Volume 181 Issue 10

Women’s health in mid-life. A primary care guide. Jo Ann Rosenfeld (editor). Cambridge: Cambridge University Press, 2004 (xi + 374 pp). ISBN 0 521 82340 4. WITH FEW EXCEPTIONS, our youth-obsessed culture either ignores middle-aged women or indulges in stereotypes. So I was pleased to learn that, at a recent conference, the US Census Bureau had extended my youth by redefining middle age as commencing at age 50. Despite this, here is a new textbook which focuses on women aged 40 to 65 and has a positive outlook. It encourages consideration of the variety of social and health circumstances that these women may enjoy, from single and childfree to a grandmother raising her grandchildren, from the peak of her career to pensioner. The messages are that “midlife is far more than hormones”; that it is an opportunity for women to take stock and explore health promotion opportunities; and that the doctor’s role is to facilitate this process. The book is divided into four parts: Health promotion, Hormonal changes, Disease prevention and Cancer prevention. Each chapter is evidence-based and well referenced, and includes many US institutional websites for up-to-date information. Realistic case vignettes and algorithms could be helpful for general practitioners. As an example of the useful content, the chapter discussing physical activity and exercise takes us through the considerable evidence base for resistance training, endurance training, yoga and t’ai chi, including the underlying physiological changes; provides 16 examples of what constitutes moderate exercise; and finally, summarises practical advice for prescribing exercise for both healthy women and those with various medical conditions, such as arthritis, osteoporosis or diabetes. The chapter on hormone therapy explores in detail the ramifications of the recent large hormone replacement therapy (HRT) trials. Many alternatives to HRT are offered, including a detailed section on complementary therapies, and the author cites many ongoing studies. The only small negative about this text is that it uses almost exclusively US data, references, acronyms and drug trade names. This means that chapters such as those on Pap testing have recommendations and pathology categories that differ from those used in Australia. These are minor issues, however, and overall this is an excellent textbook. Marie V PirottaDepartment of General Practice University of Melbourne, VIC

Marie V Pirotta

Aspirin: the story of a wonder drug. Diarmuid Jeffreys. London: Bloomsbury, 2004 (x + 335 pp). ISBN 0 7475 7443 X. To enjoy one of Monet’s haystacks, it’s best to stand back to take in the wonder of the light and form, without worrying that individual stalks aren’t identifiable — this book is like that. It tells, with great verve, the story of aspirin, the emblematic story of 20th-century medicine — but the reader is well advised not to look too critically at the scientific detail. The style is historical fiction. For example, the author describes in great detail how the room in Luxor looked when Edwin Smith bought the Ebers Papyrus in 1862. Still, the author has read widely, if not deeply, and delivers a fast-paced narrative. The pharmaceutical industry of the 20th century began with the successful synthesis and exploitation of aspirin, and the drug’s path illustrates the factors that will probably still determine developments in the 21st century. The virtue of willow bark was established by experience, but the synthesis of pure aspirin captured that virtue without much of its vice. Here was a synthetic drug that worked and a new alchemy was established which transmuted pharmacology into gold. For the first three-quarters of the 20th century the proportion of scientific fact to marketing fiction heavily favoured the latter, and the drug’s protean actions were a source of amazement. The explanation — that these properties were due to cyclooxygenase inhibition — opened a new chapter for aspirin. It also exemplified how new drugs now come as the dividend of resources put into fundamental research. The journalistic style, factual approximations and the many examples of spell-check autonomy do not prevent this from being a good read, worth the money. M Laurence MashfordPharmacologist, Parkville, VIC

M Laurence Mashford

We need processes in place to follow up suspicions about serious adverse events Rofecoxib and a second cyclooxygenase-2 (COX-2) inhibitor, celecoxib, were approved by the Therapeutic Goods Administration in 1999 after large phase III randomised trials showed they were as effective as “traditional” non-steroidal anti-inflammatory drugs in reducing pain and inflammation and less likely to cause gastric ulceration.1,2 Since then, COX-2 inhibitors have become one of the 10 most widely used prescription medicines in Australia, at a cost to the federal government of more than $200 million annually.3 However, uncertainty has surrounded the cardiovascular safety of rofecoxib (Vioxx; Merck Sharp & Dohme), and COX-2 inhibitors as a class, ever since an increased risk of cardiovascular events was reported among patients randomly allocated to the rofecoxib group in the VIGOR trial.1 . . . what are the lessons learned by pharmaceutical and regulatory bodies. . . On 7 September this year, Merck Sharp & Dohme faxed a “Dear Doctor” letter to Australian doctors to reassure them of the cardiovascular safety of rofecoxib. Yet, 3 weeks later, Merck Sharp & Dohme suddenly announced an immediate worldwide withdrawal of rofecoxib; this action is the largest prescription drug withdrawal in history. In response, the United States Food and Drug Administration (FDA) immediately issued a public health advisory on rofecoxib, while Australia’s Therapeutic Goods Administration issued a customer-level recall for an estimated 250 000–300 000 Australians taking the drug.4 The first concern about the cardiovascular safety of rofecoxib emerged with the VIGOR study, reported in 2000. It involved a fivefold increase in myocardial infarction and a twofold increase in myocardial infarction, stroke or cardiovascular death among 8076 rheumatoid arthritis patients treated for a median of 9 months with rofecoxib compared with naproxen1 (see Box). Further questions about the cardiovascular safety of rofecoxib were raised in 2001 by an overview of the clinical trial data.6 These data prompted the FDA to initiate a label change in 2002, highlighting the potential cardiovascular risks of rofecoxib. Despite more recent observational studies also suggesting an increased early (within the first 30 days of treatment) and late (beyond 30 days) risk of acute myocardial infarction or sudden cardiac death with rofecoxib,7,8 conclusive evidence of increased cardiovascular risk from adequately powered randomised trials was lacking.9 The decision by Merck to withdraw rofecoxib worldwide was prompted by an unexpected source. APPROVe (Adenomatous Polyp Prevention On Vioxx) was a multicentre, placebo-controlled trial of 2600 patients designed to examine the effects of treatment with rofecoxib on the recurrence of neoplastic polyps of the large bowel in patients with a history of colorectal adenoma.4 An interim analysis of this trial demonstrated an almost twofold increase in cardiovascular events in patients treated with rofecoxib (25 mg daily) compared with placebo (see Box). When these data are extrapolated to the Australian population, the increased risk of 16 events per 1000 patients treated for up to 3 years equates to a potential excess of several thousand cardiovascular events caused by rofecoxib. This may represent an underestimate of the number of events caused by rofecoxib, because patients with inflammatory arthritis are likely to be at higher baseline risk of cardiovascular events than the “low risk” population included in APPROVe.4 The dramatic withdrawal of rofecoxib raises important questions for clinicians, pharmaceutical companies and regulatory authorities. What is the basis for the increased cardiovascular risk?Traditional non-steroidal anti-inflammatory drugs (NSAIDs) suppress prostaglandin synthesis by inhibiting both constitutively expressed COX-1 (primarily responsible for “housekeeping” functions such as gastric protection and haemostasis) and the inducible COX-2 (which is upregulated in inflammatory conditions). The coxibs (COX-2-selective NSAIDs) do not inhibit production of platelet thromboxane (a potent platelet agonist and vasoconstrictor), but selectively suppress endothelial prostacyclin (an intrinsic vasodilator and platelet inhibitor). It has been hypothesised that selective inhibition of prostacyclin production by coxibs without concomitant platelet inhibition leads to thrombosis in at-risk individuals.10,11 However, alternative hypotheses suggest that blockade of COX-2 in atheromatous plaques may reduce vascular inflammation and the progression of vascular disease, and perhaps even prevent events.9,12 Is the thrombotic risk a class effect?The celecoxib studies have not demonstrated an increased risk of thrombosis,2,7,8 but there are no long-term safety studies. Several second-generation coxibs have recently been approved for use in the United States (Lumiracoxib, Valdecoxib) and Europe (Etoricoxib, a derivative of rofecoxib). While randomised trials involving these drugs have not shown a significant increase in thrombosis risk,13,14 they have not excluded it. Consequently, their potential risk for causing cardiovascular events has also been questioned.8,11 Given the clear demonstration of increased cardiovascular risk with rofecoxib, it is now incumbent on drug manufacturers and regulatory authorities to demonstrate cardiovascular safety for all existing and new coxibs. What are the alternative therapeutic options?Paracetamol-based analgesia is widely recommended as first-line therapy to reduce chronic pain. However, when used alone, paracetamol appears to be less effective than NSAIDs,15 and there are no studies of the safety of the long-term intake of paracetamol. NSAIDs are indicated for patients with inflammatory arthritis. For those at increased risk of gastrointestinal complications, the options include celecoxib or a traditional NSAID combined with a proton-pump inhibitor. Neither of these strategies has been tested in patients with cardiovascular disease. What can be done to prevent a recurrence of similar problems with future (new) drugs?Regulatory authorities in Australia and overseas were prepared to accept that an increased rate of cardiovascular events in the VIGOR study was the result of a protective effect of naproxen rather than a toxic effect of rofecoxib. In retrospect, it would have been better if systems had been put in place to further investigate the increased risk of cardiovascular events with rofecoxib when these were first evident. Robust and consistent processes to suspect and actively examine such outcomes need to be established and implemented, particularly when life-threatening effects are possible with symptomatic treatments for non-life-threatening conditions. At the end of the day, the real question is what are the lessons learned by pharmaceutical and regulatory bodies from this sorry tale? Pfizer, the manufacturer of Celebrex, has recently announced that it will sponsor a major clinical study to reassess the cardiovascular safety of its product.16 However, the outcome is some time off. Cardiovascular outcomes in major phase III randomised trials of the cyclooxygenase-2 (COX-2)-selective inhibitors approved for use in Australia COX-2-selective agent Trial No. of patients Comparator Cardiovascular outcome Absolute risk (absolute risk increase; 95% CI) No. needed to harm* Rofecoxib VIGOR 20001† 8076 Naproxen MI, stroke, death 1.1% v 0.5% (0.6%; 0.3%–1.0%) 167 ADVANTAGE 20035† 5557 Naproxen MI, stroke, death 0.4% v 0.3% (0.1%; –0.2 to 0.4%) — APPROVe 20044 2600 Placebo MI, stroke 3.5% v 1.9% (1.6%; 0.3–2.8%) 62.5 Celecoxib CLASS 20002 8059 Ibuprofen or diclofenac MI, stroke, angina 0.9% v 1.0% (–0.1%; –0.5 to 0.4%) — MI = myocardial infarction. * Number of patients who need to be treated in order to cause one adverse cardiovascular outcome. † Patients taking aspirin were not eligible for inclusion.

Paul E Langton BSc, MB BS (Hons), FRACP · Graeme J Hankey MD, FRACP, FRCP · John W Eikelboom MB BS, MSc, FRACP

Weight loss occurs in the short term, but not enough is known to recommend long term use After health professionals have promoted a low fat, high carbohydrate model of eating for more than 20 years, the prevalence of overweight and obesity in Australia (as elsewhere) has climbed.1 Very few people are able to attain and maintain a truly low fat eating plan, but that has not stopped the low fat orthodoxy being blamed for the obesity epidemic.2 Yet, it is not sufficient to focus on a single aspect of diet — low fat diets are not intrinsically “healthy”, especially if they contain high levels of simple sugars, low levels of complex carbohydrates and are nutrient poor. In contrast to the low fat, high carbohydrate diet, a popular approach to weight loss is the Atkins diet,3 a “controlled carbohydrate” dietary regimen. One of the many reasons for its popularity is that, as society has become increasingly concerned about body image and weight, the Atkins regimen promises quick weight loss without hunger, allows a wide range of foods and has simple “rules”. All this is supported by consumer “how-to” books, celebrity endorsement, and food product innovation and marketing. The Atkins diet — “kerbing the carbs”Atkins’ theory rests on a belief that a high intake of refined carbohydrate, especially simple sugars, causes overstimulation of insulin and results in uncontrolled hunger and eating, while the excess insulin also favours fat storage. Thus, the Atkins diet relies primarily on controlling carbohydrate intake and progresses through four phases. The strict induction phase, intended to produce ketosis, allows only 20 g of carbohydrate a day for a minimum of 2 weeks. Fruit, bread, grains, starchy vegetables or dairy products other than cheese, cream or butter are eliminated. Sugar and alcohol are not allowed, and caffeine is discouraged. Mineral and vitamin supplementation, dietary fibre, and eight glasses of water a day are recommended. During this restrictive phase, weight loss is rapid. While this initial weight loss may be due in part to water loss as body glycogen stores are depleted, low carbohydrate diets also result in a reduced caloric intake.4-7 Factors contributing to the lower caloric intake may be the satiating effect of a high protein diet, a lower absolute fat intake due to restricted food choice, and possibly appetite suppression due to ketosis.8-10 However, the exact mechanisms of the weight loss are as yet unknown.10 The second and third phases of the diet allow a gradual liberalisation of food intake by an incremental increase in total carbohydrate: fruits, nuts, more vegetables and some cereal foods are added. The final, maintenance phase is intended to be permanent, and aims to keep daily dietary carbohydrate intake to a known (relatively low) amount. Advice for patients wanting to follow the Atkins diet While low carbohydrate diets appear to work for weight loss in the short term (6 months), not enough is known to recommend them in the long term. All weight-reduction diets are difficult to follow over a long period of time and have limited long term success. Follow the complete Atkins plan (not only parts of it), including regular physical activity, vitamin and mineral supplementation, a daily fibre supplement, eight glasses of water a day, and minimally processed foods. Maintain a high daily intake of fruit and vegetables (at least two serves of fruit and five serves of vegetables from the “allowed” foods) and avoid saturated fats. A dietitian can help with your dietary intake plan if you are having difficulties. Does the Atkins diet work?If weight loss is the goal, the answer appears to be a qualified “yes”. For obese people, it works a little better than a low fat diet over 6 months. Recently, four randomised controlled trials in obese men and women (two lasting 6 months, two lasting 12 months) compared a low carbohydrate diet to a conventional low fat weight-loss diet.5-7,11 Although the studies differed in design and had different subjects, in each study the weight loss at 6 months was 4–6 kg greater for the low carbohydrate group than for the low fat group. However, the weight loss difference between groups at 12 months was no longer statistically significant.6,11 The dropout rates in all of the trials were high (21%–43%), with a general non-significant tendency for better retention in the low carbohydrate group. So, in the long term, low carbohydrate diets do not necessarily offer better weight control than lower fat, higher carbohydrate diets. Is the Atkins diet safe?During weight loss, a low carbohydrate regimen appears to have no adverse effects on cardiovascular risk factors such as serum lipid levels (total and low-density lipoprotein cholesterol) or blood pressure, or on fasting glucose and fasting insulin levels.6,7 In fact, randomised controlled trials comparing a low carbohydrate diet with a low fat diet up to 12 months consistently indicate a beneficial effect on serum triglyceride and high-density lipoprotein cholesterol concentrations. However, the low carbohydrate regimen is associated with a greater incidence of constipation, headache, halitosis, muscle cramps, diarrhoea, general weakness and rash.5 Strictly limiting carbohydrates could also reduce intake of plant-based foods rich in phytochemicals, bioflavinoids, carotenoids and other micronutrients now regarded as important in a healthy diet.12 The regimen developed by Atkins3 encourages fruit and vegetable intake, and minimally processed food, so a low carbohydrate diet should not necessarily imply an intake low in fibre and low in plant-based food. Low carbohydrate diets may also be beneficial by removing simple sugars and sugary foods, including fructose sweeteners, which could be responsible for excess energy intake.8 Overall, however, the safety of low carbohydrate diets beyond 12 months is largely unknown, and there is speculation that the regimen may have adverse health implications for cardiovascular disease, renal function (through an observed cross-sectional association of high dietary protein intake with proteinuria) and bone health (through relatively low calcium intake and the association of high protein intake with hypercalcinuria).13 Information is also lacking on the long term effect of a low carbohydrate regimen for the young, the elderly, people of normal weight (or for people who are not losing weight), and those with chronic conditions, such as diabetes or cardiovascular disease. As with many dietary regimens, the nutritional quality of low carbohydrate diets varies according to how the dietary rules are applied. The Atkins diet calls for a drastic dietary reduction of foods with a significant starch and sugar content — in doing so, the intake of many energy-dense but micronutrient-poor foods is reduced. There is the potential for these to be replaced with foods that are moderate in energy intake, and rich in fibre and micronutrients. However, in any regimen to reduce or control weight, particular attention should be given to ensuring that the reduced food intake is of high nutritional quality. A sensible way to follow an Atkins diet is to include plenty of the allowed fruits and vegetables, and to prefer food sources of unsaturated fat over those with saturated fat.

