts and culture.5 By contrast, in the US, the average gift to health causes by the most modest households is US$173, ranging to US$92 289 in households with incomes over a million dollars.7 Philanthropy worldwide has been the crucible of fine medical research institutes and the trusts that fund them: consider our Walter and Eliza Hall Institute, the US Howard Hughes Medical Institute and the Wellcome Trust in the United Kingdom. Indeed, through the Wellcome’s input, UK charitable funding matches that of its nation’s Medical Research Council. Where is Australia’s Wellcome equivalent? The possibilities for a luminary local funder to alter the landscape are profound. With mean affluent household income growing by 36% in the decade to 2005, it is concerning that charitable giving by this income band has not kept apace. The most common affluent band of Australians (taxable incomes from $100 000 to $500 000) give less than 0.5% of their income to charitable causes.8 Longitudinal corporate research provides an international benchmark, with an average of 3%–11% of portfolios allocated to giving in some other countries.9 Despite comparable wealth levels, Australian givers trail the US, the UK and Canada. Yet Australia is said to have one of the world’s fastest growing rates of millionaires. Ironically, US philanthropist Chuck Feeney, a founder of the conglomerate Duty Free Shoppers, is thought to be Australia’s most generous philanthropist. His approach of leveraging funding sources through his foundation, Atlantic Philanthropies, has catalysed potent funding partnerships. Atlantic Philanthropies offers a significant amount, providing the recipient organisation can convince governments and others to match the pledge. Consider, for example, the $900 million research program at the University of Queensland generated by leveraging state, federal and other monies from Feeney’s $150 million input.10 People commonly believe medical research is the government’s responsibility. However, as a Nature editorial asserted last year, “In scientific funding, as in agriculture, monoculture is risky”.11 The lithe and flexible philanthropic dollar can trek where more risk-averse government or corporate dollars cannot. Untrammelled by politics, elections, profit, shareholders, disease numbers, or directives not to fund infrastructure, the philanthropic dollar can more readily finance risky ideas, chart cumulative progress over decades, consider orphan diseases, and trial venturesome backing that generates social profit. The future for the US, and most likely Australia, looks set to see more of this “venture philanthropy” model. A growing number of organisations (Box) are using their philanthropic agility to fund promising science through its pre-proof of principle, “Valley of Death” phase — the critical translational funding gap between basic research and later stage drug development. The concept of successful people “investing” donations to move innovative research to the point where venture capital may kick in is an enticing model that is working. For instance, the Alzheimer’s Drug Discovery Foundation reports seeding 22 biotechnology companies and supporting 148 academic international researchers who have created new classes of drugs for Alzheimer’s disease, screened millions of compounds, and are now entering clinical trials of several new drugs. Still, more debate is needed. Is it appropriate that philanthropy influences the research agenda? How valid is “personal whim” funding over majority need? Discovering better treatments sometimes means more expensive medicines, and is this progress for all? Change in the Australian health and medical research philanthropic landscape is needed, and the climate is right. Research Australia Philanthropy now exists to foster contribution to research (http://thankyouday.org/ra/philanthropy.aspx). The National Health and Medical Research Council added philanthropy to its strategic plan in 2006 and is working on fruitful partnerships with health and medical research charities (eg, co-funding with the Junior Diabetes Research Foundation Australia of the Diabetes Vaccine Development Centre). The national peak body, Philanthropy Australia (http://www.philanthropy.org.au/), provides forums for interested existing and potential funders to collaborate and exchange. The challenge is one of communication and culture change: convince philanthropic trusts, companies, individuals and households that funding medical research is not just a job for government, but a task for all Australians to shoulder. With governments increasingly unlikely to meet the spiralling costs of complex medicine for an ever-ageing population, the funding drought needs to be broken. Everyone can — and maybe should — play rainmaker. Organisations exploring “venture philanthropy” for medical research Goldman Philanthropic Partnerships was set up by a former merchant banker and his wife to accelerate the way cures are discovered through a business model of research funding partnerships (http://www.goldmanpartnerships.org) The Alzheimer’s Drug Discovery Foundation was set up by the Lauder family, of cosmetics renown (http://alzdiscovery.org/) The Washington, DC-based think tank, FasterCures (http://www.fastercures.org) The Epilepsy Therapy Development Project acts as a catalyst and a clearing house for innovative research and early commercialisation of new epilepsy therapies (http://www.epilepsy.com/epilepsy_therapy_project) CFF Therapeutics, a non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation (http://www.cff.org/research/CFFT/) Accelerate Brain Cancer Cure supports researchers and creates collaborations between medical, academic, industry and government partners (http://www.abc2.org)

Myles McGregor-Lowndes BA/LLB, MAdmin, PhD · Wendy Scaife BBusComm, MBusMgnt, PhD

It’s time for genuine partnerships as all Australians strive together to Close the Gap A year ago in this Journal, Indigenous health leaders outlined the emergent health equality campaign for Aboriginal and Torres Strait Islander peoples,1 now known as the Indigenous Health Campaign or “Close the Gap”. An early indicator of the depth of support for Close the Gap was the large number of health, human rights, advocacy and community organisations that enthusiastically signed up or offered support for the campaign. Since then, the Indigenous Health Campaign coalition, led by Aboriginal and Torres Strait Islander health leaders and the Aboriginal and Torres Strait Islander Social Justice Commissioner, has worked in genuine partnership with non-Indigenous organisations. Key milestones along the Close the Gap campaign journey are shown in the Box. On 20 December 2007, the Council of Australian Governments (COAG; comprising representatives of federal, state and local governments) committed to: close the life expectancy gap within a generation; halve the gap in mortality rates for Indigenous children under five within a decade; and halve the gap in reading, writing and numeracy achievements within a decade in a partnership between all levels of government and with Indigenous communities. They added: The pathway to closing the gap is inextricably linked to economic development and improved education outcomes.5 On 13 February this year, Prime Minister Rudd delivered the Apology to Australia’s Indigenous people, hopefully heralding a new and promising partnership between governments and Indigenous Australians. He stated: We today take this first step by acknowledging the past and laying claim to a future that embraces all Australians. A future where this Parliament resolves that the injustices of the past must never, never happen again. A future where we harness the determination of all Australians, Indigenous and non-Indigenous, to close the gap that lies between us in life expectancy, educational achievement and economic opportunity. A future where we embrace the possibility of new solutions to enduring problems where old approaches have failed. A future based on mutual respect, mutual resolve and mutual responsibility. A future where all Australians, whatever their origins, are truly equal partners, with equal opportunities and with an equal stake in shaping the next chapter in the history of this great country, Australia.6 The opportunity for every government in this country to seriously tackle the entrenched disparity and unacceptable outcomes in Aboriginal and Torres Strait Islander health, through strong national leadership, should not be missed. It is time for a long-term approach that secures all of our futures — Indigenous and non-Indigenous — together, as a healed and healthy nation. The success of the campaign for Indigenous health equality will be measured by progress towards clearly stated goals within set timeframes. It is unacceptable to continue with the current situation, in which the health outcomes and life chances of an Indigenous child are substantially worse than those of their non-Indigenous peers. As stated in the Aboriginal and Torres Strait Islander Social Justice Commissioner’s 2005 report2 (the initial trigger for the genesis of the Close the Gap campaign), it is simply not defensible for governments and health and human services systems to argue that inadequate infrastructure, bureaucratic mechanisms or persistent complexity are justifiable speed humps to real change. It also does not hold that championing the rights of human beings is contrary to health gain. The outcomes of the National Indigenous Health Equality Summit will be delivered by June 2008 to the Australian Government and COAG. The Summit deliberations will not only provide governments with a set of specific evidence-based targets for action and investment, but affirm the commitment to genuine partnership by signing the Statement of Intent (Box).8 A whole-of-government response across all levels of government is necessary to address the social determinants of health. COAG’s commitment to employment, education, housing and health are strong indicators of such commitment. The time for genuine partnerships is now; that is, partnerships that strengthen us all in mutually respectful and sustaining ways. Medical bodies, including the Royal Australasian College of Physicians, Royal Australian College of General Practitioners, Australian College of Rural and Remote Medicine, Australian General Practice Network and the Australian Medical Association, have been key partners in this campaign. We must not allow “Close the Gap” to become another shallow slogan. It is a glaring reminder of the continuing inequity in health and life outcomes within this wealthy nation of ours. The commitment to act now — to guarantee a future where Indigenous health inequality is a thing of the past — requires concerted, tangible and immediate action. Our call is for current and future medical leaders to show their commitment by doing what they can within their area of influence and expertise. Key milestones along the “Close the Gap” journey

Tamara Mackean BSc (Med), MB BS · Mick Adams BSocWk, MAppSci, PhD · Sally Goold RN, DipNEd, MNSt · Christopher Bourke BDSc, GradDipPublicHealth, GradDipClinDent · Tom Calma

Training in a variety of skills while caring for patients, without the burden of unnecessary tasks, and with meaningful feedback and supervision and time for reflection and self-care — too much to ask? In this issue of the Journal, Westbrook and colleagues studied the work of interns, residents and registrars across four wards in a Sydney teaching hospital (→ All in a day’s work: an observational study to quantify how and with whom doctors on hospital wards spend their time).1 Their findings are limited by the study’s small sample size, and the fact that each participant was observed, on average, for just under 8 hours, and not during evening or night shifts. Nevertheless, their key findings are pertinent to understanding a day in the life of a doctor-in-training. As a group, interns, residents and registrars spent about a third of their time in “professional communication”, including meetings, requests for consultations and planning care, about another third on direct or indirect (predominantly reviewing results and planning care) patient care, and a surprising 17% of time on “social” activities (defined as all non-work activity or communication, including meal breaks); 7% of time was viewed as being related to education, the same amount as that devoted to medication tasks, including searching for charts. Finally, about 2% of tasks related to administrative activities that were not a part of patient care, and about another 2% of tasks were carried out while not officially on duty.1 The findings are different from those of an unpublished survey in an Auckland hospital, which found that only 15% of employed time was spent doing things for which a medical education was necessary.2 So what should a day in the life of a doctor-in-training look like? The ideal day should be one that consists of training in a mixture of skills while caring for patients, without the burden of unnecessary tasks,3 and with time for reflective education and self-care. Is this ideal “warm and fuzzy” and totally impractical, or is it a realistic goal? Let’s begin by doing away with the conflicting notions that one is either learning or is involved in direct patient care (ie, “service”). The two are not mutually exclusive, provided appropriate supervision and feedback is given by more senior doctors in the medical team; this is the key to integrating clinical service provision by interns, residents and registrars with their “on the job” training. Does this time-honoured “apprenticeship” model still work now that the medical team encompasses as a minimum, not only doctors, but also nurses, and allied health and clerical staff? There is a push for doctors-in-training to be allocated to a ward rather than to a traditional medical team, but the risk in this is that many doctors-in-training may lose the supervision they require. On the other hand, it is clear that supervision and feedback is not always given in the present system. The solution is simple: if consultants want the privilege of doctors-in-training on the team, then they need to support them and help structure their days towards learning. Meaningful performance agreements between consultants and their clinical or hospital managers could resolve this, but such agreements must reflect genuine support and appreciation from hospitals and universities for the consultants providing this supervision.4,5 In this context, the Australian Curriculum Framework for Junior Doctors6 serves as a useful document, not only to guide the learning experiences of doctors-in-training, but also to assess the ability of hospitals to provide adequate resources and support for such experiences. What unnecessary tasks should be removed from the doctor-in-training’s daily activities? Westbrook et al point out that sometimes things that seem most burdensome are those that are frustrating rather than those that take up much time.1 For example, doctors had included writing discharge summaries among a small number of activities that consumed “all our time”, but Westbrook and colleagues found that only about 5% of time was spent on this activity.1 With appropriate feedback, writing discharge summaries can be a valuable learning experience, as doctors must be able to liaise professionally with colleagues throughout their careers. This emphasises the need for meaningful day-to-day feedback about the role and value of individual tasks. We should also acknowledge that the in-hospital consultation process has become unwieldy; it probably occupied a large proportion of the 33% of time spent on “professional communication” reported in Westbrook and colleagues’ study.1 This could be reformed relatively easily by ensuring that all consultations were approved first by the clinician in charge, and by specialist medical teams continuing to practise general medicine for their patients, thereby reducing the number of consultations required. This would do away with reams of paperwork and duplication of tests. A further “clerical” issue that needs to be addressed is the time-honoured process of charting admissions. It is not unusual for interns and residents in emergency departments, and then emergency or specialty registrars and ward interns to write (similar) admission notes, with no added benefit to the patient or doctor. Finally, given the stress of the job of a doctor-in-training and the high rate of psychological and psychiatric morbidity among our junior medical staff,7 it would be a good thing if some time each day were truly spent on activities such as speaking with their own friends and family, which might allow them to debrief and reflect on the stresses that confront them. The early training years should be an exciting time; learning is rapid, and patients actually benefit from what the doctor-in-training does. We need to promote a strong work ethic whereby our patients come first and we work in support of, and are supported by, our colleagues; this will, by necessity, mean work after-hours, but we still need to move away from the view that “the harder I work, the better a doctor I am”.8 The New South Wales Institute of Medical Education and Training believes true progress can be made in improving the quality and value of a doctor-in-training’s day through the establishment of a training and education agreement between the doctor and the hospital. This has already been introduced in some specialty training areas, but needs to be applied very quickly to the junior medical officer workforce so that doctors-in-training can know what daily education and supervision they should expect, and the hospital knows that these doctors agree to participate actively in their learning opportunities and their service provision to patients and their colleagues. Importantly, we need to begin training in more meaningful places, such as the private sector, general practices, and other community settings, to define appropriate educational goals (which can now be guided by the Australian Curriculum Framework for Junior Doctors)6 and provide proper feedback, supervision and caring for our next generation of doctors. There has been progress, but we can do better.

