Volume 194 Issue 7

What can we do to prevent this from becoming the most common health care-associated infection in Australia? Clostridium difficile, a gram-positive, anaerobic, spore-forming, toxigenic bacterium, is the most common infectious cause of nosocomial diarrhoea. The severity of infection varies from mild diarrhoea to pseudomembranous colitis, toxic megacolon and death.1 In the United States, C. difficile now rivals methicillin-resistant Staphylococcus aureus (MRSA) as the most common health care-associated infection, accounting for US$3.2 billion in excess costs annually.1,2 Since 2000, there has been an increase in the rates of C. difficile infection (CDI) in some health care facilities in the US, Canada and Europe, associated with an epidemic strain of C. difficile. This strain (B1/NAP1/027, toxinotype III or PCR ribotype 027) is characterised by its increased resistance to fluoroquinolones, increased toxin production (toxins A, B and binary toxin), increased sporulation, and increased morbidity and mortality.1,3 Risk factors for CDI include exposure to antimicrobial drugs, gastric acid-suppressive therapy, advanced age, prolonged hospitalisation, cancer chemotherapy, comorbidity and immunosuppression.3 Although most cases have been in hospital inpatients, increasing numbers of community-associated cases are now being reported in the US and Europe.4,5 Australia is now also in the grip of this new strain of C. difficile. The first infected patient was reported in 2009 in Western Australia, but the infection was thought to have been acquired in North America.6 In this issue of the Journal, Richards and colleagues report the first case of C. difficile ribotype 027 thought to have been acquired in Australia (→ Severe infection with Clostridium difficile PCR ribotype 027 acquired in Melbourne, Australia).7 The strain was identified after clinicians alerted the laboratory to the severity of the infection and the possibility of a hypervirulent strain. Since this case was first reported, there have been further clusters of C. difficile ribotype 027 infection centred around residential aged care facilities. Currently, surveillance for C. difficile is not consistent across Australia, so rates of CDI across the continent are unknown. However, some states have commenced surveillance and show overall rates varying between 1.27 and 2.3 CDIs per 10 000 bed-days.8 This contrasts with a reported overall rate in Canada of around 3.8–9.5 CDIs per 10 000 bed-days based on surveys conducted in 1997 and 2005.9 Clinicians need to be aware of the clinical picture, diagnostic methods and new therapeutic approaches to this disease. The Australasian Society for Infectious Diseases has published guidelines in this issue of the Journal that clearly outline clinical assessment, diagnostic issues and treatment guidelines (→ Australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection).10 Identification of hospitalised patients with CDI is the key to preventing transmission. Hospitals need to have an optimal surveillance program in place to expedite patient testing and identification. As a minimum standard, all patients with hospital onset of diarrhoea (> 48 hours after admission) should be screened for CDI. The case definition for CDI should include: (i) symptoms (usually diarrhoea); and (ii) a stool test positive for toxigenic C. difficile or its toxins, or colonoscopic or histological findings of pseudomembranous colitis.9 Similarly, clinicians working in residential aged care facilities need to be alert to the possibility of CDI in residents, to undertake testing in the presence of symptoms and to focus on decreasing transmission of the infection within the facility. In the hospital setting, infection control precautions around cases of CDI need to be enforced. Infection control guidelines for CDI from the Australasian Society for Infectious Diseases and the Australian Infection Control Association have recently been released.11 The main management principles for control of CDI include: all health care organisations, including residential aged care facilities, giving CDI prevention and control the highest priority, even if the prevailing incidence of CDI is low; surveillance being integrated into quality improvement programs to optimise prevention and control of CDI and clinical care of infected patients; antimicrobial stewardship programs being in place that are aimed at minimising the frequency and duration of antibiotic use and promoting a narrow-spectrum antibiotic policy; emphasis on compliance with hand disinfection and glove use for care of patients with CDI to minimise spore contamination; contact precautions being employed for symptomatic patients with CDI, including the donning of gowns or aprons and gloves on entry to patient rooms; use of sporocidal environmental cleaning and disinfection in high-risk areas such as toilets, bathrooms and rooms of patients with CDI, and elimination of other potential fomites by either using disposable equipment or ensuring that equipment is adequately cleaned and disinfected before reuse; and education of all health care staff, patients and visitors about CDI, its prevention and management. It is sobering to contemplate that what has occurred in the US, Canada and Europe is potentially and imminently on our doorstep. We must learn from the experience of experts in these countries so that Australia can avoid a similar experience — we already have the benefit of their hindsight to guide us. Our challenge is implementing the necessary interventions — enhanced surveillance and diagnosis, antimicrobial stewardship, environmental cleaning and stringent infection control. Although this solution re-echoes the usual infection control mantra, it is essential that we act pre-emptively to prevent CDI from occurring, especially to the most vulnerable of our patients.

Rhonda L Stuart MBBS, FRACP, PhD · Caroline Marshall FRACP, PhD, GradDipClinEpi

Screening plus equitable provision of vitamin D supplements could mitigate many adverse outcomes For nothing worthy proving can be proven, Nor yet disproven: wherefore thou be wise, Cleave ever to the sunnier side of doubt. Alfred, Lord Tennyson, The ancient sage Tennyson may not have been alluding to the need for high-level evidence from randomised controlled trials (RCTs) to alter clinical practice, but he would have been aware of children with rickets. Evidence has accumulated linking vitamin D deficiency to adverse outcomes in pregnancy, such as pre-eclampsia, hypertension, higher rates of caesarean section and preterm delivery. Lau and colleagues (→ Serum 25-hydroxyvitamin D and glycated haemoglobin levels in women with gestational diabetes mellitus) contribute to this evidence by demonstrating that, in women with gestational diabetes mellitus (GDM), a lower serum 25-hydroxyvitamin D (25[OH]D) concentration was independently associated with poorer glycaemic control.1 Of 147 women who were studied late in pregnancy (at a mean of 35 weeks’ gestation), about 40% had vitamin D insufficiency or deficiency (serum 25[OH]D concentrations ≤ 50 nmol/L). Most of the women in this study were not white, and ethnicity, occupational status and season, not surprisingly, all influenced 25(OH)D concentrations, while body mass index did not. Perhaps more surprisingly, however, 25(OH)D concentrations were inversely associated with fasting and 2-hour glucose levels measured during an oral glucose tolerance test and with the marker of glycaemic control, glycated haemoglobin. Most importantly, serum 25(OH)D was an independent predictor of glycaemic control. In adults, a number of large cross-sectional studies have shown a consistent, independent and positive relationship between serum 25(OH)D and insulin sensitivity, and an inverse relationship with risk of diabetes.2-5 Serum 25(OH)D levels have been shown to account for 42% of the variation in insulin sensitivity assessed by hyperglycaemic clamp.3 Consistent with Lau et al’s findings, fasting and 2-hour levels of glucose and insulin have been shown to be independently and inversely associated with serum 25(OH)D levels.3-5 In a United States study, the odds ratio for diabetes was 0.25 (95% CI, 0.11–0.60) for non-Hispanic white participants in the highest versus the lowest serum 25(OH)D quartile.2 The highest-level evidence to date comes from a large prospective study with a 17-year follow-up that showed people in the highest quartile of serum 25(OH)D had a 40% decreased risk of type 2 diabetes compared with those in the lowest quartile.6 Based on these data, RCTs of vitamin D supplementation in adults to improve insulin sensitivity and reduce diabetes risk are underway. GDM is becoming increasingly more common, affecting up to 10% of pregnancies. The presence of GDM is not trivial and has long-term implications for the health of mothers and their children. The former have an increased risk of developing type 2 diabetes, while their offspring have an increased risk of obesity and diabetes later in life. Vitamin D deficiency is also very common in pregnancy. The prevalence of inadequate levels of vitamin D in Lau et al’s study is comparable with rates of vitamin D insufficiency of 47.1% and 83.5% in white and black pregnant women, respectively, in the northern US (defined as 25[OH]D < 80 nmol/L)7 and 65.3% in pregnant women in rural Victoria (defined as 25[OH]D < 75 nmol/L).8 RCTs of vitamin D supplementation, initiated early in pregnancy, are now required to demonstrate whether vitamin D supplementation might reduce the incidence or severity of GDM. International debate is currently focused on the optimal level of serum 25(OH)D. Based on meta-analyses using musculoskeletal end points in older individuals, cut points of 60 nmol/L and 75 nmol/L seem appropriate to prevent falls and fractures, respectively.9 However, a recent Institute of Medicine report recommended at least 50 nmol/L,10 which appears overly conservative and does not take season into account. The public health implications of vitamin D deficiency in pregnancy are far broader than glycaemic control. In Australia, there has been a resurgence of rickets — partly owing to an increased refugee population comprising dark-skinned and veiled women with vitamin D deficiency, and also because of decreased exposure of babies to sunlight, lack of supplementation of infant feeds with vitamin D and weaning of infants onto non-milk liquids. Milder forms of bone disease may also occur with vitamin D deficiency. Recently, a study that used three-dimensional ultrasonography in pregnant women showed that vitamin D deficiency was associated with increased femur metaphyseal cross-sectional area and increased femur splaying (the ratio of femoral metaphyseal cross-sectional area to femoral length) at as early as 19 weeks’ gestation.11 In addition, it was previously shown that children born to mothers with vitamin D deficiency (< 50 nmol/L) during pregnancy exhibit deficits in total body bone mineral content as great as 11% at 9 years of age.12 This could lead to an increased risk of osteoporotic fracture later in adult life, but this is unlikely to be evaluated in long-term studies. In addition, maternal or early life vitamin D deficiency has been linked to an increased risk of several other disorders, including neonatal craniotabes, prematurity, type 1 diabetes mellitus, schizophrenia, and childhood respiratory infections and wheeze.13,14 Current evidence strongly supports routine screening for vitamin D deficiency early in pregnancy. Furthermore, vitamin D supplementation to correct deficiency should be initiated early in pregnancy as it might reduce the incidence or severity of GDM and because changes in skeletal morphology of the fetus associated with deficiency are seen as early as 19 weeks’ gestation. The most common recommended daily doses of cholecalciferol are 1000 IU–2000 IU, however, daily doses of up to 4000 IU have recently been shown to be safe in pregnancy (Bruce W Hollis, Professor, Department of Paediatrics, Medical University of South Carolina, USA, personal communication). What is problematic is the equitable provision of vitamin D supplements to pregnant Australian women with deficiency. Pregnant and breastfeeding women who are most at risk of vitamin D deficiency are often the least likely to be able to afford supplements. In the United Kingdom, vitamin D supplements are provided free of charge to such women through the Healthy Start program.15 There is evidence to support more widespread use of vitamin D supplements during pregnancy in Australia, although more research is required. One way to increase access might be to alter the scheduling of higher-dose, lower-cost vitamin D supplements.

