Volume 184 Issue 4

The Canberra Heart Study findings are a wake-up call to those unaware of the extent of the condition Chronic heart failure is a major and growing public health issue that affects all Western countries. Accordingly, many countries (eg, Scotland1 and Sweden2) systematically monitor its population prevalence and overall impact on the health care system. However, public awareness of the condition remains low.3 Unfortunately, in Australia, apart from sporadic initiatives such as the NSW Chronic Care Collaborative, heart failure remains the “Cinderella” of health issues — hardly registering on the radar of key health care providers, regulators, relevant government bodies and the general public. For example, less than one in five eligible patients receives specialist heart failure management after hospitalisation for acute heart failure.4 Undoubtedly this is at least partly explained by the fact that we do not know the true magnitude of the problem in Australia. It is time for us to recognise heart failure as a major public health issue that cripples hundreds of thousands of Australians and places a substantial burden on the health care system. . . . heart failure remains the “Cinderella” of health issues . . . The facts from overseas population studies are plain and startling. Depending on how the condition is defined, anywhere between 3% and 9% of the adult population has heart failure, and a similar proportion has “silent” left ventricular dysfunction.5 Moreover, the incidence of heart failure is still rising. Indeed, it is the only cardiovascular condition not to experience a substantial decline in both incidence and prevalence over the past 20 years (taking into account the progressive ageing of populations).1 There are several reasons for this increase. Firstly, the incidence of heart failure increases with advancing age. In Australia, the proportion of people aged over 65 years (in whom heart failure prevalence is > 10%) will double over the next 50 years.2 Secondly, improvements in diagnostic techniques such as echocardiography have enhanced the ability to make a definitive diagnosis. Thirdly, treatment of heart attack has improved to the extent that patients who previously died of large myocardial infarctions are now able to survive. Finally, heart failure treatments themselves are keeping patients alive for longer and thus contributing to an ever-expanding pool of affected Australians. Can overseas data on prevalence be extrapolated to the Australian population? While the answer to this question is a qualified “yes”, specific issues in Australia relating to treatment approaches, access to diagnostic and health care services and the ethnic mix of the population may affect prevalence figures.5 Moreover, given the public health importance and impact of heart failure, it would seem reasonable to develop an Australia-specific response based on known rather than speculative facts. Thus there is an urgent need for a large-scale, definitive, Australia-wide epidemiological study to ascertain aetiological factors, diagnostic approaches and management of this condition in the Australian community. In this context, the Canberra Heart Study,6 published in this issue of the Journal, is an excellent start in helping to determine the true magnitude of the heart failure problem in Australia. The findings of this well conducted community-based study are a wake-up call to those unaware of the extent of the condition. Not only were 6.3% of the population surveyed found to have overt symptomatic heart failure, but there was a high proportion of patients with subclinical heart failure (left ventricular dysfunction in the absence of symptoms).6 The study also noted a significant proportion of patients with so-called “preserved systolic function” heart failure (ie, symptoms of the condition but with preservation of systolic ventricular function and pointers on echocardiography to impaired relaxation of the ventricle during diastole). The Canberra Heart Study is not without some methodological problems (eg, a relatively small sample size, and thus few positive diagnoses for heart failure; under-participation of elderly women, who may well have added to the burden of diastolic heart failure). Moreover, as with any study of heart failure, the definition of the condition is always fraught with uncertainty, although it appears to have been quite reasonably addressed in this analysis. Complexity in diagnosing heart failure is one of the main reasons for under-recognition of the condition. Indeed, there is no single agreed definition, and the forthcoming update of the current National Heart Foundation/Cardiac Society of Australia and New Zealand guidelines on heart failure7 will propose a further modification to earlier definitions. Heart failure is a syndrome — a cluster of signs and symptoms that require detailed investigation before arriving at a presumptive diagnosis. There are no definitive tests to confirm the diagnosis. Furthermore, as presenting symptoms may be non-specific, heart failure can masquerade as, and be masked by, many other conditions, particularly in elderly people. A recent Australian analysis describing barriers to diagnosis and management of heart failure in the primary care setting points to some of the difficulties of making a definitive diagnosis.8 Nevertheless, it is important that a definitive diagnosis be made because, at least for systolic left ventricular dysfunction (whether symptomatic or not), appropriate management can have a great impact on disease progression, symptoms and survival. Heart failure management is complex, involving a multidisciplinary approach, polypharmacy in drug prescribing, and ancillary modalities that may include exercise, device therapies (eg, cardiac resynchronisation, implantable defibrillators) and surgical procedures. Early detection of subclinical heart failure (to prevent progression to symptomatic disease) and treatment of known risk factors will be major foci of research and clinical interest in the evolution of future heart failure management strategies. In summary, the authors of the Canberra Heart Study6 have done the Australian community a great service in providing epidemiological data to show that heart failure truly is a major public health issue in Australia. The problem requires the type of national response that has been initiated in other Western countries. This regional study should be regarded as the critical stimulus for a national study that would provide a broader, more detailed analysis of the epidemiology, health care burden and management of heart failure in Australia. Without this, Australia will continue to fall behind other Western countries in improving the nation’s health by focusing on prevention and treatment of this highly debilitating and deadly condition.

Henry Krum MB BS, PhD, FRACP · Simon Stewart PhD, FESC, FAHA

One way to tackle social forces that lead to disease is to recruit the putative culprits The world is in the grip of an epidemic of non-communicable disease. We have known this in affluent nations for decades, but have not understood just how large a problem it has become in developing economies.1 Chronic diseases such as cardiovascular disease (CVD), type 2 diabetes, cancer and obstructive pulmonary disease are increasingly undermining prospects for a stable economic future, especially in lower- and middle-income countries2,3 and the poorer segments of society in the developed world. The origins of these diseases are largely social. What and how much we eat, how physically active we are, and whether we smoke are individual behaviours that we might wish to change but which emerge from a maze of causes, including our job, school, suburb, education, religion, car, and money. Philosophers refer to “wicked” problems — ones of great complexity to which there are no simple or stable solutions4 — and non-communicable disease is as wicked as the White Witch, and then some. If only there was a vaccine, if only there was one drug, if only . . . Yet an inventory of our assets in dealing with these diseases is far from depressing. We Australians have quit smoking in droves; we have developed medical and surgical approaches that stabilise risk and more than halved mortality from CVD.5 We have moved death from heart disease from middle to old age. Supermarket shelves relax with the reduced weight of “lite” foods. The success bears scrutiny. Some of it is medical (antihypertensives, lipid-lowering therapies, coronary artery bypass surgery, newer antidepressants, chemotherapy), but not all. Some of it is due to relentless health promotion (Life. Be in it; Quit for life), but not all. Some of it is due to regulation (tobacco tax, seatbelts, and urban planning taxes on developers devoted to healthy suburbs). Some is due to commerce and industry sensing a market advantage in selling healthy products. On 28 November 2005, the Australian Health Policy Institute at the University of Sydney launched its membership as a major centre in the Oxford Health Alliance. The purpose of the Oxford Health Alliance is to influence the macroeconomic and policy environment to favour fitness, good nutrition and reduced smoking, accepting that these behaviours are social as well as personal phenomena that require community involvement in the widest possible sense.6 The Alliance seeks to capitalise on research and to build a global partnership to pursue its mission. It aims to assist institutions, including the World Health Organization, control non-communicable chronic disease. What is unique about the Oxford Health Alliance is its inclusive nature. The Alliance includes not only academia and government, but the private sector and a host of non-government organisations. The Oxford Health Alliance was established under an academic–industry partnership between the University of Oxford and Novo Nordisk, Denmark, a company whose pharmaceutical branch produces insulin. Novo Nordisk looked with Scandinavian horror upon the rising rates of diabetes worldwide, despite these being excellent for their bottom line. In combination with Professors John Bell and David Matthews at Oxford University and Professor Derek Yach, formerly director of the non-communicable disease cluster at WHO but now working at the Rockefeller Foundation, the nascent Oxford Health Alliance has begun to explore ways to reduce the epidemic of chronic disease. John Bell is Regius Professor of Clinical Medicine at the University of Oxford. As Nuffield Professor of Clinical Medicine, he oversaw the largest research department at Oxford University, which encompassed activities spanning structural biology through to epidemiology. David Matthews is Chairman of the Oxford Centre for Diabetes, Endocrinology and Metabolism and has published extensively in the fields of insulin resistance. The Alliance has grown steadily. It has supported three annual 3-day conferences: two at Oxford, and one on 31 October 2005 at Yale in New Haven, Connecticut, where 170 people from 25 countries assembled, from a diverse array of backgrounds, including academia, government, the private sector (PepsiCo, Nestlé, McDonalds), non-government organisations, finance and media, consumer organisations, and professional bodies such as the World Nursing Federation, World Medical Association and World Heart Federation. Topics covered included the economic rationale for investing in chronic disease prevention, patient power, the intersection between health and business, the current framing of chronic diseases in the international agenda, and design for a healthy world. “Oh, my!” said one colleague when he heard that the University of Sydney, through its health policy institute, was joining the Alliance. “So! The Oxford Health Alliance has discovered nutrition!” Fair enough: knowing about risk factors and behaviour is hardly new. The starting point for the Alliance is exactly that: that “discovery” is not enough. Knowing about the nature of risk factors for chronic disease is akin to realising that the pain in your foot is due to an elephant standing on it — moving the elephant is another matter entirely. Our purpose in the Oxford Health Alliance is to bring to the table those businesses and non-medical interests that traditionally have been seen as the Dark Side. This is not about “selling out to industry”, but seeking points of agreement whereby what is done in future is less harmful to health. Academics at the Alliance meetings have enjoyed beating up the representatives from McDonalds and PepsiCo: this is a familiar and exciting, if useless, attempt at solving problems. At the meeting at Yale, the baiting had subsided somewhat, especially in response to an impressive list of marketing and product formulation changes presented by industry representatives. McDonalds, for example, now buys more apples than any restaurant chain in the United States.7 In Australia, it has introduced a range of salads and now cooks with canola oil. The Economist, commenting on PepsiCo’s rising economic fortunes that put it ahead of Coca-Cola for the first time, notes PepsiCo’s diversification “away from a reliance on sugary colas”, deriving only 20% of its revenue from soft drinks, in comparison with 80% at Coca-Cola.8 Of course there is a risk: skills in Defence against the Dark Arts would be helpful. (By contrast to big business, academia is, we all know, blessedly free of self-interest — and it rarely makes a profit!) But if we are seeking to modify the major social forces that entrain damage and cause chronic disease, new ways must be found to do this by recruiting the putative culprits. The answer will probably be expressed as policy — a practical, feasible commitment of many players, amid muddle and ambiguity, to a course of action to mitigate a wicked problem. It is a messy process. But for the Oxford Health Alliance, it is core business.