Malcolm D Riley PhD · John Coveney PhD

Guidelines from the National Health and Medical Research Council are now available A recent World Health Organization report on the burden of musculoskeletal conditions in 2002 noted that these were a major cause of morbidity throughout the world. While much of this burden of disease is due to chronic arthropathies such as rheumatoid arthritis and osteoarthritis, the commonest problems by far involve acute musculoskeletal pain in the back, neck and large joints. “Acute” is defined as duration of symptoms not exceeding 3 months. There is a perception that the management of acute musculoskeletal pain is poor, and mainly driven by individual experience, clinical consensus, and descriptive studies. The absence of an accessible and rigorous evidence base has led to variations in practice, unnecessary investigations and imaging, and inappropriate and ineffective treatments with their potential for increasing morbidity, and unnecessary costs. Key messages of the guidelines 1. Most acute musculoskeletal pain is non-specific, and serious causes are rare. 2. Patient history enables screening for features of serious conditions, but reliability and validity of individual features have low diagnostic significance. 3. Clinicians need to be alert for the development of fragility fractures in those aged over 60 presenting with thoracic pain. 4. Clinical signs detected during physical assessment need to be interpreted cautiously, as many tests lack reliability and validity. This is true in most of the acute conditions, including those of the shoulder, where many eponymous tests are performed to try to reach an accurate diagnosis. This is not necessary for effective management of most pain, but is important in identifying disorders likely to become chronic or to have a serious underlying cause. 5. Plain x-rays are not routinely recommended in acute conditions, as they are of limited diagnostic value. The exceptions are the “red flag” features (infection, fracture, tumour, aneurysm) signifying possible serious underlying abnormality. 6. Common findings (eg, osteoarthritic changes) occur in both symptomatic and asymptomatic patients and might not be the cause of pain. 7. Education about the limitations of x-rays and their risk is recommended. 8. Most acute conditions settle within 3 months, although a few persist with some disability and recurrence is not uncommon. In the case of shoulder pain, the 12-month recovery rate is only 60%. 9. Psychosocial and occupational factors appear to be associated with progression from acute to chronic pain and should be addressed early. 10. Although published data are limited, advice to remain active, providing an educational booklet and community-based exercise appear to be cost-effective first-line interventions for acute low back pain. 11. In acute neck pain, an exercise program at home appears as effective at 2 months and more effective at 2 years than institutional-based therapy. 12. There are no randomised controlled trials of manipulation therapy for acute neck pain. Adverse effects of manipulation are rare but potentially serious. Non-steroidal anti-inflammatory drugs (NSAIDs), transcutaneous electrical nerve stimulation, soft collars and similar treatments all lack Level I or II evidence for benefit. There is evidence of a moderate benefit of NSAIDs in acute shoulder pain over 4 weeks compared with placebo. 13. It is preferable to use terms such as “anterior knee pain” than attempting to be more specific in acute knee pain. Although lacking specificity, examination is important to exclude serious disorders. 14. Specific eccentric quadriceps strengthening exercises produce better outcomes in anterior and non-specific knee pain than standard exercises. Choosing best clinical practice in the care of acute musculoskeletal pain has been made easier with the recent release of guidelines for managing acute musculoskeletal pain by the National Health and Medical Research Council (NHMRC).1 Five multidisciplinary review groups were formed to address draft guidelines developed by the Australian Faculty of Musculoskeletal Medicine. The groups involved representatives from such diverse disciplines as general practice, rheumatology, orthopaedics, chiropractic, physiotherapy, pain medicine, rehabilitation, sports medicine and consumer groups. This wide representation was deliberate and aimed to minimise possible bias of different craft groups. The brief for each group was to formulate guidelines based on the best available evidence for management of acute musculoskeletal pain in the lower back, thoracic spine, the neck, shoulder or anterior aspect of the knee. The methods of the evidence review were based on NHMRC standards,2 and the Cochrane proposal of rationalisation of diagnostic and therapeutic intervention.3 Where no good evidence existed, consensus statements were made by a steering committee, or no recommendation was made, except to signal the need for research to gain appropriate data. For each site of pain, the guidelines provide information on diagnosis, prognosis and interventions. Three pertinent questions which arise from all the guidelines are discussed below. How can we use the guidelines? Management of patients with acute musculoskeletal pain has to be individualised, and tailored to patients’ response and compliance. This will obviously vary between patients and locations depending on resources and availability of services. However, the delineation of the treatment options in the NHMRC guidelines will improve knowledge and, it is to be hoped, enhance standards of care. As patients seeking help may find their condition altered by the diagnostic and therapeutic approach, and usually not for the better in a self-limiting, acute condition,4 the guidelines may also allow patients to rely on their own resources to cope with a disorder that is acute, but of short duration. Are the guidelines unique? Several evidence-based guidelines for the management of acute low back pain exist.5 However, the NHMRC acute musculoskeletal pain guidelines are the most extensive that are currently available for the problems they cover. In addition, the guidelines for acute low back pain have been assessed for safety, efficacy and cost effectiveness in a primary care setting.5 Compliance with the guidelines achieved marginally better symptomatic relief, resulting in less need for continuing care, achieved greater rates of full recovery, was less expensive, and attracted higher consumer satisfaction.5 How good is the evidence? This varies within each condition. Acute low back pain only has consensus statements (as opposed to any level of evidence) about effective communication. In the diagnosis, prognosis and intervention sections, the level of evidence ranges from Level I to Level IV. There is Level I and II evidence that oral and injectable non-steroidal anti-inflammatory drugs (NSAIDs) are no more effective than placebo or no treatment for acute low back pain. Heat-wrap therapy was more effective than NSAIDs, paracetamol or placebo in reducing pain in the first 3–4 days. This information alone could save the community considerable expense and morbidity. The main purpose of guidelines is to improve the quality of care for patients, but their existence does not guarantee their use in practice.6,7 Propagation of guidelines by publication or through special societies is a start, but more active strategies are needed to maximise the likelihood of the clinical guidelines becoming effective.8 Computer software would be most helpful for doctors in incorporating the NHMRC acute musculoskeletal pain guidelines into practice. As with all guidelines, the evidence base is unstable and will need to be regularly updated to remain useful. The remedy proposed by the Committee was that funding should be made available for an annual survey of the members of the steering and review committees to update the information, and for searches of the literature and electronic databases to determine the need for revision. Whether this will happen is not clear. We believe these guidelines are unique in their comprehensiveness, the rigour of evaluation of the evidence and the usefulness to the community as a whole. They also contain information sheets produced specifically for the public which are free of jargon and have simple explanations. The sheets summarise the benefits and minimise the harm of available options and should empower patients to make more informed choices and to consider their needs and priorities in selecting the best option.

Julien P de Jager FRACGP, FRACP · Michael J Ahern MD, FRACP

Patients with severe disease now have access to promising new drugs To have lived through a revolution, to have seen a new birth of science, a new dispensation of health . . . is not given to every generation. – William Osler (1913) Driven by evidence from well designed clinical trials, infliximab, a monoclonal antibody that targets tumour necrosis factor alpha (TNF-α), was recently listed on the Pharmaceutical Benefits Scheme (PBS) for treatment of ankylosing spondylitis.1 This is welcome news for patients with a disorder for which, until now, there have been few effective therapeutic options. Ankylosing spondylitis affects about 0.5%–1.0% of the population and typically begins between the ages of 15 and 40 years. It causes painful stiffness of the spine, progressive disability and loss of independence during the prime productive years. About 70% of patients go on to develop bony fusion of the spine, and the mortality rate for people with the condition is 1.5–4 times higher than that of the general population.2 To date, the treatment of ankylosing spondylitis has been unsatisfactory. Rheumatologists have combined physiotherapy and non-steroidal anti-inflammatory drugs, with the modest goal of relieving pain and stiffness, but such therapies do not alter the underlying disease process. Drugs that modify the disease process and prevent joint damage in rheumatoid arthritis (eg, corticosteroids, methotrexate and leflunomide) are of marginal benefit in ankylosing spondylitis. Randomised controlled trials have shown that sulfasalazine is of some benefit in ankylosing spondylitis, but only for peripheral joint involvement.3 Clearly, novel approaches for treating ankylosing spondylitis have been long overdue. Over the past decade, advances in basic medical research have seen the emergence of biological response modifiers that target critical mediators of the inflammatory response, such as TNF-α. Since August 2003, three biological agents that inhibit TNF-α have been listed on the PBS for severe rheumatoid arthritis: infliximab and adalimumab (monoclonal antibodies directed against TNF-α), and etanercept (a soluble receptor that acts as a “decoy receptor” for TNF-α). In 1995, it was recognised that TNF-α occurs in high concentrations in inflamed sacroiliac joints in patients with ankylosing spondylitis,4 thus identifying TNF-α as an important target for development of therapeutic agents. In the same year, international experts in ankylosing spondylitis established the Assessments in Ankylosing Spondylitis (ASAS) working group. This group included clinical epidemiologists, representatives of the pharmaceutical industry, and individuals with ankylosing spondylitis. The first goal of the ASAS group was to select and test the validity of a set of standardised clinical, serological and radiographic endpoints for clinical research and routine practice. Otherwise, rheumatologists were faced with the real possibility that new therapies would emerge from basic research but fail to find their rightful place in the treatment of patients with ankylosing spondylitis because the available tools to measure efficacy were too insensitive. By consensus, the following domains were selected to assess the efficacy of disease-controlling therapy: functional capacity, pain, spinal mobility, patient global assessment, spinal stiffness, peripheral joint swelling, erythrocyte sedimentation rate, spine and hip x-rays, fatigue and enthesitis (inflammation at sites of ligament, tendon or joint capsule insertion into bone).5 These endpoints are now used almost uniformly in studies of anti-TNF therapy in ankylosing spondylitis. Another outcome measure to emerge from the ASAS group was the “ASAS-20”, representing a 20% improvement in a composite score of efficacy.6 Recently, the group released a consensus statement for selection of appropriate candidates for treatment with anti-TNF therapy.7 This statement formed the basis of the current PBS restrictions on the use of infliximab in ankylosing spondylitis. Early data to emerge from uncontrolled studies of anti-TNF therapy in ankylosing spondylitis paved the way for randomised controlled trials. In a 3-month clinical trial, 18 of 34 patients (53%) treated with infliximab met the predefined response criterion, compared with 3 of 35 (9%) patients receiving placebo.8 There was significant improvement in almost all outcome measures, including quality-of-life and functional measures. These improvements persisted during an open-label extension study in which all participants were given infliximab for an additional 42 weeks.9 In the largest anti-TNF randomised controlled study to date, 277 patients with ankylosing spondylitis received either etanercept or placebo.10 At 24 weeks, 59% of the etanercept group and 28% of the placebo group met the ASAS-20 criteria for response. Although the mean disease duration among participants in the study was over 10 years, there were significant improvements in seemingly irreversible measures of spinal mobility. Anti-TNF therapy is not without risk. Importantly, most side effects of anti-TNF therapy did not emerge from randomised controlled trials but from post-marketing reports. Mild injection-site reactions occur in 10%–35% of patients using the subcutaneous formulations (etanercept and adalimumab), while infusion reactions can occur with the intravenous preparation (infliximab). The risk of reactivation of latent tuberculosis is well recognised. Thus, patients must be screened with a chest x-ray and Mantoux test before initiation of anti-TNF therapy. As TNF is important in preventing dissemination of intracellular organisms, anti-TNF therapy increases the risk of Aspergillus, Listeria and Cryptococcus infections, and live vaccinations are contraindicated. To date, post-marketing surveys have not shown an increase in risk of malignancy from anti-TNF therapy. There have been case reports of anti-TNF therapy being associated with autoimmune disorders, demyelination (optic neuritis and multiple sclerosis), exacerbation of cardiac failure, and abnormal liver function tests. However, the absolute risk of developing these complications after anti-TNF therapy is yet to be defined. In order to claim that anti-TNF therapy truly modifies the disease, researchers need to demonstrate that the treatment can slow down or prevent bony fusion and ankylosis. To date, this has not been achieved. A major limiting factor has been the requirement for study participants to demonstrate unequivocal radiographic evidence of sacroiliitis. As this is a late clinical feature of the disease, patients with early ankylosing spondylitis have been excluded from anti-TNF studies. Yet it is this cohort that is most likely to respond to anti-TNF therapy and in whom disease modification may be most readily apparent. Recently, a novel algorithm-based protocol for identifying patients with early ankylosing spondylitis in general practice recommended magnetic resonance imaging of sacroiliac joints for all people with inflammatory back pain and HLA-B27 positivity.11 Anti-TNF therapy has revolutionised the way in which we think about ankylosing spondylitis. By approving anti-TNF therapy for people with severe ankylosing spondylitis, the PBS has allowed clinical investigators in Australia to remain at the front line of this revolution.

