Editorials

Manufacturers’ claims in well funded marketing campaigns cannot replace the test of time Declaring war and prescribing drugs are decisions dependent on information, and the consequences can be calamitous if that information is incomplete or inaccurate. The calamity which threatened the sustainability of the Pharmaceutical Benefits Scheme (PBS) in 2000 and 2001 was the volume of prescriptions for cyclooxygenase (COX)-2 inhibitors. Celecoxib was listed on the PBS on 1 August 2000, and by the end of December 2000 over 1.5 million prescriptions had been written, costing the government more than $76 million.1 By the end of June 2001, the cost had exceeded $160 million.2 In this issue of the Journal (page 403), Kerr and colleagues confirm the rapid rise in prescriptions for celecoxib and rofecoxib.3 However, their research cannot explain why the general practitioners in their study were so enthusiastic about the new drugs. The doctors’ decisions to prescribe would have been based on the available information. At the time the drugs were launched in Australia, most of that information would have been supplied directly or indirectly by the manufacturers. There was little independent information, and the major randomised trials of celecoxib (CLASS4) and rofecoxib (VIGOR5) were only published in late 2000. The information from the manufacturers emphasised the relative safety of the new drugs. Compared with non-selective non-steroidal anti-inflammatory drugs (NSAIDs), the new drugs caused fewer peptic ulcers. This was an important message, as doctors are often warned about the serious gastrointestinal complications of NSAIDs. There is evidence that some patients were prescribed the new drugs because they had suffered adverse effects from NSAIDs.6 However, this did not result in a fall in the prescribing of NSAIDs. The availability of celecoxib and rofecoxib increased the number of people being treated for musculoskeletal disorders,3 suggesting the new drugs were being prescribed for conditions beyond the restrictions of the PBS. Such conditions include non-specific back pain, sprains and sports injuries.3,6 Some general practitioners believe that COX-2 inhibitors are more effective than NSAIDs.6 This belief is not confirmed by the clinical trials, and now even the evidence of their improved safety is being questioned.7 The published results of VIGOR5 and CLASS4 did not include all the data submitted to the United States Food and Drug Administration (FDA).7,8 The favourable results of CLASS were based on only the first 6 months of the trial. Analysis of the 12 months’ data that was available to the FDA suggests that celecoxib was associated with a similar number of ulcer complications as were diclofenac and ibuprofen.7,9 Similarly, analysis of the complete data for rofecoxib suggests it may be associated with an increased risk of cardiovascular events10 and that serious adverse effects may be more frequent than with naproxen.8 The Therapeutic Goods Administration (TGA) probably had access to the complete data when it evaluated the drugs for use in Australia. However, unlike the FDA data, which are published on its website,8,10 the TGA’s evaluations are kept secret. Would publication of the TGA’s evaluations have alerted Australians to the possible problems with COX-2 inhibitors? Concerns about the drugs only arose months after they were marketed. Even if they had been aired earlier, they are likely to have been lost in the excitement surrounding the launch of the drugs. Even the Minister for Health and Aged Care put out a press release listing some of the benefits of celecoxib and describing it as a “major breakthrough in arthritis therapy”.11 Enthusiasm for the COX-2 inhibitors waned slightly with experience. In Kerr and colleagues’ study, rofecoxib was not embraced to the same extent as celecoxib. Nearly a third of the patients prescribed rofecoxib had previously been prescribed celecoxib, suggesting they had been disappointed by the response.3 Initial enthusiasm followed by a slower increase or plateau in prescribing is a common pattern with new drugs. If the new drugs are not as good as they were thought to be, can they justify being twice the price of other NSAIDs? What coaxes doctors to expose their patients to new products when so little information is available? I believe that manufacturers’ marketing strategies play on doctors’ desire to give their patients the best possible care. Much of the variation in the prescribing of new drugs depends on the personality of the doctors, and probably on their susceptibility to these marketing techniques.12 The prospect of reduced adverse effects is likely to have a strong influence on prescribing practice. If adopting new drugs quickly actually puts patients at risk, prescribers must be presented with information to balance the claims of the drug companies. Achieving this balance is difficult, partly because independent information (such as Therapeutic guidelines and the Australian medicines handbook) sometimes comes at a cost, while drug company information — supported by massive advertising budgets — is free. In 2000, the amount spent on promoting rofecoxib to Americans (US$160 million) exceeded the advertising budgets for Pepsi and Budweiser beer.13 In view of the popularity of the new drugs in the United States, perhaps Australia should have been prepared for the demand. If the TGA had been able to provide its evaluations to publishers of independent information, they could have prepared prescribing guidelines before the drugs were marketed. The National Prescribing Service has recently received funding to provide doctors with independent information about new additions to the PBS. To ensure advertising does not swamp these messages, perhaps there should be limits on promotional activities around the date of PBS listing. While governments are unlikely to ban advertising, they could at least mandate that it provides quantitative information about the outcomes for patients.14 Another approach to new drugs is not to use them. This will spare patients from the serious adverse effects which sometimes only emerge after marketing. The Health Research Group in the US now recommends waiting 7 years before using a new drug that provides no clear advantage over current therapies.15 While this may be an extreme position, there is no need to feel pressured into immediately prescribing the latest drug. New is not always better.

John S Dowden MRCGP, FRACGP

Treating substance misuse might not significantly reduce the number of offenders According to recent estimates, crime costs the community $32 billion annually. Of this, $1960 million is directly attributable to drugs, and, if indirect costs were included, the proportion attributable to drugs would be higher.1 Clearly, interventions that target potential risk factors for crime, such as drugs and mental health problems, will have significant payoffs for individuals and the wider community. However, the relationship between drugs and crime is complex. Policy development in this regard needs to take into account the multifaceted nature of the problem. In this issue of the Journal (page 408), Heffernan et al present the first Australian publication that seeks to clinically assess the level of substance-use disorders and psychological distress among police arrestees.2 This article makes a constructive contribution to the evidence base. The study highlights that the overwhelming majority of arrestees suffer from clinical substance-use disorders and psychological distress, and that they are a population who may be in need of treatment. Replication of these findings is important to furthering our understanding of the need for treatment among this group. In Australia, evidence is emerging (building on overseas research) that criminal behaviours among arrestee and prison populations vary widely, from minor disorderly conduct through to homicide, with different factors contributing to these behaviours. Illegal drug use is just one of many risk factors, but there is no doubt that it is significant in the behaviour of a subset of offenders. Recent analyses of police detainees and the incarcerated adult male population estimate that this is the case for between 34% and 52% of offenders.3,4 This clearly suggests that effective treatment interventions could significantly reduce crime rates. Criminological studies that track when people start, persist with and desist from drug use and offending demonstrate that most offenders become involved in minor crime before experimenting with and using illegal drugs.5,6 For example, the onset of crime preceded regular heroin use in 69% of one sample of offenders.5 Illegal drug use seems to compound a pre-existing problem, and so produces higher levels of offending.7 Thus, treating substance misuse among offenders, although an essential public health measure, might not necessarily result in significant reductions in the number of offenders. This is because crime and drug use may be caused more by factors external to the individual, such as early-childhood experiences and development, access to labour markets, access to local drug markets and their supply routes, the social and cultural environment, lifestyle choices, and other determinants that are not easily amenable to treatment.8 The links between drug use and crime and the policy implications that flow from this will be affected by the nature of the local drug market. The Australian Institute of Criminology’s Drug Use Monitoring in Australia project has conclusively shown that police detainees’ drug use patterns vary across the country. Higher rates of amphetamine use have been detected in Queensland, Western Australia and South Australian sites; while higher rates of heroin use have been detected in New South Wales sites.9 Furthermore, breakdowns by offence type indicate that users of amphetamines are arrested for a range of offences, not just violence, and similarly heroin users are arrested for a range of offences, not just property. The links between drugs and offending types appear more variable than is often thought. Changing human behaviour is difficult. Some people take drugs because they like the effects, some because they are risk takers, and some to self-medicate for past and current painful situations and events; others take them because they are addicted and simply cannot stop. Not everybody who is defined as dependent will want or seek treatment. In this complex environment, public policy responses, such as drug courts and court diversion systems, need to be cognizant of what drives behaviours and develop appropriate responsive systems (of which levels of dependency will be only one factor). Recent evaluations of the south-east Queensland and NSW drug courts10,11 have shown that, even with a 12-month, structured, supervised program, some people continue to be criminally active and use illegal drugs. Estimates from the early stages of the Queensland study suggest about a third of graduates reoffended within the follow-up period after graduating from the court. Similarly, police diversion schemes need careful targeting, as good longitudinal research shows that, after a “first” contact with the criminal justice system, many young offenders (upwards of 60%) do not come back into contact with the juvenile system again.12-15 Because of the intersection between illegal drug use and crime, the criminal justice systems in Australia have developed a range of policy innovations to divert offenders into treatment and other programs. These include early police diversion programs, court-based initiatives to divert offenders into treatment, and formal drug courts for serious offenders. There have also been attempts to provide treatment programs within prisons. However, opportunities for diversion could be strengthened in other areas. The first area is at the “end” of the criminal justice system, by providing postrelease support programs for prisoners leaving custody. Given that some 58% of prisoners have been imprisoned previously and 22% of police detainees have been imprisoned in the past 12 months, interventions to break the cycle of reoffending would have a significant beneficial effect on both the individual and the wider community — drug treatment is clearly one of those interventions. The second opportunity to improve diversion to treatment is in the gap between police diversion and the drug court: targeting people who are arrested and processed but whose offence is not sufficiently serious to meet the criteria for a formal drug court program. The study by Heffernan et al includes a significant number of these people, providing support for “arrest drug referral” schemes, as undertaken in the United Kingdom.16 However, there could be very large numbers of people suitable for such schemes. Policymakers first need to know how many of those people would avail themselves of treatment. In addition, treatment options must exist — at present, there is a range of effective treatments for heroin, but options for other illegal drugs are extremely limited. Reducing crime requires a multipronged approach that goes beyond criminal justice and treatment responses, to include a whole-of-government approach. Building the evidence base with valuable contributions such as that by Heffernan et al is vital to ensuring our interventions are successful.

Toni Makkai PhD

We should do all we can to ensure that every baby benefits from this important preventive activity Newborn screening is a wonderful example of preventive medicine. Pioneered by Dr Robert Guthrie in the early 1960s, the blood-testing of newborns for treatable disorders has become almost universal in developed countries. From the first programs for phenylketonuria testing, the scope has widened to include disorders such as hypothyroidism and cystic fibrosis. More recently, analysis by tandem mass spectrometry, which can detect over 30 rare inborn errors of protein and fatty-acid metabolism, has been introduced.1 Soon all babies in Australia will be able to be tested by tandem mass spectrometry. A simple heelprick is all that is needed. More than one baby in every 1000 (over 250 babies a year in Australia) will have a detectable disorder needing treatment. Without early detection, some of these babies would develop intellectual disability, some would develop acute life-threatening illness, and a few avoidable deaths would result. Screening for phenylketonuria alone, with subsequent treatment, has saved over 700 Australian children from moderate to severe disability since screening began. The consequences of not having a screening test might seem trivial to an individual family — only about one chance in 1000 that anything threatening would be missed. But, for every 1% of babies in Australia that are not tested, two or three babies per year with a treatable disorder could die or suffer permanent damage. In this issue of the Journal, Metz and colleagues (page 412) report the results of a systematic investigation of the coverage of newborn screening in South Australia for the year 1999.2 The team not only examined coverage, but carefully analysed who it was that missed out on screening. Some of the results are not surprising, but some are. Being Aboriginal, having a home birth, being in hospital for less than three days, or suffering neonatal death were all risk factors for missed screening, as were having a gestational age of less than 32 weeks, being in intensive care, having a congenital anomaly, or having a mother who normally lived in another state. (Being a twin or triplet, however, was protective — they rarely missed being screened.) Metz and colleagues concluded that, overall, about 2% of babies did not get a screening test. The methodology used was thorough, matching newborn screening data with the SA perinatal data collection using sophisticated software. Of course, data matching is never perfect. Baby’s-surname changes are common soon after birth (even the mother’s indicated surname can change), and babies are sometimes transferred from one hospital to another. In the end, there were 413 births to which Guthrie screening cards could not be matched, and 44 unmatched cards. Even if the unmatched cards represented babies who were born interstate then transferred to South Australia, as was suspected, this would not have materially altered the finding that about 1 in every 50 babies born was not screened in 1999. This should sound a warning note to those who oversee other screening programs, many of whom have assumed a greater than 99% coverage without adequate supporting data. There has indeed been little published on newborn screening coverage, although a recent survey from London did suggest an enviable coverage of 99.9%.3 Newborns are an ideal population to screen, being “captive” for the crucial time, but the problem of early discharge is threatening this, just as screening is poised to expand into new fields. Newborn hearing screening is becoming universal in Australia, and for this, too, it will be important to ensure a very high coverage.4 Biochemical screening by means of the routine dried blood spot is also very likely to expand as new possibilities, supported by new technology, are being explored.5 The lessons from the SA study are clear. To achieve close to 100% coverage, strategies must especially target groups at high risk of not being screened, and healthcare providers need to be reminded and re-reminded about the importance of the test. In relation to the SA study, it would have been interesting to know whether some birth units had particularly high rates of missed tests — if that were the case, such units could be targeted for kindly reminders. As the authors point out, it is also important to collect a sample from newborns who die. Now that expanded testing by tandem mass spectrometry is available, firm diagnoses can sometimes be made from dried blood samples of babies who have died. In New South Wales, over a 4-year period, we have diagnosed fatty-acid-oxidation disorders in this way in three children who died 2–3 days after birth. Achieving a diagnosis makes possible either prenatal diagnosis in a future pregnancy, if desired, or early management of a subsequent baby to avoid clinical problems. For better coverage, perhaps screening should become mandatory in Australia, as it largely is in the United States. In Australia, we have felt that parents have a right to refuse neonatal screening on behalf of their baby. But should parents be able to refuse a procedure that carries such a tiny risk and has an obvious potential benefit, and would this not infringe on the baby’s right to have what ethicists call an “open future”?6 This is a difficult question, but one that is growing in importance as the potential for well targeted newborn screening increases. At present, in our experience, only a very small number of parents refuse newborn screening, for a variety of reasons. If we feel that newborn screening tests are valuable, then we need to ensure that every baby has a chance to benefit. Few preventive medicine programs are so effective.

Bridget M Wilcken AM, FRACP

Referrals should be offered to all patients, and the individual needs of each patient considered Cardiac rehabilitation has progressed markedly since it was introduced into Australia by the National Heart Foundation in 1961. At that time, the focus was on restoration of a sense of wellbeing and encouraging return to work for survivors of acute myocardial infarction and other cardiac illness. The first cardiac rehabilitation programs in Europe and the United States involved mainly supervised, high-intensity exercise training with electrocardiographic monitoring. As data accumulated that similar benefits could be achieved from low, moderate and high levels of exercise intensity,1,2 an Australian hospital model evolved, based on group light exercise and patient education.3 Recognition that psychosocial factors (rather than heart disease) were the main causes of disability after a myocardial infarction led to greater emphasis on counselling, education and support. This led, in turn, to the development of a multidisciplinary team approach to cardiac rehabilitation, with the aim of focusing on and dealing with the range of factors influencing patients’ quality of life. As evidence from large clinical trials emerged showing that modifying risk factors through both pharmacological interventions and lifestyle change could significantly reduce mortality and morbidity, the aims of cardiac rehabilitation broadened to include preventing progression of cardiovascular disease. . . . a majority of eligible Australians are failing to achieve the potential gains available from our network of outpatient cardiac rehabilitation programs. By 1986, cardiac rehabilitation had advanced sufficiently for it to be seen as an important component of cardiac care. Dr William A Seldon, a cardiologist at St Vincent’s Hospital, Sydney, and the first Director of the National Heart Foundation Cardiac Rehabilitation Centre in Sydney, wrote in the Journal: It is not difficult to envisage that a failure to provide cardiac rehabilitation services to patients with myocardial infarction will be regarded as medical negligence in the not too distant future.4 Since then, there has been a progressive increase in the provision of such services throughout Australia. The National Heart Foundation’s 2001 Directory of Australian cardiac rehabilitation programs5 lists 265 hospital- and community-based out-patient programs, compared with only 26 in 1985.6 The growth and development of these programs in Australia over the past two decades has occurred alongside the publication of several evidence-based guidelines summarising the benefits of structured cardiac rehabilitation and secondary prevention programs.7-9 Defined benefits include reduced mortality and reduced risk of further cardiac events; improvements in physical and social functioning, risk factor profiles and quality of life; and reduced prevalence of depression. Despite the convincing evidence and the increased availability of cardiac rehabilitation programs, the report by Scott et al10 in this issue of the Journal (page 341) highlights suboptimal rates of referral to and utilisation of outpatient cardiac rehabilitation programs in Queensland: 29% of patients with cardiac diagnoses discharged from participating hospitals were referred to an outpatient cardiac rehabilitation program, while 49% of discharged patients were eligible for such a referral. Fewer than a third of patients referred completed the program. It was estimated that only 40% of available outpatient cardiac rehabilitation program places were fully utilised. Similarly, a study of data from the NSW Hunter Region Heart and Stroke Register11 identified that only 39% of the patients on the register who were eligible for outpatient cardiac rehabilitation were invited to attend. This figure is likely to be an overestimate, as only 62% of all discharged patients consented to be on the register. It is clear that a majority of eligible Australians are failing to achieve the potential gains available from our network of outpatient cardiac rehabilitation programs. This distressing failure reflects both a lack of initial referrals and a failure of patients to attend, despite having been referred. Key factors contributing to these deficiencies include the following: data have not been collected to establish cardiovascular health indicators for monitoring the proportion of patients entering and completing a cardiac rehabilitation program;12 routine referral, although recommended in Australia,8 is not standard practice; cardiac rehabilitation programs are not available or accessible to all patients, especially those in rural and remote areas;12 and cardiac rehabilitation programs are not sufficiently accessible and attractive to certain population groups, such as Indigenous people, older women, those unable to speak English, and the indigent.12 What strategies can be implemented to address these issues? System factors resulting in failure of referral should be investigated and rectified. It is well known that discharge planning and linkages between hospitals and primary care services are often poor or non-existent. In addition, the attitude of the treating physician is a major predictor of patient non-participation in cardiac rehabilitation.13 Scott et al found that patients having coronary revascularisation procedures were more likely to attend rehabilitation programs than those with acute coronary syndromes.10 Is it that some patients perceive a greater need for rehabilitation programs as part of the recovery process and that this need is also appreciated by their key healthcare providers? Patient “denial” of severity of illness and a history of depression have both been found to be significant predictors of participation,13 and may also account for the varying participation rates by diagnosis or procedure. Patient preferences for different program models and methods of delivery should be canvassed. Referrals should be offered to all patients, and the individual needs of each patient considered. Medical practitioners and healthcare authorities need to understand and accept that not all patients’ needs can be met by so-called “usual” medical care.

