Volume 187 Issue 3

Our democratic processes have moved on — so must our science In April 2007, Victoria became the first Australian state to enact legislation (the Infertility Treatment Amendment Bill 2007) that followed the passage by federal Parliament in December 2006 of the Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research Amendment Act 2006 (Cwlth). This Act gave effect to most of the recommendations of the Legislation Review Committee, chaired by the late John S Lockhart, which reported in December 2005. The Lockhart Committee engaged in wide community consultation and considered expert advice from many sources before making its recommendations on what was inevitably an issue arousing passionate public debate. Similar intense debate had crossed party lines in both federal and Victorian Parliaments, but with a “conscience vote” in both houses in each instance (allowing members to vote as they personally wished rather than along set political party lines), legislation was passed containing major provisions for strict regulation of all aspects of research involving human embryonic material and the strict prohibition of human cloning for reproductive purposes — with draconian penalties for transgression. Many other prohibitions set out in the previous Research Involving Human Embryos Act 2002 (Cwlth) have been firmly retained. Similar legislation has now passed both houses of the New South Wales Parliament, following vigorous public controversy over the respective roles of the legislature and of the Catholic church on the issue. Corresponding legislation is expected to be considered in other states and territories, as Australia moves to permit further progress in this critical and fast-moving area of scientific development. Legislative protection from both federal and state governments allows greater freedom in the quest to understand disease mechanisms by studying stem cells containing abnormalities underlying genetic disorders, and the development of new approaches to treatment of hitherto unyielding diseases. The new science of regenerative medicine can move ahead in Australia, with the research and technological developments now permitted having great implications for human medicine. A new international system for collaboration in this important field is also emerging.1 Human embryonic stem cell lines were first created in 1998 from blastocysts;2 the techniques used were based on at least a decade of research on mouse embryonic stem cells. The key characteristic of embryonic stem cells, not shared with adult stem cells, is their capacity for long-term or immortalised culture, permitting extended research and growth of the large number of cells necessary for human implantation. The process of somatic cell nuclear transfer allows human embryonic stem cells to contain the nucleus of the recipient cell, so an individual’s immunological constitution will be conferred to the stem cell and its progeny. Technological developments to date have included: Better methods for growth and maintenance of human embryonic stem cells in vitro, including Good Manufacturing Practice (GMP) compliance and industrial scale production; Better methods to more reliably drive embryonic stem cells along particular cell and tissue pathways; Differentiated embryonic stem cell progeny have been used for drug screening and toxicology testing; Demonstration of the medically relevant capabilities of human embryonic stem cells in animal models; and Isolation of new embryonic stem cell lines and creation of collaborative cell banks and networks. Regulatory compliance still presents challenges, as expected of any living-cell therapy. The potential applications to human disease are many, as shown by real advances made recently with human diseases in animal models. Studies transplanting cells derived from human and monkey embryonic stem cells into animal models have shown correction or partial correction of Parkinson’s disease.3,4 Growth of cardiac myocytes derived from human embryonic stem cells has been demonstrated in pigs, with correction of electromechanical function;5 human embryonic stem cell-derived oligodendrocytes have improved spinal cord injuries in rats;6,7 and human embryonic stem cell-derived islet cells have functioned in animals with diabetes.8 However, regenerative medicine in human subjects using transplanted stem cells or their progeny faces three serious technical hurdles: Transplant rejection (and the monitoring of this); Efficient guidance of embryonic stem cells down correct pathways of differentiation using growth factors; and Ensuring cells of such great proliferative potential do not, on rare occasions, develop into cancers. Strongly held views in the community on all aspects of research involving human embryonic stem cells must be acknowledged. Similarly, unrealistically high hopes for rapid advances in developing new treatments for distressing and debilitating diseases fail to grasp the long lead times that inevitably apply; medical practitioners will probably be asked for their advice on such matters. Our democratic processes have moved on — so must our science. It is important to recognise that there will continue to be strict regulatory oversight of all research involving human embryonic stem cells, and regular reviews of progress will be important.

David G Penington AC · Graham F Mitchell AO

CABG offers a cost-effective and better long-term clinical outcome for many patients Coronary artery disease is still the single largest cause of premature death in Australia, according to the Australian Institute of Health and Welfare.1 Also documented is the dramatic decline in age-related mortality from heart disease, which is largely attributed to reductions in smoking and better intervention for hyperlipidaemia and elevated blood pressure.2 As many as 85% of elective percutaneous coronary intervention (PCI) procedures are done in patients with stable coronary artery disease.3 However, the only data showing prognostic benefit of intervention in reducing death and infarction in such patients come from subgroup analyses in old surgical trials,4-6 which showed benefits for patients with left main, triple vessel or proximal left anterior descending stenoses, especially if there was additional left ventricular damage. These benefits lasted up to 11 years, but the surgery was compared with medical therapy that did not include aspirin, β-blockers or lipid-lowering therapy for most patients. The surgical group did not receive arterial conduits. Subsequently, 11 randomised trials comparing PCI with coronary artery bypass graft (CABG) surgery for patients with multivessel coronary artery disease showed that the frequency of death and myocardial infarction was similar in both arms.7 These results cannot be used to claim an outcome benefit for PCI, as the trials entered only about 5% of screened patients, and the patients were not equivalent in the severity of their coronary artery disease to those in the original CABG trials. Further, analysis of the comparative trials shows that the highest-risk group (those with diabetes) showed benefit with CABG over PCI.8 Outcomes after CABG now show that, despite this surgery being performed in increasingly sick and complex patients, the overall mortality is less than 2%.9 Average length of hospital stay is now 3–5 days and return to work is usual in less than 2 months. Improved techniques have reduced the problem of cognitive impairment, and comparative studies have shown no difference with PCI in this respect.10 Long-term outcomes of CABG have improved due to the increased use of arterial conduits. Repeat CABGs now make up only 3%–4% of total CABG surgery, although this low figure may reflect a preference for PCI in repeat procedures. PCI has flourished since its introduction 30 years ago, with its offer to patients of a sound and timely intervention for coronary artery disease — but it has not been without problems. Recoil restenosis with balloon angioplasty was largely solved by the introduction of bare-metal stents. Acute stent thrombosis is less of a problem with better anticlotting agents, and drug-eluting stents have significantly reduced the problem of late restenosis. Despite these improvements, no reported studies have shown convincing evidence that PCI reduces the finite end points of death or myocardial infarction for patients with stable coronary artery disease. Controversy has recently arisen over the finding that patients with drug-eluting stents have an ongoing excess risk of late stent thrombosis of around 0.5% a year, presumably due to failure of endothelialisation of the stent. These events are usually associated with acute myocardial infarction, which carries a 50% mortality rate. It is now recommended that patients with drug-eluting stents stay on combined treatment with clopidogrel and aspirin for at least 12 months after implantation, and possibly permanently.11 This adds to patients’ financial costs and places them at extra risk of bleeding. Two recent reports provoke additional comment. First, Griffin et al used a complicated analysis of previous data to assess the cost-effectiveness of PCI and CABG in patients with multivessel disease considered suitable for revascularisation. CABG reached the accepted level of cost-effectiveness (US$60 000 per quality-adjusted year of life gained) but PCI did not, mainly due to the ongoing need for repeat procedures in PCI patients.12 Second, Boden et al reported a randomised trial comparing PCI with medical therapy in patients with stable coronary artery disease, which found no difference in the rate of death or non-fatal myocardial infarction at a median follow-up of 4.6 years. The PCI group initially had a reduced rate of angina, but this difference had disappeared at 5 years, largely because the medical therapy group had improved.3 The best interpretation of currently available data is that, for patients with severe coronary artery disease, the more invasive procedure with a longer recovery time (CABG) has a better long-term clinical outcome and is more cost-effective than the less invasive fast-recovery procedure (PCI). Three ongoing randomised clinical trials (CARDia, SYNTAX and FREEDOM) should further clarify the roles of PCI and CABG in treating severe coronary artery disease. The question then arises of whether, in current practice, PCI is being used in patients with severe coronary artery disease who would be more appropriately treated with CABG. Surgeons and cardiologists have argued that patients are not being adequately advised of the surgical option.13 Indeed, use of CABG is in such decline that training programs for young surgeons are at risk.14 In practice, the patient decides between CABG and PCI following discussion with a cardiologist, often while still in the angiography suite. This arrangement bypasses one of the recommendations on self-referral issues: to undertake consultation with other providers.15 It has been suggested that the technical suitability of a lesion for angioplasty determines the advice given to patients, rather than the relative benefits of CABG, PCI or even medical treatment alone.16 Smoking cessation and treatment to lower lipids and blood pressure are remarkably effective in improving the outlook for patients with stable coronary artery disease. Both CABG and PCI will provide benefits if revascularisation is performed for relief of symptoms, and patients may be influenced in their choice by both the less invasive nature of PCI and by the fewer recurrent procedures offered by CABG. However, for patients with prognostically important stable coronary artery disease (ie, severe left main or triple vessel disease), current evidence indicates that CABG offers a better long-term outcome.

