Editorials

No cause for panic, but an incentive to improve clinical practice The use of selective serotonin reuptake inhibitors (SSRIs) in depressed children and adolescents has received consider-able attention in the past year; this attention has included concerns about increased suicide risk, revised evidence about effectiveness, growing prescription numbers, and revelations of drug companies withholding data.1 The discovery of unforeseen risks in other drugs such as cyclooxygenase-2 inhibitors has intensified the climate of uncertainty and mistrust about drug treatment. Some argue that to diagnose major depression in children is to medicalise the unhappiness caused by affluence, permissiveness, a decaying family and society.2 By contrast, medical practitioners and governments have been told during the last quarter century that depression is a serious illness that can lead to suicide, poor physical health, and personal, professional and social difficulties. Thus, the Australian community has invested considerable resources in trying to tackle this scourge (eg, The National Depression Initiative3). If experts disagree, it is little wonder that the public and clinicians are confused, yet severely depressed teenagers continue to come to doctors for management. Do SSRIs increase the risk of suicide?Although SSRIs have been used “off label” in children and adolescents from the early 1990s, none is formally approved for paediatric depression in Australia. Evidence of benefit is ambiguous enough for scholars to be divided,1,4 and we do not discuss it here. Findings of the few epidemiological and ecological studies available conflict about suicide risk. First, SSRIs are less toxic than the older tricyclic antidepressants, particularly in overdose.5 Second, youth suicide rates, after rising for about 40 years, inexplicably declined in Australia and other Western countries in the late 1990s.6 While its cause is probably multifactorial in origin, the decline correlates with increasing SSRI use.7 More prescriptions did not result in higher suicide rates, as might have been expected if SSRIs induce suicide, although this might have been disguised within the general decline.8 Third, SSRIs are not found more often than expected in post mortem examinations of people who have committed suicide.9,10 Conversely, some studies suggest that deliberate self-harm (DSH) episodes are slightly increased in adults taking SSRIs.11,12 Another study reported elevated suicidal behaviour during the first month of tricyclic antidepressant or SSRI treatment13 (this was not replicated in the paediatric trial data14). Clinicians have long recognised an increased risk of suicide in patients starting antidepressant treatment. A recent review commissioned by the Food and Drug Administration (FDA) of 24 controlled trials with more than 4400 children and adolescents showed a higher incidence of suicidality (suicidal thoughts, attempts) in those receiving antidepressants (4%), mostly SSRIs, compared with placebo (2%).14 There were no known suicides. Despite methodological shortcomings (eg, post hoc analyses, varying trial methods, suboptimal assessment of suicidality, exclusion of suicidal youth), this effect seems robust, if small (2%). Thus, the FDA issued the latest in a series of advisories about suicidal behaviour in children and adolescents treated with antidepressants, recommending the strongest labelling warnings, but not contraindicating their use. The meaning and mechanisms underlying increased suicidality in those taking antidepressants are unclear. Suicidal behaviour results from complex interactions in which individual and psychosocial factors, as well as depression and other mental health problems, play a role. In the review commissioned by the FDA, SSRIs induced akathisia, agitation, and irritability more often than placebo.14,15 Patients with these symptoms, often described as “activation”, were up to seven times more likely to show suicidality than those without activation.14 Like other antidepressants, SSRIs can trigger manic switches, often with unstable mood and higher suicide risk. Sex, age, history of suicide attempt, and non-completion of the trial did not influence suicidality, but statistical power was weak because of low numbers.14 It is also possible that non-compliance, which may set off withdrawal symptoms,15 plays a part. Handle with careGrowing knowledge about the risks of antidepressants is an incentive to improve clinical practice for a disorder that, if left untreated, is associated with significant morbidity and mortality. Large increases in the use of SSRIs in adolescents and children suggest we have become casual about prescribing them. We may be giving SSRIs to mildly depressed adolescents and neglecting regular review, counselling, and cognitive behaviour therapy (CBT). The association between “activation” and suicidality highlighted above14 emphasises the importance of monitoring and managing side effects, which are dose-related.15 As in all medicine, practice should be guided by a careful appraisal of benefit and risk based on best external evidence and individual clinical experience. While the credibility of antidepressant medications has been undermined, evidence for CBT and related treatments has not received the same level of scrutiny, and is flimsy for moderate and severe depression,16 particularly in non-research settings. Besides, psychosocial treatments require more cooperation from depressed teenagers who are often hostile, unmotivated, demoralised, or lack insight. This could easily lead to therapeutic nihilism or a regression to treating depression primarily as a moral or social problem.2 There is no definite answer yet about whether to prescribe or not; clinicians must weigh the pros and cons for each patient. Children and families must be informed of the risks of medication — parents who believe their children killed themselves because they were taking SSRIs consistently complain they “were not told”. Until the ambiguities are resolved, based on our clinical experience, we believe that SSRIs (chiefly fluoxetine1) can be considered, but only for severe depression, when it produces serious impairment and fails to respond to psychosocial treatment over a few weeks. Combining SSRIs and CBT may be more effective, and might reduce suicide risk17 However, apprehension about SSRIs should not lead us back to using tricyclic antidepressants (which are more toxic), to blaming sufferers or their families, or to refusing to treat depressed adolescents at all.

Joseph M Rey PhD, FRANZCP · Michael J Dudley FRANZCP

Advantages to patients of a single anaesthetic for more than one operation are obvious; attracting generalist surgeons, training them and ensuring they have adequate credentials remain hurdles With the inexorable increase in specialised surgery, the concept of “general” surgeons, what they do, and what they represent, is difficult to categorise. Indeed, is there a need for a generalist surgeon when it seems that most areas of our bodies have a designated subspecialist? . . . credentialling, clinical governance and continuing professional development are of critical importance for the practising surgeon. In this issue of the Journal (page 337), Wilson, a general practitioner–surgeon makes a compelling case for the continuing existence of the general surgeon.1 He presents an affirmative argument through the details of his experience in performing multiple elective surgical procedures on individual patients. Most of the procedures were relatively minor, yet traversed a wide range of subspecialties. The complication rates were low, and there can be no doubt that the patients benefited from a single visit to an operating theatre to have multiple problems treated. Where can a trainee gain experience in many of the minor procedures described by Wilson? Emphasis in tertiary hospitals has traditionally been on major caseloads, yet a veritable gold-mine of minor operative cases are present in day-surgical units. With a little imagination and cross-specialty cooperation, a 6-month term exclusively in a day-surgical unit would provide a trainee with a solid grounding in minor operative surgery. Rotations through regional surgical centres, where general surgical operative lists continue to remain varied,2 would provide another significant learning opportunity for trainees. However, the role of the GP–surgeon in major population centres seems limited, especially in view of credentialling requirements imposed by health care authorities. The issues of credentialling, clinical governance and continuing professional development have been highlighted by the Royal Australasian College of Surgeons (RACS) as being of critical importance for the practising surgeon, and much effort has been invested in formulating policies to reflect this and, in turn, maintain a high standard in surgical care. Who is responsible for ensuring that practitioners who are not fellows of the RACS comply with accepted surgical guidelines? While Wilson describes himself as a “GP–surgeon”, he is a fellow of both the Royal Australasian and Edinburgh Colleges of Surgeons, a factor that would certainly ease the path of credentialling in his case. The ongoing need for GP proceduralists in rural regions is unquestionable, and the various support and training mechanisms have been described at length in the Journal.3 The RACS has clearly outlined the general surgical curriculum.4 It states, “trainees should gain sufficient experience in operative surgery to achieve competency in managing common surgical conditions and emergencies as outlined”, and subsequently lists a comprehensive range of surgical conditions. Currently, most advanced trainees seem to attain competency in a core group of the listed procedures and then move into subspecialty regions, rarely to venture outside their chosen field. The lack of young, qualified surgeons to serve the community in a range of generalist procedures will become magnified by the ageing and eventual retirement of a substantial proportion of the Australian surgical community.5 It is precisely this group of surgeons who, by virtue of previous training and experience, remain adept at a wide range of general surgical procedures. There appears to be an opportunity for senior surgeons, perhaps wishing to step back from on-call emergency work, to become “day surgery specialists” and impart invaluable knowledge and skill to junior colleagues. The concept of a general surgeon able to perform a range of procedures on a single patient under a single general anaesthetic is worthy. While there is no rigorous evidence to prove it, anecdotally, at least, there is a definite need for such individuals within the medical community. The importance of performing minor surgical procedures well needs to be re-emphasised, and while the major cases may have more “lustre” for trainees, it soon becomes apparent during surgical practice that much patient satisfaction can be derived from successfully curing ingrown toenails, carpal tunnel syndrome or anal fissure.

Martin H Bruening FRACS, FRCSEd, MS · Guy J Maddern FRACS, PhD, MD

Environmental strategies must be complemented by behavioural approaches to help children learn to use roads safely In Australia, pedestrian injury is the leading cause of death among 1–14-year-olds.1 In 2000, 38 child pedestrians in this age group died2 and about 1140 (29 per 100 000) were hospitalised, often with lengthy stays, because of injuries sustained when hit by a vehicle.1 These rates decrease with age and are lowest for 10–14-year-olds.1 The most recent comparison with other OECD countries shows that Australia has the 13th lowest pedestrian fatality rate for 0–14-year-olds,3 with slightly more pedestrian deaths among 0–5-year-olds than the median rate for all OECD nations (1.03 per 100 000 versus 0.89 per 100 000).4 The primary predictors of this child pedestrian trauma relate to the interaction between the characteristics of the child and the design and nature of the road environment to which the child is exposed. A Western Australian case–control study of child pedestrians aged 1–14 years identified four key environmental and behavioural factors that independently predicted the likelihood of child pedestrian injury.5 These comprised the volume of traffic encountered by the child, presence of visual obstructions, availability of footpaths on the child’s street of residence, and the child’s behaviour. Predictors also vary according to the age of the child. Whereas 1–2-year-olds are more likely to be hit by a reversing vehicle, the most common cause of pedestrian trauma in 3–9-year-olds is mid-block “dart-out” (entering the road between intersections and not seeing, or misjudging, a gap in traffic).6,7 Pedestrians aged under 10 years are particularly vulnerable because of their small physical size and underdeveloped abilities for dealing with traffic situations, both cognitive (attention focus, interpreting traffic signs) and perceptual (locating sounds, judging speed, peripheral vision).6 Given these limitations, children under the age of 10 do not have the ability to cross roads without adult help. Ten to 14-year-olds are also vulnerable, but more because of their failure to apply safe pedestrian skills than because of their lack of skills. Further, road trauma in this age group may also be associated with general delinquency and problem behaviour.8 Many of these predictors of pedestrian trauma can be prevented or modified and are therefore amenable to intervention.7 While debate continues about the merits of environmental (passive) versus behavioural (active) intervention strategies to reduce this road trauma, evidence suggests that all are necessary, and no single strategy is sufficient.6 A multifaceted approach that combines strategies targeting the behaviour of all road users (including education, training and publicity), the road environment and vehicle design have been found to be the most effective.3 Strategic approaches involving public health, education, health promotion, urban planning, engineering and motor vehicle design are required. Consequently, while efforts are needed to make the road environment safer for pedestrians by reducing the speed and volume of traffic to which they are exposed, it is also necessary for pedestrians (particularly children) to learn how to use these road environments safely. Yet research into behavioural approaches to pedestrian safety has lagged behind environmental research.9 Behavioural programs for children need to be developmentally appropriate and include modelling and training by an adult in a social context and road environments relevant to the child. Programs also need to be interactive and involve problem-solving with consistent and prompt feedback from a caring adult, rather than merely following rules.10 The use of didactic knowledge-only strategies (such as rote learning of rules) is inappropriate, as younger children are not able to generalise this learning to real roads.11 Roadside training and, to a lesser extent, realistic simulations appear to improve visual timing and gap selection, to increase the ability to identify safe and dangerous crossing locations, and to enhance learning of appropriate strategies for crossing at parked cars. Such training has produced positive results with children as young as 5 years.12,13 Several new approaches to children’s pedestrian safety education are being tested. These include programs targeting younger children and adults who care for children, and use of new technologies. Two Australian reviews recommend targeting 0–5-year-olds, arguing that, with good quality pedestrian safety training, young children could demonstrate a rudimentary conception of danger, which improves with age.14,15 Some Australian jurisdictions have developed curricula and materials based on these approaches, such as the Victorian “Starting Out Safely” program. Engaging parents and helping them recognise their important role in their children’s pedestrian safety has the potential to significantly enhance children’s safety on and near roads.14 Parents provide the best role models and one of the only means for children to receive the necessary personalised one-on-one training and to practise crossing real roads. Technologies that use interactive simulations (eg, visual reality computer) coupled with real road experience and “pretend” road practice (the “pretend” road is set up parallel to a real one) can enable children to practise their skills, receive consistent and instant feedback and repetition, and be introduced with careful control to the complexity of traffic.16 While reviews of the impact of behavioural and environmental programs on preventing road trauma in children have demonstrated mixed success, it is apparent that programs need to take a comprehensive preventive approach with modifications to the road environment, enforcement, engineering and education. While much still needs to be done to determine the optimal mix and “dose” of these approaches to reduce child pedestrian trauma, every effort must be made to keep children safe near traffic and roadways that are becoming increasingly busy and complex.

Donna S Cross EdD · Margaret R Hall PhD

Early experience confirms that riluzole improves survival and is well tolerated The recently established Australian Motor Neurone Disease Registry estimates that 1200 Australians are living with motor neurone disease (MND), and 370 new patients are diagnosed each year. Most patients die within 3 years of diagnosis. Aetiological mechanisms implicated in the development of MND have been linked to the glutamatergic neurotransmitter system, with excessive activation of glutamate receptors at the synaptic cleft now believed to trigger destruction of motor neurones.1 This “excitotoxicity” theory of MND gave rise to the development of new therapeutic approaches and, ultimately, clinical trials involving riluzole. This drug was initially thought to act solely as an inhibitor of glutamate release, although subsequent postulated effects include indirect antagonism of glutamate receptors and inactivation of neuronal voltage-gated sodium ion channels. Regardless of the precise mode of action, two large trials in the 1990s established the efficacy of riluzole in the treatment of MND.2,3 A double-blind, placebo-controlled study undertaken in 155 patients with MND showed a significant prolongation of survival and an improvement in functional outcome measures for those treated with 50 mg of oral riluzole twice daily.2 A larger, dose-ranging study undertaken in 959 patients confirmed the beneficial effect of riluzole on survival, being in the order of 3–6 months.3 In the original study,2 the therapeutic effect of riluzole was more prominent in patients with bulbar-onset MND, while the second study found no significant differences in the responses of bulbar- and limb-onset groups.3 Subsequent retrospective analyses suggest a survival benefit even longer than 6 months in both patient groups, but these data have been confounded by recent general improvements in the care of MND patients, particularly the use of percutaneous endoscopic gastrostomy for nutritional support and non-invasive ventilation for respiratory insufficiency, in the setting of a multidisciplinary approach to care.4 Riluzole remains the only medication to slow the progression of a neurodegenerative disease, leading to an increased survival for patients with MND.5 In some countries including Australia, riluzole’s manufacturer had difficulty gaining a listing for the medication on pharmaceutical benefits schemes, in part due to issues related to “quality of life”, despite trial data documenting improvement in patient longevity.2,3 Quality of life is a nebulous measure and the findings using quality-of-life scales in MND clinical trials have proved inconsistent to date.6 After dissecting arguments related to quality-of-life issues, and with intense lobbying by the MND community — patients, clinicians and care groups — riluzole was finally listed by the Australian Pharmaceutical Benefits Scheme (PBS) in June 2003 (see Box for criteria). Linked to the original riluzole trials were studies conducted to establish the safety profile of riluzole in MND patients, including the Riluzole Early Access Program run here in Australia. The primary objective of these open-label, single-treatment studies was to enable patients with MND to receive riluzole therapy pending its commercial availability, health authority approval and, in the case of Australia, listing on the PBS. Through such a process, the safety profile of riluzole was expanded. These later studies established that riluzole was generally well tolerated by patients with MND. Adverse events were predominantly gastrointestinal, with nausea, weight loss and dysphagia being the most frequent,7 although it may be argued that the latter symptoms more likely reflect disease activity itself. Measurement of full blood count before initiation of therapy is suggested, as, rarely, blood dyscrasias may develop with riluzole. As riluzole is metabolised hepatically and significant hepatotoxicity occurs in about 0.2% of patients,7 testing liver function monthly for the first 3 months and then at 3 monthly intervals remains important. However, patients with MND can have or develop abnormal liver function for many reasons other than taking riluzole, including the use of alternative therapies, emphasising the need for baseline measurements before initiating riluzole therapy and withholding the drug if liver function is grossly abnormal (eg, liver enzymes elevated above five times normal). When should MND patients commence taking riluzole? Certainly, any patient with clinically probable or definite MND (based on a combination of upper and lower motor neurone abnormalities in two to three spinal regions) warrants consideration. It could be argued that, given suggestions that patients benefit most from therapeutic intervention in the early stages of MND, the earlier riluzole is started the better. It is inevitable that, by giving riluzole to patients in whom MND is suspected, a few patients in the “possible” and “probable” clinically diagnosed categories will receive this treatment for conditions other than MND, with the correct diagnosis only becoming apparent over time.8 However, given the putative neuroprotective properties of riluzole, this approach has no identifiable drawbacks. Giving riluzole to patients with advanced disease is problematic, and the current PBS guidelines for authority prescriptions of riluzole stipulate that the date of MND diagnosis (disease duration, ≤ 2 years) and the results of respiratory testing (forced vital capacity, ≥ 60%) must be supplied with the initial authority application. Obtaining adequate measures of vital capacity may be difficult in patients with bulbar onset, although the use of face masks in specialised respiratory units may circumvent this difficulty. Finally, patients must be aged ≤ 75 years to qualify for PBS subsidisation, primarily because there is limited information regarding the benefits of riluzole in the older age group.9 Questions remain about the benefits of riluzole on survival in patients with advanced MND, and whether the effect of riluzole on motor neurones diminishes over time. Certainly, there is no evidence to suggest that riluzole reverses motor neurone degeneration and, despite extensive counselling about what to expect, patients may have unrealistic expectations of riluzole therapy. My own experience in the trial setting was that when their deficits did not diminish, some patients ceased taking riluzole, believing it not to be beneficial. This reinforces the need for a detailed discussion between the treating physician and the patient with MND at the time of commencing riluzole. Patients need to understand the role of riluzole therapy; specifically, that it is not a cure, but that it has been established to slow the rate of deterioration in muscle function and thereby increase longevity and quality of life. Clearly, good communication skills and empathy are needed when conveying this information to the patient and their family. Pharmaceutical Benefits Scheme (PBS) criteria for riluzole authority (June 2003) Approved indication Treatment of motor neurone disease PBS indication for authority Initial treatment of motor neurone disease, as diagnosed by a neurologist, in patients aged 75 years or less, with disease duration of 2 years or less and who have at least 60% of predicted forced vital capacity within 2 months prior to commencing riluzole therapy and who: 1) are ambulatory, and a) have not undergone tracheostomy, and b) have not experienced respiratory failure; OR 2) are not ambulatory, and a) have not undergone tracheostomy, and b) have not experienced respiratory failure, and c) are either able to use upper limbs or able to swallow. The date of diagnosis and the results of spirometry (in terms of percentage of predicted forced vital capacity) must be supplied with the initial authority application.