Stephen J Bunker PhD, RN · Alan J Goble MD, FRACP, FRCP

Has enthusiasm overwhelmed judgement? Although advocates of the use of tissue plasminogen activator (tPA) in acute ischaemic stroke suggest that this “is one of the most important advances in stroke medicine”,1 a recent Cochrane meta-analysis also supports “clinicians who choose . . . not to use the treatment at all”,2 and all three major emergency medicine associations in North America have declined to endorse it as “standard of care”.3 In a recent issue of the Journal, Szoeke and colleagues’ audit of tPA use in a tertiary-care hospital concluded that “favourable outcomes . . . were similar to those achieved in international . . . trials in specialised centres”,4 while an accompanying editorial highlighted that “the absolute benefits of stroke care unit management clearly outweigh those of . . . tPA administration”.1 Several letters in this issue of the Journal raise important concerns about the report of Szoeke et al, as well as the overall risks and benefits of the use of tPA in ischaemic stroke (page 386).5-7 A single dose of aspirin provides benefit to about 15 times as many stroke patients as does tPA,1 at far less risk. This is true even assuming tPA benefits one in every eight patients treated, which is based on a point estimate taken from the National Institute of Neurological Diseases and Stroke (NINDS) trial,8 the only randomised controlled trial which found a benefit for its primary endpoint. This does not take into account the wide confidence intervals in the NINDS trial, the negative results of multiple other randomised controlled trials,9,10 and the far worse results in non-expert hands. Even under a “maximum benefit” scenario, with further assumptions that overestimate the impact of tPA (including that it could be given safely and effectively to 10% of acute stroke patients, rather than the 1%–3% non-protocol-violation treatments in typical community studies),11,12 tPA would have only minimally greater impact than aspirin. Ultimately, regardless of who is correct about the available evidence, the overall impact of tPA in acute ischaemic stroke is at most marginal, which makes it difficult to understand why “so much has been made of so little”.7 Perhaps it has to do with enthusiasm for what is frequently called the “first treatment for stroke”, although, as noted, there are far more important (but far less dramatic) treatments available. Readers will have to decide for themselves whether it also has something to do with money,3 or if this is truly “extending conspiracy theory to its limits”, as Donnan and colleagues claim (page 388).13 Previous critiques of the use of tPA in ischaemic stroke have raised the following issues: There is a paucity of positive evidence; all but one small randomised controlled trial failed to find benefit in the primary outcome, or found substantial harm.14,15 Even in the NINDS trial, the benefit was primarily in patients treated less than 90 minutes after symptom onset16 (almost no such patients exist in actual community practice), so the number needed to treat in the 91–180-minute group is surely far higher than the “eight patients needed to treat” widely quoted. “Effectiveness” in a community setting is far different from “efficacy” as reported in the NINDS trial (even if NINDS is taken at face value).15,16 Let me add the following observations. Most supporters of tPA claim that three trials involving streptokinase are irrelevant (including one done in Australia, with very negative results10). However, in the absence of studies directly comparing them, there is no reason to believe that tPA should be better than streptokinase for treating ischaemic stroke. In head-to-head cardiac megatrials (ISIS III, GISSI II, and GUSTO I), tPA consistently caused more intracerebral haemorrhage than streptokinase, which is likely to be even more important in patients with stroke. Furthermore, the GUSTO I trial, which provided the only remotely credible (albeit controversial) evidence suggesting tPA might be a bit more effective than streptokinase in coronary patients, was explicitly based on the notion that adjunctive intravenous heparin must be given with tPA — an approach contraindicated in stroke. Excluding streptokinase trials from the analysis of thrombolytics in stroke because they happened to be negative is simply inappropriate. Although Szoeke et al’s report is not strictly an “efficacy” study, neither is it a community practice “effectiveness” study, as treatment was by experts in a tertiary care facility. Thus, in no case should the results be extrapolated to other practice environments. Furthermore, it is critical to note the report’s limitations: Most obviously, there were no randomised controls, and outcomes were measured unblinded to the use of tPA, creating enormous potential for measurement bias. The study failed to meet most of the methodological criteria considered critical for chart reviews17 (eg, use of trained abstractors [ideally other than the authors], standardised abstraction forms and multiple independent reviewers for at least some of the charts, with some measure of agreement between reviewers; use of explicit criteria for coding of outcomes and explicit definitions for interpreting absent or inconsistent data). Outcomes among 30 patients receiving tPA may have been “consistent with” the NINDS result, but, given the small numbers and extremely wide confidence intervals, were also consistent with virtually any result. The report may well represent publication bias. Indeed, the most positive “effectiveness” study reported results from 57 of 83 centres that participated in a proprietary randomised controlled trial18 — what happened to the other 26? The only two reports that included all patients receiving tPA in a given community each documented unacceptable outcomes.11,12 Finally, there is the problem of interpretation bias. Szoeke et al classified one of the deaths after tPA therapy as a protocol violation, which will allow advocates to claim the results “would have been even better if . . .”. But this was based on an exclusion criterion that was not part of the NINDS protocol (ie, “early signs on computed tomography [CT] suggesting infarct of more than a third of the territory of the middle cerebral artery”), and despite the fact that the study’s expert CT readers did not agree whether this patient even met that criterion! This example (out of many) should provide insight into the way the “spin” of enthusiastic authors can lead to conclusions that are rosier than results actually justify. Many of us believe that thrombolytic therapy in stroke remains far from proven, so that its use should be restricted to further randomised controlled trials. This would not only enable us to determine whether this therapy produces more good than harm, or vice versa, but might also allow identification of subgroups in whom it is, or is not, indicated. We could then avoid giving a potentially fatal drug to a patient in whom it increases risk unacceptably, while also allowing current sceptics to use it in a different patient likely to benefit — assuming such patients, in either category, could be identified. If tPA use becomes more widespread, a very small number of patients may receive great personal benefit, while a very few others may be subjected to great personal harm. However, the broader implications of this debate are substantial. Modern health policy traditionally rests on the “precautionary principle”, which requires that no new practice be widely introduced until it is shown to be safe. This principle is under fierce attack in postmodern society by advocates of the contrary “Kehoe principle”, which asserts that if something may have value it should be accepted unless it’s proven dangerous.19 It is, of course, almost impossible to prove such danger, and, once approval is given, it may take many years — and a great deal of harm — before the decision can be reversed. Such was the case with leaded gasoline, which was termed “a gift of God” by its discoverer, Robert Kehoe, after whom this dangerous principle is named,19 and which was used ubiquitously for over 60 years, despite widespread understanding of its terrible public health impact. Whether or not the medical community insists on real evidence that tPA will do more good than harm in acute ischaemic stroke will also reflect how we feel about the introduction of all manner of potentially beneficial, but also potentially dangerous, new treatments.

Jerome R Hoffman MA, MD

A new model of depression with meaningful subtypes will avoid simplistic treatments When you hear the term “major depression”, you imagine a clinically meaningful entity. Think “pseudoentity”, know “paradigm failure”.1 If I took my tegument for dermatological inspection, a diagnosis of “major” or “minor” blotches would be uninformative. I would need more categorical information (eg, freckle, melanoma) to make rational treatment choices. However, non-specificity now rules in depression modelling and treatment. “Depression” is currently viewed as a single disorder, varying dimensionally. The World Health Organization’s international classification of diseases, 10th revision (ICD-10), specifies “mild”, “moderate” and “severe” episodes.2 The US Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV)3 categorises depression as “major depression” (episodes requiring at least five symptoms present for two weeks) and other (including “minor”) disorders. The Plimsoll line for “caseness” (ie, for diagnosis of a depressive disorder) has been further lowered, with two or more depressive symptoms held to define “new” (“subsyndromal” or “subclinical”) mood disorders.4 If the criteria for caseness are progressively loosened so as to capture most of the “blue” population, isn’t the meaning of a “depressive disorder” lost? The logical inconsistency of positing a “subclinical” disorder as a clinical disorder has not, however, discouraged efforts to prove high prevalence, functional impairment and need for treatment. The dominant Zeitgeist views depression as an “it”, a disease having nothing to do with the individual’s personality, and, because “it” is caused by chemical brain changes, requiring an antidepressant drug. However, for those with an antipathy to antidepressants, there are equally effective psychotherapies. Thus, all roads lead to Rome. Such “homogenising” has resulted in efficacy studies (the largest database in psychiatry) producing quite meaningless results.5 “Evidence-based psychiatry” is at risk of becoming an oxymoron. Mere polemic? Let’s consider some data. For “major depression”, efficacy studies quantify all antidepressants (old and new classes compared between and within classes) as equally efficacious,6 and the overall antidepressant drug response as comparable to that for St John’s wort, cognitive behaviour therapy (CBT), other psychotherapies and counselling.5 Why? Data from efficacy studies submitted by pharmaceutical companies for product licensing are problematic. One analysis of data for antidepressants submitted to the US Food and Drug Administration (FDA) showed that, of 47 trials for major depression, there was no drug effect in nine, and a drug–placebo difference of questionable significance for the remainder.7 In another analysis of 52 pivotal placebo-controlled FDA-submitted studies,8 half showed no advantage to the antidepressant drug. “Homogenising” depression and implying “universal” application for treatments leads to the inability to distinguish between differing effects according to differing depressive subtypes. Furthermore, trial selection of pristine subjects (eg, those without comorbidity, in whom melancholic depression is rare) ensures a high response rate in trials (to both active treatment and placebo) and thus their minimal separation. Yet these are the data on which current practice and treatment guidelines are based.9 So, everyone’s a winner — and a loser. Winners? All therapies can claim efficacy. Treatment then risks being determined more by the therapist’s discipline or interest — a Procrustean approach that fits the patient to the therapist’s preferred treatment. Losers? The pharmaceutical companies are challenged for “overselling” the properties of antidepressant drugs, patients feel demeaned in reading that antidepressant drugs are akin to placebos, and practitioner credibility is challenged. Moving along the “overselling” dimension, we are informed that the benefits of CBT have been scientifically proven and that it is the benchmark non-drug therapy. While CBT has credibility, a recent review10 of its efficacy returned the Scottish verdict of “not proven”, in that it lacked any superiority over other psychotherapies or “clinical management”. Despite CBT being held to be useful for multiple psychosocial problems, a recent Cochrane review11 of psychosocial interventions delivered in general practice found “good evidence that problem-solving treatment by general practitioners is effective for major depression”, but limited or conflicting evidence for CBT. As for antidepressant drugs, a potentially useful treatment may “fail” or appear weak if it is not tested on people with subtypes of depression who are likely to benefit. Let’s broaden the argument. Would we be sanguine about grouping all breast lumps (ranging from benign cysts to malignant cancers), testing myriad treatments as universal ones, interpreting the “homogenised” group data as indicative of comparable efficacy, and having an individual’s treatment determined largely by the treating practitioner’s discipline or enthusiasm? We would surely expect that a subtyping diagnosis would be made and that any treatment would be empirically based. Such a standard should also be demanded for diagnosing and managing the depressive disorders. While it is important that the mood disorders be destigmatised and that people be encouraged to seek assessment, it is equally important that they then receive appropriate diagnosis and treatment. Unpublished data from our clinics suggest that bipolar disorder is often missed or misdiagnosed, that the more biological (“black”) depressive disorders are undertreated, and that there is too much reliance on pharmacological treatments for managing non-melancholic disorders. We favour a model for identifying meaningful depressive subtypes that incorporates aetiology, development of a matrix linking subtypes to specific (and non-specific) treatments, testing the model’s utility in “real-world” clinical studies, and promoting broader education of professionals. The model is not intrinsically complex. The complexity lies in recognising and changing the Zeitgeist (see Box). While there is an argument for destigmatising depression with a simple message, there is no argument for doctors continuing to buy simplistic “one-size-fits-all” management recommendations for patients who present for assessment. Recommendations Treatment guidelines for managing the depressive disorders that rely on efficacy data should be regarded as providing tentative information at best. There is no “universal treatment” for depression. As it encompasses mood disturbances, syndromes, disorders and diseases, clinicians should expect heterogeneity, resist simplification, and reject the plausibility of any “universal treatment” model. Clinicians should seek to identify and address the causes of an individual’s disorder, allowing that causes may be biological, psychological and/or social. Assessing disorder “pattern” and aetiology (as against depression severity) allows clarification of the differential impact of various treatments on different disorder “types”. Clinical effectiveness data (assessing the full range of mood disorders and associated comorbidity in “real-world” conditions) should be given more airtime in developing a disorder–treatment matrix.