Keith V Woollard MRCP, FRACP · Mark A J Newman DS, FRACS

Objectives: To determine the proportion of patients who have a diagnosis of migraine in a sample of Australian general practice patients, and to review the prophylactic and acute drug treatments used by these patients.Design, setting and participants: A cohort of general practitioners collected data from about 30 consecutive patients each as part of the BEACH (Bettering the Evaluation and Care of Health) program; this is a continuous national study of general practice activity in Australia. The migraine substudy was conducted in June–July 2005 and December 2005–January 2006.Main outcome measures: Proportion of patients with a current diagnosis of migraine; frequency of migraine attacks; current and previous drug treatments; and appropriateness of treatment assessed using published guidelines.Results: 191 GPs reported that 649 of 5663 patients (11.5%) had been diagnosed with migraine. Prevalence was 14.9% in females and 6.1% in males. Migraine frequency in these patients was one or fewer attacks per month in 77.1% (476/617), two per month in 10.5% (65/617), and three or more per month in 12.3% (76/617) (missing data excluded). Only 8.3% (54/648) of migraine patients were currently taking prophylactic medication. Patients reporting three or more migraines or two migraines per month were significantly more likely to be taking prophylactic medication (19.7% and 25.0%, respectively) than those with less frequent migraine attacks (3.8%) (P < 0.0001). Prophylactic medication had been used previously by 15.0% (96/640). The most common prophylactic agents used currently or previously were pizotifen and propranolol; other appropriate agents were rarely used, and inappropriate use of acute medications accounted for 9% of “prophylactic treatments”. Four in five migraine patients were currently using acute medication as required for migraine, and 60.6% of these medications conformed with recommendations of the National Prescribing Service. However, non-recommended drugs were also used, including opioids (38% of acute medications).Conclusions: Migraine is recognised frequently in Australian general practice. Use of acute medication often follows published guidelines. Prophylactic medication appears to be underutilised, especially in patients with frequent migraine. GPs appear to select from a limited range of therapeutic options for migraine prophylaxis, despite the availability of several other well documented efficacious agents, and some use inappropriate drugs for migraine prevention.

Richard J Stark FRACP, MACLM · Lisa Valenti BEc · Graeme C Miller PhD, FRACGP

Objective: To measure the prevalence of overweight, obesity and the metabolic syndrome (MetS) in rural Australia.Design, setting and participants: Cross-sectional surveys were conducted in two rural areas in Victoria and South Australia in 2004–2005. A stratified random sample of men and women aged 25–74 years was selected from the electoral roll. Data were collected by a self-administered questionnaire, physical measurements and laboratory tests.Main outcome measures: Prevalence of overweight and obesity, as defined by body mass index (BMI) and waist circumference; prevalence of MetS and its components.Results: Data on 806 participants (383 men and 423 women) were analysed. Based on BMI, the prevalence of overweight and obesity combined was 74.1% (95% CI, 69.7%–78.5%) in men and 64.1% (95% CI, 59.5%–68.7%) in women. Based on waist circumference, the prevalence of overweight and obesity was higher in women (72.4%; 95% CI, 68.1%–76.7%) than men (61.9%; 95% CI, 57.0%–66.8%). The overall prevalence of obesity was 30.0% (95% CI, 26.8%–33.2%) based on BMI (≥ 30.0 kg/m2) and 44.7% (95% CI, 41.2%–48.1%) based on waist circumference (≥ 102 cm [men] and ≥ 88 cm [women]). The prevalence of MetS as defined by the US National Cholesterol Education Program Adult Treatment Panel III 2005 criteria was 27.1% (95% CI, 22.7%–31.6%) in men and 28.3% (95% CI, 24.0%–32.6%) in women; based on International Diabetes Federation criteria, prevalences for men and women were 33.7% (95% CI, 29.0%–38.5%) and 30.1% (95% CI, 25.7%–34.5%), respectively. Prevalences of MetS, central (abdominal) obesity, hyperglycaemia, hypertension and hypertriglyceridaemia increased with age.Conclusions: In rural Australia, prevalences of MetS, overweight and obesity are very high. Urgent population-wide action is required to tackle the problem.

Edward D Janus MD, PhD · Tiina Laatikainen MD, PhD · James A Dunbar MD · Annamari Kilkkinen MSc, PhD · Stephen J Bunker PhD · Benjamin Philpot BSc, GradDip (Actuarial Studies) · Philip A Tideman MB BS · Rosy Tirimacco BSc · Sami Heistaro MD, PhD

Objectives: To examine the relation between treatment intensity and level of risk in routine hospital care of patients with acute coronary syndromes (ACS), and to identify independent predictors of use or omission for each of eight evidence-based treatments.Design: Retrospective cohort study of patients fulfilling case definition for ACS in whom absolute risk of adverse outcomes was quantified (as low, moderate, or high risk) using formal prediction rules, and for whom treatment eligibility was determined using expert-agreed criteria.Participants and setting: 3912 consecutive or randomly selected patients admitted to 21 hospitals in Queensland, Australia between 1 August 2001 and 31 December 2005.Results: The proportions of eligible patients receiving treatment varied inversely with risk level in regard to reperfusion therapies of fibrinolytic therapy or primary angioplasty (low risk, 88.3%; moderate risk, 61.9%; high risk, 18.2%; P < 0.001), heparin (91.4%; 83.7%; 72.8%; P < 0.001) and early invasive intervention (33.6%; 24.0%; 18.5%; P < 0.001). Significantly more low- and moderate- than high-risk patients received β-blockers (87.0%; 88.5%; 79.1%; P < 0.001), lipid-lowering agents (87.3%; 84.8%; 65.8%; P < 0.001), and referral to cardiac rehabilitation (51.8%; 46.0%; 34.4%; P < 0.001) at discharge. The most frequent independent predictors of treatment omission in all patients included increasing age (5 of 8 treatments), previous ACS or atrial tachyarrhythmias (4 of 8), and past history of cerebrovascular accident or congestive heart failure (3 of 8). Conclusion: In routine care of ACS, eligible patients at high risk receive treatment less frequently than those at low and moderate risk. Reforms in professional education, routine use of risk stratification tools, guideline recommendations tailored to population-specific reductions in absolute risk, and better hospital networking with standardised triage and referral procedures for invasive procedures may help reduce selection bias in the delivery of indicated care.

for the CPIC Cardiac Collaborative

Objectives: To examine the effect of the debate on the safety of non-steroidal anti-inflammatory drugs (NSAIDs) on decision making by Australian general practitioners and patients with osteoarthritis (OA), and to explore issues concerning the use of NSAIDs from both prescriber and consumer perspectives.Design and setting: A qualitative study in which five focus groups (three for GPs, and two for patients with OA) were conducted between 15 May and 4 August 2006 in south-western Sydney.Participants: Five advanced general practice registrars, six experienced GPs, and 20 patients with OA aged 54–85 years.Main outcome measures: Key themes and issues identified by content analysis of focus group transcripts.Results: GPs reported adopting a cautious approach to prescribing NSAIDs because of uncertainty about safety and medicolegal concerns. They were sceptical about information provided by the pharmaceutical industry and found the literature about the safety of NSAIDs confusing. Time was identified as a major barrier to adequate discussion with patients, and explaining the risk to patients in a meaningful way was perceived as a challenge. Patients wanted information and sought it from a range of sources, most commonly pharmacists and GPs. Most patients made active decisions about using or not using NSAIDs, with some favouring physical function over safety. Patients were also using other forms of treatment including alternative medicine.Conclusion: Our findings reflect the need to provide clear, unbiased information about NSAIDs to help both GPs and patients negotiate this decision-making dilemma.

