Volume 182 Issue 11

Trial registration, transparency and less reliance on industry trials are essential Over the past 20 years, politicians, hospital administrators and university deans have encouraged academic researchers to increase their participation in projects sponsored by the pharmaceutical industry, and the industry’s share of biomedical research has increased dramatically in that time (from 32% to 62% in the United States).1 Increasingly, the wisdom of this development has been challenged. It would be even better if testing drugs in patients was a public enterprise . . . The research agenda predominantly serves the interests of industry rather than those of patients. Surveys have shown that manipulation of clinical trials — whereby, if the results are published at all, the control treatment is disadvantaged by design, analysis, or interpretation2-5 — is common. Even when the results for the active and control therapies are no different, industry-sponsored trials come to a positive conclusion in favour of the sponsor’s drug five times more often than do not-for-profit-sponsored trials.4 This sponsor bias can have serious consequences. A meta-analysis supported by Merck concluded that there was no increased risk of arterial thrombosis with the company’s cyclo-oxygenase-2 (COX-2) inhibitor, rofecoxib.6 However, another meta-analysis, not sponsored by industry, showed an increased risk, which was apparent in publications available to the authors of the industry-sponsored meta-analysis 4 years before the drug was withdrawn because of thromboses.7 Such down-playing of harms in published papers has often required the collaboration, or acquiescence, of academic clinical researchers. It is likely that the widespread use of COX-2 inhibitors has caused thousands of premature deaths. An article by Henry and colleagues in this issue of the journal (page 557) reports important breaches in research integrity in industry-sponsored research, based on the experience of medical specialists in Australia.8 There are several reasons why the prevalence of the problems probably represents only the tip of the iceberg. Firstly, the authors note that their findings are limited by reliance on self-report, and only 39% responded. Secondly, while only about 9% of respondents reported one or more episodes of potentially serious research misconduct, the authors note that this is equivalent to 21% of those who had an active research relationship with industry. Thirdly, the authors did not consider protocol changes to be serious research misdemeanours. They need not be, but we found that at least one primary outcome was changed, introduced, or omitted while research was under way in 51 of 82 trials (62%).5 We think this is a serious problem as, with a median of 27 outcomes per trial,5 one would expect one outcome to become statistically significant by chance, even if the compared treatments were identical. Finally, 2% of respondents in the paper by Henry et al reported changes to study protocols while trials were under way.8 Our study comparing protocols with corresponding publications showed that formal changes submitted to scientific ethics committees are not common, but that informal changes are. We found that 86% of the respondents in a survey of triallists denied the existence of unreported outcomes, despite clear evidence to the contrary — we did not reveal to them until later that we had access to their trial protocols through the scientific ethics committees.5 Research misconduct and bias in intervention research could be markedly reduced if ongoing initiatives to register all trials at their inception, and ensure public access to trial protocols and all data generated by a trial, become successful. The International Committee of Medical Journal Editors have made a very positive and strong move towards this goal. They have agreed that after 1 July, 2005, its member journals, as a condition of considering a trial for publication, will require that it be registered in a public trials registry before patients enter the trial.9 Ethics committees would also have to play a central role to make this happen, and to ensure that commercial considerations will not be allowed to block access to the collected data, whether or not they are formally published. It would be even better, of course, if testing drugs in patients was a public enterprise (whether or not financed by industry) with blinding during data analysis and writing of manuscripts, till everyone involved had approved them.10 This would ensure that commercial influences on trial design, analysis, manuscript preparation and publication would no longer distort our views of the value of drugs and other treatments. It would also ensure that the comparison treatment was relevant, that the outcomes were directly relevant for patients, and that the patient population was relevant (eg, elderly patients in the case of COX-2 inhibitors, who are also those most likely to develop thromboses). A case in point is the publicly sponsored ALLHAT trial, the biggest trial ever performed on hypertension, which showed that the cheapest drug available was also the best.11 It is clear that governments could save money and treat patients better by investing much more in trials and academic trial centres than by relying on industry’s own trials and conclusions. Who would buy a washing machine that is five or 10 times more expensive than other machines just because its manufacturer has compared it with other machines and claims that it is the best? Unfortunately, such absurdities are often seen in health care, and are allowed to happen even in the absence of any direct head-to-head comparisons.

Peter C Gøtzsche MD, DrMedSci

We need to increase our investment to maintain and improve our position in the global knowledge economy Of all human endeavours, health and medical research arguably offers the greatest potential to improve human life. Research discoveries have extended and enhanced our lives, reduced the burden of many diseases in our society, and are changing the shape of health care. In an era of unparalleled promise offered by genomics, bioinformatics, stem-cell technology, biomedical devices, and therapeutic vaccines, the very nature of clinical practice could shift profoundly over the coming decades. There is, however, another very positive outcome of health and medical research — with the right support from government and industry, it could hold the key to Australia’s future prosperity in a global knowledge economy. The reality of this assertion is exemplified by the vibrant biotechnology and pharmaceutical industries so evident in the United States today. This powerhouse status is the outcome of political strategies put into place 25 years ago. The success of these strategies is reflected in a tenfold increase in the number of patents, royalty and licensing fees (amounting to one billion dollars US per year), strong links between academia and industry, and a fourfold increase in corporate research funding.1 Many overseas governments are now emulating this success by promoting the link between a country’s ability to foster and grow knowledge-based industries and its future economic prosperity. Developed countries, such as the US, Japan, Canada and the UK, are also implementing significantly resourced strategies to encourage citizens to become literate in science and technology, cultivate and attract the brightest minds, build infrastructure and capacity in basic sciences and research, develop commercial competence and grow new businesses. In April this year, the European Commission announced it would double its research budget to i70 billion over 7 years to bolster growth and competitiveness, catch up with American and Japanese spending on innovation, and transform the European Union (EU) into a knowledge-based economy.2 This spending is in addition to funds committed by the individual EU member states to support research within their own borders. The UK Medical Research Council (MRC), a taxpayer-funded organisation that supports and promotes biomedical research, lists among its goals “contributing to the wealth of the nation”. In the most recent financial year, the MRC spent nearly £450 million on research and earned about £15 million in licensing revenue. In Australia, the recommendations of the government’s 1999 Health and Medical Research Strategic Review (the “Wills Report”) were based on data showing that Australia had fallen behind other developed countries in its relative funding of health and medical research. The report found that additional investment would reap significant returns over the long term by improving the health of the Australian population, building the economy, and creating valuable jobs.3 Following its acceptance of the report, the government made an historic decision to increase National Health and Medical Research Council (NHMRC) funding over a 5-year period by injecting an additional $614 million, effectively doubling the annual NHMRC budget to about $412 million by 2005.4 State governments have focused on capturing the commercial potential of research outcomes and creating new business and industry. Initiatives like Queensland’s Smart State, BioMelbourne, BioInnovation SA and BioFirst NSW reflect the recognised importance and economic realities of catching the biotech wave. In December 2004, the Australian government released the report of the Investment Review of Health and Medical Research (the “Grant Report”) conducted by a committee of eminent experts from the commercial and research arenas.5 The government initiated this review to determine the impact of the additional investment made in response to the Wills Report and to revisit the Wills Report’s vision and assess if any changes of emphasis would be beneficial. Although it was carried out only 4 years after the government’s decision to accelerate the medical research investment cycle, the Grant Report’s independent assessment of the outcomes and returns generated by health and medical research showed that there had already been some successes, and that further commercial and health care benefits are likely in the near and long term. Two key success indicators are Australia’s comparatively high research productivity and quality, and the formation of 350 new businesses in the biomedical field from 1992 to 2003. Besides recommending continued strong growth in government funding to remain internationally competitive, the Grant Report also suggested that innovative new policies and incentives were needed to encourage greater private industry investment in research, targeting an increase in annual spending in Australia by multinational pharmaceutical and biotech companies from the current about $420 million6 to $1 billion. The Grant Report, completed in May 2004, was not released until December, and it has since slipped off the radar at this crucial time. If the Australian Government takes no further action, we could see Australia quickly drop away from the front-runners in biomedical research and innovation. Even flatline funding would be a reduction in real terms, and would see us fall further behind other countries as their investment and policy environments focus on optimising their leadership position. The Australian community supports increased health and medical research efforts. Research Australia’s annual health and medical research public opinion polls in 2003 and 2004 showed that most Australians wanted to see increased government and industry investment, and are prepared to contribute to that investment themselves.7 In fact, 47% of Australians said they would rather see surplus government funds invested in health and medical research than in tax cuts.8 Securing a strong, enduring, sustainable economic future for Australia requires a long-term view for building on the valuable investment to date. This will be achieved only by continued focus and leadership by national, state and territory governments in partnership with researchers, industry, and the community. Government commitment to the recommendations of the Grant Report would be a good first step towards showing this leadership.

Christine C Bennett MB BS, FRACP MPaed · Michael R Vitale PhD, MBA

We still have no national program for detecting this potentially lethal disorder In 1985, Brown and Goldstein were awarded the Nobel Prize in Physiology and Medicine for unravelling the regulation of cholesterol metabolism in man. A key feature of their work was the elucidation of the molecular mechanism for autosomal dominant familial hypercholesterolaemia (FH), a potentially lethal disorder caused by defective endocytosis of low-density lipoprotein (LDL) cholesterol by its receptor (LDLR).1 This, in turn, led to the development of “statin” drugs, which potently lower plasma LDL cholesterol and reduce coronary heart disease (CHD) mortality. But, 20 years later, what have we achieved in detecting and treating FH? FH is characterised by lifelong marked hypercholesterolaemia (LDL cholesterol > 5 mmol/L) that leads to tissue cholesterol deposition — in such forms as tendinous xanthomata (particularly involving the Achilles), corneal arcus and palpebral xanthomas — and greatly increased risk of fatal CHD.2 Unfortunately, most people with FH are at present undiagnosed or only diagnosed after their first coronary event. We estimate that, of the roughly 40 000 cases of FH in Australia, about 20% are diagnosed and less than 10% are being adequately treated. Atherosclerosis in FH begins in early childhood. Children with FH are known to have endothelial dysfunction (the earliest phase of atherosclerosis) and increased carotid intima media thickness (CIMT), both surrogate markers of cardiovascular disease.3,4 Carotid atherosclerosis in FH rapidly progresses during childhood, at a rate proportional to plasma LDL cholesterol levels.4 FH typically involves mutations in the LDLR gene, with homozygotes having a more severe phenotype that heterozygotes. To date, about 1000 mutations have been identified in the LDLR gene (www.ucl.ac.uk/fh), most being unique, which makes the search for an unknown mutation challenging and expensive. Although heterozygous FH affects about 1 in 500 people overall,2 it occurs much more frequently in some populations such as Afrikaners, Christian Lebanese and French Canadians2 because of “founder” effects that occur when a few members of a population migrate and start a new colony. FH can be caused by mutations in genes other than LDLR. A mutation in the apolipoprotein B gene (APOB) may result in a clinical and biochemical picture that is indistinguishable from classic FH, although cholesterol levels are generally not as elevated and tendon xanthomas are less common.5 An autosomal recessive form of FH has also been described.6 The clinical picture of this condition is similar to that of homozygous FH, although it is generally less severe and more variable, with greater responsiveness to therapy. Except in “founder” populations, homozygosity for any of these conditions is exceedingly rare (about 1/1 000 000 people), and, without special intervention, such as LDL aphaeresis and liver transplantation, is typically lethal at an early age. Early statin treatment in children with FH improves endothelial function.3 A recent 2-year randomised controlled trial of pravastatin treatment (40 mg daily) in 214 children aged 8–18 years with FH showed regression of carotid atherosclerosis with no adverse effects on growth, sexual maturation, hormone concentrations, or serum liver and muscle enzyme levels.7 Despite this, the long-term safety and efficacy of statin use in children with FH is yet to be established. The Atorvastatin versus Simvastatin on Atherosclerosis Progression trial compared the effect of “aggressive” lipid-lowering treatment in FH with “conventional” lipid-lowering therapy.8 Over 2 years, LDL cholesterol lowering by high-dose atorvastatin resulted in regression of CIMT, whereas reduction with conventional-dose simvastatin did not. Moreover, the change in CIMT was proportional to the reduction in LDL cholesterol. These results support the concept that intensive lowering of LDL cholesterol levels in patients with CHD is beneficial. Although heterozygous FH patients are responsive to statins, additional treatment in combination with statins (for example, statin plus cholestyramine) is often required to achieve the desired LDL-cholesterol-lowering target.9 Moreover, combination therapy often permits use of a lower statin dose, which can benefit patients in whom adverse effects have occurred. Ezetimibe, a new drug that specifically inhibits intestinal cholesterol absorption alone, can reduce plasma LDL cholesterol concentrations by about 18%. Used in combination with a statin, it can achieve a further 25% reduction in LDL cholesterol levels over statin alone, by reducing both cholesterol supply to the liver and cholesterol biosynthesis.10 The long-term effects of ezetimibe on FH cardiovascular morbidity and mortality are unknown. The most cost-effective strategy for finding subjects with FH is to screen close relatives of patients already diagnosed with FH. Screening involves measurement of plasma LDL cholesterol, combined with either a clinical examination and family history or molecular genetic testing.11 Children born to an affected parent have a one in two risk of inheriting FH, and should be screened, at least biochemically, after the age of 2–3 years, when a cholesterol-lowering diet can be safely implemented.12 It is important to appreciate that a normal lipid profile does not rule out heterozygosity for an FH-causing mutation, particularly in early childhood.13 International experience shows that a family screening program must incorporate ethically acceptable protocols for approaching and interacting with relatives, follow-up communication with family members and their health care practitioners, as well as access to genetic counselling services, if required. Despite all these advances, it remains a tragedy that after 20 years of burgeoning knowledge about FH and the parallel development of powerful cholesterol-lowering drugs, Australia does not have a national program for detecting the vast majority of patients with FH in our community, let alone diminishing their risk of CHD.

