Volume 176 Issue 8

For most of the 20th century, Australia's Medical Colleges have played an important role in our healthcare system. The Colleges were founded to maintain and enhance professional standards in medicine's various disciplines. This was achieved through providing opportunities for the continuing medical education of College Fellows, by certifying that aspiring specialists could practise independently, and by encouraging research. The training role of Colleges was progressively developed, with evolution of training curricula, and through involvement in selection of trainees, appointment of supervisors and accreditation of hospitals and other healthcare providers as suitable sites for specialist training. Over the years, the Colleges have attained considerable professional and community respect. This respect has underpinned the freedom that Colleges enjoy and allowed for their participation in the medical profession's regime of self-regulation. However, this respect and standing could rapidly diminish if the Colleges do not jealously guard their independence, while acknowledging their accountability to society. In this, they should be concerned primarily with the knowledge, competence and performance of their Fellows and with ways to assist in the maintenance of these attributes. More recently, Colleges have sought to have the expertise of their Fellows contribute to community debates on the safety and quality of healthcare and broader health policy issues. This has been facilitated, in a number of instances, by the establishment of health policy units such as that of the Royal Australasian College of Physicians, which provides an evidence base for College views. For this expertise to be widely accepted, the Colleges must not be subject to external influences, nor have a major role in protecting their Fellows' financial and narrow professional interests. Our Colleges increasingly recognise that they must be actively involved with the community and other key organisations in the healthcare and educational systems and that their activities should be open to external scrutiny. The acceptance of this move to external scrutiny is demonstrated by the strong support of the Colleges for the Australian Medical Council (AMC) to become the accrediting body for specialist education and professional development programs. Already, trial accreditation of two Colleges (the Royal Australian and New Zealand College of Radiologists and the Royal Australasian College of Surgeons) has demonstrated the rigour and value of the process.1,2 Areas requiring improvement have been identified and the Colleges taking part have to report to the AMC on a regular basis on how these shortcomings are being addressed. Accreditation is helping the Colleges to ensure that they are meeting the expectations of their Fellows, trainees, providers of healthcare and consumers, and that they are publicly accountable. Hopefully, it will ensure that College trainees are not only skilled clinicians but also appreciate the issues associated with the delivery of safe, high-quality care in the Australian healthcare system. AMC accreditation is also providing a transparent pathway for other organisations to seek accreditation for training and professional development programs in competition with those of existing Colleges. No other country has developed such a robust external system of accreditation of specialist education and training, and the process is attracting considerable international interest. Our Colleges are also working closely with the AMC and Medical Boards to establish specialist medical registers in all States and Territories. Among other benefits, these registers will allow the community to more readily identify medical practitioners as recognised specialists. As part of this process, Colleges are contributing to the development of the criteria for regular re-registration and examining how these can reflect the maintenance of professional standards. Rightly, the community expects that all medical practitioners will maintain their competence and behave in a professionally appropriate way. While it may seem appropriate for Colleges to consider complaints that one of their Fellows has failed to meet these standards, Colleges in Australia do not have this role. Medical Boards, but not Colleges, have the statutory authority to investigate complaints against doctors and can give protection to the complainant. The legal position of Colleges in undertaking such investigations is far from certain. The appropriate role of the Colleges in such difficult matters should be to provide independent advice on standards to Medical Boards and other statutory bodies, and to provide assistance to the Board in the re-education and retraining of underperforming Fellows. The traditional discipline base of the Colleges may impede innovative developments in healthcare delivery. Increasingly, there is overlap and close collaboration in clinical activities (such as in radiation oncology and medical oncology) and there is a trend to bring together, in one service unit, physicians and surgeons dealing with the same body system. Strengthening the intercollegiate body (the Committee of Presidents of Medical Colleges), while maintaining individual College autonomy, may well assist this process by promoting multiple College training and professional development programs. This would seem preferable to formation of new Colleges, although the AMC now has a more robust and transparent process for these to be recognised. If Colleges are to continue to command the respect and confidence of the medical profession and society, they must not become financially or otherwise dependent on government or other organisations with a vested interest in their opinions and contributions to public debate. While it is understandable that Colleges, because of their unique expertise, may undertake some contractual work for governments or other organisations to assist in improvements to healthcare, this must be done with great caution. Colleges should ensure they are not influenced by the provider of the funds; furthermore, it would be extremely unwise to build up a significant College bureaucracy or facilities that are dependent on such external funding. Equally, Colleges should be extremely reluctant to become fundholders for government-sponsored training programs or to build up organisations dependent on such funding. Political decisions, as has recently happened with the training program for general practitioners, can place a College in a very difficult position. The threat of removal of such funding and the resulting impact on the financial viability of a College could temper criticism of the policies of government or other organisations. These issues have received considerable attention in North America and Europe. Pellegrino and Relman3 recently argued strongly that a professional organisation such as a Medical College can not become involved in protecting its members' financial welfare or other narrow professional interests: "It would be far better . . . for physicians to promote patients' interests on ethical and medical grounds as members of medical associations than to seek confrontation as union members. In our view, unions and truly professional associations are simply incompatible." These sentiments obviously have parallels in Australia. As the eminent ethicist Sullivan4 points out, true professionalism depends on the moral contract between the professional and society. It is only when the responsibility to patients and to the public interest is held to be paramount that members of the medical profession can expect society to accept self-regulation of the profession and to listen carefully to proffered opinions and advice. Colleges must continue to promote these principles to their Fellows and trainees, and Colleges and their Fellows must demonstrate to society their commitment to them.

Peter D Phelan MD FRACP

We are making progress in our understanding of the hepatitis C virus, but there is still a long way to go The identification of the hepatitis C virus (HCV) in 19891 delineated a disease previously masquerading under the title of "non-A, non-B hepatitis". In the ensuing years, hepatitis C has become a national epidemic, with more than 150 000 Australians known to be infected. It is estimated that an additional 11 000 new infections occurred each year during the 1990s.2 Escalating rates of HCV infection will have enormous consequences, as 10%–15% of people infected have the potential to progress to end-stage liver disease, with all the implications that has for healthcare services in the years ahead.3 Australia has taken many unique steps in its handling of the hepatitis C epidemic. In 1994 and 1997, the National Health and Medical Research Council published two major reports from working parties comprised of specialists, general practitioners and community representatives.4,5 These were seminal in directing approaches to the diagnosis, treatment and management of HCV-infected people and, to a lesser extent, prevention of further spread. Indeed, Australia was the first country to develop a National Strategy for HCV.6,7 NSW Health has held successful Hepatitis C Awareness Weeks in 2000 and, more recently, in 2002, which have increased public awareness of many issues relating to HCV. NSW Health has recently released a Treatment and Care Plan for HCV, which, among other things, emphasises the importance of GPs in the evaluation and management of HCV-infected people.8 The possibility of accrediting appropriately trained GPs to prescribe anti-viral therapy for HCV is also discussed. So, where are we going? The recent report by the Anti-Discrimination Board of NSW on hepatitis-C-related discrimination presents compelling evidence that there is still much to be done if we as a society are to be seen to be dealing caringly and rationally with this disease.9 The report highlights the disturbing reality that most discriminatory actions against people infected with HCV are perpetrated in healthcare settings. The HCV Projections Working Group of the Australian National Council on AIDS, Hepatitis C and Related Diseases, which advises the federal Minister for Health on these diseases, will report later this year on the increasing rate of HCV acquisition, highlighting the imperative of improving our prevention strategies. The rate of infection is increasing, in large part, because an increasing number of young people are choosing to commence injecting drug use. While public messages on safe injecting practices are promoted widely, many young people ignore these messages in their early phase of drug use. The HCV antibody prevalence rate in those injecting for less than three years fell from 22% in 1995 to 13% in 1997,10 but, despite enormous efforts to increase the availability of clean needles to users, the rate has not dropped any further. Treatment availability and efficacy also remain problematic. Australia offers, through the "highly specialised drugs" program, combination therapy with alpha interferon and ribavirin, providing a sustained viral response rate of 40% overall (ie, in 40% of treated patients, HCV RNA remains undetectable by polymerase chain reaction) (patients with HCV genotype 2 or 3 can expect a 60%–70% sustained response rate).11 By limiting treatment to patients with fibrosis on liver biopsy, the Pharmaceutical Benefits Advisory Committee led, rather than followed, a trend to downplay the need for treatment of all patients. This has highlighted the need for management strategies for those not eligible for, or choosing not to have, treatment. Many major centres now offer support services and education programs, allowing individuals to defer treatment, awaiting better options in the future. Progress is being made in providing better services for prison inmates, among whom there is a high prevalence of HCV infection. In the past, access to therapy has been limited, but the appointment of specialists to Corrections Health services and the funding of a health study of the Tasmanian corrections system is changing that. Prevention strategies are harder to implement. Bleach is made available in most prisons, and methadone programs are expanding, but needle/syringe programs are not available. HCV-infected people from non-English-speaking backgrounds have the added problem of a language barrier. Treatment facilities have become increasingly aware of the need to provide special support for these patients. This is particularly needed if antiviral therapy is to be commenced. What needs to be done better? Greater attention must be directed to reducing spread within the most at-risk community, namely our population of injecting drug users. This group remains marginalised for reasons that are easy to explicate but difficult to overcome. Debate must continue on optimal ways to reduce the risk of young people contracting HCV infection. Needle/syringe programs, while unpopular with many people in our society, have the potential to reduce the risk and must be supported by those who are in a position to influence policy. We need to increase public awareness of the improved efficacy of treatments. We also need to direct more effort towards improving the evaluation and assessment of patients by GPs before referral to busy liver clinics, so that only those who are eligible for and wanting treatment are referred. The HCV research effort requires further support from major funding bodies, and relevant groups are pursuing this actively. A greater understanding of the virus, the mechanisms of viral clearance and the immunopathogenesis of the disease is required urgently. Research is under way to develop a vaccine. In summary, we are some of the way there, and making progress, but there is still a long way to go!

