Medical practices

Richard X Davey Chemical Pathologist, Melbourne Health Shared Pathology Service, Western Hospital, Gordon Street, Footscray, VIC 3011. richard.daveyATwh.org.au To the Editor: In 1996, the Journal published my assessment of the scientific validity of a 1994 decision by the Australian Health Insurance Commission (HIC) to limit the Medicare rebate payment for assessment of thyroid function to thyroid-stimulating hormone level (TSH), except in certain more complex clinical conditions.1 For these, levels of TSH and of other indicators of thyroid function, such as thyroxine, are tested simultaneously and a rebate given for the group of tests. Although discussion concerning this diagnostic strategy persists,2 nearly a decade later it is appropriate to assess the outcome of this initiative. Publicly accessible HIC data3 on privately ordered, then publicly refunded, thyroid function tests in Australia for the fiscal years 1994–2002 were retrieved and are presented graphically (Box). Figure A shows the change in thyroid function test ordering sought by the HIC occurring in 1997 through to 2000 and probably now consolidating. Overall, before the initiative, there were 1.55 TSH tests ordered for each thyroid function group test, and in 2002 this increased to 2.65. The outcome in the elderly is similar, but the change is even more noticeable for thyroid testing in young women and men (with ratios of about 5 to 1 and 7 to 1, respectively). Clinicians have presumably come to accept the high negative predictive value of a normal TSH result for ruling out primary thyroid disease as both necessary and sufficient to finalise thyroid diagnoses in the young. By contrast, thyroid disorders are more common among the elderly, who thus more readily satisfy the HIC requirements for thyroid function group tests. The approximately fourfold increase in absolute terms in the number of single TSH tests performed over 9 years (from 2731 per 100 000 persons per annum in 1994 to 10 763 in 2002) can also be seen as vindicating the HIC’s decision to run with a “TSH first” testing protocol. The same pattern is seen in the age and sex groups illustrated (15–24 years and 75–84 years). The present speed, ease and relative economy of obtaining a TSH test, and the reliability, particularly at low TSH levels, of using this measure for thyroid disease case finding, make ordering a TSH test no longer an indulgence,4 but a clinical necessity. The national cost-of-living index for 30 June of each fiscal year5 was used to standardise the annual expenditure on thyroid function tests to 1994 dollar values, thus allowing comparison across the decade (Figure B). From 1995 to 2002, the HIC has contained annual expenditure to under $20 million for thyroid function group testing. This is both desirable and appropriate. That this has been sustained for 7 years in the face of increasing numbers of first-line TSH tests is both astonishing and commendable. Most of the increase in costs of TSH testing is probably explained by the acceptance of its use as a first-line test. Between the 1996 and 2001 censuses, the population grew from 17.9 to 18.8 million, and the proportion over 65 years also increased (from 12% to 12.5%). Both these trends are continuing,5 and both also explain some of the increase in ordering of TSH tests. It is unclear if any of this change is also due to testing moving from the totally public, hospital sector, not funded by the HIC, to the HIC-funded sector. Effect of changes to the Health Insurance Commission rebate for thyroid function testing A: Ratio of the number of single tests ordered (thyroid-stimulating hormone [TSH]) to the number of thyroid function group tests ordered (TSH and thyroid hormones). Data are tests per 100 000 persons per annum. B: Annual expenditure on thyroid function testing in Australia.

Richard X Davey

Jan R Stockigt Senior Endocrinologist, Alfred Hospital, Commercial Road, Prahran, VIC 3181. jrsATnetspace.net.au Comment: In his timely review of changing patterns of thyroid function testing, Davey suggests that Australian Health Insurance Commission (HIC) policy is responsible for the increased emphasis on a “TSH-first” strategy, with consequent containment of costs for other thyroid function tests. While this may in part be true, the trend towards initial TSH testing has been advocated worldwide1 following the development of TSH assays sufficiently sensitive to distinguish the typical suppressed TSH levels of thyrotoxicosis from normal levels. The developments documented by Davey are a consequence of technological development, perhaps enhanced by selective rebating as a result of HIC policy. It is unfortunate that current HIC policy is sometimes described as prohibiting more complete thyroid function testing, unless TSH level is abnormal. Rebate policy does not prohibit any line of testing and it is because the “TSH-first” approach has some serious, well-documented deficiencies.2 Measurement of levels of thyroid hormone in addition to TSH is clearly sanctioned in HIC regulations when TSH level alone can be misleading, for example in suspected pituitary dysfunction, or in monitoring the treatment of thyroid dysfunction. The adverse consequences, both human and financial, of relying on TSH measurement alone in such situations can be serious and may outweigh the savings achieved by restrictive testing. It must be noted again that a normal concentration of immunoreactive TSH has no predictive value in ruling out potentially life-threatening hypopituitarism,3 which may present with prominent hypothyroid features. The effective integration of clinical and laboratory investigation of potential thyroid dysfunction requires an active laboratory–clinical interface. There are over a dozen patterns of thyroid function — some trivial or inconvenient, some quite serious — that can be misdiagnosed or incorrectly managed if communication across this interface is inadequate.4 Effective communication requires relevant information from the clinician and a response to this information within the laboratory. It is a reality that current patterns of investigation in Australia frequently fall short of this ideal. If, as a result of automation and effective competition, the unit cost of assays can eventually be reduced in relation to the total cost of medical care, it may become appropriate to revert to a more complete panel of initial testing that integrates tropic hormone and target gland secretion, a strategy that remains the cornerstone of definitive endocrine investigation.

Jan R Stockigt

The benefits of whole-body CT screening need to be carefully weighed against the risks Whole-body computed tomography (CT) screening is currently marketed to asymptomatic individuals as a form of proactive and preventive healthcare. Commonly, the chest, abdomen and pelvis are scanned, but the head and neck are also included in the “five-region” scans offered by some commercial companies. In the United States, it has been estimated that, over the past 3 years, 15 million whole-body scans have been performed in about 400 centres.1 In Australia, clinics in Brisbane and Sydney are offering whole-body CT screening. Despite the growth in demand for whole-body scans, there is no evidence that they are effective in detecting serious, treatable disease without undue cost or undesirable effects. The value of many applications of imaging technology for diagnosing and monitoring disease and planning treatment is accepted. But sceptics of whole-body screening note the lack of evidence of benefit, the likelihood of clinically unimportant findings that may result in possibly needless further investigations, and the risks of radiation. There have been no published studies of the safety or efficacy of whole-body screening. In Australia, we identified only one ongoing study: researchers at the University of New South Wales are currently assessing 1500 people who have had whole-body CT scans, measuring significant pathological findings and their eventual outcomes (Fred Ehrlich, Professor of Public Health and Community Medicine, University of NSW, personal communication). The prevalence of findings on whole-body CT is high. In a recent conference presentation, it was reported that, of 1200 whole-body CT scans, 87% showed at least one finding, and nearly a third of patients were advised to undergo further testing or follow-up.2 In a study using CT to screen for lung cancer,3 700 ancillary findings (not related to lung cancer) were noted in about 1520 screened individuals. Most were false-positive results, and the follow-up adversely affected the patients’ quality of life and resulted in unnecessary diagnostic and interventional procedures.3 It has been estimated that, in healthy people, about 80% of abnormalities detected on CT screening studies may not be life-threatening;4 however, this estimate requires confirmation. Follow-up of non-significant findings has health, psychosocial and cost implications. In Australia, Medicare and private health insurance agencies do not cover the costs of a whole-body scan (currently over $800), but may reimburse follow-up diagnostic evaluations. What are the risks of whole-body screening? The radiation exposure has been estimated to be somewhere between 1 and 24 mSv per CT scan.5,6 However, owing to technical and anatomical factors, the dose can vary by a factor of 10 or more between patients.6 A 10 mSv radiation exposure is associated with an increased risk of fatal cancer of about 1 in 2000 (this can be compared with a lifetime risk of about 1 in 5).6 If screening were undertaken in Australia at 3-year intervals, the risk of radiation-related death would be an estimated 0.4%, 0.3% and 0.1% for men starting screening at 40, 50 and 60 years, respectively, and 0.6%, 0.4% and 0.2% for their female counterparts.7 Compared with 10 other types of x-ray, CT scans are responsible for the largest number of radiation-induced cancers per year in nine cancer sites examined.8 In Australia, the Radiation Advisory Council and the NSW Environment Protection Authority concluded in 2003 that whole-body screening by CT is inappropriate for the general diagnosis of healthy individuals. Similarly, the Royal Australian and New Zealand College of Radiologists and the Radiation Health and Safety Advisory Council have each published statements indicating that there is insufficient scientific evidence to support whole-body CT screening in asymptomatic patients with no family history suggesting disease.9,10 In the United States, several professional groups, including the American College of Radiology and the American Association of Physicists in Medicine, do not recommend whole-body CT screening for asymptomatic healthy individuals.11,12 In New South Wales, it has been illegal since 2003 to perform a whole-body CT scan without a written request from an independent medical practitioner. The radiation dose and health risks involved must be fully explained, individuals under the age of 50 must be told that they are more at risk of developing cancer as a result of the procedure, and written and informed consent must be obtained before the scan can be performed.13 Breaches of these new regulations may attract fines of up to $27 500 for individuals, $165 000 for corporations and/or a maximum of two years’ imprisonment.13 This approach disallows self-referral. We made enquiries to medical defence providers and professional organisations regarding the referral of asymptomatic patients for whole-body CT screening. One medical indemnity provider indicated that, in the event of an untoward incident, members would not be indemnified if they practised whole-body CT screening for asymptomatic patients or referred patients using particular referral formats supplied by commercial CT screening companies. We suggest that practitioners check with their own indemnity provider regarding their coverage under these circumstances. The key question is whether whole-body CT screening will lead to detection of unsuspected diseases, resulting in earlier treatment and improved outcomes, or simply reveal abnormalities for which follow-up and treatment will result in no overall gain. This question can only be answered with well designed studies. In the interim, the community interest in whole-body CT screening is growing, and GPs, especially, may be put in a difficult position by patients requesting a referral for a whole-body scan. Some Internet sources of information on whole-body CT screening are listed in the Box. Consumers and medical practitioners need to be wary of the many claims that are made in support of whole-body CT screening for early disease. Guidelines — based on the current evidence of benefits and risks of whole-body CT screening, assessed by reputable professional and consumer bodies — would be valuable to assist the decisions of both medical practitioners and consumers and to provide a better basis for informed consent. In conclusion, the current evidence suggests that patients should be advised that there is no proven benefit, and indeed possible detriment, from undertaking whole-body CT screening. Internet sources of information on whole-body computed tomography Australian professional and government organisations Royal Australian and New Zealand College of Radiologists www.ranzcr.edu.au/open/policies/diagnostic_imaging/pol2_2.htm Radiation Health and Safety Advisory Council www.arpansa.gov.au/pubs/rhsac/st1_aug02.pdf NSW Environment Protection Authority www.epa.nsw.gov.au/radiation/ctbodyscans.htm NSW Health www.ppc.health.nsw.gov.au/news/2002/September/26-09-02ct.htm www.health.nsw.gov.au/news/2003/June/08-06-03ct.htm www.chs.health.nsw.gov.au/pubs/factsheet/pdf/body_scan_fs.pdf International professional organisations US Food and Drug Administration wwwfda.gov/cdrh/ct American College of Radiology www.acr.org/departments/pub_rel/press_releases/total-bodyCT.html Health Physics Society hps.org/documents/CTPosStm.pdf Other sources of information your patients may be using Life Span Medical Imaging www.lifespanmedical.com.au Total Health Screening www.totalhealthscreening.com.au Health Imaging CT www.openmrimgt.com/healthscreen/index.htm Be Well Body Scan www.bewellbodyscan.com Full Body Scanning www.fullbodyscanning.com/sanfrancisco/full-body-scan.jsp The Oprah Winfrey Show www.oprah.com/tows/pastshows/tows_2000/tows_past_20001002_b.jhtml www.oprah.com/tows/pastshows/tows_2000/tows_past_20001002_c.jhtml