John R Burnett MD, PhD, FRCPA · David Ravine DM, FRACP, FRCPA · Frank M van Bockxmeer BSc(Hons), PhD · Gerald F Watts DSc, MD, FRACP

Questions of cost-effectiveness, vaccine efficacy and feasibility are yet to be answered In the United States, routine immunisation of all healthy children aged 6–23 months against influenza has recently been introduced. The principal justification for this is the relatively high morbidity and mortality from this disease in very young children.1 The United States is also considering routine influenza immunisation of all children aged over 6 months, in view of the herd protection it would provide to the adult population. Currently, Australian guidelines recommend immunisation of children in groups considered at high risk of severe influenza.2 Should Australia introduce universal childhood immunisation? There is no doubt that children have an extremely high incidence of influenza. It is estimated that, on average, 20%–43% of children are infected during typical influenza seasons.3-5 The incidence is highest in young children less than 2 years old, who are often hospitalised.1,3-5 The mortality due to influenza in infancy is second only to that in the most elderly patients.1 In the severe 2003–04 influenza season, 143 children died from influenza in the United States, of whom 58 (41%) were less than 2 years old and 65 (45%) had no underlying condition.1 These data emphasise the importance of protecting children with annual influenza immunisation, if feasible. Another reason to consider universal childhood influenza immunisation is herd protection. In what turned out to be an illuminating natural experiment, 50%–85% of Japanese schoolchildren were immunised annually against influenza from 1962 to 1987, but there was no routine immunisation of the elderly. When mandatory immunisation of schoolchildren was relaxed in 1987 and repealed in 1994 (because of doubts about safety and effectiveness), influenza immunisation rates dropped to very low levels. A retrospective study comparing excess mortality from pneumonia and influenza in Japan and the United States concluded that the vaccination of Japanese schoolchildren prevented about 37 000 to 49 000 deaths per year, mostly of elderly people. (This represented about one death for every 420 children vaccinated.)6 In considering the feasibility of universal childhood vaccination, vaccine efficacy is one of the factors that needs to be taken into account. In healthy adults under 65 years of age, inactivated influenza vaccine is 70%–90% effective when the match between vaccine and circulating viruses is close.1 However, the same vaccine may be less immunogenic in children. Studies in children aged 6 months to 15 years show a vaccine efficacy of 31%–91% against influenza A and 45% against influenza B.7,8 However, very few of the studies have examined children aged 6–23 months,9,10 the age group currently recommended for routine influenza vaccination in the United States. An alternative form of vaccine administration is on the horizon — live attenuated influenza vaccines. A recent systematic review10 suggested that live vaccines may be more effective than inactivated vaccines in children over 2 years of age (79% versus 65%). Live attenuated influenza vaccines have been licensed in the United States, and might be more acceptable because they are given intranasally.11 However, live vaccines cost a lot more and are not licensed for use in children under 5 years in the United States (because of limited safety data). They are not yet licensed in Australia for use in any age group. The high morbidity of influenza in children and the likely benefits due to herd immunity do make annual childhood influenza immunisation appear economically attractive. However, against this must be weighed the need to immunise with a new influenza vaccine each year, because of antigenic drift in influenza strains, and the need to give two doses of vaccine to children under 9 years in the first year they are immunised.1,2 In addition, the severity of influenza seasons varies unpredictably from mild to severe, and it costs as much to immunise in a mild year as in a severe one. In the United States, indirect costs (mainly days of work lost by parents) dominate economic analyses supporting the use of influenza vaccines in children.12 In Australia, by contrast, the Pharmaceutical Benefits Advisory Committee considers only direct costs of illness, so it is unlikely that a universal, publicly funded childhood immunisation program could be justified using such cost-effectiveness criteria. There may also be practical problems with attempts to introduce routine childhood immunisation. In 2004–05, the uptake of influenza vaccine for children aged 6–23 months in the United States, when the vaccine was recommended universally, was estimated to be only 48%.13 In Ontario, Canada, where all residents aged over 6 months have been offered free annual influenza immunisation since 2000,14 the 2003 uptake in children was only 27%.15 Parents of unimmunised children were more likely to believe that immunisation resulted in a flu-like illness, caused adverse effects more severe than the disease, or weakened the immune system.15 Such immunisation myths are common, although studies have repeatedly shown inactivated influenza vaccine align="right" to be safe, with low rates of adverse events and the benefits clearly outweighing the risks.1,2,9 Another practical issue is the question of how to fit the vaccine into an already crowded childhood vaccination schedule. In general, annual immunisation against influenza is recommended in autumn at the start of the influenza season; there is no fixed age of administration of vaccine. Implementing universal influenza vaccination would place a substantial extra burden on primary care practices.16 Considering all the available information, I believe that there is currently insufficient reason for introducing universal childhood vaccination for this disease in Australia. There are too many unanswered questions about the cost-effectiveness, efficacy and feasibility of universal immunisation of healthy children, whether infants or school-aged. For the time being, we should maintain a watching brief. Future data emanating from Ontario and the United States may provide us with a clearer answer as to whether large-scale programs of routine childhood influenza immunisation are feasible and effective. Further, if the US experience with live vaccines shows consistent immunogenicity and improved ease and acceptability of administration, live vaccines may yet prove to be a cost-effective way to implement universal childhood influenza immunisation in Australia. One thing is clear: influenza vaccination is most cost-effective for children considered at high risk of severe influenza, such as those with chronic cardiopulmonary and other chronic illness. These children should clearly be vaccinated annually against influenza.1,2 Yet vaccine coverage of high-risk groups aged 2–17 years is only 35% in the United States,13 and probably lower in Australia, although we lack age-specific data. Australian immunisation providers should redouble their efforts to ensure that children at high risk are immunised annually.2 Also, it should be remembered that the Australian immunisation handbook2 does not preclude vaccinating others who are not at high risk. It states that “influenza vaccine should be administered to any person who wishes to reduce the likelihood of becoming ill”.

David Isaacs MD, FRACP, FRCPCH

Health services need state-of-the-art health information systems One could be forgiven for expecting that a nation that cracked the Enigma code, and, more recently, assigned all of its citizens a unique health service number, would possess an enviable health information system that made the planning, delivery and evaluation of medical services a seamless and simultaneously sophisticated exercise. But the United Kingdom is a nation where trains are regularly stopped by snow, leaves and even clouds — the latter apparently because clouds interfere with the onboard geographical positioning systems “talking” to geostationary satellites. The lack of interconnection and compatibility between health service computers is not unique to the UK. While the travails of the UK transportation industry regularly provoke tantrums in the tabloids, the state of the National Health Service’s computing systems is yet another test of the traditional grin-and-bear-it demeanour of the British public. In fairness, the NHS is not alone. But it is distinguished by the UK Government’s plan to inject £5 billion to “wire up” the nation’s health services properly. There are three issues that stalk health industry computing: fear on the part of health professionals (arising from ignorance about computer systems); outdated “hardware”; and lack of interconnection and systems compatibility. When faced with a computer for the first time, many otherwise confident, capable and experienced health professionals are genuinely afraid that a mistake on their part may damage the equipment. And their ignorance is profound — most medical students, for example, do not immediately grasp that entering an individual’s date of birth into an appropriate program allows the system to derive the person’s age. It is a fair bet that basic informatics, beyond searching databases of publications, is still missing from most undergraduate curricula for health professionals in Australia as well as in the UK. In the case of the NHS, after failure to train the “wetware”, the second strand of the Gordian knot is the hardware — there is not enough of it; a good deal of what is available is old and slow; and incompatibility is widespread. In the UK, many non-medical staff members working in community health do not have access to a computer. Their lack of access to email is increasingly a poor economic choice in the face of pay-by-the-minute telephone calls, and the difficulty in locating and coordinating many busy individuals. Difficulties can only mount as continuing care of patients with complex chronic diseases shifts out of hospitals. Recently, there has been a large investment in infrastructure for networking computers, although there remains a need for staff to become more proficient at using the network and demonstrating its value. The lack of interconnection and compatibility between health service computers is not unique to the UK. If one tries to compile a comprehensive register of patients with cancer managed by an Australian teaching hospital, it soon becomes evident that we too have the same informatics diseases. The common experience is that radiology, radiotherapy, histopathology, nuclear medicine, pharmacy and oncology all have different, mutually unintelligible systems, many of which cannot readily be searched for particular diagnoses or keywords. Furthermore, the medical record is still paperbound. In the UK, the persistence of separation between health and social services frequently means not only duplication of records — computers are meant to save time! — but physical duplication of terminals and keyboards. UK primary care, by contrast, is steadily converging on two dominant medical record packages, and an increasing proportion of practices are becoming “paper-frugal”. However, until very recently, the NHS insisted that a patient’s lifelong medical record could only be passed on in hard-copy format when that individual registered with a new practice. The advent of the DICOM (Digital Imaging and Communications in Medicine) standard for medical imaging is slowly stimulating alignment of certain hospital computer systems, but patients transferred as emergencies from local hospitals to teaching hospitals are still likely to have all their investigations repeated at the teaching hospital, as the results obtained at the first hospital can not be accessed electronically from the second. Again, time and money are wasted. Even if there were good, secure internet connections between the various parts of the NHS, finding the right record would still be a challenge, as most sites use their own numbering systems for patients and very few employ the NHS number. This is not a matter of overt, or even covert, resistance, because National Insurance (pension) numbers have to be produced and used regularly in the course of employment and taxation. Rather, there is no structural incentive for either patient or doctor to know or use a long, clumsy number; patients are not denied access to health services if they do not know their NHS number, and doctors do not suffer loss of income for failing to provide it. Consequently, the scope for exploiting the unique cradle-to-grave records — individuals’ NHS files — for planning and running health services better, or for epidemiological research, is surprisingly limited. Special projects in the Oxford region and in Dundee are two of the exceptions, but even the (now rather dated) Oxford Record Linkage Study omits information from primary care. However, collections such as the national General Practice Research Database are slowly becoming more user-friendly, even if they charge for access! Meanwhile, Accident and Emergency Departments, the scene of all the long trolley-waits beloved by the tabloids, remain a computing black hole. Most, but not all, have electronic systems, and what they collect and how they record it are institutionally idiosyncratic. An NHS with state-of-the-art health information systems! Cynics will believe it when they see it — it has all been promised before. Perhaps they’ll read about it while standing in their commuter trains, waiting for the clouds to clear.