Mark A Brown FRACP, MD · Stephanie Arnold BSc, MB BS

Cervical cancer prevention relies on two different age-specific technologies, and consumers should not be misled about the role of HPV vaccines The introduction of human papillomavirus (HPV) vaccines to clinical practice is the end result of a remarkable distillation of basic science, new technology, epidemiological understanding, clinical research and commercial development. It has brought together stakeholders from a variety of backgrounds to consider these developments, and Australia is now the first country to implement a population-based mass vaccination program against HPV. The Australian HPV vaccination program was commenced after cost-effectiveness of the quadrivalent vaccine was demonstrated,1 anticipating that the expected reduction in the cost of treating HPV-related disease in Australian women would compensate for the cost of the vaccine. This program, an Australian Government initiative,2 appears to have been very successful in terms of coverage, and offers young Australian women the opportunity to be among the first national cohort to be vaccinated against the virus types that cause most cervical cancers and a variety of other HPV-related diseases. The natural history of HPV infection and the consequent risk of developing cervical cancer are well documented. HPV infection, replication and particle maturation occurs in the stratified squamous epithelia of skin and mucous membranes, with virus spread occurring by skin-to-skin contact. Most people encounter genital HPV soon after the onset of sexual activity,3 with the highest risk of contracting the infection in the first 5–10 years after commencing sexual activity. The clinical consequences of infection will vary according to the type of HPV encountered, and most infections resolve spontaneously, presumably relying on the host’s immune system to clear the infection. For whatever reason, some individuals do not clear their infections, and if these infections are caused by some oncogenic or high-risk varieties of HPV, this persistence will lead to activation of oncogenic viral proteins, the loss of cellular control mechanisms and the potential for malignant transformation. Screening programs based on cytology have had significant impacts on the incidence and mortality of cervical cancer by detecting these potential cancer precursors, but HPV vaccines allow the opportunity to enlist the vaccinee’s own immune system to develop neutralising antibodies before exposure, and to primarily prevent the infection. The two currently available vaccines (a quadrivalent vaccine against HPV types 6, 11, 16 and 18, and a bivalent vaccine against types 16 and 18) have both been developed by recombinant genetic technology that allows expression of the major structural protein of HPV, the L1 protein, that spontaneously assembles into virus-like particles (VLPs) which are both type-specific and highly immunogenic. Both available vaccines contain VLPs, but the products differ in the types of HPV L1 proteins included as antigens, substrates used for production, adjuvant properties and in the final formulation. Antibodies raised to the VLPs provide protection against HPV infection, probably by transudation of IgG from serum to local mucosal/epithelial areas, especially at sites of trauma where HPV can otherwise gain access to basal epithelial cells.4 Published efficacy studies suggest subtle but probably insignificant differences between the two vaccines in preventing type-specific HPV infections and disease.5,6 It seems unlikely that cell-mediated immunity is involved as a direct effector mechanism of vaccine protection.7 Clearly, this mode of action highlights that the current vaccines will only be effective if administered before exposure. These vaccines have shown no therapeutic efficacy for pre-existing infections.8 Trials of both commercially available vaccines, while demonstrating very high efficacy (approaching 100%) in HPV-naïve populations, have shown diminished efficacy in populations with high rates of previous exposure.4,5 The results so far have indicated that women already infected with one of HPV types 16 or 18 can be protected against development of cervical intraepithelial neoplasia grade 2/3 or cervical adenocarcinoma in situ associated with the other type by vaccination. Both trials were conducted in young populations (generally in women aged between 16 and 25 years). Preliminary results indicating significant efficacy (greater than 90%) of the quadrivalent vaccine in an older population aged between 24 and 45 years have been presented, and these data form the basis of the vaccine sponsor’s application to regulatory authorities in both Australia and the United States for expansion of their age indication for this formulation.9 Doctors are used to being exposed to marketing from drug companies, and are susceptible to commercial persuasion with competing claims of superiority and product distinction. The quadrivalent vaccine, Gardasil (Merck), is available at no cost to Australian girls and women between the ages of 12 and 26 as part of the National Immunisation Program. The bivalent vaccine, Cervarix (GlaxoSmithKline), has to date not been included in the program, having initially been rejected by the Pharmaceutical Benefits Advisory Committee (PBAC) on the basis of uncertain cost-effectiveness,10 but subsequently recommended for inclusion.11 This recommendation has not yet been endorsed by the Australian Government. The sponsoring company appears to have decided to promote Cervarix specifically to older women,12 despite the absence of efficacy data and the uncertain population benefits in this age group. Indeed, the decision by the Australian Therapeutic Goods Administration (TGA) to register Cervarix for use in this population, in which no efficacy has been shown, is not easily understood. Under the Therapeutic Goods Act 1989 (Cwlth), the TGA is responsible for evaluating the quality, safety and efficacy of medicines.13 The World Health Organization has issued guidelines for the evaluation of HPV vaccines, indicating that studies that use immunogenicity data to bridge efficacy from younger to older women are not appropriate.14 In Australia, these guidelines have not been adhered to, and Cervarix has been licensed for use in women up to 45 years of age, despite lack of demonstrated efficacy in women over 26 years. To suggest that the vaccine will offer patients some theoretical potential benefit if they are prepared to pay for it does not reflect sound evidence-based, equitable health care provision. The promotion and media coverage of HPV vaccines in Australia have been extensive, and with this has come an increased awareness of HPV, its relation to cervical cancer, and the national HPV vaccination program. The promise of a cancer vaccine is alluring to women who perceive a risk of cervical cancer. Principles of consumer protection, however, demand that expectations should not be raised unduly, and that the available vaccine does not promise to deliver beyond its capacity. Excessive promotion in the older age group, when the vaccine is likely to be of substantially reduced efficacy because of either previous exposure or reduced risk of future exposure, potentially diverts attention and compliance with established methods of cervical cancer prevention based on cervical cytology. HPV vaccines are about preventing future infections. Cervical cytology detects cytological abnormalities from previous infections. It is important that the benefits of these two approaches to cervical cancer prevention are not confused, and that all women receive the best and most appropriate combination of two effective technologies.

Gerard V Wain FRANZCOG, CGO

Reducing the growing burden of food allergy requires a chronic disease management model, clarification of responsibilities, and better communication of both risks and uncertainties Food allergy and anaphylaxis are increasing in the Australian community, particularly in preschool-aged children,1,2 although, paradoxically, mortality occurs almost exclusively in school-aged children and adults.3 Food allergy and anaphylaxis are high-stakes and highly uncertain issues, where the outcome may be the sudden and unpredictable death of a child.4 The concept that a patient is “at risk” inevitably invokes uncertainty. It is possible to prospectively identify those at risk by virtue of having food allergy, but diagnostic tests are not highly predictive of anaphylaxis. The population with food allergy is substantially larger (about 10–20-fold) than the population who will experience anaphylaxis. Patients and their carers therefore live with being at risk, while not knowing exactly what the nature or extent of the risk is. In clarifying what we mean by “anaphylaxis risk”, the conventional wisdom in risk communication literature is to avoid essentially meaningless terms such as “potential risk” or “high risk” and to instead employ techniques that more accurately convey quantitative estimates of risk. This is risk as numbers, or “the probability that an event will occur, eg, that an individual will become ill or die within a stated period of time”.5 Mortality figures for food anaphylaxis in New South Wales show that the numerical risk that a teenager allergic to peanut or tree-nut will die from anaphylaxis in the next year lies between 1 in 10 000 and 1 in 100 000 — in the same order as the chance of an Australian resident being murdered in the next year.6 The risk that a child aged under 5 years will die from food anaphylaxis in the next year lies between 1 in 1 million and 1 in 10 million — the same order as the risk of death from being struck by lightning.6 However, there are problems with this numerical approach to risk assessment: the data to calculate probabilistic risk for anaphylaxis are either unavailable or not generalisable; numerically small risks are difficult to communicate; and death by lightning or violence is not necessarily viewed in the same way as a child dying from eating food. Due to its emotive characteristics, the risk of food anaphylaxis is likely to be appreciated by experiential rather than analytical cognitive processes,7 which are intuitive, automatic, and greatly influenced by associations and affect. Fear of the unpredictable death of a child may outweigh any rational consideration of its numerical likelihood. Care must therefore be taken when discussing anaphylaxis risk with patients and parents, with a key consideration being the need to sensitively communicate uncertainty as much as communicate risk. As food is essential, some exposure to risk is unavoidable. Although food labelling is becoming clearer, there are persistent uncertainties about mislabelling and cross-contamination with allergens, coinciding with broader concerns about food quality and production, and societal expectations that parents and others will provide safe food for children. Accordingly, food allergy is as much a sociocultural as a medical issue, and, for some, the constant obligation to make careful decisions about what to eat or feed their child, together with ongoing uncertainty about the risks, can create an enormous burden. Reducing this burden requires a coordinated and intersectoral response, from consumers, the health care, teaching and childcare professions, the food and pharmaceutical industries, and statutory bodies at both state and federal level. Clarification of responsibilities is required for food labelling and production, care in schools and preschools, anaphylaxis education (involving anaphylaxis recognition and risk minimisation, as well as correct use of EpiPen autoinjectors [CSL Limited, Melbourne, Vic]), and monitoring EpiPen use. It is encouraging that, in recent months, the Victorian Government has announced legislation mandating a school anaphylaxis management standard8 and the Western Australian Government has committed $6.6 million to a program of interventions.9 Nevertheless, as with other “messy” and uncertain problems, pure science and rationality alone are not sufficient.10 In formulating policy, the process of representation, clarification of common aims and interests, and debate over what we mean by “anaphylaxis risk” may be more important for developing a coherent and coordinated framework for action than would identifying an elusive “right” response. At the service provision level, there has been a tendency for medical treatment of an acute emergency to be the focus of food allergy management. Emergency treatment itself brings additional uncertainties — guidelines for EpiPen prescription leave much to individual judgement, and one study found that only 2% of doctors in a major Australian paediatric teaching hospital could correctly demonstrate all steps in EpiPen administration.11 Fortunately, despite the many uncertainties, most food-allergic patients are generally well and the EpiPen is appropriately unused. Nevertheless, it is more appropriate for food allergy, with its unpredictable “exacerbations” or reactions, and its requirement for community management of risks, to adopt a chronic disease management model, centring on self-management, patient and carer education, continuity of care and multidisciplinary services. Such an approach, including ongoing support from dietitians and nurse educators, is likely to reduce the uncertainties of daily management. The need for parent and carer education is evidenced by an Australian survey of EpiPen use, which found that only 29% of parents administered the EpiPen when indicated.12 Parental satisfaction with information provision is also associated with less seeking of second opinions.13 Thus, adequate parent and carer education and follow-up may ease pressure on referral services, which currently have 10–14-month waiting times for hospital paediatric allergy consultations. The uncertainties surrounding food allergy arise from a lack of scientific, epidemiological and personal knowledge, the need to negotiate between different sectors and interests, and ambiguous language and concepts that are difficult to communicate. Different responses are required at interpersonal, service delivery and policy levels. While some uncertainties are irreducible, patients and carers are also experiencing unnecessary uncertainties. What is certain is that food allergy has become a significant concern for public health, paediatric and general medical practice.

