Volume 177 Issue 8

A case of public policy confusion In recent years, there has been an increasing focus on the mental health of children and adolescents.1 This is part of the broader process of reform of Australian mental health services, which now emphasises mental health promotion, the development of preventive approaches, early detection of mental disorders and early treatment interventions.2 At the same time, there is now clearer recognition that, in a country as culturally and linguistically diverse as Australia, specific attention must be paid to the cultural dimensions of mental disorder and mental health service design and the specific needs of Indigenous people, immigrants and refugees.3 Major national mental health policy statements now recognise these issues, and funding for State-based transcultural mental health units and centres for the treatment and support of torture and trauma survivors is one aspect of implementing this policy. This is consistent with increased attention being paid to the mental health of immigrants and refugees internationally.4 Of the 6.1 million refugees worldwide for whom demographic data are available, 45.6% are aged under 18 years, although the proportion of children and adolescents varies considerably by region (eg, 56% of refugees in Africa, 23% of refugees in Europe).5 In 2001 there were 900 000 asylum applications pending worldwide.5 The article by McKelvey and colleagues6 in this issue of the Journal (page 413) is important for several reasons. Firstly, research data on the mental health of immigrant and refugee children and adolescents are scarce. The study contributes to knowledge about one of the largest immigrant/refugee communities in Australia in a way that cannot be achieved even by large-scale and expensive studies that aim to be representative of the Australian population.1,7 The recent national survey of 4500 children and adolescents "provides only very limited information about the mental health of children and adolescents living in non-English speaking families".1 Secondly, the authors carefully avoided methodological pitfalls commonly seen in cross-cultural mental health research. They used appropriate translation methods for the questionnaire, worked in partnership with community leaders and Vietnamese-speaking mental health professionals, and conducted research interviews in either English or Vietnamese, using bilingual research staff who were trained and supervised in interview administration. Such attention to appropriate cross-cultural research methods is essential to ensure the validity of information obtained. Thirdly, the study is important because of the finding that the prevalence of psychiatric disorders in Vietnamese children and adolescents was not significantly different from that found in a general Western Australian sample8 and in a national sample,1 despite the fact that many of these children and adolescents had been affected by the stresses of migration to a vastly different cultural environment and that many came from families who had lived through the traumas of war. The data of McKelvey and colleagues relate to Vietnamese refugees settling in Western Australia at one point in time. The same rigorous research process is highly desirable when comparing other refugee populations, especially those experiencing different traumas before migration or different experiences of settlement within Australia. A clinical challenge is to identify subgroups who have suffered, or are at risk of developing, adverse psychiatric consequences. In the study by McKelvey et al, the low rates of mental health problems identified by parents highlights but one of the difficulties that young people from migrant families have in accessing mental health services. There may be a range of explanations for the relatively low rate of mental disorders identified in the study. However, if corroborated by studies of other ethnic groups and research in other settings, these data may reflect a feature of Australian society that has been a considerable success. That is, our capacity to accept immigrants and refugees from all over the world; to integrate new arrivals into a generally harmonious and well-functioning multicultural society; to create the conditions necessary for refugees to recover from trauma; and to provide an environment that is conducive to normal development, especially in children and adolescents. Underpinning this success have been legal and policy frameworks for multiculturalism, extensive services that have supported the successful permanent settlement of immigrants and refugees, and the general goodwill shown by the Australian population to immigrants and refugees. Unfortunately, recent years have seen a substantial bipartisan policy shift in Australia's treatment of asylum seekers, particularly of people arriving unauthorised by boat.9 The policy of mandatory detention of unauthorised "boat people" is now the subject of heated debate. One component of the debate has been the question of whether prolonged detention has harmful effects on the mental health of detainees in general,10 and on the mental health and development of children and adolescents in particular.11 On this latter issue, the subject of an inquiry by the Human Rights and Equal Opportunity Commission, there is remarkable unanimity of medical opinion: prolonged detention is causing harm to the mental health and development of children and adolescents.12 Also of concern is the plight of refugees who have been granted temporary protection visas and live within the community. In comparison with refugees who have obtained permanent residency visas, these people have substantially restricted rights, including the preclusion of family reunion and limited access to social services, English-language training and other services. There is concern that such restrictions may contribute to mental health problems in this group.13,14 Children's emotional and social development may be adversely affected if they are living with parents who are functionally impaired because of depression, anxiety or other mental health problems relating to the stresses and uncertainties of being a temporary visa holder. Current immigration policy, in the form of prolonged detention of asylum seekers and the move to temporary visas for some, is resulting in harm to the mental health of already vulnerable children, adolescents and adults. The mental health impact of this aspect of immigration policy appears at odds with national mental health policy and with the successful settlement policies that still apply to authorised immigrants and some refugees. The study by McKelvey and colleagues6 shows that we can do very much better than this.

