General medicine

Objective: To determine changes in morbidity and management of disease in children in Australian general practice.Design and setting: A comparative study of general practice consultations in children under 15 years, using data from cross-sectional general practice surveys (1990–91 and 2000–01), and a descriptive comparison with a similar study from 1971.Main outcome measures: Relative rates of management (rate/100 general practice encounters) of the most common children’s problems and treatments.Results: Problems with significantly higher management rates in 2000–01 compared with 1990–91 included vaccination (11.1 v 7.6 per 100 encounters in 1990–91) and contact/allergic dermatitis (3.1 v 2.5). Those managed significantly less often in 2000–01 v 1990–91 included acute otitis media (7.7 v 9.4), asthma (5.4 v 8.8), tonsillitis (4.4 v 6.0), acute bronchitis (3.8 v 5.3) and gastroenteritis (1.7 v 2.7). Asthma management rates rose from 2.4% of all problems managed in 1971 to 7.2% in 1990–91, then fell in 2000–01 to 4.6%. More frequent rates of counselling and advice in 2000–01 (28.4% of encounters v 22.9% in 1990–91) were associated with a decrease in rates of prescribing and supply of medication (56.6% of encounters v 64.3% in 1990–91). Antibiotic prescribing declined significantly (from 33.8 per 100 encounters in 1990–91 to 25.2 in 2000–01), as did prescribing of respiratory medications (from 15.5 to 9.9 per 100 encounters), while prescribing of vaccines and systemic corticosteroids doubled (from 9.6 to 18.8 per 100 encounters, and from 0.6 to 1.2, respectively). (All comparisons between 1990–91 and 2000–01 are significant at P < 0.01.)Conclusions: These findings point to the emergence of a generation of Australian children who are generally well vaccinated and are less likely to present to GPs with “traditional” childhood illnesses.

Janice Charles BA, MSc(Med) · Ying Pan MCH · Helena Britt BA, PhD

Objective: To assess if there are any differences in statin prescribing across Australia by socioeconomic status or sex and to relate prescribing rates to coronary heart disease (CHD) mortality rates.Design: Cross-sectional study using data on statin prescribing by age, sex and patient postcode for the period May to December 2002.Setting and participants: The Australian population, stratified by sex and quintile of Index of Relative Socio-Economic Disadvantage (IRSD).Main outcome measures: Age-standardised rates of statin scripts per 1000 population per month for each sex and IRSD quintile.Results: 9.1 million prescriptions for statins were supplied between May and December 2002, for a total cost of $570 million. The age-standardised rates for statin prescribing in women varied from 56.9 (95% CI, 56.6–57.2) scripts per 1000 population per month in the most disadvantaged socioeconomic quintile through 53.4 (95% CI, 53.0–53.7), 50.3 (95% CI, 50.0–50.6), 48.4 (95% CI, 48.1–48.7) to 46.3 (95% CI, 46.0–46.6) in the least disadvantaged quintile. For men the figures were 52.6 (95% CI, 52.3–52.9), 50.9 (95% CI, 50.6–51.2), 48.8 (95% CI, 48.6–49.1), 47.7 (95% CI, 47.4–47.9), and 51.9 (95% CI, 51.6–52.2). There was a significant linear association between statin prescribing and CHD mortality by quintile of socioeconomic disadvantage in women (weighted least squares slope, 0.380; 95% CI, 0.366 to 0.395; P < 0.0001), but not in men (slope, − 0.002; 95% CI, − 0.010 to 0.006; P = 0.65).Conclusions: Our results suggest that in men there is either overprescribing of statins in the highest socioeconomic quintile or underprescribing in the lowest. Furthermore, contrary to expectation, women — relative to men — are prescribed statins at higher rates at lower levels of risk (using CHD deaths as a proxy measure of risk).

Nigel P Stocks MD · Heather McElroy DipStats · Philip Ryan MB BS · James Allan MB BS

Anna Peeters,* Jason Ting,† Mark R Nelson,‡ John J McNeil§ * Research Fellow, Department of Epidemiology and Preventive Medicine, Monash University, and Department of Public Health, Erasmus Medical Centre, PO Box 1738, Rotterdam, 3000DR, The Netherlands; † Intern, Geelong Hospital, Geelong, VIC; ‡ NHMRC Research Fellow; § Head, Department of Epidemiology and Preventive Medicine, Monash University, Prahran, VIC. a.peetersATerasmusmc.nl To the Editor: Coronary heart disease (CHD) risk prediction for primary prevention now focuses on multifactorial risk,1-3 and various risk calculation tools exist.1-3 The need for such tools depends on the degree to which risk status can be estimated by healthcare professionals. We performed a study to assess general practitioners’ intuitive calculation of multifactorial CHD risk for patients likely to be considered for lipid-lowering therapy. In 1999 we posted a survey to a random sample of 400 GPs in Victoria, and received back 155 completed surveys (39% response rate). The respondent population was demographically similar to the Australian GPs and trainees who billed Medicare in 1998–99. GPs were asked to estimate 5-year absolute risk of CHD for four vignettes (two primary prevention and two secondary prevention), each based on the average characteristics of a published lipid-lowering clinical trial cohort4-7 (vignette descriptions are available from the authors). For the primary prevention vignettes, GPs were also requested to estimate the risk relative to other Australians of the same age and sex. Estimated risks were compared with reported risks to derive risk ratios. GPs accurately estimated the relative CHD risk for the two vignettes of patients with no prior CHD, with mean risk ratios of 0.84 (95% CI, 0.77–0.91) and 1.23 (95% CI, 0.97–1.49). However, they overestimated absolute risk, with risk ratios ranging between 2.79 (95% CI, 2.61–2.96) and 6.43 (95% CI, 5.59–7.27). The proportion of GPs estimating within 10% of the actual risk was 9% for a 62-year-old man with prior CHD and average cholesterol level, 13% for a 60-year-old woman with prior CHD and high cholesterol level, 17% for a 55-year-old man with no prior CHD and high cholesterol level, and 43% for a 58-year-old man with no prior CHD and average cholesterol level. Although the two primary prevention vignettes had 5-year absolute CHD risks below 10%, most GPs’ estimates (93% and 71%, respectively) were greater than 10%. In conclusion, GPs in Victoria have a good understanding of a patient’s relative risk of CHD, but they consistently overestimate absolute risk. The problem with absolute risk estimation may not be the sophisticated multifactorial calculations required, but rather a general overestimation of risk within the population, at least for middle age. The GPs’ estimates of absolute risk for the four vignettes were correctly ranked, suggesting that they recognised the degree to which a risk was lower or higher, but were unfamiliar with the scale. This overestimation led most GPs to categorise patients such as those from the AFCAPS/TexCAPS trial, with only a 3.3% 5-year risk of CHD,6 as having a risk of greater than 10%. GPs would therefore incorrectly consider these patients appropriate for lipid-lowering therapy according to national and international guidelines. 1-3 Education may improve understanding and accuracy of risk communication for CHD in middle-aged patients, but tools for accurate assessment of coronary risk are needed in routine clinical practice.

Anna Peeters · Jason Ting · Mark R Nelson · John J McNeil

Objective: To determine whether medical graduates who spent their intern year at a non-metropolitan hospital were more likely to practise outside metropolitan areas on completion of training than were interns in metropolitan hospitals.Design: Retrospective follow-up of doctors who held year-long internships at a non-metropolitan hospital and interns from metropolitan hospitals.Setting: Ballarat Base Hospital (BBH) (Rural, Remote and Metropolitan Area [RRMA] rural zone) and hospitals in Melbourne and Geelong (RRMA metropolitan zone).Participants: 57/63 (90%) Victorian medical graduates completing internships at BBH between 1989 and 1997 and 126/126 (100%) sex-matched metropolitan interns, chosen at random.Main outcome measures: Practice location in 2002.Results: More BBH interns were practising as GPs outside metropolitan areas (44%) than metropolitan interns (13%) (difference, 31%; 95% CI, 17%–45%). The proportion of interns in specialist practice outside metropolitan areas was small for both groups — zero and 3%, respectively (difference, − 3%; 95% CI, − 6% to 0). None of the specialist training posts held by interns were outside metropolitan areas. Of BBH interns entering general practice, 41% (95% CI, 24%–58%) did so in the local health region.Conclusions: Regional interns are a good source of non-metropolitan GPs, especially locally. Prospective studies to determine the precise influence of regional internships on eventual practice location, and whether more such posts would lead to more graduates entering non-metropolitan practice, would be worthwhile.

Hedley G Peach PhD, FFPH · Maxine Trembath · Bernie Fensling BSc, MB BS

Mark R Nelson NHMRC Research Fellow, Department of Epidemiology and Preventive Medicine, Monash University, Commercial Road, Prahran, VIC 3181. mark.nelsonATmed.monash.edu.au To the Editor: The lessons from the introduction of COX-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), related by Kerr et al,1 have a corollary in the introduction of angiotensin-II-receptor antagonists 2 years previously. Both cases involved common conditions (osteoarthritis and hypertension), with extensive prescribing of newly developed and marketed agents, which blocked an enzyme further down the cascade of reactions to avoid adverse outcomes — the gastrointestinal upset and bleeding associated with non-selective NSAIDs, and the cough and angioedema caused by angiotensin-converting enzyme inhibitors. In both conditions, off-patent, low-cost alternative drug therapies were available — paracetamol and acetylsalicylic acid, and thiazide diuretics and β-blockers, respectively. My quantitative investigation of general practitioners’ perceptions of newer versus older antihypertensive agents suggested that they thought newer agents were more efficacious, and were safer in the short term and long term, but were more expensive.2 These beliefs were held despite the lack of long-term safety data. Younger doctors were more likely to hold these beliefs. It is possible that the experience of using older medications permitted older doctors to maintain a healthy scepticism towards the marketing claims of medical representatives. It may be interesting for Kerr and colleagues to look at the demographics of GPs in the General Practice Research Network to see if these findings hold true for this cohort.

