Volume 180 Issue 2

Adolescents and young adults fare worse than children, yet do not have the same access to clinical trial therapy In almost half a century of clinical trials in children with cancer, survival rates have increased from less than 20% to over 80%. The national and international cooperation for such results has been an enormous feat of organisation. However, older adolescents and young adults, while having a higher and increasing incidence of cancer, have not fared so well.1 As shown by Mitchell and colleagues in this issue of the Journal (page 59), few are recruited into clinical trials, and improvement in survival has lagged behind that in younger patients.2 Some cancers that affect adolescents have a good prognosis (eg, Hodgkin’s disease and gonadal tumours), and little difference in survival is seen between patients who are treated in trials and those who are not. Yet clinical trials are still necessary to find the least toxic therapy while maintaining excellent survival. On the other hand, other cancers common in adolescents, such as acute myeloid leukaemia, acute lymphoblastic leukaemia, rhabdomyosarcoma, osteogenic sarcoma and Ewing’s sarcoma, are associated with considerably lower 5-year disease-free survival rates in adolescents than in younger patients.3 With increasing intensity of therapy, the importance of supportive care and a multidisciplinary approach cannot be over-emphasised. Outcomes of adolescents with acute lymphoblastic leukaemia have been reported to be markedly better with paediatric-based, high-risk (intensive) therapy performed in large teaching hospitals with appropriate support and a commitment to multidisciplinary coordinated care. In Children’s Cancer Group trials between 1989 and 1995, older adolescents had a 6-year event-free survival of 64%, compared with 38% for similar patients on (adult) Cancer and Leukemia Group B trials.4 Cooperation between paediatric and adult groups is essential to encourage entry into clinical trials. In France in 1993 and 1994, 15–20-year-old patients with acute lymphoblastic leukaemia treated within the paediatric FRALLE-93 study had a 5-year event-free survival of 67%, compared with 41% for 15–20-year-olds treated within the adult LALA-94 study.5 How can the lessons learnt in the large, multi-institutional, national and international paediatric cooperative groups be translated into better outcomes for adolescents and young adults with cancer? The Children’s Oncology Group (United States, Canada, Australia, New Zealand) and adult cooperative groups sponsored by the National Cancer Institute have identified four initiatives to improve the accrual of adolescents and young adults with cancer into clinical trials:2 Improving access to care through understanding barriers to participation. These barriers remain largely unstudied, but might include the time, cost and effort of being involved in a clinical trial, which may deter both physician and patient. Oncologists in private practice may retain these patients rather than referring them to a tertiary-care facility or cooperative group member institution. Also, clinicians and patients may not be aware of opportunities for clinical trials, the age policies of hospitals may prevent access to clinical trials for eligible patients, eligibility criteria may exclude some adolescent and adult patients, or there may be no available clinical trial for a patient. Developing a cancer resource network to provide information about clinical trials to patients, families, healthcare professionals and the public. Enhancing adherence to protocol therapy among adolescents. Although compliance was not found to be poor in the study by Mitchell et al,1 adolescent and young adult patients are often perceived as having difficulty in complying with treatment while keeping up their normal lives. Ancillary medical, psychological and educational support should be directed towards their specific needs.6 Increasing adolescent and adult participation in sarcoma trials specifically designed for patients in this age group. Just as paediatric oncologists have little experience with epithelial tumours, some adult oncologists have limited experience managing rare sarcomas.7 Cooperation between paediatric and adult groups is essential to encourage entry into clinical trials. For example, many Children’s Oncology Group trials will admit patients up to 30 years of age. It is imperative that alliances are formed to enable haematologists and oncologists who treat adults to enrol their younger patients in these trials. Although institutions that are members of the Children’s Oncology Group undergo rigorous performance monitoring to maintain high quality of care and data, this should not be a hindrance to such associations. Managing cancer patients in clinical trials requires significant financial support for administration and data management, but the benefit in improved survival will prove to be highly cost effective. Current funding models for research in Australia may not be suitable for the funding of clinical research such as cancer trials. National Health and Medical Research Council funding is tied strongly to researchers’ previously published research. Clinical research as part of a large cooperative group will not lead to numerous publications for individual clinicians. Nevertheless, commitment to such trials must be acknowledged by funding groups so that appropriate financial support to treat patients in trials is forthcoming. Only in this way will Australians of all ages with cancer have the benefit of the best evidence-based treatment within randomised controlled clinical trials in centres of excellence.

Catherine H Cole FRACP, FRCPA

Attention to known contraindications and intercurrent illness can avoid life-threatening acidosis Metformin, a biguanide derivative, has been used in the treatment of type 2 diabetes for nearly 50 years. It acts as an insulin-sensitising agent, lowering fasting plasma insulin concentrations by inducing greater peripheral uptake of glucose, as well as decreasing hepatic glucose output. In 1998, the United Kingdom Prospective Diabetes Study reported that, in overweight patients with type 2 diabetes, treatment with metformin compared with diet alone resulted in statistically significant absolute risk reductions (ARRs) in all-cause mortality (ARR, 7%), diabetes-related deaths (ARR, 5%), any diabetes-related endpoint (ARR, 10%), and macrovascular disease (myocardial infarction, sudden death, angina, stroke, peripheral vascular disease).1 This was achieved without hypoglycaemia or weight gain. As a result, metformin is now regarded as the oral hypoglycaemic agent of choice in the treatment of overweight people with type 2 diabetes. More recently, the use of metformin has broadened, with evidence for its benefit in other insulin-resistant states. In polycystic ovary syndrome, metformin decreases insulin resistance, restores ovulatory menses, facilitates conception, and reduces the rate of first-trimester spontaneous abortion.2 Metformin also delays progression to type 2 diabetes in people with impaired glucose tolerance.3 It is currently being evaluated in the treatment of gestational diabetes mellitus, and has shown promising results in selected individuals with type 1 diabetes.4 But this increase in the use of metformin is not without risk. The manufacturer’s product information on metformin reminds prescribers that life-threatening lactic acidosis can occur, caused by accumulation of metformin, and that risk factors for this include renal impairment, old age and doses over 2 g per day. The estimated prevalence of life-threatening lactic acidosis is one to five cases per 100 000,5 with mortality in reported cases up to 50%.6 Traditionally, this complication has been thought of as secondary to an accumulation of the drug. Metformin is excreted unchanged in the urine, with the half-life prolonged and renal clearance decreased in proportion to any decrease in creatinine clearance.6 This may occur chronically in chronic renal impairment, or acutely with dehydration, shock, and intravascular administration of iodinated contrast agents, all of which have the potential to alter renal function. Tissue hypoxia also has a significant role, and acute or chronic conditions that may predispose to this condition, such as sepsis, acute myocardial infarction, pulmonary embolism, cardiac failure and chronic liver disease, may act as triggers. Between 1985 and 2001, 48 cases of lactic acidosis with metformin were reported to the Australian Adverse Drug Reactions Advisory Committee (ADRAC). In 15 of these cases, the complication was fatal. In 35 of the 48 cases, known risk factors were identified. Over the past 4 years, the average number of cases reported to ADRAC has been six per annum. In Australia in 2002–2003, about 200 000 patients were prescribed metformin, giving a reported frequency of lactic acidosis of one in 30 000. However the actual rate of occurrence is likely to be higher, given that under-reporting is an inherent problem with voluntary pharmacovigilance programs. At the Princess Alexandra Hospital in Brisbane, since January 2000, we have identified 13 patients with lactic acidosis thought to be related to use of metformin. Of these 13 patients, two died, while three require ongoing dialysis for renal failure; another was left with severe neurological disability requiring nursing-home care. The average age of the affected patients was 67 years (range, 47–79 years), and the baseline serum creatinine concentration (known in 10 patients) ranged from 0.12 mmol/L to 0.48 mmol/L, with a mean of 0.21 mmol/L (reference range, 0.05–0.11 mmol/L in women, and 0.06–0.12 mmol/L in men). Seven of the 13 patients were taking a metformin dose of 3 g per day, three were taking 2 g, while the remaining patients were taking between 500 mg and 1.7 g. How well do we currently comply with recommendations on prescribing metformin? A study at the University of Pittsburgh Medical Center in the United States reported on 263 hospital admissions involving 204 patients who were taking metformin. Patients had at least one absolute contraindication to metformin in 27% (71) of admissions. In 41% (29) of these, treatment with metformin continued despite the contraindication.7 A Scottish study of 1847 patients taking metformin found that 24.5% (452) had a contraindication.8 It follows that metformin must be prescribed appropriately to avoid potential adverse effects, while offering patients the best treatment possible. In well, ambulatory patients, renal function should be monitored regularly. A cut-off serum creatinine concentration above which metformin should be discontinued has been arbitrarily set at 0.15 mmol/L.9 Obviously, this needs to be individualised, and age, muscle mass, and protein turnover need to be considered. This can be achieved using the Cockcroft–Gault equation, which estimates creatinine clearance from age, weight and serum creatinine concentration. For example, with this equation, a 75-year-old woman, weighing 65 kg, with a serum creatinine concentration of 0.11 mmol/L, has an estimated creatinine clearance of 40 mL/min, which is significantly reduced. We propose: setting an absolute cut-off point (a creatinine clearance of 30 mL/min), below which metformin should be discontinued; and using metformin with extreme caution in patients with a creatinine clearance in the range 30–50 mL/min. No clear guidelines exist on reducing the dose of metformin as renal function declines, but reports of lactic acidosis have occurred with doses as low as 500 mg per day. Alternative strategies for managing diabetes in this situation include the use of insulin, thiazolidinediones and sulfonylureas. The second adverse situation to be considered is the previously well patient with a significant intercurrent illness. This includes illnesses with the potential to alter renal function, such as dehydration, shock, and sepsis. Metformin should be ceased completely while the patient is unwell, and recommenced when the illness has resolved, and renal function is shown to be normal. In addition, illnesses that increase the risk of tissue hypoxia and acidosis, such as acute myocardial infarction, pulmonary embolism, and cardiac failure, can trigger lactic acidosis, and the dose of metformin should be significantly reduced (or the drug discontinued altogether) under these circumstances. Patients need to be educated about these risks. Finally, a special situation is the use of iodinated contrast agents. The current recommendation is that metformin be withheld for 24–48 hours before the procedure and be recommenced 48 hours afterwards and only when renal function is shown to be normal.10 Without doubt, metformin remains the drug of choice for most patients with type 2 diabetes. Careful and thoughtful use of this drug has the potential to avoid life-threatening adverse events.

