Volume 192 Issue 3

Two phenomena are shaping physician assistants and their futures: change in human societies and change in health care delivery The physician assistant (PA) is a global phenomenon: a product of medicine that enjoys unparalleled success within the health profession in many societies. Born in the 1960s, nurtured in the 1970s, and grown in the 1980s, the PA proved to be a capable player in American health policy in the 1990s. By 2000, the PA had emerged in a handful of countries, and by 2015, PAs will surpass 100 000 worldwide.1 Various explanations regarding why this profession is growing have been advanced. Clearly, PAs fit well in the entrepreneurial American health care system; economic advantages, clinical flexibility and dependence on doctors are factors that contribute to their success. But it is other countries that are building on the original model. With a worldwide shortage of 4.5 million doctors and an inadequate number of medical schools, the sheer weight of population growth demands more medical personnel and resources.2 In addition, improvements in childhood survival and the control of archaic diseases (eg, malaria, tuberculosis, dengue fever, smallpox, polio) have resulted in people living longer and more comfortably than their parents. Technological advancements are limited only by the logistics of delivery to populations, both urban and remote.3 The increasing years of productivity of individuals indicates the need for an unprecedented cadre of health workers. Without more doctors and nurses, the next group of providers to look to is PAs. Canada, the United Kingdom, South Africa and the Netherlands are examining not only their present workforces, but also what will be needed in decades to come. The alternative to not growing their own workforces is recruiting overseas-trained doctors — a strategy with its own ethical considerations.4,5 A sociological explanation for the emergence of PAs is an evolution in the division of medical labour, not a loss of autonomy for doctors. Medicine has become infinitely more complex over the past several decades and the information base required to practise medicine is enormous, leading to greater levels of team-based care. Health care knowledge was once a vaunted supremacy of doctors, but now diagnostic and therapeutic tasks are shared with other health care professionals (in part because modern-day doctors cannot know and do everything in so vast a field). Throughout the 20th century, analytical technologies and therapeutic approaches produced new specialties, and today we have genetics, interventional radiology, robotic surgery and the resurgence of midwifery. Further expansion of medical activities and capabilities will necessitate the inclusion of additional trained personnel who share the domains of doctors but remain dependent on doctors for directing care. Other social forces have had a major influence on the PA movement. Changing lifestyles — doctors’ preferences for greater work–life balance grew during the 1970s. Today, most are eager to work (though not as hard as their predecessors) and desire help. Gender shifting — women have entered the workforce in a major way. They have tried out careers that are traditionally dominated by men, and have found them to their liking. For PAs, the education path is shorter than for medicine but has similar rewards. The opportunity to be engaged in a well respected career and successfully raise a family ranks high with many female applicants. Doctor dependency — the unwavering commitment of the PA profession to remain dependent on doctors bolsters widespread acceptance of PAs by medical professional bodies. National competency — the establishment of program accreditation and an independent national board overseeing the specific skills and competencies of PAs allows states to focus on licensure, roles and supervision. Primary care — for PAs, the emphasis on training in general medical care and obtaining core competencies creates a known entity. Such a model permits more role flexibility and mobility (beneficial characteristics in a changing health care environment) than exists for doctors and nurse practitioners. The PA succeeds, in part, because of the attributes of individuals. Early entrants saw themselves as change agents who wanted to prove that allied health individuals trained in this PA model could benefit society safely and effectively. The PA profession continues to attract those who feel dead-ended in their current health care roles but do not want the burden of a protracted medical school experience or investment. For example, an experienced military medic may seek to use his or her skills in civilian life or an indigenous health care worker who is isolated without options for career progression may wish to upgrade his or her role to enable a return to cultural roots. Looking forward, key questions emerge. What does the future hold for the PA profession? How will the changing faces of various health care systems affect the PA profession? Will a PA trained and certified in Utrecht, the Netherlands, be able to work in Mt Isa, Australia, and be effective? Two phenomena are shaping PAs and their futures: change in human societies and change in health care delivery. These are on convergent paths that predict the growth of PAs for many years to come — at least in many countries. How Australia will fit this new provider into its health care system is contentious for some. For those who want to expand the capacity of its highly skilled workforce, the pace of change leaves few options.6

Roderick S Hooker PhD, PA

The latest evidence for the essential elements of surgical prophylaxis protocols There is no question that antibiotic prophylaxis for cardiac surgery reduces surgical site infections.1 The successful implementation of prophylactic regimens, however, is often inconsistent or inadequate. The use of prophylaxis protocols or decision-support systems as either a single measure2 or as part of a patient care pathway3 has been demonstrated to improve adherence to prophylaxis, with a reduction in surgical site infections. In this issue of the Journal (page 141), a study by Haydon and colleagues4 shows that antibiotic prophylaxis protocol use in 45 Australian cardiac surgery units increased significantly between 2004 and 2008 (from 58% to 80%), but concordance with version 13 of the Australian Therapeutic guidelines: antibiotic5 was poor when both choice of agent and duration of administration were considered. In particular, there was an increased use of multidrug regimens, an increased use of vancomycin for routine prophylaxis, and a prolonged duration. The study did not examine surgical site infection rates. As prophylaxis protocols improve patient outcomes, and adherence to protocols in Australian cardiac surgery units seems to be high, it is timely to consider the optimum elements of such protocols in terms of timing of prophylaxis, duration of prophylaxis, and choice of agent. There have been a number of studies that show the relationship between timing of antibiotic administration and surgical site infections. An observational cohort study in a consecutive series of 3836 surgical procedures (vascular, trauma and abdominal) showed the optimal time for administration of β lactams was 30–60 minutes before incision.6 The risk-adjusted odds ratio of surgical site infections was 3.16 (95% CI, 1.4–7.0) if given 75–120 minutes before, 2.82 (95% CI, 1.5–5.3) for administration 15–29 minutes before, and 1.75 (95% CI, 0.9–3.4) if given in the last 14 minutes before incision. In a prospective study of 2048 patients given vancomycin prophylaxis for cardiac surgery (coronary artery bypass graft [CABG] or valve replacement), the optimum time for the start of a vancomycin infusion was shown to be 16–60 minutes before incision.7 The relative risk of infection was 7.8 (95% CI, 2.5–24.7) if started 0–15 minutes before incision and 2.2 (95% CI, 0.99–5.09) if started 61–120 minutes before. Duration of prophylaxis has been a controversial issue. The Society of Thoracic Surgeons practice guidelines8 recommend that prophylactic antibiotics be given for 48 hours or less, citing some evidence for effectiveness of single-dose or 24-hour regimens, but comment that additional studies are required to confirm the effectiveness of shorter courses. This has been addressed in a study on 838 patients undergoing CABG or valve replacement.9 Patients received cephazolin as either a single dose before incision or a prolonged regimen, with a dose before incision, then 8-hourly for 24 hours. There was a statistically significant difference in surgical site infections between the two groups (8.3% v 3.6%; P = 0.004). The choice of agent is mainly between a β lactam and vancomycin, although alternative choices are possible (eg, flucloxacillin plus gentamicin). The Society of Thoracic Surgeons practice guidelines10 recommend cephazolin for standard practice in populations that do not have a high incidence of methicillin-resistant Staphylococcus aureus (MRSA). Haydon et al’s study showed that routine vancomycin use for CABG surgical prophylaxis increased from 13% in 2004 to 44% in 2008, with similar increases seen for valve surgery — from 31% to 62% over the same period.4 Vancomycin prophylaxis for cardiac surgery is recommended in the current Therapeutic guidelines: antibiotic for institutions with a high prevalence of MRSA, for β lactam-allergic patients, or for procedures where there is a higher risk of infection with a coagulase-negative staphylococcus (eg, valve surgery, reoperations).5 Excessive vancomycin use is to be discouraged, as its activity is inferior to β lactam antibiotics for susceptible organisms and it will add selective pressure for hVISA (heteroresistant vancomycin-intermediate S. aureus), particularly if the duration of administration is prolonged. With the advent of rapid MRSA molecular detection tests, it is now possible to screen patients before surgery and use vancomycin selectively in those found to carry MRSA. An alternative is to use intranasal mupirocin routinely in the absence of a documented negative test for MRSA (and methicillin-sensitive S. aureus [MSSA]), as this agent has been shown to reduce both MSSA and MRSA surgical site infections.11 How do these recommendations relate to the Therapeutic guidelines: antibiotic? The current guidelines, version 13 (published in 2006),5 are concordant, except for the duration of therapy. It is very likely that this is the major issue that has resulted in the lack of adoption of the guidelines’ cardiac surgery prophylaxis regimens found by Haydon and colleagues. Version 14 of Therapeutic guidelines: antibiotic is currently in preparation and due to be published in 2010, and the recent studies described here have been noted by the writing committee. It is very likely that version 14 will recommend a 24-hour prophylaxis regimen and that the recommended antibiotic agents will remain unchanged. The purpose of any surgical prophylaxis protocol is to ensure adherence to the optimum choice of agent, timing of administration and duration of prophylaxis. With such adherence, surgical site infections will be minimised, thereby reducing morbidity and mortality for patients undergoing cardiac surgery.

