Editorials

Editorial Accidental drug toxicity associated with methadone maintenance treatment As patient tolerance varies widely, methadone prescribers and users need to be better informed about the risks of overdose MJA 1999; 170: 100-101 Methadone, a long-acting oral opioid agonist, was first used to treat opioid dependence in the United States in 1964, and was introduced into Australia in 1969. While countries such as the United Kingdom have also shown interest in the use of methadone for heroin withdrawal, Australia has more commonly used it as a maintenance therapy. Currently, there are around 23 000 clients in methadone treatment throughout Australia, and this number is growing at around 15% per annum. Methadone treatment is the main clinical response to heroin addiction in Australia. Randomised controlled trials and controlled observational studies have shown methadone to be effective in reducing heroin use.1 Methadone treatment has also been found to be effective in reducing criminality, the risk of contracting HIV infection and the risk of deaths from overdose, and is associated with improvements in health and social functioning.1 The report by Caplehorn and Drummer in this issue of the Journal reminds us that, as with all medical treatments, there are risks associated with methadone treatment.2 Looking at deaths associated with New South Wales methadone maintenance programs in 1994, the authors identified two problem areas -- the period of induction into methadone treatment and the diversion of methadone to non-treatment populations. Despite the mortality associated with methadone maintenance treatment, Caplehorn and Drummer estimate that the New South Wales program saved 68 lives in 1994. The risk of overdose during induction into methadone therapy can be reduced by better training of prescribers in assessing the degree of opioid dependence and tolerance. These skills are now included in learning objectives developed at the request of the National Methadone Committee,3 and methods for assessing prescribers' competence in this area are currently being developed by an expert group (Robert Hughes, Director, National Drug Strategy, Drug Strategy and Population Health, Social Marketing Branch, Public Health Division, Department of Health and Aged Care, Canberra, ACT, personal communication). Routine regular monitoring for signs of intoxication and withdrawal is also an important consideration, and shared care protocols to improve the relationship and communication between prescribers and dispensers of methadone during patients' induction phase are under development in several jurisdictions -- such protocols need national consistency. In Australia, contention persists among clinicians and policymakers about the most appropriate dosing regimen for initiating methadone therapy. The dosing range and recommended increments in the first weeks of methadone treatment set out in the current National policy on methadone treatment4 have been criticised for being too rigid and not able to take account of variation in "real-world" practice. At the National Methadone Conference (Melbourne, 21-23 November, 1996), prescribers argued that inadequate starting doses will drive patients who experience withdrawal symptoms to "top up" the prescribed dose of methadone with heroin, benzodiazepines or illicit methadone. Thus, there is a need to find a balance between effective dosing while minimising the risk of overdose, and allowing flexibility in clinical judgement. To maintain the good reputation of methadone programs in Australia, it is crucial to establish credible guidelines on safe and effective induction into methadone treatment. To that end, a meeting to be held in early 1999 aims to establish evidence-based guidelines. This scientific review should provide a useful framework for informing the development of policy for induction, stabilisation and assessment of patients in methadone treatment. Illicit methadone use has been found to be widespread both overseas and in Australia.5 The most common reason reported for this use has been self-treatment of opiate withdrawal.6 Rarely, users report using methadone for its euphoric effects, and this is much more likely if the methadone is injected.7 There have been a variety of approaches to limiting the potential for diversion of methadone supplies. For example, in South Australia, the volume of takeaway doses is expanded to up to 100 mL to reduce the likelihood of injection. Other States have limited the timing and numbers of takeaway doses. A systematic review of these approaches is required to determine the most effective way of responding to this problem. In view of the mortality associated with methadone maintenance treatment highlighted in this issue of the Journal,2 there is a risk that there will be calls for further restrictions on methadone availability. While this may reduce the number of methadone-related deaths, it may inadvertently lead to an increase in the number of heroin-related deaths. Thus, it seems that the important lesson in methadone-related mortality is that we must ensure that both prescribers and potential users of methadone are aware of the risks of overdose, particularly for those who are not opioid tolerant. Robert L Ali Chair, National Expert Advisory Committee on Illicit Drugs Adelaide, SA Allan J Quigley Director, Clinical Research and Policy Development WA Alcohol & Drug Authority, Perth, WA Ward J, Mattick RP, Hall W. Methadone maintenance treatment and other opioid replacement therapies. Amsterdam: Harwood Academic Publishers, 1998. Caplehorn JRM, Drummer OH. Mortality associated with NSW methadone programs in 1994: lives lost and saved. Med J Aust 1999; 170: 104-108. Allsop S, Bell J, Brough R, et al. Learning objectives for methadone prescribers. Canberra: AGPS, 1997. National Drug Strategy. National policy on methadone treatment. Canberra: AGPS 1997. Darke S, Ross J, Hall W. Prevalence and correlates of the injection of methadone syrup in Sydney, Australia. Drug Alcohol Depend 1996; 43: 191-198. McLellan AT. Methadone diversion in the USA (1998). In: Hall W, editor. Proceedings of an international opioid overdose symposium. Sydney: National Drug & Alcohol Research Centre, 1998. (Monograph No. 35.) Darke S, Hall W. Levels and correlates of polydrug use among heroin users and regular amphetamine users. Drug Alcohol Depend 1995; 39: 231-235.

Robert L Ali · Allan J Quigley

Editorial Confusion about secondary prevention for bowel cancer: resolving issues at the front line MJA 1999; 170: 102-103 An effective, clearly enunciated national policy is needed for secondary prevention (screening and surveillance) of bowel cancer in Australia. Bowel cancer meets the World Health Organization criteria for screening, and is the commonest internal malignancy affecting both sexes in Australia, causing more deaths than any other cancer except lung cancer.1Three randomised controlled trials have shown that screening average-risk populations (aged 50 years and over) by the crudest of faecal occult blood tests (Hemoccult) is effective in reducing population mortality from bowel cancer on an intention-to-screen basis.1 Furthermore, calculations of cost-effectiveness using Australian cost data and screening outcomes of the poorly specific rehydrated Hemoccult test show that screening for bowel cancer is about as cost effective as screening for breast cancer.2Given that neither mortality from bowel cancer nor cancer stage at diagnosis has improved in various Australian States,3 we can assume that current secondary prevention activities are only minimally effective. Indeed, the incidence of bowel cancer continues to rise in men.3 Why are we not conducting screening and surveillance? Why are we missing out on their demonstrable benefit? From a national perspective, two key issues arise: How should we implement screening to reduce population bowel cancer mortality rates?; and While this question is being answered, what is reasonable action for individuals interested in being screened or for those at risk of bowel cancer? Unfortunately, failure to separate these two issues has led to confusion and misunderstanding of promulgated guidelines. The issue of an effective population screening program was addressed in the Australian Health Technology Advisory Committee (AHTAC) report released in April 1998.1 A recent editorial in the Journal called for the issues raised in that report to be addressed and resolved.4 The AHTAC report proposed "pilot and feasibility studies" to examine aspects of screening, such as logistics, choice of screening tool, risks, costs, acceptability, resources and education. It took an evidence-based approach and considered the issues from a population perspective. Early in 1998, the National Cancer Control Initiative submitted a proposal to government seeking funds for pilot and feasibility studies in the general population. These funds have not yet been provided -- we will not have an effective program for the general population until results of pilot studies are available. In the meantime, doctors, and especially general practitioners (GPs), remain confused as to what is reasonable practice. Evidence for this confusion is presented by Sladden and Ward in this issue of the Journal.5 They found that many GPs are unaware of the evidence that screening is effective and are uncertain about intervals for testing, the age to start, and how to apply the screening/surveillance tools to an individual in a manner appropriate to the individual's risk profile. Few GPs are "highly likely" to recommend faecal occult blood screening (and presumably any other type of screening for bowel cancer) during a health check, even though we know that people who have biennial screening with Hemoccult have about a 40% reduction in risk of dying from bowel cancer.6Sladden and Ward point out that guidelines available in Australia are partly responsible for the confusion, because of their inconsistency in recommendations. This inconsistency arises partly because the issue is complex and the evidence is incomplete. Also, there is a failure to appreciate the difference in the guidelines between what is acceptable as a population strategy and what is reasonable for the individual who seeks screening. Given that the value of early-detection programs in average-risk individuals is supported by three randomised controlled trials of faecal occult blood test-based screening and by several case-control studies of flexible or rigid sigmoidoscopy screening, it is difficult to ignore the individual seeking help. The soon-to-be-promulgated Guidelines for the prevention, early detection and management of colorectal cancer of the National Health and Medical Research Council (NHMRC) and the Australian Cancer Network have been developed by a process of consensus, incorporating a national workshop and analysis of the evidence. These guidelines should provide a path through the confusion, provided they are endorsed and used by the medical colleges and other professional and educational bodies. They will also partly solve the problem of access to, and resourcing of, the colonoscopies needed for effective secondary prevention. Adherence to guidelines for colonoscopic surveillance of those at increased risk of bowel cancer might then free this limited resource for more effective deployment to a larger proportion of the population. The issues for the primary healthcare provider are complex: the GP needs to check the presence or absence of symptoms, profile the asymptomatic individual's risk, tailor the screening or surveillance program to that risk, and deal with the population's aversion to things anal or faecal. The media have been unhelpful in this respect, with little publicity given to bowel cancer.1,4 As pointed out by Sladden and Ward, GPs' actions might be suboptimal if they cannot immediately recall the necessary (rather complex) detail or access the services needed. When a GP considers that secondary prevention might be indicated, support in terms of education and access to carefully coordinated secondary prevention services should be provided by regional health services. The GP's role is important to the success of secondary prevention, whether it is part of a future coordinated mass program, or dealing with the individual seeking guidance or needing motivation. Clearer guidance will come from the NHMRC-Australian Cancer Network best practice guidelines. However, the continued rise in the incidence of bowel cancer and failure to lower its mortality will not be adequately controlled by such an ad hoc approach;7 population pilot studies are desperately needed, and so is government funding! Graeme P Young Professor of Gastroenterology, Flinders University of South Australia Head, Gastrointestinal Services, Flinders Medical Centre, and Repatriation General Hospital, Adelaide, SA Australian Health Technology Advisory Committee. Colorectal cancer screening. Canberra: Commonwealth Department of Health and Family Services, 1997. Salkeld S, Young G, Irwig L, et al. Cost-effectiveness analysis of screening by faecal occult blood testing for colorectal cancer in Australia. Aust J Public Health 1996; 20: 138-143. Bell JC, McCredie M, Coates MS, Armstrong B. Trends in colorectal cancer incidence and mortality in New South Wales 1973-1992. Med J Aust 1997; 166: 178-181. Collett JA, Olynyk JK. Colorectal cancer screening in average-risk, asymptomatic Australians [editorial]. Med J Aust 1998; 169: 14-15. Sladden MJ, Ward JE. Australian general practitioners' views and use of colorectal cancer screening tests. Med J Aust 1999; 170: 110-113. Hardcastle JD, Chamberlain JO, Robinson MHE, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472-1477. Neugut AI, Young GP. Screening for colorectal cancer: an overview. In: Young GP, Levin B, Rozen P, editors. Prevention and early detection of colorectal cancer. London: WB Saunders, 1996: 357-368. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Graeme P Young

