Editorials

It all depends on compliance Earlier this year, public trust in research was dealt a severe blow when evidence emerged that a renowned Norwegian researcher, John Sudbo, had fabricated and falsified data in articles on oral cancer published in The Lancet and the New England Journal of Medicine.1 This news followed hot on the heels of the exposure of fraudulent research by the Korean stem-cell researcher, Woo Suk Hwang, published in Science and Nature.2 There is no doubt these events are but the tip of the iceberg, as research misconduct is endemic,3 and may well become more prominent as the competitiveness and commercialisation of research escalates.4,5 Currently there is strong public support for research, but this is linked to notions of honesty and altruism, and the ability of researchers to regulate themselves. The public expects that a framework is in place to prevent misconduct and to investigate and punish the perpetrators should misconduct occur. These expectations were aired when the Hall affair was played out at the University of New South Wales in 2001–2003.6 Allegations of research misconduct were levelled at Bruce Hall, a professor of medicine at the university, and a renowned immunologist. The investigation was painfully drawn out, with a legal challenge and at least three inquiries. As it progressed, the media had many field days, the reputation of the university was compromised, and the medical faculty and the university’s council were divided. My editorial published in this Journal soon after the controversial ending of the Hall affair proffered a set of principles for managing allegations of research misconduct (Box).6 It now appears that these principles have been incorporated into policy. The National Health and Medical Research Council, the Australian Research Council, and the Australian Vice Chancellors Committee have recently released for public consultation the second draft of the Australian code for the responsible conduct of research.7 The code outlines comprehensive directives for issues such as research data and record management, the supervision of researchers in training, publication of research, authorship, peer review, conflict of interest and matters related to collaborative research. It stresses the need for research institutions to “establish a climate of open exchange of ideas with peers, mutual cooperation, and respect for academic freedom of expression, in which responsible and ethical behaviour in research is expected.” Furthermore, it requires research institutions to have in place active and formal programs for induction of trainee researchers along with continuous professional development of all researchers in the culture and performance of research, including mentorship and effective research supervision. The more contentious aspects of the code are its details for managing research misconduct. Its definition of misconduct as “deviation from the Australian code for the responsible conduct of research” 7 casts a wide net, and raises the possibility that institu-tions as well as individuals can be guilty of research misconduct. Furthermore, the code’s criteria for misconduct, reflecting current patterns of researchers’ misbehaviour,8 extend well beyond fabrication, falsification and plagiarism. It lists 17 examples of research misconduct, including abusive supervision; failure to declare, avoid or manage serious conflict of interest; and inaccuracy and carelessness in record keeping or in the preparation of grant applications or publications. This new and expanded perspective of research misconduct is welcome, but needs to be debated. When does misbehaviour become misconduct, and is the distinction between the two warranted at all? The code proposes two key players in managing misconduct: an institutional advisor on research integrity, and a designated person. The former is a counsellor on research integrity and a confidant to whom the aggrieved and those with complaints can turn for advice. The latter is the institutional inquisitor empowered to conduct a preliminary investigation as to whether allegations have substance and advise whether to pursue a formal inquiry. And herein lies the rub. The principles previously espoused (Box) recommend this be an external and independent inquiry with statutory power. The draft code allows for this, but also allows an alternative option of an internal inquiry. Is an internal inquiry a good idea? Research institutions, including universities, live in fear of adverse publicity associated with misconduct,9,10 and have an inherent and glaring conflict of interest in pursuing an internal inquiry. The community expects that “justice must not only be done but should manifestly and undoubtedly be seen to be done”. The notion of an institution investigating itself will not go down well with a society afflicted by a mistrust of authority and institutions.11 The code is silent on two requirements which will have to be in place if it is to work at all: compliance and accreditation of research institutions, and the establishment of a national body to oversee and evaluate the handling of research misconduct. The research community has long resisted any interference with its privileged status, but the time for scrutiny of research institutions for compliance with the Australian code for the responsible conduct of research is long overdue. After all, research funding is public money, and the public has every right to expect that research institutions pursue “responsible and ethical behaviour in research”. One way to ensure this is through accreditation, with failure to be accredited placing institutions at risk of losing access to public funding. Currently, the United States and Denmark, Finland and Norway have overarching bodies to oversee and evaluate instances of research misconduct.12,13 In the US, the Office of Research Integrity (ORI) has a mandate that for institutions to receive federal funding for biomedical research, they must investigate all instances of alleged research misconduct. Although the US system is far from perfect, the ORI has been active in helping research institutions to conduct their own investigations. If the institutional investigation is deemed inadequate, the ORI can intervene and initiate its own investigation. The ORI’s substantial power lies in the threat to institutions of the potential loss of federal funding.10,14 This power may sit uneasily with Australia’s broad anti-authoritarian culture and with university autonomy, but the competitive and commercial nature of today’s research, and its limited funding, dictate that such a national body should be explored and debated in the Australian context. The creators of the Australian code for the responsible conduct of research7 are to be congratulated. The code represents the first milestone along the long and tortuous road towards maintaining the integrity of research. The six lessons from the Hall affair6 Allegations of serious scientific misconduct should be dealt with from the start by an external and independent inquiry. The inquiry should have statutory power to investigate and inquire. The inquiry should have sufficient scientific expertise to ensure credibility. To preserve public confidence, the inquiry should aim for the highest degree of transparency and accessibility of the final report. There is a need for uniform processes and procedures for dealing with and adjudicating on scientific research and fraud. There is a need to shift the emphasis from managing misconduct and fraud to preventing them.

Martin B Van Der Weyden MD, FRACP, FRCPA

Falls and related injuries among seniors are a compelling ongoing priority for Australian health research Falls and fall-induced injuries among older people are a major public health concern worldwide, accounting for over 80% of all injury-related admissions to hospital of people over 65 years.1-3 Falls are also the leading cause of unintentional injury death in these individuals and responsible for appreciable morbidity, including bone fracture, head injury, joint disruption, and soft tissue contusion and laceration resulting in pain, functional impairment, disability, fear of falling, depression, loss of independence and confidence, and admission to residential care.1,4,5 Moreover, this major health problem is likely to increase, as the number and mean age of older people are increasing worldwide and epidemiological studies suggest that, for some types of fall-related injuries, the age-standardised incidence (ie, average individual risk) of injury is also rising.1,6 . . . a hospital setting is not a safe place for elderly people but is actually associated with increased risk of falling. Somewhat paradoxically, a hospital setting is not a safe place for elderly people but is actually associated with increased risk of falling. On admission, the older patient accumulates additional falls risk factors including a new, strange environment with poorly recognised external dangers for falling. This is often combined with confusion, acute illness and balance-affecting medication, in addition to chronic risk factors such as comorbidities, muscle weakness and impaired balance and gait.2,7 A recent systematic review found no consistent evidence for the effectiveness of interventions to prevent falls among older inpatients.8 Since then, two large randomised trials have shed light on this issue. Healey and colleagues,9 using a cluster randomised study design, examined the effect of a simple core-care plan targeting risk factor reduction in elderly care wards of a general hospital. They observed that the relative risk of falls in the intervention wards was 30% lower than in the control wards. Haines and coworkers10 reported that a targeted falls prevention program in a subacute rehabilitation hospital resulted in a 30% reduction in falls after 45 days of observation. Although these studies did not show a significant reduction in fall-related injuries, the results are encouraging and require verification in other hospital settings.5,11 In this issue, Fonda and colleagues12 report the results of a prospective quality improvement project in which they used a hospital-based, multistrategy prevention approach to reduce the risk of falls and fall-induced serious injuries among frail, older patients in hospital aged-care wards. This large study included 1905 inpatients in the year 2001 as a baseline or historical control group and 2056 inpatients in 2003 as the intervention group (mean age of both groups, 82 years). In both time periods, over 60% of the patients were women. The multistrategy intervention, phased in towards the end of 2001, was a hospital staff-led program incorporated into all levels of the organisation. The intervention consisted of various strategies to reduce falls and injuries, including risk screening with the Falls Risk Assessment Scoring System, after-fall assessments, appropriate modifications of patient and environmental risk factors, work practice changes, environmental and equipment changes, and staff and family support and education. Staff compliance with the risk assessment was also studied as part of evaluating the success of implementing the intervention. The total number and incidence (per 1000 occupied bed-days) of falls and fall-induced serious injuries were key outcome variables. The intervention program was associated with a 19% reduction in the risk of falls and a 77% reduction in the risk of falls resulting in serious injury. Staff compliance with completing the falls risk assessment tool increased from 42% to 70%, and 60% of the staff reported that they had changed their work practices to prevent falls. While Fonda and colleagues are to be congratulated on having successfully conducted this important trial, with impressive results, hospitals need to be cautious about applying this type of falls prevention strategy without first weighing up the limitations of the study. Firstly, as the authors point out, the study was not a randomised controlled trial — the “gold standard” of all clinical studies — but a prospective quality improvement project, and so a direct cause and effect relationship between the intervention and reduction in falls and serious injuries cannot be established. Secondly, a critical reader would like to see more detailed analysis of the success in executing the multistrategy falls prevention program. The article does not detail the level of compliance or adherence of the individuals in the intervention group to each recommendation and protective action throughout the 12-month period — information that is crucial to interpret the data. Thirdly, more information about the fallers and the fall and injury data collection system would allow the reader to draw firmer conclusions from the study. The authors note that they recorded many minor events in the follow-up data that were unlikely to have been coded during the baseline year, thus blurring the falls (although not injury) comparison between the baseline year and follow-up year (albeit in favour of underestimating the benefit of the intervention). A limitation of falls prevention research to date has been that fall definition and registration systems have not been standardised. However, the PROFANE (Prevention of Falls Network Europe) Collaboration Group has recently provided soundly based recommendations to address this problem and has suggested strategies for more uniform scientific reporting of falls data and outcomes.13 In various settings, not only in the hospital environment, multifactorial intervention strategies have been shown to prevent falls among elderly adults by 20%–45%,5 but many interesting and important questions remain unanswered.5 Firstly, even in randomised controlled trials, it is not always clear which components of the intervention are effective and which are not. A great deal of time and effort may be put into implementing a complex intervention, when, in truth, using one or two of its components might be equally effective.5,11 Secondly, the cost-effectiveness of interventions is seldom evaluated. Thirdly, little is known about elderly people’s long-term compliance with the recommendations and actions to prevent falls. We may deem the content of an intervention ineffective, when the truth may be that there was insufficient effort to implement the intervention (type III error).5 An additional difficulty with multifactorial falls prevention interventions is that they can be very labour intensive. So, in view of all the above considerations, should we now abandon the results by Fonda and colleagues12 especially since the study was not a randomised trial? Definitely not! Instead, we should pick up all the positive tips from the project, analyse them carefully and try to apply them in the hospital environment. The importance of careful selection of the content of a multifactorial falls prevention program and the target group to which it is applied cannot be overemphasised. The new evidence-based guidelines on preventing falls in older people14 can greatly assist in this implementation. If future clinical experience proves to be as positive as that of Fonda and colleagues, the next step should be a large-scale randomised falls prevention trial, which would probably need cooperation between several centres. The importance of this health problem — falls and related injuries among seniors — makes it a compelling ongoing priority for Australian health research.

Pekka Kannus MD, PhD · Karim M Khan MD, PhD, FACSP · Stephen R Lord PhD, DSc

The differences between community-acquired and health care-associated MRSA explained Staphylococcus aureus is one of the most important bacterial pathogens globally. About a quarter of us carry one or other strain at any one time, and, if we develop an infection, our own colonising strain is likely to be responsible.1 All clinicians, from urban general practitioners to remote-area nurses, encounter S. aureus infections. In hospitals, S. aureus is responsible for most surgical-site infections, and their control poses a major challenge. We have no effective vaccine against S. aureus, so for 50 years we have depended on the safe and affordable β-lactam antibiotics. However, in many large Australian hospitals, patients run the risk of becoming colonised with a hospital strain of S. aureus, many of which are β-lactam resistant — “golden staph” in the vernacular.2 As β-lactam resistance is detected in the laboratory using methicillin or oxacillin, microbiologists call these strains “methicillin-resistant Staphylococcus aureus” (MRSA) (see Box 1 for acronyms). All MRSA harbour the mecA gene that encodes a modified cell wall protein to which no β-lactam antibiotic is able to bind.3 Strains of health care-associated MRSA (HA-MRSA) are usually not only resistant to β-lactam antibiotics, but also carry several other resistance genes or mutations. Typically, Australian HA-MRSA isolates are not only “methicillin-resistant” but also “multiresistant”, leaving only vancomycin and a very short list of alternatives as the last line of defence. Fortunately, when clinicians have to prescribe antibiotics for S. aureus infections, the decision has been relatively straightforward — a β-lactam such as flucloxacillin or cephalexin if the infection is community-acquired (because MRSA has been rare in the community), or vancomycin if the patient has recently been in hospital. However, in the article by Nimmo and colleagues in this edition of the Journal,4 this neat epidemiological distinction is under attack. MRSA appears to be at large in the community, and the types of infections we associate with MRSA are changing. What is going on out there? Has MRSA escaped from the hospitals? Evolution occurs far more rapidly in bacteria than in more complex organisms such as humans. Bacteria are constantly deleting and acquiring genes or mutations and trying out their new configurations in new situations. It does not particularly matter from where the genes come; any DNA will do provided it is useful. S. aureus has prospered because it is carried and spread by humans, but there is a silent competition going on between different strains of S. aureus to see which one can colonise and spread most successfully. How do we know this? Using increasingly sophisticated laboratory methods, it is possible to identify and track different strains (or clones) of S. aureus. The data reported from the Australian Group on Antimicrobial Resistance (AGAR) by Nimmo and colleagues reveal the spread in Australia of new strains of MRSA, which may actually be more virulent than HA-MRSA. These “community-acquired” MRSA (CA-MRSA) carry a distinct variant of mecA that is small enough to efficiently move between bacteria. Epidemiologically, a CA-MRSA infection is one that arises in a patient who has not had contact with the health care system (no admissions to hospital in the previous 12 months, no indwelling catheters, and not a resident of a long-term care facility). The AGAR study shows that CA-MRSA has not broken out of the hospitals, but has instead emerged independently when community strains of S. aureus have acquired mecA from other bacteria.4 And S. aureus is not just in the market for antibiotic resistance genes; any DNA that can give a competitive edge is being progressively collected and amplified. One example is the gene for Panton–Valentine leukocidin (PVL), which probably provides some selective advantage to S. aureus, but in humans contributes to necrotising pneumonia and aggressive soft tissue infection. PVL, first described in 1932,5 is now present in more than 90% of the Queensland and south-west Pacific epidemic clones of CA-MRSA reported by AGAR.4 Paradoxically, these “superbugs” are sensitive to more antibiotics than HA-MRSA. β-Lactams such as flucloxacillin and cephalexin are not active, but clindamycin and trimethoprim–sulfamethoxazole may be useful alternatives. This characteristic resistance profile has also led to yet another acronym: “NORSA”, for non-multiresistant oxacillin-resistant S. aureus.6 Confused? The picture is confusing, and it is not static. AGAR has documented the stepwise increase in the proportion of community isolates of S. aureus that are MRSA in Australia, from 4.7% in 2000 to 7.3% in 2004.4 However, these data are drawn from teaching hospitals and private pathology laboratories and do not reveal the true extent of CA-MRSA carriage in the general community. To really understand what is happening, we require a population-based study to document the prevalence and movement of these new strains in the healthy majority. Who is carrying them? Do antibiotic prescribing practices play a role? Can we “profile” the typical CA-MRSA carrier, so that we can better select which antibiotics to prescribe empirically? What if CA-MRSA gets into a hospital; will it spread and replace HA-MRSA and cause even more serious hospital-acquired infections? What will we call it then? The emergence of MRSA infections in patients without apparent risk factors poses a difficult problem for clinicians who see patients with infections likely to be caused by S. aureus, especially if the infections are severe. For patients with mild to moderate infections, obtaining appropriate cultures for susceptibility testing is important. For those with severe infections possibly caused by S. aureus, intravenous flucloxacillin remains the drug of choice, as it is more effective therapy for methicillin-susceptible S. aureus bacteraemia.7 However, if the patient is critically ill or has risk factors for CA-MRSA infection, the addition of intravenous vancomycin is warranted (see Box 2). Fifty years ago, all S. aureus strains were susceptible to penicillin, but 30 years later 80% of community strains worldwide had become penicillin-resistant, forcing us to respond with penicillinase-stable β-lactams, such as flucloxacillin and cephalexin. Nimmo and colleagues have shown that strains of CA-MRSA originally identified in Queensland, Western Australia and overseas do not respect state and national boundaries, and we are likely to see increasing rates of CA-MRSA in coming years. Some of this change results from the overuse of antibiotics, and some is the inevitable result of rapid bacterial evolution to which we will have to adapt. Meanwhile, be alert, not alarmed, but some modification of the standard approach to S. aureus infections is indicated (Box 2). 1 The ABC of MRSA MRSA = methicillin-resistant Staphylococcus aureus CA-MRSA = community-acquired MRSA HA-MRSA = health care-associated MRSA NORSA = non-multiresistant oxacillin-resistant S. aureus (also an MRSA) PVL = Panton–Valentine leukocidin, a virulence factor present in some S. aureus strains 2 Suggested interim guidelines for suspected Staphylococcus aureus infections in community patients Obtain cultures for bacterial identification and drug susceptibility testing whenever possible. Discuss with the microbiology laboratory the patterns of resistance in the local area. Incision and drainage should be considered in all cases, and may be the only treatment required. For mild infections that require antibiotics but not admission to hospital: Prescribe a β-lactam antibiotic initially (eg, flucloxacillin or cephalexin) unless allergy or documented previous CA-MRSA in the patient or the patient’s family. Review the patient. Check the culture result. If CA-MRSA is identified, follow the sensitivity pattern; clindamycin or trimethoprim–sulfamethoxazole are likely to be effective. For severe suspected community-acquired S. aureus infection: Obtain cultures, commence intravenous flucloxacillin empirically. Consider combining flucloxacillin with intravenous vancomycin if the patient is critically ill. Continue flucloxacillin and cease vancomycin if methicillin-resistant S. aureus is excluded, as flucloxacillin is more effective than vancomycin for methicillin-susceptible S. aureus infections.