Janelle C Nisbet MB BS · Joanna M Sturtevant BPharm, BSc · Johannes B Prins PhD, FRACP

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

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

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

Objectives: To describe the location of treatment, recruitment to clinical trials and outcomes for adolescents and young adults treated for cancer in Victoria.Design and setting: Retrospective review of all adolescents and young adults aged 10–24 years diagnosed with cancer between 1992 and 1996, identified from the Victorian Cancer Registry.Main outcome measures: Treatment regimen (clinical trial, treatment protocol or neither), compliance with treatment and 5-year survival.Results: Questionnaires were completed for 576 of 665 eligible adolescents and young adults (87% response rate). Recruitment into clinical trials decreased with increasing age. Adolescents aged 10–19 years were more likely to be recruited to a clinical trial if treated at a paediatric hospital. For all cancers, 5-year survival was similar across the age groups and was not influenced by the place of treatment. Only 1% of adolescents and young adults failed to complete planned therapy due to non-compliance.Conclusions: Despite a similar incidence of cancer to that in younger children, adolescents and young adults with cancer are poorly recruited into clinical trials in Victoria. Establishment of a cancer resource network in Victoria may provide information to both paediatric and adult oncologists about currently available clinical trials.

Anne E Mitchell MB ChB, FRACP · Deborah L Scarcella BSc, GradDip · Gemma L Rigutto BSc, GradDip · David M Ashley PhD, FRACP · Vicky J Thursfield BSc, GradDip · Graham G Giles MSc, PhD · Maree Sexton MB BS, FRANZCR

Objective: To determine how familiar human research ethics committees (HRECs) are with the principles of natural justice and whether they apply these principles.Design and setting: A postal survey conducted between April and September 2002 of the Chairs of all HRECs registered with the Australian Health Ethics Committee of the National Health and Medical Research Council (NHMRC) in 2001.Main outcome measures: HRECs’ reported familiarity with, and application of, three principles of natural justice: (1) the hearing rule, requiring a decision maker to allow a person affected by a decision to present his or her case; (2) the rule against bias, requiring a decision maker to be unbiased in the matter to be decided; and (3) the evidence rule, requiring that a decision be based on the evidence provided, and not irrelevant issues.Results: From 201 Chairs of HRECs Australia-wide, we received 110 completed questionnaires (55% response rate). About 33% of respondents were very familiar with the principles of natural justice, and 25% completely unfamiliar. Most respondents felt that natural justice should be, and usually is, applied by HRECs. In cases of possible positive bias of an HREC member towards a research proposal, 70% of respondents said they would exclude the member from decision making. In cases of possible negative bias, 43% said they would exclude the HREC member.Conclusion: The degree of familiarity with principles of natural justice varies widely among Chairs of HRECs. While many respondents felt that HRECs usually apply natural justice, responses to questions about bias suggest that HRECs do not always exclude members with possible bias, contrary to NHMRC guidelines.

Gabrielle L Van Essen CertNurs, MB BS, FANZCA · David A Story BMedSci(Hons), MB BS(Hons), FANZCA · Stephanie J Poustie BN, CritCareCert, MPH · Max M J Griffiths MBE, BA, BD · Cynthia L Marwood LLB, LLM

Objectives: To estimate the magnitude of access block and its trend over time in New South Wales hospitals, using different definitions of access block, and to explore its association with clinical and non-clinical factors.Design and setting: An epidemiological study using the Emergency Department Information System datasets (1 January 1999 to 31 December 2001) from a sample of 55 NSW hospitals.Main outcome measures: Prevalence of access block measured by four different definitions; strength of association between access block, type of hospital, year of presentation, mode and time of arrival, triage category (an indicator of urgency), age and sex.Results: Rates of access block (for all four definitions) increased between 1999 and 2001 by 1%–2% per year. There were increases across all regions of NSW, but urban regions in particular. Patients presenting to Principal Referral hospitals and those who arrived at night were more likely to experience access block. After adjusting for triage category and year of presentation, the mode of arrival, time of arrival, type of hospital, age and sex were significantly associated with access block.Conclusions: Access block continues to increase across NSW, whatever the definition used. We recommend that hospitals in NSW and Australia move to the use of one standard definition of access block, as our study suggests there is no significant additional information emerging from the use of multiple definitions.

Roberto Forero MA, MPH, PhD · Lis Young FAFPHM, RCAP · Hai N Phung MD, MPH · Kenneth M Hillman MB BS, FRCAnaes(Eng), FFICANZCA · Mohammed Mohsin MSc(Stats), MSc(Demography) · Adrian E Bauman MPH, PhD, FAFPHM · Sue Ieraci MB BS, FACEM · Sally M McCarthy MB BS, FACEM, MBA · C David Hugelmeyer FAAEM, FACEM

On a per capita basis, Australia spent more than seven times as much on its Sydney Olympic team as did Canada, to win four times as many medals. Compared with Australia, Canada spent an additional amount per capita (standardised to the purchasing power parity rate at year 2000) of US$1605 per life-year gained on healthcare in 2000. Neither country is “right” or “wrong” in making these funding choices, but they highlight the need for more explicit discussion about what is being spent, what is obtained for the given expenditure and what society actually values.