Andrew S Kemp MB BS, PhD, FRACP · Wendy Hu MB BS, PhD, FRACGP

How to safeguard academic integrity when working with Australian governments A recent study revealed that Australian governments regularly suppress embarrassing information by hindering public health research or publication of its findings (Box 1).1 The results resonate with concerns raised in the Report of the independent audit into the state of free speech in Australia.2 Two issues of immediate relevance to Journal readers are the protection of academic independence, and the crucial role of objective evidence in improving outcomes of the Australian health system. Editors of medical journals have rightly opposed contracts with sponsors (such as pharmaceutical companies) that deny researchers the rights to work independently and publish results without the sponsor’s consent.3 While emphasis has been placed on funding support, the same objections apply to conditions imposed by government agencies for data access and representation on research teams. Public health and health services researchers are too often presented with pro-forma contracts for data access or commissioned research funding, on a “take it or leave it” basis, with contractual terms that give the agency a right of veto over publications. Strong institutional guidance is needed to clarify that such contracts can lead to severe publication bias, as evidenced by the Australian suppression study1 and overseas research.4 These contracts are therefore anathema to academic independence. The Australian Code for the Responsible Conduct of Research5 is inconsistent on this point and should be amended in line with the position of the International Committee of Medical Journal Editors (ICMJE).1,3 Incorporating this view is important, because results of public health and health services research are published in a wide range of non-medical and technical media, in addition to medical journals. This is not to say that academic researchers should never undertake research that is strictly for internal use within a government agency. From the outset, research should be either for internal or public consumption; it should not be for public consumption only when the results place the government in a favourable light. The latter creates a conspiracy that will eventually erode the public’s trust in the integrity of researchers and their employing academic institutions. An ethical approach, consistent with the standpoint of the ICMJE, would be to allow government agencies the right to comment on a draft report within a defined period of 30–60 days.3 This will often enhance the quality of the final report by unearthing additional facts that can affect interpretation. It also provides the government agency with a head start on an appropriate response. This would be a constructive process, given that the purpose of public health research is usually for the public to benefit from better informed government decisions. Smith-Merry and colleagues have bemoaned the impediments to a flourishing research culture in Australian health policy circles.6 Moves now afoot through the National Collaborative Research Infrastructure Strategy7 to develop population health and clinical data linkage stand to strengthen the evidence base for a more informed national health policy debate. However, the development of better national health information platforms will fall short of expectations unless careful attention is paid to the rules of engagement between government departments (as the main sources of health data) and researchers (as the major users).1 Key areas where interventions are needed to safeguard academic integrity are shown in Box 2. The challenges ahead will be familiar to leaders of the medical profession who have struggled to introduce adverse incident reporting and other quality assurance programs, with admirable, even if incomplete, degrees of success. The champions of clinical quality and safety have faced up to the suppression of health information at a more local level and have overcome the barriers of cynicism, fear and the cycle of blame.8,9 Analogous tensions exist when researchers work with governments, although a fear of tortious liability is then paralleled by concerns that government agencies and their ministers will be pilloried in the media when a researcher exposes a new health problem. What can we learn from successful clinical quality assurance programs that will reduce the desire of governments to suppress health information and increase their commitment to evidence-based decision making? The answer lies in a complex, gradual, yet not unattainable “culture change”. The existing culture of governmental health decision making needs to change, and there are three steps involved. The first step is to realise that the amount of independent academic research has no net effect on the quantity of bad press that the health system receives. There is an endless supply of anecdotal material for headline stories on the “health care crisis”, which will continue regardless of whether or not public health and health services researchers are suppressed. The second step is to appreciate that there is political mileage (the equivalent of a clinical profession’s credibility) to be gained by supporting ideals and principles that are morally strong — academic independence, a commitment to truth and honesty, and a desire to learn and improve. The third step — the threshold step — is to implement lasting changes to the culture through strong leadership. Unlike the avoidance of publication bias, culture change requires more than adherence to a code of practice. It is also the product of communicating and doggedly enacting a compelling vision. This is most easily achieved when led from the top. Prime Minister Rudd has promised new freedom-of-information laws and a “pro-disclosure” attitude among government and public service staff.10 Senator Carr, Minister for Innovation, Industry, Science and Research, has taken steps to strengthen the independence of the Australian Research Council because “research is not a political plaything to be toyed with at the whim of the Government”.11 These are encouraging signs. The proof of leadership is now to turn the rhetoric into reality, so that an open culture becomes the established norm. 1 Key results of A survey of suppression of public health information by Australian governments1 A national survey of 302 public health academics at 17 Australian universities was conducted in August 2006. They reported 142 witnessed suppression events, including 85 separate instances where 64 respondents (21%) had their own research affected. Suppression took place where a government agency that provided data or commissioned the research put conditions on the release of the results, or where government employees were part of the research team and were restricted in what they could do. Governments most commonly suppressed research by sanitising the results or by delaying or prohibiting the publication of results (66% of events), but no part of the research process was unaffected. In 48% of cases, the affected researchers believed their work was targeted for suppression because it drew attention to failings in health services. Another 26% of cases related to the health status of a vulnerable group (such as Indigenous Australians, refugees or people with mental illness), while in a further 11% the research had pointed to an environmental harm. In 87% of instances, the government agency succeeded, leaving the public uninformed or giving it a false impression. 2 Interventions to safeguard academic integrity when working with governments Public awareness of the issue and its importance Guidelines for managing conflict of interest in the public service Guidelines for avoiding result-dependent publication in academia Mandatory statements by authors that works have not been subject to a right of veto by government Agreements between government and academic bodies that support researcher independence Independent mechanisms to resolve complaints about suppression of health research Best-practice models of synergistic partnerships between government and academic bodies Organisational values that avoid blame and welcome constructive criticism Inclusion of oversight of government–researcher relations in the role of institutional ethics committees Publicly reported surveillance systems to monitor suppression events

C D’Arcy J Holman MB BS, PhD, FAFPHM

The problems are already well known; what we need are solutions and health care reform The New South Wales Government has announced another investigation into the health care system. This latest inquiry was triggered by the Deputy State Coroner, Carl Milovanovich, who called for a “full and open inquiry into the delivery of health services in NSW”.1 The stimulus for this call was his review of the case of 16-year-old Vanessa Anderson, who died after being admitted to Sydney’s Royal North Shore Hospital. Although mooted to be broader in scope, this inquiry swiftly follows an external review2 and a parliamentary inquiry3 into another patient mishap at the same hospital. In this issue of the Journal, Joseph and Hunyor, two of the Royal North Shore Hospital clinicians who gave evidence at the parliamentary inquiry, provide a first-hand account of the inquiry process and argue the case for clinicians’ active involvement in health care reform (→ The Royal North Shore Hospital inquiry: an analysis of the recommendations and the implications for quality and safety in Australian public hospitals).4 This most recent examination of the health system is yet another in a series of investigations in NSW, reaching back to the Chelmsford Inquiry into deep-sleep treatment between 1988 and 1990,5 and, more recently, to the reviews into Camden and Campbelltown Hospitals, where, earlier this decade, aggrieved whistleblowers asserted that the quality of care was poor.6 That grievance was subject to a Health Care Complaints Commission inquiry,7 the Walker Special Commission of Inquiry8 and several Independent Commission Against Corruption investigations.9 This multiplying effect suggests that inquiries seem to have a way of taking on a life of their own. In the Anderson case, the coroner found that the young woman’s death was due to the depressant effects of opiate medications, which led to respiratory failure. These medications were given as a result of a combination of factors at the hospital, including a lack of communication, poor management, staff inexperience, and poor record-keeping.10 Will another inquiry identify additional systemic problems of which we are not already aware? The answer, the evidence suggests, is no. Our research shows that patient safety inquiries across the world consistently identify the same recurring problems as the cause of iatrogenia: health care below promulgated standards; lack of quality-monitoring processes; patients, family members and concerned staff being ignored and excluded; whistleblowers being vilified; and persistent deficiencies in teamwork, systems and communication.11 If the problems are well known, what is the actual purpose of another inquiry? Peay, reviewing the role of inquiries after homicides committed by psychiatric patients, found that inquiries generally serve four functions: learning, discipline, catharsis and reassurance.12 The learning function incorporates understanding the determinants of problems, as well as learning about solutions. The catharsis and reassurance elements appear self-evident. Announcing an inquiry serves as a way of regaining public confidence that the issue will be investigated in an open manner, and that witnesses, including patients, the community and staff, might be considered as important stakeholders, not only in compiling the evidence but in any activities leading to reform, or even healing, of the health system. As for discipline, inquiries of the type recently announced are generally more concerned with establishing broad principles of system reform than with disciplining individuals, which is most often left to the courts and professional bodies.12 In theory, the discipline function of an inquiry is intended to ensure that the government and relevant department are held accountable not only for inquiry processes, but for implementing recommendations. In practice, however, implementing recommendations is not necessarily a straightforward task that will result in the desired outcome. Two fundamental questions need to be considered before naïvely assuming the government will implement inquiry recommendations. First, is it possible and appropriate to implement the recommendations? Taking the commonly cited issue of deficiencies in teamwork as an example, how does one begin to break down barriers to the way people work together? Who is primarily responsible for addressing deficiencies in teamwork: universities, governments, hospitals or professional groups? Second, what evidence is there to say that implementing the recommendations will improve the quality of patient care? The answer to this invariably requires significant research, thought and expertise. As soon as this latest inquiry was announced, the state Liberal Opposition argued on the front page of the Sydney Morning Herald for a Royal (rather than Special) Commission, as this, it was asserted, would have greater powers to “overhaul” the system.1 There is no doubt that an inquiry can result in an overhauling. The Walker Inquiry was at least partially responsible for the restructuring of the whole NSW Health system, which took years to accomplish and is still not “bedded down”. However, in the aftermath of that restructuring, there is no clear evidence that the number of errors is decreasing across the NSW Health system, nor that restructuring health systems will contribute to a reduction in errors13 — nor that inquiries will, either. The latest inquiry will provide a space for the witnessing of the experiences of patients and staff. It has already begun to fill the newspapers and nightly news slots with interest stories. It will also seek to identify systemic and institutional issues affecting the delivery of health care in NSW.14 Explaining why things went wrong seems to be the underlying purpose of inquiries. Identifying solutions to these problems and undertaking health care reform that results in improved quality of patient care — in other words, actively learning from what occurred — is a separate and undoubtedly more difficult issue. Too often, these fundamentally important tasks are left untouched by the ever-growing number of inquiries.

