Volume 194 Issue 1

Reports of adverse events related to calcium supplementation should be supported by rigorous evidence Calcium is an essential nutrient, not only because of its major role in bone, where 99% of it is stored, but because of its central role in neuromuscular function. It is this latter role that explains why ionised calcium in the blood and tissue fluids is one of the most tightly controlled analytes of those that are commonly measured.1 However, maintenance of the calcium level in tissue fluids carries with it the penalty of continuous loss of calcium through the kidneys, bowel and skin, even on a low calcium intake, which is why the recommended daily calcium allowance for adults is relatively high, at 1000 mg.2 Nutritional deficiencies of other minerals, such as magnesium and phosphate, are rare because their tissue fluid levels are not tightly controlled but vary with intake and, therefore, so does their excretion. Calcium is different; reducing calcium intake has a marginal effect on extracellular calcium (and therefore on calcium excretion) because bone is mobilised to maintain the calcium level, which leads sooner or later to the development of osteoporosis. This is the case in laboratory animals3 and, by implication, in humans. Osteoporosis is therefore the index disease for calcium deficiency,4 just as rickets and osteomalacia are the index diseases for vitamin D deficiency; however, there is some overlap between them because the secondary hyperparathyroidism associated with hypovitaminosis D5 increases bone resorption. This is not to suggest that all adult osteoporosis is due to calcium deficiency, but simply to point out that the increase in bone resorption which follows menopause6 can be largely or wholly explained by the fall in calcium absorption and rise in obligatory calcium excretion which occur at this time,7 and also occur in oophorectomised animals.8,9 (The loss of a direct antiresorptive action of oestrogen on bone at menopause cannot be excluded but is probably quantitatively much less important.) For these reasons, it has become standard practice to recommend calcium supplementation to postmenopausal women, increasingly with vitamin D, to prevent or delay bone loss and reduce fracture risk. In the largest meta-analyses, calcium with vitamin D in adequate dosage reduces fracture risk by 25% or more, but vitamin D alone is not effective.10,11 Until very recently, calcium supplementation was not thought to cause any significant side effects. However, a New Zealand team recently reported an increase in the mean rate of mainly self-reported myocardial infarction in participants who were allocated to receive calcium supplements in five prospective trials for which patient-level information was available.12 Although the effect was not significant in any of the trials individually, it was significant at the 5% level in the whole series and has attracted sufficient media attention to endanger the use of calcium in the prevention of osteoporosis in postmenopausal women. An extension of this case against calcium recently appeared in this Journal, in a position statement on fracture prevention in aged-care facilities that was co-authored by one member of the New Zealand team.13 The article not only ignores the seminal work of Chapuy and colleagues on fracture prevention with vitamin D and calcium in aged care homes,14 but specifically opposes the general use of calcium supplementation on four separate grounds, none of which are directly referenced. The first is that long-term compliance with calcium supplementation is very poor, whereas in most trials it is not significantly different from compliance with placebo.15 The second is that the anti-fracture efficacy of calcium is marginal, despite overwhelming evidence to the contrary in the largest meta-analyses.10,11 The third is a bizarre claim that calcium could increase the rate of hip fracture; this is only supported by one trial (by one of the co-authors of the position statement) in which the adverse effect was not remotely significant in participants who complied with calcium supplementation,15 which is widely regarded as an anomaly and is contradicted by a later meta-analysis.16 The final is that calcium supplementation could increase the risk of myocardial infarction, which is highly contentious and negated by the latest meta-analysis of 17 trials.17 These negative statements about calcium (which are not reflected in the article’s abstract) are coupled with the promotion of bisphosphonates — particularly the intravenous variety — despite the fact that virtually all the bisphosphonate trials have incorporated calcium supplements. It may therefore be relevant that this article arose from a meeting financed by a pharmaceutical company that happens to market an intravenous bisphosphonate and gave some form of assistance to six of the 10 authors.13 Since it is clearly stated that this meeting was endorsed by the Royal Australian College of General Practitioners, the Australian and New Zealand Bone and Mineral Society and Osteoporosis Australia, there is a strong implication that these bodies also support the article itself. It is questionable whether such public bodies should lend their authority to a position statement of uneven quality and which runs the risk of being seen as commercially driven.

B E Christopher Nordin MD, FRACP, DSc

Timeliness is important only to the extent that high-quality patient care is preserved Increasing demand for emergency care has worsened access to acute hospital services across the developed world. Australia’s response has been a mixture of time-based emergency department (ED) targets to drive process improvements, efforts to divert patients from EDs into community-based services and changes to accelerate hospital-wide processes and patient discharges. There has also been increased investment in bed capacity, although not commensurate with rising demand. Seasonal planning has been undertaken for both acute and sub-acute sectors. Despite these initiatives, access to acute hospital care has become measurably worse.1 The Australian Government has announced the introduction of a 4-hour rule that guarantees all emergency patients access to a hospital bed within 4 hours of arrival if clinically appropriate; the target will apply to critically ill patients (triage category 1) by January 2011, and to all patients by January 2015.2 Almost simultaneously, the United Kingdom Government has announced that it will replace England’s 4-hour standard with measures of patient outcome and safety,3 designed to deliver continuous improvements in standards in EDs. A look at the experience in England and why the decision has now been taken to move away from a time-based standard may reveal lessons for Australia about how to implement its new rule. The 4-hour emergency access standard in England is different from the guarantee announced in Australia because it allows for fewer exceptions, requiring that all ED patients be admitted, transferred or discharged within 4 hours of arrival in the ED. It has been in place for nearly 10 years, with a 98% operational threshold since 2003 to allow for the small number of patients who need more than 4 hours of ED care. Despite some obvious attempts at gaming and data manipulation,4 it has genuinely reduced length of stay overall in EDs and won patients’ approval.5 Before the introduction of the standard, there was evidence of patients having long waits in EDs before being seen by a doctor and before being transferred to a ward. The causes of delays were variable between hospitals.6 Also as a direct consequence of the 4-hour standard, innovations7 to manage patient care more efficiently have been introduced, including new models of care (eg, clinical decision units to fast-track care of patients with minor injuries). However, initiatives to reduce ED attendances have had little success. In fact, they may have led to poor practice in some hospitals, such as premature discharge and transfer of patients from the ED, resulting in preventable deterioration and mortality.8 Investment in the UK National Health Service (NHS) has doubled in recent years,9 with increased hospital staffing and capacity, increased resourcing of EDs and increased investment in community social care. The 4-hour standard has been the single major performance measure of the processes of the UK’s emergency care system. NHS organisations were strongly performance managed against this standard, with penalties for not achieving it. Hence, a lot of effort was expended to meet the target. In most EDs, accurate data collection systems are now in place to track patients, but are not necessarily available throughout the rest of the patient journey. Research has shown a link between length of stay in the ED and various outcomes, but it is not known whether overall patient outcomes have improved or deteriorated as a result of the 4-hour target. The Mid Staffordshire Trust review10 found that an excessive focus on time-based targets caused a significant increase in patient mortality and a major outbreak of hospital-acquired infection. But an independent report from Harvard University found “no evidence for any of the dysfunctional effects”.11 A recent Nuffield Trust report5 suggested that the emphasis on time in EDs had resulted in increased referral of patients between agencies, but no real improvement in efficiency and possible decline in efficiency. The over-focus on time-based medicine may result in work dissatisfaction for staff and decreased training opportunities. Additionally, the patient contact time may be reduced or hurried, potentially decreasing both patient and doctor satisfaction. The evolving approach in England aligns to the incoming UK coalition government’s commitment to freeing the NHS from what it sees as unnecessary micro-management through the imposition of process targets. Its more holistic approach is to hold the NHS to account for clinical outcomes and the quality of patients’ experiences, and to allow local decisions on processes and structure; results of a dashboard of clinical quality indicators will be published to encourage continuous improvement. Nevertheless, the UK Government recognises the clinical importance of timeliness of care and has said that it will include it in the dashboard of indicators. The lesson for Australia is that although introduction of a rigid time-based target to empty EDs is seductively simple and potentially effective in solving a single problem, there are significant dangers. Measurement systems should be in place to ensure that patient safety and quality of care are not compromised at any stage of the emergency care pathway. This requires a significant investment in information technology and highly developed monitoring of patient care processes and outcomes, including national registries for high-risk, high-cost patients and national audits of important standards of care. Clinicians in both countries agree that best care combines optimal outcome, patient experience and timeliness, and involves looking at the whole emergency care pathway from the first call for help until return home.