Matthew C Kiernan PhD, FRACP

We need a patient safety initiative that captures the imagination of politicians, professionals and the public Nearly 10 years have elapsed since the Journal published the ground-breaking Quality in Australian Health Care Study (QAHCS)1. With its disturbing findings, the study seared “patient safety” into the public’s psyche. The QAHCS methodology focused on the safety aspects of healthcare quality, without providing systematic data on other domains, such as access, efficiency and acceptability, and provided only some insight into effectiveness and appropriateness of care. The role of QAHCS was to estimate the size and nature of the problem of unsafe healthcare. . . . the absence of recent system-wide data on patient safety . . . makes a mockery of the tenets of continuous quality improvement. Now, 10 years on, most patients in our healthcare system do not suffer preventable harm, and receive good care. But it is still possible that up to 16% of hospitalised patients will suffer an adverse event: 50% of these events will be preventable and 10% of these preventable events will lead to permanent disability or death.1 Studies from the United Kingdom,2 Canada,3 Denmark,4 and France,5 using similar methodology to the QAHCS, indicate that Australian healthcare is no safer than that provided in these countries. The magnitude of the problem worldwide is reflected in the World Health Organization’s recent launch of the Patient Safety Alliance,6 which aims to improve patient safety in all 192 member nations. What has been achieved since the release of the QAHCS? In 2000, 5 years after the study’s release, the Australian Council for Safety and Quality in Health Care (ACSQHC) was formed to provide leadership in improving patient safety and quality through advice to all federal, state and territory health ministers. The ACSQHC has championed an extensive work program,7 including: developing an “open disclosure” standard for patients and their families when care processes go wrong; developing a national standard for credentialing and defining the scope of practice of medical practitioners; involving consumers in improving healthcare safety by producing the booklet Ten tips for safer health care: what everyone needs to know; establishing a national Centre for Research Excellence in Patient Safety; testing strategies to ensure safer medication use at the point of care by involving more than 100 healthcare facilities in the National Medication Safety Breakthrough Collaborative; introducing the “Ensuring correct patient, correct site, correct procedure protocol” to reduce “wrong site” or “wrong patient surgery” and launching a “high risk medication alert” on the use of concentrated potassium chloride solutions in hospitals. Furthermore, each state and territory has developed peak advisory bodies, and many elements of patient safety programs (eg, the reporting and investigation of serious incidents) have been incorporated into hospital practice in all states and territories. Professional bodies such as the Royal Australasian College of Physicians have strengthened activities for maintenance of their members’ professional standards,8 and hospitals and other healthcare facilities have formed committees and created departments to oversee patient safety activities. All this has involved considerable effort and resources. However, much of the investment has been in “top down” activities (in the form of policy or monitoring) rather than “bottom up” activities. This can result in a considerable gap between what patient safety strategies are supposed to have been implemented in the workplace and what strategies are actually in place. Instances of poor healthcare outcomes for individual patients, or adverse events involving particular hospitals, have rightly been highlighted in the media. The outcries reached deafening crescendos when perceived healthcare “scandals” in three Australian jurisdictions were revealed.9 This year, the NSW government’s Patient Safety and Clinical Quality Program released the “First report on incident management in the NSW public health system 2003–2004”10 452 incidents were reported that were regarded as “very high risk, can result in serious patient harm, and must be followed by immediate action . . .” This followed a similar report by the Victorian government in 2004.11 Ten years on can we confidently state that healthcare is safer for patients? Unfortunately, the answer is no. There is insufficient information at a state or national level to determine whether any or all of the efforts over the past 10 years have increased safety in our hospitals. It is regrettable that we have not measured the frequency of adverse events in Australia in a way that allows us to assess how we have fared since 1995; how we compare with other countries; and whether any of the initiatives described above have been effective in reducing patient harm. Given the truism we “manage what we measure”, the absence of recent system-wide data on patient safety seriously hinders our ability to manage the problem and make improvements. Its absence makes a mockery of the tenets of continuous quality improvement. We need a thorough understanding of the strengths and weaknesses of data derived from medical record audits, voluntary reporting systems, clinical indicators, and existing large datasets if we are to seriously tackle the size and nature of the problem, and determine whether a particular intervention or program has been successful in improving safety. This information gap is recognised in the 2005 national productivity report on government services.12 Despite all the developments in the last 10 years, and in the context of the current Australian Health Ministers’ review of the governance arrangements for safety and quality of healthcare,13 there are still four areas that require more action and greater urgency. Leadership — to provide clarity of vision and the will to change. As part of that leadership, we need an explicit and agreed goal, such as “to eliminate preventable patient harm from healthcare within 10 years”. A recent challenge from Don Berwick — the 100 000 lives campaign — is to avoid 100 000 preventable deaths in the United States between January 2005 and July 2006 and every year thereafter. The campaign aims to enlist thousands of hospitals across the US in a commitment to implement changes in care that have been proven to prevent avoidable deaths.14 Transparency — fears that open discussion will reduce patient trust in the healthcare system, leading to patients failing to present for care in a timely manner, seem to be unfounded.15 Measurement — to provide information about where to direct our improvement efforts and whether our interventions have been effective. Dependence on voluntary reporting systems will lead to a gross and inconsistent underestimate of the size of the problem. Improvement tools — there is a body of evidence on methodology for improvement projects at the local level, from the pioneering contributions of W Edwards Deming and Walter A Shewhart to the more recent Institute for Healthcare Improvement’s Breakthrough Collaborative methodology,16 which, through a collaborative learning model involving multiple organisations, helps health professionals to bring about breakthrough improvements in patient care outcomes. There has been a lack of appreciation that the use of tested methods increases the likelihood of success of a particular project. Hence, many efforts have not delivered their full potential, or discussion and learning have been prevented because successful efforts have not been publicised. The failure to successfully implement existing knowledge or policy is a worrying characteristic of healthcare systems,17 and demands greater rigour. Creating this capacity within our organisations is a major challenge to be addressed. The responsibility is on all of us — politicians, health administrators, clinicians and the public. Finally, the governance arrangements for transparency of performance of health service delivery, and the accountability for that performance at an individual, organisational, state and national level, need public negotiation and agreement. Currently, there seems to be an imbalance: much more attention is being paid to the accountability of individual healthcare providers than to improving healthcare safety at an organisational and whole-system level. Of equal importance is that the ACSQHC appears to have limited relevance to or influence on the daily lives of health professionals. It is sorely in need of an initiative that captures the imagination of politicians, professionals and the public.18 It could do no better than to emulate the US Institute of Medicine’s “Crossing the quality chasm” healthcare quality initiative19 by selecting a limited number of clinical conditions which have a high healthcare burden and resource use, and which clinicians agree are high priority. The task then is to apply the six aims for healthcare improvement to management of patients with these clinical conditions — their healthcare should be safe, effective, patient centred, timely, efficient, and equitable.18 Finally, the process must be driven from the bottom up. Alternatively, joining the Berwick challenge to save 100 000 lives by reducing unsafe healthcare could have a galvanising influence.14 The magnitude of the challenge of eliminating preventable patient harm is daunting, the progress slow, and the need for our efforts to be successful huge. A significant increase in resolve on the part of all Australians, regardless of their role in healthcare, is needed if we are to meet the challenge of eliminating preventable patient harm over the next 10 years.

Ross McL Wilson MB BS, FRACP, FJFICM · Martin B Van Der Weyden MD, FRACP, FRCPA

Using clinical trials to assess long-term drug safety is problematic; in Australia, simple data linkage based on Medicare numbers may provide useful monitoring information The era of pharmaceutical medicines began with the synthesis of acetylsalicylic acid (ASA) in the late 19th century. The reason for its synthesis was that natural salicylic acid was irritating to gastric mucosa, and the synthesised product less so. Subsequently, more potent non-steroidal anti-inflammatory drugs (NSAIDs) were introduced and, more recently, cyclooxygenase-2 (COX-2) inhibitors, also with a lesser risk of gastric irritation and bleeding. 1 The rapidly widespread and often prolonged use of these agents meant that even a small increase in the risk of a serious adverse event could be very significant in population health terms. This theoretical concern became a reality when rofecoxib (a COX-2 inhibitor) was found to confer an increased risk of cardiovascular disease — a risk uncovered in a trial to determine whether rofecoxib could prevent the recurrence of colorectal polyps. 2 Subsequently, the United States Food and Drug Administration has issued warnings on the cardiovascular safety of celecoxib and naproxen.3,4 More recent information links long-term use of celecoxib and short-term use of parecoxib and valdecoxib (though non-significantly for the latter two) with adverse cardiovascular events. 5,6 This is consistent with a class effect. Although the mechanism underlying the increased cardiovascular risk with COX-2 inhibitors is unknown, there is a biological rationale that might have predicted it and which, in retrospect, should have led to intense postmarketing surveillance of these inhibitors. The non-selective COX inhibitors (ASA and NSAIDs) inhibit platelet aggregation, whereas selective COX-2 inhibitors do not. 7 Selective COX-2 inhibitors may also be prothrombotic through prostacyclin, which has a markedly enhanced action in atherosclerosis.8 The widespread use of COX-2 inhibitors has been part of the historic trend from short-term use of drugs to treat acute conditions to prolonged use of drugs to treat symptoms and prevent disease. This change has brought to light shortcomings in the current methods of drug safety monitoring. In the past, the linchpin of postmarketing surveillance has been the spontaneous reporting system in which doctors, pharmacists and others report recognised adverse reactions to drugs. However, this mode of reporting is useful only for detecting narrow spectrums of adverse events, particularly those occurring soon after drug administration or those that have overt effects (eg, rash, hepatic inflammation or blood dyscrasia). This spontaneous reporting is particularly unsuitable for long-term monitoring of drug safety. These realities are poorly appreciated by healthcare professionals, who often assume that, in comparison with older drugs, a newly registered drug has superior short-term and long-term safety.9 However, the events with the COX-2 inhibitors, which follow on the heels of similar, unsuspected concerns about anti-arrhythmic therapy and hormone replacement therapy, has again highlighted the need for a more systematic approach to long-term safety monitoring of long-term drug therapy.10,11 The accepted gold standard for establishing the balance of long-term drug safety and efficacy is the controlled clinical trial. In 2005, it should not be possible for any long-term medicine to be approved without the security of a large-scale morbidity–mortality trial, or the commitment of the pharmaceutical industry to perform one as soon as practicable. Licensing should be conditional on these requirements being met, and the onus should be on regulators to make these changes in the interests of both the end-users and the pharmaceutical industry. However, even large-scale morbidity–mortality trials have their limitations. They are very costly to establish, and ethical considerations may preclude the use of placebos. Comparisons with other active drugs may be difficult to interpret, as illustrated by the comparison of rofecoxib and naproxen.1 Study inclusion criteria may lead to the exclusion of patients with comorbidity or polypharmacy, and yet these individuals are both more likely to be prescribed drugs and be at higher risk of adverse reactions. In addition, it has proven difficult to continue large-scale trials beyond 5–6 years, so adverse events with prolonged latency, such as malignancy, may not be identified. A solution to long-term drug safety monitoring might include observational epidemiology. Methods must be developed for early identification of users of new drugs and their subsequent disease history determined by data-linkage to various mortality and morbidity databases (such as hospital admissions, cancer and death registries). The inclusion of Medicare numbers on prescriptions in Australia provides a simple means for participation in these studies. An ongoing hurdle is the issue of confidentiality. We do not claim that data-linkage will provide a foolproof answer to drug safety issues. The future mortality and morbidity experiences of any cohort of drug recipients may be influenced by the underlying disease for which the drug has been prescribed. This makes it desirable to have one or more control groups (typically individuals receiving a different drug for the same disease) for comparison. Even if there are control groups, there may still be confounding by differences in indications or contraindications. Therefore, the gathering of linkage data is often relatively low grade, retrospective and useful mainly as a screen for further study if an unexpected finding arises. Such linkages were used in the US to bring into question the cardiovascular safety of rofecoxib before the VIGOR trial.12 Large linked databases are increasingly seen as the only reliable means of gaining the information necessary for monitoring long-term drug safety.13 Our unified healthcare system in Australia, with its standardised Medicare numbers and national databases, has the potential for providing Australia with a strategically important role in this crucial area of drug research.