I Harry Minas FRANZCP · Susan M Sawyer MD FRACP

The most direct way to reduce percutaneous injuries is to make devices safer In this issue of the Journal, Whitby and McLaws (page 418) provide a thorough epidemiological account of occupational exposure to bloodborne pathogens by hollow-bore needles in one hospital.1 More studies such as theirs are needed in Australia, where there has been relatively little attention focused on this issue, as indicated by the few references to studies by Australian investigators cited in their article. As an American I find this surprising, because many successful prevention programs introduced in Australia have earned the admiration of public health professionals in other countries. Three examples come to mind: laws requiring seatbelt use and advanced passenger protection in motor vehicles; progressive HIV prevention programs; and programs to prevent ultraviolet light exposure and skin cancer. I am among the admirers of Australia's strong prevention record. In light of these progressive programs, how might one explain the relative neglect in Australia of such a serious occupational risk as bloodborne pathogen exposure? Some answers may be extrapolated from the United States, where I have observed a culture of self-sacrifice among healthcare professionals that compels them to place self-interest at the bottom of their priority scale. I have also seen administrators make healthcare worker safety a low priority when protective measures for their employees require a financial commitment. Finally, resistance to new prevention policies for healthcare workers is likely to be strongest where there is a lack of surveillance data. This is the "no data, no problem" syndrome. In Australia, an awareness of the significance of the problem of exposure to bloodborne pathogens is necessary before a national commitment can be made to its solution. Percutaneous injuries are the most frequent type of injury sustained by healthcare workers, and the most life-threatening.2 This remains true despite important advances, including the availability of the hepatitis B vaccine and post-exposure chemoprophylaxis for HIV-exposed healthcare workers.3,4 Therefore, I am convinced that the only choice is to accept the responsibility of caring for our caregivers — in Australia and elsewhere. The first step towards overcoming neglect is documenting the problem. The report by Whitby and McLaws provides a fine example, on a small scale. With reported annual percutaneous injury rates of 4–15 injuries per 100 full-time-equivalent staff,1 and device-specific injury rates occurring usually in the range of 1–20 injuries per 100 000 devices used,5 the participation of numerous institutions and a long term commitment are required to maintain a database that can guide and sustain large-scale prevention programs.6,7 Active surveillance programs support strong policy initiatives, as has been seen in the US, where surveillance data have supported new regulations, guidelines and advisories issued by our government agencies, as well as state and national legislation.8,9 Widespread surveillance should become a national goal for Australia. There is a global network of countries in Europe, Asia and South America with advanced surveillance programs eager for collaborative exchange. Surveillance data reveal the causes of bloodborne pathogen exposures and they lead to conclusions that are difficult to ignore. Surveillance data from the International Health Care Worker Safety Center, University of Virginia, from 1996 to 2000 (84 hospitals, 23 243 injuries) show that 98.5% of percutaneous injuries sustained by healthcare workers were caused by sharp medical devices (exceptions include injuries from windshield glass, teeth, fingernails and bone fragments). Therefore, the most direct route to preventing percutaneous injuries is to make injurious devices safer to handle. I find it incredible that the debate still persists whether educational programs or safer devices should be the preferred method of protecting healthcare workers. If you asked a soldier dispatched to the frontlines of battle whether he would prefer a protective shield or an educational poster, there would be no need for discussion. Let us move quickly to get protective devices into the hands of healthcare workers, while providing the best educational methods to support the use of safer technology. The lack of data on the effectiveness of safety devices is often raised as a barrier to their adoption. Although there are several studies demonstrating the efficacy of safety-engineered needle devices, there nevertheless remains a need for further well-designed clinical trials as new and safer technology comes into the market place.10-11 But where data are lacking on potentially life-saving