Keryn J Christiansen MB BS, FRCPA

Rebecca Nicole Hannah Zajac is not a name two people are likely to have. Yet, my daughter, living in the United States, found that someone with this name and the same birthday as her had opened three bank accounts and overdrawn these accounts substantially. Thus, when Rebecca came to open a bank account in New York City, she was told it was not possible because she already had three accounts on which money was owed at another bank. This is a real and not uncommon scenario in the US where, because of the complexity of the banking system, identity fraud is rife. For Australians visiting or living in the US since the new homeland security laws came into force, it is quite difficult to open a bank account there. On the other hand, having one’s credit card skimmed to duplicate the cardholder’s name, the card’s number and other data is easy. What might surprise you is that medical identity fraud is now becoming a significant issue in the US. An article in the New York Times in July 2009 described a person who discovered, on checking his credit rating, that he owed tens of thousands of dollars for medical bills.1 This included visits to emergency rooms and an air-ambulance flight. According to a 2006 World Privacy Forum report, more than 250 000 Americans were affected by medical identity theft in 2005.2 For us, it is quite difficult to conceive how this process works. An Australian who goes to a public hospital emergency room incurs no cost. In the US, a visit to the emergency room, whether public or private, incurs substantial fees. For uninsured patients, these fees are often payable in advance, unless the patient has a life-threatening illness, in which case the money will be collected later. Using another person’s identity, including his or her name and Social Security number shifts the bill to that unfortunate person. A slight variation on this theme involves patients going to the doctor and using someone else’s name and insurance identification number to get free treatment, including, apparently (according to the New York Times article), major elective surgery. As some forms of US health insurance have a lifetime cap on financial benefits, someone else using your insurance could, in fact, use it all up. Medicare fraud in Australia, which was reported to occur in the early days of Medicare, involved doctors billing patients whom they had not seen, or billing patients for additional and longer visits. If President Obama’s public insurance scheme is passed, it is possible that a similar problem could occur in the US. President Obama stated that a significant goal of his new health policy would be the generation of transportable, up-to-date, reliable electronic medical records. This is a worthwhile goal, and if it comes to pass and develops technology that can be used in Australia, it will have a substantial and positive effect on our health care system. However, in the US, if someone were to get hold of your electronic record and use it as part of a medical insurance identity fraud, their medical information could become entangled with yours. Obviously, for patients with relatively short medical records, regular review would pick this up immediately. However, for many older patients with very complicated medical histories, this may not be readily apparent, and could potentially cause a major health problem. It could lead to incorrect blood transfusion, incorrect drug prescription or incorrect surgery. The possibility of incorrect data within an electronic medical record is a major issue. Anyone used to dealing with large computer files will recognise the problem at once. Misfiling in paper hospital records occurs, but it is usually obvious when a result or history relates to a patient other than the owner of the file. In an electronic record, if the content is divorced from the name, or if fraud is involved, medical staff seeing the patient for the first time might not detect the error. As in many things, future developments in Australia are seen first in the US. It is to our advantage that foresight is a wonderful gift. However, we must remain mindful that, like many clever ideas originating in the US, this one may have a substantial downside if we are not very careful.

Jeffrey D Zajac MB BS, PhD, FRACP

Objective: To explore 5 years of drowning deaths in Australia compared with a previous Australian study a decade earlier, and to assess the feasibility of achieving a 50% reduction in unintentional drowning deaths by 2020.Design and setting: An audit of all unintentional drowning deaths in Australia using data from the National Coroners Information System for 1 July 2002 to 30 June 2007.Main outcome measures: Number and rate of drowning deaths, by age, sex, location, activity, place of birth, visitor status, and involvement of alcohol or drugs.Results: There were 1452 drowning deaths during the study period (76.4% male). The age-adjusted rate per 100 000 people ranged from 1.61 in 2002–03 to 1.23 in 2006–07. Children aged 0–4 years had the highest rate (2.63 per 100 000 people), and 29% of deaths were of people aged 55 years or older. Over half of all deaths occurred in rivers (20.3%), at beaches (18.3%), or in swimming pools (13.3%). Alcohol was involved in 21.6% of all drowning deaths, although this varied by age.Conclusions: This audit suggests that a 50% reduction in drowning fatalities by 2020 may be achievable using current knowledge and preventive systems in certain types of immersions. However, further research and new initiatives will be required, particularly to prevent drowning deaths in rivers and of older people.

Richard C Franklin BSc, MSocSc, PhD · Justin P Scarr BEd, MBA · John H Pearn MD, FRACP, FRCP

Objectives: To determine population lipid profiles, awareness of hyperlipidaemia and adherence to Australian lipid management guidelines.Design and setting: Population survey in rural south-eastern Australia, 2004–2006.Participants: Stratified random sample from the electoral roll. Data from 1274 participants (40%) aged 25–74 years were analysed.Main outcome measures: Population mean total, low-density lipoprotein and high-density lipoprotein cholesterol (TC, LDL-C and HDL-C) and triglyceride (TG) concentrations, prevalence of dyslipidaemia, and treatment according to 2001 and 2005 Australian guideline target levels.Results: Population-adjusted mean TC, TG, LDL-C and HDL-C concentrations were 5.38 mmol/L (95% CI, 5.30–5.45), 1.50 mmol/L (95% CI, 1.43–1.56), 3.23 mmol/L (95% CI, 3.16–3.30) and 1.46 mmol/L (95% CI, 1.44–1.49), respectively. Prevalence of hypercholesterolaemia (TC > 5.5 mmol/L or on treatment) was 48%. Lipid-lowering medication use was reported by 12%. Seventy-seven of 183 participants with established cardiovascular disease (CVD) or diabetes were untreated, and of the 106 treated, 59% reached the target LDL-C. Of those without CVD or diabetes already treated, 38% reached target LDL-C, and 397 participants at high absolute risk did not receive primary prevention. Ninety-five per cent of treated individuals with CVD or diabetes and 86% of others treated had cholesterol measured in the previous year. Sixty-nine per cent of individuals at low risk aged over 45 years had their cholesterol measured within the previous 5 years.Conclusions: A comprehensive national strategy for lowering mean population cholesterol is required, as is better implementation of absolute risk management guidelines — particularly in rural populations.

Edward D Janus MD, FRACP, PhD · Philip A Tideman MB BS, FRACP · James A Dunbar MD, FRCPE, FRACGP · Annamari Kilkkinen MSc, PhD · Stephen J Bunker PhD · Benjamin Philpot BSc, GradDip(ActuarialStud) · Rosy Tirimacco BSc · Kevin Mc Namara BSc, MSc · Sami Heistaro MD, PhD · Tiina Laatikainen MD, PhD

Objective: To examine the performance in tropical northern Australia of SMART-COP, a simple scoring system developed in temperate Australia to predict the need for intensive respiratory or vasopressor support (IRVS) in pneumonia patients.Design, setting and patients: A prospective observational study of patients admitted to Royal Darwin Hospital in the Northern Territory with sepsis between August 2007 and May 2008. Chest x-rays were reviewed to confirm pneumonia, and each patient’s SMART-COP score was assessed against the need for IRVS.Results: Of 206 patients presenting with radiologically confirmed pneumonia, 184 were eligible for inclusion. The mean age of patients was 50.1 years, 65% were Indigenous and 56% were men. Overall, 38 patients (21%) required IRVS, and 18 patients (10%) died by Day 30. A SMART-COP score of ≥ 3 had a sensitivity of only 71% for predicting the need for IRVS and 67% for 30-day mortality. As the variables most strongly associated with IRVS were serum albumin level < 35 g/L (odds ratio, 6.8) and Indigenous status (odds ratio, 2.3), we tested a modified scoring system (SMARTACOP) that used a higher weighting for albumin and included Indigenous status. A SMARTACOP score of ≥ 3 had a sensitivity of 97% for IRVS and 100% for 30-day mortality.Conclusions: The SMART-COP score underestimates the severity of pneumonia in tropical northern Australia, but can be improved by using locally relevant additions.