Mark R Nelson PhD, FAFPHM · Andrew M Tonkin FRACP, MD · Flavia M Cicuttini PhD, FRACP · John J McNeil PhD, FRACP

The annual death toll from tuberculosis in the Indian Ocean region is 2–3 times higher than the toll from the recent tsunami A major earthquake measuring 8.9 on the Richter scale occurred off the west coast of Sumatra on 26 December 2004. 1 The quake even caused the earth to wobble in orbit. 2 The ensuing tsunami hit countries bordering the Indian Ocean. The estimated death toll exceeds 220 000. 1 The human and economic tragedy was evident to all, and national governments and international organisations have mounted an enormous relief effort. Coincidentally, seven of the tsunami-affected countries (India, Indonesia, Thailand, Bangladesh, Burma–Myanmar, Tanzania and Kenya) are among the 22 nations with the highest burdens of tuberculosis (TB). 3 Over three million new TB cases and 772 000 TB deaths occurred in these seven countries in the year 2000. 3 Similar annual statistics have been reported from these and other high-burden countries for more than 10 years. But the earth does not move! The human and economic toll is not appreciated, and an enormous global response is not mounted. The global TB situation is full of such paradoxes. It also highlights the global inequities in the distribution of healthcare services and other resources. 4 An estimated 8.3 million new TB cases and nearly 2 million TB deaths occurred worldwide in 2000. 3 Ninety-five percent of the TB cases and 98% of the deaths were in low-income countries. 4 Importantly, from Australia’s perspective, 60% of this global TB burden occurred in our neighbouring countries in South East Asia and the Western Pacific. 3 What is happening in low-income countries? In Africa, 38% of new adult TB cases in 2000 were in people who were HIV-positive. 4 HIV infection increases an individual’s susceptibility to infection and disease progression, and the increased burden of HIV-associated cases may increase TB transmission to those who are HIV-negative. HIV-related TB has swamped TB-control efforts in Africa, where case numbers increased 6.4% between 1997 and 2000. 3 Multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis strains with resistance to at least isoniazid and rifampicin, is also perceived as a great threat to TB control. However, only an estimated 273 000 (3.2%) of new TB cases worldwide were multidrug resistant in 2000. 5 Mathematical modelling and other observations based on imperfect data suggest that MDR-TB strains are generally of lower reproductive fitness, and that MDR-TB will remain localised in foci such as the former Soviet Union. 5 Effective TB control in these MDR-TB-endemic foci may require additional measures, such as wider availability of drug-susceptibility testing and the use of second-line drugs under close expert supervision. 5 More mundane factors than MDR-TB are the real confounders of TB control in low-income countries. These factors include inadequate infrastructure (eg, roads, transport, electricity), weak primary healthcare systems, poor laboratory services, and insufficient engagement of private practitioners and other health providers in TB control. 6 A major impediment to TB control that must be highlighted is the lack of trained staff, particularly in HIV-endemic countries, where the epidemic has decimated the healthcare workforce. 6 What can be done in low-income countries? Effective TB control relies on halting transmission through the rapid detection and cure of infectious cases. International targets have been set to detect at least 70% of all new infectious cases and to cure at least 85% of those detected by 2005. 6 Attainment of these goals would result in a decline in TB incidence of 6%–7% per year. The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease have recommended and validated a policy package entitled DOTS to achieve these case detection and cure rates. The DOTS strategy contains five elements: government commitment, accurate diagnosis principally by sputum-smear microscopy, standardised short-course chemotherapy with direct observation of treatment, provision of reliable drug supplies, and systematic program monitoring. 6 Unfortunately, the WHO annual TB reports to 2003 suggest that the global targets for case detection and cure rates may not be met by 2005. Additional initiatives have been recommended, including increasing government stewardship of TB-control programs, engagement of private health practitioners in DOTS programs, and involvement of local community groups. 6 Tuberculosis and HIV-control programs in Africa and other HIV-prevalent areas must also be coordinated and integrated to achieve enhanced TB and HIV case-finding, to institute TB preventive treatment, and to establish interventions against HIV, such as antiretroviral treatment (which will also indirectly control TB). 6 High-income countries with a low incidence of TB, such as Australia, confront different challenges.7 The incidence of TB in Australia was 4.9 cases per 100 000 population in 2003, which is one of the lowest rates globally, and this incidence has remained stable since the mid-1980s.8 However, people born overseas and Indigenous Australians remain at increased risk of TB (with 9.9 and 8.5 cases per 100 000 population, respectively).8 Maintaining awareness about TB among the medical profession and governments is difficult when the overall TB incidence is so low.7 Undergraduate and postgraduate education programs must ensure that clinicians consider TB, particularly in patients from at-risk subgroups.7 Governments must continue funding specialist TB treatment services (including specially trained staff and reliable drug supplies).7 The TB services themselves must realign policies and procedures towards TB elimination, and consider innovative measures for controlling TB in the subgroups who remain at increased risk of TB.7 The National Tuberculosis Advisory Committee has addressed these issues and published a strategic plan that includes performance indicators for evaluating our national TB-control efforts.9 World TB Day on 24 March is a reminder to Australian doctors that TB is not a vanishing disease. Rather, a “tsunami of TB” occurs every year overseas. What can we do? At the clinical level, Australian doctors must “think TB” when seeing patients, particularly those from subgroups at risk of TB. Australia has laboratory and clinical expertise in TB which is being shared increasingly with our neighbouring countries. Finally, we must advocate for the Australian and other governments to provide funds for TB-control programs in our neighbouring countries, as has happened for the tsunami relief effort. Australia must do so for humanitarian reasons and for self-interest.

Ivan Bastian PhD, FRCPA

Identifying these reactions is a good start, now we must focus on managing and preventing them Australia’s voluntary reporting system for adverse drug reactions has one of the highest per capita reporting rates in the world. Reports to the Australian Adverse Drug Reactions Advisory Committee have played a significant international role in identifying previously unrecognised adverse drug reactions (ADRs), such as hepatitis with flucloxacillin and amoxycillin–clavulanic acid. However, in this issue of the Journal (page 267), Burgess and colleagues remind us that, although identifying ADRs is important, managing and preventing them are equally critical. Their study in Western Australia showed that the rate of ADRs associated with hospitalisations in people aged 60 years and over more than doubled between 1991 and 2002. South Australian data for all age groups showed a similar rise and correlated strongly with changes in medication use in the community.3 National data also show increases,3,4 although the correlation with medication use is less clear. As the Australian coding standards allow ADR codes to be applied to any diagnosis, not just the principal diagnosis,5 the WA data may represent all ADRs, not just those linked to admission or length of stay. Efforts to improve coding will have contributed to some of the observed rise as, for example, rates in SA increased in the year casemix funding was introduced. Increases in the number of hospital admissions over time will also have contributed, but the strong correlation with medication use in SA suggests an exposure effect. The rise in ADRs is not inevitable. The Quality in Australian Health Care Study estimated that 43% of adverse drug events were potentially preventable.6 Similarly, an Australian study of ADRs in oncology patients demonstrated that 48% of predictable ADRs were potentially preventable.7 The questions raised by Burgess et al’s study are: why are ADR rates rising and why have we been unable to prevent the rise, given the preventability estimates? Burgess et al suggest the rise represents a failure of the national strategies to improve the quality and safety of medicine use. There are many data available with which to dispute this claim. Over 100 performance indicators are used to routinely monitor the National Strategy for Quality Use of Medicines, with more than 85% of them demonstrating improvements over time and significant development of services and resources.4 The National Prescribing Service (NPS) has driven cultural change about quality prescribing in general practice, with more than 50% of general practitioners now voluntarily participating in initiatives to improve prescribing.8 Improvements in antibiotic, antidiabetic, analgesic and antihypertensive use have been seen, in keeping with NPS messages.8 The Safety and Quality Council are also driving cultural change, supporting the National Medication Safety Breakthrough Collaborative, which has worked with 100 hospitals and over 480 staff. This initiative is now focusing on disseminating knowledge of and sustaining successful practices. What the data on ADRs in hospitals indicate is our failure to focus on management strategies for ADRs as a specific topic within the national initiatives. Quality use of medicines and safety initiatives have generally focused on development of services, appropriate selection of medicines and error reduction. The focus for ADRs has remained predominantly on reporting and identification, with less emphasis on management. To improve ADR management, we must improve our information sources. Product and consumer information list ADRs but usually fail to provide management strategies. Incidence estimates in product information are based on the initial clinical trials and not easily updated when postmarketing surveillance is based on voluntary reporting. Information on the duration of side effects and consumer experience with medicines is also limited. Providing lists of ADRs does little to change behaviour; management strategies are required.9 The data-linkage studies now under way will enable better incidence data to be developed, as well as identify population groups most at risk of ADRs. The newly established consumer reporting service will also facilitate better understanding of consumer perspectives. This must be incorporated into information sources and supported by clear instruction on management. Detection of ADRs in routine clinical practice must also be improved, with more training needed in this area for health professionals. An Australian study of older people considered at high risk of medication misadventure found that 19% had had an ADR which had not been detected in routine clinical care, even though most were using multiple medicines, had comorbidities and were aged over 65 years.10 The other major requirement is to increase participation in services demonstrated to improve use of medicines and to help prevent ADRs. While consumer medicine information is now available for over 2000 products, it is not provided routinely and continues to be regarded negatively among some health professionals, despite consumer calls for information on side effects.11 Home-medication reviews involving general practitioners, pharmacists and patients have been shown to resolve or ameliorate ADRs in 56% of cases.12 However, the 26 000 home-medication reviews undertaken in 2003–200413 represented about 10% of the population likely to benefit from the service. Other multidisciplinary approaches such as clinical pharmacy, hospital discharge planning and case conferencing services have all been shown to reduce adverse drug events,3 but only 13 000 case conferences and 96 000 discharge-planning services were funded under Medicare’s Enhanced Primary Care packages in 2003–2004.14 The latter services account for 3% of hospital admissions involving overnight stays. These services are relatively new, which may contribute to the low uptake. However, their administrative requirements also need to be streamlined, as general practitioners have found them to be bureaucratic and onerous.15 In addition, trying to incorporate new services on top of existing practice may be adding to the burden and low uptake. It may be necessary to redesign general-practice systems to accommodate these new ways of working. Finally, we require a cultural and attitudinal change to the preventability of ADRs and to multidisciplinary practice. ADRs are often considered part of the price to be paid for the therapeutic benefit of medicines. The rise in ADRs despite preventability estimates suggests that we are currently paying too high a price. Preventing ADRs requires active participation by everyone.

Elizabeth E Roughead PhD

Desperate people seek desperate remedies The treatment alternatives available to Australians with endstage kidney failure are dialysis, transplantation or no active treatment. The last of these options allows kidney failure to progress spontaneously to uraemia and death. Over the past decade the number of Australians on dialysis has grown by 6% per annum, adding an additional $25 million yearly to healthcare expenditure.1 This growth is caused by both increasing numbers of people entering dialysis programs and a low rate of transplantation because of a shortage of donor kidneys. Kidney availability in Australia remains low and, if anything, is worsening, with only 6.8% of those on dialysis receiving transplants in 2002, compared with 11.7% a decade earlier.1 It is remarkable that Australia has been so slow to fully examine and take up systems that appear to work Dialysis is the only initial treatment option for most patients with endstage kidney failure. Transplantation without prior dialysis is increasingly popular, but requires a live donor available at the right time; currently, only 3% of patients undergoing transplantation have not been on dialysis beforehand. Of those on dialysis, only 23% overall and 39% of those aged under 65 years are on the waiting list for a deceased-donor transplant.2 Those not on the list are either not interested in undergoing transplantation, have medical barriers to safe transplantation, or are deemed too frail to tolerate the procedure and subsequent immunosuppression. Both patients and healthcare professionals believe that transplantation, when feasible, is the preferred therapeutic option. The scientific justification for this belief appears well founded. In particular, there is strong evidence that patients who receive transplants have a significant survival advantage. The annual mortality rate of an age-matched population maintained by transplantation is reduced about 80% beyond the first year compared with those remaining on dialysis on the waiting list.3 The major difference is an up to 30-fold increase in relative risk of cardiovascular events and death experienced by those on long-term dialysis.4 In most Australian states, the average wait for a kidney from a deceased donor is about 4 years, and some patients wait much longer. The prospect of an extended wait on dialysis, as well as the possibility that a suitable kidney may never become available, drives some patients to consider more drastic options. One pathway that is illegal in Australia, but open to those able to afford it, is to travel overseas to purchase a kidney transplant. It is not known how often Australians are choosing this option. The report by Kennedy et al in this issue of the Journal (page 224) describes the outcomes for 16 Sydney-based patients who travelled overseas for kidney transplantation over the past 14 years. The risk of going down this path is evident, with an increased risk of serious infection being a major hazard. The annual rate of deceased-donor kidney transplants in Australia for 2004 was a low 11 donors per million population.5 In 2003, the rate in Australia was 9.0 per million population, compared with 33.8 in Spain, 23.9 in Austria, 24.8 in Belgium, 18.3 in France and 22.1 in the United States. 6 Thus, the rate of organ donation in this country is low compared with other developed countries, and remains so despite the publicity campaign promoting organ donation following the untimely death following a brain injury of Australian cricket icon David Hookes. One response to the shortage in deceased-donor organs has been an increase in live kidney donation, and the proportion of live donations in 2003 was 40% of total transplants. The source of live kidney donors, previously restricted to close blood relatives, has broadened in recent years to allow unrelated and poorly matched emotionally connected donors. In the past 12 months, there have been several kidney transplants from altruistic strangers donating to the pool of waiting dialysis patients (so-called non-directed donations). We can now add overseas commercial sources as another contributor to live kidney donation for Australian residents. The real reasons for Australia’s poor performance in deceased-donor organ procurement have not been fully established. Clearly, there is no lack of public support, which has exceeded 80% in repeated surveys over many years.7 One outstanding observation that has received little prominence and no systematic study is the high and internationally competitive organ donor rate achieved in South Australia. Over the last decade, South Australia has consistently doubled the rate in all other Australian states.5 A similar variation in performance is seen in the teaching hospitals in capital cities, with some having double the rate of others. This marked variation in the donation rates between states and hospitals points to the probability that the barriers to increased organ donation are within the hospital system. The situation in Australia appears ripe for a collaborative approach, such as one reported from the United States that sought to “identify, learn, adapt, replicate and celebrate ‘breakthrough’ practices associated with higher donation rates”.8 It is remarkable that Australia has been so slow to fully examine and take up systems that appear to work in some regions or hospitals. Positive moves are being made. A special working group of the Australian Health Ministers’ Council has recently made 11 recommendations for change in the arrangements and process for organ donation. The most fundamental recommendation is for intensive care staff to routinely interrogate the Australian Organ Donor Registry to ascertain the recorded intent of all suitable patients with severe brain injury after the first set of brain death tests. Relatives will then be informed of the intent recorded on the Registry and be asked only if they are aware of any change. Importantly, in this approach, the family will not need to be asked for consent. If Australia’s organ donation rate could match that of its best-performing hospitals and states, the embarrassing situation driving dialysis patients to take the risks involved with travelling overseas for kidney transplantation would not exist. Much remains to be accomplished, but there are grounds for optimism in believing Australia’s deceased-donor organ donation rate could double if the barriers existing in the hospital system could be removed.

Timothy Mathew FRACP · Randall Faull PhD, FRACP · Paul Snelling FRACP

If Indigenous Australians are at high risk of H. pylori infection, the associated risks of peptic ulceration and gastric cancer may make screening and treatment necessary Interest in asymptomatic Helicobacter pylori infection seems largely to have waned in much of the developed world.1-3 It is almost universally accepted that H. pylori causes chronic gastritis and peptic ulcer disease,1-3 and the evidence that the infection also causes gastric adenocarcinoma is virtually unassailable.1-4 In high-risk populations, at least, prevention of gastric cancer by H. pylori eradication is theoretically feasible, although convincing clinical-trial evidence is lacking.2-5 However, perhaps because the incidence of gastric cancer is steadily declining in developed nations (and because H. pylori infection seems to be much less often acquired these days), interest in its prevention remains remarkably low key.1,2 Australian Aboriginals and Torres Strait Islanders are much more likely to suffer ill health and die at a younger age than non-Indigenous Australians.6 However, one health scourge that the Indigenous population seemed to have missed, despite their lower socioeconomic status, was H. pylori infection and its complications.7 For example, seroprevalence studies suggested H. pylori infection was very rare.7 The report by Windsor and colleagues in this issue of the Journal (page 210) is at variance with these earlier findings,8 and strongly suggests that H. pylori infection is as common in Australia’s Indigenous population as it is in developing countries in South America, Africa and parts of Asia.3 If confirmed, these findings may have major health implications; indeed, the high prevalence identified in children8 implies a public health risk which will continue long into the future unless this situation is rectified. Notably, the findings of Windsor et al are limited to a small and possibly unique Indigenous group, and may not be more widely generalisable — more data are needed. However, the fact that over half the population in the remote rural communities studied were tested gives some confidence that H. pylori is remarkably widespread in this community (where 91% were found to be infected by means of a “gold standard” test). On the other hand, in urban Perth, referral bias can not be ruled out as accounting for the high H. pylori prevalence (60%), although the burden of infection remains strikingly high — if bias is the sole explanation, it would have to be particularly pervasive. What are the potential implications of these findings? Gastric adenocarcinoma remains a major health problem in the developing world.2 In the developed world, the consequences of H. pylori infection have arguably been underappreciated. In the United Kingdom, it has been calculated on the basis of relatively conservative assumptions that by age 85, and allowing for competing causes of mortality, the cumulative risk of dying from gastric cancer arising because of H. pylori infection is a staggering 1 in 51 for men and 1 in 96 for women.9 Data from the Northern Territory suggest that the rate of mortality from gastric cancer among Indigenous people has not increased.10 However, gastric cancer may become a much greater burden for the Indigenous population if, as is hoped, life expectancy improves from the current unacceptable median age at death of just 51 years.6 Older studies have suggested that peptic ulcer is uncommon in the Indigenous population,8 but, if Indigenous people undergo fewer endoscopies, this impression might be driven purely by referral bias. It has been calculated that, in the UK population, 1 in 154 men and 1 in 173 women die from peptic ulcer caused by H. pylori.9 The ulcer rates may, however, be truly low in Indigenous Australians, as undernutrition and lower socioeconomic status are associated with lower gastric acid secretion. This allows H. pylori to spread throughout the stomach (causing pan-gastritis and increasing the risk of cancer if people live long enough), but protects against ulcer disease.2,3 Circulatory disease, particularly ischaemic heart disease, is a major cause of mortality in the Indigenous population.6,10 Is H. pylori an important and modifiable risk factor for ischaemic heart disease? Unfortunately, the evidence for this is mixed and, at best, equivocal.11 Overall, widespread eradication of H. pylori to try to reduce ischaemic heart disease in this population is not currently justifiable. Other health problems in the Indigenous population just might be attributable to H. pylori, at least in part. Indigenous Australians have been reported to be more likely to give birth to infants who are small for gestational age,12 and H. pylori infection has been associated with growth restriction in young children.13 A Sydney study also found (among 448 pregnant women attending for routine examinations in the third trimester) that intrauterine growth restriction was twice as common in H. pylori-seropositive women than in seronegative women.14 This association was not explained by smoking or maternal height, although these were also independent risk factors for intrauterine growth restriction.14 While the data clearly need confirmation, the general health risks of a high carriage rate of H. pylori in Indigenous people may have been underestimated and may be another antenatal risk factor. Might H. pylori offer protection from some other diseases, and, if so, might attempts at its widespread eradication lead to more ill health in the Indigenous population? Such concerns have been raised,15 but seem overexaggerated and unlikely. In particular, recent data suggest that H. pylori eradication in peptic ulcer disease neither provokes reflux oesophagitis nor aggravates symptoms of gastroesophageal reflux.16 We need large, population-based intervention trials to define any risks, but whether it is wise to wait for such results before actively intervening remains debatable. H. pylori may be very common in Indigenous Australians, particularly among those living in remote parts of Australia. Future research needs to focus on the prevalence of H. pylori (and strains of different virulence) and the burden of dyspepsia in these populations. Although the exact route of transmission of H. pylori remains controversial, close contact within families is probably at least one key risk factor, and faecal–oral spread is feasible.2,3 Thus, strong consideration needs to be given to trying to reduce the acquisition of the infection in Indigenous children by reducing family crowding, and providing adequate sanitation and clean water. Doctors need to be aware that there may be a high risk of H. pylori infection in subpopulations within Australia. They should consider testing and treating Indigenous patients who present with dyspepsia (or non-ulcer dyspepsia), have a history of peptic ulcer complications, or have a family history of gastric cancer.2,3,17 However, to reduce the disease burden of H. pylori in the next 50 years, population screening and treatment may be the only solution. Assuming the data of Windsor et al are generalisable, a randomised controlled trial to test the health benefits (and risks) of population-based screening and antibiotic treatment in Indigenous Australians should be a government research-funding priority.