Cleola Anderiesz PhD, BSc · J Mark Elwood MD, DSc · Brian R McAvoy MD, FRACGP, FRCP · Lizbeth M Kenny MB BS, FRANZCR

Stacey L Emmett,* Joseph E Ibrahim,† Amanda Charles,‡ David L Ranson§ * Research Officer, † Physician, ‡ Clinical Research Nurse, § Deputy Director, Clinical Liaison Service, Victorian Institute of Forensic Medicine and the State Coroner’s Office, 57–83 Kavanagh Street, Southbank, VIC 3006 staceyeATvifm.org To the Editor: The Royal College of Pathologists of Australasia Autopsy Working Party highlighted the decline in the numbers of hospital autopsies.1 Forensic and hospital autopsies are a valuable safety and quality tool for improving healthcare systems. Autopsies provide an accurate cause of death and are a valuable audit tool to evaluate medical diagnostic processes and therapeutic interventions. Declines in both types of autopsies are cause for concern. A forensic autopsy is an integral part of the coronial process. The Coroner’s role is to establish the identity of the deceased, where he or she died, the cause of death and, perhaps most importantly, how the person died.2 Without an autopsy, it can be difficult to determine the cause of death. At the Victorian Institute of Forensic Medicine (VIFM), about 80% of all deaths that are reported to the State Coroner (in Melbourne and Geelong) undergo a full forensic autopsy. Senior next-of-kin can object to an autopsy being performed. Section 29 of the Coroner’s Act 1985 (Vic) details the objection process.2 The decision to grant an objection is dependent on the opinion of the Coroner and his or her view on the circumstances of death. We reviewed the number and rate of forensic autopsies performed by the VIFM between 1992 and 2002, as well as the number and rate of objections under Section 29. The rate of forensic autopsies remained relatively stable over the decade, at 80% of deaths reported to the State Coroner. There were 94 successful Section 29 applications in 1992. This accounted for 3.25% of all deaths reported to the Coroner. Objections to autopsies have been steadily increasing since 1992. In 2002, there were 212 successful applications, accounting for 7.1% of all deaths reported to the Coroner and representing about a 4% rise over the decade. When a coronial autopsy has been requested, but not carried out because of a Section 29 objection, substantial additional work is required. This includes medical record reviews; external forensic examinations; reviews of statements from treating doctors, independent experts and family; and inquests. The other major ramification associated with objections to autopsies is the discrepancies between causes of death that are determined clinically and at autopsy (with 28% of presumed causes wrong in one study).3 Without an autopsy, important pathology may remain unrecognised, and this can substantially affect the accuracy of the stated cause of death. The inherent right of next-of-kin to object to coronial autopsies will remain. However, healthcare professionals and coroners need to be aware of the public health implications associated with objections to autopsies.

Stacey L Emmett · Joseph E Ibrahim · Amanda Charles · David L Ranson

In November 1999, in the United Kingdom, a woman was convicted of the murder of her two infant sons. An appeal against the conviction was dismissed in October 2000, but the conviction was quashed by a second court of appeal in January 2003. Review of the autopsy findings showed that standard procedures had not always been followed, thus limiting verification of the alleged findings. Some potentially important diagnoses and conclusions were also altered over time. This case and its sequelae demonstrate the difficulties that may arise if cases are not fully investigated by pathologists with specific training or experience in paediatric forensic pathology, with all of the results being clearly summarised and discussed in autopsy reports. Trying to clarify findings, diagnoses and circumstances of death at a later stage may simply not be feasible, owing to a wide variety of possibilities other than inflicted injury. This type of case has unfortunately led to mistrust of the medical and legal systems and has made the investigation of such emotive and tragic cases all the harder.

Roger W Byard MD, FRCPath

Winston Chong Chair, Interventional Radiology Reference Group, Level 9, 51 Druitt Street, Sydney, NSW 2000. ranzcrATranzcr.edu.au To the Editor: I refer to the recent editorial on “Metformin and serious adverse effects”.1 I would like to highlight the position of the Royal Australian and New Zealand College of Radiologists (RANZCR) on the use of metformin hydrochloride when administering intravascular contrast media. The RANZCR has adopted an evidence-based approach in formulating its guidelines. The College guidelines on metformin hydrochloride and intravascular contrast media are available at <www.ranzcr.edu.au/open/policies/diagnostic_imaging/pol1_2.htm>. The current guideline is that there is no need for patients to stop taking metformin hydrochloride for 24–48 hours before administration of an intravascular contrast medium. Stopping or continuing to take metformin depends on the patient’s renal status, and the likelihood of inducing renal dysfunction when intravascular contrast is administered. If discontinuation is required, then the drug only needs to be stopped for 48 hours, commencing on the day of administration of intravascular contrast.

Winston Chong

Janelle C Nisbet,* Joanna M Sturtevant,† Johannes B Prins‡ * Endocrinology Registrar, † Renal Specialist Pharmacist, ‡ Director of Diabetes and Endocrinology; and Professor of Endocrinology, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102. jprinsATsoms.uq.edu.au In reply: Chong’s letter highlights some important issues, and his points are well made. As we imply in our editorial,1 the evidence base on which to base guidelines and decisions is poor, which is one of the reasons that the guidelines differ widely between countries and organisations. Specialty-specific guidelines must also take into account practicalities. We elected to follow the more conservative end of the guideline spectrum in our suggestions, accepting that, in many circumstances, these would be difficult or impossible to follow. From a radiological perspective, it would require a significant change in practice to implement guidelines such as those we suggested, and the evidence base supporting such a change does not exist. Metformin is a short-acting drug and stopping it at the time of a potentially hazardous procedure will almost always be effective in preventing drug-related complications. Overall, the aim of our article was to raise awareness of the potential hazards of metformin use, and to encourage practitioners to follow available and relevant guidelines.