Paul D R Johnson MB BS, PhD, FRACP(Infectious Diseases) · Benjamin P Howden MB BS, FRACP(Infectious Diseases), FRCPA(Microbiology) · Catherine M Bennett MAppEpid, PhD

A recent review shows how much more we need to find out about this important problem Perioperative ischaemic cardiac events include myocardial infarction, cardiac arrest and cardiac death, and are estimated to occur in 2%–5% of patients over 40 years of age.1 Mortality rates associated with perioperative myocardial infarction and cardiac arrest may be as high as 25% and 65%, respectively.2,3 In the Australian context, precise data on the numbers of patients at risk are not available, but with more than 440 000 general anaesthetics performed annually, this is likely to be an issue facing many physicians. A recent narrative review of the problem is therefore of timely importance.1,4 What is the risk of perioperative myocardial infarction? As the review points out, perioperative myocardial infarction may be difficult to diagnose, and often unrecognised. Three studies were identified totalling 1309 patients, with myocardial infarction diagnosed by creatine kinase MB elevations with new Q waves, with or without autopsy or positive pyrophosphate scan evidence. Myocardial infarction was identified in 30 patients (2.3%); notably, more than half of these did not have symptoms or signs. Creatine kinase MB assays may result in false negative and positive results, and troponin assays — the biomarker currently used in the European Society of Cardiology and American Heart Association guidelines for diagnosis of myocardial infarction — are now preferred. However, in the perioperative setting, troponin elevation may also arise from non-cardiac causes such as pulmonary embolism and renal failure, and limitations exist in the specificity of individual assays.5 Further, the pathophysiology of perioperative ischaemic events may differ from the non-perioperative acute coronary syndromes, and these differences may affect risk prediction and treatment. Non-perioperative acute coronary ischaemia results from rupture of an often mild, non-obstructive atherosclerotic plaque and superimposed coronary thrombosis.6,7 Although such plaque rupture and thrombosis is also thought to occur perioperatively, there are other important influences. The perioperative state is associated with activation and release of multiple inflammatory mediators and cytokines, sympathetic nervous system activation and catecholamine release, hypercoagulability, and hypoxia. These contribute to both plaque rupture and thrombosis. Additionally, the perioperative stress state may contribute to increased myocardial oxygen demand, in the setting of reduced oxygen supply from blood loss, hypoxia, and other factors. This adverse environment may be present up to 3 days into the postoperative period.8 How can we assess this risk? Given this propensity for perioperative ischaemic events, individual preoperative risk assessment has been keenly pursued by surgeons and anaesthetists, often resulting in referral to a cardiologist. Two methods are commonly used: clinical assessment, and noninvasive testing. A number of clinical assessment tools have been advised, a commonly used one being the Lee index.9 This defines a number of features of patient history, physical examination, baseline investigations, and proposed surgical procedure. Based on the presence of one to five of these clinical characteristics, patients’ risk can be stratified from 0.4% to 5.4% likelihood of a major perioperative event.9 Noninvasive exercise or pharmacological stress testing, usually with echocardiographic or nuclear imaging, is generally reserved for those at higher risk. In Australia, dobutamine stress echocardiography is a commonly used technique, achieving sensitivity and specificity of 85% and 70%, respectively, for a positive test predicting perioperative events in a meta-analysis,10 with similar results for nuclear imaging techniques.10 However, the relatively modest sensitivity and specificity of these tests mean a number of high-risk patients will be missed, and many with high risk will not have an event. The advice to patients about their risk must also be tempered by whether the planned surgery is elective or should go ahead regardless of the risk. How can we manage this risk? Coronary angiography is often advised for patients assessed to be at higher risk, but there is uncertainty in how to respond to the finding of significant coronary artery disease. Revascularisation — either percutaneous or surgical — has been suggested for patients with high grade coronary stenosis, particularly for widespread disease.11 However, supportive data are scarce; several retrospective studies suggest benefit, but a large recent randomised trial in selected stable patients undergoing vascular surgery showed no improvement in outcomes, and possibly an increased risk of events.11,12 At a practical level, if revascularisation is performed, observational data support delaying non-cardiac operations for at least a month following revascularisation surgery.13 Following coronary stenting, a window of 6 weeks after bare metal stenting is suggested, to allow endothelialisation of the stent struts and reducing stent thrombosis,14 but also reducing the possibility of in-stent restenosis, occurring maximally at 3–6 months.15 There are as yet no comparative data following drug-eluting stents, although these appear less attractive, given that stent-strut endothelialisation takes longer, and combined antiplatelet therapy with aspirin and clopidogrel is likely to be needed for longer, further increasing perioperative bleeding risk if these agents are continued, and increasing the risk of acute stent thrombosis if they are stopped early to allow surgery.16 Perioperative coronary events: risk management strategies for those at increased risk Consider not performing surgery if elective Smoking cessation: can be advised for all patients β-Blockade: some evidence, but disputed Aspirin, nitrates, statins: little evidence Revascularisation: little evidence of benefit, some evidence of harm; a particular problem with drug-eluting stents Similar uncertainty surrounds pharmacological methods of perioperative risk reduction. β-Blockers, by reducing myocardial oxygen demand and blocking sympathetic and catecholamine responses, would seem a logical option. Their use is widely promoted, and included in the joint American College of Cardiology and American Heart Association guidelines for perioperative management.17 However, these recommendations are based largely on two randomised controlled trials: one, a small unblinded study,18 the second, a larger study, which showed no survival benefit for β-blockade assessed on an intention to treat basis.19,20 Further trials are currently underway.20 Use of aspirin or statins also seems appropriate, given their previous efficacy in prevention of non-perioperative events,21 but aspirin may increase the perioperative bleeding risk,22 and statins have not yet shown robust benefit, although this is likely an area for future investigation. How then, should the physician put together what is at times confusing information? Firstly, perioperative ischaemia is relatively common and often unrecognised. Clinical assessment and non-invasive imaging are useful, but far from perfect, in risk stratification. Stopping smoking before surgery is a useful intervention to reduce risk.23 Revascularisation, while often used for patients with angiographically important disease, has little evidence to support it, delays subsequent surgery, and has a number of associated problems. Lastly, while statins, aspirin and β-blockers may appear intuitive and are commonly used, there is likewise little evidence to support these approaches. The review by Devereaux et al1,4 is a timely reminder of how little is known about such an important problem, a call to obtain better data, and a suggestion to discuss the rationale for surgery and its possible attendant risks carefully with patients.

Harry C Lowe FRACP, PhD · Saul B Freedman FRACP, PhD

To tackle this problem we need a systems approach involving multiple strategies An article in this issue of the Journal by Miller and colleagues1 provides further evidence of the magnitude and seriousness of the problem of adverse drug events (ADEs) in general practice. Their study highlights our ongoing failure to address the problem of ADEs — medication-related incidents that cause patient harm. “Consumer Medicine Information needs to be routinely used in medical encounters, so that patients can recognise ADEs and know what to report to their GP . . .” Each year in Australia, about 17.5 million people make 95 million visits to their general practitioner.2 Based on Miller et al’s estimate — that 10.4% of patients attending general practice experience an ADE — almost 2 million people have an ADE annually. Moreover, their findings show that these ADEs are not trivial, with about 1 million being moderate or severe and 138 000 requiring hospitalisation, a finding consistent with previous estimates.3 Many of these ADEs are preventable, although the exact proportion of preventable events can be debated. There have now been more than 30 Australian studies estimating the number of ADEs in different settings.3 It is clear that counting is not enough — it is time for action, but what can be done? Every developed country is trying to cope with the problem of ADEs. Australia has many structures and initiatives in place to reduce the occurrence of ADEs, and preventing ADEs necessarily involves them all.3 Regulatory agencies, the medicines industry, quality use of medicines organisations and information providers, safety and quality organisations, professional bodies, health professionals and consumers can all assist. Prevention of ADEs cannot occur without better knowledge. It is noteworthy that the Therapeutic Goods Administration has adopted the European Medicines Agency guideline on pharmacovigilance planning. Increased pharmacovigilance, including observational studies, will require a substantial increase in resources. In Canada, less than 10% of the budget for drug regulation is allocated to issues concerning marketed products, including safety. Yet, in 50% of new drugs, serious adverse drug reactions are detected after market approval.4 We need systems that can deal with the reality that only limited numbers of highly selected patients are studied before a drug is marketed. Regulators may have to consider restricting prescribing of new medications if they have limited safety information, particularly when equally efficacious therapy is available. New systems for detecting early signals of potential adverse drug reactions in expanded populations could complement the current reporting system for adverse drug reactions. An example is the Drug Safety Research Unit in the United Kingdom, which captures information on the first 10 000 patients using a newly marketed drug.5 We need to capitalise on and expand the importance and significance of consumer reporting. Instead of relying on pharmaceutical representatives (as a considerable proportion do), health professionals require easily accessible, balanced information sources that can be used in a timely manner for their clinical decisions.6 Pharmaceutical representatives frequently fail to supply safety information,7 and their promotional techniques may lead to more widespread use of new medications. In Canada, there were almost 50 000 visits by pharmaceutical representatives to doctors for rofecoxib, and over 1 million samples were handed out in its first year on the market. This helped increase rofecoxib prescriptions by 125% in the following year and, in Ontario, led to increased hospital admissions for gastrointestinal bleeds.8 By the time rofecoxib was withdrawn for safety reasons, it accounted for 40% of Australian expenditure on non-steroidal anti-inflammatory agents,9 possibly exposing excessive numbers of people to unnecessary risk. The activities of pharmaceutical representatives are regulated by Medicines Australia’s code of conduct governing pharmaceutical promotion.7 Medicines Australia must find ways to improve the provision of information to health professionals by the medicines industry through active monitoring of the code. If this is not possible, other methods of regulating promotion may need to be considered. Leadership from professional bodies and quality use of medicines agencies is required. Promoting balanced information sources, as a key element of professional standards, may assist in preventing ADEs. Activities sponsored by the National Prescribing Service also should have just as much of a role in preventing ADEs as they do in promoting appropriate management options. Developing a culture of safety in community practice will require leadership from the newly established Australian Commission on Safety and Quality in Health Care. We need a no-blame culture, supporting safer systems in practice, as well as incident monitoring, with timely feedback to practitioners and consumers. Medication safety improvement toolkits, similar to those developed for hospital practice,10 may be suitable for community practice, but their effectiveness in this setting must first be assessed. A study monitoring all incidents of potential or actual harm to general practice patients, including ADEs, found that the most common contributing factor was poor communication between practitioners and patients.11 Professional bodies and medical schools might help by providing educational programs to improve GPs’ communication skills about ADEs. Failure to recognise the signs and symptoms was another contributing factor to incidents.11 Consumer Medicine Information needs to be routinely used in medical encounters, so that patients can recognise ADEs and know what to report to their GP, even if he or she fails to ask. Case-conferencing and reviewing patients’ medication at home have the potential to reduce ADEs.3 These services are funded, but still underutilised. Poor communication between health professionals was another common cause of incidents,11 highlighting the need for better information systems in community practice. It is health professionals, in consultation with patients, who must identify ADEs in practice. Therefore, computerised systems should alert GPs when patients receive new prescriptions and identify all medications they are receiving from any provider.12 This knowledge can trigger GPs to ask about ADEs when patients first return after a new medication has been prescribed, as this is the interval in which most ADEs occur. Knowledge of what their patients are taking can help GPs flag which of their patients are at high risk; ADEs in this group are more likely to be fatal.13 If we do not develop a culture of safety, we will continue to have an extra 140 000 hospitalisations per year caused by ADEs. Although ADEs commonly occur in general practice, preventing them is not solely the responsibility of GPs. We need a systems approach involving multiple strategies to tackle this problem. Otherwise, patients will continue to suffer needlessly from ADEs.

Elizabeth E Roughead BPharm, MAppSci, PhD · Joel Lexchin MSc, MD

This European approach to insulin management is now being introduced in Australia Since the publication of the Diabetes Control and Complications Trial (DCCT) in 1993,1 improved glycaemic control in type 1 diabetes has been acknowledged as a desirable goal in theory, but frustratingly difficult to achieve in practice. Although bodies such as the American Diabetes Association recommend a glycated haemoglobin (HbA1c) target of < 7%,2 only around 20% of adults with type 1 diabetes under specialist supervision in Australian centres achieve this goal (data from the Australian National Diabetes Information Audit and Benchmarking Survey; Associate Professor Jeff Flack, Director, Diabetes Centre, Bankstown–Lidcombe Hospital, NSW, personal communication). Intensive insulin treatment in the North American-based DCCT involved an initial inpatient stay of 2–4 days. Patients received formalised dietary and insulin prescriptions, emphasising consistent distribution of carbohydrate across the day and intensive glucose monitoring. The program was medically directed and labour intensive, with patients maintaining weekly telephone contact and attending monthly clinic visits. No Australian diabetes centre has been able to routinely offer this level of support to patients. The reduction in microvascular complications seen with intensive treatment in the DCCT was accompanied by a threefold increase in severe hypoglycaemia and a 33% increase in the risk of becoming overweight.1 Overall quality of life did not improve.1 These adverse effects have been seen by many as inevitable consequences of tight glycaemic control and may have discouraged many clinicians and patients from pursuing a “DCCT-style” approach to intensive insulin treatment. As in other endeavours, the Europeans took a different approach from that used in North America. The Dose Adjustment for Normal Eating (DAFNE) program3 is a UK-based adaptation of the German Diabetes Training and Treatment Programme (DTTP).4 DTTP has been progressively developed in Germany since the late 1970s, under the leadership of the late Michael Berger (former President of the European Association for the Study of Diabetes). It is a 5-day structured inpatient education program facilitated by diabetes educators and dietitians. It aims to encourage and equip people who have type 1 diabetes to manage their insulin regimens actively and independently. DTTP has also been adopted in Romania,5 Austria6 and Russia,7 with positive results reported by all groups. In DTTP, patients follow a normal diet and receive intensive training in precise, but not restrictive, estimation of dietary carbohydrate in terms of 10 g carbohydrate portions. Prandial short-acting insulin doses are calculated as a ratio to intake of carbohydrate portions at each meal and major snack (eg, 1 unit per carbohydrate portion). Basal insulin generally comprises twice daily isophane (NPH) insulin or once or twice daily long-acting insulin analogues. Insulin ratios and basal insulin doses are adjusted to meet defined preprandial and bedtime glycaemic targets, with corrective insulin or carbohydrate given as required. General care of diabetes, adaptations of insulin for exercise and alcohol intake, and management of “sick days” are also addressed in the 35-hour program. The 5-day inpatient DTTP course has become part of standard care for type 1 diabetes in Germany. Active clinical audits involving a network of 96 diabetes clinics across Germany continue to demonstrate clinically meaningful improvements in HbA1c (especially for those with poor baseline control) and reduced hypoglycaemic episodes (especially for those with good baseline control) after DTTP training.8,9 Reduced rates of ketoacidosis and hospital admissions have also been noted.9 In Austria and the UK, DTTP has been adapted to a 5-day outpatient program with eight patients per group. Content remains very similar to the German program. The UK DTTP (DAFNE) approach was evaluated in a formal randomised controlled trial.3 Reported benefits in a cohort of 169 patients with poorly controlled type 1 diabetes included a fall of 1% in HbA1c without increased hypoglycaemia or mean weight gain. Quality of life was also improved.3 However, DAFNE is a complex intervention, and it remains unclear which element of the program is most important in improving diabetes control. Aside from the efficacy of the insulin algorithms per se, the effect may be in part due to increased contact with health care professionals and peer group support. Further, there are some weaknesses in the DTTP–DAFNE approach. Only two randomised controlled trials have been conducted,3,5 and, by current standards, the first3 would not be considered of high quality. Also, DAFNE is more expensive than current “routine” diabetes education. To benefit from DAFNE, patients need to perform regular glucose testing and self-adjustment of insulin doses, so it is unlikely to benefit those who struggle with the day-to-day demands of basic diabetes self-care. DAFNE insulin adjustment requires reasonable English literacy and numeracy, which may exclude some patients. Developed in the 1980s, DAFNE was designed around soluble and isophane insulin, rather than more recent insulin analogues. It does not include glycaemic index concepts. The standard glucose targets used in DAFNE (eg, fasting glucose 5.5–7.7 mmol/L) are higher than those recommended for pregnancy10 and will require revision in patients planning to become pregnant. Participation in a DAFNE course is clearly not the only possible pathway to improved glycaemic control in type 1 diabetes. Some people with this condition have been able to achieve excellent glycaemic control over many years without such a program, generally using either multiple-dose insulin regimens or continuous subcutaneous insulin infusion (or insulin pump) therapy. A recent randomised controlled crossover trial reported HbA1c values 0.25 percentage points lower with subcutaneous insulin infusion than with multiple dose insulin therapy,11 but this must be weighed against the increased cost. DAFNE has been costed in the UK at $A1300 per patient,12 and a published health cost modelling analysis suggested mean savings of $A5500 per patient over 10 years, arising primarily from a reduction in microvascular complications.12 Even the most conservative analyses have suggested that DAFNE is cost-saving rather than simply cost-effective.12 The use of DAFNE as one means of improving care for people with type 1 diabetes has been supported by reviews conducted by the UK National Institute for Clinical Excellence13 and the UK Department of Health.14 In January 2006, provision of structured patient education for people with type 1 diabetes became a requirement of the National Service Framework for diabetes in the UK, with DAFNE recognised as the one program which currently meets all the Framework’s requirements for type 1 diabetes.15 DAFNE courses are now provided in 39 centres across the UK, with 3537 DAFNE “graduate” patients reported in January 2006.16 In November 2004, clinicians from four centres in Australia completed DAFNE course observation and post-course training in the UK. The UK DAFNE course materials were then adapted to the Australian health care context. These four centres have now conducted around 12 DAFNE courses in Australia, with positive patient feedback. All centres have committed to the collection of baseline and follow-up data. An “OzDAFNE” collaborative, with strong links to the UK, has been established to ensure consistent standards of course resources and delivery across Australia, and to facilitate training and accreditation of further DAFNE centres within Australia. The processes of accreditation, peer review and quality assurance are seen as essential by all groups involved in the DTTP–DAFNE collaboratives and represent a great strength of the program. The capacity of current OzDAFNE centres to make DAFNE available to people with type 1 diabetes is limited. We hope that other diabetes services will undertake DAFNE training and join the OzDAFNE collaborative. This requires a doctor, diabetes educator and dietitian to observe a 5-day DAFNE course, attend further training and participate in peer review and quality assurance. Two further centres in Queensland have recently completed training and plan to provide courses, while further training is planned in Victoria in the near future. The study reported by Davis and colleagues in this issue of the Journal clearly demonstrates that poor glycaemic control affects people with type 2 as well as type 1 diabetes in Australia.17 The authors also note distinct therapeutic procrastination in proceeding from diet to oral agents to insulin in patients with type 2 diabetes. Previous studies have described “provider frustration” in dealing with diabetes care,18 and this may represent a further barrier to effective implementation of published guidelines. DAFNE was designed with type 1 diabetes in mind, but type 2 patients with marked insulin deficiency, requiring intensive insulin treatment, might also benefit. However, the DAFNE insulin algorithms have not been formally evaluated in patients with type 2 diabetes. The “dietary freedom” of DAFNE may be less appropriate in type 2 diabetes, in which obesity is a common comorbidity. DESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed) is a 1-day structured education program for type 2 diabetes developed in the UK, primarily targeted at the earlier stages of this condition.14 Currently, most people with type 1 and type 2 diabetes in Australia have suboptimal glycaemic control and remain at risk of the devastating long-term complications of diabetes. Active strategies to improve glycaemic control and meet other therapeutic targets, including the expansion of DAFNE programs for patients with type 1 diabetes, should be developed across Australia.