Robert G Batey MD FRACP FRCP

Stress is a normal part of everyday life, but it can lead to psychological strain and difficulty coping with life's demands. Although a variety of non-specific symptoms such as headaches, disturbed sleep, depression, anxiety, irritability or substance misuse may result when individuals are stressed, there is generally little evidence that such symptoms are a direct result of particular stressful events. Rather, they are non-specific and can be precipitated by a variety of other causes, including other stressors to which the individual may be exposed. The issue becomes more complex when stress occurs in the occupational arena because of issues of confidentiality and the sometimes competing interests of patients, insurers and employers. In addition, organisational problems related to work stress, such as high absenteeism, high staff turnover, industrial disputes and poor quality control (leading to inferior products and reduced competitiveness for the organisation) may further complicate matters. In this issue of the Journal, the cross-sectional survey of Western Australian general practitioners by Russell and Roach (page 367) attempts to start gathering information on the variety of approaches taken by GPs when faced with symptoms of anxiety which are apparently caused predominantly by occupational stress.1 Obviously, the article has been written in the context of a political agenda in Western Australia, with a desire by some to consider accreditation for general practitioners in managing work-related stress claims. This was clearly opposed by about 70% of respondents to the survey. The findings of Russell and Roach suggest that GPs with experience in the practice of occupational medicine are less likely to recommend time off work. Additionally, those who had knowledge of the specific requirements for lodging a work-related stress claim (which is likely to include those with experience in occupational medicine) were more likely to recommend initiating a claim. Many of the GPs surveyed were concerned about practising medicine in a workers compensation environment, and the implications this has for patient confidentiality. Many also reported reluctance to get involved in the workers compensation system. Some of the reasons for this include a lack of confidence in their knowledge of legislative requirements for opening workers compensation claims and concerns that such an approach has the potential to further compromise their patients' health. In Australia, whether a claim is eligible for compensation is determined by the relevant insuring authority. While some jurisdictions have the option of allowing payment of medical and rehabilitation expenses and reimbursement of salary while claims are being determined, until a claim is accepted no benefits are technically payable, and, if reimbursements have been paid, these may have to be repaid if the claim is subsequently rejected. Thus, incurring treatment expenses while the claim is being determined can have substantial financial complications for an already stressed worker. This is further compounded by the sometimes significant time delays in the determination of some stress claims. For example, in South Australia (which is the only jurisdiction from which I was able to obtain data), 500 claims with stress as the primary cause of injury were lodged in the 1998–99 financial year. It took an average of 77 days to determine whether a claim was compensable or not; 223 claims were initially rejected, but 88 of these were eventually accepted after litigation (H Woznitza, Program Manager – Education, WorkCover Corporation SA, personal communication). There is no reason to expect that this sobering picture is substantially different in other jurisdictions. Obviously, this uncertainty and tardiness cannot assist the mental health of someone who already has a stress-related illness. As Russell and Roach note, guidelines support a therapeutic benefit from early return to work,2 although the evidence for this is scanty. There is some support for the benefits of early return to work in the South Australian data. For claims lodged between July 1996 and 30 June 1998 (see Box ), in cases of occupational stress where there was an early return to work the likelihood of patients requiring long term ongoing support was reduced. However, these data need to be treated with caution because they are not controlled for severity of illness. In contrast, there is good evidence to suggest that people who are injured and claim compensation for the injury have poorer health outcomes than those not involved in the compensation process.3-5 A recent report produced by the Australasian Faculty of Occupational Medicine of the Royal Australasian College of Physicians highlighted the deficiencies in knowledge in this area.5 In particular, research into causes of poor health outcomes for individuals in the compensation system is limited and inconclusive, and not enough is known of the effects of different types of schemes or methods of case management. Not so long ago in the Journal, Cameron outlined some of the technical and ethical problems doctors face when working within the workers compensation system framework.6 Issues of role confusion (gatekeeper versus patient advocate), objectivity in the face of coercion, and patient and insurer mistrust all contribute to many practitioners shying away from workers compensation cases. These concerns were reflected in the issues perceived by the GPs in the survey by Russell and Roach as barriers to effective management of patients with work-related stress.1 So, what messages can be drawn? Given the recognised adverse health outcomes that commonly occur after lodging a compensation claim, and the obvious stress involved in the process, it is not surprising that many general practitioners elected to temporise rather than immediately commence a compensation claim. However, patients have rights under workers compensation legislation to receive benefits for work-related illness and injury. These benefits are more generous than those available under the Medicare system (eg, the payment of treatment from a psychologist is able to be reimbursed through workers compensation). Indeed, claiming benefits from Medicare for a workers compensation injury is specifically precluded. There is also a need for systems that enable treatment to occur with certainty of reimbursement of costs while claims are being determined and disputed. Obviously, practitioners would benefit from increased education and skills, and the proposed Western Australian accreditation system may be one way to assist this process. Increased education and skill sharing of all participants (including consumers and the legal profession) in the compensation system may address some of the concerns about the adversarial system. Another approach may be to change the system itself, particularly by reducing its adversarial nature so that more time and effort is available for patient care. Exploring solutions that recognise "work stress" as a multifactorial problem, often with some of its origins outside the workplace, may be a worthwhile approach. This would necessitate a collaborative approach to managing work-related stress, with all stakeholders contributing their particular skills and perspectives. Finally, confidentiality issues in workers compensation stress claims remain significant barriers in the minds of medical practitioners and their patients. Clearly, there is a need for appropriate research strategies to examine and address these issues systematically to optimise health outcomes in a cost-effective way. Stress claims for which salary reimbursements were received from the South Australian WorkCover Corporation between 1 July 1996 and 30 June 1998* Claims still receiving reimbursement of all or part of salary Time from date of injury to return to work Number of claims 12–15 months from date of injury 24–27 months from date of injury Up to 4 weeks 81 16 (20%) 11 (14%) 4 weeks to 3 months 87 23 (26%) 14 (16%) 3–15 months 90 36 (40%) 24 (27%) * H Woznitza, Program Manager – Education, WorkCover Corporation SA, personal communication.

Ian D Steven MB BS, MD, MPH, FRACGP, FAFPHM · E Michael Shanahan BM BS, MPH, FAFOM, FRACP

To fill this important gap in our knowledge would require collaboration between researchers from the manipulation disciplines and neurologists Manipulation of the spine is a popular treatment which is used frequently by chiropractors. In the past 25 years, its use has been evaluated by increasingly sophisticated randomised trials. In a recent review of the emergence of the chiropractic profession from "alternative" to more "mainstream",1 the results of 20 randomised controlled trials of cervical manipulation (for migraine and tension headache, cervicogenic headache or neck pain) were described: 11 were positive, and nine equivocal. Given this supporting evidence, as well as the frequency of use of manipulation2 and the health and social impact of the conditions treated, it is important to consider any suggestions that manipulation may do more harm than good with some care. In this issue of the Journal, Ernst (page 376)3 reviews case reports of serious adverse events associated with cervical spine manipulation. Although Ernst acknowledges the considerable doubt about a causal relationship between the manipulation and the adverse event, he is inconsistent in suggesting that the anecdotal and uncontrolled evidence of the case reports favours the adverse events, often strokes, being an effect of manipulation. Elucidating a causal relationship calls for greater clarity, less ambivalence and generally better science in the present evidence-based climate. Thus, the important question to be answered in the light of Ernst's article is whether the association between neck manipulation and stroke is actually causal and, if so, in what direction? The incidence of cerebrovascular accidents after neck manipulation has been estimated by various authors to range from 1 in 400 000 to between 3 and 6 per 10 million manipulations.1 Ernst's article suggests that the mechanism of the strokes associated with neck manipulation tends to be dissection of the vertebral or carotid arteries, an observation also made by others.4 However, dissection is not the only mechanism proposed in Ernst's review. Of the 42 cases tabulated, 20 were not attributed to dissection (although only two such cases appear to have been confirmed by angiography). Of these 20, nine seem to be either intracranial events or lesions such as cervical canal stenosis, intradural mass or cervical disc hernias, which are more likely to have been pre-existing conditions. Strokes following manipulation could also be linked to other pre-existing conditions, such as vasospasm, or kinking of the vertebral arteries and thrombus without dissection.5 Smith and Estridge, reporting two cases of stroke after manipulation, suggested that smaller forces than those used in neck manipulation may be all that is required to precipitate stroke in the presence of such pre-existing lesions.5 They proposed that some premanipulation testing of the neck in rotation and extension might warn of the presence of such lesions. However, a recent review of the literature6 and a study of patients with positive premanipulation tests7 failed to demonstrate such a link. In favour of neck manipulation causing stroke is the fact that it is a mechanical intervention. Particularly if a dissection were already in progress, a mechanical intervention might accelerate it. However, an argument can also be made that the dissection, before manifesting itself as a stroke, causes head or neck symptoms requiring treatment from a chiropractor, osteopath or other manipulation practitioner. The ensuing stroke could be the natural progression of the condition regardless of the manipulation. This hypothesis is further supported by recent evidence that the strain to the vertebral artery conferred by a high-velocity neck manipulation is almost an order of magnitude lower than that required to mechanically disrupt it.8 Both hypotheses are reasonable, but bring us no closer to answering the question of whether or not it is more likely that a stroke will follow neck manipulation than occur without manipulation, and, if it is more likely to occur after manipulation, which subgroups of patients are susceptible. If practitioners of manipulation are precipitating certain types of strokes then they must be made aware of how to recognise these. If, on the other hand, they are mere bystanders in an ongoing process, this also needs to be established. Either way, they may have an important role to play in detection. There are no high-quality data available to provide the denominator to enable us to calculate either the risk or the odds ratios of stroke following manipulation and to thereby assess causation. To fill this important gap in our knowledge would require collaboration between researchers from the manipulation disciplines and neurologists. Community-based studies could examine exposed and unexposed groups who have or have not been affected by strokes or transient ischaemic attacks. A stroke registry employing rigorous case-ascertainment methods could support this. Considerable care would be needed in selecting controls, matching for stroke risk as well as age and sex. Exposure data would need to be detailed for both cases and controls, including an account of the intervention itself. Careful consideration would need to be given to whether to examine the relationship between manipulation and all strokes, or limit studies to vertebral and carotid artery dissections in younger patients only. The latter subgroup approach would help to provide the statistical power needed to draw conclusions, but the case for dispensing with a more global approach would need to be made carefully. The increased use of spinal manipulation for its demonstrated benefits in healthcare means that, in the future, even without any causal link to stroke, more of the strokes that do occur will follow manipulation, just as they follow other common events. Given the expectation that has been generated, this is likely to increase public alarm unless this logical fallacy is appreciated and manipulation professionals come to be regarded as responsible partners instead of pariahs.