Peter A Cameron MD, FACEM · Matthew W Cooke PhD, FCEM, DipIMC

A national policy forum in Sydney connected researchers, clinicians, advocates, consumers and policymakers The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) is Australia’s first population-based study designed to identify modifiable factors that will enhance resilience and reduce vulnerability to the psychosocial and economic impacts of epilepsy. SEISMIC involves collaboration between The George Institute for Global Health, Epilepsy Action Australia, the Epilepsy Society of Australia, Sydney South West Area Health Service, the University of Sydney, hospitals and clinicians in Sydney, and Austin Health in Melbourne. The study is funded by research grants from the National Health and Medical Research Council and the Australian Research Council. A key aspect of SEISMIC is the inclusion of a series of policy forums to ensure appropriate translation of evidence into policy and practice; the first forum was convened on 4 August 2010. The burden of epilepsyWorldwide, epilepsy is one of the most common neurological disorders. With a prevalence of 7 per 1000,1,2 an estimated 140 000 people are living with epilepsy in Australia. One-third of these people have had the diagnosis since childhood and, for many, it has a significant, life-long impact.3 The fundamental characteristic of epilepsy — recurrent, unprovoked seizures manifested by sudden, variable, transitory disturbances of consciousness and motor, sensory, autonomic or psychic function — can be successfully controlled by medication in most people. However, the diagnosis has wide-ranging ramifications, including significant disability (which is difficult to quantify). Medication compliance is often problematic, and there are many barriers to effective management (Box 1). Help-seeking behaviour and adherence to recommended care are adversely influenced by ignorance, fear, misunderstanding, cultural attitudes, fragmentation of health and social services, inconsistent referral practices, variable support systems across jurisdictions, exclusionary eligibility criteria for services and costly treatment options.4 Even with effective treatment, people are often affected in many aspects of everyday life, such as in their education, employment, relationships and mobility. Stigma, whether experienced or perceived, continues to be a major issue.4-7 Strategies for translating research evidence into policyFifty key stakeholders from academia, medicine, government and the community were introduced to practical strategies that are essential for development of health policy. Some preliminary lectures outlined the clinical and epidemiological aspects of epilepsy and gave an overview of the SEISMIC study and perspectives on consumer services from the non-government sector (Epilepsy Action Australia). Professor Stephen Leeder, Director of the Menzies Centre for Health Policy — who likened developing health policy to making sausages (“messy but effective”) — and Dr Andrew McDonald, Parliamentary Secretary for Health for the New South Wales Government, reinforced the importance of ensuring that the issues being addressed in SEISMIC are clearly defined so that feasible and cost-effective solutions can be proposed. The key “take-home” messages are summarised in Box 2. Priority areas identifiedWithin several working groups, the attendees went on to define the key health and social issues that require a policy response. Four priority areas were identified: (1) to develop a model of care; (2) improve systems to maintain education, employment and mobility; (3) address stigma; and (4) identify research needs. 1. Develop a model of care for patients diagnosed with epilepsyThere was collective concern about the absence of a defined “best practice” standard of care for people with epilepsy. Importantly, from a medical perspective, epilepsy is not one disorder, but a large group of conditions needing specific diagnosis to determine the best treatment and prognosis. Determination of specific diagnoses in a community cohort is an important aspect of SEISMIC. The development of an optimal pathway which specifies a continuum of care, inclusive of medical and community services, would streamline the referral process and overcome some of the barriers people face while navigating the health, social welfare and community sectors. Such a model of care would make explicit the roles of the various health professionals involved in the initial assessment, diagnosis and management of patients with epilepsy, including general practitioners, general physicians (adult and paediatric), neurologists and epilepsy specialists. This could address the current gap in transition care — the gap between paediatric and adult care — which affects the special needs of adolescents. A suite of services could be “packaged” to simplify the patient journey. Essentially, a standard model of care would improve the quality of epilepsy care to ensure successful adjustment and outcomes from the condition. 2. Improve systems to maintain education, employment and mobilityPeople with epilepsy are often restricted in their ability to live independently. This is most evident in the barriers to employment and education, and the negative impact that driving restrictions have on people’s mobility and quality of life. While support services are available to assist in the completion of Centrelink and Medicare forms, and there are various community transport schemes and taxi voucher programs in place, efforts are required to raise awareness of the range of services available, address the inconsistency in the services being offered across jurisdictions, and refine eligibility criteria to reflect the diverse needs of people with epilepsy. The strong disincentives to maintaining employment must also be eliminated. Although people with epilepsy want to gain and maintain employment, they lose access to subsidies by doing so, and working conditions limit sick leave or medical attendance allowances. There also needs to be improvement in the education system to foster more awareness about people with epilepsy and to encourage greater tolerance towards them. Information about whether disclosure of illness is mandatory, when disclosure is necessary and to whom individuals are required to disclose their illness must also be clarified in this process. There are likely to be societal benefits to supporting people with epilepsy and allowing them to become and maintain themselves as productive citizens. 3. Address the stigma of epilepsy by normalising the conditionThe stigma of epilepsy continues to negatively affect self-esteem, educational performance, productivity and health outcomes. Redefining epilepsy to encompass “fits, faints and funny turns that affect one in ten individuals” could improve public and government perception of the condition and its importance. Several other strategies were considered, including using prominent figures with epilepsy as “ambassadors”, expert “champions”, and harnessing the influential role of the media to raise awareness about epilepsy. Efforts to “normalise” epilepsy would help combat the associated stigma. 4. Identify further research needsValuable new evidence, with wide applicability, about the impact of epilepsy will be generated by SEISMIC. As the study plans to recruit several hundred children and adults soon after their diagnosis, it has the scope for being a repository of “whole-of-life” information on the long-term outcomes of the illness and impact of interventions. Securing ongoing funding was therefore acknowledged as a priority of the research group. Concluding remarksThe forum was closed by Dr Andrew Bleasel, President of the Epilepsy Society of Australia, who reaffirmed SEISMIC’s raison d’être (in fewer than 18 words, as recommended): to identify strategies to improve the lives of people with epilepsy and their families. 1 Impacts of epilepsy Clinical impacts: diagnostic assessment and investigation, usually involving hospital and specialist services requirements for long-term medication, sometimes with multiple agents, and for regular medical review potential for repeat investigations, and sometimes surgery, in those with poor seizure control the unpredictable paroxysmal nature of epilepsy with associated life disruption for variable periods of time afterwards seizure-related illness, injury and acute medical care potential for cognitive and physical adverse effects of medication, either dose-related or idiosyncratic risk of premature mortality including unexplained sudden death, and long-term complications associated with medications or injury Psychosocial impacts: depression and anxiety fatigue, drowsiness and reduced quality of life social restriction related to driving restriction, alcohol avoidance, and maintenance of adequate sleep hygiene stigma and exclusion from sports, work, education, and in relationships and marriage Economic impacts: costs of medication and primary and specialist health care indirect costs related to lower educational attainment and job opportunities lost income and productivity related to illness lost economic opportunities and costs to households associated with caring 2 Recommendations for negotiating with government on health policy issues Have a consistent and coherent message about what needs to be done, and stick with it (“life in 18 words or less”). Be reasonable, realistic and persistent in options being put forward, but always be ready to offer alternatives. Plan to effect change by strategically using research evidence to influence the policy process, including reframing the issue (or solution) in light of the current political priorities. Learn to spot and harness opportunities for policy engagement as they arise unpredictably, and have research evidence readily at hand at these times. Don’t annoy the minister.

Beverley M Essue MPH · Stephen Jan · Maree L Hackett PhD · Andrew F Bleasel MB BS, PhD, FRACP · Carol A Ireland Dip(RehabCouns), AFAIM · Samuel F Berkovic MD, FRACP, FRS · Craig S Anderson PhD, FRACP

Objective: To model the impact of both population and high-risk strategies on cardiovascular disease (CVD) outcomes.Design, setting and participants: A CVD risk-factor survey was carried out in rural south-eastern Australia from 2004 to 2006. Using a stratified random sample, data for 1116 participants aged 35–74 years were analysed. Applying the Framingham risk equations to risk-factor data, 5-year probabilities of a coronary heart disease event, stroke and cardiovascular event were calculated. The effect of different changes in risk factors were modelled to assess the extent to which cardiovascular diseases can be prevented by changing the risk factors at a population level (population strategy), among the high-risk individuals (high-risk strategy) or both.Results: Among men, a population strategy could reduce cardiovascular events by 19.3% (193 per 1000 per 5 years), the high-risk strategy by 12.6% (126 per 1000) and a combined strategy by 24.1% (241 per 1000); and among women, by 21.9% (219 per 1000), 19.0% (190 per 1000) and 28.7% (287 per 1000), respectively.Conclusions: For prevention of CVD in Australia, it is important both to treat high-risk individuals and to reduce the mean risk-factor levels in the population. We show how risk-factor survey data can be used to set targets for prevention and to monitor progress in line with the recommendations of the National Preventative Health Taskforce.

Erkki A Vartiainen MD, PhD · Tiina Laatikainen MD, PhD · Benjamin Philpot BSc · Edward D Janus MD, PhD · Nathalie Davis-Lameloise PhD · James A Dunbar MD, FRACGP

Objective: To quantify and characterise the reports of syncope and seizures following quadrivalent (4v) human papillomavirus (HPV) vaccination.Design and setting: Retrospective case series of notifications to SAEFVIC (Surveillance of Adverse Events Following Vaccination In the Community), May 2007 – April 2009.Main outcome measures: Incidence of syncope and seizure following 4vHPV vaccination; clinical outcomes.Results: 97/1653 SAEFVIC reports met the study criteria: afebrile seizures (3), syncopal seizures (31) and syncope alone (63). Median age at vaccination was 15 years (range, 8–26 years). Injuries were reported in seven cases, including one vertebral fracture. A SAEFVIC clinic review was undertaken in 41% (40/97) and 22 patients received further 4vHPV vaccine doses administered supine, with no recurrences. The reporting rate after 4vHPV vaccine for syncope and syncopal seizures was 7.8/100 000 and 2.6/100 000 doses distributed, respectively.Conclusion: Syncope and syncopal seizures occurred after 4vHPV vaccination in Victoria at rates similar to those seen internationally. Clinical review allowed clarification of the diagnosis and management, including safe administration of further doses under supervision.

Nigel W Crawford · Hazel J Clothier MEpid · Sonja Elia RN · Teresa Lazzaro MB BS · Jenny Royle MB BS, MD · Jim P Buttery MB BS, MSc

Objective: To assess background pre-pandemic cross-reacting antibodies to the pandemic (H1N1) 2009 virus in older populations in Australia.Design, setting and participants: Data were opportunistically generated from three cross-sectional pre-pandemic studies involving people aged 60 years or older: a 3-year (2006–2008) study of influenza outbreaks in aged care facilities (ACFs) in Sydney; an investigation of a respiratory virus outbreak in an ACF in rural New South Wales in June 2009; and a non-influenza serosurvey undertaken in NSW in 2007 and 2008.Main outcome measure: Prevalence of pandemic (H1N1) 2009 haemagglutination inhibition (HAI) antibody titres ≥ 1:40 (putative protective level) in pre-pandemic sera.Results: In total, 259 serum samples from individuals aged 60 years or older (range, 60–101 years) were tested. More than half of the individuals tested were women (151/259; 58.3%). About a third of individuals (37.5%) had cross-reacting HAI antibody titres ≥ 1:40. The prevalence of cross-reacting antibodies was highest in the oldest age groups (≥ 85 years), with more than 60% of these people having HAI antibody titres ≥ 1:40. The proportion of subjects with HAI antibody titres ≥ 1:40 decreased significantly and successively in younger groups to only 12% of those aged 60–64 years.Conclusions: Our study suggests a pre-existing influenza A antibody reserve in most of the oldest group of people that was cross-reactive to the new pandemic (H1N1) 2009 virus; this is likely to be lifelong and to have provided them with clinical protection against the first wave of the pandemic. Pandemic influenza control measures need to focus more on younger adults naive to the pandemic virus and at increased risk of severe disease.