Mark R Nelson

To boldly go . . . These famous words from Star Trek have current resonance in general practice here in the United Kingdom, although the optimism of the star ship Enterprise’s voyages is balanced with doses of anxiety. While many in the UK believe that the new contract with general practitioners may be the last chance for the profession, it will, as with the Star Trek voyages, take general practice in this country into uncharted worlds. Repeatedly, surveys find a GP workforce that is despondent, demoralised and overburdened by bureaucracy. Although the reasons for low morale are complex, it’s not all about money: there aren’t the same income disparities between GPs and consultants in the UK National Health Service (NHS) as there are in Australia. . . . in UK general practice the goodwill that has sustained the GP workforce is waning. There appears to be a more fundamental shift in UK general practice — the goodwill that has sustained the GP workforce is waning. There is a sense that something important has been lost, and that core commitment to the national public good can no longer be taken for granted. The fabric of Aneurin Bevan’s uncompromising vision for a new, socialised health service in 1948 (to quote: “We know what happens to people who stay in the middle of the road; they get run down.”) may be lost forever in New Labour’s reforms. An average GP here might earn in the vicinity of £70 000, depending on where in the UK he or she practises, and, under the new contract, earnings could rise by as much as £15 000–£20 000. It’s often recalled that Bevan remarked that in order to sell the idea of the NHS to doctors he “stuffed their mouths with gold”. Some of that ethos is alive in the new general practice contract negotiations, but the GP workforce is weary, demoralised and distrustful — and a bit more streetwise than in 1948. They want improved pay and conditions, and to be able to treat their patients unencumbered by bureaucracy. But, instead, they seem to be getting a very complex package in their new contract, and very few people can confidently predict how it will work. There is no doubt that general practice has become more complex over time. There are more meetings, recurring bed-capacity crises, long waiting lists, and the constant struggle with an increasingly dysfunctional secondary care sector. General practice here is facing a workforce crisis, as it is in Australia. Medical students in Edinburgh don’t seem to want to go and work as GPs in the outer Hebrides or rural Fife; they want to be consultants in England! General practice registrars won’t commit to permanency in practices, preferring more mobile, portfolio-style careers. Will the new general practice contract arrest this decline? It may turn out to be the GPs’ saviour, but it has had some unglamorous moments. They reached a peak in April 2003 with the release of the “Carr-Hill” formula (Box),1 which allowed practices to calculate their incomes under the new arrangements. Despite widespread anticipation of 30% pay rises, many practices found to their amazement that their incomes would in fact decrease! Then the GP tabloids had a field day when, at the height of the crisis, the architect of the funding formula, Professor Roy A Carr-Hill, a highly respected economist from York, was sighted in the mountains of Nepal. The contract targets several sacred institutions in UK general practice. Instead of capitation payments being tied to individual principals’ lists, the contract will be between the “primary care organisation” (usually, but not always, a primary care trust) and the entire practice. GPs will be able to “opt out” of certain non-core services, depending on their skills and interests — hence there will be incentives for practices to join up and jointly provide such services. There will be no compulsion to provide after-hours services — it will be the responsibility of the local primary care organisation to make sure there is after-hours cover. Most importantly, incentive payments will be linked to quality targets. In terms of its quality components, the contract has been described as “the boldest such proposal on this scale ever attempted anywhere in the world”.2 There will be 76 quality indicators in 10 clinical domains of care (eg, hypertension, diabetes management), 56 in organisational areas (eg, record-keeping, training, practice management), four in assessing patients’ experiences (eg, satisfaction, consultation length), and others for additional services. For the first time, there is to be a serious attempt to link remuneration in general practice with quality — not a small undertaking. About 80% of GPs voted in favour of the contract, yet many harbour deep suspicions. This stems in part from the perception that GPs will lose their “independent contractor” status — something they’ve always valued highly in a nationalised health service. Critics suggest that the contract is biased towards those areas of primary care for which there is “evidence” — which naturally tends to favour management of hypertension or cholesterol lowering, possibly at the expense of more complex areas of primary care such as mental health and cancer. Many believe that GPs will become administrators of disease management and prevention programs, and the focus on outcomes may undermine the holistic values of general practice. There are inevitably narrow definitions of good performance in the contract, largely centred around achieving certain markers of clinical outcomes. Undoubtedly, there will be a huge administrative burden on practices, and the need for better information technology systems. Further, there has been no attempt so far to measure the health gain that this initiative will offer to the population served. All complex contracts are unavoidably incomplete, and they contain inevitable “gaps, errors and omissions”.3 Many argue that the need for contracts such as these has arisen out of the erosion of the relationship of trust between doctors and their patients. The government has trusted the profession to deliver high-quality care to the NHS — but events such as the Bristol paediatric cardiac surgery inquiry and the long-undetected Shipman serial murders have effectively undermined this trust. However, it is argued that, instead of replacing this old-fashioned trust with complex contracts, there should be greater emphasis on transparency, with “acknowledgement of deficiencies in patient care and clear, incentivised policies for remedying them”.4 So what will happen when the new general practice contract takes effect in April 2004? At one level, the government must surely be anxious, with all the disaffection and criticism that has been expressed. But perhaps politicians don’t care — if the whole thing unravels there are always organisations distant from the centre of government to blame. There are also established, simpler alternatives to escape to such as Personal Medical Services — a scheme by which providers and local primary care organisations can negotiate local service contracts (often quite financially attractive) which encourage better integrated care and multidisciplinary teams. It’s hard to interpret the values behind current healthcare reforms in the UK, and this has been part of the problem in selling the contract. The old Labour principles of equal access for equal need and of universality do not figure highly in the current government’s agenda; for example, foundation trusts seem designed to increase the distance of government from the provision of healthcare. The trend towards selection of patients, treatments and services on the basis of financial risk rather than healthcare needs seems unstoppable.5 At least, though, there is a plan for general practice. This is in stark contrast to the lack of a coherent approach to the problems facing general practice in Australia. There is no doubt that the Divisions of General Practice in Australia have become a significant lever for change, and the investment through the Primary Health Care Research, Evaluation and Development Program is welcome. However, broader developments, such as the ill-fated flirtation with corporatisation, as well as changes to Medicare, give an impression of drift. At the very least, the new UK general practice contract is taking it somewhere — probably “where no man has gone before”, but let’s hope it’s a journey that leads to renewed hope and vision. Key components of the Carr-Hill formula for the new UK general practice contract1 The various payments that make up the new contract are weighted for factors that influence relative needs and costs. The formula includes adjustment for: the age and sex structure of the population, including patients in nursing and residential homes; the additional needs of the population, relating to morbidity and mortality; level of turnover of patients on the practice list; and the unavoidable costs of delivering services to the population, including variations in costs of hiring staff, and rurality.

David P Weller MPH, PhD, FRACGP, FAFPHM · Konrad Jamrozik DPhil, FAFPHM, MFPH · Richard F Heller MD, FRCP, FRACP, FAFPHM

Treatment for chronic low back pain (pain persisting for over 3 months) falls into three broad categories: monotherapies, mulitidisciplinary therapy, and reductionism. Most monotherapies either do not work or have limited efficacy (eg, analgesics, non-steroidal anti-inflammatory drugs, muscle relaxants, antidepressants, physiotherapy, manipulative therapy and surgery). Multidisciplinary therapy based on intensive exercises improves physical function and has modest effects on pain. The reductionist approach (pursuit of a pathoanatomical diagnosis with the view to target-specific treatment) should be implemented when a specific diagnosis is needed. While conventional investigations do not reveal the cause of pain, joint blocks and discography can identify zygapophysial joint pain (in 15%–40%), sacroiliac joint pain (in about 20%) and internal disc disruption (in over 40%). Zygapophysial joint pain can be relieved by radiofrequency neurotomy; techniques are emerging for treating sacroiliac joint pain and internal disc disruption.

Nikolai Bogduk MD, DSc, FFPM (ANZCA)

Bryan G Walpole Emergency Physician, Australian Antarctic Division, Channel Highway, Kingston, TAS 7050. bwalpoleATtassie.net.au To the Editor: Your otherwise excellent issue on chronic illness (1 September 2003) was timely and appreciated. However, the article by Zajac on the future of public hospitals1 left me pondering how frequently he patrolled the wards and the emergency department. Most public hospitals have undergone the very revolution he adumbrates. Patients now arrive with automated medication records and problem lists from their general practitioner; GP liaison doctors from the Divisions attend discharge planning committees; discharge summaries are delivered by fax on discharge; multidisciplinary clinics abound for complex and chronic illness, but invited GPs claim that time commitments and insufficient payment often preclude attendance; there are target waiting times for clinic appointments; often there is a quality assurance unit, with a complaints or grievance procedure; day surgery and day of admission surgery is now the norm (and strict guidelines help control the morbidity Zajac bemoans), with vastly improved throughput; endoscopy and emergency cardiac catheterisation or angioplasty on demand are commonplace; we now acknowledge, document and rectify system errors with alacrity, without the rancour and recrimination of years ago; and evidence has replaced the wise maxims of the physician. Admittedly, all is not rosy and funding remains a perennial problem, but within available resources the public hospital is a completely different place from 15 years ago. A major issue, and Zajac agrees, is the place of general medicine in the public hospital, being rapidly subsumed by sub(super)-specialists together with emergency physicians, as they are available round the clock, skilled and equipped to perform the assessment and early management of most medical patients, while the physicians are in rooms or at home. We welcome the presence of general physicians in the emergency department, and encourage twice-daily rounds on admitting day with shared care, but so far the rhetoric of general medicine has rarely been matched by attendance. The real challenge for public hospitals at present is to effectively manage and discharge frail elderly patients, and those with cognitive impairment, thus keeping beds free to reduce access block; otherwise general medicine may suffer the fate Zajac reserves for public hospitals and become “a thing of the past”.

Bryan G Walpole

Jeffrey D Zajac Head, Department of Medicine, Austin Hospital, Level 7, Lance Townsend Building, Studley Road, Heidelberg, VIC 3084. j.zajacATunimelb.edu.au In reply: Walpole and I agree that public hospitals have changed significantly. Where we seem to disagree is that he suggests that we have got to where we are going and all the problems have been solved. Walpole clearly works in a different world from me. Even a short visit to the wards and emergency department reveals that, despite good will, planning and many of the changes Walpole lists, things are far from perfect. System errors, major and minor, occur far more commonly than they should, elderly patients spend more time as inpatients than they should, and stresses in the system continue to impair quality and efficiency. I think we need to keep working on these issues, and not pretend that they are fixed. I note with dismay the description of general physicians occasionally visiting Walpole’s emergency department, while other specialists work diligently, 24 hours a day, to heal the sick. These comments demonstrate one of the main problems with doctors in public hospitals, namely, the territorial imperative in full flight. We should be finding ways to work together.

Jeffrey D Zajac

Pocket guide to diagnostic tests. Australian edition. Robert Dunstan, Diana Nicol, Stephen J McPhee, et al (editors). Sydney: McGraw-Hill, 2003 (viii + 488 pp). ISBN 0 074 710362. The concept of a pocket guide to assist clinicians in their choice of diagnostic tests is an excellent one — unfortunately, here, the authors have set themselves too ambitious a task. If they had limited themselves to common laboratory tests for common diseases they would have fulfilled their intent. This edition is described as "especially adapted for the Australasian market", but the adaptation is not comprehensive and the manual remains very North American in its perspective. In addition, where costs are mentioned, it is unclear whether they are quoting Australian dollars, and whether the costs are based on test performance or cost to the patient. The quantity and quality of the information varies widely. The chapter on basic principles and interpretation of test results provides sections on patient preparation, specimen collection and interfering factors, which are extremely useful. However, the section on reference intervals mars this chapter, as these are often population and method specific, and those in the book should only be used as a guide. Much of the remaining information is too detailed and technical to be of real use to busy clinicians. Many of the "common bedside laboratory procedures" described are not easily performed at the bedside. For example, the Gram stain for microbiological assessments and Wright stain for examination of the peripheral blood require considerable expertise both in performance and interpretation. At the same time, some common procedures which could be conducted under these circumstances, such as measuring blood glucose, cholesterol and haemoglobin levels, are not mentioned. Some instructions are clearly wrong — tubes should not be filled "completely", but rather to the specified level; and glass tubes are no longer used when measuring arterial blood gases. Also, no mention was made of evacuated blood sample containers, which are in almost universal use in Australia. Similarly, many of the examples of "commonly used laboratory tests" described in chapter three are not "common", and to label them as such is misleading and may lead to overordering. Several of the references in the "Comments" column in this chapter are too old to be useful, with some dating as far back as 1967, and many being from the 1980s. All references to blood banking quote the 13th edition of the Technical manual of the American blood banks, whereas the 14th edition is the current benchmark. Calculations for low-density lipoprotein (LDL) cholesterol are only given for conventional units, not for SI units, and the glucose tolerance test uses United States protocols and not World Health Organization or Australian guidelines. While there are many drawbacks in the chapter, many of the tests, together with interpretation and comments, are well presented and could be useful for reference purposes. The excellent introduction to therapeutic drug monitoring is clearly set out with all the requisite information, including half-life and requirements for dosage adjustment. There is microbiological information about "clinically important diseases", but again some very uncommon situations are described. The categorisation by body area is commendable and useful. The authors do make some helpful introductory comments relating to medical imaging in chapter six; however, this chapter is quite inadequate, with insufficient information to be of real value. For instance, indications for CT scan of the brain are restricted to intracranial or subdural haemorrhage, and there is no mention of space-occupying lesions, thrombotic events or hydrocephalus. There is no apparent correlation between chapters, as abdominal imaging makes no reference to imaging for diverticulitis, which is recommended in the microbiology chapter. The chapter on basic electrocardiography is more comprehensive and, overall, is useful. It could be the basis for an excellent small pocket guide in its own right. The final chapter provides algorithms, nomograms and tables and is a mixture of useful and less useful facts, figures, interpretations and recommendations. The layout is complicated and difficult to negotiate. In summary, this book cannot be recommended as a quick, reliable and easily portable reference for investigating clinical problems in the Australian setting. Eva RaikHaematologist Royal North Shore Hospital, St Leonards, NSW