Editorial Databases and evidence-based medicine in general practice We have built it, but will they come? MJA 1999; 170: 52-53 In the early 1990s, evidence-based medicine (EBM) became the focus for improving healthcare.1 Since then, there has been a steady stream of rigorously researched clinical practice guidelines,2 the birth of specialised extracting journals such as Evidence Based Medicine, Evidence Based Mental Health and Evidence Based Nursing and the inception and growth of the Cochrane Collaboration and the Cochrane Library. The latter includes the Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness, available either online or on CD-ROM.3 The essence of EBM is that decision making in healthcare should be influenced by the best available evidence and clinical experience, and the practice of EBM means integrating individual clinical expertise with the best external evidence from systematic research.4 Integral to this is access to, and interpretation of, the evidence in systematic reviews, meta-analyses, evidence-based practice guidelines and evidence databases. The usefulness of evidence databases in real-time clinical practice was recently highlighted in the Journal by the report that 72% of Australian neonatologists and 44% of obstetricians regularly used evidence databases to guide their care of patients.5 In this issue of the Journal, Young and Ward report on Australian general practitioners' use of the Cochrane Library.6 Although 43% of GPs (14% at work) had access to the Internet and 22% were aware of the Cochrane Library, only 6% had access to it and 4% had ever used it. These findings are mirrored in the United Kingdom, where the Cochrane Library Database of Reviews has a higher recognition rate among GPs (40%) but the rate of use (4%) is remarkably similar.7 What the findings of Young and Ward mean for the current use of EBM in general practice awaits a comprehensive national study on the usefulness, relevance and framework of the tools of EBM in Australian general practice. Simplistic explanations for their findings include the low connectivity of our GPs to databases or the limited relevance of these databases -- which emphasise therapeutic interventions rather than diagnosis and prognosis or other types of clinical questions8 -- to general practice. General practice, which centres on the individual patient-doctor relationship and the interaction between biomedical, personal and contextual perspectives, may require different research strategies and allowance for more "circumstantial" evidence rather than the "watertight" evidence accrued by randomised controlled trials.9 It is ironic that with the emphasis on evidence in EBM there is so little published information on the attitudes of Australian GPs towards EBM, the education and skills they require to access and interpret evidence, and the support they need to incorporate EBM into everyday general practice. A recent UK survey of GPs has shed some light on these issues by showing that, although most GPs welcomed the move to EBM and agreed that this would improve patient care, there was a low level of awareness of extracting journals, review publications and relevant databases such as the Cochrane Library.7 While UK GPs expressed a desire to increase their knowledge of the methods and vocabulary of EBM, the major barrier they perceived to practising EBM was a lack of time.7 This finding strongly suggests that for EBM to succeed in general practice information needs to be relevant and available in the clinic within minutes rather than hours.8 Such information might be provided by an intermediate service,10 in the way that pathology or radiology services are currently provided to support GPs. What are Australian GPs' perceptions of EBM? Although there is no information directly comparable with the UK findings, two local surveys11,12 have found that: Topics identified by health policymakers for the development of guidelines are not necessarily synchronous with GPs' perceived needs;12 The source of guidelines is critically important for the perceived credibility of guidelines (eg, in 1995 the Australian Cancer Society and the Australian Medical Association outranked nine other organisations, including the National Health and Medical Research Council [NHMRC] and the Royal Australian College of General Practitioners);12 and Online dissemination of evidence is perhaps before its time, as GPs express a strong preference for guidelines in a booklet compiled in one official document -- a preference perhaps consistent with the respondents' low rate of Internet access at the time of the survey.12 Nonetheless, there is a need for comprehensive information on the context and use of EBM in Australian clinical practice. This requirement has recently been addressed by the NHMRC through its Evidence Based Clinical Practice Program, which promotes and funds research into strategies for implementing and sustaining the use of EBM in different Australian healthcare environments, and into the effect of EBM on patient outcomes.13 Answers for these critical questions are not expected before the year 2000. Interventions to promote behavioural change among healthcare professionals Consistently effective interventions Educational outreach visits Reminders Multifaceted intervention combining two or more of: audit and feedback, reminders, local consensus processes, or marketing Interactive educational meetings in which healthcare providers participate in workshops Interventions of variable effectiveness Audit and feedback (or any summary of clinical performance) Promotion by local practitioners identified by their colleagues as influential Including participating practitioners in discussions to ensure that they agree that the chosen clinical problem is important and the approach to managing the problem is appropriate Any intervention aimed at changing the performance of healthcare providers for which specific information was sought from or given to patients Interventions that have little or no effect Distribution of recommendations for clinical care, including clinical practice guidelines, audiovisual materials, and electronic publications Didactic educational meetings such as lectures All of these considerations revolve, of course, around the perception and usefulness of EBM in general practice. Another prerequisite for the widespread use of the paraphernalia of EBM in general practice is a change in GPs' behaviour. Interventions for influencing behaviour which may have some bearing on introducing research into clinical practice have been identified by Bero et al,14 and are summarised in the Box (above). The effectiveness of such interventions among Australian GPs remains to be explored. In the movie Field of Dreams (1989, Universal Studios), a farmer (Kevin Costner) builds a baseball stadium in the isolation of the midwestern cornfields of the United States to summon the ghosts of past players. With poignant conviction, he says, "Let's build it, and they will come". Although the framework of EBM has been built, will our profession come? What are appropriate tools and interventions for encouraging doctors, and particularly GPs, to practise EBM? On these questions, we need some real evidence. Martin B Van Der Weyden Editor, The Medical Journal of Australia Evidence Based Medicine Working Group. Evidence based medicine: a new approach to teaching the practice of medicine. JAMA 1992; 268: 2420-2425. Smallwood RA, Lapsley HM. Clinical practice guidelines: to what end? Med J Aust 1997; 166: 592-595 The Cochrane Collaboration <http://wwwsom.fmc.flinders.edu.au/FUSA/COCHRANE/>. Sackett DL, Richardson WS, Rosenberg WR, Haynes RB. Evidence-based medicine: how to practice and teach EBM. New York: Churchill Livingstone, 1997: 2. Jordens CFC, Hawe P, Irwig LM, et al. Use of systematic reviews of randomised trials by Australian neonatologists and obstetricians. Med J Aust 1998; 168: 267-270. Young JM, Ward JEW. General practitioners' use of evidence databases. Med J Aust 1999; 170: 56-58. McColl A, Smith H, White P, Field J. General practitioners' perceptions of the route to evidence based medicine: a questionnaire survey. BMJ 1998; 316: 361-365. Glasziou PP. Applying the evidence to the individual. Evidence-Base Health Advice Workshop. Nov 4-5 Melbourne. Melbourne: The Menzies Foundation and National Health and Medical Research Council. 1998. Jacobson LD, Edwards AGK, Granier SK, Butler CC. Evidence-based medicine and general practice. Br J Gen Pract 1997; 47: 449-452. Fowler C. Evidence-based learning in general practice. Br J Gen Pract 1996; 46: 754-755. Gupta L, Ward JE, Hayward RSA. Clinical practice guidelines in general practice: a national survey of recall attitude and impact. Med J Aust 1997; 166: 69-72. Gupta L, Ward J, Hayward RSA. Future directions for clinical practice guidelines: needs, lead agencies and potential dissemination strategies identified by Australian general practitioners. Aust N Z J Public Health 1997; 21: 495-499. Rubin GL, Frommer MS, Vincent N, Phillips PA. Disseminating and implementing the evidence. Evidence-base Health Advice Workshop. Nov 4-5 Melbourne. Melbourne: The Menzies Foundation and National Health and Medical Research Council. 1998. Bero LA, Grilli R, Grimshaw JM, et al. Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings. BMJ 1998; 317: 465-468. Make a comment Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Editorial Posthumous conception and the need for consent We should require prior consent to safeguard the interests of the deceased MJA 1999; 170: 53-54 The spectre of a bereaved family member attempting to cope with the tragic death of a loved one by harvesting the deceased's gametes for procreative purposes is indeed a moving one. But sympathy alone should not inform law and public policy. Rather, we need to grapple with the complex moral issues emerging from the advent of medical techniques that, for the first time in history, have made posthumous conception a reality. Any attempt to formulate a coherent ethical framework in this area must be sensitive to the many interests at stake. In addition to considering the grieving family member's desire to produce a child, policymakers must identify and evaluate other important interests. For example, protecting the psychological well-being of the resulting child should receive serious attention. Might the child be adversely affected by being knowingly denied access to one biological parent? Also, the interests of the deceased's family are important, as posthumous conception of a child will probably have enduring emotional, psychological and financial implications for the family. However, the issue most easily overlooked, as the dead have no voice, concerns the interests of the deceased. Specifically, what significance ought to be afforded the deceased's interests when we have little or no evidence regarding his or her wishes for, or objections to, posthumous procreation? Some may claim that we cannot speak sensibly of the dead as having "interests" which can be "harmed" by the conduct of surviving parties because, once a person dies, that individual no longer has any interests and therefore concepts of "harm" or "benefit" are inapposite.1 It is clear, though, that certain acts committed after a person's death can either harm or promote that individual's interests. For example, a posthumous event that destroys a deceased person's reputation harms his or her interests because it adversely affects the way that individual is remembered after death.2 Posthumous conception likewise affects the deceased's interests, because it recasts the content and contours of the deceased's life. When it occurs without the person's consent, it deprives an individual of the opportunity to be the conclusive author of a highly significant chapter in his or her life. Indeed, this is one of the reasons why any attempted analogy between posthumous conception and organ donation fails. Controlling the fate of gametes is different from -- and more significant than -- controlling the fate of cadaveric organs, because procreation is central to an individual's identity in a way that organ donation is not. As the consequences of posthumous conception profoundly affect core values held by the deceased while alive, respect for autonomy requires that this procedure should not be permitted unless the deceased's consent is clear. The interests of the living can also be adversely affected by permitting the harvesting of a deceased person's gametes without his or her consent. As a society, we recognise that most people find it important to attempt to control certain postmortem events.3 Consequently, we have developed procedures that allow us to control certain matters after death, such as the transfer of property, the nomination of beneficiaries, or the transplantation of organs.1,3 Given that it is important to individuals that their wishes be respected after death, it is also important that they have the assurance that their bodies will not be used in a manner inconsistent with their expectations. In our culture today, most people do not expect that their gametes will be used for procreation after death. As this possibility is rarely contemplated, people generally do not make their views regarding this practice explicit. In the vast majority of cases, then, considerable uncertainty exists concerning the deceased's wishes in this regard. The claim might be made that, as it is possible that using the deceased's gametes for procreation would have been consistent with that person's wishes, a request to do so should be granted. However, it is both unfair and undesirable to place the onus upon individuals to state their opposition to posthumous conception. As posthumous conception is not the norm in our society, there is no reason to expect people who might be opposed to the practice to make their objections known. When the living can only speculate about the deceased's wishes, posthumous conception should not be permitted. Even if there is evidence that the deceased desired parenthood in life, it is a considerable leap to assume that he or she would have wished to become a parent posthumously. Evidence indicating a desire for the former does not necessarily support a conclusion that the latter was also desired. If the deceased person's wishes are to be safeguarded adequately in posthumous reproduction, clear evidence of intent to reproduce after death should be required. The strong procreative interest of family members seeking posthumous conception may tempt them to portray the deceased's values and desires in ways that are not necessarily compatible with the interests of the deceased. Given that posthumous procreation, unlike organ donation, entails significant and permanent implications for the deceased's family, the potential for a serious conflict of interest justifies a far more limited decision-making role for the family. Despite the finality of death, the relationship of the living to the dead does not altogether cease with the grave. To some extent, it continues through the actions of the living as they carry out the last wishes of the dead. A presumption against the unauthorised use of gametes after death represents an important statement about the value of bodily integrity and self-determination. We should approach posthumous procreation with great caution, even when the deceased's wishes are known. When these wishes are unknown, respect for individual autonomy and dignity requires that the deceased's body should not be used in a way that, in all probability, was never contemplated in life. Anne Reichman Schiff Associate Professor of Law University of Pittsburgh School of Law, Pittsburgh, PA, USA Partridge E. Posthumous interests and posthumous respect. Ethics 1981; 91: 244-247, 259-261. Feinberg J. Harm and self-interest. In: Hacker PMS, Raz J, editors. Law, morality, and society: essays in honour of HLA Hart. Oxford: Clarendon Press; 1977: 304-308. Feinberg J. The rights of animals and unborn generations. In: Blackstone WT, editor. Philosophy & environmental crisis. Athens: University of Georgia Press; 1974: 57. Reprints: Associate Professor A R Schiff, University of Pittsburgh School of Law, 3900 Forbes Avenue, Pittsburgh PA, 15260 USA. Make a comment Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Editorial Clinical pathways A practical tool for specifying, evaluating and improving the quality of clinical practice MJA 1999; 170: 54-55 The article by Dowsey et al1 in this issue of the Journal is significant. This is the first report in the Australian medical literature that documents the impact of clinical pathways in a tertiary care setting, and is also one of the first randomised trials to show that the use of pathways can improve clinical outcomes. A clinical pathway is a tool that sets locally agreed clinical standards, based on the best available evidence, for managing specific groups of patients. The pathway forms part or all of the patient's record and allows the care given by members of the multidisciplinary team, together with the progress and outcome, to be documented. Variations from the pathway are recorded, and analysis allows a continuous evaluation of the effectiveness of clinical practice.2,3 Information thus obtained is used to revise the pathway to improve the quality of patient care. Pathways were introduced into the United Kingdom in the early 1990s and are used for treating patients with a wide variety of clinical conditions in primary, secondary and tertiary care. They may be diagnosis-based (as in the management of myocardial infarction), or symptom-based (as for the investigation and treatment of patients presenting with chest pain). They may also include a specific procedure, such as renal biopsy, or encourage the use of therapeutic guidelines, such as postoperative analgesia. Standardisation of care has been shown to improve outcomes4 and poor quality healthcare is often associated with unjustifiable variation in clinical practice.5Dowsey and colleagues1 have shown that when they introduced pathways for hip and knee joint arthroplasty better patient outcomes were achieved. The use of clinical practice guidelines based on the best available evidence has generally been welcomed,6 but implementation requires specific action at a local level.7,8 Pathways facilitate the use of guidelines by the multidisciplinary team, as they are locally agreed and are available in the patient's record when decisions are being made. Analysis of the causes of variation further encourages adherence to the guidelines when they are clinically appropriate. Some clinicians believe that guidelines and pathways over-emphasise the clinical condition at the expense of individual patient care. In our experience, pathways provide patient-focused care, as they constantly monitor quality, and any deviation from the pathway identifies complications early. The plan of care is clearly defined and shared with the patient; in some instances patients are involved in the development of this plan. Pathways also facilitate discharge planning as the median length of stay is defined. As Dowsey et al and others have shown,1,9 pathways reduce the length of hospital stay without an increase in complications or unscheduled reattendance. In our clinical experience, pathways have been used successfully to coordinate care across the primary-secondary care interface. Chronic conditions such as asthma, obstructive pulmonary disease, diabetes and palliative care have been managed in this way.10 Some hospitals and general practices coordinate care using pathways for investigating and managing patients who present with conditions such as a breast lump or acute rectal bleeding. While few papers have been published, the National Pathways Association in the UK has information on the successful use of pathways in many clinical settings (a website is currently being developed, but is not yet available; Australian readers can contact D J K by emailing Denise. KitchinerATRLCH-TR. NWEST. NHS. UK). Pathways also have a part to play in clinical risk management. When the pathway is developed, current practice is reviewed and the most recent evidence incorporated into the pathway. Potential risks can be identified and procedures established to minimise them. By including these in the pathway, changes in practice can rapidly be communicated to all members of the multidisciplinary team. Analysis of variation from the pathway can be used to monitor areas of potential risk. Poor documentation can fail to indicate whether a guideline has been followed, and this can readily be addressed by the introduction of the pathway. Another aspect of risk management is preventing the recurrence of untoward events. Pathways can include guidelines that ensure all health professionals are aware of potential risks and take appropriate action to prevent them from recurring. The National Pathways Association in the United Kingdom is undertaking research into the factors that contribute to the successful implementation of pathways. Most clinicians involved in this process agree that making changes that lead to improved outcomes requires active involvement from senior medical staff. There must also be a commitment from management to provide resources to establish and run the program, as time is needed to develop pathways and educate staff. Analysis of variation from, and regular revision of, the pathways is also essential to maintain the improvements in clinical practice. The concept of pathways is based on sound principles, but evaluation of their use is essential, and the article by Dowsey and colleagues contributes towards that evaluation. There is a need for further research into the use of pathways, the outcomes that they achieve and the costs involved. Recently, the National Health Service in the UK introduced the concept of Clinical Governance.11 This involves a process of continuous quality improvement for which senior clinicians and managers are directly responsible. It has moved the emphasis from cost containment, as demonstrated in the North American model of managed care, to a process of managing clinical care to improve quality within the resources available. Pathways have been recognised as one option for facilitating this process,12 allowing changes to be driven by clinicians rather than managers. Denise J Kitchiner Consultant Paediatric Cardiologist, and Past Chairman, National Pathways Association Royal Liverpool Children's Hospital, Liverpool, United Kingdom Peter E Bundred Reader in Primary Care, University of Liverpool Liverpool, United Kingdom Dowsey M, Kilgour M, Santamaria N, Choong PFM. A prospective study of clinical pathways in hip and knee arthroplasty. Med J Aust 1999; 170: 59-62. Campbell H, Hotchkiss R, Bradshaw N, Proteous M. Integrated care pathways. BMJ 1998; 316: 133-137. Kitchiner D, Bundred P. Integrated care pathways. Arch Dis Child 1996; 75: 166-168. O'Connor GT, Plume SK, Olmstead EM. A regional intervention to improve the hospital mortality associated with coronary artery bypass graft surgery. JAMA 1996; 275: 841-846. Chassin MR. Quality of health care. Part 3: Improving the quality of care. N Engl J Med 1996; 335: 1060-1063. Dwyer P. Legal implications of clinical practice guidelines. Med J Aust 1998; 169: 292-293. Thomson R, Lavender M, Madhok R. How to ensure that guidelines are effective. BMJ 1995; 311: 237-242. Ward JE, Boyages J, Gupta L. Local impact of the NHMRC early breast cancer guidelines: where to from here? Med J Aust 1997; 167: 362-365. Rossiter DA, Edmondson A, Al-Shahi R, Thompson AJ. Integrated care pathways in multiple sclerosis rehabilitation: completing the audit cycle. Multiple Sclerosis 1998; 4: 85-89. Ellershaw J, Foster A, Murphy D, et al. Developing an integrated care pathway for the dying patient. Eur J Palliat Care 1997; 4: 203-207. Scally G, Donaldson LJ. Clinical governance and the drive for quality improvement in the new NHS in England. BMJ 1998; 317: 61-65. Information for health: an information strategy for the modern NHS. Leeds: NHS Executive, 1998. Make a comment Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> We appreciate your comments.

Peter E Bundred

Participatory, non-punitive involvement of healthcare practitioners is needed MJA 1999; 170: 8-9 Increasing use of pathology services is a worldwide phenomenon in countries with substantially different healthcare systems.1 In Australia, for almost a decade and a half the annual growth rates of Medicare-funded services have shown that the rates for pathology services have generally exceeded, and often been more than double, those of other medical services.2-4 In the financial year 1997-98, pathology, diagnostic imaging and general practitioner services grew by 4.28%, 3.86% and 0.59%, respectively, compared with the previous 12-month period. In the same period, the Medicare outlays (ie, "benefits") paid by the Health Insurance Commission for total medical services were $6.334 billion, of which 14.59% were for pathology services and 14.81% for diagnostic imaging services. Together with general practitioner services (37.39%), these account for two-thirds of Medicare outlays. By the turn of the century, the Medicare outlays for pathology and diagnostic imaging services will each exceed $1.0 billion per year. Pathology services in the public health sector, or for workers compensation and traffic accident insurance, are largely funded at State level by arrangements distinct from Medicare. The extent of pathology services and outlays in these sectors is largely unknown, but service growth rates at hospital level are not uncommonly of the order of 1%-3% per year. At the National Pathology Forum (Canberra, 1995) the annual public health sector pathology expenditure was estimated to be $450 million to $600 million. What is the explanation for the growth of pathology services? There is no consensus, but many real, speculative, anecdotal and even light-hearted reasons are given:2,5 among these are diagnosis, monitoring, screening and prognosis; availability and accuracy of prior result; pressure from patients, relatives and peers; reassurance; medicolegal issues; profit; fraud; research; insecurity; and habit. Given this list, some services would clearly be unnecessary and wasteful in the clinical setting,2 but these reasons do not obviously explain the increasing use of pathology services in Australia2-4 and similar trends in other countries.1 Other suggestions for consideration include improved technology allowing larger throughput with shorter turnaround of services, cost-shifting from publicly funded to Medicare-funded services, and altered clinical practice, such as the increasing need in general practice to exclude organic disease when faced with non-specific symptoms. The nature of Medicare data does not allow for conclusive evaluation of these possibilities. Do we really know whether the growth in use of pathology services is appropriate or inappropriate? In a recent review of 44 published studies of laboratory test use,1 11 studies used implicit criteria that were not provided, were very broad, or had not been adequately assessed for their reliability as criteria. In the other studies, explicit criteria were based on the appropriateness of test choice, frequency, timing, and the probability of a positive result. Estimates of inappropriate laboratory test use ranged from 4.5% to 95%! The review authors concluded that the criteria used in these studies did not meet methodological standards suggested for audits of therapeutic interventions, and suggested that researchers should develop alternative evidentiary standards for measuring inappropriateness of pathology service use. They also concluded that, while the evidence supporting the explicit criteria was weak by methodological standards, it was strong according to principles of physiology, pharmacology, and probability. Perhaps the real issue is how to modify the use of pathology services rather than to seek a definitive explanation for the growth in services. The Commonwealth government has sought to reduce Medicare outlays for these services by restructuring the relevant sections of the Commonwealth Medical Benefits Schedule, by informing those requesting these services of their patterns of use, by licensing and reducing the number of pathology collection centres, and by limiting the number of pathology services allowed per episode (ie, per patient each day) that attract benefits. A three-year agreement to cap outlays within predetermined limits was reached between the Commonwealth government and pathology services in 1996. At State level, many hospitals are applying the principles of competitive neutrality (which aims to ensure that government businesses do not enjoy competitive advantage simply because of their public ownership) and even market testing6 to their own pathology departments in an attempt to reduce expenditure, if not use. Such measures are effectively cost-cutting activities, and are seen to be imposed by the funders, often without effective incentives for the users or providers to change.7 Passive information and educational material accompanying these activities is usually prepared by the funders, and may be seen by the users as of little relevance or of poor quality. Moreover, such measures may not prevent the development of further distortions in use of services (through, for example, inappropriate use of other clinical procedures or marketing of other pathology services). Are there ways, other than externally imposed cuts in outlays, to modify use of pathology services? In this issue of the Journal, Isouard reports on the impact of a total quality management approach on the appropriateness of pathology service use in acute myocardial infarction.8 His study used a team which included doctors, nurses and pathologists to determine unnecessary variation in ordering of tests. The outcome was an increase from 77.5% to 88.2% in the proportion of clinically indicated tests that were ordered, and an 81.7% reduction in the use of non-clinically indicated tests. This is associated with the potential to reduce expenditure. It would be all too easy to criticise Isouard's article as being overly enthusiastic about total quality management, as research based around modification of human behaviour, and for the difficulty in rigidly controlling such experiments. Further criticisms might include the need to verify such major improvements independently, and the observed reduction in compliance with the guidelines once the interventions ceased. However, the importance of Isouard's report is that it provides an alternative, non-punitive way to modify pathology service use. It focuses on the processes of ordering and using services, it uses the knowledge and expertise of all the healthcare practitioners involved in the processes, it has the potential to eliminate inefficient and redundant process steps, and it is more likely to provide incentives to healthcare practitioners to reduce variation and hence costs. It also allows for re-engineering the processes to maintain or enhance quality. Favourable outcomes have been reported for similar studies with total hip replacement,7 elective surgery,9 and addressing adverse drug events.10 In these difficult times of rapid change, healthcare practitioners face increasing pressures to reduce costs while providing high quality patient care. Reductions in funding and the use of the traditional scientific method, accoutred with reductionism and concepts developed in "wet" laboratory experiments, may prove inadequate as tools to deal with situations such as the growth in use of pathology services. Healthcare practitioners now need to include in their armamentarium quality improvement techniques,7,9 critical pathways analysis,7 process re-engineering,7,9 and other methods such as qualitative research.11 Robert A J Conyers Medical Director, Gribbles Pathology (Vic) Pty Ltd South Yarra, VIC Van Walraven C, Naylor CD. Do we know what inappropriate laboratory utilization is? A systematic review of laboratory clinical audits. JAMA 1998; 280: 550-558. Deeble J, Lewis-Hughes P. Directions for pathology. National Health Strategy Background Paper No 6. July 1991. Health Insurance Commission web site. <http://www.hic.gov.au>. Accessed 23 November 1998. Australian Medical Association Ltd. Medicare volume and expenditure report. Canberra: AMA Federal Council, August 1998. Lundberg GD. Perseveration of laboratory test ordering: a syndrome affecting clinicians. JAMA 1983; 249: 639. Knowles R. "Significant opportunities" for private sector in Victoria's public health services. Healthcover 1997; 7(5): 11-20. Evans J, Hwang Y, Nagarajan NJ. Cost reduction and process re-engineering in hospitals. J Cost Management 1997; May-June: 20-27. Isouard G. A quality management intervention to improve clinical laboratory use in acute myocardial infarction. Med J Aust 1999; 170: 11-14 Caplan GA, Brown A, Crowe PJ, et al. Re-engineering the elective surgical service of a tertiary hospital: a historical controlled trial. Med J Aust 1998; 169: 247-251. Jones BC. Every defect a treasure: learning from adverse events in hospitals. Med J Aust 1997; 166: 484-487. Peat JK, Toelle BG, Nagy SA. Qualitative research: a path to better healthcare. Med J Aust 1998; 169: 327-329.