H David McIntyre FRACP

It is time for less talk and more action In Australia each year, close to 1600 medical graduates set off on the long and lonely road of prevocational and vocational education and training. To a casual observer, this journey might seem a simple matter, but two articles in this issue of the Journal1,2 refute this. Systemic shortcomings that these authors and others3 raise include a lack of coordination in the provision of education and training to junior doctors and a lack of integration of undergraduate prevocational and vocational training programs. For possible solutions, both McGrath et al1 and Paltridge2 look overseas to Canada and the United Kingdom. In Canada, the university medical schools are responsible for training medical specialists. There are strong links between medical schools and training hospitals, and a major commitment by hospitals to education and training. As well, senior clinical staff are committed and appropriately well paid to teach. Furthermore, medical students in Canada must decide before or at graduation which specialty they wish to enter — there is no internship. The different but comprehensive UK program is of two years’ duration, and “shifts medical education away from the apprentice-style of training to working and learning in teams.”4 Postgraduate deans, attached to each National Health Service Trust, fund and manage postgraduate programs across all specialties, and a new statutory body, the Postgraduate Medical Education and Training Board, will oversee all programs. Neither of these programs would sit comfortably in Australia. Our medical school graduates lack the skills and experience to enter directly into specialist training; medical schools lack the resources to oversee all postgraduate programs; and the current thrust in Australian medical education is to attempt to shorten the overall training period. Currently, accreditation and registration focus on process rather than outcomes, and a more flexible approach to linking progress to competencies rather than time spent in training is being considered.5 What both the Canadian and UK systems have that we do not is appropriate funding of undergraduate teaching. We also lack adequate numbers of medical students, recognition that good clinical teaching is as important as research or clinical practice, delineation of our overall medical workforce needs, medical student intakes that reflect projected workforce needs and the training to meet these needs and, finally, an appropriately coordinated and integrated system of undergraduate and prevocational and vocational medical education and training. Let us examine these issues in greater detail, beginning with the issue of appropriate funding of undergraduate teaching. Reduced federal government funding in recent years for undergraduate teaching supported by the Higher Education Contribution Scheme (HECS) has meant an increased intake of full-fee-paying overseas and also local students. The February 2006 meeting of the Council of Australian Governments (COAG) announced an increase in Australian full-fee-paying students from 10% to 25%, and a further increase of HECS places through to 2008.6 The fees generated by these full-fee-paying students will assist medical schools, but the tensions with clinical teachers who are required to teach overseas students, and who gain no recompense for this training, will remain even though pragmatic changes to the immigration act are allowing overseas students to remain in Australia. It should be noted that university administrations retain some 40% of medical student fees for “general revenue”. Medical schools should not be fundraisers for the whole university. Secondly, clinical teaching requires appropriate recognition. Most medical practitioners are willing to teach junior colleagues, but are hindered by time and money. Time needs to be set aside within teaching hospitals for teaching postgraduate students; a prerequisite for appointment to the staff of teaching hospitals should be a willing commitment to teach; and teaching time should be appropriately funded. Further, all hospital administrators and health bureaucrats must recognise the dual role of teaching and clinical service within teaching hospitals. The days of pro-bono teaching are long gone, and there must be budgeting for clinical training.5,7 Thirdly, overall workforce needs need to be delineated. Workforce planning is not a precise science and has many inherent difficulties, as shown in the Productivity Commission’s 2005 health workforce report.8 This report recommends establishing a single workforce secretariat to replace both the Australian Health Workforce Advisory Committee and the Australian Medical Workforce Advisory Committee, which would report directly to the Australian Health Ministers’ Advisory Committee. In making this recommendation, the Productivity Commission accepted the advice of many submissions, and stated that workforce projections undertaken by the secretariat should be directed at advising government that meeting different levels of health service demands requires equal consideration of the need for training and education of health care workers. Simply put, service demands require similar demands in education and training. Fourthly, both intakes and training of medical students need to meet projected workforce needs. The major problem in planning medical student numbers is the 8–10-year lag between entering medical school and unsupervised medical practice. The reduction in medical school intakes in the early 1900s led to a shortage of medical practitioners and the need to recruit overseas-trained doctors. This recruitment has not been without difficulties.1 The pendulum is now swinging in the opposite direction, with a recent increase in HECS places, the decision to allow overseas students to remain in Australia and enter specialist training, the creation of new medical schools, and the very recent COAG decision to increase the number of local fee-paying students and increase the number of HECS places through to 2008. These decisions will increase student numbers, but it is not clear how, where, and by whom they and future postgraduate trainees will be trained. This important issue is well recognised. Olson and colleagues, writing in this Journal, point out that medical students cannot acquire appropriate clinical experience because of the unavailability of patients in teaching hospitals.9 They state, “. . . it is clear we must find alternatives to teaching hospitals for acquiring clinical skills.”9 Crotty takes the matter further, pointing out the multiple factors that reduce the value of the so-called teaching hospitals for student training, and the lack of consultation in developing new medical schools.10 He advocates teaching in private hospitals and private clinics, simulation-based clinical teaching, and increasing teaching in general practice and the community. This would require adequate funding, and agreements forged between universities, public and private hospitals and federal, state and territory governments. Finally, we come to the issue of needing a coordinated, integrated, and accredited system of undergraduate, prevocational and vocational medical education and training. McGrath et al1 and, to a lesser extent, Paltridge,2 lament our current lack of coordination and planning. While there is some ad-hoc integration of education, by and large, the various “units” involved in education act separately. There are at least 10 different agencies involved in postgraduate training. This modern Tower of Babel includes: the Australian Government Department of Education, Science and Training and Department of Health and Ageing; state and territory governments and health departments; teaching hospitals and training units; specialist colleges; Committee of Presidents of Medical Colleges; Confederation of Postgraduate Medical Education Councils; university medical schools; Australian Medical Council (AMC); state prevocational medical councils; and the Medical Training Review Panel. Overlying each of these are the special requirements for assessing standards for overseas-trained doctors. In an article on this subject, Dowton et al concluded by saying, “It is time to comprehensively review the oversight and governance of postgraduate medical education and training.”3 There have been numerous national workshops, national conferences, and review articles suggesting the way forward, but little has been achieved. A recent conference hosted by the Committee of Deans of Australian Medical Schools and the AMC recommended that registration, accreditation and clinical progress be linked to competencies rather than time spent in training.5 The conference also recommended the establishment of a National Healthcare Education Council, which should be independent, funded by and reporting to the Australian Health Ministers’ Conference (AHMC), and should include all stakeholders. The Productivity Commission also recommends a body along these lines — the Advisory Health Workforce Education and Training Council — to provide the AHMC with independent and transparent assessments of health care workforce and education and training needs, and of the implications of courses, curricula and accreditation. The importance of combining assessments of workforce (ie, service delivery) needs with education and training cannot be overestimated, and cooperation between the federal health department and DEST is essential. The overall solution also requires changes at state and territory levels. New South Wales has long been a leader in postgraduate medical education, with the formation of the Postgraduate Medical Council of NSW (PMCNSW) in 1988. The recent establishment of the Institute of Medical Education and Training,11 combining the roles of PMCNSW and the Medical Training and Education Council, is a major step forward. The new Institute has a broad brief to: provide high quality and appropriate medical education and training for trainees, supporting quality and safe care and services to patients; provide support to area health services and other public health organisations that control public hospitals in relation to postgraduate medical education and training; develop systems and processes to enable the distribution of medical training positions within area health services and other public health organisations that control public hospitals in a manner aligned with their service and training and education; and develop postgraduate medical training networks and other training support infrastructures for area health services and other public health organisations that control public hospitals. The Institute has broad professional representation and reports through its advisory board directly to the NSW Minister for Health. Each state and territory needs to establish such an independent body reporting directly to the Minister for Health, and so create order and coordination in the medical workforce and in education and training. This will require political will and less talk and more action. It is time.

Geoffrey W Dahlenburg OAM, MD, FRACP, FRCPCH

Recommendations for primary prevention in women need to be different The efficacy of low-dose aspirin for the secondary prevention of cardiovascular disease among men and women is established.1,2 However, the risk-to-benefit ratio for aspirin in primary prevention is much less clear.2,3 The National Heart Foundation has recommended that low-dose aspirin be considered for people without symptoms but at increased (> 1% annual) risk of a coronary heart disease event.4 This recommendation is based on earlier primary prevention trials, with over 55 000 participants, showing a significant 32% reduction in the risk of myocardial infarction, but no significant change in risk of stroke or cardiovascular death.3 However, women comprised only 20% of trial participants, and fewer than 180 of the 2402 cardiovascular events occurred in women.3,5 Until recently, there has been limited direct evidence for the efficacy of aspirin in primary prevention among women. The Women’s Health Study (see Box) not only addressed this important sex issue, but suggested a significant difference in the cardiovascular response to aspirin between women and men.5 In this study, confined to healthy women aged 45 years or older, aspirin prophylaxis did not lower the risk of a first major cardiovascular event (non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes) — the primary endpoint. However, it did significantly reduce the risk of all strokes by 17%, and ischaemic stroke by 24%, without affecting the risk of myocardial infarction or cardiovascular death.5 This differs from previous aggregate data derived from mostly middle-aged men, and confirmed by a recent sex-specific meta-analysis, which showed that aspirin therapy significantly reduced the risk of myocardial infarction but not ischaemic stroke in men.6 Are there any apparent reasons for the seemingly opposite results for stroke and myocardial infarction in men and women? One possibility is that aspirin lowered the risk of stroke in women, but not men, simply because women have a higher risk of stroke than myocardial infarction. For instance, the ratio of incident stroke to myocardial infarction was 1.4 : 1 among women in the placebo group of the Women’s Health Study, compared with 0.4 : 1 among men of a similar age in the placebo group of the Physicians’ Health Study (a randomised, double-blind, placebo-controlled trial examining whether low-dose aspirin [325 mg every second day] decreases cardiovascular mortality and whether b-carotene reduces the incidence of cancer).7 Conversely, the Women’s Health Study may have lacked statistical power with respect to the risk of myocardial infarction. The study enrolled a group of largely healthy women, 85% of whom had a 10-year Framingham coronary risk score of less than 5%. Women also have a lower age-adjusted incidence of coronary heart disease than men; the rate of myocardial infarction among women in the Women’s Health Study was 97.3 per 100 000 person-years, about one-fifth the rate of myocardial infarction among men in the Physicians’ Health Study.7 Women tend to develop heart disease between 10 and 15 years later than men. This may explain why consistent benefits of aspirin on all major cardiovascular endpoints, including myocardial infarction and stroke, were observed only among women aged 65 years or older in the Women’s Health Study.5 This subgroup comprised 10% of the study population, but accounted for nearly a third of all cardiovascular events. In this subgroup, aspirin, compared with placebo, led to 44 fewer myocardial infarctions, strokes, or deaths from cardiovascular causes, but also caused 16 more gastrointestinal haemorrhages requiring transfusion, emphasising again the importance of balancing benefits and risks.5 A recent overview has also suggested that the risk of gastrointestinal and other bleeding with aspirin use may increase with age, and that the true balance of risks and benefits in the healthy aged population has not yet been established by randomised trials.8 The 100 mg alternate-day dose of aspirin used in the Women’s Health Study is lower than doses employed in previous trials. However, this regimen of aspirin was sufficient to reduce the risk of ischaemic stroke, and hence is likely to be an adequate dose for cardiovascular prevention. Nonetheless, sex differences in salicylate metabolism, platelet responses, vascular reactivity, and the nature of atherosclerotic disease may well cause different biological responses between men and women.9-11 This further highlights the need for women to be well represented in cardiovascular trials. What are the clinical implications of the Women’s Health Study? Overall, this study indicates that clinicians should be very cautious about advising women under the age of 65 years to take low-dose aspirin for primary prevention unless their global risk score is high. Even the benefit of aspirin for prevention of stroke in women needs to be carefully weighed against the increased risk of bleeding complications, and the low risk of stroke and other major cardiovascular events among apparently healthy women. To put this into perspective, the absolute risk reduction with aspirin therapy was about two stroke events per 1000 women treated.5 Thus, as with men, any decision about the use of aspirin for primary prevention among women requires an assessment of the net absolute benefit of therapy in an individual, and such a decision should be made only in association with an overall program of lifestyle measures to reduce cardiovascular risk.2 Reflecting these developments, the National Heart Foundation of Australia has recently amended its position statement on aspirin for cardiovascular disease prevention.12 Summary of the Women’s Health Study5 A large randomised placebo-controlled trial of aspirin (100 mg on alternate days) for primary prevention among 38 876 initially healthy women, aged 45 years or older, followed for 10 years for the occurrence of a first major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). The study recruited healthy women, 85% of whom had a 10-year Framingham risk score of less than 5%. The 10-year absolute cardiovascular event rate was low, and among placebo recipients there were more strokes than myocardial infarctions (266 v 193). At the end of the trial, major cardiovascular events (the primary endpoint) occurred in a non-significant 9% fewer aspirin recipients than placebo recipients (2.4% v 2.6%; P = 0.13). With regard to secondary endpoints, there was a significant 17% reduction in the risk of stroke in the aspirin group (1.1% v 1.3% with placebo; P = 0.04), owing to a 24% reduction in risk of ischaemic stroke; the two groups did not differ significantly in their incidence of myocardial infarction or cardiovascular death. Subgroup analyses showed that aspirin significantly lowered the risk of major cardiovascular events, ischaemic stroke, and myocardial infarction among women 65 years of age or older (6.4% v 8.5% with placebo; P = 0.008). The aspirin group had a higher frequency of gastrointestinal bleeding (4.6% v 3.8% with placebo; P < 0.001), and a non-significant increase in risk of haemorrhagic stroke (0.26% v 0.21% with placebo; P = 0.31). Overall, this trial indicates that caution is necessary when advising apparently healthy women to take low-dose aspirin for cardiovascular disease prevention.