Peter R Ebeling MB BS, MD, FRACP

Objective: To test the hypothesis that lower 25-hydroxyvitamin D (25[OH]D) levels in late pregnancy are associated with poorer glucose control in gestational diabetes mellitus (GDM).Design and setting: Retrospective cross-sectional study, in a GDM clinic at a tertiary referral centre.Patients: Women attending the GDM clinic at Westmead Hospital from 1 February 2007 to 1 February 2008, excluding those with prepregnancy glucose intolerance.Main outcome measures: Levels of glycated haemoglobin (HbA1c) and 25(OH)D measured during the third trimester; maternal age, ethnicity, body mass index (BMI) and occupational status; and results of oral glucose tolerance testing (OGTT).Results: 147 women with a mean gestational age of 35 ± 2 weeks were included, of whom 41% had insufficient or deficient levels of 25(OH)D (≤ 50 nmol/L). Ethnicity, occupational status and season significantly influenced 25(OH)D levels (P < 0.01 for all) but BMI did not. 25(OH)D levels were inversely associated with fasting and 2-hour blood glucose levels during OGTT (Spearman r = − 0.16; P = 0.05 for both) and with log[HbA1c] (Spearman r = − 0.32; P < 0.001). BMI and insulin doses were also associated with HbA1c levels. Multivariable analysis identified 25(OH)D and blood glucose levels during the OGTT as independent predictors of HbA1c levels.Conclusions: Lower 25(OH)D levels are independently associated with poorer glycaemic control. Future randomised trials are needed to determine whether vitamin D plays a role in glycaemic control in GDM. Regardless, maternal vitamin D insufficiency has adverse effects including neonatal hypocalcaemia and rickets. The 41% prevalence of inadequate 25(OH)D levels in the women in our study is unacceptably high. We propose routine 25(OH)D testing of all pregnant women at screening for GDM or earlier, and treatment of women who are found to be deficient.

Sue Lynn Lau MB BS, FRACP · Jenny E Gunton MB BS, FRACP, PhD · Neil P Athayde MB BS(Hons), FRANZCOG, CMFM · Karen Byth PhD · N Wah Cheung MB BS, FRACP, PhD

Objective: The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has proposed new criteria for the diagnosis of gestational diabetes mellitus (GDM). The aim of this study was to compare the prevalence of GDM when IADPSG criteria were used with the prevalence when the current Australasian Diabetes in Pregnancy Society (ADIPS) criteria were used.Design, setting and participants: This was a prospective study over a 6-month period, examining the results of all glucose tolerance tests (GTTs) conducted for the diagnosis of GDM in Wollongong, a city using the public and private sectors.Main outcome measures: The prevalence of GDM using the existing (ADIPS) and the proposed (IADPSG) criteria.Results: There were 1275 evaluable GTTs (571 public and 704 private). Using the current ADIPS diagnostic criteria, the prevalence of GDM was 8.6% (public), 10.5% (private) and 9.6% (overall). Using the proposed IADPSG criteria, the prevalence of GDM was 9.1% (public), 16.2% (private) and 13.0% (overall).Conclusions: The proposed IADPSG criteria would increase the prevalence of GDM from 9.6% to 13.0% (P < 0.001). In our study in the Wollongong area, which has a population with a predominantly white background, this increase came mainly from older women attending a private pathology provider. Data from both the public and private sectors need to be included in any discussion on the change in prevalence of GDM.

Robert G Moses MD · Gary J Morris BAppSc · Peter Petocz PhD · Fernando San Gil PhD · Dinesh Garg MD

Objective: To determine the predictive validity of the Undergraduate Medicine and Health Sciences Admission Test (UMAT) for academic performance at university.Design, setting and participants: We studied all 339 students who entered medical study at the School of Medicine, University of Queensland, directly from high school, between 2005 and 2009.Main outcome measures: UMAT scores before entry compared with grade point averages (GPAs) during university study.Results: Mean overall UMAT score at entry was 60/100 and mean GPA during university study was 6.1 (range, 1–7), with a correlation coefficient of 0.15 (P = 0.005). This relationship existed only in the first year of university study. For UMAT Section 1 score, the correlation coefficient was 0.14 (P = 0.01); for UMAT Section 2, the correlation coefficient was 0.06 (P = 0.29); and for UMAT Section 3, the correlation coefficient was 0.09 (P = 0.11). UMAT overall score for men (60.2) and women (59.8), and GPA for men (6.1) and women (6.2) were similar. However, men performed better in Section 1 (mean score 61.6 v 61; P = 0.05) and Section 3 (63.2 v 60.7; P < 0.001), whereas women performed better in Section 2 (58.5 v 55.8; P = 0.009). In multivariate analysis, only correlation between GPA and UMAT Section 1 score remained significant but was weak and lasted for 1 year of university study.Conclusions: Our findings suggest that UMAT has limited predictive validity for academic performance.

David Wilkinson MB BS, DSc, FRCP · Jianzhen Zhang BMed, MPH(TH), PhD · Malcolm Parker MB BS, MLitt, MD

Objective: To examine the feasibility of balancing sunlight exposure to meet vitamin D requirements with sun protection guidelines.Design and setting: We used standard erythemal dose and Ultraviolet Index (UVI) data for 1 June 1996 to 30 December 2005 for seven Australian cities to estimate duration of sun exposure required for fair-skinned individuals to synthesise 1000 IU (25 μg) of vitamin D, with 11% and 17% body exposure, for each season and hour of the day. Periods were classified according to whether the UVI was < 3 or ≥ 3 (when sun protection measures are recommended), and whether required duration of exposure was ≤ 30 min, 31–60 min, or > 60 min.Main outcome measure: Duration of sunlight exposure required to achieve 1000 IU of vitamin D synthesis.Results: Duration of sunlight exposure required to synthesise 1000 IU of vitamin D varied by time of day, season and city. Although peak UVI periods are typically promoted as between 10 am and 3 pm, UVI was often ≥ 3 before 10 am or after 3 pm. When the UVI was < 3, there were few opportunities to synthesise 1000 IU of vitamin D within 30 min, with either 11% or 17% body exposure.Conclusion: There is a delicate line between balancing the beneficial effects of sunlight exposure while avoiding its damaging effects. Physiological and geographical factors may reduce vitamin D synthesis, and supplementation may be necessary to achieve adequate vitamin D status for individuals at risk of deficiency.