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

Objectives: To characterise research relationships between medical specialists and the pharmaceutical industry in Australia.Design and setting: Questionnaire survey of medical specialists listed in the Medical Directory of Australia and believed to be in active practice, conducted in 2002 and 2003.Main outcome measures: Details of medical specialists’ involvement in pharmaceutical industry-sponsored research, and reports of potentially undesirable research outcomes.Results: Of 2120 specialists approached, 823 (39%) responded. Participation in pharmaceutical industry-sponsored research was more commonly reported by those in salaried practice (49%) than those in private practice (33%); P < 0.001. 216 reported that industry had made initial contact, compared with 117 who had initiated contact with industry. 14.0% of respondents reported premature termination of industry-sponsored trials, which they considered appropriate when in response to concerns about adverse drug effects. 12.3% of respondents reported that industry staff had written first drafts of reports, which they viewed as an acceptable practice for “internal” documents only. Of greatest concern to respondents were instances of delayed publication or non-publication of key negative findings (reported by 6.7% and 5.1% of respondents, respectively), and concealment of results (2.2%). Overall, 71 respondents (8.6%) had experienced at least one event that could represent breaches of research integrity.Conclusions: These data indicate a high level of engagement in research between the pharmaceutical industry and medical specialists, including those in private practice. Examples of possibly serious research misconduct were reported by 8.6% of respondents, equivalent to 21% of those with an active research relationship with industry.

David A Henry MB ChB, MRCP, FRCP · Suzanne R Hill PhD, GradDipEpi, FAFPHM · Evan Doran BA, PhD · David A Newby BPharm, PhD · Kim M Henderson BNurs, GradDip(HealthSocSci) · Jane Maguire BA, BNurs(Hon) · Barrie J Stokes BSc, MMath · Ian H Kerridge MPhil, FRCPA, FRACP · Paul M McNeill MA, LLB, PhD · Richard O Day MD, FRACP · Graham J Macdonald MD, FRACP, FRCP

Objective: To review acute spinal cord injuries (ASCIs) in all Australian codes of football (rugby union [RU], rugby league [RL], Australian Rules football [ARF] and soccer) for 1997–2002 and to compare data with those of a 1986–1996 survey.Design: Retrospective review of hospital records, and structured interviews with injured players.Participants and setting: Patients admitted to any of the six Australian spinal cord injury units with a documented football-related ASCI over the period 1997–2002.Outcome measures: Average annual incidence of ASCIs per 100 000 players in the different codes, final Frankel grading of injuries, and wheelchair status.Results: Fifty-two footballers (45 adult men and seven schoolboys) suffered ASCIs between 1997 and 2002. The average annual incidence of ASCIs per 100 000 players was 3.2 for RU, 1.5 for RL, 0.5 for ARF and 0.2 for soccer. While there has been little change in incidence since the 1986–1996 survey, there has been a trend towards less severe injuries in RU and RL, but not in ARF. There have been no scrum injuries in RL since 1996, when the scrum stopped being contested. Seven injuries occurred in RU scrums, six at the moment of engagement of the opposing teams. The incidence of 2-on-1 and “gang” tackles (involving multiple tacklers) in RL is disturbing. Overall, 39% of injured players became permanently wheelchair-dependent.Conclusions: There continues to be good reason to revise the laws of scrum engagement in RU. The laws relating to multiple tacklers in RL should be examined. The insurance cover for injured players is grossly inadequate. The longstanding need for a registry of spinal cord injuries for all football codes regrettably remains unmet.

David J Carmody MB BS · Thomas K F Taylor DPhil(Oxon), FRACS · David A Parker FRACS · Myles R J Coolican FRACS · Robert G Cumming MB BS, MPH, PhD

Objective: To assess the prevalence and causes of vision loss in Australia and to project these data into the future.Design: Synthesis of data from two cross-sectional population-based cohort studies — the Melbourne Visual Impairment Project and the Blue Mountains Eye Study — and extrapolation to the entire Australian population.Setting and participants: 8376 community and 533 nursing home residents recruited between 1992 and 1996 in urban and rural Victoria and New South Wales.Main outcome measures: Age-standardised prevalence of low vision (visual acuity < 6/12) and blindness (visual acuity < 6/60) (both measured in the best eye, with spectacles if usually worn for distance vision), and their causes for the Australian population for 2000 to 2024, projected from Australian Bureau of Statistics population data.Results: In 2004, 480 300 Australians were estimated to have low vision, including 50 600 with blindness. The most common causes of low vision were undercorrected refractive error (62%), cataract (14%) and age-related macular degeneration (10%). The latter was responsible for almost half of all cases of blindness. The numbers of people with low vision and blindness are projected to almost double by 2024.Conclusions: Vision loss in Australia is a much bigger problem than is usually recognised; 76% of low vision is caused by uncorrected refractive error or cataract, both readily treatable. However, the prevention and treatment of macular degeneration poses a major challenge.

Hugh R Taylor AC, MD · Jill E Keeffe PhD · Hien T V Vu PhD · Jie Jin Wang MMed, PhD · Elena Rochtchina MApplStat · Paul Mitchell MD, PhD · M Lynne Pezzullo BEc

Pulmonary embolism (PE) affects 0.5–1 per 1000 people in the general population each year, and is one of the most common preventable causes of death among hospitalised patients. The clinical diagnosis of PE is unreliable and must be confirmed objectively with ventilation perfusion scanning or computed tomography pulmonary angiography. The diagnosis of PE can be reliably excluded, without the need for diagnostic imaging, if the clinical pretest probability for PE is low and the D-dimer assay result is negative. The initial treatment of PE is low-molecular-weight heparin or unfractionated heparin for at least 5 days, followed by warfarin (target international normalised ratio [INR], 2.0–3.0) for at least 3–6 months. Patients with a high clinical pretest probability of PE should commence treatment immediately while awaiting the results of the diagnostic work-up. Thrombolysis is indicated for patients with objectively confirmed PE who are haemodynamically unstable. Percutaneous transcatheter or surgical embolectomy may be life-saving in patients ineligible for, or unresponsive to, thrombolytic therapy. Unresolved issues in the management of venous thromboembolism include the roles of thrombophilia testing, thrombolysis for the treatment of stable PE patients who present with right ventricular dysfunction, and new anticoagulants; and the duration of anticoagulation for first unprovoked venous thromboembolism.

Cindy H Lee MB BS · Graeme J Hankey MD, FRACP, FRCP · Wai Khoon Ho MB ChB, FRACP, FRCPA · John W Eikelboom MB BS, FRACP, FRCPA

Since the human genome was sequenced, there has been intense activity to understand the function of the 30 000 identified genes; attention has now turned to the products of genes — proteins. Proteomics is the large-scale study of the structure and function of proteins; it includes the rapidly evolving field of disease proteomics, which aims to identify proteins involved in human disease and to understand how their expression, structure and function cause illness. Proteomics has identified proteins that offer promise as diagnostic or prognostic markers, or as therapeutic targets in a range of illnesses, including cancer, immune rejection after transplantation, and infectious diseases such as tuberculosis and malaria; it has the potential to allow patient-tailored therapy. Some major challenges remain, both technical (eg, detecting “low-abundance” proteins, and maintaining sample stability) and in data management (eg, correlating changes in proteins with disease processes).

Maria Kavallaris BAppSc, PhD · Glenn M Marshall MD, FRACP

Setting The hospital and the colleges keep sending forms for you to complete about your junior staff. They are variously titled “Assessment”, “Appraisal” or “Evaluation”, but they all look the same. You are confused by the terms and the purpose of the forms and are unsure about how to accurately complete them. Doctors find the terms “assessment”, “appraisal” and “evaluation” difficult and confusing. This is understandable given that there are no agreed definitions and the terms are commonly used interchangeably. As supervisors, we are asked to make judgements on the suitability of junior staff for medical registration, entry into vocational training programs or receiving the fellowship of a clinical college. In short, we are asked to assess junior staff. Clinicians also have roles as teachers and supervisors/mentors.1 As junior doctors both learn and are assessed on the job, they require feedback about their progress in learning outcomes and about their strengths and weaknesses, so that they can plan how to improve. All these processes are integrally linked, as shown by the learning cycle (“Tips 1”).1 Poor understanding of their role in assessing junior doctors’ performance may cause problems for some doctors. Furthermore, many of us have never been appraised or received feedback on how we are doing, yet we are expected to do it for our junior staff. DefinitionsThe following are some working definitions to help clinicians understand the roles and processes:2-6 Assessment: a judgement about how someone’s performance meets defined criteria. The standards are usually set by external bodies (eg, medical boards or colleges), and the result of the assessment will affect progress of trainees in their career. It is also known as “summative” assessment. This means your recommendation to the hospital, medical board or college allows it to decide, “Yes, the trainee can progress to the next stage” or “No, the trainee has not satisfied the criteria”. “Formative” assessment mimics the summative, but the purpose is to “inform” the learner of his or her progress before the summative assessment. Along with the quality of your observations, essential ingredients for accurate assessment are the explicit learning outcomes, which must be clearly stated. The assessment forms used should list the learning outcomes and provide a scale to help assessment. Appraisal: a process that is primarily educational and developmental, in that it reviews current performance and develops plans to address the learning needs of an individual. It is jointly developed by the trainer and trainee and should be seen as confidential and non-threatening. This involves you and the trainee having a discussion about your respective impressions of how the training is going, giving your advice, and jointly developing a plan on how to address any problems. Although similar to a formative assessment, appraisal is usually much broader, including not only criteria that might be listed on the assessment form, but other things such as personal progress, career interests, and how the trainee is coping with the workload, study and family life. Appraisal is a key role of a good supervisor. Giving feedback on how junior doctors are doing and helping them to address concerns increase the likelihood that they will pass their assessment and feel fulfilled in professional life. Evaluation: the trainee’s judgement of the trainer (clinician) or program (hospital, unit). This gives the trainee the opportunity to tell you how good the training program was, enabling you to change and improve your practice. If you really want to know how good you have been as a supervisor, evaluation should be collected, preferably anonymously, at a time that is separate from when you are giving feedback. A clinician who asks, “Why don’t you tell me how you’ve found the training program and then I’ll tell you how you’ve performed” won’t elicit much meaningful information. Conflicts2As clinicians, we appraise and assess the same trainee. The information on which both are based, gathered while we work with the trainee, is the same. It might not be in the candidate’s best interests to reveal in an assessment confidential information gathered during an appraisal. On the other hand, a trainee needs to be honest, open and capable of self-assessment in order to benefit from appraisal. Most of the time there is little conflict between the processes of appraisal and assessment, as our trainees are keen to improve, but occasionally a conflict may arise. For instance, the clinician may be torn between the wish to support and the need to fail a poorly performing trainee, or may be unable to develop a good supervising relationship, which in turn may prejudice the assessment. In such circumstances, we should recognise the conflict and call for external help from, for example, a director of clinical training. Key features of good in-training assessment2-4 and appraisal2,4 are: Clear outcomes and criteria Appropriate timing Accurate evidence Learner input Constructive, regular feedback. Take-home message Assessment is making a judgement about someone’s performance, using defined criteria. Appraisal is an educational process jointly carried out by the trainer and trainee to review progress and plan educational needs. Evaluation is the learner’s judgement of the trainer (clinician) or program (hospital, unit). If conflicts between the clinician’s roles as an assessor and appraiser arise, external help should be sought.