Lionel Schachna MB BS, FRACP, PhD

An important Australian initiative that sets an international precedent We’ve got major problems at a really early age . . . to do these elderly health assessments, are they going to dig us up? We’re dead and buried by then. We might as well set up a clinic next to the cemetery.1 These poignant words were spoken by Dr Puggy Hunter, recipient of the Human Rights and Equal Opportunity Commission’s Human Rights Medal in 2001 and former Chair of the National Aboriginal Community Controlled Health Organisation (NACCHO), who passed away at the age of 50 years in 2001. He made these observations after the federal government’s launch of the Enhanced Primary Care Package in November 1999. Among other things, the package was designed to assist general practitioners to provide preventive care for Australians over the age of 75 years through Medicare Benefits Schedule rebates. For Aboriginal or Torres Strait Islander people the age limit was lowered to over 55 years.2 As 53% of Aboriginal men and 41% of Aboriginal women die before reaching the age of 50 years,3 representatives from NACCHO,4 general practice groups and the Australian Medical Association expressed concern that relatively few Aboriginal people would benefit from these rebates. Moreover, an evaluation in 2003 found that few Aboriginal and Torres Strait Islander people over 55 years had accessed the Enhanced Primary Care rebates.5 In this population, preventive health assessments are obviously needed earlier, given the occurrence of preventable chronic disease at younger ages and higher rates than in other Australians.6 Preventive healthcare can both reduce costs to the health sector and enhance health equity for Aboriginal peoples and Torres Strait Islanders, as most of the factors underpinning health disparities relate to social disadvantage (Box). For example, if renal disease is detected early, end-stage renal failure can be avoided and treatment will reduce mortality by 50%.12 However, during 1997–2002, Aboriginal and Torres Strait Islander Australians (compared with non-Indigenous Australians) were twice as likely to be referred late for dialysis treatment. (Late referral is defined as first attending a renal unit or being seen by a nephrologist less than 3 months before the initiation of dialysis.) In the intervening years, NACCHO has lobbied hard for the Medicare Benefits Schedule to make preventive health checks accessible to younger Aboriginal people.4 On 5 May 2004, the Federal Minister for Health launched a new Medicare Benefits Schedule rebate for an adult health check of Aboriginal and Torres Strait Islander people aged 15–54 years (Item 710).13 The challenge now is for GPs to make use of this rebate. Firstly, they need to understand what comprises an effective preventive health assessment for this population. In 2001, NACCHO led an alliance of eight non-government organisations — the Chronic Disease Alliance — to undertake a review of the evidence for preventive interventions, with the support of the Royal Australian College of General Practitioners and the Australian Government Department of Health and Ageing. The outcome — The national guide to a preventive health assessment in Aboriginal and Torres Strait Islander peoples — was completed in 2004,6 and a pilot study has been conducted with over 40 GPs. The guide lists a range of health problems and risk factors that are amenable to prevention, and supplements the “red book” of the Royal Australian College of General Practitioners.14 It takes into consideration the differing demographic and epidemiological factors that influence the development of disease in Aboriginal and Torres Strait Islander populations and was the basis for the descriptor for the new rebate. Secondly, changing practice to align with the evidence requires more than guidelines. Multifaceted strategies are needed, including decision-support systems, clinical audit, feedback, and support from opinion leaders.15 A health system that relies on free market provision of preventive healthcare can perpetuate inequity, as those who need the interventions are least able to afford and access the provisions. Proactive encouragement of preventive health assessments requires incentives and penalties, as well as removal of administrative and legislative barriers. Even with the rebate, implementing adult health checks in general practice may not be easy. According to 2001–02 data from the BEACH study (Bettering the Evaluation And Care of Health), at least 70% of GPs in Australia have, to their knowledge, not provided care for a single Aboriginal or Torres Strait Islander person in that period.8,9 Thus, changing practice to maximise the uptake of adult health checks for this population will require a range of supportive activities, such as: Distributing the guide to every GP; Promoting a suite of resources to assist GPs to better identify Aboriginal or Torres Strait Islander people and to improve cross-cultural communication;13 Developing ancillary resources such as case studies; Upskilling GPs using the expertise of Aboriginal community-controlled health services through coordinator positions established within NACCHO affiliates; Enhancing and supporting the role of Aboriginal health workers; Developing a communication strategy for the broader Aboriginal and Torres Strait Islander population to increase the demand for adult health checks;8,10 and Introducing clinical audit points for professional development. Bulk-billing for these assessments is critically important given the significant socioeconomic disparity between Aboriginal and Torres Strait Islander people and the broader Australian population.16 Mechanisms for improving access to medications under the Pharmaceutical Benefits Scheme for Aboriginals and Torres Strait Islanders are also required. This has been proposed by the Australian Pharmaceutical Advisory Council, NACCHO, the AMA and the Pharmacy Guild in a series of new reforms.17 2004 is the final year of the United Nations International Decade of the World’s Indigenous Peoples, and the development of this Medicare Benefits Schedule rebate removes a significant cost barrier from the delivery of preventive healthcare to Australian Indigenous people. The adult health check is an important Australian initiative that sets an international precedent. A total of 1977 services were claimed against Item 710 (Health Insurance Commission data18) from May to August 2004. This appears slower than the initial claim rate of elderly health assessment items (Enhanced Primary Care) for which an extensive implementation strategy was funded by the government. It is now time to finance an appropriate implementation strategy for the adult health check. General practice groups, including Divisions, should assist GPs to use the new adult health-check rebate for the identification and timely management of unrecognised health problems among Aboriginal and Torres Strait Islander Australians — the populations in which this is most urgently needed. Justification for a Medicare Benefits Schedule rebate for adult health checks for the Aboriginal and Torres Strait Islander population Aboriginal people and Torres Strait Islanders: have lower participation rates in preventive health programs (eg, cervical screening and breast cancer detection).7 have high rates of undetected risk factors and chronic disease.6 are referred late for end-stage disease, making treatment options more expensive (eg, if renal failure develops).6 are less likely to ask for preventive health assessments (significantly lower rates of requests for check-ups).8 have unequal access to Medicare (rate of use of the Medicare Benefits Schedule by Aboriginal people and Torres Strait Islanders is less than half that of other Australians, yet their overall health needs are about three times greater).9 General practitioners: miss opportunities for prevention (eg, significantly lower rates of vaccination by GPs in encounters with Aboriginal and Torres Strait Islander people10), leading to higher rates of hospital admissions for preventable diseases.11 find the preventive assessment process complex (comorbidity, sociocultural considerations).6 experience difficulties in delivering preventive healthcare to the Aboriginal and Torres Strait Islander population (inadequate remuneration for the time required, lack of knowledge of relevant health issues and inability to identify Indigenous Australians).6

Naomi R Mayers · Sophie Couzos MPH

Increasingly, the NHS is dependent on overseas-trained health professionals The British are past masters at harnessing the energy of their Anglo-Celtic offshoots. The names of the battles on the tombstones of returned servicemen interred in the cemetery in Halifax, Nova Scotia, are very familiar to any Australian with some knowledge of the Western Front of 1914–1918. And in the Commonwealth War Cemetery in Kraków, Poland, Australians, New Zealanders, South Africans and Canadians lie side by side, linked in death, so very far from the sunburnt country, the long white cloud, the burnt-brown veldt or the rolling prairie. Britain has been habitually suspicious, even untrusting, of the quality of [overseas] medical degrees . . . Today, Australians, New Zealanders, South Africans, and occasionally Canadians, continue to serve side by side as doctors, nurses and other health professionals in the United Kingdom’s modern, dependable National Health Service. They are renowned for their energy, excellence of care, and exuberant intolerance of persisting with the old, outmoded UK approaches, justified only by “that is the way things are done here”. Partly, this is a result of selection bias — those who come to the UK want to see the world, to see how things are done elsewhere, and to challenge this and themselves — and partly it is the lazy monolinguality of many native English-speakers, the air routes (and the shipping routes before them) that terminate in London, and the reciprocity of recognition of basic qualifications in the relevant professions. However, the greeting extended here to “foreigners”, even white, English-speaking foreigners from far-flung corners of the former Empire, is paradoxically patchy. Australians are welcome to pay taxes, and even to vote. They are happily accepted as lecturers and tutors of home-grown doctors for the NHS, but those without patriality (at least one grandparent born in the UK) or “indefinite leave to remain” will have considerable difficulty obtaining a mortgage. In other words, you are free to cure our sick, pay into our public purse, teach our children and participate in our parliamentary process, but we do not guarantee that you will be allowed to own the roof over your head. “Foreign”, of course, has connotations of the unfamiliar, even the unnatural, and certainly something against which a hostile immunological response should normally be raised. Like Australia, Britain has been habitually suspicious, even untrusting, of the quality of medical degrees obtained in countries that were not part of the former British Empire. Even Commonwealth countries can be problematic if their inhabitants are not white. On the one hand, there are reasons for having a single, demanding standard applied uniformly to all, even if that arrangement does oblige highly specialised, very experienced practitioners to go back and learn their general medicine all over again. On the other hand, in the big British cities, there are large populations of refugees and asylum-seekers, for whom the languages, cultures and endemic medical problems of their places of origin are completely unknown to practitioners trained in comfortable countries at high latitudes. Dealing with these patients is extraordinarily time-consuming, not just because of their different backgrounds, but also because of the continuing medical and psychological consequences of events surrounding their leaving their homelands and the ongoing economic, social and legal disconnection experienced after their arrival. Only recently have pilot schemes begun that allow overseas-qualified health professionals (including doctors) in these communities limited rights of practice, under supervision, to help alleviate their compatriots’ burdens. A number of people in the UK are now raising the issue of the dependence of the NHS on overseas-trained health professionals and the detrimental consequences for the source countries. Many of the suppliers of this workforce are low- to middle-income nations that can ill-afford to lose significant numbers of their graduates. The NHS is also a source of emigrants as well as a mecca for immigrants. Remote Australia has its fair share of British graduates manning the medical frontiers — one British practitioner in rural Western Australia famously evacuated an extradural haemorrhage using a brace-and-bit borrowed from the local carpenter and guided telephonically by a neurosurgeon in Perth. But, however interesting these individuals and their experiences, they tend to be itinerants who ultimately return to the “Mother Country” (just as most Antipodeans here eventually return to their “dominions of origin”). This pattern differs sharply from the sizeable cohort whose opposition to the creation of the NHS, in the late 1940s, was sufficiently strong that they “upped stumps” and moved permanently to less socialist settings in the English-speaking world, including Australia and New Zealand. Arguably, one result of this efflux has been a significant and lasting divide between the internal medicopolitical cultures of the NHS and the Australian healthcare system. Although acrimonious occasionally, and feeling disgruntled and downtrodden for much of the rest of the time, most of the medical profession in the UK openly supports a system that is almost always free at the point of care and in which every citizen and most residents have been nominally tied to a single general practitioner. This is the paradigm (and attitudes) that we see passed down to our British students and withstanding the test of time. Beyond the commonality of the GP as gatekeeper to specialist services, Australia’s healthcare system has long had higher levels of entrepreneurialism and market forces, and the publications of medical organisations that reach us here in the UK are forever reporting clashes with governments. A little reflection reveals that the young, pre-Thatcherite émigrés of 1948 would have been at the peak of their medical and political powers when the Whitlam government wanted to introduce Medibank in 1974. They were as trenchant in their opposition to what they saw as the intrusion of government into the sanctity of the doctor–patient relationship in Australia in the 1970s as they had been in Britain in the 1940s, perhaps kindling, or certainly entrenching, a tradition of energetic awkwardness that has bred true in every succeeding generation of Australian practitioners. Both the UK and Australia are the more interesting, then, for the consequences of their medical slave-trades.

Konrad Jamrozik DPhil, FAFPHM, MFPH · David P Weller MPH, PhD, FRACGP, FAFPHM · Richard F Heller MD, FRCP, FRACP, FAFPHM

Objective: To assess effectiveness and side effects of thiazolidinediones (TZDs) as adjunctive therapy in suboptimally controlled patients with type 2 diabetes.Design and setting: Review of a prospectively recorded database at the Royal Melbourne Hospital diabetes clinic.Participants: 203 patients with type 2 diabetes who received pioglitazone or rosiglitazone between 1 May 2000 and 31 October 2002.Outcome measures: Response in glycohaemoglobin (HbA1c) level, lipid profile changes and side effects, including hypoglycaemia, weight gain, oedema and precipitation of cardiac failure.Results: Both pioglitazone and rosiglitazone improved glycaemic control, with a reduction in the HbA1c level of 1.02% (range, 0.85%–1.19%) and 0.96% (range, 0.81%–1.11%), respectively, in the first 6 months of therapy. Rosiglitazone was associated with a 0.45 mmol (range, 0.31–0.59 mmol) increase in cholesterol level and 0.99 mmol (range, 0.60–1.38 mmol) increase in triglyceride level, while pioglitazone was associated with insignificant declines in cholesterol and triglyceride levels. There was reduced requirement for insulin, but not for oral hypoglycaemic agent (OHA), in most patients who used these agents. Pioglitazone and rosiglitazone were associated with increased rates of hypoglycaemia (17% and 11% of patients, respectively), significant weight gain (48% and 58%) and oedema (33% and 21%). There were four cases of acute left ventricular failure and two cases of reversible liver dysfunction in patients treated with TZDs.Conclusions: Adding pioglitazone or rosiglitazone therapy to OHA or insulin in patients with type 2 diabetes significantly improved glycaemic control. However, the use of these drugs in routine clinical practice was associated with more frequent adverse events than previously reported in clinical trials.

Zanariah Hussein MB BS · John M Wentworth MB BS, PhD · Alison J Nankervis MD, FRACP · Joseph Proietto FRACP, PhD · Peter G Colman FRACP, MD

Objective: To determine whether mental illness is associated with accessibility and remoteness.Design: A cross-sectional, population-based, computer-assisted telephone interview survey, stratified by Accessibility and Remoteness Index of Australia (ARIA) categories.Setting: Secondary analysis of data collected from 2545 South Australian adults in October and November 2000.Outcome measures: Psychological distress and depression as determined by the Kessler 10 Psychological Distress Scale, the SF-12 measure of health status, and self-reported mental illness diagnosed by a doctor in the previous 12 months.Results: Overall, mental illness prevalence estimates were similar using the three measures of psychological distress (10.5%), clinical depression (12.9%) and self-reported mental health problem (12.7%). For each measure, there was no statistically significant variation in prevalence across ARIA categories, except for a lower than expected prevalence of depression (7.7%) in the “accessible” category. There was no trend suggesting higher levels of mental illness among residents of rural and remote regions.Conclusions: The prevalence rates of psychological distress, depression and self-reported mental illness are high. However, we found no evidence that the prevalence of these conditions varies substantially across ARIA categories in South Australia. This finding may challenge existing stereotypes about higher levels of mental illness outside metropolitan Australia.