Alan Breen DC, PhD

Objectives: To identify approaches to and barriers associated with the management of patients with work-related stress by general practitioners (GPs).Design: Cross-sectional postal survey using a self-administered questionnaire which included a case vignette of a patient with work-related stress and questions ascertaining perceived barriers to the effective general practice management of work-related stress.Participants and setting: 450 Western Australian GPs on the mailing list of a GP journal. The survey was conducted between 22 March and 28 April 2000.Main outcome measures: Likelihood that GPs would (i) choose to open a workers compensation claim and (ii) provide time off work for the patient described in the vignette.Results: Response rate was 50.1%. Eighty-five per cent (95% CI, 79.6%–89.7%) of respondents advised the hypothetical patient to take time away from work; however, only 44.0% (95% CI, 37.2%–50.7%) chose to initiate a workers compensation claim. GPs with training or experience in occupational health were less likely to advise the patient to stay away from work (odds ratio [OR], 0.30; 95% CI, 0.12–0.73), but were just as likely to initiate a claim. GPs were reluctant to involve the employer in management decisions, because of concern about patient confidentiality and the potential to make matters worse for the patient. These, and the adversarial nature of the workers compensation system, were the strongest perceived barriers to effective management of the condition.Conclusions: Our findings indicate that general practitioners take a pragmatic and varied approach to the management of work-related stress. The perceived difficulties with contacting employers challenges the principles of injury management within a workers compensation system which is dependent on liaison between system stakeholders.

Grant M Russell FRACGP MFM (Monash) · Sally M Roach PhD, PostGradDip, BAppSc

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology. Clinically, it may present with systemic symptoms (eg, malaise, fever, anorexia), arthritis, photosensitivity, or organ injury (eg, glomerulonephritis). Myocarditis occurs in up to 10%1 of patients with SLE, but severe cardiac failure is very uncommon. We report our clinical experience of fulminant cardiac failure complicating SLE. Clinical recordA 24-year-old Vietnamese woman with intermittent haemoptysis was investigated as an outpatient. Culture of early-morning sputum was negative for tuberculosis, and a computed tomography (CT) scan of her chest showed right middle-lobe consolidation with no perihilar lymphadenopathy. Bronchoscopy showed active bleeding from the middle lobe of the right bronchus. Bronchial washings were negative for mycobacteria on acid-fast stain and culture, and no abnormal cells were found. Full-blood examination showed no abnormality; in particular, she did not have anaemia or lymphopenia. The erythrocyte sedimentation rate was mildly elevated at 29 mm/h (normal range, 0–15 mm/h) and rheumatoid factor was elevated at 30 kIU/L (normal range, 0–20 kIU/L). The presumptive diagnosis at this time was low-grade pneumonia. Subsequent investigations revealed a positive antinuclear antibody titre of > 1:1280 (normal, < 1:160), with a speckled pattern. As there was also a past history of Raynaud's phenomenon, small-joint hand arthritis and intermittent pleuritic chest pain, she was referred for rheumatological opinion. Two months after the onset of haemoptysis and before she could attend her rheumatology appointment, she presented to our emergency department feeling unwell, with a history of four days of fever, lethargy, dyspnoea, non-productive cough, nausea, vomiting and diarrhoea. Physical examination showed sinus tachycardia (130 beats/minute), a systolic blood pressure of 95 mmHg, cool peripheries and a dry tongue. Her jugular venous pulse was not visible. She was tachypnoeic (respiratory rate, 24 breaths/min), but auscultation of her chest showed no abnormality. She was given 1.5 L of normal saline intravenously over one hour for presumed dehydration. Subsequently, her condition deteriorated, with respiratory distress and pink, frothy sputum, and a chest x-ray revealed acute pulmonary oedema. Short runs of ventricular tachycardia were noted on her monitor. Electrocardiography showed sinus rhythm, right-axis deviation, Q waves in leads V1–V3, I and aVL, with high take-off in the ST segment in V1–V3. In subsequent ECGs, there was no evolution of the ST-segment change, indicating active myocardial ischaemia was unlikely. The level of cardiac troponin I was elevated at 9.6 µg/L (normal, < 0.04 µg/L). Her lymphocyte count was low at 0.81 × 109/L (normal, 1.0–4.0 × 109/L). The working diagnosis at this stage was acute heart failure secondary to a myocardial process such as acute myocarditis or valvular heart disease. Because of her respiratory distress, intubation was required and during this procedure her blood pressure fell further to 75/50 mmHg. Inotrope support was commenced with adrenaline at 10 µg/min. Urgent echocardiography confirmed severe global reduction in both left and right ventricular systolic function. Neither ventricle was dilated. There were no significant valvular abnormalities. A small pericardial effusion was present with no evidence of cardiac compression. Over the next two hours, despite an increasing inotrope infusion rate and insertion of an intra-aortic balloon pump, she had a low mean arterial pressure of 62 mmHg (generally, > 65–70 mmHg is required for major organ perfusion) and a low cardiac index of 2.1 (normal range, 2.5–3.6 L.min-1.m-2) (cardiac index = cardiac output per body surface area). She had no urine output. She was then placed on to extracorporeal membrane oxygenation (ECMO), and intravenous methylprednisolone (250 mg daily) was commenced. Over the next 24 hours, she developed acute renal failure — serum creatinine concentration peaked at 625 µmol/L (normal range, 40–120 µmol/L); ischaemic hepatitis — alanine transaminase level peaked at 3528 U/L) (normal range, 7–56 U/L); and coagulopathy — international normalised ratio (INR), 3.4 (normal range, 1.0–1.2); activated partial thromboplastin time (APPT), 44 s (normal range, 23–34 s); platelet count, 270 × 109/L (normal range, 150–450 × 109/L); fibrinogen level, 2.2 g/L (normal range, 1.5–4.0 g/L). Consequently, endomyocardial biopsy was not performed. After institution of ECMO, her condition stabilised and four days later she was able to be weaned off both ECMO and inotrope support. Renal and liver function returned to normal. Repeat echocardiography performed 10 days after admission showed a marked improvement in left ventricular systolic contraction, which was now only mildly reduced globally. Right ventricular function was normal. Other relevant test results are shown in the Box. Based on these results and the patient's clinical presentation, the rheumatologist diagnosed SLE. She was prescribed prednisolone (50 mg daily), azathioprine (50 mg daily), hydroxychloroquine (200 mg twice daily) and bone protective agents including alendronate sodium (70 mg once a week), calcium carbonate (600 mg at night) and ergocalciferol (1000 units daily). She was discharged 17 days after admission to a rehabilitation hospital and a week later she returned home. Six weeks after her emergency department presentation, she returned to work. DiscussionAcute myocarditis with severe cardiac failure and shock is a rare manifestation of SLE, with only a few cases reported.2-4 To our knowledge, this is the first in which ECMO was used and the patient survived. This case emphasises the importance of aggressive circulatory support to keep the patient alive and allow time for the potential recovery of the myocardium, either spontaneously or with corticosteroids. The reported use of ECMO support has predominantly been for postcardiotomy cardiogenic shock,5 and in cardiogenic shock related to acute myocardial infarction6 and acute myocarditis.7,8 Although the reported benefits of ECMO in these small studies vary considerably, for any patient to survive cardiogenic shock refractory to inotrope and intra-aortic balloon pump, with ECMO support, is a significant result. ECMO provides a bridge to recovery or to a decision about either heart transplantion or a ventricular-assist device. Partial or complete recovery of the myocardium in acute myocarditis with shock while receiving ECMO may be spontaneous or possibly facilitated by immunosuppressive therapy.7 The use of corticosteroid and other immunosuppressive therapy in acute myocarditis is controversial. A randomised trial,9 which studied patients with histological evidence of myocarditis and an ejection fraction less than 45%, did not find that prednisolone with either cyclosporin or azathioprine for 24 weeks improved ejection fraction or survival. However, a more recent trial10 found a significant improvement in ejection fraction and clinical status at two years in the group treated with three months of prednisolone and azathioprine. An immunohistological marker (upregulation of human leukocyte antigen [HLA]) was used on biopsy specimens to identify chronic myocarditis. Compared with histology alone, this marker selected a more homogeneous group of patients with inflammatory cardiomyopathy caused by active immune processes who may respond better to immunosuppression.10 There have been anecdotal reports of improvement in symptoms,2,3 and in left ventricular function,4 with the use of corticosteroids or immunoglobulins11 in severe cardiac dysfunction caused by SLE-related myocarditis. There is also some evidence of a better transplant-free survival in patients with fulminant, rather than non-fulminant, myocarditis if circulatory support was provided when they were critically ill.12 This suggests that more severe myocardial disease is associated with potentially greater reversibility of myocardial impairment. With the possibility of improvement, either spontaneously or with immunosuppressive therapy, it would be prudent to implement aggressive circulatory support with ECMO for patients with cardiogenic shock due to fulminant myocarditis who have failed to respond to inotrope support and intra-aortic balloon pump therapy. Results of immunological investigations Tests Results Reference range Antinuclear antibodies Positive (> 1:1280 titre), speckled pattern < 1:160 titre Anti-dsDNA 4 IU/mL 0–7 IU/mL Antibodies against extractable nuclear antigens Anti-La Positive Anti-Ro Positive Anti-RNP Negative Anti-Sm Negative Anti-Jo Negative Anti-Scl-70 Negative IgG anticardiolipin antibody 2.7 1.0–9.0 IgM anticardiolipin antibody 1.0 0.4–5.0 Lupus anticoagulant antibody Negative

Michael C H Leung MB BS(Hons) · Richard W Harper MB BS, FRACP · John Boxall MB BS, FRACP

Objective: To summarise recent evidence from case reports (published January 1995 – September 2001) of adverse events after cervical spine manipulation.Data sources: Five computerised literature searches (MEDLINE – Pubmed; EMBASE, the Cochrane Library, AMED [Allied and Complementary Medicine Database], and CISCOM [Centralised Information Service for Complementary Medicine]) were performed. No language restrictions were applied.Study selection: All case reports containing original data of adverse events after cervical spine manipulation were included.Data extraction: All articles were evaluated and key data extracted according to pre-defined criteria: patient's age, sex and diagnosis; type of therapist; type of treatment; nature of adverse event; method of diagnosis; and clinical outcome.Data synthesis: Thirty-one case reports (42 individual cases) were found. The patients were equally distributed between the sexes (21 male, 20 female, one unknown) and mostly middle-aged (range, 3 months to 87 years). Most were treated by chiropractors. Arterial dissection causing stroke was reported in at least 18 cases.Conclusions: Serious adverse events after cervical spine manipulation continue to be reported. As the incidence of these events is unknown, large and rigorous prospective studies of cervical spine manipulation are needed to accurately define the risks.