Joseph Hung MB BS, FRACP, FACC

All stakeholders should contribute to enhancing Australia’s guidelines for ethical research Health and medical research involving human participants in Australia has been subject to guidelines promulgated by the National Health and Medical Research Council (NHMRC) since 1966. Currently, the key documents are the National statement on ethical conduct in research involving humans (1999)1 and the Joint NHMRC/AVCC statement and guidelines on research practice (1997).2 The former, better known as the “National Statement”, is endorsed by a number of peak national bodies, including the Australian Research Council (ARC) and the Australian Vice Chancellors’ Committee (AVCC). The “Joint Statement” is issued under the aegis of the NHMRC and the AVCC. The National Statement encompasses the ethical principles to be followed in proposing research involving humans, and advises institutions on the requirements for establishing human research ethics committees (HRECs). The Joint Statement provides guidance on good research practice, including details related to data collection, authorship and publication, supervision and mentoring and like matters, as well as providing the framework by which institutions should handle allegations of research misconduct. The system of oversight of human research based on these documents has been updated and modified from time to time and has served the nation reasonably well. However, the guidance provided in the documents has not been without its critics, and weaknesses in relation to the National Statement have been identified. These include under-resourcing of overworked HRECs,3 deficiencies in transparency and accountability of HRECs,3 absence of explicit application of the guidelines to the private sector,3 the failure of institutions and their HRECs to accommodate the vast increase in multicentre research4 and the “one size fits all” process of ethical review.5 The provisions of the Joint Statement for handling research misconduct allegations were severely tested and found wanting in a high profile case in 2004;6 furthermore, compared with Scandinavian countries,7 the education of new researchers in research ethics is patchy, especially outside our universities. As health and medical research has expanded in our teaching hospitals, there have been accusations that these institutions have not paid sufficient attention to the important task of research governance.8 In some instances, this has led to HRECs playing research governance roles for which they are neither equipped nor authorised — a development termed “mission creep”.9 The National Statement was extended by agreement to cover human research beyond the health and medical field, such as sociology, criminology and the humanities.1 However, this extension has led to criticisms of “ethics creep”; that is, the ethical review by HRECs of research of very low risk, thereby discouraging and frustrating some researchers and at the same time creating unnecessary work for HRECs.10 NHMRC guidelines are subject to regular review and any review includes obligatory public consultation. In addition, the Commonwealth National Health and Medical Research Council Act 1992 requires that the NHMRC, its principal committees and any working parties must “have regard” to any submissions received. Currently, both the National Statement and the Joint Statement are under active review by separate working parties of the NHMRC, the ARC and the AVCC. The two documents have already had an initial round of public consultation, and second draft revisions incorporating the responses to those consultations are now available for comment.11,12 Both documents contain important new sections. The necessity for institutions which support research to have solid policies and practices of good research governance (Box 1) is emphasised in both documents. For most institutions, this requirement should not have significant cost implications; rather, it will be a matter of more formally identifying and allocating existing responsibilities and reporting lines.8 The draft revised National Statement11 has been significantly modified. Researchers in fields beyond health and medical research should find it more responsive to their specific needs, and institutions should find it a more flexible document to use when deciding the level of independent review required for any research proposal. For health and medical researchers, interest will focus on several areas of new guidance, including risk in research and research with human stem cells, as well as extensively rewritten chapters such as those on data banks, clinical trials, genetics and tissue. Institutions and their HRECs should carefully consider the new final section on “Processes for research governance and ethical review”, which proposes significant alterations to matters including complaints handling, annual compliance reporting and monitoring of research. The draft revised Joint Statement, now to be known as the Australian code for the responsible conduct of research12 makes the roles and responsibilities of institutions and researchers much clearer. It calls for institutions to be much more active in providing education and induction of researchers in the realms of research ethics, research methods and research governance (Box 2). It spells out the conditions under which authorship of research publications is legitimate. It covers general principles for good research practices, data and records management, supervisory responsibilities, publication and dissemination of findings, peer review and conflicts of interest. Importantly, the new “Australian Code” presents a new look at dealing with research misconduct and fraud, including a proposed new framework for institutional responsibilities in handling allegations of research misconduct. This section was not available in the first round of public consultation, but incorporates material discussed at a stakeholder workshop on research misconduct held in Canberra in October 2005. It provides a more encompassing definition of research misconduct and calls for institutions to appoint “advisers on research integrity” as well as a senior “designated person” to take responsibility for the preliminary investigation of research misconduct allegations. For allegations of a serious nature, the inquiry established by an institution must be made up of people independent of the institution and must follow procedural fairness principles. We believe that these two draft documents herald a new era in the governance of research involving humans in Australia. At a time when commercial and other pressures on researchers may be increasing the risk of fraud and misconduct,13 it is crucial that our system for the oversight of research be sufficiently robust to protect participants and maintain community confidence in research. By emphasising the importance of research governance, reasserting the important roles that researchers and institutions have in the system of oversight, insisting on mechanisms for handling allegations of misconduct that are independent, prompt, fair and just, and making the processes of ethical review more responsive to the needs of different fields of research, the revised documents should be welcomed by all stakeholders. It is important that these stakeholders, including researchers, institutional leaders, sponsors of research, potential research participants, federal, state and territory governments and interested members of the community, consider and comment on the two draft documents. Input from as many stakeholders as possible in this second public consultation will enhance the guidelines and bring a greater sense of shared ownership. 1 Research governance Research governance is the framework by which institutions support, monitor and attest to the safety, ethical acceptability and quality of the research they undertake. Standards which underpin effective research governance exist in the domains of ethics and law, science, information protection, health and safety, intellectual property and commercialisation, financial management and public relations. For a more detailed discussion see reference.8 2 Education, training and induction* “To maintain a culture of responsible research conduct, it is important that institutions provide induction, formal training and continuing education for all research staff, including students and research trainees. Training should cover research methods, ethics, principles of confidentiality, data storage and records retention, as well as regulation and governance. Training should also include the institution’s policies and procedures regarding responsible research conduct, all aspects of this code, and the other sources of guidance that are available. Smaller institutions may make joint arrangements for induction and training with other institutions.” * Extracted from reference.12

Warwick P Anderson PhD · Christopher D Cordner PhD · Kerry J Breen MB BS, MD, FRACP

There is much to be gained by reducing children’s intake of soft drinks and little — except excess weight — to be lost Childhood obesity is a major health issue in Australia. In recent months, a number of organisations, including the Australian Medical Association,1 have released statements demanding stronger action on this issue, including a call to restrict access to and marketing of soft drinks to help reduce children’s consumption. However, the soft-drink industry rejects these proposals and argues that their product is being unfairly singled out for action. Further, many parents are confused as to why a drink they often consider to be a harmless treat should be labelled so damaging to their children’s health. In considering the suggested policy changes, it is therefore important to weigh up the information we currently have about the extent of soft-drink consumption, its impact on childhood obesity, and the potential of a reduction in consumption to contribute to improved weight control. The term “soft drink” covers a number of different beverages, but in Australia it is generally used to refer to carbonated beverages, and more specifically sugar-sweetened carbonated beverages. It may be assumed that other sugar-sweetened beverages, such as cordials and sweetened fruit drinks, which are consumed more regularly by young children, would have a similar impact on energy and nutrient intake. However, sugar-sweetened carbonated beverages and electrolyte drinks are usually singled out for specific attention because they are well identified products, which are readily available, marketed aggressively to teenagers, and make the largest overall contribution to the beverage intake of children. While it is widely reported that children consume too much soft drink, lack of continuous nutrition monitoring makes it difficult to provide accurate current data. Information on soft-drink consumption is available from a variety of sources using different dietary assessment methods and thus needs to be interpreted in different ways. However, the various sources of data are reasonably consistent in relation to the quantity of soft drinks consumed. A recent phone survey by Food Standards Australia and New Zealand found that 78% of all 12–17 year olds had consumed soft drink in the previous week,2 while the 1995 National Nutrition Survey found that around half of all teenagers and a surprising 26% of 2–3 year olds had consumed soft drink during the previous 24 hours. Boys tended to consume more soft drink than girls, with boys aged 16–18 years drinking an average of 480 mL each day (or 836 mL per day among those who consumed soft drink), double the consumption of girls of that age (unpublished data from the 1995 National Nutrition Survey recalculated by us to include soft drinks only. Complete data in National Nutrition Survey: foods eaten, Australia, 19953). This was equivalent to 5.5% of the average total energy consumed by 16–18 year olds or 10.8% of the energy intake of the consumers. Apparent consumption data from the Australian Bureau of Statistics, as well as industry data, suggest that the intake of soft drinks in Australia has grown rapidly in the past 30 years from around 47.3 L per person per year in 1969 to 113 L per person (children and adults) in 1999.4 While this is some way below the per capita consumption of 200 L per year in the United States, it does put Australia within the top 10 countries for consumption and represents a market of around $1.6 billion per year.5 There is reasonable evidence that a high intake of soft drinks is associated with a greater risk of weight gain and obesity. A number of US studies show a strong cross-sectional association between soft-drink consumption and excess energy intake in adolescence,6,7 and NZ children who drank soft drinks more than once a day also were found to have a significantly higher mean body mass index (BMI) than children drinking soft drinks less than once a week, even after controlling for other known risk factors for weight gain.8 Longitudinal studies provide stronger evidence of a role for soft drinks in weight gain in children, with a large observational study of 10 000 children showing a consistent relationship between consumption of sugar-added beverages and weight gain over a 2-year period.7 A smaller 19-month study of 548 children aged 11 years found that both initial consumption and increases in intake levels of soft drink were associated with increased BMI and risk of obesity.9 A 10-week feeding trial found that when overweight adults were given a supplement of sucrose, mostly in the form of soft drink, they gained on average 1.6 kg, while a control group fed an artificially sweetened supplement lost 1.0 kg.10 The low satiating properties of energy-rich fluids compared with solids has been proposed as a possible reason for the close association between energy from soft drinks and weight status.11 Only a few studies have examined the effect on weight status of interventions aimed at reducing energy intake from sugar-sweetened soft drinks. These studies support the potential of such action, while leaving many questions unanswered about how best to achieve the desired outcomes. A school-based intervention that encouraged children (7–11 years old) to reduce their intake of “fizzy” drinks was able to achieve within 1 year a significant reduction in overweight and obesity in the intervention group compared with the control group, although the design and statistical analysis of this study have been criticised. The evidence linking soft-drink consumption to weight gain and obesity, while not complete, is consistent and strong enough to support action. Soft drinks are consumed in large amounts by young people in Australia and thus the calls for curbing intake appear to be justified. As soft drinks have been linked to other health concerns such as dental disease and, moreover, provide no valuable nutrition (apart from fluids), there is potentially much to be gained by reducing the intake of these (and other) sugar-sweetened beverages by Australian children and little (except excess weight) to be lost.

Timothy P Gill PhD GradDipDiet · Anna M Rangan PhD, GradDipNutrDiet · Karen L Webb MPH, PhD

Managing access block involves reducing hospital demand and optimising bed capacity Hospital overcrowding causing “access block” — a lack of available inpatient beds for emergency department patients — remains a major impediment to the delivery of good health care both in Australia and overseas. It is obvious that making elderly or disabled patients wait on uncomfortable emergency trolleys in corridors, with sleep deprivation and minimal privacy, is inhumane. Previous research has shown that hospital overcrowding is actually inefficient: it is associated with increased length of hospital stay,1,2 thus potentially reducing throughput. The number of adverse events has also been shown to increase with worsening access block.3,4 An overcrowded hospital should now be regarded as an unsafe hospital Two articles in this issue of the Journal have put pressure on efforts to solve this problem. Sprivulis and colleagues5 and Richardson,6 using different methods and different populations, have shown a strong association between access block and mortality rate. Their findings now make access block a patient safety issue for which all health care workers and the community must be responsible. It is incumbent on governments and administrators to prevent overcrowding by improving management of the health care system and, where necessary, providing increased resources. These two studies have certain methodological issues that require comment. Firstly, both studies used administrative databases. These are convenient and allow very large populations to be studied. Sprivulis et al, in their study, have also taken advantage of the linked databases in Western Australia and looked at outcomes beyond hospital admission, thus avoiding the potential bias of only studying outcomes in hospital. Unfortunately, many data elements are not available on administrative databases. Data on physiological variables, details of treatment and past medical history, for example, were not available to more accurately adjust for risk within patient groups. It is also likely that unknown confounders may have been present, such as changing referral patterns, patient choice, and non-seasonal changes to illness patterns. Despite this, the association between periods of overcrowding and increased mortality is quite strong. Both studies have attempted to adjust for obvious confounders such as age, type of illness, seasonal effect, and so on. What Sprivulis et al and Richardson have shown is that there is an association between overcrowding and mortality, not that overcrowding causes mortality. It is possible (but unlikely) that an influx of sick, elderly patients at high risk of death may actually cause overcrowding, thus resulting in the apparent association. Without a controlled intervention study, it is not possible to conclude that reducing overcrowding would reduce mortality. There are good reasons for assuming a causal relationship: known effects of overcrowding include delays in patient management, poor hospital processes, poor infection control, patients not being placed on the appropriate ward, and so forth. Given that it is logical that there is a causal relationship and that there is no known increased risk to patients under conditions of normal hospital bed occupancy, it is unacceptable to continue to allow hospital overcrowding to occur. There have been many attempts to ameliorate the problem of access block across Australia7 and internationally.8 The exacerbation of access block seen in the past few years is symptomatic of much larger changes occurring within the health system. Changes to workforce, working hours, aged care, and funding, as well as fewer hospital beds, and increasing demand for seemingly limitless new treatments and procedures, have all contributed to access block. Governments have responded to these challenges by increasing resources (health care now consumes 9.6 % of Australia’s gross domestic product9), improved monitoring of performance through various indicators, and myriad initiatives to improve efficiency within hospitals as well as divert some patients away from hospitals. This effort has alleviated access block in some jurisdictions,10 but there are still major difficulties across Australia. What should be done?There are two broad strategies for managing access block resulting from hospital overcrowding — reducing hospital demand and optimising hospital bed capacity. Reduce hospital demandDiversion/substitution: The major focus of this strategy has been to divert patients to community services and provide more services in the community that traditionally occur in hospital (eg, hospital outreach programs, hospital in the home, and improved after-hours general practice services). Reducing expectations: Reducing community expectations of what a public hospital system can provide is a politically sensitive strategy that has not been systematically addressed. Access block cannot be controlled without some limits being placed on the provision of services. Demand for health care is elastic and potentially unlimited, especially in an essentially free health care system. There must be public debate about what is essential versus what is desirable, and how much the community is willing to pay. Prevention: There is potential to reduce demand by disease prevention strategies, and improved management of patients with chronic ill health. Optimise hospital bed capacityImproved processes: There has been an enormous effort by health care workers to increase capacity by improved efficiency of health care delivery. Many initiatives with quick returns have already been implemented. Further significant improvements will need major investments in infrastructure, especially information technology. Workforce reform is necessary to increase the flexibility of the workforce and the capacity of the health care system. There is presently a shortage of virtually every type of skilled worker in the health care sector. Balancing elective and emergency workload: Contrary to popular opinion, the emergency workload is highly predictable across metropolitan areas. Elective treatment must be tailored to match the capacity allowed by predicted emergency work. Better discharge: Moving patients quickly from acute hospitals to more appropriate facilities increases hospital bed availability. Access to rehabilitation, residential aged care and community outreach programs is an essential component of an efficient and well managed health system. Addressing physical, social and psychological issues through care coordination in the emergency department and after hospital discharge can also help reduce hospital length of stay and readmission. Increased bed numbers: It is important to note that access block does not correlate well with the absolute number of hospital beds. Increasing the number of hospital beds temporarily alleviates access block, but does not solve the problem — the beds quickly fill and the problem recurs. Nevertheless, governments must fund an adequate number of beds to provide the health care that the community demands. An overcrowded hospital should now be regarded as an unsafe hospital. Health care workers should not have to provide services in an environment that potentially jeopardises patient safety. Government and communities must decide whether they want a well managed, adequately resourced health care system where demand is matched to available resources or to take their chances with the present system.

Peter A Cameron MB BS, FACEM, MD

Public trust depends on promoting good practice and protecting the public from poor practice Traditional medical professionalism derives from medical practice in the late 18th and early 19th centuries. In the past 10 years, the search has been on in the United Kingdom — and in other countries — for a “new professionalism” more in harmony with patients’ expectations and the nature of medical practice today.1-5 Last month, the Royal College of Physicians of London affirmed its commitment to professionalism as the foundation of good quality medical practice through a Working Party report titled “Doctors in society: medical professionalism in a changing world”.6 That commitment is important, and has relevance beyond the UK. It comes at a time when some consider the very notion of “profession” and “professionalism” to be outmoded. The report and a supplement of excellent evidence7 (underpinning the report) is seen as the starting point for further development. The case for rethinking medical professionalism is presented with conviction and passion. Located in the social context and environment of today’s practice, medical professionalism is defined as a “set of values, behaviours, and relationships that underpin the trust the public has in doctors”.6 Medicine is described as a “vocation in which a doctor’s knowledge, clinical skills, and judgement are put in the service of protecting and restoring human well-being. This purpose is realised through a partnership between patient and doctor, one based on mutual respect, individual responsibility, and appropriate accountability”.6 In their everyday practice, doctors are committed to integrity, compassion, altruism, continuous improvement, excellence and partnership in health care teams. These values should form the basis for a new “moral contract” between the medical profession and society. Professionalism, the report argues, is as important as ever today because it codifies the idea that a doctor’s responsibilities go beyond a “mere” contract of employment. It advocates a concept that “recognises the complexity and uncertainties within clinical practice and which is based on an indissoluble partnership between patient and doctor in a radically new social context”.6 To this end, notions of knowledge, skills, science, practice, profession, society, service, commitment and integrity are retained. The report discards notions of “mastery”, “autonomy”, “privilege”, and “self-regulation” as out-dated or inappropriate. Competence, which describes “mere” capability, is replaced by excellence reflecting abilities of an “eminent” degree. The long tradition of the “art” of medicine yields to “judgement” as a characteristic more in tune with the application of clinical reasoning. Altruism and the idea of vocation are still there, but only just. And accountability is valued provided that it is “appropriate”, that it avoids creating a culture of suspicion and blame. All these ideas, some deeply controversial, will give doctors and the public much food for thought. So far so good. Then we come to the implications and 19 recommendations for implementation. These cover six areas: leadership, teams, education, appraisal, careers, and research. Professional bodies in the UK are urged to create a common forum that would speak on behalf of medicine with a unified voice. The proposals are sensible but lack bite. They are full of gentle, permissive words like “review”, “revise” and “consider”. Moreover, the report shies away from areas where tough decisions are needed if public trust in the institutions of the UK medical profession is to be restored.8 For example, it is tentative about the profession’s responsibility for defining the boundaries of medical practice and the standards, both the acceptable and the unacceptable, which it will expect individual doctors to observe consistently. In rejecting self-regulation — without discussion — it says nothing about the regulatory framework within which the profession and its professionalism must function. Revalidation, the most important recent development in medical regulation likely to improve patient safety if done thoroughly, is scarcely mentioned. Similarly, there is nothing about the role of rigorous peer review in quality assurance of doctors’ professionalism. This may be no accident. The authors say that they are attempting to usher in a major philosophical shift in attitudes to medical practice in the UK. They believe that the regulatory pendulum has swung too far towards a new, rule-based orthodoxy in which good standards of medical practice are a matter of rigorously enforced dutiful conduct. They seek to revert to a “more balanced position” where there is an understanding that an environment that encourages a doctor’s “goodness” is one that will promote positive patient outcomes. This is a false dichotomy. Modern professionalism is about both the encouragement and celebration of good practice and the protection of patients and the public from suboptimal practice. They are one of a piece — indivisible. Public trust is dependent on both. Achieving that will require some hard, creative thinking and courageous leadership by doctors’ organisations if professionalism, medical education and professional regulation are to put — and be seen to put — the interests of patients unequivocally first.8,9 The College has made a good start. However, fine words are no substitute for a track record of decisive action. The General Medical Council has had to learn that the hard way.10 Dame Janet Smith, who conducted the Shipman Inquiry,10 said to the Working Party that the public ought not even have to think about whether they trust their doctors — it should be something they are able to take completely for granted. Quite so. Everyone expects to have a good doctor.