Joanne F Travaglia MEd · Jane E Lloyd BAppSc, MPH · Jeffrey Braithwaite PhD

Naltrexone implants have not been subject to the usual rigorous scrutiny required for new devices in Australia, but are widely used through the Special Access Scheme In this issue of the Journal, Lintzeris and colleagues report eight patients with naltrexone implants who developed serious medical complications considered to be related to the implant (→ Unplanned admissions to two Sydney public hospitals after naltrexone implants).1 Intuitively, naltrexone is an attractive treatment for opioid dependence, as it is inexpensive, long-acting and generally well tolerated, and blocks the actions of heroin when taken orally. However, empirical support for naltrexone has been unimpressive,2-4 with research showing that poor adherence to treatment limits its effectiveness. An Australian study found that, while patients who adhered to treatment did well, only 2% were still taking the drug 3 months after conventional inpatient detoxification.5 Naltrexone was registered by the Therapeutic Goods Administration (TGA) in 1998 as “an aid in the maintenance of previously opiate-dependent patients who have ceased the use of opioids”.6 However, the Pharmaceutical Benefits Advisory Committee twice rejected applications for the inclusion of naltrexone in the Pharmaceutical Benefits Scheme as a treatment for opioid dependence on the grounds of lack of evidence of efficacy. Controversy over efficacy was followed by growing doubts about naltrexone’s safety. Intermittent naltrexone consumption lowers opioid tolerance, thereby increasing the risk of heroin overdose. An Australian study found the death rate for those leaving naltrexone treatment was eight times that recorded among participants leaving treatment with agonists such as methadone or buprenorphine.7 As the weakness of the case for oral naltrexone became clearer, a range of interventions were developed to overcome the inherent problems of treatment initiation and poor adherence. The publication in 1997 of an article entitled “I woke up . . . cured of heroin” in a popular Australian magazine8 sparked intense community and political interest in the initiation of naltrexone treatment during general anaesthesia or heavy sedation, followed by oral administration. This was said to be a novel, dramatically effective treatment for heroin dependence. However, subsequent evaluation showed that these approaches increased the cost of oral naltrexone without increasing efficacy.9 More recently, depot injections10 and implants of naltrexone have become the focus of public and political hope. In this historical context, it is concerning that the recent research on naltrexone implants in Australia has not followed usual scientific processes. In particular, naltrexone implants have not been subject to the usual rigorous scrutiny required for new drug products seeking registration in this country. Nevertheless, they are available through the TGA Special Access Scheme; there is no requirement for TGA approval for access to unapproved goods in Australia for Category A patients under this Scheme, and no apparent requirement for collection of efficacy or safety data. Supporters of the naltrexone implant have argued that heroin injectors meet the criteria for Category A patients under the Scheme as “persons who are seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment”.11 Most Category A patients have malignant conditions or rare life-threatening diseases. The annual mortality of heroin injectors is in the order of 1%12 — almost 15 times higher than expected for persons of the same age and sex with no history of heroin use, but hardly in the range generally considered appropriate for the Special Access Scheme. But the inclusion of naltrexone implants in the Scheme and their widespread use (reportedly by more than 1500 individuals) means the product has achieved a substantial market while not undergoing the rigorous evaluation usually applied to drugs before registration. Some of the implants used in Australia are produced locally, while others are manufactured overseas. There are doubts about the quality of manufacture, as well as deficiencies in the safety and efficacy data. As far as we are aware, no major national drug regulatory authority has licensed naltrexone implants for management of opioid misuse. However, a depot injection of naltrexone has been approved by the Food and Drug Administration in the United States, but only for alcohol, not opioid, dependence.10 Although the effectiveness, safety and cost-effectiveness of methadone and buprenorphine treatments for heroin dependence are supported by substantial and compelling evidence, a greater range of pharmacological treatments suited to the broad range of individual patients is required. A recent randomised controlled study of depot naltrexone for the treatment of opioid dependence had encouraging results.13 The strong theoretical rationale for the usefulness of naltrexone in treating heroin dependence justifies further rigorous investigations. However, the uncontrolled use of unregistered products of uncertain quality hampers the development of proper clinical trials. Since the thalidomide disaster in the 1960s, all new medications introduced into Australia have been regarded as ineffective and unsafe until proven otherwise. Constant vigilance is required to ensure that only new medications and devices of proven effectiveness and safety are permitted widespread use. The disturbing suggestions of mortality and morbidity from unregistered naltrexone implants make a strong case for an independent review to determine whether this treatment is sufficiently safe for such widespread use. This review should also assess whether the TGA Special Access Scheme has been used to circumvent the requirement for rigorous assessment of the quality, safety and efficacy of naltrexone implants. This assessment is the cornerstone of a drug regulatory system designed to protect the public from ineffective and unsafe medicines. The TGA has the power under the Therapeutic Goods Act 1989 (Cwlth) (s. 31A(2) and s. 41JD) to seek clarification of the Category A classification of patients, and should do so urgently regarding access to unapproved naltrexone products in Australia.

Alex D Wodak FRACP · Robert Ali FAChAM · David Henry FRCP(Edin) · Lloyd Sansom AO, PhD

The main objectives of medical negligence law relate to substandard care — the direction the law will take when new treatment approaches come along is not always clear If two heads are better than one, then four should be much better, and six should be truly formidable. The axiom is especially likely to hold true when the problem at hand is multifaceted, and each head carries knowledge that is relevant, different, and complementary. Therein lies the allure of multidis-ciplinary care (MDC) teams in cancer care. An age has passed since any surgeon, radiologist, pathologist, radiation oncologist, medical oncologist, or general practitioner could legitimately claim to be working both in splendid isolation and safely. Consultation among clinicians is integral to modern medical care. But the physical meeting of so large and diverse a group of busy clinicians, together with their allied health colleagues, for purposes of devising treatment plans for individual patients is a relatively recent phenomenon. Twenty years ago, the notion would surely have been met with disbelief in many hospitals. Today, the growing complexity of cancer treatment, coupled with new knowledge about the promise of team-based management in health care,1,2 are quickly establishing MDC teams as a standard feature of high-quality cancer care. Evidence of the effect of MDC on quality of care is still emerging. Recent studies suggest that cancer patients managed through MDC teams may have better decisions made about their care,3 live longer,4 enjoy better quality of life during treatment,5 and receive services more efficiently.6 However, substantial gaps remain in understanding the impact of MDC.7-9 From a medicolegal perspective, the salient aspect of MDC is that it shifts aspects of clinical decision making away from single actors and toward groups. How will courts handle allegations of substandard decision making levelled at all members of the team, or the team itself? Will team members with second-hand know-ledge of the patient’s condition assume less responsibility for faulty plans than those directly involved in the patient’s care? What of members who opposed the care path chosen? And what obligations do hospitals have to ensure MDC teams are established and that they play a meaningful role in clinical decision making? The short answer to these questions is that we don’t know yet. The absence of negligence claims targeting MDC in Australian courts and Anglo-American jurisdictions abroad means that we must speculate (although it is surely just a matter of time before litigation on point materialises). A threshold question in any negligence claim is whether the wrongdoer owed a duty of care to the person wronged. In medical negligence claims, the defendant’s duty is rarely disputed. In fact, tort law textbooks present the patient–doctor relationship as a paradigmatic example of a dutiful relationship. Occasionally, however, the assumption is challenged. Telemedicine10 and supervision of trainees by senior doctors at a distance11 are two recent examples of circumstances that force close consideration of the contours of the patient–doctor relationship. In both situations, duties may be imposed, even when the defendant clinician works at a considerable remove from the injured patient. The wise course is for each member of an MDC team to assume that, by virtue of their involvement in a team meeting, they assume certain responsibilities to the patient. (Indeed, responsibilities arise in virtually any setting in which doctors turn their mind to a particular patient and give advice.) Fulfilling those responsibilities requires sound judgement and informed input, commensurate with what would be expected of a team member’s professional peers were one of them seated at the same table and presented with the same information. If the first step in a medicolegal analysis of MDC is to recognise that the team and its members may be exposed to liability for their activities, the second step is sober assessment of how large that exposure is, and what can be done to minimise it. In this vein, the article by Evans and colleagues in this issue of the Journal (→ Medicolegal implications of a multidisciplinary approach to cancer care: consensus recommendations from a national workshop)12 is a welcome addition to the literature. The authors outline consensus recommendations developed at a workshop of experts. Their suggestions are clear and useful, particularly the need for attention to MDC activities in the informed consent process and careful documentation of team membership and resolutions. To these, I would add a simple exhortation to participants in MDC team meetings. Speak up! Your professional responsibilities entail weighing in wherever your expertise is relevant. If information is insufficient to render an informed opinion, say so. Group consensus is helpful, and learned clinical colleagues acting in good faith will often arrive at it, but, as Sidhom and Poulsen point out, MDC meetings should not be regarded as a strictly democratic process in which majorities rule.13 Disgruntled wallflower is the wrong part to play in an MDC team. Standards of care in medical negligence law are fluid and progressive. Today’s cutting-edge treatment may become a routine and expected treatment in the future, as it diffuses through clinical practice and evidence of its efficacy mounts. A curious aspect of negligence law is that novel treatments or approaches to care tend to raise heightened liability risks in their innovation phase, but once they gain currency, the risk profile flips: failure not to employ them becomes the greater liability risk. Recognition of this legal reality brings special resonance to the investigation of the uptake of MDC approaches among breast surgeons by Marsh and colleagues in this issue of the Journal (→ National Breast Cancer Audit: the use of multidisciplinary care teams by breast surgeons in Australia and New Zealand).14 Standards of care are not defined purely by reference to the prevalence of particular practices in the medical community; nor are recommendations and guidelines from august professional bodies, such as the National Breast Cancer Centre, accepted as definitive proof as to whether a particular practice has become an accepted standard. On the other hand, both factors are highly relevant considerations in determining the applicable standard of care. In Australia today, at least in some settings, MDC has probably become the standard of care for treatment of some cancers, particularly breast cancer. For other cancers, it likely stands on the cusp of becoming so. Thus, Marsh and colleagues’ findings14 should grab the attention of administrators and practitioners working in hospitals that have not adopted MDC practices. Rural and private facilities appear particularly likely to be in this situation. Many rural and private hospitals will face barriers to MDC that their counterparts in urban and public settings do not, as the article’s authors point out.14 Standards of care can bend to accommodate unavoidable resource and manpower constraints. However, in institutions where an MDC approach is feasible but is not being pursued, hospital leaders should carefully review their position. It is conceivable that a claimant may allege that the appropriate approach for breast cancer treatment was not followed and that, had it been, the harm in question would not have occurred. Such accusations would be likely to fall particularly heavily on the institution itself for failing to organise for effective MDC. Success for the plaintiff in this type of claim will not be easy. The evidence that MDC systematically improves quality of cancer care remains quite thin,7-9 which makes proving that it would have done so in an individual case an uphill climb. Nonetheless, it is quite possible that litigation along these lines may be brought. In that event, defendant institutions will no doubt find the attendant publicity unsavoury, whatever the claim’s outcome. The law aims to promote high-quality care, not retard it. Legal doctrine is neither static nor vacuum-sealed. As practices change, and promising initiatives like MDC emerge, the law must evolve to accommodate them, without abandoning its commitment to holding providers accountable for substandard care. Timely scholarship, like the articles in this issue of the Journal,12,14 can help guide that evolution at the right pace and in the right direction.