Fiona R Lake MD, FRACP · Gerard Ryan MB BS, FRACP

We report on an elderly couple who presented with a syndrome that included severe generalised tremor and incoordination after eating soup from a damaged can. Black mould contaminating the can was subcultured and the fungus Penicillium crustosum was identified. This fungus usually produces a potent neurotoxin called penitrem A. The couple displayed symptoms consistent with penitrem A ingestion, all of which resolved fully. Penitrem A intoxication has been well documented in animals, but not in humans. Clinical recordsAn elderly couple was admitted to hospital after sudden onset of severe muscle tremors. The husband (aged 89) and wife (aged 84) described an uneventful morning. At about 12:00, they had shared a can of soup and toast, followed by chocolate cake, before catching a bus to the local shopping centre. They noticed the soup had a bitter taste, but dismissed the finding because it was a new brand and type to them. There had been no recent changes to their medications, and no recent exposure to garden sprays, insecticides or pesticides. Patient 1The man was first to develop symptoms. He reported feeling slightly shaky as the bus arrived at the shops at about 13:00. He had difficulty getting off the bus, his legs felt “wobbly” and he had to sit down. He developed uncontrollable shaking throughout the body, and felt sticky and sweaty. Initial assessment by ambulance officers at about 13:10 was that he had severe muscle tremors and was unable to walk, and that it was difficult to understand his speech. He had no nausea or vomiting, and his abdomen was soft. He was diaphoretic, with blood pressure 160/76 mmHg, pulse rate 80 beats/min, respiratory rate 32 breaths/min, and Glasgow Coma Score 15 out of 15. His oxygen saturation level was 85%, improving to 97% with high-flow oxygen. Subsequent assessment in hospital at 13:40 revealed that the patient’s Glasgow Coma Score had fallen to 11. Although his speech was incomprehensible, he was able to obey commands; he also displayed generalised weakness and intention tremor. He remained hypertensive and diaphoretic, but was afebrile. He later recounted (to P R L) that he had thought he was going to die. All symptoms, apart from the intention tremor, had subsided by 16:30. The patient’s medical history included chronic airway limitation, asthma, hypertension, episodic atrial fibrillation, osteoarthritis, a left total hip replacement, and an essential tremor. He had no known allergies. His medications included verapamil, digoxin, aspirin, salbutamol, tiotropium bromide, salmeterol xinafoate, quinine bisulfate prn, paracetamol and rofecoxib prn. His essential tremor remained untreated because of the contraindicated use of β-blockers in asthma. A chest x-ray was unremarkable, but electrocardiography revealed a right bundle branch block. A computed tomography brain scan showed generalised volume loss with no intracranial haemorrhage or early changes of infarction; a small low-density focus present in the right basal ganglia region was consistent with chronic lacunar infarction. The results of haematological and biochemical tests were within normal limits, except for urea (8.7 mmol/L; reference range [RR], 2.5–6.4 mmol/L), white cell count (11.2 × 109/L; RR, 4.0–11.0 × 109/L), and haemoglobin (128 g/L; RR, 130–165 g/L) (red cells were normocytic and normochromic). The patient’s blood glucose level (measured by glucometer) was 7.3 mmol/L (RR, 3.5–8.0 mmol/L). Pseudocholinesterase (13.5 U/mL; RR, 7.0–19.0 U/mL) and serum digoxin (1.5 nmol/L; RR, 1.3–2.6 nmol/L) levels were within normal limits. No urine screen for drugs was carried out. The patient was admitted for observation and investigation. The following day he was lethargic, exhausted, and displayed minimal tremor. He was eventually able to mobilise with the aid of a walking stick, as usual. Patient 2The woman had a similar presentation. She complained of feeling dizzy and shaky, but had no nausea or vomiting. Ambulance officers described her as being anxious, diaphoretic, and with uncontrollable shaking. Her blood pressure was not palpable because of severe shaking, but she was well perfused. She was tachycardic (pulse rate, 110 beats/min, taken from electrocardiographic monitoring), with a respiration rate of 20 breaths/min, temperature 36.5ºC, Glasgow Coma Score of 15, and blood glucose level (measured by glucometer) 7.0 mmol/L (RR, 3.5–8.0 mmol/L). Although she was no longer tachycardic on admission to hospital, she remained anxious and diaphoretic, with a generalised tremor that increased with stimuli (eg, being questioned). Her oxygen saturation level on room air remained above 95%. All symptoms, apart from the intention tremor, subsided by 16:30. The patient’s medical history included a left nephrectomy for calculi, right renal calculi and lithotripsy, chronic airway limitation, asthma, hypertension, and a left-eye cataract. Her medications included hydrochlorothiazide, frusemide, nitrofurantoin, aspirin, trimethoprim, salbutamol prn, beclomethasone dipropionate, quinine bisulfate prn, paracetamol prn, and Macu-Vision tablets (containing ascorbic acid, vitamin E, zinc oxide and cupric oxide). A chest x-ray and electrocardiogram were normal. A computed tomography brain scan showed no abnormality apart from a polypoid density in the inferior maxillary sinus. The results of haematological and biochemical tests were normal, except for urea (9.1 mmol/L; RR, 2.5–6.4 mmol/L) and creatinine (0.13 mmol/L; RR, 0.06–0.12 mmol/L). The level of pseudocholinesterase was within normal limits (18.7 U/mL; RR, 7.0–19.0 U/mL). A urine screen conducted for drugs of abuse (including amphetamines, methamphetamines, benzodiazepines, cocaine, opiates and cannabis) was negative. The patient was admitted for observation, and gradually improved the following day. Follow-upBoth patients were discharged 2 days after admission with a very slight residual intention tremor. When assessed by their general practitioner 2 weeks later, the man had only a mild increase in his usual essential tremor and the woman’s tremor had completely resolved. Identification of mouldThe damaged soup can was retrieved from the couple’s residence on the day of onset of their illness and sent to Food Science Australia for analysis. Examination of the can revealed a dent in the top adjacent to the ring-pull on the lid. There was black mould inside the can at the top near the damaged area, and a small amount on the underside of the lid (Box 1). The mould was subcultured onto three different media suitable for growth of common food spoilage moulds.2 The plates were incubated at 25ºC for 4 days. All plates grew a pure culture of a Penicillium species. The mould was then cultured onto identification media, incubated at 5ºC, 25ºC and 37ºC for 7 days and examined again.2 Both microscopic and colony morphology characteristics identified the mould as Penicillium crustosum. It had typical sporing structures for this species (Box 2), and its colonies on malt extract agar shed spore masses in a manner typical of the species. No mycotoxin analyses were attempted. DiscussionPenicillium crustosum is a common foodborne fungus that causes spoilage in a wide variety of foods, including meat, cereals, nuts, cheese, eggs, fruit, and processed and refrigerated foods. Almost all P. crustosum isolates produce the mycotoxin penitrem A.1-3 Its potent neurotoxic effects have been demonstrated in various laboratory animals,4,5 and naturally acquired intoxication has been reported in sheep, cattle, horses and domestic dogs.4,6-9 In animals, symptoms include ataxia, tremors and severe muscle fasciculations.4-9 Larger doses may cause seizures, massive liver necrosis and death.5 To our knowledge, there has been only one case documented in humans of a tremorgenic syndrome following ingestion of P. crustosum.10 A man who had ingested about 30 mL of beer from a can contaminated with a fungus later identified as P. crustosum developed tremorgenic syndrome. About 4 hours later, he developed headache, vomiting, diplopia, weakness and bloody diarrhoea. After 12 hours he developed a tremor. All symptoms resolved within 30 hours. In this case, the fungus isolated was found to produce the mycotoxin roquefortine, but penitrem A was not reported. The authors acknowledged that the isolate lacked a feature typical of P. crustosum. As isolates of P. crustosum almost always produce penitrem A, it is quite possible that the mould involved in this mycotoxicosis was not actually P. crustosum, but some other closely related species such as P. roqueforti.11,12 Inhalation of mouldy silage was implicated in a similar tremorgenic illness in a 16-year-old male.13 Malaise, fatigue, headache, pyrexia and vomiting occurred within hours, progressing to coarse fasciculations and tremors. Symptoms had resolved by the 7th day. A variety of fungi were isolated from the silage, including Aspergillus and Penicillium, both of which produce tremorgenic mycotoxins. Aspergillus fumigatus, which is particularly common in silage, can produce tremorgenic toxins known as fumitremorgens, but not penitrem A.14 There are strong similarities between the cases we report here and numerous documented cases of penitrem A intoxication in animals. Domestic dogs are at particular risk when they have access to household waste.6-9 P. crustosum also produces the mycotoxin roquefortine,15 whose neurotoxic effects have been implicated concurrently with those of penitrem A in some cases.7-9 However, roquefortine has been found experimentally to be far less toxic than penitrem A.15 The elderly couple experienced a comparatively rapid onset of symptoms, but had no nausea or vomiting. The differential diagnosis included a reaction [from exposure] to either a food toxin or an environmental pollutant such as a pesticide or insecticide. The canned soup was a common source of exposure, and its unusual taste further implicated the can as the toxin source. Although we did not attempt to identify the mycotoxin in the cases reported here, isolates of P. crustosum usually produce penitrem A (in one study, of 308 isolates tested, all produced penitrem A12). The highest levels of penitrem A production by P. crustosum isolates occur in liquid media,11 so the soup can in this case would have provided optimal conditions for mycotoxin synthesis. Unfortunately, none of the implicated soup remained for analysis. Most mycotoxins are heat-resistant and comparatively stable,3 so would have survived the mild cooking process. Visual impairment may have contributed to this illness occurring, in that the elderly couple were not aware that the soup can was damaged and discoloured. Experimentally, penitrem A inoculation has been found to produce a tremorgenic syndrome that leads to convulsions and death when larger doses are given.4,5 Administration of pentobarbitone has been found to be effective in controlling muscle tremors and seizures in animals.7,8 This case study highlights the need to avoid ingesting food from damaged cans. Medical and food-authority personnel should be aware of the possibility of P. crustosum ingestion and its potent neurotoxic effects. Limited reporting of this syndrome in humans suggests that it is either rare or under-reported. 1 Damaged can, showing black mould around lid 2 Sporing structures of Penicillium crustosum* * Scale bar is 10 m in length.