Donald H Irvine CBE, MD, FRCGP

New tumour testing methods can improve the accuracy of diagnosis Although a strong genetic predisposition to colorectal cancer (CRC) is rare, it is important because of its large contribution to CRC diagnosed before the age of 50 years and because mortality from CRC can be reduced by appropriate management. There are currently limitations in determining whether a case of CRC is “sporadic” or whether it might be related to an inherited predisposition. However, Australian research that examines the utility of new diagnostic tools to help diagnose genetic tendency to CRC may be showing us a way forward.1,2 What is hereditary non-polyposis colorectal cancer?The two best-characterised high-risk inherited syndromes are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer (HNPCC) — sometimes known as Lynch syndrome. Both are inherited as autosomal dominant traits. Familial adenomatous polyposis can usually be readily diagnosed on the basis of clinical findings alone, when an individual develops CRC at a relatively young age on a background of colorectal adenomatous polyposis (mostly with more than 100 adenomas). HNPCC cannot usually be readily diagnosed. HNPCC accounts for about 1%–4% of all CRC, but up to 10% in patients younger than 50 years at diagnosis. It is caused by a germline (heritable) mutation in one of a family of genes known as the DNA mismatch repair genes: hMLH1, hMSH2, hMSH6 and hPMS2.3 HNPCC is characterised clinically by an early age of onset of CRC, a predisposition for proximal colonic cancers, and a tendency to develop multiple CRC, along with an increased risk of some extra-colonic malignancies, including cancers of the uterus and ovary, stomach, small bowel, biliary tree, ureter, renal pelvis, pancreas and brain. The family history is often complex. What are the difficulties in diagnosing HNPCC?Traditionally, HNPCC has been suspected in families where the family history of cancer meets the modified Amsterdam criteria.4 These require a family to have at least three close relatives in two generations diagnosed with cancer of the colon, rectum, endometrium, small bowel, ureter or renal pelvis, with at least one diagnosed before age 50 years. One problem is that not all “Amsterdam positive” families will be proven to have HNPCC and, conversely, some families with proven HNPCC do not meet these criteria. Family history alone is not enough — a diagnosis of “suspected HNPCC” may be based on verified clinical and pathological information from the family pedigree, but the diagnosis of HNPCC is ultimately confirmed by the demonstration of a family germline mutation in one of the mismatch repair genes. This is done by taking blood from one of the affected family members and searching the mismatch repair genes to determine whether a causative mutation can be found. However, a mutation cannot be found in every family, as mutations may be missed or mutations may be present in other genes that are not yet identified. This means that if the family history is strong (Amsterdam positive) and the genetic test (mutation search) fails to identify a mutation in an affected family member, the test result should be considered “inconclusive” and all relatives remain at potentially high risk. Only when a causative mutation in one of the mismatch repair genes has been identified can other at-risk adult family members be offered “predictive” genetic testing to determine their risk. Importantly, those found not to carry the family mutation should be considered at the average population risk for cancer, and they (and their offspring) can be spared additional cancer screening and concern. At present, many families with a family history that meets or approaches the Amsterdam criteria are offered this expensive approach to germline genetic testing; few are found to have proven HNPCC. How are these difficulties being addressed?The accurate detection of HNPCC has improved recently for a number of reasons. The first is an increasing awareness of family history as a risk factor for CRC. Clinical practice guidelines assist in estimating CRC risk based on family history.5,6 For those with a more complex family history, referral to a family cancer clinic may be appropriate. These clinics have been developed to provide cancer risk assessment, surveillance, and prevention strategies, with genetic counselling and testing when appropriate. Finally, we now have improved diagnostic tools, including molecular testing of tumours for microsatellite instability and immunohistochemical staining of tumour tissue for mismatch repair proteins, which can be used to help investigate a history of “suspected HNPCC”. Additional molecular tumour tests are in development. Molecular testing for microsatellite instabilityMicrosatellite instability is one of the hallmarks of HNPCC-related cancers and is due to unrepaired mutations in repetitive sequences of DNA known as microsatellites. CRCs that occur in patients with HNPCC tend to be right-sided, mucinous, poorly differentiated and characterised by the presence of tumour infiltrating lymphocytes. On molecular testing, these tumours show high levels of microsatellite instability. The Bethesda guidelines7 were developed to provide criteria for testing tumours for microsatellite instability in an individual affected family member to assist in the diagnosis of HNPCC. These guidelines suggest that all people with CRC diagnosed before the age of 50 years should have microsatellite instability testing to look for possible HNPCC. However, another limitation presents itself. Although high levels of microsatellite instability are seen in most HNPCC-related tumours, microsatellite instability is not exclusive to HNPCC. Some people develop sporadic cancers with high levels of microsatellite instability, unrelated to an inherited defect in mismatch repair; around 10%–15% of sporadic colorectal cancers will exhibit high levels of microsatellite instability. This tends to occur in older women with right-sided cancers, often mucinous, with poor glandular differentiation (as per HNPCC), but with no associated HNPCC family history. In patients with sporadic CRC with high levels of microsatellite instability, the defect in mismatch repair is not heritable and occurs only in the tumour as a result epigenetic silencing of the promoter region of hMLH1. It does not alter the risk of CRC in offspring, so it is important to differentiate this from HNPCC. Tumour BRAF gene mutations occur in most of these sporadic cancers, but virtually never in HNPCC-associated cancers with high levels of microsatellite instability. The presence of a BRAF gene mutation in a tumour with high levels of microsatellite instability makes it more likely to be a sporadic CRC; however, the use of tumour testing for BRAF mutation is speculative at this stage and it is not yet readily available. Immunohistochemical stainingAnother approach used to improve the accuracy of diagnosis of HNPCC is the use of immunohistochemical staining in suspected cases. Immunohistochemical staining uses antibodies to the proteins encoded by the four relevant mismatch repair genes (hMLH1, hMSH2, hMSH6 and hPMS2) to test for the expression of these proteins in tumour tissue. Absence of mismatch repair proteins is often seen in HNPCC and may be specifically related to the gene in which a germline mutation may subsequently be found; that is, the absence of hMSH2 protein in cancer cells usually indicates a germline mutation in hMSH2. However, once again, this absence of staining is not specific to HNPCC — loss of expression of hMLH1 due to somatic inactivation of hMLH1 does occur in sporadic cancers. How is Australian research contributing in this field?Southey et al have recently conducted an analysis of the use of tumour testing to prioritise mismatch repair germline testing in an Australian population-based study of early onset (< 45 years old) CRC.1 In 131 patients, unselected for family history, they found 18 with germline mutations in one of the mismatch repair genes (indicating HNPCC). Based on family history alone (the Amsterdam criteria), only half of these would have been identified, indicating that tumour testing (specifically immunohistochemical staining) is a very useful adjunct to diagnosis, and more sensitive than family history. Ward et al, also Australian, have since published similar findings.2 Immunohistochemical staining has an advantage over microsatellite instability testing in that it is relatively inexpensive, can be conducted in a routine pathology laboratory (rather than a molecular laboratory), and the immunohistochemical staining test identifies the specific mismatch repair gene in which to search for a germline mutation, thereby saving money by directing the mutation search. However, although immunohistochemical staining is promising as a tool to increase diagnostic accuracy for HNPCC, it may be too early to apply this test routinely at diagnosis to all patients with CRC. There are still some problems with tumour testing. Some patients have loss of staining on immunohistochemical staining without a demonstrable mismatch repair germline mutation, indicating a lack of specificity, although this may change as germline testing improves. Immunohistochemical staining utilises antibodies that are not commonly used in pathology laboratories, and staining may be patchy and difficult to interpret for those who do not use these antibodies routinely. Moreover, there is generally a lack of understanding concerning the interpretation of loss of stain — loss of hMLH1 in a patient with an older onset CRC, without family history, usually indicates a sporadic cancer rather than HNPCC, but some of these families are now inappropriately being referred to family cancer clinics as “possible HNPCC”. Finally, some argue that tumour testing is a surrogate genetic test and so requires genetic counselling and fully informed consent. However, tumour testing should be simply viewed as a useful adjunct to HNPCC diagnosis, in that an abnormal finding on immunohistochemical staining raises the possibility, rather than the certainty, of a familial predisposition to CRC. Where to from here?Tumour testing could now be used as a “triage” measure to assist referral to a family cancer clinic for further assessment and germline testing, if appropriate. It is especially applicable when the family history approaches, but does not quite meet, the Amsterdam criteria for suspecting HNPCC or when CRC is diagnosed at an early age (younger than 50 years). However, before this can become routine, immunohistochemical staining testing for HNPCC may need to be standardised, and laboratories validated through the Royal College of Pathologists of Australia to ensure reliable results. Even so, for now, the best diagnostic precision is still achieved by a combined analysis of all the variables: family history, and clinical and pathological findings, as well as results of genetic tests.

Judy A Kirk MB BS, FRACP

The Canberra Heart Study findings are a wake-up call to those unaware of the extent of the condition Chronic heart failure is a major and growing public health issue that affects all Western countries. Accordingly, many countries (eg, Scotland1 and Sweden2) systematically monitor its population prevalence and overall impact on the health care system. However, public awareness of the condition remains low.3 Unfortunately, in Australia, apart from sporadic initiatives such as the NSW Chronic Care Collaborative, heart failure remains the “Cinderella” of health issues — hardly registering on the radar of key health care providers, regulators, relevant government bodies and the general public. For example, less than one in five eligible patients receives specialist heart failure management after hospitalisation for acute heart failure.4 Undoubtedly this is at least partly explained by the fact that we do not know the true magnitude of the problem in Australia. It is time for us to recognise heart failure as a major public health issue that cripples hundreds of thousands of Australians and places a substantial burden on the health care system. . . . heart failure remains the “Cinderella” of health issues . . . The facts from overseas population studies are plain and startling. Depending on how the condition is defined, anywhere between 3% and 9% of the adult population has heart failure, and a similar proportion has “silent” left ventricular dysfunction.5 Moreover, the incidence of heart failure is still rising. Indeed, it is the only cardiovascular condition not to experience a substantial decline in both incidence and prevalence over the past 20 years (taking into account the progressive ageing of populations).1 There are several reasons for this increase. Firstly, the incidence of heart failure increases with advancing age. In Australia, the proportion of people aged over 65 years (in whom heart failure prevalence is > 10%) will double over the next 50 years.2 Secondly, improvements in diagnostic techniques such as echocardiography have enhanced the ability to make a definitive diagnosis. Thirdly, treatment of heart attack has improved to the extent that patients who previously died of large myocardial infarctions are now able to survive. Finally, heart failure treatments themselves are keeping patients alive for longer and thus contributing to an ever-expanding pool of affected Australians. Can overseas data on prevalence be extrapolated to the Australian population? While the answer to this question is a qualified “yes”, specific issues in Australia relating to treatment approaches, access to diagnostic and health care services and the ethnic mix of the population may affect prevalence figures.5 Moreover, given the public health importance and impact of heart failure, it would seem reasonable to develop an Australia-specific response based on known rather than speculative facts. Thus there is an urgent need for a large-scale, definitive, Australia-wide epidemiological study to ascertain aetiological factors, diagnostic approaches and management of this condition in the Australian community. In this context, the Canberra Heart Study,6 published in this issue of the Journal, is an excellent start in helping to determine the true magnitude of the heart failure problem in Australia. The findings of this well conducted community-based study are a wake-up call to those unaware of the extent of the condition. Not only were 6.3% of the population surveyed found to have overt symptomatic heart failure, but there was a high proportion of patients with subclinical heart failure (left ventricular dysfunction in the absence of symptoms).6 The study also noted a significant proportion of patients with so-called “preserved systolic function” heart failure (ie, symptoms of the condition but with preservation of systolic ventricular function and pointers on echocardiography to impaired relaxation of the ventricle during diastole). The Canberra Heart Study is not without some methodological problems (eg, a relatively small sample size, and thus few positive diagnoses for heart failure; under-participation of elderly women, who may well have added to the burden of diastolic heart failure). Moreover, as with any study of heart failure, the definition of the condition is always fraught with uncertainty, although it appears to have been quite reasonably addressed in this analysis. Complexity in diagnosing heart failure is one of the main reasons for under-recognition of the condition. Indeed, there is no single agreed definition, and the forthcoming update of the current National Heart Foundation/Cardiac Society of Australia and New Zealand guidelines on heart failure7 will propose a further modification to earlier definitions. Heart failure is a syndrome — a cluster of signs and symptoms that require detailed investigation before arriving at a presumptive diagnosis. There are no definitive tests to confirm the diagnosis. Furthermore, as presenting symptoms may be non-specific, heart failure can masquerade as, and be masked by, many other conditions, particularly in elderly people. A recent Australian analysis describing barriers to diagnosis and management of heart failure in the primary care setting points to some of the difficulties of making a definitive diagnosis.8 Nevertheless, it is important that a definitive diagnosis be made because, at least for systolic left ventricular dysfunction (whether symptomatic or not), appropriate management can have a great impact on disease progression, symptoms and survival. Heart failure management is complex, involving a multidisciplinary approach, polypharmacy in drug prescribing, and ancillary modalities that may include exercise, device therapies (eg, cardiac resynchronisation, implantable defibrillators) and surgical procedures. Early detection of subclinical heart failure (to prevent progression to symptomatic disease) and treatment of known risk factors will be major foci of research and clinical interest in the evolution of future heart failure management strategies. In summary, the authors of the Canberra Heart Study6 have done the Australian community a great service in providing epidemiological data to show that heart failure truly is a major public health issue in Australia. The problem requires the type of national response that has been initiated in other Western countries. This regional study should be regarded as the critical stimulus for a national study that would provide a broader, more detailed analysis of the epidemiology, health care burden and management of heart failure in Australia. Without this, Australia will continue to fall behind other Western countries in improving the nation’s health by focusing on prevention and treatment of this highly debilitating and deadly condition.

Henry Krum MB BS, PhD, FRACP · Simon Stewart PhD, FESC, FAHA

One way to tackle social forces that lead to disease is to recruit the putative culprits The world is in the grip of an epidemic of non-communicable disease. We have known this in affluent nations for decades, but have not understood just how large a problem it has become in developing economies.1 Chronic diseases such as cardiovascular disease (CVD), type 2 diabetes, cancer and obstructive pulmonary disease are increasingly undermining prospects for a stable economic future, especially in lower- and middle-income countries2,3 and the poorer segments of society in the developed world. The origins of these diseases are largely social. What and how much we eat, how physically active we are, and whether we smoke are individual behaviours that we might wish to change but which emerge from a maze of causes, including our job, school, suburb, education, religion, car, and money. Philosophers refer to “wicked” problems — ones of great complexity to which there are no simple or stable solutions4 — and non-communicable disease is as wicked as the White Witch, and then some. If only there was a vaccine, if only there was one drug, if only . . . Yet an inventory of our assets in dealing with these diseases is far from depressing. We Australians have quit smoking in droves; we have developed medical and surgical approaches that stabilise risk and more than halved mortality from CVD.5 We have moved death from heart disease from middle to old age. Supermarket shelves relax with the reduced weight of “lite” foods. The success bears scrutiny. Some of it is medical (antihypertensives, lipid-lowering therapies, coronary artery bypass surgery, newer antidepressants, chemotherapy), but not all. Some of it is due to relentless health promotion (Life. Be in it; Quit for life), but not all. Some of it is due to regulation (tobacco tax, seatbelts, and urban planning taxes on developers devoted to healthy suburbs). Some is due to commerce and industry sensing a market advantage in selling healthy products. On 28 November 2005, the Australian Health Policy Institute at the University of Sydney launched its membership as a major centre in the Oxford Health Alliance. The purpose of the Oxford Health Alliance is to influence the macroeconomic and policy environment to favour fitness, good nutrition and reduced smoking, accepting that these behaviours are social as well as personal phenomena that require community involvement in the widest possible sense.6 The Alliance seeks to capitalise on research and to build a global partnership to pursue its mission. It aims to assist institutions, including the World Health Organization, control non-communicable chronic disease. What is unique about the Oxford Health Alliance is its inclusive nature. The Alliance includes not only academia and government, but the private sector and a host of non-government organisations. The Oxford Health Alliance was established under an academic–industry partnership between the University of Oxford and Novo Nordisk, Denmark, a company whose pharmaceutical branch produces insulin. Novo Nordisk looked with Scandinavian horror upon the rising rates of diabetes worldwide, despite these being excellent for their bottom line. In combination with Professors John Bell and David Matthews at Oxford University and Professor Derek Yach, formerly director of the non-communicable disease cluster at WHO but now working at the Rockefeller Foundation, the nascent Oxford Health Alliance has begun to explore ways to reduce the epidemic of chronic disease. John Bell is Regius Professor of Clinical Medicine at the University of Oxford. As Nuffield Professor of Clinical Medicine, he oversaw the largest research department at Oxford University, which encompassed activities spanning structural biology through to epidemiology. David Matthews is Chairman of the Oxford Centre for Diabetes, Endocrinology and Metabolism and has published extensively in the fields of insulin resistance. The Alliance has grown steadily. It has supported three annual 3-day conferences: two at Oxford, and one on 31 October 2005 at Yale in New Haven, Connecticut, where 170 people from 25 countries assembled, from a diverse array of backgrounds, including academia, government, the private sector (PepsiCo, Nestlé, McDonalds), non-government organisations, finance and media, consumer organisations, and professional bodies such as the World Nursing Federation, World Medical Association and World Heart Federation. Topics covered included the economic rationale for investing in chronic disease prevention, patient power, the intersection between health and business, the current framing of chronic diseases in the international agenda, and design for a healthy world. “Oh, my!” said one colleague when he heard that the University of Sydney, through its health policy institute, was joining the Alliance. “So! The Oxford Health Alliance has discovered nutrition!” Fair enough: knowing about risk factors and behaviour is hardly new. The starting point for the Alliance is exactly that: that “discovery” is not enough. Knowing about the nature of risk factors for chronic disease is akin to realising that the pain in your foot is due to an elephant standing on it — moving the elephant is another matter entirely. Our purpose in the Oxford Health Alliance is to bring to the table those businesses and non-medical interests that traditionally have been seen as the Dark Side. This is not about “selling out to industry”, but seeking points of agreement whereby what is done in future is less harmful to health. Academics at the Alliance meetings have enjoyed beating up the representatives from McDonalds and PepsiCo: this is a familiar and exciting, if useless, attempt at solving problems. At the meeting at Yale, the baiting had subsided somewhat, especially in response to an impressive list of marketing and product formulation changes presented by industry representatives. McDonalds, for example, now buys more apples than any restaurant chain in the United States.7 In Australia, it has introduced a range of salads and now cooks with canola oil. The Economist, commenting on PepsiCo’s rising economic fortunes that put it ahead of Coca-Cola for the first time, notes PepsiCo’s diversification “away from a reliance on sugary colas”, deriving only 20% of its revenue from soft drinks, in comparison with 80% at Coca-Cola.8 Of course there is a risk: skills in Defence against the Dark Arts would be helpful. (By contrast to big business, academia is, we all know, blessedly free of self-interest — and it rarely makes a profit!) But if we are seeking to modify the major social forces that entrain damage and cause chronic disease, new ways must be found to do this by recruiting the putative culprits. The answer will probably be expressed as policy — a practical, feasible commitment of many players, amid muddle and ambiguity, to a course of action to mitigate a wicked problem. It is a messy process. But for the Oxford Health Alliance, it is core business.