Janelle C Nisbet · Joanna M Sturtevant · Johannes B Prins

Health policy decisions are based on more than evidence Benjamin Franklin’s 18th-century slice of wisdom that “In this world nothing can be said to be certain except death and taxes” still rings true today. But, in these modern times, adding “and rising health costs” would not be inappropriate. The inexorable increase in public spending on healthcare is a political issue for much of the developed world, and Australia is no exception. Our healthcare expenditure rose from 7.5% of GDP in 1989 to 8.5% in 1999, and it shows no sign of abating.1 Indeed, the federal treasurer recently observed that “When we look across the next forty years we find that the largest area of pressure in relation to Government spending is going to be in the health area.”2 So what are we to do? Commenting on a North American view of the United Kingdom’s National Health Service,3 the President of the Royal College of Physicians recently wrote: To contain the costs of growing needs and expectations for health and care services, there is an increasing emphasis on the clinical and cost effectiveness of health care, with evaluation of procedures and technologies, targeting of resources to services and interventions of proven effectiveness . . .4 This endorsement of evaluation of evidence, effectiveness and efficacy is the stuff of which evidence-based medicine (EBM) is made, and must be a godsend for governments, health ministers and their public servants. For, as noted by a UK social scientist, “EBM offers the vision . . . of solving all health care funding problems by eliminating unnecessary and unproven health care.”5 In short, stringent evidence is required if the public purse is to pay for new drugs, medical technology or other interventions. Policing bodies exist to effect this policy. For decisions regarding government funding support in Australia, the Federal Minister for Health seeks the advice of the Pharmaceutical Benefits Advisory Committee (PBAC) for new drugs and the Medical Services Advisory Committee (MSAC) for emerging medical technologies or procedures. How do these committees arrive at their advice? What are their modi operandi and tensions? Answers to these questions have not been readily forthcoming, as these bodies work behind closed doors, the details of their deliberations are confidential, and participants are bound by a code of silence. In this issue of the Journal (page 627), the door of a bureaucratic conclave is opened slightly as Ware and his colleagues examine the government’s deliberations regarding public funding of positron emission tomography (PET) services.6 Much of their information was obtained through freedom of information requests and, despite its inherent limitations, their account was of sufficient interest to the Journal for us to pursue the long road to publication. Each story has two sides and we also sought the views of the Australian Government Department of Health and Ageing (page 633).7 The “exposé” by Ware and colleagues raises issues about the political pressures that come to bear on potential “big ticket” medical technology roll-outs, the processes involved in technology assessment and the values attending this exercise. As certain as death and taxes is that new technology spawned by research and commercial concerns will increase pressure on the already runaway cost of healthcare. PET is one such technology. It is the latest in a stream of imaging modalities, following computed tomography and magnetic resonance imaging. PET capitalises on the differential metabolism of glucose by malignant cells and is of significant clinical utility in cancer diagnosis and staging, and for following the effects of treatment. But it is expensive, and not readily seen as cost-effective if judged exclusively through standard outcomes such as survival or mortality. PET fell victim to the health bureaucracy doctrine that new technology should not be comprehensively funded by the public purse in the absence of high levels of evidence of both clinical and cost effectiveness. Supposedly because of this, and much to the disappointment of Ware and colleagues, the current Commonwealth government funding arrangements for PET limit the number and location of publicly funded PET services8 and the clinical indications for its use.9 Ware’s qualms about MSAC’s deliberations raise questions about the hype of EBM in health policy. Nobody would disagree with the then Health Minister’s ideal that with the establishment of MSAC “the gap between research knowledge and clinical practice will narrow and patients will benefit earlier from the most advanced procedures drawing on the best scientific medical evidence”10 — in short, EBM. But it appears that the rhetoric surrounding EBM has led to a misunderstanding of policymaking. Indeed, the certainty value of EBM in this setting is more fanciful than real, as other considerations are involved.5,11 These include: competing goals other than clinical effectiveness (social, financial and political); beliefs that some of the research is irrelevant to circumstances in which assessments are taking place; lack of consensus in understanding, interpretation and applicability of the research; other types of competing evidence (personal experience, local information, eminent opinions and evidence provided by advocacy groups); a social or political environment that is not conducive to policy change; and scientific information being poorly presented to the policymakers. Ware et al’s critique of MSAC’s deliberations is not unique. Similar concerns have been raised about Britain’s National Institute of Clinical Excellence in its regulatory role for the introduction of new technology, interventions and pharmaceuticals in the NHS.12 Finally, the experience of Ware et al in extracting information through freedom of information provisions raises the issue of transparency and accountability of health-policy formulation. Most Australians would accept that even healthcare resources are finite. Most would expect our governments to make the tough decisions about how public funds are spent, however unpalatable the decisions may be to sections of the community. But the public is not impressed by the secret milieu in which this occurs. It leads to mistrust and suspicion. Professional disquiet can also arise when expert opinions proferred in committees are not reflected in the final outcome. Onora O’Neill, in the 2002 BBC Reith Lectures, counselled that, to confront society’s burgeoning culture of suspicion, “We need genuine rights, genuine accountability, genuine efforts to reduce deception and genuine communication”.13 More transparency in decision-making that affects the public is not unreasonable. Meanwhile, for the foreseeable future, rising healthcare costs will remain one of life’s certainties. Evidence-based medicine alone will not contain this.

Martin B Van Der Weyden MD, FRACP, FRCPA · Ruth M Armstrong BMed

Ware, Francis and Read (page 627) express some concerns about the processes used in the Australian government’s decisions about funding for positron emission tomography (PET). We appreciate the Journal’s invitation to comment. I will briefly describe the workings of the Medical Services Advisory Committee (MSAC), the particular processes that have been undertaken in respect of PET, and the recommendations and funding decisions that flowed from those processes. MSAC advises the Minister for Health and Ageing on the strength of evidence pertaining to new and emerging medical technologies and procedures. In doing so, the committee considers safety, effectiveness and cost-effectiveness, and under what circumstances public funding should be supported. MSAC consists of eminent surgeons, physicians, health economists and experts in epidemiology and medical research, as well as representatives of consumers and of the Australian Health Ministers’ Advisory Council. In addition, for each technology under review, MSAC appoints experts in the relevant fields to supporting committees to help interpret the evidence. Since its inception in 1998, MSAC has established a reputation as one of the foremost sources of advice to government on new healthcare technologies. The processes surrounding the consideration of PET, including MSAC’s assessment, have been as follows: In 1999, PET first came to MSAC’s attention through applications from the Peter MacCallum Cancer Institute (Melbourne) and the Wesley Hospital (Brisbane). In August 1999, the then Minister for Health and Aged Care asked the department to conduct a broader review of PET to determine its proper role in the Australian clinical setting. The review incorporated an assessment by MSAC of PET in six clinical indications, but also considered a range of other matters, including the distribution of services, and workforce and accreditation issues. The review was guided by a steering committee comprising representatives of the medical profession, state and territory governments, and consumers. It received submissions from professional associations, states, hospitals, technology suppliers and medical service providers.1 In May 2000, MSAC concluded that there was insufficient evidence to draw definitive conclusions about PET’s clinical effectiveness and cost-effectiveness for the six indications.2 However, it did recommend that interim funding be made available on condition that facilities collect data to inform longer-term decisions about the role of PET in Australian clinical practice. In August 2000, the Minister agreed to implement the recommendations of the broader review, incorporating MSAC’s findings. This included a limited expansion of funded PET facilities through a tendering process. In May and August 2001, MSAC published further assessments of PET in respect of seven additional indications.3,4 MSAC again concluded that there was insufficient evidence to warrant unrestricted Medicare funding, but that interim funding should be provided under certain conditions, including that data should be collected to aid further assessment. The PET tendering process was completed in September 2001. By April 2003, eight facilities were receiving Medicare funding to provide PET services: three in Victoria, two in New South Wales, and one each in South Australia, Western Australia and Queensland. Funded facilities are participating in a data collection and evaluation program, as recommended by the PET review. This is expected to be completed in 2006. MSAC considered PET within the context of a broader review of the technology, but it applied its normal methods and evaluation criteria. The committee recommended funding for PET both in its initial report in 20002 and in subsequent reports in 2001.3,4 The Minister accepted that advice, and a wide range of PET services now attracts a Medicare benefit. This will continue until MSAC next reviews the technology. In addition to offering Medicare benefits for PET services, the government is funding the collection of data by service providers to improve the evidence base relating to the use of PET in a wider range of indications. The government does not routinely fund such data collection, but has done so in this case in acknowledgement of the potential impacts of PET on patients and the Australian healthcare system. Finally, one of the concerns that has been raised about the PET reviews is that the government did not follow the views of individuals who were involved in the processes. But that is by no means unusual. It is common for advisers appointed to MSAC supporting committees to bring a range of views to the table. Indeed, the supporting committees and MSAC itself are constructed to enable a diversity of perspectives to contribute to constructive and rigorous debate and decision making. MSAC’s challenge is to marry the published evidence with a diverse range of opinions and come to a definitive conclusion. The examinations of PET have been no exception. Having provided significant interim funding for PET, and substantial support for further data collection to build the evidence base, the Australian government has accepted MSAC’s advice to leave the door open, and will consider further evidence of PET’s safety, effectiveness and cost-effectiveness as it emerges in 2006.

Philip Davies MSc

Although the risk from medical radiation is small, we should not become complacent Ionising radiation is one of the most extensively researched agents in our society. Indeed, more is known about its effects than the effects of most other things in our environment. High doses are known to be harmful, with the main long-term adverse effect being cancer induction. The best evidence for this comes from survivors of the atomic bomb explosions in Japan, where models have been developed relating increased cancer induction to the dose of radiation received. Although the magnitude of the effect is small, the link is well established. When people are exposed to radiation, its use must be justified by ensuring that it does more good than harm. Diagnostic x-rays are the largest man-made source of exposure of the general population to radiation. Even if the risk from radiation to an individual is very small, exposure of a large number of people over time could translate into a considerable number of cancer cases. A recent report in The Lancet attempts to quantify the risk of cancer induction from diagnostic x-ray procedures, averaged over the population.1 From surveys of medical radiation use in a number of countries, the authors obtained information on the average annual frequency of various x-ray procedures and estimated the doses to various organs from those procedures. They then applied a model of radiation-induced cancer cumulative risk to the doses received by the various organs to derive an estimate of the attributable risk of developing cancer. Their analysis suggests that in Australia about 431 cancers per year (1.3% of all cancers) could be attributable to diagnostic x-rays. The corresponding percentages for 14 other countries considered ranged from 0.6% in the United Kingdom and Poland to 3.2% in Japan. Their study does not provide any new evidence that radiation from diagnostic medical procedures causes cancer. Rather, the researchers rigorously applied an existing model to medical diagnostic radiation exposure of the population to derive the best estimate to date of the magnitude of the risk of cancer induction. They acknowledge that there is considerable uncertainty attached to this estimate and that a number of assumptions had to be made in performing the analysis. There is uncertainty about the number and types of radiological procedures, the derivation from these data of doses to individual organs, and the applicability of the cancer induction model at the low doses used in diagnostic radiology. Nevertheless, it is probable that medical radiation procedures do lead to a small increase in cancer incidence in the population. The lowest dose of x-radiation for which there is epidemiological evidence of increased cancer risk is 10–50 mSv for an acute whole-body exposure.2 Some of the higher-dose diagnostic radiological procedures such as computed tomography (CT) produce effective doses at the lower end of this range.3 At lower radiation dose levels, in the absence of epidemiological evidence, there is some uncertainty as to whether there is any effect. However, a linear relationship between risk and dose with no threshold is commonly accepted and is supported by some laboratory data.2 Radiation protection agencies have adopted this linear-no-threshold hypothesis in their approach to risk management.4 The total population dose of radiation from medical diagnostic procedures is increasing worldwide, mainly due to the increase in CT scanning. CT entails the use of higher radiation doses than other common radiological procedures.3 In Australia, Medicare data indicate that CT use has increased 140% over the decade 1992–2002. The reason for the increased use of CT is that it is now able to provide much better and more valuable clinical information, and to do so more easily, than in the past. As the technology has improved, the image quality has improved and scanning times have been reduced to just a few seconds. CT can now image fine detail, even in mobile organs, and hence the indications for its use have expanded. It is easy to overlook the possible side effects of radiation, particularly if the risk is very low and the effect may not become apparent for years. Cancer may not develop until 20 to 30 years after radiation exposure, and so the group most at risk are people with a long life expectancy. Children are also more susceptible to the carcinogenic effects of radiation than adults. When people are exposed to radiation, its use must be justified by ensuring that it does more good than harm. If radiological investigations are done for a specific clinical problem, the potential benefit significantly outweighs the very small risk. However, if there is no valid clinical reason for a procedure, the risk is still present for no tangible benefit. One area in which risk is considered to outweigh benefit is whole-body CT screening of healthy asymptomatic people. The Royal Australian and New Zealand College of Radiologists has produced imaging guidelines on the appropriate use of diagnostic radiological procedures.5 The Australian Radiation Protection and Nuclear Safety Agency is in the process of drafting guidelines on radiation safety in medicine.6 Modern radiological equipment has the potential to reduce the radiation dose compared with older equipment. Radiologists also need to optimise their procedures to obtain the required diagnostic information using the lowest radiation dose.7 The Lancet article serves as a reminder that the potential dangers of radiation need to be respected.