Edzard Ernst MD, PhD, FRCP(Edin)

The recent AusDiab data show that 7.2% of Australians over 25 years of age have type 2 diabetes mellitus and a further 16.1% have impaired glucose tolerance. In fact, 20% of Australians over 65 years have type 2 diabetes and it is well known that morbidity and mortality are significantly increased in affected patients.1,2 However, there is evidence from the United Kingdom Prospective Diabetes Study (UKPDS) that good glycaemic control can improve morbidity by improving microvascular complications of type 2 diabetes, such as retinopathy, nephropathy and neuropathy3 (E2). (See Box 1 for an explanation of level-of-evidence codes.) There is a well-recognised and strong association of type 2 diabetes with obesity and the insulin resistance syndrome. "Syndrome X"5 refers to a collection of pathophysiological sequelae resulting from insulin resistance and includes type 2 diabetes, as well as hypertension, dyslipidaemia, hyperuricaemia and elevated plasminogen-activator-inhibitor-1 levels.6 Pathophysiologically, type 2 diabetes is characterised by defects in insulin action (ie, insulin resistance) and secretion (ie, β-cell dysfunction), and increased hepatic glucose output.2 It is also well established that type 2 diabetes is a progressive condition, and that β-cell failure ensues in many patients. The UKPDS showed that, although monotherapy with sulfonylureas, metformin or insulin can achieve good glycaemic control initially, sustained control with these agents fails in 50% of patients after three years. Most patients will require multiple therapies to obtain adequate long term glycaemic control (E2).7 Currently available therapiesCurrently available therapies for type 2 diabetes include various oral agents such as sulfonylureas, metformin, α-glucosidase inhibitors (such as acarbose) and insulin. These agents can be used as monotherapy or in combination therapy. They have been used extensively, are efficacious and have a low incidence of serious adverse events. Recently, a new class of oral agents, the thiazolidinediones (TZDs), which act to improve the insulin sensitivity of peripheral tissues, has become available for use in clinical practice. Troglitazone was the first agent in this class and was effective, but was withdrawn because of severe and unpredictable hepatic failure. Newer TZDs such as rosiglitazone and pioglitazone are now available and have been approved by the Therapeutic Goods Administration (TGA) for use as monotherapy in patients with type 2 diabetes inadequately controlled by lifestyle measures, and also for use in combination with sulfonylureas or metformin in patients with inadequate glycaemic control.8,9 Pioglitazone is also licensed for use in combination with insulin.9 To date, hepatotoxicity does not appear to be a significant problem with these newer agents. Neither drug is listed on the Pharmaceutical Benefits Scheme yet. A profile of these two drugs is shown in Box 2. Thiazolidinediones and peroxisome proliferator-activated receptor γTZDs reduce hyperglycaemia by improving insulin sensitivity in a manner distinct from that of metformin. These drugs increase peripheral glucose utilisation in skeletal muscle and adipose tissue, reduce hepatic glucose output, increase fatty acid uptake and reduce lipolysis in adipose cells. This ultimately leads to a reduction in fasting and post-prandial plasma glucose, insulin and circulating free fatty acid (FFA) levels.10 TZDs are believed to exert most of their effects through binding to and activation of the gamma isoform of the peroxisome proliferator-activated receptor (PPARγ). PPARγ is a member of the steroid hormone nuclear receptor superfamily, and is found in adipose tissue, cardiac and skeletal muscle, liver and placenta. On activation of this nuclear receptor by a ligand such as a TZD, PPARγ–ligand complex binds to a specific region of DNA and thereby regulates the transcription of many genes involved in glucose and fatty acid metabolism.10 An endogenous ligand for this receptor has not been identified. Activation of PPARγ also leads to stimulation of adipogenesis,11 and this occurs more so in the subcutaneous rather than the omental fat depot.12 There are other isoforms of PPAR, and one of these, PPAR-α, is predominantly expressed in liver and is activated by hypolipidaemic agents such as fibrates. It mediates the triglyceride-lowering and high density lipoprotein (HDL)-raising effects of fibrates. Recent research has identified agents which are capable of activating PPARγ and PPARα simultaneously, and which could potentially have even greater beneficial effects than current TZDs. The development of TZDs has also led to the identification of non-TZD compounds which are capable of acting as full or partial agonists or as antagonists of PPARγ, depending on the tissue type and the specific target gene, in a manner analogous to the selective oestrogen receptor modulators (SERMs). It is therefore possible that future agents will be more selective and specific in their effects and potentially safer and more efficacious.13 Clinical trialsAlthough the evidence for therapy with these two agents is Level II, some of the data have either been published in abstract form only, or are only available from pharmaceutical company sources or websites or other organisations like the United States Food and Drug Administration (FDA). There are few studies which directly compare these agents as monotherapy or combination therapy with current standard treatment regimens. There are also no long term data on safety or effects on morbidity or mortality related to diabetes and cardiovascular disease. There are no studies directly comparing rosiglitazone and pioglitazone. The clinical trial data are summarised below. ◆ Both drugs lower HbA1c and fasting plasma glucose (FPG) levels when used as monotherapy8,9,14-22 (E2)For rosiglitazone, there was a dose-dependent reduction in HbA1c. The greatest effect was seen with a divided dose of 4 mg twice daily. In the various studies, this resulted in a reduction in HbA1c level of between −0.6 and −0.8 percentage points compared with baseline, and −1.5 to −1.8 compared with placebo. The FPG level was reduced by 2.3–3.6 mmol/L compared with baseline and 3.4–4.6 mmol/L compared with placebo. For pioglitazone, there was also a dose-dependent reduction in HbA1c level of −0.9 percentage points compared with baseline, and −1.6 compared with placebo, for patients taking 45 mg per day. The FPG level was reduced by 3.1 mmol/L compared with baseline, and 3.6 mmol/L compared with placebo. For both drugs, patients who were already receiving treatment with other agents at recruitment into the studies responded less well when swapped to monotherapy with the TZD than drug-naïve patients. ◆ Rosiglitazone and pioglitazone lower HbA1c and FPG levels when used in combination with a sulfonylurea or metformin8,9,23-26 (E2)Rosiglitazone (2 mg twice daily) added to various sulfonylureas over 26 weeks resulted in a reduction in HbA1c level of −0.8 percentage points compared with baseline, and −1.0 compared with placebo plus sulfonylurea. The FPG level was reduced by 2.09 mmol/L. When added to metformin (2.5 g), rosiglitazone (8 mg per day) reduced the HbA1c level by −0.78 percentage points and the FPG level by 2.7 mmol/L compared with baseline, and reduced the HbA1c level by −1.2 percentage points and the FPG level by 2.9 mmol/L compared with placebo plus metformin. Pioglitazone (30 mg) added to sulfonylurea reduced the HbA1c level by −1.3 percentage points compared with baseline and the FPG level was reduced by 2.9 mmol/L. When pioglitazone was added to metformin, the HbA1c level was reduced by about −0.7 percentage points, and the FPG level fell by 2.4 mmol/L compared with baseline. Compared to placebo plus metformin, pioglitazone (30 mg) plus metformin reduced the HbA1c level by −0.83 percentage points and the FPG level by 2.1 mmol/L. ◆ Rosiglitazone and pioglitazone lower HbA1c and FPG levels when used in combination with insulin8,9,27,28 (E2)Rosiglitazone (4 mg or 8 mg per day) added to insulin reduced HbA1c levels by −0.6 and −1.2 percentage points (respectively) compared with baseline and −0.7 and −1.3 compared with placebo plus insulin. Congestive heart failure was reported in two patients in each rosiglitazone group (comprising 106 and 103 patients) and one in the placebo group (103 patients). Rosiglitazone is not registered for use in combination with insulin.27 Pioglitazone (15 mg or 30 mg) per day added to insulin reduced HbA1c levels by −0.99 and −1.26 percentage points (respectively) compared with baseline and −0.73 and −1.00 compared with placebo plus insulin. Sixteen per cent of patients in the 30 mg pioglitazone plus insulin group had a reduction in their insulin dose of more than 25%.28 In these two studies, the incidence of oedema was significantly increased in the groups treated with TZD plus insulin.27,28 ◆ Both drugs lower fasting insulin and C-peptide levels when used as monotherapy or in combination therapy8,9,14-26 (E2)The significant reduction in insulin and C-peptide levels is consistent with the mechanism of action of these drugs as insulin sensitisers. ◆ Both drugs increase HDL and LDL and decrease FFA levels; pioglitazone lowers triglyceride levels8,9,14-32 (E2)Rosiglitazone significantly increased low-density lipoprotein (LDL) levels (mean increase, 15%–20%29) compared with baseline and controls, whereas, although pioglitazone increased LDL levels compared with baseline, there was no difference compared with controls. Rosiglitazone also tends to increase total cholesterol level and studies have reported variable effects on ratios of total cholesterol to high-density lipoprotein (HDL) and of LDL to HDL. In patients taking rosiglitazone, the ratios are either unchanged or increased. In studies over six months, the ratios tended to be unchanged because LDL reached a plateau and HDL continued to increase. There is a trend for these ratios to decrease in patients treated with pioglitazone. A recent, small, non-randomised and unblinded study suggested that pioglitazone increased levels of HDL to a greater, and LDL to a lesser, extent than rosiglitazone30 (E4). No randomised comparative study has been undertaken. It is known that modest increases in LDL levels correlate with increased cardiovascular risk. However, as has been reported for troglitazone,6 the increase in LDL level associated with rosiglitazone and pioglitazone is mainly in the larger, more buoyant and less atherogenic particles of LDL.31,32 Pioglitazone significantly reduced triglyceride levels. The long term effects of these alterations in lipid profile are unknown. Comparison with current antidiabetic drugsIn a published abstract and in the product information, rosiglitazone (2 mg twice daily and 4 mg twice daily) was directly compared with glibenclamide (or glyburide) at "optimally titrated dose". Patients in all three groups showed a statistically significant improvement in glycaemic control. The HbA1c level fell 0.27% and 0.53%, respectively, for the two rosiglitazone groups and 0.72% for the glibenclamide group at one year.8,33 Rosiglitazone was said to be "statistically equivalent" to glibenclamide at lowering HbA1c at one year, although the mean dose of glibenclamide is not stated (but, according to the FDA website, is 7.5 mg/day),29 and the graph in the product information shows that there was a deterioration in glycaemic control in the first six months in the two rosiglitazone groups. There was no statistical analysis provided for any time points other than one year. Rosiglitazone at 4 mg twice daily resulted in a significantly greater reduction in FPG level at one year than glibenclamide (−2.3 mmol/L v −2.0 mmol/L, respectively; P < 0.033).33 A study comparing rosiglitazone with metformin has not been published, but some information can be accessed through the FDA website.29 Patients were placed on metformin therapy at recruitment and the dose was increased to 2.5 g per day. They were then randomly allocated to continue to take metformin, to stop taking metformin and start taking