Kellie L Stalgis-Bilinski BSc, MNutrDiet, APD · John Boyages MB BS(Hons), FRACR, PhD · Elizabeth L Salisbury MB BS(Hons), FRCPA, FFOP · Colin R Dunstan PhD(Med), MSc, BSc(Hons) · Stuart I Henderson BSc, PhD(Applied Physics) · Peter L Talbot BSc, PostgradDipNutrDiet, MSc

Objectives: To describe the development and uptake of a new self-directed learning program for interns, and to evaluate interns’ attitudes towards the program.Design, setting and participants: Using design-based research methodologies, a facility education program was developed to provide flexible learning options, complement the situated learning that occurs at the bedside and foster the development of self-directed and self-regulated learning behaviour. From 2008 to 2010, interns at a large regional Australian hospital (Townsville Hospital) were required to accrue a minimum 100 continuing medical education (CME) points.Main outcome measures: Mean number of CME points accrued per intern and attitudes of interns towards the CME points system.Results: A total of 30, 39 and 59 interns participated in the program during 2008, 2009 and 2010, respectively. The mean number of points accrued by interns increased from 114 points (range, 60–168; median, 113) in 2008 to 132 points (range, 85–298; median, 127) in 2010. There was a corresponding decrease in failure to accrue 100 points, from 20% of interns (6/30) in 2008 to 8% of interns (5/59) in 2010. Evaluations showed that the majority of interns (surveyed at the end of 2009 [n = 22] and 2010 [n = 46]) liked the flexible learning options of the CME points system, and also felt that the professional development helped them gain better knowledge and skills and develop as a clinician. However, about half of them felt pressured to accrue points.Conclusions: A CME points system is acceptable to and used by interns. This system has the flexibility to be expanded to other junior doctor years and implemented in all Australian facilities to ensure that self-directed and self-regulated learning occurs across the entire prevocational continuum.

Allyson J Agnew MContempSc, GradDipEd, GradCertMedEd · Carl J O’Kane MB BS, FACEM, GradCertClinEd

Enhancing patient care. A practical guide to improving quality and safety in hospitals. Alan Wolff, Sally Taylor. Sydney: MJA Books, 2009 (234 pp, $49.95). ISBN 9780977578665. Wimmera Hospital, in Horsham, western Victoria, has a well deserved reputation for promoting quality and safety. Here, Alan Wolff, Wimmera’s medical director, and Sally Taylor, its clinical risk manager, outline the steps they followed in developing a rigorous quality management process at the hospital. This is indeed, as claimed, a practical guide and is recommended for all those interested in clinical governance. The Wimmera model appropriately distinguishes between safety and quality, and outlines steps to promote quality and assure safety. In terms of how the book might have been strengthened, I think a chapter outlining what a board safety and quality committee might do would have been useful. Further, the book has its provenance in a regional hospital and there is a question in my mind about whether all the elements of the Wimmera model are scalable. The book also de-emphasises the role of routine data for tracking safety in hospitals. Although hospitals can track their own trends over time using routine data, this sort of monitoring is much more powerful when it involves comparison with other like facilities. The model’s approach to management of adverse events focuses too much on the visible, the “event”, and tends to de-emphasise the myriad small things (eg, the incidence of pneumonia) which might together contribute to a poorer experience of hospitalisation. The book could also have been strengthened by incorporating guidance on how to structure investigations, when they are called for. The Queensland approach (“pyramid model”) of looking at data, casemix, resources, processes of care and professional issues is a valuable one.1 The book rightly identifies the health professional involved in an adverse event as the “second victim”. The medical director might also be seen as the “third victim”. The role of the medical director is a hard one, especially in a small hospital. It means holding to account local colleagues, often people with whom one has worked for many years. It is an isolated role and one deserving of more support. The authors are to be commended for making this hard journey an easier one.

Stephen J Duckett

Clostridium difficile is the most common cause of health care-associated and antibiotic-associated diarrhoea. These guidelines are intended to provide advice to clinicians on the clinical assessment, diagnosis and management of C. difficile infection (CDI). Hypervirulent strains of C. difficile, including PCR ribotype 027 strains recently identified in Australia, have been associated elsewhere with epidemic spread and high rates of severe disease and death. Diagnostic tests include stool culture, polymerase chain reaction-based assays, cell-culture cytotoxicity assays and enzyme immunoassays detecting C. difficile glutamate dehydrogenase, and/or toxin A and/or B. To treat an initial episode and a first recurrence, metronidazole is the preferred antibiotic, with oral vancomycin reserved for severe disease and subsequent recurrences. Surgery should be considered for fulminant disease.

Allen C Cheng FRACP, MPH, PhD · John K Ferguson FRACP, FRCPA, DTMH · Michael J Richards MB BS, FRACP, MD · Jennifer M Robson FRACP, FRCPA, FACTM · Gwendolyn L Gilbert MD, FRACP, FRCPA · Alistair McGregor MB BS, FRACP · Sally Roberts MB ChB, FRACP, FRCPA · Tony M Korman MB BS, FRACP, FRCPA · Thomas V Riley MAppEpid, PhD, FRCPath

Australia is developing a national performance framework aimed at measuring health outcomes across the health system. Clinical registries provide a clinically credible means of monitoring health care processes and outcomes, yet only five Australian registries currently have national coverage. At a national level, clinical registry development should be prioritised to target conditions or procedures that are suspected of being associated with large variations in processes or outcomes of care and that impact significantly on health care costs and patient morbidity. Registries should also aim to capture information across care interfaces and to monitor the medium and long-term safety and effectiveness of specific devices, procedures and drugs.

Sue M Evans PhD · Ian A Scott MEd, MHA, FRACP · Niall P Johnson PhD · Peter A Cameron MB BS, MD, FACEM · John J McNeil MSc, PhD, FRACP

Interprofessional learning and practice can be positively self-reinforcing and can promote improved care. Australia is showing leadership in the field of interprofessional collaboration. Changing attitudes to interprofessional collaboration is a key to improving health care. Implementing interprofessional collaboration requires a multifaceted approach, and research to underpin it.

David R Greenfield PhD · Peter Nugus PhD · Joanne F Travaglia PhD · Jeffrey Braithwaite PhD

Kenneth Hugh Atkinson’s death late last year ended the career of one of Sydney’s most accomplished gynaecologists. Ken was born on 1 August 1939 in Moss Vale, New South Wales. He grew up in Armidale, where he attended The Armidale School and finished as dux of his year. He studied medicine at the University of Sydney, living at St Paul’s College and graduating with honours in 1963. He then worked at Royal Prince Alfred Hospital (RPAH) and, 2 years later, became a registrar at the associated King George V Memorial Hospital for Mothers and Babies (KGV). In his second year there, he sat the membership examination for the Royal College of Obstetricians and Gynaecologists (RCOG) and received the top mark in Australia. In 1968, he was appointed clinical superintendent at KGV. He single-handedly altered the whole ethos of the hospital — introducing formal resident training and running regular seminars incorporating interaction with other clinical specialities. In 1970, Ken was awarded a Joseph Foreman Fellowship. This took him to Massachusetts General Hospital in Boston, where he was surgical resident to Howard Ulfelder, one of the greatest gynaecological surgeons of the time. In 1971, he returned to Sydney and was appointed visiting medical officer in obstetrics and gynaecology at KGV and then, from 1974, at Ryde Hospital, Poplars Private Hospital and Sydney Adventist Hospital. After he gave up obstetrics in the mid 1990s, Ken concentrated on gynaecological cancer surgery. He handled most of the gynaecological cancer surgery on Sydney’s upper north shore, and was on call at RPAH for surgical emergencies. He never complained about being called in at any time of the day or night; he did it all with good humour and no one equalled him “when the chips were down”. In 1974, Ken became a member of the NSW state committee of the RCOG. In 1984, he served on the executive committee of the Australian Society for Colposcopy and Cervical Pathology and became chairman of the committee in 1994. In the same year, he was elected to the council of the NSW Medical Defence Union and, in 1995, he served on its executive committee. In 1996, he became a director of United Medical Protection and later deputy chairman. Ken’s interests included art, oriental snuff bottles and rugs, sport, good food and fine wine. He died on 25 November 2010 from complications after a myocardial infarction. He is survived by his wife Susan, and children Tracey, Josephine and Bill.