David M Studdert LLB, ScD, MPH

The benefits are greater efficacy and faster onset of action; the price is increased risk of bleeding . . . The mainstay of antiplatelet therapy for patients with acute coronary syndromes (ACS), including those undergoing early percutaneous coronary intervention (PCI), is the combination of aspirin and clopidogrel.1-3 Aspirin inhibits platelet thromboxane A2 production and platelet activation, and reduces the relative risk of recurrent ischaemic events in patients at high risk of vascular events by about 22% (absolute risk reduction [ARR], about 2%) at the expense of an increase in the odds of major bleeding events by about 60% (absolute risk increase [ARI], about 0.5%).1 Clopidogrel inhibits ADP-induced platelet activation by blocking the platelet P2Y12 receptor. When added to aspirin therapy in patients with ACS, it reduces the risk of recurrent ischaemic events by a further 20% (ARR, about 2.1%) at the expense of an increase in major bleeding events by approximately 38% (ARI, about 1%).2,3 Clopidogrel has several potential limitations, however. First, the onset of action is delayed, with a “therapeutic” level of 50% inhibition of ADP-induced platelet aggregation, as measured by light transmission aggregometry (LTA), not being reached until 4–6 hours after a 300 mg loading dose, and 2 hours after a 600 mg dose. Second, there is a “ceiling” effect — even a 900 mg dose achieves only around 60% inhibition of ADP-induced platelet aggregation. Third, laboratory testing suggests that “therapeutic” platelet inhibition is not achieved in a substantial proportion of patients because of individual variability in platelet inhibition by clopidogrel.4 Finally, there is uncertainty about the clinical benefit with higher loading doses of clopidogrel of 600 mg or 900 mg compared with 300 mg.5,6 Prasugrel is a novel thienopyridine prodrug whose rate, magnitude and consistency of platelet ADP inhibition is greater than for clopidogrel. It achieves more than 50% inhibition of platelet aggregation (measured by LTA) within 1 hour of a 60 mg loading dose.7,8 The safety and effectiveness of prasugrel have been compared with standard-dose clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel — Thrombolysis in Myocardial Infarction (TRITON–TIMI 38).9 A total of 13 608 patients with moderate-to-high-risk ACS scheduled for PCI were randomly assigned to receive prasugrel (60 mg loading and 10 mg daily maintenance dose) or clopidogrel (300 mg loading and 75 mg daily maintenance dose) for 6 to 15 months. Aspirin 75–162 mg daily was recommended for all patients. After a median duration of 14.5 months, the primary efficacy outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke occurred in 12.1% of patients taking clopidogrel and 9.9% of those taking prasugrel (hazard ratio [HR], 0.81; 95% CI, 0.73–0.90). Stent thrombosis was also reduced (2.4% clopidogrel v 1.1% prasugrel; HR, 0.48; 95% CI, 0.36–0.64). However, the key safety endpoint of major bleeding not related to coronary artery bypass graft (CABG) was increased (1.8% clopidogrel v 2.4% prasugrel; HR, 1.32; 95% CI, 1.03–1.68). All major bleeding (including CABG-related) was increased (1.7% v 2.5%; HR, 1.31; 95% CI, 1.16–1.50), as was fatal bleeding (0.1% v 0.4%; HR, 4.19; 95% CI, 1.6–11.1). Overall mortality did not differ significantly between treatment groups. A post-hoc subgroup analysis identified less clinical efficacy and greater bleeding among patients with a history of stroke or transient ischaemic attack, older people (age > 75 years), and those with bodyweight less than 60 kg. It is likely that these results are externally valid. However, by design, the study drug was only given after the coronary anatomy had been defined by angiography. This does not reflect usual clinical practice where clopidogrel is given at the time of presentation with ACS. Because there is a delay in the onset of action of clopidogrel, the design was biased in favour of prasugrel. Also, the prescribed standard 300 mg loading dose of clopidogrel was lower than that now adopted by many clinicians following reports of an improved inhibition of platelet aggregation with higher loading doses of clopidogrel such as 600–900 mg in patients with PCI.6 These caveats aside, the data suggest that treating 1000 patients with ACS at moderate-to-high risk of vascular events with prasugrel (compared with clopidogrel at the standard approved dose) for a median duration of 14.5 months would prevent about 22 major vascular events and cause eight major haemorrhages, including three fatal bleeds. The implications for clinicians, should prasugrel gain regulatory approval, are that it may allow cardiologists to delay their decision to administer a P2Y12 inhibitor until after coronary angiography (thus avoiding the bleeding risk of clopidogrel in patients who need urgent CABG), and to use prasugrel instead of clopidogrel in the acute phase of ACS, possibly using clopidogrel for long-term maintenance therapy. The implications of these results for researchers are that it is important to determine whether the risk of long-term bleeding with prasugrel may be reduced, without compromising efficacy, by using lower doses and by avoiding its use in those with previous stroke or low bodyweight, and older people. A lower dose of prasugrel is presently being compared with clopidogrel in the TRILOGY study, involving 10 000 patients with ACS who are treated medically. Research is also needed to evaluate the potential for individualised antiplatelet therapy based on the results of point-of-care testing of platelet function and genetic polymorphisms. Meanwhile, large randomised trials are presently comparing: the efficacy and safety of a high loading dose and maintenance dose of clopidogrel (versus a low loading dose and maintenance dose); the oral reversible non-thienopyridine ADP receptor antagonist, AZD6140, with clopidogrel; and the parenteral reversible non-thienopyridine ADP receptor antagonist, cangrelor, with clopidogrel, all in patients with ACS treated with an early invasive strategy.

Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MB BS, FRACP, FRCPA · Paul E Langton MB BS, FRACP

Global environmental change is threatening the health and survival of humankind — are we doing enough to ensure the environmental and social bases for health? Global warming and resultant climate change pose serious risks to human health.1-3 However, global warming is only one of a nested series of threats to the health — and even survival — of humankind. With this in mind, is our current approach to both clinical and public health sufficient? Parallel threats to the health and wellbeing of humanity arise from a myriad of anthropogenic problems (Box). All such problems, acting synergistically, stress the ecological and social foundations upon which humanity relies for air to breathe, water to drink, food to eat, and disposal of waste, and without which there can be no civilisation and no economy. Taken together, they comprise what has been described as global environmental change (GEC).4 There are many drivers of GEC. Our complex society is heavily dependent on oil to function, even though the supply of easily recoverable oil has peaked or is about to peak.5 However, the fossil fuel bonanza over the past century and a half has enabled a human population explosion that, in turn, has been driving GEC. As populations expand and encroach into new areas, destroying natural habitats and putting animals and humans into close proximity, humans are being increasingly exposed to novel animal diseases. HIV and emerging diseases such as Ebola virus, severe acute respiratory syndrome and H5N1 avian influenza may be manifestations of this.6 The rising population, ecological stress, and neoliberal-driven economic disparity all contribute to political unrest and human violence,7,8 which drive further GEC. Consequently, humanity is facing a series of serious, unprecedented ecological and social changes caused by ourselves. Of these, it is global warming that, if not the most dangerous threat, is the fulcrum about which to coordinate analysis and action. To express concern about the survival of humankind is not being alarmist. Our understanding of the threats facing humanity has moved to a point where the full range of possibilities confronting us can be appreciated. Where we end up consequent to GEC in the next two centuries will be somewhere on a continuum that extends from the extinction of Homo sapiens, through collapse or patchy disintegration of complex industrialised society, to a sustainable industrial civilisation. Exactly where we find ourselves on this continuum depends on how quickly and effectively we act environmentally, economically and socially. Our survival also depends on our ability to control weapons of mass destruction, which are more likely to be used as the consequences of GEC generate conflict over access to ever scarcer resources. As health carers, we are involved on several levels. Individually, we are both part of the cause of GEC and recipients of its effects. As health care professionals, we will need to modify both our health systems and the way we practise to meet the challenge of new health problems, and to adapt to old health problems in new guises. As health professionals, we also have a duty of care to our patients to strongly advocate for action. Serendipitously, GEC also presents unique opportunities. GEC and economic inequity have related causes. Thus, a strategic approach would enable humanity to derive a set of solutions that will make the world both environmentally sustainable and more economically just,7 with flow-on benefits for health. Indeed, Jonathan Patz proposed that “global climate change could be the greatest public health opportunity we’ve had in over a century”.9 Changes needed to mitigate and adapt to GEC present specific health opportunities; for instance, less car use means more exercise. Howard Frumkin has explained how redesigning cities and rearranging traditional work practices can enhance exercise, build social capital, and make a healthier society.10 While beneficial, such changes are not in themselves sufficient. GEC is adversely affecting our society and will continue to do so. The medical community can no longer limit its focus to hospital waiting times, fee levels, workforce shortages, obesity and diabetes. These issues all become starkly irrelevant if the ecological and social systems on which we depend for both our survival and our capacity to deliver services, save lives and care for people stop working. We need a profound shift in our paradigm. The health care sector is not only responsible for delivering health care, but must also ensure the environmental and social bases for health itself. To meet this responsibility, we can act personally — buy a hybrid car, for instance. Individually, we can join and financially support organisations that are working for change: Doctors for the Environment Australia, the Medical Association for Prevention of War, the Australian Conservation Foundation, and others. But collectively, our academic colleges and professional associations must advocate strongly and clearly to government about the gravity of our predicament and the need for urgent, wide-ranging action. Humanity needs a new vision for health for the year 2100: to make sure we have an economically equitable society on an ecologically healthy planet. The stakes are high — we must not fail. The challenge I put to all of us and to our health and political leaders is to work together to make this vision a reality. Serious current environmental problems* Destruction/loss of natural resources natural habitat (ecosystem services) wild food sources biological diversity soil (erosion, salinity, fertility) Ceilings on natural resources (soft ceiling, raising the ceiling costs) energy (fossil fuel and alternatives) fresh water photosynthetic capacity of plants Harmful things made or moved around toxic chemicals alien species atmospheric gases (greenhouse gases → climate change, ozone destruction) Increasing human population actual numbers impact per capita on the environment (resource use and waste) * Derived from Diamond J. Chapter 16. In: Collapse: how societies choose to fail or survive. London: Allen Lane, 2005.