Suzi S Mikhail MB Bch, AMC, FRACGP · Nicholas A Zwar MPH, PhD, FRACGP · Sanjyot Vagholkar MB BS, MPH, FRACGP · Sarah M Dennis MSc, PhD · Richard O Day AM, MD, FRACP

Objective: To investigate the prevalence and format of medical morning handover report (MMHR) in Australian hospitals.Design, setting and participants: Questionnaire survey faxed to 76 Australian hospitals accredited for basic physician training by the Royal Australasian College of Physicians (RACP). The survey was conducted in 2005.Main outcome measures: Use of MMHR; structure and format of meetings.Results: 53 of 76 (70%) hospitals responded. However, some data (1.7% of possible responses) were missing or illegible. Prevalence of the use of MMHR in respondent hospitals was 58% (31/53). Analysing the data by RACP accreditation level, 18/24 Level 3 hospitals (75%) conducted MMHR compared with 5/9 Level 2 hospitals (56%) and 7/18 Level 1 hospitals (39%) (odds ratio [OR] for trend, 2.17; 95% CI, 1.12–4.23; P = 0.023). 44 of 53 respondents reported their Rural, Remote and Metropolitan Areas (RRMA) classification. MMHR is less likely to be held in hospitals in regions classified as RRMA 2–4 (8/21 [38%]) than those in capital cities (RRMA 1) (16/23 [70%]) (OR, 0.27; 95% CI, 0.08–0.95; P = 0.042). In 62% of hospitals, MMHR was chaired by a consultant, and at most hospitals (23/31 [74%]), meetings were 15–30 minutes long.Conclusions: In spite of RACP accreditation requirements, the use of MMHR in Australian hospitals accredited for basic physician training is low.

Matthew J Fassett BInfoSys(Hons) · Terry J Hannan MB BS, FRACP · Iain K Robertson MB BCh, MPH · Steven J Bollipo MB BS, FRACP · Robert G Fassett MB BS, FRACP

Objective: To use short-term indicators (hospital internship choice, and interest in a future rural career) to assess how the University of Queensland rural clinical school is meeting its program objectives.Design: Cross-sectional quantitative data collected through self-report questionnaires.Setting: University of Queensland rural clinical school (UQRCS).Participants: Year 4 students who attended the UQRCS for their entire clinical year in 2006.Results: Most students were from an urban background. Over the year, interest in a future rural medical career increased measurably across the cohort. The most important factors in choosing to study at the UQRCS were the quality of teaching, level of student contact with clinical teachers, increased patient access, and accommodation facilities. Comparison of graduates’ choice of internship location for 2006 compared with 2005 showed a trend away from urban or metropolitan toward regional or rural hospitals.Conclusions: Our results suggest that the primary attraction of UQRCS is the quality of education, and rural undergraduate training is a popular choice for urban students. Although the long-term effect on rural medical workforce remains to be determined, the trend at UQRCS of new graduates choosing non-urban internships is encouraging.

Diann S Eley MSc, PhD · Peter G Baker FRCP, FRACGP, FACRRM

Organ donation after cardiac death increases organ availability, but raises several legal and ethical issues, including consent. Medical interventions for people who are unconscious usually require guardian consent and must meet patients’ best-interests standards. Antemortem procedures can improve the success of organ transplant after cardiac death, but do not serve the patient’s medical interests, and it is contentious whether consent for antemortem interventions is legal under current Australian guardianship legislation. We argue that consent decisions should take patients’ wishes as well as their medical interests into account. Antemortem interventions are ethically and legally justified if the interventions are not harmful and the person concerned wished to be an organ donor.

Bernadette Richards BA, DipEd, LLB(Hons) · Wendy A Rogers BM BS, FRACGP, PhD

Mifepristone (RU486), which is used for early medical abortion, can only be obtained in Australia under the Authorised Prescriber legislation (Section 19[5] of the Therapeutic Goods Act 1989 [Cwlth]); two of the authors have permission to obtain, prescribe and administer this drug in Cairns, Queensland. From July 2006 to April 2007, 10 women who fulfilled the Therapeutic Goods Administration (TGA) criteria of “life-threatening or otherwise serious” indications underwent medical abortion with mifepristone/misoprostol, and 12 women conforming with abortion requirements of Queensland law, but not TGA legislation for mifepristone administration, had medical abortions with the less preferable methotrexate/misoprostol combination. Although it is now more than a year since the cross-party vote in federal Parliament in February 2006 confirmed wide support for the right of Australian women to a medical abortion, we believe we are at present the only medical practitioners in Australia with permission to use mifepristone. Obtaining Authorised Prescriber status from the TGA is of necessity a complex and protracted process, involving ethics committee approval and auditing, and regular reporting to the TGA. Because of the current restrictions, we believe that women seeking medical abortion in Australia face barriers not experienced by women in other comparable countries, and that drug manufacturing and distributing companies may be discouraged from seeking to market mifepristone in Australia.

Caroline M de Costa FRANZCOG, FRCOG, MPH · Darren B Russell FRACGP, DipVen, FAChSHM · Naomi R de Costa LLB(Hons), GradDipLegalPrac · Michael Carrette MB BCh, FRANZCOG · Heather M McNamee MB ChB, FRACGP

Web 2.0 is a term describing new collaborative Internet applications. The primary difference from the original World Wide Web is greater user participation in developing and managing content, which changes the nature and value of the information. Key elements of Web 2.0 include: Really Simple Syndication (RSS) to rapidly disseminate awareness of new information; blogs to describe new trends; wikis to share knowledge; and podcasts to make information available “on the move”. The medical community needs to be aware of these technologies and their increasing role in providing health information “any time, any place”.

Rick McLean MD, FRACP · Brian H Richards BSc(Med)(Hons), MB BS · Janet I Wardman BSc, BA, GradDipInfMan – Librarianship, ALIA

During 1994–2006, 10 cases of invasive breast cancer were diagnosed among 550 women employed for some time at a broadcast media site in Brisbane, Queensland. These cases represented a more than sixfold increase in risk compared with the female population of Queensland. After an initial unsatisfactory inquiry, an independent assessment was successful when the investigation addressed environmental factors of concern to the employees, as well as agents that may have accounted for the cluster. The perceptions of the women affected were documented in the television program Australian Story. No specific cause of the cluster was identified, but staff concerns were allayed by relocation from the site. The outcome suggests a specific duty of care involving adequate attention being paid to community needs in such situations.

Bernard W Stewart PhD, FRACI, DipLaw

Measles is now rare in Australia, and cases can usually be linked to its importation from endemic countries. To prevent measles outbreaks in Australia, high vaccination coverage with two doses of vaccine must be sustained. All medical practitioners should consider a diagnosis of measles in a patient of any age who presents with fever and a non-vesiculating, non-itchy rash. If measles is suspected clinically, public health authorities should be immediately notified, so that testing and management of patients can be discussed and contact tracing initiated. When a patient is suspected of having measles, testing of a serum sample for measles-specific IgM and IgG antibodies should be requested urgently. Pathology laboratories should have effective protocols for immediately reporting positive measles-specific IgM antibody tests, or other results indicative of measles, to public health authorities.

David N Durrheim DrPH, MB ChB, FAFPHM · Heath Kelly MB BS, MPH, FAFPHM · Mark J Ferson MD, FRACP, FAFPHM · David Featherstone BSc

The obesity epidemic and global warming are linked through energy use. A personal carbon trading scheme aimed at reducing fossil fuel usage could act as a “stealth intervention” for reducing obesity by increasing personal energy use. Such a scheme would complement a corporate “cap and trade” system for carbon emissions, which should increase the relative price of processed, energy-dense foods. The scheme would work by reducing global carbon emissions to a sustainable level (contraction), while offering potential for trade of emission rights between frugal and profligate users of non-renewable energy (convergence). A key goal would be changed attitudes to conspicuous (and obesogenic) consumption. Adoption of the scheme would make healthy choices the easy choice.