Eva Raik

During the 20th century Australians have benefited immensely from improvements in their general health and life expectancy. Our average life span has increased by 25 years, and even in the century’s dying decade we managed to gain another two years!1 As with many success stories, there have been numerous contributors, but there is no doubt that basic medical research has played a prominent part. Indeed, the interplay between basic research and advances in medicine is succinctly captured by the phrase “from bench to bedside” or by the term “translational highway”2 — an autobahn for taking basic research advances and transferring these into clinical practice. The powerhouses of basic research in Australia are our universities and research institutes. Their financial underpinnings are the competitive grants provided by both government and non-government organisations. In 2002, for example, the National Health and Medical Research Council’s expenditure on health research and development was $276 million. Of this, the universities received $190 million (69%) and the medical research institutes received $74 million (27%).3 Since 1995, the Christmas issue of the Journal has regularly featured Australian medical research institutes, beginning with portraits of the Walter and Eliza Hall Institute in Melbourne and the John Curtin Institute of Medical Research in Canberra, and featuring most recently the Menzies Centre for Population Health Research in Hobart in 2001 (now the Menzies Research Institute). This year, we sought to explore a different avenue. In 1998, the then Minister for Health, Dr Michael Wooldridge, empowered a prominent committee chaired by Peter Wills, then Chairman of the Garvan Institute of Medical Research, Sydney, to review health and medical research in Australia and report on strategies for these efforts in the first decade of the 21st century. In its final report,4 the committee identified a number of issues including: the need to sustain and expand an effective health and medical research sector underpinned by innovative and high impact basic research; a greater need for research that contributes directly to the health of the people and the healthcare system; and the need for links between research and industry to capitalise on the potential commercialisation of research findings.4 In short, the report recommended an increased emphasis on “bench-to-bedside” research, focused on the health and economic wellbeing of the nation. To gain some perspective on the vitality of this research in Australian medical research institutes, we recently conducted a poll of institute directors (see Box). Their responses are given on the following pages. What inferences can we draw from this snapshot? Survey of Medical Research Institutes in Australia The directors of Australian medical research institutes were contacted in September 2003 and asked : “Most Australian medical research institutes have been operative for more than 25 years and the theme we wish to pursue is . . . what has come out of [name of your institute] that has been translated into population health or clinical practice; ie, what has made it from ‘bench to bedside’? We want you to restrict these to two major impacts.” Twenty-eight research institutes were approached and we accepted 22 submissions (Australian Capital Territory, 1; New South Wales, 5; Northern Territory, 1; Queensland, 2; South Australia, 1; Tasmania, 1; Victoria, 9; and Western Australia, 2). Firstly, it is apparent that “bench-to-bedside” research is alive and well in Australian medical research institutes, and is wide-ranging in its scope. It includes public health advances relevant to South-East Asian and Australian Indigenous communities, clinical advances in areas such as assisted reproduction and cancer, and improved treatments for chronic disorders, such as diabetes or visual impairment in older people. Secondly, this research is achieved by teamwork between clinician–scientists and scientists working together in a collegial spirit. Thirdly, and most importantly, it takes time. Finally, it is apparent that our research institutes are increasingly forging closer links with industry. However, there is one overriding message — that success in basic research cannot be solely developed from imposed priorities and schemes. Research is driven by human imagination, inquisitiveness, insight and a generous sprinkling of serendipity. For, as observed by the Nobel laureate Albert Szent-Gyorgi, “. . . research means going out into the unknown with the hope of finding something new to bring home. If you know in advance what you are going to do or even to find there, then it is not research at all: then it is only a kind of honorable occupation.”5 In short, basic research has two defining features: uncertainty and surprise.6 As long as these twin principles are treasured in our medical research institutes, meaningful “bench-to-bedside” research will continue to advance the practice of medicine. Australian Capital TerritoryEradication of smallpoxIn 1988 Frank Fenner of the John Curtin School, along with Donald A Henderson of the Johns Hopkins University School of Hygiene and Public Health and Isao Arita, Director of the Kumamoto National Hospital, Japan, were awarded the Japan Prize for Preventive Medicine in recognition of their international team effort in eliminating smallpox from the world. This feat is one of the greatest accomplishments of modern medical science. Fenner’s work at the John Curtin School on pox viruses (ectromelia, myxoma and vaccinia) through the 1950s, 60s and 70s had uniquely qualified him to lead the WHO smallpox eradication team which announced to the World Health Assembly in 1980 that the disease had been eradicated worldwide. Doherty and Zinkernagel with their Nobel prize medals. Discovery of MHC restriction In the early-to-mid 1970s, Peter Doherty and Rolf Zinkernagel, working on the response of mice to viruses discovered a major property of the immune system — major histocompatibility (MHC) restriction. In order for T lymphocytes to destroy cells infected by foreign invasion, their receptors must simultaneously recognise on the cell’s surface a complex of foreign antigen and a self molecule, one of the MHC antigens. Their discovery revolutionised our understanding of how the immune system works and won Doherty and Zinkernagel the 1996 Nobel Prize for Physiology or Medicine. MHC restriction has many clinical implications for organ transplantation and for the treatment of diseases involving the immune system. Peter Jeffrey, Public Affairs Manager, JCSMR Western AustraliaFolate supplementationPerhaps the longest established and best known research from the Institute that has had an enduring impact on health is the case–control study of neural tube defects conducted in Western Australia in the early 1980s by Carol Bower and Fiona Stanley.7 This showed that maternal dietary and supplemental folate intake around the time of conception protected against neural tube defects in the offspring. Further international studies showed that 70% of neural tube defects could be prevented by folate intake. Based on these findings, the Institute, in collaboration with the WA Health Department, embarked on a health promotion project in 1992, the first in Australia and one of the first in the world. There was an increase to 30% of women taking folic acid supplements periconceptionally, and a 29% fall in neural tube defects in WA. FunhalerA more recent contribution from the Institute addresses a major problem for children with asthma, who typically show poor adherence to prescribed frequency and technique of inhaled medication. The Funhaler (Visiomed Group Ltd, Australia), invented by the Institute’s Paul Watt, is a small volume spacer device incorporating an incentive toy module. A pilot study showed that the Funhaler reduced problems in giving children asthma medication, improved child and parental adherence to the medication regimen and created a more positive attitude towards treatment.8 A recent grant from the US National Institutes of Health (US$700 000) supports further study of the device, which is due to be launched throughout Australia by the end of 2003. Fiona Stanley, Director, TICHR AlphaCor artificial corneaStarting in 1990, polymer chemistry research by Traian Chirila and Celia Hicks resulted in the world’s first soft artificial cornea, now marketed by the WA company, Argus Biomedical Pty Ltd. Hundreds of novel polymers were formulated and tested for physical characteristics, including optical clarity, tensile strength and elasticity as well as biocompatibility in tissue culture and after implantation in animals. Novel chemical methods were developed to create a porous outer rim into which human cells would grow and establish a firm bond. This porous outer rim was co-polymerised with the same polymer materials under differential conditions to create an optically clear centre via an interpenetrating network. Human trials of the novel artificial cornea started in 19979 and CE-Mark European approval was followed in 2002 by FDA approval in the United States. Laser-induced surgery and central retinal vein blockageIn the early 1990s, Ian McAllister, Ian Constable and Dao-Yi Yu began developing a method to bypass the outflow from blocked retinal venous circulation, which commonly causes rapid loss of vision in older people with hypertension. After experiments in animals, Ian McAllister realised that a very powerful laser was required to break the structural barrier (called Bruch’s membrane) between the retinal and overlying choroidal circulation. In addition, rupture of the obstructed retinal vein was required to create an anastomosis between the two circulations and this was best achieved with a Yag cutting laser.10 Further experiments and observations identified a group of patients with incomplete central retinal vein occlusion for trials. Case–control studies showed that a successful shunt could be achieved in about two-thirds of the target population, and that visual acuity markedly improved as a result. This procedure has been taken up in a number of centres around the world. A randomised controlled clinical trial is under way in four Australian locations. Ian J Constable, Director, Lions Eye Institute VictoriaMobilising myelopoiesisBasic research at WEHI and LICR has had a profound impact on cancer treatment. Don Metcalf’s tenacious research at WEHI over three decades transformed understanding of blood cell production and haemopoietic diseases. He and his colleagues, including Nic Nicola (WEHI) and Tony Burgess (then at WEHI, later at LICR), purified two of the hormones involved in white blood cell production. Known as colony-stimulating factors (CSFs), these hormones (GM-CSF and G-CSF) accelerate white blood cell regeneration in patients undergoing chemotherapy or radiotherapy and have helped treat over 3.5 million patients worldwide.11 During the first clinical trials of CSFs at the Royal Melbourne Hospital (directed by George Morstyn, LICR), Uli Duhrsen (WEHI) and the team made the unexpected observation that CSFs mobilise blood stem cells into the bloodstream, a discovery which led to bone marrow transplantation being replaced by blood stem cell therapy.12 The CSFs are now finding new applications in in-vitro fertilisation and treatment of Crohn’s disease. Suppressing autoimmunityIan R Mackay, Head of the Clinical Research Unit at WEHI, formally defined the concept and key features of autoimmune diseases in a book co-authored by Frank Macfarlane Burnet in 1963.13 Despite considerable scepticism about the concept, Mackay pioneered the treatment of autoimmune (lupoid) hepatitis with the immunosuppressive drugs, azathioprine and prednisolone. This approach continues to be the gold-standard for immunosuppression and has saved the lives of countless patients with autoimmune hepatitis and other autoimmune diseases. Suzanne Cory, Director, WEHI Antony W Burgess, Director, LICR Concepts and conceptionAlan Trounson, together with Carl Wood and his colleagues from Monash University Department of Obstetrics and Gynaecology, pioneered studies of in-vitro fertilisation and other reproductive technologies for the management of human infertility. Building on the work of Edwards and Steptoe in the UK, they integrated ovarian stimulation into the routine IVF protocol,14 providing multiple oocytes for fertilisation. When combined with the capacity to freeze embryos these technologies contributed to improved IVF success rates.15 The Monash group also developed the conditions necessary for oocyte donation to become a routine procedure and extended the capacity for IVF to women without ovaries.16 The ability to biopsy a blastomere from an embryo17 and determine its genetic status18 has enabled preimplantation genetic diagnosis to be successfully performed for fertile couples with a history of genetically based disease. Y Chromosomal defectsIn 40% of infertile men the cause of the spermatogenic defect is unknown, but the observation of small Y chromosomes in some of these men suggests a genetic cause. Scientists from the Institute, together with colleagues at Charles Drew University Los Angeles, further defined the deleted regions of the Y chromosome causing azoospermia or severely reduced sperm counts.19 These observations, together with others, showed that some Y chromosome deletions did not completely prevent sperm production, raising the possibility of using intracytoplasmic sperm injection (ICSI). The Institute’s scientists, together with colleagues at Monash IVF, demonstrated transmission of Y chromosome deletions from father to son by the use of ICSI.20 They also developed a routine clinical test to screen men with sperm counts less than 5 million/mL, enabling genetic counselling for couples where the man has a Y chromosomal deletion. Current estimates indicate that 3%–8% of men with idiopathic infertility have a Y chromosomal disorder. David M de Kretser, Director, MIRD Murray Esler and Gavin Lambert performing noradrenaline spillover measurements to quantify sympathetic nervous system activity in a patient during head-up tilting. Noradrenaline in heart failureIn the 1980s scientists led by Murray Esler developed a unique radiotracer technique for neurochemical quantification of