Stephen R Leeder AO, FRACP, FFAPHM, FFPHM · Ruth Colagiuri BEd, GradCertHealthPolicyManagement

Australia’s effective monitoring system shows that serious reactions are rare Australia has achieved very high levels of vaccination coverage in the past 10 years, with 91% of children fully vaccinated at 12 months of age and 92.1% at 2 years.1 Consequently, rates of vaccine-preventable diseases are very low. As the incidence of vaccine-preventable diseases declines, the safety and side effects of vaccines gain prominence, and an increasingly important role of health care professionals is to communicate the benefits and risks of vaccination to parents.2 Worries about vaccines date back more than 200 years, when Jenner’s introduction of cowpox vaccine prompted cartoons in the satirical magazine Punch depicting vaccine recipients turning into cows. More recently, unproven and unjustified concerns about pertussis vaccine3 and measles–mumps–rubella vaccine4 have resulted in falls in vaccination uptake in the United Kingdom, and the needless deaths of children.3,4 Vaccine constituents, such as preservatives, stabilisers, adjuvants and biological growth media used in vaccine production, are necessary to ensure the efficacy, stability and safety of vaccines, but can also contribute to consumer concerns.5 A recent review concluded that the amounts of aluminium, formaldehyde, antibiotics and yeast proteins in vaccines have not been found to be harmful to humans and animals in exposure studies.5 Currently, if providers have concerns about constituents of vaccines, they can consult the excellent booklet Myths and realities.6 In addition, the National Centre for Immunisation Research and Surveillance (NCIRS) website (<http://www.ncirs. usyd.edu.au>) has a fact sheet relating to thiomersal: <http://www.ncirs.usyd.edu.au/facts/f-thiomersal.html>. The US Centers for Disease Control and Prevention have fact sheets on vaccine components at <http://www.cdc.gov/node.do/id/0900f3ec8006587f>. The article by Eldred et al7 in this issue of the Journal is an important overview of vaccine components and constituents of vaccines in use in Australia, and is an important reference for vaccine providers to answer consumer concerns and questions. Serious adverse events following vaccination are rare, and the risk of morbidity associated with these adverse events is generally far less than the risk from catching a vaccine-preventable disease. Nevertheless, it is extremely important to have in place adequate surveillance for adverse events associated with vaccines. Both the public and health care professionals need to feel confident of vaccine safety. Australia has had local reporting mechanisms for many years, but only since 2000 has there been a national reporting system.8 Under the current system, which was driven by the dynamism of John McEwen, former Principal Medical Adviser of the Therapeutic Goods Administration (TGA), all adverse reports are coordinated by the Australian Adverse Drug Reactions Unit (ADRU) of the TGA. Adverse events associated with vaccines can be reported to ADRU by health care professionals or the public by telephone (02 6232 8386) or by prepaid reporting form (“blue card”) or online at <http://tga.gov.au/adr/bluecard.htm>. The data are further analysed by NCIRS and regularly reported in Communicable diseases intelligence.9-11 The data are extremely reassuring: serious adverse events are rare. Between 2000 and 2004, only seven of 5128 adverse events reported following vaccination were reported as having persisted and resulted in sequelae.9-11 Furthermore, the reporting of an adverse event following vaccination implies an association in timing with vaccine administration, but does not necessarily mean the vaccine caused the reported adverse event. Australia has an effective system for monitoring vaccine safety. In future, privacy laws permitting, it is hoped to link Australia’s database of immunisations, the Australian Childhood Immunisation Register, with hospital admissions to be able to look actively at questions regarding the safety of specific vaccines. It is vital that parents and providers are fully informed about the risk of vaccines and of the diseases they prevent. Australia’s monitoring system will continue to gather the data for informed decision-making.

Nicholas Wood MB BS, DCH, FRACP · David Isaacs MB BChir, MD, MRCP, FRACP, FRCPCH

The profession should speak with one voice in the debate about task transfer In mid December last year, a group of senior doctors, nurses, allied health professionals, hospital administrators and consumers in New South Wales publicly announced that they had had enough. So great was their frustration with the failure of the government to creatively confront the continuing workforce crisis in NSW public hospitals that they had banded together as the Hospital Reform Group to initiate open debate in the community and to find solutions. The media dubbed them the “health rebels”.1 Listed in the group’s manifesto is the statement: We see an urgent need for major workforce reform. The health workforce and workplace practices must be modernised. The traditional divide between professional disciplines and responsibilities is not necessarily appropriate for the future.2 In short, the group believes that public hospitals need to be dragged into the 21st century and their workplaces need to capitalise on current professional capabilities and not be bogged down by 19th century professional boundaries.3 . . . it is patients and the public who need to be convinced. The Hospital Reform Group workforce challenge follows closely on the back of similar calls from: the Australian Government Productivity Commission, which, in its draft report Australia’s health workforce (released in September 2005), called for an independent assessment of the opportunities to extend the role of some health workers so as to make best use of their skills while maintaining safety and quality.4 the Health Workforce Innovation Conference organised by the University of Queensland and Queensland Health and held in Brisbane in November 2005. A report of the conference is published in this issue of the Journal (page 105).5 Speakers from the United Kingdom and the United States described how their respective countries have responded to health workforce crises by introducing task transfer roles. These roles are played by nurse practitioners, physician assistants and a new professional species in the UK — the medical care practitioner. To the cynic, this is a watered-down version of a general practitioner. The UK speakers also outlined a new model for health care education — an education escalator, based on competence rather than time spent in training. Health care workers can “jump on” the escalator at different levels, depending on previous attainment of knowledge, skill and work experience, acquire further expertise, and then “jump off” the escalator at a higher level. The system’s apparent value is its capacity to encourage flexibility and multiskilling. Australia is traditionally an importer of educational and health care ideas. There is no doubt that debate about the education escalator concept, along with the push for medical task transfer to other health care professionals, will escalate. This will be especially so if the Council of Australian Governments (COAG) endorses the major recommendations of the Productivity Commission’s report. These developments should come as no surprise, as the drivers for changes have been with us for some time. These include: the prevailing shortage of doctors, exacerbated by the federal government’s cap on medical graduates in the 1990s, early retirement of doctors, shortened working hours, the feminisation of the workforce, and generational attitudes to work;6 the continual increasing demands for medical services, driven by the increasing burdens of ageing and chronic diseases, along with new technology and the medicalisation of daily living; the ascendancy of multidisciplinary and multiskilled teams, which already blur some professional boundaries;7 and ever-narrowing subspecialisation, in which many medical tasks are reduced to discrete and limited knowledge and skill bytes which, it is argued, do not require a broad clinical perspective and have the potential to be undertaken by other health workers at lower costs.8,9 But there are deeper undercurrents. Sir Graeme Catto, President of the UK General Medical Council, recently observed that: . . . the exclusivity of medical knowledge and skill is being broken down. Interprofessional learning is now commonplace in medical education and seems likely to increase. Professional boundaries are being blurred as more and more of the things that were once the sole domain of doctors are being undertaken by other healthcare professionals. None of us works alone any longer, but in multidisciplinary teams in which we depend upon the expertise of others. This is not a diminution of medicine, but a strengthening of healthcare. We must also acknowledge that, more than ever before, knowledge is available to patients and the public.10 So how should the profession respond to the inevitable debate on task transfer? Most of the doctors who attended the plenary sessions of the Brisbane conference were surprisingly silent. Others were singularly dismissive of any encroachment by other health care professionals into the traditional domains of doctors. And the limited evidence for, and the value-laden opinions surrounding, task transfer came to the fore in the conference’s breakout sessions. It was the epitome of tribalism! In this context, it is worth noting that: The most common temptation facing any long-established profession is to cling on too long to practices, privileges and traditional craft skills that have simply become outmoded. This can happen for many reasons including changes in demand or technology. It is an uncomfortable experience for a professional when technical mastery is commoditised and overtaken by some creative innovation. But the wise professional should not feel threatened by the impact of, for example, paralegals or paramedics, or simply computers. It is the task of the true professional to remain intellectually curious and to continue acquiring new skills. That said, knowing when to let go and to delegate responsibilities hitherto reserved to the profession is a task not just for the individual practitioner to face alone, but for the profession as a whole to confront.11 And therein lies a problem. To be effective, the profession needs to speak with one voice and not in the babble of its many tribes. The latter will only be seen by the public as negative, defensive and self-serving. The profession needs to unite and develop a position that is evidence-based and has at its centre quality and safety for patients. In this debate, it is patients and the public who need to be convinced.

Martin B Van Der Weyden MD, FRACP, FRCPA

An Australian document now has an important role in acute pain management worldwide More than 50% of patients continue to have severe pain after surgery and trauma.1 This situation not only results in unnecessary suffering, but occurs despite evidence that inadequate treatment of acute pain increases the risk of postoperative complications and may lead to persistent (chronic) pain. Indeed, operations and injuries are considered to contribute to at least 25% of the burden of chronic pain.1 These points were highlighted at a forum cosponsored by the International Association for the Study of Pain (IASP), the European Federation of IASP Chapters, and the World Health Organization on 11 October 2004. This forum launched the Global Day Against Pain in support of the declaration that in acute, chronic non-cancer and cancer pain, “the relief of pain should be a human right”, and that improvements in the management of pain, including acute pain, require “global education of health professionals, patients and their families”.1 In Australia, there has been long-standing awareness of the need to improve the management of acute pain. This was supported by the publication of the first edition of Acute pain management: scientific evidence by the National Health and Medical Research Council (NHMRC) in 1999.2 At that time, the NHMRC and the Agency for Health Care Policy and Research in the United States were the only organisations worldwide to have produced evidence-based documents on the treatment of acute pain. More recently, this awareness has been highlighted by a number of high-level activities including the Pain Management Project of the National Institute of Clinical Studies,3 the development of the Operational principles for acute pain management by the Victorian Quality Council4 and the release of a Statement on patients’ rights to pain management by the Australian and New Zealand College of Anaesthetists (ANZCA) and the Faculty of Pain Medicine (FPM), a multicollegiate Faculty under ANZCA.5 International awareness of the need to improve the management of pain also continues to grow. The IASP held another Global Day Against Pain on 17 October 2005, which focused on pain in children.6 The Global Day Against Pain is to become an annual event. The IASP is also forming a special interest group on acute pain, which will further promote better management.7 Over recent years there has been an enormous increase in the amount of evidence available on the management of acute pain. Therefore, ANZCA and the FPM convened a working party to oversee a revision of the 1999 NHMRC acute pain document. To summarise the substantial amount of new evidence in a concise and easily readable form to help health care professionals and consumers, a large panel of contributors was appointed to draft sections of the document, and a multidisciplinary consultative committee (including medical, nursing, allied health and complementary medicine providers as well as consumers) was chosen to review drafts of the document and contribute more broadly as required. Evidence was annotated according to the levels recommended by the NHMRC.8 In addition, many practical recommendations for the treatment of aspects of acute pain were included by the working party as “clinical practice points” because of their clinical relevance, even though they are not purely evidence-based. The revised document9 was approved by the NHMRC in June 2005 and launched at the World Pain Congress in Sydney in August 2005. It has already received widespread recognition with formal endorsement by the IASP and the Australian Pain Society. As it forms the basis for the section on acute and postoperative pain in the third edition of the IASP’s Core curriculum for professional education in pain, its use worldwide is ensured.10 It has also been endorsed by the Royal College of Anaesthetists in Britain and recommended by the American Academy of Pain Medicine to its members. Much of the evidence relating to acute pain management comes from the hospital setting, but many of the principles can be extrapol-ated to other acute pain settings, such as managing pain from renal colic or migraine or the use of opioids and non-steroidal antiinflammatory drugs (NSAIDs). Examples of updated key messages and clinical practice points for the use of opioids, paracetamol, NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors are listed in the Box. As the field of acute pain medicine is changing rapidly, new information emerging in areas considered to be of importance will be reviewed by the working party and posted periodically on the ANZCA website (http://www.anzca.edu.au/publications/acutepain.htm). A third edition of Acute pain management: scientific evidence is planned for 2010. A revision of the consumer guide to acute pain management will also be available shortly at the above website. Knowledge about acute pain medicine is growing too rapidly for individuals to keep abreast of it unaided. It is hoped that the updated guidelines will help clinicians and others approach acute pain treatment more effectively and safely, thus going some way towards reducing the suffering and improving outcomes of patients in our community. Selected updated key messages and clinical practice points*9 Opioids Dextropropoxyphene has low analgesic efficacy (Level I evidence). In the management of acute pain, one opioid is not superior over others but some opioids are better in some patients (Level II evidence). Tramadol has a lower risk of respiratory depression and impairs gastrointestinal motor function less than other opioids at equi-analgesic doses (Level II evidence). Pethidine is not superior to morphine for treating pain of renal or biliary colic (Level II evidence). In adults, age is a better predictor of opioid requirements than weight, although there is a large interpatient variation (Level IV evidence). Assessing sedation level is a more reliable way of detecting early opioid-induced respiratory depression than a decreased respiratory rate (clinical practice point). The use of pethidine should be discouraged in favour of other opioids (clinical practice point). Paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (COX-2) inhibitors Paracetamol is an effective analgesic for acute pain (Level I evidence). NSAIDs and COX-2 inhibitors are effective analgesics with similar efficacy for acute pain (Level I evidence). NSAIDs given in addition to paracetamol improve analgesia (Level I evidence). COX-2 inhibitors and NSAIDs have similar adverse effects on renal function (Level I evidence). Paracetamol, NSAIDs and COX-2 inhibitors are valuable components of multimodal analgesia (Level II evidence). COX-2 inhibitors do not impair platelet function (Level II evidence). Gastric ulceration rates with short-term use of COX-2 inhibitors are similar to those for placebo (Level II evidence). Adverse effects of NSAIDs are significant and may limit their use (clinical practice point). The risk of adverse renal effects of NSAIDs and COX-2 inhibitors is increased in the presence of factors such as pre-existing renal impairment, hypovolaemia, hypotension, use of other nephrotoxic agents and angiotensin-converting enzyme inhibitors (clinical practice point). Levels of evidence designated according to those recommended by the National Health and Medical Research Council.8 * Reproduced with permission from the Australian and New Zealand College of Anaesthetists.

Pamela E Macintyre MB BS, FANZCA, FFPMANZCA · Stephan A Schug MD, FANZCA, FFPMANZCA · David A Scott MB BS, PhD, FANZCA