technology there should also be a responsibility to collect those data, rather than merely rejecting the technology by reason of their absence. But we should also not dismiss the use of common sense in weighing the potential safety impact of many safer devices: intravenous infusion systems with needleless access ports and needleless line connections cannot cause needlestick injuries (as long as one does not override the system and use needles with them); plastic capillary tubes and vacuum tubes all but eliminate the possibility of lacerations; blunt-tipped suture needles do not cause needlestick injuries. Not every device category requires a clinical trial to prove a reduction of injuries, especially if that device eliminates a needle or sharp item. Another area of time-consuming debate is whether safety devices are cost-effective. We now have a law in the US, the first in the world, requiring healthcare employers to provide safety-engineered devices for the prevention of percutaneous injuries, without consideration of their financial impact on individual healthcare facilities.9 Whitby and McLaws say that "such a situation should not be allowed to occur in Australia". Perhaps they need not worry about the potential cost burden in Australia. As the first customers of this new technology, US healthcare institutions, which comprise the largest medical device market in the world, are bearing the brunt of the cost burden. The new law has caused medical device companies to shift into high-volume production of safety-engineered devices. Economies of scale are already bringing prices down, as is the intense competition to gain market share in this new product area. These benefits will no doubt spill over to other countries. But I would hope for the sake of its healthcare workers, and in keeping with its strong tradition in the field of prevention, that Australia's response would be more active than simply waiting to see what washes up on shore.

Janine C Jagger MPH, PhD

The benefits of statin therapy do not come without financial cost The aim of the recently reported Heart Protection Study1 in the United Kingdom, with over 20 000 participants aged 40–80 years, was to establish whether statin therapy is of benefit to people who are at high risk of cardiovascular disease (CVD) but have average-to-low levels of total cholesterol and LDL-cholesterol. High-risk patients (defined as those having previous coronary heart disease, diabetes, stroke, or peripheral vascular disease) were treated with simvastatin (40 mg daily), antioxidant vitamins (20 mg beta-carotene, 250 mg vitamin C and 600 mg vitamin E daily) or placebo in a 2 × 2 factorial design. Among patients allocated to the antioxidant arm of the trial, there was no change in incidence of any prespecified endpoints, and there were small but significant increases in blood levels of LDL-cholesterol and triglycerides, which have the potential to increase CVD risk with long-term antioxidant use.2 High-dose antioxidant therapy is therefore not recommended.3 Reductions in cardiovascular events (including myocardial infarction, stroke and either coronary or peripheral arterial revascularisation) occurred with simvastatin therapy in women, elderly people, and people with previous cerebrovascular disease, peripheral artery disease, renal impairment or diabetes (see Box). Translating the results of the HPS into clinical practice, patients with an absolute overall CVD risk of more than 17% over five years (the lowest rate occurring in any subgroup of the HPS treated with placebo) should receive high-dose statin therapy, equivalent to 40 mg/day simvastatin, independent of baseline levels of total cholesterol; and other cardioprotective therapy, such as β-blockers and aspirin. Overall CVD risk can be estimated with the National Prescribing Service charts,4 which refer to CVD rather than coronary heart disease risk — a strategy flowing from the HPS outcomes.1,4 These charts, based on the Framingham study, provide only an approximation of absolute risk, but serve as a useful guide. Examples of patients with five-year CVD risk above 17% include most men over 60 years who smoke and have diabetes, and a 60-year-old non-smoking, non-diabetic man with blood pressure of 160/95 mmHg and a total cholesterol/HDL-cholesterol ratio of 6: 1.4 Benefits are likely to occur after 12 months of statin therapy, with greater benefits occurring the longer therapy is continued. Allowing for non-compliance, the HPS showed that about a third of major CVD events are likely to be prevented by statin therapy over five years. In the HPS, 23% of patients in the simvastatin group were smokers, 22% were being treated with antihypertensive agents, 20% with β-blockers, 25% with angiotensin-converting enzyme inhibitors (ACE inhibitors) and 