Garry Egger MPH, PhD

Until recently, liver transplantation was contraindicated in Jehovah’s Witness patients because of recipient-imposed restrictions on use of blood products. However, recent improvements in surgical and anaesthetic techniques and new procoagulant agents challenge this practice. We describe two Jehovah’s Witness patients who had successful liver transplantation without blood transfusion. To our knowledge, these are the first such cases in Australasia. The techniques used to minimise blood loss and transfusion requirements could potentially benefit all patients undergoing major surgery. Clinical recordsPatient 1A 48-year-old farmer with end-stage cirrhosis due to α-1 antitrypsin deficiency had evidence of moderate portal hypertension with splenomegaly and ascites (Child–Pugh score B), but no significant lung disease. He met minimum recipient suitability criteria for liver transplantation, according to the Transplantation Society of Australia and New Zealand (TSANZ) liver standing committee.1 As a Jehovah’s Witness, he would not accept transfusion of red blood cells, fresh frozen plasma or platelets. However, he indicated that he would accept blood fractions and recirculated autologous blood and cell-saved blood. A relative, also a Jehovah’s Witness with similar restrictions on use of blood products, offered to be a live liver donor, but this offer was rejected by the treating team on the basis of unacceptable donor risk. The patient was placed on the transplantation waiting list, and was treated with erythropoietin. Over 6 months, this increased the haemoglobin concentration from 112 g/L to 151 g/L (reference range [RR], 135–180 g/L). Results of other preoperative blood tests included: platelet count, 74 × 109/L (RR, 150–400 × 109/L); international normalised ratio (INR), 1.2 (RR, 0.9–1.3); serum concentration of bilirubin, 60 μmol/L (RR, < 20 μmol/L); albumin, 26 g/L (RR, 35–50 g/L); alanine aminotransferase (ALT), 102 U/L (RR, < 40 U/L); and creatinine, 143 μmol/L (60–110 μmol/L). Liver transplantation was performed using an organ from a 54-year-old deceased donor. The piggyback implantation technique, without venovenous bypass, was used. Coagulation was monitored intraoperatively using routine coagulation tests and thromboelastography (Haemoscope, Skopie, Ill, USA). The latter technique measures the kinetics and tensile strength of clot formation. Prophylactic aprotinin was administered as a bolus followed by a constant infusion. The patient also received cryoprecipitate, albumin, haemodilution, and autotransfusion of cell-saved and recirculated blood. On arrival in the intensive care unit, haemoglobin concentration was 118 g/L. The patient received recombinant factor VIIa to treat an INR of 3.4, and erythropoietin was continued. There was significant primary graft dysfunction, and ascites was slow to resolve. Three months after transplantation, the patient developed a pulmonary embolism and required anticoagulation. Currently, at 4 years after transplantation, the patient is well and works full time. Patient 2A 43-year-old woman with chronic hepatitis B infection was found to have an unresectable multifocal hepatocellular carcinoma at laparotomy. She had well compensated cirrhosis (Child–Pugh score A) with no evidence of portal hypertension, and met listing criteria for transplantation. A Jehovah’s Witness, she would not accept transfusion of red blood cells, fresh frozen plasma or platelets, but determined that she would accept blood fractions and recirculated autologous blood and cell-saved blood. Pretransplant laboratory results were: haemoglobin concentration, 129 g/L; platelets, 203 × 109/L; INR, 0.9; bilirubin, 7 μmol/L; albumin, 38 g/L; ALT, 58 U/L; and creatinine, 70 μmol/L. Liver transplantation was performed using an organ from a 42-year-old deceased donor. An inferior vena cava interposition technique was used without venovenous bypass because of the proximity of the tumour to this vessel. The central venous pressure was maintained below 5 cmH2O to minimise blood loss. The patient received cryoprecipitate, haemodilution, autotransfusion, and cell-saved and recirculated blood. Unfortunately, she had an allergic reaction to the colloidal plasma-volume substitute, gelofusine; coagulation studies and thromboelastography showed fibrinolysis, which was treated with aprotinin and recombinant factor VIIa. On arrival in the intensive care unit, haemoglobin concentration was 75 g/L, and INR was 1.3. Erythropoietin and iron supplements were started. Postoperative recovery was uncomplicated, and the patient remains well 3 years after the operation. DiscussionTo our knowledge, these are the first reported cases of liver transplantation in Jehovah’s Witness patients in Australasia. While the two patients filled accepted criteria for recipient suitability for liver transplantation,1 the likely need for blood transfusion would until recently have precluded this procedure. Liver transplantation is a well established and successful intervention for liver failure that results in long-term survival (70% at 10 years) in individuals who otherwise have minimal 1-year survival.2 The shortage of deceased donor livers remains the major factor limiting the number of liver transplantation operations in Australia and New Zealand. In 2000, the death rate while waiting for a donor liver in Australia and New Zealand was 40% for acute liver failure and 5%–8% for chronic liver disease.3 This donor shortfall creates an ethical dilemma in which the potential benefit to individual patients has to be balanced against the need to maximise the benefits of this scarce resource. Following a well publicised case in Edinburgh of a death due to acute liver failure, a recommendation was made for a colloquium to address the question of patient selection for liver transplantation and the need for a uniform code of practice in the United Kingdom. The colloquium, held in 1999, recommended that liver transplantation should be performed in patients when their expected survival is less than 12 months and the expected post-transplant survival is over 50% at 5 years.4 These recommendations have been incorporated into the minimum recipient listing criteria used by the TSANZ liver standing committee,1 and were met by both the reported patients. Over the past decade, improvements in surgical and anaesthetic techniques, combined with new procoagulant agents, have resulted in a dramatic reduction in the requirement for transfusion of blood and blood products during liver transplantation. In selected patients, the need for blood transfusions can be avoided completely.5,6 These advances have resulted in reassessment of the use of liver transplantation in Jehovah’s Witness patients. The first-ever reported liver transplantation in a Jehovah’s Witness patient was in 1994.7 Since then, transplantation has been successfully performed in selected individuals for acute and chronic liver failure without the need for blood products.8,9 Outcomes of liver transplantation in adult Jehovah’s Witness patients have been reported as 92% survival with a mean follow-up of 2.2 years (range, 0.3–5.6 years).10 Live-donor liver transplantation using Jehovah’s Witness donor/recipient pairs has more recently been reported.10 However, the risk to the potential live donor in the case of our first patient through refusing blood products, added to the known 0.5% mortality associated with donation of the right lobe of the liver, was thought to be excessive, and this option was rejected.11 As always, careful selection of the recipient is required. Two other Jehovah’s Witness patients referred to us for liver transplant assessment rejected, or were rejected for, transplantation: one, after lengthy consideration, refused to accept a donor liver; while the other had multiple hepatocellular cancer tumours which fell outside the minimal listing criteria. By way of comparison, in a previously reported series, only nine of 29 Jehovah’s Witness patients were found to be suitable for liver transplantation.9 The Jehovah’s Witness church teaches that blood transfusion (whole blood, red blood cells, white blood cells, platelets and plasma) should not be accepted, but individuals themselves are to decide whether to accept organ transplantation and blood fractions. Both our patients accepted the use of cryoprecipitate, albumin, recombinant factor VIIa, recirculated autologous blood and cell-saved blood, and signed a preoperative agreement to this effect. Consent to the use of these factors and techniques were minimum listing criteria required by the treating teams to proceed with liver transplantation. In selected Jehovah’s Witness patients with hypersplenism (not present in our patients), the use of partial splenic artery embolism increased platelet count, allowing transplantation to proceed.9,10 Transjugular intrahepatic portosystemic shunt formation has been less successful in reversing hypersplenism, and should not be used for this indication.12 Jehovah’s Witness patients with severe decompensated liver disease and coagulopathy (Child–Pugh score C), severe portal hypertension and renal failure are at high risk for perioperative mortality and should not receive liver transplantation. Preoperative use of erythropoietin to increase haemoglobin levels has a number of potential benefits. The most obvious is that the patient begins the procedure with a higher blood haemoglobin level. This also enables use of haemodilution to minimise red cell loss during the explant procedure, and autotransfusion to raise the haematocrit after haemostasis is secure. Maintaining a low central venous pressure also decreases blood transfusion requirements during liver transplantation.13 Although recombinant factor VIIa is expensive (average $6000 per patient), it reduces coagulopathy and transfusion requirements.14 Overall, use of these blood conservation techniques may result in a cost benefit, compared with use of large volumes of blood product.7,10 Successful liver transplantation is possible in selected Jehovah’s Witness patients, but early referral before the development of severe, decompensated liver disease is mandatory. Also, we believe that techniques that minimise blood loss and transfusion requirements for liver transplantation should be more widely practised to benefit all those undergoing major surgery.