Nicholas J Talley MD, PhD, FRACP

Vaccination programs can act as a paradigm for effective health programs in Indigenous people The inferior health status of Indigenous Australians has been extensively reported1 and is linked inextricably to their ongoing social and economic disadvantage.1,2 Measures to decrease this health inequity are best focused on prevention and primary care as early in life as possible.2 Infectious diseases, although accounting for only a minority of the excess disease burden in Indigenous Australians,1,3 are particularly promoted by features of their disadvantage, such as overcrowding, poor infrastructure for health and hygiene, and poor nutrition. They are also more readily and rapidly targeted for intervention than chronic diseases.3 Vaccine-preventable diseases are particularly amenable to rapid and cost-effective prevention,4 and targeted vaccination programs have been shown to reduce health disparities.5 However, delivery of these programs, like other healthcare interventions, depends on culturally appropriate health services.2 The achievements and opportunities for vaccination programs to reduce morbidity and mortality among Indigenous Australians were highlighted in a recent report from the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS). This provided the first national assessment of the burden of vaccine-preventable diseases and vaccine coverage in Indigenous Australians.6 It showed that universal vaccination programs with highly effective vaccines (eg, measles, mumps, rubella, poliomyelitis, diphtheria and tetanus vaccines) have achieved excellent disease control in Indigenous people, similar to that in non-Indigenous people. Findings are similar in other countries with comparable Indigenous populations.4 In contrast, when vaccination programs are more limited (eg, hepatitis A, hepatitis B, influenza and pneumococcal disease), hospitalisation and death rates continue to be higher for Indigenous Australians than for non-Indigenous Australians.6 The report also showed gaps in vaccination coverage for both children and adults. Children identified as Indigenous had comparable coverage to other children at age 2 years, but lower coverage at age 12 months, suggesting greater delay in receipt of vaccines. Among adults aged 50–64 years (for whom influenza and pneumococcal polysaccharide vaccine have been funded since 1999 for Indigenous people alone), vaccination coverage was higher for Indigenous people than for non-Indigenous people (47% v 26% for influenza vaccine and 20% v 3% for pneumococcal vaccine), but still suboptimal. For both vaccines, Indigenous adults had higher coverage in remote areas than in non-remote areas (75% v 45% and 48% v 19% for influenza and pneumococcal vaccines, respectively). These findings highlight two key issues: the potential for expanded vaccination programs; and the need to improve delivery of current programs, especially in non-remote areas. The value of expanded vaccination programs is compellingly demonstrated by data on hepatitis A and influenza. The recognition of high infection rates and three deaths from hepatitis A in far north Queensland in the 1990s7 led to a regional vaccination program targeting Indigenous children aged under 5 years from 1999. This virtually eradicated hepatitis A in both the Indigenous and non-Indigenous population.8 Similar results after vaccination of high-incidence populations have been documented in the United States and Israel.9 Yet, the NCIRS report documented hepatitis A as an issue for Indigenous Australians outside north Queensland, with national hospitalisation rates 57 times higher in Indigenous children aged under 5 years than in non-Indigenous children the same age.6 This highlights the potential of broader national application of the strategy, which is currently being examined by the Australian Technical Advisory Group on Immunisation. In addition, deaths attributed to influenza and pneumonia are significantly higher in Indigenous Australians.6 Among age groups either not targeted for influenza vaccination (0–4 years), or where only those with risk factors such as chronic cardiac or pulmonary disease are targeted (25–49 years), the respective mortality rates are 17 times and 28 times higher for Indigenous Australians than for non-Indigenous Australians.6 In contrast, among Indigenous adults aged 50 years and over, in whom universal influenza and pneumococcal vaccination is funded, the differential mortality rate is much less (three times higher). This suggests that the vaccination program has had an impact and justifies examining more closely the expansion of universal vaccination of Indigenous people to younger age groups. As to the delivery of current programs, several presentations at the Public Health Association of Australia’s national immunisation conference in 200410 were pertinent. The conjugate pneumococcal vaccine program (introduced in 2001) provided another example of the success of appropriately targeted vaccination programs, reducing for the first time, in 2003, the national incidence of invasive pneumococcal disease in Indigenous children under 2 years of age to the levels in non-Indigenous children.11 This is similar to the impact of such a program in the United States.4 Other conference presentations highlighted the problems of vaccination delivery to Indigenous Australians in general practice. Although general practice is crucial for vaccine delivery in non-remote areas, only 27% of respondents to a national survey of GPs had a routine system for ascertaining whether their patients are Indigenous.12 Yet, Aboriginal and Torres Strait Islander people are happy to be asked about Indigenous status, provided it is done respectfully, and the reasons are explained.13 Improving GPs’ identification of Indigenous status could help increase vaccination rates of Indigenous Australians in general practice, which are lower than those of non-Indigenous Australians,14 and is vital for targeted vaccination. Improving identification is particularly important in non-remote areas, where vaccination coverage of Indigenous people is consistently lower than in remote areas,6 and where the characteristics of successful programs — accurate data on vaccination status, active promotion and outreach services, and effective collaboration across community, health authorities and providers15 — are less likely to be found. Vaccination is a safe, well accepted intervention which offers an opportunity to develop solutions in healthcare delivery that can be applied more generally. Although vaccination programs targeted only to Indigenous Australians will have less impact than universal programs, particularly in urban areas where Indigenous status may not be identified, the higher burden of disease in Indigenous people will continue to make targeting attractive. However, to translate the success shown by regional targeted programs8 to the national level requires substantial investment to improve both data collection (eg, ascertainment of Indigenous status in general practice and completeness of the Australian Childhood Immunisation Register) and service delivery (through culturally appropriate and accessible services). Provision of resources for active program monitoring and coordination equivalent to that found in successful programs in more remote areas is needed.

Peter B McIntyre PhD, FRACP · Robert I Menzies MPH

Despite recent and largely undeserved adverse publicity, mefloquine remains a useful antimalarial Although malaria causes most suffering among children in the tropics, it should not be forgotten that it remains a major cause of military casualties. In September 2003, about 300 US Marines and support staff were deployed to Liberia, West Africa. Of those troops who spent at least one night ashore, 69 contracted falciparum malaria, an attack rate of 44%.1 Forty-four required evacuation for medical care to Europe or the United States. While none died, several developed cerebral malaria and required mechanical ventilation. Malaria was also common among Australian Defence Force (ADF) personnel deployed to East Timor between 1999 and 2000, with 385 cases reported, an attack rate of 5%.2 Eighty-four per cent of these cases were caused by Plasmodium vivax, which, while not life-threatening, causes significant morbidity. Relapse of P. vivax infection, caused by the re-emergence into the bloodstream of parasites lying dormant in the liver (so-called hypnozoites), was a major problem in this group, with 96 relapses reported despite 2 weeks of primaquine therapy.2 This pattern of infection is frequently observed in patients who contract malaria elsewhere in Asia and the Pacific, as reported by Charles and colleagues in this issue of the Journal.3 Nevertheless, effective chemoprophylaxis is readily available for Australian travellers. The challenge for medical practitioners is to select the most appropriate regimen and then to convince patients to use it. Malaria chemoprophylaxis for areas with chloroquine-resistant malaria* (including the Pacific Islands, South-East Asia, the Indian subcontinent, China, Africa and South America)4 Atovaquone + proguanil 250 mg + 100 mg (child > 40 kg and adult) 1 tablet orally, daily (starting 1 to 2 days before entering, and continuing until 7 days after leaving, malarious area) OR Doxycycline (child > 8 years: 2 mg/kg up to) 100 mg orally, daily (starting 2 days before entering, and continuing until 4 weeks after leaving, malarious area) OR Mefloquine (child 15 to 19 kg: tablet; 20 to 30 kg: tablet; 31 to 40 kg: tablet) 250 mg orally, weekly (starting 2 to 3 weeks before entering, and continuing until 4 weeks after leaving, malarious area). * Whatever chemoprophylaxis is prescribed, patients should be counselled that no prophylaxis is 100% effective, and the importance of mosquito avoidance should be emphasised. Mefloquine as chemoprophylaxisMuch has been written (and broadcast) about the neuropsychiatric side effects of mefloquine. While a number of class actions have been instituted, none has as yet reached resolution. Identifying malaria chemoprophylaxis with any confidence as the cause of major psychiatric illness or behavioural disturbance is problematic,5 even more so during or soon after exposure to an extremely stressful military environment. This issue is illustrated by allegations that mefloquine was responsible for fatal assaults committed by Canadian soldiers in Somalia and British soldiers in Sierra Leone, and that it contributed to the killings of spouses by US soldiers recently returned from Iraq. Similarly, it was alleged that psychiatric morbidity among ADF personnel who had been deployed to East Timor was attributable to mefloquine therapy. While it is reassuring that in this issue of the Journal, Kitchener and colleagues report no excess morbidity among ADF personnel taking mefloquine prophylaxis,6 the issue of tolerability of mefloquine is a real one. A double-blind, randomised controlled trial of malaria chemoprophylaxis comparing mefloquine and atovaquone–proguanil (Malarone [GlaxoSmithKline]) found that 139 of 483 (29%) participants taking mefloquine experienced an adverse neuro-psychiatric side effect, most commonly insomnia or strange or vivid dreams.7 Such side effects were reported in 69 of the 493 (14%) participants taking atovaquone–proguanil. The overall frequency of adverse events was similar in the two groups (71% and 67%, respectively), but the events were sufficiently severe to require discontinuation of the drug in 5% of those taking mefloquine versus 1.2% of those taking atovaquone–proguanil. Assessing tolerance to mefloquine before exposure (as undertaken by the ADF) might identify many of those intolerant of this drug, allowing an alternative agent to be selected. Alternative agents for chemoprophylaxisIn Australia, doxycycline is the most widely prescribed drug for malaria chemoprophylaxis. While its side effects are relatively benign (eg, thrush, photosensitivity and oesophagitis), the challenge is to ensure compliance. Numerous studies have demonstrated that adherence to a daily prophylactic regimen is unsatisfactory, especially among those requiring long-term protection.8 Atovaquone–proguanil is highly effective for chemoprophylaxis, but is costly and, like doxycycline, must be taken daily. There has been a resurgence of interest in primaquine as chemoprophylaxis, a drug generally used to prevent relapse of P. vivax. However, it too must be taken daily for prophylaxis and, like many other old “off-patent” orphan drugs, it is inordinately expensive. Tafenoquine, a much-anticipated drug related to primaquine, is now in phase III clinical trials. After three well-tolerated loading doses, a single monthly dose appears protective.9 However, like primaquine, it can cause severe haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Thus, it is necessary to screen for this condition before beginning the drug. New agents for treating malariaAs Davis and colleagues discuss in this issue, artesunate is a highly effective and well tolerated antimalarial agent.10 It belongs to the artemesinin class of drugs derived from the Chinese wormwood plant qinghaosu, and is taken by many expatriates as “emergency standby treatment” at the first sign of fever (unpublished observation). While this practice is effective, particularly when combined with appropriate diagnostic tests, such as the rapid antigen test used in the case reported in this issue by Howden and colleagues,11 it is not without risk. The very short half-life of the active metabolite, dihydroartemesinin, means that any parasites remaining in the blood after a short course of therapy may not be cleared, leading to recurrent parasitaemia.10 Suitable drugs to combine with artesunate include mefloquine, doxycycline (if taken for one week), or, in the few regions where these drugs remain effective, combined pyrimethamine and sulfadoxine.10 Further risks of relying on emergency standby treatment alone include failing to recognise non-classical symptoms of malaria (such as diarrhoea), and exhausting drug supplies through premature self-medication for non-malarial illnesses. Of note, counterfeit artesunate is offered for sale in several Asian countries where pharmaceuticals are unregulated; the only artemisinin derivative available in Australia is artemether in combination with lumefantrine.10 A malaria vaccineAn effective malaria vaccine suitable for non-immune soldiers, travellers and the even larger population of residents of malaria-endemic countries remains a priority. The long-standing search for a vaccine has been invigorated by the creation of the Malaria Vaccine Initiative, a public–private partnership supported by the Bill and Melinda Gates Foundation. The recently published phase II malaria vaccine trial in Mozambique involving this initiative and GlaxoSmithKline Biologicals is an example of the productivity of this partnership.12 While the vaccine produced a statistically significant level of protection (29.9% to 57.7%), it is likely that, for now, doctors will continue to advise mosquito avoidance and to reach for the prescription pad rather than the vaccine refrigerator when preparing patients for trips to malarious areas.

James S McCarthy FRACP, MD

What is the evidence? Venous thrombosis and pulmonary embolism continue to be significant complications of hip or knee replacement surgery. Seven to 10 days of anticoagulant prophylaxis starting before or soon after surgery fail to prevent 20%–30% of venous thromboembolic events. It is this residual thrombosis rate that provides a spur for adding pre-discharge screening to routine prophylaxis, with the aim of detecting and treating silent thrombosis before it progresses to clinical disease. In this issue of the Journal, O’Reilly and colleagues (page 154) report on routine venous ultrasound examination performed on almost 6000 patients before discharge from hospital 6–7 days after major joint surgery. Within this large cohort, subclinical deep vein thrombosis (DVT) was detected in 9%, 26% and 37% of patients after hip, knee or bilateral knee replacement, respectively. This was despite intensive in-hospital prophylaxis using an anticoagulant (mostly low-molecular-weight heparin) plus intermittent calf compression and the use of elastic stockings. Thrombosis was proximal (affecting the popliteal, femoral or iliac veins) in 1.5%, 1.3% and 1.1% of patients after hip, knee or bilateral knee replacement, respectively. When considering how best to use this information, we should ask several questions. First, is ultrasonography reliable for detecting subclinical DVT? Although it is preferred for investigating clinically suspected disease, opinions are divided about its value in screening for subclinical thrombi, which are often no more than a few centimetres long. Ultrasonography is observer-dependent, and screening by this method has not been validated through large, blinded comparisons with the “gold standard” of bilateral venography. However, an excellent systematic overview of ultrasonography2 has reported a positive predictive value for subclinical proximal DVT of over 80% if disease prevalence is low and the false positive rate is no more than 5% (results with calf DVT were less impressive). So the 1%–1.5% proximal DVT rate reported by O’Reilly et al is probably valid. Second, are the DVT rates seen by O’Reilly et al consistent with previously reported results of routine venography? The answer is yes. Overall DVT rates 5–10 days after hip replacement in people given warfarin, low-molecular-weight heparin, fondaparinux (a specific inhibitor of activated factor X) or ximelagatran (an oral thrombin inhibitor) have been shown to be about 20%, 10%, 4%, and 8%, respectively, while proximal DVT rates are about 5%, 2%, 1.5%, and 3%, respectively.3, Reported rates of DVT after knee replacement are also consistent.3, If anything, the rate of proximal DVT found by O’Reilly et al is on the low side, perhaps because they combined chemical with physical prophylaxis and/or because ultrasound examination is less sensitive for detecting proximal DVT than is venography. Third, does ultrasonographic screening at discharge bring any clinical benefit? We just do not know. Logic suggests it should, but attempts to validate the value of pre-discharge screening by randomised trials have failed. Perhaps the trials were underpowered to detect real but small reductions in rates of venous thromboembolism. Or perhaps it is a wrong assumption that new thrombus formation is not a problem once patients leave hospital. We now know that thrombosis risk after major joint (especially hip) surgery persists for at least 4–6 weeks and that duration of prophylaxis is a major determinant of success. The rates of venous thromboembolism (subclinical, symptomatic and confirmed) in randomised comparisons are substantially reduced by persisting with preventive therapy until 4–5 weeks after a hip fracture or hip replacement rather than stopping (as in the study by O’Reilly et al) when patients are discharged from hospital.3,5,6 Hence, the recent recommendation by the American College of Chest Physicians (ACCP) for at least 10 days’ prophylaxis after major joint surgery, extending to 28–35 days after hip arthroplasty or hip fracture.3 The obvious explanation for reduced rates of venous thromboembolism is suppression of late thrombus formation. More intriguing is the apparent resolution of small venous thrombi formed soon after surgery — an effect best seen in one of the fondaparinux trials (the “PENTHIFRA-Plus” trial),5 in which the venographically detected thrombosis rate with ongoing prophylaxis was negligible (1.4%) 4 weeks after hip fracture surgery and well below the 8.3% rate previously found after 7 days of preventive therapy.6 (The latter rate is similar to the 9% DVT rate observed by O’Reilly et al after 1 week of intense prophylaxis.) By contrast, the thrombosis rate after 4 weeks among PENTHIFRA-Plus trial patients given a placebo following 1 week of fondaparinux therapy was 35%,5 a figure much higher than the 8.3% observed after 7 days in the earlier trial.6 The high DVT rates observed by O’Reilly et al confirm that in-hospital prophylaxis alone is not enough. Many would argue that extended prophylaxis is likely to be the simplest, cheapest and perhaps safest solution. Even if pre-discharge screening for subclinical disease might pre-empt the need for continued prophylaxis, there remain significant questions of resource availability, cost and possible harm. Ultrasound examination alone, if done in all patients and followed by further testing in the 9% or 26% of patients with thrombosis after unilateral hip or knee surgery, would cost (at current Medicare Benefits Schedule rates) about $200 000 per 1000 patients. The approach of O’Reilly et al was to treat all clots, regardless of their extent or position, with full doses of an anticoagulant for at least 2 weeks. This includes silent clots in the soleus or gastrocnemius muscle veins whose natural history is uncertain and perhaps mostly benign.7 But any decision to use anticoagulant therapy must balance potential benefit with likely bleeding risk. In this case, both remain unknowns, as the authors do not report on treatment complications. Evidence-based recommendations by expert groups are not prescriptions, and require judgement when applied to clinical practice. Even so, we should note the recent, firm (Grade 1A) recommendation by the 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy3 against routine screening for DVT after major joint surgery, based on the lack of any demonstrable clinical effectiveness or cost-effectiveness of such screening.