Joshua S Davis MB BS, DTM · Gail B Cross BSc, MB BS · Patrick G P Charles MB BS, FRACP, PhD · Bart J Currie MB BS, FAFPHM, FRACP · Nicholas M Anstey MB BS, FRACP, PhD · Allen C Cheng MB BS, FRACP, PhD

Objective: To compare the weight status of women and children living in socioeconomically disadvantaged rural and urban neighbourhoods in Victoria.Design, setting and participants: Cross-sectional study of data collected between August 2007 and July 2008 as part of the Resilience for Eating and Activity Despite Inequality (READI) study. Women aged 18–45 years living in 40 rural and 40 urban socioeconomically disadvantaged Victorian areas were surveyed by postal questionnaire. Data from a subset of their children aged 5–12 years were also analysed. Weight and height were self-reported for women and measured for children.Main outcome measures: Women’s weight status based on body mass index (BMI): underweight; healthy; overweight; or obese Class I, II or III; children’s weight status based on International Obesity Taskforce BMI cut-off points.Results: Of 11 940 women randomly selected, 4934 (41%) replied to a postal invitation to participate. After exclusions for various reasons, data were available on 3879 women and 636 of their children. Twenty-four per cent of urban and 26% of rural women were classified as overweight; a further 19% of urban and 23% of rural women were classified as obese. Twenty per cent of both urban and rural children were classified as overweight; a further 10% of urban and rural children were classified as obese. In crude analyses, rural women had higher odds of Class I and II obesity (odds ratio [OR], 1.34 and 1.72, respectively) compared with urban women. After adjusting for sociodemographic factors (age, number of children, country of birth, education level, employment status and marital status), there was no difference between urban and rural women in odds of overweight or obesity Class I, II or III. No significant urban–rural difference in odds of overweight/obesity was evident among children.Conclusions: The higher prevalence of obesity in rural women compared with urban women was largely explained by individual-level sociodemographic factors, such as age, number of children, country of birth, education level, employment status and marital status. This suggests that higher obesity levels among women in rural areas may be attributable to the sociodemographic composition of these areas.

Verity Cleland PhD · Clare Hume PhD · David Crawford PhD · Anna Timperio PhD · Kylie Hesketh PhD · Louise Baur MB BS, PhD · Nicky Welch PhD · Jo Salmon PhD · Kylie Ball PhD

Objective: To evaluate national practice for antibiotic prophylaxis in cardiac surgery with respect to the use of protocols, agent selection and duration of administration.Design, setting and participants: Two point-prevalence surveys of intensive care units in 24 public and 27 private hospitals performing cardiac surgery in Australia, conducted in 2004 and 2008, using a structured telephone questionnaire of the attending senior intensive care clinician in each unit.Main outcome measures: Existence of a protocol in the unit for antibiotic prophylaxis, specific antibiotic agents used and their duration of administration.Results: Between 2004 and 2008, reported protocol use increased from 58% to 80% (P = 0.02), while concordance with version 13 of the Australian Therapeutic guidelines: antibiotic for both choice of agent and timing (duration of administration) remained around 10%. Use of multiple agents was common, as was continued antibiotic administration after completion of surgery. Over 4 years, the proportion of cardiac surgical units reporting vancomycin administration for routine valve surgery prophylaxis doubled to 62% (P < 0.001).Conclusion: Despite an increase in reported protocol use for antibiotic prophylaxis in cardiac surgery, concordance with national antibiotic guidelines remained low, with duration of antibiotic administration deviating most from recommendations. Prophylactic vancomycin use appears to have increased substantially in recent years. Clinical implementation of recommended perioperative cardiac surgical antibiotic prophylaxis may not occur until supported by evidence from either a large prospective randomised study or standardised national surveillance of cardiac surgical site infection rates.

Timothy P Haydon FRACP, FJFICM, FANZCA · Jeffrey J Presneill MB BS, MBiostat, PhD · Megan S Robertson FRACP, FJFICM, FANZCA

Parkinson disease (PD) is a multisystem neurodegenerative disorder that affects about 1% of the population over the age of 55 years and has mean age of onset of about 60 years. The Braak hypothesis proposes that the earliest pathological evidence of PD is found in the enteric nervous system, medulla and olfactory bulb, and only subsequently progresses (over years) to the substantia nigra and cortex. Non-motor symptoms, such as constipation, hyposmia and sleep disorders, may precede typical motor features of PD by several years. No treatment has been convincingly shown to slow PD progression (ie, a neuroprotective drug remains elusive). Symptomatic benefit from dopaminergic therapy is usually maintained throughout the course of the disease. The decision as to whether to commence treatment with either levodopa or a dopamine agonist needs to be individually tailored, but long-term outcomes appear to be equivalent. Advanced PD is complicated by the loss of non-dopaminergic neurones, resulting in symptoms that are largely unresponsive to dopaminergic therapy. Treatment with apomorphine, Duodopa or deep-brain stimulation surgery may be beneficial for selected patients with advanced PD. Non-motor symptoms, such as mood disorders, cognitive impairment, autonomic dysfunction and sleep disorders, are responsible for significant morbidity. Management often requires a multidisciplinary approach.

Michael W Hayes MB BS, MSc, FRACP · Victor S Fung MB BS(Hons), PhD, FRACP · Thomas E Kimber MB BS(Hons), PhD, FRACP · John D O’Sullivan MB BS, MD, FRACP

Objective: Community-based medical education is growing to meet the increased demand for quality clinical education in expanded settings, and its sustainability relies on patient participation. This study investigated patients’ views on being used as an educational resource for teaching medical students.Design: Questionnaire-based survey.Setting and participants: Patients attending six rural and 11 regional general practices in New South Wales over 18 teaching sessions in November 2008, who consented to student involvement in their consultation.Main outcome measures: Patient perceptions, expectations and acceptance of medical student involvement in consultations, assessed by surveys before and after their consultations.Results: 118 of 122 patients consented to medical student involvement; of these, 117 (99%) completed a survey before the consultation, and 100 (85%) after the consultation. Patients were overwhelmingly positive about their doctor and practice being involved in student teaching and felt they themselves played an important role. Pre-consultation, patients expressed reluctance to allow students to conduct some or all aspects of the consultation independently. However, after the consultation, they reported they would have accepted higher levels of involvement than actually occurred.Conclusions: Patients in regional and rural settings were willing partners in developing skills of junior medical students, who had greater involvement in patient consultations than previously reported for urban students. Our study extends the findings from urban general practice that patients are underutilised partners in community-based medical training. The support of patients from regional and rural settings could facilitate the expansion of primary care-based medical education in these areas of workforce need.

J Nicky Hudson BM BS, MSc, PhD · Kathryn M Weston PhD · Elizabeth E Farmer FRACGP, BSc, PhD · Rowena G Ivers FRACGP, MPH, PhD · Russell W Pearson FRACGP, FACRRM

Paying incentives above the baseline Medicare Benefits Schedule to health services for the additional work required to meet the health needs of Aboriginal people or Torres Strait Islanders might mitigate inequalities of care, but evidence supporting this is lacking. The proposed “Indigenous health” incentive payment to reduce Aboriginal health disadvantage, which is largely aimed at increasing the responsiveness of mainstream general practices, provides an opportunity to examine the assumptions behind this and other recent health reform bids. Contentious implementation issues include: the ineligibility of several Aboriginal community controlled health services (ACCHSs) to receive this payment; determining Aboriginality and the potential for misappropriation of payments; the difficulty accounting for practice population diversity and patient mobility; and concerns about the benefits or otherwise to the Aboriginal community. Evaluation of the measure will present problems: to attribute outcomes, an evaluation must disaggregate outcomes by type of service provider (general practice or ACCHS). If these challenges are not addressed, this initiative may end up merely funding coordination of care for those Aboriginal people and Torres Strait Islanders who are already regular users of the health system.

Sophie Couzos FRACGP, FACRRM, FAFPHM · Dea Delaney Thiele PGDipHlthMgt

Objective: To describe the prevalence of depressive symptoms in older male Italian-born Australian immigrants.Design, participants and setting: Cross-sectional study of 335 Italian-born and 849 Australian-born men aged 70 years and over who completed written questionnaires and were interviewed in the baseline phase of the Concord Health and Ageing in Men Project (CHAMP).Main outcome measures: Depressive symptoms assessed by the short (15-item) form of the Geriatric Depression Scale; associations between depressive symptoms and country of birth.Results: The prevalence of depressive symptoms in Italian-born men was 18%, almost twice the prevalence of 10% in Australian-born men (odds ratio [OR], 1.9; 95% CI, 1.2–3.0). After adjusting for socioeconomic and health factors, the relationship between country of birth and depressive symptoms was attenuated and no longer statistically significant (OR, 1.7; 95% CI, 0.9–3.0). The strongest confounders of the relationship between country of birth and depressive symptoms were source of income and satisfaction with social support.Conclusion: Male Italian-born immigrants aged over 70 years report more depressive symptoms than their Australian-born counterparts. This association appears to be explained by increased reliance on a government pension as the sole source of income and lower satisfaction with social support among Italian-born men. However, these findings need to be confirmed longitudinally.