Graeme J Dickie FRANZCR, FRACP, MBA · Robert S Fitchew MSc, MACPSEM, MAIP

Even with new diagnostic modalities, autopsy remains an important tool for quality and safety assurance. A systematic review of reports from 1996 to 2002 found autopsies detected, on average, 23.5% of clinically missed diagnoses involving the principal or underlying cause of death, and 9% of errors that would or could have affected the patient’s outcome. We surveyed pathology laboratories and hospital administrators across Australia, and found a decline in the hospital autopsy rate from 21% (210/1000 deaths) in 1992–93 to 12% (118/1000 deaths) in 2002–03. This decrease is in adult autopsies (66% of all autopsies in 1992–93; 39% in 2002–03). Perinatal autopsies increased from 29% to 58% of all autopsies in this period, mainly due to more examinations of fetuses less than 20 weeks’ gestation. Factors contributing to this decline may include community attitudes, clinicians’ reluctance to request autopsy (partly because of administrative burdens in making the request), hospital concern about legal action if a misdiagnosis is detected, and funding priorities. Reversing this decline will require cooperative action at several levels of the healthcare system, and from government bodies.

The Royal College of Pathologists of Australasia Autopsy Working Party

Radiotherapy should be an integral part of a comprehensive national cancer control plan In June 2002, the Radiation Oncology Inquiry (ROI), chaired by Peter Baume, delivered its report, A vision for radiotherapy.1 The inquiry was, some might say, a cynical attempt by the then Federal Minister for Health and Ageing to defuse the furore created by a series of questions-without-notice by the Federal Opposition. The questions arose from the 2001 National radiation oncology strategic plan of the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists (RANZCR).2 However, the strategic plan disclosed nothing that should have taken the Government by surprise. Over the past two decades, nearly 50 reports have delivered the same messages: that radiotherapy is a vital part of cancer treatment, that radiotherapy services have been chronically under-resourced, that this deficiency has been deteriorating rapidly, and that correction of the lack of resources and manpower is long overdue. In this article we review the progress over the past year, since the release of the ROI report. What, then, are the problems? There is strong evidence that about 50% of all patients with cancer should receive radiotherapy at some stage during their illness.3 Using that benchmark, a survey for the abovementioned strategic plan estimated that each year in Australia about 10 000 patients who might have benefited from radiotherapy did not receive it. The survey also revealed a catalogue of insufficient and antiquated treatment facilities and an inadequate supply of radiation oncologists, radiation therapists and medical physicists — the three professions that are central to radiation oncology. For example, in New South Wales alone, a third of the linear accelerators in public radiotherapy departments were closed because of a lack of radiation therapists, and the effects of closure were reflected in long waiting times for radiotherapy. In a report on 25 000 patients treated between 1999 and 2001,4 the Australian Council on Healthcare Standards found that, over that period, the proportion of patients who waited more than 21 days for treatment had doubled. A recent survey by the RANZCR Faculty of Radiation Oncology confirms that long waiting times persist.5 Delay in receiving radiotherapy results in higher cancer recurrence rates and lower survival rates.6,7 Underlying the problems in service delivery, the ROI noted, Radiation therapy has suffered most seriously from the fragmentation of responsibilities between different organisations and governments. In itself, this is not unusual in the health care industry, but its effect has also been serious, as this fragmentation of responsibilities is to blame for the lack of action in the past 20 years — even though all parties are in general agreement about what problems need to be addressed. (p 14) The ROI made 96 recommendations, of which the five key action items are summarised in Box 1. In response, the Australian Health Ministers’ Advisory Council established a Radiation Oncology Jurisdictional Implementation Group (ROJIG), with representatives of each state and territory government, in an attempt to get all jurisdictions together at the same table. Paradoxically, the professions are not directly represented in ROJIG. The group has met several times during 2003 and established subcommittees to address issues of patient access, workforce, funding and quality. Although these subcommittees have some professional representatives, committee members have to sign stringent confidentiality agreements, resulting in the perception that the professions are not adequately consulted. ROJIG reported to the Health Ministers in November 2003,8 and has already endorsed, accepted and completed 35 of the 96 ROI recommendations. A further 50 recommendations were endorsed. Due in large part to the representations of consumer groups as well as the professions, the need to improve radiotherapy services has become a political priority. At the time of the 2001 federal election, the Australian Government committed $72.7 million to improve regional access to radiotherapy, including the funding of new facilities.9 In 2002, the Victorian Government pledged $78 million to build a new radiotherapy department at the Latrobe Regional Hospital in Gippsland, expand facilities at Geelong and Moorabbin hospitals, and replace old linear accelerators at existing metropolitan facilities. The Australian Government is also contributing $12 million to these projects.10 In 2003, the New South Wales Government budgeted $85.2 million to build new facilities, replace old equipment and improve training in radiation therapy and physics.11 Projects under way to improve radiotherapy services in various states are summarised in Box 2. Because of the long lead times involved, no new facilities have been brought into service since the ROI report was released. Long waiting times persist and are worsening in many centres. In the private sector, which treats more than a third of all patients, patient out-of-pocket costs are escalating, because outdated Medicare Benefits Schedule rebates fall far short of the cost of delivering quality radiotherapy. Although increased government investment in capital equipment is now taking place in the public sector, operational funding constraints continue to limit the ability of departments to meet service requirements. To us the solutions are clear. Workforce planning is required both in the short and long term. The recent initiatives, while laudable, were a stopgap response rather than a step towards building a rational framework for expanding the workforce. Working the staff harder and longer is not cost-effective12 and leads to higher staff resignation rates.13 Radiotherapy needs a sustainable funding model that supports the real cost of quality radiotherapy and a strong, profession-led quality improvement program to ensure that quality is achieved. The outstanding problem for radiotherapy and, indeed, all cancer services in Australia is that there is no nationally coordinated cancer care policy. Australia needs to develop and implement a comprehensive cancer control plan that incorporates radiotherapy in the overall context of cancer management. Fortunately, there are signs that things may be changing. The Australian Government has embarked on developing a National Service Improvement Framework for cancer, driven by the National Cancer Control Initiative’s report, Optimising cancer care in Australia.14 Victoria has just completed a framework for cancer services,15 and New South Wales has published a framework16 and established a Cancer Institute with the task of developing a cancer control plan by June 2004. Western Australia and Queensland have also started to develop cancer plans. Cancer is a complex disease that requires a diverse range of specialist and generalist treatment services. There is no single government agency responsible or accountable for the outcomes of cancer management in Australia. Without an accountable nation-wide approach, the ROI report will become just another in the series of mirages that have promised, but not delivered, the access to quality care that Australians with cancer require and should expect. 1: Major recommendations of the Radiation Oncology Inquiry1 Establish an independent national body to oversee radiotherapy, reporting to the Ministers for Health, to address the fragmentation of healthcare delivery. The national body would be responsible for quality and productivity issues, such as facility accreditation, clinical protocols, benchmarking and coordinating data collection. Improve the availability of radiotherapy in rural and regional Australia. Ensure adequate workforce, especially in radiation therapy and medical physics. Ensure appropriate quality of services by accrediting facilities and having mandatory continuing professional development. Resolve the disputes over who should be paying for radiotherapy, and tensions between public and private providers, by pooling state, territory and Commonwealth funding. 2: Projects under way, in various government jurisdictions, to improve radiotherapy services in Australia Federal Increasing the number of undergraduate radiation therapy students by 50% Helping establish a national uniform training program in medical physics Introducing a postgraduate radiation therapy course at Monash University (VIC) Providing partial funding to replace outdated linear accelerators in all jurisdictions Funding a new radiotherapy centre in Toowoomba (QLD) Funding a skills mix and work analysis project New South Wales Employing more radiotherapy tutors Employing physics registrars for the first time in Australia Building new radiotherapy departments at hospitals in Port Macquarie and Coffs Harbour Victoria Building a new radiotherapy department at Latrobe Regional Hospital Providing a new linear accelerator at Moorabbin Hospital Replacing outdated linear accelerators at all public facilities Establishing a Ministerial Taskforce for Cancer South Australia Replacing three linear accelerators Western Australia Providing two new linear accelerators for hospitals in Perth Appointing a Chief Cancer Officer Northern Territory Conducting a feasibility study of local radiotherapy services

Michael B Barton MB BS, FRANZCR · Lester J Peters AM, MD, FRANZCR · Lizbeth M Kenny MB BS, FRANZCR