Alexander S Gallus MB BS, FRCPA FRACP

Congenital heart disease is often regarded as a chance occurrence affecting only a small number of children. In fact, it affects nearly 1 in 100 newborn infants1,2 and is the leading non-infectious cause of death in this age group. A third of those affected will need surgical or catheter-based intervention in the first year of life. In 2002, congenital heart disease accounted for 224 deaths in Australian children.2 In the United States there are more than 35 000 new cases each year and over 1 million survivors of congenital heart disease in the community.3 Studies of gene expression in animal models have provided a window into how the human heart is constructed . . . Diagnosis and treatment of congenital heart disease has improved dramatically over the past 15 years. The mortality rate for surgical repair of some common conditions, such as tetralogy of Fallot, is currently less than 3%,4 and innovative catheter-based therapies, including closure of certain septal defects, have been developed. Preservation of ventricular function, avoidance of repeat surgery and freedom from arrhythmias are the next goals to be achieved. The first question affected families usually ask is: “What is the risk of having an affected offspring or another affected sibling?”. Population studies suggest that the risk is relatively small (2%, or double the background risk). The reason the risk is relatively modest may be that most congenital heart disease is the result of multiple gene defects and/or an interaction between single or multiple defective genes and the fetal environment. As the genotype and experience of each individual is unique, the occurrence of congenital heart disease in most individuals will not be in the context of a strong familial trait. However, there are many rare examples of families in which congenital heart disease is strongly inherited, and apparently caused by single-gene defects. Even in these families, cardiologic phenotypes can vary enormously, presumably because of the effects of modifier genes and/or influences other than genetic. Such families, if large enough, can be studied using classical genetic techniques (such as linkage analysis), but so far only a small number of clinical cases can be matched to a specific mutation. Thus, family genetic studies are currently not indicated for isolated, non-syndromal cases of congenital heart disease. With the advent of high-throughput genetic screening technology and improved cost benefit, indications for screening may be extended in the future. Recently, cardiac developmental and molecular biologists and geneticists have started to unravel the molecular circuitry underpinning heart formation. Significant progress has come about partly because we can now dissect the morphological and genetic basis of human congenital heart disease in animal models from zebra fish to mice. Aspects of cardiac development are, in fact, highly conserved through evolution, and many of the regulators that transform embryonic mesoderm to myocardium are similar across species. One example is the cardiac regulatory gene NKX2.5, which was first isolated because of its similarity to a gene present in the fruit fly, a laboratory model for genetic studies. The developmental approach has defined a number of key cardiac regulatory genes subsequently found by conventional linkage studies to underpin familial congenital heart disease.5 Mutations in NKX2.5 itself cause atrial septal defect and conduction abnormalities, while TBX5 mutations underpin heart and hand malformations of the Holt–Oram syndrome, and mutations in GATA4 cause atrial septal defect and more complex congenital heart disease. In clear cases of familial inheritance, genetic screening for mutations in these genes may be beneficial. Studies of gene expression in animal models have provided a window into how the human heart is constructed, and recent insights have led to a revision of traditional concepts of how cardiac chambers and valves develop. The heart begins as a rudimentary vascular tube,6 which, cardiologists are taught, is composed of anatomical segments that develop into chambers. Yet mapping of the cardiac precursor cell populations in the embryo has revealed a more complex picture. Gene expression patterns now show us that chambers arise from discrete zones, not segments, and that non-chamber myocardium gives rise to the central conduction system.7,8 Another significant advance is the discovery of a second distinct pool of cardiac precursor cells in the embryo that migrate into the forming heart tube from the region of the developing pharyngeal arches. These cells, the so-called “secondary heart field”, contribute importantly to the right ventricle, outflow tracts and atria.9 Characterisation of the secondary heart field has unified genetic, developmental and clinical observations in congenital heart disease. Abnormal development and/or deployment of the secondary heart field cells causes underdevelopment and malpositioning of the outflow tracts over the ventricles. This occurs in velocardiofacial syndrome (VCFS, incorporating DiGeorge syndrome), which is caused by microdeletions in chromosome 22q11.10 The TBX1 transcription factor gene is expressed in the secondary heart field and is deleted in VCFS. Its loss in mice has been causally related to abnormalities of the outflow tract that can arise in VCFS. One such abnormality is tetralogy of Fallot, in which unequal partitioning of the rudimentary outflow vessel produces a large aorta and a right ventricular outflow tract obstruction, with subsequent complications. Malalignment of the outflow vessels over the interventricular septum causes a large ventricular septal defect. Although fewer than a third of cases of tetralogy of Fallot are associated with the 22q11 microdeletion, single-gene mutations may prove to be a significant cause. In the case of interrupted aortic arch type B and truncus arteriosus, however, more than 50% of cases are associated with the 22q11 microdeletion. Recent developments in genome-wide screening technology have the power to detect microdeletions in individual patients on an unprecedented scale. This may revolutionise the detection of congenital heart disease genes. Pathological circumstances also provide deep insights into development. In the fetus, even simple primary structural disease (eg, a pulmonary valve that fails to develop) can cause complex secondary disorders as a result of disturbed blood-flow patterns. In heart development, function (flow) dictates form, and loss of normal blood-flow patterns can contribute to underdevelopment of chambers. In these circumstances, it is often difficult to predict from primary lesions the extent to which abnormal development and remodelling will occur as the fetus grows — this is one of the challenges of fetal echocardiography. Now, surgical correction during fetal life, long taboo, is being explored experimentally for valve correction,11 as this would allow more time for normal ventricular development. While only a small proportion of congenital heart lesions currently have identifiable gene markers, the number is growing rapidly. The next decade of research into congenital heart disease will see an exciting convergence of the disciplines of developmental biology, genetics and paediatric cardiology, and, we hope, will not only go further towards answering the question “Why did this happen to us?”, but also provide more secure grounds for genetic counselling and intervention.

David S Winlaw MB BS, MD, FRACS · Gary F Sholler MB BS, FRACP · Richard P Harvey PhD

We need restrictions on night driving and peer passenger numbers for novice drivers Road trauma remains one of the leading causes of death for young Australians.1 Of particular concern is the fact that more than a quarter of all fatal road injuries (27%) and hospitalisations (26%) are in the age group 17 to 25 years,2 and yet this age group comprises only 15% of licensed drivers.3 As well, despite continued funding and the implementation of effective road safety strategies, road fatalities in this age group have remained relatively constant since 1998. To achieve the national road safety strategy target of reducing the population-based road fatality rate by 40% (from 9.3 to 5.6 per 100 000) by 2010,4 various road safety strategies must receive priority. These include greater investment in the road infrastructure and adoption of further standards for motor vehicle safety, as well as enhancements to existing programs such as speed management and random breath testing. Importantly, implementation of promising new road safety initiatives that target the over-representation of newly licensed young drivers in the road crash statistics is necessary. Newly licensed or novice drivers are at increased risk of crashing, especially in the first months of licensing, with a recent study finding 14% of young drivers crash within the first 12 months of driving.5 The risk remains whether the drivers are licensed at 16 years of age (as in many states of the United States6) or at age 17 or 18 years (as in Australia7). The disproportionately high number of newly licensed drivers in the crash statistics has been attributed to factors such as inexperience, an inability to identify hazards, night-time driving, carrying same-age or peer passengers, and risky driving behaviour such as speeding.8,9 A response that has achieved some success in reducing the disproportionate number of crashes of young drivers has been the introduction of graduated licensing systems throughout Australia. The aim of graduated licensing systems is to moderate the effect of risk taking and inexperience, and thereby reduce a young driver’s risk of crashing and the concomitant risk of trauma to the passengers of young drivers and associated third parties. Graduated licensing can be described as a process whereby novice drivers begin their driving careers with significant restrictions, which are removed in stages depending on driving experience or successful test results. An elementary graduated licensing system exists in all Australian states and territories — Learner drivers are required to drive only under the supervision of an experienced driver, and Probationary/Provisional drivers have significant restrictions placed on blood alcohol content and, in some states, maximum speed. Integral to the effectiveness of the graduated licensing system is late night driving and peer passenger restrictions during the early probationary period of licensing. To date, no Australian jurisdiction has incorporated these restrictions into the system, although, in the first half of 2005, NSW will introduce passenger restrictions for provisional drivers who have previously lost their licence.10 Graduated licensing systems that include the three stages and the late night and peer passenger restrictions have shown significant reductions in fatal and injurious crashes involving young drivers. In New Zealand, where the licensing system has included these restrictions, reductions of between 7% and 23% in serious injury have been observed.11 Importantly, evaluations of graduated licensing systems that include late night driving restrictions have shown crash reductions of up to 60% during the late night hours.6 Discussions surrounding whether late night and peer passenger restrictions should be introduced in Australia have met with a number of objections: law enforcement officials perceive the restrictions would be difficult to enforce; politicians perceive a potential backlash from constituents; and young drivers (particularly rural drivers) believe the restrictions would place an undue burden on them given the absence of alternative transport. Despite these concerns, studies in countries that have implemented the restrictions have reported overwhelming support. For example, enforcement appears not to be onerous, as many parents play a significant role in policing the restrictions.12 With reductions in road trauma due, in part, to the comprehensive graduated licensing system, politicians in these countries have seen support rather than retribution. Finally, and most significantly, feedback from young rural drivers in the United States following the introduction of restrictions shows overwhelming support — young rural drivers either strongly agreed (10%) or agreed (53%) with the restrictions.13 A road safety policy that attempts to identify at-risk young drivers and to impose restrictions only on those drivers is unlikely to succeed, because there is no reliable screening test for at-risk drivers. Identifying at-risk young drivers on the basis of prior traffic violations (as proposed by the NSW government10) would not be useful, as most fatally injured young drivers have no prior traffic violations.6 Instead, a whole-population approach such as graduated licensing, which targets all newly licensed drivers, is likely to achieve reductions in young driver fatalities and serious injury. Of importance, however, is the unequivocal evidence that graduated licensing systems that incorporate late night and peer passenger restrictions reduce road fatalities and serious injury and convey a benefit to cost ratio of 74 to 1.6 It is evident that our current graduated licensing systems have been steering young drivers in the right direction. However, until night driving and peer passenger restrictions are incorporated into the graduated licensing system throughout Australia, it is unlikely that the national road safety strategy target for 2010 — to reduce the road fatality rate by 40% — will be achieved.

Mark R Stevenson PhD, MPH

Considering the clinical implications of new research data on migraine and brain lesions Migraine has received considerable attention in the past 15 years as it has come to be better understood as a brain disorder with new and efficient treatment strategies.1 The World Health Organization considers a day with severe migraine to be in the highest category of disability, comparable to quadriplegia.2 Migraine is classically described and defined as an episodic disturbance manifest primarily as head pain and sensitivity to afferent stimuli, such as light (photophobia), sound (phonophobia) and head movement.3 Against this background, new data have emerged that open the issue of whether migraine may be progressive in some way. Kruit and colleagues recently published a cross-sectional, population-based study of Dutch adults aged 30–60 years. They compared the prevalence of brain infarctions and white-matter lesions between people with migraine and control subjects matched for age, sex, place of residence and potential risk factors for cerebrovascular disease.4 Overall, there was no difference between people with migraine and controls in prevalence of infarction. There was an increase in posterior circulation lesions in patients with migraine with aura, and more deep white-matter lesions in women with migraine. The authors concluded that some patients with migraine are at increased risk for subclinical lesions in certain brain areas. These data come at a time when others have suggested a link between migraine and right-to-left cardiac shunts5 (which may predispose to stroke), and when there are known risks for stroke in women under 35 years with migraine.6 It has been suggested that these data may mark migraine as a progressive, rather than simply episodic, disorder.7 This is not a trivial question for migraineurs or their physicians. A progressive disorder is one where there is a continuous increase in severity or extent (Oxford English Dictionary). This may relate to symptoms or some objective measure, such as brain imaging. Migraine certainly does not, in general terms, increase in severity with time, as the natural history is to abate and disappear in later life.8 So, with very few exceptions, it could not be called progressive on the basis of increasing severity with time. This does not negate the fact that some migraine sufferers go through enormously disabling periods of frequent attacks — chronic migraine. 9 This smaller group10 needs attention, but progression should not be ascribed to the vast majority of sufferers. Whether migraine causes permanent, progressive brain lesions is also not established. The relationship between migraine and cardiac right-to-left shunts is at best cloudy. These shunts may arise from a patent foramen ovale (found in about a quarter of the population), atrial septal defects and arteriovenous malformations; they have been implicated in stroke and decompression illness as a result of paradoxical embolism. However, studies of the association with migraine were not population-based, and case definitions were very poor, mixing migraine with aura with isolated aura. The latter makes it impossible to be sure whether the events described were migrainous or ischaemic in nature. Stroke risk is certainly increased for women under 35 with migraine with aura, but the increase is small, and one wonders if this highlights a prothrombotic or vasculopathic comorbidity in a particular subset, rather than a general pathophysiological principle for all patients. The new study by Kruit and colleagues4 gives pause for thought, but, as it is cross-sectional, it provides a hypothesis, not proof. It certainly does not provide evidence that lesions in the brain produce chronic migraine. Only a longitudinal study would give information on accumulation of lesion load that would provide evidence for a progressive course. While the authors of a recent meta-analysis of observational studies of ischaemic stroke risk in migraine conclude that there is an association,11 their review, unfortunately, adds nothing to our understanding. Most studies show an association, and half of the 14 studies in the meta-analysis did not divide their patients with migraine into those with and without aura. Thus, the really interesting possibility suggested by Kruit and colleagues4 of patients with migraine with aura being at increased risk of subclinical brain lesions could not be explored. What are the clinical implications of the new data? First, we can assure patients with migraine without aura that there seems little risk of any progressive or serious problem in terms of brain lesions. Unfortunately, we can also assure them that they will suffer, losing time from work and their personal life, year on year, unless we can help them manage their attacks properly by appropriate advice and use of acute attack and preventive medicines. For patients with migraine with aura, I explain that the risk of stroke is small. Indeed, it is smaller, even for those taking oral contraceptives, than the risk of stroke during pregnancy itself. The available data do not, in my view, justify antiplatelet agents in patients with migraine with aura, nor do they provide intellectual justification for paternalistic limitations on patient choice in, for example, contraceptive use. As a rule, I investigate the unusual: one might target those with prolonged aura (ie, over an hour3) with standard stroke investigations. Migraine is a horrible, disabling, biologically determined, inherited brain disorder rendering life much less tolerable, but for the moment there is no sustainable position that it is progressive for most patients. We can look forward to new data with which to qualify and quantify the issue.