sympathetic nervous system activity and measurement of the spillover of the sympathetic neurotransmitter, noradrenaline, from individual organs. With this advance they were able to isolate neurophysiological mechanisms in heart failure. At that time the accepted view was that the failing heart was functionally and anatomically sympathetically denervated and β-adrenergic blocking drugs were said to be contraindicated. An innovative series of research projects at the Baker showed that in many patients with heart failure the sympathetic nerves of the heart were, in reality, stimulated at an exceedingly high level.24 A prospective study of patients with severe heart failure showed that the cardiac sympathetic tone was the strongest predictor of death.25 This research provided the pathophysiological evidence for the use of β-adrenergic blocking drugs in cardiac failure. The renin–angiotensin system (RAS) in diabetesOver the last 15 years it has become apparent that blockade of the RAS plays a central role in diabetic nephropathy, the leading cause of endstage renal disease in the developed world. Basic research, including that of Mark Cooper’s group, showed that, despite RAS suppression, intervention with angiotensin-converting enzyme inhibitors or angiotension II antagonists could reduce the functional and structural manifestations of diabetic nephropathy.26-30 Over the last decade the underlying molecular and cellular pathways whereby angiotensin II promotes renal injury have been unravelled and may provide new targets for further renoprotection. This basic research was the impetus for three landmark studies exploring blockade of the RAS in type 2 diabetic patients with incipient and overt renal disease. More recently, research has linked the RAS to other diabetic complications involving the retina, heart and vascular system. Multicentre clinical trials are now investigating the benefits of interrupting the RAS for diabetic complications at these extrarenal sites. Garry Jennings, Director, BHRI Linking research with health outcomesOver the past 15 years the Institute’s major achievements have involved the development of appropriate and sustainable technologies to prevent or control infectious diseases in resource-poor regions. Immunisation programsIn the early 1990s the Institute pioneered the introduction of routine hepatitis B immunisation in Lombok, Indonesia, and demonstrated the feasibility of implementing universal hepatitis B vaccination without damaging other vaccine programs. This was the first demonstration of the usefulness of hepatitis B vaccination in a developing country’s immunisation program,21 and contributed to the models used now by Global Alliance for Vaccines and Immunization and the Gates Foundation to support universal hepatitis B immunisation in the world’s 70 poorest countries. Harm reductionSince 1989 the Institute has championed the application of harm-reduction approaches to mitigate the impact of HIV and hepatitis C infection, and has played a major role in driving the acceptance and implementation of these approaches, especially in South-East Asia.22 Cheap sustainable diagnosticsThe Institute has led the development of cheap and sustainable CD4 cell assays23 to support the widespread implementation of antiretroviral drug therapy to treat HIV infection in developing nations. It has also developed, and is now commercialising, new technologies for the diagnosis of hepatitis E and hepatitis A infections. Steven L Wesselingh, Director, Burnet Institute Cellular therapiesThe stem cell biology program at Peter Mac, a major node of the National Stem Cell Centre, is studying fundamental properties of stem cells in adult tissues and using their unique biological properties in novel cellular therapies. The stem cell facility at Peter Mac has good manufacturing process (GMP) accreditation and is licensed by the Therapeutic Goods Administration. It has been used for stem cell therapy in several patient groups, including Australia’s first clinical trial with ex-vivo expanded haematopoietic stem and progenitor cells for breast cancer patients after repetitive high-dose chemotherapy. A significant reduction in neutropenia and platelet transfusion requirements was demonstrated in these patients. The Peter Mac propagated mesenchymal stem cells (MSC) to treat a non-union fracture of the ulna. This pioneering proof-of-principle procedure was the first use of prospectively isolated autologous MSC in a clinical setting. Characterising cancerIn about 5% of cancer patients, extensive clinical workup fails to reveal the primary carcinoma. Researchers at Peter Mac are using microarray-based gene expression profiling, a method of molecular diagnostics that may assist in diagnosing and treating this kind of cancer. Metastatic tumours have been shown to maintain gene expression patterns that are consistent with tissue of origin. Clinically plausible prediction of the origin of the metastatic tumour has been made in numerous cases of carcinoma of unknown primary, suggesting that the test will facilitate clinical management. David Bowtell, Director of Research Division, PMCI In-situ gene expression In the 1980s, researchers John Coghlan, Jennifer Penschow, Geoffrey Tregear and Hugh Niall developed the technique of hybridisation histochemistry using oligonucleotides for detection of in-situ gene expression in tissues.31,32 The Institute holds patents on this technique, which is now widely used for the diagnosis of viral and infectious diseases and in research. Fortifying bone with ForteoA peptide comprising part of human parathyroid hormone (PTH[1-34]) was recently approved by the US Federal Drug Administration for the treatment of osteoporosis. Marketed by Eli Lilly & Co as Forteo, or teriparatide, it is the first approved agent for the treatment of osteoporosis that stimulates new bone formation. Hugh Niall and Geoffrey Tregear played a pivotal role in the discovery and development of PTH(1-34). Working initially at the Massachusetts General Hospital, Boston, and then at the Howard Florey Institute in the 1970s, they were the first in the world to isolate and sequence parathyroid hormone.33 They subsequently synthesised parathyroid hormone fragments and established that the amino terminal 1–34 region of the sequence had full biological activity.34 Forteo is the peptide originally designed and synthesised by Tregear. Frederick A O Mendelsohn, Director, HFI InhibinA major focus of the Institute has been reproductive endocrinology, particularly the relationship between the hypothalamus, anterior pituitary and the gonads. The most significant outcome of this research was the first isolation, purification and characterisation of a new gonadal hormone, inhibin. Inhibin acts as a feedback signal regulating the secretion of follicle stimulating hormone (FSH) by the pituitary. This achievement was the result of collaboration between scientists as Prince Henry's, Monash University, St Vincent's Institute of Medical Research and La Trobe University. The major impact on clinical practice came with the finding that concentrations of inhibin were markedly elevated in the serum of patients with ovarian granulosa cell tumours or mucinous epithelial cancers.35-36 The marker commonly used for ovarian cancer diagnosis and monitoring, CA125, is not especially helpful in these two types of ovarian tumour. Work at the Institute has shown that combining inhibin and CA125 measurement can diagnose 95% of ovarian cancers.37-39 Inhibin measurement is now standard practice in following up patients with ovarian granulosa cell tumours. Research on inhibin has also clarified the mechanisms involved in the hormonal changes in women as they approach the menopause, and has indirectly led to the realisation that measurements of FSH and oestrogen are of little value in the assessment of perimenopausal women. Henry G Burger, Emeritus Director, PHIMR Automating amino-acid sequencesSt Vincent’s Institute has a long heritage of studying protein structure and function. The founding director, Pehr Edman (1957–1972), discovered how to sequence the order of amino acids within proteins and ways to automate this process.40 Protein sequencing enabled characterisation of proteins for diagnostic (eg, radioimmunoassay) and therapeutic use, as well as the unravelling of protein mutations in genetic diseases such as phenylketonuria and thalassaemia. Salmon calcitonin, for example, was sequenced using the Beckman commercial version of Edman’s automated sequencer by Hugh Niall (who had been a student of Edman) and then synthesised by Sandoz (now Novartis) for widespread therapeutic use in Paget’s disease. Obtaining amino acid sequence using Edman’s technology has been a necessary step in cloning many recombinant molecules used as drugs, such as growth hormone, tissue plasminogen activator and erythropoietin. Calcium and cancerJack Martin and his team discovered parathyroid hormone-related protein (PTHrP), a hormone secreted by cancers that causes the syndrome known as humoral hypercalcaemia of malignancy41 and contributes to bone metastasis. This discovery established a molecular explanation for this common clinical syndrome, and led to its accurate diagnosis by radioimmunoassay and immunohistochemistry for PTHrP. A humanised monoclonal antibody against PTHrP is now in Phase III clinical trials, having been developed by Chugai as a result of proof of principle supplied by this Institute’s research. Protein kinases as drug targetsBruce Kemp has made pivotal discoveries about the structure and function of protein kinases, particularly the amino-acid sequences used by kinases to interact with their substrates. Most recently these have been applied to adenosine monophosphate-activated protein kinase (AMPK), which Kemp and colleagues purified and sequenced.42 This is an enzyme involved in fuel metabolism that is activated by drugs that increase insulin sensitivity, including metformin and the glitazones.43 The Institute’s intellectual property in this area has been licensed to Mercury Therapeutics and Aventis, who are searching for new drugs that activate AMPK. The pharmaceutical industry has the protein kinases as one of its three top targets for drug development. Thomas W H Kay, Director, SVIMR TasmaniaSIDSBy the 1980s sudden infant death syndrome (SIDS) had become the commonest cause of death in postneonatal infants in Australia and some other developed countries. However, little was known about its causes or prevention. As early as 1944, it had been proposed that placing a baby prone (on the abdomen) might increase risk.44 Despite the gradual accumulation of retrospective evidence from case–control studies of an association between prone position and SIDS,45,46 concerns about recall bias (particularly at a time when many hospitals advised prone sleeping) limited the acceptance of sleeping position as a cause. Prospective data were needed. The Menzies team reported the first prospective evidence, obtained from the Tasmanian infant cohort, in the Lancet in 1991,47 confirming a higher risk for infants sleeping in the prone position. This research work led to a rapid policy response. A national meeting in July 1991 provided a new recommendation that healthy infants should not sleep prone. SIDSAustralia incorporated the finding into health education advice to new parents. In Australia the number of SIDS deaths declined from 507 in 1990 to 101 in 2001 (rate, 1.93 to 0.41) — a fall of about 80%.48,49 Similar successful campaigns occurred internationally. Subsequent research at the Menzies Institute has continued to inform international policy and contributed to a continued decline in SIDS deaths.50 Terence Dwyer, Director, MRI South AustraliaCause and prevention of discitis after discographyFor more than 50 years discography has been used to confirm a diagnosis of internal disc disruption and the presence of normal discs adjacent to the level of an intended spinal fusion. Discitis following discography is a serious complication and, although the presence of infection is occasionally confirmed, numerous authors have suggested that it is caused by a chemical or aseptic process. Fraser, Osti and Vernon-Roberts showed that the injection of a single Staphylococcus epidermidis into an intervertebral disc in a sheep was sufficient to produce radiographic, macroscopic and histological discitis, but that organisms could not be isolated from the lesion after 6 weeks.51 They found also that in 7 patients with discitis no bacteria were isolated from the 3 biopsied 6 weeks after discography but bacteria were isolated in 3 of the 4 biopsied within 6 weeks. These findings indicated that discitis after discography is initiated by needle-tip infection, but the causative bacteria are rapidly eliminated after the inflammatory destruction of the plate of bone separating the avascular disc from the richly vascular bone marrow of the vertebral body. Changing from a single needle lacking a stilette to stiletted needles and a two-needle technique reduced the incidence of discitis from 2.7% to 0.7%. Combining the two-needle technique with a single prophylactic dose of broad spectrum antibiotic effectively prevented discitis in a follow-up study. Barrie Vernon-Roberts, Director, Institute of Medical and Veterinary Science QueenslandThe Institute for Molecular Bioscience was formed in 2000 by the amalgamation of the Centre for Molecular and Cellular Biology (which focused on mammalian cell and developmental biology) and the Centre for Drug Design and Development (which focused on pharmaceutical development), both at the University of Queensland. Inflammation and painIn the past 6 years researchers at the IMB have discovered three candidate molecules to treat rheumatoid arthritis, chronic pain and neuropathic pain. The first orally active small molecule C5a-receptor antagonist (an anti-inflammatory drug which blocks an important component of the complement system) was designed and developed by David Fairlie and Steve Taylor and has progressed to Phase II clinical trials for rheumatoid arthritis patients.52 The molecule was licensed to the spin-off company Promics to undertake full development. Model of the inflammatory protein C5a and a small molecule C5a receptor antagonist. Antagonist (yellow) mimics a key turn