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

Eva Raik

Big clinical breakthroughs begin with basic science The 2003 Nobel Prize in Medicine or Physiology was awarded to a chemist, Paul Lauterbur (US), and a physicist, Peter Mansfield (UK), for their discoveries concerning magnetic resonance imaging,1 while the Nobel Prize in Chemistry was awarded to two medical graduates: Peter Agre (US) for the discovery of water channels and Roderick MacKinnon (US) for structural and mechanistic studies of ion channels.1 The prizes were awarded for seminal discoveries that have had major impacts on medicine and biology. The fascinating story of these discoveries illustrates the value of pursuing basic science research and how breakthroughs at a fundamental level can lead to revolutionary advances in medical care. The Nobel Prize in MedicineBackground to magnetic resonance imagingMany atomic nuclei possess the property of spin. When placed in a magnetic field they wobble (precess) on their axis, like a spinning top near the end of its twirl. The precession frequency is directly proportional to the strength of the magnetic field in which the nuclei are immersed, and lies in the frequency range of radio waves. When radio waves at the same frequency as the nuclear precession are applied to a sample, resonance energy transfer takes place and the nuclei become “excited”. Hence, radio waves can be used to detect (observe) atomic nuclei based on their characteristic absorption frequency. This discovery by the groups of Bloch and Purcell in the US led to their award of the Nobel Prize in Physics in 1952. Nuclear magnetic resonance (NMR) is extraordinarily useful in biology and medicine for two reasons. Firstly, because the nuclear spins are observed with radio waves, biological samples can be studied in a non-invasive and non-destructive way. Radio wave photons have about 1/1011 of the energy of x-ray photons, so they produce no radiation damage to biological samples. Secondly, the absorption frequency is precisely determined by the local magnetic field of the nucleus in an atom in a molecule. Since it is possible to measure changes in this field to better than 0.01 parts per million, chemical compounds are able to be identified even in complex mixtures. The incredible precision with which one can determine the frequency of nuclear resonance, and hence the local magnetic field experienced by a nucleus, means that we can (for example) distinguish a hydrogen atom in a methyl group of an alanine side chain in a protein from one in a methyl group of valine in the same protein. The Nobel Prize for Chemistry was awarded to Richard Ernst (1991) and Kurt Wüthrich (2002) for the development of techniques to use NMR to determine protein structure. Remarkably, this is possible within living cells; so metabolism can be followed in real time in a totally non-invasive way. Both of these features make NMR ideal for medical imaging. The discovery of magnetic resonance imagingIn the early 1970s, Paul Lauterbur (at the State University of New York at Stony Brook, US) surmised that if one could vary the magnetic field across a sample in a defined way then it should be possible, by measuring the frequency at which a given ensemble of nuclei were precessing, to determine the exact location of the ensemble in the sample. Lauterbur’s first images were of a “phantom sample” of two tubes of water located within a larger tube of heavy water (ie, water in which the hydrogen atoms are replaced with deuterium atoms).2 Heavy water is chemically almost identical to water and to the eye is indistinguishable. But deuterium nuclei are very different from hydrogen nuclei, so they give no signal when radio waves at the frequency absorbed by hydrogen are applied. By applying a graded magnetic field across the entire sample, Lauterbur reconstructed an accurate cross-sectional image of the two water-filled tubes (Box 1a). At the time this seemed a rather esoteric experiment, but it was a wonderful model to use for the human body, which is essentially a series of water-filled tubes (eg, arteries) and containers (eg, organs) located within a larger water-filled tube (ie, the body walls). Lauterbur’s water-filled tubes were geometrically simple, making it relatively easy to solve the mathematics required to reconstruct the images from the radiofrequency output. Although Peter Mansfield (at the University of Nottingham, UK) was working on a different physical system, it was he who was responsible for sorting out the complicated mathematics required to derive images rapidly from NMR spectrometers, thereby making magnetic resonance imaging a feasible clinical application. He also developed the technique of very fast gradient variations (so called echo-planar scanning) that enabled very rapid imaging.3 The journey from the first images of tubes of water to the installation of the first magnetic resonance imaging (MRI) scanner in a hospital required a huge amount of research and development both in the private and public sector, but it only took about 10 years. This involved mathematicians, physicists, engineers, computer scientists, biomedical scientists and medical practitioners in one of the best modern examples of “translational research”. It is estimated that in 2002 about 60 million MRI examinations were performed throughout the world. MRI has had a major impact on many aspects of clinical practice; probably most notably in neurology (Box 1b). The Nobel Prize in ChemistryBackground to water and ion transport in the bodyAll cells, from bacteria to plants and animals, are surrounded by a lipid membrane that forms a barrier between the inside of the cell (where most of the important events such as gene transcription and metabolism take place) and the extracellular environment. The maintenance of a stable intracellular environment is crucial for cell survival. The first barrier of defence is the lipid membrane, which is largely impermeable to water and water soluble substances, such as ions. Equally important, though, is the ability of cells to interact with the outside world; to respond to stresses imposed from the outside and to communicate with other cells. This is achieved by having proteins embedded in the lipid membrane that can selectively allow the passage of water or ions into or out of the cell. Discovery of aquaporinsWe now know that channels that permit the selective flow of water across cell membranes (aquaporins) are present in almost all cells, but they were only definitively identified 15 years ago. Why did it take so long for them to be discovered? In a sense it was because they are so difficult to measure and because they are so common. Often the easiest way to identify something is to compare two similar objects (in this case, cells) and then determine what it is that is different between them. This of course was not possible for water channels, as almost all cells have them. In the late 1980s, Peter Agre, while working on the rhesus blood group antigens at Johns Hopkins University, US, serendipitously discovered a new membrane protein that he called CHIP28 (channel integral membrane protein of molecular weight 28k). At the time he had no idea what it did.4 Previously and independently, Gheorghe Benga and his group in Romania5 had shown that the water transport inhibitor p-chloromercuribenzoate is selectively bound to a protein in red blood cell membranes. Subsequent studies showed that this was a glycosylated form of CHIP28. After extensive analysis of the CHIP28 protein Agre’s group recognised that it must form a channel in the red blood cell membrane. The crucial experiment they performed was to over-express the new protein in another cell type (the Xenopus oocyte); they found that the cells became much more permeable to water.6 Since then, Agre and colleagues have shown that there is a whole family of genetically related aquaporins in almost every cell type,7 with some also permeable to glycerol and urea. In addition to all fluid transporting epithelia, one obvious place where water channels serve a crucial function is in the kidney, where they permit the reabsorption of hundreds of litres of water that pass through the renal glomeruli each day.7 Discovering the channels was one thing, but how do they work? How can these channels allow the passage of water at a very high rate but not allow the passage of hydrated protons (ie, hydronium ions, H3O+)? This question was answered by Agre in collaboration with Fujiyoshi’s group in Kyoto and Engel’s group in Basel when they solved the structure of aquaporin-1 using electron microscopy (Box 2, a,b).8 Structural basis of ion selectivity in potassium channelsIn contrast to water channels, those that selectively allow the transmembrane flux of ions, such as sodium, potassium or calcium, were first implied in a functional assay and theoretical simulation over 60 years ago, and genes encoding for ion channels were first cloned over 20 years ago.9 We now know that there are hundreds of different ion channels in human cells. Despite extensive analysis of ion channel function, one of the most intriguing conundrums has been how these proteins allow the selective passage of one type of ion at very high rates, while preventing the passage of all others. In the mid 1990s, after electrophysiological measurements combined with molecular biological manipulations of ion channel proteins initially made in Christopher Miller’s laboratory and later in his own laboratory at Harvard University, Roderick MacKinnon realised that the only way to answer this question was to determine the structure of an ion channel using x-ray crystallography. Determining the structure of membrane proteins is extraordinarily difficult, and many people suspected it would not be possible for an ion channel. However, in 1998, MacKinnon and his team (having moved to Rockefeller University) succeeded in crystallising the bacterial potassium channel, KcsA;10 and, just as they had hoped, the structure provided the answer to the riddle of how potassium channels permit the selective passage of potassium ions at a high rate (Box 2, c,d). Furthermore, the combination of x-ray crystallography, electrical measurements and mathematical simulations enabled them to make fundamental predictions about how the channels select ions and open and close to regulate their passage.11 The selectivity of ion channels and the exquisite control of their opening and closing is central to the role they play, for example, in neurotransmission and controlling the heart beat. Indeed, recently it has been shown that even subtle mutations in the genes that encode ion-channel proteins are a potent cause of diseases including epilepsy and cardiac arrhythmias.12 The meaning of the PrizeThe stories behind the discoveries that lead to the award of a Nobel Prize are always fascinating, while the act of singling out individuals among many who have contributed to a field of research is frequently controversial. However, this should not distract from the real message behind the Nobel Prizes in Medicine or Physiology and Chemistry, which is that pursuing basic science research has enormous practical value. Discoveries made regarding the fundamental properties of molecules, whether by physicists, chemists or biologists, can and do lead to major advances in medical care. Particularly at a time when researchers in Australia are under pressure to pursue applied research at the expense of basic science, this year’s Nobel Prizes provide a potent reminder of the importance of fundamental research. 1: Magnetic resonance imaging a) Lauterbur’s first published image of a section of a water phantom. Left: model of the phantom. Right: the reconstructed magnetic resonance image (reproduced from reference 2). b) Modern magnetic resonance sagittal section of a human head. 2: Ion channels a) Ribbon diagram showing structure of aquaporin-1 (water channel). b) Model illustrating mechanisms of water permeation in a water channel. The positive charge on the wall of the channel repels hydronium ions, thereby excluding them from crossing the transmembrane region (from reference 8, reproduced with permission of Nature Publishing Group). c) Structure of the KcsA potassium channel. The channel is a tetramer, but only two subunits are shown, illustrating the cavity and the narrow selectivity filter region formed by the pore helices, labelled ‘P’ (from reference 11, reproduced with permission of Nature Publishing Group). d) Model illustrating K+ permeation. The orientation of the pore helices is such as to produce an electronegative well in the cavity, which attracts K+ ions. The narrow selectivity filter region is just the right diameter to accommodate dehydrated K+ ions. K+ permeation occurs in single file. As one K+ ion enters the selectivity filter it repels the K+ ion ahead of it (from reference 10, reproduced with permission of the American Academy for the Advancement of Science).