Stephen R Leeder AO, FRACP, FFAPHM, FFPHM · Ruth Colagiuri BEd, GradCertHealthPolicyManagement

Australia’s effective monitoring system shows that serious reactions are rare Australia has achieved very high levels of vaccination coverage in the past 10 years, with 91% of children fully vaccinated at 12 months of age and 92.1% at 2 years.1 Consequently, rates of vaccine-preventable diseases are very low. As the incidence of vaccine-preventable diseases declines, the safety and side effects of vaccines gain prominence, and an increasingly important role of health care professionals is to communicate the benefits and risks of vaccination to parents.2 Worries about vaccines date back more than 200 years, when Jenner’s introduction of cowpox vaccine prompted cartoons in the satirical magazine Punch depicting vaccine recipients turning into cows. More recently, unproven and unjustified concerns about pertussis vaccine3 and measles–mumps–rubella vaccine4 have resulted in falls in vaccination uptake in the United Kingdom, and the needless deaths of children.3,4 Vaccine constituents, such as preservatives, stabilisers, adjuvants and biological growth media used in vaccine production, are necessary to ensure the efficacy, stability and safety of vaccines, but can also contribute to consumer concerns.5 A recent review concluded that the amounts of aluminium, formaldehyde, antibiotics and yeast proteins in vaccines have not been found to be harmful to humans and animals in exposure studies.5 Currently, if providers have concerns about constituents of vaccines, they can consult the excellent booklet Myths and realities.6 In addition, the National Centre for Immunisation Research and Surveillance (NCIRS) website (<http://www.ncirs. usyd.edu.au>) has a fact sheet relating to thiomersal: <http://www.ncirs.usyd.edu.au/facts/f-thiomersal.html>. The US Centers for Disease Control and Prevention have fact sheets on vaccine components at <http://www.cdc.gov/node.do/id/0900f3ec8006587f>. The article by Eldred et al7 in this issue of the Journal is an important overview of vaccine components and constituents of vaccines in use in Australia, and is an important reference for vaccine providers to answer consumer concerns and questions. Serious adverse events following vaccination are rare, and the risk of morbidity associated with these adverse events is generally far less than the risk from catching a vaccine-preventable disease. Nevertheless, it is extremely important to have in place adequate surveillance for adverse events associated with vaccines. Both the public and health care professionals need to feel confident of vaccine safety. Australia has had local reporting mechanisms for many years, but only since 2000 has there been a national reporting system.8 Under the current system, which was driven by the dynamism of John McEwen, former Principal Medical Adviser of the Therapeutic Goods Administration (TGA), all adverse reports are coordinated by the Australian Adverse Drug Reactions Unit (ADRU) of the TGA. Adverse events associated with vaccines can be reported to ADRU by health care professionals or the public by telephone (02 6232 8386) or by prepaid reporting form (“blue card”) or online at <http://tga.gov.au/adr/bluecard.htm>. The data are further analysed by NCIRS and regularly reported in Communicable diseases intelligence.9-11 The data are extremely reassuring: serious adverse events are rare. Between 2000 and 2004, only seven of 5128 adverse events reported following vaccination were reported as having persisted and resulted in sequelae.9-11 Furthermore, the reporting of an adverse event following vaccination implies an association in timing with vaccine administration, but does not necessarily mean the vaccine caused the reported adverse event. Australia has an effective system for monitoring vaccine safety. In future, privacy laws permitting, it is hoped to link Australia’s database of immunisations, the Australian Childhood Immunisation Register, with hospital admissions to be able to look actively at questions regarding the safety of specific vaccines. It is vital that parents and providers are fully informed about the risk of vaccines and of the diseases they prevent. Australia’s monitoring system will continue to gather the data for informed decision-making.

Nicholas Wood MB BS, DCH, FRACP · David Isaacs MB BChir, MD, MRCP, FRACP, FRCPCH

Objective: To estimate the prevalence of heart failure (HF) and left ventricular (LV) systolic dysfunction in a population-based sample of older Australians.Design, setting and participants: A cross-sectional survey of 2000 randomly selected residents of Canberra, aged 60–86 years, conducted between February 2002 and June 2003. Participants were assessed by history, physical examination by a cardiologist, and echocardiography.Main outcome measures: Age- and sex-specific prevalence rates of clinical HF and LV systolic dysfunction (defined as LV ejection fraction ≤ 50%).Results: Of 1846 people eligible for our study, 1388 (75%) agreed to participate and 1275 completed all investigations (mean age, 69.4 years; 50% men). In the study sample, 72 subjects (5.6%; 95% CI, 4.4%–7.1%) had clinical HF that had been previously diagnosed and was confirmed by our assessment. A further 0.6% (95% CI, 0.3%–1.2%) had undiagnosed clinical HF (ie, evidence of structural heart disease and symptoms/signs of cardiac insufficiency without a previous diagnosis of clinical HF). Thus, the overall prevalence of clinical HF in the sample was 6.3% (95% CI, 5.0%–7.7%). Clinical HF increased in prevalence with advancing age (a 4.4-fold increase from the 60–64-years age group to the 80–86-years age group; P < 0.0001). Of the 75 subjects (5.9%; 95% CI, 4.7%–7.3%) with LV systolic dysfunction, 44 (59%) were in the preclinical stage of disease.Conclusion: Diagnosed HF cases represent the “tip of the iceberg” for the national burden of HF and LV systolic dysfunction. Clinically identifiable HF cases can remain undiagnosed, and the majority of people with LV systolic dysfunction are in a preclinical stage of the disease.

Walter P Abhayaratna MB BS, FRACP · Niels G Becker BSc, MSc, PhD · Wayne T Smith BMed, MPH, PhD · Thomas H Marwick MB BS, PhD, FRACP · Ian M Jeffery MB BS, FRACP · Darryl A McGill MB BS, PhD, FRACP

Objectives: To calculate the cost of assisted reproductive technology (ART) treatment cycles and resultant live-birth events.Design: Cost-outcome study based on a decision analysis model of significant clinical and economic outcomes of ART.Setting and participants: All non-donor ART treatments initiated in Australia in 2002. Treatment cycles, maternal age and birth outcome data were obtained from the Australian and New Zealand Assisted Reproduction Database. Direct health care costs were obtained from fertility centres, and included government, private insurer and patient costs.Main outcome measures: Average health care cost of non-donor, fresh and frozen embryo ART treatment cycles. Average and age-specific costs per live-birth event following ART treatment.Results: Average health care cost per non-donor ART live-birth event was $32 903 (range, $24 809 for women < 30 years to $97 884 for women ≥ 40 years). The cost per live birth for women aged ≥ 42 years was $182 794. The average treatment cost of a fresh cycle was $6940, compared with $1937 for a frozen embryo transfer cycle.Conclusions: Debate regarding funding for ART services has been hindered by a lack of economic studies of ART treatments and outcomes in Australia. This is the most comprehensive costing study of ART services to date in terms of resources consumed during ART treatment. It confirms that ART treatment is less cost-effective in older women. Alongside economic considerations of ART, community values, ethical judgements and clinical factors should influence policy decision-making.

Georgina M Chambers BAppSci(MLS), GradDip(Comp), MBA, Doctoral Candidate · Elizabeth A Sullivan MB BS, MPH, MMed(Sexual Health) · Maria T Ho MBBS, MHP, MD

In January 2001, a daily morning handover meeting (“morning report”), involving medical staff and students, began at the Launceston General Hospital, Tasmania. Periodic questionnaire surveys have been conducted to assess whether the morning report is fulfilling the quality improvement and educational needs of medical staff. The format of meetings has been successively modified in response to feedback. Participants have expressed a preference for patient-focused meetings, with less emphasis on formal teaching. A 12-month pilot study beginning in January 2004 has assessed the impact of adding a bed-management focus to the morning report. Over the period of the pilot study, there has been reduced bed access block, reduced average length of stay and increased bed availability. This suggests that a longer, more formal study may be warranted.