Craig R Mitton PhD · H Dele Davies MD, MSc · Cam R Donaldson PhD

We report a man with longstanding undiagnosed adrenal insufficiency. At 37, our patient is the oldest reported case. Although most cases of Allgrove syndrome are diagnosed during childhood, awareness of this condition when undiagnosed in adults is crucial, as it is life threatening, and can severely affect neurological, sexual and psychological function. Allgrove syndrome was first described in 1978.1 It is an autosomal recessive condition associated with adrenal insufficiency due to adrenocorticotrophic hormone (ACTH) resistance, alacrima, and achalasia of the oesophageal cardia.1,2 Affected patients usually present as children, with achalasia and alacrima,3 but clinical features may be heterogeneous, sometimes including neurological involvement, and they present over a variable time course.4 The disease gene, ALADIN, localises to 12q13,5 with mainly nonsense mutations, resulting in expression of a truncated protein.3 Case reportA 37-year-old man with known achalasia was admitted for investigation of an 18-month history of extreme tiredness, recurrent cough, and weight loss of 10 kg. Previous historyOne year before admission, he had a 2-day history of lethargy, dizziness, and collapse with hypotension. On admission to an intensive care unit, he required crystalloid resuscitation, with inotropes for blood pressure maintenance for 2 days, after which he recovered slowly. Serotonin syndrome was proposed as a diagnosis, because he had recently started taking paroxetine for management of presumed psychogenic impotence. At age 31 he had begun to experience progressive generalised weakness, with soreness of lower limbs. A neurological report described mixed motor neurone abnormalities, with symmetrical four-limb weakness, predominantly distal muscle wasting, bilateral pes cavus, symmetrical hyperreflexia and positive Babinski reflexes. Bulbar involvement and optic atrophy were observed. Computed tomography (CT) scanning and magnetic resonance imaging of his brain showed no abnormality. No clear diagnosis was reached. Over several years he had sought professional help for erectile dysfunction and ejaculatory failure, from urologists, sexual counsellors, psychiatrists and neurologists, without success. Marital separation followed this difficult period. Twenty years before these events the patient had developed swallowing difficulties. Achalasia was diagnosed on radiological and endoscopic findings, with symptomatic improvement following pneumatic dilatation. His family history was unremarkable and did not include consanguinity. Muscle weakness and clumsiness was recognised from age 4 years, but he had always participated in sports activities. Growth and puberty occurred normally. Current admissionAn endocrinological consultation was sought because of increasing lethargy, weakness and reported testicular atrophy. Examination showed minimal pigmentation of skin and palmar creases, severe generalised weakness, proximal and distal myopathy and hypotension (95/50 mmHg) with a postural drop to 60 mmHg systolic on standing. Testicular volume was 25 mL (adult normal range, 12–25 mL) with normal virilisation and no gynaecomastia. Extremely indistinct “bulbar” speech was noted, with nasal escape rendering speech almost incomprehensible. Direct questioning confirmed alacrima, the patient stating that he never produced tears at any age. He also reported extreme difficulties with swallowing, taking an hour to eat a meal, constant cough, poor saliva control and accompanying inhalation of food. A diagnosis of Allgrove syndrome was made clinically, and adrenal insufficiency was confirmed with the discovery of elevated ACTH and low basal cortisol levels (see Box 1). An intramuscular injection of hydrocortisone (100 mg) resulted in rapid improvement of blood pressure and muscle strength, so that he could stand and walk without dizziness. There was significant improvement in his speech, cessation of cough and reported normalisation of eating habits. Replacement therapy with hydrocortisone (20 mg/m2 daily) was initiated. Plasma renin activity was normal. Fludrocortisone was not required as the patient’s blood pressure had returned to normal with no postural drop after glucocorticoid replacement, confirming intact mineralocorticoid function. After discharge from hospital 3 days after the diagnosis was made, he reported ongoing marked improvement in strength and coordination and returned to full-time manual trade work. DiscussionThis patient with Allgrove syndrome, who developed symptoms of severe life-threatening adrenal insufficiency at age 36, but retained normal mineralocorticoid function, is the oldest reported case surviving with undiagnosed adrenal insufficiency. In cases reported previously, adrenal insufficiency was usually diagnosed in the first decade6 (with a few exceptions2,7,8), accompanied by hypoglycaemia and increased skin pigmentation.5 Most patients had normal mineralocorticoid function, but deficiency has been reported.5,9 Achalasia is usually diagnosed at the same time or after the diagnosis of adrenal insufficiency.5 In our patient, achalasia preceded the diagnosis of adrenal insufficiency by 20 years. Such a late diagnosis emphasises the need for assessment of adrenal function in any young person with achalasia or alacrima. The gene is defined for this rare autosomal recessive disorder (ALADIN at 12q13); fewer than 100 cases have been reported, usually in family clusters. Our patient had no family history of the disorder, indicating that he was likely to be the first (index) case with the mutated gene. Diagnosing adrenal insufficiency: Diagnosis of hypocortisolism is frequently delayed for patients with adrenal insufficiency, because of the subtle nature of clinical complaints (weakness, tiredness, dizziness and slow weight loss). When mineralocorticoid function is intact, postural hypotension and electrolyte disturbance, with an acute medical emergency presentation, is less likely. ACTH insensitivity due to adrenocortical atrophy is the resultant clinical picture. Skin pigmentation varies, and is often missed unless a careful search for buccal, crease and scar pigmentary change is sought. A diagnosis of primary adrenal insufficiency usually includes consideration of an autoimmune basis where adrenal antibody status should be tested (with or without other pointers to polyautoimmune endocrinopathy), infective causes (tuberculosis, viruses and mycoses) and, in older patients, malignant infiltration. These problems usually result in extensive adrenal destruction and associated mineralocorticoid deficiency, often with a more dramatic presentation of ill health and electrolyte imbalance. Neurological features: Peripheral motor and sensory neuropathy are common,10 and may be subtle in childhood.5 Impotence is infrequently reported with Allgrove syndrome5,7,8 perhaps because of underreporting, or a diagnosis of psychogenic impotence. Erectile dysfunction in our patient was neurological in origin, and so it is not surprising that it failed to respond to usual therapies. The differential diagnosis includes adrenoleukodystrophy (ALD) in childhood or adolescence, with either neurological abnormality or adrenal insufficiency as the first presentation. Adrenomyelodystrophy occurs when patients with this progressive demyelinating disorder first present in adulthood. As our patient’s first neurological complaint occurred when he was 4 years of age, ALD could be excluded. Similarly, the gene for Duchenne muscular dystrophy is located adjacent to the DAX-1 gene, producing neurological deterioration and adrenal insufficiency, but is generally diagnosed earlier. Although neurological disorder constitutes part of the condition, the severe and progressive muscle weakness of long-term undiagnosed adrenal insufficiency makes a major contribution to reduced motor function and quality of life, as seen in our patient. Unlike other neurological disorders associated with adrenal insufficiency, neurological change with Allgrove syndrome is extremely slow. With adequate cortisol replacement, monitoring of ACTH levels and education to ensure appropriate increases in corticosteroid treatment during intercurrent illness or anaesthesia, the prognosis for health and quality of life is improved. 1: Patient’s blood test results before diagnosis Investigation Results Reference values Sodium 139 mmol/L 135–145 mmol/L Potassium 3.8 mmol/L 3.5–5.0 mmol/L Chloride 102 mmol/L 95–107 mmol/L Bicarbonate 25 mmol/L 23–32 mmol/L Urea 3.4 mmol/L 3.2–7.3 mmol/L Creatinine 57 μmol/L 40–130 μmol/L Cortisol (08:00 h) 43 nmol/L 200–750 nmol/L Adrenocorticotrophic hormone 864 pmol/L < 20 pmol/L Plasma renin activity 1.0 ng/mL/h 0.3–1.4 ng/mL/h 2: Clues to recognising the syndrome Clinical suspicion of adrenal insufficiency in the presence of achalasia in any patient, children or adults. Alacrima — ascertaining this usually depends on direct questioning about tear production. Neurological dysfunction — not universal, but the combination of achalasia and neurological dysfunction should prompt specific questions about symptoms of adrenal insufficiency. Elevated adrenocorticotrophic hormone and low basal cortisol levels confirm the diagnosis.

Clarissa C Pedreira MD · Margaret R Zacharin MB BS, FRACP

There is growing interest in involving the public in decisions about healthcare provision. Citizens’ juries, whose members were randomly selected from the electoral roll (rather than derived from consumer interest groups), have been trialled in Western Australia. When asked to take a community focus, presented with balanced evidence and given time to discuss and deliberate, the juries were able to identify and debate issues of broad principle, such as equity. Such issues seem to be best handled by referring to community values. Any public consultation process should provide sufficient information, opportunity for reflection and deliberation, and recognition of the scarcity of resources.

Gavin H Mooney MA · Scott H Blackwell MB BS

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

Nikolai Bogduk MD, DSc, FFPM (ANZCA)