Gordon B Parker DSc MD PhD

It’s time to stop applying bandaids and get on with real change Despite their protests that it was a “hold-up” and that it “may tragically be the death warrant for some people”,1 last month our state premiers capitulated and signed the 2003–2008 Australian Health Care Agreements (AHCAs). Since then, the healthcare crisis has all but disappeared from the front pages of newspapers and television screens, but, for the community, the crisis remains a daily reality. The desire for healthcare reform, so evident at the recent Australian Health Care Summit,2 will continue, and the demand for the AHCA’s reform blueprint3 to be implemented will only increase in the face of the ongoing inertia of our health ministers. In short, there is now widespread expectation of less political rhetoric and more action. However, sustainable reform requires a change in the political and professional landscape of Australian healthcare. In a keynote address at the Australian Health Care Summit, leading health reform expert John Menadue diagnosed the ailments of our healthcare system, and proffered some cures. His address, Healthcare reform: possible ways forward, appears in this issue of the Journal (page 367)4 as the first in a series of selected addresses to the Summit. Menadue’s diagnostic skill comes from his role in promoting healthcare reform as chair of the New South Wales Health Council,5 and, more recently, as chair of the South Australian Generational Health Review.6 It would seem that Australia’s healthcare system is not at all well. In the upper echelons of healthcare, Menadue has identified a multitude of ailments, including: endemic political buck-passing across jurisdictional divides; lack of public honesty by governments as to what the healthcare system can provide given its limited funding; and a preoccupation on the part of health ministers and their advisers with media management and health micromanagement, much to the detriment of more significant healthcare issues. In essence, our health system is overpoliticised. Short electoral cycles, constant ministerial turnover and the body politic’s demand for instant solutions are not compatible with reforming a large and complex system.7 At a middle level the ailments include: isolated healthcare professionals who run insider debates with little involvement of the community; a system that is hospital-centred at the expense of primary care, population health and community-based care; and a pervading executive ethos of decision paralysis. Menadue’s diagnosis of Australian healthcare is that it is institutionalised, introverted, and wary of innovation and change — a system constantly crying out for “more money please”.4 However, all is not doom and gloom. Menadue also offers possible cures. Most prominent among these is to have Commonwealth and state governments involve the community in setting priorities in healthcare spending. After all, it is about their health and their tax dollars! Reform means change, and change is always difficult to achieve, but a real life example of healthcare reform and change management has been in train in NSW since 1999 (see Box). In that year, the then NSW Minister for Health, Craig Knowles, initiated a major review of the state’s health system by two independent bodies comprising health and other experts, consumer representatives, and headed by prominent individuals from outside the health system. After an extensive and consultative process, the overarching recommendations from one of these bodies, the NSW Health Council, were the need for metropolitan-wide planning of clinical services (including the role of district hospitals in clinical networks) and increased engagement of senior clinicians in planning and administering health services.5 The NSW government promptly accepted the major thrust of the report, and the health minister initiated a cascade of processes to improve healthcare delivery in the greater metropolitan region (see Box).8 The change process is driven by the Greater Metropolitan Transition Taskforce (GMTT), an independent external body established to monitor progress and facilitate progress (see Box). The principles for achieving reform and managing change evident in this NSW experience include: a health minister with vision and political clout; use of respected outsiders to lead independent bodies in exploring frameworks for reform through extensive and inclusive consultation; timely acceptance of major recommendations by the government; delegating implementation of change and progress monitoring to an independent body, outside the bureaucratic stream, but with “buy in” of professional expertise; and, most importantly, giving “experts” the freedom and time to achieve the task. Overriding all of this, however, is the need for a collective political will for meaningful reform. The AHCAs have been signed and our health ministers have an interlude of no more than 4 years. Over a year ago, all our health ministers agreed on an agenda of reform and change.10 If there is no meaningful movement within the next year or so, patients, doctors, nurses and other health professionals have every right to say “a plague on both your houses”.11 Healthcare reform in New South Wales July 1999: The NSW health minister initiated an extensive independent review of the NSW healthcare system which included establishing the NSW Health Council to examine the way the NSW healthcare system delivers care. March 2000: The NSW Health Council recommended developing a single, coherent, long-term, organised plan for metropolitan Sydney.5 May 2000: The Greater Metropolitan Services Implementation Group (GMSIG) was convened by the health minister to examine hospital services. June 2001: GMSIG report, incorporating 162 recommendations related to a broad range of acute hospital services,8 was accepted as NSW government policy. November 2001: Health minister established the Greater Metropolitan Transition Taskforce (GMTT) to implement the GMSIG recommendations, specifically to examine hospital services in the greater metropolitan region, including Sydney, the Central Coast, Hunter and Illawarra. July 2002: $64.5 million annual recurrent enhancement funding ($30.9m to the 22 smaller “District” metropolitan hospitals) targeted to areas that clinicians considered the highest priority.9 December 2003: GMTT to report on achievements in 15 clinical program areas identified by GMSIG and seven additional clinical programs reviewed at the request of clinicians. GMTT convened working groups across these 22 specialty areas, and held open meetings at hospitals across the greater metropolitan region. Over 2000 doctors, nurses, allied health professionals and consumers were involved in the working groups. Selected outcomes to date Establishment of collegiate approach between doctors, nurses, allied healthcare professionals and consumers, and of clinical networks to coordinate services. Sustainable clinical governance with consumer involvement established in 24 hospital disciplines in the greater metropolitan region. 300 new clinical positions established in metropolitan hospitals; 19 stroke units with common treatment protocols established; three new cardiac units established on the periphery of the metropolitan area to provide cardiac angiography; five computed tomography scanners and staff provided; and interhospital transport upgraded. Statewide services coordinated in severe burns, spinal cord injury, brain injury rehabilitation and major trauma.

Martin B Van Der Weyden MD, FRACP, FRCPA

The new guidelines should be useful to all medical practitioners and fair to patients Driving a motor vehicle is a complex task involving perception, good judgement, adequate response time and reasonable physical capability. A range of medical conditions, as well as certain treatments, can impair any of these factors. Such impairment may adversely affect driving ability, possibly resulting in a crash causing injury or death (Box). Case report An eight-year-old girl was walking with her family on a footpath. A car driven by a driver who had poorly controlled diabetes and was suffering a hypoglycaemic episode mounted the kerb, killed the girl, and injured members of her family. The coroner was critical of the driver who failed to take responsibility for his condition, failed to attend medical appointments and education as requested, ignored the obvious risk of his continuing to drive, and deliberately sought to retain his driver licence by “doctor shopping”. The various doctors involved in the driver’s treatment were also criticised for the lack of clarity and consistency of information given to the driver regarding driving restrictions and the lack of action in response to “red flags”. They were also criticised for not notifying the driver licensing authority of concerns about the person’s continued driving.1 Although South Australia differs from most states and territories in explicitly requiring a medical practitioner to notify the authorities of patients who have conditions likely to impair driving, the issue has ethical resonances for the profession nationwide: doctors have significant medicolegal responsibilities regarding their patients and safe driving, and should act accordingly; although doctors must respect patient confidentiality, nearly all states and territories provide indemnity for a doctor to notify the driver licensing authority if an unsafe patient cannot be persuaded to self-notify and continues to drive; and conditional licences may be recommended for patients if certain treatment, compliance, response and review criteria are met. This helps ensure the quality of life for the patient. Doctors should be aware of these options. The newly published Assessing fitness to drive 20032 gives guidance to healthcare practitioners faced with various clinical situations. It also provides specific guidance on conducting medical examinations required by the licensing authorities. The overall intent of these national guidelines is to help clinicians: identify and manage patients who may not be capable of adequately controlling a vehicle (and who are thus a risk to public safety); counsel patients regarding the impact of their condition on their driving ability; inform patients of their legal obligations to report long-term or permanent illnesses or injuries likely to affect their driving to the driver licensing authority; and if needed, because of inaction by the driver and immediate concerns about public safety, advise the driver licensing authority regarding the patient’s fitness to drive. The new publication replaces the existing booklets Medical examinations for commercial vehicle drivers (1997)3 and Assessing fitness to drive (2001) for private vehicle drivers,4 and combines both these booklets into one reference for ease of use. The medical criteria for commercial drivers are more stringent than those for private vehicle drivers, reflecting their extensive time on the roads and the likelihood of more serious consequences of loss of control of, say, a petrol tanker or bus compared with a domestic car. These different criteria are set out in colour-coded format throughout the new book. In addition to combining the standards for commercial and private vehicle drivers, the content has been extensively revised to reflect advances in diagnosis, treatment, and prognosis of various conditions affecting driving ability. For example, increasing recognition of the importance of fatigue and sleep disorders in accidents5 has led to inclusion of the Epworth Sleepiness Scale as a screening tool in the health questionnaire,6 and the more accurate and cross-culturally validated AUDIT questionnaire has replaced the CAGE questionnaire for alcohol dependency screening.7 Similarly, advances in treatment of diabetes, epilepsy, and psychiatric disorders have been incorporated. Much attention has been given to “conditional licences”, whereby a person who does not meet the medical criteria may be supported in retaining a driving licence that is conditional on supplementary criteria relating to compliance and response to treatment, possible driving restrictions, and a detailed plan for monitoring the patient’s condition. This should help in rehabilitation of patients with various conditions, and address concerns about disability discrimination and equal employment opportunity issues. Several legal and ethical issues are also identified in the guidelines. The book emphasises the legal responsibility of drivers to notify the driver licensing authority if they have any permanent or long-term condition likely to affect their driving ability. The relevant state legislation in this regard is included as an appendix. The legislation relating to reporting by healthcare practitioners is also summarised in the book. Most states (with the exception of South Australia and the Northern Territory, where legislation is under review) do not require mandatory reporting by healthcare professionals. However, there remains a duty of care in cases where the healthcare practitioner is aware of the patient’s continuing driving and there is a definite risk to public safety.8 Practitioners who are unsure about confidentiality and notification should consult their medical defence organisation or state driver licensing authority regarding their legal position. The introduction of privacy legislation in most states has also been a consideration, and has led to clarification of the information to be recorded and kept by the practitioner (and to be readily available to the patient/driver), as distinct from the medical information to be provided on a “need to know” basis to the licensing authority. The exception is information required to be provided to the authority under law. This has led to new forms and procedures to guide practitioners. Although overall there is a move to uniformity of licensing procedures in the different states and territories, there are still some important differences. Tables set out these differences for easy reference. In summary, Assessing fitness to drive 2003: outlines clear medical criteria for driver capability, based on available evidence and expert medical opinion; clearly differentiates national minimum standards for licensing drivers of commercial and private vehicles; outlines the legal obligations for medical practitioners and drivers; provides medical examination proformas to help guide the assessment process; provides a reporting template to guide reporting to the licensing authority if required; and provides links to supporting and substantiating information. The new guidelines have been developed through extensive consultation with the medical profession, the licensing authorities, the trucking industry and unions, and lay groups. The development of the book is one of a series of initiatives by the National Road Transport Commission to create uniformly efficient and safe transportation in Australia.9 In recognition of its importance, the book has been signed into force by the ministers of transport of all states and territories. The book has been assessed by general practitioners and found to offer clear clinical and procedural advice for various situations. It is intended the new guidelines will be useful to all practitioners, be fair to patients, and contribute to road safety. Copies of the new guidelines are being distributed to all GPs, and may also be obtained free of charge from state driver licensing authorities. The guidelines are also accessible online from the Austroads website (www.austroads.com.au), and an online tutorial package is being developed to support implementation.

Bruce Hocking FAFOM, FAFPHM, FRACGP · Fiona Landgren B Pharm, Grad Dip Hosp Pharm

The recording process needs to become more efficient, more useful to clinicians and multipurpose Medical records serve a variety of purposes: they reflect the care process, provide a line of communication between clinicians and health services, and constitute legal evidence of referral, presentation, assessment and care given. If it is not in the medical record, it did not happen! They are also used for quality assurance, casemix funding, deriving statistics on diseases and procedures, and research. However, many clinicians seem to regard record-keeping as a chore. Why is it important and how can it be made more efficient and exciting? In this issue of the Journal, the report by Lee and colleagues (page 289) demonstrates an important use of medical records.1 Their study of survival of patients after stroke in Western Australia was made possible by linking morbidity data derived from hospital medical records with death reports using unique patient identifiers. This data linkage project and associated efforts to improve the quality of hospital data are well known in Australia and internationally for their contributions to understanding outcomes of care. Moves to introduce data linking over time and place using probabilistic matching or unique patient identifiers are gathering momentum throughout Australia.2-4 Studies such as that of Lee and colleagues depend on accurate, consistent coding of information on diseases and procedures from patient medical records. The coding process is multifaceted, involving: abstracting from the patient record the diagnoses and procedures to be coded; choosing codes for each diagnosis and procedure; and “sequencing” (ranking) of codes to identify the principal diagnosis, which determines the diagnosis-related group5 for that episode of care. In Australia, considerable effort has gone into developing standards for the coding process. The National Centre for Classification in Health (NCCH), with input from clinicians and clinical coders in all states and territories, has developed an Australian modification of the World Health Organization’s classification of diseases, The international statistical classification of diseases and related health problems, and an accompanying Australian classification of procedures, originally based on the items in the Medicare Benefits Schedule — together making up the ICD-10-AM.6 This publication also includes the Australian coding standards, the “rules” for applying and interpreting the ICD codes. The NCCH maintains these systems, updating not only the categories within the ICD-10-AM, but also colloquial clinical terms, so that coders can match the language in patient records with that in the classification. The NCCH also produces the ICD-10-AM chronicle,7 which maps categories and terms from one ICD-10-AM edition to another, so that coded data can be used for longitudinal studies. Use of the morbidity coding process as the foundation for casemix grouping, and in turn casemix funding or contracting, has turned the spotlight on the accuracy of the coding process. While the emphasis has been on obtaining the “correct” diagnosis-related group, this is possible only if the coding is a true reflection of patient characteristics and care. However, coders can only work with what they are given. To produce quality data, they require accurate, comprehensive medical records that are clearly and concisely expressed and in predictable format. Yet, the quality of many medical records leaves much to be desired, with little change in format or content in the past 40 years. In 1995, the Quality in Australian Health Care study found that over half the medical records reviewed were missing one or more key elements, such as assessment, progress notes, discharge summary, or diagnostic and therapeutic procedures, and that adverse events are less likely to be detected if documentation is missing.8 All this points to the need for revolution rather than evolution. There have been many attempts to improve the quality of medical records, such as the development of problem-oriented medical records9 and, more recently, the move towards electronic medical records. The Clinical Casemix Committee of Australia recently commissioned the NCCH to produce the Good clinical documentation guide10 to help clinicians understand the process of coding and to enhance the quality of coded data. This guide reflects the change in focus from coding for casemix to reinforcing the conjunction between good clinical care, good recording and good morbidity data. To promote a uniform approach to information and communication technologies in the health sector, the federal government has initiated Health Online, a national strategic plan for health information management.11 One Health Online project, HealthConnect, proposes a national approach to electronic health records, with patient “event summaries” collected in standard electronic format at the point of care (eg, hospital or general practice) for retrieval and exchange with other healthcare providers.12 Although this project holds out hope, so far health information has not seen the technological advances that have occurred in other information intensive industries. Much clinical time is devoted to recording the care provided to patients. It is our challenge to make that recording as efficient as possible, to free as much time as possible for clinical rather than administrative functions, and to make the data work for clinical care and for research. Clinicians need to feel that the recording process is useful to them, tied to decision support and the literature, including information about drug interactions and evidence of treatment outcomes. Data extraction should not be an after-the-event exercise but a continuous, real-time process and an intrinsic part of care, occurring at the bedside and integrated with ordering of investigations and prescribing. While electronic health records will impose more discipline on how information is recorded, they will not be a panacea for poor recording practices. We must get our collective act together to promote the goal of recording information once at the point of care for the many subsequent uses, with research a by-product of clinical care. While techniques of data linkage, such as those used in Western Australia, already make a major contribution to this, there is still a long way to go in rationalising record-keeping by clinical staff within and between health services.

Rosemary F Roberts MPH, MBA · Ralph M Hanson FACEM. MPH. MRACPA, FRACP

If we address the obstacles, high quality CAM research is possible About half the general population in developed countries uses complementary and alternative medicine (CAM).1 Yet many conventional healthcare professionals refuse to take CAM seriously — one often-voiced argument is “there is no research in CAM”.2 Certainly, for some modalities there is no compelling evidence base,3 and some of the research into CAM has methodological flaws and biases.4,5 On the other hand, many doctors and medical educators are uninformed about the quality evidence that does exist.6 In this article, I discuss some of the obstacles to developing an evidence base for CAM. Financial obstaclesIn most countries, CAM research funding is on a very small scale. For instance, only 0.08% of the British National Health Service research budget goes towards CAM research.7 Even though recent initiatives in the United Kingdom, United States and Australia have specifically freed up funds for CAM research, these amounts are minute compared with funding in other areas of medicine. It is likely that lack of plausibility of many CAM therapies deters scientific review committees from defining CAM as a priority. A vicious circle may ensue: little plausibility means no funds, therefore no preliminary research, therefore little plausibility. Clinical trials of CAM can be even more expensive than those of conventional medicine. CAM treatments are often therapist-led, effect sizes are often small (requiring large sample sizes), and therapeutic effects may appear only after long treatment periods, all of which mean greater expense. For most CAM modalities, intellectual property cannot be protected; thus commercial investments are rarely forthcoming. This shortage of CAM research funds has three important consequences: it prevents relevant projects from happening; it hinders the development of a research infrastructure similar to that of conventional medicine; and it keeps well-trained career scientists from entering into the field. Methodological obstaclesMany CAM therapies (eg, massage therapy) are physical by nature, which creates methodological challenges. What, for instance, is an acceptable “placebo” control for a trial of massage treatments? Like several other areas of conventional medicine (eg, physiotherapy, surgery, psychotherapy), blinding patients in clinical trials can be difficult or even impossible. Thus the highest level of scientific rigour can be barred to trials of CAM. Many CAM researchers also believe that their holistic approach can not be readily put into the “straitjacket” of a randomised controlled trial (RCT).8 This argument is demonstrably wrong, and its persistence in CAM circles continues to impede efficacy research. One can, of course, conduct an RCT comparing a complex, individualised, “holistic” treatment package to the standard care for that condition. This may require some innovative adaptations to the standard design, but, in principle, RCTs are usually feasible.9 For many people, CAM is an emotive subject. As a result, patients may not want to take a chance with randomisation, and many CAM practitioners may oppose scientific evaluation of their treatments, further hindering clinical trials. There is more to most CAM interventions than meets the eye. For instance, some are based on theories that fly in the face of science. Researchers might conduct a clinical trial of traditional acupuncture, spiritual healing or homoeopathy and see this as a relatively straightforward exercise. Proponents of these therapies may, however, view it as a test of some ancient theories of life forces, spiritual energies or ultramolecular phenomena. Such discrepancies can (and usually do) create unforeseeable methodological problems, as well as obstacles for research and interpretation of results. Ethical obstaclesIt is an important ethical requirement for randomised clinical trials that the investigators be in the state of equipoise (ie, they must believe that the test intervention is at least as good as the control intervention or placebo). If this is not the case (as for many CAM researchers), it is, strictly speaking, unethical for investigators to conduct the study. “Randomisation is only ethical if there is substantial uncertainty about the best treatment for that patient”.10 A further important ethical requirement for clinical research is informed consent from patients or healthy volunteers.11 As mentioned above, this may be difficult or impossible to obtain in an environment where patients’ enthusiasm often is strongly in favour of CAM and against receiving a control (placebo or non-CAM) treatment. Such problems constitute further impediments to good CAM research. ConclusionAlthough high quality CAM research does exist,3 many projects have, in the past, been less rigorous than they could have been. Before we condemn CAM for this situation, we should ask what the obstacles to CAM research are. Removing these obstacles will require dedicating adequate funds to CAM research, attracting career scientists into the field, adequately addressing the complexity of CAM and minimising bias with carefully designed studies.