Fiona F Stanaway MB BS, MPH · Robert G Cumming MB BS, MPH, PhD · Vasi Naganathan FRACP, MMed(Clin Epi), PhD, Grad Cert Med Ed · Fiona M Blyth MPH, FAFPHM, PhD · Helen M Creasey MB BS, FRACP · Louise M Waite MB BS, FRACP, PhD · David J Handelsman MB BS, FRACP, PhD · Markus J Seibel MD, FRACP, PhD

Clinical record On 1 June 2009, a 79-year-old man presented to the emergency department of a tertiary hospital in Melbourne with a 1-week history of dyspnoea and a productive cough. He had underlying chronic obstructive airways disease (COAD) and type 2 diabetes mellitus. He reported no history of fever and no recent travel or contact with people with influenza-like illness (ILI). On examination, his temperature was 37.0°C, oxygen saturation was 97% in room air, and he had an expiratory wheeze. No abnormalities were seen on chest x-ray. Full blood examination showed a peripheral white cell count within the reference range (RR), and a raised C-reactive protein level (27 mg/L; RR, < 5 mg/L). The patient was admitted to a four-bed hospital ward and treated with oral doxycycline, corticosteroids and nebulised salbutamol. A nasal swab was sent to the state reference laboratory for polymerase chain reaction (PCR) testing for respiratory viruses to identify any potential viral precipitant for the apparent exacerbation of COAD. Results received 2 days later were positive for influenza A virus, which was confirmed to be the pandemic (H1N1) 2009 strain. Treatment was then begun with oseltamivir, and the patient was placed in a single room with droplet precautions. The patient’s contacts within the hospital were traced through review of his bed movements and all staff rosters (medical, nursing, allied health, patient support services and clerical staff of the emergency department and wards). All health care workers who had come into contact with the patient were telephoned, and the extent of their contact and individual risk factors were assessed. High-risk contact was defined as having spent more than 15 minutes within 1 m of the patient without wearing appropriate personal protective equipment. Twenty-one people with high-risk contact were identified, comprising nine medical staff, six nurses, three allied health staff and three patients. All were given oseltamivir prophylaxis. By this time (2 days after the patient’s admission), three of the medical staff who had high-risk contact with the patient (eg, taking a history or examining the patient while he was receiving nebulised therapy) reported the new onset of an ILI. They were therefore given treatment doses of oseltamivir. Furthermore, one of these medical staff reported having had significant contact, while symptomatic, with nine medical registrars during a 1-hour radiology tutorial in a confined space. At that stage of the pandemic, the reference laboratory was testing a high volume of specimens for H1N1 2009 influenza, and the average time for results of specific tests to be returned was, in our experience, 2 working days. Consequently, we decided to assume that the three medical staff with ILI had pandemic 2009 influenza and to initiate a second round of contact tracing. This included contacting all patients and health care workers who had come into contact with any of these staff. We identified a further 17 medical staff and seven patients and offered them oseltamivir prophylaxis. All accepted this prophylaxis. Symptomatic staff were asked to stay home from work, but it was considered impractical to redeploy asymptomatic health care workers receiving prophylaxis to areas with less patient contact. The evaluation of exposed health care workers and dispensing of medication were conducted by infection control practitioners, infectious diseases staff and microbiology staff, in addition to their normal duties. The extra workload was estimated to be almost 2 full days for at least two staff members. Four days later, the swab results from the three symptomatic medical staff showed they were negative for influenza A, and prophylaxis for their contacts was ceased. None of the other 18 people who had significant contact with the index patient developed ILI. This case illustrates some of the practical challenges of infection control during the recent influenza (H1N1) 2009 pandemic. The patient’s presentation was atypical for pandemic influenza, and a number of health care workers and patients had significant exposures before the illness was diagnosed. Each exposed person required follow-up, counselling and management, which created a significant workload for infection control staff. This case illustrates the need for additional infection control resources — “surge capacity” — to protect staff and their contacts both inside and outside hospitals. Influenza A has been associated with exacerbations of COAD.1 However, at the time our patient was admitted to hospital, he did not meet the case definition for pandemic (H1N1) 2009 influenza proposed by the Victorian Department of Health: “acute onset of illness with a measured temperature of greater than or equal to 38°Celsius or significant history of fever (rigors, sweating, chills) plus two or more of cough, sore throat, body aches, fatigue/tiredness or shortness of breath”.2 As the pandemic progressed, clinicians began to recognise atypical presentations of influenza (H1N1) 2009. Soon after our patient’s presentation, our hospital began isolating all patients who presented with any respiratory symptoms and testing them for influenza (H1N1) 2009 as part of a more proactive strategy. However, this strategy became practical for us only when our hospital had access to “in-house” PCR testing with a reliable turnaround time of less than 24 hours. Before this, despite the extraordinary efforts of the state reference laboratory in the face of huge numbers of specimens, the logistic problems and consequent delays in obtaining results3 led to practical concerns about “bed block”. This patient was admitted early in the pandemic, and thus the management of exposed health care workers had not been well tested. Transmission of the virus to staff members had been reported elsewhere,4 and, as observed during the pandemic of severe acute respiratory syndrome, the risk of occupational exposure to respiratory pathogens is real and can be fatal.5 It was therefore essential that staff members who had significant exposure to the patient were promptly contacted, counselled and appropriately managed. Management had to be tailored to confounding factors, such as pregnancy and immunosuppressive states. This process was time-consuming and required extra staff. Novel communication methods, such as group emails and intranet updates, were used to ensure consistency and accuracy of advice to staff. New links were forged between hospital administration and infection control services to ensure appropriate information was circulated. New channels of communication between infectious diseases physicians across several hospitals, and with representatives of the state Department of Health, also allowed for discussion of management strategies. This case illustrates some of the practical problems for infection control services that were probably mirrored in hospitals across the country as the influenza (H1N1) 2009 pandemic evolved. Management of staff exposure is difficult, and a single missed case can affect many staff members. Given our experience, we believe it is crucial that additional infection control resources be provided during such an outbreak to deal with staff exposure. The Australian Health Management Plan for Pandemic Influenza6 is a useful resource, but needs to be tailored to the context. Reflection is now needed on how we might improve our response. Lessons from practice In the early stages of a pandemic, the case definition should be broad to capture atypical presentations. Diagnostic test results need to be rapidly available to allow early diagnosis and appropriate treatment, and to assist bed management in hospitals for appropriate infection control. It is important that infection control departments have extra staff available to facilitate contact tracing across the hospital and thus prevent transmission to high-risk patients and health care workers.