Clinical records Case 1: An 89-year-old woman was admitted to hospital from a nursing home with a 12-hour history of drowsiness, progressing to an unrousable state and inability to eat or drink. A low dose of long-acting morphine had been commenced 2 days earlier for painful arthritis. A capillary blood glucose (glucometer) reading taken in the nursing home on the morning of hospitalisation was 4.1 mmol/L. Past history included well controlled type 2 diabetes mellitus associated with corticosteroid use, for which she had been prescribed glimepiride 0.5 mg daily 2 months previously. The last dose was given on the morning of hospital admission. She was taking multiple other medications for comorbid conditions. The ambulance officers transporting her to hospital had recorded a “Lo” glucometer reading and administered 25 mL of 50% glucose. Within 5 minutes, a repeat glucometer reading was 14.7 mmol/L. On arrival at hospital the woman was opening her eyes and responding appropriately to pain, but not verbalising. Her Glasgow Coma Score was 9/15. In emergency triage, a glucometer reading showed 4.8 mmol/L, but shortly afterwards her venous serum glucose concentration was 1.3 mmol/L and serum creatinine level was 0.19 mmol/L (normal range, 0.05–0.09 mmol/L). Results of a cerebral computed tomography scan were unremarkable. Over the next 15 hours, there were six more glucometer readings with levels < 3.5 mmol/L, including readings of 0.6 mmol/L and 1.8 mmol/L (18 and 27 hours after the last dose of glimepiride, respectively). Despite a total of 250 mL of 50% glucose in eight bolus doses and a 5% glucose infusion commenced at admission and continued throughout hospitalisation, her level of consciousness deteriorated. She died 18 hours after presentation. Case 2: A 79-year-old woman living in a nursing home had been discharged from hospital several days earlier after internal fixation of a fracture of the femoral neck. She was readmitted after a sudden deterioration, characterised by drowsiness, decreased response to questions and dyspnoea. Her past history included type 2 diabetes mellitus for 4 years, for which she was taking glibenclamide 2.5 mg twice daily, a dose which had not been changed for 3 years. Glucometer readings had ranged between 7 mmol/L and 9 mmol/L during her recent hospitalisation. Other major comorbidities included a dominant middle cerebral artery stroke resulting in persisting hemiplegia and dysphasia, atrial fibrillation, hypertension and congestive cardiac failure. Because of her multiple comorbidities she was taking numerous medications. A glucometer reading was not performed before transfer to hospital. In the emergency department, the woman was initially treated for pulmonary oedema and pneumonia, which were evident clinically and radiologically. Her venous serum glucose concentration was 0.6 mmol/L and her serum creatinine level was 0.04 mmol/L (normal range, 0.05–0.09 mmol/L). Over the ensuing 27 hours, five more glucometer readings were < 3.5 mmol/L, including one of 0.7 mmol/L, and another of 2.3 mmol/L (24 and 36 hours after the last dose of glibenclamide, respectively). In total, she required 300 mL of 50% glucose in six bolus doses and a 5% glucose infusion for 48 hours. Over the ensuing days, her condition improved and she was able to take a purée and thickened fluid diet. One week after presentation, she appeared to vomit and aspirate while eating, and suffered an asystolic cardiac arrest from which she could not be resuscitated. Sulfonylureas act by stimulating insulin secretion from the pancreas and augmenting glucose-stimulated insulin secretion. Some, such as glibenclamide and glimepiride, are long acting and have metabolites that are excreted renally. Others, such as gliclazide and glipizide, are shorter acting and do not have active metabolites.1 Hypoglycaemia is the major risk associated with the use of sulfonylureas, particularly in elderly people. Serious hypoglycaemia is usually defined as that causing death, or requiring hospitalisation or emergency department admission. The rate is probably between 1% and 2% per year.2 Previous reports suggest, and the cases described here demonstrate, that this may occur even with very low doses of a sulfonylurea. The resultant hypoglycaemia can be prolonged and recur for a period of more than 24 hours despite treatment. Case fatality rates of 4%–10% are reported and 5% of survivors may have permanent neurological impairment.3 In elderly people, the classical autonomic adrenergic symptoms and signs of hypoglycaemia may not be present (or evident), and neuroglycopenic features, such as drowsiness or confusion, may dominate the picture (as in the cases described), so the diagnosis can be easily missed.4 Elderly patients with these symptoms who are taking medication for hypoglycaemia need immediate (and repeat) measurement of blood sugar level (BSL). If the BSL is low and the patient is alert and able to swallow, oral carbohydrate loading is the preferred management regimen — otherwise an ambulance should be called and the patient transported to hospital as a matter of urgency. While 10–25 g of carbohydrate delivered in 50% glucose is essential to restore the patient to euglycaemia in the short term, in the presence of sulfonylurea it stimulates more insulin secretion by the pancreas, and therefore can contribute to recurrent hypoglycaemia. The 50% glucose bolus should be followed immediately by an infusion of 5% or 10% glucose, usually at a rate of 100–200 g of carbohydrate daily, and BSL should be monitored for at least 24 hours. Subcutaneous synthetic somatostatin analogues may be used to reduce the likelihood of rebound hypoglycaemia and reduce glucose requirements, but there is no role for glucagon in the management of sulfonylurea-induced hypoglycaemia.5 Numerous studies show that longer-acting sulfonylureas are associated with a higher risk of hypoglycaemia, including serious hypoglycaemia. Gliclazide and glipizide have been shown to cause less hypoglycaemia than glibenclamide, and one study also suggested that glimepiride was safer than glibenclamide.6-9 There are no published reports comparing glimepiride directly with gliclazide or glipizide for hypoglycaemia. Other risk factors for hypoglycaemia, evident in the cases described here, include advanced age, recent hospitalisation, multiple medications, and drug accumulation caused by renal or hepatic impairment (keeping in mind that renal function usually declines linearly with age). Medication changes, including an increase in hypoglycaemics while a patient is unwell in hospital, may not be adequately communicated to the patient’s general practitioner, and recent hospitalisation is perhaps the major risk factor for sulfonylurea-induced hypoglycaemia. The presence of any of these risk factors should affect the choice and dose of medication and increase vigilance in monitoring BSL and renal function. In conclusion, the above cases serve to remind us of the dangers of long-acting sulfonylureas, which should perhaps be avoided in elderly people. Shorter-acting sulfonylureas such as gliclazide and glipizide are safer options. Elderly patients with altered mentation taking sulfonylureas require an urgent BSL measurement and, if they are unable to take food or fluids orally, they should be referred to hospital promptly. Lessons from practice Long-acting sulfonylureas, such as glibenclamide (and perhaps glimepiride) should be used with extreme caution in frail elderly people. Recent hospitalisation is a major risk factor for sulfonylurea-induced hypoglycaemia and necessitates increased vigilance in monitoring the patient’s condition and blood sugar levels. The classical adrenergic features of hypoglycaemia may be absent (or not evident) in frail elderly people. Drowsy or confused elderly patients taking sulfonylureas should have their blood sugar level measured urgently. Once sulfonylurea-induced hypoglycaemia is confirmed, oral carbohydrate loading is the preferred management regimen in alert patients, but those unable to take oral food or fluids should be transferred to hospital as a matter of urgency. Even with low-dose sulfonylurea therapy, hypoglycaemia can be severe, prolonged and recurrent over at least 24 hours.

Peter C Veitch MB BS, FRACP · Rory J Clifton-Bligh MB BS, PhD

A 53-year-old Asian man with type 2 diabetes mellitus presented to the Emergency Department with acute onset of generalised muscle cramps. He reported a 2-month history of polydipsia, polyuria and passing “milky” urine with blood clots. He had travelled widely throughout subtropical Asia. On examination, he was normotensive, with no lymphadenopathy, abdominal masses or oedema. Urinalysis showed marked proteinuria, glycosuria and haematuria. The urine protein excretion rate was later confirmed to be 15.57 g/24 h (reference interval [RI], 0.02–0.15 g/24 h). Urine triglyceride measurement and lipoprotein electrophoresis confirmed the appearance of chylomicrons in the urine after an oral fat tolerance test (Box 1). Biochemical analysis of serum showed the following levels: sodium 121 mmol/L (RI, 134–146 mmol/L), potassium 4.6 mmol/L (RI, 3.4–5.3 mmol/L), creatinine 46 μmol/L (RI, 60–105 μmol/L), glucose 19.7 mmol/L (RI, < 5.5 mmol/L), ferritin 16 mg/L (RI, 30–620 mg/L), 25-hydroxyvitamin D 11 nmol/L (RI, > 50 nmol/L), total cholesterol 5.2 mmol/L (RI, <5.5 mmol/L), and triglyceride 1.8 mmol/L (RI, < 1.8 mmol/L). The patient had marked hypoproteinaemia and hypoalbuminaemia, with a total protein level of 39 g/L (RI, 63–80 g/L) and albumin level of 21 g/L (RI, 35–50 g/L), respectively. The serum IgE level was also raised (2300 kU/L; RI, < 210 kU/L). The patient was mildly anaemic (haemoglobin level, 120 g/L [RI, 130–170 g/L]), with a normal erythrocyte sedimentation rate and C-reactive protein level. There was lymphopenia but no eosinophilia. No microfilariae or acid-fast bacilli were detected in thick blood films taken at midnight or in a urine sample. Serological and intradermal tests for filariae were also negative. A chest x-ray and computed tomography scan of the abdomen and pelvis were normal. A biopsy of the right kidney showed evidence of mild mesangial change, consistent with diabetes mellitus. Lymphoscintigraphy showed delayed lymphatic transport, particularly on the left side, but no physical obstruction to lymphatic drainage. Contrast lymphangiography demonstrated a grossly abnormal lymphatic system in the pelvis and groin with a unilateral left-sided lymphorenal communication (Box 2). A presumptive diagnosis of filariasis was made and the communication between the left kidney and the lymphatics was surgically disconnected. The chyluria recurred after surgery, but within 4 weeks of a therapeutic course of the antifilarial diethylcarbamazine there was complete resolution. Furthermore, the biochemical abnormalities reversed, consistent with urinary loss as the mechanism. At 3-year follow-up, the patient remained symptom-free and without chyluria. DiscussionChyluria is rare in Australia but common in many parts of the world, particularly where Wuchereria bancrofti, the main agent of filariasis, is endemic. It occurs, on average, 5–10 years after the worm has died, and so there may be no evidence of active filariasis. However, a therapeutic trial of diethylcarbamazine should be considered before undertaking surgery. As spontaneous remissions of chyluria have been reported, we can not be certain whether the antifilarial therapy was responsible for resolution of the chyluria in this case. 1: Oral fat tolerance test Urine of patient before a 75 g oral fat tolerance test (0 h) and at serial time points (0.5, 1, 2, 3, 4, and 5 h) after the test. 2: Contrast lymphangiography Contrast lymphangiogram, showing a grossly abnormal lymphatic system with a unilateral left-sided lymphorenal communication (arrow).