21% with aspirin. Relative risk reductions in CVD incidence of up to 80% may be expected when statins are combined with standard cardioprotective agents (aspirin, β-blockers and ACE inhibitors) and stopping smoking.3 Given that CVD reduction in the HPS was independent of baseline cholesterol levels, it has been suggested that lipid levels need not be measured before commencing statin therapy in high-risk patients.3 However, fasting levels of triglycerides and HDL-cholesterol should be measured after 1–2 months, as therapy may need to be modified if these lipids are inadequately controlled by statin therapy alone. For example, gemfibrozil therapy may be considered for patients with low HDL-cholesterol levels.5 The HPS included about 6000 individuals with diabetes — the largest number in any statin trial reported to date. The CVD event rate for placebo-treated diabetics without coronary heart disease was 18.6%, compared with 22.5% for non-diabetics with coronary heart disease. Thus, the HPS confirms diabetes as a "coronary-equivalent" risk disorder for CVD.6 However, risk of CVD may vary from low to very high, depending on age and other risk factors, so it is still necessary to determine the global risk of CVD for an individual with diabetes when assessing the need to treat with a statin.4 Subjects at highest risk of CVD in the HPS had slightly elevated baseline serum creatinine levels (> 200 μmol/L), although only results of univariate analysis have been provided. The HPS confirms the high CVD risk in patients with impaired renal function and also supports the need for treatment of their dyslipidaemia.7 Caution is required in giving statin therapy to patients with more severe renal impairment, as they are at increased risk of myopathy.8 In the HPS, the safety profiles for statin and placebo therapy were similar. This finding may partly be a consequence of the exclusion of patients who showed adverse reactions to simvastatin during a 4–6-week run-in period leading up to the trial. However, only 32% of 63 603 screened patients were allocated to receive simvastatin in the study, so the low adverse event rate in the study may not necessarily apply to an unselected population. Of particular importance with regard to safety was the low incidence of myopathy (defined as serum creatine kinase levels exceeding 10 times the upper limit of normal), which occurred in only 11 simvastatin-treated patients and six placebo-treated patients. These results are reassuring, but muscle symptoms and creatine kinase levels should still be monitored periodically, and withdrawal of statin therapy should be considered if myalgia occurs or creatine kinase levels rise to more than three times the upper limit of normal.9 There were no apparent safety concerns in patients with low baseline LDL-cholesterol levels (< 3 mmol/L), in whom average LDL-cholesterol levels during the trial were 1.8 mmol/L in the simvastatin-treated group and 2.7 mmol/L in the group receiving placebo. The association between low levels of total cholesterol and increased cerebral haemorrhage found in a study by Iso et al10 was not borne out by the HPS. The safety and efficacy of treatment with 40 mg/day of simvastatin demonstrated by the HPS will probably result in a higher average dose being used in Australia, where the current average dose is 25 mg/day (Glen Godresse, Specialist/Hospital Product Manager, Merck Sharp and Dohme Australia Pty Ltd, personal communication). The benefits of statin therapy do not come without financial cost, although the long-term savings as a result of statin therapy are very likely to outweigh that cost.11 As CVD remains the single most important cause of mortality in Australia, consideration should be given to extending the availability of statins under the Pharmaceutical Benefits Scheme to include patients shown in the HPS to benefit from therapy: diabetics, women over 40 years, elderly people, and those with peripheral vascular disease, renal disease and low-to-average cholesterol levels, if their estimated global CVD risk exceeds 17% over five years.4 Absolute risk reductions and numbers needed to treat to prevent one cardiovascular event1 Event ARR (%)* NNT† All-cause mortality 1.8% 56 Mortality due to CHD 1.5% 83 Non-fatal myocardial infarction 2.1% 48 Coronary revascularisation 2.6% 38 Ischaemic stroke 1.2% 83 MVE without baseline CHD 4.7% 21 MVE with baseline CHD 5.7% 18 MVE with baseline creatinine > 200μmol/L 9.0% 11 MVE in patient aged < 65 years 5.2% 19 MVE in patient aged ≥ 70 years 5.1% 20 CHD = coronary heart disease. MVE = major vascular event (includes CHD, stroke, revascularisation). * Absolute risk reduction (%), simvastatin therapy v placebo. † Number needed to treat with simvastatin 40 mg/day to prevent one event over 5.3 years.