Uma Devi MB BS · Kirsty L Buising FRACP, MPH, MD

After a 10-day course of oral oseltamivir for pandemic (H1N1) 2009 influenza infection, a renal transplant recipient developed rapid-onset severe primary viral pneumonia due to oseltamivir-resistant virus. Respiratory failure progressed despite high-dose oral oseltamivir, nebulised zanamivir and cessation of immunosuppressive medications, but his condition improved with intravenous zanamivir. He subsequently died of non-respiratory complications. This is the first case of oseltamivir-resistant pandemic (H1N1) 2009 in Australia and the first report of resistance in a solid organ transplant recipient. (MJA 2010; 192: 166-168) Clinical recordA 38-year-old cadaveric renal transplant recipient had remained well on a standard immunosuppressive regimen until he presented 7 weeks after transplantation with coryzal symptoms and fever. Nose and throat swabs were collected for influenza testing, and he was empirically commenced on oral oseltamivir at the recommended dose of 75 mg twice a day,1,2 to be taken at home. The swabs were subsequently confirmed as positive for pandemic (H1N1) 2009 influenza (Box), and he continued taking oseltamivir for 10 days, with clinical improvement. Three days after ceasing treatment, the patient was admitted with high fever, myalgia and a cough productive of clear sputum. A chest x-ray showed pulmonary infiltrates in both upper–mid zones and the right lower zone. He was commenced on antibiotics for presumptive community-acquired pneumonia, but over the next 5 days he became hypoxic and tachypnoeic with increasing lung infiltrates and required intubation for ventilatory support. His nose and throat swabs taken on admission were negative for influenza, but 2 days after admission, a sputum sample was positive for pandemic (H1N1) 2009, as was a bronchoalveolar lavage performed 7 days after admission. His antimicrobial therapy was broadened and oral oseltamivir reintroduced at 75 mg twice daily, despite renal dysfunction, as higher oral doses have been shown to achieve therapeutic blood levels in severely ill patients.3 On Day 11, oseltamivir was reduced to 75 mg daily due to anuria, but the patient’s absorption of oral fluids subsequently ceased and pandemic (H1N1) 2009 was again detected by polymerase chain reaction (PCR) testing of samples taken on Days 17 and 19. Nebulised zanamivir 15 mg four times a day was added on Day 23, and from this point on, influenza was not detected from respiratory specimens. His immunosuppressive therapy was reduced and subsequently ceased on Day 25, but his condition continued to deteriorate, with worsening lung infiltrates and a partial pressure of oxygen/fraction of inspired oxygen (Pao2/Fio2) ratio of 55 (Pao2/Fio2 ratio < 300 indicates acute lung injury) by Day 29. On Day 30, we identified an oseltamivir resistance mutation in the neuraminidase (NA) gene — a point mutation resulting in a histidine-to-tyrosine substitution at position 275 (H275Y) — in the virus from the patient’s Day 3 sample, though it was not present in virus from his first illness preceding admission. As his clinical progress with nebulised zanamivir was still poor, intravenous zanamivir was obtained through an emergency investigational drug application for compassionate use and commenced at a modified dose of 60 mg twice a day, based on a predicted ultrafiltration rate of 10 mL/min. Two days later, this was increased to 150 mg twice a day; however, due to a sudden deterioration in his liver function tests (alanine aminotransferase, 825 U/L [normal, < 40 U/L]), the dose was reduced 3 days later to 60 mg twice daily, with prompt improvement in liver function. Oral oseltamivir and nebulised zanamivir were also continued because of uncertainty about the correct intravenous zanamivir dose for a patient on continuous venovenous haemofiltration. After 7 days of treatment with intravenous zanamivir, the patient’s condition slowly improved and he eventually became ventilator-independent, but he subsequently died on Day 78 from intraperitoneal sepsis. At that time he had ceased all antiviral therapy, and repeated tests of upper and lower respiratory tract samples were negative for influenza. Surveillance of close contacts for respiratory illness found no evidence of acquisition of pandemic (H1N1) 2009. During his admission, he was isolated in a single room under full respiratory precautions. For virological testing of respiratory specimens, dry swabs were tested by PCR only, while swabs in viral transport medium and other fluid specimens were also cultured for influenza virus using a centrifuge-enhanced shell vial culture in Madin–Darby canine kidney cells. Real-time reverse transcription PCR (rRT-PCR) assays were directed at the matrix genes of influenza A and B and the haemagglutinin genes of seasonal A/H1, A/H3 and pandemic (H1N1) 2009 viruses. Cycle threshold (CT) values ≤ 40 were regarded as positive. Samples and cultures testing positive for pandemic (H1N1) 2009 were then tested for oseltamivir resistance (Box) using an NA gene rRT-PCR with separate probes specific for the wild-type sequence and the H275Y mutation, by sequencing of the NA gene product (ABI Prism 3130xl Genetic Analyzer, Applied Biosystems Inc, Foster City, Calif, USA) for the presence of the H275Y mutation, and by testing phenotypic susceptibility to oseltamivir on isolated viruses using a fluorometric assay to determine the oseltamivir 50% inhibitory concentration (IC50).4 Samples collected during the patient’s first illness contained only wild-type pandemic (H1N1) 2009, and the isolate collected prior to antiviral therapy was phenotypically susceptible to oseltamivir, with a low IC50 of 0.43 nM (Box). In contrast, all samples testing positive to influenza during his admission contained the mutant strain, with a markedly elevated IC50 of 382.5 nM for the Day 7 isolate, compared with 649.9 nM for the reference oseltamivir-resistant pandemic (H1N1) 2009 virus strain A/Osaka/180/2009. Interestingly, the Day 7 sputum sample appeared to contain a mixture of wild-type and mutant virus on the rRT-PCR test, and sequencing of the Day 19 sample also indicated a possible mixed infection. DiscussionTo our knowledge, this is the first report of infection with oseltamivir-resistant pandemic (H1N1) 2009 virus in Australia, and the first such report in a solid organ transplant recipient with an ultimately fatal outcome. Oseltamivir and zanamivir act by specifically inhibiting the NA of influenza viruses. The H275Y mutation — the major mechanism for oseltamivir resistance in influenza A/H1N1 — was rare until it emerged in seasonal influenza A/H1N1 in 2007, but it soon became the dominant type throughout the world,5 including Australia.6 Importantly, these oseltamivir-resistant viruses remain susceptible to zanamivir. As of 9 October 2009, there had been only 31 reports of oseltamivir resistance in pandemic (H1N1) 2009 influenza virus,7 despite the large amounts of oseltamivir used internationally. All of these resistant viruses have contained the H275Y NA mutation. Most cases have occurred in patients taking oseltamivir as post-exposure prophylaxis, with few in immunosuppressed patients on long-term oseltamivir treatment.8 One immunosuppressed patient was treated with intravenous zanamivir after inhaled zanamivir was not tolerated.9 All reported cases due to resistant virus have been sporadic, with no evidence for onward transmission, and no fatal cases have been reported previously. Our patient was initially infected with wild-type virus, but his first positive sample following relapse, collected 5 days after ceasing his initial course of oseltamivir and 3 days before its reintroduction, detected only oseltamivir-resistant virus. This suggests that the resistant virus emerged in the few days after ceasing his first course of oseltamivir, possibly due to declining blood and tissue levels of the antiviral drug. During his subsequent admission, the oseltamivir-resistant strain predominated, but there was evidence of a persistent mixed infection, based on the detection of both wild-type and resistant virus by rRT-PCR on Day 7 of admission, and supported by the intermediate elevation of IC50 of that isolate. Interestingly, despite the emergence of the resistant virus, there were declining levels of both resistant and susceptible virus, in spite of the patient’s clinical deterioration and even before commencing zanamivir on Day 23, as indicated by a progressive increase in the rRT-PCR CT values (Box). In accordance with our policy for patients with proven or suspected lower respiratory tract involvement, we used twice the standard dose of oseltamivir, adjusted for the patient’s renal function. It is possible the oseltamivir therapy had continued to provide some useful antiviral activity, but we were unable to test blood levels of oseltamivir carboxylate to investigate this further. Despite the negative virological results from respiratory specimens taken while he was receiving nebulised zanamivir and oral oseltamivir, our patient’s condition continued to deteriorate, with dense pulmonary consolidation. There was concern that he was not getting adequate levels of antiviral drug in the lung tissue, so intravenous zanamivir was introduced. As there was no suitable established treatment regimen for patients on continuous venovenous haemofiltration, dosing was based on the ultrafiltration rate. This was calculated as 10 mL/min, correlating to an intravenous zanamivir dose of 60 mg twice daily, but was subsequently increased to 150 mg twice daily due to the patient’s continued respiratory deterioration. Liver function rapidly deteriorated following the dose increase but promptly recovered when the dose was reduced, suggesting that the deterioration had been drug-related hepatic dysfunction. After 7 days of intravenous zanamivir, the patient’s respiratory function had stabilised. This may have been an effect of the intravenous zanamivir and/or his improving immune function following the earlier cessation of immunosuppressive therapy. After cessation of his antiviral therapy, there was no evidence of reappearance of the virus, and his death 38 days later was due to non-respiratory complications. The management of this patient was complicated by the uncertainty surrounding correct dosing of oseltamivir and zanamivir in a severely unwell patient, with the inability to perform therapeutic drug monitoring, and the difficulties in interpreting non-invasive respiratory specimen virological results in the setting of dense pulmonary consolidation. Where absorption is suspected to be unreliable, intravenous zanamivir may prove to be a useful antiviral therapy for severely unwell influenza patients, including those with oseltamivir-resistant pandemic (H1N1) 2009 infection. Clinicians caring for immunosuppressed patients with pandemic (H1N1) 2009 should be aware of the potential for development of oseltamivir resistance during therapy and for prolonged viral shedding. Strict adherence to infection control measures is recommended until immunosuppressed patients have clinically improved and respiratory specimens test negative by both PCR and viral culture. Laboratory testing results for detection of influenza Cycle threshold value (> 40 considered negative) Day of admission Sample Influenza A matrix gene Pandemic (H1N1) 2009 H gene NA gene wild-type NA gene H275Y mutant NA gene sequence Oseltamivir IC50 of cultured virus − 13 Nose/throat swabs 29 29 32 Negative Wild-type* 0.43 nM − 9 Nose/throat swabs Negative 40 Negative Negative Wild-type* — 1 Nose/throat swabs Negative Negative — — — — 3 Sputum 17 22 Negative 28 H275Y mutant* — 7 Sputum 17 22 35 27 H275Y mutant† 382.5 nM 7 Bronchoalveolar lavage 19 23 Negative 24 H275Y mutant‡ — 8 Nose/throat swabs 23 25 Negative 27 H275Y mutant‡ — 17 Nose/throat swabs 32 40 Negative 38 H275Y mutant* — 19 Sputum 35 34 37 Negative Mixed* — 24 Nose/throat swabs Negative Negative — — — — 24 Sputum Negative Negative — — — — 28 Endotracheal aspirate Negative Negative — — — — 28 Nose/throat swabs Negative Negative — — — — 33 Nose/throat swabs Negative Negative — — — — 33 Endotracheal aspirate Negative Negative — — — — NA = neuraminidase. IC50 = 50% inhibitory concentration. — = test not done. * Sequence from patient sample only. † Sequence from cell culture isolate only. Wild-type virus was detected in this sample by polymerase chain reaction, but sequencing detected only the mutant strain. ‡ Sequence from patient sample and cell culture isolate.