John R Burnett MB ChB, FRCPA, PhD · Gary G Sturdy MB BS · Suzzanne J Smith BSc(Hons) · Yuli Ten MB BS · Michael J McComish MB BS, FRACP

Alan E Dugdale Principal Honorary Research Fellow, Department of Paediatrics and Child Health, Medical School, University of Queensland, Herston, QLD 4006. A. DugdaleATuq.edu.au To the Editor: Chronic suppurative otitis media (CSOM) is a long-term problem which often has serious effects on hearing, speech and learning. Couzos and colleagues have shown that local treatment with ciprofloxacin (CIP) eardrops clears episodes of purulent discharge more efficiently than the commonly used framycetin, gramicidin and dexamethasone (FGD) eardrops.1 This hardly ranks as a “cure” as suggested by the authors. The natural history of CSOM is known2-4 (see Box). The disease commonly starts in infancy with painless perforation of the ear drum and purulent discharge. The perforation is usually central and often large. It remains for several years. During this time there are episodes of painless discharge of foul-smelling pus associated with a blocked ear canal and poor hearing. Between these episodes, the perforation remains, but the ear is usually dry and hearing can be normal or at least adequate. By mid-childhood the perforation often closes spontaneously. In some children this leaves a scarred retracted eardrum, but, in others, fluid collects behind the now intact drum, and this chronic serous otitis media decreases hearing. Eventually, this chronic serous otitis media clears, leaving a scarred, retracted eardrum. Hearing then improves and is often functionally normal. Cholesteatoma and other medical complications are uncommon, but the loss of hearing during childhood has severe social and educational effects on the child. Attempts to hasten closure of the perforation and limit the episodes of purulent discharge have had incomplete success.5,6 Any treatment that hastens recovery is welcome, but we should ask: Does local CIP treatment retain its effectiveness in repeated episodes of purulent discharge? (The most common organisms are Pseudomonas spp which rapidly develop resistance to antibiotics); Does CIP treatment alter the interval between purulent episodes compared with other treatments?; and Is there any evidence that local CIP treatment alters the natural history of the disease or lessens the hearing loss? (it is probably too early to detect this). CSOM is a disease of poverty and overcrowding, but the mechanism leading from social disadvantage to ear disease is not clear. In Cherbourg Aboriginal Community where I work, social and living conditions have improved and CSOM is now much less common than reported by Stuart and co-workers more than 25 years ago.2 I hope that treatment with local CIP eardrops will maintain its promise as a significant improvement in the management of this disease in children who have already acquired it, while we work towards eliminating the disease in the long term. Changes in the incidence of ear disease with age in an Aboriginal community (from Dugdale et al3)

Alan E Dugdale

David R Brewster Clinical Dean, Northern Territory Clinical School, Royal Darwin Hospital, PO Box 41326, Casuarina, NT 0811. david.brewsterATnt.gov.au To the Editor: Although the study by Couzos et al1 is important, I have serious concerns about (i) the lack of “intention-to-treat” analysis and (ii) the implication that the use of ototopical aminoglycosides is unethical and could lead to litigation. The CONSORT statement indicates that analysis by intention-to-treat (ITT) is a key measure of methodological quality in reporting of randomised trials.2,3 Of 147 children randomly allocated to the two treatments in this trial, the primary outcome (resolution of otorrhoea) is only reported for 111 children (75.5%), and the secondary outcomes of healed tympanic membrane perforation in 64 (43.5%), and of improved hearing in 49 (33.3%). In addition, although the difference in cure rates is indeed 24.6% if drop-outs are ignored, the authors report incorrect 95% confidence intervals (15.8%–33.4%, instead of 7.3%–41.8%). Analysis by intention-to-treat means that the 36 children lost to follow-up are assumed to still have ear discharge, so 33 of 75 in the ciprofloxacin group and 43 of 72 in the combined framycetin, gramicidin and dexamethasone group would not have “clinical cure”. This reduces the absolute difference to 15.7% (95% CI, 0–32%; P = 0.07), which is no longer a significant difference. It is also unlikely that the clinical cure rates of 50%–70% in the study can be replicated in the real world of remote Top End Aboriginal communities with a high prevalence of chronic suppurative otitis media (CSOM). Cleaning ears twice a day with gentle syringing with 0.5% povidone-iodine, followed by ototopical ciprofloxacin for 10–14 days is not a feasible intervention among the competing priorities in most Aboriginal communities in the Northern Territory. The really important clinical outcomes for CSOM are the two secondary outcomes of healed perforations and improved hearing, but these outcomes were not significantly improved by ciprofloxacin compared with combined framycetin, gramicidin and dexamethasone. Couzos and colleagues conclude that the use of aminoglycosides in CSOM is unethical and could lead to litigation on the basis of potential ototoxicity. Were this true, it would make this trial unethical. This misuse of ethics and law in the medical literature must be denounced. Nearly all drugs have potential side effects which have to be measured against their potential benefits. The potential ototoxicity of ototopical aminoglycosides (and other antibiotics) is not an absolute contraindication to their use, and has not been documented in any of the randomised controlled trials that have measured hearing before and after use of topical aminoglycosides.4 Couzos and colleagues misinterpret the strength of evidence for changing to ototopical ciprofloxacin. Although it is probably true that ciprofloxacin is superior to combined framycetin, gramicidin and dexamethasone in eradicating Pseudomonas aeruginosa, and for the short-term resolution of ear discharge, it is still unclear whether this transient benefit will be maintained in the long term, or whether resistant organisms will emerge in the middle ear, mitigating any benefit from the new drug. Haphazard use of ototopical ciprofloxacin in Top End Aboriginal communities is likely to result in resistance (indeed there is already anecdotal and unpublished evidence of this), so I believe that its use should currently be restricted to studies and programs whose outcomes are healed perforations and improved hearing (rather than only transient resolution of ear discharge).