rosiglitazone (4 mg twice daily) or to add rosiglitazone (4 mg twice daily) to their metformin therapy. The combination of the two agents was better than either used as monotherapy, but there was also a subset of patients in the group converted from metformin to rosiglitazone monotherapy who showed an abrupt deterioration of glycaemic control over the 24 weeks.29,34 However, no statistical analysis is provided. There are no similar studies published for pioglitazone. DeFronzo has reviewed studies of monotherapy with conventional agents and compared the efficacy of sulfonylureas, metformin, acarbose and troglitazone. From a similar starting HbA1c level, sulfonylureas and metformin reduced the HbA1c level by 1.5%–2.0% and the acarbose level by 0.7%–1.0%. Troglitazone reduced the HbA1c level by 1%–1.2%.2 The monotherapy studies described above indicate that the reduction in HbA1c level with rosiglitazone and pioglitazone is probably less than that with sulfonylureas or metformin. Concerns about hepatotoxicityTroglitazone was the first agent in this class to be marketed in the United States and was withdrawn by the FDA in March 2000 because of severe and unpredictable hepatotoxicity and 61 related deaths.35 The incidence of troglitazone-induced acute liver failure is estimated to be 1 in 8000 to 1 in 20 000 patients treated.36 The side chain of troglitazone, an α-tocopherol (vitamin E) moiety, or its quinone metabolites, may be the reason for its hepatotoxicity, and therefore this may not represent a class effect.17 To date, there have been three case reports of hepatotoxicty potentially caused by rosiglitazone and one potentially caused by pioglitazone. The agent was not proved to be the cause in any of these cases, all of which resolved with supportive care and withdrawal of the agent.37-40 In clinical trials, asymptomatic, reversible elevations of hepatic enzymes during treatment with both drugs have been noted, but rates were similar to those with placebo and resolved without withdrawal of the drug.41 The product information for both drugs states that these agents are contraindicated in patients with alanine aminotransferase (ALT) levels more than 2.5 times the normal level at baseline. Caution should be exercised when using these drugs in patients with hepatic enzyme level elevations of 1–2.5 times normal at initiation. It is also recommended that liver function tests (LFTs) be performed at baseline and every second month for the first year of therapy, and then periodically thereafter. If symptoms of liver dysfunction occur, LFTs should be checked. If the ALT remains elevated to more than three times the normal level, with or without symptoms, the drug should be discontinued.8,9 Adverse reactions and side-effectsIn all clinical trials for both rosiglitazone and pioglitazone, the incidence of adverse events, with the exception of weight gain and peripheral oedema, was similar to placebo. As monotherapy, neither drug caused hypoglycaemia, but in combination therapy mild hypoglycaemia has been reported and, in some cases, the dose of sulfonylurea, insulin or metformin was reduced8,9,23-28 (E2). Dose-dependent weight gain of 0.5–3.7 kg has been noted in the clinical trials and seems to be a class effect. The least weight gain was seen when used in combination with metformin.8,9,14-17,20-28 Weight gain is likely to be multifactorial in nature and could be the result of increased adipogenesis, increased appetite and oedema.11-15 Despite the weight gain, there are clearly improvements in insulin sensitivity and glycaemic control. Some studies report that the weight gain is associated with a reduction in waist : hip ratio, supporting the theory that there is a "shift" in fat distribution from visceral to subcutaneous fat depots, which confers less cardiovascular risk.15 In all studies, oedema occurred more frequently in the TZD treatment groups, although it was generally mild and did not lead to withdrawal from treatment. The incidence of oedema is about 3%–5%, although, when rosiglitazone or pioglitazone was combined with insulin therapy, the incidence rose to 13%–16%, compared with 5%–7% in the group receiving insulin plus placebo.8,9,14-17,20-28 There is also an increase in plasma volume of 6%–7%, and patients with New York Heart Association Class III and IV cardiac status were excluded from the studies (both drugs are contraindicated in these patients). This increase in plasma volume is also likely to be responsible for the mild reduction in haemoglobin level seen with all TZDs.6 PrecautionsThere are no data on the use of these drugs in pregnancy or lactation. In animal studies both drugs cross the placenta, and fetal loss, retarded fetal development and suppression of postnatal growth have been seen in rats.8,9 There were no significant effects on levels of the oral contraceptive pill in healthy women taking rosiglitazone, and the drug's manufacturer reports that no impairment of efficacy would be expected.8,42 There is no similar study for pioglitazone, but the product information recommends that alternative modes of contraception be used.9 Women with polycystic ovarian syndrome and insulin resistance should be advised that treatment with TZDs may result in resumption of ovulation and advice regarding suitable contraception should be given.8,9 Both drugs are contraindicated in moderate to severe liver dysfunction. Dose reduction is not required in elderly patients or those with renal impairment.8,9 Although animal studies have shown tumour-inducing effects for familial adenomatous polyposis and sporadic colon cancer in mice, there are no clinical data yet.43 However, mutagenicity and carcinogenicity studies have not raised any other significant concerns.8,9 These agents should be avoided in patients with significant cardiac dysfunction. There are no data in humans under 18 years of age. Conclusions and recommendationsThe thiazolidinediones are a unique class of drugs for the management of type 2 diabetes and they act to improve insulin resistance. Current evidence suggests that they are effective in the treatment of type 2 diabetes, but there is no evidence to suggest that they are better than currently available drugs and no data on long term safety or effects on morbidity and mortality related to diabetes and cardiovascular disease. Since the mechanism of action of TZDs is different from other currently available antidiabetic agents, it seems logical that they would be useful in combination therapy. So far, there are no studies assessing the effect of the TZDs when added to the combination of sulfonylurea and metformin, or to insulin combined with sulfonylurea or metformin. There is little difference between the two agents, although pioglitazone may have a more favourable effect on lipid profile than rosiglitazone. There are some data that show that these drugs may preserve beta-cell function, and it has been suggested that they should therefore be used early in the disease process, but there are no studies to support this hypothesis. Until there are more data available, these agents should probably be reserved for use in combination therapy in patients who are unable to be managed with current standard treatment combinations (ie, metformin, sulfonylurea, acarbose and insulin),44,45 and who fulfil the current prescribing guidelines. The development of thiazolidinediones has opened the door to some exciting research and to the development of other new agents for the treatment of type 2 diabetes mellitus. Important messages for patients are shown in Box 3. 1: Level-of-evidence codes Evidence for the statements made in this article is graded according to the NHMRC system4 for assessing the level of evidence. E1 Level I: Evidence obtained from a systematic review of all relevant randomised controlled trials. E2 Level II: Evidence obtained from at least one properly designed randomised controlled trial. E31 Level III-1: Evidence obtained from well-designed, pseudo-randomised controlled trials (alternate allocation or some other method). E32 Level III-2: Evidence obtained from comparative studies with concurrent controls and allocation not randomised (cohort studies), case–control studies, or interrupted time series without a parallel control group. E33 Level III-3: Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group. E4 Level IV: Evidence obtained from case-series, either post-test, or pre-test and post-test. 2: Drug profile of rosiglitazone and pioglitazone Action: TZDs activate peroxisome proliferator-activated receptor γ (PPARγ) and thereby regulate a number of genes involved in glucose and lipid metabolism. They act to improve insulin sensitivity. Onset: Both rosiglitazone and pioglitazone are rapidly absorbed and have high bioavailability. The timing of dose in relation to food does not significantly affect absorption or serum levels. Changes in fasting plasma glucose may start to be seen within two weeks, but maximal effects on glycaemic control may not be evident until 6–14 weeks after commencement of therapy. Dosing: Both rosiglitazone and pioglitazone are available as oral formulation. Rosiglitazone comes in 2 mg, 4 mg and 8 mg tablets and pioglitazone in 15 mg, 30 mg, and 45 mg tablets. No dosage adjustment is required for renal impairment. Recommended dose for rosiglitazone (Avandia; GlaxoSmithKline) — Commence at 4 mg per day, and, if necessary, increase to 8 mg per day after 6–8 weeks as a single or divided dose given with or without food. There is no additional benefit from doses higher than 8 mg per day. The largest dose given in combination with sulfonylurea in clinical studies was 2 mg twice daily. Recommended dose for pioglitazone (Actos; Eli Lilly) — Commence at 15 mg per day, and, if necessary, increase to 30 mg per day up to a maximum of 45 mg per day after 4–6 weeks. Give as a single dose with or without food. The largest daily dose used in clinical studies of pioglitazone in combination with insulin or sulfonylurea was 30 mg. Metabolism: Both drugs are extensively metabolised by hepatic cytochrome P450. Rosiglitazone metabolites are essentially inactive and mainly excreted in the urine. Some of the pioglitazone metabolites are active and are excreted in faeces and urine. Neither drug inhibits cytochrome P450. Although no significant drug interactions have so far been identified, prescribers should be vigilant for possible interactions, especially with drugs metabolised by or affecting the cytochrome P450 system. Adverse effects: Both drugs are well tolerated. There have been some case reports of hepatic dysfunction in patients taking the two drugs but causation was not definite. The incidence of elevations in enzyme levels on liver function tests was the same in treatment and placebo groups. The most common adverse effects include weight gain, oedema and dilutional anaemia. Because of fluid retention, these drugs may exacerbate heart failure and should not be prescribed to patients with New York Heart Association III-IV cardiac status. The drugs are also contraindicated in pregnancy and lactation and have not been tested in children. In women with polycystic ovarian syndrome with insulin resistance, treatment with these drugs may restore ovulation and appropriate advice regarding contraception should be given. When used in combination with other antidiabetic drugs, rosiglitazone and pioglitazone have been associated with mild hypoglycaemia requiring dose reduction of sulfonylurea, metformin or insulin. 3: Important messages for patients Thiazolidinediones (TZDs): Are a new type of drug for the treatment of type 2 diabetes. Improve diabetic control by increasing the body's sensitivity to insulin. Can cause mildly low blood sugar levels if they are used in combination with other medications for diabetes. Can cause some weight gain and mild fluid retention. Should not be taken if you are pregnant or breastfeeding or if you have significant heart or liver problems. Your doctor may need to advise you about methods of contraception, as you should not become pregnant while taking these medications. You will need to have regular liver function tests.