conformation (red) in human C5a (white). A molecule, CVID (a conotoxin from Conus catus, a fish-eating marine cone snail on the Great Barrier Reef), which blocks N-type voltage-gated calcium channels, was discovered by Paul Alewood and Richard Lewis.53 The molecule, which has the potential to alleviate neuropathic pain, was licensed to AMRAD and Phase I/II clinical trials have been successfully completed in cancer patients with pain refractive to morphine treatment. Another molecule from cone snails, MrIA (a conotoxin from Conus marmoreus), was discovered by the Lewis and Alewood team.54 It is a potent blocker in vitro and in vivo of the reuptake of noradrenaline by the noradrenaline transporter and has shown excellent efficacy in preventing chronic pain in rats. It is now under pre-clinical development by the spin-off company Xenome. John J S Mattick, Director, IMB Controlling dengue in VietnamBrian Kay, head of mosquito control at QIMR, realised that the copepod predator of young mosquito larvae, Mesocyclops, had enormous potential for dengue fever control in Asia. Mesocyclops inhabit freshwater ponds and lagoons, but, from surveys in Vietnam, were also found in water storage containers (eg, concrete tanks, jars, wells).55 Brian Kay inspecting water storage tanks in central Vietnam. In 1989, Kay began working with Vu Sinh Nam from the National Institute of Hygiene and Epidemiology, Hanoi, to develop community-driven programs for dengue vector control, using new sampling technologies, key container prioritisation and Mesocyclops. Nine years later they reported the first eradication of Aedes aegypti without insecticide, in the 400 households of Phan Boi.56 By 2002 the program had expanded to 6 communes (11 675 households) in 3 other provinces.57 At the project’s completion, local leaders committed themselves to maintaining and expanding dengue control, supported by the national dengue budget. To date 40 of 46 communes (93 111 households and 386 544 people) are free of Ae. aegypti, and all 46 have no further reports of dengue and dengue haemorrhagic fever. Vaccine to prevent rheumatic feverMichael Good, Michael Batzloff, Colleen Olive and Sri Sriprakash have been developing a vaccine to prevent group A streptococcus (GAS, Streptococcus pyogenes) infection and its associated diseases such as rheumatic fever. GAS is a serious problem in developing countries58 and in Indigenous communities of developed countries including Australia.59 The vaccine is based on a conformational peptide antigen from the conserved region of the M-protein.60 In preclinical studies the peptide was immunogenic in inbred mice. In outbred mice, the peptide was conjugated to the carrier protein, diphtheria toxoid, and formulated with the human-compatible adjuvant alum. Mice immunised with this formulation had significantly enhanced survival following challenge with several GAS serotypes.61 We have used our peptide in combination with several experimental intranasal adjuvants in outbred mice to induce a local mucosal immunoglobulin-A response capable of significantly reducing GAS colonisation of the throat following intranasal GAS challenge. We are now planning to commence the “Good Manufacturing Process” production of our peptide-conjugate/alum formulation for Phase I human clinical trials. Michael F Good, Director, QIMR Brian Kay, Director, Australian Centre for International and Tropical Health and Nutrition Northern TerritoryScabies and skin health: Scabies and complicating streptococcal pyoderma are major causes of morbidity in Indigenous communities in central and northern Australia. The templates for communities to develop their own skin-health programs have resulted from a mix of clinical, public health and laboratory initiatives leading to evidence-based best practice. The first molecular genetics studies ever undertaken on scabies mites were specifically directed at determining whether current dog and human scabies infections are separate epidemics.62 This research enabled the focus of programs to be on prevention and treatment of scabies in children — rather than targeting the dogs. Community-based healthy skin programs have resulted in large decreases in both scabies and streptococcal pyoderma, and current initiatives are directed at sustaining the programs.63,64 Reversing Indigenous renal failureAboriginal people in many remote parts of Australia are experiencing an epidemic of diabetes, cardiovascular disease and end-stage renal disease. The introduction of a systematic pharmacotherapy program over several years on the Tiwi Islands (NT) addressing albuminuria, hypertension, dyslipidaemia and diabetes was associated with a marked fall in rates of renal failure and natural death, reversing a consistent historical trend for both to increase. Rates of the combined endpoints of renal failure and natural death per 100 person-years were 2.9 for the treatment group and 4.8 for the control group.65 Current challenges are how to resource and sustain such activities within the day-to-day clinic activities. Improving dietary quality in remote Aboriginal communities: Poor nutrition in remote Aboriginal communities is linked to high rates of obesity, diabetes and cardiovascular disease. Two well evaluated community-based intervention programs to improve the quality of diets through improved quality of foods in the communities’ local stores have been accompanied by a marked reduction in risk markers for vascular disease across the adult populations. The focus of the Minjilang Nutrition Program66 and the Looma Healthy Lifestyle Program67 has been to reduce the high consumption of sugar and fat, and to increase consumption of fresh fruit and vegetables. Kerin O’Dea, Director Menzies School of Health Research New South WalesDeveloping microsurgeryEarl Owen returned to Australia in 1967 from postgraduate studies in the UK where he had been involved in developing surgical techniques for whole-organ transplantations. An appointment to the Children’s Medical Research Institute from 1967–1970 as the James Fairfax Surgical Research Fellow provided him with the opportunity and resources to develop his expanding interests in the field of microsurgery. This had evolved from his appreciation of the importance of surgical repair of blood vessels and nerves in transplant survival.68 He designed or modified a range of instruments and magnifying devices which facilitated these procedures. His enthusiasm and skill in promoting the advantages of microsurgical techniques led to their rapid widespread adoption in Australia and internationally, particularly in the disciplines of plastic and reconstructive surgery. Gene therapyIn 1995 the Institute and the Children’s Hospital Westmead created a Gene Therapy Research Unit, based on a longstanding interest within the Institute in the use of retroviral gene vectors in biomedical research. Directed by Dr Ian Alexander, the unit has established a gene-vector production unit which is unique in Australia. In March 2002 in conjunction with the Hospital Necker in Paris, this unit and the Immunology Department of the Hospital treated a child with X-linked severe combined immunodeficiency by transducing the infant’s haemopoetic stem cells with a normal copy of the mutant gamma-c subunit of the interleukin receptors.69 This has resulted in a successful reconstitution of the T cell compartment and the patient remains free of infection 18 months later. While gene therapy is far from being routine clinical practice, there is no doubt that it will play a major role in future therapy of a range of diseases from single gene defects to cancer. Peter B Rowe, Director, CMRI l-Arginine and vascular adhesionResearch by Mark Adams, David Celermajer and Wendy Jessup, in a collaboration between the Institute and the Department of Cardiology at Royal Prince Alfred Hospital, found that l-arginine reduces human monocyte adhesion to vascular endothelium and endothelial expression of cell adhesion molecules.70 Subsequent clinical studies showed that oral l-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease.71 This research has translated into the clinical use of oral l-arginine as a treatment in patients with intractable angina. A surrogate marker for advanced atherosclerosisLen Kritharides and co-investigators are developing non-invasive tests for the presence of vascular disease. Using samples obtained from patients undergoing bypass surgery and coronary angiography, they found that coronary arteries release a number of molecules into the blood stream. One of these is haptoglobin, a protein not normally measured in patients with atherosclerosis,72 but which is present at elevated levels in the circulation in patients with advanced coronary disease. This non-invasive test has the potential to identify the presence of vulnerable atherosclerotic plaques before their rupture. Philip J Barter, Director, Heart Research Institute Diabetes and obesityIn 1973 a small team led by Les Lazarus at the Garvan developed the low-dose intravenous insulin infusion method to treat a major complication of diabetes, ketoacidosis.73 This has saved the lives of innumerable Australians and has been taken up around the world. Over the past 20 years, the diabetes research team, including Ted Kraegen, Lesley Campbell and Don Chisholm, has made major contributions to our understanding of the impact of lifestyle on type 2 diabetes. They were one of the first groups to show that exercise training improves whole-body insulin sensitivity.74 They were also one of the first to unravel the impact of dietary lipids on insulin sensitivity75,76 and to show that fat deposition in specific regions plays a key role in the development of insulin resistance.77 These findings have made major contributions to the management of this extremely complex and common human disease. Breast cancerGarvan scientists led by Professor Rob Sutherland carried out an extensive series of studies which helped elucidate the mode of action of the breast cancer drug, tamoxifen.78 Garvan scientists pioneered research demonstrating the role of the cell cycle regulatory protein cyclin D1 in development and progression of breast cancer.79 Recently, this research was judged by the international ISI Essential Science Indicators as one of the top 20 advances (and most cited papers) in breast cancer in the past decade. Further work has confirmed this molecule as an adverse prognostic marker and therapeutic target in breast cancer. John Shine, Executive Director, GIMR Established 3 years ago, the ANZAC Research Institute is one of Australia’s youngest medical research institutes, located on the campus of Concord Hospital and affiliated with the University of Sydney. Its primary research focus is on ageing. Hepatic pseudocapillarisation and cardiovascular diseaseDavid Le Couteur’s observations that ageing is accompanied by obliteration of endothelial pores that allow the liver to metabolise circulating macromolecules80 has led him to a novel approach to examining the liver and postprandial hyperlipidaemia as pivotal elements linking ageing and cardiovascular disease. Genetics of neurodegenerationGarth Nicholson’s discovery of the gene for hereditary sensory neuropathy81 provides an elegant and unique neurogenetic model for classical sensory neuropathies of leprosy and diabetes which both feature painless damage to joints and extremities. Hormonal male contraceptionRecently published work by David Handelsman first proved the efficacy of a hormonal male contraceptive using a prototype combination depot.82 This proof of principle has been adopted by a collaboration between two major multinational pharmaceutical companies, Organon and Schering, to develop a marketable product. David J Handelsman, Director, ARI New antiviral strategies for herpesThe herpes virus periodically reactivates from dormancy and is transported down sensory nerves to skin causing genital lesions. WMI virologists including Tony Cunningham, Russell Diefenbach and Monica Miranda first showed that the virus is transported down these nerves as two components, the inner core and outer (glyco) proteins, subsequently assembling at the nerve terminus. Transport along microtubules (the “railway tracks” of the nerve) was found to be mediated by the interaction of a virus core protein (US11) with a cellular protein, kinesin.83,84 The exact regions of the interaction were mapped and patented as a drug target. A collaboration with Pharmacia is now seeking small molecule inhibitors of this interaction as a new drug strategy for herpes. First success in herpes simplex vaccinesThe first success in vaccine development for genital herpes by GlaxoSmithKline (GSK) has just been reported. This development was partly guided by, and depended upon, key discoveries by WMI scientists, Tony Cunningham and Zorka Mikloska, who showed that the immune control of herpes lesions was mediated by an early influx of CD4 and later CD8 lymphocytes. Both cell populations secrete interferon gamma, which controls viral transmission from nerve to skin and viral mechanisms for evading immune control. The key viral stimulant for CD4 lymphocytes was glycoprotein D (gD).85 The GSK vaccine incorporated gD and an adjuvant to stimulate these mechanisms. This proved 75% successful.86 Refined advice for those at genetic risk of melanomaCancer researchers at WMI, led by Richard Kefford and Graham Mann, have been unravelling melanoma susceptibility genes. They confirmed that the major melanoma gene, CDKN2A (“p16”), is located on chromosome 9p, and went on to perform the largest analysis of mutations in this gene in 132 Australian families.87 WMI researcher Helen Rizos and her team have established the importance of p14ARF, an alternate product of the CDKN2A gene, in the genesis of melanoma, and have recently described a number of highly novel functions of this molecule in regulating the cell cycle at several key points.88,89 Collaborative research between WMI and Nicholas Hayward of the Queensland Institute of Medical Research, together with the members of the international Melanoma Genetics Consortium, has enabled this genetic information to be translated into clinical guidelines for managing those at high risk of developing melanoma, including the use of genetic testing.90,91 Anthony Cunningham, Director, WMI