Peter R Lewis MB BS, DipObs, FAFPHM · Michael B Donoghue MB BS, FACEM · Lucy Cook BA(SocSc), RN · Linda V Granger BHSc, MPH · Ailsa D Hocking PhD, FAIFST, FASM

Clinical record A 22-year-old woman who was 12 weeks pregnant presented to a country hospital with uncontrollable nausea and vomiting. This was initially controlled with antiemetics, but over the next 4 weeks, she continued to vomit five to six times a day. She presented again at 16 weeks’ gestation when the vomiting became more frequent, and also complained of poor visual acuity and diplopia of several days duration. At the time, there was no gait disturbance, no change in mentation, nor any associated headache. At this stage she was admitted and treated with intravenous fluids including glucose. One week into her admission, her vision deteriorated and she became confused and unsteady on her feet; she was referred to the Royal Melbourne Hospital. On initial examination in Melbourne, she was normotensive (120/80 mmHg) but drowsy. There was no neck stiffness or rash. She now had a prominent gait ataxia and a corresponding mild lower-limb peripheral neuropathy with absent deep tendon reflexes. Additionally, she had bilateral horizontal nystagmus and poor visual acuity (right, 6/36; left 6/18). There was an associated mild right gaze paresis with intact visual fields on confrontation. There was no pain with eye movements. The results of fundoscopy are shown (Figure 1). Her past history was unremarkable. She did not take regular medications, and this was her first pregnancy. Ultrasonography of the fetus and placenta at 17 weeks’ gestation excluded multiple and molar pregnancy. She did not drink or smoke. Haematological and biochemical test results were largely normal, but her serum levels of creatinine (0.04 mmol/L; normal range [NR], 0.05–0.10 mmol/L) and urea (2.2 mmol/L; NR, 2.5–6.1 mmol/L) were slightly low, and her INR (international normalised ratio) was 2.0 (NR, 0.8–1.2). There were also some elevated levels in her liver function test results: γ-glutamyl transferase, 60 U/L (NR, < 50 U/L); alanine aminotransferase, 486 U/L (NR, < 55 U/L); and bilirubin, 32 U/L (NR, 0–19 U/L). Cerebrospinal fluid (CSF) examination and magnetic resonance imaging (MRI) were also undertaken to exclude intracranial causes. The CSF findings were normal, but the MRI revealed bilateral thalamic lesions (Figure 2). Given the new clinical features and her MRI result, a diagnosis of Wernicke’s encephalopathy was made. Thiamine deficiency was suspected to be secondary to hyperemesis gravidarum. Interestingly, her serum thiamine level was only marginally low at 64 nmol/L (normal range, 66–200 nmol/L). Therapy with pyridoxine, folic acid and intravenous thiamine replacement was commenced. She made a rapid clinical recovery. Visual acuity returned to normal within 3 days and her ataxia, gaze limitation and neuropathy improved. Repeat MRI imaging 7 days later showed moderate resolution of the hyperintensities. Our patient went on to successfully deliver a healthy baby girl at 37 weeks’ gestation. 1 Fundal photographs showing gross papillitis of both the right and left optic discs, respectively. A small retinal haemorrhage is shown in the left eye. 2 Magnetic resonance imaging (T1-weighted, T2-weighted axial, and diffusion-weighted image, respectively), with arrows showing bilateral symmetrical thalamic hyperintensities with restricted diffusion. Bilateral thalamic ischaemia is most often seen in thiamine deficiency. This patient’s rapid response to intravenous thiamine replacement confirms the diagnosis of Wernicke’s encephalopathy secondary to thiamine deficiency. Thiamine, or vitamin B1, plays an important role in carbohydrate metabolism through decarboxylation of alpha-keto acids. Moreover, it also functions as a co-enzyme to the apoenzyme transkelotase in the pentose monophosphate pathway for glucose.1 Low thiamine levels can be associated with poor intake or absorption, increased demand, or poor utilisation. It is well understood that thiamine requirements are increased in pregnancy, and this is thought to be the result of sequestration of the vitamin by the fetus and placenta.2 With hyperemesis gravidarum, the deficiency is further compounded by the impaired absorption related to the intractable vomiting.3 In some situations, prolonged use of intravenous glucose without thiamine can be a potent precipitant of Wernicke’s encephalopathy.4 This phenomenon is well documented,5 and in our patient, might have contributed to the evolving deficiency. Abnormal liver function test results are also seen in Wernicke’s encephalopathy, and it is possible that hepatic derangement may have also played a pathogenic role in the evolution of our patient’s disease. 6 Our case is unusual in that visual deterioration was the first symptom of an evolving thiamine deficiency. There was a delayed presentation of the classical triad of Wernicke’s encephalopathy — ataxia, mental confusion and ocular gaze problems. Moreover, in our case, MRI scanning was able to detect sensitive neurological changes, raising the suspicion of thiamine deficiency. This information was important in prompt treatment of the condition when clinical signs began to emerge. Indeed there are reports of the usefulness of MRI imaging in diagnosing cases of Wernicke’s encephalopathy.7 Our patient’s vitamin B1 level was only mildly reduced, but this may have been the result of partial correction with food intake while an inpatient at the country hospital. Unfortunately, intracellular thiamine levels could not be measured before replacement. Intracellular thiamine level is usually a more accurate marker of thiamine deficiency, measured as erythrocyte thiamine diphosphate by high pressure liquid chromatography, and is often abnormal in such cases of Wernicke’s encephalopathy, even when the serum thiamine level is normal. If left untreated, thiamine deficiency can lead to severe neurological, cardiovascular and gastrointestinal sequelae. If not treated, the result is often death. Delayed correction of low thiamine levels may lead to persistent nystagmus, ataxia and poor concentration with multiple tasks.8 For the fetus of an affected mother, slow in-utero development is possible. Ophthalmic symptoms may include subacute, progressive visual loss, with central field defects and associated poor colour vision. Papillitis can be seen in cases of nutritional optic neuropathy. In severe cases, blindness may occur as a result of complete optic atrophy.9 As thiamine deficiency has severe consequences, we believe that vitamin B1 replacement should be considered in all pregnant women with hyperemesis gravidarum. We further suggest that in such cases MRI imaging may play an important role in early diagnosis. Lessons from practice Visual deterioration may sometimes be the first presenting sign of thiamine deficiency. The visual symptoms of Wernicke’s encephalopathy are reversible with prompt administration of thiamine. Early correction of thiamine deficiency is essential in all patients with hyperemesis gravidarum. Intravenous glucose should be given together with thiamine for patients being treated for hyperemesis gravidarum. The best laboratory measure of thiamine deficiency is erythrocyte thiamine diphosphate by high pressure liquid chromatography. Magnetic resonance imaging may help in early diagnosis of patients with Wernicke’s encephalopathy where optic neuropathy is the first clinical sign.

Mervyn D Ferdinands MB BS(Hons) · Janaka Seneviratne FRACP · Owen White MD, PhD, FRACP

Minor injuries in children (those that could reasonably be expected to heal with minimal medical intervention) are extremely common. The possibility of more serious injuries should be considered and excluded early. Successful examination requires gaining the child’s trust, relieving pain early, and using a flexible and creative examination technique. Bruising may suggest a more serious underlying injury, or the bruising pattern may indicate non-accidental injury or a bleeding disorder. Superficial abrasions and lacerations can be safely cleaned with good quality water, and all foreign material should be removed. Deeper wounds with suspected damage to nerves, tendons or circulation need formal exploration under a general anaesthetic. Good local anaesthesia can be produced by topical preparations, and many wounds can be closed with tissue adhesives with an excellent cosmetic result. Antibiotics should be prescribed for specific circumstances, such as wounds with extensive contamination or tissue damage, and all children with injuries should be checked for adequate tetanus cover for prophylaxis.

Simon J Young MB BS, DipCrim, FACEM · Peter L J Barnett MB BS, FRACP, FACEM · Ed A Oakley MB BS, FACEM

Elizabeth A Hender,* Corrine R Balit† * Scientific Officer, Hazardous Substances Section, Environmental Health Service, Department of Health, PO Box 6 Rundle Mall, Adelaide, SA 5000; † Research Pharmacist, New South Wales Poisons Information Centre, The Children’s Hospital, Westmead, NSW. elizabeth.henderAThealth.sa.gov.au To the Editor: Although there are few deaths due to poisoning in Australian children, from 1993 to 1997 there was an average of more than 2500 admissions to hospital per year for assessment of poisoning with medicines in children younger than 5 years.1 Child-resistant packaging has been effective in preventing accidental poisoning with prescription medicines and aspirin in young children in the United States.2,3 In the US, both reclosable and non-reclosable (blister or strip) packaging used for pharmaceuticals required to be in child-resistant packaging is tested to confirm its effectiveness in preventing access by children.4 In Australia, only reclosable packaging is required to be child-tested. Blister or strip packaging, which has not usually been child-tested, is accepted as an alternative to child-resistant reclosable packaging.5 We conducted a study at the New South Wales Poisons Information Centre (NSWPIC) over 9 weeks from 18 July to 17 September 2003. Our aims were to ascertain which medicines children younger than 5 years access directly from blister or strip packaging, and whether assessment at a hospital was recommended. The study was approved by the Ethics Committee of the Children’s Hospital, Westmead. Callers ringing about a suspected accidental ingestion of a solid dose medicine in a child younger than 5 years were asked whether the child accessed the medicine directly from a blister or strip pack. There were 318 accidental exposures to solid dose medicines in these children during the study period. In 186 exposures (58%), the caller said the medicine was normally in a blister or strip pack and the child obtained it directly from the pack. A wide range of medicines (40 different drugs or drug groups) were associated with the exposures; the most common were oral contraceptives (49 exposures) and paracetamol (27 exposures). Some of the exposures involved medicines that can cause severe toxicity when children ingest a small number of dose units, such as clonidine, olanzapine, narcotic analgesics, and tricyclic antidepressants. In 36 exposures where the child obtained the medicine directly from the pack, the caller was advised to take the child to hospital (Box). Many of the medicines associated with these exposures (eg, paracetamol, preparations containing narcotic analgesics, antidepressants, antihistamines, iron and clonidine) are required to be in child-resistant packaging.5 Our study shows that blister or strip packs currently in use did not prevent children accessing drugs. This finding calls into question whether blister or strip packaging that has not been child-tested presents an adequate safety barrier. No outcomes of drug ingestion are known in this study, which is a limitation. However, assessment of these children in hospital represents a financial burden to the health care system regardless of the outcome. Further studies would be required to quantify the harm associated with exposures to medications packaged in blister or strip packaging in young children and to assess the effectiveness of such packaging in the prevention of poisoning. Drugs accessed from blister or strip packs where child required referral to hospital Drug or drug group Number of exposures Paracetamol 8 Paracetamol/narcotic combination analgesics 3 Selective serotonin re-uptake inhibitors 3 Antidepressant: other/unknown 2 Antiemetics 2 Antihistamines 2 Cough/cold preparations, no paracetamol 2 Iron 2 Other (eg, clonidine, olanzapine) 12 Total 36