David J Speers MB BS, FRACP, FRCPA · Simon H Williams BSc · Mary Pinder MB BS, FRANZCA · Harry R Moody MB BS, FRACP · Aeron C Hurt BSc(Hons) · David W Smith BMedSc(Hons), MB BS, FRCPA

To the Editor: A 69-year-old Indigenous Australian man, with no known Caucasian ancestry, presented in 2008 with a 7-week history of depigmentation of the face and neck, which was initially intensely pruritic and erythematous. He had neither a personal history nor family history of vitiligo, but a 2 mm thick, Clark level III, superficially spreading melanoma had been widely excised from his right lateral calf in 2001; results of a right inguinal sentinel node biopsy had been negative. In 2005, multiple small local recurrences on the right lower leg had been surgically removed. Two years later, further histologically confirmed local cutaneous and subcutaneous recurrences were excised, but new lesions continued to develop. His medical history included type 2 diabetes mellitus, hypertension, atrial fibrillation and coronary artery bypass grafting. He had no family history of melanoma. The onset of facial inflammation and depigmentation over a few days in 2008 was associated with complete regression of some leg lesions and partial regression of others. The facial inflammation settled spontaneously within a week. Computed tomography of the abdomen and pelvis at this time did not show any distant disease. The patient was unconcerned by the depigmentation and declined treatment. Over the following 5 months, the extent of his head and neck depigmentation increased (Box, A) and he developed more melanomas on his right lower leg, including one with a depigmented rim (Box, B). Positron emission tomography identified several areas of focally increased metabolism corresponding to the right lower leg lesions, but no evidence of disease elsewhere. The leg lesions have demonstrated only slow progression, and the patient continues to have 6-monthly follow-up at our department, as well as ongoing local review. Cutaneous melanoma is rare in Indigenous Australians, with only two reported cases of acral lesions.1,2 In melanoma, immunogenic factors may play a key role in disease course. Antibodies that cross-react with antigens on melanocytes and melanoma cells, such as tyrosinase, tyrosinase-related-protein-1 and tyrosinase-related-protein-2, can lead to both vitiligo-like autoimmune depigmentation and tumour regression.3 T-cell-mediated responses to melanoma antigens, such as MART-1 (melanoma antigen recognised by T-cells-1), are also enhanced in melanoma patients with depigmentation,3 which has been reported in approximately 3% of patients with stages III and IV melanoma.4 Vitiligo is a positive prognostic factor and has been reported in association with tumour regression distant from the depigmentation.4 In conclusion, this case of vitiligo-like depigmentation, affecting both the head and neck and a cutaneous metastasis, highlights the immune responsive potential of metastatic melanoma. Vitiligo-like depigmentation associated with melanoma in a 69-year-old Indigenous Australian man A: Extensive depigmentation of the face and neck 5 months after the onset of vitiligo. B: Depigmentation around the largest subcutaneous metastasis on the right lower leg.

Elizabeth M Christou · Diona L Damian · John F Thompson

To the Editor: I read with interest the article by Grange and colleagues suggesting that vaccination with BCG vaccine or past severe infections may help protect against the development of melanoma.1 They do not mention the work of Coley. Coley was a surgeon at the Hospital for the Ruptured and Crippled in New York, who, after observing the regression of tumours in patients who developed erysipelas involving the tumour site, reported in 1891 in the Annals of Surgery,2 and again in 1893 in the American Journal of the Medical Sciences,3 that injecting Streptococcus pyogenes from erysipelas isolates into the patient’s tumour induced regression. Thus the relationship between neoplasia and bacterial infection has been recognised for 118 years. Coley is considered the father of cancer vaccines.

Michael G E O’Rourke

To the Editor: We report a case of desmoplastic small round cell tumour (DSRCT) in the liver of a 23-year-old woman who presented with a recurrent non-pruritic rash. The woman had a generalised macular rash, predominantly on the back and upper thighs. She reported recurrent similar skin rashes over the previous 4 months that had been treated with intermittent courses of oral antibiotics. She had felt mild fatigue during the 3 weeks prior to presentation. She was otherwise well, but had non-tender hepatomegaly (17 cm) on examination. There was no peripheral lymphadenopathy. Levels of cholestatic liver enzymes were mildly raised (γ-glutamyl transpeptidase, 198 IU/L; alkaline phosphatase, 246 IU/L), but bilirubin and immunoglobulin levels were normal. The serum level of cancer antigen 125 (CA125) was 141 U/mL (reference range, < 35 U/mL). A computed tomography scan of the chest and abdomen showed multiple hepatic lesions (Box 1). A radiologically guided biopsy was taken, and histological examination revealed the typical morphology and immunophenotype of DSRCT (Box 2). Our patient was counselled regarding diagnosis and likely poor prognosis. We did not attempt to preserve fertility, because we felt treatment should not be delayed and that life expectancy was limited. Chemotherapy with alternating VAC (vincristine, doxorubicin and cyclophosphamide) and IE (ifosfamide and etoposide) cycles was started promptly. Molecular testing for EWS1/WT1 (see below) was not performed, as there was insufficient biopsy tissue available. The patient’s rashes disappeared after one treatment cycle, and we postulate that the rashes were paraneoplastic and immune-mediated. Restaging scans after four cycles of chemotherapy demonstrated a partial response. Stem cells were pre-emptively mobilised to store for possible subsequent autologous transplantation. The patient will be reassessed after eight cycles. If there is a significant response, the options of high-dose chemotherapy with autologous stem cell transplantation and/or debulking surgery will be explored. To our knowledge, this is the first Australian report of DSRCT in a woman presenting with recurrent rash. DSRCT is a rare, aggressive tumour that predominantly affects males in early adulthood.1 There is a single Australian report of a 15-year-old boy who died of DSRCT 20 months after diagnosis.2 The histogenesis of DSRCT is unknown, but it exhibits divergent differentiation, expressing epithelial, muscular and neural proteins. It is characterised by the chromosomal translocation t(11;22)(pl3;ql2), formed by fusion of the Ewing sarcoma gene (EWS1) to the Wilms tumour suppressor gene (WT1).3 Patients typically present with non-specific symptoms, and the tumours are usually intra-abdominal. The level of CA125 is often raised, but this does not assist with diagnosis or monitoring.1 Diagnosis is by histology and immunohistochemistry, complemented by cytogenetic identification of an EWS1/WT1 translocation. Patients with DSRCT have a poor prognosis, with a median survival of 15 months. Given the rarity of the tumour, there are no data from randomised phase III trials to guide management. Aggressive multimodality treatment offers the highest chance of disease control and prolonged overall survival.1,4 Palliative debulking can be of benefit if curative resection is not feasible. Radiotherapy is best employed as consolidation treatment after chemotherapy and surgery.1,5 Combination chemotherapy is the backbone of therapy and offers improved progression-free survival. The P6 protocol,6 which uses alternating cycles of VAC and IE with 21 days between cycles, is most widely employed. Subsequent high-dose myeloablative chemotherapy with autologous stem cell support may be beneficial.4 1 Pre-treatment computed tomography scan of the patient’s abdomen, showing multiple hypodense lesions in the enlarged liver 2 Histological sections from a core biopsy of a desmoplastic small round cell tumour (DSRCT) in the liver A: Irregular nests of small round hyperchromatic tumour cells were embedded in a prominent fibrotic stroma (haematoxylin–eosin stain, original magnification ×250). A diagnosis of DSRCT was confirmed by immunohistochemical stains (B–D). B: The muscle marker desmin. C: An epithelial marker AE1/3. D: The Wilms tumour marker WT1. (Original magnification of images B–D ×100.)