Peter W Tait MB BS, FRACGP

Medical students should be selected on criteria that include desirable personal qualities, using procedures with demonstrated reliability and validity How best to select medical students (ie, future doctors) is a topic that has rarely been out of the medical journals and the daily newspapers during the past 30 years. In this Journal in 1974, Campbell et al wrote: “Although mounting criticism and concern are expressed for the manner in which our medical students are selected, the status quo continues”.1 The status quo alluded to was selection of medical students solely on the basis of academic marks obtained in high school matriculation examinations. Fifteen years later, John Best, in one of his regular articles for the Journal,2 acknowledged that to be a good doctor required skills and personal qualities additional to academic aptitude, and wrote: The leap of logic that equates high marks in an examination at the terminal end of adolescence with a humane and caring medical profession is a nonsense, but is sustained because nobody has any other solution which is strong enough to combat ... the “high-enough mark method”. The University of Newcastle led a major change in medical education in Australia in the late 1970s by introducing problem-based learning, early clinical skills acquisition, community orientation, and the addition of personal qualities evaluation to the student selection process. The first Newcastle students were admitted in 1978. The Foundation Dean, David Maddison, anticipated the current debate and planned accordingly. The “Newcastle Experiment”3 involved half the students being admitted on the basis of academic marks alone (top 1%–2%), irrespective of personal qualities assessed by test and interview; the other half were admitted on the basis of personal qualities after applying an academic threshold (top 10%). After a 9-year period, prior academic performance and personal qualities at the time of selection were compared with two outcome measures: a negative measure — non-completion of the course — and a positive one — graduation with honours. The results showed no relationship between either outcome and prior academic performance. However, there were important associations for both the negative and positive outcomes with personal qualities at the time of selection. The interview had the most predictive power in the selection procedure — those who did well in the areas of communication skills, motivation to be a doctor, and capacity to provide support to those in distress had a greater likelihood of completing their studies at medical school and of graduating with honours.4 The Newcastle Experiment was followed by another study, on interns in New South Wales hospitals, which demonstrated that Newcastle graduates at the beginning of internship were the equals of graduates of the other NSW medical schools in clinical competence, and had higher scores in the four personal characteristics evaluated5 — a desirable endpoint in the context of being a professional doctor. It is probable that the findings documented in these two studies and others from Newcastle influenced selection procedures across the country, for by the mid to late 1990s nearly all Australian medical schools had begun to select students on the basis of both academic ability and personal qualities assessed by tests and interview. Ten years down the track, the evaluation of personal qualities by interview is now being abandoned by some schools. Why is this happening? A study from the University of Queensland, reported in this issue of the Journal, gives some indication (→ Medical school selection criteria and the prediction of academic performance).6 Its major finding is that criteria other than prior academic grades only modestly predict academic performance in the medical course. That prior academic achievement should predict subsequent academic achievement is no surprise;7 indeed it is almost axiomatic. However, given the current view that graduating doctors should be more than just academically competent, it is of some concern that academic performance was the sole outcome measured in the study. In the present-day context of what we expect in a graduating doctor, the important finding in the Queensland study is the significant association of the interview scores with assessment outcome, especially the increased association for Year 4 (when, presumably, more clinically relevant matters are tested) compared with Year 1. The size of the effect is small, but medicine is accustomed to important small effects, such as the link between passive smoking and lung cancer. The finding that the written Graduate Australian Medical School Admissions Test (GAMSAT) does not predict within-course academic performance is very interesting, particularly given GAMSAT’s emphasis on scientific knowledge and understanding. It is puzzling that the University of Queensland has decided to abandon the interview, given the significant results of their study. Even more puzzling is the stated intention to retain GAMSAT, which had no predictive power at all. In another recent study published in the Journal, GAMSAT was found to be a negative predictor of clinical reasoning.8 The most logical explanation for the proposed selection strategy is one founded on cost. No one questions the fact that having a selection process based on anything other than prior academic performance at school or university is expensive. It is expensive in time and effort for university staff, for community interviewers and for the applicants themselves. It is also politically expensive, especially when applicants with exceptionally high prior academic scores are not selected. The outrage expressed in a number of recent media reports9,10 reflects the passion with which sections of the public regard admission to medical school. Is the interview being abandoned because it is too expensive in terms of time and resources? Is GAMSAT being retained because it costs the medical school nothing, since applicants pay for it, and its numerical scores are a convenient way to differentiate between applicants? The evidence from these two Australian medical schools,3-6 together with community expectations of the skills and competencies of a graduating doctor, supports the retention of methods to evaluate personal qualities during selection. However, this approach, especially the interview, comes at a cost. The question for medical schools is whether the effectiveness is worth the cost. If it is not, we should be honest with ourselves and the public and say that the cost is too much, even though it works. My view is that we should continue to select medical students based on criteria that include desirable personal qualities, using procedures that have demonstrated reliability and validity. We also need to build into medical curricula objective barrier assessments of professional skills and personal qualities relevant to future medical practice. If we do this, we will not only graduate doctors who have the required skills, but we will have the appropriate outcome measures against which to evaluate our personal qualities selection procedure. If we elect not to take these two steps, we will be destined to go through yet another cycle of questioning selection methods. Campbell and colleagues’ 1974 comments1 will be reprised by others.

David A Powis PhD

Should we be devoting energy and resources to reversing obstructive sleep apnoea in patients without symptoms? Over the past four decades, obstructive sleep apnoea (OSA) has emerged as a prevalent, clinically important disorder. Snoring, which is often a hallmark of OSA, is seemingly ubiquitous in middle-aged men. Over 80% of Australian middle-aged men snore for more than 10% of the night.1 Snoring is also common in women. Although it is undoubtedly an important social nuisance, it remains unclear whether snoring alone (in the absence of sleep apnoea) carries with it any serious health risk. Twenty-five per cent of middle-aged men and 10% of women have OSA, defined as > 5 obstructed breathing events per hour of sleep.2 The prevalence in women rises sharply after menopause. Other risk factors are obesity, older age and a family history of OSA. Population-based studies in China and India indicate that its prevalence is at least as high as that reported in Western countries. A complex interplay between regulation of breathing during sleep, facial anatomy and obesity predicts the development of OSA.2 In contrast to the uncertainty of the effects of simple snoring, OSA clearly has significant health consequences. Many patients with OSA experience excessive daytime sleepiness and impaired cognitive function, increasing the potential for traffic crashes, work accidents and reduced productivity at work.3 Over 50% of Australian truck drivers have mild OSA or worse.4 Moreover, Access Economics has estimated that the cost of sleep disorders to the Australian community is over $7 billion, and much of this cost relates to OSA.5 Increasing awareness of OSA has been followed by an appropriate increase in clinical investigations of sleepy patients with suspected OSA. This is further driven by the availability of cost-effective treatments, notably continuous positive airway pressure (CPAP) and mandibular advancement splints. Recent studies have suggested that OSA is associated with an increased risk of cardiovascular disease.6 Publicity about this research has led to an increasing tendency for people who are not sleepy or who have minimal symptoms to be referred for assessment and treatment of OSA. However, in contrast to the sleepy patient, for whom CPAP usage is reinforced by reduction in sleepiness, asymptomatic patients have more variable compliance.7 Should we be devoting substantial clinical energy and resources to reversing OSA in such patients to prevent cardiovascular disease and death? Certainly, data from cross-sectional and prospective population studies and sleep clinic studies indicate that OSA is associated with a higher prevalence of cardiovascular and cerebrovascular disease and insulin resistance.6 Untreated male patients with severe OSA have significantly greater risks of fatal and non-fatal cardiovascular events than healthy controls (odds ratios, 2.87 and 3.17, respectively).8 However, cross-sectional and observational studies have unmeasured confounders, such as visceral obesity.6 In addition, observational studies can be affected by treatment bias. Patients who refuse to use CPAP and seemingly have higher cardiovascular risk than those who comply with CPAP treatment8 may be the same people who refuse to stop smoking or take lipid-lowering or blood pressure-lowering medication. In contrast, there is good evidence from randomised controlled trials that CPAP lowers blood pressure (mean decrease in systolic and diastolic blood pressure of 2.46 and 1.83 mmHg, respectively), but most studies are relatively short (less than 8 weeks), and treatment effects are hard to demonstrate in patients who are not sleepy.9 The remaining short-term CPAP trials that have focused on other intermediate markers of cardiovascular disease (lipids, glucose control, high-sensitivity C-reactive protein) have been inconclusive. For example, a recent short-term randomised trial failed to show any improvement in insulin sensitivity in patients with type 2 diabetes and OSA.10 No data are available from long-term, well powered, randomised controlled trials assessing the effect of CPAP on hard cardiovascular endpoints, such as myocardial infarction and stroke, in patients with OSA. Medical research is well populated by “positive” results from cross-sectional, observational or short-term intervention studies, but their results have not been reproduced in rigorous, long-term, large-scale clinical trials. To remedy this lack of information, several long-term trials of CPAP treatment in OSA are being planned or have commenced, including one initiated by Australian investigators (Sleep Apnea CardioVascular Endpoints Study [http://www.savetrial.org]). These trials will determine whether treatment of OSA decreases the incidence of new cardiovascular events. In the interim, how should we manage patients with a diagnosis of repetitive OSA who present with complaints of snoring but have minimal or no daytime sleepiness? First, it is important to establish whether such patients are genuinely asymptomatic or simply underreport symptoms that are obvious to their families or work colleagues.11 Second, the disorders of these patients typically are characterised by higher rates of central adiposity, glucose intolerance and other vascular risk factors.6 Given that middle-aged men often neglect to monitor such risk factors, referral for snoring may provide an excellent opportunity for a general health assessment and to institute an intervention, such as advice to exercise and lose weight. Moreover, it would be reasonable to prescribe a trial of CPAP for a patient with asymptomatic OSA and hypertension refractory to maximal medical therapy and to monitor the blood pressure response over 24 hours. Finally, it would be reasonable also to inform asymptomatic patients with severe OSA and coexisting cardiovascular disease of the possible association between OSA and a risk of future vascular events. However, it would be inappropriate to coerce these patients into accepting a treatment that might falsely make them feel secure about future risk and might result in neglect of proven risk factors. Future research, ideally, will enable clinicians to get to the “heart of the matter” when discussing cardiovascular risk management and sleep apnoea with these patients.