Robert G Fassett FRACP, FASN · Steven J Bollipo FRACP

Objective: To describe the workload profile in a network of Australian skin cancer clinics.Design and setting: Analysis of billing data for the first 6 months of 2005 in a primary-care skin cancer clinic network, consisting of seven clinics and staffed by 20 doctors, located in the Northern Territory, Queensland and New South Wales.Main outcome measures: Consultation to biopsy ratio (CBR); biopsy to treatment ratio (BTR); number of benign naevi excised per melanoma (number needed to treat [NNT]).Results: Of 69 780 billed activities, 34 622 (49.6%) were consultations, 19 358 (27.7%) biopsies, 8055 (11.5%) surgical excisions, 2804 (4.0%) additional surgical repairs, 1613 (2.3%) non-surgical treatments of cancers and 3328 (4.8%) treatments of premalignant or non-malignant lesions. A total of 6438 cancers were treated (116 melanomas by excision, 4709 non-melanoma skin cancers [NMSCs] by excision, and 1613 NMSCs non-surgically); 5251 (65.2%) surgical wounds were repaired by direct suture, 2651 (32.9%) by a flap (of which 44.8% were simple flaps), 42 (0.5%) by wedge excision and 111 (1.4%) by grafts. The CBR was 1.79, the BTR was 3.1 and the NNT was 28.6.Conclusions: In this network of Australian skin cancer clinics, one in three biopsies identified a skin cancer (BTR, 3.1), and about 29 benign lesions were excised per melanoma (NNT, 28.6). The estimated NNT was similar to that reported previously in general practice. More data are needed on health outcomes, including effectiveness of treatment and surgical repair.

David Wilkinson MB ChB, DSc, FRACGP · Deborah A Askew BAppSci, MHlthSci, PhD · Anthony Dixon MB BS, FACRRM

Objective: To document the population iodine nutritional status in Australian schoolchildren.Design and setting: Cross-sectional survey of schoolchildren aged 8–10 years, based on a one-stage random cluster sample drawn from all Year 4 school classes in government and non-government schools in the five mainland Australian states of New South Wales, Victoria, South Australia, Western Australia and Queensland. The study was conducted between July 2003 and December 2004.Participants: 1709 students from 88 schools (881 boys and 828 girls), representing 85% of the estimated target number of students. The class participation rate was 65%.Main outcome measures: (i) Urinary iodine excretion (UIE) levels (compared with the criteria for the severity of iodine deficiency of the World Health Organization/International Council for the Control of Iodine Deficiency Disorders: iodine replete, UIE ≥ 100 μg/L; mild iodine deficiency, UIE 50–99 μg/L; moderate iodine deficiency, UIE 20–49 μg/L; severe iodine deficiency, UIE < 20 μg/L); (ii) Thyroid volumes measured by ultrasound (compared with new international reference values).Results: Overall, children in mainland Australia are borderline iodine deficient, with a national median UIE of 104 μg/L. On a state basis, NSW and Victorian children are mildly iodine deficient, with median UIE levels of 89 μg/L and 73.5 μg/L, respectively. South Australian children are borderline iodine deficient, with a median UIE of 101 μg/L. Both Queensland and Western Australian children are iodine sufficient, with median UIE levels of 136.5 μg/L and 142.5 μg/L, respectively. Thyroid volumes in Australian schoolchildren are marginally increased compared with international normative data obtained from children living in iodine sufficient countries. There was no significant association between UIE and thyroid volume.Conclusion: Our results confirm the existence of inadequate iodine intake in the Australian population, and we call for the urgent implementation of mandatory iodisation of all edible salt in Australia.

Mu Li PhD · Creswell J Eastman AM, MD, FRACP · Kay V Waite Biological Technicians Certificate · Gary Ma PhD · Karen Byth PhD · Margaret R Zacharin MB BS, FRACP · Duncan J Topliss MD, FRACP · Philip E Harding MB BS, FRACP · John P Walsh PhD, FRACP · Lynley C Ward BS, SRN · Robin H Mortimer MB BS, FRACP · Emily J Mackenzie MB BS · Zelda Doyle MSc(Epidemiology)

Vaccination remains a vital strategy in the prevention of infectious disease. Commercial vaccine formulations contain a range of additives or manufacturing residuals, which may contribute to patient concerns about vaccine safety. Primary health care professionals are well placed to address patient concerns about vaccine safety. We describe the key constituents present in vaccines, discuss issues related to safety and acceptability of these constituents, and provide a table highlighting constituents of commercially available vaccines in Australia.

Barbara E Eldred BPharm · Angela J Dean BPharm, PhD · Treasure M McGuire BPharm, BSc, PhD · Allan L Nash BPharm

Loss of bone mineral density with androgen deprivation therapy (ADT) for prostate cancer is well recognised, with significant loss of bone mineral density (BMD) occurring within 12 months of starting therapy. With ADT, annual loss of BMD is about 2%–8% per year at the lumbar spine and 1.8%–6.5% at the hip; the loss appears to continue indefinitely while treatment continues, and there is no recovery after therapy is ceased. 19.4% of men surviving at least 5 years after diagnosis of prostate cancer have a fracture if treated with ADT compared with 12.6% of men not receiving ADT; this is equivalent to one additional fracture for every 28 men treated with ADT. Vitamin D deficiency exacerbates the development of osteoporosis, so vitamin D status should be evaluated before commencing ADT in men with prostate cancer. Treatment with bisphosphonates (zoledronate, pamidronate and alendronate) in men treated with ADT have been shown to prevent bone loss in prospective studies and to increase BMD in one randomised controlled trial; bisphosphonates have not been shown to prevent fractures in men with prostate cancer. Further prospective trials are required to assess the efficacy and cost-effectiveness of bisphosphonates in men with prostate cancer who require treatment with ADT. All doctors need to take an active role in monitoring bone health in patients with prostate cancer requiring ADT.

D Jane Holmes-Walker PhD, MB BS, FRACP · Henry Woo MB BS, FRACS · Howard Gurney MB BS, FRACP · Viet T Do MB BS, FRANZCR · David R Chipps PhD, MB BS, FRACP

Multiple pregnancy, with its adverse outcomes, is a significant problem in assisted reproductive technology. Single embryo transfer (SET) is the only feasible solution for reducing the rate of multiple pregnancy. Many patients and some clinicians remain to be convinced that SET is a better clinical option. Adequate education, based on available evidence, is one important way to promote the use of SET.

Jim Wang PhD · Michelle Lane PhD · Robert J Norman MD

Clinical record Computed tomography of the thorax showed bilateral pleural effusions (PE) and diffuse thickening of the oesophagus (O). An 84-year-old woman presented to the emergency department following the sudden onset of retrosternal chest pain with associated nausea and sweating. The pain was exacerbated by swallowing, but this symptom was not felt to be significant at the time. She had no past history of ischaemic heart disease or diabetes and did not smoke, but did have a weak family history of heart disease, and a personal history of mild hypercholesterolaemia and refractory hypertension despite aggressive medical management (baseline systolic blood pressure consistently 150–220 mmHg, according to previous medical records). An electrocardiogram (ECG) showed a left bundle branch block, with no previous ECG available for comparison. Acute myocardial infarction was diagnosed. However, coronary angiography showed no abnormalities, and serial measurements of serum troponin and creatine kinase levels failed to confirm an infarction. The next morning, the patient developed profound dysphagia and had an episode of haematemesis. Full blood examination showed normocytic anaemia (haemoglobin concentration, 70 g/L; reference range [RR], 115–165 g/L), with mean cell volume of 91 fL (RR, 78–99 fL), neutrophilia (12.7 × 109 cells/L [RR, 2.0–8.0 × 109 cells/L]), and platelet count in the RR (172 × 109 cells/L [RR, 150–450 × 109 cells/L]). She developed a cough, and a chest x-ray showed left lower lobe consolidation. Intravenous ceftriaxone therapy was begun to treat this. Computed tomography was arranged to investigate the oesophageal symptoms. This showed a diffusely thickened oesophagus from the thoracic inlet to the gastro-oesophageal junction, bilateral pleural effusions, and left lower lobe collapse and consolidation (Figure). Endoscopy showed blackened oesophageal mucosa with extensive mucosal bleeding. The procedure was abandoned because of these findings, and the patient was intubated and transferred to our tertiary referral centre for ongoing care. On arrival, chest x-ray showed progression of the pulmonary effusion, obscuring the entire left lung field. At bronchoscopy, a substantial volume of old clot was evacuated from the left bronchial tree. Repeat endoscopy again showed an extensive mucosal lesion. A percutaneous endoscopic gastrostomy (PEG) tube was placed, and a provisional diagnosis of malignancy was made (biopsies subsequently showing benign tissue only). The patient remained haemodynamically stable throughout, and was extubated 2 days later. She remained asymptomatic and was able to eat a full diet 6 days later. A final diagnosis was made of dissecting haematoma of the oesophagus. The patient remained in excellent health at follow-up a month later, at which time the PEG tube was removed without incident. Dissecting haematoma of the oesophagus is a rare, relatively benign condition that mimics much more common and serious illnesses.1 The onset of sudden severe retrosternal chest pain in an elderly person, who often has other cardiovascular risk factors, may lead to an erroneous diagnosis of cardiac pain. In some cases, subsequent thrombolytic treatment has led to fatalities. In others, the appearance of intramural thrombus on radiological or endoscopic views has been mistaken for advanced oesophageal malignancy or rupture.2,3 Lessons from practice Dissecting haematoma of the oesophagus should be included in the differential diagnosis in elderly patients presenting with cardiac-type chest pain, and oesophageal symptoms should be specifically sought in the history. The presence of oesophageal symptoms (dysphagia or odynophagia) in the context of cardiac-type chest pain should prompt investigation with appropriate imaging studies (barium swallow or computed tomography of the thorax before administration of fibrinolytic agents. Concern about dissecting haematoma of the oesophagus can be clarified rapidly with a water "sip test". The course of dissecting haematoma of the oesophagus is essentially benign if unnecessary intervention is avoided. Because of the rarity of dissecting haematoma of the oesophagus, diagnosis depends on an accurate history and a high index of suspicion. Those affected are usually women (relative risk, 1.8 — the inverse to the male bias in cardiovascular and malignant oesophageal disease),3 elderly (median age, 63 years),3 and not uncommonly taking anticoagulant or antiplatelet agents. Patients present with a variable combination of chest pain (usually sudden in onset and of short duration), haematemesis (mainly small volume and occurring after the pain), and dysphagia and/or odynophagia. In one meta-analysis, 99% of patients had at least one of these symptoms, and 32% had all three.3 In particular, the presence of dysphagia or odynophagia in a patient otherwise thought to have angina or myocardial infarction should prompt oesophageal imaging before administration of fibrinolytic agents. A simple test is to ask the patient to take a sip of water as part of the examination. If this exacerbates symptoms or unmasks new ones, a more specific focus on the possibility of oesophageal abnormality is warranted. Dissecting haematoma of the oesophagus has a typical appearance on imaging.4,5 Barium swallow shows a long, smooth tubular filling defect in the lumen of the oesophagus, sometimes with the dissection space filled with a stripe of contrast (the “double-barrelled oesophagus”). As the dissection most commonly occurs along the posterior wall, the lateral view is most useful. Computed tomography demonstrates an obliterated lumen with thickening of the wall. This extends over a long length of the oesophagus, and can mimic oesophageal rupture or extensive malignancy. The haematoma is large, fluctuant, and blue or purplish when viewed at endoscopy. Delayed endoscopy shows a long ulcer, where the overlying mucosa has sloughed, followed by rapid regeneration and an ultimately normal appearance.3 For a condition with such dramatic presentation, the natural history is refreshingly benign. The best intervention is non-intervention: the haematoma almost always resolves, and full oesophageal function is restored. Intravenous hydration, supplemented by parenteral or enteral nutrition in appropriate cases, is usually all that is needed. Anti-ulcer medications have no proven benefit.3 Surgery is indicated if there is uncontrolled arterial bleeding, or if the partial rupture has been converted to a full thickness tear through endoscopy.3 A further indication for surgery is a focus of infection within the false lumen, preventing healing. In two such cases, endoscopic division of the overlying mucosal flap resulted in complete resolution of fever, odynophagia and neutrophilia.1,6 Unfortunately, aggressive intervention has led to fatalities.3