Elizabeth A Hender · Corrine R Balit

Timothy C Crowe,* David Cameron-Smith† * Lecturer, † Senior Lecturer, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC 3125. tcroweATdeakin.edu.au To the Editor: Low-carbohydrate diets have re-emerged into the public spotlight and are enjoying widespread popularity. However, current evidence indicates that low-carbohydrate diets have no significant advantage over more traditional energy-restricted diets for long-term weight loss and maintenance.1-3 While these diets have shown short-term efficacy in modifying some lipid parameters and measures of insulin sensitivity, questions remain about the risk of adverse effects with long-term carbohydrate restriction.4 The scientific literature has not addressed the questions of how the general public perceive these diets, and what dieting approaches they adopt. Dieting perceptions and practices within the community may be far removed from the strictly controlled situation of published research. A national telephone survey of 1200 adults aged 18 years and over was conducted by the private market research company Newspoll from 6 to 8 August 2004. The survey asked about knowledge of and attitudes to carbohydrates and dieting. Telephone numbers were randomly selected, with a quota for capital city and non-capital city areas. Selection of an individual in each household was based on the last birthday. Response rate to the survey was 11%. Sex, age, marital status and working status demographics were representative of the Australian adult population. The main findings are summarised in the Box. Most of those surveyed correctly identified foods such as pasta and bread as “carbohydrate foods”. Only a third of people identified soft drinks and lollies as carbohydrate foods, and 20% incorrectly identified cheese and eggs as carbohydrate foods. Almost 17% of people had either tried, or intended to try, a low-carbohydrate diet, with women more likely to have tried this diet. Half of those surveyed believed that carbohydrate foods should make up a quarter or less of the daily diet (current health recommendations are that about half the diet should comprise carbohydrates). Almost 70% of those surveyed believed they needed to cut back on carbohydrates to lose weight. Based on this survey, low-carbohydrate dieting practices are as widespread in Australia as in the United States.5 Interestingly, the US study noted a greater propensity to use carbohydrate-reduced diets among those who were obese, had diabetes, hypertension or high cholesterol. Our data demonstrated widespread misunderstanding of what constitutes a high-carbohydrate food, which may leave many individuals at risk of choosing a diet that selectively excludes wholegrain foods, fruits and some dairy products. Health professionals should be aware that low-carbohydrate diets remain popular, that the people who are following these diets may represent a more “at risk” population, and that the food choices made by those following this dietary pattern may have adverse long-term health effects. Respondents’ knowledge of and attitudes to carbohydrate foods and low-carbohydrate dieting Question Total (n = 1200) Men (n = 600) Women (n = 600) Which of the following foods, if any, do you regard as carbohydrate foods? Bread 89% 85% 93% Pasta 90% 88% 93% Rice 80% 76% 83% Breakfast cereal 79% 77% 80% Lollies 35% 36% 35% Soft drink 34% 31% 36% Cheese 20% 22% 19% Eggs 18% 20% 16% Have you tried or do you intend to try the Atkins diet, or some other low-carbohydrate diet? 17% 11% 22% Based on official recommended guidelines for a healthy diet, about how much of a person’s diet should be made up of foods such as bread, breakfast cereal, pasta and rice? Less than a quarter 7% 7% 7% About a quarter 43% 34% 51% About half 29% 31% 26% About three quarters 6% 8% 4%

Timothy C Crowe · David Cameron-Smith

Ian W Boyd Executive Officer, Adverse Drug Reactions Unit, Therapeutic Goods Administration, Australian Government Department of Health and Ageing, PO Box 100, Woden, ACT 2606. ian.boydAThealth.gov.au To the Editor: Labate and colleagues note that tramadol is the most frequently suspected cause of provoked seizures at their First Seizure Clinic.1 Early in 2003, the Adverse Drug Reactions Advisory Committee (ADRAC) reported to Australian prescribers the results of the first 4 years of experience with tramadol in Australia.2 At the time, ADRAC noted that 26 cases of convulsions had been reported among a total of 354 reports on tramadol. By January 2005, ADRAC had received a total of 921 reports involving tramadol, of which 66 described convulsions. (Labate et al reported that 83 cases of convulsions associated with tramadol had been reported to ADRAC. This is incorrect, but the mistake probably resulted from an error in interpretation of information supplied by the Adverse Drug Reactions Unit.) In 27 cases, tramadol was the only suspected drug, but in the other 39 cases there were various other suspected drugs. This included 20 reports in which there was a suspected drug interaction. Both oral and injected tramadol have been implicated. The product information for tramadol states that convulsions have been reported in patients using tramadol at the recommended dose levels and that the risk may be greater when doses of tramadol exceed the recommended limits.3 In addition, tramadol may increase the seizure risk in patients taking other medications that lower the seizure threshold. Drugs specifically mentioned in this context include the selective serotonin reuptake inhibitors, tricyclic antidepressants and antipsychotic drugs. In the 39 cases reported to ADRAC in which there were one or more suspected drugs in addition to tramadol, tramadol was being used with selective serotonin reuptake inhibitors (10 cases), tricyclic antidepressants (6 cases) and, in 13 cases, other drugs that may also have the potential to lower the seizure threshold, such as pethidine (2 cases), venlafaxine (2), propofol (2) and bupropion (2). In two of the cases in which tramadol was the only suspected cause and two of the cases with multiple suspected causes, the patients were also taking anticonvulsant drugs for seizure control. ADRAC data indicate that, although tramadol alone can induce seizures, these are more likely to occur in the setting of the concomitant use of other drugs that also have the potential to lower the seizure threshold.

Ian W Boyd

Graham R Wicks Medical Hypnotherapist, Department of Psychological Medicine, Women’s and Children’s Hospital, North Adelaide; 9 Collins Street, Collinswood, SA 5081. grwicksATbigpond.net.au To the Editor: I was interested to read the article about managing nocturnal enuresis in children,1 but was surprised and disappointed that there was no mention of the place of medical hypnotherapy. Hypnotherapy can be particularly valuable in the treatment of monosymptomatic nocturnal enuresis in children aged from 7 or 8 years upwards, and has the advantage of being completely non-invasive with no side effects. It focuses on empowering the children to take control of their own bodily functions.2 Hypnotherapy is also of value in the management of nocturnal enuresis associated with day-time symptoms, such as urgency with or without incontinence, and can also be used to enhance the efficacy of treatments like enuresis alarm systems. While there are few well documented comparative studies3 on the benefits of hypnosis versus other treatments for nocturnal enuresis, there are numerous anecdotal reports and studies involving a series of patients being successfully treated with hypnotherapy. Hypnosis should only be used by properly trained doctors or psychologists who have access to the full range of medical investigations. Hypnosis is of course not a panacea, but is an excellent first-choice treatment for monosymptomatic nocturnal enuresis, the commonest type seen by general practitioners. If, after three or four treatment sessions, hypnosis is not effective, other approaches can be employed. A quick search of the internet using the terms “enuresis and hypnotherapy” will reveal over 700 sites with information on the subject, and there are several highly respected professional journals that publish clinical and research papers and articles on the use of hypnosis in medicine and psychology. All of these are published by reputable professional societies whose membership is limited to registered health professionals. The Australian Society of Hypnosis (http:// www.ozhypnosis.com.au) conducts ongoing training courses in all states of Australia for graduates in medicine, psychology and dentistry. Hypnotherapy is now becoming more and more accepted worldwide as a valuable and legitimate tool that can be used, in conjunction with the more traditional approaches, in a wide variety of medical and psychological problems. It is a great pity that many clinicians are either not aware of its value or are still loathe to accept it because of negative connotations associated with its use for entertainment purposes and in the hands of non-professional therapists.

Graham R Wicks

Patrina H Y Caldwell,* Denise Edgar,† Elisabeth Hodson,‡ Jonathan C Craig§ * Staff Specialist and Lecturer, † Head, Department of Nephrology, § Associate Professor and Head of Clinical Research, NHMRC Centre of Clinical Research Excellence in Renal Medicine, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, NSW 2145; ‡ Clinical Nurse Consultant, The Continence Foundation of Australia in NSW, Sydney, NSW. PatrinacATchw.edu.au In reply: Thank you for your interesting comments regarding hypnotherapy in the treatment of nocturnal enuresis in children. There are a number of therapies, such as hypnotherapy, electrotherapy and acupuncture, which show great promise for the management of nocturnal enuresis. We only included in our article1 treatments that were supported by evidence from well documented comparative studies. Using comprehensive search strategies, we have not found comparative studies for these complementary therapies. We would be very interested to be directed to studies that have formally evaluated other interventions. There is a huge need for randomised controlled trials comparing alternative treatment strategies with conventional therapy in this area.

Patrina H Y Caldwell · Denise Edgar · Elisabeth Hodson · Jonathan C Craig

Edwin P Kirk,* Annette Hattam,† Anne Turner‡ * Co-ordinator of Advanced Training, † Chair, Specialist Advisory Committee in Clinical Genetics, Royal Australasian College of Physicians; and Geneticists, Department of Medical Genetics, Sydney Children’s Hospital, High Street, Randwick, NSW 2031; ‡ Chairperson, Board of Censors in Genetic Counselling, Human Genetics Society of Australasia. kirkedATsesahs.nsw.gov.au To the Editor: Genetic risk estimation is a key element of the practice of clinical geneticists and genetic counsellors. Given this, it was with some concern that we read the findings of Bonke and colleagues regarding the performance of (mainly European) geneticists and counsellors in the application of Bayesian analysis to risk estimation.1 Bayesian analysis is taught as part of Australasian training in both clinical genetics and genetic counselling, and has been for as long as there have been formal programs. Thus, most Australian geneticists and counsellors should be familiar with the application of Bayes’ theorem to risk estimation. In actual clinical practice, it is rare to need to perform this type of analysis. This is partly because of the rapid progress in molecular genetic testing, which often obviates the need for such calculations, and partly because situations in which Bayesian analysis is clinically helpful are uncommon. Pedigrees like those in the study by Bonke et al do not come along often; when they do, the modification of prior risk by Bayesian analysis is not often important. For example, modification of a risk from 50% to 33% or from 25% to 17% (as in two of the examples used by Bonke et al) is unlikely to alter decision-making for the families involved. Specifically, as these examples all involve testing for Huntington’s disease, in which molecular analysis is usually quite straightforward, we would expect very few individuals would decide whether to proceed with testing based on being given information about modification of risk expressed this way. Moreover, when you are not performing this type of calculation regularly, it is time-consuming to do. It seems possible that many of those who completed the questionnaire would have taken greater care, and achieved greater accuracy, if faced by a real clinical situation. Nonetheless, for those of us who are involved in training clinical geneticists and genetic counsellors, the article is a useful reminder of the importance of this skill, and we will communicate with supervisors to reinforce the importance of teaching Bayesian analysis to our trainees.

Edwin P Kirk · Annette Hattam · Anne Turner

In reply: Geneticists and counsellors must be able to calculate risks according to professional standards, regardless of whether modified risks lead to decision changes. Does training in genetic risk calculation help? Only 21% of our respondents who had had such training recently (< 3 years ago) estimated all target risks correctly. In response to Kirk et al, calculating conditional risks need not be time-consuming in scenarios similar to our target pedigrees,1 and is often helpful when at-risk (grand)parents do not wish to be tested but their offspring do. Given n children at 25% prior risk tested negative and no other (grand)children tested, the conditional risk for at-risk individuals in generation g (with g = 0 at 50% prior risk, g = 1 at 25% prior risk, etc) is 1/[2g(2n+1)]. Thus, in target #4 (n = 1), the father’s risk (g = 0) equals 1/[20(21+1)] = 0.33. In target #9 (n = 2), the unborn’s risk (g = 2) equals 1/[22(22+1)] = 0.05. Similar formulas for more complicated scenarios are available upon request. In calculating risks, however, care must be taken that the pedigrees and target individuals are comparable to our scenarios. In target #7, for instance, the risk for the untested aunt does not increase simply because of the decreased risk for her brother (gambler’s fallacy).2

Benno Bonke · Aad Tibben · Dick Lindhout · Angus J Clarke · Theo Stijnen

Scott Kinlay Director, Vascular Medicine and Endovascular Therapy, Veterans Affairs Medical Center and Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA. skinlayATpartners.org To the Editor: Wang and Hoy1 deserve much credit for highlighting yet again the poor state of health of Indigenous Australians. However, their conclusion that the Framingham equation underestimated risk and that better prediction equations are needed may miss the point. The Framingham equations work well in other populations if the aim is to rank groups of individuals into higher or lower risk categories. Box 4 in the article by Wang and Hoy shows that they do this pretty well across increasing age groups. Framingham equations fall down when they are used to estimate absolute risk in populations whose coronary heart disease (CHD) rates are different from those in the Framingham study. Some years ago, we showed that adjusting the Framingham risk estimates in line with the overall incidence of CHD in the population modestly improved their performance.2 This is all very nice, but is better risk estimation the solution? We don’t estimate risk in other high-risk groups (eg, patients with CHD), because all are at high risk and all need risk factor reduction. A brief look at the risk factor profile in Box 2 of Wang and Hoy’s article reveals an alarming picture of uncontrolled CHD risk factors in a relatively young population (average age, 33–36 years). Cigarette smoking, dyslipidaemia, diabetes and overweight prevail. Perhaps, rather than concentrating on quantifying the exact risk in such a high-risk population, we should look at the reasons for the high rates of risk factors. What motivates some Indigenous people to smoke more, be more overweight and have a higher incidence of dyslipidaemia and diabetes than other Australians?3,4 Do they feel disenfranchised when governments infer they are “dirty” by tying financial aid to face-washing?5 Do they have attractive employment opportunities? Do they have enough sense of control over their lives to reduce their need to indulge in cigarettes and other short-term pleasures? Are there adequate supplies of healthy foods that they like? These factors may differ, as some rural Abori-ginal communities have much lower rates of smoking, overweight and diabetes6 than others. Exploring these issues will aid preventive methods aimed at the whole community. In the meantime, I would suggest that the Framingham equation does rank members of this community — into modest, high, and very high risk (the average 45–54-year-old has a 20% risk of a CHD event over 10 years1). This may help guide the medical treatment of risk factors and the pursuit of the medical model of prevention while social changes dictated by Aboriginal communities take effect.