We ignore global inequalities at our peril Nearly 10 years ago, the Simons Review of the Australian Aid Program proposed that eradicating poverty should be a major focus, that the voices of recipient countries should be heard, and that greater accountability, as well as evaluation, information sharing and research, were crucial.1 Fast forward to 2005, to a globalised world with the “war on terror” and national security at centre stage. From the Indian Ocean tsunami to Hurricane Katrina, from the Kashmir earthquakes to the silent emergencies in Darfur, Niger and Uganda, disasters disproportionately affect the poor and marginalised. There are now increasing inequalities within and between states, heightened concerns about peace, security and development, and threats to human rights and fundamental freedoms. In September 2005, world leaders assessed the progress made towards meeting the Millennium Development Goals (MDGs), a set of globally agreed development objectives for the year 2015. Three goals — reducing child mortality, improving maternal health and combating HIV/AIDS, malaria and other diseases — have a specific health focus. For each goal, targets have been established, but are unlikely to be met (Box).2 The United Nations Development Program identifies aid, trade and security as crucial to achieving the MDGs.3 AidAs the federal government is preparing a White Paper on its aid program, Australia has an opportunity to reshape its role as a global citizen. The Prime Minister, John Howard, announced on 13 September 2005 that Australia’s official development assistance will be increased to $4 billion by 2010. While this commitment is welcome, Australia’s contribution will still be only 0.35% of its Gross National Income in that year, well below the UN-proposed target of 0.7% by 2015. It is particularly important to ensure that the available funds are used to eliminate poverty and support development, the objectives of the MDGs. This will mean focusing on the core issues of poverty eradication, enhancing social justice, promoting equity, and delivering basic health and education services. In Asia and the Pacific, five countries, including Timor-Leste and Papua New Guinea, are not expected to achieve even one of their targets for the high priority indicators — and 14 other countries are not on track for more than half of them.4 TradeTrade and the economy influence a state’s ability to meet basic needs and redress inequalities. Eighteen countries, with a combined population of 460 million people, have shown declines in the Human Development Index (a comparative measure of poverty, life expectancy, education, literacy, and other factors) — revealing poorer health, education and wellbeing since 1990.3 Trade should be seen as a means to development and not as an end in itself. Structural inequalities in international trade must be addressed; fair trade rules should be put in place and tariff barriers inhibiting trade with developing nations removed. Trade concerns in the health sector range from access to pharmaceuticals to establishing and retaining an adequate health workforce. A key MDG indicator is the “proportion of the population with access to affordable essential drugs” on a sustainable basis. Australia’s Department of Foreign Affairs and Trade is promoting bilateral free-trade agreements that jeopardise developing countries’ access to affordable pharmaceuticals, including antiretrovirals, by strengthening and enforcing patent monopolies globally.5 Bilateral agreements have been described as a covert form of private governance, threatening to undermine hard-won public gains in health regulation.6 Failure to ensure access to drug therapy and combat neglected diseases will lead to widening gaps in health status, and the threat of emergent disease. A valuable intervention would be to support countries to collectively procure drugs at competitive prices. Australia benefits greatly from the immigration of skilled health workers, including those from developing countries. While AusAID spends aid monies on building human resource capacity in the health sector in developing countries, Australia’s immigration system, by design, attracts doctors, nurses and other scarce health professionals from these countries to overcome skills shortages in our own health workforce. More engagement with the countries providing personnel is needed: recruitment and migration should be accompanied by government-to-government negotiation, and commitments to strengthening the health workforce in developing nations in our region and investing in developing our own health capacity. In addition, long-term twinning and partnership agreements to build capacity, and the use of new technologies to facilitate training and bridge geographic divides, are likely to be of value. SecurityThe recent UN publication, Report on the world social situation 2005. The inequality predicament,7 highlights the significant links between poverty and conflict: social disintegration and violence increase where inequalities are extreme and competition over scarce resources is greatest. Countries with high rates of poverty and inequality generally have poorer social supports, more unequal access to health and education, and fewer opportunities for young people, contributing to heightened risks of armed conflict. Moving from a narrow framework of national security to considering human security in its broadest sense is a fundamental challenge;8 ultimately, human security will be achieved only if there is equitable development in the region, support for governance structures, and increasing responsiveness to community needs. In Australia, establishment of a dedicated unit within AusAID to concentrate on fragile states recognises the potential threat they pose to health and security in the region, and the need to understand and work more closely with them. Fragile states are those which are hard-pressed to govern, to deliver services, and to ensure the safety and security of their citizenry. The Solomon Islands has one of the fastest growing youth populations, lacks educational and employment opportunities and, until recently, was flooded with small arms. Papua New Guinea struggles with corruption, governance, and the difficulty of delivering basic services. Timor-Leste, while making massive strides in building a new nation, remains fragile, with the government under enormous pressure to rapidly bring the benefits of independence to the majority rural population. While previous policy advice was to stay away from fragile states and donors withdrew to avoid “wasting” aid, it is increasingly recognised that maintaining service delivery and governance are crucial. “Strengthening weak states against failure is far easier than reviving them after they have definitively failed or collapsed.”9 For the health sector, supporting the resilience of health professionals and peripheral services, and assuring the delivery of essential care, must be a priority. This better positions the sector to move forward from a more secure base when violence and instability recede. In the longer term, this may position the health sector to lead in promoting quality, responsiveness and good governance in these fragile states. ConclusionBy articulating more equitable, whole-of-government responses that take account of national and regional interests, Australian engagement can make a difference. Meeting the MDGs and tackling poverty remain central.10 Identifying and mitigating the adverse effects of globalisation — the widening gaps between those with and without access to resources — and strengthening the economies of marginalised countries, deserve attention. Australia can be innovative, progressive, strategic and ethical at the same time. Doing so requires more explicit support for the MDGs, as well as: A long-term view which places constructive global citizenship at the core; Appreciation that national security rests on human security and more equitable arrangements within and between states; A commitment to linking aid, trade and security and adopting whole-of-government approaches; A commitment to building system capacity in public health, supporting human resources and securing health in fragile states; and An investment in development-related research — monitoring trends, evaluating interventions, and learning and sharing lessons from aid delivery and its effects. Millennium Development Goals — update on progress and achievements, May 2005 1. Eradicate extreme poverty and hunger Global poverty rates are falling — however, in sub-Saharan Africa, millions more people are now experiencing extreme poverty and the poor are getting poorer. 2. Achieve universal primary education Five developing regions are approaching universal enrolment; however, sub-Sahara, Southern Asia and Oceania have a long way to go. School enrolment among the most disadvantaged groups (low-income households, indigenous communities) is much worse. 3. Promote gender equality and empower women The gender gap is closing — albeit slowly — in primary school enrolment. However, women represent a smaller share of wage earners, are more likely to be relegated to insecure and poorly paid jobs, and lack equal representation at the highest levels of government. 4. Reduce child mortality Death rates in children under 5 are dropping, but not fast enough. 30 000 children die every day from preventable or treatable causes. 5. Improve maternal health Some progress has been made in reducing maternal deaths, but not in those countries where giving birth is most risky. 6. Combat HIV/AIDS, malaria and other diseases AIDS is the leading cause of premature death in sub-Saharan Africa and the fourth largest killer worldwide. Tuberculosis is on the rise, partly as a result of HIV/AIDS. 7. Ensure environmental sustainability Access to safe drinking water has increased, but half the developing world still lacks toilets or other forms of basic sanitation. Urban slums are an increasing problem — nearly one in three city dwellers live in slum conditions characterised by overcrowding, scarce employment, poor water, sanitation and health services and insecurity, including violence against women. 8. Develop a global partnership for development Developed countries have fallen short of targets they have set for themselves. To achieve the MDGs, increased aid and debt relief must be accompanied by further opening of trade, accelerated transfer of technology, and improved employment opportunities for young people in the developing world. Source: The Millennium Development Goals Report 2005.2

Anthony B Zwi MB BCh, PhD, FFPHM, AFPHM · Natalie J Grove MPH, BOccThy

Further complications of the “obesity epidemic” The potential health burden to our community of escalating overweight and obesity is well documented and publicised. Attention has focused on the association with chronic diseases such as hypertension, diabetes, cardiovascular disease and all-cause mortality. The effects of obesity on reproductive function and outcomes have received less attention. The ability to conceive spontaneously is reduced by obesity. While many overweight women can conceive easily, they are over-represented among subfertile groups and those presenting with menstrual disorders.1 Overweight women, both with and without polycystic ovary syndrome, present with menstrual irregularity and anovulation more frequently than women with normal body mass index (BMI). The US Women’s Health Study concluded that even a slightly elevated BMI at age 18 was a risk factor for subsequent anovulatory infertility.2 Several studies have confirmed the association between obesity and reduced fertility.1,3 Elevated BMI is also associated with poorer outcomes from assisted reproduction.3 Obesity also affects pregnancy outcomes. The article in this issue by Callaway et al4 is an important and timely reminder of the high prevalence of obesity in women of reproductive age and the serious adverse effects of overweight during pregnancy. Risks are increased for both mother and baby. Maternal problems can result from pre-existing obesity-related illnesses such as hypertension and type 2 diabetes. The increased pregnancy-related risks of obesity include increased rates of miscarriage,1 gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, thromboembolism, haemorrhage, caesarean section, sleep apnoea, wound infection and anaesthetic complications.5,6 These risks persist, even when adjusted for pre-existing illness. The offspring of overweight and obese women are more likely to require admission to neonatal intensive care and to have congenital abnormalities such as neural tube and cardiac defects. Birth-related injuries and fetal death in utero are also higher in this group, and babies are more likely to be macrosomic, placing them at risk of birth trauma and possible subsequent childhood (and, indeed, lifelong) obesity.5,7 What are the effects of weight loss on fertility and pregnancy outcomes? Weight loss alone often leads to improvement in conception rates. Clark et al,1 evaluating a 6-month diet and exercise program in overweight anovulatory women, found that participants in the program tended to lose weight and resume ovulation. Pregnancy rates, self-esteem and endocrine parameters improved, while rates of miscarriage fell. Seventy-eight per cent of the women conceived, with 67% achieving a live birth. Weight loss of dramatic proportions was not required — a relatively small weight loss (6–10 kg) could lead to resumption of spontaneous ovulation. The effects of weight loss on pregnancy outcomes have recently been reported by Dixon et al.8 Their prospective study sought to examine the effects of laparoscopic adjustable gastric banding (LAGB) in severe obesity. They concluded that “pregnancy outcomes after LAGB are consistent with general community outcomes rather than outcomes from severely obese women”. Callaway et al4 comment on the implications for health care delivery costs of obesity-related increases in maternal and neonatal morbidity. This problem will only worsen. The AusDiab study9 reported that the prevalence of obesity in 2003 was 2.5 times higher than in 1980. Moreover, obesity is occurring at a younger age, the problem increases with time, and women are becoming pregnant later in life.10 Solutions to such a complex problem will inevitably be multifaceted and costly. Callaway and colleagues recommend that maternal BMI should be recorded at the booking visit for all pregnancies. While this will assist in documenting the problem, any meaningful intervention must occur before presentation with an established pregnancy. Given the potential for adverse health outcomes for both mother and baby, and the potential lifelong effects of neonatal macrosomia, there is a pressing need for action well before conception. As part of general public health efforts to combat obesity, we strongly recommend pre-pregnancy counselling for all women, with every effort being made to intervene in the case of women who are overweight or obese. The majority of women are highly motivated to strive to have healthy babies, and the power of this commitment could well be used to achieve behavioural change that could have short-term (and potentially lifelong) benefits for both mothers and children.

Alison J Nankervis MB BS, MD, FRACP · Jennifer J Conn MB BS, MClinEd, FRACP · Rachael L Knight MB BS, MD, FRANZCOG

Clinical trials show partial meal replacement products to be safe, acceptable and effective when used as part of an overall low-energy diet Overweight (body mass index [BMI] > 25 kg/m2) and obesity (BMI > 30 kg/m2) are now major health concerns, being causally related to a number of metabolic disorders, and affecting at least one in two adult Australians.1 However, the long-term evidence on treatment of these conditions is disappointing. A strategy recommended in the recent clinical guidelines from the National Health and Medical Research Council is the use of low-energy meal replacement products.1 These have been marketed for many years, but have only recently been considered seriously in large clinical trials. If effective, this strategy offers promise as: it provides a discrete option for doctors dealing with a difficult condition; it is easy to administer and supervise; and it is relatively cheap. However, questions remain about the long-term outcomes and safety of meal replacement products, their effects in comparison with other strategies, and their acceptability to patients. What are meal replacements? Meal replacements are defined as “a single food or pre-packaged selection of foods that is sold as a replacement for one or more of the daily meals, but not as a total diet replacement”2 (Box 1). These replacements exert their effect through reducing portion size, and consequently energy intake.3 In patients with morbid obesity requiring large weight losses (BMI > 40 kg/m2), specially formulated very low calorie diet (VLCD) forms of meal replacement may be used in place of all meals. However, more commonly, partial meal replacements are used for one or two meals a day, with at least one usual meal consumed as part of an overall low energy diet. Here, I focus on the use of partial meal replacements, because of their wider potential clinical use. Why are partial meal replacements returning to favour? Traditionally, there has been concern about the use of any meal replacements, probably based on concerns about: the nutritional balance of some commercial mixes; potential “bounce back” weight gain on discontinuing use, when this use is unsupervised (as for any low-energy diet plan); and the fact that they may not teach users good long-term eating habits. These concerns have now been largely overcome by: advances in food technology, which allow more complete and better balanced nutrient mixes; a move towards better training of clinicians about weight control; and the fact that most reputable products are now part of a broader weight loss program, with accompanying nutritional education about non-replacement meals (Box 2). While different forms of meal replacements have been used for weight loss over many years, controlled research on the effectiveness of partial meal replacements is relatively recent. Several studies, reviews and meta-analyses now attest to the benefits of partial meal replacements. Their use commonly results in weight loss of around 9%–10% of total body weight in the short term (6–12 months), and 6%–8% in the long term (eg, 1–5 years), with no reported adverse effects when used as part of an overall low-energy diet plan.3-6 This compares favourably with a 3%–7% loss on some other types of diet plans,3-6 although at least one study showed similar short-term weight losses from meal replacements and a prescriptive, structured low-fat diet plan.7 The benefits of partial meal replacements are even more obvious when compared with no treatment. In a 5-year study, an average weight gain of over 1 kg per year occurred in control subjects, compared with a loss of 5.8 kg in men and 4.2 kg in women using partial meal replacements.8 It has been suggested that replacing two meals a day, while maintaining one other main meal, is most effective for initial weight loss, while replacing one meal a day (preferably a meal which is usually high energy, such as lunch or dinner) is enough for long-term maintenance.6 Quick effects from supervised short-term use might be expected to have the added benefit of increasing motivation for long-term lifestyle change. Several studies have also shown improvements in metabolic risk factors with use of partial meal replacement products, exceeding the changes achieved by dietary change alone (even structured low-energy diets).6,8 Partial meal replacements have particular benefits for patients with diabetes.9,10 The effects on glucose control occur within days, and last for as long as weight loss is maintained, enabling a reduction in diabetic medications, but there are also improvements in blood pressure, and serum cholesterol and triglyceride levels (probably more due to the weight loss than the meal replacement per se). Partial meal replacements appear to have an effect across a range of ages and in both sexes (although men generally have better results than women).8,11 They can be used with minimal supervision,11 but are probably most effective when closely supervised with regular follow-up.12 Most studies show greater patient satisfaction and lower drop-out rates with partial meal replacements than with other diets, possibly because use of meal replacements results in less hunger.13 Partial meal replacements also seem effective in people from low socioeconomic backgrounds,14 who are currently more likely to be overweight, and hence in greater need of weight loss treatments.1 Importantly, partial meal replacements are generally cheaper than other diet plans (Box 2), and certainly more so than non-diet meals. Meal replacements are not contraindicated in common weight-related diseases (eg, diabetes and heart disease), but food sensitivities, such as lactose intolerance or food allergies, need to be taken into account when choosing specific products. Which product should I recommend? Selection of a commercial meal replacement product in Australia is complicated by the food standards, product marketing, the different conditions under which the products can be mixed (eg, with milk or water), and confusion with VLCD foods, which are based on total meal replacements, and for which only draft standards exist. There are currently few products that satisfy all requirements for a meal replacement, although some are still promoted as such. For example, low-energy “weight loss” drinks and other (usually supermarket-supplied) products are sometimes labelled to imply they can be used as a meal replacement, despite not meeting minimum Food Standards Australia New Zealand (FSANZ) requirements (Box 1). Box 2 shows a cross section of popular products from different outlets in Australia that meet or approach the minimum standard for nutritionally balanced meal replacements. Partial meal replacements seem to be safe, acceptable to patients, and more effective over the long-term than most other diet-based weight loss techniques, although it is likely that best results will be achieved with the supervision of a clinician skilled in weight control.11 Because most individuals in modern societies consume too much energy in relation to expenditure, there now seems little reason not to prescribe properly constituted partial meal replacements for overweight patients for whom this treatment is appropriate, in line with the emerging realisation that one treatment does not necessarily fit all.15 In fact, with the trend to modern sedentary lifestyles and escalating levels of obesity, it is not difficult to imagine much of our population needing to use partial meal replacements judiciously at some time in the future for prevention or treatment of overweight and obesity. 1 Food Standards Australia and New Zealand requirements for commercial meal replacements2 Meal replacements (minimum requirements per meal) 12 g protein 850 kJ 25% of the recommended daily intake of 16 prescribed vitamins and minerals Very low calorie diets (VLCDs) (draft requirements) 1.7–3.3 MJ per day Omega-3 and omega-6 fatty acids 50 g carbohydrate per day 50 g protein per day Minimum and maximum levels for 24 prescribed vitamin and minerals 2 Characteristics of some examples of commercially available meal replacement products in Australia* KicStart VLCD (Pharmacy Health Solutions) Optifast VLCD (Novartis) Dr MacLeod’s (Orfam) Ultra Slim (Associated British Foods) Availability Pharmacies Pharmacies Doctors, clinics Supermarkets Presentation 24-sachet box 21-sachet box Single sachets Tin of powder Price per meal to patient $2.04 $2.33 $2.65 $1.00 Protein per serve† (g) 17.9 17.3 15.2 4 Carbohydrate per serve† (g) 9.8 15 19.2 20.5 Fat per serve† (g) 3.0 2.3 1.8 2.6 Omega-3 and -6 fatty acids Yes Not listed Not listed Not listed No. of vitamins and minerals 26 27 16 24 Fibre Yes Not listed Not listed Yes Total energy of prepared drink (kJ) 584 (water), 883 (skim milk) 638 (water) 640 (water) 875 (skim milk) Accompanying material on weight loss Yes Yes Yes No Qualifies as VLCD Yes Yes No No * Characteristics apply to the chocolate variety of each product. † Protein, carbohydrate and fat levels are for the dry powder. If directions are to mix with skim milk, levels of protein increase by approximately 7 g, carbohydrate by 10 g and fat by 0.2 g.

Garry Egger BA, MPH, PhD

We recommend screening all infants whose mothers are HCV antibody-positive Perinatal transmission of hepatitis C virus (HCV) is the main source of newly diagnosed paediatric HCV infections in Australia.1 About 5% of infants born to women who are positive for both HCV antibody and HCV RNA during pregnancy will acquire HCV infection.2 The risk of transmission is increased by HIV coinfection during pregnancy. It is estimated that 1%–2% of women of childbearing age in Australia are infected with HCV.3 Assuming that 75% of these have chronic hepatitis and viraemia in the third trimester of pregnancy, we would expect about 75–100 new cases of vertically acquired childhood HCV infection in Australia per year. However, rates reported from national deidentified laboratory data4 and from the Australian Paediatric Surveillance Unit1 are much lower, suggesting that paediatric HCV infection may be underrecognised in Australia. We thus recommend a more standardised approach to identification and follow-up of infants exposed perinatally to HCV. Why identify infants with HCV infection? Although most HCV-infected children have good health for at least the first two decades of life, HCV-induced chronic liver disease and liver failure have both been reported in childhood.5,6 As it is not possible to predict which children will develop severe liver disease, long-term monitoring of HCV-infected children is needed.6 In addition, children identified as HCV-positive should be offered vaccination against both hepatitis A (after 2 years of age) and hepatitis B. Superinfection of HCV-infected individuals with hepatitis A virus increases the risk of fulminant hepatitis and death, while coinfection with HCV and hepatitis B virus is associated with a higher risk of cirrhosis and hepatocellular carcinoma.7 HCV-infected children with severe hepatic involvement should be offered antiviral therapy. A number of treatments (interferon-alfa, ribavirin and pegylated interferon) successfully eradicate HCV in 40%–80% of HCV-infected adults, depending on the HCV genotype. Although data about their efficacy in childhood are limited, these treatments have been used safely and effectively in children. Identifying Australian children with HCV infection could also allow them access to novel therapies and ongoing international multicentre randomised controlled trials.5 Why is HCV infection underdiagnosed in childhood? Children with HCV infection may not be identified for several reasons: They are unlikely to attract medical attention, as most have no symptoms or signs of liver disease, while a small proportion have mild hepatomegaly.1,5 Consequently, their identification relies on careful follow-up of offspring from at-risk pregnancies. Antenatal HCV screening practices vary widely around the country,8 and therefore many HCV-exposed infants are missed. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists recommends universal antenatal screening for HCV.8 However, other national bodies recommend selective testing for HCV infection in pregnant woman with identifiable risk factors (eg, intravenous drug use, tattooing, body piercing, needle sharing, or receipt of blood products or invasive procedures overseas or before 1990 in Australia).8,9 Appropriate methods of testing HCV-exposed infants and children are not widely understood, and national guidelines for testing and follow-up of offspring of HCV-infected mothers8,9 are not detailed or widely known to child health care providers. In children aged under 18 months, persistence of maternal antibody complicates the interpretation of HCV antibody tests, while in infants aged under about 2 months qualitative HCV RNA polymerase chain reaction (PCR) testing is insensitive.10 How should we screen for vertically transmitted HCV infection? For diagnosing perinatal HCV infection, the most cost-effective strategy may be to screen offspring of HCV RNA-positive women. However, as HCV RNA levels can fluctuate in pregnancy, and as antenatal HCV screening practices vary, we recommend: Screening all infants born to women who are HCV antibody-positive, using HCV antibody and liver function tests, at 18 months of age or older. If results are negative, then the infant can be safely assumed not to have HCV infection. If antibody results are positive or liver function is abnormal, then the child should be referred to a paediatric gastroenterologist. Testing infants who are considered unlikely to attend for 18-month follow-up, using HCV RNA and liver function tests at 3 months of age, when they are more likely to be receiving local medical care. Those with positive HCV RNA results or abnormal liver function should be referred to a paediatric gastroenterologist. If both tests give negative results, we recommend repeating HCV antibody testing at age 18 months, as both viraemia and transaminitis can be intermittent in HCV infection. HCV RNA testing for the diagnosis of vertically transmitted HCV infection (in isolation) is not an approved item on the current Medicare Benefits Schedule11 and costs about $90 (ie, six times the cost of HCV antibody testing). Testing for HCV should be performed only after pre-test family counselling and with the consent of the infant’s parent(s) or guardians. There is an urgent need to disseminate clinical practice guidelines in Australia for the screening, diagnosis and management of children born to women with HCV infection during pregnancy. Ongoing collection of national data on HCV infection in children is needed to document the scale of this emerging disease in the paediatric population, and the groups of children at risk of infection. Identification and referral of HCV-infected children will allow early initiation of therapy and monitoring of outcomes.