Martin B Van Der Weyden

The AdWatch section of the Healthy Skepticism website (www.healthyskepticism.org/adwatch.asp) aims to improve medical decision-making by illuminating the techniques used in drug advertising. AdWatch draws on 20 years of dialogue about drug promotion plus ideas from many disciplines, especially logic, psychology and marketing. A small group known as Healthy Skepticism . . . has consistently and insistently drawn the attention of producers to promotional malpractice, calling for (and often securing) correction. These organisations [Healthy Skepticism, Médecins Sans Frontières and Health Action International] are small, but they are capable; they bear malice towards no one, and they are honest. If industry is indeed persuaded to face up to its social responsibilities in the coming years it may well be because of these associations and others like them.1 Graham Dukes (Professor of Drug Policy Studies, University of Oslo, Norway) The quality of care delivered by doctors and our consequent incomes depend on our decision-making skills in the face of information and promotion of variable quality. However, few doctors have much training in the basic sciences for decision-making, such as logic and psychology. A database of 2178 references on drug promotion compiled by the World Health Organization provides evidence that many doctors are more vulnerable to being misled than they realise.2 Healthy Skepticism is an international organisation based in Australia that aims to improve health by reducing harm from misleading drug promotion. In October 2003, Healthy Skepticism launched AdWatch, a monthly webpage that explains the techniques used in drug advertisements.3 The story of Healthy Skepticism’s predecessor, MaLAM (the Medical Lobby for Appropriate Marketing), was told in the 1997 Christmas issue of the Journal.4 This update describes the ideas behind the transition from MaLAM to Healthy Skepticism and the launch of AdWatch. From MaLAM to Healthy SkepticismIn the 1980s, open letters from MaLAM achieved improvements in advertising and some drugs were withdrawn.5 During the 1990s, there were fewer obviously inappropriate drugs to target. Although many serious problems with misleading promotion persist,6 they are more subtle and thus less amenable to open-letter campaigns. To understand these problems better, we developed a stronger multidisciplinary team with expertise in medicine, marketing, psychology, pharmacy, pharmacology, statistics and logic.7 We were inspired to change our name to Healthy Skepticism by a 1963 speech from drug advertising executive Pierre Garai.8 Garai urged doctors to stop blaming drug companies for misleading drug promotion and argued that the quality of drug promotion depends on the quality of medical decision-making; “. . . indeed, [if] candor, accuracy, scientific completeness, and a permanent ban on cartoons came to be essential for the successful promotion of [prescription] drugs, advertising would have no choice but to comply”. Garai challenged doctors to accept responsibility for improving their decision-making and to develop healthy scepticism. We accept that effective promotion is a mirror to our souls, reflecting how we really make decisions. The image it reveals differs from what we would prefer to believe about ourselves. However, accepting our human limitations is the best first step towards improved medical care. Consequently, we accept Garai’s challenge, but we feel that blaming the targets of promotion for human vulnerability to promotional techniques is not helpful. Many techniques have been effective in fooling many of the people much of the time for centuries;9 others are products of recent sophisticated research on ways to increase sales.10,11 We prefer to focus on changing the current system in which misleading promotion leads to inappropriate prescribing and higher profits for drug companies, thus funding more misleading promotion. This vicious cycle harms patients and may reduce incomes for doctors and drug companies in the long run. The concept of healthy scepticismThere were two schools of extreme scepticism in ancient Greece. The Pyrrhonian Sceptics suspended judgement on all claims, including the Academic Sceptics’ claim that nothing could be known for certain. Moderate healthy scepticism started with the 16th century theologian Castellio, who advocated accepting reasonable beliefs rather than aiming for certainty.12 In the 1990s, a US business academic developed a questionnaire for measuring scepticism.13 She characterised sceptics as slow to accept claims or form judgements, but keen to ask questions in pursuit of knowledge and understanding, and found that sceptical auditors were more effective and efficient at detecting problems in company accounts. Thus, healthy scepticism involves selectively accepting claims that are justified by good evidence or argument, while resisting those that are not. Understanding misleading promotionFrom Aristotle onward, logicians have observed many types of misleading arguments, which are now called fallacies.9 Psychologists have studied similar concepts, calling them heuristics, biases and influence techniques.14,15 We prefer the term shortcuts. These are quick and easy processes for reaching conclusions that are correct only when common assumptions are justified. For example, “newer is better” is usually a reliable shortcut for choosing the best vegetables or computers, but often unreliable when choosing drugs. It is common to assume that most new drugs are superior, but only about 3% of new drugs offer real advances.16 It is normal to use shortcuts when faced with inadequate time, skills or resources to examine the evidence fully, or when the evidence required is not available. Some common shortcuts are listed in the Box. Drug companies are skilled at influencing prescribing by triggering the shortcuts that doctors rely on. For example, the “experts know best” shortcut underpins company-funded education. Drug companies also carefully choose visual and verbal images that appeal to our normal desires for power, respect, wealth, speed, simplicity, security and sex.10 There is evidence that advertising can be effective at influencing behaviour despite being given little attention.11 Subtle messages that might be rejected if carefully considered can sneak “under the radar” to create links between the indication, the product and the motivation. Repetition strengthens these links so that the product moves up the mental agenda to be the first to come to mind during decision-making. Promotional techniques are tools for good or ill depending on how they are used and what they are used for. Shortcuts often lead to correct conclusions, and desires can be appropriate. It is not possible to advance good causes without using promotion. To be successful at advancing the aims of Healthy Skepticism, we have to use the same techniques that we want people to be more sceptical about. However, we aim to use promotion honestly. This article uses all the shortcuts listed in the Box and appeals to most of the desires listed above. Developing healthy scepticism with AdWatchHealthy scepticism is difficult to promote because most people are confident that they already have an optimal amount. It is common to believe that only other people are susceptible to being misled. Dispelling this illusion of unique invulnerability is the key to improving discrimination between misleading and justified claims.15 One effective method for dispelling this illusion is to mislead people and then show them how they have been deceived. In one study, hospital pharmacists used the techniques of drug company representatives to mislead medical students and then explained the techniques.17 After the intervention, the students were less certain about the value of interactions with drug company representatives. We hope AdWatch will produce similar benefits by explaining the logical, psychological and pharmacological techniques used in drug advertisements. We will also use feedback from visitors to the AdWatch section of the Healthy Skepticism website (www.healthyskepticism.org/adwatch.asp) for dialogue with the companies responsible for the advertisements, the Medicines Australia Code of Conduct Committee and the government regulatory agencies. We have started with advertisements targeting Australian general practitioners but hope to develop editions for specialists and for other countries. Initial feedback to AdWatch from general practitioners, specialists, pharmacists and members of the public worldwide has been positive. An Australian doctor commented: “Unfortunately [the advertisement] had me sucked in for a period, but no longer.” Commonly used shortcuts for choosing therapies Newer is better. Experts know best. If there is mechanism for how it works, it works. If my peers are using a therapy, so should I. If the manufacturers give gifts, I should support them in return. If I see changes after prescribing a therapy, that therapy must be the cause.

Peter R Mansfield BM BS

To the Editor: Are we doctors, physicians, MDs, MBs or what? In the past 50 years or so, the address form “doctor” seems to have lost much of its meaning. Of course, academics holding non-medical doctorates in Australia have long nursed a grievance that graduates in medicine have no rightful claim to the title. Perhaps so, but, like it or not, it was thrust upon us at graduation as a courtesy title, and there is no doubt that in the 50s it was of value to patients in establishing the status of their medical advisers. The rightfulness of the use of the title “doctor” by medicos is supported by antiquity, although divinity, law and music might claim precedence over medicine in using the title. The ancient word “doctore” can be translated simply as “teacher”, and the title, or its equivalent, was so used in Roman and ancient Greek times. There is a reference to the term in its medical sense in a quote from Chaucer (c 1386) in the Oxford English Dictionary: “WiÞ vs Þere was a Doctur of Phesike”.1 At present in Australia we have dentists, veterinary surgeons and others who identify themselves as “doctors”. And then there are legions of PhDs in such diverse disciplines as demography, political science, nursing, economics, leisure industries, and so on. In Australia, where we have inherited much of our general medical culture from the United Kingdom, surgeons are often addressed as “Mr” (a legacy of the days of the barber-surgeons) within their hospitals, but “Dr” by their patients. In North America, where medicos acquire the letters “MD” on graduation, “physician” seems to be the generic term in professional circles, while for journalists, “a doctor” or “an MD” are interchangeable identifiers. We could anticipate that any trend away from “doctor” to “physician” in Australian medical literature to follow the US example would meet with strong opposition from internists protecting the integrity of their “physician” status conferred by the Royal College. Understandable opposition to the adoption of “MD” as a generic identifier could be expected from holders of Australian MDs gained by thesis. So is it time for a title change? Change would not be unprecedented. The University of Sydney changed the qualifying degrees from MB, ChB (1882) to MB, ChM (the by-laws being altered in 1884 so that the latter degree was conferred on those who elected to receive it). The first degree in surgery was changed again to BS in 1922 but remained optional until 1974.2 Several Australian universities have recently made radical changes to the content and duration of medical-school courses. Perhaps the indefinite term “an MB” could be adopted as a surrogate for the popular US term “an MD”. Perhaps a new, uniform Australian medical identifier will evolve. Or perhaps we will just muddle on, letting sleeping dogs lie and confusion continue. This seems to be the probable outcome, as good reason rarely prevails in the minds and hearts of men.

Dennis D Arnold MB BS, FRCS, FRACS · Thomas KF Taylor DPhil, FRCS, FRACS

To the Editor: Patiens in Latin refers to someone who is suffering. However, in the real world the word “patient” also, ironically, takes on elements of the more conventional meaning of the word in its adjectival form. A person becomes a patient when he becomes ill. From that moment onwards he begins to comprehend the indubitable reason for being tagged as a “patient”. He patiently bears the ride to the doctor’s office and waits with a dutiful patience, in a room appropriately dubbed the waiting room, until he is called into the consulting room. Like a zombie, he patiently waits in the consulting room, obeying the dictates of the nurse to either stand on a weighing scale or sit on a chair for blood pressure measurements, while he patiently answers a volley of insipid questions about his health. In between, he waits patiently, with a thermometer perched precariously in his mouth, as the nurse stares at her watch or waits for the thermometer to beep. Then he patiently submits to the discomfort of donating blood or the indignity of providing urine or sputum samples. Ultimately he gets the golden opportunity to understand the real meaning of patience as he patiently waits for the doctor to arrive. The doctor, knowing full well the patience of patients, takes his time to arrive at the clinic. Steadfastly ignoring calls from the clinic, he works diligently on grant proposals/lectures/administrative matters until finally, unable to quench persistent calls, he dashes out to see his patient patients. Now that the interminable wait is finally over, the patient patiently submits to an expert examination. He patiently describes his symptoms (again) and patiently listens to what the doctor has to say. The need to draw on a seemingly immense reserve of patience does not cease once the patient leaves the doctor’s surgery. After patiently waiting at the pharmacy for his prescription, he patiently takes the medicines according to the doctor’s orders. He then patiently waits for the medicines to take effect. Therefore, calling a sick person a “patient” is particularly apt. It becomes slightly complicated when the terms “inpatient” and “outpatient” are used. Does a lack of patience eventually turn a patient patient into an inpatient? When all’s said and done, it is always better to be a patient patient than an impatient patient who tries the patience of potentially impatient doctors who rely greatly on the potential patience of patients.

Biji T Kurien

Human fetal tissue is a scarce resource that has been used in Australia for biomedical research since 1980. From 1994 to 2002, it has been used for research by 19 biomedical researchers at 12 separate Australian institutions (four universities, six major teaching hospitals and two research institutes). With an average of 265 samples distributed annually, researchers have conducted experiments in biomedical research with the approval of their Human Ethics Committees, and published 74 manuscripts in peer reviewed journals over the past decade. The tissue is obtained from therapeutic termination of pregnancies at 8–20 weeks’, but mostly 14–18 weeks’, gestation. The average number of fetuses obtained over the past 10 years was 108 per annum. Our understanding of the pathogenesis of human diseases such as diabetes, multiple sclerosis, retinopathy of prematurity and osteoporosis has been advanced because of such experiments, and better drug treatment of disorders such as osteoarthritis has been made possible with the use of human fetal tissue. The benefits of human fetal tissue research need greater recognition.

Bernard E Tuch FRACP, PhD · Hayley Scott BScAg · Muhammad T Tabiin PhD · Liping P Wang MSc · Patricia J Armati PhD

William J Glasson,* Robert A Bain† * Federal President, † Secretary General, Australian Medical Association, PO Box E115, Kingston, ACT 2604. To the Editor: The workforce article by Brooks et al1 identifies key factors causing the medical workforce shortage and notes, correctly in our view, that: “The full impact of these factors is yet to be felt, but might occur very rapidly”. However, the authors fail to address why this has occurred and what should be done. The answer as to why is quite simple. In the 1990s, the Labor and Coalition federal governments introduced a series of measures to ration the supply of doctors and the provision of services in order to restrain the health budget. Measures such as restrictions on medical student places, reduced training places, restricted provider numbers, failure to properly index the Medicare Benefits Schedule or introduce the Relative Value Study, and the move away from fee-for-service with the rapid expansion of red tape, were all designed to restrict services that cost the government money. The current doctor shortage, falling participation rates (the trend to doctors retiring early or working part-time) and demoralisation of significant sections of general practice are a tribute to the success of these policies. As the recent Australian Medical Workforce Advisory Committee careers study shows, the much-discussed feminisation of the GP workforce is as much a consequence of a declining number of young male doctors considering general practice to be a rewarding career as it is the result of a need by both male and female doctors for an occupation that allows a flexible work and family lifestyle.2 Nevertheless, the outcome — the falling participation rate among current and future general practitioners — is at the heart of the problem. The solution will require a total shift in policy direction from sticks to carrots. It will need to cover Medicare, training, working conditions, and the removal of red tape and all forms of restrictions not required to ensure good clinical practice. Attempts to use regulations or commercial levers to enforce bulk-billing in an already depleted workforce will only serve to exacerbate the current situation.