Kerena A Eckert MPH · Anne W Taylor BA, MPH · Graeme R Tucker BSc · David D Wilkinson MB ChB, DSc

Psychotic illness and its treatment are associated with an increased rate of diabetes and worsening blood sugar control. The newer, second-generation antipsychotic agents are more likely to produce this effect than the first-generation agents, but both contribute to the problem. The effect is usually related to insulin resistance through weight gain, but other mechanisms may exist. Diabetic ketoacidosis is rare. Management of psychosis takes priority over concerns about the potential metabolic sequelae of treatment, but the prevalence of the latter requires that all patients taking antipsychotic agents be actively screened and treated. Patients treated with antipsychotic agents need baseline and regular checks, including weight, blood glucose and lipid levels and blood pressure. Management of psychosis with its attendant medical problems requires a multidisciplinary approach, with primary health practitioners playing a central role. Mortality and medical morbidity is higher in those with psychosis than expected; preventive measures, combined with early detection and treatment of hyperglycaemia and other metabolic problems, is a key public health issue.

Tim J R Lambert BSc, FRANZCP · Leon H Chapman FRACP

The emergence and spread of multidrug-resistant pathogens has increased substantially over the past 20 years. Over the same period, the development of new antibiotics has decreased alarmingly, with many pharmaceutical companies pulling out of antibiotic research in favour of developing “lifestyle” drugs. Reasons given for withdrawing from antibiotic development include poor “net present value” status of antibiotics, changes in regulations requiring larger drug trials and prolonged post-marketing surveillance, clinical preference for narrow-spectrum rather than broad-spectrum agents, and high new-drug purchase costs. Major improvements in infection control in Australia are needed to prevent further spread of resistant clones, buying some time to develop urgently needed new antibiotic agents. Perpetuating a culture of “pharma bashing” will simply lead to more pharmaceutical companies withdrawing from the market. A change in the health and research culture is needed to improve cooperation between public, academic and private sectors.

Patrick G P Charles MB BS, FRACP · M Lindsay Grayson MD, FRACP, FAFPHM

We present a rare case of spontaneous intramural oesophageal perforation after the rapid ingestion of a cold carbonated beverage. A previously well patient presented with sudden onset of severe retrosternal pain associated with pain on swallowing. A contrast computed tomography scan and gastroscopy confirmed the diagnosis. With the widespread popular practice of drinking cold carbonated beverages, especially during the summer season, clinicians should be aware of this possible serious complication. Clinical recordA 57-year-old woman presented to the emergency department with retrosternal chest pain of sudden onset immediately after the isolated intake of a large mouthful of cold carbonated beverage directly from the bottle. The initial severe pain led to a brief loss of consciousness. The pain was continuous, exacerbated by swallowing, and accompanied by mild nausea, but no vomiting. She was previously a fit, healthy woman with no past medical history relevant to the case. She was febrile (37.6oC) and distressed by the pain. Examination was normal except for epigastric tenderness with retrosternal radiation. There were no signs of peritonism. The only abnormality in the patient’s blood tests was a mildly elevated white cell count of 11.7 3 109/L (reference range, 4.0–11.0 3 109 cells/L). An electrocardiogram and chest x-ray were normal. These initial investigations ruled out a cardiovascular condition, spontaneous pneumothorax, peptic ulcer disease and pancreatitis. The differential diagnosis was oesophageal pathology, including perforation. A computed tomography (CT) scan of the thorax showed a tiny bubble of gas either within the wall of the oesophagus or just adjacent to it in the middle mediastinum (this did not definitively exclude a full perforation of the oesophagus). The patient was admitted and managed with nil by mouth, intravenous fluids, triple intravenous antibiotic therapy (ampicillin 1 g four times a day, gentamicin 5 mg/kg daily [with subsequent doses titrated according to drug level], metronidazole 500 mg twice a day), intravenous omeprazole 40 mg three times a day, and frequent observation. Her fever resolved within 24 hours, but her C-reactive protein level rose to 18.2 mg/L (reference range, 0–8.0 mg/L). A second CT scan, with water-soluble contrast, showed intramural contrast with no extravasation, consistent with a partial perforation of the oesophagus (Box 1). Gastroscopy revealed a 10 cm longitudinal mucosal/submucosal tear in the left posterolateral wall of the oesophagus 3 cm above the gastro-oesophageal junction (Box 2A), and a small sliding hiatus hernia. The rest of the oesophagus, stomach and duodenum were normal. The patient’s symptoms improved with conservative treatment. She started clear fluids on Day 4, progressed to a soft diet, and was discharged on Day 7 with a prescription for oral omeprazole 40 mg daily. After 4 weeks, she still had occasional mild discomfort on swallowing. A repeat gastroscopy showed the healed scar of the tear, with no evidence of stricturing (Box 2B). Gastroscopy also revealed uncoordinated peristalsis of the oesophagus, but video fluoroscopy excluded dysmotility. DiscussionSpontaneous oesophageal perforation (Boerhaave’s syndrome) was first described by the Dutch physician Hermann Boerhaave in 1724.1 The classical presentation follows forceful vomiting. Boerhaave’s syndrome is a form of barogenic rupture caused by a rapid rise in intraluminal pressure when there is sudden distension of the oesophagus in a closed space.2-4 In this case, we postulate that the rapid ingestion of the cold beverage led to spasm of the distal oesophagus followed by effervescent expansion, resulting in a sudden build-up of intra-oesophageal pressure. A similar case, in which a healthy 67-year-old man sustained two oesophageal tears after rapidly ingesting a cold Alka-Seltzer beverage, has been reported by Oriscello and Mahal.5 The vast majority of perforations occur in the left lateral wall of the distal oesophagus, 3–6 cm above the gastro-oesophageal junction, as this part is particularly weak.2,3 Although Boerhaave’s syndrome is relatively uncommon, it is a serious disorder. Weakening of the oesophageal wall (in conditions such as reflux oesophagitis, infectious oesophagitis, Barrett’s ulceration, benign stricture, oesophageal carcinoma, dysmotility and neurogenic abnormalities) predisposes to this syndrome.4,6 Among people who experience complete perforation, mortality is 13%–25% if treated within 24 hours of symptom onset, 33%–65% if treated 24–48 hours after onset, and 89% if treated after more than 48 hours.3,6 The clinical features of Boerhaave’s syndrome range from a subtle presentation to cardiovascular collapse. Complications include septicaemia and shock.2,4,7 The most common symptom is retrosternal chest pain. Associated symptoms include dysphagia, odynophagia, pleuritic chest pain and dyspnoea.2 Examination reveals fever in 50% of patients, subcutaneous emphysema in up to 60%, and the Hamman’s sign of pneumomediastinum in 20% (ie, a crunching sound with each heartbeat).2 Pneumothorax and pleural effusion are more likely to be revealed on investigation than on physical examination. Blood tests are usually normal, apart from leukocytosis in up to 85% of patients.2 An erect chest x-ray may show subcutaneous emphysema, pneumomediastinum, mediastinal widening, mediastinal air–fluid levels, pleural effusion, pneumothorax and/or hydropneumothorax.4,6 However, a chest x-ray is normal in 12%–33% of patients.6 With a high suspicion of oesophageal rupture, an oesophagram with water-soluble contrast should be requested, with progression to barium if the former is negative. However, contrast studies can have false negative results in more than 10% of patients.6,7 A CT scan may show pneumomediastinum, abscess cavities adjacent to the oesophagus, or an actual communication between the air-filled oesophagus and an adjacent mediastinal or paramediastinal air–fluid collection.4,7 Gastroscopy can be diagnostic, but should not be performed routinely, as it can increase the size of the rupture.3,7 If a pleural effusion is present, aspiration by thoracocentesis may show food particles and squamous cells from saliva. The aspirated fluid may have pH < 6 and a high amylase content.6,7 Conservative management can be tried in patients with intramural tears or stable transmural ruptures. Otherwise, surgical treatment should be sought.6 The case we describe here is typical of Boerhaave’s syndrome with partial perforation in terms of the presentation of retrosternal chest pain, odynophagia, fever, leukocytosis and normal chest x-ray, but unusual in its association with carbonated beverage ingestion rather than vomiting. In cases like this, it remains vital to conduct further investigations to rule out a full perforation, for which the presentation may be similar but the outcome rapidly fatal. The role of gastroscopy is controversial, but we chose in this case to use a gentle procedure to confirm the diagnosis. 1 Contrast computed tomography scan of the thorax The scan shows intramural contrast in the oesophagus (arrow) with no extravasation. 2 Gastroscopic images of the oesophagus A: Initial gastroscopy revealed a 10 cm tear in the left posterolateral wall. B: Healed scar of the tear after 4 weeks.

Hui Jern Loh MB BS (Hons) · David A P Cooke MS, FRCSE, FRCS

Trial: Hatakka K, Savilahti E, Pönkä A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ 2001; 322: 1327-1329. QuestionIn children attending daycare centres (population), does long term consumption of probiotic milk (intervention) prevent infections (outcome)? Trial detailsObjective: To examine whether long term consumption of a probiotic milk could reduce gastrointestinal and respiratory infections in children in daycare centres. Design: Randomised, double-blind, placebo-controlled study over 7 months. Setting: 18 daycare centres in Helsinki, Finland. Participants: 571 healthy children aged 1–6 years; 282 in the intervention group (mean age, 4.6 years; SD, 1.5 years) and 289 in the control group (mean age, 4.4 years; SD, 1.5 years). Intervention: Milk with or without Lactobacillus GG. Average daily consumption of milk in both groups was 260 mL. Main outcome measures: Number of days with respiratory and gastrointestinal symptoms, absences from daycare because of illness, respiratory tract infections diagnosed by a doctor, and courses of antibiotics. Results: Children in the Lactobacillus group had fewer days of absence from daycare because of illness (4.9 days [95% CI, 4.4–5.5] versus 5.8 days [95% CI, 5.3–6.4]; absolute difference, 16% [P = 0.03]). Corresponding age-adjusted findings were 5.1 days (95% CI, 4.6–5.6) for the Lactobacillus group versus 5.7 days (95% CI, 5.2–6.3) for the control group; age-adjusted difference, 11% (P = 0.09). There was also a relative reduction of 17% in the number of children having respiratory infections with complications and lower respiratory tract infections (unadjusted absolute reduction, 8.6%; 95% CI, -17.2% to -0.1%; P = 0.05; age-adjusted odds ratio, 0.75; 95% CI, 0.52–1.09; P = 0.13) and a 19% relative reduction in courses of antibiotic for respiratory infection in the Lactobacillus group (unadjusted absolute reduction, -9.6%; 95% CI, -18.2 to -1.0; P = 0.03; adjusted odds ratio, 0.72; 95% CI, 0.50–1.03; P = 0.08). Conclusions: Lactobacillus GG may reduce respiratory infections and their severity among children in daycare. The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction. CommentaryRationale for the trialChildren attending daycare centres are more likely to suffer gastrointestinal and respiratory infections than children cared for at home or in small family groups.1 There are public health and economic consequences, including direct medical costs and the indirect cost of parents taking time off work to care for sick children.2 Studies support the use of probiotics to reduce the incidence of antibiotic-associated diarrhoea3,4 and to hasten recovery from rotavirus diarrhoea.5 Probiotic bacteria may have a beneficial effect on the host immune response by altering intestinal microbial balance. Trial methodsThis was a randomised, double-blind, placebo-controlled trial carried out in 18 daycare centres in children aged 1–6 years over 7 months, which included winter. Daycare staff, parents, children and investigators were blinded or unaware of treatment allocation. Randomisation was effectively concealed, as children were allocated to intervention or control groups by a computer-generated block-randomisation procedure, with stratification on the basis of age and daycare centre. The randomisation procedure was successful in equalising baseline characteristics between placebo and active groups, apart from the control group having slightly younger children and more children with more than five recent infections. There was excellent follow-up, with nearly 90% of children completing the study, although reasons for withdrawal were not stated. Groups were analysed on an intention-to-treat basis. A random selection of 100 faecal samples was assessed to confirm compliance. Outcome measures included days of respiratory or gastrointestinal symptoms, days of absence from daycare because of illness, and number of upper respiratory tract infections complicated by lower respiratory tract infections. In summary, this trial was well designed and conducted. The average compliance in both groups was 60%. Unfortunately, there was a difference in age distribution between the two groups after randomisation. The investigators decided before the study that a minimum clinically relevant beneficial effect would be a 20% difference between the groups. Thus, based on previously reported episodes of illness in children attending daycare, they used a power calculation to estimate that, to detect a 20% difference with a power (or sensitivity) of 90% with 95% confidence, they needed to enrol 250 children per group. They were able to achieve this goal. New informationThe authors claim that milk containing Lactobacillus GG slightly reduced the incidence of respiratory infections and antibiotic treatment in children. The effect of probiotics was modest when adjustments were made for age. Of the measured variables — days of any illness, days of respiratory or gastrointestinal symptoms, and absence because of illness — only for absence because of illness was there a difference between the intervention and control groups that approached statistical significance, although there was a trend towards less illness for the other variables in the Lactobacillus group. It is useful to look at the tables of results in the article in question. Table 2 presents the raw data, and it is clear from scanning both the unadjusted and age-adjusted results that the effect is modest at best. The unadjusted days of absence because of illness was 4.9 days in the probiotic group and 5.8 days in the control group (ie, an improvement of 0.9 days); when adjusted for age, the difference between the probiotic group and the control group was 0.6 days. This raises the question of whether a reduction of 0.6 days in duration of absence because of illness is actually clinically useful. When the episodes of illness were diagnosed by a doctor (Table 3 of the article), the overall episodes of illness and courses of antibiotics prescribed for infections were significantly reduced for the probiotic group. Of all antibiotic courses prescribed, there were 119 in the probiotic group versus 144 in the control group, with an absolute percentage reduction of 8.0% (95%CI, -16.6 to 1.0). The P value was 0.07, thus approaching, but not reaching, statistical significance. However, the age-adjusted results (reported as odds ratios) are less impressive and the statistical significance of these findings is further reduced, with a 95% confidence interval crossing unity, and a P value of 0.17 — not significant. The results are thus entirely consistent with a chance difference. Implications for clinical practice This is the first large, high quality study to examine this interesting research question.6 There were no reported harmful effects of the Lactobacillus GG; costs were not fully explored in the report. The author of the accompanying editorial stated that probiotics “show promise but bigger studies are needed”.7 This is not entirely correct, as the study was adequately powered to detect a 20% difference and it failed to report a convincing clinical effect. However, it is likely that further clinical research will be undertaken in this and related areas, such as the use of probiotics to hasten recovery from acute gastroenteritis in children and the prevention of antibiotic-associated diarrhoea.