Robert Booy MD, FRACP, FRCPCH · Gulam Khandaker MB BS, MPH, DCH · Leon G Heron MB ChB, FRCPA, FAFPHM · Jiehui Yin MB BS, MPH(Hons) · Bridget Doyle BAppSci, GradDipEd · Katherine K Tudo BMedSci · Linda Hueston BSc, MSc · Gwendolyn L Gilbert MD, FRACP, FRCPA · C Raina MacIntyre MB BS(Hons), PhD, FRACP · Dominic E Dwyer MD, FRACP, FRCPA

Objective: To determine the prevalence and diagnosis rates of Klinefelter syndrome (KS) in Victoria, Australia, and compare these to previous international findings.Design, setting and participants: A Victorian population-based descriptive study of all cytogenetic examinations resulting in a diagnosis of KS, including prenatal diagnoses from 1986 to 2006 and postnatal diagnoses from 1991 to 2006.Main outcome measures: Birth prevalence and diagnosis rates of KS.Results: The birth prevalence of KS in Victoria is estimated to be 223 per 100 000 males (95% CI, 195–254), with about 50% of cases remaining undiagnosed.Conclusions: KS may be occurring more frequently than has been reported previously, yet many cases remain undiagnosed. Our results highlight the need for increased awareness leading to timely detection.

Amy S Herlihy BSc, GradDipGenCounsel · Jane L Halliday BSc(Hons), PhD · Megan L Cock BSc(Hons), PhD · Robert I McLachlan MB BS, PhD

Objective: To compare the level and determinants of job satisfaction between four groups of Australian doctors: general practitioners, specialists, specialists-in-training, and hospital non-specialists.Design, participants and setting: National cross-sectional questionnaire survey as part of the baseline cohort of a longitudinal survey of Australian doctors in clinical practice (Medicine in Australia — Balancing Employment and Life [MABEL]), undertaken between June and November 2008, including 5193 Australian doctors (2223 GPs, 2011 specialists, 351 hospital non-specialists, and 608 specialists-in-training).Main outcome measures: Job satisfaction scores for each group of doctors; the association between job satisfaction and doctor, job and geographical characteristics.Results: 85.7% of doctors were moderately or very satisfied with their jobs. There were no differences in job satisfaction between GPs, specialists and specialists-in-training. Hospital non-specialists were the least satisfied compared with GPs (odds ratio [OR], 0.56 [95% CI, 0.39–0.81]). For all doctors, factors associated with high job satisfaction were a good support network (OR, 1.72 [95% CI, 1.41–2.10]), patients not having unrealistic expectations (OR, 1.48 [95% CI, 1.25–1.75]), and having no difficulty in taking time off work (OR,1.48 [95% CI, 1.20–1.84]). These associations did not vary across doctor types. Compared with GPs, on-call work was associated with lower job satisfaction for specialists (OR, 0.48 [95% CI, 0.23–0.98]) and hospital non-specialists (OR, 0.25 [95% CI, 0.08–0.83]).Conclusion: This is the first national survey of job satisfaction for doctors in Australia. It provides an important baseline to examine the impact of future health care reforms and other policy changes on the job satisfaction of doctors.

Catherine M Joyce BA(Hons), MPsych, PhD · Stefanie Schurer MSc, PhD · Anthony Scott BA, MSc, PhD · John Humphreys BA(Hons), DipEd, PhD · Guyonne Kalb MEc, PhD

Professional ethical codes identify the issue of conflict of interest, which can distort doctors’ objective judgements concerning the best interests of patients. Legal fiduciary duties may be owed by doctors to patients in situations of potential conflict of interest. Prescribing and dispensing functions have been largely legally separated to prevent conflicts of interest arising. The advent of integrative medicine has been accompanied by an apparent growth of in-house selling of therapeutic products. Medical merchandising constitutes a prima-facie conflict of interest and may amount to notifiable conduct under the Health Practitioner Regulation National Law provisions. We believe that doctors who sell therapeutic products should adhere to strict conditions to avoid significantly departing from accepted professional standards. Doctors who have a reasonable belief that a colleague is failing to comply with these conditions could consider notifying the Medical Board of Australia.

Malcolm H Parker MB BS, MLitt, MD · Jon L Wardle BHSc(Nat), MPH · Michael Weir BA, LLM, PhD · Cameron L Stewart BEc, LLB(Hons), PhD

The national health reform agenda appears to have omitted public health. In this article, I outline how public health is different from primary care, and why a holistic approach to reform should include public health. The current reform agenda is very much focused on addressing the problems in acute care and the hospital system, with the focus on primary care being a means to this end. Until the health system is addressed as a whole, with all its essential components integrated and interlinked, truly successful reform of the health system, with genuine long-term vision and sustainability, will not be possible.

C Raina MacIntyre FRACP, FAFPHM, PhD

Human infection with Rickettsia felis has been reported in most parts of the world, and R. felis has recently been confirmed in cat fleas in Western Australia. The clinical presentations of R. typhi and R. felis are similar, and in the past, the incidence of R. felis infection may have been underestimated. We describe the first reported cases of probable human R. felis infection in Australia. Two adults and three children in Victoria contracted a rickettsial disease after exposure to fleas from kittens. Molecular testing of fleas demonstrated the presence of R. felis but not R. typhi. Clinical recordsPatient B, a previously well 9-year-old girl, was admitted to a children’s hospital in Melbourne, Victoria, in April 2009 with severe abdominal pain, fevers to 39°C and a non-pruritic erythematous macular rash, initially present on the trunk and then spreading to the upper limbs and face (Box 1). The patient described a prodrome of 5 days of fever and malaise, with occasional vomiting and diarrhoea. She had been appropriately vaccinated, had no drug allergies, and did not regularly take any medication. On initial examination, the girl appeared unwell, with pitting oedema of the ankles and a generalised macular rash. There was no hepatosplenomegaly or significant lymphadenopathy. Initial laboratory test results indicated leukopenia (white blood cell count, 3.0 × 109/L [reference range (RR), 4.5–13.5 × 109/L]), lymphopenia (lymphocytes, 0.42 × 109/L [RR, 1.5–6.5 × 109/L]), thrombocytopenia (platelet count, 38 × 109/L [RR, 150–400 × 109/L]), hyponatraemia (Na+, 133 mmol/L [RR, 135–145 mmol/L]), hypoalbuminaemia (serum albumin, 19 g/L [RR, 33–47 g/L]), and elevated transaminase levels (aspartate aminotransferase, 168 IU/L [RR, < 55 IU/L]; alanine aminotransferase, 177 IU/L [RR, < 55 IU/L]). Treatment with ticarcillin–clavulanic acid and gentamicin was commenced. Urine and blood cultures were ordered, as well as serological tests for a range of infectious diseases. The patient lived with her parents and two siblings in suburban Melbourne on a hobby farm next to a wooded reserve notable for stagnant water and mosquitoes. The family had many pets, including a dog, goat, ducks, budgerigars, mice and a domesticated rat. They had never travelled outside Australia, and had not recently had visitors from overseas. About 3 weeks before the onset of the illness, the family had acquired a pair of kittens (Cat 1 and Cat 2) from a farm in Lara, a rural suburb in Victoria, and had given Cat 2 to a neighbour. Patient B had ongoing persistent fever and severe abdominal pain. Her platelet count remained low, and her hepatic function, coagulopathy, hyponatraemia and hypoalbuminaemia worsened. On Day 3 of her admission, she developed pulmonary oedema and required a short stay in the intensive care unit, during which she received azithromycin, albumin and frusemide, as well as intensive supportive therapy and monitoring. She was given intravenous immunoglobulin (IVIG) 2 g/kg for possible Kawasaki disease but showed no response. Also on Day 3 of Patient B’s hospitalisation, her 8-year-old sister (Patient C) presented with fevers to 40°C, mild abdominal pain and a rash on her torso. On examination, she appeared to be well, but had florid facial flushing, a macular rash spreading to the limbs, tender cervical lymph nodes and a mildly tender abdomen. Patient C’s initial laboratory test results indicated mild leukopenia (white blood cell count, 4.5 × 109/L) and hyponatraemia (Na+, 132 mmol/L). Treatment with ticarcillin–clavulanic acid and gentamicin was commenced. Over 48 hours she became thrombocytopenic (platelet count, 77 × 109/L), with worsening abdominal pain and hyponatraemia (Na+, 132 mmol/L), and elevated alanine aminotransferase (75 IU/L). She was given IVIG 2 g/kg for possible Kawasaki disease. Her condition improved rapidly. On Day 7 of Patient B’s hospitalisation, Patient D, the girls’ 4-year-old brother, presented with a fever of 39.6°C and five erythematous macules on his legs and trunk. He was otherwise well. Laboratory test results for Patient D showed leukopenia (white blood cell count, 4.0 × 109/L), with no other abnormalities. He was admitted for observation without treatment. The three siblings were discharged home on Day 11 of Patient B’s hospitalisation, without definitive diagnoses. Patients C and D had episodes of fever for 1 week, but remained well otherwise. A phone review on Day 18 found that the three children were well and afebrile. However, their maternal grandmother (Patient E) had had 3 days of fever and rigors and had been admitted to another hospital for observation. On advice from the children’s doctor, Patient E’s treating doctor administered doxycyline and her condition subsequently improved. It was also discovered that the neighbour who had been given Cat 2 (Patient A) had become unwell 2 days before Patient B, with a non-specific febrile illness that had settled by the time Patient B was admitted to hospital. She was therefore the initial case in the cluster. All patients had had extensive close contact with one or both of the cats. The children’s parents had minimal contact with the cats and were asymptomatic. The family reported that both cats had flea (Ctenocephalides felis) infestations when they acquired them. Cat 1 no longer had fleas after having been treated topically with insecticide, but its serum was tested for typhus-group rickettsial species. Because it was unwell, Cat 2 had been euthanased before blood samples could be taken. As collecting fleas from the two kittens was not possible, fleas from other cats of the group into which they were born, including the kittens’ mother, were collected for molecular analysis to identify any rickettsial species they carried. Serological testing was performed using indirect microimmunofluorescence assay (IFA).1,2 Initial serological analysis (in April 2009) for the presence of both spotted-fever-group and typhus-group rickettsial antibodies was undertaken on Patients B and C. The results showed the presence of typhus-group but not spotted-fever-group rickettsial antibodies. A month later (May 2009), serological testing was repeated for Patients B and C, and initial testing was done for Patients D, E and A. The tests showed rising typhus-group rickettsial antibody titres in patients B, C and E and high titres in patients A and D. In addition, Patient C showed clear evidence of seroconversion (Box 2), while both parents were negative for rickettsial antibodies. Serological testing undertaken on Cat 1 also showed the presence of typhus-group rickettsial antibodies (Box 2). DNA was extracted from the serum of Patient C (buffy coat [white cell layer] was not available), and Cat 1, and from pooled and crushed cat fleas that were collected from cats in the group that Cat 1 and Cat 2 had come from. A rickettsial real-time polymerase chain reaction (PCR) test was performed on the extracted DNA samples.3 The fleas, but not the patient’s or cat’s serum, were positive for rickettsial DNA. A 1077 base-pair fragment of the rickettsial citrate synthase gene was amplified and sequenced.4 This sequence was compared with the validated rickettsial species5 and showed closest phylogenetic similarity to Rickettsia felis, with a sequence similarity of 99.7% (1074/1077 base pairs). Rickettsia typhi DNA was not detected in the cat fleas. The citrate synthase gene (gltA) sequence analysis using the neighbour-joining algorithm is shown in Box 3. DiscussionThe five patients described here are the first reported cases of probable human R. felis infection in Australia, and the analyses provide the first molecular evidence of R. felis in cat fleas in Victoria. It has been previously detected in cat and dog fleas in Western Australia by molecular analysis.6 Human infection with R. felis has been reported in most other parts of the world.7-10 While genetically a member of the spotted-fever rickettsia group, R. felis behaves clinically and serologically like a typhus-group rickettsia and is transmitted by fleas. Antibodies induced by R. felis react with typhus-group rickettsiae in serological tests, rather than with spotted-fever-group rickettsiae. A petechial rash is an infrequent sign of infection, and a macular or maculopapular rash is present in only 50% of patients (Box 1). The high attack rate and severity of infection noted in this cluster may be due to the heavy flea infestation that was reported. Resolution without therapy is well described in rickettsial infection. Only two patients (B and C) received antimicrobial therapy with known activity against rickettsial species. The five patients showed a strong positive result for the presence of typhus-group antibodies. Patient C’s clear seroconversion was consistent with recent acute R. felis or R. typhi infection.7 While exposure to either R. felis or R. typhi could have led to Cat 1 producing typhus-group antibodies, only R. felis DNA was detected in the cat fleas. It is common for blood from cats infected with R. felis to be negative for rickettsial DNA,8 as in this case. Cat 1 still had antibodies to R. felis but either had cleared the infection, or the organism was present in tissues other than peripheral blood. In a previous experimental exposure of cats to R. felis-positive fleas, 13 of 16 cats were positive by serological testing using IFA, but only five of the 16 were positive by PCR.11 The human cases reported in this study were only identified serologically, and as the clinical presentations of R. typhi and R. felis are similar, R. typhi cannot be completely ruled out as the causative agent. However, given the molecular data from the cat fleas, R. felis is the more likely causative agent. In the past, the incidence of R. felis infection in patients with raised typhus group antibody levels may have been underestimated, with the causative agent probably reported as R. typhi when it may have been R. felis — a confusion that has been seen in other studies.8,9 1 Widespread erythematous macular rash, Patient B 2 Serology results of five seropositive patients and a cat exposed to rickettsial infection, 2009 Patient/ cat Sex, age in years Day of onset* Status in family Rickettsia group Serum antibody titre April May June A F, 63 − 2 Neighbour SFG nd < 1/128 nd TG nd 1/16 384 nd B F, 9 1 Child SFG 1/128 1/128 nd TG 1/1024 1/8192 nd C F, 8 3 Child SFG 1/128 1/256 nd TG < 1/128 1/16 384 nd D M, 4 7 Child SFG nd 1/128 nd TG nd 1/16 384 nd E F, 59 15 Grandmother SFG nd < 1/128 < 1/128 TG nd 1/1024 1/2048 Cat 1 F, < 1 na Pet SFG nd nd < 1/128 TG nd nd 1/512 na = not applicable. nd = not done. SFG = spotted-fever group (ie, Rickettsia australis and R. honei). TG = typhus group (ie, R. prowazekii and R. typhi). * Compared with Patient B’s admission (Day 1). 3 Condensed phylogenetic tree comparing the DNA fragment sequenced in this analysis (“Rickettsia felis [Lara]”) with validated rickettsial species Relationship of a 1077 base-pair fragment of the gltA gene of Rickettsia felis (Lara) among other validated rickettsial species, with the core spotted-fever-group rickettsiae truncated. The tree was prepared using the neighbour-joining algorithm.* Bootstrap values are indicated at each node. The scale bar represents a 2% nucleotide divergence. * Molecular Evolutionary Genetics Analysis (MEGA) software, version 4.0, 2007 [free internet download].