Deborah H Amott MB BS(Hons) · Gavin M Wright FRACS

Clinical record Patient 1* Histopathology of colonic biopsies from the patients described† A: Biopsy from Patient 1 shows mild diffuse increase of lymphocytes within the crypt and surface epithelium (arrows). Inflammatory cell infiltration of the lamina propria is minimal and there is no collagen deposition.‡ A 78-year-old woman who normally had one to two bowel motions a day presented with a 3-week history of gradual onset of more frequent and looser motions up to six times a day and occasionally at night. She had urgency and episodes of faecal incontinence. Her motions were watery. There was no improvement after she was treated with tinidazole. Her regular medications were alendronate, hydrochlorothiazide, irbesartan, raloxifene, thyroxine, temazepam, aspirin, thiamine, vitamin C, glucosamine, and evening primrose oil. She had also taken lansoprazole (30 mg capsules) daily for 2 months to treat possible reflux. Sigmoidoscopy showed yellowish, watery stool with mucus and a few tiny scattered patches of intramucosal haemorrhage. Biopsy (Figure A) showed mild lymphocytic colitis (defined by the presence of more than one lymphocyte per 20 epithelial cells). Lansoprazole therapy was ceased and the diarrhoea settled within 24 hours. Patient 2* B: Biopsy from Patient 2 shows mild increase in plasma cells in the lamina propria and an obvious subepithelial band of collagen (arrows). There is patchy detachment of the surface epithelium.§ A 53-year-old woman presented to hospital with a 2-month history of diarrhoea and abdominal pain. She was admitted with suspected diverticulitis. Nine months before presentation, she had started taking lansoprazole (30 mg capsules) daily for heartburn. She described having bowel motions seven or eight times per day, and occasionally at night. The diarrhoea had not responded to tinidazole, metronidazole or norfloxacin. Her regular medications were gemfibrozil, tibolone, indapamide and perindopril. Colonoscopy did not detect significant abnormalities. Biopsy showed mild collagenous colitis (Figure B). Lansoprazole therapy was ceased. She was treated with loperamide, then cholestyramine and budesonide. Within 6 months, she was symptom-free without antidiarrhoeal medication. Patient 3* C: Patient 3, there is a mild increase in lymphocytes within the epithelium, and of plasma cells in the lamina propria. The surface epithelium is mildly degenerate, and there is a suggestion of abnormal subepithelial collagen deposition (arrow).‡ A 79-year-old woman had been seen in hospital with a sudden onset of diarrhoea 5 weeks before admission, associated with 10 kg weight loss. She had taken lansoprazole (30 mg capsules) daily for 2 weeks before the diarrhoea began. She had had up to 12 watery motions per day. The diarrhoea had not responded to norfloxacin. Her regular medications were alendronate, perindopril, potassium chloride, chlorthalidone and celecoxib. Appearance on sigmoidoscopy was normal, but biopsies (Figure C) showed mild lymphocytic colitis with occasional subepithelial collagen suggesting transition to collagenous colitis. Lansoprazole therapy was ceased, and she was treated with codeine. Her condition was much improved without antidiarrhoeal medication within a month. When reviewed 6 months later, she was having two loose motions daily, and the celecoxib (200 mg daily) was withdrawn. * All three patients had negative results on serological tests for coeliac disease (transglutaminase and endomysial antibody) and normal serum IgA levels. † Follow-up biopsies were not taken. ‡ Stained with haematoxylin and eosin. § Stained with Masson Trichrome, which shows collagen in green. Microscopic colitis is increasingly recognised as a major cause of persistent diarrhoea.1 It is an idiopathic clinicopathological syndrome of chronic watery non-bloody diarrhoea associated with a normal appearance on colonoscopy and specific histopathological changes of lymphocytic and/or collagenous colitis. There is a high rate of spontaneous resolution and relapse in microscopic colitis, and effective treatment is limited. The pathogenesis of microscopic colitis is poorly understood and is thought to be related to a poorly regulated epithelial immune response to luminal or epithelial antigens including bile acids, toxins, or infectious agents.2 Microscopic colitis has been associated with autoimmune diseases and with exposure to medications, predominantly non-steroidal anti-inflammatory drugs, and, rarely, salicylates, simvastatin, ticlopidine, ranitidine, carbamazepine, Cyclo 3 Fort (a combination of Ruscus aculeatus extract, hesperidin methylchalcone, and ascorbic acid), flutamide, gold salts, and, recently, lansoprazole.2 Lessons from practice Microscopic colitis should be considered as a cause of persistent watery non-bloody diarrhoea; the two major histological forms of microscopic colitis — lymphocytic and collagenous — are probably variations of the same disorder. Even if the bowel appears macroscopically normal on colonoscopy, multiple biopsies should be routinely taken for histopathology, and the pathologist informed of the possibility of microscopic colitis. The possibility of medications as the cause of diarrhoea and microscopic colitis should always be considered; drugs that may cause the symptoms should be investigated, withdrawn, and the effects observed. Not all adverse drug events occur immediately and not all are class effects. Suspected adverse drug reactions should be reported to the Adverse Drug Reaction Advisory Committee for evaluation. Lymphocytic and collagenous colitis are probably aetiologically related, and may be a spectrum of the same disease.3 This is supported by our report of three lansoprazole-associated cases, in which one showed lymphocytic colitis, one showed collagenous colitis and one showed transitional features of both on histopathological examination. The inflammatory infiltrate and collagen deposition in these cases was less severe than that seen in typical cases of lymphocytic and collagenous colitis, probably because of the limited periods of exposure to the inciting agent. Interestingly, Patient 2 had the greatest collagen deposition and the longest exposure to lansoprazole. The rapid resolution of the symptoms on cessation of lanzoprazole therapy in Patient 1 may be related to the very mild lymphocytic infiltrate and lack of collagen deposition, or perhaps lansoprazole caused diarrhoea through another mechanism in this case. Adverse drug reactions can only be recognised if doctors maintain a high index of suspicion. It is not possible to know every possible reaction to the medications that patients are exposed to, and some may not have been recognised before. The absence of an immediate temporal relationship between a drug and the associated disorder (as was seen in the cases presented here) may contribute to failure to diagnose a drug-induced disease. Drugs and their metabolites may affect the colon directly through their pharmacological actions, or through hypersensitivity reactions. Drugs also act indirectly on the colon by altering colonisation by gastrointestinal organisms.4 The association between lansoprazole and microscopic colitis may be related to its action on the colonic proton pump, affecting colonic secretions and pH, which may affect colonic flora and bile salt solubility.5 Alternatively, there may be an idiosyncratic direct hypersensitivity reaction by the colonic mucosa. The association between lansoprazole and microscopic colitis has been reported previously,5-7 and before our patients presented, the Adverse Drug Reaction Advisory Committee had received a single report of a probable association between rabeprazole and unspecified colitis. In a previous report of lansoprazole-associated microscopic colitis,5 substituting omeprazole for lansoprazole did not lead to recurrent diarrhoea. One explanation for the absence of a class effect is that while all proton-pump inhibitors bind the parietal cell proton pump covalently at cysteine 813 or 822, only lansoprazole and rabeprazole bind to cysteine 321.8 Binding of cysteine 321 also inhibits the colonic proton pumps.9 This may affect colonic secretion and pH, predisposing to diarrhoea and microscopic colitis. However, the rarity of the association between lansoprazole and microscopic colitis favours an idiosyncratic immune reaction. Minor variations in the structures of the proton-pump inhibitors may result in different immunological activation, although allergic cross-sensitivity has occasionally been reported among the proton-pump inhibitors.10 Our cases illustrate the importance of considering exposure to medication as a cause of chronic diarrhoea and particularly microscopic colitis, and that adverse drug reactions are not always class effects. Stopping the causative medication may reverse the abnormality in this difficult-to-treat condition. In patients with persistent watery diarrhoea, biopsies should be performed even if colonoscopic appearances are normal, and pathologists should be informed of the clinical possibility of microscopic colitis, as the histological changes may be subtle.