Peter J Goadsby MD, PhD, DSc FRACP, FRCP

A national rollout of faecal occult-blood screening, federally funded, is the best approach Bowel cancer is Australia’s commonest internal cancer.1 There is indisputable evidence that population screening with faecal occult-blood testing (FOBT), allowing early detection of cancer and detection and removal of the precursor adenomatous polyp, could save close to 2000 lives each year.2 The federal government is to be commended on its orderly approach to the issue through the Bowel Cancer Screening Pilot Programme (www.cancerscreening.gov.au/bowel/). It is important that this commitment to colorectal cancer screening continues, given also its clear cost-effectiveness.3-6 But who pays? There is no Medicare rebate for almost all screening in Australia, and definitely not for bowel cancer. But what about other methods of screening? Arguments centre on whether we need evidence from meta-analyses of multiple randomised-controlled trials (RCTs) of screening showing mortality reduction before recommending a particular method, or whether less rigorous proof will suffice. Colonoscopy has the highest level of sensitivity and specificity for detection of colorectal neoplasia, but there are no RCTs of screening using colonoscopy, let alone any meta-analyses. Because the FOBT trials have shown a link between a favourable shift in staging and mortality reduction in populations invited to participate in screening, the standard of proof for considering any screening program to be effective can now be the less stringent demonstration of a favourable shift in staging compared with controls. But, without controlled trials, even that information is unavailable for colonoscopy. Colonoscopy is not without risk, with rates of postpolypectomy transfusion requirement, perforation and death being 1 : 500, 1 : 1000, and 1 : 10 000, respectively.7 These complication figures may be too high when applied to the more robust screening population, but they nevertheless underpin the need to be careful before advocating an invasive screening procedure for a healthy population. Flexible sigmoidoscopy is another option, supported by level III evidence and some cost-effectiveness calculations. Controlled trials of flexible sigmoidoscopy are ongoing. So what about computed tomography (CT) colonography (virtual colonoscopy)? Great expectations have been generated by the lack of need for sedation, a low complication rate, short examination time, safety (apart from radiation8), and potential (not yet actual) avoidance of the need for bowel preparation. In the best centres, the sensitivity and specificity for neoplasia detection is equal to conventional colonoscopy, and it is cheaper.9,10 However, once it is positioned beyond its dedicated pioneers, the performance becomes less certain.11 The Royal Australian and New Zealand College of Radiologists has reservations about its widespread implementation for screening (Clinical Associate Professor Richard Mendelson, Colorectal Cancer Reference Group Member, RANZCR, personal communication). For best results, the hardware needs to be advanced (eg, 16-detector spiral scanners), the software optimised (providing three-dimensional endoluminal “fly through” views), scans obtained in supine and prone position, and the radiologists skilled and experienced.12 Conventional colonoscopy is needed to confirm and remove detected lesions (in an Australian study, 27% of participants needed colonoscopy13). Managing the small polyps found by CT colonography, which many would consider an incidental finding of minimal risk, inflates the necessity for colonoscopy both immediately and at follow-up. The chance that two bowel preparations will be required is unpalatable, partly explaining the lack of preference for virtual over actual colonoscopy.14 Having both procedures after one bowel preparation is possible but difficult to organise. Finally, there is not level I, II or even III evidence for cancer mortality reduction or stage shift with CT colonography. Determining an individual’s best screening strategy involves assessing familial and personal risk factors, and age-specific risk for colorectal cancer for the 5- to 10-year period over which colonoscopy affords protection against the risks of screening. FOBT is advocated in average-risk people aged 50–75 years, based on RCT evidence, validating taxpayer funding. Whether the uncertainty (with respect to risks versus benefits) of more invasive screening is acceptable becomes an individual choice. The “What would you do, Doc?” question, which is often personality rather than evidence driven, may tip the balance. In the United States, colorectal cancer screening guidelines emphasise “choice”15 — “Just do something”. Participation in population screening is very important, but whether offering “choice” improves rather than paralyses participation is uncertain. But who pays? There is no Medicare rebate for almost all screening in Australia, and definitely not for bowel cancer. Indeed, the Medicare-rebatable FOBT strategy is inappropriate for screening for colorectal cancer. It specifies a guaiac and an immunochemical test, a combination that has unknown performance characteristics in screening. For average-risk people, there is certainly no Medicare rebate for any of the more invasive endoscopic or CT screening techniques. All this information needs to be considered in the informed-consent process. So what would you do, Doc? A well organised (rather than once-only) screening program is important. A national rollout of faecal occult blood screening, federally funded, is the commendable approach being tested in the pilot program. But beyond or outside that? I would choose one of the two tests (Bayer “Magstream” or Enterix “!nform”) used in the national pilot program — both have adequate performance characteristics for bowel cancer screening — favouring perhaps the Australian “!nform” test because of its associated program of implementation, and ready applicability in general practice.16 Virtual colonoscopy? Not yet, and certainly not until I have identified a neighbourhood CT facility with performance characteristics equal to the best published to date.8 Self-funded colonoscopy? No, and certainly not before my risk for colorectal cancer death over 5–10 years overtakes my risk of serious complications from colonoscopy by an order of magnitude — that is, at age 55–60 years.2 And, for any colonoscopy required in the screening pathway, I would choose a colonoscopist with a good performance “score card” and a licensed centre.

Finlay A Macrae MD, FRACP, FRCP

The medical community has important roles in reducing harm from alcohol and other drugs A contemporary vision of how to prevent harmful alcohol and drug use is emerging, at a time when a new approach is vitally needed. In 1998 (the most recent year for which mortality data on all recreational substances are available), substance use killed some 23 000 Australians.1 Licit drug use accounted for 96% of these deaths, with tobacco the leading cause. In the same year, drug use cost the Australian community $34.7 billion, representing almost 2% of GDP for alcohol, 1.71% for tobacco and 1.76% for illicit drugs.2 Rates of tobacco and alcohol use have increased over the past decade among adolescents and young adults. Although the problem is of large scale,3 there have been major recent advances in the understanding of how to prevent much harmful drug use. One such advance is the “developmental pathways” approach, emphasised in Australian mental health4 and crime prevention5 strategies. This approach draws on life-course development research, community epidemiology and preventive intervention trials.6,7 Studies have demonstrated that from early in life similar developmental, social-risk and protective factors lead to a range of problem and risk behaviours in adolescence and young adulthood, including problematic substance use.8 Attention to these underlying factors is an essential element in preventing problematic substance use. Hence, we need to consider how these forms of prevention can be integrated into Australia’s existing harm-minimisation framework. Recent evidence also warrants an increased acknowledgement of the significant and influential role regulation and legislation play in prevention,9 including the symbolic role of law in reinforcing social norms against harmful drug use.10 The challenge is to integrate this new knowledge while accepting that there have also been clear advances through the use of harm-reduction strategies for people who are unable or unwilling to abstain from risky drug use .11 In recognition of the need for these different approaches to prevention to be integrated into national drug policy, the Australian Department of Health and Ageing commissioned a major review of Australian and international literature. The review was recently published as a monograph, The prevention of substance use, risk and harm in Australia.12,13 As part of the focus of integrating different prevention approaches, 159 preventive interventions were reviewed. The highest level of evidence for effectiveness was found for eight interventions (Box). What can the medical profession do to assist?Interventions for families and adolescentsA number of effective interventions for families and adolescents are implemented predominantly by healthcare professionals: Antenatal and postnatal home visiting by nurses to support high-risk parents in effectively meeting the child’s basic needs and to encourage healthy bonding; Early identification of fetuses or infants at risk of manifesting the effects of drug exposure, including early intervention to encourage reduction of harmful maternal drug use, particularly smoking; Child development support for families with problems associated with alcohol and drug use; Assistance for parents and families in developing skills and gaining support to enhance healthy child development and prevent substance use beginning at an early age or occurring regularly during adolescence; Identification of training and evaluation strategies to improve the preventive screening and health promotion offered to adolescents by primary healthcare professionals. Interventions within the general communityAs well as specific medical interventions, the medical profession plays an important role in supporting the development of evidence-based alcohol and other drug policy.14,15 Evidence attests to the value of interventions in the general community which prevent the sale of tobacco to minors,16 encourage responsible alcohol marketing and distribution,17 integrate treatment and harm reduction services18 and reduce the availability of illicit drugs.19 Behavioural risk factors for a variety of health issues can be managed in general practice using initiatives such the Smoking, Nutrition, Alcohol and Physical activity (SNAP) Framework to address cardiovascular health.20 Brief interventions by general practitioners appear effective for reducing both smoking and early-stage alcohol problems.21 Despite this, GP uptake of brief interventions has been poor, and many GPs fail to detect individuals at risk of developing alcohol and other drug problems.22 Professional support for GPs can improve rates of screening and brief interventions. Practice nurses should also be considered as alternative service delivery agents.22 There is a solid research base to show that treatment for a range of drug and alcohol problems is effective and can improve mental and physical health and social functioning. Treatment is an essential aspect of prevention, having population-level effects on levels of crime and disorder. Treatment of families minimises the intergenerational transmission of substance-use problems. However, most treatment programs engage only a small proportion of the people with drug and alcohol dependence. Including advice from a GP, only one in three people with an alcohol problem will receive any kind of treatment from a healthcare professional in a 12-month period.23 ConclusionAn integrated vision of prevention brings together action from many areas, including health, with a common goal of creating healthy social environments. Healthcare providers play a critical role and are encouraged to see the provision of services to drug- and alcohol-dependent individuals as a core responsibility.24,25 The evidence supports an increase in the capacity of mainstream healthcare providers to provide brief and early interventions and treatment. Further funding for drug-dependency services, training for healthcare practitioners in managing drug-dependent patients, improved access for GPs to specialist support, and the recognition of medical practice in the drug-dependency field as a legitimate medical specialty have all been recommended.24 GPs are ideally placed to identify children at risk of developing psychosocial problems because of their family backgrounds, particularly where adults and children present with problems associated with substance use by parents. Early identification of these children and appropriate treatment or referral of both the child and the parent may help to prevent the intergenerational transfer of alcohol and drug problems within families. Finally, advocacy by the medical and healthcare professions for effective non-medical interventions such as taxation, law enforcement and harm reduction is vital to ensure their wider and more effective application. Eight interventions with the highest level of evidence to prevent harms associated with substance use Tobacco taxation to create and maintain price disincentives Enforcement of environmental tobacco smoke regulations Alcohol taxation based on alcohol content of drinks Random breath testing of drivers Brief interventions by primary healthcare providers in relation to alcohol and tobacco use* Treatment for dependent alcohol and other drug use* Needle and syringe distribution programs Hepatitis B vaccination* * There is a role for the medical profession in these three interventions.

Wendy M Loxley BA(Hons), M.Psych, PhD · John W Toumbourou BA(Hons), MA, PhD · Timothy R Stockwell MA(Oxon), MSc, PhD

Robust safety specifications and funding arrangements are needed A recent review of the safety of helicopter emergency medical services (HEMS) in the United States found that the risk of death for a HEMS crewmember (per hour engaged in the activity) was similar to that of rock climbers and skydivers.1 The study on the accident and fatality rate of HEMS by Holland and Cooksley (page 17) in this issue of the Journal2 is a timely reminder of the risks faced by HEMS crew in Australia. . . . at least one Australian state government is yet to conduct any independent audits of its contracted HEMS operators . . . Aviation safety, like patient safety, is a complex interaction of systems, human factors and technology. Many of the lessons learned in aviation in improving safety and management of risk, such as incident reporting, crew resource management and simulator training, have crossed over into medical practice. The underlying issues affecting safety are similar, and are frequently unrelated to operator error. Investigation of major incidents and accidents worldwide, in industries such as transport, mining, and indeed health, has revealed many common contributing factors identified as “latent conditions”, or failures of the system.3 These include the lack of a positive safety culture through poor governance, limited resources or misallocation of resources. Blame for accidents often lies with operator error, or active failures (slips, lapses and mistakes — errors at the level of the frontline operator), but it is the mitigation of latent failures that is likely to have the biggest impact on safety. HEMS in Australia operate in a risky environment for flight crew, medical crew and patients alike, for several reasons. First, HEMS in Australia are generally required to fulfil multiple roles, performing critical care interhospital transfer, land-on-scene response, hoist operations and search and rescue (SAR). In North America and Europe, there is generally a distinction between hoist and SAR operators and those who undertake interhospital transfers and land-on-scene response. Second, Australian HEMS operations are further complicated by the vast distances and the predominantly hot conditions, which challenge both aircraft and crew performance. All incidents with injuries or fatalities reported by Holland and Cooksley2 were flights conducted in helicopters without sufficient instrumentation for flight in cloud. Under the current regulatory requirements, flight in such aircraft over water or in rural areas at night is acceptable but is not viewed as best practice. Aircraft not equipped to fly in cloud have much lower acquisition costs than aircraft that are so equipped. Crew training and experience levels are also substantially less. Such aircraft continue to be used for HEMS in Australia, operating with minimal safety margins, as a result of inadequate funding arrangements. In Australia, the Civil Aviation Safety Authority (CASA) certifies aircraft operators to provide specified levels of service. However, CASA certification does not necessarily mean a safe operator, any more than accreditation by the Australian Council on Health Care Standards means a safe hospital. Furthermore, the supervision provided by CASA varies with the category of operation. HEMS is situated at the lower end of the oversight spectrum by virtue of the category of operations in which CASA has placed it, resulting in a level of scrutiny that, given the complexity and risk involved, is lower than perhaps required. Recategorisation of HEMS into a higher category requiring higher standards of compliance, and hence scrutiny by CASA, is probably appropriate. However, effecting regulatory change is a slow process. Given the low level of regulator scrutiny in some categories of aviation operations, the industry has recognised a need to enforce its own standards by commissioning aviation safety experts to conduct independent safety audits. For example, in high-risk areas, such as the off-shore oil industry, oil companies conduct independent safety audits of contracted helicopter operators as frequently as every couple of months. Although HEMS carry greater risk than off-shore oil work, at least one Australian state government is yet to conduct any independent audits of its contracted HEMS operators, despite this being a requirement of contract. Recent accidents in Australia2 have highlighted latent factors, such as equipment and crewing issues. However, to operate the equipment specified by either regulations or contracts, operators will only put in place systems they can afford. Maintaining the high standards mandated by this complex operating environment requires that health systems work in partnership with HEMS providers to ensure robust contract and auditing processes. This does not come without cost, and adequate funding of HEMS needs to be accepted and achieved. Cost cutting to ensure financial survival compromises the safety systems that HEMS operators endeavour to put in place. These are designed to mitigate error, and include hazard and incident reporting, training and education, audit programs, and safety officer appointment. Against this background, a group of community HEMS providers in NSW and Queensland have commissioned, at their own expense, the development of a safety and integrated risk-management framework for HEMS. This is being facilitated by a specialised aviation risk-management company, which has been responsible for the development of similar programs for the Royal Australian Air Force, commercial airlines, airports and other aviation organisations. This program is a collaborative effort by HEMS operators to exceed regulatory compliance and lead the way for best practice. The program has subsequently expanded to a trans-Tasman initiative, with a number of New Zealand operators joining the consortium. The framework will be formally launched in February 2005. Robust safety specifications and funding arrangements are essential to ensure that HEMS operations in Australia are performed at a more appropriate level.