Molly Williams MB BS · Leonard Izzard BSc, PhD · Stephen R Graves MB BS, PhD, FRCPA · John Stenos BSc, PhD · Julian J Kelly MB BS, FRACP

Clinical record A 56-year-old woman, with a history of a right adrenal phaeochromo-cytoma excised in 1974, presented to the emergency department in 2008 with a hypertensive crisis characterised by 3 days of severe headache, malignant hypertension (blood pressure, 200/115 mmHg) and seizures complicated by bilateral humeral fractures. After her surgery in 1974, she had unresolved hypertension and raised urinary catecholamine levels suggestive of residual or metastatic disease. However, no additional tumour could be identified despite venous sampling studies. The patient declined further treatment and was lost to follow-up from 1978. She subsequently had three uncomplicated, successful pregnancies. During the patient’s 2008 hospital admission, her levels of urinary catecholamines and plasma metanephrines were elevated (Box 1). She was treated with phenoxybenzamine and diltiazem (extended release), doses of which were titrated up to 60 mg twice daily and 360 mg daily, respectively, before uneventful surgical repair of both humeral fractures. Localisation studies with a 123 I-metaiodobenzylguanidine scan identified increased tracer uptake within both the left adrenal region and left anterior mediastinum. Computed tomography and magnetic resonance imaging (MRI) scans showed large bilateral renal angiomyolipomas (AMLs), a right renal artery aneurysm, a bulky left adrenal gland with no discrete mass lesion, and a 15 mm calcified lesion within the left anterior mediastinum (not related to the sympathetic chain). Results of a positron emission tomography scan were negative. However, an octreotide scan showed mild tracer uptake in the left adrenal region and marked focal uptake within the left anterior mediastinum (Box 2). It was felt unlikely that the left adrenal gland image represented a phaeochromocytoma and likely that the mediastinal lesion was a phaeo-chromocytoma lymph node metastasis. After the addition of atenolol 100 mg daily to the patient’s drug regimen, the left anterior mediastinal lesion was excised via a cervical approach without complication. Histological examination confirmed a phaeochromo-cytoma metastasis within a lymph node. After the operation, blood pressure improved significantly. Plasma metanephrine levels have remained normal for over a year. Tests for phaeochromocytoma genetic syndromes revealed a missense mutation (Gly144Arg) on exon 2 of the von Hippel–Lindau (VHL) gene, and we are awaiting testing of the patient’s eight siblings to determine whether or not this is a de novo mutation causing VHL disease. Although two of her three children have inherited the mutation, they have had no disease manifestations. Further investigations of the patient have revealed mild sensorineural hearing loss, but no evidence of haemangio-blastomas via fundoscopy or on MRI scanning of the brain and spinal cord. While there is an increased risk of renal cell carcinoma with VHL disease, recent imaging has shown no change in the patient’s presumed bilateral AMLs and she has declined surgery or embolisation. The left adrenal gland and right renal artery aneurysm have also remained stable on serial imaging. Malignant phaeochromocytoma has been reported to be a risk factor for osteoporosis,1 but the patient’s bone mineral densitometry showed only osteopaenia of her lumbar spine, while her left hip bone measurements were within normal limits. Our patient’s history shows the need for long-term periodic follow-up of people treated for phaeochromocytomas. It also illustrates the association between von Hippel–Lindau (VHL) disease and phaeochromocytoma. VHL disease, an autosomal dominant condition, is caused by a mutation of the VHL tumour suppressor gene on chromosome 3p; the mutation rate is one in 36 000 live births.2 The VHL gene is involved in regulating the transcription of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and other hypoxia-inducible proteins. Inactivation promotes tumour angiogenesis and growth through overexpression of VEGF and PDGF receptor agonists, resulting in haemangioblastomas of the central nervous system or retina, pancreatic neuroendocrine tumours and cysts, renal clear cell carcinomas, phaeochromocytoma, endolymphatic sac tumours, and papillary cystadenomas of the epididymis (men) or broad ligament (women).3 In a series report of 246 patients with VHL disease, 26% of patients developed phaeochromocytomas at a mean age of 29 years, 39% had bilateral adrenal phaeochromocytomas, and extra-adrenal disease occurred in up to 30%.4 The adrenal medulla is the main site in the body where the enzyme that converts noradrenaline to adrenaline, phenylethanolamine N-methyltransferase, is localised, and, consequently, adrenal phaeochromocytomas typically have raised levels of both noradrenaline and adrenaline. By contrast, extra-adrenal phaeochromocytomas and phaeochromocytomas in patients with VHL disease do not usually express phenylethanolamine N-methyltransferase and are therefore characterised by raised levels of noradrenaline and normetadrenaline with relatively normal levels of adrenaline and metadrenaline. For our patient, elevations in noradrenaline levels exceeded those of adrenaline both at the time of the original phaeochromocytoma diagnosis and subsequently, with adrenaline levels normalising after the original operation, in keeping with extra-adrenal or metastatic disease. Kindreds with VHL disease can be divided into two types (Types I and II) based upon the incidence of phaeochromocytoma, with Type I generally unaffected and Type II at high risk.5 Type II is further divided — IIA and IIB have a low or high incidence of renal clear cell carcinomas, respectively, while IIC is characterised by the development of phaeochromocytomas without other VHL manifestations. Of the 1548 reported mutations in the VHL gene, 52% are missense mutations and the one previously reported Gly144Arg mutation was associated with polycythaemia.6 Renal angiomyolipomas (AMLs) occur in 0.1% of the population, and although those with bilateral renal AMLs have a greater chance of having tuberous sclerosis, this patient has no other features of the condition.7,8 However, it is possible that she has a new phenotype of Type II VHL disease associated with AMLs. Between 12% and 24% of patients with ostensibly sporadic phaeochromocytomas harbour phaeochromocytoma genetic syndromes, including VHL disease. A study of 271 such patients detected a germline VHL mutation in 11%, increasing to 42% in those who presented at age 18 years or younger.9 Therefore, it is recommended that patients diagnosed with a phaeochromocytoma before the age of 50 years should undergo screening for underlying germline mutations.10 For relatives identified as having predisposing germline mutations, investigations and follow-up are dictated by the underlying disease, but should include clinical genetics and endocrinological input. In the case of VHL disease, biochemical screening for phaeochromocytomas should start at age 4 years, and tumours should be removed if functional, as indicated by elevated catecholamine levels.4 While our patient’s experience highlights the importance of screening for underlying germline mutations, it also reinforces the unpredictable nature of phaeochromocytoma metastases. 1 Patient’s levels of urinary catecholamines and plasma metanephrines at phaeochromocytoma diagnosis and post-treatment, and metastasis diagnosis and post-treatment Investigation 1974 1976 Investigation 2008 April 2009 Feb 2010 Urine noradrenaline (RR, < 80 μg/d) 1681.8* 851.4* Urine noradrenaline / Cr (RR, 0–60 nmol/mmol) 152.3 58.2 48.5 Urine adrenaline (RR, < 20 μg/d) 86.5* 4.7* Urine adrenaline / Cr (RR, 0–10 nmol/mmol) 17 < 1.3 < 2.5 Plasma normetadrenaline Assay not available Assay not available Plasma normetadrenaline (RR, < 900 pmol/L) 3680 658 692 Plasma metadrenaline Assay not available Assay not available Plasma metadrenaline (RR, < 500 pmol/L) 591 113 122 Cr = creatinine. RR = reference range. * Noradrenaline and adrenaline / Cr ratios unavailable. 2 Octreotide scans of patient with phaeochromocytoma metastasis showing abnormal focal tracer uptake in anterior mediastinum (arrows in anterior views) * Scan 24 hours after intravenous injection of radioactive octreotide. † Scan 48 hours after intravenous injection of radioactive octreotide. Lessons from practice Persistent hypertension and elevated catecholamine levels after excision of a phaeochromocytoma are suggestive of residual or metastatic disease. Patients with a history of phaeochromocytoma require long-term surveillance. Between 12% and 24% of patients with ostensibly sporadic phaeochromocytomas harbour predisposing genetic syndromes, including von Hippel–Lindau (VHL) disease, and genetic screening is recommended in patients diagnosed under 50 years of age. VHL disease is a dominantly inherited syndrome, involving mutation of the VHL tumour suppressor gene — the mutation occurs in one in 36 000 live births.