Edzard Ernst MD, PhD, FRCP

All is not well with Australia’s health system Internationally, Australia’s health system is held in high regard. Our citizens enjoy life spans second only to those in Japan.1 The World Health Organization measures a nation’s health attainment as a composite of the average level of population health and the general distribution of population health or health equality, the level and extent of the health system responsiveness, and the fairness of contributions to health financing by households. According to the WHO’s benchmark — the overall health system attainment index — in 1997, we ranked 12th among 191 nations.1 But all is not well with Australia’s health system. Its edifice is cracking under the strains of a growing mismatch between its capacity to deliver quality healthcare and the changing demands of our communities. Symptoms of the system’s stresses include: the free fall in the number of general practitioners who bulk bill,2 and the consequent threat to Medicare’s principles of universality and equity of access; the short supply of health professionals, particularly nurses3 and general practitioners;4 the increasing occurrence of hospital access block and hospital ambulance bypass,5 and the growing elective surgery queues; the problem of hospital exit block, reflecting the short supply of community-care services, particularly for older people,6 and the breakdown in social networks; the inherent inability of a system organised for acute, episodic care to efficiently provide continuous long-term care;7 and finally the conflict between society’s increasing demand for health services, the high cost of technology-driven medicine and new pharmaceuticals, and the political and fiscal imperatives of the guardians of the public purse. Critical to the viability of our health system are the Australian Health Care Agreements (AHCAs). These 5-yearly political pacts define the joint funding responsibilities of federal and state or territory governments in providing free public hospital services.8 One of the drawbacks of the AHCAs is their impotence in promoting reform. And our health system is sorely in need of reform! This imperative was recognised by Australian ministers of health in April 2002, when they collectively adopted a reform commitment, underpinned by the principles that the federal and state or territory relationship in health funding should ensure that: the provision of optimal care and health outcomes be independent of jurisdictional boundaries; the respective jurisdictions work cooperatively to improve the health and wellbeing of the community; and the next round of AHCAs (2003–2008) be outcome-oriented.8 Suddenly, the winds of change were stirring in Australian healthcare and fanning expectation of reform. The ministers promptly established nine reference groups to address and advise on issues affecting current healthcare. These briefs included the continuum across preventive, primary, chronic and acute care; improving the interface between aged care and acute care; cross jurisdictional cooperation on workforce training and education; the interaction between hospital funding and private insurance; improving Indigenous health, mental health and rural health; quality and safety; and, concluding this impressive and inclusive list, was information technology and research.8 The nine expert groups met, deliberated, and, in record time, in September 2002, presented to Australia’s health ministers a comprehensive agenda for reform.9 The ministers considered the road maps for reforms, and highways were identified for their implementation, but, to date, the reform vehicles have remained locked up in bureaucratic and ministerial garages. In the meantime, the ministers have resumed their adversarial political rhetoric, punctuated as always by fiscal bickering and buck-passing. This return to tiresome political form has undoubtedly fuelled widespread mistrust and cynicism among health professionals and consumers. One outcome of this despair and discontent has been the Australian Health Care Summit held in Canberra on August 17–19, 2003. The Summit was attended by more than 250 delegates, drawn from across the healthcare spectrum. They included academics; administrators; allied health and other professionals; clinicians; consumers, economists; experts in health policy, mental and public health; politicians; and people and health professionals from Indigenous, rural and remote communities. Despite the Summit’s claim to be an independent, bipartisan gathering, the absence of the Federal Minister for Health and Ageing, Senator Kay Patterson, and the minimal representation of the Australian Department of Health and Ageing, were duly noted. Furthermore, the Summit’s claim of independence did not deter lightning forays by the Premier of New South Wales, Bob Carr, and the Leader of the Federal Opposition, Simon Crean. Despite the politics, what did the Summit achieve? It reaffirmed the egalitarian and socially cohesive principles underpinning Australia’s healthcare (Box). It identified inhibitors of and promoters for health reform, which are detailed in the Summit Communiqué.10 The Summit’s sixteen workshops spawned detailed suggestions for reform. Finally, there was a recommendation for an independent national body to drive health reform.10 However, the real message emanating from the Summit was the depth of desire for healthcare reform among consumers and professionals, and the wealth of innovative ideas and solutions that the healthcare community has to offer when committed to the cause. If only one message comes from the Summit it is that Australian healthcare reform is in dire need of political champions and cooperative federalism to harness the people and professional power so evident at the Summit. Without the spirit of cooperation, future health ministers may well look back to 2003 and say “we did nothing”. And that would be a shame. Australian Health Care Summit Statement of principles We believe the following principles must underpin our Australian health system: Universal access – in a timely fashion, to an appropriate service, available because of health needs, not one’s ability to pay; Equity of health outcomes – irrespective of socioeconomic status, race, cultural background, disability, mental illness, age, gender or location; Health care services must be focused on the needs of patients and their carers and the needs of Australians wishing to avoid illness; Health promotion – preventing disease and maintaining health must be appropriately emphasised and balanced with our duty of care to those already unwell; Personal and corporate tax contributions should fund our health care. This is the way we wish to provide health insurance to each other; A fair balance of public and private resources and investment is needed [to] ensure equitable health outcomes for all Australians; The health outcomes of Aboriginal and Torres Strait Islander Australians must be improved so that they match those of other Australians; Health services must be appropriate, safe and of high quality; The community – especially consumers and carers, must play an integral part in the development, planning and implementation of our health services; The health workforce must be valued and appropriately supported.

Martin B Van Der Weyden MD, FRACP, FRCPA

“Illness is the night side of life . . . Every one who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick”. — Susan Sontag Were we too successful in the 19th and 20th centuries? Public health and medicine vanquished many infections and injury as causes of death and disability in the developed world. But a “burden” of chronic disease now rises to challenge us: chronic disease affects at least one in ten Australians,1 and cardiovascular disease, chronic obstructive pulmonary disease and depression are endemic.2 It would be heartening to think that a Polypill might be the answer to our (chronic) ills.3 But the problem lies in the fundamental mismatch between 21st century morbidity and 20th century management — and a better match for the former is unlikely to be simple. We’re coming to realise, as the World Health Organization has, that “as long as the acute care model dominates health care systems, health care expenditures will continue to escalate, but improvements in populations’ health status will not”.4 Take Zajac’s provocative statement on page 250 of this issue, that “if supermarkets offered the same level of customer service as . . . public hospital(s), they would not survive”.5 His unique master proposal will turn hospital organisation (and staff leisure activities) on its head. MacDonald (doctor and BMJ Assistant Editor, who has scleroderma; page 267)6 and Fels (ex-chairman of the Australian Competition and Consumer Commission, who cares for a daughter with schizophrenia; page 268)7 eloquently attest to the deficiencies of our system in this special issue. How would a revamped healthcare system attuned to chronic illness look? Well, we have a dream. It is that Australia’s healthcare system will provide: quality Care that is Centred on the patient, Community-based, Coordinated, Continuous and Cost-effective, and utilises Clinical information systems Can the dream do any better than our current system?The dream is an evidence-based reality, albeit patchily applied, in several parts of the world. A systematic review of trials testing such chronic care models for people with diabetes showed that these improved health outcomes and lowered healthcare costs or use of health services.8 A comparison between Britain’s National Health Service and Kaiser Permanente, a Californian non-profit health maintenance organisation (HMO), showed that, although per capita costs were similar, patients in the HMO received more comprehensive and convenient primary care services, faster access to specialist services and inpatient treatment, and used acute hospital services less.9 These advantages were attributed to an integrated system (including chronic disease management programs and partnerships between physicians and administrators) that efficiently managed hospital use, competition and greater investment in information technology.9 The chronic care paradigm encompasses preventive and therapeutic care, and both must incorporate risk-factor management. As many of the top risk factors for disease burden (such as smoking and physical inactivity)2 involve behavioural change, working in continuous partnership with patients to find common ground is crucial. Such patient-centred care is not a new concept, says Bauman on page 253, but is becoming more evidence-based and can increase adherence to management, reduce morbidity and improve quality of life.10 Evidence is mounting, too, that well-coordinated interdisciplinary teams (intuitively desirable but only recently supported by evidence) can actually benefit people with chronic illness, if team members have the right training, clearly defined roles, and clinical and behavioural skills.11 The evidence that a healthcare system modelled on chronic care benefits its users is compelling. So what will it take to overhaul the system?That nothing succeeds like largesse is a belief dispelled by those who argue that it is the methods of health financing that must change for appropriate healthcare delivery.8,12 Visionary professional and political leaders are vital to the process. For beleaguered healthcare professionals at the frontline, Brooks weighs in with “task substitution” (page 260), freeing up some to focus on their particular expertise.13 Turf-threatening anathema to some, but perhaps it is more important to ensure that our patients get the best care possible. No one can be all things to all patients with chronic illness. Nair and Finucane explore the reforms needed for this postmodern approach on page 257.14 The quest requires a shared vision that echoes our dream: to serve society; to foster generalism and decrease fragmentation; to address the changing nature of illness and the changing nature of practice.15 But, as Nair and Finucane observe, reform will be difficult where health education systems are diffuse, divided and embedded in high-tech, acute or curative medicine, while low-tech chronic and caring medicine is left to drift.14 The supremacy of curative medicine also spills into our research agenda, where reductionist research currently holds sway. According to Professor A Pettigrew, CEO of the National Health and Medical Research Council (NHMRC) (personal communication), more than 60% of the objectives of current research supported by the NHMRC fall within our National Health Priority Areas (asthma, cancer control, cardiovascular health, diabetes, injury prevention and control, mental health, and arthritis and musculoskeletal conditions). Yet much of the supported research is likely to lead to high-tech curative paths. Considering its burden, chronic illness must shoulder its own defined and targeted research agenda: to identify the factors necessary for successful primary and secondary prevention, then evaluate community-tailored programs arising from these data; to explore integrated health delivery systems that embrace our C’s for chronic care management; to be scientifically rigorous and have meaningful performance indicators, allowing evidence-based decision making. The Box recounts the experiences of a man with complex chronic problems being let down by the current health system. In stark contrast is his treatment in a dream system evincing the seven C’s we espoused above. Our biggest success with chronic disease will be to live the dream by dragging our healthcare system into the 21st century. After all, “when you cease to dream you cease to live” (Malcolm S Forbes, publishing mogul and founder of Forbes magazine). Care for a man with chronic illness: as it is and as it could be The reality Lee, a 44-year-old retrenched bank teller, presents with lethargy and heartburn to his GP, Dr Bilius. The GP orders blood tests (normal, apart from mildly raised serum γ-glutamyl transferase levels) and refers Lee to a gastroenterologist for an endoscopy. This confirms mild reflux oesophagitis. Lee is prescribed proton pump inhibitors, which he ceases as soon as his symptoms resolve. One night, he presents to hospital with a sore neck after a minor car accident, and tells the medical officer, Dr Stressius, that his perpetual tiredness contributed to the accident. Dr Stressius notes that Lee smells of alcohol, his blood pressure is raised and there is no serious injury. Blood tests (duplicating previous tests) are performed, and Lee is discharged with a letter for Dr Bilius. Lee loses the letter, but returns to Dr Bilius, who spends 10 minutes chasing the hospital test result by phone. They run out of consultation time, and Lee is advised “not to drink too much”. He does not return until injured in a brawl a month later. The alternative: We have a dream . . . As Lee presents with a “new” problem, Dr Harmonius takes a full history and examination. A picture emerges of someone with dyspepsia, possible depression, alcohol misuse, high blood pressure, and financial difficulties. Dr Harmonius asks Lee to express his biggest problems (“feeling worthless”, “being tired all the time”) and goals (“to get a job”), then explains how his problems may be linked; a few of their adverse effects may obstruct his goals. Together, they decide on a management plan to meet his goals: appropriate tests (including a breath test instead of endoscopy,16 as per Dr Harmonius’s ESP — Evidence Support Program), cycling instead of driving, reducing alcohol intake, and possible medication. Lee is happy to return for regular review by Dr Harmonius. Lee is also referred to a community mental health worker for problem-solving skills and strategies to handle his alcohol problem. He chooses to have his blood pressure monitored by the practice nurse (instead of home telecare17 or ambulatory monitoring) while he’s unemployed. Each time Lee visits Dr Harmonius, the practice nurse initially checks his blood pressure, medications and adherence. Each healthcare professional involved in Lee’s care charts findings and interventions in a central electronic database, which they can access with Lee’s consent. At hospital after Lee’s car accident, the medical officer, Dr Dextrous, notes from the database that Lee has had the appropriate tests to exclude organic causes of tiredness. Dr Dextrous’s own database entry is emailed to Dr Harmonius.

Mabel Chew · Martin B Van Der Weyden

Disease prevention, access to services, and continuity of care are the important areas Health inequities are systematic differences in health status between different groups in the population, and may or may not be changeable. Health inequity is taken here to mean inequalities that “are unnecessary, avoidable, unfair and unjust”.1 Inequities in health usually relate to socioeconomic position, ethnicity or sex. Examples associated with chronic disease in Australia include: Higher mortality rates from cardiovascular disease, diabetes, and renal disease among Aboriginal and Torres Strait Islander populations;2 Higher mortality rates from coronary heart disease, stroke, and chronic respiratory conditions among lower socioeconomic groups;3 and Higher mortality rates from vascular diseases, suicide and accidental death, and lower survival from cancer among people with mental illness.4 One estimate of the size of this effect is that, if disease and injury incidence and mortality in all areas were reduced to the level in the least disadvantaged quintile, the potential savings in lost years of “healthy” life would be 17% of the total disease burden.5 Only some inequalities in mortality are potentially avoidable through the activities of the health and related sectors; analysis of these can indicate opportunities to reduce health inequities. Interventions against potentially avoidable mortality can be divided into three levels: primary (preventing a condition from developing; eg, by treating hyperlipidaemia), secondary (preventing the worsening of a condition at an early stage; eg, screening for and treating early disease), and tertiary (curing disease or extending life through treatment).6 An analysis of trends in avoidable deaths in New South Wales from 1980 to 2000 showed: The burden of potentially avoidable mortality decreased overall and across all socioeconomic status (SES) groups during the 20 years; however, the rate of reduction was higher in the highest SES group than in both the lowest SES group and the rest (middle 60%) of the population. Ischaemic heart disease, lung cancer and colorectal cancer contributed most to this burden in 2000. About half the potentially avoidable deaths are preventable through primary prevention, a quarter through secondary prevention (mainly ischaemic heart disease, stroke, and colorectal cancer), and a quarter through tertiary prevention and rehabilitation (mainly ischaemic heart disease). The proportion of primary preventable causes rose slightly, indicating a relatively greater reduction in causes associated with secondary and tertiary interventions during the period.7 Information on inequities other than mortality is not extensive in Australia, owing to lack of suitable data collections. One study suggests timely and effective ambulatory care (encompassing preventive care and early disease management) may reduce the risk of hospitalisation by preventing an illness, controlling an acute episodic illness, or managing a chronic condition.8 Hospitalisation rates in NSW and Victoria for conditions potentially avoidable through ambulatory care were similar (6.2% and 7%, respectively).7,8 The five most common such conditions were angina; asthma; chronic obstructive pulmonary disease; convulsions and epilepsy; and ear, nose and throat infections. Targeting disease preventionPotential health system responses to health inequities include health promotion, higher treatment levels for targeted populations, more effective treatment (eg, given earlier, or with better compliance) and improved use of resources through better coordination and information sharing.9 The data above indicate that, although a multi-pronged approach will be necessary, the largest population benefit will be through making prevention programs more effective. Well-documented differences in chronic disease risk behaviours include higher prevalence of smoking, obesity, and high blood pressure in low SES groups.3 How prevention strategies can be more effective among low SES groups is the subject of much controversy and little systematic research. Many authors believe that traditional approaches to health promotion will not be effective because the capacity to make “healthy” choices is strongly linked to environmental and social factors that accompany poverty and disadvantage. Determinants of health can be considered at upstream (social, physical, economic and environmental), midstream (psychosocial and health behaviour), and downstream (individual) levels.10 Health promotion within clinical services has traditionally focused on the individual level, although public health preventive activities have generally had the most effect when implemented at upstream levels. Given the limitations of the existing evidence for reducing socioeconomic health inequities, interventions that have been effective with other health problems are a good starting point.11 Targeting access inequitiesAustralian data on potential differential access to services are limited and largely confined to geographic access for people in rural and remote areas. There is no whole-of-population dataset that systematically looks at the quality and effectiveness of care for chronic disease in groups experiencing health inequities. However, studies suggest there is much room for improvement. For example, in 98 000 general practitioner encounters, holders of healthcare cards (who are on aged, disability, unemployment or other low-income pensions) were more likely to have chronic diseases and fewer preventive measures (such as Pap smears).12 At the tertiary care level, patients of lower SES had less access to invasive procedural treatments following admission for coronary heart disease in Queensland.13 As our healthcare system is oriented to acute care, chronic care treatments that reduce disability (eg, joint replacement surgery) are likely to have lower priority and therefore be more difficult to access. Such inequities of access may be greater for dental care, physiotherapy, speech therapy, dietetics and podiatry, which are not subsidised outside public hospitals. Thus, in redistributing resources for health problems where inequities exist, it is important to ensure that the investment is made where the effect is likely to be greatest. Targeting continuity of careAchieving continuity of care across healthcare sectors is a major problem in the care of people with chronic disease, especially those disempowered by way of income, language, or culture. Delivery of care and support services by multiple professionals and agencies compounds the problem. Appropriate rationalisation of such arrangements and good coordination of care can lead to better outcomes. Any attribute of our healthcare system that impairs any health outcome will be compounded for people who are poor or otherwise disadvantaged. Indeed, it will be difficult to redress health inequities for people with chronic disease without addressing the broader problems in the system. However, without specific attention to health inequities in research, planning and policy (see Box), the current differences will not go away, and may even increase. Requirements for addressing health inequities in the care of people with chronic disease Better data on health inequities across the continuum of care, to produce key indicators for regular monitoring. The available data already indicate that a high priority should be given to prevention and management of cardiovascular disease. Appropriate use of data in decision making. The National Health and Medical Research Council (NHMRC) has recognised the potential for clinical practice guidelines to affect health inequities both positively and negatively, and has produced a guide on how to use socioeconomic evidence when developing guidelines.14 Greater investment in prevention, with particular attention to disadvantaged groups. Funding for programs needs to recognise the lack of primary healthcare infrastructure to deliver prevention in many disadvantaged communities and the need to make longer-term funding commitments (5–10 years) for such programs. Local or regional initiatives to ensure active coordination of all care. Funding mechanisms that provide better access to non-medical therapies such as podiatry and dietetics.