Andrew R Korda

Frank Fenner was one of Australia’s greatest scientists, internationally recognised for his research into viral diseases and for his achievements in the eradication of smallpox and the control of Australia’s rabbit plague. He was born in Ballarat on 21 December 1914, the second son of Emma and Charles Fenner. After schooling in Adelaide, he studied medicine at the University of Adelaide, graduating in 1938. As a university student, he gained his Blue in hockey, presaging a lifetime of participation in sport and a love of tennis. In 1940, he joined the Australian Army Medical Corps, serving in the Middle East, New Guinea and Borneo. His Army service was predominantly as a malariologist, reflecting his studies in tropical medicine. At Hughenden Hospital in Queensland, he treated servicemen and women returning from Papua New Guinea with malaria, and it was there that he met and married Bobbie Roberts in 1943. Fenner’s extensive achievements in controlling malaria were recognised in 1944 when he was made a Member of the Order of the British Empire. Fenner joined the Walter and Eliza Hall Institute in Melbourne in 1946, working with Sir Frank Macfarlane Burnet. A landmark achievement was their publication of The production of antibodies (2nd edition. Melbourne: MacMillan, 1949), in which they proposed that the exposure of a young, immature animal to foreign cells or tissues would confuse the animal’s immune system into regarding other foreign transplants from the same source as “self”. Fenner’s laboratory research at the Institute focused on mousepox. This work would lead to his commitment to ridding the world of smallpox a quarter of a century later. In 1949, he was appointed Foundation Professor of Microbiology at the John Curtin School of Medical Research (JCSMR) at the Australian National University (ANU) in Canberra. His first major research there was on using myxomatosis to biologically control the rabbit plague that was wreaking havoc on Australian farming land. The introduction of the myxoma virus into the rabbit population coincided with an outbreak of encephalitis in the Murray–Darling basin. Perceptions that the two events were associated gained currency and, in one of the legendary episodes in the history of Australian epidemics, Fenner and two colleagues inoculated themselves with the myxoma virus to successfully refute that association. The relevance of Fenner’s work on myxomatosis has increased over time, with the emergence of diseases such as AIDS, variant Creutzfeldt–Jakob disease and severe acute respiratory syndrome, which are caused by agents that have crossed from other species rather than coevolving with human hosts. Fenner’s research progressed to another pox virus, vaccinia or cowpox, which was used clinically in vaccination against smallpox. His growing reputation in the 1950s was reflected in his election as a Fellow of both the Australian Academy of Science and the Royal Society. Further recognition of his scientific standing came in the 1960s with a Leeuwenhoek lectureship of the Royal Society and a Britannica Australia award. In 1967, he left bench for books to become the first Director of the JCSMR. His most notable publications were The biology of animal viruses (New York: Academic Press, 1968) and Medical virology (New York: Academic Press, 1974). His experience with pox viruses led to an invitation to join an international scientific project to eliminate smallpox and, in 1977, to his appointment as Chairman of the Global Commission for Certification of Smallpox Eradication. He later nominated 8 May 1980, when he announced the eradication to the World Health Assembly, as the proudest day of his life. Fenner’s environmental interests underpinned his appointment as founding Director of the Centre for Resource and Environmental Studies at the ANU in 1973. They also found expression in his roles as Vice President of the Australian Conservation Foundation (1971–1973) and as a member of the Senior Scientific Advisory Board of the United Nations Environment Programme. During this period, recognition of his achievements included being made a Companion of the Order of St Michael and St George in 1976, followed in 1977 by election as a foreign associate of the United States National Academy of Sciences. On retirement in 1979, he returned to the JCSMR to work with undiminished intensity. Perhaps the most visible aspect of his retirement was the succession of awards he received. Among these were the 1980 Anzac Peace Prize, the 1988 Japan Prize, being made a Companion of the Order of Australia in 1989, the Copley Medal of the Royal Society in 1995 and the Prime Minister’s Prize for Science in 2002. He wrote a number of books dealing with historical aspects of science and was coauthor of the encyclopaedic Smallpox and its eradication (Geneva: World Health Organization, 1988). In an instructive illustration of the durability of scientific knowledge, more than 20 years after his nominal retirement he was advising national expert groups on the potential for pox viruses in bioterrorism. As well as his more widely publicised achievements in retirement, his philanthropy and his unstinting accessibility to academics and students were notable. As a Visiting Fellow at the JCSMR, he represented a repository of information on virology. If he did not have the required information at his fingertips, he could invariably tell one exactly where it could be found. Frank Fenner died on 22 November 2010 after being admitted to hospital with septicaemia. He is survived by his daughter Marilyn.

Peter McCullagh

Clinical record A 75-year-old man presented with a 2-month history of lethargy, nausea and poor appetite. His medical history included widespread plaque psoriasis. He had used Chinese herbal products for 3 years to treat the psoriasis, with significant improvement. The products included long dan xie gan wan, lei gong teng and ke yin wan, which he had obtained from outside Australia by mail order. He was not taking any other medications. On physical examination, he was hypertensive (blood pressure, 200/100 mmHg) and exhibited “metabolic flap”. The rest of the physical examination showed no abnormalities. Laboratory investigations revealed renal failure with a serum creatinine level of 965 μmol/L (reference range [RR], 60–120 μmol/L), serum urea level of 43.1 mmol/L (RR, 3.0–8.0 mmol/L) and a normocytic, normochromic anaemia with a haemoglobin level of 70 g/L (RR, 130–170 g/L). Results of a serum electrophoresis and tests for antinuclear antibody, antineutrophil cytoplasmic antibody, antiglomerular basement membrane antibody, complement C3 and C4 and serum immunoglobulins were all unremarkable. Urinary microscopy revealed an inactive urine sediment with minimal proteinuria (0.13 g/L [RR, 0.16g/L]). A renal ultrasound revealed unobstructed, small kidneys with cortical thinning bilaterally. A renal biopsy showed severe tubulointerstitial fibrosis and atrophy. There was no evidence of glomerulonephritis, nor of acute tubular necrosis (Box). These findings were consistent with chronic exposure to a nephrotoxin. As the patient’s Chinese herbal products were suspected as the source of the nephrotoxin responsible for his nephropathy, they were sent to the Australian Therapeutic Goods Administration (TGA) to be analysed. High-performance liquid chromatography and mass spectrometry identified aristolochic acid in the Herbal International brand of long dan xie gan wan,1 and the product was subsequently recalled from the Australian market by the TGA. Haemodialysis was initiated and later converted to continuous ambulatory peritoneal dialysis. The patient died 4 years after initial presentation, following withdrawal from dialysis. In Australia, the use of complementary and alternative medicine (CAM), including Chinese herbal products, is increasing. However, scientific evidence on the safety, efficacy and quality of CAM, as well as regulatory controls, does not appear to support such popularity.2 Some herbal products contain aristolochic acid (AA), which is known to be nephrotoxic and carcinogenic.3 Aristolochic acid nephropathy (AAN), first reported in Belgium as “Chinese herbal nephropathy”,4 is characterised by progressive fibrosing interstitial nephritis leading to renal failure and severe anaemia. AAN is a worldwide problem, but its true incidence is unknown and probably underestimated,5 and though many cases of AAN have been reported, to our knowledge this is the first reported case in Australia. Many countries have prohibited the production and sale of herbal products containing AA,6 but despite bans, these products continue to be available through the internet or supplied through mail order. In most of the reported cases, when the patient discontinued use of the drugs their renal disease still progressed rapidly to end stage.3 After exposure to AA, there is also a very high incidence of uroepithelial atypia and transitional cell carcinoma, and AA is now recognised as a potent urological carcinogen.7 Tissue samples from some patients with AAN and urothelial malignancy have revealed AA-related DNA adducts, which may be carcinogenic through a defect of DNA repair.8,9 The pathophysiological mechanisms of AAN are still unknown. In a rat AAN model, AA renal tubule toxicity has been associated with defective activation of antioxidative enzymes and mitochondrial damage. Activation of renal fibroblasts has also been proposed as the main source of collagen deposition leading to renal interstitial fibrosis.10 Therapeutic strategies have consisted mainly of supportive care in patients with AAN and renal failure. One study suggested that corticosteroids may slow the rate of renal deterioration.11 Renal transplantation may be an effective treatment strategy for those who progress to end-stage renal failure, with one report indicating no recurrence of AAN in five such patients after a follow-up period of 1 year.12 The clinical course of AAN has been related to the intensity and duration of AA exposure.13 A mean cumulative dose of 192 g of Aristolochia fangchi was ingested by one group of patients who developed end-stage renal failure related to AA.13 However, in most cases, the accumulated AA dose is difficult to ascertain because the dose is recalled retrospectively by patients; the patient may ingest herbal medicines irregularly and there is no strict recommendation of dosing on labels; the AA levels in the herbal mixtures vary due to different manufacturing processes; and the quantity of AA also varies in different herbs and even in the same herb grown in different areas.14 Also, patient factors such as genetic polymorphism, environmental chemicals and drugs may result in individual differences in susceptibility to AA toxicity.5 Many different brands of long dan xie gan wan are available and are commonly sold as a “liver tonic” containing the herb Caulis aristolochiae manshuriensis. This herb is known to contain AA, and there have been cases of nephropathy with similar clinical presentations reported after its ingestion.15 C. manshuriensis was not labelled as an ingredient in our patient’s brand of long dan xie gan wan. Although AA in long dan xie gan wan is the most likely aetiology for his nephropathy, other potential contributing nephrotoxins such as heavy metals and ochratoxin A, found in other products he was taking concomitantly, cannot be excluded.16,5 In Australia, the sale of CAM is regulated by the TGA.17 In July 2001, alerts to health practitioners were distributed by the TGA,18 and in January 2002, bans on herbal products suspected to contain AA were instituted,19 but this patient was still able to purchase the product by mail order. Chinese herbal medicines containing AA remain available for purchase over the internet and through Chinese herbal retailers.6,20 Internet commerce has revolutionised accessibility to herbal medicines and has made regulation more difficult. A South Australian public survey in 2004 found that about half of CAM users believed that CAM products were independently tested by the TGA, and did not report their use to their general practitioner.2 It is therefore apparent that tighter regulations on CAM are needed. The occurrence of this case in Australia highlights the need to review CAM regulations and for clinicians to be vigilant in their assessment regarding the use of CAM, especially when the aetiology of renal dysfunction cannot be identified. Until more stringent regulations are put in place to ensure quality, safety and efficacy of CAM, public awareness of their dangers should be raised. Renal tissue showing severe, diffuse interstitial fibrosis and tubular atrophy, with no evidence of significant interstitial inflammation Lessons from practice Herbal remedies can be sources of nephrotoxins. Aristolochic acid found in herbal remedies can cause rapidly progressive interstitial nephritis, leading to end-stage kidney disease and urothelial malignancy, therefore requiring regular surveillance for abnormal urine cytology and cystoscopy. In clinical assessments, clinicians need to enquire specifically about use of herbal products. Drug regulatory authorities should maintain more stringent surveillance on herbal products.