David R Brewster

Sophie Couzos,* Traven Lea,† Margaret Culbong,‡ Reinhold Mueller,§ Richard Murray¶ * NACCHO Public Health Officer, National Aboriginal Community Controlled Health Organisation, PO Box 927, Broome, WA 6725; † Former Clinical Project Officer, ‡ Chair, NACCHO Research Subcommittee, National Aboriginal Community Controlled Health Organisation, Deakin, ACT; § Senior Biostatistician and Epidemiologist, School of Public Health and Tropical Medicine, James Cook University, Townsville, QLD; ¶ Medical Director, Kimberley Aboriginal Medical Services Council, Broome, WA, and Associate Professor, School of Public Health and Tropical Medicine, James Cook University, Townsville, QLD. scouzosATtpgi.com.au In reply: Dugdale correctly refers to the natural history of chronic suppurative otitis media (CSOM), and the spectrum of endpoints. The primary endpoint chosen in our trial after ototopical treatment was a dry ear1 (commonly referred to as a “clinical cure” by other trials2), an outcome to be expected after short-term follow-up. Surgical closure of the tympanic membrane (TM) has also been defined as “curing” CSOM. Attaining a dry ear is essential to TM healing, and is therefore a functionally important outcome. Brewster seems to confuse intention-to-treat (ITT) analysis with sensitivity analysis. Patients for whom there is no data after random allocation to study groups fall into the “missing” category, and may be included as “failures” in a sensitivity analysis. This may reveal additional information if missing data occurred differentially (ie, in some way associated with the treatments). However, in an ITT analysis, patients (with recorded data) are analysed in the group to which they were randomly allocated, irrespective of the actual treatment they received.3 Our analysis followed this principle and included all children, irrespective of the completeness of their treatment regimen.1 A sensitivity analysis revealed no new information, which was not surprising as the missing data were lost for (ascertained) reasons exclusively unrelated to the treatment, and double-blinding excluded any differential follow-up efforts by the healthcare workers. Consequently, the missing values occurred randomly and our analysis not only follows the ITT principle but is also unbiased (ie, valid with respect to “missing” patients). We are surprised that our treatment regimen is not feasible in the Northern Territory given that it has been used for years in remote Aboriginal communities in Western Australia. We also confirmed the effectiveness of twice-daily use of ototopical medications, which is simpler than current four-times daily schedules. In 1996, the World Health Organization recommended that topical aminoglycosides (AG) not be used for CSOM because of ototoxicity.4 Such use is also contraindicated by manufacturers.1 Given the availability of a safer alternative, healthcare professionals face potential medicolegal challenges if they choose ototopical AG to treat CSOM. The relative superiority of ototopical fluoroquinolones (FQ) over AGs in effecting a dry ear is likely to persist with repeated treatments, as the risk of bacterial resistance generated in CSOM pathogens appears to be very small,5 and is far outweighed by the risks of resistance found with oral or parenteral FQs. In our trial, bacterial resistance to ciprofloxacin in ear isolates was not demonstrated in the short term. Systemic absorption of FQ through ototopical use is also negligible.5 In Japan, ototopical ofloxacin has been used as treatment for CSOM since 1992. Based on repeated nationwide surveys from 1995, increased FQ resistance attributed to ototopical use has not been seen in chronic otitis media isolates (Professor K Suzuki, Department of Otolaryngology, The Second Hospital, Fujita Health University School of Medicine, personal communication).6 Whether antibiotics can affect the interval between purulent episodes of CSOM is predicated on host and environmental factors, as well as the duration of effective drug therapy. A multifaceted approach to the problem of CSOM, requiring the political will to improve the living conditions of Aboriginal families, access to appropriate primary healthcare, ototopical FQs, and surgery will see a reduction in the rate of this disabling disease.

Sophie Couzos · Traven Lea · Margaret Culbong · Reinhold Mueller · Richard Murray

Terry J Coyne,* Michael G Findlay,† Torukiri I Ibiebele,‡ David W Firman§ * Senior Lecturer, School of Population Health, University of Queensland, Public Health Building, Medical School, Herston Road, Herston, QLD 4029; † Acting Senior Analyst, ‡ Assistant Analyst, Epidemiology Services Unit, Queensland Health, Brisbane; § Team Leader, Surveys and Social Statistics, Office of Economic and Statistical Research, The Treasury, Queensland Government, Brisbane.t.coyneATsph.edu.au To the Editor: While the rates of overweight and obesity among Australian adults, as determined by the Australian Diabetes, Obesity and Lifestyle Study (AusDiab),1 may be alarming to some, they may in fact be underestimates of the true prevalence of overweight and obesity. The AusDiab study design2 and its low response rates indicate that the results will need to be interpreted with caution. Firstly, the AusDiab study design excluded rural and predominantly Indigenous census collection districts (CDs). In Queensland, all CDs selected were capital city or other major urban centres (Rural and Remote Areas Classification, categories 1 and 2);3 thus, people living in major rural centres (such as Rockhampton or Bundaberg) or major remote centres (such as Mt Isa) were excluded (ie, in Queensland, about 20% of the population were excluded). Secondly, another potential bias may have been introduced by the Socio-Economic Indexes for Areas (SEIFA) scores of the CDs sampled in the AusDiab study. For example, the overall SEIFA score for the CDs included in Queensland was 1035 (73rd percentile), well above the state average. Finally, the response rates in the AusDiab study were low: only 29% of those estimated to be eligible, and only 52% of those invited, actually completed the study. Our analysis of risk factors of Queensland-AusDiab participants suggests that these participants may have been more health conscious than the general Queensland population. Rates of smoking reported for men and women were considerably lower in the Qld-AusDiab cohort compared with those in the Queensland phase of the 2001 National Health Survey4 (17.3% and 14.5% v 28.4% and 19.8%, respectively). Compared with results of a Queensland Omnibus telephone survey5 conducted at about the same time, higher proportions of Qld-AusDiab participants reported greater intakes of vegetables (≥ 4 serves/day: 27.4% Qld-AusDiab v 16.4% Omnibus) and fruit (≥ 2 serves/day: 28.9% v 24.3%), and less frequent consumption of fast foods (> 1 day/week: 37.3% v 49.5%). Given the low response rate and possible selection bias in the AusDiab study, we suggest that the overweight and obesity data should be interpreted with caution. Several indicators suggest that these data could be underestimates of the true prevalence of overweight and obesity, and that the AusDiab population may have been of higher socioeconomic status, more health conscious (lower rates of smoking, better dietary intake), and more willing to participate in a lengthy examination than the general Australian population. These factors may all be associated with lower rates of overweight and obesity, and therefore future national surveys will need to take these factors into consideration to obtain more accurate estimates of important determinants of health.

Terry J Coyne · Michael G Findlay · Torukiri I Ibiebele · David W Firman

Adrian J Cameron,* Paul Z Zimmet,† David W Dunstan,‡ Jonathan E Shaw§ * Epidemiologist, † Director, ‡ Research Fellow, § Physician in Diabetes, and Director, Clinical Research; Epidemiology Department, International Diabetes Institute, 250 Kooyong Road, Caulfield, VIC 3162. acameronATidi.org.au In reply: Coyne suggests that, based on comparisons within Queensland, the national prevalence of obesity in our article1 is an underestimate. It should be noted that the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) was designed primarily to produce national, not state-specific, data. Forty-two census collection districts (CDs) were selected Australia-wide, with only six CDs selected within each state. The primary objective of this sample selection was to obtain a nationally representative population, not necessarily one representative of each state. Coyne states that none of the Queensland CDs were in major provincial centres. Of the six Queensland CDs, four were outside Brisbane. From the national sample, 17 of 42 CDs (40.5%) were outside capital cities. As a comparison, 36% of the Australian population lives outside capital cities.2 Regarding selection of CDs, we excluded only those in Statistical Local Areas defined as 100% rural, and those where the Indigenous population made up 10% or more of the overall population.3 This excluded only 5.8% of the total eligible population. If the prevalence of obesity among this group was double the overall prevalence, this would not significantly alter the national rate. While the smoking rates in AusDiab were lower than reported elsewhere, the prevalence of obesity, hypercholesterolaemia and hypertension were in line with trends in a series of surveys over the past 20 years.4 In an extensive analysis of food consumption between AusDiab and the 1995 National Nutrition Survey, the rates of fruit and vegetable consumption were within 4% between the surveys for those most commonly eaten. Since our conclusion was that obesity has increased, the possibility of an underestimate only reinforces our message.

Adrian J Cameron · Paul Z Zimmet · David W Dunstan · Jonathan E Shaw

Johan H A Janssen,* David Henshaw† * Cardiologist, † General Physician, Kalgoorlie Regional Hospital, PO Box 8035, Hannans, Kalgoorlie, WA 6433. Johan. JanssenAThealth.wa.gov.au To the Editor: We read with interest the article by Hung on aspirin for cardiovascular disease prevention,1 and would like to alert readers to the fact that, from the same studies Hung discussed, it is clear aspirin fails to prevent 80% of recurrent serious vascular events, and that one in eight high-risk patients will suffer from another “event” in the next 2 years while taking aspirin.2 Recent studies have triggered discussion about the concept of aspirin resistance and competitive binding issues as possible causes for the observed failure of aspirin, or indeed the increased risk of all-cause mortality when aspirin is used in combination with ibuprofen.3,4 Although it may still be premature to recommend routine testing for aspirin resistance, the possibility that testing might lead to improved strategies for reducing the risk of thrombotic complications means that it should be considered. Another point for consideration is whether primary prophylaxis with aspirin might induce aspirin resistance, thereby nullifying the effect of taking it in the first place. We agree with Hung that the current main alternative to aspirin is clopidogrel, and that this agent could be used in cases in which there is any doubt about the efficacy of aspirin.