Editorial Ethics committees: is reform in order? Ethical review of multicentre studies is necessarily complex, but the system is improving MJA 1999; 170: 9-10 The introduction by the National Health and Medical Research Council (NHMRC) of the requirement for ethical approval of all grant applications in 1973 marked the beginning of the present institutional ethics committee (IEC) system in Australia. This ended the "closed shop" research era, reflecting a wider community demand for more open government, greater public accountability, expanded civil liberties and respect for human rights. It also came at a time when public confidence in "experts" was declining, when complex new technologies were being introduced, and when details of grossly unethical research, such as the Tuskegee syphilis study in the USA, were revealed.1Until the early 1990s, most research involving humans was conducted within individual institutions; this was reflected in the NHMRC Statement on human experimentation and supplementary notes,2 where emphasis was placed on institutional responsibility for ethical oversight. Only passing reference was made to the possibility of multicentre research, with the stipulation that an IEC shall "give its own consideration to projects that involve research in more than one institution", accompanied by a footnote indicating that "An IEC is free to discuss a project with other IECs if it chooses, with due regard to confidentiality." In 1991, in response to perceived bureaucratic delays within the Therapeutic Goods Administration in its centralised approval process for clinical trials, the Baume Report recommended decentralisation of the system, with IECs assuming responsibility for evaluating study design and safety as well as ethical aspects.3 Despite initial uncertainties and difficulties, the clinical trials notification system has proved enormously popular. Notifications have risen from 147 trials at 350 sites in financial year 1991-92 to 400 trials at nearly 1500 sites projected for 1997-98. These figures demonstrate not only increased overall clinical trial activity in Australia, but also a substantially greater number of multicentre studies. Difficulties in the handling of multicentre studies within the IEC system soon became apparent, and were a major focus of discussion at a series of ethics workshops organised by NHMRC in 1995.4 From the researchers' point of view, problems identified included duplication of effort, inconsistencies in documentation requirements and in decisions between IECs, and delays in approval. For IECs, problems included inadequate resources, and uncertainties about the implications of an IEC accepting another committee's decision without its own detailed consideration of the proposal. In this issue of the Journal, Jamrozik and Kolybaba5 raise the possibility of centralised ethics approval of multicentre studies, a suggestion which has been advocated by others in the pages of the MJA recently.6-9 Similar ideas were canvassed at the 1995 NHMRC workshops, and discussed in a 1996 review of the role and functioning of IECs,10 but were not recommended for several reasons. First, institutions have ethical obligations and legal duties towards their own patients, students or staff who become research subjects, and IECs are loath to transfer these responsibilities. Second, important aspects of ethical review are "local". For example, local IECs have the best knowledge of the expertise of investigators, the availability of facilities and resources to support particular types of research, institutional administrative requirements, and the ethnic and cultural mix of the local community.11 Thus, centralised review could assist, but not substitute for, local IEC review of multicentre research. Similar considerations in other countries have led to the conclusion that central review is likely to increase rather than decrease unnecessary bureaucracy and paperwork.12,13 Are other solutions possible? National introduction of a standardised application form, acceptable to all IECs, is currently under consideration by the Australian Health Ethics Committee (AHEC) as a means of minimising inconsistencies and reducing the duplication involved in preparing applications for multiple IECs. Independent initiatives are already under way in NSW and Victoria, where common application forms, developed collaboratively, are undergoing evaluation by local IECs, and there have been expressions of interest from other States. Also, in the not-too-distant future, electronic submission of applications via the Net will become a practical proposition, further reducing the amount of time and paperwork involved in making multiple submissions. Jamrozik and Kolybaba highlight the lack of consistency in decisions reached by different IECs considering the same proposal. Two approaches are relevant. First, to maintain scientific and ethical validity in multicentre studies it is essential for there to be agreement on study design and safety aspects. This could be achieved by participating IECs being prepared to accept a single scientific assessment by an appropriate expert panel. This would not preclude an IEC from drawing on additional advice from its own assessors, but scientific disagreements should be resolved collectively before final ethical approval by the participating IECs. Approaches of this kind have already been suggested,14,15 and the NSW Health Department has established a working party to explore the practicalities. Secondly, participating IECs can be encouraged to harmonise their views on general ethical concerns through better communication (via email, for example, or by teleconferences of the secretaries and chairmen of the IECs involved). Is reform of the IEC system necessary? Although it may not yet be apparent, this is already under way. New NHMRC guidelines on ethical conduct of research involving humans are currently undergoing the final stages of public consultation and revision, and are due for release in early 1999. The need for better resourcing of IECs and training of their members is now recognised. In relation to multicentre research, the guidelines will allow for more procedural flexibility and will shift the emphasis towards a more cooperative approach. Electronic communication, thought to be impractical at the 1995 NHMRC Ethics Workshops, is now a reality. An electronic discussion forum has been enthusiastically embraced by NSW IECs, and is now becoming national. Ultimately, it is to be hoped that widespread formal and informal networking among IECs and researchers will encourage a convergence of views on the solutions to ethical problems, promoting a more consensual culture in the ethical review of research.16 Robert H Loblay Chairman, Ethics Review Committee Central Sydney Area Health Service (RPAH Zone) Email: roblobATmed.usyd.edu.au Donald R C Chalmers Chairman, Australian Health Ethics Committee National Health and Medical Research Council McNeill P. The ethics and politics of human experimentation. Melbourne: Cambridge University Press, 1993: 61-62, 65. National Health and Medical Research Council. Statement on human experimentation and supplementary notes 1992. Canberra: NHMRC, 1992. Baume P. A question of balance: report on the future of drug evaluation in Australia. Canberra: AGPS, 1991. Australian Health Ethics Committee. Report of 1995 ethics workshops. Canberra: NHMRC, 1995. Jamrozik K, Kolybaba M. Are ethics committees retarding the improvement of health services in Australia? Med J Aust 1999; 170: 26-28. Beran RG. Should there be an accredited ethics committee system for centralised review of multicentre clinical research? Med J Aust 1998; 168: 174-176. Clarke CW. Should there be an accredited ethics committee system for centralised review of multicentre clinical research [letter]? Med J Aust 1998; 169: 283. Henman MJ, Tattersall MHN, Brown RF. Should there be an accredited ethics committee system for centralised review of multicentre clinical research [letter]? Med J Aust 1998; 169: 283-284. O'Brien EA, Saltman DC, Berglund CA. Should there be an accredited ethics committee system for centralised review of multicentre clinical research [letter]? Med J Aust 1998; 169: 284. Report of the review of the role and functioning of Institutional Ethics Committees. Report to the Minister for Health and Family Services. Canberra: AGPS, 1996. Weeramanthri T, Currie BJ. Isn't one institutional ethics committee's approval enough [letter]? Med J Aust 1994; 161: 398-399. Moran J. Local research ethics committees: Report of the 2nd national conference. J Roy Coll Physicians Lond 1992; 26: 423-431. Montgomery J. Improving review of multi-centre trials. Bull Med Ethics 1994 (February): 19-22. Cohen M. Should there be an accredited ethics committee system for centralised review of multicentre clinical research [letter]? Med J Aust 1998; 168: 528. Gandevia SC, McKeown T, Wright M, et al. Should there be an accredited ethics committee system for centralised review of multicentre clinical research [letter]? Med J Aust 1998; 169: 285. Chalmers D, Pettit P, on behalf of the Australian Health Ethics Committee. Towards a consensual culture in the ethical review of research. Med J Aust 1998: 168; 79-82. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1998 Medical Journal of Australia.

Robert H Loblay

Editorial Biodiversity loss: a human health issue What do Wollemi pines and a sea squirt with "kidney stones" have in common? MJA 1998; 169: 568-569 The environmental issue most often linked to human health has been the damaging effects of toxic substances and pollutants. Lately, however, the health effects of climate change and loss of biodiversity1 have attracted increasing attention. The Australian State of the Environment report2 has identified biodiversity loss as the most significant environmental problem of the next millennium. Biodiversity loss is generally attributed to degradation of ecosystems, with accompanying loss of species. It is implicated in the rise of infectious diseases3 and in the loss of potential new medicines and medical models. Moreover, the scale and rate of current biodiversity loss is such that the continued viability of our own species is threatened by the disruption of vital ecological processes. The general public has a limited understanding of the concept of biodiversity. Even the more informed regard it as a simple tally of all the plant and animal species. However, biodiversity is a systems concept that refers to the variation of life at different levels of organisation (Figure). It refers to the function of the species known as the "environmental engineers", which provide us with clean air and water, and fertile soils, as well as much of our food, shelter, medicines and industrial products. The value of biodiversity to human health has been highlighted in a recent forum.5 The most obvious benefit is the large proportion of the pharmaceutical armamentarium that is derived from the natural world. Over 50% of commercially available drugs are based on bioactive compounds extracted (or patterned) from non-human species.6 Of the top 100 prescribed drugs in the United States, 55% are natural or semisynthetic, and these percentages are even greater for drugs used for respiratory, dermatological, gastrointestinal, gynaecological and infectious diseases.6 A recent example is taxol, first identified in yew trees (Taxus) of North America. It is one of the most promising drugs for the treatment of ovarian and breast cancer.7 Importantly, taxol has now been isolated from fungi associated symbiotically with the Wollemi pine, a living fossil discovered recently near Sydney. Furthermore, it is not generally acknowledged how widespread the use of traditional medicines is in developing countries. It has been estimated that 80% of the world's population rely on plant-based medicines for their primary health care.8 The value of this ethnobiological knowledge is also recognised by pharmaceutical company researchers, who use this information source routinely in the acquisition phase of drug discovery. Of the 265000 species of flowering plants, it is estimated that less than half of 1% have been screened for their beneficial pharmaceutical properties.9 It has been argued that the loss of species will also result in loss of medical models which can increase our understanding of human physiology and disease.10 Numerous examples exist in species closely related to humans. However, examination of invertebrates is also yielding important models, such as a species of sea squirt (Molgula manhattensis) that develops stones in kidney-like organs. Study of this species has increased our understanding of how both uric acid and oxalate kidney stones form in humans.10 The consequences of such losses pale in comparison with the dire effects of the emergence and re-emergence of infectious diseases. In many cases these events are attributed to the erosion of biodiversity and human ecology. Any disturbance of ecosystems can result in loss of species diversity, a population explosion of competitive species, and host switching of pathogens from primary hosts to humans. For example, the emergence of hantavirus pulmonary syndrome in the south-western United States can be traced to an explosion in the population of deer mice,11 the natural host of the virus, and the subsequent exposure of humans to the excreta of the mice. A similar population explosion of mice in agricultural areas in South Australia occurred in 1993, and, although no infectious diseases were associated with this outbreak, it serves as a warning. The capacity of pathogenic microorganisms to switch hosts is well known. This, coupled with their high reproductive rate and mutation rate, increases their potential to cause serious illness and death in humans. For example, HIV has most likely switched hosts, possibly originating from a mutant simian immunodeficiency virus strain. The outbreak of infection caused by a morbillivirus in horses and humans in Brisbane in 1994,12 resulting in fatalities in both species, is an Australian case that indicates that such switches can occur in any country. Unfortunately, biodiversity loss occurs incrementally and is not apparent to most people. The extent of this loss is measured in terms of species extinction and destruction of habitats. Some scientists estimate that we are losing 100 species per day and that more than a quarter of all species may vanish within 50 years. This rate of loss would be at least 1000 times greater than modelled natural extinction rates. Some studies indicate that as many as 60000 plants could be extinct by the middle of next century.13 The disappearance of vertebrates continues unabated, with Australia having the worst mammal extinction record in the world.2 But the most severe losses are occurring among the invertebrates, most of which are undescribed and yet play critical roles in ecological processes. The habitats of these species are being destroyed at an alarming rate. In the 20 countries with the greatest identified biodiversity, it is predicted that about a quarter of the remaining natural habitats will be cleared by the middle of the next century.14 Australia has an appalling record in this regard, and in the past decade has been identified as one of the worst land-clearing countries in the world.15 Aside from land clearance, the major threats to biodiversity are the impact of alien species, the indiscriminate harvesting of species, and the effects of pollution, urbanisation, and climate change. Fundamentally, living in an ecologically sustainable way is essential, and there is an urgent need for humans to accept that natural resources are limited and, once exploited, are unlikely to be repaired. There is a pressing need for an assessment of human population and consumption.16 Causation in science is empirically difficult to establish. None the less, the argument is persuasive that human population size, urbanisation and malnutrition in sections of the population enhance the emergence of diseases. Human health and well-being can be seen as indicators of the health of global biodiversity. The signs of a difficult future are gathering. The conservation ethic advocated by biological scientists needs to be embraced by all sectors of the community. There is a unique opportunity for the healthcare sector to promote the principles of biodiversity, conservation and sustainable development.17 The obvious links between human health and biodiversity have not been exploited. It would be timely for major medical associations and members of the medical profession to be engaged in public debate on this issue and to support the need for an education program in schools, among doctors and for the general public. Gerry Cassis Centre for Biodiversity and Conservation Research Australian Museum, Sydney, NSW GerrycATamsg.austmus.gov.au Perrings C, Maler K-G, Folke C, et al. Introduction: framing the problem of biodiversity loss. In: Perrings C, et al, editors. Biodiversity loss: economic and ecological issues. Cambridge: Cambridge University Press, 1995: 1-17. Commonwealth of Australia. Australia, State of the Environment. An independent report presented to the Commonwealth Minister for the Environment by the State of the Environment Advisory Council. Melbourne: CSIRO Publishing, 1996. Garret L. The coming plague. Newly emerging diseases in a world out of balance. London: Virago Press, 1994. Commonwealth of Australia. The National Strategy for the conservation of Australia's biological diversity. Canberra: Commonwealth Department of the Environment, Sport and Territories, 1996. Grifo F, Rosenthal J. Biodiversity and human wealth. Washington, DC: Island Press, 1997. Grifo F, Newman D, Fairfield AS, et al. The origins of prescription drugs. In: Grifo F, Rosenthal J, editors. Biodiversity and human health. Washington, DC: Island Press, 1997: 131-163. Nicolaou KC, Guy RK, Potier P, et al. Taxoids: new weapons against cancer. Sci Am 1996; 274(6): 94-98. Farnsworth NR, Akerele O, Bingel AS, et al. Medicinal plants in therapy. Bull World Health Organ 1985; 63: 965-981. Cox PA. Biodiversity and human health conference. Session III: Biodiversity and traditional health systems. Washington, DC: Smithsonian Institution, 1995. Chivian E. Global environmental degradation and biodiversity loss: implications for human health. In: Grifo F, Rosenthal J, editors. Biodiversity and human health. Washington DC: Island Press, 1997: 7-38. Dobson A, Campbell MS, Bell J. Fatal synergisms: interactions between infectious diseases, human population growth, and loss of biodiversity. In: Grifo F, Rosenthal J, editors. Biodiversity and human health. Washington, DC: Island Press, 1997: 87-110. Murray K, Selleck P, Hooper P, et al. A morbillivirus that caused fatal disease in horses and humans. Science 1995; 268: 94-97. Farnsworth NR. Screening plants for new medicines. Wilson EO, Peters FM, editors. Biodiversity. Washington DC: National Academy Press, 1988: 83-97. United Nations Environment Programme. Global environment outlook. Oxford: Oxford University Press, 1997. Glanznig A. Native vegetation. Australia still in top ten land clearing country club. Life Lines: Bulletin of the Community Biodiversity Network, 1998; 4(2): 14. Cohen JE. How many people can the Earth support? New York: WW Norton and Company, 1995. Shearman D, Sauer-Thompson G. Green or gone. Health, ecology, plagues, greed and our future. Kent Town, South Australia: Wakefield Press, 1997. Reprints: Dr Gerry Cassis, Centre for Biodiversity and Conservation Research, Australian Museum, 6 College Street, Sydney, NSW. Photograph courtesy Land Information Services Division, Department of Primary Industries, Water and Environment, Hobart, Tasmania. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Gerry Cassis

Editorial Cancer immunotherapy: new leads on an elusive goal Emerging data increase optimism for mobilising immune cells against cancer MJA 1998; 169: 570-571 The prospect of mobilising the body's immune defences against cancer cells has been an elusive goal in cancer therapy for many decades. The optimism held for this idea has fluctuated over the years, but there are now concrete data emerging from a number of fronts that give good reason to be optimistic about cancer immunotherapy in the medium term. The new data on prospects for cancer immunotherapy were brought together at a recent meeting in Canberra.* Australia has outstanding researchers in this field, and this meeting was an opportunity to assess the current hopes and limitations from multiple perspectives. One chief limitation to cancer immunotherapy has been the difficulty in finding good, cancer-cell-specific target antigens. Immunological tolerance to self antigens on healthy tissues has mistakenly been thought of as an absolute process, barring the prospect of ever getting immune cells to react against cancer cells unless antigens unique to the cancer could be found. Two new developments dispel this perceived limitation. Firstly, many of the cellular processes responsible for immunological self-tolerance are at last being illuminated, through new technologies to genetically engineer transgenic mice.1-4 Definitive work on the process of tolerance to tissue-specific antigens was presented by B Scott (University of Western Australia, Perth), W Heath (Walter and Eliza Hall Institute, Melbourne), F Alderuccio (Monash University Medical School, Melbourne), D Hanahan (University of California, San Francisco) and myself. The data show that tolerance to tissue-restricted antigens, such as proteins made only by specific epithelial, neuronal or endocrine cells, is acquired by regulatory processes that still allow circulation of T cells and B cells with tissue-reactive antigen receptors. If these regulatory processes can be defined and temporarily relaxed by specific drug antagonists, this potential reservoir of immune cells might, in principle, be called into action to destroy cancer micrometastases. One potential target for such antagonists is suggested by inherited mutations in a novel gene, Autoimmune Regulator (AIRE); mutations of AIRE cause a failure of tolerance to multiple endocrine tissues in patients with autoimmune polyendocrinopathy- candidiasis syndrome (N Shimizu, Keio University). Conversely, a potential immune agonist is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a potent inducer of immunity and appears essential for destructive autoimmunity in experimental diabetes mellitus (T Kay, Walter and Eliza Hall Institute, Melbourne). Notionally, such an immunotherapeutic course would follow after a primary tumour is surgically resected or debulked by radiotherapy or chemotherapy. The second development that opens the field of cancer antigen targets is coming from a clinical serum analysis technique called SEREX, which shows that tumours induce "autoimmune responses" much more frequently than has been appreciated.5,6 Autoantibodies against neuromuscular receptors have long been known to cause paraneoplastic syndromes of myasthenia gravis and Lambert-Eaton syndrome in patients with specific types of tumours such as thymoma or small cell lung carcinoma. Results obtained using SEREX show that patients who have any of a broad range of tumours are often making autoantibodies against various tissue-restricted antigens carried by the tumour cells (J Cebon, Ludwig Intitute, Melbourne; B Robinson, University of Western Australia, Perth). These results make it likely that immune defences can be mobilised against many tumours, but how effective will this be and how can they be improved? J Cebon summarised data suggesting that some patients with high antibody responses to tumours survive somewhat longer, but it is still uncertain that immune surveillance is a factor even in these cases, and it is clear that, ultimately, the tumour exceeds or escapes any immune surveillance.5 Genetically engineered mouse models of pancreatic cancer or skin cancer display spontaneous immune responses to cancer antigens,7,8 but augmenting these immune responses only delays tumour progression,9 and the extent to which the spontaneous immune responses restrict tumour growth appears quite limited (D Hanahan and D Daniel, University of California, San Francisco; C Parish, John Curtin School of Medical Research, Canberra). A review of individual case studies provides provocative examples of patients where squamous cell carcinomas or melanomas have spontaneously regressed, accompanied by vigorous immune cell responses to the tumour (G Halliday, University of Sydney).10 The potential for immune control of cancer cells is best illustrated by cancers of viral origin and by organ-specific autoimmune diseases. Only a small proportion of people infected with Epstein-Barr virus or human papillomavirus 16 develop lymphoma or cervical cancer, and there is clear evidence that this is due partly to effective immune responses against the viral antigens carried by the tumour cells (R Khanna, Queensland Institute of Medical Research, Brisbane; I Frazer, Princess Alexandra Hospital, Brisbane).8,11 The devastating destruction of pancreatic islet beta cells in type 1 diabetes mellitus, where no virus is known to be involved, is testimony that immune defences can be unleashed against common tissue antigens as well. Why do most tumours not remit despite ongoing immune responses? Several factors were clearly indicated at the meeting. Firstly, K Lafferty (John Curtin School of Medical Research, Canberra) reviewed recent studies in diabetes showing that vigorous immune responses can be "benign" (non-destructive) or "malignant" (destructive).12 Islet tissues can be heavily inflamed by a benign autoimmune response without any damage to beta cell mass because of poorly understood regulatory processes for self-tolerance.1,3,4 Genetic predisposition only allows a switch to malignant inflammation in certain individuals. As discussed above, the solution to this problem lies in charting the molecular pathways regulating tolerance and developing specific ways to interfere with them transiently. Secondly, tumour cells are genetically unstable and constantly evolving. In viral tumours, cancer cells escape immune surveillance by losing antigens or by losing the machinery needed to present antigens to T cells.11 Tumour instability is a serious problem for any single therapeutic approach, as it is for radiotherapy or chemotherapy, and successful application of immunotherapy will probably also depend on the tumour type and tailored combination with other measures. Thirdly, D Hanahan, B Robinson, G Halliday, and C Parish each drew attention to fragmentary evidence that secreted products from tumours -- such as activins -- and tumour influences on local vasculature and extracellular matrix may create suppressive or non-permissive environments for immune responses.13 It is conceivable that some of these products, such as transforming growth factor b, are key elements of normal mechanisms to prevent organ-specific autoimmunity. This is the least understood of all the obstacles facing immunotherapy. Counteracting such tumour products should not be an insurmountable barrier, but it may take considerable time and effort to define the molecular pathways involved and develop small-molecule antagonists against the best targets. Christopher C Goodnow Professor, Australian Cancer Research Foundation Genetics Laboratory Medical Genome Centre, John Curtin School of Medical Research The Australian National University, ACT Scott B, Liblau R, Degermann S, et al. A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. Immunity 1994; 1: 73-83. Heath WR, Kurts C, Miller JF, Carbone FR. Cross-tolerance: a pathway for inducing tolerance to peripheral tissue antigens. J Exp Med 1998; 187: 1549-1553. Forster I, Hirose R, Arbeit JM, et al. Limited capacity for tolerization of CD4+ T cells specific for a pancreatic beta cell neo-antigen. Immunity 1995; 2: 573-585. Akkaraju S, Ho WY, Leong D, et al. A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis. Immunity 1997; 7: 255-271. Old LJ, Chen YT. New paths in human cancer serology. J Exp Med 1998; 187: 1163-1167. Robinson C, Robinson BW, Lake RA. Sera from patients with malignant mesothelioma can contain autoantibodies. Lung Cancer 1998; 20: 175-184. Skowronski J, Jolicoeur C, Alpert S, Hanahan D. Determinants of the B-cell response against a transgenic autoantigen. Proc Natl Acad Sci U S A 1990; 87: 7487-7491. Frazer IH. Immunology of papillomavirus infection. Curr Opin Immunol 1996; 8: 484-491. Ye X, McCarrick J, Jewett L, Knowles BB. Timely immunization subverts the development of peripheral nonresponsiveness and suppresses tumor development in simian virus 40 tumor antigen-transgenic mice. Proc Natl Acad Sci U S A 1994; 91: 3916-3920. Halliday GM, Patel A, Hunt MJ, et al. Spontaneous regression of human melanoma/nonmelanoma skin cancer: association with infiltrating CD4+ T cells. World J Surg 1995; 19: 352-358. Khanna R, Burrows SR, Moss DJ. Immune regulation in Epstein-Barr virus-associated diseases. Microbiol Rev 1995; 59: 387-405. Gazda LS, Charlton B, Lafferty KJ. Diabetes results from a late change in the autoimmune response of NOD mice. J Autoimmun 1997; 10: 261-270. Jarnicki AG, Fitzpatrick DR, Robinson BW, Bielefeldt-Ohmann H. Altered CD3 chain and cytokine gene expression in tumor infiltrating T lymphocytes during the development of mesothelioma. Cancer Lett 1996; 103: 1-9. * Autoimmunity workshop: the interface between autoimmunity and cancer immunity, sponsored by the John Curtin School of Medical Research, Australian National University. 11-13 September 1998. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Christopher C Goodnow