Christopher J Yates MB BS · Sybil A McAuley MB BS · Simon Grodski MB BS, FRACS · Peter Shane Hamblin MB BS, FRACP · Peter R Ebeling MB BS, FRACP, MD

To the Editor: It is regrettable that research published by Studdert and colleagues suggests that barriers remain to the open disclosure of medical error in Australia.1 Although all states have enacted legislation to protect defendants who apologise to plaintiffs, such protection is variable and inconsistent across Australia.2 Most significantly, the definition of what constitutes an apology varies greatly from jurisdiction to jurisdiction, as do the various protections afforded to the apology. Unfortunately, this only serves to complicate what should be an open and candid discussion of the circumstances surrounding a medical error. However, the fear of legal action is not the only barrier preventing doctors from disclosing harm-causing medical errors to patients and their families. Acknowledging that an error has caused serious harm to a patient is extremely distressing to doctors, most of whom enter the medical profession with the aim of relieving the suffering of others. When their actions inadvertently result in harm to patients, the impact can be devastating.3 The emotional reaction to a medical error is usually one of intense anxiety and concern for the patient’s welfare, then deep reflection on how the error occurred and how the outcome might be mitigated. This may be followed closely by the doctor’s anxiety about his or her own welfare and the professional and legal consequences of the mistake, including the potential loss of reputation or even job. Consequently, doctors are sometimes tempted to rationalise away their role in causing harm or minimise their responsibility for disclosing mistakes and failures.4,5 However, an apology is a powerful tool to facilitate healing of the emotional scars of a patient’s injury. Furthermore, from the perspective of a medical indemnity insurer, while open and transparent disclosure of medical error would seem an improbable risk-management strategy, there is no doubt that a truthful and compassionate explanation of some errors that cause harm may actually reduce the risk of litigation.6 So, as Studdert and colleagues conclude, doctors should be and are supported and encouraged to enter into these difficult discussions by their insurer, without a presupposed fear that the actual process of open disclosure might contribute to the risk of litigation. One hopes that stakeholders will continue to work towards removing barriers to this process, with a greater focus on clinical risk management and less on recrimination and blame within the Australian health care system in years to come.

Julian L Rait · Elizabeth H Van Ekert

To the Editor: Readers of the Journal’s editorial on the importance of clinical patient-outcome monitoring asking “Where are the clinical data?”1 will be pleased to know that the state of Victoria collects considerable data on surgical outcomes. Since 2001, the Department of Health’s Victorian Surgical Consultative Council (VSCC; http://www.health.vic.gov.au/vscc/) has monitored surgical outcomes in the state’s public hospitals. Monitoring of both morbidity and mortality outcomes is combined with voluntary and mandatory case reporting and a high level of participation of hospitals and surgeons. It is compulsory for hospitals to report a range of sentinel adverse events and undertake corrective strategies. Data about surgical inpatients are obtained from discharge coding in medical records statewide, and the chief executive officers and directors of surgery of health services with “outlying performance” are invited to analyse the case records and provide their findings to the VSCC. A VSCC subcommittee, the Surgical Outcomes Information Initiative, promulgates the conclusions in a de-identified manner to hospitals, surgeons and trainees, with a view to improving safety, systems and surgical outcomes. Since 2008, deaths of public hospital patients that occur under surgical care are monitored by the Victorian Audit of Surgical Mortality (VASM, derived from the VSCC), which covers most surgical specialties, and is soon to embrace private hospitals and, hopefully, gynaecological surgery as well. De-identified educative information from autopsies and case analyses is offered to surgeons and trainees, whose participation in case reporting and assessing is now a professional requirement of the Royal Australasian College of Surgeons (RACS). Surgical mortality as monitored by the VASM is now bi-nationally compared through the RACS’s overarching Australian and New Zealand Audit of Surgical Mortality. Victoria’s Department of Health has longstanding collections of data for anaesthetic, obstetric and perinatal outcomes, with similar consultative councils. Several surgical specialties have for over a decade collected and promulgated their morbidity and mortality information. The Melbourne Vascular Surgical Association requires its members to participate in clinical outcome audits, as does the Australian and New Zealand Society for Vascular Surgery. Other specialties that audit outcomes are orthopaedic surgery (the bone and joint registry), transplantation surgery and cardiac surgery. Surgeons’ general experience of clinical patient-outcome monitoring is that of enthusiasm for its professional and community benefits, including the benefit of knowing that Australia’s overall surgical standards are comparable with the world’s best. The incentive remains to improve data capture, patient safety and eternal clinical vigilance, and these endeavours deserve support.

Peter L Field

To the Editor: We would like to report the deaths of three young children in Australia as a result of hanging from bicycle helmets. Our aim is to draw attention to this rare but entirely preventable cause of childhood death. Helmets are required to be worn when bicycles are ridden, and have been the subject of mandatory standards since 1989.1 A number of accidental deaths have, however, been reported in the United States, Scandinavia and Canada as a result of young children becoming suspended by their bicycle helmets while playing on playground equipment. This has led to a series of warnings about not allowing children to wear helmets in playgrounds.2,3 The National Coroners Information System (NCIS)4 is an electronic database containing information on coronial cases from all Australian states and territories since 2001. We undertook a review of the NCIS for all deaths of children in Australia that were associated with bicycle helmets from 2001 to 2009. Three cases of deaths due to hanging were identified; these involved a 2-year-old boy who was suspended by his helmet strap between a bunk bed and a wall (in 2003), a 3-year-old boy who was suspended by his helmet strap when he tried to climb out of a home window (in 2007), and a 5-year-old boy who was suspended from an overhead clothesline while jumping on a trampoline (in 2009). These cases show that accidental hanging is still occurring among young children who wear bicycle helmets while engaging in activities other than bicycle riding. Importantly, hanging from bicycle helmets can occur in places other than playgrounds, sometimes by quite unusual mechanisms. Although such deaths are rare,5 it is important for parents and child carers to ensure that bicycle helmets are only worn by children for their intended purpose, and not during other activities.

Roger W Byard · Allan Cala · Donald Ritchey · Noel Woodford

To the Editor: We read with interest the letter by Baschera et al1 regarding the retrieval of non-permanent inferior vena cava filters (IVCFs) in trauma patients. With the advent of retrievable devices, there has been a renewed interest in the use of prophylactic IVCFs after trauma. Retrievable IVCFs are a particularly attractive option for trauma patients, who are often young, with only a transient predisposition to develop venous thromboembolism (VTE). They theoretically provide prophylaxis against pulmonary embolism (PE) in high-risk patients for whom chemoprophylaxis is contraindicated, while avoiding long-term complications associated with permanent IVCFs. However, we share the authors’ concern about low retrieval rates of IVCFs due to loss of patients to follow-up.2,3 The decision to place an IVCF in a patient who has undergone trauma is based on a risk–benefit ratio. If such decisions are made on the presumption that IVCFs will be retrieved, while in practice many IVCFs are not retrieved, the increasing popularisation of retrievable filters may be under false pretences. At our institution, a level 1 trauma centre, all IVCFs are inserted by interventional radiologists under fluoroscopic guidance. At the time of insertion, patient and device details are entered into a purpose-built IVCF database that is run and maintained by the Department of Radiology. At this time, a follow-up appointment is also booked for the patient to attend the IVCF outpatient clinic run by the interventional radiologists. Here, ongoing VTE risk factors are evaluated and the timing of IVCF retrieval is determined. The timing of IVCF retrieval after trauma is controversial, and the occurrence of PE after retrieval is well documented. The risk period for PE after trauma is difficult to quantify, but likely to extend beyond the discharge date for many patients, especially if ongoing surgery is scheduled. For this reason, our practice is to retrieve IVCFs in the outpatient setting 3–4 months after injury. Prolonged IVCF dwell times must be balanced against the increasing difficulty of retrieval because of IVCF endothelialisation, but we feel that a timeframe of 3–4 months does not compromise retrieval rates. Successful retrieval of filters has been reported up to 317 days after insertion.4 As in the case described by Baschera et al,1 it is not uncommon to find a clot in the filter at the time of attempted retrieval, for which multiple causes have been proposed.5 In this situation, it is our practice to rebook patients for a repeat cavogram and second retrieval attempt after therapeutic anticoagulation for 1–2 months.