Jamie I Vandenberg MB BS, PhD · Philip W Kuchel MB BS, PhD

Computed tomography (CT) scan of the abdomen and pelvis was performed for staging of prostatic carcinoma in a 50-year-old man. The “X” is formed by the two ureteric jets in the bladder in this intravenous contrast-enhanced CT of the pelvis.

David C Wong FRANZCR

It’s not Harry Potter or 007. It’s the Wicked Witch of the West coming to town at this time of the year. She was first detected by this 3D CT reconstructed image!

Bit Lock Wong

Frequently, I call on colleagues for help with a radiological diagnosis. This time I received assistance from a higher authority! The image is a non-contrast axial computed tomography scan of the brain, showing haemorrhage into the central pons.

Chris J O’Donnell FRANZCR

We received an appendix in our anatomical pathology laboratory and were struck by the resemblance of the luminal contents to our wide brown land.

Alison M Skene FRCPA · Alastair J Veitch FRCPA · Piero L Nelva BappSci

Confident localisation of ectopic parathyroid adenomas, particularly those outside the neck, can be difficult. Even preoperative radiological imaging may not be helpful, as there are few characteristic findings. We report a case in which hyperfunctioning ectopic parathyroid tissue in the mediastinum was detected with technetium-99m-sestamibi single-photon emission computed tomography and accurately localised non-invasively with image-fused computed tomography. This technique directly modified management. Ectopic parathyroid adenomas are uncommon, but can complicate the surgical treatment of primary hyperparathyroidism. In particular, those outside the neck, and thus not found on neck exploration, produce a substantial diagnostic challenge. Clinical recordA 60-year-old woman was found incidentally by a life insurance blood screening test to be hypercalcaemic. She did not complain of specific symptoms referable to hypercalcaemia, but bone mineral density assessment 2 months previously had shown osteopenia. Her past medical history was unremarkable. She was taking no medications and gave no family history of parathyroid disease. Clinical examination showed no abnormality. The results of investigations (Box 1) showed raised plasma corrected calcium, intact parathyroid hormone and ionised calcium levels, but levels of creatinine and serum phosphate were normal. Alkaline phosphatase and osteocalcin levels were mildly elevated. Urinary N-telopeptide level was within the reference range, and the fasting urine calcium : creatinine ratio was slightly elevated. A dual-phase, dual-tracer technetium (Tc)-99m-pertechnetate/Tc-99m-sestamibi nuclear medicine study revealed a solitary focus of abnormal tracer uptake in the anterior mediastinum on both initial and delayed sestamibi images and on subtracted images (Box 2, Figure A). Retained activity in the left subclavian vein was noted incidentally. No abnormality was seen within the thyroid bed. It was suspected that the activity indicated ectopic parathyroid tissue, although it may have represented retained activity within a large vessel. Single-photon-emission computed tomography (SPECT) imaging confirmed the finding in the right mediastinum (Box 2, Figure B). Thoracic computed tomography (CT) showed a 9 mm soft-tissue mass, lying anterior to the aorta at the level of the carina (Box 2, Figure C). Its appearance was non-specific, but incidental lymphoid tissue was considered most likely. Utilising a software co-registration package (Philips/ADAC Laboratories, Milpitas, Calif, USA), the sestamibi SPECT images were fused onto the CT images. The resulting views showed abnormal mediastinal sestamibi activity localised to the soft-tissue mass, suggesting the presence of ectopic parathyroid tissue (Box 3). Thoracoscopic excision of the mediastinal mass was performed. No discrete abnormality matching the usual macroscopic appearance of a parathyroid adenoma was seen. A small fat pad, lying anterior to the ascending aorta, below the brachiocephalic vein and superior to the pericardium, was found and excised. Digital palpation of this tissue revealed an area of focal hardening. Histology of the operative specimen confirmed the presence of parathyroid tissue, weighing 100 mg, within the fat pad. Differentiation between adenoma and parathyroid hyperplasia was not possible. Incidental thymic and lymphoid tissue was also seen in the pathology specimen. After the operation, plasma corrected calcium and intact parathyroid hormone levels normalised almost immediately and the patient recovered uneventfully. DiscussionWe have described successful preoperative localisation of an ectopic adenoma using image-fusion software, which directed the successful excision of the tissue. In this patient, either a conventional bilateral neck exploration, or a single image study without image co-registration before minimally invasive surgery, would have been less likely to result in successful or certain management. The conventional approach for parathyroid disease is bilateral neck exploration under general anaesthesia to expose and identify all parathyroid tissue, without preoperative imaging.1 Obviously enlarged parathyroid glands are resected. If intact parathyroid hormone levels do not fall intraoperatively, a partial parathyroidectomy, including thymectomy, may be considered. In our patient, however, it was felt that even thymectomy may not have been curative, as the position of the ectopic parathyroid adenoma made it inaccessible by a conventional approach. The minimally invasive approach used in selected patients involves directed and limited neck exploration under local anaesthesia, and is usually preceded by preoperative localisation of the parathyroid adenoma with sestamibi scintigraphy. An intraoperative γ probe can also be used to help identify or confirm the adenoma (minimally invasive radioguided surgery).2,3 The role of preoperative parathyroid localisation using imaging techniques in patients who have not had previous neck exploration is currently debated.2-5 While local cost-effectiveness data are still pending, additional advantages of preoperative imaging are being found,4,5 including the detection of unsuspected ectopic parathyroid adenomas, which may otherwise be missed on routine surgical neck exploration. Some advantages of this approach include avoidance of general anaesthesia, improved cosmetic result, and a shorter operating and recovery time. Multiple diagnostic modalities exist for imaging the parathyroid glands. These include radionuclide scintigraphy, ultrasonography, CT and magnetic resonance imaging (MRI). Dual-phase, dual-tracer Tc-99m-pertechnetate/Tc-99m-sestamibi SPECT scintigraphy has increased the sensitivity of detection of parathyroid adenomas (up to 90%).6-9 The increased tracer uptake by hyperfunctioning parathyroid tissue is explained by the abundance of mitochondria within these abnormal cells, for which sestamibi demonstrates high avidity.10 Occasionally, as in our patient, the sestamibi scan may indicate ectopic parathyroid tissue. Developmentally, the parathyroid glands are derived from the pharyngeal pouches. The two inferior glands arise from the third brachial cleft, descending with the thymus during embryogenesis, which would account for the presence of ectopic tissue within the mediastinum.11 In ectopic disease, imaging experience is limited. Ishibashi et al,12 in a blinded, comparative study, suggested superior sensitivity of scintigraphy compared with CT or magnetic resonance imaging (MRI) in detecting such adenomas, with the sensitivity and specificity of sestamibi imaging calculated to be 70% (14/20) and 88%, respectively. The sensitivity and specificity of CT were 40% (8/20) and 88%, and of MRI, 60% (12/20) and 88%.12 Our finding on initial sestamibi scanning could have represented retained activity within a large vessel, and, as false-positive results may occur with all imaging, many investigators have advocated the need for concordance on at least two diagnostic modalities before surgical excision.4,13 On further investigation, the mediastinal abnormality seen on CT was so small that its clinical significance could not be confidently assessed. Traditionally, such a problem is unlikely to be resolved non-invasively. In our patient, the use of new image-fusion software allowed the accurate integration of both functional and anatomical data on the one image set. This image fusion clearly confirmed abnormal sestamibi activity arising from the mediastinal mass seen on CT, implying the presence of ectopic parathyroid tissue. A similar case of ectopic adenoma detection using this technique has been described previously.14 However, in that report, the CT findings of a 2.0 × 1.0 cm mediastinal mass were clearly abnormal and strongly suggestive of an adenoma.14 Our case is the first to highlight the incremental diagnostic value of image fusion, as the CT, and indeed intraoperative, findings in isolation were inconclusive. After confirming the presence of ectopic parathyroid tissue, a thoracoscopic approach to surgery was undertaken rather than a conventional approach. Advances in both nuclear scintigraphy and, more recently, image fusion have expanded our ability to accurately and confidently localise ectopic adenomas non-invasively. In our patient, the preoperative imaging techniques used significantly altered surgical management. 1: Clinical laboratory measurements Investigation Value (reference range) Plasma corrected calcium 2.9 mmol/L (2.15–2.55 mmol/L) Intact parathyroid hormone 27.8 pmol/L (0.8–8.0 pmol/L) Ionised calcium 1.46 mmol/L (1.14–1.29 mmol/L) Creatinine 75 mol/L (45–90 mol/L) Serum phosphate 0.8 mmol/L (0.8–1.5 mmol/L) Alkaline phosphatase 109 U/L (< 105 U/L) Osteocalcin 53.5 μg/L (< 46 μg/L for postmenopausal women) Urinary N-telopeptide (N-terminal telopeptide of collagen) 57 nmol BCE/mmol creatinine (5–65 nmol BCE/mmol creatinine) Fasting urine calcium : creatinine ratio 0.65 (0.10–0.58) BCE = bone collagen equivalence. 2: Preoperative imaging in a patient with raised levels of plasma corrected calcium, intact parathyroid hormone and ionised calcium A: Tc-99m-pertechnetate-sestamibi subtraction imaging, confirming an ectopic focus of tracer activity in the chest to the right of midline (red arrow). Retained activity in the left subclavian vein is incidentally noted on the 30-minute sestamibi scan and on the subtraction image (blue arrow). B: Transaxial, coronal and sagittal single-photon-emission computed tomography (SPECT) slices, indicating focus of increased sestamibi activity (red arrow) in the right anterior mediastinum. C: Oval lesion (9 mm) in anterior mediastinum to the right of midline, thought initially to be non-pathological lymphoid tissue (red arrow). 3: Localisation of an ectopic parathyroid adenoma Fusion of single-photon-emission computed tomography (SPECT) and computed tomography data, showing the site of ectopic parathyroid tissue (red arrow).