Trisha M O'Moore-Sullivan MB BS, FRACP · Johannes B Prins MB BS, PhD, FRACP

Acute meningitis and encephalitis are medical emergencies that require prompt assessment (usually by cerebral imaging and lumbar puncture) and treatment; specialist consultation is recommended.

Miles H Beaman FRACP, FRCPA · Steven L Wesselingh FRACP, PhD

To the Editor: I read with interest the accounts of de Costa, Walton, and Flynn and Atkinson dealing with the Professional Standards Committee (PSC) of the NSW Medical Board and the behaviour of the Health Care Complaints Commission (HCCC).1-3 I would like to add a few comments arising from my personal experience of appearing before the PSC. The PSC is supposed to be non-adversarial. The Medical Practice Act 1992 (NSW) states that the doctor under investigation and the HCCC are not to be represented by a solicitor or barrister, but could be assisted by one. In my case, I soon realised that the HCCC Hearings Officer opposing me was dauntingly competent in court craft. She was, in fact, a very experienced solicitor who had for a long time been in practice outside Australia but was not registered as a solicitor in New South Wales. As a result of my application to the Supreme Court, this malpractice was stopped by Justices Dunford and O'Keefe.4, 5 Note that Justice O'Keefe ruled that a person qualified in law could represent the HCCC in PSC hearings, provided the person had never been registered as a legal practitioner. I would like to pose three questions. Firstly, why was it left to me, someone inexperienced in legal processes, to call a halt to this inequity? Secondly, why did the Medical Board countenance this malpractice, when it was manifestly in breach of the Medical Practice Act and most unfair to the medical practitioners whose welfare is its responsibility? And thirdly, why did legal representatives of the medical defence organisations continue to permit this obvious imposition on the doctors whom they had been paid to defend? In my case, evidence obtained in confidence from peer reviewers has been published in the journal of the Health Care Complaints Commission, even though the action against me has not yet come to hearing. The HCCC's practice of publishing such information prior to hearings has been sanctioned by the Medical Tribunal.6 It is my belief that the HCCC has brought the NSW medical regulatory bodies into disrepute by its malpractices, its disrespect for the wishes of Parliament and its lack of a long-term perspective.

Richard F Gorman MBBS DO FRACO

To the Editor: I am a general practitioner who has specialised solely in the field of cosmetic medicine since 1988. I have been the subject of an investigation by the Health Care Complaints Commission (HCCC) and a resultant Professional Standards Committee (PSC) hearing, in which peer reviewers with significant conflicts of interest were used. The process was triggered by a complaint from a patient who had developed blisters and superficial crusting after facial laser hair removal treatment. This is a recognised complication that the patient was aware of when giving consent for the procedure. The HCCC briefed a dermatologist, Dr "X", to comment on the treatment of which the patient had complained. The HCCC further instructed Dr X: "Your report need not be confined to the above questions [relating to such treatment] but should include any other matters you consider relevant and significant." I was referred to the PSC primarily on matters unrelated to the treatment that had led to the patient's complaint. Before the PSC hearing I submitted various documents to the HCCC: (a) a copy of a newspaper advertisement for laser hair removal in which Dr X had stated "Trust only a dermatologist to recommend a safe and reliable method of managing unwanted hair" and "Prospective clients should closely check the qualifications of their laser practitioner and look for the letters FACD"; (b) a report from another dermatologist stating that Dr X "does have a history of a negative attitude to general practitioners who specialise in lasers. He has been seen on television on several occasions espousing this view."; (c) expert reports from two dermatologists expressing views contrary to the opinions of Dr X that had triggered my PSC referral; and (d) statutory evidence from a patient treated in his practice that Dr X's own clinical practice was contrary to that which he had advised the HCCC I should have followed. The NSW Medical Board appointed as a PSC representative at my hearing a dermatologist who was a co-advertiser for laser hair removal with Dr X. The dermatologist in question was later removed (with difficulty) on objection. The PSC systematically disregarded expert evidence I had presented in favour of evidence presented by the HCCC. I have been told that this is a common occurrence. I sincerely hope that the NSW Government Inquiry into the HCCC, to be released in 2002, will address the abuse of this system by biased reviewers. However, justice cannot be guaranteed when the HCCC and NSW Medical Board both effectively collude to prosecute these cases. PSC hearings should be administered by an independent body.

Geoffrey K Heber MB BS DipRACOG MBA

To the Editor: The Acts constituting the NSW Medical Board and Health Care Complaints Commission (HCCC) unfortunately permit inequitable joint functioning of these agencies. The provision that the complainant may appeal an unsatisfactory decision of a Medical Board's Professional Standards Committee (PSC) to the Medical Tribunal is misleading.1 The HCCC chooses its peer reviewer in any matter, investigates, recommends that the Board take action (or not), prosecutes matters at a hearing (or not) and is the only complainant allowed to appeal.2 Clearly, the skills, methods, and decisions of the HCCC and the Board must be beyond reproach. The HCCC selects peer reviewers to consult during the investigation of a complaint.3 They are paid to report on documents and to appear as witnesses before any committee or tribunal of inquiry — either before an in camera PSC of the Board or at a Medical Tribunal, chaired by a judge in open court. Peer review reports, which are legally privileged and generally inscrutable, may be selectively biased. My own involvement (as a complainant disallowed appellant standing from the PSC, and as an occasional consultant to a complainant and to the defence in other, separate psychiatric complaint matters) has led me to conclude that some peer review reports are inconsistent with minimal professional requirements or even duplicitous. Blind faith in a system comprising these two statutory bodies and an anonymous peer reviewer is inappropriate. The NSW Administrative Decisions Tribunal (ADT) has judged disclosure of the membership lists of HCCC peer review panels to be in the public interest. In 1999, the ADT inquired into the selection of the list of psychiatrist peer reviewers when dealing with an application for disclosure based on the Freedom of Information Act 1989 (NSW).4 The list proved to have evolved over an unknown period, through unknown differing methods (such as recommendations from unidentifiable practitioners or staff), for unknown precipitating reasons, and at unknown times. There was no general awareness within Medical Colleges or other medical associations of the selection process or of the members who may be thus empowered. This, when we know that, as a profession, we cannot be uniformly sensible, ethical or emotionally stable. The HCCC and the NSW Medical Board are thus vulnerable to corrupt influence. The NSW Parliamentary Committee on the HCCC has sought submissions from the public and has been conducting an inquiry since November 2001 to determine necessary improvements to the functioning of the HCCC. I believe professional bodies need to take a resolute lead, declare their intentions, identify their roles, consult with their members and heed their responses. Ideally, each will clarify its policies and procedures for regulation and will demand proper functioning from the agencies with statutory responsibilities.

Eleanor Dawson

In reply: A Medical Board's role is to protect the public by ensuring that appropriate standards of conduct and practice are maintained by registered medical practitioners. In New South Wales, the NSW Medical Board administers the disciplinary provisions under the Medical Practice Act 1992 (NSW). Included in this legislation is the Medical Tribunal/Professional Standards Committee (PSC) model that has been the subject of comment in recent correspondence. It is important to note that the Medical Board, the Health Care Complaints Commission (HCCC), the Medical Tribunal and PSCs are all independent bodies in their own right. The Medical Board welcomes constructive comment on the system and its administration. It meets regularly with the major parties (HCCC, United Medical Protection, and the Australian Medical Association [AMA] as the doctors' professional body) to discuss the workings of the disciplinary system, to identify problems and shortcomings, and to develop solutions. Inevitably, there will be aspects of the process that participants do not like — who enjoys being taken to court, in any circumstances? As in all legal and quasi-legal processes, the parties are unlikely to uniformly praise the impartiality or quality of witnesses, experts, and the judiciary. Processes are in place to minimise the possibility of conflict of interest, or the perception of bias. On the rare occasion when a panellist is challenged, a conservative approach is generally taken, and a replacement found. Heber raises concerns about an inquiry extending beyond the parameters of the original patient complaint. In a protective jurisdiction, it would be quite wrong to limit a case to what the complainant had been able to articulate. Not infrequently, a patient's unhappiness is focused on what, from a medical perspective, is relatively minor, while seriously poor conduct or practice is not recognised as such. The legislation specifically envisages an "inquiry", which, subject to natural justice requirements, may go beyond the original complaint. To deny this would be inconsistent with the protective nature of the jurisdiction. The issues raised by Dawson and Gorman concentrate on procedures adopted by the HCCC regarding peer review and representation before hearings. The Board understands that the HCCC has a detailed policy document, prepared in consultation with stakeholders including the AMA and United Medical Protection, regarding the selection and utilisation of peer reviewers and expert witnesses. The Board is also aware of wider concerns in the legal system regarding the use of "hired guns" as distinct from impartial peers or experts, and when concerns have been brought to its attention suggesting even a perception of bias it has taken steps to address them. The Board and members appointed to sit on PSCs and Medical Tribunals take their roles very seriously, and do so with a sense of professional responsibility, while acknowledging the difficulty of sitting in judgement on their peers. Criticisms are carefully considered and practices changed where appropriate. At all times, the Board must ensure that it acts fairly and in accordance with its charter of public protection.