Winnie Chau BPharm(Hons) · Richard Ross MB BS, BSc(Hons) · Jordan Y Z Li MB BS, FRACP · Tuck Y Yong MB BS, FRACP · Sonja Klebe MD, PhD, FRCPA · Jeffrey A Barbara MB BS, PhD, FRACP

We report the first recognised case of infection with Clostridium difficile PCR ribotype 027 acquired in Australia. This pathogen has caused significant morbidity and mortality in widespread hospital-based outbreaks in the northern hemisphere. Clinicians need to be aware of the clinical picture, limitations of diagnostic tests, availability of further testing for epidemic strains, new therapeutic approaches, and in-hospital control strategies for this infection. (MJA 2011; 194: 369-371) Clinical recordAn 83-year-old Latvian man underwent an aortic valve replacement for aortic stenosis in late January 2010 at a hospital in Melbourne, Australia. He had a history of hypertension and chronic renal failure. He lived alone in his own home, and had not travelled outside Australia since September 2009 when he returned from a 3-month trip to Latvia. Between his return to Australia and the surgery, he had not received any antibiotics except for a single preoperative dose of cephalothin. His regular medications included various supplements, but no proton-pump inhibitor. He was admitted to the hospital the day before surgery. Two days after the surgery, he developed severe sepsis from a urinary tract infection, for which he received ticarcillin–clavulanate and a noradrenaline infusion. A coagulase-negative Staphylococcus was isolated from blood cultures, and he was given vancomycin. He later developed an infiltrate at the left lung base, but no change was made to his therapy. Five days after the surgery, he developed watery diarrhoea. Clostridium difficile was isolated from stool samples, although the results of enzyme-linked fluorescent assays (VIDAS, bioMérieux, Sydney, NSW) for C. difficile toxins were negative at this time. His leukocyte count was 9.5 × 109/L (reference range, 4.0–11.0 × 109/L) and his serum albumin concentration was 42 g/L (reference range, 35–50 g/L). Therapy with metronidazole (400 mg orally, 8-hourly) was commenced for presumed C. difficile infection (CDI), and the patient was placed under contact precautions. Alcohol-based hand rub was replaced with traditional soap and water hand washing (see below). Therapy with ticarcillin–clavulanate was subsequently ceased. After 9 days of metronidazole therapy, the diarrhoea became more frequent and vancomycin (250 mg orally, 6-hourly) was substituted. Repeat stool specimens were tested. This time, C. difficile toxins were identified by enzyme-linked fluorescent assay, and C. difficile was isolated again. Because of the patient’s deteriorating condition, the laboratory was alerted to the possibility of a hypervirulent strain. The isolate was tested for susceptibility to moxifloxacin (Etest, bioMérieux, Sydney, NSW) and found to be resistant, with a minimum inhibitory concentration of > 32 μg/L. The stool sample was positive by real-time polymerase chain reaction (PCR; GeneXpert, Cepheid, Sunnyvale, Calif, USA) when tested for the presence of C. difficile organisms carrying genes for toxin B (tcdB), binary toxin (cdtB) and an 18-base-pair deletion within the tcdC gene that is characteristic of the PCR ribotype 027 strain. These findings were confirmed by sequencing the tcdC gene, and this also identified a point mutation at nucleotide position 117, which is also characteristic of this strain. PCR ribotyping was undertaken using a previously published method1 that confirmed the isolate as PCR ribotype 027 (Box). Nineteen days after surgery, the patient’s condition deteriorated further. His temperature was 39.2°C, his leukocyte count was 31.2 × 109/L and his serum albumin concentration was 25 g/L. The diarrhoeal frequency fell to a single bowel action per day, and an abdominal x-ray showed a distended right colon. The oral vancomycin dose was increased to 500 mg, 6-hourly, and therapy with intravenous metronidazole was commenced along with vancomycin enemas (500 mg in 500 mL normal saline, 6-hourly). Ticarcillin–clavulanate therapy was recommenced. A surgical opinion was sought and subtotal colectomy discussed. As there was felt to be a high risk of mortality with surgery, medical management was preferred. After 5 days, the fever and diarrhoea improved. The enemas were ceased after 8 days and metronidazole therapy after 14 days. The patient subsequently recovered, and the diarrhoea had not recurred at 3-month follow-up. DiscussionAn epidemic strain of C. difficile (PCR ribotype 027) was first identified in Quebec Province in Canada in 2005, as a cause of hospital outbreaks of severe infection with high mortality rates.2 Retrospective analyses suggested that this strain had caused outbreaks across North America since 2000.3 The organism later spread to Europe, and cases have now been described in Asia and Central America.4 Increased toxin production by C. difficile PCR ribotype 027 may be responsible for its increased virulence,5 and fluoroquinolone resistance is likely to be contributing to its spread.6 Infection with this strain more often leads to severe disease, and is associated with more recurrences and a greater risk of death.2 Until now, only one case has been described in Australia in a patient who was thought to have acquired the infection in North America.7 This is the first case of hypervirulent CDI diagnosed in Australia with apparent local acquisition. Several factors support the conclusion that the infection was not acquired overseas. First, although the patient had travelled to Latvia 4 months before being admitted, the possibility that he acquired C. difficile PCR ribotype 027 then and remained colonised is remote. C. difficile does not colonise the normal adult gastrointestinal tract, and the patient received no antibiotics that may have disrupted his gut flora in the time between returning from Latvia and admission to hospital. Second, a recent publication from Latvia indicates that C. difficile ribotype 027 was not present in the country when our patient was there.8 Finally, there were at least two other subsequently confirmed cases of infection with C. difficile PCR ribotype 027 in the hospital at the time the patient developed symptoms of infection (it is not known where these cases were acquired). The case illustrates important features of hypervirulent CDI. The identification of severe disease is critical in guiding management. For surveillance purposes, severe disease may be simply identified as infections requiring ICU admission or surgery, or infections resulting in death, or a diagnosis of toxic megacolon.9 More sensitive diagnostic criteria for severe disease in addition to those above are required to guide patient care. While no such criteria have yet been prospectively validated, proposed markers of severe disease include age greater than 65 years, leukocytosis greater than 20 × 109 cells/L, deterioration of renal function, temperature greater than 38.3°C, serum albumin concentration less than 25 g/L and an elevated serum lactate concentration.10 Our patient met all these criteria except for the serum lactate concentration, which was not recorded. Although metronidazole remains the recommended first-line agent for mild to moderate CDI, oral vancomycin is now recommended for severe disease.9,10 Although there is no evidence that high-dose oral vancomycin (500 mg, 6-hourly) is any better than standard doses of 125 mg 6-hourly, higher doses are favoured by many clinicians. Evidence of benefit for vancomycin enemas is limited to case series; eight of nine patients with refractory severe disease had complete resolution with this therapy.11 In the setting of ileus with toxic megacolon, oral vancomycin will not reach the colon and intravenous delivery of metronidazole is preferable.12 Surgery should be considered if severe disease is unresponsive to medical therapy after 48 hours, or if there is bowel perforation or multiorgan failure.13 Elevation of plasma lactate to between 2.2 and 4.9 mmol/L has been identified in a retrospective review of a selected group of severely ill patients as a guide to when colectomy is most beneficial.14 Other strategies requiring further investigation for use in severe disease include intravenous immunoglobulin, alternative antibiotics such as tigecycline, and monoclonal antibodies. C. difficile spores are highly resistant to killing by alcohol and most other disinfectants. In outbreaks of CDI, health care workers should be instructed to wash their hands with soap and water in addition to using alcohol-based hand disinfection when caring for infected patients. Patients should be isolated and contact precautions with gowns and gloves are recommended. Environmental cleaning with hypochlorite-based solutions is necessary to eliminate the spores.9 Antibiotic stewardship is also an important element in control strategies, with studies of antibiotic restriction showing benefit.15 In Australia, laboratory diagnosis of CDI is most commonly made through detection of C. difficile toxins A and B using enzyme immunoassay (EIA) kits. EIA kits have reported sensitivities of 75%–95%, but most of the evaluations reporting these sensitivities use faecal cytotoxin detection (a flawed test) as the gold standard.16 In addition, the positive predictive value of these tests declines markedly in situations where the prevalence of disease is low.16 Poor sensitivity of the assay is the likely explanation for the initial negative result of the enzyme-linked fluorescent assay in our case. Despite this limitation, EIA kits remain widely used because of their simplicity and relatively low cost. Commercial real-time PCR testing for toxin genes (usually tcdB), has better sensitivity (93%) and specificity (97%),16 and is now available in several Australian laboratories. Toxigenic culture — isolation of the organism followed by toxin testing of the isolate — is extremely sensitive, but it is labour intensive and takes at least 3 days.16 There is currently great debate about the value of an algorithmic approach to diagnosing CDI, whereby a sensitive screening test is used to screen out negatives, thus improving the positive predictive value of a secondary test, particularly when the prevalence of infection is low.17 Distinguishing C. difficile PCR ribotype 027 from other strains of C. difficile does not affect individual patient management, but is important for surveillance purposes. Some commercially available PCR methods can presumptively identify PCR ribotype 027 based on detection of binary toxin genes and the characteristic 18-base-pair deletion in the tcdC gene. An alternative, less expensive, approach is to screen for moxifloxacin resistance by using a 5 μg moxifloxacin disc on a lawn culture of C. difficile on Mueller-Hinton agar. Worldwide, most PCR ribotype 027 isolates are resistant to moxifloxacin,2 while, in Australia, the prevalence of resistance in all strains of C. difficile is 1%. (T V Riley, B Elliot and colleagues, unpublished data). Zones of inhibition for resistant strains (potentially PCR ribotype 027) are > 16 mm while for susceptible strains, they are ≥ 16 mm (T V Riley and colleagues, unpublished data). Isolates of moxifloxacin-resistant C. difficile identified in this way can then be sent for further typing. Given the arrival of C.difficile PCR ribotype 027 in this country, periodic PCR ribotyping of a representative sample of isolates now needs to be performed at designated reference laboratories Australia-wide, and recurrent funding is required for this task. This will be an important adjunct to local screening measures, and will also detect the emergence of virulent PCR ribotypes other than 027. An Australian Commission on Safety and Quality in Healthcare recommendation for hospital surveillance programs in all states and territories to monitor C. difficile was approved by Australian Health Ministers in November 2008. As yet, the states and territories have not implemented this recommendation, and there has been no collation or analysis of national surveillance data. With the identification of the first case of PCR ribotype 027 C. difficile infection acquired locally, it is important that clinicians in Australia are aware of the clinical picture, limitations of diagnostic tests, availability of further testing for PCR ribotype 027, new therapeutic approaches,18 and in-hospital control strategies for this infection.19 The solution to the bigger problem of the emergence of virulent strains of C. difficile continues to lie in the basics of surveillance, antimicrobial stewardship, infection control and environmental cleanliness. Ribotyping pattern of the Clostridium difficile strain isolated from the patient compared with a reference and an unrelated strain Patient isolate Unrelated strain PCR ribotype 027 reference strain 100-base-pair DNA ladder PCR = polymerase chain reaction.