William J Glasson · Robert A Bain

Lloyd K Morgan Retired General Practitioner, PO Box 150, Lorne, VIC 3232. To the Editor: New imaging and pathology investigations continually improve diagnostic accuracy. But tests must be used because they supplement clinical deduction, not because they are available, and the constellation of clinical features should not be ignored. The case report by Chatterjee and colleagues is valuable for describing delayed diagnosis of meningitis, based on imaging which suggested subarachnoid haemorrhage and aspiration pneumonia.1 The 4-day history, examination (raised respiratory and heart rates, high fever) and results of initial investigations (neutrophilia, raised C-reactive protein level, lung consolidation) suggested a primary respiratory infection. The absence of a typical history of onset of subarachnoid haemorrhage is excused by the 5.5- hour hiatus before the patient was found semicomatose. Subarachnoid haemorrhage was diagnosed because of density in the subarachnoid space on computed tomography (CT). The authors noted a 1980 report of this appearance in a patient with bacterial meningitis.2 They also noted only one previous report of purulent meningitis mimicking subarachnoid haemorrhage on CT scan (in 1994),3 but there is reluctance to publish “negative” outcomes. Aspiration as the cause of upper-lobe consolidation was unlikely. Bacterial pneumonia and chemical pneumonitis affect the lower lobe.4 Clinical findings were not consistent with subarachnoid haemorrhage, and meningitis was the differential diagnosis, so only the overweighted CT results prevented lumbar puncture on Day 0, which would have resulted in earlier, broader antibiotic therapy and possibly resumption of warfarin. By Day 1, it was too late to prevent permanent blindness (it was possibly too late on Day 0, but pupils were reactive at that time). Even on Day 1, repeat cranial CT showed infarction but less evidence of bleeding; “a disparity between the amount of [alleged] subarachnoid blood and the patient’s clinical condition” was followed by magnetic resonance imaging then angiography and venography, instead of lumbar puncture as suggested by hindsight in the last sentence of the report. Shadows do not always equate with pathology. Compare an article on the clinical diagnosis of meningococcaemia.5 Holistic care of Chatterjee et al’s patient included anticoagulation therapy. “It probably could have recommenced earlier” than after “a large pulmonary embolus” on Day 13 — perhaps, given the presence of long-term indications (lupus inhibitor, anticardiolipin antibody and previous thrombosis) and cerebral vessel inflammation causing infarction, on Day 1. The main lesson, which we were all taught as students but needs career-long reinforcement, is in the penultimate sentence of the case report: “Investigations should not be interpreted in isolation from the clinical picture”.

Lloyd K Morgan

Taposh Chatterjee,* John R Gowardman,† Tony D Goh‡ * Registrar, † Intensivist (corresponding author), ‡ Radiologist, The Canberra Hospital, PO Box 11, Woden, ACT 2605. John.gowardmanATact.gov.au In reply: We agree with Morgan that the symptoms, signs and laboratory investigations in our case report, although non-specific, supported a diagnosis of infection.1 The C-reactive protein level was not available for 24 hours. The unwitnessed drop in level of consciousness that occurred between 09:00 and 14:30 could have been secondary to meningitis or an acute cerebral event, and, while it is true that the lower lobes are predominantly involved in aspiration, they are not solely involved. Consolidation in other gravity-dependent segments, including the posterior segments of the upper lobes, can occur.2 The suggestion that “permanent blindness” could have been prevented is not supported. Fortuitously, an appropriate antibiotic to which the organism was fully sensitive was given from Day 0 (ceftriaxone). Adjunctive supportive care was quickly provided. In retrospect, anti-coagulation therapy could have recommenced earlier, but this remained a difficult decision in the context of the computed tomography findings. It remains unclear how this would have modulated the meningeal process, but it possibly contributed to the complication of pulmonary embolism. We agree that there is a reluctance to publish what may be perceived as “negative” outcomes, but, educationally, these may be the most rewarding. This case was an uncommon presentation of a common disease, and we considered it sufficiently important to notify other practitioners. Of most importance in this era when technology in medicine advances exponentially, any investigation must be considered only an adjunct to, and not a replacement for, thorough clinical evaluation.

Taposh Chatterjee · John R Gowardman · Tony D Goh

Christopher M Pearce Senior Lecturer in Rural General Practice, Department of General Practice, University of Melbourne, 200 Berkeley Street, Carlton, VIC 3053; Director, Australian Division of General Practice; and PhD student. chris_pearceATmac.com To the Editor: The recent issue on general practice (7 July 2003) contained many statements that were inaccurate and unfair to a profession that has existed before most specialties and will exist beyond their passing. It is unfortunate that the issue represents an opportunity missed. Notwithstanding the funding issues, general practice is not “in crisis”, as many of your authors would attest.1 It is vibrant and leading the way in healthcare reform in this country, and much of its loss of appeal to new doctors has to do with the attitudes of many of the authors, who talk it down rather than up. The quoted comment from Donald Berwick — “we are carrying the nineteenth-century clinical office into the twenty-first-century world”2 — is surely the most inaccurate statement. Modern general practices bear no relationship to even their mid-20th-century counterparts, whereas the average specialist office still looks the same and functions in a similar way. General practice is over 80% computerised,3 unlike the practices of our specialist colleagues. General practice has been responding to the challenges of a community-centred approach, while specialists still respond to a disease-centred model. Indeed, many members of the profession correctly talk about research as a means of raising the profile of general practice — in this regard, the specialties have been hiding behind the power and influence of research institutes. Until funding bodies such as the National Health and Medical Research Council give general practice research priority over such esoteric areas as “Major porcine antigens for the generation and modulation of immune responses to neovascularised pig tissue xenografts” ($480,000)4 in allocating research grants, things will not change. Further, many of your articles still reflect a degree of discomfort with general practice as a distinct discipline — reflected in the confusion over “general practice” versus “primary care”. These are two separate areas, and, while general practice is well defined, primary care is not. Several authors5,6 in the recent general practice issue speak of Divisions of General Practice and of the opportunities for collaborative research therein. Unfortunately, academia has failed to engage with Divisions. Although the Board of the Royal Australian College of General Practitioners has several professors, the Board of the Australian Divisions of General Practice sports a couple of part-time senior lecturers. Divisions report that academics often have a paternalistic attitude towards general practice, without understanding the true potential of partnerships with GPs. General practice remains the most important, popular, and utilised part of the healthcare system, both in Australia and overseas. It is embracing change and responding to demands, often in innovative ways. We should be celebrating its achievements, rather than talking about imagined “crises”. Martin B Van Der Weyden Editor, Medical Journal of Australia, Locked Bag 3030, Strawberry Hills, NSW 2012. editorialATampco.com.au In reply: I would be heartened to believe that all is well in Australian general practice, that it is indeed “vibrant and leading the way in healthcare reform in this country”. But the reality appears to be otherwise. Surveys attest that doctors are unhappy, and Australian general practitioners have not escaped the mood of discontent and disillusionment.1,2 That more than 80% of our general practices are computerised is laudable. But is this technology being used in a patient-centred way? Are visits coordinated so that waiting times are minimal and queues a thing of the past? Do practices use their computers in a way that efficiently integrates office processes, patient care, patient records, prescribing, pathology, referrals and health outcomes over time? In short, is this technology being used as a vibrant tool for practice efficiency and quality patient care? It appears that there is still some way to go, as a recent survey of GPs revealed that less than 50% use their computers for prescribing and less than 30% for managing appointments and clinical records.3 Whether specialists hide behind the façades of research institutes is uncertain. But what is certain is that research output in the field of general practice in Australia lags far behind that of medicine, surgery or public health.4 Furthermore, the National Health and Medical Research Council awards research grants on merit, not on a subjective assessment of what each sector “deserves”. I am disturbed to learn that all is not well between some Divisions of General Practice and general-practice academia. A recent review of the Divisions’ role5 makes no mention of this divide, but submissions to the review did outline the need for stronger relationships between Divisions and academia. It takes two to tango and the solution lies with both parties. Finally, I am encouraged that, despite the alleged “crisis” theme of the Journal’s recent issue on general practice, there are those who believe that “general practice remains the most important, popular and utilised part of the healthcare system”. However, on the issue of whether there is a “crisis”, participants in the recent Australian Health Care Summit would beg to differ: the general opinion was that not only is general practice “in crisis”, but so too is the whole healthcare system.6

Christopher M Pearce

Joachim P Sturmberg,* Carmel M Martin† * Associate Professor of General Practice, Monash University, Melbourne, VIC; † Associate Professor of General Practice, Ottawa University, Ottawa, Canada. Correspondence: Associate Professor Joachim P Sturmberg, PO Box 3010, Wamberal, NSW 2260. jp.sturmbergATbigpond.com To the Editor: As much as we agree with the general sentiments of Del Mar and colleagues’ views about the malaise of general practice,1 we feel they simply listed some of the well known symptoms without elaborating on the underlying pathology or analysing the failure to provide appropriate treatment. Their conceptualisation of general practice focused on clinical performance within a disease-centred model of medical care, which includes the issues of published and cited papers, critical appraisal and evidence-based medicine. Their analysis did not address systems issues, including the funding of general practice/practitioners, organisational change (such as amalgamation and corporatisation), and the establishment of Divisions of General Practice that have largely failed the community as well as the discipline. We would argue that redressing the problems in general practice requires a fresh start in thinking. We need a much broader conceptualisation of general practice and its role within the healthcare system. Firstly, the specialty of general practice is patient-focused generalism — that is, a focus on patients’ bio-psychosocial healthcare needs and understanding of their illness experience. Secondly, we need to recognise the important place of general practice in healthcare delivery and population health. After all, an average 217 patients per 1000 seek medical care each month, of which only nine will be hospitalised and one will require tertiary care.2 A broader conceptualisation of general practice must embrace the discipline’s patient-centred approach to patient care and an explicit understanding of systems approaches within the context of the populations served by the discipline. This can only be achieved if we embrace different research models and understand modes of healthcare system organisation, both of which are based on dynamic, non-linear models. Such an approach implies that we continually revise our models of clinical practice around patient and community needs. In fact, the greatest strength and the greatest opportunity of our discipline is our grassroots involvement — our ability, based on our individual experience, to advocate on behalf of our patients for a system based on their care needs and our ability to deliver such care. We don’t underestimate the challenges inherent in reorienting our discipline away from the mechanistic disease model of the 20th century towards a dynamic, patient-focused model relevant to the 21st century. Christopher B Del Mar,* George K Freeman,† Chris van Weel‡ * Director, and Professor of General Practice, Centre for General Practice, University of Queensland Medical School, Herston, QLD 4006; † Professor of General Practice, Centre for Primary Care and Social Medicine, Imperial College, London, UK; ‡ Professor of General Practice, University Medical Centre, Nijmegen, the Netherlands. c.delmarATcgp.uq.edu.au In reply: We agree wholeheartedly with Sturmberg and Martin that it is often hard to separate cause from effect. Are the symptoms actually the cause? The old villains — amalgamation and corporatisation — are only two of the main culprits. After all, they have had influence on specialist practice too. The point we tried to make is simply that the intellectual deficiencies in the discipline of general practice, which attracted a public flaying1 after an international conference on general practice research this year in Canada,2 are too often ignored. Addressing them in the context of biomedical research, rather than embracing a different paradigm, may be one solution. The approach advocated by Sturmberg and Martin (ie, emphasising healthcare system organisation and using novel research methods) is fine — we need innovation in healthcare systems and new ways of improving them. Nor do we trivialise patient-focused healthcare, in which huge advances have been made based on general practice research. Patient-focused healthcare was one of the themes of the recent research conference.2 But, if general practice enquiry remains limited to health services research, and if specialists do research on disease without involving general practitioners (however old-fashioned and “mechanistic” that might appear), we will always have difficulty clawing our way out from an intellectually inferior position. A recent example to illustrate the importance of clinical research in general practice is the latest hormone replacement therapy (HRT) uproar. For many years, the benefits of HRT have been simply projected on and promoted in the general population. Now that breast cancer risks have become clearer,3,4 it is obvious that earlier research could have prevented this negative fall-out.5 As Sturmberg and Martin so rightly point out, many illnesses are principally managed in primary care. Should we not become experts (through research and teaching) in their management too?