Lachlan M Batty · Jim Koukounaras · Stuart M Lyon

To the Editor: Significant morbidity and mortality are associated with excessive alcohol use, which, for Aboriginal Australians, generally occurs within a context of disadvantage. During 2007–2009, we assessed cognitive and psychological factors (using CogState1 and Strong Souls2 [CogState Ltd, Melbourne, Vic]) of 21 men and 11 women on admission to a 2-month Aboriginal residential treatment program in the Northern Territory. Participants’ mean age was 32 years (SD, 8.7 years) and the mean length of time for which they had used alcohol was 13.3 years (SD, 7.7 years). To determine the effect of age, number of years of drinking and other factors on continued alcohol use, we reinterviewed and reassessed participants in their home community with the same cognitive and psychological measures used at the initial assessment after a mean period of 11 months (SD, 4.4 months). At both baseline and follow-up, the number of participants for whom data were available varied for some characteristics. The Human Research Ethics Committee of the Northern Territory Department of Health and Community Services and Menzies School of Health Research (including the Aboriginal Ethics Sub Committee) approved the study. At baseline, 14 of 23 alcohol users reported drinking every day or most days, and 26 of 31 drank more than 10 standard drinks on each occasion. At follow-up in the community, 23 had resumed drinking at the same level, and nine had reduced their use (six had stopped using alcohol, and three had resumed drinking at lower levels). Compared with users who reduced their alcohol intake, users who did not showed poorer paired associate learning at the time of admission for treatment, and poorer performance at follow-up in visual attention, learning and executive function, visual learning and recall, and paired associate learning tasks (Box). This suggests that while subtle cognitive impairment may be a risk factor for continued heavy alcohol use after treatment, heavy alcohol use is also a likely cause of additional cognitive deficits.3 While reduced alcohol use may be associated with improvements in cognitive function, continued use may lead to further cognitive decline. Alcohol users who resumed drinking at the same level were significantly more likely to experience the psychological symptom “worry” after treatment (4/6; Fisher exact test, P < 0.05) than were users who reduced their alcohol use (0/6), which suggests that alcohol may have been used for self-medication or that excessive alcohol use may mask underlying psychological problems. Interestingly, a greater proportion of alcohol users who resumed drinking at the same level (10/16) were also using cannabis at follow-up, compared with those who reduced their use (1/9; Fisher exact test, P < 0.05). Cannabis use has been independently associated with psychological symptoms in other Australian studies, but with no impact on cognition.2,4 Our data indicate that there is a need to treat mental health problems concurrently with alcohol misuse problems among alcohol users undergoing treatment. Alcohol users who resumed drinking at the same level were less likely to return to remote communities with restricted alcohol availability (11/23), compared with those who reduced their alcohol use (9/9; Fisher exact test, P < 0.01), lending some support to the effectiveness of alcohol restrictions. Overall, our data show that cognitive problems and alcohol availability may be underlying factors in ongoing alcohol misuse by Aboriginal Australians. Charactersitics of alcohol users who resumed drinking at the same level and those who reduced their alcohol use after a 2-month residential treatment program, at baseline and at follow-up (n = 32) Characteristic Unchanged alcohol use, median Reduced alcohol use, median Z Significance No. of alcohol users 23 9 Age at baseline, years 31.3 29.0 − 0.15 ns Years of drinking, at baseline 13.0 11.6 − 0.59 ns Visual attention, speed (log transformed)* Baseline 2.81 2.76 − 1.67 ns Follow-up 2.79 2.71 − 2.10 P = 0.04 Working memory, accuracy (arcsine transformed)† Baseline 0.70 0.70 − 0.19 ns Follow-up 0.80 0.74 − 0.53 ns Psychomotor speed, moves per second† Baseline 0.77 0.95 − 0.35 ns Follow-up 1.17 1.37 − 0.75 ns Learning and executive function, moves per second† Baseline 0.44 0.47 − 0.39 ns Follow-up 0.58 0.76 − 2.32 P = 0.02 Visual learning and recall, moves per second† Baseline 0.48 0.46 − 0.21 ns Follow-up 0.73 0.84 − 2.20 P = 0.03 Paired associate learning, duration (seconds)* Baseline 307.81 214.11 − 2.52 P = 0.01 Follow-up 286.51 168.48 − 2.67 P = 0.008 ns = not significant; P > 0.07. * Higher values indicate poorer performance. † Higher values indicate better performance.

Kylie M Dingwall · Paul Maruff · Sheree Cairney

To the Editor: The article by Philip Sambrook et al on the impact of adverse news media on prescriptions for osteoporosis1 contains a number of serious errors and ignores more recent data. Their article quotes the estimated incidence of osteonecrosis of the jaw (ONJ) after oral bisphosphonate treatment for osteoporosis to be between 1 in 10 000 and 1 in 100 000 patient treatment-years. This is in fact a gross underestimate.2 The results of an independent study funded and conducted by the United States Food and Drug Administration (FDA) found an incidence of between 1 in 537 and 1 in 1537.3 This result is similar to that of an independent Australian study, which found an incidence of 1 in 296 to 1 in 1130.4 Thus, there is evidence that bisphosphonate-associated ONJ is much more common in patients treated with oral bisphosphonates for osteoporosis than the authors claim. Bisphosphonate-associated ONJ is also much more serious than presented. Patients with ONJ can be affected for years. The condition causes considerable morbidity, with greater interference in a patient’s life than the condition of osteoporosis and vertebral fractures. It should be noted that the FDA study3 and the Australian study4 were based on documented cases of ONJ, whereas the study by Sambrook et al1 was not based on actual fractures. It is unfortunate that, despite the wording of the Pharmaceutical Benefits Scheme (PBS) regulations, the Pharmaceutical Benefits Advisory Committee has let it be known that osteoporosis diagnosed by bone mineral density is not a requirement for PBS-supported bisphosphonate therapy — all that is required is a minimal trauma fracture, although it is well known that most patients with minimal trauma fracture do not have osteoporosis (however that is defined).5 The issue of adverse effects of bisphosphonate treatment for osteoporosis is currently being tested by a US class action. In the bellwether case of Boles v Merck & Co,6 the issue being tested is whether it was appropriate to prescribe alendronate for a patient with osteopenia but no fractures, and how much this treatment contributed to the patient’s end-stage ONJ. The plaintiff had exposed bone, constant pain, a pathological fracture, and pus dripping from her chin. The New York Supreme Court found in her favour. Despite the claim by Sambrook and colleagues that unbalanced media coverage “has the potential to do more harm than good”,1 the media do have an important role to play in exposing to the public the risks of pharmaceutical products and the actions of some pharmaceutical companies. It should be noted that Professor Sambrook was not only involved in The 7:30 Report current affairs program, but was also subsequently granted the unusual right of reply on that program. Following these two programs, the public made its decision based on facts about the incidence and morbidity of ONJ that have been confirmed by recent independent studies.3,4,6

Paul J Sambrook · B E Christopher Nordin · Alastair N Goss

In reply: Readers will probably deduce that Paul J Sambrook is no relation of Philip N Sambrook. The Australian Broadcasting Corporation, which aired The 7:30 Report that Paul Sambrook and colleagues refer to, subsequently acknowledged in writing that there were a number of factual errors in the original program. Under these circumstances, a right of reply was entirely appropriate. There is ongoing debate about the incidence of osteonecrosis of the jaw (ONJ), but as the modelling used in our study1 did not involve any assumptions about this, it is irrelevant to our findings. The studies by Lo et al2 and Mavrokkoki et al3 did not report incidence of ONJ — they reported prevalence. Moreover, one of the coauthors of the letter by Paul Sambrook et al (above) has published that the estimates by Mavrokkoki et al, being from a retrospective postal survey, must be viewed with caution.4 The Lo et al study was approved by an institutional review board of the United States Food and Drug Administration (FDA), not “funded and conducted” by the FDA, as Sambrook and colleagues state in their letter. There have been numerous studies of the effects of vertebral fractures and osteoporosis on quality of life. The authors claim that ONJ causes greater interference to a patient’s life than osteoporosis or vertebral fractures, but cite no references to justify this bald assertion. The US court case of Boles v Merck & Co5 was not an “independent study” (as implied in the last paragraph of the letter by Sambrook et al), but a legal proceeding that is being appealed. One of the coauthors of the letter was a paid expert for the plaintiff. ONJ is a serious complication of bisphosphonate therapy in the small proportion of affected individuals. We agree that patients need to be informed of the risks of therapy, but they also need to be informed of the consequences of not taking therapy (ie, the benefits forgone) to make a really informed decision. Our article was intended to let patients understand what those consequences might be. The courts are certainly not the place for informed debate. And the media should appreciate that unbalanced reporting can have significant consequences.

Philip N Sambrook · Jiang S Chen · Judy M Simpson · Lyn M March

To the Editor: Clarke and Fitzgerald showed that substantial savings could arise from the implementation of alternative pricing arrangements for off-patent statins that provide incentives to reduce prices and increase generic substitution.1 This is exemplified by comparing statin prices between Australia and England. Europe offers some more lessons with respect to savings based on generic medicine usage and how they can be attained. The size of savings reported by Clarke and Fitzgerald needs to be interpreted with caution. A scenario of 100% generic substitution is proposed. Such a scenario has not been observed in any European country and, for therapeutic reasons, is probably not desirable.2 Furthermore, the comparator country matters: for instance, generic medicine prices in England are lower than in France, the Netherlands and Germany, but are higher than those in Scandinavian countries.3 Finally, the implementation of a tendering system for statins may create unintended effects, such as a switch in prescribing behaviour. For example, the Belgian tendering system for simvastatin reduced expenditure on off-patent medicines containing simvastatin by 30%, but increased expenditure for patented medicines containing atorvastatin or rosuvastatin by 16% and 40%, respectively.4 Clarke and Fitzgerald’s article does not go into detail on how savings can be attained through use of generic medicines. The majority of European countries regulate generic medicine prices by pricing rules or reference pricing. For instance, the implementation of a minimum price difference between originator and generic medicines is the driver of savings arising from generic substitution in some countries, including France, Portugal and Spain. The reference pricing system in Norway stimulated generic competition to a greater extent and led to lower prices than regulation that imposed maximum prices.4 However, price regulation may constitute a barrier for further price competition: no additional price reductions may occur beyond those imposed by regulation.4 The European experience also indicates that the ability of the generic medicine industry to deliver competitive prices can be achieved if it is assured a high volume of the pharmaceutical market. High volume is dependent on demand-side measures that create incentives for physicians, pharmacists and patients to use generic medicines. For example, a European study showed that savings as a result of price competition are higher in countries that have a higher market share of generic medicines.5 Therefore, demand-side measures are critical to increase the generic substitution rate and to maximise the effect of competition based on generic medicine prices.