Michael Richards MB BS, MD, FRACP · James Knox BSc(Med), MB BS, DTM · Briony Elliott BSc(Hons) · Kate Mackin BA/BSc(Hons) · Dena Lyras BSc(Hons), PhD · Lynette J Waring MB BS, FRCPA · Thomas V Riley PhD, FASM, FRCPath

A 20-year-old man presented with a well defined, brown, mildly erythematous, reticulated patch lesion on his left thigh (Figure). Although livedo reticularis could be suggested, the clinical presentation was in keeping with erythema ab igne. On questioning, the patient described the frequent use of a laptop on his thighs, with the heat source on the left side. Erythema ab igne can be precipitated by any heat source (eg, hot water bottles, heating pads). We recommended that he cease using the laptop directly on his lap or place the laptop on a hard surface. Clinicians should be aware of this condition to avoid unnecessary medical examinations, and users of laptops should be advised about the effect of heat on their skin. [[{"type":"media","view_mode":"media_large","fid":"39839","attributes":{"alt":"","class":"media-image","typeof":"foaf:Image"}}]]

Niranthari Chinniah · Pablo Fernández-Peñas

To the Editor: A 61-year-old man presented to the emergency department (ED) of a tertiary hospital seeking treatment for alcohol withdrawal after 36 hours of abstinence. He reported central chest pain radiating to the jaw and left arm that had been present for 2 hours before his arrival at the hospital. He had no history of cardiac disease and no known risk factors for coronary artery disease. An electrocardiogram (ECG) showed sinus tachycardia with T-wave inversion in leads V1, V2 and V3. Two hours after the patient’s arrival at the ED, he tested positive for troponin-T. Over the next hour, his ECG showed development of ST elevation of 1–2 mm in leads V3, V4 and V5. Because of severe alcohol withdrawal, his clinical status precluded urgent coronary angiography; and after treatment with diazepam was commenced, the ST elevation that was evident no longer met criteria for urgent angiography. The patient was given standard medical therapy for acute coronary syndrome, including aspirin, clopidogrel and intravenous heparin, while in the ED, along with ongoing diazepam for alcohol withdrawal. He was later admitted to the coronary care unit with a diagnosis of acute coronary syndrome. The next day, an ECG showed development of widespread T-wave inversion in leads V1 to V5. The dynamic ECG changes were not associated with ongoing chest pain. On Day 3 of the patient’s admission, coronary angiography showed normal coronary arteries, and ventriculography showed apical ballooning of the left ventricle, consistent with a diagnosis of takotsubo cardiomyopathy (Box). Treatment with an angiotensin-converting enzyme inhibitor and a β-blocker was commenced. Three months later, follow-up echocardiography showed a return to normal regional and global left ventricular function. Takotsubo cardiomyopathy takes its name from a traditional Japanese octopus trap that has a similar shape to the abnormally contracting left ventricle seen with this condition.1 Typical findings in a patient with takotsubo cardiomyopathy are chest pain associated with emotional or physical stress, with ST segment changes on electrocardiography and apical ballooning on ventriculography, which is generally expected to resolve within weeks to months; troponin level may or may not be positive. The mechanism of this condition has not yet been determined, but it appears likely that it is due to hyperadrenergic-hypercatecholaminergic states (such as alcohol withdrawal) resulting in localised or diffuse coronary vasospasm.2 Takotsubo cardiomyopathy has only rarely been associated with alcohol withdrawal, and has once been reported in a patient with alcohol withdrawal associated with seizures.3,4 Coronary ventriculography image showing apical ballooning of the left ventricle