Ronald R Grunstein MD, PhD, FRACP · Craig L Phillips BSc

An integrated comprehensive approach to medication error is a national imperative Medication errors are among the most common incidents reported in public hospitals.1,2 This is not surprising, given that every admitted patient receives some medication. If medication is one of the hallmarks of treatment in our institutions, it, more than any part of our practice, should be made safer and, wherever possible, error-proof. In New South Wales public hospitals, the Incident Information Management System (IIMS) report for 2005–20063 included 17 367 medication incidents in which medication error was the primary cause of harm. In another 968 incidents, medication error was a secondary cause. Most incidents were notified from the services of general medicine or pharmacy, but all clinical services, including surgery, reported medication errors. The severity of most reported medication errors is minor. In the IIMS report, less than 0.3% of notified medication incidents in NSW were given a severity assessment code of 1 (SAC 1), compared with 0.8% SAC 2, 25.9% SAC 3 and 56.2% SAC 4 (SAC 1 = severe harm; SAC 4 = trivial or no harm). In this issue of the Journal, Nichols and colleagues4 examine medication errors and highlight the types and context of errors at Fremantle Hospital, Western Australia (→ Learning from error: identifying contributory causes of medication errors in an Australian hospital). Although the study was based on a small sample, its principal strength was that it examined not only the incident but also the environment, the team, the tasks being undertaken, and the individual circumstances of those “responsible” for the error. The study cohort was selected by pharmacists during regular ward rounds over a 6-month period. Fremantle Hospital participates in the Australian Incident Monitoring System and has patient safety committees. The Fremantle Hospital study did not give error rates, but the IIMS data3 suggest that the problem of medication errors is not small. We need to reinvigorate attempts to provide secure prescribing environments. Practitioners must be able to concentrate, without distraction, on the patients for whom they are prescribing. They must have adequate information on the indications for prescription, potential complications, contraindications and drug interactions of the prescribed medications. Nichols et al reported that 7/26 members of staff (27%) indicated there was lack of guidance from senior colleagues when they were prescribing unfamiliar medications, 8/26 (31%) were dealing with an unfamiliar patient when the error was made, and 5/26 (19%) were working in an unfamiliar ward! Hastily scribbled notes during a rushed ward round from a senior consultant who presupposes competencies to a newly posted intern are not a prescription for safety, but a recipe for error! Root-cause analysis data from NSW5 have shown that major factors leading to severe incidents (SAC 1) include deficiencies in policy (25%), communication (25%) and knowledge/competency (18%). These data are consistent with the study of Nichols et al, in which poorly defined policies or inadequate drug information were found to be a factor in 23% of medication errors. In the Fremantle Hospital experience, communication within the team was a factor in medication errors in 31% of incidents, and communication with others was also a factor in 31%. Various initiatives that may lessen the risk of medication errors in Australian hospitals require more evaluation. The National Inpatient Medication Chart,6 commissioned by the Australian Council on Safety and Quality in Health Care, is an important advance. All junior staff now know where to prescribe, how to look for and how to document medication. This evidence-based best practice initiative, led by the Safe Medication Practice Unit of Queensland Health, addresses key problems, such as the prescribing and dispensing of warfarin. It is important that the national initiative not be undermined as individual hospitals, units or clinicians make local modifications. Rather, local lessons must contribute to the national debate and the standard document should be improved by consensus. Standardised formats for multiple-drug protocols must also be developed. Many hospitals do not yet use electronic prescribing. The drug advice available to junior staff often consists of a dilapidated, torn and hard-to-find MIMS publication that is often many months out of date. Although MIMS is now available online in all public hospitals (except in South Australia), and NSW Health has a state licence for personal digital assistants (PDAs) for all staff, neither technology (online or PDA) is fully utilised in the public sector. Other electronic sources of drug information available include the “Therapeutic guidelines” series (http://www.tg.com.au/index.php?sectionid=97), the Australian medicines handbook (http://www.amh.net.au) and the Clinical Information Access Program (http://www.ciap.health.nsw.gov.au). Whatever the technology or software used, it is essential that teams develop, with hospital pharmacists, relevant orientation procedures, including information on medication usage, for new members of the team. Medication reconciliation7 (the formal process of obtaining a complete and accurate list of each patient’s current home medications and comparing the clinician’s admission, transfer or discharge orders with that list) and pharmaceutical review8 (the systematic appraisal of all aspects of a patient’s medication management to optimise patient outcomes) provide opportunities for minimising “slips and lapses”, but are not yet seriously “on the radar”. Multidisciplinary hospital drug committees could provide local champions for such programs, collect and evaluate data and develop the evidence base. These issues demand systematic attention from hospitals, administrators and clinicians. The NSW Therapeutic Advisory Group and the Clinical Excellence Commission (NSW) have adapted a Medication Safety Self-Assessment (MSSA) tool developed by the Institute for Safe Medication Practices (ISMP) in Canada and the United States for use in the Australian health care environment.9 A similar antithrombotics tool10 addresses the critical issues around the narrow therapeutic index of antithrombotic medicines. These tools, which are complementary to the Indicators for quality use of medicines in Australian hospitals,11 allow hospitals to assess their own performance and provide national information about safe medication use. Their effectiveness in reducing medication harm is yet to be proven in Australia. The ISMP MSSA tool was evaluated in the US12 in 2002 and again in 2004. Collaborating members did demonstrate continuing improvement in key elements of medication safety (Cohen MR, Vaida AJ. ISMP Medication Safety Self-Assessment — Australian version: experience in the United States. International video conference launch of MSSA. Sydney: ISMP, Feb 2007 [unpublished]). These and other tools could enable all clinicians to measure medication practice, monitor new protocols and minimise the types of slips, lapses and incidents reported in the study by Nichols and colleagues. An integrated comprehensive approach to medication error is a national imperative. We should not be afraid to compare and contrast systems, as long as designs allow an interface between core national and state platforms. Nichols and colleagues have given the problems of medication error human faces — both staff and patient. Only serious system-wide measurement and evidence-based change can return smiles to those faces!

Clifford F Hughes AO, FRACS, FACS, FACC

Excessive reliance on intraocular pressure to detect glaucoma leaves many affected patients undiagnosed and untreated; visualisation of the optic disc is a dying art that needs to be revived Intraocular pressure (IOP) is measured by tonometry. In our community, mean IOP is around 15 mmHg, with a normal range (mean ± 2 SD) regarded as 10–21 mmHg. This information is irrelevant to the diagnosis of glaucoma. Misconceptions about the importance of IOP in diagnosing and screening for glaucoma continue to result in unnecessary blindness in Australia from glaucomatous optic neuropathy. An aggressive realignment in our thinking is required. The classic diagnostic triad for glaucoma of raised IOP, arcuate visual field loss and optic nerve head cupping has been inverted. Glaucoma may now be defined as a characteristic, progressive, optic neuropathy showing optic disc cupping as a consequence of neural rim loss. It tends to produce arcuate visual field loss. It is frequently associated with an elevated IOP, but may be diagnosed at any IOP if there is characteristic optic disc and/or visual field damage. This damage indicates susceptibility of that optic nerve to a given IOP. Early work established a population mean IOP, with an about normal distribution.1 It is regrettable that this result came to be interpreted as indicating a “normal” (ie, safe) IOP for an individual patient, particularly as that report recognised that glaucoma could occur despite an IOP of less than 21 mmHg. In the Baltimore Eye Survey, more than 50% of patients with newly diagnosed glaucoma had a “normal” IOP on a single tonometry measurement.2 The term “normal pressure glaucoma” (NPG) has been coined for such eyes, and they may comprise a third to a half of all open-angle glaucoma cases.2,3 Conversely, there is a subset of the population that has IOP elevated above normal, yet does not have glaucoma. This status is labelled ocular hypertension. Detection of elevated IOP remains important at any time. The prevalence of glaucoma at successive levels of IOP greater than 21 mmHg rises exponentially.4 IOP is the single greatest risk factor for glaucoma, and its reduction is the cornerstone of all current treatment. Screening on the basis of IOP alone, however, clearly produces a high rate of potentially disastrous false negatives. Patients continue to undergo “eye-checks” and be reassured that they do not have glaucoma solely on the basis of an IOP measurement. This represents an inadequate standard of care. Visual field loss is no longer a sine qua non of diagnosis. In recognition that up to 40% of axons may be lost from the optic nerve before visual field loss is evident on standard automated perimetry,5 the term “preperimetric glaucoma” connotes this early disease. Rather than being a distinct entity, preperimetric glaucoma really indicates the inadequate sensitivity of this standard psychophysical test in detecting early glaucoma (as compared with its invaluable role in confirming and monitoring established disease). Early detection of disease can thus depend entirely on identifying optic disc cupping, notching or rim loss, and associated retinal nerve fibre layer defects, perhaps in the absence of raised IOP or visual field loss. Newer and more sensitive tests of specific visual processing such as frequency doubling perimetry or short wavelength automated perimetry may detect glaucoma earlier, and may thus shift the boundary in defining preperimetric glaucoma.6 We must also disabuse ourselves of any convenient dichotomy between chronic open-angle glaucoma and acute angle-closure “glaucoma”. (Acute primary angle closure [APAC] causes a painful, unilateral red eye with markedly elevated IOP: patients with APAC may not have optic disc cupping or visual field loss.) It is increasingly evident that a massive and untreated burden of chronic angle-closure glaucoma exists, particularly in Chinese and South-East Asian people,7 and therefore in our immigrant populations and their families. Glaucoma, whether open-angle or closed-angle, is an insidious disease — “the sneak thief of sight”. Its prevalence increases exponentially with age; progression is slow, painless and irreversible; visual acuity is affected only late; and symptoms of peripheral vision loss with mobility difficulties do not occur until gross levels of field constriction have developed. For all these reasons, affected patients tend not to present but instead need to be found. Prevention — or at least slowing — of further vision loss is possible with an effective range of medical, laser or surgical therapies directed at lowering IOP to an individualised target level (which may be considerably lower than 21 mmHg). The limitation to our preventing blindness in Australia is not so much a lack of therapies, but inadequate case detection. Awareness of the newer concepts in glaucoma has been variable among general practitioners, optometrists and even ophthalmologists. Glaucoma has a prevalence of around 3% in the population aged over 50 years, yet 50% of cases of glaucoma in Australia today remain undiagnosed.8 The Melbourne Visual Impairment Project provides a further indictment: of the patients whose glaucoma was detected during the survey and who had seen an eye-care practitioner in the preceding 12 months, nearly half (many of whom had established visual field defects) had not had their glaucoma diagnosed.9 Highly sensitive screening programs of the general population for glaucoma are, however, not cost-effective, producing low case yields and a high number of false positives.10 Despite a panoply of technological wizardry, there remains no device that in a single or screening test can identify early glaucoma with appropriate sensitivity and specificity. Local research is progressing with international collaborators to identify genetic loci responsible for glaucoma,11 but a blood test to identify those genetically at risk is not generally available. What is to be done? Ophthalmologists diagnose and manage glaucoma, but are referral-dependent and thus see a selected sample. The aim that every Australian aged over 40 years have a general eye examination by an eye-care practitioner remains an elusive goal, but such a strategy could detect glaucoma as well as other ocular abnormalities, particularly if glaucoma sufferers could be prompted to reveal their diagnosis to first-degree relatives. “More funding” is a mantra so tired as to engender indifference, but would certainly enable more targeted, resource-intensive testing.12 While the benefit of disease detection seems self-evident, legitimate public health arguments could be mounted that, as progression of glaucoma is slow, diagnosis and treatment of early disease (particularly in older patients with preperimetric glaucoma) is not justifiable. We must also be mindful of the burden of the diagnosis and treatment for the patient.13 Screening protocols would therefore be directed not to detecting early glaucoma per se, but rather to finding those with a greater lifetime risk of loss of functional vision (ie, advanced disease, younger age or higher IOP). In the absence of such a structured program, we are dependent on “opportunistic screening”. In this issue of the Journal, Zegers and colleagues present two clinical vignettes illustrating the importance of a family history of glaucoma,14 which is an excellent starting point in case detection (→ Primary open-angle glaucoma: the importance of family history and role of intraocular pressure). Glaucoma suspects can also be identified by general practitioners and optometrists prepared to examine the optic disc. For the former, ophthalmoscopy is a dying art that needs to be rejuvenated in training programs so that visualisation of the optic disc can resume its place in the routine medical check-up. Optometrists, on the other hand, are technologically equipped and trained to detect and diagnose eye disease, are frequently primary eye-care practitioners, and are numerous. The recent move by a vanguard of optometrists into therapeutics and comanagement remains politically vexed. Nonetheless, medical practitioners must accept and encourage the major contribution to glaucoma detection that many optometrists make. Vision loss from glaucoma is most often preventable. Current therapies are effective if the diagnosis is made early enough. Many treatable patients continue to lose visual field because case-detection strategies are haphazard, incomplete, or suffer from a lingering and inappropriate fixation on elevated IOP as the sole diagnostic criterion. The two simple tasks of asking for a family history of glaucoma and assessing the optic disc (with referral onward of patients with positive findings) represent opportunities to diminish the impact of the commonest preventable cause of irreversible blindness in Australia today. To heighten awareness of glaucoma, the first-ever World Glaucoma Day has been designated for 6 March 2008 (http://www.wgday.net). Glaucoma Australia provides patient and community education and support, and can be contacted at http://www.glaucoma.org.au.