Editorial Email: editors, doctors and patients We had better learn to live with it, and to use it wisely MJA 1998; 169: 571-572 Recently, my personal computer at the Journal office was linked to the Internet, and thus, belatedly, electronic mail (email) became part of my life. Great were my expectations -- no more lonely and frustrating journeys through voicemail systems with their network of black holes, no more interminable periods of being suspended, "on hold", on the telephone or being bounced along the speaknet from receptionist to personal assistant to doctors.1 Even better, the telephone messages left on my desk, only to be lost amidst piles of wanted and unwanted paper, were to be a thing of the past! Email was to be my salvation -- my escape from the tyranny of the telephone. Despite my initial euphoria, the jury is still out! In the United States the use of email has increased dramatically from 100 000 users in the late 1970s to about 50 million in 1997, and it is predicted that there will be over 100 million users by 2000.2 In Australia, over 1.5 million people have access to email, and the number of subscribers is increasing at a phenomenal rate. These subscribers include about 500 000 home users, but educational institutions are the main users.3 This unprecedented expansion and the uptake of electronic communication have revolutionised effective and efficient communication, but there is also a downside. The release of my personal email address into cyberspace has meant that e-"junk"-mail and e-"chain"-mail can now be added to the irritating influx of irrelevant letters, facsimiles and brochures I already receive. It has also made me feel a loss of privacy. My office is now nakedly exposed to the world and I live in fear of 24-hour-a-day bombardment with irrelevant and inappropriate email. Thus, I have had to confront my first email crisis -- how will I manage this unwanted avalanche? The answer came from an illuminating speaker at a recent local communication conference who, when asked how he managed the large volume of email he received, explained that he does not read emails from people he does not know, as, if a message is important enough, the sender will usually phone him (Dr Karl Sveiby, Visiting Research Fellow, Queensland University of Technology, personal communication). What an elegant solution! In essence a hybrid between a telephone conversation and a conventional letter,2 email has its own language and defined protocols. Telephone conversations are valued for their spontaneity, flexibility and the important nuances of voice inflexions; letters have a long-standing tradition of etiquette, format, punctuation, capitalisation and observance of the rules of syntax. Email offers more permanence than telephone conversations, but its expression is often more spontaneous than that of letters. Thus, emails may be dispatched without editing, punctuation or capitalisation (the ee cummings email), or with no identification or contact details beyond those of the email address (the orphan email). The language of email is developing its own peculiar acronyms and abbreviations and, as its use proliferates, this "espeak" may eventually threaten the current vernacular. An email esperanto may yet evolve! However, despite my personal reservations, there is no doubt that email can and will revolutionise communications between physicians and their patients.4 Not only will email augment patient-doctor communication, it also has the potential to facilitate communications between the consumer, the medical practitioner and other healthcare providers. An overriding concern in the use of email in healthcare involves issues of security and confidentiality of medical information, protocols governing doctor-patient communication and potential medicolegal issues. The American Medical Information Association has recently published guidelines for email communication and for administrative and medicolegal aspects of the use of email.2 The communication guidelines include not using email for urgent matters, informing patients about who actually processes messages, establishing the types of transactions permitted over email, and instructing patients to put the type of transaction in the subject line of the message for filtering. The administrative and medicolegal guidelines include instructing patients on when and how to escalate to phone calls and hospital visits; not forwarding patient-identifiable information to a third party without the patient's express permission; double-checking all "To" fields prior to sending messages; using email encryption whenever practicable, but waiving this at the patient's request; and backing up email onto long term storage media at least weekly. Similar issues are touched upon by Carter in this issue of the Journal,5 but, to date, there are no comparable published Australian guidelines for the use of email in healthcare. With the progressive invasion of our lives by the Internet, surely the time has come for explicit local guidelines. Martin B Van Der Weyden Editor, Medical Journal of Australia Van Der Weyden MB. Hospital doctors and telephones. Med J Aust 1990; 103: 568-569. Kane B, Sands DZ, for the AMIA Internet Working Group Task Force on Guidelines for the Use of Clinic-Patient Electronic Mail. Guidelines for the use of electronic mail with patients. JAMIA 1998; 5: 104-111. Summers A. E-mail: first past the post. The Sydney Morning Herald 1997 Nov 13: 17. Mandl KD, Kohane IS, Brandt AM. Electronic patient-physician communication: problems and promise. Ann Intern Med 1998; 129: 495-496. Carter M. Should patients have access to their medical records? Med J Aust 1998; 169: 596-597. Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

How much should we be spending on health services for Aboriginal and Torres Strait Islander people? By redeploying about 1% of the healthcare budget we could increase spending on indigenous health services by about 50% MJA 1998; 169: 508-509 The health of Australia's indigenous people is much worse than that of other Australians, and worse than that of people in many Third World countries. The life expectancy of Aboriginal and Torres Strait Islander people is about 17 years less than that for other Australians, and their average mortality rate is three times higher. Those living in remote areas have 10-20 times higher death rates from specific diseases, such as diabetes, cervical cancer, and infectious, parasitic and respiratory diseases.1 In attempting to redress this situation, it may be that factors such as housing, sewerage, clean water supplies, education, nutrition, and employment are as important as health services, or perhaps even more important. Nevertheless, improving health services would make a valuable contribution, particularly if the improvements raised the services to a level comparable with those of other Australians. The amount that is spent on health services for indigenous people in Australia has until recently been the subject of much speculation. The newly published Deeble Report on Expenditure on Health Services for Aboriginal and Torres Strait Islander People2 has at last given a more accurate estimate of this figure (Box). Answering the question of what is spent immediately raises the question of what should be spent on health services for indigenous Australians. That question can be answered in a number of ways depending on how one views fairness and equity. One possibility is that health expenditure per capita should be equal for all Australians. This might be fair if everyone had the same health needs, but that is not the case. The elderly, for example, have greater health needs than middle-aged people. The greater health needs of indigenous people mean that equality per capita of health expenditure on indigenous and non-indigenous people -- which is close to what Deeble and his colleagues suggest is currently the case -- is not equitable. How unequal should allocations be to be equitable? In most resource allocation formulas, allocation is on a pro rata basis according to need. However, unless the productivity of healthcare resources is higher for those in greater need, then this may do no more than stop any health gap becoming wider. There is a need to do much more than that. Rather than arguing that all nominally equal health service improvements should have the same value irrespective of who receives them, and allocating resources pro rata with needs, one way to narrow the gap would be to attach a greater weight to health improvements for indigenous people. Thus, a weight of 2, for example, would mean that, in any cost-benefit analysis or evaluation in general, the health benefits to indigenous people would be valued at twice their normal value. This would provide a transparent basis for favouring health services which will benefit indigenous people when allocating health service resources. The precise size of the weighting factor might be determined through consultation with the community, relevant decision makers and stakeholders. In Queensland, a weight of three was formerly proposed for Aboriginality. Apparently this was based solely on the fact that Aboriginal mortality rates were about three times greater than the rates for all Australians.3 In the New South Wales Resource Distribution Formula (RDF) there is now a weighting of 2.5 in an attempt to reflect the "vertical equity" weighting that the State attaches to improvements in Aboriginal health compared with similar gains in the rest of the population.4 It has also been shown that the relevant figure for primary healthcare in the Alice Springs Rural District is in excess of four (and these estimates do not take account of all the factors listed above).5 There is no right level, but there is certainly a case for higher levels of spending for at least the next 10 years. This would be a substantial investment in raising the health status of Australia's indigenous people and would need to take account of the fact that the increase in primary care will lead, in the short term, to even greater demands on hospitals. Beyond that, when the health gains have occurred, then it may be possible to reduce the level of investment again. There also needs to be recognition, as Deeble indicates, of the higher levels of spending needed for delivering services to Aboriginal communities, many of which are in remote locations, and of the need to make the services culturally appropriate. As health status improves in any community there is the prospect that "diminishing returns" will set in. Once the easily achieved gains have been made further health improvements become more difficult. However, providing more resources for those in very poor health may well prove not just equitable but cost-effective, as the improvements in health outcomes per dollar spent on those with poor health status are likely to be higher. From the point of view of the person whose health improves, the lower the starting point, the more the health gain will be valued. The enormous health gap in Australia means that a massive catch-up program is required. Comparisons with New Zealand, Canada and the United States, for example, further emphasise this need. In each of these countries the gap between the health of indigenous and non-indigenous people is much smaller than in Australia.6 Australia is the only First World country that has failed to make real progress in indigenous health (see Ring and Firman)7. Substantially greater investment in research into health services for indigenous people is required. The epidemiology of many areas of indigenous health has been investigated, but there is now a need for a change in research emphasis. We know far too little about the most cost-effective way of delivering culturally appropriate health services to indigenous communities. Certainly, any policy involving a substantial increase in resources should have a major evaluation component built into it. The resource burden on all Australians of investing more in the health of Aboriginal and Torres Strait Islander people is small, simply because they are few in number and there are, by comparison, large numbers of non-indigenous people. Redeploying about 1% of the healthcare budget would increase spending on indigenous health services by about 50%, and could be achieved with very little health sacrifice for non-indigenous Australians (given the low return on the margin of some of the services currently provided). Can such a redeployment not be justified? Put more starkly, the question is: what price a national disgrace? Gavin H Mooney Professor of Health Economics Virginia L Wiseman Health Economist Stephen Jan Health Economist Social and Public Health Economics Research (SPHERe), Department of Public Health and Community Medicine, University of Sydney, NSW Nossal G. We need to spend more on indigenous health. The Sydney Morning Herald 1998; Sep 23: 21. Deeble J, Mathers C, Smith L, et al. Expenditures on health services for Aboriginal and Torres Strait Islander people. Canberra: Commonwealth Department of Health and Family Services, 1998. Queensland Health. Queensland Health Resource Allocation Formula. Brisbane: Policy and Planning Branch, Queensland Health, 1994. NSW Health Department. Implementation of the economic statement for health. Sydney: NSW Health Department Structural and Funding Policy Branch, Policy Development Division, 1996. McDermott R, Beaver C. Horizontal equity in resource allocation in Aboriginal health. Aust N Z J Public Health 1996; 20: 13-15. Kunitz SJ. Disease and social diversity. The European impact on the health of non-Europeans. New York: Oxford University Press, 1994. Ring IT, Firman D. Reducing indigenous mortality in Australia: lessons from other countries. Med J Aust 1998; 169: 528-531. Make a comment Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Gavin H Mooney · Virginia L Wiseman · Stephen Jan

Should research ethics change at the border? The use of placebos in HIV drug trials has raised concerns about research ethics in developing countries MJA 1998; 169: 509-510 Research on mothers with HIV in poor countries has attracted vehement criticism. The researchers (largely funded from the West) are accused of changing their ethics "at the customs desk."1 In defence of their own position researchers (and their sponsoring bodies) claim that ethical standards are unrealistic and that local conditions require studies "that might not be found ethically acceptable in developed countries."2 They argue for achievable standards that depend on local circumstances.2-4 The controversy concerns the use of placebos in zidovudine drug trials on mothers with HIV in Thailand, Africa and the Caribbean. The trials aimed to test the effectiveness of a short course of low-dose zidovudine in preventing transmission of HIV from mothers to infants by comparing transmission rates of mothers given zidovudine with those offered only a placebo. The short course is an alternative to a more expensive regimen of treatment with zidovudine for both mother and infant previously demonstrated to be effective in the trial known as ACTG 076.5 Although the ACTG 076 regimen has been effective in reducing transmission rates by almost 70%, it is not available in resource-poor countries because of the cost and lack of necessary facilities and support.3 Placebo trials in Thailand have recently shown that a simplified regimen of zidovudine was effective in reducing the transmission of HIV between infected mothers and their infants by 51%. This finding is from studies with women who did not breastfeed and who were given zidovudine orally for three to four weeks before birth. No zidovudine was given to their infants.6 This result now makes it clear that placebo comparisons are no longer ethical in mother-to-child HIV transmission studies, even in poorer countries. However, it does not answer the charge that they were unethical in the first place. It is an issue that is still current because there are other diseases for which treatments are available in the West, but not in resource-poor countries. Could placebo trials be justified to test cheaper alternative treatments for these diseases? Furthermore, to continue the logic of the Thai HIV transmission trials, is it ethical to test an even cheaper (shorter course and lower dose) zidovudine regimen? In broad terms the issue is whether ethical standards in research apply across borders, irrespective of poverty and lack of supporting health care systems. The concern with "ethical relativism" in HIV research1,7 is an instance of a long-standing debate between universalism and relativity in ethics, with the universalists arguing for an "irreducible set of ethical standards" that apply internationally.8 These include requirements that the interests of participants in research be given priority over potential benefits for science and society;9 that there be "genuine doubt" as to whether an alternative is as good as standard accepted treatment;10 that studies be approved by an independent committee;9 and that no study be conducted in a foreign country unless it meets the standards of the sponsoring country.11 Failure to accept these minimal conditions, it is argued, is an invitation to unscrupulous researchers and companies to exploit poorer countries.11 Lurie and Wolfe ask ". . . why not select the approach that minimizes loss of life?"11 Although these authors opposed the placebo studies, the answer to their question may well support the placebo trials in Thailand, in that they were quicker and their results support immediate implementation of an effective treatment program (albeit one not as effective as the ACTG 076 regimen). The indications are that in the long run these particular placebo trials will save more lives. Does this end result justify research that withheld effective treatment from HIV-infected mothers and their infants? I admit to being caught between the arguments: on the one hand it is abhorrent to accept that mothers were recruited for studies in which some of them were deprived of a treatment that might have protected their child from contracting HIV. On the other hand, a great many more (future) lives may have been saved. The pragmatic argument is that we must do what we can to test and find effective treatments which can be made available in conditions of poverty. The inequity lies, not in researchers withholding effective treatment, but in a callous world that tolerates gross disparities between rich and poor countries. Researchers are trying to reduce (where they can) some of those inequities. Could there be a middle way between the extremes of universalism and relativity? Nussbaum, while supporting a universalist approach to ethics, argued for "a delicate balancing between general rules and a keen awareness of particulars, in which process . . . the particular takes priority . . . in the sense that a good rule is a good summary of wise particular choices, and not a court of last resort."12 From this perspective, the rule that research must meet the standards of the sponsoring country may need "modification in the light of new circumstances".12 If we take this lead, there may be no simple answer. Each situation would require a careful analysis, guided by internationally accepted rules, and applied with a keen sense for the most humane decision in those circumstances. Certainly, we should be on our guard and block research which simply exploits those in poverty. However, the "wise choice"12 that most benefits people in poor countries may not always conform to Western standards. In this issue of the MJA Studdert and Brennan13 call for "dialogue about whether a universal standard of care is applicable." Although this debate may no longer be relevant to studies of mother-to-child HIV transmission, it remains an important ethical question in responding to dire health needs of those in poor countries. Paul M McNeill Associate Professor in Ethics and Law Faculty of Medicine, University of New South Wales Sydney, NSW Acknowledgement: My thanks to Gregory J Dore, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, for information on recent developments and his many helpful comments. Cohen J. Ethics of AZT studies in poorer countries attacked. Science 1997; 276: 1022. Varmus H, Satcher D. Ethical complexities of conducting research in developing countries. N Engl J Med 1997; 337: 1003-1005. Levine RJ. The "best proven therapeutic method" standard in clinical trials in technologically developing countries. IRB -- A Review of Human Subjects Research 1998; 20(1): 5-9. Merson MH. Ethics of placebo-controlled trials of zidovudine to prevent the perinatal transmission of HIV in the third world [letter]. N Engl J Med 1998; 338: 836. Centers for Disease Control and Prevention. Administration of zidovudine during late pregnancy and delivery to prevent perinatal HIV transmission -- Thailand, 1996-1998. JAMA 1998; 279: 1061-1062; also in MMWR - Morbid Mortal Wkly Rep 1998; 47(8):151-154. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994; 331: 1173-1180. Angell M. The ethics of clinical research in the third world. N Engl J Med 1997; 337: 847-849. Angell M. Ethical imperialism? Ethics in international collaborative clinical research. N Engl J Med 1988; 319: 1081-1083. McNeill PM. The ethics and politics of human experimentation. Sydney and London: Cambridge University Press, 1993: 165-183. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317: 141-145. Lurie P, Wolfe SM. Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. N Engl J Med 1997; 337: 853-856. Nussbaum N. Non-relative virtues: an Aristotelian approach. In: Nussbaum N, Sen A, editors. The quality of life, Oxford University Press, 1993: 242-269, at 257. Studdert DM, Brennan TA. Clinical trials in developing countries: scientific and ethical issues. Med J Aust 1998; 169: 545-547. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Paul M McNeill