Scott Kinlay

In reply: We agree with Kinlay that it is important to prevent risk factors at the population level (a population strategy). However, there is also a need to properly identify high-risk individuals who require immediate medical intervention (a high-risk strategy) and to understand the full spectrum of factors that determine such risk. The primary focus of our study was to assess whether the widely used Framingham risk functions were applicable to Aboriginal people in remote communities. Our data show that the Framingham functions significantly underestimated the risk of coronary heart disease (CHD). 1 The high CHD risk in Aboriginal people cannot be fully explained by traditional risk factors. Some major risk factors such as abnormal total cholesterol level and obesity in the study population are actually not as prevalent as those in the general Australian population. 2 Evaluation of traditional risk factors and identification of novel factors in this population are useful for the development of intervention strat-egies. Novel factors such as infection, inflammation, albuminuria and low birthweight have been suggested as predictors of CHD risk in this population. 3,4 Kinlay suggests that Framingham functions should be used to predict CHD risk in Aboriginal people. We disagree. Guidelines for the management of Aboriginal people need to recognise the serious underestimation of risk that the Framingham formulas provide. We agree that some high-risk groups, such as patients with established CHD, do not need additional risk estimates. With our current knowledge, however, we can not say whether the whole Aboriginal community should be treated as a very high-risk population.

Zhiqiang Wang · Wendy E Hoy

Anna Peeters,* Reannan L Cashen,† Paul E O’Brien‡ * Senior Research Fellow, † Honours Student, Epidemiology and Preventive Medicine, ‡ Director, Centre for Obesity Research and Education, Monash University, The Alfred Hospital, Commercial Road, Melbourne VIC 3004. anna.peetersATmed.monash.edu.au To the Editor: We support the warning of Talbot and colleagues regarding the inequities of the current system for provision of bariatric surgery to the morbidly obese in Australia.1 We recently analysed data on the number of separations for bariatric surgery for morbid obesity in Australia. The two most common procedures in Australia are gastric reduction surgery (procedure code 30511, which includes gastric stapling, laparoscopic adjustable gastric banding [LAGB] and gastroplasty) and gastric bypass surgery (procedure code 30512). The number of separations for procedure 30512 has remained quite stable and relatively low (around 200 a year) over the past few years. By contrast, the number of separations for procedure 30511 has been continually increasing. While the exact number of LAGB procedures can not be identified from this single code, it is assumed that the majority of the increase is due to LAGB, as it is a less invasive pro-cedure and therefore generally more acceptable to patients.2 However, the number of separations for gastric reduction surgery in public hospitals is low and has remained so. In the financial year 2000–01 there were 1529 separations for gastric reduction for morbid obesity across Australia, only 194 (13%) of which were performed in public hospitals (see Box). In 2001–02 the total number increased to 2351, but the number performed in public hospitals increased only marginally, to 238 (10% of the overall number). In 2002–03, the last year of available data, there were 2612 separations, of which only 287 (11%) were performed in public hospitals (unpublished data, courtesy of the Australian Institute of Health and Welfare). Clearly, if this issue is not addressed systematically, it will only serve to widen the socioeconomic inequalities in health associated with obesity in Australia. Separations for all gastric reduction surgery for morbid obesity, Australia

Anna Peeters · Reannan L Cashen · Paul E O’Brien

Colleen T Bruce,* Paul S Thomas,† Deborah H Yates‡ * Research Assistant, † Associate Professor, Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW 2033. ‡ Respiratory Physician, St Vincent’s Hospital, Sydney, NSW. Paul. ThomasATunsw.edu.au To the Editor: The recent article by Willcock and colleagues on the high psychological morbidity and level of burnout that interns experience during their first year in hospital highlights an important topic.1 Willcock et al point out that there is an increase in psychiatric morbidity over the intern period in first-year medical graduates. This corroborates the findings of a larger study we conducted among interns during their first year, in which we showed that psychiatric morbidity rises, particularly during the middle of this first year as a doctor, but then decreases by the end of the year.2 The point made by Willcock et al1 is that psychiatric morbidity is not limited to first year graduates — senior doctors are also susceptible to psychological morbidity and burnout.3 Their article highlights the continuing need for workplace reform and support for the medical profession. In addition to reducing working hours, other interventions need to be considered to prepare medical students for their profession, and to reduce the factors which contribute to morbidity (eg, workload, multiple tasking, incessant paging). It should be feasible to test the efficacy of such interventions with the same instruments (such as the General Health Questionnaire) in future generations of interns, and to compare these results with the above studies. Showing that such interventions are effective will provide a strong platform from which to implement wider change in the workplace.

Colleen T Bruce · Paul S Thomas · Deborah H Yates

Simon M Willcock Director, Academic General Practice Unit, Hornsby Hospital, Palmerston Rd, Hornsby, NSW 2077. simonwATmed.usyd.edu.au In reply: Bruce and colleagues are correct to call for ongoing workplace reform and support for the medical profession in general. Our study, which followed medical students to the end of their intern year, did not show a significant fall in psychiatric morbidity towards the end of the intern year as theirs did. Our review of the recent literature suggests that any “improvement” in psychological morbidity after the mid-year peak during internship is likely to be transient, with the early postgraduate period representing a period of transition from normative population values of burnout and morbidity to levels which remain high throughout a medical career, when compared with the general population. The traditional interpretation of the internship as a “baptism by fire”, which tests and ultimately strengthens the new medical graduate, does not hold up to scrutiny. A realistic assessment of this period suggests that it is one where stress and distress often reach unhealthy levels, and where dysfunctional coping strategies may be developed which persist throughout a medical career. The development of mature personal coping strategies along with systemic changes to promote engagement with work have been identified as the most likely means of limiting burnout and its sequelae among medical practitioners.1

Simon M Willcock

Linsey S Hart,* Jane Vernon-Roberts† * AMC Liaison and Resource Officer, Postgraduate Medical Council South Australia, 71 Edward Street, Norwood, SA 5069. † Head of Clinical Studies, Royal Adelaide Hospital, Adelaide, SA. linseyATpmcsa.org.au To the Editor: McGrath’s article on integrating overseas-trained doctors (OTDs) into the Australian medical workforce noted that the areas of difficulty in this area have been well defined.1 McGrath challenged us to “get on with it”. We interpret this challenge to mean that there has been enough regurgitating and redefining of the problem, and it is time for some action. In South Australia, the difficulties of integrating overseas doctors into the workforce mirror those experienced by other states. The Department of Health Overseas Trained Doctor 2004 database listed 93 OTDs as eligible to work in SA. Seventy were employed. All of these doctors had only completed the Australian Medical Council (AMC) Multiple Choice Question (MCQ) examination. Since its inception in April 2003, the Postgraduate Medical Council of South Australia (PMCSA) AMC doctors subcommittee has worked to put in place a number of educational initiatives to support and assist OTDs to complete the Australian Medical Council Exams, and to advocate for their ongoing needs for better orientation to the workplace and protected education time at work. The programs initiated by the PMCSA are both Government-funded and self-funded. They are: culture and medical communication for doctors, MCQ tutorial program, ready for work program, hospital tutorials, objective structured clinical examination practice exam, clinical bridging program, and study groups. Examination results in 2004 for candidates undertaking the PMCSA programs bettered the national average. Of the 16 enrolled participants in the MCQ tutorial program, which ran from January to April 2004, nine sat the May AMC MCQ exam and seven deferred. Eight of the nine passed, giving a pass rate of 89% (AMC pass rate 56%; Australian Medical Council, personal communication). In the AMC clinical examinations, our candidates achieved an overall pass rate of 67%; 30 sat the exam, 20 passed and 10 were given a re-sit or a fail result. (AMC pass rate 59%; Examinations Officer Clinical, Australian Medical Council, personal communication). Twenty chose to defer after using the various programs and tutorials on offer to gauge their level of preparedness. These doctors are planning to undertake the exam in 2005. These programs constitute the South Australian Action Plan for OTD inclusion in the workforce. 2 All of these programs are available and appropriate for any OTD (permanent resident or temporary resident). To the best of our knowledge, no temporary resident wishing to work in “areas of need” has enrolled in our programs yet.

Linsey S Hart · Jane Vernon-Roberts

Barry P McGrath Professor of Medicine, Monash University; and Chair, Confederation of Postgraduate Medical Education Councils of Australia, Dandenong Hospital, Dandenong, VIC 3175. Barry.mcgrathATmed.monash.edu.au In reply: Hart and Vernon-Roberts outline the South Australian Action Plan by the Postgraduate Medical Council of South Australia Australian Medical Council (AMC) doctors subcommittee to support and assist overseas trained doctors (OTDs). Their worthy efforts are directed predominantly towards the many OTDs preparing for their AMC examinations, with associated bridging and “ready-for-work” programs to facilitate entry into the hospital medical workforce. However, the question that needs to be addressed, and which was the main thrust of my article,1 is why we don’t have a national coordinated approach to all elements of the pathway to integrating OTDs into the Australian health care system. This cannot be a largely political approach, as is the Australian Government’s Strengthening Medicare initiative, which is particularly weak in the areas of assessment for safe practice and support in training. A recent article has highlighted the need for a national approach to coordinated governance for postgraduate medical education in Australia and the unsatisfactory complexity of medical education and training systems in this country.2 This excellent article includes only very brief reference to OTDs, using the term “international medical graduates”, 2 which is becoming the more acceptable term and the one recognised by other countries. It does not address the many gaps and problems in the pathways for this group. The number of international medical graduates seeking employment and/or being actively recruited into the medical workforce in Australia each year is far greater than the number graduating from our own medical schools. Thus, there is a degree of urgency about the debate on postgraduate medical education in Australia. We need a national authoritative body, like the new United Kingdom Postgraduate Medical Education and Training Board.