Sarah N Hilmer PhD, FRACP · Timothy R Heap MB BS, FRACP · Robert P Eckstein MB BS, FRCPA · Gillian M Shenfield DM, FRACP · Christopher S Lauer MB BS, FRCPA

Hospitals use appropriate sterilisation to prevent transmission of infection among infants from such items as reusable feeding bottles. But what happens when the sterilisation process results in potential harm to the infant in other ways? We describe an incident in which a wrong sterilisation method resulted in an infant being fed with a shrunken feeding bottle. A full-term male infant weighing 2290 g at birth was prescribed formula feeds for low birthweight and neonatal abstinence syndrome. An agency nurse handed the mother a sterilised 120 mL plastic bottle for formula feeding. It was amazing to see how this small infant managed to take the full 90 mL with each feed, which was twice his daily requirement. The explanation became apparent when the nursing unit manager compared the bottle in question with a new 120 mL bottle. While the older bottle was similar in height and even fitted the same teat, it was narrower than the new bottle (Figure). In fact, when the older bottle was filled to the 120 mL mark on the outside, it held only 50 mL! How had this occurred? Further enquiry established that, before use, this particular bottle, designated as unsuitable for autoclaving by the manufacturer, had mistakenly been autoclaved in the Central Sterile Supply Department (CSSD) instead of being chemically sterilised on the ward. Fortunately, the problem was picked up quickly enough to prevent the infant from getting dehydrated. Sterilisation of feeding bottles can be achieved by thermal or chemical means.1 While some recommend boiling as the preferred option, the use of a sodium hypochlorite solution (eg, Milton, Milton Australia Pty Ltd, Brisbane) is widely accepted by hospitals as a superior form of sterilisation.2 In our hospital, feeding bottles are not normally autoclaved. The only other method of sterilisation at CSSD involves ethylene oxide. This method is felt unsuitable for feeding bottles, given the potential for absorption of ethylene oxide into the plastic. But, every now and then, a bottle finds its way down to CSSD and returns as a slimmer version of its old self. While some types of feeding bottle can be safely autoclaved, this particular range of bottles is unsuitable for autoclaving. We have now replaced the implicated bottles with glass and other autoclave-safe plastic bottles so that this type of incident does not occur again.

Sarah Newton MB BS · Hemant Jain MB BS · Joane Coleman RN · Srinivas Bolisetty FRACP

Magnetic resonance imaging and arthroscopy of the hip have shown that labral injuries, chondral injuries, rim lesions, synovitis and tears of the ligament teres are common causes of hip, groin and low-back pain. Hip arthroscopy is used both as a diagnostic and therapeutic tool; it has been shown to be of benefit in recent traumatic labral injury, but disappointing in the management of chronic hip pain (which may be associated with degenerative change, and chondral lesions of the acetabulum). The McConnell multimodal physiotherapy regimen is effective in treating patellofemoral pain. Anterior cruciate ligament rupture is three to five times more common in women, but neuromuscular training appears to decrease its incidence. Patellar tendon and hamstring grafts appear to be equally effective in anterior cruciate ligament reconstruction. Articular cartilage defects remain a significant problem, and the efficacy of treatments such as autologous chondrocyte implantation is still unclear.

Peter D Brukner MB BS, FACSP · Kay M Crossley BAppSci(Physio), PhD · Hayden Morris MB BS, FRACS · Simon J Bartold BSc, FASMF, FAAPSM · Bruce Elliott PhD, FAAKPE, FISBS

A loved and respected general practitioner in Sydney’s Eastern Suburbs for many years, John Watson came from humble beginnings. Excelling in many intellectual pursuits, he was an eternal student. He loved teaching, and always had a close association with the University of Sydney and Sydney Hospital. John was born in Sydney on 26 May 1917. He always wanted to be a doctor, but during the Depression no child of a poor family could afford the fees. He won a Teachers’ College scholarship and became a science teacher. While teaching by day, he attended evening classes in economics at the University of Sydney. After serving in the Australian Military Forces from 1941 to 1946, John returned to teaching. At the same time, he completed Bachelor of Arts and Bachelor of Economics degrees as an evening student, while saving to enrol in medicine. In 1948, he began to study medicine at the University of Sydney, supplementing his income by working as a bookmaker’s clerk. His sharpness as a mathematician was valued, although his knowledge of and interest in racing was nil! In 1950, he married Rose Wicks, also a teacher, who helped to support him through medical school. After graduation in 1954, John was appointed Junior Resident at Sydney Hospital. In 1956, approaching the age of 40, he established a 24-hours-a-day, 7-days-a-week general practice in South Coogee, living on the premises. Many of his patients became lifelong friends. When Medicare was introduced, John felt he could not work under a system that “put the clock” on time spent with a patient, so he went into hospital administration, becoming Deputy Superintendent at Sydney Hospital. Although a capable administrator, he found some aspects of the work very tedious and missed the contact with patients, and so eventually returned to limited general practice in South Coogee. He served many years as an Honorary Medical Officer in the Sydney Hospital general medicine and neurology outpatient clinics. John’s love of learning, teaching and patient care continued all his life. He was one of the first “radio talk-back doctors” to answer listeners’ questions over the air. For many years he was a member of the Editorial Board of The Medical Journal of Australia. He taught medicine and medical principles at the School of Occupational Therapy, and later became a director of the Sydney Medical Emergency Service Co-op, which provided an out-of-hours locum service to GPs. He was also in great demand as an after-dinner speaker and as a lecturer for the University of the Third Age. His other interests, as a student and beyond, included debating (the University of Sydney’s J G Watson trophy for debating was named after him) and compering and scriptwriting for the annual Sydney University revue. He was President of the Sydney University Union and later a student representative Fellow of the University Senate. He had a keen interest in many sports, including surfing, fishing, cricket, rugby, athletics and hockey. At an advanced age, he took up piano playing and landscape painting. John died on 6 July 2005 after several cerebral vascular incidents and eventual multiple organ failure. He was a truly good man, who touched many people in his different roles. He will be sadly missed by Rose, his sons John, Ian and Andrew, and their families and many friends.

Frederick O Stephens FRCS, FRACS, MD

John Colvin made an outstanding contribution to ophthalmology in Australia. He also (with the technical assistance of spectacle maker Martin Hogan) played a role in the successful US Apollo space flights and extended the flying time of Royal Australian Air Force (RAAF) and civilian airline pilots. Born on 14 January 1929 in Hobart, John was educated mainly in Queensland. After graduating in medicine at the University of Queensland in 1953, he spent 5 years in England training in ophthalmology, spending part of that time at the Leeds General Infirmary. Returning to Melbourne in 1961, he entered private practice and was appointed to the honorary staff of the Royal Victorian Eye and Ear Hospital. On Saturday mornings at the hospital he gave free lectures to medical students (whose attendance was voluntary). He estimated that, over a period of 37 years, he gave 1000 lectures to 12 000 students. In recognition of this unique service, the hospital’s management committee named the John Colvin Clinical School in his honour. John joined the University of Queensland Air Squadron in 1950 and gained a pilot’s licence in 1954. As an RAAF reservist, John became consultant ophthalmologist to the RAAF, serving for 45 years and reaching the rank of group captain. He designed spectacles that allowed presbyopic Air Force and airline pilots to read instruments above their line of sight, thus enabling them to continue to meet visual standards. He also designed spectacles with polycarbonate lenses that could withstand high gravitational forces, as well as an anti-glare docking aid, that were adopted by the US National Aeronautics and Space Administration (NASA) for its astronauts. He was invited to be a keynote speaker at an aerospace conference in Las Vegas, and visited NASA at Cape Kennedy. For 25 years, John gave honorary service to Royal Flying Doctor Service clinics from Broken Hill to the Queensland border. A dedicated teacher, he lectured to the Royal Australian College of General Practitioners, the College of Pharmacy, the Mobile Intensive Care Ambulance Service, and dental and nursing students. He was also a visiting speaker in New Zealand, Fiji, New Guinea and Vietnam, where he advised Air Vietnam on the selection of pilots. His pamphlet “Golden eye rules” was distributed to hospitals and general practices, and was translated into many languages. His article “Effective management of penetrating eye injuries in remote Australia”1 became the basis of standard practice. In his spare time, John enjoyed watching football. He was a supporter of the Hawthorn Football Club and its honorary ophthalmologist, and received the Club’s Service Award. Disabled by a stroke in 1995, John died on 7 August 2005 after a long period of failing health. He is survived by his wife Sylvia and their three children, David, Alan and Andrea.