Something particular in the air we breathe? Australian research is needed to refine recently set Australian standards for air pollution MJA 1998; 169: 452-453 There is now a mounting body of evidence that fine airborne particles have significant adverse health effects. In this issue of the Journal, Lewis and colleagues report the results of a cross-sectional study of school children conducted as part of the Hunter Illawarra Study of Airways and Air Pollution (HISAAP).1 In brief, the HISAAP investigators found that, in children, outdoor PM10 (particles with an aerodynamic diameter less than 10 µm) concentrations are associated with chest colds and night time cough, but not with wheezing. An important point is that these associations were found at relatively low particulate concentrations -- the most polluted area had an annual average PM10 of 43.7 µg/m3. A good response rate was achieved and appropriate multivariate statistical analysis was conducted to control for confounders such as indoor environmental and individual factors. These results are consistent with previous time series, cross-sectional and cohort studies of the effects of air pollution on both children and adults, predominantly conducted in Europe and North America. The Box contains a summary of the overall health effects found in these studies. Although many of the criteria for causation have now been satisfied (such as a dose-response relationship, consistency of association, and correct sequence of exposure and effect), the lack of data from controlled clinical trials or relevant animal experiments means that the underlying biological mechanisms are not yet understood. Epidemiological studies consistently find associations between exposure to airborne particles and short-term human health effects, and there is no threshold concentration below which these associations disappear. These facts have spurred some regulatory agencies to action. In July 1997, the United States Environment Protection Agency (EPA) set 24-hourly average concentration limits of 65 µg/m3 and an average annual limit of 15 µg/m3 for PM2.5 (particles less than 2.5 µm diameter). These complement the 1987 limits for PM10 of 150 µg/m3 for a 24-hour average and 50 µg/m3 for an annual average. There is some evidence that fine particles (PM2.5) may be even more relevant to public health than PM10.3 In Australia, the development of airborne particle standards to protect public health has proceeded more slowly. In 1990, Streeton first proposed PM10 objectives of 120 µg/m3 for a 24-hour average and 40 µg/m3 for an annual average not to be exceeded for "acceptable" air quality.4 Shortly afterwards, one of us (MJA) expressed the hope that "politicians and bureaucrats would not shirk the task" of introducing the necessary legislation and regulations.5 On 26 June 1998, the National Environment Protection Council finalised the National Environment Protection Measure (NEPM) for Ambient Air Quality.6 This has at last set an air quality standard of 50 µg/m3 for a 24-hour average for PM10. However, because Australian cities are subject to bushfire smoke, the NEPM still permits five allowable exceedance days per year. Closer examination of the evidence summarised in the Box reveals some inconsistencies. It is difficult to envisage a mechanism which results in less exacerbation of mild effects such as cough (1.2% increase per 10 µg/m3) than of respiratory mortality (3.4% increase per 10 µg/m3). Issues such as these have led to continuing controversy over the role of particles in short term health effects.7,8 This was acknowledged in Australia when the National Environment Protection Council agreed, in response to input during the consultation process, that the NEPM and the standards within it will need review within 10 years. There was also agreement that the particle standard needed review, especially the need for a PM2.5 standard. Such a review should be commenced by 2001. Furthermore, a review of the whole NEPM and all six criteria pollutants (airborne particles, sulfur dioxide, ozone, oxides of nitrogen, carbon monoxide, and lead) should be started by 2005. The US National Research Council recently recommended that the US EPA develop a long term (14-year) research program to examine particulate matter.9 Their top 10 priorities are to: investigate quantitative relations between particulate matter and individual exposure; assess the most biologically important constituents of particulate matter; identify the most susceptible subpopulations; analyse exposure to the most biologically important constituents; develop advanced mathematical, modelling and monitoring tools; apply modelling to link sources to exposed individuals; investigate deposition patterns and fate of particles; analyse interactions between particulate matter and gaseous pollutants; explore toxicological mechanisms; and develop advanced methods for statistical analysis of epidemiological studies. Australia needs to conduct similar research because the air quality, the population's exposure to it, and the resulting health effects will differ from those in other countries. The composition, size distribution, and other characteristics of particles differ from those in the United States, as does the mix of background air pollutants in which the particles are suspended, and the susceptibility of the population exposed to such particles. For example, the prevalence of asthma and other allergic disorders is significantly higher in Australia than in either the United States or Europe.10 The results from studies such as HISAAP allow Australian researchers to contribute to this process of examining, in greater detail, the relations between particles and health. It is to be hoped that during the time-frame for revision of the NEPM for ambient air quality, the necessary environmental, epidemiological and toxicological research will be supported to resolve some of the uncertainties. Indeed, although not without considerable economic pain, the forthcoming closure of the steel mills offers a unique opportunity to determine whether improved air quality will actually result in any improved health outcomes for Newcastle residents. Only when such evidence is available can we be confident of setting airborne particle standards that will adequately protect the health of the Australian population. Michael J Abramson Associate Professor, Department of Epidemiology and Preventive Medicine Monash University, Melbourne, VIC Tom Beer Coordinator, Environmental Risk Network, CSIRO Atmospheric Research Melbourne, VIC, and Adjunct Professor of Risk Management Southern Cross University, Lismore, NSW Lewis PR, Hensley MJ, Wlodarczyk J, et al. Outdoor air pollution and children's respiratory symptoms in the steel cities of New South Wales. Med J Aust 1998; 169: 459-463. Dockery DW, Pope CA III. Acute respiratory effects of particulate air pollution. Annu Rev Public Health 1994; 15: 107-132. Abbey DE, Ostro BE, Petersen F, Burchette RJ. Chronic respiratory symptoms associated with estimated long term ambient concentrations of PM2.5 and other air pollutants. J Expo Anal Environ Epidemiol 1995; 5: 137-159. Streeton JA. Air pollution, health effects and air quality objectives in Victoria. Melbourne: Environment Protection Authority, 1990. Abramson M. Air pollution, health effects and air quality objectives. Med J Aust 1991; 154: 716-717. Ambient air quality. National environment protection measure and revised impact statement. Adelaide: National Environment Protection Council, 1998. Reichhardt T. Regulators face questioning on particulate rules. Nature 1996; 380: 11-12. Cooney CM. NRC advises long-term particulate matter research plan needed. Environ Sci Technol 1998; 32: 209A. US National Research Council Committee on Research Priorities for Airborne Particulate Matter. Research priorities for airborne particulate matter: I. Immediate priorities and a long range research portfolio. Washington, DC: National Academy Press, 1997. European Community Respiratory Health Survey. Variations in the prevalence of respiratory symptoms in the European Community Respiratory Health Survey. Eur Respir J 1996; 9: 687-695. Reprints: Associate Professor M Abramson, Department of Epidemiology and Preventive Medicine, Monash University, Clayton, VIC 3168. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Michael J Abramson · Tom Beer

"You've gotta have HAART"* Highly active antiretroviral therapies have changed the prospects for people living with HIV MJA 1998; 169: 456-457 The past two years have seen extraordinary advances in the practice of HIV medicine. In Australia, this is reflected in a dramatic drop in morbidity and mortality associated with the introduction of highly active antiretroviral therapy (HAART), as reported by Correll and colleagues in this issue of the MJA .1 The advent in 1996 of the very potent protease inhibitors and the growing list of reverse transcriptase inhibitors enabled the development of combination therapy with three or four drugs aimed at durable suppression of viral replication. Durability is a critical aspect of treatment, as HIV is capable of rapidly developing resistance to single agents. Fortunately, in 1997 the measurement of HIV plasma RNA concentration (viral load) became routine practice, allowing physicians and patients to monitor the effectiveness and durability of combination therapy. Publications on the efficacy of HAART have mostly reported its effects on the important surrogate markers (viral load and CD4+ T-cell count), although there are already clinical endpoint data showing a reduction in progression to AIDS and death.2,3 Clinical trials, however, do not always reflect clinical practice. How effective have these drugs been in the real world? In this regard, the report in this issue from the National Centre for HIV Epidemiology and Clinical Research (NCHECR)1 is of particular importance. In the years 1994-1997 there were 80% fewer deaths and 43% fewer AIDS cases among a cohort of people with advanced HIV infection (CD4+ T-cell count below 200/µL) than in a matched patient cohort from 1990-1993.1 These findings are similar to those reported from Switzerland4 and the United States.5 Although such studies have methodological difficulties, the emerging pattern is very clear. Moreover, the benefits escalate each year.5 This is not surprising as the change in prescribing has been stepwise: the first phase, sequential monotherapy, ended with the publication in 1996 of the definite but modest advantage of combining two reverse transcriptase inhibitors (eg, zidovudine-didanosine).6 In the same year, protease inhibitors became accessible, and the practice of multiple drug regimens including a protease inhibitor became widespread during 1997. It is likely that the analyses for 1998 will show even greater benefits. "What you really need is HEART"* The highly active regimens become highly effective antiretroviral therapy (HEART) by slowing the damage to the immune system and, in part, by restoring lost function. HAART leads to an immediate rise in the CD4+ T-cell count, due initially to a redistribution and expansion of memory T-cells followed by a very gradual replenishment of naive T-cells, the latter filling in gaps in the T-cell repertoire and providing the host with the ability to respond to a broader range of invaders.7,8 While the goal for HAART is to reduce the viral load to an undetectable level, a rise in CD4+ T-cell count occurs in patients in which this is not achieved.9 Moreover, the elevated CD4 cell count and clinical benefit from HAART may persist long after virological failure (rising viral load) in some patients. Yet much remains to be learned. For HAART to remain HEART in 1999 and beyond, three major problems must be overcome: drug resistance, long term side effects, and compliance with difficult regimens that may be taken for many years. A sizeable proportion of patients have developed some resistance to each of the current drug combinations. Many agents are available (see Table, below), but a high rate of cross-resistance exists within members of each class of antiretroviral drugs. Second generation protease inhibitors are in development, as are nucleotide analogues and inhibitors of viral integrase. However, the use of the powerful protease inhibitors is limited in some patients by metabolic toxicity, involving lipodystrophy, hyperlipidaemia and insulin resistance, the mechanisms for which are still a matter of hypothesis.10 Poor compliance encourages drug resistance; a strong commitment to HAART is necessary before starting treatment. Simple, easily tolerated regimens are still years away. These issues are driving the need for new approaches. In this regard, the past two years have brought remarkable advances in HIV science with the discovery of the major co-receptors used by HIV (with CD4) to infect and damage the cells of the immune system. Mutations in the genes encoding these receptors are associated with protection against HIV infection in homozygotes (about 1% of Caucasians are all but uninfectable with HIV-1) and a slower rate of progression to AIDS and death in heterozygotes.11 These discoveries are underpinning a frenzy of commercial activity12 aimed at developing a range of antireceptor agents, several of which have reached phase I/II clinical trials.13 The future looks promising for those early in the course of their HIV infection; for those whose infections are already overcoming HAART, it is a major challenge to find the best approach to "salvage therapy" while awaiting new drugs. A HAART-less world In Australia, HIV physicians have the option of prescribing HAART, despite its expense, for all appropriate patients. But there is no access to HAART for the vast majority of the world's 30-40 million people living with HIV, mostly in Africa and Asia. In a US study, Medicaid patients were less likely to receive a protease inhibitor and had a higher mortality rate than privately insured patients.5 The remarkable success of HAART has brought into focus the disparity in healthcare between rich and poor and between the developed and developing countries -- gaps to be bridged in the new millennium. Critical research question In addition to the benefits for patients, the positive effect on HIV doctors has been considerable, both through relief from sadness and through the affirmation of the scientific paradigm under which we practice. The viagra-like change in therapeutic potency carries, however, the danger of assuming that because we have a proud new tool we know exactly how to use it. In reality, it is still not known when to start HAART, which agents to start with, when to change and to what. National treatment guidelines depend, by necessity, on the lowest level of evidence: consensus opinion of experts.14 There is high biological plausibility to justify striving for an undetectable viral load from early in infection, but there are no data to support the long term benefits of "going early and going hard", nor long term data on side effects. There are few data on whether virological failure (rising viral load) equals clinical failure, or on what best to do for patients who have "failed" all available drugs. It is essential that clinical trials continue to address these questions, but the benefits of HAART and the licensing of many drugs makes this more difficult. Future prospects While there are strong grounds for expecting that simple, well-tolerated, effective and durable conbination regimens will emerge from current science, the real therapeutic hope is that HAART might eventually eradicate the virus in HIV-infected individuals. This outcome requires effective viral suppression beyond the life span of the long-lived cells that form a reservoir of latent virus. Initial enthusiasm15 has been tempered by a gradual realisation of the difficulties,16 but it is not an unrealistic hope given the extraordinary pace of discovery in HIV science and medicine. Graeme J Stewart Chairman, Research Advisory Committee Australian National Council on AIDS and Related Diseases Westmead Hospital, Sydney NSW Correll PK, Law MG, McDonald AM, et al. HIV disease progression in the time of combination antiretroviral therapies. Med J Aust 1998; 169: 469-472. Cameron DW, Heath-Chiozzi M, Danner S, et al. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. Lancet 1998; 351: 543-549. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. N Engl J Med 1997; 337: 725-733. Egger M, Hirschell B, Francioli P, et al. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. BMJ 1997; 315: 1194-1199. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853-860. Sherer R. Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet 1996; 348: 283-291. Roederer M. Getting to the HAART of T cell dynamics. Nature Med 1998; 4: 145-146. Li TS, Tubiana R, Katlama C, et al. Long-lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease. Lancet 1998; 351: 1682-1686. Kaufmann D, Pantaleo G, Sudre P, et al. CD4-cell count in HIV-1 infected individuals remaining viraemic with highly active antiretroviral therapy (HAART). Lancet 1998; 351: 723-724. Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia and insulin resistance. Lancet 1998; 351: 1881-1883. Stewart G. Chemokine genes - beating the odds. Nature Med 1998; 4: 275-277. Cohen J. Exploiting the HIV-chemokine nexus. Science 1997; 275: 1261-1264. Cairns JS, D'Souza MP. Chemokine and HIV-1 second receptors: the therapeutic connection. Nature Med 1998; 4: 563-568. Gazzard B, Moyle G. 1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1998; 352: 314-316. Wain-Hobson S. Down or out in blood and lymph. Nature 1997; 387: 123-124. Balter M. HIV survives drug onslaught by hiding out in T cells. Science 1997; 278: 1227. * With apologies to Ross and Adler's 'Heart' from Damn Yankees (1954), and to readers too young to know this high point in American immediate postwar culture. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Graeme J Stewart

Melanoma in the elderly -- a neglected public health challenge Successful strategies for early detection in the young are not benefiting older people MJA 1998; 169: 403-404 Melanoma has long been recognised in Australia for its relatively high incidence in young adults, compared with other cancers, and its significant contribution to premature mortality.1,2 Twenty-five years ago it was recognised that many melanomas begin with a flat, superficial growth pattern and the term "radial growth phase" was coined by the late Wallace Clark.3 Diagnostic criteria were adjusted to direct attention to flat lesions with what are known as "ABCD" features (Asymmetry, Border irregularity, Colour variation and large Diameter) and away from raised, nodular lesions. This promoted the early detection of radial growth phase melanomas (superficial spreading, lentigo maligna and acral lentiginous melanomas) and has been associated with a progressive decline in tumour thickness and a corresponding improvement in prognosis. Further, benchmark public education campaigns such as the Anti-Cancer Council of Victoria's Sunsmart program have contributed to significant changes in behaviour aimed at primary prevention.4 The new and recently demonstrated decline in melanoma incidence among people under 35 years of age5 may be a result of these behavioural changes. These, then, are among the success stories in the fight against melanoma. But where are we failing? In this issue of the Journal Hanrahan et al direct our attention to a group that appears to have been bypassed by the advances -- elderly men.6 The elderly comprise an important group among those affected with melanoma. The age-specific incidence of melanoma continues to rise throughout life, most steeply in men.1 While incidence rates have levelled off or are falling in younger age groups, they continue to rise steeply in the elderly.5 However, it is not incidence, but mortality, that most strongly conveys the predicament of the elderly in our population with respect to melanoma. Mortality from melanoma for Australian men aged between 80 and 84 years is 10 times that of those aged between 40 and 44 years (48.16 v. 4.92 per 100 000 person-years).7 As Hanrahan and colleagues point out, some 50% of deaths from melanoma in New South Wales occur in males over 50 years, even though this group accounts for only 12%-14% of the population. In light of this high mortality, and with tumour thickness being the most important prognostic indicator, as might be expected, tumours diagnosed in the elderly are thicker at the time of diagnosis.8 Why have the elderly so comprehensively failed to follow the trend toward early detection of melanoma that has been shown in younger members of the community? Obviously, they may be disadvantaged by age-related handicaps, such as failing eyesight, loss of a partner and the development of numerous seborrhoeic keratoses that may appear similar to melanoma. Surprisingly, however, the work of Hanrahan et al suggests that it is not primarily these difficulties, but the greater proportion of nodular melanoma compared with superficial spreading melanoma (particularly in men), that inhibits early detection of melanoma in the elderly. The direction of attention to flat lesions, while greatly improving the detection of those tumours that are easiest to detect early, has ignored the problem of early detection of nodular melanomas (which exhibit only vertical growth and have no radial growth phase). An additional difficulty for elderly men is that their melanomas occur predominantly on the back (48%). Hanrahan and colleagues found that once tumour type, site and thickness, and age were taken into account, men were no less likely than women to detect their melanomas. While people aged 50 years or over were somewhat less likely than younger people to identify the changes of melanoma (62% v. 72%), Hanrahan et al have demonstrated in a related study that older people are no less able to identify the changes of early melanoma in computer-altered images of pigmented lesions.9 These findings suggest that the elderly are not making use of their skills in detecting melanomas, and that public education campaigns might usefully encourage them to do this. Where have we gone wrong for the elderly with melanoma? By directing public education about primary prevention at the young we have also generated early detection behaviour primarily in this group. Marks et al10 and Del Mar et al11 have drawn attention to the mismatch between the age at which pigmented lesions are being excised, and the later age at which melanoma is more likely to occur. Among people aged 21-40 years the ratio of benign naevi to melanomas among excised lesions was 27.2, compared with 1.4 in those aged 60 and over.10 By focusing early detection efforts on flat lesions we have distracted attention from the clinical features of the nodular melanomas that more frequently affect the elderly. Nodular melanoma is, of course, more difficult to detect in its early stages because these lesions are invasive from the outset and grow in both depth and diameter, while the invasive, vertical growth phase of other melanomas is preceded by a flat, radial growth phase that may last many months or years. However, my own clinical experience suggests that it is generally possible to diagnose nodular melanoma lesions in patients undergoing regular surveillance when they are about 1.0 mm in thickness. We must make the elderly aware that melanoma is a significant and potentially curable health problem in later life. Further research is needed to define the most useful clinical features for early detection of nodular melanoma and to explore the best methods of promoting earlier detection. The article by Hanrahan et al in this issue provides some clues: changes in colour are found less frequently and changes in sensation more frequently in nodular melanomas; bleeding is associated with thick melanoma and is therefore not useful in early detection. Healthcare practitioners who work with the elderly need to be particularly aware of the clinical features of nodular melanoma, and the role of opportunistic screening by general practitioners is of special importance for elderly men in view of the greater impediments to self- diagnosis (nodular melanomas and location on the back). This role needs emphasis in the education of general practitioners. John W Kelly Head, Victorian Melanoma Service, Head, Dermatology Unit, and Clinical Associate Professor, Monash University Department of Medicine, Alfred Hospital, Melbourne, VIC Jelfs PL, Giles G, Shugg D, et. al. Cutaneous malignant melanoma in Australia, 1989. Med J Aust 1994; 161: 182-187. Gold J, Yuerning L, Kaldor JM. Premature mortality in Australia 1983-1992, the first decade of the AIDS epidemic. Med J Aust 1994; 161: 652-656. Clark WH, Ainsworth AM, Bernadino EA, et al. The developmental biology of primary human malignant melanomas. Semin-Oncol 1975; 2: 83-103. Hill D, Boulter J. Sun protection behaviour -- determinants and trends, Cancer Forum 1996; 20: 204-211. Giles G, Thursfield V. Trends in skin cancer in Australia. Cancer Forum 1996; 20: 188-191. Hanrahan PF, Hersey P, D'Este CA. Factors involved in presentation of older people with thick melanoma. Med J Aust 1998; 169: 410-414. Giles G, Armstrong BK, Burton RC, et al. Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994. BMJ 1996; 312: 1121-1125. Hersey P, Sillar R, Howe CG, et.al., Factors related to the presentation of patients with thick primary melanomas. Med J Aust 1991; 154: 583-587. Hanrahan PF, Hersey P, Menzies SW, et al. Examination of the ability of people to identify early changes of melanoma in computer-altered pigmented skin lesions. Arch Dermatol 1997; 133: 301-311. Marks R, Jolley D, McCormack C, Dorevitch AP. Who removes pigmented skin lesions? A study of the ratio of melanoma to other benign pigmented tumors removed by different categories of physicians in Australia in 1989 and 1994. J Am Acad Dermatol 1997; 36: 721-726. Del Mar C, Green A, Cooney T, et al., Melanocytic lesions excised from the skin: what percentage are malignant? Aust J Public Health 1994; 18: 221-223. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