Gary P Jeffrey FRACP, MD, MRCP · John McCall FRACS · Edward Gane MD, FRACP · Andrew W Mitchell FRACS · Neville M Gibbs MD, FANZCA · Vanessa Beavis FANZCA · Kerry Gunn FANZCA · Stephen Munn FRACS · Anthony K House MS, FRACS

To the Editor: Awareness about atypical and malignant modes of presentation of a clinical condition can avoid catastrophic outcomes, assist in correct diagnosis in the appropriate clinical setting and, as typified by the following case, offer complete cure. A 39-year-old woman presented with a 5-year history of intermittent, recurrent brief syncopal episodes. During an episode at presentation, telemetry showed torsade de pointes with ventricular fibrillation (Box), and external defibrillation was required to restore sinus rhythm. Amiodarone infusion was initiated at a local hospital before the patient was referred to our institution for further investigation and management. On presentation, her heart rate was 50 beats/min and her blood pressure was 170/95 mmHg. No other abnormalities were detected on examination. A resting electrocardiogram (ECG) showed prominent U waves, with a long QT interval (QTc of 540 ms). As the patient had mild hypokalaemia (serum potassium level, 3.1 mmol/L), mild hypocalcaemia (serum calcium level, 2.10 mmol/L) and a prolonged QT interval, the amiodarone infusion was discontinued, and supplementation with potassium and calcium was initiated. In view of the hypertension and hypokalaemia, primary aldosteronism was suspected. Serum cortisol, 24-hour urinary cortisol and 24-hour urinary catecholamine levels were normal. The plasma aldosterone/renin ratio was markedly elevated (1920/1.2 = 1595; normal, < 99). Failure of aldosterone suppression after acute saline loading was also noted. Computed tomography of the abdomen showed a right adrenal ovoid mass (1.9 × 1.2 cm). Adrenal vein sampling confirmed right lateralisation (right to left ratio, 40 : 1; aldosterone level in the right vein was 224 000 pmol/L while that in the left vein was 5570 pmol/L). Despite initial potassium supplementation, the hypokalaemia persisted and only improved after initiating diuretic therapy with amiloride. Two weeks later, laparoscopic right adrenalectomy was performed, and adrenocortical adenoma was confirmed histologically. After surgery, plasma aldosterone and renin levels normalised to 106 pmol/L and 8.9 mU/L, respectively. Nine months later, the patient was normotensive (without treatment) and had a normal ECG with no further recurrence of arrhythmias. This was a case of primary aldosteronism presenting as aborted sudden cardiac death and malignant syncope secondary to hypokalaemia-induced torsade de pointes. Most patients with primary aldosteronism are either asymptomatic or have symptoms related to hypertension or hypokalaemia (eg, polyuria, cramps, paraesthesia or muscle weakness); the diagnosis is often missed because of the non-specific clinical features. Primary aldosteronism presenting with cardiovascular collapse caused by hypokalaemic torsade de pointes and recurrent ventricular fibrillation is extremely rare, as is presentation as sudden cardiac death secondary to ventricular fibrillation.1 A prolonged QT interval has been reported in cases of primary aldosteronism,2 with values normalising after adrenalectomy.3 Torsade de pointes noted on telemetry in a 39-year-old woman

Aditya Kapoor · Timothy A Wells · Daniel Wong · John P O’Shea

To the Editor: Childhood overweight and obesity have become a major public health concern in Australia. Between July 2003 and December 2004, we conducted the Australian National Iodine Nutrition Study (NINS) among schoolchildren.1 While visiting primary schools across Australia, we observed that many children were overweight or obese. The NINS data allowed us to estimate the prevalence of overweight and obesity among 8–10-year-old Australian schoolchildren, and to determine whether the prevalence was associated with socioeconomic background. The study population comprised a one-stage random-cluster sample from all Year 4 school classes in 92 government and non-government schools.1 Children were aged 8–10 years (mean, 9.3 years). Height and weight were measured by standard techniques and were used to calculate body mass index. Overweight and obesity were identified using international standard definitions.2 Socioeconomic status was defined by the Index of Relative Socio-Economic Advantage/Disadvantage of the Census of Population and Housing’s Socio-Economic Indexes for Areas (postal areas).3 This index is a continuum of advantage to disadvantage. A higher score indicates that an area has a relatively higher proportion of people with higher incomes or a skilled workforce. The prevalence of overweight and obesity in 8–10-year-old schoolchildren was 18.5% and 6.5%, respectively. There was no significant sex difference in prevalence and no significant evidence of an association between socioeconomic status and overweight or obesity (Box). The prevalence of overweight and obesity combined and of obesity alone was similar to previously reported prevalence,4,5 although the age range of the participants was more limited than in other studies. We minimised measurement error bias by using the same equipment throughout, in the same setting. Furthermore, most measurements were taken by the same person. We could not demonstrate an association between socioeconomic status and the prevalence of overweight and obesity combined, or of obesity alone. This suggests that childhood overweight and obesity is common to all Australian communities, irrespective of socioeconomic background. Preventing overweight and obesity in children may reduce the risk of adult overweight and obesity and related diseases. Regular monitoring and surveillance of the situation is needed. Australia is one of the first countries in the world to develop a national strategy for overweight and obesity.6 However, the strategy needs to be communicated to the wider community and turned into action to combat this public health problem. Proportion (number) of boys and girls categorised as overweight or obese by index of advantage/disadvantage* SEIFA percentile Not overweight or obese Overweight Obese n Overall Boys Girls Overall Boys Girls Overall Boys Girls Lowest 10 130 79% (102) 77% (56) 82% (46) 12% (16) 12% (9) 13% (7) 9% (11) 11% (8) 5% (3) 10–25 286 72% (207) 72% (103) 73% (103) 22% (64) 22% (31) 23% (33) 5% (15) 6% (9) 4% (6) 25–50 210 74% (156) 72% (72) 76% (84) 17% (35) 18% (18) 16% (17) 9% (19) 10% (10) 8% (9) 50–75 505 75% (379) 72% (183) 79% (195) 19% (98) 21% (53) 18% (45) 6% (28) 8% (20) 3% (8) 75–90 427 75% (319) 78% (179) 71% (140) 18% (78) 17% (39) 20% (39) 7% (30) 6% (13) 9% (17) Highest 10 225 77% (174) 79% (84) 76% (89) 17% (39) 16% (17) 19% (22) 5% (12) 6% (6) 5% (6) Total 1782 75.0% (1337) 74.4% (677) 75.6% (657) 18.5% (330) 18.4% (167) 18.8% (163) 6.5% (115) 7.3% (66) 5.6% (49) * Overall χ2 = 11.42, P = 0.33; Boys χ2 = 8.73, P = 0.56; Girls χ2 = 12.36, P = 0.26. SEIFA = Socio-Economic Indexes for Areas (a higher score corresponds to higher socioeconomic status).