Angus G Thompson · Joseph Hung

To the Editor: We would like to congratulate Gandy and colleagues on their recent article in which they assess outcomes and patient flow in an acute care surgery (ACS) model.1 We have also performed a retrospective historical control study that examined the effect of an ACS model on assessment time and time to operation for acute appendicitis. Our findings were presented in poster format at the Royal Australasian College of Surgeons Annual Scientific Congress in Perth in May 2010.2 We introduced an ACS model in 2007 at Nambour General Hospital, a 350-bed regional hospital on Queensland’s Sunshine Coast. Our model differs in certain details from the model used by Gandy and colleagues at Prince of Wales Hospital, but is similar in principle. The aim of the ACS model was to provide an in-house consultant surgeon to be more available and more directly involved in the care of emergency surgical patients. In our study, the outcome measures included time to assessment of the patient in the emergency department by the surgical registrar, and time to operation after this assessment. We performed a retrospective chart audit of 569 patients who underwent emergency appendicectomy in the calendar years 2006 and 2008. The ACS model resulted in an increase in both time to assessment (198 minutes in 2006 compared with 263 minutes in 2008; P < 0.0001 [t test]) and time to operation (597 minutes in 2006 compared with 793 minutes in 2008; P < 0.0001 [t test]). These results surprised us. Various explanations were postulated, including the trend of an expanding local and regional population on the Sunshine Coast placing a greater demand on the emergency theatre through the study period. Like us, Gandy and colleagues did not see a reduction in time to theatre and in fact “observed no significant change in time from presentation to arrival in theatre”. This was explained on the basis of “an increase in the number of patients treated conservatively overnight”. We have reviewed our data and found a similar trend, with 35% of patients in 2006 and 54% in 2008 managed conservatively overnight. This may, to some extent, explain our surprising results. Our appendicectomies in both historical control patients and those treated in the ACS model were all performed laparoscopically, thus removing one of the confounders experienced in the Prince of Wales Hospital data. A comparison of these two sets of data emphasises the fact that to measure time to assessment and time to operation in isolation misses the important concept of reduction in complication rates, as successfully demonstrated by Gandy and colleagues1 (we did not record complication rates in our study). This process of assessment could be taken a step further with a cost–benefit analysis looking at the presumed reduction in costs associated with the anticipated lower rate of complications resulting from the involvement of the consultant surgeon.

Simone L Geere · Ratna Aseervatham · David Grieve

To the Editor: Further to the recent article by Anstey and colleagues on community-acquired Klebsiella pneumoniae liver abscesses,1 we report two similar cases at our hospital in late 2010. Case 1: A 55-year-old Indonesian-born man was referred from general practice in October 2010 with a 5-day history of fever and progressive epigastric pain. He did not have diabetes, but did have dyslipidaemia. He had migrated from Indonesia in the 1980s; his most recent visit to Indonesia was in January 2010, for 3 weeks. As he had mildly deranged liver function test results, he was investigated with abdominal ultrasound and computed tomography (CT). Both showed a large multiseptate collection in the left lobe of the liver (Box, A). The liver collection was drained under radiological guidance, yielding a pure growth of K. pneumoniae. Urine culture was also positive for an identical isolate of K. pneumoniae. This man had a rapid clinical response to percutaneous drainage and was discharged on oral ciprofloxacin therapy. Case 2: A 25-year-old Indonesian-born man presented to our emergency department in early November 2010 after 2 days of headache, high fever and abdominal cramps, culminating in an acute confusional state. He had no significant medical or surgical history and had last visited Indonesia in March 2010, for 2 weeks. Initial therapy and investigations were aimed at excluding a diagnosis of meningitis. Results of a CT scan of the brain and of cerebrospinal fluid analysis were unremarkable. The patient remained acutely unwell and developed diarrhoea and right upper quadrant abdominal pain. Blood cultures were positive for K. pneumoniae within 48 hours of admission. Abdominal CT showed a large multiloculated abscess in the right lobe of the liver (Box, B). The liver abscess aspirate grew a pure culture of K. pneumoniae. The patient responded to treatment with ceftriaxone and large-volume percutaneous drainage. In both these cases, an antibiotic sensitive mucoid strain of K. pneumoniae was cultured. These cases add weight to the possibility raised by Anstey and colleagues that community-acquired K. pneumoniae liver abscess is indeed an emerging phenomenon in Australia. Further, the extended length of time between our patients’ travel to Indonesia and the clinical presentation (9 and 8 months, respectively) is suggestive of local (Australian) acquisition of the disease. Clinicians should consider abdominal imaging in cases of bacteraemia due to K. pneumoniae. Abdominal computed tomography scans showing Klebsiella pneumoniae liver abscesses

Kudzai N Kanhutu · Jeffrey J Post · Kate R Clezy · Hong Y L Foo

To the Editor: Interest in alternative therapies for Clostridium difficile infections (CDIs) is increasing as these infections become important causes of patient morbidity and mortality. Recurrent CDIs can be severe and difficult to treat. In-vitro data,1 followed by reports of the efficacy of tigecycline in the treatment of severe refractory cases of CDI,2 suggest that tigecycline should be considered as an alternative or adjunctive antimicrobial agent in these situations. To date, it has been used mostly as a “salvage” strategy in combination with other antibiotics in the face of clinical deterioration.2,3 We report the successful use of tigecycline monotherapy in the treatment of a patient with recurrent C. difficile colitis. An 83-year-old woman was admitted to hospital in July 2009 with acute diverticulitis. She was treated with intravenous cefotaxime (1 g three times daily for 6 days): her presenting fever and abdominal pain resolved but she developed watery diarrhoea. Despite positive stool cultures for toxigenic C. difficile, initial toxin testing by enzyme immunoassay (EIA [TechLab C. Difficile Tox A/B II]) of stool specimens was negative. After a 7-day course of oral metronidazole 200 mg three times daily, the diarrhoea abated. One month after discharge, our patient re-presented with anorexia, severe abdominal pain and diarrhoea. Six days of oral metronidazole, prescribed by her local doctor, had little effect. A computed tomography scan of the abdomen revealed diffuse thickening of the colon from the ileocaecal junction to the rectum, consistent with a pancolitis. Sigmoidoscopy showed grossly abnormal mucosa with pseudomembranes present. A diagnosis of C. difficile pseudomembranous colitis was made. After 10 days of oral vancomycin 250 mg, four times daily, her symptoms had resolved, and repeat sigmoidoscopy showed reversal of the mucosal changes. Six days later, the pseudomembranous colitis recurred. She rapidly responded to the recommencement of oral vancomycin, given as a tapering course over 6 weeks. Twelve days after completing the 6-week course of vancomycin, the patient presented with her third episode of colitis. Most reported strategies for recurrent CDI, such as faecal transplantation, probiotics or novel antimicrobials,4 were not practicable or available for timely use for our patient. Tigecycline, a broad-spectrum glycylcycline antibiotic, is available as part of the hospital formulary for the treatment of complicated skin and soft-tissue infections and complicated intra-abdominal infections. Encouraged by recent reports of success using tigecycline as adjunctive therapy for severe cases of CDI,2 we prescribed, as monotherapy, intravenous tigecycline 50 mg twice daily for 2 weeks. Our patient’s condition improved over 1 week. At 3-month follow-up, she remained asymptomatic, with repeat stool cultures and polymerase chain reaction (PCR) testing for C. difficile toxin negative at Days 75 and 107 following the last episode of colitis. Our case also highlights a diagnostic matter. In general, use of EIA to detect C. difficile toxin A or B is highly specific. However, in clinical settings where the prevalence of CDI is low, the positive predictive values for these assays are inadequate to rule in the diagnosis of CDI. Confirmatory laboratory testing using an alternative method (in this case, PCR) proved more reliable in the diagnosis of our patient’s recurrent CDI. Typing showed that our patient’s isolate was not PCR ribotype 027, a hypervirulent strain in Europe and North America associated with high mortality.5 We recommend consideration of tigecycline as a useful antimicrobial agent in the management of both recurrent and severe CDI.

Elaine Y L Cheong · Thomas Gottlieb

To the Editor: In their editorial, Terpening, Hodges and Cordato argue for routine screening for dementia in Australia.1 Most of the editorial is devoted to discussing which test should be used, and the authors contend that the most-used test — the mini-mental state examination — has such poor test characteristics that it would be a very poor basis for routine screening. However, the discussion about which test to use ignores the elephant in the room — should we screen for dementia in the first place? In their 1968 World Health Organization public health paper on screening for disease, Wilson and Jungner stipulate that “There should be an accepted treatment for patients with recognized disease”.2 There is no evidence whatsoever that this is the case with dementia. Terpening and colleagues cite an article in their editorial in support of their assertion that “development of effective dementia treatments depends on earlier and more accurate identification of disease”.3 However, that article only states that early intervention might help to slow some forms of cognitive decline or progression to dementia. This is a very slim evidence base for routine mass screening. The development of effective treatments can never be a justification for routine population-wide screening. Even in a study environment, screening the study population with a view to developing treatments rather than testing them, would struggle to find ethics approval. The evidence is clear — there is no basis for screening for dementia. It would produce many false positives and false negatives, and would cause much anxiety without any benefit from early treatment. As long as no effective treatments are available, the case for screening for dementia is void.