Joachim P Sturmberg · Carmel M Martin

Umberto Boffa General Practitioner (vocationally registered), 31–35 Burgundy Street, Heidelberg, VIC 3084. Umberto. BoffaAThba.com.au To the Editor: It is fitting for the Journal to recognise the crisis facing Australian general practice (7 July 2003). Every thinking person in the profession knows general practice needs to alter course if it is to survive. They are not lulled by the widely touted sophistry of practice accreditation, vocational registration, “cookbook” talk of disease management and other distractions. However, nothing in the contributions gave me hope for the future of general practice and the community it serves. To paraphrase, Australian general practice is really a specialty, requires postgraduate training as long as that of rocket scientists and needs to be even more dependent on government involvement. It had also better look more like a specialty by doing some research. General practice training may suit the training industry and government, but does not look like producing better doctors. The product looks like a medically qualified hybrid between a social worker and a case manager, something that may titillate government but does not appear to impress the rest of the profession. General practice training relegates to the past the absolute necessity of acquiring the sharpest clinical skills as a diagnostician, and fosters instead the mantra of “better communication skills” and, worse, a disdain for core knowledge. The political nature of this training does not appear to fool potential entrants, who are shunning general practice, nor does its professional façade fool some of our more astute medical leaders.1 But the plight of general practice is posing a hidden danger to the whole profession. The move away from core knowledge in general practice has inspired a “dumbing down” of the profession that is now influencing undergraduate medical education. Under the guise of “problem-oriented learning”, core knowledge is being seriously neglected, such that physiotherapists and nurses will soon be better trained than medical graduates. I believe grassroots general practitioners (not their myriad representatives) need to rebel against government involvement in their professional training (ie, the Royal Australian College of General Practitioners) and reaffirm their “medicalness”. We can not be professionals and have governments determine our future, as suggested by Kidd of the RACGP.2 Australian general practice should look now to the august independence and academic robustness of the Royal Australasian College of Physicians to give us a new flag — not one of specialty, as we are not specialists, but one of independent professional standards and allegiance. Michael R Kidd Professor, and Head, Discipline of General Practice, University of Sydney, 37A Booth Street, Balmain, NSW 2041; and President, Royal Australian College of General Practitioners. michaelATgp.med.usyd.edu.au In reply: Boffa appears to have overlooked the key messages in my editorial, which clearly outlined the risks inherent in government involvement in vocational training for general practice. These risks include a lack of long-term funding commitments, reliance on professional support for success, and the current challenge posed by the poor image of general practice and training requirements among potential registrars. My editorial also clearly stated the need to distinguish medicopolitical objectives from the requirement for high standards of education and training. Boffa’s presumably tongue-in-cheek suggestion about general practitioners joining the Royal Australasian College of Physicians overlooks the success of the Royal Australian College of General Practitioners (RACGP) in setting and maintaining standards for high quality clinical practice, education and training, and research in Australian general practice for nearly 50 years. The RACGP is independent of government. Our core activities are funded by our members. The RACGP remains the largest medical college in Australasia, with over 10 000 GPs as financial members and over 18 000 GPs as members of our Continuing Professional Development program.

Umberto Boffa

Keith S Jones Bayview, NSW. rgjones1ATbigpond.com To the Editor: The Journal’s recent, extremely interesting issue on general practice (7 July 2003) has prompted me to look back at a symposium held at Sydney Hospital on 1 April 1966 (April Fools Day!). The subject was “The future of medicine”. The three speakers were Sir Charles McDonald, Chancellor of the University of Sydney; Mr Harry Jago, NSW Minister for Health; and myself, on behalf of the Australian Medical Association (NSW). My contribution on that day concluded as follows:1 From the facts, figures and trends which I have given you, I would forecast as follows (and again, this must be subject to no radical changes in the international, political or economic framework of the country). There will be a relative decrease in the numbers of doctors available to the community, and the greatest fall will be in the group most needed, the general practitioners. On the other hand, I expect a greater demand by the population for medical services. The average age of the patients will slowly increase, and geriatric problems will make up the bulk of day-to-day medical problems. It is likely that universities will have different types of medical training for those who plan to undertake general practice and those who intend to specialise. The State and other third parties will provide the main channel by which medical practitioners are remunerated, and I hope (but by no means feel certain) that most will be remunerated on a fee-for-service basis. Small country towns will have even less resident medical attention than they command at present, but better transportation and communications will enable them to be serviced from the large towns with base hospitals. In the hospitals, increasing use will be made of full-time and part-time paid specialists, and in addition new hospitals will arise in the form of geriatric hospitals and hospitals staffed by general practitioners. Finally, the social, financial and professional status of the medical practitioner will ultimately depend on professional unity and wise leadership. Loss of status will inevitably occur with breakdown of either of these conditions. Perhaps I should have been a fortune teller!

Keith S Jones

Peter M Brooks Executive Dean, Faculty of Health Sciences, University of Queensland, Edith Cavell Building, Royal Brisbane Hospital, Herston, QLD 4006. p.brooksATmailbox.uq.edu.au To the Editor: Let me congratulate the Editor and his team for their provocative issue on general practice in Australia (7 July 2003). Some of the major challenges are clearly delineated — particularly that of providing care to a chronically ill and ageing population. While general practice in particular may be suffering from decreasing interest among young doctors, medicine in general is not seen by school leavers of today as the profession it was 30 years ago. Many bright school leavers are pursuing the “corporate world” in economics, law and business, but we can promote the overall satisfaction and variability of medicine in general and general practice in particular. The critical issues are outlined in the editorial.1 Taking a leaf from our “economically” driven society, we need to present to governments and the public the evidence that healthcare systems focusing on primary care are associated with higher patient satisfaction, lower overall health expenditure, better population health indicators and lower per capita rates of drug prescribing.2 Surely, governments (and, more importantly, treasuries) will listen to these arguments. We also need to adopt a “whole-of-profession” approach. I am concerned that specialists (particularly in the hospital environment) continue to portray a negative image of general practitioners, particularly to young doctors.3 We can all remember, in our “resident” days, hearing negative comments from consultants: “If only the GP had done this or that or referred the patient earlier”. Part of the problem is that there is still not enough vertical integration between undergraduate and graduate medical school education, postgraduate years 1, 2 and 3 and specialist training. A particular problem is that, after having had increasing exposure to general practice as a student, medical graduates then spend 2–3 years in a hospital environment where they have little or no contact with general practice. During this time they are influenced by hospital specialists who encourage them to pursue the “illth agenda” in hospital medicine and perpetuate negative stereo-types of general practice. Trainee doctors need exposure to positive general practice experiences in these immediate postgraduate years, including general practice terms (especially in rural general practice) along with hospital attachments. This would require significant dialogue between the federal and state health departments but would go some way towards renewing interest in general practice and continuing to provide Australians with one of the best healthcare systems in the world in terms of equity, access, cost and outcomes. Graham Chaffey General Practitioner, Hazelbrook General Practice, 9 Rosedale Avenue, Hazelbrook, NSW 2779. chaffeyblowAToptusnet.com.au To the Editor: Like Julian White, I was deeply moved to read the final chapter in the fable of the white-tail spider.1 White comments that “The lack of strong evidence to support [the association of white-tail spider bites with necrotic ulcers] seemed to be a triviality to be ignored”. However, I wish to take issue with the attitude to GPs reflected in his statement “General practitioners regularly and confidently diagnosed skin lesions as ‘white-tail spider bite’.” What is the evidence for this statement, or does White view it as too trivial to deserve scrutiny? As a GP, I rarely come across a case of spider bite in which a confident diagnosis can be made. However, I am frequently asked questions such as “Could this be a white-tail spider bite?”, and frequently witness patients latching onto one of a list of possibilities, or unwilling to be dissuaded from the diagnosis they have arrived at independently of any medical advice. Furthermore, it is only after the publication of Isbister and Gray’s evidence2 that I am able to define clearly for my patients the effects of white-tail spider bites, rather than leaving room for doubt. It is a cheap shot for a specialist in such a narrow field to malign GPs on the basis of their failure to critically appraise the evidence relating to aetiology of a rare problem for which there was said to be no treatment. It has become common to read de-rogatory statements about GPs by specialists unsupported by evidence. Interestingly, such comments are not aimed at emergency department nurses, resident medical officers, physiotherapists or other specialists. I would argue that this may be of some importance. Denigration of the value of medical training and skills may contribute to negative attitudes towards GPs in the community. This may translate into adverse behaviours such as unwillingness to seek medical advice, reluctance to have children vaccinated, inadequate use of antenatal care services, degradation of communication between medical practitioners, and demoralisation of the medical workforce. It may also make it difficult for people to accept advice about white-tail spider bites. Perhaps White could afford GPs the respect that he does the white-tail spider, rather than taking a random opportunity to malign the competence of GPs. Max Kamien Research Fellow, Department of General Practice, University of Western Australia, 328 Stirling Highway, Claremont, WA 6010. mkamienATcyllene.uwa.edu.au Comment: Chaffey and Brooks draw attention to the negative effects of specialists badmouthing general practitioners: undermining GPs’ self-image and community status, and discouraging medical students and young doctors from pursuing a career in general practice. Hays has made similar observations about problem-based learning exercises, written by specialists, wherein the mismanaged rural patient is “rescued by clinicians in the nearest large teaching hospital”.1 Medical badmouthing has been defined as “unwarranted, negative and denigratory comments made by doctors about other doctors in different branches of medicine”.2 It is most visible when uttered by specialists in teaching hospitals, but is almost equally as common from GPs criticising some real or imagined lack of common sense in the treatment received by one of their patients in a teaching hospital.2 The underlying psychological mechanism of badmouthing stems from a common human need for self-aggrandisement and defining of group membership by aggressively putting down people outside the “in-group”.3 So, while badmouthing is maladaptive behaviour for the medical profession as a whole, it does have some adaptive features for different subgroups. Specialists in private practice usually have good working relationships with GPs — indeed, their practice would suffer if they didn’t. But, in my (non-evidence-based) experience (I haven’t done a study on the topic), nearly all specialists see themselves as part of a medical elite who have achieved their status through having the ambition, energy and fortitude to complete a rigorous postgraduate training and examination process beyond that required of GPs. And we GPs are appropriately grateful for their skills, especially when one of our patients is faced with a life-threatening emergency. Also, most continuing medical education is given by specialists “teaching” GPs. Reciprocal opportunity for constructive GP feedback about patients’ hospital outcomes is rarely given or gratefully received. Specialists and their junior staff are frequently inconvenienced by overloaded outpatient clinics and by emergency patients, referred by GPs, who arrive at 6 pm instead of 9 am. And on rare occasions they see a patient with a necrotic ulcer due to a basal cell carcinoma, referred by a GP who agreed with a patient’s diagnosis of “spider bite”. What the specialist doesn’t see is the other 100 patients bitten by an uncaptured white-tail spider who are managed solely, logically and effectively by GPs. Extrapolating from one or two cases to the whole of general practice is bad epidemiology and evidence of sloppy scientific thinking. Badmouthing is an ingrained feature of human nature and a historically unattractive part of medical culture. It will continue until all doctors realise that they are on the same team, fighting the same war against the many facets of disease and disability. GPs and specialists need to understand and respect each other’s role and task. This requires mechanisms to enable already time-poor doctors to interact regularly with each other. In one survey, about 10% of students admitted that negative comments by specialists about GPs had influenced their decision to reject a career in general practice.2 This was part of the rationale for setting up a medical school counterculture through rural student clubs.4 But even more harmful than badmouthing is the perception by students and young doctors that general practice is an unattractive branch of medicine, beset with governmental red tape, a divided leadership, and, after failure of the Relative Value Study initiatives,5 a guaranteed continuation of poor remuneration for heavy responsibility taken and long hours worked.

Peter M Brooks

Oh’s intensive care manual. 5th edition. Andrew D Bersten, Neil Soni (editors). Edinburgh: Butterworth Heinemann, 2003 (xiii + 1175 pp). ISBN 0 7506 5184 9. In an era of instantaneously available, Internet-based medical information, why would we buy a textbook? The new editors of Oh’s intensive care manual address this question in their preface to the fifth edition: it is to provide information which is “weighed and measured” as opposed to “raw and unfiltered”. Weighed, presumably, against the best available published evidence, and measured against the yardstick of personal experience. Evolving from a collection of handouts, through a handy “bench book” into an international textbook over 25 years, this new edition is remarkably contemporary, with references from late 2002. How these references were selected is not clear, but the book has never pretended to appeal to evidence-based-medicine (EBM) buffs. It owes its popularity more to its succinct and practical style, with lots of tables, algorithms and definitive statements. We Australian intensivists put our trust in acknowledged experts (with rolled up sleeves) rather than in the distant promises of EBM. So who are these experts, and should we believe them? Andrew Bersten (Adelaide) and Neil Soni (a long-time émigré to London) are the new editors, and are clinically and academically highly credible in both countries. Their team of contributors (89 in total, 49 of them new to this edition) are drawn from the UK and Australia, giving this edition an international flavour lacking in the past. There are few completely new chapters, and many of the old ones are much the same, but 40 of the 104 chapters have been extensively rewritten by these new contributors, and this is the main reason why owners of the much-loved fourth edition should invest in the fifth. For the rest — students, junior or senior medical staff and nurses — if you are ever likely to encounter a patient shocked or unable to breathe, this text remains the definitive guide to diagnosis and management. As Bersten and Soni might say — try doing that with Medline. W Peter SaulIntensive Care Unit John Hunter HospitalNewcastle, NSW Order this book

W Peter Saul

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