Mu Li · Karen Byth · Creswell J Eastman

To the Editor: Obesity in adults presents significant issues for health care providers, including practical problems in transporting and accommodating large individuals, and in performing standard tests and investigations.1 However, this issue has been little addressed in the mortuary setting, although a recent media report detailed the need for larger crematorium furnaces to accommodate oversized coffins, as well as larger graves for burials.2 We reviewed the body mass index (BMI) of individuals who had undergone coronial autopsies in South Australia in the first 3 months of 2007. Weight and height of all bodies were measured using standardised equipment and were used to calculate BMI by the usual formula.3 A total of 255 individuals aged over 17 years were included in the study (male to female ratio, 2 : 1; age range, 17–97 years). A third of individuals were classified as obese (BMI ≥ 30 kg/m2), and 6% as morbidly obese (BMI ≥ 40 kg/m2). The highest BMIs were: 132.3 kg/m2 (175 kg, 115 cm); 109.0 kg/m2 (315 kg, 170 cm); 82.8 kg/m2 (220 kg, 163 cm); and 79.5 kg/m2 (201 kg, 159 cm). In comparison, over a similar time period at the same institution in 1986, 17% of individuals were obese, and 3% were morbidly obese, with the four highest BMIs being: 55.2 kg/m2 (137 kg, 157.5 cm); 48.3 kg/m2 (148 kg, 175 cm); 44.7 kg/m2 (137 kg, 175 cm); and 41.9 kg/m2 (104 kg, 157.5 cm). This study demonstrates that forensic facilities are now dealing with individuals of considerable body mass. Despite government and industry guidelines for manual handling practices,4 these bodies are difficult to lift, move and store, and present major logistical problems for pathologists and technicians attempting to perform standard examinations. Mechanical lifting hoists, x-ray tables and trolleys are often not designed to cope with such weights. Putrefaction is hastened in morbidly obese individuals, and associated skin slippage and purging makes the bodies even more difficult to handle. Given that autopsies are often required in such individuals to determine the cause of death, consideration must be given to the significant occupational health and safety issues they create for staff in facilities with substandard equipment (ie, designed for normal-sized bodies). The construction of specially designed mortuaries will be required if this trend continues, with larger storage and dissection rooms, and more robust equipment engineered to cope with increasing numbers of individuals with BMIs sometimes considerably greater than 30 kg/m2. Failure to provide these may compromise the postmortem evaluation of markedly obese individuals, in addition to potentially jeopardising the health of mortuary staff.

Roger W Byard · Maria Bellis

To the Editor: The increase in medical graduates expected over the next decade presents a huge challenge to the many stakeholders involved in providing their prevocational and vocational medical training.1 Increased numbers will add significantly to the teaching and supervision workload for registrars and consultants, while specialist training and access to advanced training positions may be compromised. However, this predicament may also provide opportunities for innovation in the way internships are delivered. Although facing these same challenges, regional and rural hospitals could use this situation to enhance their workforce by creating opportunities for interns and junior doctors to acquire valuable experience in non-metropolitan settings. We surveyed a representative sample (n = 147; 52% of total cohort) of Year 3 Bachelor of Medicine and Bachelor of Surgery students at the University of Queensland about their perceptions and expectations of their impending internship and the importance of its location (ie, urban/metropolitan versus regional/rural teaching hospitals) to their future training and career plans. Most students (n = 127; 86%) reported a high degree of contemplation about their internship choice. Issues relating to career progression and support ranked highest in their expectations. Most perceived internships in urban/metropolitan hospitals as more beneficial to their future career prospects compared with regional/rural hospitals, but, interestingly, felt that they would have more patient responsibility and greater contact with and supervision by senior staff in a regional setting (Box). Regional and rural hospitals should try to harness these positive perceptions and act to address any real or perceived shortcomings in order to enhance their future workforce.2 They could look to establish partnerships with rural clinical schools3 to enhance recruitment of interns as early as Year 3. To maximise competitiveness with their urban counterparts, regional and rural hospitals need to offer innovative training and career progression pathways to junior doctors, to combat the perception that internships in urban hospitals are more beneficial to future career prospects. Partnerships between hospitals, medical schools and vocational colleges, with input from postgraduate medical councils, should provide vertical integration4 in the important period between student and doctor. Work is underway to more closely evaluate and compare the intern experience across regional/rural and urban/metropolitan hospitals, and track student experiences and career choices longitudinally. This information may benefit teaching hospitals and help identify the optimal combination of resources necessary to provide quality teaching and a clear career pathway for the expected influx of new interns. Year 3 medical students’ perceptions of internship in a regional/rural hospital versus an urban/metropolitan hospital Perception Strongly disagree Disagree Not sure Agree Strongly agree My acceptance onto a training program will be influenced by the reputation of the hospital in which I do my internship 4% (5) 18% (24) 28% (38) 43% (59) 8% (11) I would have less responsibility for my patients in a regional/rural hospital 21% (29) 67% (92) 12% (17) 0 0 There would be more contact with senior staff in an urban/metropolitan hospital than in a regional/rural hospital 11% (15) 48% (66) 29% (39) 11% (15) 2% (2) I would have more clinical supervision in an urban/metropolitan hospital than in a regional/rural hospital 11% (15) 47% (64) 25% (34) 15% (20) 2% (3) I would feel more part of a team in an urban/metropolitan hospital than in a regional/rural hospital 11% (15) 60% (83) 27% (38) 2% (3) 0 Numbers are percentage of respondents (number of respondents). Denominators vary due to missing responses.

Diann S Eley · David K Morrissey

To the Editor: We report that the internship location choices of the second cohort of medical students to graduate from James Cook University (JCU) are very similar to those of the first cohort.1 Of the 75 students who graduated in the second cohort in 2006, 65 (87%) are working in Queensland; 42 (56%) in North Queensland (roughly the area north of Mackay). Fifty-three (71%) are in non-metropolitan hospitals, including three of the 10 graduates who moved or returned interstate. These proportions reflect the cohort’s geographic origins. As in the first cohort, a small number of students (13; 17%) of North Queensland origin moved away and a similar number (14; 19%) from elsewhere stayed in North Queensland. Further, a majority of the first cohort have remained where they undertook internship: 24 of 29 (83%) have remained in North Queensland and one commenced remote practice, consistent with the group’s stated intentions to work in regional locations.2 Hence, JCU’s first two graduating cohorts had a combined effect of strong recruitment to non-metropolitan hospitals, particularly in Queensland, some of which have experienced difficulty in recruiting junior staff. These results have two implications. First, they contribute to the debate on selection into medicine.3 JCU gives weight to rural schooling, with about two-thirds of each cohort having a rural background, and a similar proportion coming from North Queensland.4 Second, there are workforce policy implications. The growth in medical school numbers over the past 3 years has not evenly reflected workforce needs or availability of postgraduate training places. As some urban areas become oversupplied with junior doctors, it will be important not to neglect areas of maldistribution that are drivers of growth. Regional training pathways for specialist and generalist careers need urgent definition; graduates in Queensland are expected to increase from 300 in 2007 to 727 in 2014, so vocational training places will need to more than double.5 An impact on the Australian medical workforce shortage will only be felt when a number of cohorts have graduated from JCU and other regional schools, and bottlenecks to subsequent training are removed. It will take another decade to obtain a clear picture of postgraduate career outcomes for this group, but the investment in regional medical education in North Queensland appears at this stage to be having the desired effect. If this effect is sustained and replicated in other new regional medical schools, Australia may soon have an adequate supply of medical graduates who both understand and choose to live and work in regional Australia.

Tarun Sen Gupta · Richard B Hays · Richard B Murray

To the Editor: The Transition Care Program (TCP) is a joint federal and state government program that provides short-term (8–12 weeks) support and therapy to improve functioning for older people who are hospitalised (either in public or private hospitals) and would otherwise require admission to a residential aged care facility.1 Participants are provided with a care package that assists with activities of daily living, and provides limited allied health, nursing and medical input, with the aim of improving functional status, if possible. The TCP is currently being implemented across Australia. We selected and audited three transition care services that commenced operation early in the program (2005 and early 2006), with the aim of describing the outcomes of these services, and determining whether the older people participating in the various services were similar. Approval was obtained from the relevant ethics committees. Three services were purposefully sampled: two services in Adelaide (Service A providing packages in a community setting, and Service B providing packages in a high-level care, residential aged care setting); and one service in Sydney (Service C providing packages in a community setting). The residential package allocates temporary residential placements for patients with defined rehabilitation goals, and thus also frees up acute care hospital beds. These services supplied de-identified audit data about the first 30 participants, who were in the program between June and December 2006. A summary of the data is given in the Box. The participants in the residential program tended to be older, more likely to be male, and less likely to have “fracture or fall” as their primary diagnosis. These older people also had more severe disability that generally does not improve, and were significantly less likely to return to community living. The two community-based programs were generally similar. The data suggest that there is considerable variation between the TCP services, with the residential service providing packages to older people with severe disability who generally remain in a residential aged care program, although some may improve from high- to low-level aged care services. By contrast, the outcome of the community-based services is generally maintenance in the community and is associated with an improvement in functioning. This profile is similar to that of a community-based rehabilitation service for older people. It is not clear from the TCP guidelines whether this level of variation in program implementation was anticipated.1 This limited audit suggests that the Australian TCP is not homogeneous and is substituting for other forms of treatment and care. Thus, there is provision of high-level residential care as a substitute for waiting for residential aged care in a hospital bed, and community rehabilitation as a substitute for rehabilitation services provided by state health departments. This situation is potentially beneficial to older people who previously did not have access to these services, but it also could mean that state governments may not establish rehabilitation services for older people, or may even cease providing these services. Comparison of background, status and outcomes for participants in three Transition Care Program (TCP) services Service A (community) (n = 30) Service B (residential) (n = 30) Service C (community) (n = 29) Statistical significance* Mean age (SD) in years 80.9 (7.9) 84.5 (5.1) 80.4 (8.0) ns Female 60% 47% 59% ns Living alone 40% 47% 62% ns Primary diagnosis — trauma (fractures and falls) 43% 20% 41% ns Barthel Index On admission to the TCP — mean (SD) 66.9 (13.8) 55.2 (26.8) 69.2 (19.1) F = 3.85; P = 0.025 On discharge from the TCP — mean (SD) 72.8 (17.6) 56.4 (34.2) 82.8 (22.0) F = 7.69; P = 0.001 Mean change (SD) 5.9 (21.3) 1.5 (19.0) 11.6 (13.3) ns Discharge status — in the community† 60% 20% 76% χ2 = 35.6; P = 0.000 * Based on a comparison between the three groups (χ2 test for categorical data, and analysis of variance [F test] for continuous data). † Patients were in the Program for 12 weeks unless they left early because of admission to hospital or permanent admission to a residential care facility. ns = not significant.