Barry P McGrath

Ken Vincent was born in Waverley, Sydney, on 18 December 1916 and died peacefully in Bowral, on 22 February 2005, after a protracted illness. He was the only son of Ernest and Ethel Vincent. Except for a period during World War II, Ken spent his entire life living and working within the Sutherland shire. He attended Cronulla Public School and Canterbury Boys High School. In his last year at Canterbury, he was school captain and captain of the Rugby XV team. He studied medicine at the University of Sydney, graduating in 1941. In 1953, after working for a number of years as a general practitioner, Ken took leave from general practice to specialise in otolaryngology at the Royal Ear, Nose and Throat Hospital in London. He eventually opened his own ENT practice in Caringbah, Sydney, in 1959. He was a Visiting Medical Officer at both St George and Sutherland hospitals. It was through the support of Ken and other doctors in the Sutherland shire that the Sutherland Hospital was originally built in the 1950s, and it was there that he developed an interest in rhinoplastic and ear surgery. He was State President of the Otolaryngology Society from 1974 to 1976. Early in his career, Ken joined Sydney Legacy, caring for the widows and children of ex-servicemen, a very active interest he maintained until the last few years of his life, when poor health prevented further participation and involvement. Another part of his work was his voluntary involvement with the Aboriginal communities of western New South Wales, particularly the Murrin Bridge community at Lake Cargelligo, visiting them on a monthly basis in his capacity as an ENT surgeon. He also visited Papua New Guinea and Fiji to undertake voluntary medical work. Many of the older Cronulla locals will remember him not only as the GP who delivered their babies but also as the one who took out their tonsils, or cured their glue ears or sinus problems. Ken’s great love was his family and his life-long partner Nan, whom he adored. He had a remarkable memory, never forgetting a name or a patient’s details, even well into retirement. As an operating surgeon he was meticulous and unforgiving, especially of himself. Ken is survived by his two children, Peter and Pam, and their families. Ian E Cole

Ian E Cole

Mention the name Alistair Cooke, and his legendary Letter from America immediately springs to mind.1 For 58 years his weekly commentaries on happenings in the United States were beamed by the BBC to many countries around the world, including Australia. Indeed, Cooke’s Letter from America was the catalyst for commissioning a regular short piece on the “goings-on” in health care, the medical profession and academia in the United Kingdom. The opportunity to view these through antipodean eyes was entirely fortuitous. Three prominent Australian academics left our shores some 3 years ago to take up prestigious positions in the “old country”: David Weller moved from Flinders University to Edinburgh, Konrad Jamrozik from the University of Western Australia to London, and Richard Heller from Newcastle University to Manchester. With little ado, our expatriate trio agreed to provide regular comments on medicine in the UK. The commentaries were to be journalistic rather than academic, with a humorous or quirky edge, but were also to reflect the profession’s sensitivities and conservatism. And so the Postcard from the UK was born. But now, almost 2 years on, the Postcard will cease to be delivered, and this issue carries the last one. This unfortunate turn of events is due to the break-up of the Postcard’s triumvirate, with the return of one of its members to Australia. Thus, all parties concerned agreed to “pull the plug” on the Postcards. Since December 2003, various Postcards have amused, amazed and even affronted some of our readers, both in Australia and in the UK. The more memorable Postcards have covered such issues as: UK health inequalities, which still reflect the British class divide;2 the political crusades imploding the National Health Service;3 the dependence of the NHS on “the energy of slaves” — through recruitment of doctors and other health professionals from the former British Empire’s colonies;4 and the Sir Humphrey Appleby approach to the bureaucratic Research Assessment Exercise, which gives the lie to the commitment of UK universities “to profess”.5,6 The final Postcard in this issue of the Journal (page 556) explores the difficulties confronting the NHS in bringing IT systems on stream.7 What, then, is the lasting message of the postcards? The issues involving the UK health system, its medical profession and academia are mirrored in our system, and the solutions seem to come from the same cookbook. Both countries’ bureaucracies are incredibly insular and spawn ill-conceived ideas, reflecting their isolation. But, overall, we are left with an impression of the political impotence of the UK medical profession and its institutions compared with those in Australia, a situation to be expected if most doctors are, in reality, public servants. In the meantime, sincere thanks to the Postcard’s trio and vale to our Postcard from the UK.

Martin B Van Der Weyden MD FRACP FRCPA

An antipodean’s history of haematology. Robert E Sage. Norwood, SA: Peacock Publications, 2004 (528 pp) ISBN 1 876087 96 X. Thomas Carlyle, 19th century Scottish historian and philosopher, once observed that “History is the essence of innumerable biographies.” And this is the style of An antipodean’s history of haematology by retired Australian haematologist, R Ed Sage. The book falls into two sections. In the first six chapters, Sage attempts to cover the history of haematology from antiquity to the 1960s, but sadly, clarity is drowned in the overwhelming detail. It is the following 17 chapters that make the book “a bloody good story”. Sage traces the history of antipodean haematology according to Carlyle’s tenet; he explores the professional lives of 99 Australasian haematologists. Indeed, this is the essence of the book’s uniqueness — the alignment of the professional lives of these haematologists with the growth of Australasian haematology, the foundation and growth of the Haematology Society of Australia (1961) and the Australasian Society of Blood Transfusion (1964), and events beyond. Sage presents insights into personalities and politics, including the revelations of the intransigence between transfusionists in Melbourne and Sydney over such monumental matters as the transfusion bottle! There were also the philosophical differences over what a haematologist is — a rancorous debate, which reached its peak in the 1970s, and embroiled the Austral(as)ian Colleges of Physicians and Pathologists, along with academics and mainstream haematologists. The bad blood was to ooze for years. Other stories include: the reasons for Melbourne’s erstwhile position as the power house of Australian haematology, a supremacy sustained by attracting the cream of Sage unearths some interesting facts. William Osler is called an English physician (he was Canadian); John Hunter is claimed to have been publishing and describing syndromes in 1817 (he died in 1793); the University of St Louis is said to be located in Mississippi (St Louis University is in Missouri); and Wollongong Hospital is said to be located in Sydney (the denizens of Wollongong, some 100 km south of Sydney, would be surprised to learn this). Nonetheless, the book is a significant history, adorned by innumerable mug shots of people in their prime or decline, and precious photos of local historical events. At its price, it is a bargain and should be on the shelves of all Australasian haematologists and haematology departments. I thoroughly recommend it. Martin B Van Der WeydenFormer Haematologist, and currently Editor, Medical Journal of Australia, Sydney, NSW

Communicating in the health and social sciences. Joy Higgs, Ann J Sefton, Annette F Street, et al. Melbourne: Oxford University Press, 2004 (xiv + 274 pp). ISBN 0 19 551698 2. This volume by well-qualified Australian-based authors aims to provide a comprehensive introduction to written, electronic, visual and interpersonal communication in the health and social sciences. Its target audience is primarily students in these professional fields and it attempts to equip them with tools for the relevant written, spoken and collegiate activities. However, many of the contributions, particularly as they relate to meeting presentation, teamwork and communicating with patients, are equally valid and useful to the experienced practitioner. Moreover, while well-oriented to the Australian student, the book is equally applicable to an overseas reader required to communicate within the English-speaking academic community. Many multi-authored books suffer from a disjointed style or a high degree of repetitiveness between chapters. This book does not fall into this trap. Books such as this provide a great service in offering a clear framework for health professionals who sometimes fail to have a clear understanding of the steps they employ in communicating to colleagues, patients and students. The tables used to summarise chapters are well constructed, the only irritation being the occasional need to turn the book 90° to read the information provided. Specialists’ textbooks these days are becoming prohibitively expensive and it is a great relief to see this volume available for under $40.00, less than dinner for two at most cheap bistros and rather more digestible. Its value to students is probably from the very beginning of their studies within the health and social sciences, but most of their teachers would also gain from having access to a copy, both as a personal reference and to help students with their presentations, thesis writing or publications. The need for such a volume is undisputed. It can only be hoped that students and teachers will recognise its value. Guy MaddernRP Jepson Professor of Surgery University of Adelaide, SA

Guy Maddern

The heartiest trio Combinations of statins, aspirins and β-blockers improve survival in patients with ischaemic heart disease, say the UK authors of a case-control analysis. From a long-standing database with over 1 million general practice patients, they matched each case of a patient with ischaemic heart disease, diagnosed between 1 January 1996 and 17 December 2003, who died during that period, with four age-, sex- and year of diagnosis-matched controls. Controls had to be alive when their matched case died. In all, there were 2266 cases, 9064 controls and 43 460 person-years of observation. The medications associated with the greatest reductions in odds for all cause mortality were statins, aspirin and β-blockers; the addition of an angiotensin converting enzyme inhibitor conferred no additional benefit, the researchers said. BMJ 2005; 330: 1059-1063 Dinner, bed and breakfast New Zealand authors have reported their experience of a "hospital-avoidance scheme" — dubbed Dinner Bed and Breakfast (DBB), in which elderly patients with a self-limiting illness were cared for in a nursing home setting rather than being admitted to an acute care hospital. The DBB project was facilitated by a local surplus of nursing home capacity. Initially, the scheme seemed to inadvertently facilitate the transfer of patients from their home to long-term nursing home care; but, over time, the program better met its intention of providing short-term care for patients who were usually independent and expected to recover over 3 to 5 days and return to their own home. However, the shift of care caused strain on specialist geriatric services, which was not planned or funded. On balance, the report’s authors viewed DBB as an acceptable interim solution while continuing to develop the ideal of enhanced care at home for appropriately selected patients. www.nzma.org.nz/journal/118-1214/1439/ Lawnmower neuritis A lawnmower has been implicated in a curious case of longstanding, intermittent thigh pain. A 32-year-old gardener complained of a 2-year history of burning pain along the anterolateral aspect of his left thigh whenever he used a ride-on lawnmower, especially over uneven ground. Examination was consistent with compression of the lateral femoral cutaneous nerve of the thigh. It turned out that this gardener’s broad utility belt dug into his "sides", compressing the nerve, whenever he sat on the lawnmower. A few months later he was symptom-free, after a change in job (to warden) and belt (to a thinner one) and some weight loss. CMAJ 2005; 172: 1273 "Kavacaine" Enterprising Fijian researchers have made a topical anaesthetic gel from an extract of the pepper plant Piper methysticum, more commonly known as kava. Usually kava is made into an intoxicating drink by infusing the macerated root of the plant in water. These researchers used 96% ethanol to extract 100% of the kavalactones present in 50 g of finely cut, fresh kava roots. They then diluted the 2.9 g of crude extract obtained into a commercially available, water-based gel. According to the researchers, empirical observations indicated that the created gel had a potent topical anaesthetic effect; they say clinical trials of this agent are warranted. Fiji Med J 2005; 24(1): 8-9 Diabetes reversed A single transplant of living-donor islet cells from the distal pancreas of a healthy mother has successfully reversed brittle diabetes in her 27-year-old daughter. In January 2005, the donor mother underwent a distal pancreatectomy. More than 400 000 islet equivalents were isolated from the pancreatic tail and immediately transplanted into the recipient daughter’s liver via access to the percutaneous portal vein under local anaesthesia. The daughter became insulin-independent from the 22nd day after transplantation. Because she did not have autoimmune type 1 diabetes, the transplanted islets did not need protection against autoimmune disease. The mother had no complications. The procedure took place in Japan, where, because of cultural considerations, access to cadaveric organ donors is especially scarce. Lancet 2005; 365: 1642-1644 Low-Fat Plus diet Cholesterol-lowering diets may prove more effective if they focus attention on including certain foods rather than just reducing saturated fat and cholesterol.1 In a short, four-week randomised trial, conducted in 120 adults with moderately raised fasting plasma low-density lipoprotein (LDL) cholesterol levels, US researchers found that the Low-Fat Plus diet increased the total- and LDL-cholesterol-lowering effect of a typical low-fat diet by a further 0.18 mmol/L. The Low-Fat Plus diet had identical levels of total fat (30% of energy), saturated fat (10% of energy) and cholesterol (< 300 mg/day) as that of a typical low-fat diet, but incorporated more vegetables, legumes and whole grains. It included soy, oats, wheatgerm, almonds, peanuts, flaxseed and garlic, all of which have been independently shown to reduce serum cholesterol levels.2 1. Ann Intern Med 2005; 142: 725-733 2. Ann Intern Med 2005; 142: 793-795 Dr Ann Gregory, MJA

Ann Gregory