Mark G Coulthard MB BS, FRACP · Craig M Mellis MD, MPH, FRACP

Randomised controlled trials should be the basis for developing clinical guidelines and for decisions about individual patient management. They should also inform public health policy. However, their capacity to fulfil these roles will depend on how closely a trial’s participants reflect the general population of patients with the disorder that has been investigated. The extent to which a trial’s findings are relevant to the broader population of patients with the disorder is referred to as the trial’s generalisability, or external validity. The CONSORT statement refers to generalisability under Item 21 (Box 1).1 Well-written reports should discuss the various factors that influence the generalisability of the trial’s findings. Julian and Pocock have proposed a checklist of questions to assist with this assessment (see Box 2).2 To determine the generalisability of a trial’s findings, several aspects require scrutiny. Is the patient population representative of the broad target group?To make this assessment, it is firstly necessary to examine the inclusion and exclusion criteria for the trial. These criteria determine the characteristics of the potential participants. They are particularly important for trials assessing new drugs, because patients with any significant degree of renal or hepatic impairment, or any significant comorbidity, are often excluded. Excluding such participants may result in a trial population that represents only a subsection of the broader population with the disorder for which the drug may be indicated. Secondly, the baseline data should describe the population that participated in the trial. Demographic variables, age range, as well as clinical data such as blood pressure, staging of disease and any listed comorbidities, will help readers decide whether the trial population closely resembles the patient population (or individual patient) for which a decision about management is required. In some trials, the entry criteria are considerably broader than the population actually recruited. This discrepancy will only be evident if adequate baseline data are presented. For example, in a study of combination chemotherapy in malignant breast cancer, no radiotherapy was allowed in the protocol.3 Results were reported on the basis of the extent of lymph node involvement — 0–3 nodes or 4 or more — and readers might assume that the findings of the trial would apply to participants with many (more than 10) involved nodes. However, less than 8% of patients with more than 10 involved nodes were included in the study, as clinicians referred these higher-risk patients for radiotherapy rather than enrolling them in the trial.4 The original trial report did not tell readers that the group with more than 4 involved nodes actually comprised patients with primarily 4 to 10 involved nodes.5 Participant flow diagramThese diagrams are useful for assessing generalisability of trials. If properly completed, flow diagrams will indicate the number of participants: screened for participation; with the condition of interest; classed as ineligible (on the basis of exclusion criteria); and who did not elect to participate. If the population randomly allocated to groups within the trial represents only a small proportion of those with the condition of interest and assessed for eligibility, it is probable that the generalisability of the findings of the study will be limited. Large trials assessing warfarin therapy for atrial fibrillation have enrolled only about 15% of those who were potentially eligible, and this substantially limits the generalisability of their results.6,7 Where eligible patients who entered randomised trials have been compared with those who were eligible but did not participate, differences have emerged. In a study of therapy for temporomandibular disorders, 18 eligible patients did not consent and 60 were randomly allocated to trial arms.8 The 18 patients who did not consent reported more pain than those who participated, perhaps restricting the findings of the trial to those with milder pain. Differences were also evident between enrolled and unenrolled patients in the Thrombolysis in Myocardial Infarction (TIMI 9) trial.9 The TIMI 9 registry prospectively evaluated patients with ST-segment-elevation myocardial infarction. There were no exclusion criteria for the registry, but there were exclusion criteria for the randomised trial. Patients in the registry, but not enrolled in the trial, had higher baseline risk for adverse outcomes. Screening logsScreening logs list the numbers of individuals screened, eligible and enrolled, as well as reasons for not enrolling eligible patients. They thus allow readers to judge whether there are differences between patients who were and were not enrolled in the trial. If the two populations are similar, the generalisability of the trial is increased. A template of the typical information collected in the screening log is presented in Box 3. This information should be limited to the most important characteristics of the relevant population to minimise the burden on trial staff collecting the data. Screening logs also describe the range of participants with the disease being seen at each investigation site, and the patterns of care of these people. For those deemed ineligible, the criteria excluding them from the study are documented, providing further information as to the generalisability of the intervention to this cohort.10 The results of the study will apply more to subjects excluded because they were not available for follow-up or were just outside the age range than to those with concomitant disease. ComorbiditiesIn some trials, during random allocation, patients may be stratified by comorbidities regarded as potential confounders. In others, particularly in clinical trials of new drugs, comorbidities may be exclusion criteria. If these comorbidities are relatively common, the exclusion criteria will significantly limit the generalisability of the trial outcomes. This is an important issue in drug trials, as comorbidities are often exclusion criteria. When the drug is registered for use, the listed indication is often relatively broad, so it is necessary to scrutinise the clinical trials section of the product information to obtain a clearer picture of the patient population which was studied. If a patient for whom the drug is being considered has one of the comorbidities which was an exclusion criterion, whether the drug will be efficacious or safe is unknown. Such a dilemma exists with the “statin” lipid-lowering drugs. Over 160 000 patients have participated in trials of statins, but almost all of these trials have excluded patients with significant renal or hepatic disease.11-13 If some patients have characteristics which were not reported in the trial’s population, it is conceivable that the trial’s results are not relevant to these patients. Subgroup analysesAs adolescents and pregnant women are not usually included in trials, most clinical trials are of limited relevance to these groups. If there are a priori reasons to expect differences between subgroups, the trial may have stratified participants by these potential confounders. The findings of the trial will be most generalisable if the benefits are evident in each subgroup of the trial, as well as across the entire study population.14 In clinical trials with large numbers of patients or events, it is possible to have reliable subgroup analyses which may help prescribers to relate the trial’s findings more closely to patients for whom they are trying to select appropriate therapies. ConclusionsThe main purpose of conducting randomised clinical trials is to identify improvements in clinical care. Ideally, the findings of trials should apply to a wider population than those included in the trial. It is therefore vital that every effort is made to have a broad selection of patients from the population of interest to minimise selection bias. Numerous exclusion criteria will restrict the patient population and progressively diminish the generalisability of the findings of the intervention under evaluation. It is the responsibility of those reporting trials to include aspects of generalisability when discussing their findings. It is the task of those responsible for treating patients, producing clinical guidelines and formulating public health policy to carefully assess the generalisability of clinical trials before applying their findings.15 1 CONSORT checklist of items to report when reporting a randomised trial.1 Section and topic Item no. Descriptor Discussion Generalisability 21 Generalisability (external validity) of the trial findings. 2 Concepts covered in Julian and Pocock’s criteria for assessing generalisability2 Representativeness of patients for the condition in practice. Proportion of eligible patients participating. Conformity of the treatments and background care (doses, durations, follow-up period, etc) to standard practice patterns. Consistency of measured outcomes with conclusions drawn. Appropriate balance of surrogate and clinical outcomes. Reliability of evidence on efficacy and safety findings. Coverage of all relevant outcomes (adverse events and side-effects). Consideration of the study findings in the context of other available evidence. 3 Screening log template Site identification/name: ______________________________________ Date of visit: __________________________________________ Subject initials: ____________ Clinician initials: ____________ Age: ____________ Sex: ____________ Is the subject recruited into the study? yes / no If no: then: a) Main reason for exclusion: ______________________________ _____________________________________________________ _____________________________________________________ Reasons for exclusion: 1. Subject refusal 2. Clinician refusal (with possible reasons) 3. Ineligible (specify which inclusion criteria are not met and which exclusion criteria exist) 4. Language difficulties 5. Other b) Treatment actually given: _______________________________ _____________________________________________________ _____________________________________________________

J Paul Seale PhD, FRACP, FRCP · Val J Gebski MStat · Anthony C Keech FRACP, MClinEpi

Gastroenteritis in children is still a common reason for consulting a general practitioner and for hospital admission. Rotavirus is the most common cause of gastroenteritis in children and accounts for half of all hospital admissions for severe acute infectious diarrhoea. Most children with gastroenteritis do not develop dehydration and can be treated at home. Children with mild to moderate dehydration should be treated with low osmolarity oral rehydration solutions, and those with severe dehydration or shock need to be admitted for administration of intravenous fluids. Lactose-free feeds should not be routinely used after acute gastroenteritis, but there is some evidence that a lactose-free diet may reduce the duration of diarrhoea. Antimotility drugs are rarely indicated in children with gastroenteritis, as the potential risks outweigh the benefits. The development of a rotavirus vaccine would provide huge public health benefits and cost savings. Other preventive strategies include educating people about personal and food hygiene and encouraging breastfeeding.

Elizabeth J Elliott MD, FRACP, FRCPCH · Jacqueline R Dalby-Payne MB BS, PhD, FRACP

An 80-year-old woman with a history of hypertension presented to the emergency department with a 3-hour history of dyspnoea and precordial discomfort. Serum concentrations of troponin T, creatine kinase and creatine kinase MB isoenzyme were normal. An electrocardiogram (Box 1) showed changes consistent with myocardial ischaemia. When the patient developed haemodynamic instability, cardiac catheterisation was performed (Box 2). The patient’s condition improved after an intra-aortic balloon pump (a catheter-mounted balloon positioned in the descending aorta and timed to inflate during diastole) was placed for the management of cardiogenic shock. An echocardiogram 3 weeks later showed normal left ventricular size and function. The patient had acute transient apical ballooning with normal coronary arteries (“Takotsubo” cardiomyopathy). First described in 1990,1 the presentation is similar to that of acute transmural myocardial ischaemia, with chest symptoms and electrocardiographic changes ranging from ST-segment elevation to T-wave inversion without ST shifts.2,3 Postulated triggering factors for transient apical ballooning have included onset or exacerbation of systemic disorders (eg, cerebrovascular accident, asthma, acute abdomen) and extreme emotional distress.2 Women are 6–12 times more likely to be affected than men.2-4 The in-hospital mortality rate is less than 1%,2 and there is usually complete functional recovery of the left ventricle within 2 weeks.3,4 The 2-year recurrence rate is less than 3%.2 The optimal therapy for this condition is unknown. 1 Electrocardiogram, showing delayed R-wave progression and inverted T waves in the anterolateral leads 2 Images from cardiac catheterisation A. End-diastolic left ventriculogram. B. End-systolic left ventriculogram, showing akinesia/dyskinesia of the apical and mid portions of the left ventricle and hyperdynamic motion at the base. The left ventricular ejection fraction was 30%, with elevated left ventricular end-diastolic pressure of 35 mmHg. C. Normal end-systolic left ventriculogram (from a different patient). D. Left coronary angiogram, showing a normal left anterior descending artery.

Constantin B Marcu MD · Kristen M Andresen MD · Thomas J Donohue MD, FACC

Re: “The potential for tobacco control to reduce PBS costs for smoking-related cardiovascular disease”, by Susan F Hurley, Michelle M Scollo, Sandra J Younie, Dallas R English and Maurice G Swanson in the 6 September 2004 issue of the Journal (Med J Aust 2004; 181: 252-255). The vertical axis on the graph in Box 5 was mislabelled during the production process. The values should be reduced by a factor of 10. The correctly drawn figure is reproduced below. The html and pdf versions of the article published online were corrected on 15 November 2004. 5 Smoking-attributable PBS costs for drugs to treat cardiovascular disease

Susan F Hurley MS, PhD · Michelle M Scollo BBSc, GradDipCommHlth · Sandra J Younie P/GDipHealthEc · Dallas R English PhD · Maurice G Swanson BSc, MPH

Re the article “Are current playground safety standards adequate for preventing arm fractures?”, by Sherker S and Ozanne-Smith J, in the 7 June 2004 issue of the Journal (Med J Aust 2004; 180: 562-565). In Box 2, the slope of the head injury trend was reported as “0.030”. The correct slope should be “–0.030”. The html and pdf versions of the article published online were corrected on 15 November 2004.

Shauna Sherker PhD, MSc, BSc · Joan Ozanne-Smith MD, FAFPHM, MPH

To the Editor: Recent media reports have claimed numerous health benefits for A2 milk1,2 (eg, “new wave milk”, “wonder milk”). It is becoming more widely available, particularly in health food shops, and is advertised on Queensland television. We believe it is important to offer clear information about this product and cows’ milk allergy. A2 milk is produced by cows homozygous for the A2 polymorphic variant (his→pro) at amino acid 67 of the b-casein gene. A difference in degradation patterns of the A1 and A2 variants is purported to lead to differences in immunological or pharmacological effects,3-5 which we will not comment on here. Regarding cow’s milk allergy, β-casein is one of at least seven proteins in cows’ milk with allergenic significance (α-, β- and κ-casein, α- and β-lactoglobulin, lactoferrin and transferrin). One would not expect a single amino-acid difference in one protein to have a significant effect on milk allergenicity. We have found in discussion with parents of milk-allergic children, as well as from inquiries from the community to AllergySA, that there is a perception that A2 milk may be less allergenic than “normal” milk (which contains A1 and A2 b-casein). Although most proponents of A2 milk have made no explicit claims about allergenicity — and indeed some have cautioned against the use of A2 in milk-allergic individuals — there have been media reports that may have led to this perception.6 However, these reports are misleading. For example, it is quite likely that children with a previous history of cow’s milk allergy who have been found to tolerate A2 milk have in fact “grown out” of the allergy, which is the usual natural history. Others may never have had true milk allergy. We obtained a sample of pure A2 milk from A2 Dairy Marketers (Acacia Ridge, QLD) and used it for skin-prick testing of 11 consecutive milk-allergic children (Box). The tests compared A2 milk with “normal” (A1/A2) milk and cow’s milk protein extract. The mean diameter of the wheal raised by normal milk was not significantly different to that raised by A2 milk (8.2 mm for normal milk v 10.7 mm for A2 milk; P = 0.09, paired t test). No patient had a negative reaction to A2 milk when the reaction to normal milk was positive. We did not perform an oral challenge with A2 milk in these children, as many had experienced severe allergic reactions, and the predictive value of a positive skin-prick test in the presence of a clear recent history of clinical allergy is high. We therefore caution that A2 milk should not be used by those with IgE-mediated cow’s milk allergy, particularly those who have had recent severe reactions to milk. Mean wheal diameter* (mm) on skin-prick testing Patient Normal milk† A2 milk† Cow’s milk extract‡ Histamine positive control 1 12 10 8 4.5 2 11.5 12 11 5.5 3 4 8 6 15 4 8 11 10.5 3 5 12 8 6 9 6 3 5 2 9 7 7 15 7 10 8 7 7.5 5 7.5 9 6 7.5 4 3.5 10 13 25 4.5 3 11 7 9 3 5 Mean 8.2 10.7 6.1 6.8 * As wheals produced are not necessarily circular, it is standard to report diameter as the mean of two measurements taken perpendicular to each other. Results for all negative controls were 0 mm. † Normal and A2 milk were stored frozen, and aliquots thawed for testing. They do not produce wheal reactions in non-allergic individuals. ‡ Cows’ milk extract is manufactured for skin-prick allergy testing by Hollister-Stier, Wash, USA, and purchased from Richard Thomson, Sydney, NSW.