Patrick Ng MB BS · Nat P Lenzo BMedSc(Hons), MB BS, MMed, FRACP · Michael C McCarthy MB BS, FRACP · Ivan Thompson MB BS, FRACS · Peter J Leedman MB BS, FRACP, PhD

After the Bali bombing on 12 October 2002, once the survivors had been treated or evacuated, many dead, severely burned and fragmented bodies were left. Formal identification was required before any remains could be released to grieving families. Australia sent a team to assist the Indonesians in this daunting and disturbing task. The “disaster victim identification” process eventually confirmed 202 people as dead, including 88 Australians. Personal and professional relationships between the Indonesians and our team were important factors in our acceptance into the Indonesian emergency response. At 06:00, Sunday, 13 October, Professor John Hilton (Director of the Institute of Forensic Medicine, Sydney; Associate Professor of Pathology, University of Sydney; and Group Captain (ret.) in the RAAF Specialist Reserve) heard on the radio news that there had been an explosion in Bali, with an unknown number killed or injured, including Australians. John: Thought 1: Must have been an LPG storage tank in a hotel or restaurant or nightclub that blew. Thought 2: What’s the actual size of the problem? I had vivid memories of wild exaggerations of fatalities in East Timor in the aftermath of the independence referendum. Thought 3: Will the Indonesians need some help with the DVI [disaster victim identification], the forensic pathology and odontology? Thought 4: Ring the State DVI Commander [Detective Chief Inspector Mark Edwards] and ring Griffo [Chris Griffiths, Staff Specialist, Westmead Centre for Oral Health; Adjunct Associate Professor, University of Sydney; and Group Captain in the RAAF Specialist Reserve]. Paddy’s bar During the day, a picture of bombings, rather than a gas explosion, emerged. John Hilton and Chris Griffiths (Staff Specialist, Westmead Centre for Oral Health; Adjunct Associate Professor, University of Sydney; and Group Captain in the RAAF Specialist Reserve) worked with Superintendent Andy Telfer of the South Australian police, head of Australia’s delegation to Interpol, and, by proxy, with the Department of Foreign Affairs and Trade and the Australian Federal Police (AFP), to formulate a response plan and compile and assemble an equipment list. The AFP was appointed the lead agency in the DVI response. However, DVI is a new area for the AFP; the expertise lies with the states. On Monday, 14 October, John Hilton and Chris Griffiths flew to Bali, arriving late in the evening. Meeting the IndonesiansOn Tuesday, 15 October, we were up at 05:00 for a breakfast meeting with the AFP in Denpasar. At 08:00, we headed to the site of the bombing, but were denied access because the previous day the AFP had advised the Indonesian police to seal the crime scene and not let anyone in. We went on to Sanglah Hospital, a pleasant pavilion-style tropical hospital coping valiantly with the victims of the bombs, and met Police Brigadier General Eddy Saparwoko, the Indonesian DVI Commander, and Lieutenant Colonel Peter Sahelangi, an Indonesian police odontologist. We made it clear we were there to offer help and were entirely at their disposal. Saparwoko asked us to assist in managing the identification process according to agreed international standards. Chris: I’d been the Australian delegate to Interpol's DVI Standing Committee for the last eight years and also their Scientific Vice Chairman. Through this, I had a long association with the Indonesian police. In Makassar (in south Sulawesi) in 2002, in conjunction with the Indonesian police, this Standing Committee had organised a South East Asian Meeting that was attended by South East Asian police colleagues and the majority of the regional police chiefs of Indonesia. It was basically because of these associations that Brigadier General Saparwoko asked us both to help him supervise and oversee the identification process. We also met with the volunteers who, under self-selected leadership, had laboured mightily to start the identification and relative support process. Unfortunately, as they had no previous experience or skills in this area, many of their efforts were inappropriate. We dissuaded them from unproductive efforts and encouraged them to follow agreed standard tracks. The disaster victim identification processThe process of DVI comprises three steps: collecting ante- mortem (AM) identifying data, collecting postmortem (PM) data, and reconciling the AM and PM records to make positive identifications. Collecting antemortem dataIn Australia, AM data collection is under the control of police missing persons units. Researchers gather as much information as possible about people believed to be victims. Information gathered includes dental records, history of broken bones or surgery, tattoos and scars — anything that might assist in making a positive identification. Destroyed vehicles Russell Lain (Staff Dentist at the United Dental Hospital of Sydney; Visiting Staff at the Department of Forensic Medicine; and Lieutenant, Royal Australian Naval Reserve) and William Saunderson (Staff Specialist at the United Dental Hospital), both with many years experience in DVI, worked with missing persons police in Parramatta, gathering AM records for dispatch to Canberra and thence to Denpasar. Colleagues in other states similarly divided their duties between retrieval and analysis of the AM data and fieldwork in Indonesia. Russell: The biggest impact for me was having to deal directly with bereaved relatives. We had to quiz them about possible sources of medical and dental records, charts, x-rays and the like. Some of these people had just come back from Bali. They had been trying to ID their kids from Polaroids of the bodies. They were still shellshocked. And we’re on the phone asking them for details about dentists they might have gone to. Nothing can really train you for this, but we just had to get on with it. The families seemed to take some comfort from seeing that professionals were engaged in a proper ID process. The whole week in the Police Centre doing the AM stuff really brought home to me just how vital that side of things is. Within 10 days of the bombing, all the available AM records for NSW had been gathered. Russell Lain then flew to Bali. Collecting postmortem dataGathering PM data involves careful examination of each body, recording details of personal property, scars, tattoos, distinctive anatomical features, and dental features. The slowest part of the process is gathering the dental data, and an important lesson for future mass disasters is that, to avoid delays, more trained forensic dentists than pathologists are needed. Two features that stood out during the PM phase were the scale of the disaster, and the state of the morgue (Box, "Impressions of the morgue at Sanglah Hospital"). Bodybags packed in ice ReconciliationOnce the AM and PM data have been gathered, the records are compared to identify victims. The proposed identifications are reviewed by a Reconciliation Board. The process has an inbuilt scepticism that obliges the presenter to illustrate the concordances between AM and PM records. The greatest difficulties arise in cases of poor AM records or incomplete recovery of remains. For the Bali bombing, the Reconciliation Board consisted of Indonesia’s DVI commander (Brigadier General Saparwoko), a forensic odontologist (Professor Chris Griffiths), and an Indonesian forensic pathologist. When all members of the board were satisfied that an identification was correct, a death certificate was issued and the body released to the family. Chris: I sat on the Reconciliation Board for 21 consecutive days, overseeing the dental evidence. After three weeks of playing devil’s advocate, I was physically and mentally drained. More than 60 per cent of victims of all nationalities were identified using dental evidence within three weeks of the incident. Most of the later identifications were based on DNA evidence. This formal standard identification process is extremely important. Of the 18 victims who had been “identified” visually by families, nine were shown to have been identified incorrectly. If bodies had been released on the basis of these family identifications, we might have had nine families, or even more, whose child or parent was never identified and never able to be returned. Politics and public relationsA mass disaster naturally attracts political and frenzied media interest. A particular concern in the Bali bombing involved early release of the bodies. We needed to explain the importance of the formal DVI process to the families, the media, and the politicians. Coffins From comments he made in a radio interview, it was obvious that Australia’s Prime Minister, John Howard, was being pressured to have the Indonesian authorities release bodies on the basis of visual identification only. Chris Griffiths phoned the Prime Minister and explained the problems of visual identification and expressed to him our confidence in the Indonesian authorities. Chris also explained that, from our initial assessment, DNA techniques would be needed to identify some of the bodies, and the Indonesian government could not pay the costs of DNA matching. The Prime Minister immediately agreed that the Australian government would cover the costs of DNA matching, irrespective of the victims’ nationality. More difficult was explaining the process to the relatives of the victims. We try to involve ourselves only with the postmortem area of identification. Dealing with the families makes working in the mortuary too personal, as we pick up the grief of the families. Chris: In this case, as I walked in the door to address the relatives, Graham Ashton [Australian Federal Police Commander] said, “There is someone in the group that knows you.” Then I saw an old friend from university. I know his children well. He said simply, “James is one of those killed.” I found it very difficult to talk to the relatives after this, but I had to explain to them that releasing bodies that had been tentatively identified by families could jeopardise the identification process for everyone. From my international experience, at least one in three visual identifications turns out to be incorrect. On Thursday, 17 October, Prime Minister Howard, Deputy Prime Minister John Anderson and Opposition Leader Simon Crean, and their advisers, flew into Bali for a memorial service. We showed them the photographs that had been taken by the volunteers helping the families carry out their visual identifications. Later that evening, we attended a briefing with the Prime Minister’s party, where problems were raised and decisions were instantly made. No months of committee paralysis — just “It sounds like a good idea. Do it!” One issue raised at that meeting was the need to involve the state coroners. The state Coroners Acts require that a local state coroner make findings as to identity and cause of death of any body connected with the state when the death is caused by violence. If Australian bodies were released without a coroner’s approval, it might lead to difficulties with probate or insurance. By coincidence, the annual coroners’ conference was being held in Sydney, so John Hilton left Bali that night to address the conference. The coroners decided to send two representatives to Bali the next day. International team relationsOther countries also sent DVI teams to Bali, and there was some difficulty aligning their efforts with the agreed Indonesian–Australian process. One of the problems was that teams from some countries wanted to work independently of the Indonesian–Australian team and only examine non-Caucasian victims. We had to point out that non-Caucasian people were not necessarily nationals from South East Asian countries. The victim lists showed many victims were ethnically of Chinese origin but citizens of Canada, the United Kingdom, the United States or Australia. We also showed them the severe burning of many of the victims, which made it impossible to determine racial groupings. Eventually the various teams agreed to integrate with the international team and to examine each body in order. Time outFatigue is a major issue in this type of work. Team members will always tend to push themselves to the point where they can no longer function efficiently. This is when mistakes are made. It is up to wiser heads to enforce full meal breaks and rest days, even if the team wants to continue working. Occupational health and safety concerns are real, and need genuine commitment by managers. In DVI we talk about the different groups of victims. The first group is the dead and injured; the second group is the families, especially those of the dead. There is a third group of potential victims — the rescuers and DVI workers. Russell: I remember we had just had a visit from the cast of the Indonesian version of Neighbours. They came through the morgue like royalty, checking the scene and shaking hands. I walked away from that and was in the reconciliation room, working with a colleague to match up AM and PM records for ID. We did about five with no joy. Then we realised we were trying to match AM records with other AM records! We had the next day off. On the morning of our day off, the security adviser warned us that we were being targeted. We were not to go out alone; we were not to answer questions from locals about what we were doing or how long we would be there; we had to sign in and sign out; we had to carry an encrypted radio, water, money and passports if we were going any distance; we had to be back by dark, keep alert and “have a good day”. Apart from an uneasy feeling when any van like the one used in the bombing pulled alongside our minibus, we did have a good day. Terraced rice paddies, charming villages, nearly deserted streets decked out with colourful misspelled signs expressing sympathy for the victims of the atrocity; those classic Asian city smells of garlic, sewage, coriander and diesel, and everywhere those delightful smiles, even in the face of a devastated economy. It was a good day. During the weeks in Bali, we stayed at a luxurious hotel, which seemed a bit incongruous in the face of the suffering just outside the gate and the serious job we were doing. However, it is important for the team to have a safe haven to relax in, maybe discuss issues that had come up during the work day, and allow the battered psyche to recharge. Russell: The hotel had a pool the size of the Mediterranean. There’s a few photos — which I hope never surface — of this pale-skinned crew around the island bar with huge drinks with pink parasols. “The gathering of the Beluga whales”, I called it. The AFP paid for two drinks a day. Happy Hour — that’s half price, four drinks — was between five and six every day. Most days we got back to the hotel between five and six! ConclusionWe all learned a lot from that Bali experience, such as the importance of the AM data collection, and a better understanding of DVI fieldwork. It also became clear to us that this was as much an attack on the Balinese as on the tourists. Family member of Indonesian victims praying at the bomb site The relationships cemented during the time in Bali represent the prime benefit of the process. The value of long term associations and friendships with colleagues in Indonesia was borne out during the Bali incident. For us to go to another nation and be accepted into their organisational structure in an emergency situation was vital for the early identification of the victims and their early return to their families. Hospitals, universities and many healthcare professionals in Australia tend to form their associations with European and North American organisations, because of history and the scientific knowledge base. However, if we are going to be good neighbours, we should try to develop stronger ties with our immediate neighbours, on both a personal and a professional level. We may feel that the information flow is somewhat one-sided. But this is what being a good neighbour is all about. We are reminded of Aesop’s fable of the mouse and the lion. Sometime in the future good deeds will be remembered. This is especially so in South East Asia. Impressions of the morgue at Sanglah Hospital Russell: I had been involved in the Thredbo landslip, the Glenbrook train crash and several light plane disasters. But when we walked past the cordon of soldiers and their M-16s at Sanglah Hospital and saw 200-plus body bags and a pile of body part bags laid out on a tiled walkway, the numbers hit home. I was nervous about the smell. I’ve been doing this work for 10 years but I just hate the smell. I knew it would be too hot to wear a proper charcoal face mask, so I was wondering if I’d be sick in front of the Indonesians. Anyway, it was amazing. The morgue just did not smell. Well, not too bad anyway. The volunteers kept up a constant bucket brigade of ice and packed it around the bodies. They were fabulous and always had great smiles. The problem was that the ice melted. When the volunteers lifted a body bag onto a trolley for a PM or x-rays, brown juice just poured out of the bags. They mopped it away, but five minutes later there would be another brown pool on the floor. One of the Japanese odontologists saw me staring at this on my first day in the morgue. “Human soup”, he beamed at me cheerfully. That was one of the worst bits. That and walking in among scores of body bags — they were packed pretty close — looking for a certain number bag for a re-examination, and trying very hard not to tread on the bodies.