Ian D Cameron · Owen Davies

To the Editor: In an ironic clinician–academic dichotomy, in the same month that the Royal Australian and New Zealand College of Psychiatrists published a survey showing that 79% of Australian psychiatrists combine antidepressants and 75% of psychiatrists believe that general practitioners should be given information on this topic,1 Keks et al chose a non-psychiatric journal to “mandate that combinations be used as a last resort, and only in specialist settings”.2 Specialists have voted with their prescription pads. That a large majority of Australian psychiatrists feel ethically and clinically obliged to use combination antidepressants speaks volumes about the poor results from the suggestions outlined by Keks et al. The multiple clinical reports and reviews of the benefits of combination antidepressants,3 the suffering and death from depression, and the very low rate of complications reported to the Adverse Drug Reactions Advisory Committee from combination antidepressants do not allow the luxury of awaiting combination therapy research which may never happen. Many combinations of antihypertensives or anti-asthma medications similarly lack such rigorous proof, but are widely used. Isolated case reports of medication complications must be seen as such. Access to psychiatrists for combination antidepressant therapy is a well intentioned but currently impractical suggestion. Most psychiatrists have massive waiting lists, and research confirms treatment resistance and progressive cell death in the hippocampus of depressed patients while awaiting effective treatment. Australian GPs are just as capable of using combination antidepressant therapy as their international colleagues, if given the same simple information and training. Canadian GPs read in their journals advice about using combination antidepressants. Anecdotally, many Australian GPs combine antidepressants, but express the wish that the issue could be discussed openly, without them feeling intimidated. Even textbooks of psychiatry, drafted some years ago, teach about combination antidepressants. In the United States, the National Institute of Mental Health STAR*D study of 4000 patients approved combination antidepressants such as venlafaxine with mirtazapine years ago, with no safety concerns.4 Keks et al refer to treatments that today are unacceptable to many, ranging from electroconvulsive therapy to tricyclic antidepressants, despite GPs and psychiatry trainees having been warned for years by academics that tricyclics are outdated, “dirty” and dangerous. Informed consent requires that patients be informed of all therapies that are relevant to their care and survival, and 88% of psychiatrists believe patients should be informed of combination antidepressants.1 Recent results from the STAR*D study demonstrate the superiority of modern combination antidepressants, with no statistically based evidence that they should not be used.5

David P Horgan

To the Editor: Keks et al make a number of important points about the place of combination antidepressant strategies in the pharmacotherapy of depression.1 However, it is important for readers to note that the vigorous repudiation of combination treatments is a peculiarly Australian preoccupation. Our colleagues in Europe and North America are not nearly so troubled. Combination antidepressant treatments are widely used by specialists. A recent survey of Australian doctors working in psychiatry reported that 79% of respondents had used combination antidepressants and that 75% believed that general practitioners should be given information on their use.2 There is emerging evidence for the use of combination antidepressant strategies — from case series, open clinical trials, and randomised controlled trials (RCTs). The largest summation of the data is a meta-analysis which found that combination antidepressant treatment produced a 62% response rate when monotherapy had failed.3 Although this finding alone cannot be convincing because of the acknowledged lack of large sample RCTs, it is quite another matter to decry combination prescribing as clinically unsound based only on the history of augmentation treatments such as lithium and, to a lesser extent, thyroid hormone treatment when, anecdotally, they provide such clinically disappointing results. It is not unreasonable to assert the primacy of good clinical reasoning, including sensible prescribing of combination antidepressants, over rigid adherence to evidenced-based algorithms. This sort of thinking is allowable because the evidence base for the treatment of depression is poor. Meaningful guidelines cannot be produced while the evidence is predicated on the flawed proposition that depression is an “it” (a homogenous construct).4 GPs might well be puzzled by the zeal in academic psychiatry for monotherapy. They are advised to “optimise” monotherapy, but not told what this means. They are very familiar with models of staged polypharmacy for common chronic illnesses such as hypertension, epilepsy, diabetes, and asthma, but in psychiatric pharmacotherapy this is apparently unwise or too risky. The way such admonishments are usually framed is by reference to serious but rare adverse reactions (like the serotonin syndrome), without proper attention to the equally serious and probably more common problems with the current “simple” psychotropic drug options already used by GPs. Failure to contextualise these risks leads to a distortion of risk–benefit prescribing decisions and an unnecessary restriction of treatment choices. We must have a commonsense approach to the treatment of depression that recognises the proper context of our knowledge base. Combination antidepressant treatments may be “beyond the evidence”, but this alone is not a sufficient justification to stop using them.

Murray J Walters · Alston M Unwin · Sean B Gills

In reply: The letters by Horgan and Walters et al underline our motive for reviewing antidepressant combinations. The conclusions of the survey are at least questionable, given that the response rate was only 36%, 18% of respondents were not psychiatrists, and affirmative responders may have only used combination antidepressants once.1 In any case, should clinical popularity substitute for evidence? If so, once popular but now research-discredited treatments such as insulin coma therapy would still be used. Equating combination antidepressants to combination drugs for asthma and hypertension is misleading. How often are two β-blockers given together in maintenance treatment? Major depression causes severe suffering, but this does not justify the use of unproven treatments ahead of those supported by evidence. General practitioners should be informed about antidepressant combinations, but the information must be evidence-based. We described the process of dose optimisation, and stand by our advice that complex cases that require unproven treatment (such as combination antidepressants) be referred to a psychiatrist. Patients should also be informed about combination antidepressants, including the paucity of evidence concerning efficacy and safety, the absence of information about consequences of long-term treatment, and that some combinations are lethal and others frequently unsafe. Published data from the STAR*D study provide equivocal support for the combination of citalopram and bupropion, as we noted. Evidence of modest effectiveness (remission rate, 13.7%) for the combination of mirtazapine and venlafaxine has appeared.2 Our conclusion was that some antidepressant combinations could be used in certain clinical situations where evidence-based treatments have failed, with safeguards. Given that 17% of respondents to the survey1 observed serious complications with combination antidepressants, this is good advice.

Nicholas A Keks · Graham D Burrows · David L Copolov · Richard Newton · Nick Paoletti · Isaac Schweitzer · John W G Tiller

To the Editor: In his “Personal perspective” piece, Allen1 reminded us all of how medicine can at times truly be the noblest of professions. Writing to the next of kin after the death of a patient is occasionally a difficult task, but more usually provides an appropriate form of closure, not only to the relationship with the deceased patient, but also to relationships with the person’s partner, family members and friends whom you may have met during the treatment episode and whom you may not see again. Since I began practice as a consultant 20 years ago (a practice that involves a substantial number of patients who require surgery for cancer), I have tried to write to the next of kin or significant other of every patient who has died while under my care. The letter allows me the opportunity to say perhaps how brave the patient had been in the face of adversity or to acknowledge the support the next of kin had provided. A simple expression of condolence and an indication of how much a loved one may be missed seems to be the best way to “sign off”. Such letters are only a small gesture, but I have often been gratified by how much comfort they seem to provide to those who receive them, and in all this time I have never had a response that could even remotely be considered “negative”. In this current day, when practising clinicians appear to have a diminished role in our medical schools, may I suggest that Allen’s article — which I think is a great example of what is meant by the “art of medicine” — be distributed to our universities and colleges to be considered for inclusion in their teaching material and curricula.