Jan J Barendregt

To the Editor: Roberts-Thomson and colleagues1 raise important questions about the implications of introducing masters-level medical degrees with doctorate-level nomenclature (ie, Doctor of Medicine [MD]) to Australia. In particular, the potential consequences for postgraduate training deserve further attention. As graduate numbers rapidly increase,2 competition for training positions will further intensify. At the prevocational level, perceptions of enhanced work-readiness could favour applicants with masters-level MD qualifications, such that other graduates might be displaced from popular, metropolitan teaching hospitals. At the vocational level, rigorous college selection processes (which typically include assessing a candidate’s interview performance, curriculum vitae and academic achievements) could favour graduates of new-age MD programs if they specifically reward the attainment of postgraduate qualifications (as is currently the case for some specialties3). Graduates might also lay claim to advanced standing and additional recognition of prior learning on the basis of their academic status. The extent to which these situations materialise will depend on whether masters-level medical programs claim, and deliver, a superior quality in education. For example, the University of Melbourne has committed to producing “outstanding graduates with advanced clinical skills”4 through its new model.5 In the short term, there is unlikely to be any objective evidence of difference in outcomes between the pathways, and demonstrating this would be both complex and contentious. At present, Australian Medical Council standards do not differentiate between qualifications, and new programs will continue to be accredited according to the same rigorous process. Alternatively, if masters-level MD programs lay no claim to enhanced quality over their undergraduate cousins, then the rationale for change should be examined. A purely market-driven deviation from recognised nomenclature could have important unintended consequences, and would be out of step with international efforts to standardise nomenclature (such as the Bologna Process in Europe). An important aspect of the University of Melbourne graduate-school model is the reintroduction of full-fee-paying places for professional-entry degrees. This brings with it significant implications for student debt, both for the trainee (in terms of debt accumulation, career choice and wellbeing) and the community (in terms of workforce distribution).6 Some commentators have suggested that the principle of merit-based entry is compromised by the presence of full-fee-paying places.7 It is unknown exactly how masters-level MD courses will differentiate themselves from undergraduate programs, and what their impact will be. The divide between so-called academic and vocational programs will probably be exaggerated,8 with potential implications for postgraduate training and workforce development. Whatever eventuates, the call for national consistency in higher education nomenclature deserves serious consideration, and the drivers behind any such process must be enhanced quality and equity of access at all stages of training.

Rob D Mitchell · Michael A Bonning · Alex L Markwell

CorrectionIncorrect subheadings in box: In “Increased mortality associated with after-hours and weekend admission to the intensive care unit: a retrospective analysis” in the 21 March 2011 issue of the Journal (Med J Aust 2011; 194: 287-292), two subheadings in Box 8 (B and C) were transposed. The correct subheading for Figure B is “Elective surgical patients — day of the week SMR” and the correct subheading for Figure C is “Emergency medical and surgical patients — hourly SMR”. The correct version can be viewed online at http://www.mja.com.au/public/issues/194_06_210311/bho10921_fm.html.

Deepak Bhonagiri · David V Pilcher · Michael J Bailey

CorrectionIncorrect confidence intervals: In “When do I know I am cured? Using conditional estimates to provide better information about cancer survival prospects” in the 17 January 2011 issue of the Journal (Med J Aust 2011; 194: 73-77), there were several minor errors in the 95% confidence intervals given in Box 1: Conditional 5-year relative survival estimates, by type of cancer and number of years after diagnosis, for patients aged 15–89 years at diagnosis, Queensland 1998–2007. These errors applied to survival estimates for stomach cancer, pancreatic cancer, lung cancer, kidney cancer, bladder cancer, non-Hodgkin lymphoma and leukaemia. The 95% CIs have been corrected in the online version of the article, and can be seen at: http://www.mja.com.au/public/issues/194_02_170111/baa10523_fm.html.

Peter D Baade · Danny R Youlden · Suzanne K Chambers

Trauma deaths delayed Even if trauma patients don’t die in hospital, they are still at significant risk of death following discharge. So say Davidson and colleagues from the University of Washington, Seattle. They conducted a retrospective cohort study of 124 421 injured adult patients during a 14-year period up to 2008 who were admitted to hospital trauma units in Washington State. Of these, 7243 died before discharge and 21 045 died after discharge. Although in-hospital mortality rates fell from 8% to 4.9% over the period of the study, long-term cumulative mortality rates increased from 4.7% to 7.4%. Hence, in-hospital mortality rates are not reliable indicators of overall mortality rates from trauma, they concluded. Patients who were older and those who were discharged to a skilled nursing facility had the highest risk of death. Other predictors of mortality were advanced age, serious head injury and loss of functional independence. JAMA 2011; 305: 1001-1007 AF increases stroke dementia risk Stroke survivors who have atrial fibrillation (AF) may be at increased risk of developing dementia, according to Kwok and colleagues from Norfolk and Norwich University Hospital and University of East Anglia, Norfolk, UK. They conducted a systematic review and meta-analysis of 15 studies reporting on the association between AF and dementia, covering 46 637 participants in all, with a mean age of about 71 years. They found that AF was associated with a significant increase in dementia in stroke patients, increasing the likelihood of dementia by 2.4 times, but the association between AF and dementia was of borderline significance in the general population. Fluctuating cardiac output causing thromboembolism or poor cerebral blood flow may explain these findings, say the researchers. Future studies may help determine whether intervention to treat AF will make a difference in the timing of onset of dementia in people who have had a stroke, they say. Neurology 2011; 76: 914-922 Gene therapy for parkinson’s Gene therapy shows promise as a treatment for Parkinson disease, according to LeWitt and colleagues from the Henry Ford West Bloomfield Hospital, Michigan, and other US centres. From 2008 to 2010, they treated 22 patients aged 30-75 years with progressive Parkinson disease with injections of the gene for glutamic acid decarboxylase (GAD) carried within a viral vector into the patient’s subthalamic nuclei. Twenty-three others were given sham surgery as controls. Six months after treatment, the treated group showed a 23% improvement in symptoms, compared to a 12% improvement in the controls. Adverse effects were mild and not related to the gene transfer treatment. The treatment is thought to work by modulating the production of GABA (γ-aminobutyric acid) in the subthalamic nuclei to improve basal ganglia function. The Lancet Neurology, Early Online Publication 17 March 2011 doi:10.1016/S1474-4422(11)70039-4 Spirits and pancreatic cancer Alcohol use has been linked to several cancers, including oesophagus, liver, colon and rectum and breast cancers. Heavy alcohol intake also causes acute and chronic pancreatitis; but has not been linked definitively to pancreatic cancer. So Gapstur and colleagues from the American Cancer Society, Atlanta, did a prospective study of about one million US adults aged 30 and over from 1982 to 2006, using data from the Cancer Prevention Study II. After adjusting for confounding factors such as smoking and family history of pancreatic cancer, they found a significant increased risk of pancreatic cancer death in men who consumed three more drinks per day, and in women who drank four or more drinks a day. The association was observed for liquor consumption (ie spirits) but not for beer or wine. Whether the subjects smoked or not made no difference. The findings strengthen the evidence that heavy drinking of liquor contributes to the risk of pancreatic cancer, the researchers say. Arch Intern Med. 2011; 171: 444-451 Timing of solids linked to obesity Is the timing of the introduction of solids during infancy a risk factor for obesity? It depends on whether infants are breast or formula fed. That’s the conclusion of Huh and colleagues from the Children’s Hospital, Boston, Massachusetts, and affiliated institutions. They compared the timing of introduction of solid foods with the risk of obesity at 3 years of age in a cohort of 847 children, 67% of whom were breastfed for at least 4 months, and 32% who were never breastfed or stopped breastfeeding before the age of 4 months. At 3 years of age, 9% of the children were obese. Among breastfed infants, the timing of solid food introduction was not associated with a higher risk of obesity. However, among formula-fed infants or those weaned before the age of 4 months, introduction of solid foods before 4 months was associated with a sixfold increase in the chance of obesity at the age of 3 years. Pediatrics 2011; 127: e544-e551

Peter Lavelle