William B Smith · Deryn Thompson · Margaret Kummerow · Patrick Quinn · Michael S Gold

To the Editor: There appear to be regional differences in the prescribing of amino acid infant formula in Australia. This is possibly due to differing practices in use of this formula as a first-line treatment for cow’s milk allergy or as a strategy for preventing allergy. This has financial implications, as the cost to the Pharmaceutical Benefits Scheme (PBS) of amino acid formula is $371 per prescription, compared with $106 for hydrolysed protein formula.1 In infants at high risk of allergic disease who are unable to be completely breastfed, there is evidence that prolonged feeding with a formula based on hydrolysed cow’s milk protein rather than conventional cow’s milk formula reduces infant and childhood allergy.2,3 There is no clear evidence that amino acid formula should be substituted for extensively hydrolysed protein formula as a primary preventive strategy.3 The current PBS indication for hydrolysed protein formula is treatment of intolerance to both cow’s milk and soy protein, but not primary allergy prevention. Similarly, current PBS guidelines restrict the use of amino acid formulas to proven intolerance to cow’s milk, soy protein and protein hydrolysate. Among children who are allergic to cow’s milk, 10% or less are also sensitive to protein hydrolysate formula.4 Thus, if current guidelines were followed, one might expect nine times the use of hydrolysed protein formula compared with amino acid formula. I obtained statistics on PBS items supplied for the period January 2003 to January 2004 from the Health Insurance Commission (www.hic.gov.au/statistics/dyn_pbs/forms/pbs_tab1.shtml) for hydrolysed protein formula (item numbers 2676W and 8259Q) and synthetic amino acid formula (item numbers 3066J, 8443J, 8574G and 8575H). These showed that 8374 hydrolysed protein formula items were supplied, half the number of amino acid formula items (16 886). Numbers of amino acid formula items supplied per 1000 children aged 4 years and younger were calculated using population statistics from the Australian Bureau of Statistics census figures 2001. These are compared in the Box with numbers of paediatric physicians per 1000 children (obtained from the Royal Australasian College of Physicians 2004) and paediatric allergists (derived from the Australasian Society of Clinical Immunology and Allergy membership handbook 2003). Prescribing practice varied markedly between states and territories. The Australian Capital Territory, New South Wales and Victoria had six to seven times more amino acid formula items per 1000 children than Western Australia. This did not appear related to numbers of paediatricians or paediatric allergists, as Western Australia had a similar number of paediatricians and more paediatric allergists per 1000 children than NSW and Victoria. The differences found were unlikely to be related to variation in numbers of adult immunology/allergy specialists, who are unlikely to treat many infants aged under 2 years. Nor were they likely to be due to differing prevalence of combined milk, soy and protein hydrolysate intolerance, as the prevalence of allergic disease does not differ markedly between Australian states. For example, the prevalence of atopic eczema at age 6 years in four cities (Adelaide, Melbourne, Sydney and Perth) was very similar, ranging from 10.1% to 11.4%.5 It seems unlikely that 80% of cases of combined intolerance are being missed in Western Australia. The estimated cost to the PBS for amino acid formula for 2003–2004 of $7 107 627 was 10 times that of hydrolysed formula ($757 570). Amino acid formula prescription rates, January 2003 to January 2004, compared with numbers of paediatric physicians and allergists per 1000 children aged 4 years or younger Amino acid formula items per 1000 children Paediatric physicians per 1000 children Paediatric allergists per 1000 children Australian Capital Territory 22.3 0.79 0 New South Wales 18.8 1.02 0.033 Victoria 17.8 1.00 0.030 Tasmania 12.3 0.53 0.033 South Australia 9.3 1.01 0.067 Northern Territory 9.1 0.92 0 Queensland 5.9 0.72 0.008 Western Australia 3.3 0.99 0.049

Andrew S Kemp

To the Editor: Colonic irrigation is the introduction of a large volume of fluid into the colon via the rectum. This volume may be up to 50 litres, run in and out by means of a rectal tube, in an effort to empty the bowel. This treatment is often administered by a practitioner of complementary or alternative medicine, without medical advice. The fluid may be driven by gravitational or mechanical force.1 Recognised risks from colonic irrigation are electrolyte imbalance, bowel perforation and communicable diseases such as amoebiasis.2 Colonic irrigation is different from a standard enema given to relieve constipation or to treat a primary bowel disease. An enema involves a small amount of fluid and is usually authorised by a medical practitioner and administered by a trained nurse, attendant or is self-administered. Perforation of the rectum has rarely been reported.3 We document three cases of perforation of the rectum from colonic irrigation, treated by different surgeons at different institutions (Box). All have required surgical intervention. Each patient underwent colonic irrigation to relieve chronic constipation, to “cleanse” or “clear out stale faeces”. None had primary colonic or rectal pathology. None of the three patients were warned about the complication of perforation. Importantly, one patient initially denied the use of colonic irrigation, even with direct enquiry (Case 1), presumably because of embarrassment. This has the potential to delay the diagnosis or lead to inappropriate treatment. Perforation may occur in the rectum by direct injury from the irrigation device (Case 1), or after the irrigation has commenced (Cases 2 and 3), and may be caused by the generation of a high pressure within the lumen of the bowel. Rectal perforation from colonic irrigation may be diagnosed from the history, plain abdominal x-rays or a computed tomography scan with or without meglumine diatrizoate enema. A high degree of suspicion by the attending physician will prompt the diagnosis. Intensive medical therapy with appropriate antibiotics and surgery is necessary. Plain abdominal x-ray did not show an abnormality at 12 hours in the one case where x-ray was taken. We feel that colonic irrigation is of dubious benefit, especially when delivered to remove so-called “toxic waste” when bowel function is satisfactory. There is potential for serious harm. The apparent failure of the operators to warn patients about a risk of any serious complication, the failure to diagnose the possible perforation at the time of injury, and the failure to provide any subsequent follow-up, which might have led to an earlier diagnosis of any complication, probably indicates suboptimal practice. Cases 2 and 3 occurred at the same clinic within a few weeks of each other, suggesting a possible systems failure of the irrigation device. Primary healthcare practitioners need to be aware of the dangers of this treatment. Colonic irrigation should be urgently and formally assessed from an evidence-based, risk–benefit perspective. Case descriptions for three women who had rectal perforation after undergoing colonic irrigation Case Age (years) Timing of symptoms Clinical features Investigations Management 1 59 Pain immediately on insertion of enema tube. No irrigation. Attended emergency department 24 hours after the tube insertion. Lower abdominal and deep pelvic pain. Sepsis. Abdominal computed tomography scan showing perirectal oedema and extrarectal gas. Intravenous antibiotics and transrectal drainage of perirectal abscess. 2 51 Pain started during irrigation. Attended emergency department 4 days after irrigation. Lower abdominal pain. Sepsis. Abdominal computed tomography scan showing gas and fluid in the perirectal fat and retroperitoneum. Intravenous antibiotics and initial transrectal drainage of perirectal abscess. Recurrent abscess formation required laparotomy and rectal resection with stoma formation. 3 56 Pain started during irrigation. Attended emergency department the same day, but was discharged. Re-presented 7 days later. Lower abdominal and deep pelvic pain. Constipation and urine retention leading to urinary infection. Sepsis. Abdominal computed tomography scan showing pelvic abscess posterior to the rectum. Emergency laparotomy, sigmoid loop colostomy and drainage of abscess. Residual abscess drained transrectally 2 weeks after initial surgery.

Doug V Handley · Nick A Rieger · David J Rodda

To the Editor: There is no substitute for injectable thiamine in the treatment and prevention of Wernicke’s encephalopathy, for which the oral form of thiamine is considered inadequate.1 If the condition is not treated promptly with parenteral thiamine, permanent brain damage can occur. A shortage of injectable thiamine noted in a South Australian hospital led us to enquire into the extent of the problem in Australia. In the first week of July 2004, we undertook an Australia-wide survey of major teaching hospital pharmacies. Sixteen hospitals were contacted by phone, and 15 chief hospital pharmacists provided information about thiamine stock, normal thiamine usage over a 6-month period, shortages of other drugs, and reasons for shortages. Data on thiamine are shown in the Box. Most hospitals (11/15) were unable to provide injectable thiamine for periods ranging from a few weeks to 5 months. Rationing reduced the use of injectable thiamine in 13/15 hospitals. There was a total shortfall of 2000 ampoules per month for the 13 hospitals. Given an average of six ampoules used per admission, we estimate that 330 patients a month were untreated or inadequately treated. Half the hospitals surveyed obtained some ampoules either directly from suppliers or through the Special Access Scheme (SAS) protocol of the Therapeutic Goods Administration (TGA). This protocol is time-consuming and cumbersome, while the non-SAS system is expensive (10 times the usual price per ampoule). Pharmacists reported having many other drugs (40–60) on back order. The pharmacists stated that drug shortages were caused by scarcity of raw materials and TGA restrictions. However, the current shortage of thiamine in Australia was foreseeable in 2003, when the main manufacturer stopped thiamine production. The TGA did not alert pharmacists or doctors to the potential shortage in writing, nor provide comprehensive help to prevent or alleviate the shortages. The public health response to shortages of essential medicines should include surveillance and a systematic analysis of the causes. Better communication between pharmacists, clinicians and government authorities, and the formation of contingency plans and guidelines, are needed. It was only through informal networking and the quick thinking of hospital pharmacists that a crisis was averted in Australia. It is unconscionable that an inexpensive essential medicine is not available to those Australians who may need it. In this respect, our public health system has failed. Because injectable thiamine has been unavailable or rationed, an increase in the incidence of alcohol-related brain damage may have occurred. Australian health ministers should act immediately to prevent critical shortages of essential medication, which could be tragic and costly. Stocks and usage of injectable thiamine in 15 Australian hospitals, as at 3 July 2004* Number of vials Use/month Hospital Lowest Current Previous 2 months Usual 1 0 0 0 16 2 0 0 0 50 3 0 0 0 50 4 0 0 0 65 5 0 12 0 20 6 0 10 0 35 7 0 25 0 20 8 0 200 0 130 9 0 120 0 1200 10 0 25 25 70 11 0 10 10 150 12 1 35 40 120 13 5 160 17 180 14 25 86 100 100 15 30 90 30 30 * The table compares the level of stock at its lowest during the shortage with the level at July 2004, along with estimates of use at July 2004 and before the shortage.

Simon Spedding · Matt D Gaughwin

To the Editor: Pertussis (whooping cough) is a readily transmissible respiratory infection that may cause severe respiratory illness. The burden of severe pertussis affects infants, often resulting in hospitalisation (especially those aged under 6 months) and death (1 in every 200 patients aged under 6 months).1,2 In Australia, there were nine deaths from pertussis between 1993 and 1997, predominantly in young infants, and a further five young infant deaths during the 2001–2002 epidemic.3,4 Epidemics occur every 3 to 4 years.2 Pertussis cases and hospitalisations in children aged under 6 months continue to occur in south-east Queensland, with 19 notifications since January 2003. There has been a shift in the epidemiology of pertussis in Australia and the United States, from a disease of young children to a disease of adolescents and adults of child-bearing age.1,5 In Australia, there has been a preponderance of pertussis notifications in adult females.5 Pertussis vaccine is already provided free to children at ages 2, 4 and 6 months, 4 years and 15 years, as part of the National Immunisation Program.2 However, young infants remain incompletely protected by vaccination, as the third, completion dose of the primary course of pertussis vaccination is not given until 6 months of age. A national study of hospitalised infant pertussis cases in 2001 indicated that parents were the presumptive source of pertussis infection for their children in more than 50% of cases.6 This has led the National Health and Medical Research Council to recommend that both parents should receive a (once-only) adult booster dose of pertussis vaccine, either when planning pregnancy or as soon as possible after delivery of an infant.2 The cost of the vaccine is about $30. As yet there is no suggestion that funding will be made available to provide this vaccine to all new parents as part of the National Immunisation Program. However, the amount is not a high price to pay for the protection of a new baby and its parents, particularly now that new parents will receive additional financial support from the federal government. The potential exists to promote opportunistic maternity-ward-based administration of this vaccine to post-partum mothers and their partners. We encourage all medical practitioners, especially obstetricians and paediatricians, to discuss this important issue with parents.

Brad J McCall · Rod P Davison · Michael D Nissen · Clare B Nourse

To the Editor: A recent editorial1 and article2 continue to promulgate and link the unproven concepts that patients with chronic fatigue syndrome (CFS) are “deconditioned” and exercise is beneficial in treatment. The cited study by Fulcher and White3 is open to opposite conclusions, depending on their use of the outcome descriptor “better”. If the term is restricted to “much better” and “very much better”, then, as cited by Lloyd,1 16 of 29 people with CFS rated themselves as “better” after a graded exercise program, compared with only 8 of 30 in the control group who completed a flexibility treatment regimen. However, if the “better” descriptor combines “a little better”, “much better” and “very much better”, which is the interpretation used by Wallman et al,2 then the scores for the exercise versus flexibility groups are not different, being 27 of 29 and 26 of 30, respectively, agreeing with the conclusion of Wallman et al.2 Whichever interpretation is applied, any beneficial effect of the graded exercise program in people with CFS in these studies must be independent of any training effect or change in level of “conditioning”, as this was reported in one study,2 but not in the other.3 A fundamental flaw with most exercise studies in CFS is the use of submaximal or symptom-limited tests, which provide notoriously misleading data when compared with maximal exercise testing procedures.4,5 Wallman et al2 correctly identify maximal oxygen consumption as the “gold standard” measure of exercise capacity, yet such measurements were not made in the three articles they cited. When such procedures are applied, the exercise capacity of people with CFS is not significantly different from either measured or age-predicted values for healthy sedentary people.6 Wallman et al2 suggested that maximal testing procedures could favour the recruitment of “more robust or healthier” patients and provide misleading information. In the first place this is denied by the study of Sargent et al,6 in which the illness status reported by patients who completed the maximal tests was similar to that in previous CFS studies. In the second place, the maximal test protocol chosen for a given population should be designed to exclude any influence of fatigue on the metabolic measurements. This is confirmed by the results from the study cited,6 in which the metabolic measurements met the published criteria of a maximal test.4,5 In summary, patients with CFS are not “deconditioned”. Neither their muscle strength nor their exercise capacity is different from that of other sedentary members of the community (> 70%). We remain unaware of any incontrovertible evidence that the various “exercise training” programs suggested in previous articles improve either the physiological or clinical status of people with CFS.