Derek Meyers MBBS, MD, FRACP

Elizabeth May Pepper,* Dominique A Cadilhac,† Dora C Pearce,‡ James Burrow,§ Tarun S Weeramanthri¶ * Neurology Registrar, John Hunter Hospital, Newcastle, NSW. † Manager, Public Health Division; ‡ Biostatistician; National Stroke Research Institute, Melbourne, VIC. § Neurologist; ¶ Physician, Royal Darwin Hospital, NT. hornblowerATinternode.on.net To the Editor: Although the age-standardised stroke mortality rates among Australia’s Indigenous people is more than twice that of the non-Indigenous population,1 the medical literature contains only one audit of Indigenous stroke patients in Perth metropolitan hospitals.2 No review of hospital care has been reported. Royal Darwin Hospital (RDH) is the referral centre for Australia’s “Top End”, where 8.7% of Indigenous Australians reside; 40% of RDH inpatients are Indigenous. In 2002, while planning for the RDH stroke service, we audited stroke admissions from the previous year. Among 121 eligible patients admitted between 1 July 2001 and 31 June 2002 with International classification of diseases, 10th revision, Australian modification (ICD-10-AM) codes 160–164 (haemorrhages [subarachnoid, intracerebral, other non-traumatic intracranial] and cerebral infarction), records for 116 (96%) were available, but six patients were excluded because of incorrect coding. Box 1 outlines patient characteristics, while Box 2 examines risk factors and medication use for ischaemic stroke (because haemorrhages were few). Despite the observed differences between subgroups, there were no significant differences in mortality (4/36 for Indigenous v 7/42 for non-Indigenous; P = 0.204) or stroke severity at admission or discharge. Box 3 highlights differences in risk factors between Indigenous males and females. Retrospective data, particularly from a sample identified by medical record coding, should be interpreted with caution. In addition, the potential for random error due to small numbers, and the referral bias inherent in tertiary hospital admissions, mean our results may not truly represent the “Top End” Indigenous population. However, our data corroborate findings that Indigenous Australians suffer premature cerebrovascular disease, and have higher rates of vascular risk factors than other Australians,1 with some risk factor differences between males and females. Further, recent evidence suggests differences in standards of stroke care in regional (Queensland) hospitals.3 We found disparity in hospital care of Indigenous patients, and this requires further detailed investigation. A prospective, community-based study is urgently needed. 1 Baseline characteristics for 110 patients admitted to Royal Darwin Hospital with subarachnoid, intracerebral, and other non-traumatic intracranial haemorrhages and cerebral infarction in 2001–02 Baseline characteristics Indigenous Other P Number of patients 45 65 Female sex 22 (49%) 19 (29%) 0.018 Mean age (years) 54 61 0.005 Rural dwelling 41 (91%) 22 (34%) < 0.001 Ischaemic stroke 36 (80%) 42 (65%) 0.081 2 Risk factors and medication use for the 78 patients who had ischaemic stroke Risk factors and medications Indigenous Other P All patients 36 42 Smoking 23 (64%) 11 (26%) 0.001 Diabetes mellitus 16 (44%) 10 (24%) 0.030 Rheumatic heart disease 8 (22%) 1 (2%) < 0.001 Males 19 (53%) 30 (71%) 0.089 Smoking 14 (74%) 12 (40%) 0.017 Diabetes mellitus 10 (53%) 7 (23%) 0.030 Females 17 (47%) 12 (29%) 0.089 Smoking 9 (53%) 0 0.002 Rheumatic heart disease 6 (35%) 0 0.026 Antiplatelet therapy Before admission 11 (31%) 19 (45%) 0.078 Admission 20 (56%) 38 (91%) < 0.001 Discharge 18/32 (56%) 29/35 (83%) 0.013 Anticoagulant therapy Before admission 4 (11%) 1 (2%) < 0.001 Discharge 4/32 (13%) 6/35 (17%) 0.235 3 Risk factor differences between Indigenous males and females who had ischaemic stroke Males Females P Number of patients 19 17 Hypertension 16 (84%) 6 (35%) 0.003 Non cerebral vascular disease 6 (32%) 1 (6%) < 0.001 Excessive alcohol intake 7 (37%) 1 (6%) < 0.001

Elizabeth May Pepper · Dominique A Cadilhac · Dora C Pearce · James Burrow · Tarun S Weeramanthri

Annabelle D Donaldson,* Raymond C Chan,† Iain B Gosbell‡ * Infectious Diseases Registrar, Department of Microbiology and Infectious Diseases, Liverpool Health Service, Sydney, NSW; † Infectious Diseases Physician, ‡ Director, Department of Microbiology and Infectious Diseases, South Western Area Pathology Service, Locked Bag 7090, Liverpool BC 1871, and Conjoint Associate Professor, School of Medical Sciences, University of New South Wales, Sydney, NSW. i.gosbellATunsw.edu.au To the Editor: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is usually susceptible to a wider range of antibiotics than nosocomial or multiresistant MRSA, but evidence is lacking to guide antibiotic choices. Rifampicin plus fusidic acid is commonly used in multiresistant MRSA infection, and familiarity makes this combination attractive for CA-MRSA. We report two cases of CA-MRSA infection in which rifampicin resistance developed during treatment. Non-compliance may have been a significant factor, but high bacterial load and persistent foci of infection were also likely contributors. We caution against using regimens containing rifampicin in such cases. Patient 1: A previously well 16-year-old girl presented with a 4-day history of left knee pain. She had fever and a moderate joint effusion. Plain x-rays were unremarkable, and blood cultures showed no growth. An aspirate of the knee joint had a white blood cell count of 1100 × 106 cells/L, but showed no growth on culture. Non-multiresistant MRSA (sensitive to all non-β-lactams) was subsequently grown from a synovial biopsy specimen. She was treated with 7 weeks of intravenous vancomycin, followed by 6 months of oral rifampicin (450 mg daily) plus fusidic acid (500 mg twice daily). Her compliance was uncertain, and she did not return for follow-up appointments. The patient presented again 12 months later with increasing pain in the left knee and thigh. X-ray and magnetic resonance imaging revealed extensive osteomyelitis of the distal femur. Culture of purulent material removed at sequestrectomy grew MRSA with the same sensitivity profile as previously, but now resistant to rifampicin. She was treated with clindamycin, but required further sequestrectomy. She continues to take clindamycin long term. Patient 2: A 74-year-old man developed severe cellulitis and an abscess of his left hand after a golfing injury. He had bacteraemia with non-multiresistant MRSA (sensitive to all non-β-lactams). He also had significant pain in his left prosthetic hip. After 7 weeks of intravenous vancomycin and oral moxifloxacin, levels of inflammatory markers remained high. He was treated with oral rifampicin (600 mg daily) plus fusidic acid (500 mg twice daily) for several weeks until lost to follow-up. Four months later, the patient still had pain in the hip, and rifampicin plus fusidic acid treatment was begun again. After 3 months with no improvement, he underwent surgical exploration, and the loose femoral prosthesis was replaced. Culture of debrided material showed MRSA with the same sensitivity pattern as previously, but now resistant to rifampicin. He was treated with intravenous vancomycin for 6 weeks, followed by trimethoprim–sulfamethoxazole, which was later changed to clindamycin because of intolerance. He remains taking indefinite clindamycin suppression therapy. Traditional oral therapy for MRSA infection is rifampicin plus fusidic acid, but alternative oral agents for non-multiresistant CA-MRSA include clindamycin,1 tetracyclines2 and trimethoprim–sulfamethoxazole.3 There is wider experience with clindamycin, which penetrates well into skin and soft tissues, has good oral bioavailability, and has been used successfully.1 However, a concern is erythromycin-inducible clindamycin resistance, which may lead to clindamycin failure, particularly in severe infections.4 Its prevalence varies. Studies in vitro have shown that rifampicin resistance develops as readily in CA-MRSA as in nosocomial MRSA,5 through a single-step mutation. Resistance did not develop in vitro to clindamycin,5 suggesting it may be a more reliable alternative in situations where compliance is uncertain, the bacterial load is high, or the source (eg, an infected prosthesis) cannot be removed. Further in-vitro and in-vivo investigations are urgently required to determine the optimal drug therapy for CA-MRSA infections.