Steven R A Simoens

In reply: The main purpose of our recent article1 was to quantify estimates of pharmaceutical expenditure over the next decade using various assumptions regarding the price and use of generic statins. We report estimates of billions of dollars in potential savings associated with various scenarios that increase the current off-patent statin use in Australia from around 25% of prescriptions to between 50% and 100%. Simoens misinterprets our conclusions as recommending only using generic statins in Australia. We do not advocate any particular level of generic substitution, but argue that the optimal mix of patented and generic statins should be determined by using cost-effectiveness analysis. Simoens questions whether our results would change if we had compared statin prices with a country other than England. To address this issue we have compiled a comparison of current or recent wholesale price of 40 mg simvastatin across 13 countries in the Organisation for Economic Co-operation and Development (Box). Although there is some variation between countries, the main difference is with Australia, which has the highest wholesale price — about five times greater than the average price across all comparator countries. This price ratio is similar to the one used in our original study. Also, Simoens highlights several issues relating to alternative pricing arrangements for statins and other generic drugs in European countries. We agree that Australia may be able to learn from overseas experience when reforming its system of pricing generic pharmaceuticals. The impact on expenditure of the tendering system for supply of generic pharmaceuticals may have been counteracted by changes in prescribing behaviour in Belgium, but it has been successfully used in the Netherlands to cut the price of simvastatin and other major generics by over 80%. This has been estimated to save around 310 million euros annually.2 However, tenders are not the only way to reduce the price of generic pharmaceuticals. In Canada, the Ontario Ministry of Health and Long-Term Care has recently introduced a policy which sets the subsidy for generics at 25% of the original price under patent. Generic 40 mg atorvastatin, whose patent in Canada recently expired, now costs just A$17 per month.3 In contrast, under the recent Memorandum of Understanding4 between the Australian Government and Medicines Australia, the current wholesale price of A$61 for 40 mg atorvastatin will decline by only 16% after the patent expires in Australia in 2012, and there will be no further downward adjustment until at least 2014. Wholesale price of simvastatin 40 mg in 13 countries in the OECD* OECD = Organisation for Economic Co-operation and Development. * Comparator prices were converted to Australian dollars using the average exchange rate over the past 3 years, and 1 month supply was assumed to be equivalent to 30 tablets.

Philip M Clarke · Edmund M Fitzgerald

To the Editor: I am writing about important errors contained in a letter of reply by Hamilton-Craig.1 In his response to a letter by Montgomery,2 he states: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (in which patients with aortic stenosis were treated for 52.2 months with statin plus ezetimibe or statin plus placebo) showed a 4.7% reduction in ischaemic [cardiovascular disease] events in the ezetimibe group (P = 0.02; number needed to treat, 23), driven by a reduced need for coronary artery bypass grafting. However, in the SEAS trial, patients were treated with statin plus ezetimibe or with placebo, not with statin plus placebo. Therefore, the reduction in ischaemic events in the statin/ezetimibe group cannot be attributed to ezetimibe, as it could have been caused by the effect of simvastatin alone (or by the combined effect of the two drugs). I note also that the absolute reduction in ischaemic events over the course of the trial was 4.4% (15.7% v 20.1%), not 4.7%.3 With respect to the ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) trial, Hamilton-Craig states: As no placebo group was included, neither lack of benefit nor harm from ezetimibe therapy can be inferred.1 In the ENHANCE trial, patients with familial hypercholesterolaemia were treated with simvastatin plus ezetimibe or simvastatin plus placebo. There was no significant difference in progression of mean carotid intima media thickness (CIMT) between the two groups (0.0058 mm in the simvastatin/placebo group v 0.0111 mm in the simvastatin/ezetimibe group [P = 0.29]).4 Therefore, contrary to Hamilton-Craig’s statement, there was a placebo group, and a lack of benefit from ezetimibe was shown in the trial. Thus, the SEAS trial was unable to confirm a benefit of ezetimibe, as the active treatment arm included both a statin and ezetimibe, while the ENHANCE trial showed no additional benefit of ezetimibe on the surrogate endpoint of CIMT progression in patients taking a statin. Author’s note: The United States Securities and Exchange Commission disclaims responsibility for any private publication or statement of any Commission employee or Commissioner. This letter expresses my views and does not necessarily reflect those of the Commission, the Commissioners, or other members of the Commission staff.

Marilyn K Mann

To the Editor: I would like to endorse the letter by Montgomery1 questioning the efficacy of ezetimibe. As yet there are no data to support its use in clinical trials using carotid intima media thickness (CIMT) as a measure of treatment effectiveness, and there is also some evidence to suggest it could be harmful. A randomised trial conducted by Berneis et al2 suggested that ezetimibe may induce an unfavourable pro-atherogenic low-density lipoprotein (LDL) subfraction profile by increasing small, dense LDLs. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial3 compared simvastatin/ezetimibe 40/10 mg daily with placebo, so any benefit from that treatment may have been from either the ezetimibe or the simvastatin. It tells us nothing about the effectiveness of ezetimibe alone. Until the results of clinical trials are available, I believe ezetimibe should be used with much reluctance and only considered as a last resort. I agree with Hamilton-Craig4 that it is a matter of concern that slow-release niacin, which is effective and safe, is not available under the Pharmaceutical Benefits Scheme in Australia. Searching for supplies of this drug in Australia or overseas seems the best option for treating patients whose levels of LDL cholesterol are inadequately controlled with statin therapy.

Brett H Forge

In reply: In the interests of scientific exactitude, I am indebted to Marilyn Mann for corrections regarding the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. However, as the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial did not include the control group ezetimibe versus placebo, the effects of ezetimibe on carotid intima media thickness remain somewhat speculative.1

Ian R Hamilton-Craig

To the Editor: I note the letter in the 7 June issue of the Journal by Ojaimi and colleagues, in which they express their concerns about the lack of uniform screening guidelines for patients on hydroxychloroquine therapy.1 The most obvious problem was the apparent failure of the treating rheumatologist to ensure that the patient was adequately followed up for ocular side effects associated with this treatment. The potential for these side effects has been documented for many years and, while more pertinent in earlier times when chloroquine was used more frequently, isolated case reports about retinal toxicity related to hydroxychloroquine continue to be presented in the medical literature. All patients need to be warned that there is a risk to their eyesight before they start treatment. The pertinent questions are, however, what is the risk and what is the cost of screening? One study found a single case of retinal toxicity in a series of over 1200 patients being treated long-term with hydroxychloroquine.2 Using this information and the data quoted by Ojaimi and colleagues on hydroxychloroquine use,1 there would currently be about 20 000 patients in Australia using hydroxychloroquine, and 17 potential patients with toxicity in the whole nation. Screening guidelines vary, with most recommending a baseline screen and then, depending on the presence or absence of “high risk factors” (dosage > 6.5 mg/kg/day, treatment for > 5 years, renal or hepatic impairment, concomitant eye disease, age > 60 years), testing 2 years after the baseline test and then annually,3 or 5 years after the baseline test and then annually.4,5 The cost of screening the 20 000 Australian patients being treated with hydroxychloroquine according to these guidelines and assuming a standard initial specialist consultation (Medicare Benefits Schedule item 104) and field test (Medicare Benefits Schedule item 11222) was performed would be between $20 174 000 and $28 820 000 over a 10-year period. One really has to ask, can we afford it? The patient described by Ojaimi and colleagues1 falls clearly into the high-risk group in terms of her daily dose and duration of treatment. The slit lamp findings of vortex keratopathy also indicate she had a high risk of retinal toxicity. Rather than screening all patients on hydroxychloroquine therapy, doctors prescribing the medication should be more aware of the potential consequences, and monitor the dosage carefully so that patients in the high-risk group can be referred for screening. Multifocal electroretinography and fundus autofluorescence could potentially be used for screening, but these modalities are not available routinely and their utility in screening is yet to be established. Until then, patients at high risk of hydroxychloroquine retinopathy should be referred to an ophthalmologist for examination. The minimum examination would include measurement of visual acuity, slit lamp biomicroscopy, dilated fundus examination and automated perimetry, looking specifically for changes in the central 10 degrees of visual field.

Trevor J P Hodson

To the Editor: We share the concern of Fernando and colleagues about the recent emergence of multidrug-resistant bacteria via travellers returning to Australia and the resulting reduction of therapeutic options for such patients, who may have entered a “post-antibiotic era”.1 In countries such as India that lack an integrated laboratory network, the precise magnitude of the threat of plasmids encoding blaNDM1 type metallo-β-lactamases is unknown. Molecular testing for the NDM-1 type of β-lactamases might be available at only two or three national laboratories, and most hospitals will have no such testing facilities. During replication of multidrug-resistant bacteria carrying blaNDM1 type metallo-β-lactamases, susceptibility to some older antimicrobial agents might be retained. This was evident in two multidrug-resistant Enterobacteriaceae isolates that were identified at the Sant Parmanand Hospital (a 140-bed tertiary-care, multidisciplinary hospital that serves the population of Delhi and two adjoining townships), at which blaNDM1 metallo-β-lactamase testing is not available. From March to August 2009, 509 Enterobacteriaceae isolates were identified — Klebsiella pneumoniae (368), Escherichia coli (112), Salmonella enterica serotypes Typhi, Paratyphi A, and Paratyphi B (20) and Proteus species (nine). Bacteria were identified by morphological, biochemical and serological characteristics. Antimicrobial susceptibility was tested by the disk diffusion method, according to the United States Clinical and Laboratory Standards Institute guidelines. Two of the K. pneumoniae isolates were resistant to meropenem, piperacillin–tazobactam, cefepime, amoxicillin–clavulanic acid, amikacin, gentamicin, ciprofloxacin and tigecycline. One had been isolated from the pulmonary secretions of a 45-year-old woman in March 2009; it was susceptible to ofloxacin and chloramphenicol. The other had been isolated from the urine of a 55-year-old woman in July 2009; it was susceptible to chloramphenicol and nitrofurantoin. Among all the K. pneumoniae isolates, there were 53 resistant to meropenem, 113 resistant to ceftriaxone, 82 resistant to gentamicin and 111 resistant to ciprofloxacin. Among all the E. coli isolates, there were three resistant to meropenem, 38 resistant to ceftriaxone, nine resistant to gentamicin and 35 resistant to ciprofloxacin. The proportion of meropenem- and gentamicin-resistant isolates was significantly higher for K. pneumoniae compared with E. coli (Fisher exact test, P < 0.001). Older antimicrobial agents such as ofloxacin, chloramphenicol and nitrofurantoin, developed in the 1940s and 1950s, would not be the initial choice for today’s clinicians managing patients with severe multidrug-resistant infections. However, they should be considered before declaring that the post-antibiotic era has arrived.