Johan H A Janssen · David Henshaw

Joseph Hung Associate Professor, School of Medicine and Pharmacology, University of Western Australia, and Head of Department, Cardiovascular Medicine, Sir Charles Gairdner Hospital, Verdun Street, Nedlands, WA 6009. jhungATcyllene.uwa.edu.au In reply: Janssen and Henshaw are correct to point out that aspirin fails to prevent 80% of recurrent serious vascular events among high-risk patients. However, to put this into perspective, simple treatment with aspirin produces about the same relative risk reduction as treatment with a statin or the angiotensin-converting enzyme inhibitor, ramipril, among patients at high risk of vascular events.1-3 Janssen and Henshaw raise the concept of aspirin resistance and the role of a screening test. However, aspirin resistance is a poorly defined term, and could mean the clinical inability of aspirin to protect individuals from arterial thrombotic events, or laboratory measures indicating the failure of aspirin to inhibit platelet activity. There is currently no specific, accurate, and reproducible measure of the antiplatelet effects of aspirin, nor are there methods that can reliably predict the clinical efficacy of aspirin.4 For now, with high-risk patients, doctors should: ensure that patients comply with aspirin therapy along with other proven preventive treatments; avoid regular concomitant use of non-steroidal anti-inflammatory drugs with aspirin because of the potential for competitive inhibition;5 and consider the addition of clopidogrel to therapy with aspirin, so as to block other pathways of platelet activation not blocked by aspirin, particularly in patients who experience thrombotic complications during aspirin therapy.1

Joseph Hung

Bruce Hadden President, Royal Australian and New Zealand College of Ophthalmologists, Eye Institute, 125 Remuera Road, Auckland, 1005, New Zealand. bruceATeyeinstitute.co.nz To the Editor: The article by Brooks contains valuable forward-thinking for future healthcare management of the increasing burden of chronic illness.1 However, Brooks’s suggestion that non-medical practitioners might perform cataract extraction shows his lack of knowledge of the complexity and potential complications of modern cataract surgery. Modern cataract surgery is the most commonly performed major operation, and one of the most rewarding in lifestyle improvement. It is done under local anaesthetic with almost no discomfort, and recovery is rapid. Thus, the patient sees it as being simple. However, it is far from simple for the surgeon. The small-incision, phacoemulsification technique has made the operation more demanding than ever before. The learning curve is both long and steep. Posterior capsule rupture during phacoemulsification is an ever-present threat, and if it occurs, the sight-threatening complications of cystoid macular oedema, retinal detachment and endophthalmitis all become more likely. The modern, highly technical procedure that Australians demand and deserve is comparable with coronary artery bypass and joint replacement surgery in terms of the skill required. There are three reasons that non-ophthalmologists think cataract surgery is simple. First, it is simple from the patients’ perspective. Secondly, cataract extraction can be done relatively cheaply in developing countries. However, the operation done in those countries is a different procedure, and comparisons are not valid. Thirdly, some unscrupulous ophthalmologists themselves have trivialised the procedure as a means of self-promotion. Brooks and others would pay the operation much more respect if they took the trouble to view a few procedures in real life.

Bruce Hadden

R Frank Gorman Medical Ophthalmologist, PO Box 211 Marrickville, NSW, 1475. rfgormanAThotmail.com To the Editor: Ernst raises the matter of obstacles to research in complementary and alternative medicine. With respect to spinal manipulation therapy as an alternative medical approach to constitutional ailments, such as migraine, the key evidence is the recovery of vision, which occurs with spinal manipulation in appropriately ill patients. These data have not been acknowledged by this Journal because randomised controlled trials have not been performed. Ernst says, “Randomisation is only ethical if there is substantial uncertainty about the best treatment for that patient.”1 Applied to the recovery of vision with spinal manipulation, this ethical principle prevents any randomised trials from being performed in studying that phenomenon. In 1992, I sent 12 consecutive patients demonstrating constricted visual fields to four senior fellows of the then Royal Australian College of Ophthalmologists. The patients were examined by those consultant scrutineers, who agreed that the visual fields were constricted in all occasions. The patients were seen at independent locations, and I was present only on one occasion. The patients were then treated by spinal manipulation under anaesthesia, with immediate recovery of the visual fields being noted on wakening from anaesthesia.2 This recovery of vision merely reiterated many earlier anecdotal demonstrations.3-5 In every case, the scrutineers agreed that the vision had recovered when, at an independent location subsequent to the treatment, they saw the patients. Further, when Stephens and his associates, including me, treated 17 patients by outpatient chiropractic spinal adjustments, that entire group showed immediate improvement in the visual fields, as measured by computerised static perimetry.6 Sletteberg and his associates found that 55% of patients with constricted visual fields of the type under discussion still had the visual disability on re-examination on a mean review period of 7 years after orthodox treatment.7 Kathol and his associates also found that 55% of these patients still had the visual disability at a mean review period of 4 years.8 When the 100 per cent improvement obtained by spinal manipulation is compared with results of orthodox medical treatment (45% improvement at mean review periods of 7 and 4 years), it is clear that spinal manipulation is more effective than orthodox medical treatment, so much so that to repeat the experiment would be unethical. In my personal experience, the main obstacle to research of complementary medicine precepts has been the censorship of dissenting data from orthodox medical literature. The most blatant example of this is the studied neglect of the “tunnel vision information”: the knowledge that vision improves in appropriately ill patients when the spine is manipulated.

R Frank Gorman

Edzard Ernst Director, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, UK. Edzard. ErnstATpms.ac.uk In reply: Gorman’s story is characteristic of complementary/alternative medicine (CAM): someone makes an observation inconsistent with current medical teaching, and subsequently becomes convinced that therapy X is “100 per cent” effective. Yet clinical trials are never conducted and therapy X assumes somewhat of a cult status. Its proponents name various reasons why clinical trials are unavailable. In some instances (not in the case of spinal manipulation for recovery of vision), clinical trials do eventually emerge. These show that therapy X does not work. Proponents view this as a confirmation of their conspiracy theory. Eventually the cult status of therapy X becomes established. This dangerous scenario would be avoidable if CAM proponents understood the role of science in testing emerging treatments. It is, of course, not unethical to conduct a randomised trial on spinal manipulation for recovery of vision. Sure, randomisation is only ethical if there is uncertainty, but to deny that uncertainty exists is unreasonable — as is the notion of “censorship of dissenting data from orthodox medical” journals. Gorman’s reference list shows that even CAM journals have resisted publishing the effects of spinal manipulation on vision recovery. My conclusion is simple: science and medical publishing follow certain rules for good reasons. CAM should learn to follow them.

Edzard Ernst

Vivian Lin President, Chinese Medicine Registration Board of Victoria, PO Box 5088, Alphington, VIC 3078. adminATcmrb.vic.gov.au To the Editor: The Chinese Medicine Registration Board of Victoria would like to provide updated information relevant to the debate on the article by Parker.1 All practitioners of acupuncture and Chinese herbal medicine in Victoria are now legally required to register. The Chinese Medicine Registration Act 2000 (Vic) specifically includes transitional arrangements, and the Board has developed a “grandparenting policy” for assessing registration applications until 31 December 2004. There are six key assessment areas for all applicants: adequacy of qualification (minimum requirements); recency of practice; competence; good character; fitness to practise; and having the required professional indemnity insurance, first aid and effective communication arrangements. Details are available at www.cmrb.vic.gov.au. To date, 740 practitioners have become registered, and 11.5% of applicants have had a registration refusal or conditions imposed. After the grandparenting period, new applicants will be required to complete an approved course or pass an examination set by the Board. The Board will consider advanced diploma courses for approval up until December 2007, after which the minimum level will be a bachelor degree. Complaints are handled according to the Act, which is modelled on the medical (and other health) practice Acts. The current Victorian model dictates that the Board include two non-practitioners, one legally qualified member and six practitioners with a minimum of 5 years practice experience. Very specific steps must be taken in dealing with complaints, and 28 complaints have already been investigated. The issues of concern include infection control, advertising, professional ethics and communication with patients. Other boards (not medical practitioners) have asked us to assist with endorsement of their registrants, mainly for acupuncture. The Medical Practitioners Board of Victoria plans to ask medical practitioners seeking endorsement for Chinese herbal medicine to register directly with us. We hope this information will help contribute to informed debate on the regulation of complementary and alternative medicine.

Vivian Lin

Walter James (“Bill”) Skinner died of melanomatosis on 12 July 2003, aged 88, after a long illness. Born on 3 April 1915, he was educated at Waverley College, Sydney, and studied medicine at the University of Sydney, graduating in 1940. After working as a Resident Medical Officer at St Vincent’s Hospital, Sydney, Bill enlisted in 1941 in the 2nd Australian Imperial Force. He served as a Medical Officer in the Middle East with an artillery regiment and later had various postings in the Papua New Guinea campaigns. In 1942 he married Dorothy Magee, a St Vincent’s nurse. After the war, Bill worked in country general practice in various places, including Taree, NSW, and southern Queensland. In 1955, he bought a practice in Windsor, NSW, and also the famous, historic “Doctor’s House” in Windsor’s Thompson Square. Bill practised in the Hawkesbury area for some 36 years. He was a foundation member of the Nepean–Hawkesbury Local Association of the British Medical Association (NSW) Branch, and a long-serving Secretary of the Honorary Medical Board of the Hawkesbury District Hospital. For most of his years as an Honorary Medical Officer there were no resident medical staff, so Bill and his colleagues were responsible for all emergency and in-patient care. For many years he performed most of the anaesthetics for his colleagues’ patients as well as having a very large obstetric practice. Bill’s high principles and ethics, and his loyalty to the Anglican Church, to his profession, and to his colleagues and many patients made him a highly respected member of the community. He had hoped, in retirement, to have time for his great love — cricket. His idea of a perfect day was to be in the members’ stand watching a good game of cricket and having a leisurely lunch of a bottle of beer with two cold Sargent’s meat pies. Bill is survived by his children Elizabeth, Mary and Stephen.