John W Kelly

Doctors who self-administer drugs of dependence Doctors should be able to seek help with confidence that their colleagues will be supportive MJA 1998; 169: 404-405 What causes apparently successful young doctors to decide one day to inject themselves with pethidine? In how many cases and how rapidly does such drug abuse escalate? How much harm is done to these doctors, their families and the community? What risk does this pose to patients? A renewed search for answers to these questions should be stimulated by the article by Cadman and Bell1 in this issue of the Journal. It is a valuable reminder of a continuing problem for the self-regulating medical profession: doctors who self-administer drugs of dependence. The report focuses retrospectively on a cohort of 79 New South Wales doctors confirmed to have self-administered opioids. In keeping with earlier studies, the doctors were mostly male, predominantly in their thirties, and favoured pethidine. At the end of the 10-year survey period (1985-1994), 13% had died and only 54 (68%) remained on the medical register. Of these 54, 22 had conditions on their registration. The NSW study found an over-representation of general practitioners. Rural doctors were also over-represented and the authors postulate that in rural practice drug abuse may be harder to conceal. This interesting finding warrants further study, as there are other possible factors to consider, including the stress and isolation of rural practice, the attitude of rural pharmacists and the level of survey of pharmacies by drugs of dependence inspectors. This NSW experience indicates a prevalence of drug abuse among the medical profession of 0.4%, similar to an earlier Victorian estimate of 0.5%,2 but it is likely that this is an underestimate. Information from anonymous questionnaires3 and the experience of increased notifications which followed the mandatory reporting provisions of the Victorian Medical Practice Act 19944 suggest that opioid abuse among doctors may occur at twice this prevalence. It has also been suggested that doctors familiar with the recreational use of illicit drugs may be more prone to self-administration of narcotics.5 If this is correct, recent graduates may prove to be at greater risk. What should the profession do? What is it doing at present? An ideal strategy would encompass prevention, early detection, treatment and rehabilitation. Prevention should include education and deterrence. The trends towards later entry into medical school, more sophisticated student selection procedures, and curricular content directed at personal and professional development of student doctors, augur well. Education in this subject should continue in postgraduate training programs. Deterrence through strict uniform laws relating to drugs of dependence combined with extensive surveillance of misuse is currently as well developed as is practical. We do not support tougher penalties or tighter surveillance as they might simply lead to the emergence of alternate self-destructive behaviours. The medical profession needs to be aware of, and open about, this problem, appreciative of the impairment and rehabilitation model and supportive of colleagues in trouble.6 Doctors need to recognise their vulnerability to addictive behaviours, predisposed as many are through personality traits,7 stressful work and ready access to drugs. Doctors in trouble should be able to seek help without stigmatisation and with confidence that our profession will support their rehabilitation. Where prevention has failed and drug abuse has been detected, the next step is to provide effective treatment and rehabilitation. Although self-administration of drugs of dependence is a criminal offence, medical boards deal with the problem wherever possible as an illness, and regard such doctors as impaired, rather than subject them to a disciplinary process. There may be some procedural variation from State to State, but provided the community is protected from harm, medical boards generally seek voluntary acceptance of treatment with agreed enforceable conditions on practice (including psychiatric treatment, restricted access to Schedule 8 drugs, and strict urine screening), which may be progressively lifted. While some programs aim to keep narcotic-dependent doctors at work without interruption, the experience of the Medical Practitioners Board of Victoria has indicated that an initial brief period away from practice during drug withdrawal is critical. Relapse in the first 12 months is common and is not a sign of a poor prognosis. Provided there is no comorbidity such as major psychosis or severe personality disorder, the prognosis for recovery is good. Of 38 doctors notified to the Victorian Board and confirmed to be self-administering during 1994-1997, 29 are currently practising (25 with conditions), five are suspended from practice and four have allowed their registration to lapse. Any improvement in recovery figures will require the development of better treatment and rehabilitation programs, with professional support dedicated to the care of drug-dependent doctors. Such programs have been pioneered in several United States and Canadian jurisdictions, and have involved specialised treatment and rehabilitation programs, with the capacity to accept both voluntary referrals and referrals mandated by medical boards.8 Such programs could also undertake research and play a role in undergraduate and postgraduate education of doctors. The report by Cadman and Bell is timely. The topic of impairment and drug dependence is a key item on this year's annual meeting of Australasian medical boards to be held in Brisbane in November, where the US experience will be described by an invited expert, and the existing Australian and New Zealand impaired practitioner programs will be compared. The topic of the mental health of doctors is also of increasing concern to the Australian medical colleges. The Committee of Presidents of Medical Colleges has established a widely representative mental health working party to give guidance to the Colleges on this topic. With the establishment of prevention and early intervention programs for the profession, perhaps we can dare to hope that in the next 10 years, the prevalence of self-administration of drugs of dependence will decline. Kerry J Breen President, Medical Practitioners Board of Victoria South Melbourne, VIC John M Court Member, Medical Practitioners Board of Victoria South Melbourne, VIC Cadman M, Bell J. Doctors detected self-administering opioids in New South Wales, 1985-1994: characteristics and outcomes. Med J Aust 1998; 169: 419-421. Serry N, Bloch S, Ball R, Anderson K. Drug and alcohol abuse by doctors. Med J Aust 1994; 160: 402-407. Pullen D, Cait EL, Lyle DM, et al. Medical care of doctors. Med J Aust 1995; 162: 481-484. Medical Practitioners Board of Victoria. Annual Report 1994-95. Melbourne. Wright C. Physician addiction to pharmaceuticals: personal history, practice setting, access to drugs, and recovery. Maryland Med J 1990; 39: 1021-1025. Wilhelm K, Diamond M, Williams A. Prevention and treatment of impairment in doctors. Adv Psychiatric Treatment 1997; 3: 267-274. Vaillant GE; Brighton JR, McArthur C. Physicians' use of mood altering drugs: a 20 year follow-up report. N Engl J Med 1970; 282: 365-370. O'Connor PG, Spickard A. Physician impairment by substance abuse. Med Clin North Am 1997; 81: 1037-1052. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Kerry J Breen · John M Court

Surgery and evidence-based medicine A new Australian registry promises to strengthen the push towards evidence-based surgery MJA 1998; 169: 348-349 The pace of change in surgery is increasing the pressures to assess new technologies and procedures in ever-decreasing periods of time. The rush towards new techniques and technologies in surgical practice is encouraged by increased media attention, sensational reporting and ready access of patients to unrefereed Internet information. At the same time, there is increasing attention being focused on the need for evidence-based medicine in any clinical decision making. The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.1 External clinical evidence can be ranked in a hierarchical framework with the randomised controlled trial at the top, meta-analysis or systematic reviews in the middle, and clinical experience at the bottom. From this framework of information, clinical practice guidelines are currently evolving.2 Yet the article by Solomon and McLeod in this issue of the Journal3 highlights the poor representation of randomised controlled clinical trials in the surgical literature and the consequent lack of an adequate "gold standard" by which surgeons can measure their performance and develop evidence-based management plans and treatment. The many reasons why randomised controlled clinical trials are not well conducted or pursued in surgical practice4 no doubt include the influence of the expertise and preferences of individual surgeons, poor support from competitive granting agencies and little industry support from surgical manufacturers or pharmaceutical companies when compared with the support for drug trials. Indeed, it is no coincidence that in order to attract funding many randomised controlled surgical clinical trials have needed to include a pharmaceutical agent within the study design. Furthermore, the surgical temperament does not always lead to well-developed team skills among surgeons. The ability to stage meaningful, randomised-controlled clinical trials requires recruiting support from a range of colleagues across a number of departments or hospitals and having sufficient resources to follow through not only the initial setup phase, but also collection and analysis of the data. A good example of the difficulties attending efforts to set up surgical trials was the attempt by the Royal Australasian College of Surgeons (RACS) to establish a trial to assess laparoscopic colorectal surgery for malignant disease.5 This carefully developed plan for a randomised controlled trial, with every chance of generating useful data on the success (or otherwise) of laparoscopic colorectal surgery in both malignant and benign conditions, failed to begin because Commonwealth Government funding was not provided after early encouragement had been given. Surgeons are not encouraged to give their time and effort in the pursuit of such trials when there seems little genuine support from funding bodies which should have an ongoing interest in such studies. If the purchasers of surgical services (government, insurers and patients) desire evidence-based practice, they must also be prepared to support the cost of data collection.6 Fortunately, the Commonwealth Government has recently shown some recognition of these issues by funding a three-year pilot program for the Australian Safety and Efficacy Register of New Interventional Procedures-Surgical (ASERNIP-S) through the RACS. The ASERNIP-S group was formed early in 1998 and is based in Adelaide. Its aims are to establish a mechanism for collecting data on the safety and efficacy of selected new surgical procedures and to collate and analyse this data in conjunction with other evidence available, a concept endorsed by The Lancet in 1996.7 It is hoped that ASERNIP-S will suggest which procedures are appropriate candidates for randomised controlled clinical trials and develop recommendations for the application of new procedures, indicating whether a procedure should be used with or without continuing audit, or if a more fully controlled evaluation is necessary before the procedure is generally used. One of the functions of the pilot program will be to assess the effectiveness of ASERNIP-S itself and make recommendations about the scope for developing a comprehensive audit mechanism for new surgical procedures in the Australian healthcare system. Various sources have nominated procedures for assessment by ASERNIP-S: Divisions of the RACS, credentialling committees, consumers (through the Consumer Health Forum) and the National Centre for Classification in Health. The role of ASERNIP-S will be to assist in the collection and critical analysis of the literature on selected procedures and to facilitate further evaluation of the procedure if required. So far the group has been able to consider procedures across the breadth of surgery and has been able to involve nearly all sub-specialties associated with the RACS. This may help focus surgical efforts towards conducting randomised controlled clinical trials where they are most needed, rather than where the funding can be found. The Commonwealth Government will need to support trials in those areas that clearly need more critical evaluation, but funding for such support has not yet been identified. Meanwhile, there is a large backlog of established procedures that still require critical analysis by the surgical community.8 Once this evidence is collected, analysed and made the basis of a consensus position, it will be important that surgical practice guidelines are developed. In a recent article in the Australian and New Zealand Journal of Surgery, Barraclough defended the need for practice guidelines if errors were to be eliminated and evidence-based practice was to gain a further footing in surgical care.9 The concerns regarding medicolegal implications of such practice guidelines and the cries against "cookbook surgery" seem rather hollow. Surgeons, like all healthcare workers, need to ask whether their longstanding practices, prejudices and patient wishes really reflect current best practice according to the evidence. Where the evidence remains unclear, then it behoves all in Government and the healthcare sector to pursue well-constructed studies of appropriate size likely to resolve the clinical question. The RACS has certainly made a clear commitment to this and recognises the need to redress the less-than-perfect evidence base of current surgical practice. Guy J Maddern Professor of Surgery University of Adelaide, Adelaide, SA Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine: how to practice and teach EBM. New York: Churchill Livingstone, 1997. Pelly JE, Newby L, Tito F, Redman S, Adrian AM. Clinical practice guidelines before the law: sword or shield? Med J Aust 1998; 169: 330-333. Solomon MJ, McLeod RS. Surgery and the randomised controlled trial: past, present and future. Med J Aust 1998; 169: 380-383. Sondenaa K, Nesvik I, Solhaug JH, Soreide O. Randomization to surgery or observation in patients with symptomatic gallbladder stone disease. Scand J Gastroenterol 1997; 32: 611-616. Hewett P. The Australian laparoscopic assisted resection for adenocarcinoma of the colon clinical trial [abstract]. Aust N Z J Surg 1997; 66 Suppl 1: 49. Rodarte JR. Evidence-based surgery [editorial]. Mayo Clin Proc 1998; 73: 603. Horton R. Surgical research or comic opera: questions, but few answers [editorial]. Lancet 1996; 347: 984. Howes N, Chagla L, Thorpe M, McCulloch P. Surgical practice is evidence based. Br J Surg 1997; 84: 1222-1223. Barraclough B. The value of surgical practice guidelines. Aust N Z J Surg 1998; 68: 6-9. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Guy J Maddern

Legal implications of clinical practice guidelines Clinical practice guidelines may be used as evidence, but this should not distract doctors from their advantages. MJA 1998; 169: 292-293 Clinical practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances.1 Formulated by the United States Institute of Medicine, this definition was used by the National Health and Medical Research Council (NHMRC) in its work on clinical practice guidelines. In 1995, the NHMRC published guidelines for the development and implementation of clinical practice guidelines.2 It described a worldwide focus on guidelines ". . . prompted by concern about unjustifiable variations in clinical practice for the same condition, the increased availability of new treatments and technology and uncertainty as to the effectiveness of many interventions in improving people's health and a desire to make the best use of available health resources".2 The NHMRC emphasised the need for clinical practice guidelines to be based on the best available evidence. Relevant to this need are principles of evidence-based medicine, which entail the explicit and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.3 Since 1995, the NHMRC has published nine clinical practice guidelines: on early breast cancer, coronary heart disease, depression in young people, prevention of stroke, uncomplicated lower urinary tract symptoms in men, unstable angina, preterm birth, diabetic retinopathy, and acute pain management.4 Clinical practice guidelines are not intended to replace clinical judgement, nor can they. They are not prescriptive, but serve to guide practitioners in making relevant clinical interventions. Used correctly, they can assist more informed and meaningful patient participation in treatment decisions. They can enhance and maintain professional standards and quality assurance programs. By reducing unnecessary variations in practice they may encourage cost-effective healthcare. Despite these potential benefits, some doctors are uncertain about the legal implications of clinical practice guidelines. One study found that Australian general practitioners did not regard legal implications as very important to their decision to follow guidelines.5 In another survey, 32% of clinicians were unsure whether guidelines on managing early breast cancer would be used to sue doctors and 45% agreed or strongly agreed that they would.6 In a survey of surgeons' opinions about the NHMRC clinical practice guidelines for the management of early breast cancer (published in this issue of the Journal), 41% of surgeons felt that guidelines would protect clinicians from legal implications, whereas 37% believed clinicians would be exposed to increased medicolegal problems by using them.7 The risk of legal liability is not unimportant, but for medical practitioners to approach clinical practice guidelines from a defensive perspective may well deny them and their patients the opportunity to achieve optimal health outcomes, an objective of paramount importance to the medical profession. The law imposes on a medical practitioner a duty to exercise reasonable care and skill in the provision of professional advice and treatment. This duty is a single, comprehensive one covering all the ways in which a doctor is called upon to exercise his or her skill and judgement. It extends to the examination, diagnosis and treatment of a patient, the provision of information and the processes of obtaining the patient's consent to treatment.8 The word reasonable is important. As a former Chief Justice of the High Court of Australia observed: "It is easy to overlook the all-important emphasis placed upon the word 'reasonable' in the statement of the duty. Perfection or the use of increased knowledge or experience embraced in hindsight after the event should form no part of the components of what is reasonable in all the circumstances."9 The standard of reasonable care and skill required is that of the ordinary skilled practitioner exercising and professing to have the capabilities required in the particular field of medical practice under consideration.8 In ascertaining what, in a particular case, constitutes reasonable care and ordinary skill in the relevant medical discipline, a court will usually receive evidence of the practice of medical practitioners and the state of medical knowledge at the relevant time. This evidence is usually given as expert opinion from medical witnesses and is of considerable significance when there are allegations of negligence in diagnosis or treatment. However, evidence of professional practice cannot dictate to a court the standard of care applicable to the clinical facts before it. The court will determine the standard demanded by the law in the practice of medicine (or, indeed, in the practice of any other profession). Clinical practice guidelines might be introduced into evidence before a court either by a plaintiff or by a defendant doctor. If so, it is likely that they would be included within the evidence of an expert medical witness given in the usual way. Soundly based clinical practice guidelines may well serve to make medical expert opinion more reliable and acceptable to a court,10 but are unlikely to alter the usual evidentiary processes in litigation. In considering the probative value of any clinical practice guidelines in evidence before it, a court would need to be satisfied, by appropriate evidence of their manner of formulation, of the quality and reliability of the medical/scientific evidence upon which they are based as well as their currency, acceptance and use by the profession. In an appropriate case, a medical witness called to give expert opinion evidence on behalf of a plaintiff might refer to clinical practice guidelines, offering the opinion that the defendant doctor had wrongly departed from the guidelines in the treatment of the patient. It would be open to a defendant doctor to counter this with evidence that the guidelines were not available at the time, outdated or not relevantly endorsed, or that clinical factors justified departure from the guidelines in the exercise of professional judgement, or that the treatment given did in fact comply with the guidelines. Given their purpose and evidence-based foundation, it is unlikely that clinical practice guidelines will promote litigation. Arguably, they may well reduce it by reducing any uncertainty about what constitutes reasonable medical practice. The legal implications of clinical practice guidelines were considered recently at a forum convened by the New South Wales Department of Health, together with the NHMRC National Breast Cancer Centre and United Medical Protection Ltd. A summary of the recommendations arising from the forum and the basis for their formulation are reported in this issue of the Journal.11 When properly understood, clinical practice guidelines will be appreciated for the significant beneficial purposes for which they are designed. In considering acceptance and use of clinical practice guidelines, the medical profession should not be distracted by speculation about legal implications. Nevertheless, as it appears that patients have become more litigious and doctors more vulnerable to allegations that they have failed their patients,12 clinical practice guidelines may become an important part of clinical risk management. Ultimately, care may well come to be regarded as less than reasonable should clinical practice guidelines be available but not followed, unless this can be justified on appropriate clinical grounds. Peter Dwyer Barrister 11th Floor, St James Hall 169 Phillip Street, Sydney, NSW Field MJ, Lohr KN. Clinical practice guidelines: directions for a new program. Washington, DC: Institute of Medicine. National Academy Press, 1990. National Health and Medical Research Council. Guidelines for the development and implementation of clinical practice guidelines. Canberra: NHMRC, 1995. Sackett DL, Richardson WS, Rosenberg WR, Haynes RB. Evidence-based medicine: how to practice and teach EBM. New York: Churchill Livingstone, 1997: 2. Smallwood RA, Lapsley HM. Clinical practice guidelines: to what end? Med J Aust 1997; 166: 592-595. Gupta L, Ward J, Hayward RSA. Clinical practice guidelines in general practice: a national survey of recall, attitudes and impact. Med J Aust 1997; 166: 69-72. Ward JE, Boyages J, Gupta L. Local impact of the NHMRC early breast cancer guidelines: where to from here? Med J Aust 1997; 167: 362-365. Carrick S, Benevista B, Redman S, et al. Surgeons' opinions about the NHMRC clinical practice guidelines for the management of early breast cancer. Med J Aust 1998; 169: 300-305. Rogers v Whitaker (High Court of Australia) 175 CLR 479. Per Barwick CJ in Maloney v Commissioner for Railways (NSW) [1978] 52 ALJR 292 at 292. Tjiong RTT. Reforming the law on expert evidence. Med J Aust 1998; 168: 53-54. Pelly JE, Newby L, Tito F, et al. Clinical practice guidelines before the law: sword or shield? Med J Aust 1998; 169: 330-333. Tomkins C. Recent trends in litigation worldwide -- the implications for Australia. J Med Defence Union July 1998: 2-4. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Peter Dwyer

Retaining a medical workforce in rural Australia Professional satisfaction is a major concern for rural doctors MJA 1998; 169: 293-294 For at least 10 years, the imbalance of general practitioners in rural and remote areas of Australia has been addressed by successive health policies and strategies. These activities are driven in large part by a desire for equity of access to and quality of medical care in our rural and remote communities. Seminal in the early considerations in attracting and maintaining a rural medical workforce were the reports by Kamien1 to the Western Australian and Shehadie2 to the New South Wales departments of health. Both reports disclosed a need for support for rural doctors, particularly in access to continuing medical education (CME) and provision of locums. These reports were instrumental in the formation, in 1988, of the NSW Rural Doctors Resource Network and, in 1990, of the Western Australian Centre for Rural and Remote Medicine. In 1993, the Commonwealth Department of Human Services and Health launched the General Practice Rural Incentives Program (GPRIP), which aimed to attract doctors through relocation, retraining and remote area grants, and to retain them by addressing access to CME and locum support. This issue of the Journal includes two reports which have implications for Australia's rural workforce. Bruening and Maddern3 disclose a profile of rural surgeons that is one of predominantly middle-aged men whose major concerns include continual on-call work, lack of locum relief, and peer isolation. Although the majority of surgeons intend to remain in rural practice until retirement, the ageing of our rural surgical workforce has obvious implications. Kamien4 provides unique information on why doctors stay in or leave rural practice by examining the major concerns and practice intentions of rural doctors in 1986 and their practice locations by 1996. Those doctors who remained in rural practice had successfully resolved their 1986 concerns; those who left had not. For the latter, unresolved concerns included access to CME, overwork, forced deskilling, and professional isolation. Kamien also highlights the major concerns which would influence doctors currently in rural practice to leave; these include problems in achieving professional satisfaction as pressures (such as hospital closures) on the provision of rural health services increase. The whole issue of retention of doctors in rural practice is attracting renewed attention and recently several researchers have addressed this issue. Hoyal has proposed that important influences in this are professional factors influencing the doctor, social and other factors affecting the doctor's family, and community influences.5 While listing a range of professional factors, he also highlighted the need for community backing for the local hospital as well as emotional, professional and financial hospital support for the doctor. In a survey of Queensland doctors who had recently left rural practice, Hays and colleagues6 found that these doctors emphasised the positive aspects of rural practice to be professional autonomy and support, community relationships, work variety, family lifestyle and continuity of care. The downside included after-hours workload, poor access to CME and locums, personality clashes, and lack of family educational opportunities. In proposing retention strategies, Hays et al developed a conceptual model of a balance between influences to stay or to leave, and triggers that could shift this balance. While acknowledging that personal (eg, personality clashes) and family (eg, children's education) triggers may be difficult to address, they proposed professional retention strategies that could be readily addressed. These include provision of CME, locum cover, management training for doctors, and educational packages for families. They also suggested that local support and early intervention structures could be developed through Divisions of General Practice. A recent consultancy to GPRIP has produced a discussion paper on models of sustainable practice in rural and remote Australia.7 The focus on "sustainable practice" instead of "retention" helps to highlight another element of focusing on a continuity of rural medical service. The discussion paper proposes that strategies for sustainability include those issues that promote sustainability of the individual doctor (including access to CME, locums, and family support), those that promote sustainability of the practice environment (including the relationship with the local health service provider), and those that promote sustainability of the community. It is evident that the strategies for practice sustainability are largely concentrated on the needs expressed by rural doctors over the past 10 years. In many States these have been coupled with rurally targeted financial support for services provided in public hospitals. The concept of a continuous workforce by readily available replacement of doctors has been taken up in the short term with relocation and retraining support by GPRIP, and in the longer term by early exposure of undergraduates to rural medicine and support for entrance to medical schools of students from a rural background. At the national level needs have also been identified. Those proposed in a discussion paper of the Australian Medical Association and the Rural Doctors' Association of Australia8 include a national medical workforce recruitment and retention scheme; a nationally consistent system of granting clinical privileges; continued and increasing refinement of postgraduate, vocational and continuing medical education; the introduction of retention payments and development of information technology; innovative practice structures; and Aboriginal health strategies. Some or all of these can be developed or implemented at State level. The new Rural Workforce Agencies and Divisions of General Practice are ideally placed to develop the strategies that allow both long term and emergency impact on the triggers for leaving rural practice. It would seem that a major task for the Rural Workforce Agencies and Rural Doctors Associations in each State will be to bring cohesion to retention strategies while promoting regional and local flexibility. While those support strategies that have been working must continue, the major challenge will be in promoting the autonomy and self-esteem of rural doctors that Kamien suggests. This will need to be done by negotiating with health service provider organisations and communities to develop strategies that allow doctors the professional satisfaction of providing their medical skills to those communities, thereby maximising the health status of rural Australians. Ian Cameron Chief Executive Officer, NSW Rural Doctors Network Suite 19, 133 King Street, Newcastle, NSW 2300 Western Australian Health Department (M Kamien, Chairman). Report of the Ministerial Inquiry into the Recruitment and Retention of Country Doctors in Western Australia. Perth: Western Australian Health Department, 1987. Shehadie N. Report of the Committee of Enquiry Into Services Provided by General Medical Practitioners to Country Public Hospitals. Sydney: New South Wales Department of Health, 1987. Bruening MH, Maddern GJ. A profile of regional surgeons in Australia. Med J Aust 1998; 169: 324-326. Kamien M. Staying in or leaving rural practice: 1996 outcomes of rural doctors' 1986 intentions. Med J Aust 1998; 169: 318-321. Hoyal FMD. Retention of rural doctors. Aust J Rural Health 1995; 3: 2-9. Hays B, Veitch PC, Cheers B, Crossland L. Why doctors leave rural practice. Aust J Rural Health 1997; 5: 198-203. Models of sustainable practice in rural and remote Australia. Discussion paper. Rural and Remote General Practice Program, Commonwealth Department of Health and Family Services, Canberra, March 1998. Increasing rural medical services. Discussion paper. Australian Medical Association and Rural Doctors' Assocation of Australia. Canberra, March 1998. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Ian Cameron