Andrew J Wilson PhD, FRACP · Alan D Lopez MSc, PhD · Brian F Oldenburg BA, PhD

It is time for debate to become policy Recognition is growing worldwide that chronic, non-communicable disorders (often, but not exclusively, associated with ageing) and hidden disability are acting in concert with burgeoning technologies to make healthcare more expensive. As communicable diseases are controlled, and social and economic conditions develop to support longer life expectancy, the challenge of preventing and managing chronic disease grows greater. A recent report of the Australian Institute of Health and Welfare confirms that Australia is facing an increasing economic and social burden because of chronic diseases and their associated risk factors.1 Twelve chronic diseases and conditions accounted for an estimated 42% of the total disability-adjusted life years (DALYs) lost in Australia in 1996, and all such diseases and conditions accounted for about 80% of DALYs.2 The report noted the difficulties of defining chronic disease, and concluded that “. . . though open-ended, it is usually defined by a minimum duration (for example diseases lasting 3 or 6 months, continuously or intermittently, may be termed chronic)”.2 Illustrating the semantic divide, a recent report of the United States Institute of Medicine focused on the inadequacy of care of chronic conditions, and defined a chronic condition as one which “. . . requires ongoing medical care, including monitoring, treatment, and coordination among multiple providers, limits what one can do; and is likely to last longer than 1 year.”3 In the mid-1990s, the National Health Target strategies were developed by the Australian government, following the Better Health Commission’s report in 1987. Since then, much more has been written on the need for more efficient and better-coordinated policies for preventing and managing chronic conditions in Australia. A range of viewpoints, disease targets and high-level overviews have emerged in proposals by the National Health Priority Action Council, the National Public Health Partnership, the Department of Health and Ageing Sharing Care Initiative in the 1999–2000 Budget, the Rural Chronic Disease Initiative, the Strategic Research Development Committee of the National Health and Medical Research Council, and advisers forging the next Australian Health Care Agreements.4 US leaders in the development and evaluation of integrated models of care for people with chronic illness, such as Kaiser Permanente, and Group Health Cooperative of Puget Sound, have shown that the burden of chronic disorders can be reduced by informed primary care practitioners and patients working together, supported by evidence from modern information technology.5 Yet in 2003, when other nations have moved beyond talk into detailed proposals for reforming the prevention and management of chronic conditions, Australian governments still debate.3 Gaps in our health policy research into preventing chronic illness and managing and financing chronic care are wide, confirming the lament of a recent editorial in this Journal.6 Three of these gaps deserve special mention. First, while some prevalence rates and use of hospital resources have been estimated, accurate data are lacking about how the total direct costs of managing chronic conditions vary with age, number of risk factors or number of comorbidities. Recent US research provides the first indications of the increases in direct costs as the number of risk factors increases. The increased costs are pronounced for prescribed drugs, and less so for hospital and medical services.7 Disability is a major driver of the direct and indirect costs in an ageing population.8,9 Five conditions (mood disorders, diabetes, heart disease, hypertension and asthma) accounted for 49% of direct healthcare costs in the United States in 1996, and for 42% of illness-related indirect costs.10 To obtain more accurate projections of future care costs, we need new coding systems that measure comorbidities, and linked data sets provided by all care providers and payers. Second, better data about the costs of the prevalent risk factors listed in the Australian Institute of Health and Welfare report1 are essential. The World Health Organization has laid out the empirical rationale for such a campaign against risk factors.11 With these cost data, the economic case for their prevention can be opened to public debate. Economic incentives to the community to reduce their risk and look after their health have not been conspicuous in Australia. Health economists have generally argued against investments in public education and information that might modify demand for healthcare in favour of government regulation of the supply side. They may wish to adapt their arguments in the light of evidence on the impact of demand-side strategies in US chronic disease management trials.12 Third, there is no clear evidence of the success of initial attempts to organise and pay more efficiently for the management of chronic conditions. The first trials of coordinated care in Australia were not designed, managed or funded adequately to demonstrate significant achievements in health and functional status, or cost reductions compared with usual care. The findings from the evaluations of these trials reflect these limitations13 and contrast with the results of the US Medicare Coordinated Care Demonstration14 and with US evaluations of integrated care models, such as the Program of All-Inclusive Care (PACE) for the frail elderly,15 a small subset of the chronically ill. In Australia, the second set of trials of coordinated care is under way. Unfortunately, private health insurers are not much involved. In fact, there is no incentive in the current Reinsurance Pool for private health insurers to provide coordinated care for their members with chronic disorders. This pool reimburses funds whose members receive high cost, lengthy hospital care, while extracting payments from funds with lower cost members. Some state governments, most notably the New South Wales government through the work of the NSW Health Council, have declared an interest in managing several chronic conditions, such as diabetes, chronic respiratory disorders and heart failure. Regrettably, current funding mechanisms and political timidity prevent anything as radical as cashing out all federal payments to allow the states to implement risk-rated capitation funding allocated to the continuum of care needed by chronically ill people. It is time to bring the private healthcare sector into the policy review process. The recent report of the US Institute of Medicine identified the need to make best use of all resources, public and private, in a mix of new types of care, using adequately funded demonstration projects that had the appropriate mix of information technology, evidence-based clinical practice guidelines, coordination of care by multidisciplinary teams, and linkage of universities into the learning process.3 The US government policy review strategy for coordinated care differs markedly from the Australian strategy in one other respect. In July 2000, the lead US government agency sought public comment on both the contents of its proposals and the design features of the proposed demonstrations of coordinated care before it announced awards for 15 new trials in 2002. Most comments identified how the fee-for-service payment system of US Medicare would thwart the program objectives, and, as a result, the payment system for the new trials is a monthly all-inclusive rate covering coordination with community-based services, transportation, drugs, non-covered home visits and medical equipment.13 In Australia, we have achieved reductions in heart disease mortality since the mid-1960s with a combination of prevention and treatment. This should inspire us to believe that we can do well in the future care of patients with chronic disease. Tobacco control, nutrition policies, cancer screening and preventive treatment for those with established cardiovascular disease are examples of what we have achieved to date. We now need larger injections of political will. The early prevention and better coordinated management of chronic conditions will require changes in the methods of financing and paying for healthcare, inspired and supported by strong leadership from our politicians.

Paul F Gross BE, MEngSc, MPA · Stephen R Leeder PhD, FRACP, FFAPHM · Milton J Lewis MA, PhD

Two recent RCTs have clarified the benefits In Australia, about 12% of the population, and 34% of people over 50 years of age, suffer from osteoarthritis.1 The most commonly affected joint is the knee.2 For patients with knee osteoarthritis and symptoms that are refractory to drugs, arthroscopic surgery is often performed. Arthroscopy may be diagnostic or therapeutic, and potentially may delay more extensive surgery such as replacement arthroplasty.3 It allows for resection of meniscal tears and debridement of the articular surface, as well as joint lavage to remove debris and inflammatory factors (eg, interferon gamma), which are believed to be a major but remediable source of the pain of osteoarthritis. The procedure has a low incidence of morbidity and can be repeated.4 Although the number of arthroscopic procedures undertaken for knee osteoarthritis in Australia is not available, a considerable proportion of the 56 000 knee arthroscopies performed each year would be for knee osteoarthritis.2 The role of arthroscopy for osteoarthritis of the knee [is] now challenged. Evidence for the effectiveness of lavage and debridement for knee osteoarthritis comes largely from case series and cohort studies. These have shown that about 50% of patients report pain relief after the procedure.5 Predictors of poor outcomes from arthroscopy include marked malalignment, restricted range of motion, marked radiographic evidence of osteoarthritis, and prior surgery.6,7 Better outcomes are predicted by preoperative mechanical symptoms, such as those resulting from loose bodies or meniscal tears, or radiographic evidence of only mild articular degeneration.8-10 However, other studies have not been able to identify any predictive factors for outcome.11 Two recently reported randomised controlled trials have attempted to clarify the benefits of these forms of treatment. In one, 180 patients with knee osteoarthritis were randomly allocated to tidal needle irrigation or sham irrigation (in which the knee capsule was not punctured by the needle).12 After 12 months, the study found that patients in both groups had a 17% improvement in pain and physical function scores, with no statistically significant difference between the two groups. It was suggested that most, if not all, of the benefit of irrigation was a placebo effect. In a more recent randomised controlled trial, 180 patients were randomly allocated to three treatment groups — arthroscopic lavage and debridement, arthroscopic lavage alone, or sham surgery.5 Follow-up at 12 months found little improvement in patients in each of the three groups (as assessed by outcome measures such as the Knee Specific Pain Scale, the Arthritis Impact Measurement Scales and the SF-36 Health Survey), and no statistically significant difference between the groups. The inclusion of sham procedure groups and the adequate power of these randomised controlled trials allowed them to better address questions about comparative benefits and placebo effects raised in previous smaller randomised trials. However, although selection criteria for both studies were clearly stated, specific clinical indications for arthroscopy were not clearly defined. Such indications can vary considerably between practitioners. A recent study found that agreement between two groups of surgeons (research fellows and attending staff), independently predicting which patients undergoing arthroscopic debridement for knee osteoarthritis would improve, was only slightly better than chance, with neither group predicting the correct outcome more than 59% of the time.13 One indication for which arthroscopic treatment of knee osteoarthritis has been widely regarded as successful is the presence of meniscal tears. Unfortunately, neither of the recent randomised trials analysed patients with meniscal tears separately. Such an analysis would have been especially valuable in the light of a report that meniscal tears in patients with osteoarthritis were not associated with any increase in pain or impairment.14 Few studies specify treatment failure with alternative or less invasive therapies as a prerequisite to enrolment, although this may have a substantial impact on their overall success. An earlier randomised controlled trial found that, of 200 patients screened during the enrolment period, more than half improved sufficiently with conservative medical management (exercise and medication) such that no further medical or surgical treatment was warranted at the follow-up visit.8 The authors noted that “none of the studies of arthroscopy for this population in the orthopaedic surgery literature specified previous rehabilitation treatment . . . and many patients included in previous studies would have benefited from medical and rehabilitation therapy alone”. With the role of arthroscopy for osteoarthritis of the knee now challenged, but concerns about the enrolment criteria of recent studies persisting, there remains a need for further investigation. Randomised controlled trials of surgical interventions are notoriously difficult,15 but, compared with other surgery, there are features about arthroscopic surgery for knee osteoarthritis that would facilitate undertaking such trials. Equipoise over the benefits of the procedure is now well established in the medical literature, and the high prevalence of knee osteoarthritis means that, even if only a small percentage of patients are willing to be enrolled in trials, it is likely that sufficient power could still be achieved to test most clinical hypotheses. In addition to randomised controlled trials, population-based studies are needed. A Canadian evaluation of 14 391 arthroscopic knee debridement procedures for osteoarthritis found that almost 10% of patients required total knee replacement within 1 year after debridement. Rates of arthroplasty were particularly high in those aged 70 or older, and it was suggested that debridement may currently be overutilised in elderly patients.16 Given the increasing prevalence of knee osteoarthritis with an ageing population, it is important for clinicians to recommend options such as arthroscopy with good reason. At present, both the benefits of therapeutic arthroscopy and its role among alternative treatments for knee osteoarthritis remain unclear.

Adam B Chapman BA/BSc(Hons), MPH · Julian A Feller MB BS FRACS

Necrotising arachnidism should be a diagnosis of last resort The article by Isbister and Gray (page 199),1 documenting 130 confirmed cases of bites by white-tail spiders, will, we hope, become one of the last acts in a prolonged and sad medical fable in Australia, regrettably now exported beyond our shores.2 In 1982, a paper on possible spider bite necrosis in Australia was presented at the International Society on Toxinology World Congress in Brisbane,3 and followed by an editorial in the MJA in 1983.4 In 1987, Spring reported a case of severe skin damage following a presumed spider bite;5 the article and the associated editorial6 mentioned the white-tail spider. Speculation about the causative spider continued, with two “likely” candidates charged with the crime by the non-medical media,7 supported by a few in the medical community. These spiders were the wolf spider and the white-tail spider. The former was suspected partly because of evidence from Brazil, subsequently debunked, implicating these spiders in causing skin necrosis. The actual cause in Brazil has since been shown to be recluse spiders (loxoscelism).8 However, it was the white-tail spider, Lampona cylindrata, that was the principal focus of attention. Within a short time, at least a few doctors were diagnosing necrotising arachnidism caused by these spiders, and within about five years the popular association of these spiders with skin necrosis was well established. The lack of strong evidence to support this association seemed to be a triviality to be ignored. Research projects were proposed and funded to examine white-tail spider venom to understand its necrotic potential. Calls were made for governments to fund development of an antivenom. General practitioners regularly and confidently diagnosed skin lesions as “white-tail spider bite”. A few voices called “foul”. Where was the evidence to support the veracity of this new venomous scourge of urban Australia? Some confirmed bites by white-tail spiders were published, with no evidence of skin damage.9 Early research on the venom found no necrotic activity.10 The spider is native to Australia, yet most people ignored questions about the absence of cases of necrotising arachnidism in the 200 years before Spring’s article. Arachnologists questioning the validity of white-tail spider bite necrosis were also dismissed. In both the general and the medical community, the era of “white-tail spider bite necrosis” had arrived. But the evidence cast ever stronger doubt about the veracity of white-tail spider bite necrosis, despite occasional published “cases”. What was needed was a large number of cases of confirmed white-tail spider bite to clearly show the true range of its effects. Isbister and Gray’s article defines a clear and consistent pattern of clinical effects, based on a large series, with no evidence of necrosis. As the authors point out, the inappropriate diagnosis of spider bite in cases of skin damage is not isolated to Australia or the white-tail spider, but our episode is particularly disturbing, because there was never any strong evidence to link this spider with necrosis. Publication of Isbister and Gray’s article should herald the demise of the spurious diagnosis of white-tail spider bite necrosis. This will, we hope, bring an end to conditions such as basal cell carcinoma being misdiagnosed as spider bite, and to cases of feigned white-tail spider bite necrosis (where the patient inflicts skin damage with chemicals, then claims a spider bite). This does not mean spider bite never causes necrosis. Recluse spiders have clearly been shown to cause necrosis in some parts of the world, including two cases in Australia,11 where the spiders have been introduced. However, there is no evidence recluse spiders are widespread in Australia, and it would be erroneous to now label skin damage of uncertain origin as “loxoscelism” instead of “white-tail spider bite”. When presented with skin damage of initially uncertain origin, medical practitioners must look for all the many and varied non-spider-bite causes for such damage, leaving necrotising arachnidism as a diagnosis of last resort and uncertain validity after all other possibilities are excluded. Any future research into necrotising arachnidism in Australia should focus on accurately determining the cause.