Brian C McCaughan MB BS FRACS

To the Editor: A number of recently published articles indicate that the prevalence of overweight and obesity in children is increasing at an alarming rate on a national1 and international2 level. Overweight children are more likely to become overweight adults and to experience chronic health problems associated with adult obesity. We report results obtained from a survey of primary schoolchildren on the New South Wales Central Coast which extends the time series from that in the article by Magarey and colleagues (1985 and 1995 data)1 to the year 2000. We undertook a cross-sectional study of children at a Central Coast primary school in November 2000 as part of a community study. This study was approved by the Central Coast Health Ethics Committee. All children in each class were asked to take part. With parental consent, weight and height were measured in children from all class groups (aged 7–11 years) by child health nurses using standardised procedures. Children were classified as overweight or obese using the standard international cutoffs for body mass index.3 They were compared with data obtained during the 1985 Australian Health and Fitness Survey (AHFS85) and the National Nutrition Survey of 1995 (NNS95).1 A total of 268 children (127 girls, 141 boys) were surveyed (average of 25 girls and 28 boys of each age). This represented a 70% response rate. The Table shows that the incidence of overweight and obesity in Australian children has continued to increase, with relative risks for the increase between 1985 and 1995 of 1.37 (95% CI, 1.07–1.75) for boys and 1.82 (95% CI, 1.49–2.22) for girls, and relative risks for the increase between 1995 and 2000 of 1.71 (95% CI, 1.21–1.43) for boys and 1.21 (95% CI, 0.87–1.67) for girls. Our findings indicate a marked increase in proportions for boys in only five years since NNS95. While the increase for girls was not statistically significant, the pattern is consistent. Prevalence of overweight and obesity in children aged 7–11 years for 1985, 1995 and 2000 Sex Year Number Overweight (%) Obese (%) Overweight + obese (%) Boys 19851 2425 9.7 1.5 11.2 19951 457 11.6 3.7 15.3 2000 141 16.3 9.9 26.2 Girls 19851 2443 11.0 1.9 12.9 19951 430 17.2 6.3 23.5 2000 127 21.3 7.1 28.4 Thus, the incidence of overweight and obesity in Australian children is steadily increasing. Importantly, according to the 1996 Census Socio-Economic Indexes for Areas,4 the school we surveyed is situated in an area ranked in the middle quintile for relative socioeconomic disadvantage (state and national average), and is immediately adjacent to one 4th- and several 1st-quintile and 2nd-quintile areas. We believe our findings are representative of the Australian population of children. The challenge to healthcare workers is significant. The National Health and Medical Research Council's Acting on Australia's weight5 identifies goals for preventing further weight gain in adults, and eventually reducing the proportion of the adult population that is overweight or obese, and to ensure the healthy growth of children. Recommended strategies range from national dietary and physical activity guidelines to increasing physical activity through the design of towns, transport systems and public recreational facilities. Effective strategies are urgently needed to alter food intake and physical activity at individual, school, community and population levels.

Susan Goodman · Peter R Lewis MB BS, FAFPHM · Andrew J Dixon · Cheryl A Travers

To the Editor: One concern that medical practitioners and pharmacists have about patient counselling is the uncertainty about the amount of information which should be given to patients, especially regarding possible adverse reactions to medications.1 Studies have found that providing information on possible adverse reactions can affect patients' willingness to take the medication.1 Research in cognitive psychology provides clear evidence that the order in which information is presented has a significant influence on judgement. Information received first is likely to have a disproportionately large effect on judgement, the "primacy effect".2-4 Despite clear evidence supporting the "order effect" in diverse areas, research has not been undertaken to investigate whether the order effect is present in medication information. To test the hypothesis that differently ordered sequences of the same information about a drug can result in different judgements,5 804 subjects were presented with a short description of a fictitious medication. The descriptions were presented in one of two formats (Box): (A) positive–negative (therapeutic benefits followed by potential adverse reactions) or (B) negative–positive order (potential adverse reactions followed by therapeutic benefits). The surveys were randomly distributed to university students, mindful of the limitation of extrapolating the data to the general population. Subjects rated the medication (from very bad to very good) and the likelihood of taking the medication (from very unlikely to very likely) on seven-point Likert scales. For analysis, we used the independent sample t test, which is robust and therefore considered suitable for this analysis. Two descriptions of a fictitious medicine for treatment of diabetes A: Diabetic MedicationThis medication is effective; it lowers sugar levels. It makes one feel better and boosts energy. It may cause nausea and headache. B: Diabetic MedicationThis medication may cause headache and nausea. It boosts energy and makes one feel better. It is effective; it lowers sugar levels. Of the 804 completed questionnaires, 403 were in the positive–negative order and 401 were in the negative–positive order. Participants given the positive–negative description of the medication rated it more positively (mean, 4.43; SD, 1.02) than those given the negative–positive description (mean, 3.70; SD, 1.62) (P < 0.001). Similarly, participants reported a higher likelihood of taking the medication when information was presented in the positive–negative order (mean, 4.23; SD, 1.62) compared with the negative–positive order (mean, 3.54; SD, 1.66) (P < 0.001). We found that the order of presentation of medication information significantly affected judgement of the medication. Subjects rated the medication more favourably when positive information was presented first. These results suggest a potential benefit in presenting medication benefits before discussion of possible adverse effects. Such an approach might apply to medical practitioners and other healthcare professionals when counselling patients. It might also be a consideration in the format of written information, such as Consumer Medicine Information.

Abilio C de Almeida Neto BScPsychol(Hons), PhD · Timothy F Chen BPharm, DipHPharm · Joyce H L Chan BPharm(Hons)

To the Editor: The conclusion of Holland et al that horse-related injuries in children account for a considerable number of deaths and injury is unarguable.1 In New Zealand, hospitalisation rates for falls from horses and rugby injuries are comparable.2 Despite these disconcerting facts, the data on horse-riding injuries need to be put in a balanced perspective. The frequency of injuries in adult equestrian activity, Pony Club riding, occupational riding (including professional jockeys) and riding for leisure are quite different. Collective raw data are misleading. The freak accident of actor Christopher Reeve in 1995, with the resulting much-publicised quadriplegia, brought public attention worldwide to the question of acute spinal cord injury (ASCI) in horse riding and led to widespread parental concern about "spine safety" in this sport. Spinecare Foundation was subsequently involved in a review of 32 patients with ASCIs from horse riding admitted to the spinal cord injury units at Royal North Shore and Prince Henry hospitals, Sydney, for the years 1976 to 1996.3 Occupational and leisure riding accounted for 88% of injuries. ASCIs occurred in only two riders under the aegis of the Equestrian Federation of Australia — one while competing and the other while training. There were no injuries in children younger than 14 years of age in any form of riding. Most importantly, in the study period, there had been no ASCIs in Pony Club riders, of which there were 22 000 in New South Wales in 1996. Neither had there been an ASCI in those who participated in Riding for the Disabled. In the context of these comments, it is relevant to briefly revisit the contentious topic of Down syndrome children taking part in Riding for the Disabled and in sport generally. Since 1970 (from when accurate records are available), no child with Down syndrome in NSW has had an ASCI in any sport, let alone in a well-defined non-sporting accident. There is simply no case for the radiological screening of the cervical spine for atlanto-axial instability in asymptomatic children with Down syndrome before they undertake Riding for the Disabled. The indications for this examination have been set down.4 We hold that the public and the medical profession can continue to be reassured by this information. Certainly, a child wearing a lap seat belt or other poorly fitting restraint in the rear passenger compartment of a car is at infinitely greater risk for spinal cord injury than when astride a horse at Pony Club. Further, as Holland et al have documented,1 if he or she is wearing a protective helmet the chances of head injury would be reduced significantly. Safety in all potentially dangerous sports should be foremost in the minds of those who administer, supervise and participate in such games. As yet there are no hard data to support the wearing of body protectors to reduce the risk of ASCI, or other vertebral injuries, in horse riding. In reply: One of the reasons for publishing our data was to raise the level of awareness of both the frequency and severity of horse-related trauma in Australian children.1 This trauma appeared to be associated with a low level of compliance with basic safety measures, in particular the use of a Standards-approved riding helmet.1,2 We stated clearly in our article that the risk of injury needed to be viewed in the context of the important social and health benefits of horse-riding as a sporting and leisure activity.1 Taylor and Roe have commented on the perceived benefits of Riding for the Disabled, especially in children with Down syndrome. Certainly, the available data suggest that in this strictly supervised scenario horse riding would appear to be very safe.3 However, the evidence for therapeutic benefit would appear to be relatively weak, and the risks of this form of equestrianism cannot be compared with the more common interaction that might occur between a normal child and horse.4 The incidence of spinal cord injury in children fortunately appears low, at less than 2% of children admitted with all forms of traumatic injury.5 In this context, the use of spinal cord injury as a measure of the safety of a sport for children is flawed. While children may be at greater risk of injury when inappropriately restrained in a motor-vehicle accident, this fact in itself does not make horse-riding, or indeed any other high-risk sporting activity, safe. The use of appropriate safety devices and responsible adult supervision does.

Thomas K F Taylor DPhil(Oxon), FRCS, FRACS · Justin P Roe MB BS, FRACS · Andrew J A Holland BSc, MB BS, FRACS, FRACS(Paed) · Gerard T Roy

To the Editor: In their case report entitled "Dangerous bodies", Nocera and colleagues described a case of poisoning with aluminium phosphide tablets,1 which generate the fumigant gas phosphine when exposed to moisture.2 The foul odour emanating from the patient alarmed hospital staff, leading to evacuation of the emergency department. After the patient died, they sealed his body in an impervious suit and bin. It was buried, without autopsy, using earth-moving equipment — it being considered too dangerous to do this by hand. The burial was filmed for television. The article sought to highlight risks to hospital staff from poisoned patients and indicated that phosphine gas emanating from this patient could be toxic before it was able to be smelt. Despite stated fears of extreme toxicity, no air samples were collected for analysis, and the sole symptom among staff was nausea (not unexpected given the smell). In parts of India, where wheat is commonly stored in the home before being ground into flour, aluminium phosphide tablets are widely available for household use to stem insect attack on the grain.3,4 Ingestion of these tablets is a common way to attempt suicide, with perhaps as many as 15 000 cases per year, two-thirds of which are fatal. The hospital in the city of Chandigarh, in northern India, treats about 50 cases per year. The breath of patients who have ingested aluminium phosphide has a characteristic garlic-like odour. Diagnosis is based on history and a positive result (blackening) on tests of the patient's breath with paper moistened with fresh silver nitrate solution. Hospital staff take no special precautions during resuscitation, and surviving patients are managed with routine supportive care. Autopsies are routine. No threat is perceived by hospital staff. Metal phosphides have been safely used by trained people in Australia for decades. They are Schedule 7 poisons and so require an expensive permit for purchase. Consequently, their use for suicide is rare. Nocera and colleagues understandably reacted with caution to an unusual situation. However, we consider that, in documenting their experience, they overstated the risk. Because of the legal and ethical issues involved in patient care in a situation of alleged risk, we consider that risk estimates should, when possible, be based on available evidence rather than theoretical possibilities. In general, apart from a few highly toxic, mainly anticholinesterase compounds that can be absorbed through the skin (eg, sarin and tabun), there are no known poisons that will seriously endanger hospital staff routinely caring for patients in an emergency department. Competing interests: The authors have no association with companies that manufacture or market aluminium phosphide, and had no financial support for preparation of this letter. In reply: In our article, we clearly stated that the emergency department was evacuated on the instructions of officers from the New South Wales Fire Brigades.1 The officers then placed the patient's body within a fire brigade hazardous materials encapsulated suit and, when that began to distend with phosphine gas emissions from the body, into a hazardous materials recovery bin. In contrast, Christophers and colleagues state that staff at the hospital in Chandigarh, India, take no special precautions in antemortem or postmortem care of patients who have taken aluminium phosphide tablets. I am disappointed that they provide no data on air sampling for phosphine gas during this care to justify this practice. Our case highlights the problems confronting emergency department staff with a critically ill patient and an unknown chemical hazard. In this case, the chemical hazard was not correctly identified for over 30 minutes. The risk cannot be estimated, as suggested by Christophers and colleagues, until the chemical agent and its vapour concentration are correctly identified. Retrospective determinations cannot be used to guide the immediate emergency department response, or to determine what personal protective equipment is needed by staff during the initial confusion of a hazardous materials incident. In addition to organophosphates, over 30 chemical agents have the potential to be used as chemical weapons. Furthermore, the toxicity profiles of many industrial chemicals are unknown or incomplete. We do not believe that any hospital or emergency department staff should be exposed to avoidable danger during antemortem or postmortem care of patients, or that healthcare institutions should be exempt from their statutory obligations under occupational health and safety legislation.