Russell Lain BDS, DipForOdont · Chris Griffiths BDS, LDS, DPH · John M N Hilton RFD, MB ChB, FRCPA

Barbara M Miflin,* Kevin L Forbes† * Lecturer in Teaching and Learning Development, † Deputy Head, Years 3 and 4 MB BS Program, School of Medicine, University of Queensland, Herston Road, Herston, QLD 4006. barbara.miflinATuq.edu.au To the Editor: All established disciplines that have contributed to medical curricula in the past should play, as Weedon1 argued recently for pathology, a pivotal role in contemporary medical curricula. Indeed, students should be able to acquire better knowledge of a discipline through a problem-based learning (PBL) approach than through traditional teaching methods. The crux of the PBL approach is that knowledge, skills and the other professional attributes are learnt in a way that puts them into context and thus makes them meaningful and better remembered by medical students. The trouble is, as Weedon pointed out, the number of academics in the discipline of pathology is dwindling. The scarcity of academic pathologists, combined with the increased workloads of private pathologists, means that their input into designing and developing curricula and into pathology teaching may be increasingly inadequate. Pathology is not the only discipline to be underserved in today’s medical schools. In response to concerns about the medical curriculum, the Royal College of Pathologists of Australasia and other Colleges and interest groups have developed core syllabuses for use in medical programs. These developments are most welcome in view of the diminishing resources available for teaching in universities. In a PBL-oriented curriculum, teaching staff work in a multidisciplinary team in which the aspirations and limitations of each group are acknowledged, respected and acted upon in the context of realistic expectations of what is possible and what is necessary for medical graduates in the 21st century. Currently, in Queensland, a series of pathology modules for students to use during their clinical rotations would be well received. The use and interpretation of pathology tests are already built into PBL case studies, and could be extended into a module set as prerequisite learning for an attachment to a public or private pathology laboratory. Pathologists may also be able to use the syllabus to guide their teaching in mentorships for the elective components of medical programs. The needs of disciplines such as pathology will be best achieved through genuine understanding of the aims of medical schools to ensure appropriate, realistically achievable learning for students. When students are motivated to acquire knowledge of a discipline because they can see its relevance to solving patients’ problems, their enthusiasm for the discipline will be enhanced and they will learn well.

Barbara M Miflin · Kevin L Forbes

Donald D Beard Surgeon, 134 Beulah Road, Norwood, SA 5067. To the Editor: The issues raised in the editorial by Weedon1 are a sad reflection on current medical education. Weedon voiced the serious concern of the Royal College of Pathologists of Australasia regarding the downgrading and marginalising of the teaching of pathology because of the ascendancy of problem-based learning, to the detriment of the basic sciences pathology, physiology and anatomy. Weedon reminded us of Virchow’s pronouncement that applying the doctrines of pathology “helps to deepen biological knowledge, and to light up still further that region of the unknown which still envelops the intimate structure of living matter”. That statement also applies to anatomy and physiology. It could not have been said better. Some years ago, while I was on the Curriculum Committee of the University of Adelaide, the Committee agreed to recommend that the basic sciences continue to be taught throughout the medical course. Unfortunately, the recommendation was not accepted, and now the position is even worse. I find it very difficult to understand the priorities of the current medical curricula and who is making the recommendations. I feel the excitement of the study of medicine is disappearing, and hope it is not too late to reverse the current trend.

Donald D Beard

H Reginald Magee Vascular Surgeon (retired), “Alexandra”, 201 Wickham Terrace, Brisbane, QLD 4000. reginaldmATbigpond.com To the Editor: I was most interested in Weedon’s editorial on the teaching of pathology in the present medical curriculum.1 I have lamented the demise of anatomy teaching in undergraduate courses and regret that pathology is going the same way. In my view, anatomy, physiology and pathology are fundamental to understanding the disease process. They enable physical symptoms and signs to be interpreted in a logical manner so that a provisional diagnosis can be made. Once this has been done, it is reasonable to progress to ancillary aids to confirm or refute the original diagnosis. When doing operative surgery I used to ask my assistants questions, usually on anatomical features that were being exposed. Many, including some who possessed the primary surgical fellowship, could not identify simple structures such as the sartorius muscle when the popliteal artery was being exposed. Questions on structures in the neck were even less well answered. The present medical curriculum is directed towards problem-solving methods and the patient’s condition in relation to the environment and other conditions. But how much thought goes into the mechanism of disease and understanding physical findings? I consider medicine and surgery to be applied pathology, and therefore knowledge of the basic facts is essential. Future doctors may be proficient in the general and social aspects of medicine, but it would seem that their knowledge of the basic facts of anatomy, physiology and pathology and their understanding of the mechanism of disease may be no better than that of a “medicine man”.

H Reginald Magee

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

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

Objective: To audit the appropriateness of use of a troponin I assay in three hospitals.Design: Cross-sectional survey of use of a troponin assay.Setting: Three hospitals in Melbourne, Victoria, each with an emergency department and a coronary care unit.Participants: Patients for whom a troponin I assay was requested between 1 and 7 May 2002, 27–42 months after introduction of the assay.Interventions: User-focused dissemination of relevant information, including protocols for use, from opinion leaders when the assay was introduced; continuous reinforcement of information in pathology reports.Main outcome measures: Adherence to protocol for assay use.Results: Troponin assays were requested for 333 patients during 351 symptom episodes. A single assay was used in 194 symptom episodes (55%), and serial assays in 157 (45%); proportions were statistically indistinguishable across all three hospitals (χ2; P = 0.71). Of the 194 single assays, 13 (7%) diagnosed a myocardial infarction. Serial troponin testing in all three hospitals followed the suggested protocol, with mean time between serial assays being more than 6 hours at all hospitals.Conclusions: Adherence to the protocol for serial troponin assay intervals was adequate, but single troponin assays were used extensively and probably inappropriately.

Richard X Davey FRCPA, FACB