Ian T Jones

Derek Farrar, a respected Otolaryngology, Head and Neck Surgeon, was one of the few who brought ear, nose and throat (ENT) surgery to Tasmania in the mid 20th century. Derek was born in Portsmouth, UK, on 27 December 1921. He was educated in Hong Kong and Plymouth, and studied medicine at St Bartholomew’s Medical School at the University of London. On graduating in 1943, he entered the Royal Navy as Surgeon-Lieutenant. After the War, he undertook further training at St Bartholomew’s and obtained a Fellowship of the Royal College of Surgeons in 1949. He developed an interest in ENT surgery and qualified for a Diploma in Laryngology and Otology of the Royal College of Physicians and Surgeons in 1955. Derek came to Australia in 1956 to take up a position in a private ENT practice with Dr Mills Bates in Launceston, and qualified for Fellowship of the Royal Australasian College of Surgeons in the following year. He also worked as an Honorary ENT Surgeon at Launceston General Hospital. After practising in Launceston for 20 years, Derek moved to Hobart, where he worked in private practice and at the Royal Hobart and Repatriation General Hospitals as an Honorary ENT Surgeon, while continuing to visit Launceston regularly. He was also an enthusiastic teacher of medical students, residents and ENT registrars. Derek attended the Hobart and Launceston branches of the Peter MacCallum Clinic (later W P Holman Clinic) for three decades as a Head and Neck Surgeon. He gave generously of his opinion and skills to the younger generation of Otolaryngology, Head and Neck surgeons who came to practise in Tasmania in the early 1980s. In his leisure time, Derek was very active in the Cruising Yacht Club of Tasmania (CYCT). During his period as Commodore, he instigated the publication (by the CYCT and the Tasmanian Lands Department) of D’Entrecasteaux waterways, a book of maps and local guidance for cruising yachts. This book, detailing the area from Recherche Bay in Tasmania’s southwest to the upper Derwent River at New Norfolk, remains a classic guide to locals and visitors cruising these waters. In the late 1980s, Derek retired and had more time for sailing. Northern Queensland was his destination on a number of occasions, the last being in 1997, when he saw his yacht sunk from under him, probably as a result of hitting a submerged container. Thereafter, he pursued a quiet retirement, but his health ailed in later years and he died of pneumonia on 14 February 2007. He is survived by his wife Rhonwen and also by his sons Alan and Nigel. He will be sadly missed and long remembered by his colleagues.

Philip J Moore

Re: “Management outcomes of patients with type 2 diabetes: targeting the 10-year absolute risk of coronary heart disease”, by Tuck Y Yong, George Phillipov and Patrick J Phillips, in the 18 June issue of the Journal (Med J Aust 2007; 186: 622-624). There was an editing error introduced in the Results section of the Abstract of this article. The first sentence should have read: Results: 42%, 61% and 43% of patients were receiving medication to treat hyperglycaemia, hypertension and hypercholesterolaemia, respectively; 46%, 29% and 15% of patients, respectively, had achieved the recommended RACGP target values for HbA1c, blood pressure, and total cholesterol; and 22% of patients were current smokers. The html and pdf versions of this article have been corrected. Re: “Research misconduct: can Australia learn from the UK’s stuttering system?”, a letter to the Editor by Peter T Wilmshurst in the 18 June issue of the Journal (Med J Aust 2007; 186: 662-663). In the editing of this letter, we incorrectly stated that the “Editor’s choice” column in the British Medical Journal, entitled Corruption in medicine,1 was only published online and thus was no longer available, as it had been removed, to avoid litigation, from the online version (together with the article by Wilmshurst that it was linked to). However, the column was also published in the paper journal and is still available there (as is the article2). The html and pdf versions of this article have been corrected.

Genetic key to breast cancer A multinational genome-wide association study has identified novel loci for breast cancer susceptibility. Despite the identification of the major susceptibility genes BRCA1 and BRCA2 in the 1990s, the majority of multiple-case breast cancer families do not exhibit mutations in these genes. To identify further susceptibility alleles, researchers conducted a three-stage analysis. The first two stages included a susceptibility study of over 8000 breast cancer patients and controls. In the third part of the study, 30 single nucleotide polymorphisms were tested for confirmation in over 44 000 cases and controls. Five novel breast cancer susceptibility loci were identified, and patterns of risk established for the genes. Although most previously identified genes are associated with DNA repair, the susceptibility loci in this study contain genes related to the control of cell growth or signalling. The authors comment that the results demonstrate the critical importance of study size in such genetic association studies. Nature 2007; 447: 1087-1093 More conditions — better care Concern that quality-of-care indicators do not take into account patients with multiple chronic conditions has prompted US researchers to investigate the relationship between number of medical conditions and quality of care. Using established measurements of quality of medical care, researchers studied data from three separate studies involving over 7500 patients, analysing the association between the care received and the number of chronic medical illnesses suffered by each patient. Conditions included depression, diabetes, heart failure, hypertension and chronic obstructive pulmonary disease. Even when the authors controlled for potential artefacts, such as the same care processes satisfying quality indicators for different conditions, quality of care was found to increase as the number of medical conditions increased. N Engl J Med 2007; 356: 2496-2504 Na zdorovye! The exceptionally low life expectancy of men in Russia may be related to hazardous alcohol consumption, according to a population-based case-control study. The probability for a Russian man of dying between 25 and 65 years is 0.55, compared with 0.15 for English men. In an attempt to shed light on this alarming statistic, researchers focused on a typical Russian industrial city, researching all deaths in men aged 25–54 years over a 2-year period. Information was gathered about the subjects’ alcohol consumption in the form of beverages (beer, wine and spirits) and non-beverage alcohols (including medicinal tinctures, colognes and cleaning agents). Results indicated that 43% of deaths in men aged 25–54 years in the study population were attributable to hazardous drinking alone. Men who drank non-beverage alcohol were more at risk than those who drank beer, wine or spirits, and this risk was strongly associated with frequency of consumption. The researchers comment that the consumption of such cheaper, easily accessible forms of ethanol may be a marker for hazardous drinking, and that the fluctuating but consistently high mortality of Russian men may be linked to this behaviour. Lancet 2007; 369: 2001-2009 Cold feet Imaging methods used in the investigation of lower limb peripheral arterial disease are increasingly complex, with results determining the treatment and outcome for patients. British researchers have conducted a systematic review aimed at clarifying the options by collecting data on the use of duplex ultrasonography, magnetic resonance angiography, and computed tomography angiography. Using 107 published studies, the authors extracted data on detection of stenosis, outcomes for patients, adverse events, and patient preferences. Although limited by the lack of high-quality, well reported studies and the possibility of inter-observer variability, the review indicates that contrast-enhanced magnetic resonance angiography appears to be more specific than computed tomography angiography, that is, better at ruling out stenosis over 50%. BMJ 2007; 334: 1257 Haematocritical Postoperative mortality is significantly increased in elderly patients with abnormal preoperative haematocrit levels, according to US researchers. In a large multicentre study of Veterans Affairs patients undergoing non-cardiac surgery, over 310 000 patients were stratified into categories of anaemia, normal haematocrit, and polycythaemia. The primary outcome measure in the study was 30-day postoperative mortality, with a secondary outcome being the occurrence of cardiac events. After taking into account possible confounders, the results showed a monotonic increase in mortality and cardiac events with either positive or negative deviations from normal haematocrit levels. Despite limitations such as the smaller number of polycythaemic patients involved, and the observational nature of the study, the authors concluded that even minimal deviations from a normal haematocrit result in increased postoperative risk for elderly patients. JAMA 2007; 297: 2481-2488

Tanya Grassi