Meena Okera · David Moffat · Sudarshan Selva-Nayagam

To the Editor: Over-the-counter herbal supplements to promote weight loss have become increasingly popular. Several of these products contain potentially hepatotoxic substances. We present the first reported Australian case of acute hepatotoxicity associated with the weight-loss product Hydroxycut Hardcore (Iovate Health Sciences, Blasdell, NY, USA). Hydroxycut contains various ingredients, including extracts of the herbs Garcinia cambogia and Camelia sinesis (green tea root), and the chromium salt, chromium polynicotinate. A recent review cites these three ingredients as possible causes of Hydroxycut hepatotoxicity.1 A 23-year-old, previously well, construction worker presented to his doctor with a 2-month history of lethargy and jaundice. Test results confirmed serum liver enzyme derangement, and the patient was advised to stop taking the weight-loss supplement. Results of repeat testing a week later showed worsening liver enzyme levels and he was referred to our hospital. On arrival, the patient denied any symptoms except moderate lethargy and icteric sclera. He was usually well with no relevant medical or surgical history. He weighed 83 kg. He denied drinking alcohol, using prescription or non-prescription drugs, or receiving a blood transfusion. He had had unprotected sexual intercourse 2–3 months earlier. A previously obtained tattoo was being extended by a reputable tattoo parlour. He had been using Hydroxycut Hardcore daily for 10 weeks (obtained from his local outlet of a global nutritional products retailer) in an attempt to lose weight and tone muscle. He claimed to have taken the dosage recommended by the manufacturer (six capsules daily); he was taking no other supplements. Physical examination revealed mild jaundice without other features of chronic liver disease or portal hypertension. However, in addition to abnormal blood levels of liver enzymes, bilirubin and iron, results of the patient’s liver biopsy showed severe acute hepatitis (Box). The abnormal test results were consistent with acute drug toxicity. The patient improved without specific treatment and was discharged 8 days after presentation, with near-normal serum liver enzyme levels. He was well on follow-up at 4 weeks. Two reports from the United States link Hydroxycut Hardcore to acute liver injury in otherwise well young males.2,3 The American Food and Drug Administration in May 2009 advised consumers to stop using the product, based on 23 reports linking it to serious injury, including one case of liver failure leading to death.4 In May 2009, Australia’s Therapeutic Goods Administration (TGA) issued a warning to consumers about the product, although noting that no adverse events had so far been reported in Australia.5 In view of this first reported Australian case of Hydroxycut hepatotoxicity, we advise medical practitioners and consumers in this country to be wary of the product, and call on the TGA to re-examine its continued availability. Investigation results for a 23-year-old man with liver dysfunction after using Hydroxycut Hardcore Investigation Result (reference range) Blood tests Aspartate aminotransferase (U/L) 1182 (12–36) Alanine aminotransferase (U/L) 2950 (5–40) Alkaline phosphatase (U/L) 121 (50–140) Bilirubin (µmol/L) 113 (3–18) Prothrombin time (seconds) 13 (11–15) Iron (µmol/L) 68 (11–30) Ferritin (µg/L) 1897 (30–400) Iron saturation (%) 99 (16–50) Paracetamol Not detected Hepatitis A, B, C Negative HIV Negative Autoantibodies Not detected Epstein–Barr virus, cytomegalovirus, toxoplasma, leptospira, coxiella Negative Haemochromatosis genetic testing No abnormality Other tests Abdominal ultrasound No abnormality Percutaneous liver biopsy Severe acute lobular hepatitis with areas of bridging necrosis; no bridging fibrosis or cirrhosis were seen Hepatic iron index 1.1 (< 2.0)

N Nudrat Rashid · Jason Grant

To the Editor: The editorial by Buchbinder et al suggesting that the effectiveness of vertebroplasty has been determined by the two studies she and her co-authors published1 is misleading. Both studies2,3 contain major flaws. In both, 70% of eligible patients declined to participate. No details of these patients are published, but they may have been the patients with more severe pain. The median duration of pain in the Australian study2 was 9 weeks (compared with 16 weeks in the US study3); only 30% of patients had pain for less than 6 weeks. No information on the need for hospitalisation because of severe pain was given in either study. The average length of hospital stay was not published. In the Australian study, the inclusion criteria were the presence of back pain of less than 12 months’ duration and the presence of one or two recent fractures.2 In this group of patients, whose average age was 74 years, there will be many possible causes of back pain. The fracture may be the main cause of pain, a part-player, or may not be significant. In patients with milder pain and longer duration of pain, non-fracture causes are more likely. In the US study,3 patients were selected on the basis of x-ray unless the fracture “was of uncertain age”. I have performed an audit of my practice and found that in patients with an unequivocal x-ray diagnosis of fracture level, magnetic resonance imaging (MRI) identified another fracture not seen on x-ray in 23 of 63 patients (36%), and in 10 of the 63 patients (16%), a fracture that was presumed acute showed no oedema on MRI. In the Australian study,2 the experience of the radiologists performing the vertebroplasty is not made clear; no details are given about the number of patients they had previously treated. The incidence of osteomyelitis (3.8% at best, 30% at worst, depending on which centre was involved), despite prophylactic antibiotic therapy, is unacceptable. In the US study, injury to the thecal sac in one of 78 patients suggests incompetence. The protocol stated that cement injection was ceased if “cement reached the posterior quarter of the vertebral body or leaked into intraosseous structures”. This sometimes happens after 1 mL of cement has been injected. Experienced operators will perform various manoeuvres to ensure an adequate spread of cement occurs throughout the vertebral body. It would appear this was not done. The volumes of cement injected are not published, except an estimate of “about 3 mL”. The sham procedure was not a true placebo. Injection of local anaesthetic onto the pedicle would likely block the dorsal ramus nerve and provide partial analgesia of the fracture if the fracture extended into the pedicle. Those who perform vertebroplasty regularly see patients who are bedridden, in severe pain, intolerant of analgesics, and who have undergone various procedures including epidural injections or facet joint injections without benefit, and who then respond to vertebroplasty within 24 hours. Efforts should be aimed at refining technique and patient selection, rather than throwing out the baby with the bathwater on the basis of inappropriate studies.

Paul J Graziotti

To the Editor: Clinical trials study a restricted patient group, so their results may not be generalisable to a different population subgroup or the population as a whole. The editorial by Buchbinder, Osborne and Kallmes1 about their recent vertebroplasty studies2,3 concludes that vertebroplasty offers no benefit over placebo. They suggest that, in light of their trials, the decision to list vertebroplasty on the Medical Benefits Schedule will be reviewed later this year. I understood the review to have been part of the original listing on the benefits schedule and not as a result of their studies, and I suggest that their editorial generalises results to a subpopulation of early acute vertebral fractures that they did not study. The duration of symptoms in osteoporotic vertebral fracture is critical, as most fractures heal quickly with a good outcome by 3 months, and only a very small group of patients continue to experience pain.4 A fracture that is still painful months after the event is not a “normal fracture”, and I suggest is less likely to respond to the same management concepts as an acute fracture. In the study by Buchbinder and colleagues, patients had persistent pain and were recruited up to 1 year after their vertebral fracture.2 Nearly three-quarters had significant ongoing pain for at least a month after their fracture, and most for at least 2 months. The study by Kallmes and colleagues also included symptomatic fractures up to 1 year old, with the interquartile range (8–38 weeks) suggesting that they had an even longer period between fracture and inclusion in the trial.3 While vertebroplasty appears to be unhelpful for patients who continue to have chronic pain months after an acute osteoporotic fracture, the authors have not robustly excluded vertebroplasty as improving quality of life and pain management in those who undergo vertebroplasty within days to a month of the fracture. Such an outcome is suggested by Rousing et al, who showed that vertebroplasty within 2 weeks of fracture led to a rapid reduction in pain within 12–24 hours, similar to the result of conservative management at 3 months.4 Any review of the role for vertebroplasty should consider the populations studied and, hence, should define the characteristics of patients in whom to intervene or not intervene.

Kevin D Pile

In reply: The letters by Graziotti and Pile raise spurious issues that in no way threaten the key message of our trials. Participation rates in both trials were better than other controlled trials of vertebroplasty or kyphoplasty.1,2 Eligible patients who declined enrolment in the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST) had similar levels of pain and disability to those who participated.3 Both trials adhered to stringent eligibility criteria, ensuring that only patients with pain due to acute or subacute fractures were included. All operators were trained and experienced, and the low incidence of serious adverse effects in both trials is consistent with the literature. There is no evidence that the outcome of vertebroplasty is influenced by cement distribution or volume.4 Local anaesthetic infiltration of the periosteum of the pedicles, as occurred in one trial,3 is unlikely to have a sustained effect. As Pile points out, most osteoporotic vertebral fractures heal quickly; this implies that most people would be unlikely to benefit from early invasive intervention. Consistent with this, public funding for vertebroplasty in Australia only has interim approval for patients whose pain is not controlled by conservative medical therapy. While duration of medical therapy is not specified, historically, this has ranged from at least 4 to 6 weeks. Thus, both trials included patients similar to those who would qualify for government-subsidised funding of the procedure in Australia. While Pile acknowledges that vertebroplasty appears to be of no value in patients with persisting symptoms (the group most likely to derive benefit), he seems to suggest that it may have a role in early treatment (within days to a month). As well as being at odds with his earlier statement, this is not supported by the available data. Many participants in both trials had short symptom duration (Australian trial, 32% < 6 weeks; INVEST, 20% < 6 weeks and 41% ≤ 13 weeks), and neither trial found evidence that symptom duration was a treatment effect modifier. The trial by Rousing et al reported comparable outcomes from vertebroplasty and conservative treatment in patients with acute symptoms (40 patients, < 2 weeks; 10 patients, 2–8 weeks).5 While no data were presented, the immediate (12–24 hours) benefit from vertebroplasty reported in this open study, like clinical experience, could be attributable to many factors including local anaesthesia, regression to the mean, and expectation bias. The onus remains on proponents of vertebroplasty to prove that any benefits of vertebroplasty outweigh the potential risks.