Subhash C Arya · Nirmala Agarwal

To the Editor: The article by Hawthorne and Hamilton, International medical students and migration: the missing dimension in Australian workforce planning?,1 highlights the issue of international students wanting to stay in Australia for internships and beyond. While the ethical dilemma created by keeping much-needed future doctors from their own countries has been extensively debated, the reality is that Australians, especially those in rural and remote settings, will rely on overseas-trained doctors for health care until the “tsunami” of current Australian medical students complete their training (in about 2020). The health workforce initiative of the Department of Health and Ageing Rural Clinical Schools (RCSs) promotes rural careers by funding 25% of Australian students for a year of rural clinical training. Funding is not provided for international students because of cost and limitations of rural training capacity (supervisor and infrastructure shortages). While “most” international students are interested in metropolitan practice,1 our RCS, at the Melbourne Medical School’s Rural Health Academic Centre, has had repeated, passionate requests from international students to attend the RCS. And quality rural placements increase (international) student and trainee interest in rural practice.2,3 Even if about 80% of the 25% of students who undergo a year of rural training (20% overall) return to rural health care (an optimistic assumption), Australia will still have a shortage of Australian-trained doctors willing to work in rural Australia (about 20% of medical graduates for 29% of the population). We suggest that the cost and capacity to train an international graduate of an Australian medical school may be less than the cost of recruiting, acculturating and up-skilling an international medical graduate. And targeted training and retention of international students from less disadvantaged countries will decrease recruitment from countries with severe health worker shortages.4 Thus, it might be wiser, more ethical, and perhaps more cost-effective to allocate funding to truly interested international students to attend an RCS or an extended quality placement in rural Australia; and then to support them for postgraduate training positions in exchange for rural payback (“bonding”). Of course, the challenge will be to identify international students with a true interest in rural health care and a willingness to be part of the solution. But if such students were willing and could be selected, they might fill the estimated 10% gap between the 20% of Australian students intending to practice rurally and the 29% of the Australian population that lives rurally. We hope that a cost-effectiveness analysis of trade-offs discussed here will become a priority for Australian health-workforce researchers so that the feasibility of this strategy can be determined.

Dawn E DeWitt · William R Adam

Never, ever, again . . . Why Australian abortion law needs reform. Caroline de Costa. Brisbane: Boolarong Press, 2010 (168 pp) ISBN 978 1 921555510. Caroline de Costa wrote her new book because of her belief that it is inappropriate to punish a woman for making the decision that she is unable to become a mother at this point in her life. The material has been carefully researched by the author, who is Professor of Obstetrics and Gynaecology at James Cook University, in Cairns, Queensland. It brings together into a single clear record the often confused history of abortion law and relevant court cases in both Queensland and elsewhere in Australia. The chapter on the long history of the family planning and abortion information service “Children by Choice” and its remarkable contribution to Queenslanders is enlightening. The book records gruesome personal stories of barbaric pre-1970 illegal abortions. They highlight the dangers to life and health to which Australian women, especially the poor and isolated, were exposed before court rulings that made some abortions lawful. The documentation of the history of the emergency contraceptive mifepristone (RU-486), which can be used for medical (non-surgical) abortion in early pregnancy or in the second trimester, is also valuable. The author knows the process well — she and her colleague were the first two doctors who were permitted by the Therapeutic Goods Administration to prescribe mifepristone in Australia. The book describes in detail the build-up to criminal action against Tegan Leach and her partner in Cairns, who were sent mifepristone from overseas. Leach appears to be the first Australian woman charged with procuring an abortion for herself. De Costa will publish an account of the court case on her website. De Costa’s book highlights the unclear and inconsistent abortion laws throughout Australia and the need for uniform and just laws as a first step in providing equitable access to abortion, including for mifepristone. This book documents how Australia continues to fail women who conceive but feel unable to raise a child at the time. I would strongly recommend this book to all obstetricians and gynaecologists, as well as others interested in women’s health. It adds to de Costa’s proud record as an advocate for women’s health.

Lachlan de Crespigny

Bob Barter, who contributed much to the establishment of gynaecological oncology and neonatal pathology services in Western Australia, died recently in Perth at the age of 85. Bob was born in Perth on 27 January 1925. He was educated at Scotch College, Perth, where he was dux of the school in his final year. As there was no medical school in WA at the time, he studied medicine at the University of Adelaide, completing his undergraduate degree in 1949 and a doctorate (on the pathology of lung disease in premature babies) in 1952. He was then awarded a Nuffield Fellowship to study at King’s College in London. Bob returned to Australia in 1954 and worked briefly as a Senior Lecturer at the University of Adelaide before taking an Assistant Pathologist position at the Royal Women’s Hospital in Melbourne in 1955. When a position as Senior Lecturer at the new Faculty of Medicine at the University of Western Australia became available in 1960, he returned with his family to Perth. He was subsequently appointed Associate Professor and Director of the newly established Pathology Department at King Edward Memorial Hospital for Women (KEMH). Apart from a sabbatical year spent as Visiting Professor at Ohio State University in Columbus, Ohio, in 1967, Bob remained at KEMH. During his time at KEMH, community cytological screening for cervical cancer was initiated in Australia. In its early days, it was viewed with considerable scepticism; indeed, the program in WA almost foundered due to lack of standardisation of laboratory cytological examination and reporting, but Bob took on the training and accreditation of scientific staff to a high standard and the crisis was averted. From 1970 to 1972, he was a consultant to the World Health Organization program that was establishing cytology services in Indonesia. From 1976, Bob played a crucial role in the newly established gynaecological oncology service at KEMH. He conducted weekly Tumour Board multidisciplinary meetings until his retirement, making a major contribution to the management of women with gynaecological cancer. He taught medical undergraduate and postgraduate students throughout his career, and had a long association with the Cancer Council Western Australia, serving as its president from 1974 to 1978. In 1990, he was made a Member of the Order of Australia in recognition of his services to medicine. After retirement in 1985, Bob turned his restless intellect and energy to other pursuits, including farming, travel, foreign languages and reading. The last 10 to 15 years of his life were dogged by failing health, which he faced with great fortitude. A series of strokes left him with increasingly severe dysphasia, and eventually resulted in his being unable to read. Despite his progressive incapacity, Bob remained interested in people and the world, and did not lose his sense of humour. This was in large measure made possible by the unfailing love and support of Lyle, his wife of 57 years. Bob died peacefully in hospital on 12 October 2010. He is survived by his wife Lyle, daughter Ann and son Graham, and predeceased by his older son Michael.

Toby T Nichols · Ian Hammond

Fat chance? Doctors should be brought before professionalism committees for any callous treatment of their obese colleagues, suggests a US cardiologist. In Memoirs of an obese physician, Majdan recounted various unprofessional comments he had received from other doctors when he was overweight or obese: “Hey, hey, hey, it’s Fat Albert!” one surgeon had bellowed, while some fellow residents had asked whether his lab coats were made by Omar the Tentmaker, and another had wanted to borrow his white intern trousers so that she could project slides onto them for a housestaff skit that she was organising. This constant insensitive attitude of colleagues, who preached empathy to their students and resident doctors, seemed hypocritical; Majdan called for professionalism towards obese patients to start with physicians. Ann Intern Med 2010; 153: 686-687 Asbestos wars Currently, Australia has the world’s highest national incidence of malignant mesothelioma — approximately 700 to 750 cases per year. Kao and colleagues say that its increasing incidence has lagged asbestos production and importation by two to three decades, so the incidence will continue to rise over the next 15 years, peaking around 2014-2021. In a review article, they outline the clinical management of this tragic, potentially preventable, aggressive cancer. They conclude by sharing their grave concerns that a number of countries, including some in the Asia-Pacific region, still mine and export asbestos, with the potential to lead to an epidemic in the decades to come. Intern Med J 2010; 40: 742-750 No laughing matter Nitrous oxide (N2O) — well known as “laughing gas” — may be making a comeback in an operating theatre near you, suggest Rammohan and colleagues. They say that, some decades ago, N2O was the preferred gas for creating a pneumoperitoneum in laparoscopic surgery, until two anecdotal, unsubstantiated cases of combustion and explosion during electrocoagulation via laparoscopy were reported. In 2009, they conducted a single blind case-controlled study in nearly 80 patients undergoing laparoscopic surgery, comparing the effects of N2O with those of carbon dioxide (CO2) as insufflating agents. They found that N2O had several advantages over CO2, including less postoperative pain and a decreased risk of cardiovascular side effects. Int J Surg Online, 5 Nov 2010 One in a hundred Prompt attention is needed to dispel the myth that developing countries can wait to deal with tobacco-related disease until they have dealt with infectious disease, according to international researchers. Öberg and colleagues recently reported their estimates for 2004 of the worldwide burden of disease from exposure to second-hand smoke. Passive smoking was responsible for about 603 000 deaths that year — or about one death in a hundred. About one in four of these deaths occurred in children. Passive smoking was also responsible for much non-fatal morbidity, including more than five million lower respiratory tract infections in children younger than 5 years of age. Lancet Online, 26 Nov 2010 Temporary territory General practitioner retention is an important issue in medical workforce planning, and especially so in the Northern Territory, Australia — between 2001 and 2006, a volume of GPs equivalent to 60% of the total workforce moved in and out of the Territory. Auer and Carson interviewed 19 GPs who had mostly been in the Territory for less than 3 years. They found that, for these doctors, working in the Territory is about “adjusting” — that is, temporarily setting aside a range of values and ambitions, including longer-term career ambitions, so as to benefit from the experience of “difference” in the Territory. It’s not about “place attachment”, which is the sense that a particular location is a desirable residence and likely to remain so into the future. However, various strategies aimed at increasing adjustment skills could encourage doctors to stay for longer or to make repeat visits to the Territory. Rural and Remote Health 2010; 10: 1476 (Online)

Ann T Gregory