Mark J Walland MB BS, FRANZCO, FRACS

The psychological downsides, equity of access for women, and patients’ understanding of the limitations of screening need consideration Australian states are currently rolling out colorectal cancer screening as part of the National Bowel Cancer Screening Program. Its success depends on the “physical or psychological harm to those concerned be[ing] less than the chance of benefit”.1 The benefits are clear. Randomised controlled trials show a 16% reduction in colorectal cancer mortality with faecal occult blood testing and colonoscopy of people with a positive faecal occult blood test (FOBT) result.2 In contrast, less attention has been paid to the psychological impact of colorectal cancer screening. Its effective management may also improve screening outcomes. Breast cancer screening studies show that a screening invitation may cause severe anxiety and, in some cases, non-attendance; people who do not attend for one form of screening are more likely not to attend for other screening.3 Screening studies also show that participants can experience severe anxiety irrespective of results.4,5 An audit of suicides found two occurred between notification of recall after mammography and reattending; one suicide note was written on the recall letter, the other mentioned fear of hospitalisation.4 Neither woman had cancer. These findings emphasise the importance of education, rapid outpatient review and, if required, prompt access to colonoscopy to avoid delay in managing a positive FOBT result.5 FOBT-based screening studies report distress among both those with negative and positive results, and breast and colorectal cancer screening studies show that anxieties may continue even after a subsequent negative result.4-6 Among those who screen negative, distress may be sustained, indicating that this is a risk of screening healthy adults. A general-practice-based coronary heart disease screening study found that participants with no detected abnormality had significantly more psychological distress at 3 months than their unscreened counterparts. If not done carefully, screening may distress individuals who have clinically inconsequential disease.7 Women screened for hepatitis C and found to be positive after inadvertently receiving infected anti-D immunoglobulin reported high levels of psychological distress and poorer quality of life compared with their counterparts 22 years later, despite no progression of their disease.8 These studies emphasise the importance of assessing the appropriateness and benefits of screening. For colorectal cancer screening, with direct-to-patient kit provision, the group most vulnerable are patients unlikely to benefit because of other life-threatening comorbidities. Clinicians, particularly general practitioners, have a pivotal role in counselling these patients. The implications for patients of direct-to-patient kits should become clearer as screening progresses and its analysis should improve management further. A relatively unexplored potential contributor to morbidity is lack of choice of colonoscopist.3,9,10 A United States survey of women’s attitudes to colorectal cancer screening found that almost half reported a preference for a female endoscopist. Eighty per cent of these patients were willing to wait more than 30 days for one, and 14% would pay more for one. Seventy-five per cent of women gave embarrassment as the reason for their preference.10 If this is applicable to Australia, strategies are needed to ensure that women (particularly those who are uninsured, who have fewer options) have equity of access. Currently, fewer than 10% of Australian gastroenterologists are female, and the proportion of female gastrointestinal surgeons is even lower. It will be important for the success of colorectal cancer screening to know whether this workforce shortage has a substantial impact on female participation in the program. Informed participation is the ideal. Challenges include ensuring that patients understand the limits of screening for detecting colorectal cancer; in particular, that an FOBT sensitivity of 92% misses eight per cent of cancers.2 Information supplied in the National Bowel Cancer Screening Program kits emphasises the need for patients to seek medical advice irrespective of a screening result to have any symptoms they may have assessed in their own right. It is clearly important that participants are encouraged to develop realistic expectations about screening’s capacity to prevent cancer. An important unintended outcome of screening can be the “certificate of health effect”, a sense of immunity developing as a result of a negative test. Interpreting screening as a panacea against disease can strengthen unhealthy routines and the idea that regular screening rather than healthy lifestyle maintains health. Screened individuals still need to be encouraged to continue to limit red meat and fat intake, stop smoking and increase their physical activity, not only to reduce their subsequent colorectal cancer risk, but also to improve their general health status. As people value benefits and harms differently, more information is needed, not only on the physical and economic impact of colorectal cancer screening, but also on its psychological impact and on strategies to reduce this impact. Triggers to screening such as the perceived ease of use of the FOBT kit, and social acceptability and mechanisms for encouragement, need to be further assessed, as highlighted in the National Bowel Cancer Screening Pilot Program evaluation. As fewer than 10% of Australian gastroenterologists are female, strategies to ensure equity of access for all Australians, both men and women, may need to be emphasised. Now is an appropriate time to undertake further prospective studies into the impact of colorectal cancer screening on the population groups involved to ensure that its benefits continue to outweigh its risks, and that we maximise its benefits and minimise its risks.

Emma L Rosenfeld MB BS · Anne E Duggan BMed, FRACP, PhD

Teleradiology is like a “two-edged sword” that requires careful consideration and balancing, needing uniform standards to guide quality care while ensuring patient safety The rapid and secure transfer of x-ray and diagnostic imaging studies around the world is being facilitated by new technologies, such as picture archiving and communication systems (PACS), high-speed Internet access, and secure virtual private networks. This transfer of images, usually for assessment by a radiologist at a geographically remote site from where the images were obtained, is known as teleradiology.1-4 Domestic and international teleradiology is practised by individuals and imaging practices (private radiology groups and corporate practices), as well as teleradiology groups in Australia. Based on the 2006 Royal Australian and New Zealand College of Radiologists (RANZCR) Workforce Survey,5 about 67% of Australian radiologists use teleradiology in their daily work: 92% within their own state, 22% between states, and 1.7% internationally. The international teleradiology workflow is bidirectional, with Australian imaging studies being reported overseas and overseas imaging studies being reported in Australia. Clinical teleradiology has advantages, but there are also potential problems and pitfalls. However, in teleradiology, as in any use of radiology, the provision of high-quality, appropriate clinical care and accountability must remain of utmost importance, and this principle should guide teleradiology’s further development. In Australia, there is an escalating demand for diagnostic imaging services. The RANZCR anticipates that demand will greatly outstrip current supply in the radiologist workforce for at least the next 5 years. Further, this ever-increasing demand on diagnostic imaging services is accompanied by an increasing complexity of studies and a continued expectation that they will be reported promptly, 24 hours a day, 365 days a year. Given the geography and demographics (including radiology workforce demographics) of Australia, the benefits of using teleradiology are clear. Teleradiology can provide remote interpretation for rural and regional communities; second subspecialist opinion; workload balancing for diagnostic imaging staff; education; research; and clinical/quality audits.6,7 Out-of-hours interpretation, when local radiology services are unavailable, may also be of great benefit to patients if urgent advice is required. Similarly, however, several potential pitfalls are evident. One key pitfall relates to the “distancing” of the radiologist from patients clinically, as well as geographically — a trend that is already increasing with onsite services, and may only intensify with teleradiology. Radiologists have minimal influence over referrals that occur under a capped diagnostic imaging Medicare budget for billed services or in the public hospital sector. Apart from technological considerations, current legislation, reimbursement schedules and workload demands also exacerbate the increasing distancing of radiologists from clinicians and patients. Reporting radiologists may have little or no clinical or contextual patient information or direct communication with the clinician caring for the patient, resulting in image interpretation occurring in isolation, rather than provision of an integrated expert opinion. However, if this pitfall is avoided, specialist radiologists can make a pivotal contribution to clinical decision making and management — clinicoradiological discussions can result in a change of clinical diagnosis in 50% of cases and a change in treatment in 60% of cases discussed.8 Using radiologists and diagnostic imaging wisely could reduce the burden on the entire health system by not only improving diagnosis and management but also by reducing unnecessary and repeated radiation exposure, thus optimising overall patient care. Other potential problems relate to technical and professional considerations. Transfer of images may result in less than optimal image quality, hampering interpretation. If images are sent overseas, it is possible that the reporting radiologist may not be trained to the same standard as radiologists in Australia. We need to acknowledge that when English is not a radiologist’s primary language, there may be increased potential for error. Indemnity may not be guaranteed, and protection for patients may not be available.2-4,6,9,10 Perhaps the most serious concern relates to the potential evolution of medical services, including teleradiology, as commodities instead of community services. The globalisation of health care has never been more evident than in international teleradiology. The emerging globalisation of health care generally1-4,11 and, more specifically, the progressive corporatisation of radiology providers and the prospect of commoditisation of radiology services9,12 are on our doorstep. To contain cost, maximise efficiency and meet shareholders’ expectations, health care providers increasingly use teleradiology to outsource services.3,4,9,12 In some countries, out-of-hours on-call teleradiology has fully matured, and teleradiology companies are turning to daytime and subspecialty segments to further grow their market share.9 Some observers have noted that teleradiology could be treated as a commodity and traded with forward contracts.12 This concept of forward trading of medical services seems to be quite divorced from more traditional philosophies of the practice of medicine, and, at the very least, the public at large and those who pay for these services should be made aware of this trend. From a community perspective, if teleradiology is viewed purely as a technical service, with no consideration given to the quality, appropriateness or relevance of the interpretation service, nor to patient safety; if it is driven purely by cost and workforce pressures, convenience, or desire for market share, then this would be highly undesirable. Even within Australia, it is possible that commercial leveraging may occur, resulting in disruption to local radiologists, the local clinical diagnostic imaging team, and community service provision if cost-cutting and market share are primary motives for the introduction or further development of teleradiology.2,9,13 Thus, where a local clinical radiology service exists, compelling advantages for patient care would need to be identified to justify the additional provision of teleradiology services. However, when teleradiology can facilitate good patient care, this is an excellent outcome of the application of this technology. Teleradiology, both domestic and international, can be considered a “two-edged sword”, requiring careful consideration and balancing. The rapid growth of teleradiology and the globalisation of health care have led to the need for a set of uniform standards to protect consumer rights, define responsibilities, enable inter-jurisdictional recognition, ensure quality and safety, and enable benchmarking.6,13,14 Accordingly, the International Radiology Quality Network (IRQN)13 has developed a set of international clinical teleradiology principles to guide quality care and ensure patient safety. Australian representatives actively contributed to this development, and the RANZCR has adapted the IRQN principles in a position statement applicable to Australia and New Zealand.15 In general, these principles emphasise that the entire focus of international clinical teleradiology (as for radiology in general) must be solidly based on “what is good for the patient”. For example: the correct imaging procedure should be performed; images should be of a high quality and transmitted accordingly; communication must be made between the treating team and the (appropriately credentialled and indemnified) radiologist, providing a high level of clinical information; images must be interpreted in light of the full clinical history and available previous imaging; and the radiologist’s interpretation of the images and medical opinion must be communicated clearly and in a timely manner. The position statement also addresses specific, serious concerns, including security (eg, sites should comply with all nationally specified data protection standards) and ethics (a system should be in place to document electronic “fingerprints” of interpreting radiologists, to prevent “ghosting” of reports). The position statement will be updated regularly, with additional input sourced from the RANZCR Quality Use of Diagnostic Imaging Program teleradiology projects and the RANZCR Standards of Practice and Accreditation Committee, as well as IRQN updates. Any practice or hospital considering the use of domestic or international clinical teleradiology will be well served to be guided by these principles, and must, at all times, maintain a principal focus on high-quality patient care. With time, the regulatory, legal and ethical framework applicable to teleradiology may well flow on to other medical disciplines.

Lizbeth M Kenny MB BS, FRANZCR · Lawrence S Lau MB BS, FRANZCR