Julian White MB BS, MD, FACTM

Balancing commercial patent rights and public interest is a complex matter In this issue of the Journal, Walpole and his colleagues (page 203) squarely raise the difficult issue of balancing public access to genetic health services with enforcement of gene patents.1 They explore this issue using the case study of the hereditary breast cancer gene patents (the BRCA patents).1 This timely and important article coincides with the work of the Australian Law Reform Commission (ALRC). On 5 June 2003, the ALRC released the final report of its joint inquiry with the Australian Health Ethics Committee on the protection of human genetic information.2 The report proposes that access to genetic testing for healthcare should be better regulated, and emphasises the need for ongoing development of ethical standards, particularly in relation to consent and counselling (Recommendations 11-1 to 11-4). The ALRC has now turned its attention to the separate, but related, issue of gene patenting and human health.3 The ALRC will soon be releasing its Issues Paper and calling for submissions. It is likely that limitations on the use of disease gene patents will feature prominently in the submissions and in the ALRC’s responses. The ALRC is required to report its findings by 30 June 2004. The issues associated with gene patents and genetic services are complex and warrant detailed consideration. The role of patents is to encourage innovation, but this needs to be balanced against other values, including equitable access to healthcare. The ALRC may decide that the balance needs to be adjusted. However, a simple prohibition on gene patents is unlikely, of itself, to achieve this end. More comprehensive reform options may need to be considered, including changes to the requirements for obtaining a patent and restrictions on how patents are used. One option might be to include a requirement that the usefulness of the invention be fully examined. At present, the applicant only needs to show that the invention has some commercial value. It may be appropriate to follow the United States’ lead of requiring the applicant to prove “specific, substantial and credible utility”, and restricting the scope of the patent to proven uses.4 Even if patent law is reformed, it will not necessarily assist in dealing with gene patents that are already in existence. As patents have a 20-year life, the effect of the BRCA patents and others could be felt for many years, unless their validity is challenged in the Federal Court. In Europe, L’Institut Curie started proceedings in October 2001, challenging the validity of the BRCA patents.5 Since then, other individuals and organisations across Europe have joined in, including research institutes, hospitals, ministries of health, and human genetics societies. They raise a number of grounds for invalidity, including that the invention is neither new nor inventive. Genetic service providers in Australia could challenge the equivalent Australian patents. However, the costs and risks of such litigation are such that this course of action should not be embarked upon lightly. It is equally important to consider limitations to the ways in which patents may be used. The Patents Act 1990 (Cwlth) grants patent holders the exclusive right to make, hire and sell the invention for the life of the patent. There are few controls on how this right may be used, but the controls that do exist warrant consideration. Sections 133 and 135 of the legislation allow applications to be made for compulsory licences when “the reasonable requirements of the public” have not been met. Although subject to certain limitations, a compulsory licence protects a person from infringement action for using a patented invention without the patent holder’s permission. Perhaps surprisingly, there have been few compulsory licensing applications to date. The Act also provides protection from infringement for “Crown use”: use of the patented invention “for the services of the Commonwealth or State” where “necessary for the proper provision of those services” (section 163). Examples of the applicability of this provision include use of an invention by a state rail authority for construction of rail carriages,6 and use by a local government authority of a meter for measuring water supply.7 It is debatable whether Crown use extends to the provision of public genetic services. In addition to these provisions, the Patents Act 1990 prohibits arrangements that tie use of the invention to use of other products or processes. The role of this provision and of the competition law provisions in the Trade Practices Act 1974 (Cwlth) both need further examination. Although a “research exemption” is often relied on for non-commercial research use of a patented invention, there is no specific law in Australia to support it. The ALRC may recommend that patent legislation should be amended to incorporate this exemption, perhaps together with an exemption for non-commercial clinical use, or it may recommend changes to the other limitations on use discussed above. It may be preferable to adopt the suggestion of Walpole et al and empower an expert body to require broad licensing of patented tests. In making its recommendations, the ALRC has to be mindful of Australia’s international obligations. Australia is a signatory to the World Trade Organization Agreements, one of which is the Agreement on Trade-related Aspects of Intellectual Property Rights (TRIPS).8 TRIPS lays down fairly stringent requirements for the patent laws in member countries. One stumbling block may be the requirement that there should be no discrimination in the applicability of patent rights between technologies (Article 27). Clearly, there are no simple answers to questions about what patents should be granted and what restrictions should be imposed on the ways in which granted patents are used. The ALRC faces a challenging year.

Dianne Nicol PhD, LLM

Some women with pre-eclampsia develop hypertension and cardiovascular disease in later life Pre-eclampsia Awareness Week (August 17–23) is an opportune time to reflect on what we know about this malady. Why does it develop? Can it be predicted or, more importantly, prevented? What will happen to affected women and their babies with further pregnancy? And, finally, does pre-eclampsia have long-term health effects? About one in 10 pregnancies is complicated by hypertension: about 3%–4% have pre-eclampsia, a similar proportion have gestational hypertension and 1%–2% have pre-existing chronic hypertension. The latter is apparent when hypertension is present in the first half of pregnancy, whereas pre-eclampsia and gestational hypertension usually occur later. Despite pre-eclampsia being a placental disease, the mother rather than the fetus may bear the brunt, with, commonly, increased blood pressure, abnormal kidney (proteinuria or renal insufficiency) or liver function (elevated transaminases or severe right upper quadrant or epigastric pain), neurological disturbances including convulsions (eclampsia), and thrombocytopenia or disseminated intravascular coagulation. The fetus may be affected by growth restriction (about one in four cases), and about 20 per 1000 cases die either in utero or as a result of prematurity. Why does pre-eclampsia occur?There appears to be an ill-defined genetic predisposition to pre-eclampsia, with some studies suggesting an autosomal recessive inheritance. However, discordance for pre-eclampsia among monozygotic twins questions some of the genetic postulates. Paternal influence on fetomaternal genetic mismatch is important, and being born of a pre-eclamptic pregnancy increases the likelihood for males of fathering an infant whose gestation will also be complicated by pre-eclampsia. Immune theories abound, largely arising from epidemiological observations that pre-eclampsia is more common in a first pregnancy, and that changing partners for a subsequent pregnancy increases the risk of pre-eclampsia in women with a previous normal pregnancy and decreases the risk in women with previous pre-eclampsia.1 Prolonged sexual cohabitation before pregnancy appears to protect against pre-eclampsia, the implication being that this allows development of greater maternal “tolerance” to paternal antigens present in sperm or seminal fluid.2 Shallow trophoblast invasion of the placental spiral arteries is common in pre-eclampsia, leaving blood vessels that cannot deliver the same placental blood supply as in normal pregnancies. Although this is a common finding, it also occurs in idiopathic fetal growth restriction in which there are no maternal abnormalities. Thus, the factor (or factors) linking placental underperfusion or relative hypoxia to the multisystem effects of pre-eclampsia is yet to be established. Maynard et al3 have recently reported increased placental production of the soluble fms-like tyrosine kinase 1 (sFlt1) receptor, which mops up circulating vascular endothelium growth factor (VEGF) and placental growth factor. sFlt1 given to pregnant rats caused proteinuria, hypertension and glomerular endotheliosis, all features of human pre-eclampsia.3 Whether this factor proves to be significant in humans remains to be seen. Whatever the factor(s) causing pre-eclampsia, it is best understood as a vasoconstrictive process associated with capillary leak and subsequent reduction in perfusion of maternal kidneys, liver, and brain, as well as the placenta. Can pre-eclampsia be predicted?It follows that without a precise understanding of the aetiology of pre-eclampsia there is little we can do to prevent its occurrence. Nonetheless, it now appears that endothelial dysfunction predates the clinical appearance of pre-eclampsia,4 and we know a range of situations in which pre-eclampsia is more likely. These include primipaternity, essential hypertension, renal disease, multiple pregnancies, donor sperm or donor oocyte pregnancy, history of previous pre-eclampsia or maternal or paternal family history of pre-eclampsia, obesity, diabetes and (probably) thrombophilias, such as Factor V Leiden or prothrombin gene mutations. This allows us to screen such women more often during pregnancy for the emergence of hypertension or fetal growth restriction, although this is not a fail-safe method of detecting all such cases. Taking aspirin 60–150 mg/day from about 14 weeks’ gestation until late pregnancy offers a 15% reduction in the likelihood of developing pre-eclampsia, but about 90 women need to be treated to prevent one such case, and it is difficult to select these women.5 Management of pre-eclampsiaThe development of day assessment units has changed our approach to management of hypertension in pregnancy in Australia. Women with hypertension in the second half of pregnancy previously spent weeks in hospital having their blood pressure controlled. This is now almost always done on an outpatient basis; this applies to women with gestational hypertension (about 25% of whom will develop pre-eclampsia at a later stage) and to a selected number of women with mild pre-eclampsia who have initially been observed in hospital. The Magpie trial6 has shown the benefits of magnesium sulfate for convulsion prophylaxis, but most units in Australia have such low rates of eclampsia (convulsions) that use of magnesium sulfate in all women with pre-eclampsia hardly seems justified. Antihypertensive drugs have been shown to reduce the likelihood of episodes of severe maternal hypertension and fetal respiratory distress syndrome, and several antihypertensive drugs, including oxprenolol, methyldopa, clonidine, hydralazine, and nifedipine, are widely used for this purpose. The most important aspect of managing women with pre-eclampsia is timing of the delivery. This means determining when the woman’s condition is deteriorating or when the fetus is at high risk of intrauterine death. Clearly, such management should be undertaken by highly specialised groups, with a team approach of obstetrician, physician, perinatologist and midwife. What happens after pre-eclampsia?The most common question asked by women who have had pre-eclampsia is whether it will occur in subsequent pregnancies. Estimates of recurrence vary enormously — anywhere from 5%–8% in late onset cases to 25% in early onset cases — but there is a gap in our knowledge about recurrence rates in Australian women. To help prevent pre-eclampsia, the Australasian Society for the Study of Hypertension in Pregnancy recommends low-dose aspirin. Women should take aspirin from early in their pregnancy, if, in the previous (pre-eclamptic) pregnancy, delivery was necessary before 32 weeks’ gestation or fetal death occurred.7 Perhaps the more important question is what effect pre-eclampsia has on long-term health. The traditional view was that having pre-eclampsia imposed no greater long-term cardiovascular risk than a normal pregnancy. However, a recent large study from Norway has shown that developing pre-eclampsia before 37 weeks’ gestation imposes an eightfold increased risk of cardiovascular death over a median follow-up of 13 years.8 Given the young age of women with pre-eclampsia, this is quite a significant finding. Further, a study from Scotland has found that both pre-eclampsia and gestational hypertension increase the risk of hypertension in later life, with women who have had pre-eclampsia having an increased risk of death from stroke.9 Based on these findings, it is reasonable to recommend that all women who have had pre-eclampsia should have their cardiovascular risks assessed regularly (ie, annual blood pressure measurement, assessment of fasting lipids and blood sugar every few years) and should be encouraged to maintain a healthy lifestyle to reduce these long-term risks. ConclusionIn Pre-eclampsia Awareness Week, we know that, for most women with pre-eclampsia in Australia, the outcome is a healthy mother and baby. However, pre-eclampsia should now be thought of as a lifelong disorder, with some women destined in later life to develop hypertension, and cardiovascular and cerebrovascular disease. Indeed, it is this recognition of the long-term health consequences for women with pre-eclampsia that is the more recent important achievement in this field.

Mark A Brown FRACP, MD

Australia is lagging behind other developed countries in efforts to control chlamydial infection Australian politicians are concerned about the falling fertility rate and are debating measures, such as cash incentives and paid maternity leave, to reverse the “baby bust”.1 If enacted, these measures are expected to cost several hundred million dollars per year — perhaps several thousand dollars per extra baby. Yet, Australia is at high risk of — if not already undergoing — a silent epidemic of preventable infertility and foetal loss through ectopic pregnancy caused by Chlamydia trachomatis infection. This condition can be detected by a $24 test and effectively treated with a single dose of antibiotics. Some commonly held assumptions about chlamydial infection in men need to be addressed. Chlamydial notifications have increased fourfold over the past decade (Box). However, as most infections are asymptomatic, the 26 000 cases reported in 2002 probably represent only a fraction of the true incidence and prevalence.2-4 This trend may be partly due to a reporting artefact or greater numbers or sensitivity of tests.5 Yet, if these factors were the complete explanation, the graph of notifications should have plateaued long ago. The passage of time and enhanced surveillance data6,7 indicate that most of the increase is real. The proposed National Sexual Health Strategy was shelved before the last federal election, and state-initiated Chlamydia programs designed to enhance case-finding through selective testing by general practitioners (and, therefore, Medicare) were discouraged. Australia is overdue to follow the lead of other developed nations by getting serious about controlling chlamydial infection.8 Because infected women are usually asymptomatic, and because they incur the bulk of the serious morbidity, Chlamydia programs have traditionally focused on screening women.9 Selective testing criteria for women include combinations of age under 25 years, reported change of sexual partner, non-use of condoms, unintended pregnancy, and an inflammatory Pap smear result. However, this testing is only secondary prevention — some women identified in this way will already have silent damage to their fallopian tubes and their fertility. True primary prevention mandates that women never acquire chlamydial infection. As there is no vaccine, this means avoiding infection either by behavioural means (use of condoms, non-penetrative sexual practices or sexual abstinence) or by having male partners who are not infected. In this light, some commonly held assumptions about chlamydial infection in men need to be addressed. The first is that men are less likely to be infected than women. Recent population-based surveys in Scandinavia, the United Kingdom and the United States have consistently shown similar chlamydial prevalences among heterosexual men and women.3,4,10 Higher notification rates for women (Box) probably reflect more testing of women than men.7,11,12 Longer duration of infection in women could also be part of the explanation, although how long untreated chlamydial infection can persist in either sex remains uncertain.13 Another apocryphal belief is that the bulk of men with chlamydial infection present for treatment, driven by genital symptoms.9 However, studies in the community have revealed that most men with urethral chlamydial infection, like women, are symptom-free3,4,10 — perhaps as many as three-quarters10 — and that asymptomatic men are less likely than asymptomatic women to present for testing.10 Although there are few data on the duration of chlamydial infection in men,13 it may be months or years. A better understanding of the duration of infection would enhance our ability to model potential interventions. Sweden has a long and much-acclaimed history of screening women for chlamydial infection. This has reduced the prevalence of chlamydial infection and the incidences of both pelvic inflammatory disease and ectopic pregnancy. However, these successes have begun to reverse recently, with the suggestion that Sweden’s failure to test men is a significant reason.8 Since the advent of urine tests for chlamydia, screening men has become feasible and potentially cost effective (using US parameters).12 Without this screening, the success possible with interventions aimed exclusively at women may be limited.8 To determine whether screening of men is justified, more population-based research is required on chlamydial infection in Australian men. The prevalence of infection in different subpopulations would help determine where future screening initiatives are most needed and provide a baseline for evaluating control measures. Factors associated with infection should be identified and assessed as criteria for selective screening. Studies on the natural history of infection and the cost-effectiveness of interventions would also be of global interest. While definitive screening guidelines cannot be promulgated without such data, clinicians could be remiss if a urine test for C. trachomatis was not part of the routine assessment of a young man who reports unprotected sex with a new sexual partner (female or male), regardless of symptoms. More generally, we should be asking what other factors are contributing to the re-emergence of chlamydial and other sexually transmissible infections in Australia. We also need to debate whether single-sex health models can sometimes ultimately harm women. Most women live in an environment that is also populated by men. Chlamydia trachomatis notifications in Australia Source: National Centre in HIV Epidemiology and Clinical Research (http://www.med.unsw.edu.au/nchecr/)