Annabelle D Donaldson · Raymond C Chan · Iain B Gosbell

Tania Shelby-James,* Amy P Abernethy,† David C Currow‡ * Research Fellow, Southern Adelaide Palliative Services, Repatriation General Hospital, 700 Goodwood Road, Daw Park, SA 5041; † Assistant Professor of Medicine, Duke University Medical Center, Durham, North Carolina, USA; ‡ Professor, Department of Palliative and Supportive Services, Flinders University, Adelaide, SA. tania.shelby-jamesATrgh.sa.gov.au To the Editor: Aoun and Kristjanson’s article highlighted some of the difficulties facing researchers in palliative care1 and questioned the role of randomised controlled trials (RCTs). These difficulties do not exempt palliative care from seeking to improve care through thoughtful research but, rather, highlight areas that need to be specifically designed to cope with these difficulties. In our recently completed large RCT of palliative care in southern Adelaide, for which we recruited 461 patients,2 we were able to overcome many of the obstacles cited by these authors. As they rightly stated, many trials in palliative care are pragmatic. This should not be seen as a bad thing, as pragmatic studies are designed to test clinically relevant interventions3 within diverse populations across different settings and to report on a broad range of health outcomes. Such studies are more in keeping with the realities of palliative care. We would argue that traditional RCTs that examine a specific intervention within a specific patient type are less applicable to a palliative care population. In such a population, unlike many other areas of health, the diagnosis and prognosis do not dictate care needs. Among the methodological issues, recruitment and retention are perhaps the biggest hurdles to be overcome. We found that developing systematic, evidence-based protocols, which were pilot tested before initiating the trial, significantly enhanced recruitment.4 To minimise burden, we ensured that all data collection was kept to a minimum and, where possible, data were recorded by study staff or collected from other sources as part of routine clinical encounters. Sample size calculations need to allow for attrition caused by increasing severity of disease. This will, however, inflate the numbers required for a study. Use of multiple sites for recruitment is a strategy that we have used successfully to reach sample size goals. The article states that “RCTs are seldom acceptable to patients and their families”.1 This has not been our experience. Patients are willing to participate in research and find it a meaningful way to give back to the community.5 The challenge is to ensure that this willingness to participate in research is not exploited by palliative care researchers. The other ethical concern raised by Aoun and Kristjanson is the use of a control arm in which patients “deliberately have support services withheld”. We would agree that, if that were to happen, it would be a serious ethical breach. For RCTs in palliative care, the control arm should consist of the standard care provided — the rationale for doing a trial is that there is equipoise regarding the benefit of the intervention. We feel that RCTs are feasible and appropriate for palliative care research.

Tania Shelby-James · Amy P Abernethy · David C Currow

Jennifer Tieman,* David C Currow† * Project Manager, † Head, Department of Palliative and Supportive Services, Flinders University, c/- Repatriation General Hospital, 700 Goodwood Road, Daw Park, SA 5041. Jennifer. TiemanATflinders.edu.au To the Editor: Aoun and Kristjanson’s viewpoint on palliative care research reminds us of the possible limitations of an evidence schema that is built on efficacy of intervention studies.1 For emerging fields and for care areas that cross disciplines, the possible sources of useful knowledge to guide practice — particularly in advance of the establishment of a significant evidence base — need to be recognised and valued. To further complicate the gathering of evidence for such fields are the difficulties of accessing useful knowledge. Preliminary research on search strategies suggests that even good quality searches may recover fewer than half the articles relevant to palliative care in the general biomedical literature.2 More disturbing is the possibility that much of the research and thought in this field is not published, and therefore cannot be easily and actively searched. In a systematic review of publication rates associated with conference presentation, the usual publication rate was seen to be around 45%.3 A recent investigation into publication rates associated with conference presentation in palliative care in Australia suggests a “conversion” rate of less than 20%.4 Publication represents an important step in the spectrum of knowledge dissemination. Such a low rate of publication of conference abstracts therefore represents a significant loss of information, opinion and evidence for the discipline of palliative care. Evidence issues for complex and emerging areas are complicated not only by the restrictions of an evidence hierarchy that is intervention based, but also by the difficulties in searching and retrieving existing knowledge and evidence in such fields.

Jennifer Tieman · David C Currow

C Scott Masters,* Michael J Yelland† * Vice-President, Australian Association of Musculoskeletal Medicine, Caloundra Sports Medicine Centre, 39 Minchinton Street, Caloundra, QLD 4551. † Associate Professor of Primary Health Care, Griffith University, QLD. scotty1ATozemail.com.au To the Editor: Paoloni and Orchard provided a concise summary of the evidence for injections for soft-tissue injuries,1 but omitted some important references on the mechanism of action of corticosteroids and on prolotherapy. An important action of corticosteroids is blocking of transmission in nociceptive C-fibres.2 Given the lack of evidence of inflammation in chronically painful tendinopathies,3 this is a more probable mechanism of action than the suppression of inflammation. Paoloni and Orchard correctly report that steroids have only a temporary effect in suppressing soft tissue pain. However, in low back pain, if their use is preceded by manual therapy and exercises they have the potential to give more prolonged relief of pain and disability.4 A recent Swedish randomised controlled trial (RCT) of polidocanol prolotherapy injections for chronic Achilles tendinopathy showed reduced pain and normalisation of ultrasound abnormalities.5 Similarly, a New Zealand case series of glucose prolotherapy injections showed very positive results for the same condition.6 An Australian RCT into prolotherapy for chronic low back pain (average duration, 14 years) showed sustained reductions in pain and disability with glucose prolotherapy injections, although similar results were obtained with saline injections.7 A pilot study of glucose prolotherapy in 24 elite male kicking-sport athletes with chronic groin pain (mean duration, 15.5 months) who had failed physical therapy reported a pain-free state and return to sports in 82% at an average follow-up of 17.2 months.8 This evidence would suggest there is a role for this glucose prolotherapy in managing soft-tissue pain, especially as musculoskeletal pain is one of the major presentations to primary practice in Australia. Training primary care physicians in prolotherapy injection techniques should be a priority in medical education.

C Scott Masters · Michael J Yelland

Justin A Paoloni,* John W Orchard† * Conjoint Senior Lecturer, Orthopaedic Research Institute, St George Hospital Campus, University of New South Wales, Sydney, NSW. † Sports Physician, Sports Medicine at Sydney University, Sydney, NSW. pao_26AThotmail.com In reply: We thank Masters and Yelland for their interest in this topic and their notification of additional references, some of which were published after our article was written. We stated in our article that “the mechanism of any effect of corticosteroid injections in reducing symptoms in purely degenerative tendinopathies is unknown”, and that only where bursitis or tenosynovitis is present would the implication of an anti-inflammatory effect be appropriate.1 While blocking nociceptive C-fibres in normal tendon is demonstrated in the study quoted by Masters and Yelland,2 we still believe that corticosteroids should be used with caution for any tendinopathy where tendon weakening would be potentially harmful. We agree that corticosteroids have a much greater potential role in low back pain, which is a broad entity involving both soft-tissue and joint disorder. At the time of writing our article there was a pilot study on polidocanol in painful tendons displaying neovascularisation;3 we thank the authors for advising that a randomised controlled trial has since been published.4 While undoubtedly an exciting new therapy, proponents of polidocanol do not consider its mechanism to be simply a “prolotherapy” effect; they also consider sclerosing the neovessels to be critical, and therefore, that hypertonic glucose (the most commonly recommended prolotherapy agent) may not work as well. We still maintain that prolotherapy currently lacks evidence of efficacy for the treatment of soft-tissue injury in general, although it is relatively cheap and generally free of side effects. Both chronic low back pain, and chronic groin pain, are multifactorial conditions involving joint/bone abnormality which we considered slightly beyond the scope of an article on soft-tissue injuries. We await further publications on the efficacy of prolotherapy with interest.

Justin A Paoloni · John W Orchard

Henry Ekert Haematologist, Children's Cancer Centre and Department of Haematology, Royal Children's Hospital, PO Box 2096, Brighton North, Melbourne, VIC 3186; and Haematology Advisor, Australian Government Department of Health and Ageing. ekerthenryAToptushome.com.au To the Editor: The editorial on mandatory fortification of flour with folic acid by Maberly and Stanley is subtitled: “The scientific benefit is clear, but translating this into practice requires advocacy”.1 The only benefit that is scientifically clear is the reduction in the incidence of neural tube defects. All the other “benefits” listed by the authors are observational and have occurred in a setting where myriad environmental changes have occurred concurrent with folic acid fortification. To imply that the reduction in the rate of heart attacks and stroke is the result of folic acid fortification is, at best, anecdotal, because it is not supported by any randomised controlled studies, and is an extrapolation from the relationship between reduced homocysteine levels and the incidence of stroke and heart disease. The authors also did not mention the increased incidence of multiple pregnancies that has been observed with folate supplementation (relative risk, 1.02; 95% CI, 0.97–1.07).2 While this represents only a slight increase in the risks associated with the birth process, it should not be ignored when considering perceived risks. It is also possible that in a planned pregnancy where the mother is prescribed folic acid before conception, the additional folate intake from fortified flour may further increase the risk of multiple pregnancy. It seems to me that the editorial was in fact an item of advocacy rather than a dispassionate scientific assessment of the arguments for and against mandatory folic acid fortification. At the very least, if mandatory folic acid fortification is implemented, prospective mothers will have to be made aware of the increased risk of multiple pregnancy and the as yet unknown risk of combining the fortified diet with medically prescribed folic acid.

Henry Ekert

Fiona J Stanley,* Glen F Maberly† * Director, Telethon Institute for Child Health Research, PO Box 855, West Perth, WA 6872. † Professor of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. fionaATichr.uwa.edu.au In reply: Ekert suggests that in our article advocating for mandatory fortification with folate to reduce neural tube defects,1 we omitted to mention the “increased risk of multiple pregnancies”. He then misquotes the Lumley meta-analysis “(relative risk, 1.02; 95% CI, 0.97–1.07)” — the real relative risk was 1.40 (95% CI, 0.93–2.11). This Cochrane systematic review shows that folate supplementation does not carry a statistically significant risk for multiple births, but confirms the dramatic reduction in neural tube defects.2 Another study, which did suggest an increased risk, did not control for the known increased risk of multiple births following infertility treatments, which could explain the increase observed.3 Ekert suggests that we inform women about this unsubstantiated risk and “the as yet unknown risk” which mandatory fortification might add to “medically prescribed folic acid”. Folic acid is found in leafy green vegetables and in many fruits, nuts and other components of a healthy diet. Tablets are available over the counter. What advice would he give to women about these “risks”? Our evidence is that we are not reaching many women in our society by education and voluntary fortification, and that countries that have fortified their flour have achieved much better reductions in these major defects than we have in Australia. Hence our advocacy. We acknowledge that the evidence for stroke and heart disease reduction is not as solid as that for neural tube defects. However, there is an increasing literature on the protective effects of folate on cardiovascular risk and possible mechanisms.4-8 Hence, with consideration of the proven benefits and the unsubstantiated risks, we will continue to advocate for the mandatory fortification of flour with folate.