Allen J Christophers · Surjit Singh · David G Goddard · Antony Nocera FACEM, MSc (Emergency Planning and Disaster Management)

To the Editor: Your readers might be interested to examine the full story of Dorothy Reed's initial encounter with William Osler,1 and to learn that he later apologised for his initial negative reaction to her expressed intention to enter medical school, and gave her great support. She later said of him: "He was my friend and to me William Osler has always stood for the greatest personality and the soundest medical teaching possible at that time." Some of her unpublished memoirs are included in a book edited by Jill Ker Conway.2

Tony E Seymour

To the Editor: Some of the principles underlying evidence-based medicine (EBM)* might have been around far longer than we tend to believe. Here is a fragment of one of the 8777 brief suttas (discourses) collected in the Anguttara-nikaya, or "Collection of the gradual sayings", one of the oldest Buddhist texts. The Buddha preaches to the Kalamas people: Yes, Kalamas, you may well doubt, you may well waver. In a doubtful matter wavering does arise. Now look you, Kalamas. Be ye not misled by report or tradition or hearsay. Be not misled by proficiency in the collections [citing the authority of religious texts], nor by mere logic or inference, nor after considering the reasons, nor after reflection on and approval of some theory, nor because it fits becoming, nor out of respect for a recluse (who holds it) . . . But if at any time ye know of yourselves: these things are profitable, they are blameless, they are praised by the intelligent; these things, when performed and undertaken, conduce to profit and happiness — then, Kalamas, do ye, having undertaken them, abide therein.1 This sutta shows the importance of mistrusting unquestioned tradition, even before the days of odds ratios, cost-effectiveness ratios or confidence intervals. Perhaps the lesson for innovative modern supporters of EBM2 would be to concentrate on higher ideals like "profit" (in the sense of beneficence or prosperity) and "happiness" as the really significant outcomes we should be aiming at. * The decision to send this note to the Journal is, of course, evidence-based. The Medical Journal of Australia (MJA) is second only to the BMJ in publishing the largest number of references indexed under the MeSH term "evidence-based medicine" in English-language journals. On a proportional basis, the MJA is at the top of the list: since November 1996 it has published 125 "EBM" articles out of a total of 2553, while the BMJ has published 248 "EBM" articles out of 14966 (OR, 3.06; 95% CI, 2.44–3.83). Could it be that MJA readers are three times more interested in EBM-related topics than BMJ readers?

Diego Rosselli MD EdM MSc

To the Editor: The South Pacific Underwater Medicine Society (SPUMS) recommends that, before starting scuba-diving activities, all candidates undertake a medical assessment by a doctor trained in diving medicine. SPUMS recommends a minimum age of 14 years for all entry-level scuba activities, as does Australian Standard 4005.1. This recommendation is based on the belief that younger children do not have the emotional maturity and confidence to safely manage underwater emergencies. Such emergencies, which may include running out of air, being separated from your buddy, being caught in a strong current, and equipment malfunction, can all result in panic.2,3 A diver who panics will typically make a rapid ascent to the surface, risking life-threatening pulmonary barotrauma and decompression illness.2 Commercial scuba diving instructor agencies are introducing a number of introductory activities for children as young as eight years. SPUMS urges caution in assessing young children as fit to dive. Medical practitioners making these assessments should clearly understand the nature of the activity to be undertaken, the equipment to be used and the nature of the environment in which the training is to occur. They should also understand the nature of the certification to be awarded. The presence of at least one legal guardian during this assessment is desirable to ensure that the risks are fully understood and to ensure the desire for the child to undertake the activity is not that of the parents alone. An individual may meet the criteria laid down in a standard or understand and accept the risks of an aquatic sport. However, it is not clear that a young child is mature enough to make this informed choice.4 Clearly, some 14-year-olds also lack sufficient maturity, and an experienced diving physician will advise them to delay their open-water certification course until greater maturity is demonstrated. Alternatively, some children younger than 14 years may be completely safe in undertaking a highly structured, one-on-one, supervised scuba experience in a swimming pool. However, it should be understood that trialling scuba equipment in a swimming pool has resulted in significant morbidity. SPUMS continues to recommend a minimum age of 14 years for all entry-level scuba activities involving open-water dives, and recommends caution in assessing younger children for all other scuba experiences.

Robyn M Walker MB BS, DPHM

A 29-year-old unemployed man presented with pain and swelling of the right hand. He reported two occasions of intravenous drug use during the previous three days: a single heroin dose, followed by temazepam (4 × 10 mg gel capsules, dissolved in hot water). He was right-handed. On both occasions he injected into a superficial blood vessel on the back of the right hand. On presentation, the clinical diagnosis was inadvertent intra-arterial injection of temazepam, with vascular endothelial damage secondary to macrogols (used to increase viscosity in gel capsule manufacture). The patient's condition was managed with elevation of the forearm, aspirin, heparin anticoagulation, empirical parenteral antibiotics and analgesia. Over three days the patient showed substantial improvement, allowing discharge with follow-up in one week. Four days later, he returned with increasing pain. He denied further intravenous drug use. He had normal arterial pulses, but the distal fingers were cool. Fingertip sensation and capillary refilling were diminished. To improve perfusion and limit further thrombus development, an alprostadil infusion and oral nifedipine were introduced. Over 10 days, necrotic areas, involving index, middle and little fingers, developed and required amputation. The picture shows the patient's hand after surgical debridement and amputation of necrotic areas, three weeks after injection of temazepam.*

Gerald FX Feeney MB BCh BAO FRACP · Harry H Gibbs MB BS FRACP

Food for thought A subgroup analysis of the Framingham Study found a strong association between homocysteine and the risk of dementia. The association appears to be independent of age, sex, APOE genotype, plasma vitamin levels and other putative risk factors for dementia. At their 20th biennial follow-up, 1092 dementia-free subjects had their plasma homocysteine levels measured. Over a median follow-up period of 8 years, 111 subjects developed dementia. Those with a plasma homocysteine level >14 µmol/L had almost twice the risk of those with lower levels. Vitamin therapy with folic acid, alone or with vitamins B12 and B6, can reduce plasma homocysteine levels. Prospective trials will be required to demonstrate if vitamin B supplements will reduce the risk of dementia. N Engl J Med 2002; 346: 476-483 N Engl J Med 2002; 346: 302-304 Sugar daddies In a study of (predominantly white) males, a “western” dietary pattern was associated with increased risk for type 2 diabetes. The Health Professionals Follow-up Study recruited men aged 40 to 75 years from across the United States. This analysis included 42 504 men who were free of diabetes and other medical illnesses in 1986. Each reported on any development of illness every two years until 1998, and completed detailed food questionnaires in 1986, 1990 and 1994. Over 12 years, 1321 men developed type 2 diabetes. Two dietary patterns emerged with factor analysis, characterised by higher consumption of vegetables, fruit, fish, poultry and whole grains (“prudent”); or red meat, processed meat, French fries, high-fat dairy products, refined grains and desserts (“western”). Men in the highest quintile for western diet had a relative risk of 1.59 (95% CI, 1.32–1.93) for developing type 2 diabetes compared to those in the lowest. For men who were also obese, the relative risk was 11.2 (95% CI, 8.07–15.6). Ann Intern Med 2002;136:201-209 A fish story In a recent Danish study, low consumption of fish during pregnancy was a strong risk factor for low birth weight and preterm delivery. A total of 8729 women completed questionnaires at 16 and 30 weeks’ gestation, reporting on their intake of fish, including roe, prawn, crab and mussel. Four groups were identified, ranging from women who ate no fish, to those consuming at least two fish meals a week (44.3 g/day). Occurrence of low birth weight and preterm delivery decreased with increasing fish intake. Comparing the lowest and the highest intake groups (after adjustment for confounding factors), the odds ratio for low birth weight was 3.57 (95% CI, 1.14–11.14) and for preterm delivery 3.60 (95% CI, 1.15–11.20). BMJ 2002; 324: 1-5 Use it or lose it In another prospective study, frequent participation in cognitively stimulating activities was associated with a reduced risk of Alzheimer’s disease (AD). The Religious Orders Study recruited Catholic nuns, priests and brothers aged ≥ 65 years from across the United States. Dementia was excluded at baseline, and 20 cognitive tests were completed. Involvement in seven common activities that require information processing (eg, reading newspapers, watching television) was rated on a scale of 1 (< once per year) to 5 (almost daily). The average score for each person ranged from 1.57 to 4.71 and the mean for the group was 3.57 (SD, 0.55). Cognitive testing was repeated each year. During an average of 4.5 years of follow-up, 111 of 724 persons developed AD. Taking into account possible effects of age, sex, educational level, baseline cognitive activity, APOE genotype, medical conditions, physical activity level and depression, a one-point increase in cognitive activity score was associated with a 33% reduction in risk for AD (hazard ratio, 0.67 [95% CI, 0.49–0.92]). JAMA 2002; 287: 742-748 Special babies In a Western Australian study, babies born through assisted conception were twice as likely to have a major birth defect as those conceived naturally. Researchers compared the prevalence of major birth defects in 301 infants conceived by intracytoplasmic sperm injection (ICSI) and 837 infants conceived by in vitro fertilisation (IVF) with the prevalence in 4000 naturally conceived babies, all born between 1993 and 1997. At the age of one year, 8.6% of ICSI babies and 9% of IVF babies had been diagnosed as having a major birth defect, compared with 4.2% of naturally conceived babies. It was not possible to separate the excess risk that may be associated with infertility treatment from the excess risk related to the underlying causes of infertility. N Engl J Med 2002; 346: 725-730

Med J Aust 2002; 176 (8 Suppl).