Garry C Scroop · Richard B Burnet

To the Editor: The claim in Lloyd’s editorial1 that “the criteria for diagnosis are well accepted internationally” ignores the recent publication of the Canadian consensus guidelines for the diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome,2 which were sponsored by Health Canada and written by an international group of well published researchers. The Canadian definition of chronic fatigue syndrome (CFS) requires the concurrent presence for six months of fatigue, post-exertional fatigue, sleep dysfunction, pain (including headaches) and neurological/cognitive manifestations, as well as at least one symptom from two of autonomic, neuroendocrine and immune manifestation categories (pp 12–13). These requirements add clinical specificity to the Fukuda criteria and exclude subjects who may have chronic fatigue for other reasons, such as psychiatric disorder without multiple physical symptoms. Lloyd refers to the “recent refinements to improve reliability” in the revision of the research case definition by Reeves et al.3 The SPHERE screening instrument recommended by that article was designed for psychiatric screening in primary care. It arbitrarily classifies people with multiple physical symptoms, often severe in degree and associated with major disability, as having somatisation disorder. This is akin to subclassifying people with severe multiple sclerosis as having somatoform disorder and those with fewer and less severe symptoms as the “core” multiple sclerosis group, a finding which is not supported by the evidence. Conclusions from the article by Wallman et al4 cannot be generalised to the severely ill. Recruitment was from “notices placed in medical surgeries and by advertisements in local newspapers”. Patients with severe CFS, who can barely venture outside their homes and are often too ill to read, would be unlikely to participate. Loblay, Chair of the Royal Australasian College of Physicians Working Group for CFS Clinical Practice Guidelines, urges caution about generalising from exercise studies, which never include people with severe CFS: “All these studies involve people willing and able to participate. The people who find it makes them feel lousy drop out.”5 Lloyd asserts exercise is no longer a question (“. . . graded physical exercise should become a cornerstone of the management approach for patients with CFS”). To promote such a strong, unqualified message to busy general practitioners who may be unfamiliar with the range of severity in CFS risks serious harm to patients.

Ellie Stein · Christine Hunter

In reply: Scroop and Burnet correctly identify the vagaries of the necessarily subjective measurement of outcomes in intervention studies of chronic fatigue syndrome (CFS). Given that muscle strength, endurance and recovery are essentially normal in patients with CFS,1 rather than become too focused on the best approach to measurement of exercise capacity the key issue is whether patients benefit in terms of self-reported symptom severity or functional status. The weight of evidence indicates that graded physical exercise does provide such benefits. Whether this occurs via improvements in aerobic fitness or via the well-recognised psychological and social benefits of exercise is something of a side-issue. Stein and Hunter draw attention to the recently published Canadian consensus guidelines for the diagnosis and management of myalgic encephalomyelitis/CFS. Although this document may provide a welcome recognition for Canadian patients with the disorder, unlike the Australian guidelines,2 it is devoid of an evidence base for the recommendations. Sadly, rather than “add[ing] clinical specificity”, it is also highly likely that the modified diagnostic criteria fall into the trap of preferentially identifying patients with somatisation disorder,3 as such individuals often report large numbers of unexplained symptoms, and hence the addition of 20 or more symptoms to the diagnostic criteria may well bias towards inclusion of such patients. Stein and Hunter are incorrect in the assertion that SPHERE was designed for psychiatric screening in primary care, as the instrument arose out of our studies in CFS specifically seeking to identify clinically significant fatigue states.4 I support the recommendation about caution in generalising from existing published data regarding graded exercise to patients who are severely ill, as such patients are indeed likely to be under-represented in published studies. Nevertheless, it is noteworthy that the recommendations made in the Canadian document cited by Stein and Hunter also clearly support the notion of graded physical exercise: “Patients should gently and gradually increase their level of activity.” Thus, rather than leave the severely affected to continue to “barely venture outside their homes”, I would recommend a carefully designed graded exercise program in the home, with a goal of improving functional performance sufficiently to escape those confines.

Andrew R Lloyd

To the Editor: While the article by Henry and colleagues provides food for thought and possible action,1 do they exhibit the fairness they exhort to solve the problem they perceive? There appears to be a distinct lack of logic in some of their deductions in the Box on page 517. “Body part funding” is not confined to Aboriginal health. For the 43 years I was associated with NSW Health, it was an integral part of the system and, together with its variations, increased as the years passed. The authors claim that as only $80 per head being spent on medical and pharmaceutical benefits in a remote Aboriginal community compared with the $900 spent in Double Bay is an example of racism. Surely, it is only a reflection of the lack of both a pharmacy and doctor in the remote community compared with the easy access to both in the inner-Sydney suburb. Comparison between the remote Aboriginal community and an all-white community of similar characteristics would have more validity.

Raymond S Hyslop

To the Editor: In their challenging article, Henry and coauthors assert that the poor health of Australian Aboriginals is the result of the “divided, divisive, racist, socially unjust society” of “this Australia”.1 I cannot agree. The health standards enjoyed by “white Australia” are not an isolated phenomenon, but rather a part of the fabric of an advanced technological society. Efforts to bring Australian Aboriginal health to the same standard without the Indigenous Australians being fully part of this 21st-century society will never be successful, even with limitless resources and endless goodwill. It is possible to maintain cultural identity and remain cognizant of past hurts while playing a full, if not leading, role in this technological society. If the Aboriginal elders were to lead their people into mainstream society they would find, I’m sure, an inclusive, tolerant, exciting and advancing society where they could play a full role, enjoy the same health as the rest of Australia, while still maintaining their unique identity.

Christopher R Strakosch

To the Editor: We write in response to the article by Faunce and Bolsin on the lessons to be drawn from three Australian whistleblowing sagas.1 Their summary of events at King Edward Memorial Hospital, Perth, deserves comment. Michael Moodie, the Chief Executive Officer (CEO) of King Edward Memorial Hospital, was also CEO of Princess Margaret Hospital for Children (PMH). He was stood down from PMH because of the concerns of workers in response to events at PMH unrelated to those at King Edward Memorial Hospital, as Faunce and Bolsin implied. Moodie was the senior administrator charged by the government with ensuring that appropriate standards were in place and were being met. Staff at PMH believed he was unable to fulfil his brief, culminating in votes of no confidence from the PMH Clinical Staff Association, the PMH Medical Advisory Committee, and a petition signed by 80 PMH doctors.

Francis Lannigan · Geoff Knight · Gary C Geelhoed · Alan Duncan · Peter Chauvel · Ian Hewitt · Peter Le Souëf

In reply: Our reference to Michael Moodie as a “whistleblower” merely reiterates his description as such in the report of the Inquiry into Obstetrics and Gynaecological Services at King Edward Memorial Hospital by the Australian Council for Safety and Quality in Health Care.1 That report states: “Both the Bristol and King Edward case arose from ‘whistle-blowers’ reporting serious problems rather than from established safety and quality monitoring systems. In Bristol’s case, the whistle-blower was an anaesthetist and, in King Edward’s case, it was the recently appointed Chief Executive. In both cases, either directly or indirectly, the department of health received information about management and clinical performance problems that had not been addressed over a significant period of time.” The report then lists nine examples of problems established at both institutions, ranging from a “closed culture and environment unsupportive of openly disclosing errors and adverse events” to “poor clinical and emotional outcomes for patients and families”. The report continues: “However, there were differences in the Hospitals’ response to the inquiries. Bristol welcomed an inquiry and actively supported the process. In contrast, King Edward tolerated the process and the Western Australian branch of the Australian Medical Association actively and publicly fought it.”

Thomas A Faunce · Stephen N C Bolsin

To the Editor: The complementary and alternative medicine (CAM) series raised awareness and provided balanced and thoughtful debate. The article by Kerridge and McPhee in that series1 is no exception, but we would like to question their conclusion that “not only is it unclear whether a true integration of conventional and unconventional medicines is possible, but, more importantly, whether it is even desirable”. For a variety of reasons we believe that it is both possible and desirable. There are increasing examples of situations in which medical practitioners can integrate ethical, evidence-based CAM into practice. Apart from the well-known and validated examples, such as Hypericum perforatum (St John’s wort) for depression, ginger for nausea in pregnancy, and Gingko biloba for intermittent claudication, there are other, less well known, but increasingly investigated, examples of CAM for common conditions. With quality information and a little training, these can be readily incorporated into medical practice. To illustrate, Hippocrates was known to use the herb Vitex agnus-castus (chasteberry) for treating symptoms of premenstrual syndrome. Today we have a randomised controlled trial (RCT) to support its use.2 There are RCTs to support the use of Serenoa repens (saw palmetto) for symptomatic relief of benign prostatic hypertrophy,3 and good evidence is accumulating for the use of glucosamine for osteoarthritis4 and mindfulness meditation for preventing relapse in recurrent depression.5 With systematic reviews on these CAMs doctors should be informed about them. However, the resources for promoting them are minimal compared with those used to promote pharmaceuticals. Considering side-effect profiles and patient autonomy, why shouldn’t trained medical practitioners offer effective CAM remedies as first-line therapy instead of a pharmaceutical? To say these therapies should only belong to the realm of CAM practitioners would be to deprive the medical practitioner and patient of a wider choice of treatments. Communication, holism, balance and individualised care are the hallmarks of quality general practice and do not just belong to CAM therapists. If orthodox medical practice is to remain current, evidence-based and relevant, general practitioners have no option but to integrate safe, validated and ethical forms of CAM into their practice. If they are not adequately trained in the relevant discipline they may wish to refer to an appropriately qualified CAM practitioner, although statistics indicate that GPs prefer to refer to GPs already trained in CAM.6

Vicki Kotsirilos · John R McPhee

To the Editor: Although Kerridge and McPhee stress the need to find an evidence base (if there is any) for CAM, they nevertheless claim “medical practitioners and students no longer have any choice but to gain some knowledge about CAM and the interface between conventional and complementary medicine.”1 I suppose that archaeologists, geologists, palaeontologists and biologists now need to gain some knowledge about the interface between Darwinism and Creation Science. And our astronomers need some knowledge about the interface between astronomy and astrology. Science, including effective medical care, is not advanced by pandering to unscientific consumerism about unproven theories, especially if it manages to get the law on its side. Galileo was persecuted for “his heretical view” that the earth revolved around the sun. Have we learnt nothing from his experience?

In reply: We agree with Kotsirilos and Hassed that there are many examples of successful integration of “proven” CAM into conventional medical practice. Our question, however, is whether it is possible to integrate CAM where its theoretical maxims and practices are incommensurate with allopathic medicine (eg, homoeopathy) and whether “integrative medicine” will ulti-mately fragment and diminish CAM, further isolate “non-evidence-based” CAM practi-tioners and make less visible those views of health and disease that are not consistent with modern medicine.1 It is misleading for Arnold to imply that there may be no evidence base for complementary and alternative medicines (CAMs). We suggest that medical practitioners should ask themselves not whether an “evidence base” exists, but what the existing evidence shows. The picture that emerges from a review of the literature is one of variable clinical efficacy. Thus, there is no evidence to support the use of chiropractic for childhood asthma,2 but there is good evidence that phytomedicines may reduce crises in sickle-cell disease,3 that cranberry juice may reduce the frequency of symptomatic urinary tract infections in women,4 and that horse chestnut seed extract is an efficacious treatment for chronic venous insufficiency.5 There is also clinically important evidence about harmful interactions, for example that St John’s Wort, garlic and ginseng may lower blood levels of warfarin.6 Medical practitioners should be critical and sceptical of all untested claims of therapeutic benefit. We suggest they acquaint themselves with evidence about risks and benefits of CAMs, particularly in their own area of practice. This is not pandering to anything. It is evidence-based practice. By the same token, use of CAM may reflect evidence-based decision-making by doctors and patients. It is simply divisive to dismiss it as “unscientific consumerism about unproven theories”, and it is foolish in any case to dismiss the latter. Medicine and science must compete with non-scientific perspectives in the public sphere, for the contest of ideas is never over in human history. Ideological positions are black and white. Science prefers shades of grey. We have indeed learnt much from Galileo’s experience.

To the Editor: I read with interest the article by Byles and colleagues that shows the minimal impact of health assessments in a section of the older Australian community.1 While these assessments may not be identical to the assessments covered by Enhanced Primary Care (EPC) items on the Medicare Benefits Schedule, my experience performing the latter in older people leads me to believe that they also have limited impact. I am now in part-time clinical practice, with a reasonably well-defined practice population, comprising mostly older patients with complex problems. My practice philosophy is closer to the (perhaps old-fashioned) notion of continuing, comprehensive care, which means I have not been afraid to spend the time needed to understand those patients and to document their health information. So far, I am not sure I have learned anything new in any of the EPC health assessments in which I have participated, although they have been useful for initial assessments of newer patients, as at least they remunerate practices better for the time-consuming task of doing this well. However, EPC assessments may be performed every 12 months. Is this really necessary, unless patient circumstances change? In my practice the answer is probably no, although they may be more useful in practices with less stable doctor–patient relationships. Would it not be a more effective use of resources to instead allow for better-funded initial assessments and assessments when a patient’s condition changes, irrespective of the timing?

Richard B Hays

To the Editor: Telemedicine in eye care (teleophthalmology) is one of the established technologies in medicine, providing the means for undertaking sophisticated eye care and for maintaining contact with patients in rural and remote areas.1 Telemedicine in Australia has been primarily facilitated by government, against a background of complex funding arrangements and interwoven healthcare responsibilities (it is funded mostly by project grants and state government telehealth initiatives).2 This funding mechanism impedes the efficient use and integration of telemedicine services.2 The current healthcare environment demands a detailed economic evaluation to justify continuous funding for teleophthalmology. However, some of the economic benefits of teleophthalmology may not be directly visible in the healthcare system itself. Significant benefit may be obtained by, for example, savings in time and travel expenses, thereby contributing to society indirectly. Furthermore, the cost-effectiveness of a telemedicine service improves considerably when it is integrated with existing routine healthcare services.3 But organisational and attitudinal barriers and lack of funding have delayed such integration.4 These barriers relate to human resource allocation issues in an already overstressed healthcare system and the mindset of some critics who view telemedicine as a peripheral activity and a “novelty” area for technological enthusiasts. The cost-effectiveness of telemedicine will not be improved unless the perception that it is an “add on” is changed.4 The question of whether teleophthalmology should be integrated into routine services, with Medicare reimbursement, can be judged by four criteria:5 Is the technology sound? (ie, does it fulfil its purpose?) Is the program effective compared with existing care? Is the program cost-effective? Is the program practical? (ie, are there any significant problems associated with it?). On the basis of our own comprehensive evaluation of teleophthalmology in Western Australia,6 we believe that all four questions can be answered affirmatively, and that teleophthalmology would be most efficiently provided if integrated into existing healthcare services. Its inclusion in the Medicare Benefits Schedule would benefit many patients in remote and rural areas in Australia.