Protozoa in drinking water: is legislation the best answer? A cooperative approach is a better option to protect public health MJA 1998; 169: 296-297 In late July, Australians were shocked to learn that the water supply in their largest city had been declared unsafe to drink because of protozoal contamination.1 In late August Sydney's water was again declared unsafe. The publicity surrounding these events in Sydney doubtless left most of the public, and perhaps many health professionals, with the impression that swallowing a mouthful of the affected water virtually guaranteed an episode of severe gastroenteritis. However, the magnitude of the risk to public health is far from clear as there are many limitations in our understanding of the biology of these organisms, and in the methods used for their detection in drinking water. Public and political concern has resulted in calls for legislative enforcement of water quality standards for Giardia and Cryptosporidium, but we believe that this approach is both unwise and unworkable at present. Such measures would require the setting of permissible levels for protozoa in drinking water, specification of sampling programs and approved testing methods. Uncertainties in all these aspects make it extremely difficult to define appropriate parameters to protect public health. Human infection: Information on levels of protozoa associated with illness is available from a small number of human experiments and limited data collected from outbreaks. For Giardia lamblia, a study of adult male prison inmates showed as few as 10 cysts could establish infection (determined by cysts in stools). However, none of the 40 subjects reportedly developed symptomatic giardiasis despite ingesting up to one million cysts, although 21 became infected.2 More recent human experiments,3 in which 50 000 Giardia lamblia trophozoites were inoculated into the duodenum, showed that with one strain all 10 subjects became infected and four developed clinical giardiasis. With another strain none of five subjects became infected or showed clinical disease. In human infection experiments with Cryptosporidium parvum, the minimum dose tested was 30 oocysts. Of five seronegative subjects receiving this dose, one became infected (oocysts in stools) but experienced no symptoms. At the next dose level of 100 oocysts, three of eight subjects became infected and developed symptoms.4 Waterborne outbreaks: Information derived from investigation of waterborne outbreaks is limited and difficult to interpret because of the time lag between the contamination event, the onset of symptoms in the exposed population and subsequent investigation to identify the source. For the Milwaukee cryptosporidiosis outbreak, which affected an estimated 400 000 people, the only data on oocyst levels came from samples of stored ice.5 A concentration of 13.2 oocysts per 100 L was found in ice made eight days before the outbreak was recognised. Maximum exposure to cryptosporidia probably occurred three days later (five days before the outbreak was recognised), when water turbidity rose suddenly to about seven times normal levels, signalling a failure of the water filtration plant. The process used to recover oocysts is noted for its variability,6 and this figure may be a substantial underestimate. Swimming pool outbreaks of cryptosporidiosis illustrate that illness can result from ingestion of a small volume of contaminated water, but, again, the time lag between a contamination event and examination of water samples makes it difficult to estimate actual exposure levels.7 Infected people can shed millions of oocysts per gram of faeces, so ingestion of tiny fragments of faecal matter may be sufficient to cause infection in other pool users.8 Safe drinking water: Overall, data presently available are insufficient to allow a "safe" drinking water level to be defined for these protozoa. It is theoretically possible that ingestion of even a single cyst or oocyst may carry a low risk of developing illness, but it is not feasible to test this hypothesis experimentally. Cryptosporidiosis may cause diarrhoeal illness lasting several days in healthy people, but in AIDS patients inability to clear the infection may result in severe and intractable diarrhoea which ultimately contributes to premature death. It is notable that during the Milwaukee outbreak people with HIV were not more likely to become ill than those in the general population.9 This suggests that the infectious dose for Cryptosporidium parvum is similar in both immunocompromised and immunocompetent people, although the consequences of infection are clearly different. There is evidence that the coagulation step used in water treatment to remove particulate matter causes clumping of coliform bacteria and spores, and similar effects may occur with protozoa. This would result in exposure of fewer people to larger numbers of protozoa than would be predicted from assumptions of uniform distribution in drinking water.10 Water testing: The formulation of a meaningful water sampling program is also a problem. Waterborne outbreaks are rare, and are believed to result from short term "spikes" of contamination from increases in protozoa numbers in the source water, or failure in normal water treatment processes, or a combination of both factors. A program based on spot sampling would be unlikely to detect contamination spikes, and could not provide statistically meaningful information on the very low numbers of protozoa which are normally present. Other parameters, such as turbidity or particle counts, may provide warning of abnormalities in water treatment processes (such warnings were unfortunately ignored in Milwaukee), but in some instances outbreaks have occurred without detectable changes in such measures or any identifiable breakdown in operating processes.11 Only Giardia and Cryptosporidium species of mammalian origin are believed to constitute a risk to human health, but current tests do not indicate the type of animal the protozoa originated from or the viability of cysts and oocysts. Several techniques to determine viability and species have recently been developed but are not yet fully validated. Considerable variability exists in the recovery efficiency of concentration techniques for isolating protozoa from water, making it difficult to compare levels between different studies and different laboratories.6 False positive results from algae and other particles of similar size and appearance to protozoa may also be a significant problem.12 Because of uncertainties about testing methods and the public health significance of low levels of protozoa in water, the National Health and Medical Research Council decided not to set guideline levels for protozoa in the 1996 Australian Drinking Water Guidelines, or to recommend testing for these organisms. Considerable progress has been made in detection techniques since then, but many problems are still to be resolved before we can accurately and reliably measure the number of viable protozoa of the relevant species. Nevertheless, major water companies are testing for protozoa with increasingly sensitive methods in an effort to improve the quality of their supplies, but water and health authorities are faced with a dilemma over what to do when positive results are found. Solutions: While legislation may appear to be the answer to this problem, we believe this issue is far too complex to be resolved in this way. The interests of public health would be better served by an open, cooperative approach bringing together the expertise of government, public health and the water industry. Australia would benefit from the development of best-practice programs, appropriate for the circumstances of different water supplies, and covering water quality from source to tap. Such programs are already being implemented in other countries.13 There is also a need to develop consensus protocols for graded responses to contamination incidents, and improved communication with the public and interest groups. Current surveillance mechanisms for communicable diseases are fragmentary, relatively insensitive and slow,14 and should be improved and integrated with water quality data to provide more sensitive and rapid detection of outbreaks. Cooperative research efforts are required to improve water monitoring techniques and confirmatory tests, together with appropriate measures for quality assurance. Only then will we be in a position to assess whether protozoa in drinking water are causing illness in the community, and determine appropriate measures to protect public health. Martha I Sinclair Senior Reseach Fellow Christopher K Fairley Associate Professor Margaret E Hellard NHMRC PhD Scholar Department of Epidemiology and Preventive Medicine and Cooperative Research Centre for Water Quality and Treatment Monash University, Melbourne, VIC Most of Sydney told: boil drinking water. The Sydney Morning Herald, 1998; 30 Jul: 1. Rendtorff RC. The experimental transmission of human intestinal protozoan parasites. II Giardia lamblia cysts given in capsules. Am J Hyg 1954; 59: 209-220. Nash TE, Herrington DA, Losonsky GA, Levine MM. Experimental human infection with Giardia lamblia. J Infect Dis 1987; 156: 974-984. DuPont HL, Chappell CL, Sterling CR, et al. The infectivity of Cryptosporidium parvum in healthy volunteers. N Engl J Med 1995; 332: 855-859. MacKenzie W, Hoxie N, Proctor ME, et al. A massive outbreak in Milwaukee of Cryptosporidium infection transmitted through the public water supply. N Engl J Med 1994; 331: 161-167. LeChevallier MW, Norton WD, Siegel JE, Abbaszadegan M. Evaluation of the immunofluorescence procedure for detection of Giardia cysts and Cryptosporidium oocysts in water. App Environ Microbiol 1995; 61: 690-697. Lemmon JM, McAnulty J, Bawden-Smith J. Outbreak of cryptosporidiosis linked to an indoor swimming pool. Med J Aust 1996; 165: 613-616. Chappell CL, Okhuysen PC, Sterling CR, DuPont HL. Cryptosporidium parvum: intensity of infection and oocyst excretion patterns in healthy volunteers. J Infect Dis 1996; 173: 232-236. Frisby HR, Addiss DG, Reiser WJ, et al. Clinical and epidemiologic features of a massive waterborne outbreak of cryptosporidioisis in persons with HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 16: 367-373. Gale P, van Dijk PAH, Stanfield G. Drinking water treatment increases micro- organism clustering; the implications for microbiological risk assessment. J Water Services Res Technol -- Aqua 1997; 46: 117-126. Goldstein ST, Juranek DD, Ravenholt O, et al. Cryptosporidiosis: an outbreak associated with drinking water despite state-of-the-art water treatment. Ann Intern Med 1996; 124: 459-468. Clancy JL, Gollnitz WD, Tabib Z. Commercial labs: how accurate are they? J Am Water Works Assoc 1994; 5: 89-97. The partnership for safe water. American Water Works Association. <URL http://www.awwa.org/partner1.htm> Padiglione AP, Fairley CK. The early detection of outbreaks of waterborne gastroenteritis -- a feasibility study. WaterTECH Conference, Brisbane, April 1998. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Martha I Sinclair · Christopher K Fairley · Margaret E Hellard

Restructuring hospital services We must vigorously evaluate the effects of new ways of delivering healthcare MJA 1998; 169: 239 A new drug cannot be introduced into the Australian healthcare system without exhaustive scientific trials, but we usually introduce new ways of delivering health services with little or no scientific evaluation. We rationalise, change and formulate new systems, often based on economic and political imperatives, and yet rarely evaluate their impact on patients. Significant morbidity and mortality may be associated with new models of healthcare delivery. If healthcare system changes were submitted to the same scrutiny as new drug evaluations, they would probably not even be allowed to move from the animal to the human experimentation stage. In this issue of the Journal, Caplan and colleagues1 (page 247) report the impact of a new system for managing elective surgery. Two groups of patients undergoing elective surgery were compared, one before and the other after a re-engineered system of coordinated care was introduced. The changes included preadmission assessment, improved patient education, admission to hospital on the day of surgery and postacute care after discharge.2Most patients, both day-surgery and longer-stay patients, were admitted on the day of operation, thus eliminating the need for an extra night in hospital for investigations and assessment. The new system resulted in a shorter length of stay, reduced risk of wound infection and a higher level of patient satisfaction. The results of this study, which is an Australian first, are important for several reasons. The stereotypical image of healthcare sees managers as intent on saving money with no concern for quality of care, which contrasts with clinicians, who are seen as guardians of quality of care with no concern for cost. The study of Caplan et al demonstrates that the goals of health managers and clinicians can coincide. The patients' shorter stay freed up scarce hospital beds without compromising care, the patients were in favour of the shorter hospital stay, and wound infection rates were lower. Perhaps there is a potential for implementing innovative healthcare delivery systems which are both more efficient and provide equal or even improved quality of care. We will not know until we begin to vigorously evaluate the effects of new ways of organising healthcare delivery. It is regrettable that the present health research agenda in Australia does not extend to evaluation of the performance of healthcare systems. Clinical and biological research seems to be much more highly valued. National research bodies have traditionally funded scientists with track records in more conventional and reductionist research (usually in a single specialised area) rather than in broad system evaluation. Health system research may involve moving out of one's specialty, department or laboratory. The re-engineered system described by Caplan et al1 involved radically reorganising the role of anaesthetists and surgeons, and enlisting support and cooperation from many other hospital departments. The impact of the new system was then comprehensively evaluated, which is a major achievement in itself. Randomised controlled trials involving a drug or single intervention are relatively straightforward. Evaluating a system presents greater challenges. Wide-ranging research expertise covering epidemiology, social sciences and health economics is required. Clinicians are an essential part of the research team. They are often driving the change and, as with a new drug or intervention, they need to know how the changes will affect their patients. It is important to use new or more relevant research methods that serve the scientific question,3-5 rather than to restrict the scope of the question to fit more conventional research tools. Another challenge is having research which crosses many boundaries recognised by peer reviewers with specialised expertise. Acceptance of research by scientific journals is often determined more by the small size of the P value than by the relevance, importance or originality of the research. Health system research usually requires evaluations of many issues from many perspectives by many methods, including qualitative and quantitative, with investigators from different backgrounds working together to produce an integrated evaluation.5 We must be sceptical about health system changes which concentrate only on increased efficiency and cost savings. Introducing re-engineered health systems may have important implications for patient care. For example, in the study of Caplan et al there was no provision for evaluating the effect of early discharge on carers and patients. Future studies should also address these issues. Evaluating better and more efficient ways of delivering healthcare is just as important as developing and evaluating increasingly costly drugs and procedures. Ken M Hillman Professor; and Director, The Simpson Centre for Health Service Innovation Liverpool Hospital, Sydney, NSW Caplan G, Brown A, Crowe PJ, et al. Re-engineering the elective surgical service of a tertiary hospital: a historical controlled trial. Med J Aust 1998; 169: 247-256. Kerridge R, Lee A, Latchford E, et al. The perioperative system: a new approach to managing elective surgery. Anaesth Intens Care 1995; 23: 591-596. Wyatt J, Spiegelhalter D. Evaluating medical expert systems: what to test and how? Med Info 1990; 15: 205-217. Langley G, Nolan K, Nolan T. The foundation of improvement. Quality Progress 1994; (June): 81-86. Heathfield H, Pitty D, Hanka R. Evaluating information technology in health care: barriers and challenges. BMJ 1998; 316: 1959-1961. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Ken M Hillman

Peer review on the Internet: launching eMJA peer review study 2 http://www.mja.com.au/public/information/iprs2int.html MJA 1998; 169: 240-241 Peer review is a vital part of the quality control process in medical scientific publishing, but it also has flaws.1-3 It is narrow, potentially biased, prone to error and secretive (and, because it is secretive, it is difficult to tell how serious the other flaws may be). Can the Internet be used to improve peer review? In 1996 we launched the Journal's website with an experiment in using the Internet to open up peer review. Over the next 15 months, 56 articles, together with the reviewers' reports, were published on the website after traditional peer review but before they were edited for print, and readers were invited to make further comments. In seven instances, this led to further revision of the articles before they were published in print.4 The first eMJA peer review study was limited in many ways: it included only articles that had been accepted for publication after traditional peer review, and then only when the authors and reviewers had volunteered to participate, which may have introduced a selection bias, and there were relatively few Internet readers who took the opportunity to comment on articles. Nonetheless, the study suggested that most authors and reviewers are willing to explore more open methods of peer review and that the Internet can be used to enhance peer review while accelerating the publication process. After due consideration, we are launching another study to test a more open peer review process that is entirely based on the Internet. This study will enlist 50-60 articles over the next six to 12 months. A brief outline of the experimental peer review method and its hypothetical benefits is shown in the panels. The complete protocol for the study is published on the eMJA website,5 and we hope that Journal readers will read it, offer their comments and volunteer their participation. Craig Bingham eMJA peer review study coordinator Martin B Van Der Weyden Editor, MJA Hypothetical benefits of the new peer review method The study will test whether these hypotheses are valid: This model will be preferred by authors and reviewers because it gives them greater feedback and a more direct interaction. The panel of consultants will add useful information and provide a check on the performance of the system. The open review period for accepted articles will generate a small but useful amount of comment from readers. Editorial time and resources involved in the new process will be similar to that required for traditional peer review. Reviewers will give better quality reviews. Articles published after this review process will have fewer errors and be of higher quality than those published after traditional review. We need volunteers If you are interested in participating in the eMJA Internet peer review study as a consultant panel member, please email Craig Bingham at medjaust at ampco dotcom dotau stating your areas of interest and expertise. You need not be a medical practitioner: other health professionals, biomedical scientists, lawyers, economists, psychologists and social scientists with an interest in health and medicine are encouraged to lend their expertise as well. Of course access to the Internet is required for participation in the study. However, readers without Internet access who wish to see the eMJA Internet peer review study protocol (28 pages) should contact Craig Bingham (tel. +61 2 9562 6666, fax. +61 2 9562 6699)to arrange to have a copy faxed or posted to them. The eMJA Internet peer review study protocol is available on the web at http://www.mja.com.au/public/information/iprs2int.html Lock S. A difficult balance: editorial peer review in medicine. London: BMJ, 1991: 23-55. Horrobin D. The philosophical basis of peer review and the suppression of innovation. JAMA 1990; 263: 1438-1441. Godlee F, Gale CR, Martyn CN. Effect on the quality of peer review of blinding reviewers and asking them to sign their reports. JAMA 1998; 280: 237-240. Bingham CM, Higgins G, Coleman R, Van Der Weyden MB. The Medical Journal of Australia Internet peer-review study. Lancet 1998; 352: 441-445. Draft protocol for Internet Peer Review Study II. http://www.mja.com.au/public/information/iprs2int.html Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Craig Bingham