Alan A Garner FACEM, MSc · Jeff Konemann CFS · Deanne M Keetelaar

We need improved primary care, access to expert multidisciplinary services, and appropriate coordination of the two More than a third of Australians live outside major cities, with 3% living in remote or very remote areas.1 The health disadvantage of rural and remote Australians is well documented, and includes poorer survival after a diagnosis of cancer.2 Both more advanced cancer at diagnosis and poorer treatment appear to contribute.3 Documented instances of poorer cancer care in rural and remote Australia, though not necessarily all with survival implications, include less “state of the art” diagnosis, staging and treatment of prostate cancer;4 less breast-conserving surgery for breast cancer;5 and an apparently lower probability of completing treatment when referred for radiotherapy for rectal cancer.6 Surprisingly, there appears to be little difference in women’s use of breast and cervical screening by area of residence.7 Remoteness of residence is not the only axis of disadvantage that may contribute to poorer cancer outcome in remote areas. Indigenous Australians account for 26% of the population in these areas, and have poorer survival from cancer than other Australians.1,8 Lower socioeconomic status is also associated with rural and remote residence and poorer survival.2 Poorer treatment may explain these worse outcomes. Analysis of linked cancer registry and hospital inpatient records in Western Australia suggests that Indigenous cancer patients are less likely to have surgery for lung cancer or radical surgery for prostate cancer,9 but there was no significant difference in breast-conserving surgery for breast cancer.9 Although that study could not address the possibility that differences in stage at diagnosis explained the observed treatment differences, a Sydney study has shown, after adjustment for size and stage of cancer, that socially disadvantaged women with breast cancer are still less likely to have breast-conserving surgery.10 Factors that underlie Indigenous and socioeconomic disadvantage in cancer survival, and possibly treatment, may go beyond just remoteness of residence and inability to pay. They could include knowledge, attitudes and beliefs about cancer (which may influence presentation for and acceptance or completion of recommended treatment), communication difficulties, and discrimination on the basis of race or socioeconomic status for access to travel support or more expensive care.9,11 In principle, tackling rural inequality in cancer care and outcome requires a combination of improved primary healthcare, access to expert multidisciplinary services, and coordination of the two. Evidence that could guide investment decision-making is limited. Present rural health policy is underpinned by the principle that patients should have access to high quality services as close to their homes as is clinically and geographically feasible. This policy should improve access to primary healthcare and aid in obtaining earlier diagnosis of cancer and quicker referral to expert care. That these factors will improve cancer outcomes is, however, more an article of faith than supported by evidence. Increasing specialist healthcare services in rural areas may also run counter to evidence that, for some cancers at least, the best outcome is obtained by practitioners and institutions that have high caseloads.12 Specialist medical services of all kinds are rare outside cities and large rural centres in Australia and are likely to remain so, and cancer surgery caseloads are low in a high proportion of hospitals in rural New South Wales and Victoria.6,13 Problems of low caseloads can be overcome to some degree by specialist outreach services and shared-care arrangements, in which initial treatment often requires travel to a major centre, but subsequent treatment can be delivered effectively closer to home and partly by local healthcare practitioners. Available evidence suggests that specialist outreach services can increase the proportion of patients receiving breast cancer care consistent with evidence-based guidelines.14 More generally, it appears that specialist outreach services that interact in a shared-care model with primary healthcare providers, such as Aboriginal health workers, can improve healthcare access for remote Aboriginal communities.15 A trial of breast cancer nurses in rural settings has also shown clear psychological and physical benefits to women and more coordinated care among practitioners.16 Developing the role of specialty oncology nurses in care coordination and administration of chemotherapy in rural areas is supported by oncologists, but has not been fully evaluated.17 Moves have been made to define a more coherent approach to cancer service delivery,18 but there is little evidence of successful implementation. So what, in principle, do we need? Conceptually, a well-defined pathway, appropriately tailored to needs, that each person with cancer can easily follow to timely expert care. Practically, this requires that the person and their primary care provider know how to access the pathway, that the person’s journey along it is carefully guided to ensure he or she does not get lost, and that there is effective communication between all places visited. Successful development of such pathways would require innovative information systems, effective interaction between the many services involved in cancer care, and cooperation between governments. The challenge in establishing them will be greatest in rural and remote areas. Distance and low service density may make them more difficult to operate; the social and cultural adaptations required may be a hurdle; and they will need to draw more on special provisions, such as shared and outreach care. But the broad principles will be the same. The additional costs, for pathway creation and maintenance, information provision, journey coordination and communication, should not be great, and would probably be repaid by more efficient care and a better outcome. Food for thought?

Katharine E Jong MPH · Paula J Vale GradDipIHP · Bruce K Armstrong AM, FAA, FRACP

Health statistics say we’re doing well, but our healthcare system is in crisis; we need more than just another report Australians have never enjoyed such good health as they do now. Our life expectancies reach well beyond the biblical ideal of “threescore and ten”, and we rank among the top four in the world’s longevity league.1 However, there is a caveat: the poor health and short lives of Indigenous Australians continue to be a blot on the nation’s psyche. The quality of our healthcare also ranks highly. In a recent comparison of selected health indicators in five nations — Australia, Canada, New Zealand, the United Kingdom and the United States — our survival rates for breast, cervical and colorectal cancers were high, as were our performances in screening for breast and cervical cancer.2 Furthermore, Australia’s mortality rates for asthma and acute myocardial infarction were the lowest among the nations. Our vaccination rates for polio and influenza were exemplary, but the incidence of pertussis in Australia was the highest among the five nations.2 We could do better. Australia’s general practitioners also perform well.3 Most Australian adults reported being with the same doctor or place of care for more than 5 years, and most received appointments on the day they were ill, although after-hours access to primary care remains an issue.3 Core features of the patient–doctor relationship and communication also rated highly: 71% of patients related that the quality of the care they received was excellent; 71% felt that their GPs listened carefully; 73% believed that medical matters were explained in an understandable way; 63% were satisfied that their doctor spent enough time with them; and 61% claimed that their management plans had been clearly outlined.3 With all these good tidings, you may well ask why Australia’s healthcare is beset by a pervasive sense of negativism? Our citizens are losing confidence, troubled by long hospital waiting lists,4 increasing hospital access block,5 and crises such as those at the King Edward Memorial Hospital6 or at Campbelltown and Camden hospitals.7 Our doctors are also unhappy — battle-weary from working in resource-poor and unpredictable environments. Furthermore, there is a swell in public impatience with the inability of politicians to confront the chaos. Playing the cost-shifting and blame-shifting game is more their forte. The causes of discontent were sought in a recent survey of medicopolitical leaders (see Box), and the perceived problems fell predominantly in the domains of funding, organisation and bureaucracy. Indeed, even the Chairman of the National Productivity Commission concurs with these views. In launching the draft Review of National Competition Policy Reforms in late October 2004, he noted: “It is now generally accepted that Australia’s health system is beset by structural problems that require nationally coordinated action. But there is less agreement on the best way forward. An independent review of the whole system is needed to provide a roadmap for reform.”8 Another review? Please! Australia’s healthcare has had more reviews than The Lord of the Rings epic. Our citizens and healthcare professionals want solutions to the problems that they experience and which have been enunciated ad infinitum. The possibility of a National Productivity Commission inquiry into health has been temporarily deflected by the activation of a small taskforce in the Department of the Prime Minister and Cabinet. It will examine the operations of the Australian healthcare system to: ensure optimum efficiency and effectiveness of healthcare service delivery for all Australians across the primary, acute, rehabilitative and aged-care sectors, and, in doing so, clarify responsibilities; ensure best use of the funds all jurisdictions put into healthcare, as well as improve accountability and transparency in healthcare funding; and identify barriers to seamless service delivery for patients and recommend options to address them. The taskforce will present its report early in 2005. As its members contemplate solutions, they may well keep in mind that: We need more time. Modern healthcare reforms have drastically eroded time — time for care, time for teaching and time for learning.9 In an ageing society, we need to provide the means for healthcare professionals to spend time with people. We need greater efficiency. Given our limited health dollars, we need to spend wisely. We can no longer afford unnecessary duplication and waste. We need a greater investment in and coordinated strategies for preventive healthcare. Incentives for “good health” will yield dividends for the future.10,11 We must support our greatest asset — the healthcare workforce. Above all, the taskforce needs to remember the “public” in public service. In this year’s federal election, the public endorsed Coalition majorities in the House of Representatives and the Senate. Having placed such trust in the government, the public is now looking for political leadership in tackling the chronic problems in healthcare. They certainly don’t want yet another report to gather dust in the Council of Australian Governments archives. In this task it may be apt to recall the words of John F Kennedy: “Those who make small revolutions impossible will make violent revolutions inevitable.” Will we have three more years of political rhetoric or will there be purposeful reform? What is wrong with Australia’s healthcare system At a recent meeting, 36 high-level medicopolitical leaders representing all states and territories as well as selected clinical craft groups were independently asked “In one sentence what do you consider to be wrong with our health system?”. Thirty-four participated. The top three responses were: Funding (8 respondents) Lack of indexed funding; inadequate funding; funding inappropriately targeted or managed; maldistribution of government benefits in the community — “money in wrong place” mismatch between funding and expectations. Healthcare system organisation (8 respondents) Demand exceeds capacity; lack of same standards nationally; system is fragmented; poor coordination; access problems; compartmentalisation; system silos and the gap in between; duplication. Bureaucracy (8 respondents) Jurisdictional divides; duplication of function; mismatch between bureaucratic and patient priorities; faceless; costly and inefficient; poor coordination; poor forward planning.

Martin B Van Der Weyden MD, FRACP, FRCPA

Medical researchers have a moral responsibility to communicate their findings to the public There is no greater commitment than a government’s investment in the healthcare of its citizens. If we, as medical researchers and practitioners, are to preserve public trust and support for our scientific enterprise, we need to pay more attention to translating the benefits and grandeur of science into the common language of the general community.1 Although educators and journalists also communicate the achievements of medical science, doctors and scientists have a greater responsibility to increase the availability and salience of science to the public. I believe we can move further towards realising this goal by keeping several key questions in our minds. How have and how can biomedical breakthroughs benefit humanity? The development of vaccines and immunotherapies is at the top of my list of major medical advances that have changed humanity’s lot for the better. During the past year, the medical crises created by epidemics of Ebola virus and SARS have demanded the creation of new vaccines, which are now poised for clinical trials.2 Other developments in medicine include antibiotics to combat infection, organ transplantation to extend life, high resolution imaging that has reduced the number of invasive surgical procedures and, most recently, the global Human Genome Project, which is revealing secrets about the basis of life. In April 2003, the world simultaneously celebrated the 50th anniversary of Watson and Crick’s description of the DNA double helix and the International Human Genome Sequencing Consortium’s completion of the human genome sequence. However, the completion of the human genome sequence represented only the beginning in genomics research; it has led to the unveiling of a bold new vision for its future.3 Translating genome-based knowledge into health benefits will be a major focus of future genomics research. Virtually all diseases, with the exception of trauma, have a genetic component and an environmental component. One of the projected outcomes of the Human Genome Project is the development of personalised medicine. All patients who share the same diagnosis for a certain disease do not respond the same way to treatment. In some cases, we are already able to determine, based on genetic profiles, which patients will be responsive to specific drugs, and then to specifically deliver the most appropriate to eradicate the disease.4 We have entered a new era of multigeneration, population-based research. This will facilitate innovative genetic studies to identify the paediatric precursors of specific adult diseases, based on the comparative analyses of genetic profiles of children, their parents, and grandparents. Imagine the possibility of identifying genes in newborns responsible for cardiac disease, or diabetes, or arthritis, or specific cancers — and then managing and/or preventing the onset of these diseases. The overall improvement in quality of life would be extraordinary, and we are closer than you might think to achieving this goal. Many scientists have suggested the concept of newborn genetic “passports” in which the complete genetic profiles of newborns will be documented in medical files at birth. On the one hand, this sounds quite exciting, but the social implications are profound. As doctors and scientists, we must act now and we must act together to establish rigorous guidelines and boundaries for the use of genetic informatics with respect to: health insurance; genetic information and the workplace; genetic privacy and confidentiality; and, the forensic use of genetic information. Accordingly, the US National Human Genome Research Institute in Bethesda, Maryland, has developed the Ethical, Legal and Social Implications Research Program to ensure that genetic research is conducted in an ethically sound manner; that genetic technologies are integrated appropriately into clinical and non-clinical settings; that genetic information is correctly interpreted and appropriately used; and that health professionals and the public become more genetically literate.3 How important is advocacy in supporting the mission of research and addressing critical social issues? John Porter, former Illinois Congressman and Chairman of the US Subcommittee on Labor, Health and Human Services, and Education, stated: Since most members of Congress are not scientists, citizen scientists must individually inform, educate, inspire, and direct their representatives regarding public policy decisions affecting science.4 When Americans were polled by Research!America about who they believe should have the most influence on how government medical research funds are spent, they indicated that patients (first) and scientists (second) should have the most influence.4 (Research!America is a not-for-profit, membership-supported public education and advocacy alliance for medical and health research.) Scientists must continue to remember that it is a privilege to be engaged in research, and that the relationship between science and society is growing ever more intimate. The spirit of enquiry behind science is not self-sustaining — it is increasingly dependent on societal support. Thus, we have a moral responsibility to be good stewards of this support and to communicate our findings to the public in order to build on that trust and seek broad input. It is critical for greater success that advocacy groups work together for better healthcare and biomedical research. Typically, in the US, joint advocacy on many issues will involve the Association of American Medical Colleges (AAMC), research institutes, academic institutions, hospitals, state and local organisations, voluntary health associations, philanthropic foundations, individuals, and business and industry, as well as biomedical professional societies. As a representative of American scientists, I have valued opportunities to work closely with the US Congress. From 2000–2002, I was privileged to serve as President and Immediate Past-President of the Federation of American Societies for Experimental Biology (FASEB) — over 70 000 scientists speaking with one voice. Through directed advocacy effects of “acting now and acting together” we were successful in: doubling the NIH budget (1999–2003), from $13.6 billion to $27.2 billion; securing federal funding for human embryonic stem cell research; supporting genetic non-discrimination legislation to protect the use of private, genetic information (a work in progress); and developing debt-relief programs for physician–scientists to encourage this endangered species into the pipeline. What are the economic benefits of investing in research? Simply put by the Lasker/Funding First Foundation, “Investment in research saves lives and money”. Increases in life expectancy have contributed to national budgets. For example, in Australia between 1960 and 1999, longevity improved from 73.9 years to 81.8 years for females and from 67.9 to 76.2 years for males, at an estimated worth of $5.4 trillion.5 With respect to government support of biomedical research, the statistics when comparing the US with Australia were astonishing to me. I have recently learnt that in the 2000–2001 budget year, whereas the budget for the NIH was $17.8 billion, the Australian Commonwealth budget for health and medical research was a more modest $665 million.5 This represents a fourfold difference per citizen, with the US government spending about $130 per person and the Australian government about $33. I felt humbled, acquiring a more profound respect for my world-class Australian medical research colleagues, who, with truly limited resources, have made significant contributions to the field. Among these contributions are the discovery of lithium in treating bipolar disorder, as well as major advances in childhood diseases of spina bifida and sudden infant death syndrome. Australian researchers have also discovered a powerful secret to success — working collaboratively in interdisciplinary teams towards a common goal. Researchers around the world could all learn a lesson from Australian scientists; as the US budget for research begins to shrink, American scientists will have to adopt the Aussie philosophy in order to survive in the “business”. With competing demands on government resources, who will pay for tomorrow’s discoveries? I believe that projects leading to future discoveries will be paid for by creative partnerships between academic, philanthropic, corporate and government agencies. I also believe such projects should be guided by advocacy, led by scientists, to advance treatments and cures. We should always remember the wise words of Paul Rogers, Chair of Research!America: “Without research, there is no hope.”