Rachelle Buchbinder · Richard H Osborne · David Kallmes

To the Editor: In their letter of 5 October 2009, Wong and colleagues highlight the importance of providing training for surgical specialties in the private sector.1 With 64% of surgical activity in Australia now occurring in the private sector,2 and public hospital activity constrained due to ongoing budget imperatives, the Royal Australasian College of Surgeons (RACS) has been actively exploring this idea for some years. The new Surgical Education and Training (SET) program selects trainees into one of nine specialty programs.3 Currently, there are 1254 trainees in the SET program across Australian, New Zealand and overseas positions. Once selected into a specialty program, trainees who succeed in achieving the educational goals will be able to progress through its entirety. Consequently, to enable completion of training in the program, each SET Level 1 post needs to be matched in the public or private sector with more senior training positions to ensure appropriate progression. The RACS has worked with a number of private hospitals and the federal government to identify and fund 50 training positions suitable for surgical education across Australia. The funding has predominantly been provided through the Australian Government’s Expanded Specialist Training Program. This program was established following the release of the Medical Specialist Training Steering Committee report4 to encourage training in settings other than public teaching hospitals. The RACS is keen to have this program substantially enhanced and is attempting to identify models with the federal government that can achieve this. This is where the work by Wong and colleagues1 is so important. The public and private sectors are different. Both can be highly useful for the education of a skilled surgeon. However, all educational environments need enthusiastic supervisors and trainers. The community and our patients also need to be understanding, supportive and enthusiastic for education of surgical trainees to occur. The RACS applauds Wong et al for progressing this discussion and highlighting the benefits that can result from expanding surgical training into the private sector.

Ian R Gough · Ian D Civil · Spencer W Beasley · Bruce H Barraclough · David J Hillis

To the Editor: I note, with a breath of fresh air, your recent column about managing hospital staff rosters1 and, in the same issue, the article by Dietz, calling for a simpler, more resilient health bureaucracy.2 We are stuck in an environment where process seems to be disassociated from outcome and, if the outcome is not what is wanted, then more process is added, thus compounding the problem. Surely it is time to step back a bit and look strategically at bureaucratic processes, and how they work and don’t work? No one would deny that we need good administration — it is one of the very bastions of our way of life. We seem to study most things in an evidence-based manner, or at least try to. Why can’t we have chairs of bureaucratic studies in our universities to rigorously research our bureaucratic processes? Armed with sound evidence, we could develop template systems and other tools to break the nexus in which we find ourselves. Dare I say the spin-off would be greater than just health care. Food for thought.

Robert N Atkinson

Living with bipolar. A guide to understanding and managing the disorder. Lesley Berk, Michael Berk, David Castle, Sue Lauder. Sydney: Allen and Unwin, 2008 (xiv + 298 pp). ISBN 978 1 74175 425 4. Over the past decade there has been a palpable surge of fascination with bipolar disorder in this country, generated at least in part by the moving testimonies of high-profile patients, and a resurgence of academic and pharmaceutical interest in the condition. This increasingly transparent public discourse has been a boon to those who have suffered in silence for so many years, and who now demand and expect quality information and guidance on understanding and living with the highly disabling illness. Consequently, there is now a healthy, growing market for well written, informative self-help books targeting bipolar disorder, for sufferers, their families and the lay community. Living with bipolar, written by an impressive team of Australian researchers and psychologists, is an excellent addition to the genre, complementing an Australian canon of quality books. Others include Sarah Russell’s A lifelong journey: staying well with manic depression/bipolar disorder (a self-help manual written by a researcher who has experienced bipolar disorder), Penelope and Jessica Rowe’s The best of times, the worst of times (a frank account of a family’s struggles dealing with bipolar), and Mastering bipolar disorder, a compilation of individuals’ accounts of managing their mood swings, edited by Kerrie Eyers and Gordon Parker. Living with bipolar, unlike the others, is both a highly palatable mini-monograph on bipolar disorder for the layperson, and rich, common-sense advice for managing the condition. I particularly enjoyed the chapters on modern psychological strategies that patients can use to manage symptoms, including specific guidance on “catching symptoms early” and “managing your triggers”. This is no anti-medical treatise, finishing rather with advice encouraging patients to establish a collaborative relationship with their medical practitioner. A highly recommended book for your bipolar patients.

Philip B Mitchell

Incorrect and misleading use of tense: In the Chistmas Offerings article “Cough disorder: an allegory on DSM-IV” in the 7/21 December 2009 issue of the Journal (Med J Aust 2009; 191: 674-676), in the second paragraph under the heading, “The problem with the DSM”, “is overdiagnosed” was incorrectly used in place of “was overdiagnosed”, thus giving the impression that schizophrenia continues to be overdiagnosed in the United States. Schizophrenia is no longer overdiagnosed in the US relative to Europe and Australasia.

Peter I Parry

Caffeine for kids? Did you know that, in Australia, manufacturers of “energy drinks” may be bypassing regulation through a legal loophole — if a product is called a “dietary supplement”, it is not bound by the usual caffeine limits of 80 mg per 250 mL can? So say Australian authors Oddy and O’Sullivan in a commissioned editorial in the BMJ. They also say that anectodal evidence suggests that children who regularly consume energy drinks could become dependent on them; further, that even moderate consumption at this age may be detrimental. As caffeine is not only addictive but has no nutritive value, erring on the side of caution by banning energy drinks may be warranted but requires further research before widespread bans are put in place. In the meantime, why not promote water as the preferred drink for not only children but also people of all ages? BMJ 2009; 339: b5268 Rotavirus retreats? Last year in the MJA, Lambert and colleagues presented early evidence of the effects of the universal infant rotavirus vaccine program in Queensland, reporting a fall in rotavirus notifications, not only in the very young, but in all age groups.1 Now, researchers in New South Wales report similar findings after conducting a study in infants and children aged up to 5 years.2 Belshaw and colleagues suggest their findings could be explained either by unusually low community circulation of rotavirus in the year studied (2008) or by a beneficial effect of vaccination that had a flow-on effect to older children through reduced transmission in the most susceptible age group — infants. 1. Med J Aust 2009; 191: 157-160 2. Commun Dis Intell 2009; 33: 337-340 Online doctor ratings “The internet has become the 21st century’s answer to word of mouth or over-the-garden-fence chitchat, so I think it’s wise to keep tabs on what is said about me in cyberspace”, says Jain, an adult psychiatrist in the USA. After several minutes of surfing, Jain was relieved to find her internet reputation intact. Then, she stumbled onto frank stories that patients told about other doctors and not all of it was good. However, overall, Jain found the Googling experience to be positive, reassuring her that what patients want from their doctors is not all that different from what good doctors want to offer their patients — patients want doctors who care, listen and know what they’re doing. Have you Googled yourself (or your colleagues) lately? N Engl J Med 2010; 362: 6-7 And the organs will go to . . . An Israeli incentive system aims to increase current low rates of organ donation by priorisiting individuals who are willing to donate organs to receive organs, if needed, above those who are not. The system has three allocation priority categories depending on the patient’s intention to donate and their first-degree relatives’ intention to donate or previous donation of organs. However, safeguards have been included in the system to ensure that acutely ill patients will be first to receive organs. Further, the law is thought to respect the rights of those who are strong opponents of brain death and organ transplantation — while these patients would be unlikely to donate organs, they would also choose not to receive them. However, various questions have been raised about this incentive system, including why priority privileges are not given to some previous living-directed donors. Lancet online 17 Dec 2009 No ESKAPE for MRSA The term “ESKAPE” has been coined for the group of pathogens that causes most hospital-acquired infections able to “escape” the current antibiotic arsenal in the US: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. According to Kollef, their existence mandates the discovery of new antimicrobial agents. In a review article, he describes six novel antibacterial agents in the late stages of clinical development that show potential for treating methicillin-resistant S. aureus (MRSA) infection. The six hopes for the future described include two fifth-generation cephalosporins (ceftaroline and ceftobiprole) and three glycopeptides (dalbavancin, oritavancin and telavancin). Crit Care Resusc 2009; 11: 282-286

Ann Gregory