Marcus Y Chen MRCP, DTM · Basil Donovan MD, FACSHP

Given the controversy over this strategy, Australia should be involved in its evaluation Lung cancer is the leading cause of cancer death in Australia and has a dismal prognosis, with 7800 new cases and 6800 deaths each year, and a 5-year post-diagnosis survival of only 12%. New cases increasingly occur in ex-smokers.1 Helical computed tomography (CT) is a fast and sensitive screening technique that can detect early-stage lung tumours, potentially increasing the proportion of patients who can be offered curative treatment. Newer scanners can perform studies with lower radiation exposure. However, use of this technique is controversial; the studies suggest that it has benefits that are uncontrolled, with no concurrent or randomised comparison group. Proponents of helical CT screening argue that its high sensitivity and the early results of studies showing that it detects small, early stage and operable cancers demonstrate its clear benefits.2,3 In the Early Lung Cancer Action Project in the United States, 1000 asymptomatic smokers or former smokers aged over 60 were screened with low-dose helical CT and conventional chest x-rays; 23% had non-calcified pulmonary nodules detected by CT, while only 7% had abnormalities detected by chest x-ray. Of those with nodules on CT, 12% were eventually diagnosed with malignancy, of which 85% were stage I tumours.4,5 In contrast, only 20% of lung cancers in patients presenting in Victoria in 1995 were localised.6 Other similar uncontrolled studies in the United States, Japan, Germany and Finland showed that from 5%7 to over 50%8 of people screened have an abnormality detected. While many can be investigated with non-invasive tests and reassessment, the substantial rate of false-positive scans requiring potentially hazardous interventions is a real concern. Others argue that studies with no control group are open to severe biases and give misleading results.9,10 Non-randomised comparisons between screen-detected and conventionally diagnosed patients that assess outcomes such as tumour size and survival are open to selection, lead time, prevalence–duration and overdiagnosis bias, all of which tend to make the outcomes in the screened group appear more favourable.11 The experience with previous trials of screening for lung cancer, using chest x-ray and sputum cytology, shows these problems. A randomised trial in Czechoslovakia demonstrated that, in the screening group, 53% of tumours were at an early stage, 25% were operable, and 5-year survival was 23%, compared with figures of 21%, 16% and zero 5-year survival in the unscreened group.12 However, the death rate from lung cancer over the subsequent 15 years was actually higher in the screened group; this discrepancy arises from the biases noted above. A trial at the Mayo clinic in the United States showed similar results.13 A Cochrane meta-analysis of trials of lung cancer screening shows no difference in all-cause mortality (relative risk, 1.01; 95% CI, 0.94–1.08), and a higher mortality from lung cancer in the screened groups (relative risk, 1.11; 95% CI, 1.00–1.23).14 Randomised trials of helical CT screening have begun. The US National Lung Screening Trial started in 2002 and plans to recruit 50 000 high-risk subjects aged 55–74 over 2 years; in the first 6 months, 16 000 subjects have been recruited. The intervention group will be offered helical CT, and the comparison group will be offered conventional chest x-ray, each at baseline and annually for 2 years. Follow-up will continue to 2009.15,16 The trial will have power to detect a 20% reduction in mortality, and costs are estimated at US$200 million. Other smaller randomised trials are in progress. A trial with 40 000 participants has been planned in the United Kingdom, but funding has not been approved. Many non-randomised trials, most linked to the Early Lung Cancer Action Project, are in progress. In 2002, the National Cancer Control Initiative in Australia set up a working group and a wider advisory group to review the state of knowledge of helical CT screening and make recommendations about its future in Australia. Their report recommends that a coordinated analysis of Australian clinical experience with helical CT screening be undertaken, along with a study to determine the prevalence of benign nodules in Australia, which may differ from that in other countries.17 Cost–benefit studies are recommended, largely to assess what degree of mortality benefit would have to be shown by the randomised controlled trials to fulfil acceptable economic criteria for screening. The report concludes that an Australian-based randomised trial would be impractical and too expensive, but recommends that one or more Australian centres should be involved in the international randomised trials. Such involvement would need funding of around $1 million for 3–5 years; but would let us fully contribute to the essential evaluation of a challenging new approach to our leading cause of cancer deaths.

Mark Elwood MD, DSc · Donald A Campbell MD, FRACP · Margaret P De Campo FRACR, MPH

With release of the ALRC/AHEC inquiry report, we are now in a position to develop sound policies The report Essentially yours: the protection of human genetic information in Australia,1 launched in May this year, represents the first comprehensive exploration in this country of the ethical, legal and social implications of the emerging revolution in genetic science and technology. The report is the outcome of a major, two-year, public inquiry conducted by the Australian Law Reform Commission and the Australian Health Ethics Committee of the National Health and Medical Research Council (NHMRC). Although the central themes of the inquiry were ethical standards, privacy protection and protection against unlawful discrimination, the final report examines the impact of the “new genetics” across a very wide range of social and professional contexts — accounting for the “super-sized” 1200-page document, presented in two volumes and containing 144 recommendations for reform. The inquiry covered obvious issues such as the ethical oversight of genetic research and the increasing use of DNA collection and testing by law enforcement authorities. Other questions considered by the inquiry included: the regulation of genetic testing in the workplace; the collection and use of genetic information by the insurance industry; genetic testing by immigration authorities; DNA parentage testing; the use of genetic testing as an element in the construction of kinship and identity; and the use of genetic testing to identify potential sporting champions. This may sound like the stuff of science fiction, but the report documents contemporary cases and controversies in all these areas. In the course of its extensive community consultation effort, the inquiry found significant optimism in Australia about the promised benefits of genetic science for improved diagnostics and therapies. However, there is also an underlying anxiety about the rapid pace of change and the capacity of our institutions to regulate science effectively in the public interest. Thus, the centrepiece of the recommendations is the establishment of a standing Human Genetics Commission of Australia (HGCA). The role of the HGCA would be to provide independent, high-level, technical and strategic advice to Australian governments, industry and the community generally about current and emerging issues in human genetics, and to provide a consultative mechanism for the development of policy statements and national guidelines in this area. One of the threshold questions for the inquiry was whether to accept arguments in favour of “genetic exceptionalism”. This is the idea that genetic information is so fundamentally different from, and more powerful than, all other forms of personal health information that it requires different or higher levels of legal protection. In contrast, genetic “inclusivists” argue that genetic information is neither distinctive nor unique in its ability to predict an individual’s health, but indicates only a rough range of probabilities. The inquiry concluded that an exceptionalist approach would be unhelpful to the extent that it would divorce genetic information from the principles, processes and institutions that have been developed over time to provide ethical oversight of research and ensure best practice in clinical medicine. However, the inquiry accepted that genetic information has some special features and issues that necessitate a thorough inspection of existing principles, practices and safeguards, and of the legal, ethical and regulatory landscape, to ensure these are all adequate to the task. The inquiry concluded that “big law” — an omnibus genetic regulation act — is inappropriate at this time. Nevertheless, the report makes a large number of recommendations for careful fine-tuning of existing legislation in the areas of privacy, discrimination, industrial law, and occupational health and safety, to meet the challenges of the new genetics. For example, it recommends that the federal Disability Discrimination Act 1992 be amended “to clearly prohibit unlawful discrimination based on a person’s real or perceived genetic status”, and that the federal Privacy Act 1988 be amended to cover genetic samples as well as data. The report also strongly emphasises that we need not only adequate protection against the unlawful use of genetic information, but also measures to ensure that, where genetic information may be used lawfully, it will be used fairly and intelligently. As a consequence, the inquiry’s recommendations go beyond simply changing laws — they involve a broad mix of strategies and approaches, including the promulgation of ethical codes, codes of practice and official standards (eg, by the NMHRC and the Federal Privacy Commissioner); industry codes and best practice standards; community and professional education; and better coordination of governmental and intergovernmental programs. Medical practitioners are well aware of how difficult it is to keep abreast of all the implications of the genetic information explosion. The report calls for all the parties involved in medical education (initial and continuing) to work collaboratively to greatly enhance genetics education for all doctors. The report also makes plain the increasingly important role that genetic counselling will play in everyday clinical practice. For some genetic tests, counselling will be adequately provided by medical practitioners; nevertheless, the report recommends that Australian healthcare authorities give urgent priority to assessing and responding to the need for increased, adequately resourced, genetic counselling services. The inquiry recognised the powerful “familial dimension” of genetic information — that is, the extent to which an individual’s genetic information can also reveal information about, and therefore have implications for, that person’s relatives, including those in preceding and succeeding generations. This leads to a recommendation that, despite the traditional importance of confidentiality to the doctor–patient relationship, there may be exceptional circumstances in which doctors (and familial cancer registries) should be permitted to disclose confidential information to genetic relatives without the patient’s consent, if such a disclosure is necessary to lessen or prevent a serious threat to an individual’s life, health or safety. In this sensitive area, the inquiry asks that guidelines be developed to assist healthcare professionals in this task. Some other recommendations of particular interest to the scientific and medical communities are summarised in the Box. The inquiry’s findings and recommendations have been presented to the two relevant federal Ministers — the Attorney-General and the Minister for Health and Ageing — and the government is expected to respond and outline its plans for implementation soon. However, the pervasive influence of genetic science means that recommendations for change have been addressed to more than 30 bodies across the public and private sectors — many of these organisations do not need to wait for the federal government before they can take action. We have an excellent opportunity in Australia now to develop policy based on sound principle, rather than managing emerging problems on the run. The area of genetic testing and information is so personal and so sensitive that it is critical we get this right — and do so now — to avoid the crisis of confidence and the public backlash that would inevitably follow from the revelation of poor or unethical practices. Some specific recommendations of the Australian Law Reform Commission/Australian Health Ethics Committee inquiry National ethical and privacy guidelines should be developed specifically to cover the use of genetic information held in tissue banks, research databases and genetic registers (including “inchoate” databases, such as Guthrie card collections). The support and guidance given to human research ethics committees when reviewing proposals dealing with genetic issues should be significantly strengthened. Laboratories that conduct genetic tests for medical, diagnostic or treatment purposes (rather than for research purposes) should be accredited by the National Association of Testing Authorities, and accreditation requirements should be strengthened to deal more broadly with ethical standards in genetic testing, such as proof of consent. The Therapeutic Goods Administration should be empowered to more effectively regulate medical devices used in genetic testing, as well as DNA test kits provided directly to the public, whether such kits are marketed for health purposes or for identification (such as for parentage testing). Nationally consistent standards should be developed in relation to population genetic screening programs, covering such matters as informed consent, testing standards, quality assurance, cost–benefit considerations, and reporting and data collection. Employers should not be permitted to collect or use genetic information in relation to job applicants and employees, except in rare and compelling circumstances. Such circumstances might be when this is necessary to protect the health and safety of workers or third parties, and the action complies with stringent standards developed for this purpose by the HGCA and occupational health and safety authorities.

David Weisbrot BA, JD · Kerry J Breen MD, FRACP

The recently released PREVENT trial provides some answers Venous thromboembolism (VTE) affects 1–2 people per 1000 in the general population each year.1 It most commonly manifests as deep vein thrombosis of the leg, or as pulmonary embolism. There are many acute provoking factors or triggers (eg, major trauma, recent surgery), and many chronic predisposing factors, both genetic (eg, factor V Leiden) and acquired (eg, cancer). Most patients with provoked VTE have a low risk of recurrence (0–4% per year without anticoagulation), presumably because most have no major predisposing factors for VTE.2 Treatment for provoked VTE is short term and consists of giving intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH) for at least 5 days, followed by warfarin (target international normalised ratio [INR], 2.0–3.0) for 3 months.3 Further antithrombotic therapy is usually not required unless patients are re-exposed to known triggers for VTE. Standard-intensity therapy with warfarin remains the treatment of choice for the long-term prevention of recurrent VTE in patients who are at highest risk of recurrence Most patients with unprovoked VTE, however, have a higher risk of recurrence (≥ 5% per year without anticoagulation) over many years.4,5 This is because they are chronically exposed to one or more underlying genetic or acquired predisposing factors for VTE, which may be identifiable from the clinical history or through laboratory testing. Furthermore, the absence of a provoking factor or trigger for VTE is the most important predictor of recurrence in these patients. They require longer-term or indefinite treatment, which consists of giving intravenous unfractionated heparin or subcutaneous LMWH for at least 5 days, followed by warfarin (target INR 2.0–3.0).3 This is standard-intensity anticoagulation therapy, and is highly effective in preventing recurrent episodes of VTE for as long as it is continued. In trials in which patients were treated for a median of 4–6 months, it reduced the absolute risk by 7.6%, which is equivalent to preventing one event for every 13 patients treated (odds ratio [OR], 0.15; 95% CI, 0.10–0.23).6 In patients considered at highest risk of recurrent unprovoked VTE (eg, > 10% per year; see Box), warfarin therapy is continued indefinitely, whereas in most patients, it is discontinued after 6–12 months.3 This is because long-term anticoagulation is associated with a cumulative risk of bleeding, which is perceived to outweigh its benefits in preventing recurrent VTE. Standard-intensity therapy with warfarin causes minor "nuisance" bleeding in 5%–15%, major bleeding in 2%–3%, and fatal bleeding in 0.2%–0.6% of patients each year.7 A hitherto burning question for patients with unprovoked VTE is whether there are other anticoagulant treatment regimens with a more acceptable benefit-to-harm ratio, such as lower-intensity oral anticoagulation therapy. The recently reported Prevention of Recurrent Venous Thromboembolism (PREVENT) trial was initiated in July 1998 to test the hypothesis that long-term, low-intensity warfarin therapy (target INR, 1.5–2.0) might provide a safe and effective method of reducing the risk of recurrent VTE among patients who had a previous idiopathic (unprovoked) venous thrombosis.8 After completing at least 3 months of standard-intensity warfarin therapy (target INR, 2.0–3.0), 508 patients were randomly allocated to receive low-intensity warfarin therapy or placebo in a double-blinded fashion. The trial was terminated after a mean follow-up duration of 2.1 years because there was strong evidence of efficacy of warfarin. Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), compared with 14 of 255 patients assigned to low-intensity warfarin therapy (2.6 per 100 person-years). This represents a relative risk reduction of 64% (hazard ratio [HR], 0.36; 95% CI, 0.19–0.67; P < 0.001), and an absolute risk reduction of 4.6%, equivalent to one event prevented for every 22 patients treated for 1 year. Bleeding episodes necessitating hospitalisation occurred in two patients in the placebo group (0.4 per 100 person-years), and five patients in the warfarin group (0.9 per 100 person-years); this difference was non-significant (P = 0.25).8 Although the PREVENT trial showed no significant excess of major bleeding with low-intensity warfarin therapy compared with placebo, event rates were low (5 v 2), and the 95% confidence intervals do not reliably exclude even a 13-fold increase in risk of major bleeding (HR, 2.53; 95% CI, 0.49–13.03). Yet, there is no doubt that low-intensity warfarin causes bleeding. In the PREVENT trial, "minor" bleeding was significantly increased in the warfarin group compared with the placebo group (12.8% v 6.7%; HR, 1.92; 95% CI, 1.26–2.93), with an increase in absolute risk of 6.1%, equivalent to one minor bleed caused for every 16 patients treated for 1 year. The results of the PREVENT trial indicate that low-intensity warfarin therapy is effective for long-term prevention of recurrent VTE. However, it was not shown to be sufficiently superior to placebo for low-intensity warfarin to be adopted for this indication. Standard-intensity warfarin is also superior to placebo when continued for up to 4 years after an initial thrombotic event.6,9-11 Indeed, it almost eliminates the risk of recurrent VTE in patients who continue the therapy, but is not routinely used because of the bleeding risks. Mini-dose warfarin therapy (fixed-dose, 1–2 mg daily) has never been shown to be effective for this indication, while low-intensity warfarin therapy is unlikely to offer any advantages over standard-intensity therapy in terms of convenience, and would only be a viable alternative if it were significantly safer. Indirect comparisons of the relative effectiveness and safety of low-intensity and standard-intensity therapy with warfarin, compared with placebo, are unreliable.8-11 For example, the apparently lower rates of bleeding in the PREVENT trial when indirectly compared with previous trials of warfarin might simply be explained by differences in patient selection. The PREVENT trial randomly allocated patients to treatment or placebo after they had completed a median of 6.5 months of warfarin treatment, and also included a 28-day run-in phase. It is thus likely that patients at increased risk of bleeding were excluded from the long-term phase of the study. By contrast, in most previous trials of long-term standard-intensity therapy with warfarin, patients were randomly allocated after no more than 3 months of treatment. This is as unreliable as comparing two sporting teams by their respective performances against another team rather than having them oppose each other directly. Indeed, the results of a recent direct head-to-head randomised comparison showed that low-intensity warfarin therapy was not only less effective than standard-intensity therapy for preventing recurrent VTE (absolute risk increase of 1.3% per patient year, equivalent to one event caused for every 77 patients treated for 1 year), but provided no advantage in terms of major bleeding (1.0% v 0.9% per patient-year; HR, 1.0; 95% CI, 0.4–2.7) or minor bleeding (4.9% v 3.6% per patient-year; HR, 1.3; 95% CI, 0.8–2.1).12 Taken together, these results indicate that standard-intensity therapy with warfarin is more effective for preventing recurrent VTE than low-intensity warfarin therapy, which, in turn, is more effective than placebo. However, because low-intensity warfarin therapy does not appear to be any safer in terms of bleeding and still requires close laboratory monitoring, it is difficult to justify this approach as an alternative to standard-intensity therapy for the long-term prevention of VTE, irrespective of a patient's baseline risk of recurrence or bleeding. The implications of these results for clinicians are that standard-intensity therapy with warfarin (target INR, 2.0–3.0) remains the treatment of choice for the long-term prevention of recurrent VTE in patients who are at highest risk of recurrence (eg, history of recurrent unprovoked VTE, major predisposing factor such as cancer; see Box) or with an initial life-threatening event (eg, major pulmonary embolism), and low risk of haemorrhagic complications. For patients with a first episode of unprovoked VTE or at increased risk of haemorrhagic complications, to decide about long-term treatment, doctors need to weigh the absolute risks of recurrent VTE and bleeding complications with and without warfarin treatment in each patient. In most cases, this is likely to result in the discontinuation of treatment after 6–12 months. The implications of these results for researchers are that more data are required to improve the reliability of clinical and laboratory predictors of recurrent VTE and haemorrhagic complications in individual patients, and that randomised controlled trials are required to evaluate the effectiveness and safety of alternative long-term antithrombotic therapies (eg, ximelagatran,13 antiplatelet agents) that are likely to be more convenient or have a more favourable benefit-to-risk profile than either standard-intensity or low-intensity warfarin therapy. Major determinants of the risk of recurrent venous thromboembolism Low risk (0–4% per year) Provoked event* Isolated distal deep vein thrombosis Intermediate risk (5%–10% per year) First unprovoked event Major predisposing factor(s)† Highest risk (> 10% per year) More than one unprovoked event First unprovoked event plus major predisposing factor(s)† Active cancer * Provoking factors include, in the last 3 months: hospitalisation, major surgery, trauma, leg fracture, plaster cast, puerperium. †Major predisposing factors include: prolonged immobility, neurological disease with paresis, homozygosity for factor V Leiden, combined (multiple) thrombophilic abnormalities, antiphospholipid antibody syndrome, inferior vena caval filter. Cancer is also a major predisposing factor but is mentioned separately because it is such a strong predisposing factor in its own right.