Winita Hardikar PhD, FRACP · Elizabeth J Elliott MD, FRACP · Cheryl A Jones PhD, FRACP

Artesunate reduces mortality and should now be the treatment of choice in severe malaria in adults: good news for countries in our region, but registration in Australia must wait For nearly 400 years quinine has been the principal drug used to treat severe malaria. Despite its long history of efficacy, quinine has significant limitations. Even with prompt administration, case-fatality rates in severe malaria often exceed 20%.1 Furthermore, quinine requires three-times-daily administration and has a number of adverse effects including hypoglycaemia, vomiting, headache and tinnitus.1 The identification of artemisinin from sweet wormwood (Artemisia annua) in China in the 1970s focused attention on the most rapidly acting of all antimalarial drugs,1 and raised hopes that artemisinin derivatives would reduce the high case-fatality rate in severe malaria. Initial trials using intramuscular artemether demonstrated less toxicity but no clear mortality benefit over quinine,1 most likely due to the erratic absorption of the intramuscularly administered oil-based preparation of artemether.2,3 More recent trials have used intravenous artesunate, a water-soluble derivative with a more favourable pharmacokinetic profile.3,4 The SEAQUAMAT trial, a multicentre randomised trial conducted in Bangladesh, Myanmar, Indonesia and India, recently reported a 34.7% reduction in mortality associated with intravenous artesunate compared with intravenous quinine.5 This is the largest trial ever performed in severe malaria and the first to demonstrate conclusively a mortality reduction over standard quinine therapy. This is good news for malaria-endemic areas in South-East Asia. The burden of malaria in our region is far worse than previously thought, with over 120 million cases each year in south/south-east Asia.6 The World Health Organization now advocates the use of artemisinin combination therapy for uncomplicated malaria,7 a move that is likely to reduce the number of people developing severe disease. Now there is convincing evidence that for those who do develop severe malaria, intravenous artesunate will reduce the risk of death by one-third.5 It is also safer and easier to use than quinine. What about children? In the 202 children in SEAQUAMAT, artesunate was equally safe and effective.5 But the study did not have the statistical power to demonstrate a mortality benefit in the paediatric age group. In the Asian countries that have changed policy, artesunate is first-line treatment for both adults and children. However, because the clinical pattern and rapidity of death is different in paediatric severe malaria in high transmission areas, a randomised trial comparing mortality in African children treated with artesunate and quinine has recently commenced. Several countries in our region recommend parenteral artemisinin derivatives as first-line therapy for severe malaria, including Vietnam, Thailand, Papua New Guinea and Cambodia.8 As a result of SEAQUAMAT, Indonesia has now also changed national policy from quinine to artesunate. However, quinine is still national policy for severe malaria in most other Asia–Pacific countries.8 At US85c–$1 per 60 mg vial when purchased in bulk, artesunate is only modestly more expensive than quinine. And this does not take into account the intravenous infusions and additional nursing required for quinine. The number needed to treat to save one life was between 11 and 20 in the SEAQUAMAT study, making this a very cost-effective policy change. A major issue for many national bodies faced with licensing parenteral artesunate is that neither of the current manufacturers in China and Vietnam produce a formulation approved as compliant with international Good Manufacturing Practice (GMP) speci-fications. Support from the developed country pharmaceutical industry does not appear likely. United States Army plans for independently developing a GMP-compliant formulation have been delayed by the lack of a commercial co-development partner.9 Absence of GMP certification does not necessarily mean poor quality: independent analysis of the lots used in the SEAQUAMAT trial demonstrated satisfactory quality of this drug. However, neither of the current manufacturers has yet received WHO prequalification certification, a requirement for the WHO and several other international agencies to purchase drugs centrally and distribute large quantities at low cost to ministries of health. Nevertheless, forthcoming WHO guidelines will recommend artesunate be made the treatment of choice for severe malaria in adults.10 What about Australia and other developed countries? In settings with well resourced intensive care facilities, the mortality rate from severe malaria is less than that seen in most sites involved in the SEAQUAMAT trial.11 It is possible that the benefit with artesunate (seen after 24–48 hours in the SEAQUAMAT trial) could be attenuated by better treatment of late complications in a developed country setting. However, the magnitude of the mortality reduction was remarkably consistent among the SEAQUAMAT sites, despite varying mortalities and levels of ancillary care. Parenteral artesunate should therefore be the treatment of choice for adult severe malaria in all countries.10 The lack of a GMP-compliant formulation is, however, a major hurdle and means that artesunate cannot be registered in Australia by the Therapeutic Goods Administration12 or in other countries, including the European Union and United States. This creates a paradox. In contrast to the usual situation, a life-saving drug is available and being used in many developing countries, yet cannot be registered in developed countries. Although it is clearly far more important that these drugs are available in malaria-endemic countries, and the number of Australians developing severe malaria each year is small, it is unacceptable that we must continue to use quinine when a drug that reduces mortality by one-third is available elsewhere. Pending the availability of a GMP-compliant product that can be registered, an interim strategy is available in Australia. Hospital pharmacies can import and hold artesunate for category A usage in named patients with severe malaria under the Special Access Scheme, reserved for “very seriously ill patients” with a high short-term likelihood of death in the absence of early treatment.13 This strategy could be coordinated by a consortium of state/territory hospital pharmacies in capital cities and supported by the relevant national professional bodies. Ideally, the quality of an imported lot of non-GMP artesunate should have been confirmed at a Good Laboratory Practice-compliant laboratory. From a global perspective, registration and availability of parenteral artesunate in both malaria-endemic and developed countries would be maximised if current manufacturers were given assistance to become GMP-compliant without delay.

Nicholas M Anstey PhD, FRACP · Ric N Price MD, FRACP · Nicholas J White FRCP, DSc

Contributing to health services research, implementation and effective health policy-making Some of the most pressing issues in Australian health care are not about the efficacy of particular treatments, but rather how health services can be organised to deliver optimal care. Examples of service-related initiatives familiar to most clinicians include: multidisciplinary teams to improve coordination of cancer care; designated trauma centres to optimise management of injured patients; financial incentives to encourage particular services; restricted licences for overseas medical graduates to increase the rural workforce; specialist outreach and telemedicine to improve access in remote areas; clinical audit and review to enhance care quality; and management and prescribing guidelines. Broadly speaking, these represent a spectrum of organisational, financial, regulatory and professional interventions aimed at improving service delivery and achieving best practice. Just as clinicians and patients are concerned with the effectiveness of clinical treatments, policy-makers and the public are interested in the effectiveness of health system interventions. For clinical treatments, questions about “what works” may be best answered using randomised controlled trials and other experimental designs. Those studying the effectiveness of health service interventions, however, face some specific methodological and analytical challenges, and often need to consider other types of designs. Is it possible to randomise communities to receive outreach visits, for example? What are the important outcomes of employing nurse practitioners in remote areas? Can we effectively control for other health service changes, such as closure of a hospital, or loss of staff, that may be unavoidable during a study period? In studies in which the intervention is delivered to a population, but the outcomes are measured in individual patients, how do we take clustering effects into account in the analysis? Australians have contributed to developing appropriate methods (some adapted from economics and social sciences) for addressing such questions in real-world situations. Support for the Australian health services research community has come from the Health Services Research Association of Australia and New Zealand (http://www.chere.uts.edu.au/hsraanz/), established in 2001, the longstanding interest of The Medical Journal of Australia, as well as other organisations, and the Australian and New Zealand Journal of Public Health, Australian Health Review, and a new open-access journal, Australia and New Zealand Health Policy (http://www.anzhealthpolicy.com). Syntheses of available research also contribute to rational health policy-making. The international Cochrane Collaboration maintains systematic reviews in which the research literature on a topic has been identified, selected, appraised and synthesised in a transparent way.1 Such reviews reduce the likelihood of people being misled by research findings, and increase the confidence in what outcomes can be expected from an intervention.2,3 However, reviews of health service interventions differ in that, to be useful for policy-makers and managers, the goal of methodological rigour that characterises Cochrane reviews needs to go hand in hand with an understanding of the challenges inherent in health services research. The Cochrane Collaboration’s Effective Practice and Organisation of Care (EPOC) Group, based in Ottawa, Canada, is dedicated to conducting reviews of interventions designed to improve professional practice and the delivery of effective health services, potentially spanning any clinical area.4 It has already produced 37 reviews on topics such as audit and feedback, discharge planning, hospital in the home, printed educational materials, telemedicine and specialist outreach. A particular focus of EPOC has also been how to broaden the types of included studies beyond blinded randomised trials, while at the same time optimising validity and generalisability. These include designs such as controlled before–after studies and interrupted time series studies. Recognising that evidence for policy-making is not always readily available, the Australian Government has provided for a new partnership between EPOC and the National Institute of Clinical Studies (NICS). The Australian EPOC satellite at the National Institute of Clinical Studies was officially announced at the Cochrane Colloquium in Melbourne on 22 October 2005. NICS is funded by the Australian Government to help improve uptake of evidence into clinical practice, and to use evidence about individual, organisational and system change in designing implementation programs. In addition, free access to the Cochrane Library (and a user’s guide) is available through the NICS website (http://www.nicsl.com.au). The overall goal of the satellite is to assist evidence-based policy-making through systematic reviews of interventions designed to improve health care practice and the delivery of effective health services relevant to Australia and our region. In particular, the satellite aims to: identify and help produce priority EPOC reviews relevant to Australia; support EPOC review activity through training and mentoring of researchers; and foster a culture of evidence-based health policy and knowledge translation by promoting the use of the Cochrane Library, and EPOC reviews in particular. In addition, the Australian satellite will: support the EPOC editorial base in Canada by editing, producing and updating EPOC reviews, especially reviews relevant to rural areas; collaborate with the Australasian Cochrane Centre and the other Australian-based Cochrane groups to further the work of the Cochrane Collaboration in the region; and contribute to the international effort of synthesising research to improve evidence uptake. We hope that the satellite will make an ongoing contribution to Australian health services research, implementation and effective health policy-making.

Russell L Gruen MB BS, PhD, FRACS · Heather Buchan MB ChB, MSc, FAFPHM · Jan Davies PhD, MBA · Alain Mayhew MSc · Jeremy M Grimshaw MB ChB, PhD, FRCGP

The Productivity Commission’s recent proposal to modify the roles of health professionals raises these important questions A century ago, the role of doctors was clear and simple. Sir William Osler, Regius Professor of Medicine at Oxford, noted that it was “to acquire facility in the art of diagnosis . . . to grow in clinical judgment . . . to appreciate the relative value of symptoms and the physical signs . . . to give to the patient and his friends a forecast or prognosis . . . [and] to conduct the treatment that the patient may be restored to health . . . or, failing that, be given the greatest possible measure of relief”.1 It was the age of acute care, and medicine’s knowledge base was contained in a single tome — Osler’s The principles and practice of medicine. Doctors accounted for about one in every three health professionals,2 and practised as general practitioners or consultant physicians and surgeons. The payment for health care was a contract between the patient and the doctor, and not the business of government. One hundred years on, how things have changed. Doctors now account for one in every eight workers in Australia’s health care sector.3 Unprecedented advances in science and technology have splintered medicine into myriad specialist groups, and the information explosion has led to innumerable journals, textbooks and Internet sites. Medicine’s focus has moved beyond acute care, to preventive health care and management of chronic diseases and ageing. These require the skills not only of doctors and nurses, but of professionals in fields which have emerged in the last century, such as physiotherapy, occupational therapy, nutrition and social work. These professions have distinct educational programs, different emphases of practice and different professional aspirations. The demography of doctors has also changed. Women now account for one third of the medical workforce.4 They favour disciplines such as general practice, paediatrics, obstetrics and gynaecology, pathology, psychiatry and public health, where hours of work are reliable or can be structured around other commitments.4 Furthermore, many doctors, in keeping with their generation, value matters beyond medicine: protected personal time, involvement with family and friends, and a balanced lifestyle.4 Australia’s society has also changed. Our citizens are more health conscious, access health care more frequently, live longer, and overwhelmingly support unfettered access to free and risk-free health care. This health care is consuming a growing proportion of our gross national product and is becoming a “big-ticket” item for governments. Governments have tried hard to control health care supply and demand and, in the process, have made policy blunders. For example, the restriction on medical school outputs in the 1990s has contributed in no small way to Australia’s dependence on overseas-trained doctors to provide for its health care needs.5 In this milieu, Australia finds itself in the midst of a workforce crisis. There are increasingly strident calls for task realignment among health professionals — the development of nurse anaesthetists, and nurse practitioners in general practice, emergency medicine and selected areas of hospital practice, and reporting by scientists on x-rays and pathology tests.6 Indeed, the United Kingdom’s Labour government has recently sanctioned drug prescribing by nurses and chemists for all but controlled drugs.7 It is a political dictum to respond to a crisis by activating an inquiry, and we have had a flurry of reports on potential solutions for the health workforce crisis.8,9 But it is the Productivity Commission’s recent draft position paper, Australia’s health workforce,10 that has the potential to change the face of Australian health care. Its recommendations include the establishment of: An advisory health workforce improvement agency, which will facilitate workforce innovations, particularly those that cross professional boundaries. An advisory health workforce education and training council, coupled with the transfer of responsibility for health education and training from the Department of Education, Science and Training to the Department of Health and Ageing. It is envisaged that this council will enable integration of different models of health education and training and a move towards a single national accreditation agency for university-based education and postgraduate specialist training. In the process, the council would assume existing accreditation roles, such as those of the Australian Medical Council and the clinical colleges. There is also a separate proposal by the Commission for a national registration regime based on the work of the proposed national accreditation agency. An independent review body to advise on services to be covered by the Medicare Benefits Schedule and on referral and prescribing rules, to encourage better use of available health workforce skills. The Productivity Commission’s draft position paper reflects its quest for efficiency and cost-effectiveness, and a belief that agency-led “top-down” reform will save our faltering health workforce. However, to the cynic, it appears to be a veiled attempt to downgrade the function of clinical colleges, to “demedicalise” other existing agencies, and to facilitate a change in the roles of health professionals, including doctors. It provides no evidence that its recommendations will improve the standards of health care, produce better patient outcomes, or, for that matter, solve the current health workforce crisis. All this activity begs the question: in the 21st century, what is a doctor, and what does a doctor do? Answers are to be found in the Canadian Medical Association (CMA) project to define the role of medicine in the 21st century.11 Its deliberations drew freely on other projects, such as Educating Future Physicians for Ontario (an initiative of medical groups, the Ontario faculties of medicine and the Ontario Ministry of Health) and the CanMEDS 2000 Project (Canadian Medical Education Directions of Specialists 2000, a project of the Royal College of Physicians and Surgeons of Canada).11 The CMA clearly defined the doctor’s role as a medical expert and healer, enriched with other roles (). Although no doctor will function in all roles simultaneously, doctors should have competencies to participate in each of these roles as circumstances require. The CMA’s Futures Project advanced values for a future health care system.12 These include “a team approach to the provision of health care and clarity with respect to roles and accountability”, and “a sustainable, highly qualified health care workforce with opportunities for career development and life-long learning”.12 Its values for medicine in the 21st century stress “the physician’s role as leader of the health care team” and “physician autonomy and accountable self-regulation of the profession”.12 In all this, it is assumed that the central role in 21st century medicine belongs to primary care and the generalist. What doctors are, and do, in the 21st century is thus not much different to what Osler espoused 100 years ago. Their tasks are embodied in the questions that preoccupy patients when consulting doctors: What is wrong with me? (diagnosis); What will happen to me? (prognosis); What can we do? (management plan, priorities and coordination); and Who will do it and be responsible? (competent, up-to-date and experienced practitioners, who are indemnified, and whose expertise is underpinned by broad and rigorous training). In this context, the medical profession should welcome task transfer and better use of the skills of the various health care providers, as long as it occurs within the boundaries of team care, and as long as quality and safety outcomes are established. The enactment of the Productivity Commission’s proposals has the potential to realign health care delivery for the 21st century. But it will require wide consultation, a “bottom-up” rather than “top-down” approach, and a modicum of goodwill. It should not be the slippery slope to doctor pretenders.

Martin B Van Der Weyden MD, FRACP, FRCPA