Sajeesh K R Kumar · Yogesan Kanagasingam · Ian J Constable

To the Editor: The Postcard from Heller, Weller and Jamrozik1 may reflect a nostalgic and unrealistic view of how good things are back home. They suggest that, in New South Wales, the health chances of both advantaged and disadvantaged populations are improving, and, in relative terms, social inequalities in health may also be showing “some improvement”. In fact, despite impressive overall declines in mortality, there remain important differences in health status between NSW populations. Figures for the mid-1990s show that life expectancy at birth for both Aboriginal males and females is markedly less (by 20 years and 18 years, respectively). Similarly, socioeconomic disadvantage shortens life expectancy for both rural men and women (by 14 and 10 years, respectively) and urban men and women (by 10 and 7 years, respectively).2 The relative gap is also widening for some important health indices. For example, from 1980 to 2000, the percentage difference in premature death rates (< 70 years of age) between high and low socioeconomic groups has increased from 30% to 52% for men and from 24% to 32% for women, and for potentially avoidable mortality from 34% to 63% for men and from 27% to 40% for women.3 How should one respond to such inequalities? Heller et al suggest universal rather than targeted programs, as they are based on sound population health principles. To construct this as a simple choice is not helpful. Unless we recognise and address the barriers facing people in adverse social circumstances, universal programs may unintentionally widen health inequalities. For example, universal access to healthcare in the UK and Australia has not equally benefited those from the most disadvantaged circumstances compared with wealthier and better-educated populations.4 The Postcard authors suggest that Australia is saved from class divisions by the established “fair go” tradition, where shared values overcome structural inequalities in “socioeconomic status”. In fact, social class continues to be a powerful but complex and changing influence in Australia.5 It is important to acknowledge the evidence that structural inequalities are significant and worsening in Australia,6 and that the most disadvantaged experience continued social exclusion.7 We need to shift from a “trickle down” perspective that sees the greatest health gains accruing to the most advantaged — with a hope that these benefits will eventually be achieved by everyone — to a more explicit social justice perspective that ensures that resources for health are allocated in ways that produce fair outcomes. This may help address “socially entrenched self-denial of the chance for better health”.

John Furler · Elizabeth Harris · Don Nutbeam · Mark Harris

To the Editor: Pseudoephedrine is no longer a banned substance in sport.1 It was originally banned to protect athletes from overuse and its dangers. Has it become harmless or are athletes more intelligent? This highlights much of the confusion in drug testing. Athletes with diabetes are permitted to use insulin for therapy, but those with hypertension are not allowed to take β-blockers. Both drugs are popularly believed in athletic circles to improve performance. What is to stop an athlete with diabetes from taking extra insulin for performance enhancement? Why do we discriminate against those with hypertension? There is a ban on oxygen-transport drugs and on physical environment enhancers such as hypobaric chambers. Both are alleged to produce the same result, but only use of the drug can be tested. The penalty for the drug user is disqualification, but for the hypobaric enthusiast a rousing cheer for a drug-free effort. The crime is the same, so why vary the penalty? There is never likely to be a level playing field under the present system, in which one reads of positive test results being swept under the table. How will drug testing eliminate the genetic inequalities between athletes? How will testing improve the availability of top-level coaches and training facilities to all? How can it eliminate the inequality in financial incentives, allowing some athletes to train for 6 hours daily while others have to work to enable them to train for even 2 hours daily? We have swimming costumes that decrease drag in the water,1 resulting in faster times. These are not universally available, giving their owners an advantage. A level playing field will never exist in our present system. It is incongruous that in all this mess, only drugs are available to all. The current frenzy to test blood has ethical problems which have not been addressed.2 What is to happen to an athlete who develops an infection from a dirty needle? Who is responsible for the tester who has a needlestick injury from an HIV-positive athlete? It is worth remembering that this diagnosis will only be made 3 months after the Games, when everyone has dispersed. The whole area needs to be reviewed by an outside body with no vested interest in the outcome.

Anthony P Millar

Percy James (“Jim”) White was born on 8 December 1919 —“delivered on a kitchen table by an alcoholic midwife in Murphy Forest, Benambra”, or so the story goes. He spent a life successfully combining his love for farming, medicine and family. He attended Benambra state school in northeastern Victoria, St Patrick’s College (Sale), Trinity Grammar School (Kew), then Melbourne Grammar School, where he rowed in the victorious crew at Henley on the River. He graduated in medicine from the University of Melbourne in 1944. Jim did his residency at the Royal Brisbane Hospital, then, in 1945, became a flight lieutenant in the Royal Australian Air Force. After a period in Melbourne conducting medical examinations on Air Force personnel, he was moved to Darwin as Principal Medical Officer North-Western Area (Darwin). He married Louris Larsen-Disney in 1948 and, a year later, returned to farming at “New Metunga”, in Benambra, later moving to the town of Wooragee. Returning to Melbourne in 1953, Jim began work at the Victorian Health Department as a District Health Officer, covering, at first, his beloved Gippsland area. Later, he was appointed Senior District Medical Officer (Metropolitan), and occasionally took on the role of Acting Head of Department. He was also a Member of the Faculty of Community Medicine of the Royal Colleges of Physicians of the United Kingdom and a Foundation Fellow of the College of Medical Administrators, established in 1967. In 1979, Jim retired from the Victorian Health Department to work part-time in the Department of Veterans’ Affairs. (One day, while examining a veteran, he found notes he had written when examining the same person 40 years earlier!) From 1982 to 1987, Jim was a board member for the Greenvale Hospital. He also lectured as a Foundation Member of the Early Planning for Retirement Association. He was a key player in several Probus clubs, being President of both the Brighton and Toorak clubs. Jim died in his sleep on 16 August 2004. He is survived by his wife of 57 years, Louris, and children Donald, John, Diana, Robert and Andrew.

John C White

Men’s health. 2nd ed. Roger S Kirby, Culley C Carson, Michael G Kirby, Riad N Farah (editors). London: Taylor and Francis, 2004 (xvii + 522 pp). ISBN 1 84184 258 3. THE LATEST EDITION of Men’s health is a comprehensive reference book on all aspects of men’s health. All chapters have been revised and new topics, such as men’s attitude to cancer and genital piercing, have been introduced. The preface reminds us of the mortality gap which persists between the sexes and that men need to take care of themselves and their health. The book is intended for primary care practitioners and specialists in the diseases that commonly afflict men (urology, diabetes, cardiology, HIV). The editors and contributors are American and English, and they confine themselves to information about adult men. Every possible topic and disease process that involves men is covered — some in more detail than others. Social issues, risk behaviours and suicide provide an important introduction, with the rest of the book covering medical conditions such as cardiac disease, obesity, diabetes, prostate and bladder disorders, erectile dysfunction, male cancers and Peyronie’s disease. Information is included on pathogenesis and treatment, the detail is not excessive, and the chapters are just the right size for easy reading. Plenty of references are provided for those seeking further information. I was particularly impressed by the information on alopecia, osteoporosis, and genital trauma. The chapter on androgen deficiency is surprisingly brief considering the ongoing controversy over testosterone supplementation for the so-called male “andropause”. The chapter on circumcision is balanced and objective, and the section on genital piercing is novel, providing information that few of us are aware of. The pictures are unforgettable! The recommended retail price of Men’s health is $165. I believe this is good value for the huge amount of up-to-date and well-written medical information it contains. Any healthcare professional who treats men would find this book a valuable asset. Michael P LowyGeneral Practitioner Sydney Centre for Men’s Health Bondi Junction, NSW Order this book

Michael P Lowy

Sudden death in infancy, childhood and adolescence. 2nd ed. Roger W Byard. Cambridge: Cambridge University Press, 2004 (xviii + 643 pp). ISBN 0 521 82582 2. . IN THE SECOND EDITION of this acclaimed text, Roger Byard, of the Forensic Science Centre in Adelaide, has expanded on his detailed survey of common and less frequent causes of death in childhood. The first edition, published in 1994 and written together with US forensic pathologist Stephen Cohle, was a work of great scholarship and has received extensive and justified acclaim. This new edition expands on the considerable strengths of the first and will no doubt be viewed as an excellent reference work in the field of paediatric sudden death investigation. This book is longer, has greatly enlarged chapters on non-natural death and sudden infant death syndrome (SIDS), and now has colour photographs to complement the numerous monochrome illustrations. Useful appendices include guidelines, checklists and protocols for the conduct of autopsies in specific circumstances, and an example of a “plain English” autopsy information pamphlet for parents. Reflecting Professor Byard’s lifelong interest, the section on SIDS and associated conditions is excellent, providing a detailed overview of the syndrome and the conduct of investigations into such deaths. Similarly, there are well-structured chapters on non-natural deaths, written together with Dr Cohle. The rapidly evolving field of inflicted fatal childhood injury is reviewed in detail, and provides a balanced view on the pathophysiology of conditions such as the shaken infant syndrome and retinal haemorrhage. As with all books, there are some shortcomings. Principal among these is the emphasis on the autopsy and anatomical pathology in the investigation of paediatric sudden death. Metabolic and inherited diseases are relatively under-represented, although a number of excellent encyclopaedic texts in this area are available. Similar criticism can be made on the paucity of detail on congenital heart disease and neuropathology. Again these areas have been extensively covered in other texts specific to those topics. These are minor quibbles, and do not detract from an excellent body of work. The main focus of the book is sudden death, both natural and unnatural, and this is covered admirably. What is the target audience for this book? Childhood death is relatively uncommon in developed societies, and most general practitioners will see few childhood deaths in any single year. With a recommended retail price of $450 and 643 pages in length, this book is aimed primarily at paediatricians, paediatric pathologists and forensic pathologists. No doubt the legal profession will also show an interest, especially in the section on intentional trauma. Johan A DuflouDeputy Director NSW Institute of Forensic Medicine, Glebe, NSW

Johan A Duflou

Bariatric bonus Bariatric surgery — the surgical therapy of morbid obesity — has more benefit than weight loss, say US authors. Most patients who undergo this kind of surgery will also benefit from the resolution or improvement of at least four life-shortening comorbid diseases — type 2 diabetes, hyperlipidaemia, hypertension and obstructive sleep apnoea. The authors conducted a systematic review and meta-analysis of 134 studies, including controlled trials and uncontrolled case series, involving a total of more than 22 000 obese patients. All forms of bariatric surgery reviewed had a marked effect on weight loss and all four comorbidities studied; however, resolution of diabetes was most likely after malabsorptive or mixed malabsorptive/restrictive procedures rather than purely restrictive gastroplasty and gastric banding. JAMA 2004; 292: 1724-1737 Ending with a CRASH The CRASH (Corticosteroid Randomisation After Significant Head injury) trial, a multi-centre international collaboration involving 239 hospitals in 49 countries, including Australia, has been stopped early because of an unexpected and alarming result.1,2 In CRASH, patients aged 16 years or older, with a head injury and a Glasgow coma score of 14 or less within 8 hours of injury (and who did not have a clear indication or contraindication for corticosteroid use) were randomised to receive an early 48-hour infusion of either methylprednisolone or placebo. It became apparent, when only halfway to the planned recruitment target of 20 000, that the corticosteroid group had an 18% increase in the relative risk of death from all causes in the first two weeks after treatment. The mechanism responsible for this increase in deaths was not known; however, it was not influenced by injury severity or time since injury. German commentators suggested that, during the 1980s and earlier, about 10 000 patients with brain injury could have lost their lives because of the then wide use of corticosteroid treatment.2 1. Lancet 2004; 364: 1321-1328 2. Lancet 2004; 364: 1291-1292 Stop the chocolate An Australian resident of two years’ standing has called for schools and education departments to take action to prevent school fund-raising campaigns that involve selling chocolates. Given the rapid increase in childhood obesity in our society, Gunatilaka suggests that, rather than promoting poor dietary habits, schools should instead use a child’s eagerness to support his or her school as an opportunity for promoting healthy food habits. Healthier alternatives to chocolate could include dried fruits and long-life milk packets. Aust N Z J Public Health 2004; 28: 494 Here, kitty kitty . . . Tasmanian authors say that empirical antibiotic therapy should be commenced for minor infections following cat bites of the hand, rather than waiting for microbiological results. Mitnovetski and Kimble reported a series of 41 patients treated for cat bites of the hand in which five required surgery, mainly for drainage of deep infection. The use of prophylactic antibiotics for small wounds following cat bites to the hand has previously been shown to reduce the infection rate from 28% to 2%. Aust N Z J Surg 2004; 74: 859-862 Tako-tsubo Emotional stress can trigger an acute myocardial infarction in the absence of significant coronary artery disease, say Australian authors. Connelly and colleagues reported three women, aged 40, 49 and 58 years, who had a myocardial infarct shortly after experiencing emotional distress related to a minor road crash, a heated meeting about a case of sexual harassment and an argument leading to a permanent family break-up, respectively. On angiography, none of the women had serious coronary heart disease, but all showed temporary left ventricular wall motion abnormalities. The angiogram pattern was first described by Japanese authors in 1991 as tako-tsubo, as it resembles the shape of the instrument used to trap octopuses in Japan (tako = octopus, tsubo = pot). Heart 2004; 90: e52 Cochrane report The Cochrane Collaboration has come a long way in its first 10 years, but has further to go, according to a Canadian expert. The Collaboration is a unique, worldwide, not-for-profit organisation that aims to help people make well-informed decisions about healthcare through its core business of producing systematic reviews which are regularly updated and published quarterly. The Cochrane Library (2004, Issue 3) presented 2074 systematic reviews authored by about 7000 volunteers worldwide, including reviews relevant to the top 10 causes of disability in both developed and developing countries. However, as the reviews are often interest-driven rather than priority-driven, the Collaboration has not been sufficiently responsive to the immediate needs of policy-makers; further, the reviews have not adequately assessed the potential harms of healthcare interventions. CMAJ 2004; 171: 747-749

Ann Gregory