John W Eikelboom FRACP, FRCPA · Graeme J Hankey MD, FRACP

The multisector approach to reducing smoking may be a good model for tackling physical activity Over the past year, the signals that physical activity is a critical community issue in Australia have become overwhelming. The increasing obesity of Australians has attracted the attention of our politicians and spawned obesity summits in New South Wales and Victoria; these both recognised that the energy expenditure imbalance (physical activity versus diet) is key to the obesity epidemic.1 Related to obesity is an inexorable increase in the prevalence of type 2 diabetes. The recent seminal Diabetes Prevention Program trial demonstrated that physical activity and dietary modification are effective lifestyle strategies for curbing this problem.2 In the area of cancer control, a notable event in the past year was the Eat and Run Conference hosted by the New South Wales Cancer Council, where evidence was presented that regular physical activity contributes to preventing colon and breast cancer.3 The past year has also seen reports that reinforce the benefits of regular physical activity in preventing coronary heart disease4 and falls in the elderly,5 and in reducing depression.6 Thus, physical activity is a pivotal public health issue, contributing to the prevention and management of at least six of Australia's seven current national health priorities: cardiovascular disease, cancer, mental health, diabetes, injury and musculoskeletal problems. However, the prevalence of inactivity in our communities is high and increasing. In 2000, 42% of Australian men and 44% of women did not partake in the levels of physical activity recommended by the National Physical Activity Guidelines (30 minutes of moderate-intensity activity, accumulated in bouts as short as 10 minutes, on most days of the week, or 20 minutes of vigorous-intensity activity on at least three days).7 These data revealed an increase in the prevalence of inactivity from 1997, when it was 37% among men and 39% among women.7 Over the past decade, there have been numerous calls for general practitioners to address physical activity and other behavioural risk factors. Along with these calls have come an increasing number of studies evaluating physical-activity interventions delivered in primary care. The National Institute of Clinical Studies (NICS) in Australia funded a systematic review of published studies, which was completed late in 2002 and included 20 studies.8 While most interventions entailed verbal advice and written information materials, they differed in scope (some targeting physical activity only, others addressing multiple risk factors); intensity (brief advice through to more intensive counselling with multiple contacts); method of delivery (physicians, nurses, health educators or exercise scientists); and target audience (all adults, older people only, interested volunteers or whole patient populations). The review concluded that there is evidence that interventions in primary care can increase physical activity in the short term. Notably, brief interventions appeared to be as likely to succeed as intensive interventions, although there was insufficient evidence to identify other attributes of successful interventions. The NICS review is one of several recent reviews that support the contribution that GP interventions can make to promoting physical activity.9,10 A notable dissenting opinion came from the recent United States Preventive Services Task Force review of clinician counselling to promote physical activity,11 but this review included only eight studies published since 1994. Overall, the level of supporting evidence for GP interventions offers encouragement. However, much still needs to be done to promote greater attention to physical activity in general practice, given that lack of time and a perceived lack of patient interest are major barriers reported by GPs.12 The NICS review offers a practical way forward in light of these barriers. It recommended brief physical-activity interventions specifically for patients with risk factors or health conditions that could be modified by increased activity. This approach should not require a major investment of time from already busy GPs and, by directing interventions to patients with current health problems that could be alleviated by physical activity, is more likely to be well received by patients. Despite the growing evidence about general practice-based physical-activity counselling, until recently there had been no efforts to disseminate intervention materials or protocols for GPs to use. However, agencies like the National Heart Foundation and the Victorian Council on Physical Activity and Health have been working with health authorities in several states to develop tools to help GPs to promote physical activity. An example of these is the Active Prescription protocol disseminated by the National Heart Foundation in NSW.13 It provides a format for delivering brief advice to patients about physical activity and also serves as a written record of this advice for doctors and patients. An electronic version has been included in the latest version of the Medical Director clinical management software (Health Communication Network, Sydney, NSW). These efforts are promising and require continued support, together with continued research on the effectiveness of the interventions, as well as dissemination strategies. Numerous social and environmental factors lead to physical inactivity in Australia. Thus, addressing this public health priority will require the sustained involvement of a range of sectors in addition to primary healthcare (eg, transport, urban development, education, sport and recreation). We can look to the past three decades of efforts to reduce smoking as an example of an integrated, multisector approach that has significantly reduced population levels of smoking. As with smoking, GPs — the preferred source of health information for most Australians — have a key role to play in promoting physical activity.

Ben J Smith PhD · Elizabeth G Eakin PhD · Adrian E Bauman PhD, FAFPHM

Risk factors and diseases in developing countries are becoming "westernised" Cardiovascular disease is usually considered to be the scourge of wealthy countries. However, the recent World health report1 draws attention to the increasing importance of cardiovascular disease in developing countries. The report identifies principal risk factors and diseases in regions of the world divided into three categories: developed countries, developing countries with low mortality rates, and developing countries with high mortality rates. It is no surprise that the leading risk factors contributing to disease, disability and death in developed countries are tobacco consumption, high blood pressure, high cholesterol level, overweight, low fruit and vegetable intake, and physical inactivity (Box 1). Coronary heart disease is the leading cause of death and disability, and stroke ranks third. In developing countries with high mortality rates (eg, Nepal, Myanmar, the Maldives and numerous African countries), factors such as underweight and unsafe sexual practice are more important than risk factors for non-communicable diseases. Nevertheless, tobacco consumption, high blood pressure and high cholesterol levels are still responsible for substantial morbidity and mortality (Box 1). The five leading causes of death and disability in these countries are HIV/AIDS, lower respiratory tract infections, diarrhoeal diseases, childhood diseases and low birthweight — coronary heart disease ranks eighth. Countries between these two extremes have rapidly changing profiles. In these low-mortality developing countries (eg, Cambodia, China, and Fiji), "developed country" factors have already outstripped traditional "developing country" factors in terms of importance for overall disease, disability and death (Box 1). In these countries, the juxtaposition of underweight with overweight as the fourth and fifth leading risk factors, respectively, starkly exemplifies the "double burden of disease" they carry. Following an upsurge in "developed country" risk factors in these countries, stroke is now the second most important cause of disability and death, and coronary heart disease the sixth. Unfortunately, the health services of low-mortality developing countries have not been able to adjust quickly enough to these changing disease profiles. The lack of epidemiological data on diseases and risk factors has hampered appropriate health service development and responses. A number of Australian organisations, including the Institute for International Health (IIH) at the University of Sydney,2 are trying to address these issues, with a focus on our neighbours in Asia and the Pacific region. The IIH has recently introduced initiatives, involving data collection and analysis, as well as technology transfer and capacity development, with partners in China, India and Thailand.3,4 The IIH has also worked with Asia–Pacific partners in multicentre trials and epidemiological studies, including the Asia Pacific Cohort Studies Collaboration (APCSC). The APCSC is a collaborative project that seeks to pool data from existing longitudinal studies with information on cardiovascular disease in the region. The project database now has data on 659 000 adults in eight countries (Box 2), making it one of the largest medical studies ever, and certainly the largest in the Asia–Pacific region. The collaboration aims to produce reliable regional estimates of the excess risks for coronary heart disease, stroke, total cardiovascular disease and all-cause mortality associated with a number of risk factors, and to accurately compare risk-factor associations between ethnic groups, age-specific groups and the sexes. After several years of compiling data, obtaining cooperation of key individuals and devising appropriate methodology, initial reports from the APCSC have begun to appear.5-7 These reports underline the increasing importance of cardiovascular disease in the less developed parts of the region, and show that the risk factors applicable in Australia are just as important elsewhere. This is a crucial finding that has not previously been established with large numbers. For instance, the analyses show that people with diabetes are about twice as likely to die from heart disease or stroke, regardless of whether they live in Asia or Australasia.5 Increasing levels of obesity across the region will lead to a considerable increase in diabetes and its sequelae, such as cardiovascular disease. Further, the research shows that younger people with diabetes have much larger excess risks for cardiovascular disease than older people. Asia, with its predominantly young population, can thus expect an even greater increase in cardiovascular disease than that anticipated in Australia. The challenge now is to use the results from the APCSC, and other relevant studies, as a starting point for tackling the global problem of cardiovascular disease highlighted by the World health report.1 In developing countries, substantial health gains can be made for relatively modest expenditures. In human terms, this means that much ill-health and millions of premature deaths can be avoided. As far as cardiovascular disease is concerned, a necessary step will be to develop accurate risk algorithms, specific to local situations.8 These algorithms would help in developing treatment and prevention strategies to target overall risk. For example, strategies to reduce salt intake and lower cholesterol level have been shown to be very cost-effective.1 Blood-pressure-lowering drugs are likely to benefit not only people with hypertension, but also normotensive people at high risk of cardiovascular disease.9 The ultimate aim will be to develop strategies with maximum benefit for minimum cost. This is especially the case in developing countries, where the conflicting demands on a meagre pool of resources make the need for cheap, finely-targeted strategies absolutely crucial. 1: The 10 leading selected risk factors for death and disability, by type of country1 High-mortality developing countries Low-mortality developing countries Developed countries 1 Underweight Alcohol consumption Tobacco consumption 2 Unsafe sexual practices High blood pressure High blood pressure 3 Unsafe water, poor sanitation and poor hygiene Tobacco consumption Alcohol consumption 4 Indoor smoke from solid fuels Underweight High cholesterol level 5 Zinc deficiency Overweight Overweight 6 Iron deficiency High cholesterol level Low fruit and vegetable intake 7 Vitamin A deficiency Low fruit and vegetable intake Physical inactivity 8 High blood pressure Indoor smoke from solid fuels Illicit drug use 9 Tobacco consumption Iron deficiency Unsafe sexual practices 10 High cholesterol level Unsafe water, poor sanitation and poor hygiene Iron deficiency 2: Geographical distribution of studies presently included in the Asia Pacific Cohort Studies Collaboration

Mark Woodward · Michael A Reid

Sex analyses in studies can have clinical implications In the past decade, biomedical and behavioural research has provided evidential credibility for the field popularly known as "women's health".1,2 During this time, heightened interest and increased resources were given to the study of "conditions unique to women",3 and to sex and gender differences in health.4 These efforts have increased our understanding of the aetiology, prevention, management and health outcomes of many conditions that affect women.5 In doing so, this research has progressively widened its focus from reproductive conditions to concepts of health throughout women's lives. It has also influenced the culture of science and the paradigms by which scientific studies are now designed and conducted.1,6 Policies for research supported by the US National Institutes of Health (NIH) now mandate the involvement of sufficient numbers of women in studies to determine whether sex/gender differences exist. The US Institute of Medicine of the National Academy of Sciences has recommended that researchers should disclose the sex of origin of cell and tissue cultures used in research; and biomedical journals are beginning to recommend that investigators report analysis of data by sex.7 Research continues to document many sex/gender health differences (Box 1 and Box 2) and is beginning to define gender-specific preventive measures, risk factors, or treatments. For example, different clinical manifestations of heart disease in women have been noted,8 as have potentially fatal sex-based arrhythmias for women in response to some cardiac drugs.9 Another example of how results from sex analyses in studies can have clinical implications is the demonstration that women are more likely to have a lower threshold for pain and may be more responsive to some analgesics such as kappa-opioids.10 In the United States, the drive for dedicated women's health research came from public policy and grassroots activists.11 In response, the NIH established the Office of Research on Women's Health (ORWH) within the Office of the NIH Director in 1990.12,13 The ORWH advises the NIH Director and staff on women's health research matters; ensures that NIH-supported research adequately addresses women's health issues; ensures that women are appropriately represented in biomedical or behavioural research; and, develops opportunities for and supports the involvement and advancement of women in biomedical careers. Other agencies within the US Department of Health and Human Services address aspects of women's health that fall within their mission, including healthcare services, drug regulation, or health policy.14 It was subsequent to the initial research agenda on women's health in 1992,15 that the ORWH emphasised research that encompassed the totality of factors influencing women's health across the life span. Since 1999, with the eight-volume Agenda for research on women's health for the 21st century,16 increased emphasis is now given to interdisciplinary research, disease prevention, analysis of research data by sex/gender and the inclusion of diverse populations of women in studies. This is to enable the exploration of factors that contribute to differences in health outcomes and in responses to therapeutic interventions. Research priorities are directed to: the relationships between early life activities and health or ill health in later life; the role of personal behaviours and lifestyle choices in the health and ageing processes (focusing on such issues as obesity, exercise, addiction, and smoking cessation); and many other delineated areas. These include multisystem disorders, mental health and addiction, complementary and alternative medicines, violence and quality of life. A January 2003 workshop sponsored by the ORWH in Washington, DC, "Science meets reality: recruitment and retention of women in clinical studies and the critical role of relevance", examined the lessons we have learned from the past decade such as: ways to recruit and retain women in clinical studies; the importance of community participation in the design and planning of a study to facilitate recruitment of participants from that community; how investigators can better communicate with potential volunteers, show respect for vulnerable people and avoid the use of coercive recruitment tactics; and the means to ensure that clinical research is relevant and targets questions important to public health. The workshop also identified emerging ethical and policy issues including: the need to appreciate how sex differences should be taken into account in the design of clinical research; the shift from the ethics of protectionism (that often resulted in exclusion of women, especially pregnant women or women of childbearing age, from research to "protect" them from harm) to the ethics of inclusion (recognising the need to include women of all ages in studies as long as the potential results would not cause harm); concepts of justice in research, such that potentially beneficial research would not just be offered to one group of volunteers or patients, and that all populations subject to a disease or condition have the right to be studied — a concept embodied in the NIH policies requiring the inclusion of women (and minorities) in human subject research; and, the differences between clinical care and clinical research. Finally, one of the most critically important issues is the translation of clinical research into practice, which becomes especially apparent when research outcomes contradict established clinical practice.17 This happened in 2002 when the outcomes of the oestrogen/progestin postmenopausal hormone therapy arm of the NIH-funded Women's Health Initiative randomised controlled trial became available.18,19 The study provided definitive evidence that long-term therapy with combination oestrogen and progestin does not reduce cardiovascular disease in postmenopausal women (as had long been thought), but rather had unexpected results — showing an increased risk for cardiovascular disease as well as an increase in risk for breast cancer. Such studies provide strong justification for continuing research to document risks versus benefits of common, but unproven, approaches to disease prevention and treatment of women. At present, efforts focusing on translating research findings into healthcare include the Specialized Centers of Research on Sex and Gender Factors Affecting Women's Health, an innovative initiative which supports both basic and clinical projects related to research priorities that can advance scientific discoveries from "bench to bedside".20 Research on women's health and sex and gender factors is providing the data with which to better arm the physician for possible variations in approaches, drug dosages, or diagnostic practices for not only women but also men. This new knowledge is creating new challenges to ensure that future physicians possess a full understanding of how to better provide gender-appropriate healthcare.21-23 1: Definitions Sex: refers to being male or female according to reproductive organs and functions assigned by chromosomal complement Gender: refers to socially defined and derived expectations and roles rooted in biology and shaped by environment and experience 2: Known sex/gender health differences Heart disease: presentation, outcomes, and responses to intervention HIV/AIDS: manifestations and progression Pain: response to pain and pain therapies Depression: clinical features and management Diabetes: prevalence and care, especially type 2 diabetes Musculoskeletal diseases: incidence and effect; eg, of osteoarthritis, osteoporosis and sports injuries Autoimmune diseases: mortality

Vivian W Pinn MD