John J G Bain MB BS, FAMA, JP

Whiplash and other useful illnesses. Andrew Malleson. Montreal: McGill-Queen’s University Press, 2002 (viii + 527 pp). ISBN 0 773 52333 2. Andrew Malleson is a septuagenarian Canadian psychiatrist, recently retired from years of giving medicolegal opinions and reviewing sufferers of whiplash. His Herculean task was to complete this laboriously researched book — an eye opener, presented in a most readable and interesting manner. It is as unique in style and presentation as the subject is controversial. That Malleson has a view against the organicity of whiplash is manifestly clear throughout this excellent book, and his experiences and attitudes permeate chapter after chapter. He offers many well presented arguments towards his conviction that whiplash is a fabricated illness, propagated by the legal, and other, systems. We are left with little doubt that he is probably right. He does not acknowledge much evidence for whiplash (perhaps there is none); the little presented is refuted completely, with little respect. The book is organised into several parts, with eccentric title chapters such as: Whiplash: head injury or legal headache; Lawyers, junk science and chicanery; and Copycats and fashionable illnesses. The information presented does not always flow in a logical fashion. It is extensively referenced, and detailed annotated notes are provided in a separate chapter. This causes some difficulty in crosschecking. At the end of the day, these minor points make little difference to the appreciation of the powerful message he presents. Whiplash is highly topical and has many stakeholders in medical, legal and social frameworks. That makes this book of interest to professionals across a range of disciplines. It is highly relevant to every musculoskeletal practice. A number of Australian authors are quoted in this book, as much local research has contributed to the controversy. At $66.00, this book is good value for money. Phillip C VecchioRheumatologist Princess Alexandra Hospital Woolloongabba, QLD

Phillip C Vecchio

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

W Peter Saul

Family focused grief therapy. David W Kissane, Sidney Bloch. Buckingham: Open University Press, 2002 (xviii + 254 pp). ISBN 0 335 20349 3. The mental health consequences of bereavement have long been recognised. However, the family context of grief has been relatively under-addressed and there is a limited research base to guide clinical interventions. The authors of this text have internationally recognised expertise in psychotherapy (including family interventions) and palliative care. They both have substantial clinical and academic backgrounds in psychiatry, and have a substantial body of innovative research in Australia into the psychological and psychiatric aspects of oncology and palliative care, including bereavement. Family focused grief therapy provides a scholarly overview of the research and theoretical basis of our current understanding of the impact of bereavement on the family. This work is highly relevant to many areas of healthcare and is particularly innovative in applying preventive approaches involving careful clinical screening and assessment of a family’s functioning and coping. Kissane and Bloch’s work identifying high-risk patterns of family interaction is an important and an internationally recognised contribution to this field. The authors successfully link a research framework and a strong theoretical base with practical clinical interventions to address a problem that frequently challenges clinicians. The provision of detailed clinical vignettes deepens the scope of the book and encompasses the complexities of family life and the realities of clinical practice. The examples are relevant to the broad range of cultural issues for families in the Australian community. The vignettes appropriately and sensitively recognise the multiple problems that many families contend with, but, at the same time, utilise an approach that recognises family resources. By doing so the authors walk an appropriately balanced path between acknowledgment of the significant adverse consequences of grief for families and individuals, and the resilience of many families. Underpinning this is the philosophy that family functioning and coping can be enhanced to protect the individuals who comprise the family, and that there are patterns of family functioning that can hinder recovery from bereavement. As a whole, the book demonstrates the relevance and importance of mental health approaches to this very broad area of healthcare, and the contribution that can be made by bridging the fields of psychotherapy and palliative care. While the book would be of particular interest to professionals working in oncology and palliative care, the research methods, the nature of the intervention, and the understanding that this work brings to family work, are likely to be of interest to a very broad range of clinicians. By bringing research into clinical practice, the authors have made a major contribution to this field. Brian J KellyPsychiatrist, St Vincent’s Hospital Darlinghurst, NSW

Brian J Kelly

Science for citizens Members of the general public (as well as politicians and journalists) need to understand their world, their bodies and how decisions can be made and tested rationally, according to an international expert. A personal paper by Baron says that, to achieve this understanding, they are going to need a better grasp of basic scientific principles. Above all, they need to appreciate that if event B follows event A, then B is not necessarily caused by A. It wouldn't hurt if members of the scientific community, too, kept this in mind when discussing their own research findings. J R Soc Med 2003; 96: 509-511 Practice makes perfect? An author from the US National Quality Forum says there is now enough evidence to insist that patients about to undergo high-risk elective surgery require specific information about outcomes of their surgeon’s other patients before giving informed consent.1 Dr Kizer was commenting on the findings of a US study of eight types of procedures performed in 474 108 Medicare patients aged 65 years or older in 1998–1999.2 The procedures were either cardiovascular (eg, coronary artery bypass grafting) or cancer resections (eg, lung resection). For all procedures, patients treated by "high-volume" surgeons — those who performed the procedure more frequently — had lower operative mortality rates. 1. N Engl J Med 2003; 349: 2159-2161 2. N Engl J Med 2003; 349: 2117-2127 Troubled youth Sydney researchers are concerned that children and adolescents presenting to emergency departments in Western Sydney with aggression (verbal or physical aggression to property or others) and self-harm are currently receiving limited follow-up despite being at risk of further self-harm and increased mortality.1 The researchers’ retrospective review of five years’ worth of medical charts suggested that part of the problem may be that these presentations mostly occur after working hours or on weekends, when there are usually many other urgent clinical demands to be met. An editorialist commented that access to specialist mental health services is generally poorer for children and adolescents than adults across Australia.2 1. J Paediatr Child Health 2003; 39: 651-653 2. J Paediatr Child Health 2003; 39: 645-646 Shifting the Pap paradigm In years to come, human papilloma virus (HPV) testing may become the primary screening tool for cervical cancer, with cytology reserved for triaging women who test HPV-positive, say UK researchers.1 The HART (HPV in Addition to Routine Testing) study, a multicentre screening study of 11 085 women aged 30–60 years, determined that HPV testing is 20% more sensitive than cytology in detecting high-grade lesions, but carries a 5% penalty in extra false-positive results.1,2 1. Lancet 2003; 362: 1871-1876 2. Lancet 2003; 362: 1866-1867 Echinacea: not for cure, perhaps for prevention A randomised controlled trial involving more than 400 healthy children has found an echinacea species (Echinacea purpurea) to be no better than placebo in treating upper respiratory tract infection (URTI). Further, echinacea use was associated with an increased risk of rash. However, the US researchers noted that, over a 4-month period of study, children in the echinacea group had fewer second and third URTIs than those in the placebo group. They found this result intriguing and deserving of further study. Although on the one hand the finding may be spurious, on the other it is conceivable that echinacea stimulated an immune response in children — too late to modify the URTI for which it was given but providing protection against a subsequent URTI. The active medication used in the study was the dried, pressed juice of the above-ground plant, harvested at flowering time and combined with syrup. JAMA 2003; 290: 2824-2830 The return on INVEST INVEST (International Verapamil–Trandolapril Study) researchers have reported that, in terms of measured morbidity and mortality outcomes, a calcium antagonist-based treatment strategy is equivalent to a β blocker-based strategy in managing hypertension in patients with coronary artery disease.1 INVEST was a randomised controlled trial of 22 576 patients at 862 sites in 14 countries, with a mean follow-up period of 2.7 years per patient. An editorialist said that, as INVEST was a comparison of two combinations of three drugs, it was virtually impossible to draw conclusions about the contribution of any single agent.2 He said that perhaps the message of the study was that verapamil and atenolol may be equally suitable additions for appropriate patients already taking both a diuretic and an ACE inhibitor. 1. JAMA 2003; 290: 2805-2816 2. JAMA 2003; 290: 2859-2861 — Dr Ann Gregory, MJA

Ann Gregory