Paediatric rotavirus gastroenteritis: where to now in prevention and treatment? While we await a preventive vaccine, we should concentrate on appropriate management, which means avoiding medications and giving dilute fluids to counter dehydration MJA 1998; 169: 241-242 Rotavirus is a major cause of gastroenteritis affecting young children worldwide. In this issue of the Journal, Carlin and colleagues present data which suggest that, of the approximately 20 000 children under five years admitted to hospital with acute gastroenteritis in Australia annually (a rate of 15/1000 per year), rotavirus is responsible in 50%.1 This accords with a recent New South Wales study suggesting that 56% of hospitalisations for acute gastroenteritis in this age group could be attributed to rotavirus.2The virus was first identified in 1973 by Bishop and coworkers at the Royal Children's Hospital, Melbourne, when they used electron microscopy to examine duodenal biopsies from infants admitted to hospital with severe acute non-bacterial gastroenteritis.3 Since that time, rotavirus has also been shown to be a cause of acute gastroenteritis in the young of a wide range of wild and domestic mammals. The virus, a member of the family Reoviridae, can be classified into serogroups A-G, and most human infections are caused by serogroup A. Routine diagnosis is based on rapid detection of group A antigen in faeces, generally by latex agglutination or enzyme immunoassay. In temperate climates, rotavirus infection occurs all year round, with very pronounced annual winter-spring peaks in incidence. The major epitope associated with a protective immune response is the viral outer capsid glycoprotein VP7. In mammalian rotavirus strains, monoclonal antibodies can be used to differentiate this protein into 10 serotypes, of which four, G1 to G4, are responsible for most cases of severe disease in young children. The rotavirus genome comprises 11 segments of double-stranded RNA, which readily allows genetic reassortment when coinfection is induced in vitro with strains of differing serotypes from one or more species.4 Approaches to vaccine development have concentrated on G1 rhesus strains, strains of human neonatal origin and tetravalent rhesus-human reassortants expressing G1-G4 serotypes. Large-scale clinical trials to date have shown advantages in the tetravalent vaccine candidates in protective efficacy,4 and it is likely that an oral tetravalent rhesus-human reassortant rotavirus vaccine will be approved in Australia in the next 1-2 years. Randomised controlled trials of this vaccine given as three oral doses between six weeks and six months of age were conducted among both urban and Native American populations in the United States, and in Finland. These trials showed protective efficacies of 49%-66% against any rotavirus gastroenteritis and 69%-100% against very severe infection.5-7 The vaccine was found to be relatively safe, with adverse reactions largely limited to fever and irritability after the first dose -- one-third of children had fever over 38oC, while 3% had fever over 39oC.8 Another approach to preventing rotavirus gastroenteritis is passive immunisation -- giving oral preparations containing high-titre rotavirus antibodies derived from the colostrum of immunised cows. One study showed a marked reduction in the incidence of hospital-acquired rotavirus infection when hospitalised children were given a hyperimmune bovine colostrum preparation,9 and further trials are under way to assess the value of community use. Use of either active or passive immunisation may be of particular value in children aged under three years attending long- daycare, as rotavirus infection in this group causes substantial morbidity and family disruption.10 Although preventing rotavirus gastroenteritis has obvious appeal, our medium-term focus will continue to be on managing children with acute gastroenteritis. Carlin et al note substantial differences in hospital admission rates between Australian States and raise the possibility that there are variations in hospital admission policies or practices.1 Other local data have shown that most children admitted to two NSW children's hospitals have only a minor degree of dehydration.11,12 In an editorial comment on one of these NSW studies, Barnes indicated "continuing concern as to why so many mildly dehydrated children are admitted to Australian hospitals and why so many of them receive intravenous therapy".13 We have limited information on the management of gastroenteritis in the community and in hospital emergency departments. Most of the data are based on extrapolation from children who have been admitted to hospital. Preadmission management is suboptimal -- antibiotics, antiemetics or antidiarrhoeals are prescribed for more than 20%.11,12 The use of oral rehydration solution in the community is low, although most children are offered appropriately diluted clear fluids.11,12 While hospitalised children with gastroenteritis may not accurately reflect treatment practices in the community, there remains a disparity between management guidelines14 and actual practice. Treatment of gastroenteritis in the community should include continued breastfeeding in infants or increased fluids in older children. Either oral rehydration solution or appropriately diluted fluids are acceptable. Children should be allowed to return to their usual diet if they are hungry. Regular review of the child's progress, with particular focus on fluid balance, should be regarded as good clinical practice and not as overservicing. By contrast, medications are rarely required, may be harmful and should be avoided. Undiluted cordial, fruit juice or carbonated drinks (such as flat lemonade) are hyperosmolar solutions and pose the danger of exacerbating the diarrhoea. The prospect that a future rotavirus vaccine, if widely used, will have a major beneficial impact is exciting. Coupled with this is the need to deliver more effective clinical management of acute gastroenteritis in the community. Mark J Ferson Director, Public Health Unit, South Eastern Sydney Area Health Service and Staff Specialist in Public Health, Sydney Children's Hospital, Sydney, NSW Richard Henry John Beveridge Professor, School of Paediatrics, Sydney Children's Hospital and University of New South Wales, Sydney, NSW Carlin JB, Chondros P, Masendycz P, et al. Rotavirus infection and rates of hospitalisation for acute gastroenteritis in young children in Australia, 1993-1996. Med J Aust 1998; 169: 252-256. Ferson MJ. Hospitalisations for rotavirus gastroenteritis among children under five years of age in New South Wales. Med J Aust 1996; 164: 273-276. Bishop RF, Davidson GP, Holmes IH, Ruck BT. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet 1973; ii: 1281-1283. Kapikian AZ, Hoshino Y, Chanock RM, Perez-Schael I. Jennerian and modified Jennerian approach to vaccination against rotavirus diarrhea using a quadrivalent rhesus rotavirus (RRV) and human-RRV reassortant vaccine In: Chiba S, Estes MK, Nakata S, Calisher CH, editors. Viral gastroenteritis. Vienna: Springer-Verlag, 1996: 163-175. Rennels MB, Glass RI, Dennehy PH, et al. Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines -- report of the National Multicenter Trial. Pediatrics 1996; 97: 7-13. Toensuu J, Koskenniemi E, Pang X-L, Vesikari T. Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Lancet 1997; 350: 1205-1209. Santosham M, Moulton LH, Reid R, et al. Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations. J Pediatr 1997; 131: 632-638. Joensuu J, Koskenniemi E, Vesikari T. Symptoms associated with rhesus-human reassortant rotavirus vaccine in infants. Pediatr Infect Dis J 1998; 17: 334-340. Davidson GP, Whyte PBD, Daniels E, et al. Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet 1989; ii: 709-712. Ferson MJ, Stringfellow S, McPhie K, et al. A longitudinal study of rotavirus infection in child-care centres. J Paediatr Child Health 1997; 33: 157-160. Loughlin EV, Notaras E, McCullough C, et al. Home-based management of children hospitalized with acute gastroenteritis. J Paediatr Child Health 1995; 31: 189-191. Elliott EJ, Backhouse JA, Leach JW. Pre-admission management of acute gastroenteritis. J Paediatr Child Health 1996; 32: 18-21. Barnes GL. Oral rehydration solutions in gastroenteritis before and after admission to hospital. J Paediatr Child Health 1996; 32: 16-17. Gastroenteritis. A guide for parents and caregivers. Sydney: Australian Gastroenterology Institute, 1996. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Mark J Ferson · Richard Henry

Outcome measures of an Australian breast-screening program One surrogate measure of the quality and effectiveness of screening MJA 1998; 169: 179-180 Mammographic screening for the early detection of breast cancer is a population-based measure for which randomised controlled trials have shown a 30% reduction in mortality in women aged between 50 and 69 years and who are screened.1 It is often forgotten that Australia is one of only a few countries where the State (in the form of both Federal and State governments) funds a national program of mammographic screening. From the outset of this program, there was an insistence that a quality service was essential if the predicted mortality reduction benefits were to be realised. Thus, national quality benchmarks based on international data were set. These were incorporated into accreditation standards to apply to all services in all States and Territories. This 30% mortality reduction depended on achieving a screening rate of approximately 70% of the target population, but it was recognised that even with 100% participation an inadequate, poor-quality service would not deliver the goods. The national screening program was phased in from 1992 and now covers the whole country. The accreditation standards are achievable, but screening participation has yet to reach target, and it will be several more years before mortality statistics for breast cancer can be affected by screening. Surrogate measures for the effectiveness of the service are therefore needed. One predictor of future breast cancer mortality is the small cancer detection rate, and it is gratifying that most States and Territories have already achieved the national accreditation standard.2 Another predictor of the effectiveness of the screening program is the interval cancer rate measured at State and national levels. The interval cancer rate is usually defined as the rate of diagnosis of new cases of invasive breast cancer and ductal carcinoma-in-situ in the two-year interval after a screening examination. In this issue of the Journal Rickard et al report rates and proportional incidences of interval cancers in the 12 months after screening from a New South Wales pilot mammographic screening program.3 The proportional incidence is the proportion that interval invasive breast cancers comprise of the total number of invasive breast cancers expected in the absence of screening. While the proportional incidence reported by Rickard et al is lower than that reported in studies from the United Kingdom4 and the Netherlands,5 it is higher than that found in the Swedish Two-County Study.6 As the confidence intervals found in all these studies overlap, we cannot conclude that these differences are statistically significant. However, the lack of a statistically significant difference in the proportional incidence between the study by Rickard and colleagues3 and the Swedish one6 cannot be taken to mean that they will achieve a similar mortality reduction. Larger State-based and national studies are needed to make international comparisons. The 12-month interval-cancer incidence of 4.17 per 10 000 screens in the women aged 40-49 years and 4.64 per 10 000 screens in women aged 50-69 reported by Rickard et al3 are lower than that reported by the South Australian screening program.7 However, because the confidence intervals for the New South Wales rate3 include the SA estimate, these differences are not statistically significant. To calculate rates and proportional incidences of interval cancers, we need well-functioning, complete and up-to-date BreastScreen services and cancer registries in each of the States and Territories. This requires both political will and financial resources, at national and State levels. It is also essential that each program counts interval cancers in the same way. In the UK,8 different definitions of interval cancers gave estimates of the interval cancer rate which varied by nearly 30%. While the low 12-month incidence rate found by Rickard et al is promising, it is also important to measure this in the second year after screening, when interval cancers are likely to form a greater proportion of the expected incidence of breast cancer. Also, although this study is too small to present separate interval cancer rates for the first and second screening round, future studies must do this, as these rates may differ. Nevertheless, it is essential to recognise the need to measure interval cancer rates in breast screening in a consistent fashion, in each State and Territory as well as nationally. Although interval cancers are inevitable, they are a measure of the sensitivity of a program whose object is to ensure that a high proportion of women with cancer are diagnosed by the screening process. However, achieving the lowest possible interval cancer rate must not be done at the expense (financial and emotional) of recalling a high proportion of women for further assessment that would lead to high rates of false positives (as happened in one American service where one-third of women without cancer received an abnormal screening result over 10 years).9 BreastScreen Australia is just over five years old and in its infancy. It has attained a high level of awareness among women,10 with very high levels of acceptability as shown by high rescreening levels.11 Government funding permits a quality of screening not available in the world's first national program, in the United Kingdom -- double-view mammography, double specialist reading and a two-yearly screening interval. To ensure quality and to assess whether their stewardship of this national investment in women's health is likely to have produced the expected reduction in breast cancer mortality, programs should be encouraged not only to attain the accreditation standards, but also to use nationally agreed surrogate measures for overall mortality changes, of which interval cancer rates are but one. Further, governments must support their investment by encouraging and funding the collection and interchange of these nationally agreed data. Alan Rodger Professor and Director The William Buckland Radiotherapy Centre, The Alfred Health Care Group, Melbourne, VIC Anne M Kavanagh Public Health Research Fellow Cancer Epidemiology Centre, Anti Cancer Council of Victoria, Melbourne, VIC Hurley SF, Kaldor JM. The benefits and risks of mammographic screening for breast cancer. Epidemiol Rev 1992; 14: 101-103. National Program for the Early Detection of Breast Cancer -- national accreditation requirements: March 1994. Canberra: Commonwealth Department of Human Services and Health, December 1994. Rickard MT, Taylor R, Fazli MA, El Hassan N. Interval breast cancers in an Australian mammographic screening programme. Med J Aust 1998; 169: 184-187. Woodman CBJ, Threlfall AG, Boggis CRM, Prior P. Is the three year breast screening interval too long? Occurrence of interval cancers in NHS breast screening programme's north western region. BMJ 1995; 310: 224-226. Peeters PHM, Verbeek ALM, Hendricks JHCL, et al. The occurrence of interval cancers in the Nijmegen screening programme. Br J Cancer 1989; 59: 929-932. Tabar L, Faberberg G, Day NE, Holmberg L. What is the optimum interval between mammographic screening examinations? An analysis on the latest results of the Swedish two-county breast cancer screening trial. Br J Cancer 1987; 55: 547-551. Robinson JL, Crane CEB, King JM, et al. The South Australian breast x-ray service: results from a statewide mammographic screening programme. Br J Cancer 1996; 73: 837-842. Faux AM, Richardson DC, Lawrence GM, et al. Interval breast cancers in the NHS breast screening programme: does the current definition exclude too many? J Med Screening 1997; 4: 169-173. Elmore JG, Barton MB, Moceri VM, et al. Ten-year risk of false positive screening mammograms and clinical breast examination. N Engl J Med 1998; 338: 1089-1096. Barratt AL, Cockburn J, Redman S, Perkins PC. Mammographic screening: results from the 1996 National Breast Health Survey. Med J Aust 1997; 167: 521-524. BreastScreen Victoria. Annual Statistical Report 1996. Melbourne: Victorian Breast Screening Co-ordination Unit Inc., 1996: 12. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Alan Rodger · Anne M Kavanagh

Use of complementary medicines: scientific and ethical issues We need to address questions of effectiveness, safety and regulation MJA 1998; 169: 180-181 This article has been cited in Rey JM, Walter G. Hypericum perforatum (St John's wort) in depression: pest or blessing? MJA 1998; 169: 583-586. The widespread acceptance of complementary medicines in Australia raises important scientific, social and ethical issues. The expression "complementary medicines" covers a diverse range of practices, from historically well-established therapies, such as traditional Chinese medicine, to more exotic forms, such as colour therapy and psychic healing.1 Taken together, the precise extent of their use is unknown. Certainly, the industry is a very large one: in the United States and Australia about one-fifth of the population visit alternative practitioners each year, and in Australia up to half the population have visited them at some stage.2-4 In the United States, expenditure on complementary therapies in 1990 was about $14 billion;3 for Australia, precise data are not available, but the figure is likely to be in the hundreds of millions of dollars.2,4 The use of complementary medicines is increasing. Again, data are scanty. However, over the last five years the number of raw medicinal substances imported for use in Australia has increased fourfold, and there are now about 300-400 individual medicines available.5 Since the introduction of a Medicare rebate for acupuncture in 1984, use of acupuncture by medical practitioners has increased greatly. By analysing one of the few reliable sources of data available, Health Insurance Commission records, Easthope et al,6 in this issue of the Journal, show that the number of Medicare claims for acupuncture services by general practitioners grew by nearly 50% in 12 years, to almost one million in 1996-97. Medicare reimbursements to doctors for acupuncture increased during this period from $7.7 million to $17.7 million, and in 1996 about 15% of general practitioners presented Medicare claims for acupuncture. Evidence regarding the clinical effectiveness of most complementary treatments, and the risks associated with them, is extremely limited.7,8 Randomised clinical trials have been few; indeed, it has been argued that complementary therapies in general, and traditional Chinese practices in particular, are in principle not susceptible to assessment using randomised-trial designs.7 In the case of acupuncture, significant insights have been achieved into physiological mechanisms of action; however, the few clinical studies that have been performed have often been flawed by poor design, inadequate measures and statistical analysis, and lack of follow-up data.7,8 Notwithstanding this, rigorous trials are possible, as has been shown by studies that support the use of acupuncture in the treatment of pain and nausea, and suggest possible applications in other areas, such as hypertension and asthma.7,8 It is important to recognise that complementary medicines, like orthodox ones, are not without risk. There is the possibility that use of complementary treatments might lead to withdrawal from appropriate medical therapy or to delays in diagnosis or treatment of underlying conditions. In addition, physical treatments can cause adverse effects, and herbal therapies can be either intrinsically toxic or contaminated with toxic substances. As recent discussions in the Journal have highlighted, serious reactions and even death can occur.8-11 Complications of acupuncture have included pneumothorax and puncture of other vital organs, spinal cord lesions, and infections (including HIV and hepatitis B),12,13 again associated with possible death.14 A National Health and Medical Research Council working party in 1989 found that complications occurred most frequently with acupuncturists without medical training.14 The widespread use of complementary medicines, and especially the application of acupuncture by general practitioners demonstrated by Easthope et al, raises some interesting social and ethical questions: It is widely accepted that individuals should be free to make their own choices with respect to healthcare; however, are not claims of cures matters of public interest affecting public health? Should the application of public funds be directed by consumer demand, or should it be limited to practices -- orthodox or complementary -- for which reasonable evidence of effectiveness and safety can be provided? Should the training and right to practise of complementary therapists -- at present largely unrestricted -- be subject to a formal system of regulation? Does the community have an obligation to protect vulnerable citizens from exploitation by practitioners holding uncertain qualifications, who apply practices with dubious benefits and unknown risks? Should special measures be introduced to protect children, especially from practices that may lead to their being denied conventional therapies of proven efficacy?15 Why have risk and lack of evidence not deterred potential patients and practitioners? The question of why people use complementary therapies is an important one which may have ethical implications of its own. There is evidence that people turn to alternatives because they are disillusioned with orthodox medicine. This may include dissatisfaction with doctor-patient interactions or dissatisfaction with medicine in general.16 Declining public support for hospitals and the introduction of economic practices such as managed care, which promote cost-saving at the risk of reducing the quality of service, may well exacerbate this process. Some form of regulation of complementary medicines seems to be necessary, but a delicate balance needs to be struck between control and consumer choice. A possible model, referred to as "protection of title", is presently under consideration in Victoria, following a government-sponsored inquiry into the practice of traditional Chinese medicine. It is believed that legislation will be introduced to limit the use of the titles "acupuncturist" and "practitioner of traditional Chinese medicine" to individuals who have been accredited by specified registration bodies. This approach would contribute to the establishment of standards of practice and training and provide avenues for aggrieved consumers to have their complaints addressed. Unregistered therapists could continue to practise as long as they did not claim to hold specific qualifications to do so. It is quite likely that some form of protection of title will eventually be adopted as a general approach to the regulation of various forms of complementary therapy throughout Australia. This approach, however, represents only a partial solution. It will still be necessary to consider whether therapies work and are safe -- and, indeed, whether this question can be answered at all. It will still be necessary for us to understand the cultural meaning of complementary medicines and what they have to teach orthodox practitioners. For these questions to be addressed, detailed research will be needed into not just the scientific but also the sociological, ethical and philosophical aspects of complementary medicines. It is to be hoped that such research will be undertaken, and that it will promote much-needed dialogue between practitioners of orthodox and complementary medicine. Paul A Komesaroff Associate Professor, Department of Medicine, Monash University and Director, Eleanor Shaw Centre for the Study of Medicine Society and Law Baker Medical Research Institute, Melbourne, VIC Eagle R. Alternative medicine. London: Futura, 1978. MacLennan AH, Wilson DH, Taylor AW. Prevalence and cost of alternative medicine in Australia. Lancet 1996; 347: 569-573. Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States: prevalence, costs and patterns of use. N Engl J Med 1993; 328: 246-252. Ban E. Australian alternatives. Nat Med 1998; 4: 8. Myers S, Bensoussan A. Towards a safer choice: the practice of Chinese medicine in Australia. Sydney: Faculty of Health, University of Western Sydney, Macarthur, 1996. Easthope G, Beilby JJ, Gill GF, Tranter BK. Acupuncture in Australian general practice: practitioner characteristics. Med J Aust 1998; 169: 195-198. Vincent C, Furnham A. Complementary medicine: a research perspective. London: Wiley, 1997; 181-182. National Institutes of Health. Acupuncture. NIH Consensus Statement, April 1998. Mullins RJ. Echinacea-associated anaphylaxis. Med J Aust 1998; 168: 170-171. Kelly S. Aconite poisoning [letter]. Med J Aust 1990; 153: 499. Drew AK, Myers SP. Safety issues in herbal medicine: implications for the health professions. Med J Aust 1997; 166: 538-541. Halvorsen TB, Anda SS, Naess AB, Levang OW. Fatal cardiac tamponade after acupuncture through congenital sternal foramen [letter]. Lancet 1996; 345: 1175. Norheim AJ, Fønnebø V. Adverse effects of acupuncture [letter]. Lancet 1995; 345: 1576. National Health and Medical Research Council, Acupuncture Working Party. Acupuncture. Canberra: NHMRC, 1989. Neeley GS. Legal and ethical dilemmas surrounding prayer as a method of alternative healing for children. In: Humber JM, Almeder RF, editors. Alternative medicine and ethics. New Jersey: Humana Press, 1998; 163-194. Siahpush M. Postmodern values, dissatisfaction with conventional medicine and popularity of alternative therapies. J Sociology 1998; 34: 58-70. - Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Paul A Komesaroff