Mary JC Hendrix PhD

We need processes in place to follow up suspicions about serious adverse events Rofecoxib and a second cyclooxygenase-2 (COX-2) inhibitor, celecoxib, were approved by the Therapeutic Goods Administration in 1999 after large phase III randomised trials showed they were as effective as “traditional” non-steroidal anti-inflammatory drugs in reducing pain and inflammation and less likely to cause gastric ulceration.1,2 Since then, COX-2 inhibitors have become one of the 10 most widely used prescription medicines in Australia, at a cost to the federal government of more than $200 million annually.3 However, uncertainty has surrounded the cardiovascular safety of rofecoxib (Vioxx; Merck Sharp & Dohme), and COX-2 inhibitors as a class, ever since an increased risk of cardiovascular events was reported among patients randomly allocated to the rofecoxib group in the VIGOR trial.1 . . . what are the lessons learned by pharmaceutical and regulatory bodies. . . On 7 September this year, Merck Sharp & Dohme faxed a “Dear Doctor” letter to Australian doctors to reassure them of the cardiovascular safety of rofecoxib. Yet, 3 weeks later, Merck Sharp & Dohme suddenly announced an immediate worldwide withdrawal of rofecoxib; this action is the largest prescription drug withdrawal in history. In response, the United States Food and Drug Administration (FDA) immediately issued a public health advisory on rofecoxib, while Australia’s Therapeutic Goods Administration issued a customer-level recall for an estimated 250 000–300 000 Australians taking the drug.4 The first concern about the cardiovascular safety of rofecoxib emerged with the VIGOR study, reported in 2000. It involved a fivefold increase in myocardial infarction and a twofold increase in myocardial infarction, stroke or cardiovascular death among 8076 rheumatoid arthritis patients treated for a median of 9 months with rofecoxib compared with naproxen1 (see Box). Further questions about the cardiovascular safety of rofecoxib were raised in 2001 by an overview of the clinical trial data.6 These data prompted the FDA to initiate a label change in 2002, highlighting the potential cardiovascular risks of rofecoxib. Despite more recent observational studies also suggesting an increased early (within the first 30 days of treatment) and late (beyond 30 days) risk of acute myocardial infarction or sudden cardiac death with rofecoxib,7,8 conclusive evidence of increased cardiovascular risk from adequately powered randomised trials was lacking.9 The decision by Merck to withdraw rofecoxib worldwide was prompted by an unexpected source. APPROVe (Adenomatous Polyp Prevention On Vioxx) was a multicentre, placebo-controlled trial of 2600 patients designed to examine the effects of treatment with rofecoxib on the recurrence of neoplastic polyps of the large bowel in patients with a history of colorectal adenoma.4 An interim analysis of this trial demonstrated an almost twofold increase in cardiovascular events in patients treated with rofecoxib (25 mg daily) compared with placebo (see Box). When these data are extrapolated to the Australian population, the increased risk of 16 events per 1000 patients treated for up to 3 years equates to a potential excess of several thousand cardiovascular events caused by rofecoxib. This may represent an underestimate of the number of events caused by rofecoxib, because patients with inflammatory arthritis are likely to be at higher baseline risk of cardiovascular events than the “low risk” population included in APPROVe.4 The dramatic withdrawal of rofecoxib raises important questions for clinicians, pharmaceutical companies and regulatory authorities. What is the basis for the increased cardiovascular risk?Traditional non-steroidal anti-inflammatory drugs (NSAIDs) suppress prostaglandin synthesis by inhibiting both constitutively expressed COX-1 (primarily responsible for “housekeeping” functions such as gastric protection and haemostasis) and the inducible COX-2 (which is upregulated in inflammatory conditions). The coxibs (COX-2-selective NSAIDs) do not inhibit production of platelet thromboxane (a potent platelet agonist and vasoconstrictor), but selectively suppress endothelial prostacyclin (an intrinsic vasodilator and platelet inhibitor). It has been hypothesised that selective inhibition of prostacyclin production by coxibs without concomitant platelet inhibition leads to thrombosis in at-risk individuals.10,11 However, alternative hypotheses suggest that blockade of COX-2 in atheromatous plaques may reduce vascular inflammation and the progression of vascular disease, and perhaps even prevent events.9,12 Is the thrombotic risk a class effect?The celecoxib studies have not demonstrated an increased risk of thrombosis,2,7,8 but there are no long-term safety studies. Several second-generation coxibs have recently been approved for use in the United States (Lumiracoxib, Valdecoxib) and Europe (Etoricoxib, a derivative of rofecoxib). While randomised trials involving these drugs have not shown a significant increase in thrombosis risk,13,14 they have not excluded it. Consequently, their potential risk for causing cardiovascular events has also been questioned.8,11 Given the clear demonstration of increased cardiovascular risk with rofecoxib, it is now incumbent on drug manufacturers and regulatory authorities to demonstrate cardiovascular safety for all existing and new coxibs. What are the alternative therapeutic options?Paracetamol-based analgesia is widely recommended as first-line therapy to reduce chronic pain. However, when used alone, paracetamol appears to be less effective than NSAIDs,15 and there are no studies of the safety of the long-term intake of paracetamol. NSAIDs are indicated for patients with inflammatory arthritis. For those at increased risk of gastrointestinal complications, the options include celecoxib or a traditional NSAID combined with a proton-pump inhibitor. Neither of these strategies has been tested in patients with cardiovascular disease. What can be done to prevent a recurrence of similar problems with future (new) drugs?Regulatory authorities in Australia and overseas were prepared to accept that an increased rate of cardiovascular events in the VIGOR study was the result of a protective effect of naproxen rather than a toxic effect of rofecoxib. In retrospect, it would have been better if systems had been put in place to further investigate the increased risk of cardiovascular events with rofecoxib when these were first evident. Robust and consistent processes to suspect and actively examine such outcomes need to be established and implemented, particularly when life-threatening effects are possible with symptomatic treatments for non-life-threatening conditions. At the end of the day, the real question is what are the lessons learned by pharmaceutical and regulatory bodies from this sorry tale? Pfizer, the manufacturer of Celebrex, has recently announced that it will sponsor a major clinical study to reassess the cardiovascular safety of its product.16 However, the outcome is some time off. Cardiovascular outcomes in major phase III randomised trials of the cyclooxygenase-2 (COX-2)-selective inhibitors approved for use in Australia COX-2-selective agent Trial No. of patients Comparator Cardiovascular outcome Absolute risk (absolute risk increase; 95% CI) No. needed to harm* Rofecoxib VIGOR 20001† 8076 Naproxen MI, stroke, death 1.1% v 0.5% (0.6%; 0.3%–1.0%) 167 ADVANTAGE 20035† 5557 Naproxen MI, stroke, death 0.4% v 0.3% (0.1%; –0.2 to 0.4%) — APPROVe 20044 2600 Placebo MI, stroke 3.5% v 1.9% (1.6%; 0.3–2.8%) 62.5 Celecoxib CLASS 20002 8059 Ibuprofen or diclofenac MI, stroke, angina 0.9% v 1.0% (–0.1%; –0.5 to 0.4%) — MI = myocardial infarction. * Number of patients who need to be treated in order to cause one adverse cardiovascular outcome. † Patients taking aspirin were not eligible for inclusion.

Paul E Langton BSc, MB BS (Hons), FRACP · Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MB BS, MSc, FRACP

Weight loss occurs in the short term, but not enough is known to recommend long term use After health professionals have promoted a low fat, high carbohydrate model of eating for more than 20 years, the prevalence of overweight and obesity in Australia (as elsewhere) has climbed.1 Very few people are able to attain and maintain a truly low fat eating plan, but that has not stopped the low fat orthodoxy being blamed for the obesity epidemic.2 Yet, it is not sufficient to focus on a single aspect of diet — low fat diets are not intrinsically “healthy”, especially if they contain high levels of simple sugars, low levels of complex carbohydrates and are nutrient poor. In contrast to the low fat, high carbohydrate diet, a popular approach to weight loss is the Atkins diet,3 a “controlled carbohydrate” dietary regimen. One of the many reasons for its popularity is that, as society has become increasingly concerned about body image and weight, the Atkins regimen promises quick weight loss without hunger, allows a wide range of foods and has simple “rules”. All this is supported by consumer “how-to” books, celebrity endorsement, and food product innovation and marketing. The Atkins diet — “kerbing the carbs”Atkins’ theory rests on a belief that a high intake of refined carbohydrate, especially simple sugars, causes overstimulation of insulin and results in uncontrolled hunger and eating, while the excess insulin also favours fat storage. Thus, the Atkins diet relies primarily on controlling carbohydrate intake and progresses through four phases. The strict induction phase, intended to produce ketosis, allows only 20 g of carbohydrate a day for a minimum of 2 weeks. Fruit, bread, grains, starchy vegetables or dairy products other than cheese, cream or butter are eliminated. Sugar and alcohol are not allowed, and caffeine is discouraged. Mineral and vitamin supplementation, dietary fibre, and eight glasses of water a day are recommended. During this restrictive phase, weight loss is rapid. While this initial weight loss may be due in part to water loss as body glycogen stores are depleted, low carbohydrate diets also result in a reduced caloric intake.4-7 Factors contributing to the lower caloric intake may be the satiating effect of a high protein diet, a lower absolute fat intake due to restricted food choice, and possibly appetite suppression due to ketosis.8-10 However, the exact mechanisms of the weight loss are as yet unknown.10 The second and third phases of the diet allow a gradual liberalisation of food intake by an incremental increase in total carbohydrate: fruits, nuts, more vegetables and some cereal foods are added. The final, maintenance phase is intended to be permanent, and aims to keep daily dietary carbohydrate intake to a known (relatively low) amount. Advice for patients wanting to follow the Atkins diet While low carbohydrate diets appear to work for weight loss in the short term (6 months), not enough is known to recommend them in the long term. All weight-reduction diets are difficult to follow over a long period of time and have limited long term success. Follow the complete Atkins plan (not only parts of it), including regular physical activity, vitamin and mineral supplementation, a daily fibre supplement, eight glasses of water a day, and minimally processed foods. Maintain a high daily intake of fruit and vegetables (at least two serves of fruit and five serves of vegetables from the “allowed” foods) and avoid saturated fats. A dietitian can help with your dietary intake plan if you are having difficulties. Does the Atkins diet work?If weight loss is the goal, the answer appears to be a qualified “yes”. For obese people, it works a little better than a low fat diet over 6 months. Recently, four randomised controlled trials in obese men and women (two lasting 6 months, two lasting 12 months) compared a low carbohydrate diet to a conventional low fat weight-loss diet.5-7,11 Although the studies differed in design and had different subjects, in each study the weight loss at 6 months was 4–6 kg greater for the low carbohydrate group than for the low fat group. However, the weight loss difference between groups at 12 months was no longer statistically significant.6,11 The dropout rates in all of the trials were high (21%–43%), with a general non-significant tendency for better retention in the low carbohydrate group. So, in the long term, low carbohydrate diets do not necessarily offer better weight control than lower fat, higher carbohydrate diets. Is the Atkins diet safe?During weight loss, a low carbohydrate regimen appears to have no adverse effects on cardiovascular risk factors such as serum lipid levels (total and low-density lipoprotein cholesterol) or blood pressure, or on fasting glucose and fasting insulin levels.6,7 In fact, randomised controlled trials comparing a low carbohydrate diet with a low fat diet up to 12 months consistently indicate a beneficial effect on serum triglyceride and high-density lipoprotein cholesterol concentrations. However, the low carbohydrate regimen is associated with a greater incidence of constipation, headache, halitosis, muscle cramps, diarrhoea, general weakness and rash.5 Strictly limiting carbohydrates could also reduce intake of plant-based foods rich in phytochemicals, bioflavinoids, carotenoids and other micronutrients now regarded as important in a healthy diet.12 The regimen developed by Atkins3 encourages fruit and vegetable intake, and minimally processed food, so a low carbohydrate diet should not necessarily imply an intake low in fibre and low in plant-based food. Low carbohydrate diets may also be beneficial by removing simple sugars and sugary foods, including fructose sweeteners, which could be responsible for excess energy intake.8 Overall, however, the safety of low carbohydrate diets beyond 12 months is largely unknown, and there is speculation that the regimen may have adverse health implications for cardiovascular disease, renal function (through an observed cross-sectional association of high dietary protein intake with proteinuria) and bone health (through relatively low calcium intake and the association of high protein intake with hypercalcinuria).13 Information is also lacking on the long term effect of a low carbohydrate regimen for the young, the elderly, people of normal weight (or for people who are not losing weight), and those with chronic conditions, such as diabetes or cardiovascular disease. As with many dietary regimens, the nutritional quality of low carbohydrate diets varies according to how the dietary rules are applied. The Atkins diet calls for a drastic dietary reduction of foods with a significant starch and sugar content — in doing so, the intake of many energy-dense but micronutrient-poor foods is reduced. There is the potential for these to be replaced with foods that are moderate in energy intake, and rich in fibre and micronutrients. However, in any regimen to reduce or control weight, particular attention should be given to ensuring that the reduced food intake is of high nutritional quality. A sensible way to follow an Atkins diet is to include plenty of the allowed fruits and vegetables, and to prefer food sources of unsaturated fat over those with saturated fat.

Malcolm D Riley PhD · John Coveney PhD

Guidelines from the National Health and Medical Research Council are now available A recent World Health Organization report on the burden of musculoskeletal conditions in 2002 noted that these were a major cause of morbidity throughout the world. While much of this burden of disease is due to chronic arthropathies such as rheumatoid arthritis and osteoarthritis, the commonest problems by far involve acute musculoskeletal pain in the back, neck and large joints. “Acute” is defined as duration of symptoms not exceeding 3 months. There is a perception that the management of acute musculoskeletal pain is poor, and mainly driven by individual experience, clinical consensus, and descriptive studies. The absence of an accessible and rigorous evidence base has led to variations in practice, unnecessary investigations and imaging, and inappropriate and ineffective treatments with their potential for increasing morbidity, and unnecessary costs. Key messages of the guidelines 1. Most acute musculoskeletal pain is non-specific, and serious causes are rare. 2. Patient history enables screening for features of serious conditions, but reliability and validity of individual features have low diagnostic significance. 3. Clinicians need to be alert for the development of fragility fractures in those aged over 60 presenting with thoracic pain. 4. Clinical signs detected during physical assessment need to be interpreted cautiously, as many tests lack reliability and validity. This is true in most of the acute conditions, including those of the shoulder, where many eponymous tests are performed to try to reach an accurate diagnosis. This is not necessary for effective management of most pain, but is important in identifying disorders likely to become chronic or to have a serious underlying cause. 5. Plain x-rays are not routinely recommended in acute conditions, as they are of limited diagnostic value. The exceptions are the “red flag” features (infection, fracture, tumour, aneurysm) signifying possible serious underlying abnormality. 6. Common findings (eg, osteoarthritic changes) occur in both symptomatic and asymptomatic patients and might not be the cause of pain. 7. Education about the limitations of x-rays and their risk is recommended. 8. Most acute conditions settle within 3 months, although a few persist with some disability and recurrence is not uncommon. In the case of shoulder pain, the 12-month recovery rate is only 60%. 9. Psychosocial and occupational factors appear to be associated with progression from acute to chronic pain and should be addressed early. 10. Although published data are limited, advice to remain active, providing an educational booklet and community-based exercise appear to be cost-effective first-line interventions for acute low back pain. 11. In acute neck pain, an exercise program at home appears as effective at 2 months and more effective at 2 years than institutional-based therapy. 12. There are no randomised controlled trials of manipulation therapy for acute neck pain. Adverse effects of manipulation are rare but potentially serious. Non-steroidal anti-inflammatory drugs (NSAIDs), transcutaneous electrical nerve stimulation, soft collars and similar treatments all lack Level I or II evidence for benefit. There is evidence of a moderate benefit of NSAIDs in acute shoulder pain over 4 weeks compared with placebo. 13. It is preferable to use terms such as “anterior knee pain” than attempting to be more specific in acute knee pain. Although lacking specificity, examination is important to exclude serious disorders. 14. Specific eccentric quadriceps strengthening exercises produce better outcomes in anterior and non-specific knee pain than standard exercises. Choosing best clinical practice in the care of acute musculoskeletal pain has been made easier with the recent release of guidelines for managing acute musculoskeletal pain by the National Health and Medical Research Council (NHMRC).1 Five multidisciplinary review groups were formed to address draft guidelines developed by the Australian Faculty of Musculoskeletal Medicine. The groups involved representatives from such diverse disciplines as general practice, rheumatology, orthopaedics, chiropractic, physiotherapy, pain medicine, rehabilitation, sports medicine and consumer groups. This wide representation was deliberate and aimed to minimise possible bias of different craft groups. The brief for each group was to formulate guidelines based on the best available evidence for management of acute musculoskeletal pain in the lower back, thoracic spine, the neck, shoulder or anterior aspect of the knee. The methods of the evidence review were based on NHMRC standards,2 and the Cochrane proposal of rationalisation of diagnostic and therapeutic intervention.3 Where no good evidence existed, consensus statements were made by a steering committee, or no recommendation was made, except to signal the need for research to gain appropriate data. For each site of pain, the guidelines provide information on diagnosis, prognosis and interventions. Three pertinent questions which arise from all the guidelines are discussed below. How can we use the guidelines? Management of patients with acute musculoskeletal pain has to be individualised, and tailored to patients’ response and compliance. This will obviously vary between patients and locations depending on resources and availability of services. However, the delineation of the treatment options in the NHMRC guidelines will improve knowledge and, it is to be hoped, enhance standards of care. As patients seeking help may find their condition altered by the diagnostic and therapeutic approach, and usually not for the better in a self-limiting, acute condition,4 the guidelines may also allow patients to rely on their own resources to cope with a disorder that is acute, but of short duration. Are the guidelines unique? Several evidence-based guidelines for the management of acute low back pain exist.5 However, the NHMRC acute musculoskeletal pain guidelines are the most extensive that are currently available for the problems they cover. In addition, the guidelines for acute low back pain have been assessed for safety, efficacy and cost effectiveness in a primary care setting.5 Compliance with the guidelines achieved marginally better symptomatic relief, resulting in less need for continuing care, achieved greater rates of full recovery, was less expensive, and attracted higher consumer satisfaction.5 How good is the evidence? This varies within each condition. Acute low back pain only has consensus statements (as opposed to any level of evidence) about effective communication. In the diagnosis, prognosis and intervention sections, the level of evidence ranges from Level I to Level IV. There is Level I and II evidence that oral and injectable non-steroidal anti-inflammatory drugs (NSAIDs) are no more effective than placebo or no treatment for acute low back pain. Heat-wrap therapy was more effective than NSAIDs, paracetamol or placebo in reducing pain in the first 3–4 days. This information alone could save the community considerable expense and morbidity. The main purpose of guidelines is to improve the quality of care for patients, but their existence does not guarantee their use in practice.6,7 Propagation of guidelines by publication or through special societies is a start, but more active strategies are needed to maximise the likelihood of the clinical guidelines becoming effective.8 Computer software would be most helpful for doctors in incorporating the NHMRC acute musculoskeletal pain guidelines into practice. As with all guidelines, the evidence base is unstable and will need to be regularly updated to remain useful. The remedy proposed by the Committee was that funding should be made available for an annual survey of the members of the steering and review committees to update the information, and for searches of the literature and electronic databases to determine the need for revision. Whether this will happen is not clear. We believe these guidelines are unique in their comprehensiveness, the rigour of evaluation of the evidence and the usefulness to the community as a whole. They also contain information sheets produced specifically for the public which are free of jargon and have simple explanations. The sheets summarise the benefits and minimise the harm of available options and should empower patients to make more informed choices and to consider their needs and priorities in selecting the best option.

Julien P de Jager FRACGP, FRACP · Michael J Ahern MD, FRACP