Fiona J Stanley · Glen F Maberly

Paul D Fitzgerald General Practitioner, Suite 303, 83 Mount Street, North Sydney, NSW 2060. docfitzATihug.com.au To the Editor: It is heartening to see a positive professional response to clinical quality systems in the wake of Bundaberg. However, these are secondary responses, and overlook the primary, preventive solution. Clinical monitoring systems presuppose that some damage is done before a problem becomes apparent. Hospitals already have mechanisms to examine clinical competence, and their appointments credentialing and privileging procedures. The Queensland Health Systems Review Final Report (the Forster report)1 comments repeatedly on the apparent failure of these procedures in the Patel case at Bundaberg Hospital: It appears that the process of checking credentials did not involve the College of Surgeons and no written clinical privileges appeared to have been granted on appointment. (p 169) The report draws specific attention to special purpose registration for areas of need, pointing out the inherent conflict of interest: As an employer under pressure to fill medical vacancies, Queensland Health faces a conflict of interesting making . . . determinations of area of need to allow special purpose registration of overseas trained doctors. (p 175) It adds that these doctors are not subject to the same requirements as locally trained doctors, and recommends: No overseas trained doctor should commence employment in a senior position intended to be filled by a specialist before . . . [assessment via the established Australian Medical Council / Specialist College pathway]. (p 174) Furthermore, deemed specialists should participate in the usual clinical performance management processes applicable to all doctors. (p 175) And, finally: . . . local clinical leaders and managers have a conflict between credentialing someone about whom they are uncertain and having no one to deliver the service. It appears that these issues may have been relevant at Bundaberg. (p 176) More recently, the Queensland Public Hospitals Commission of Inquiry report (the Davies report)2 confirms a practice of appointing overseas trained doctors as senior medical officers in specialist roles in hospitals in designated areas of need. Such appointments in Bundaberg, Hervey Bay, Townsville and Charters Towers not only bypassed procedures for recognition as a “deemed specialist”, but were also not considered by hospital credentialing and privileging committees. The Davies report states that, in some hospitals, these committees did not exist. It may be premature for the proponents of clinical quality systems to dance on the ashes of Bundaberg. These recent reports outline a chain of existing systems problems including the Medical Board, the Department of Health, successive Health Ministers and Cabinets, and appointments, credentialing, privileging and complaints procedures in a sample of Queensland public hospitals. According to the Davies report (section 6.173), around half of the doctors in Queensland public hospitals were appointed under area-of-need arrangements by 2002. How are other states balancing the politically sensitive area of need registration with long-standing appointments, credentialing and privileging procedures?

Paul D Fitzgerald

Concise clinical oncology. Clive Peedell. Sydney: Butterworth-Heinemann, 2005 (xiii + 320 pp). ISBN 0 7506 8836. Exactly as the title suggests — concise and to the point! It is robustly constructed, and ideal in size (190 x 130 mm — fits in a coat pocket), number of pages and detail for medical students or junior clinicians in any specialty, general practitioners, or junior trainees in one of the oncology specialties. Oncology trainees in later years would be better served by a more comprehensive textbook. The author is a radiation oncologist at James Cook University Hospital in Middlesbrough, United Kingdom, and the information presented is up-to-date, succinct and relevant. It is easy to navigate, with good use of fonts, as well as colour, tables and figures to embellish the text. It is well set out with an excellent table of contents and index. Sections include oncology principles, A–Z of cancers (which occupies about half of the book), complications and emergencies, as well as a short A–Z of chemotherapy drugs, and useful websites. There are three to five references after each chapter for readers who want more detail, mostly reviews in readily accessible online journals. With each cancer in the A–Z section, the text is divided into background, presentation, diagnosis and staging, management, and future perspectives. This allows easy navigation for the busy general clinician. All cancers are covered but, as is appropriate, the more common cancers, such as breast, colorectal and lung cancer, occupy more pages. Some of the information about cancer management and prognosis may change with time, but the future perspectives section gives this book a longer shelf life than most. Stephen P AcklandMedical Oncologist Newcastle Mater Misericordiae Hospital, NSW

Stephen P Ackland

Practical ophthalmology. A survival guide for doctors and optometrists. Anthony Pane, Peter Simcock. Edinburgh: Elsevier Churchill Livingstone, 2005 (x + 255 pp). ISBN 0 443 10112 4. This is a good book. The concept, presentation, content, quality of the printing, even the binding is good. The content is unlikely to go out of date quickly and the plastic cover, which overlaps the main pages of the book, should make it durable in a pocket or on a desk, whether for a student, a general practitioner or an optometrist. Practical ophthalmology addresses the target market in a didactic way. It sets out to keep non-ophthalmologists out of trouble. There is useful advice on what NOT to do and what is urgent. It does this by using a well laid-out colour-coded series of chapters that are symptom-based, along with flow charts to speed decision making. Symptoms, signs and management are all clearly laid out. There are good quality colour illustrations and examples. The index makes up almost 10% of the book’s 255 pages, making it easy to find any topic quickly. Practical ophthalmology is good value and it is imperative that everybody read Chapter 1, entitled “Staying out of trouble with eyes”. Recommended. Thomas D WalkerOphthalmologist, Deakin, ACT

Thomas D Walker

Diabetes drug deaths? Canadian researchers have revived a decades-old concern about whether sulfonylurea drug use can cause adverse cardiac events.1,2 They followed a cohort of 5795 patients with type 2 diabetes over an average of 4.6 years.1 All subjects were only taking one of three types of oral anti-diabetic agent — a first generation sulfonylurea (chlorpropamide or tolbutamide), a more recently developed sulfonylurea (glibenclamide), or metformin. The researchers found that the higher the daily dose of sulfonylurea (especially a first-generation sulfonylurea), the greater the risk of death, including death caused by an acute ischaemic event. This association was not found with metformin. An accompanying commentary suggested that sulfonylurea drugs should therefore be relegated to third-line agents in managing type 2 diabetes, after metformin and thiazolidinediones. Further, if they must be used, newer agents, such as glimepiride and glicizide, which have less effect on myocardial ATP-sensitive potassium channels, should be prescribed. 1. CMAJ 2006; 174: 169-174 2. CMAJ 2006; 174: 185-186 Silicone travels Silicone injection for cosmetic purposes should be considered a high-risk procedure, according to a US physician who reported a case of silicone fluid embolism. A 30-year-old woman had developed severe silicone-induced pneumonitis leading to respiratory failure within days of receiving silicone injections into her buttocks. The injections had been given by an unlicensed nurse. An open-lung biopsy showed lipoid vacuoles throughout the alveolar interstitium; microscopy confirmed the presence of elemental silicon within the vacuoles. The patient was managed successfully with elective intubation and intravenous methylprednisolone. N Engl J Med 2006; 354: 211-212 H. pylori: overcoming antibiotic resistance A sequential regimen may be more effective than standard triple therapy in eradicating Helicobacter pylori infection.1,2 In a small Italian study, researchers randomised 156 patients with H. pylori infection to receive either a 10-day sequential regimen (20 mg rabeprazole and 1 g amoxycillin for 5 days, followed by 20 mg rabeprazole, 500 mg clarithromycin and 500 mg tinidazole for 5 days) or 7 days of standard triple therapy (20 mg rabeprazole, 500 mg clarithromycin and 1 g amoxycillin). The sequential regimen achieved a higher cure rare than standard therapy, not only in patients infected with clarithromycin-susceptible H. pylori strains but also in those infected with clarithromycin-resistant strains. 1. Ann Intern Med 2006; 144: 94-100 2. Ann Intern Med 2006; 144: 140-141 Meningococcal disease: clues to an earlier diagnosis A UK study has reported newly identified, early clinical features of meningococcal disease which occur several hours before the well known classic features of haemorrhagic rash, meningism and impaired consciousness. The study examined the pre-hospital admission course of 448 confirmed and suspected cases of meningococcal disease, 103 of which were fatal, using questionnaires completed by parents and primary care records. At least one early sign of sepsis — leg pain, cold hands and feet or an abnormal skin colour — developed in most children about 8 hours after the onset of illness. The study authors called for a diagnostic paradigm shift: “Although we must avoid undermining the importance of classic symptoms, we could substantially speed up diagnosis if the emphasis was shifted to early recognition of sepsis.” Lancet Online, 11 Jan 2006 Cerebral palsy’s viral factor Australian research has determined that there is an association between cerebral palsy and perinatal exposure to several viruses, especially some herpes viruses.1,2 Gibson and colleagues conducted a case-control study, comparing the presence of a range of viral nucleic acids in the newborn screening cards (Guthrie tests) of more than 400 white cases with cerebral palsy with that in more than 800 white controls. For all gestational ages, the presence of varicella-zoster and human herpes viruses 6 and 7 increased the risk of developing cerebral palsy. However, about 40% of the controls tested positive for at least one virus, suggesting that other factors are needed for brain damage and subsequent cerebral palsy to occur. 1. BMJ 2006; 332: 76-80 2. BMJ 2006; 332: 63-64 Dr Ann Gregory, MJA

Ann Gregory