Ian Hamilton-Craig PhD FRACP

A more proactive approach by GPs would help to ease the burden on family carers In Australia, up to 2.3 million people are involved in informal care of children, adults and older persons with disabling chronic and terminal conditions.1 Their role includes managing medications, therapies and medical emergencies; providing supervision and emotional support; and assisting with personal care, mobility and household tasks.1-3 While caring can provide considerable satisfaction and strengthen relationships, carers often feel exhausted, isolated and burdened by their responsibilities.1,3,4 In a recent survey of carers, 58% reported their physical health had been adversely affected, a third said they had sustained a physical injury, and over half reported depression, anxiety, high levels of stress and other impacts on their mental health.2 There have been many calls for general practitioners to be more proactive in addressing the support needs of carers,3-6 and carers have identified how this may be accomplished (see Box). A 1998 editorial on family carers in Australia3 called for strategies to raise health professionals' awareness about carers, to keep them abreast of programs available to carers, and to encourage them to be more proactive in helping carers to obtain support. Since then, there has been limited apparent progress in Australia (unlike Britain, where there has been considerable interest in the primary care team's designated responsibility for addressing carer needs7). Projects conducted through Divisions of General Practice to inform and educate doctors, to promote carer self-identification and discussion5-6 and to promote collaborative referral with regional carer respite services5 showed encouraging outcomes, but have failed to attract further funding from government. Carer associations have also acted by providing various resources. The GP information kit, Carer Checklist and Carers Profile assessment tools (trialled in New South Wales) are time-efficient and pave the way for discussion of carer issues.7,8 In Victoria, individual carers are encouraged to raise issues and to give their GPs a tailored service-provider kit, but this approach lacks systematic coverage. In South Australia, a GP working group is seeking to collaboratively explore various approaches, including GP education and involvement of practice managers. Government initiatives have focused on raising GPs' awareness of community services and referral pathways (eg, the Commonwealth CareLinks and Victorian Primary Care Partnership8). Supporting tools initiated by governments include service directories, consumer assessment and service coordination templates, referral mechanisms (both printed and Web-based) and consumer/carer charters. The full potential of information technology has not yet been harnessed. For example, including a "carer status" field in patient records would prompt early identification of care responsibilities. Software could also alert GPs to provide information or follow-up, and could even include (or electronically link to) carer fact sheets and resources, such as those produced by the national carer organisation Carers Australia. Even GPs committed to working with carers can face considerable barriers to implementing a proactive approach. The patient may not agree to the carer participating in the consultation, or the carer may be reluctant to discuss how he or she is managing, especially if the patient is present or the carer perceives the GP to be too "busy" or very medically focused.4,5,7,10 Either the patient or the carer may be reluctant to accept external assistance.5,6,10 The carer may forgo his or her own health checks or treatment plan because of the pressures of caregiving.2 Finally, in addition to lack of training, information and resources,5-7,11 GPs have to cope with increasing demands, time constraints and inadequate remuneration,5,7,9-11 problems that are often difficult to overcome. The Enhanced Primary Care (EPC) Medicare Benefits Schedule items provide an opportunity to focus on carers and partly address the issue of remuneration for GPs.12 With the patient's consent, carers can be formally included in care planning and case-conferencing activities. This enables GPs and other healthcare workers to hear carers' views on how well they and their patients are managing at home. GPs and carers can then jointly consider options for coordinated support. Where carer wellbeing is an issue, staff of regional carer respite services (or other workers assisting the carer) can usefully be involved.6 Health assessments, another EPC item, should also include screening for carer issues. However, GPs may still need to grapple with the thorny issues of consent, conflict and reluctance — interpersonal issues arising in the relationships between patients and carers and between patients/carers and their doctor. Much of the responsibility for monitoring patient records and maintaining information resources can be delegated to the practice manager or an allied health professional. For example, practice nurses have effectively undertaken health assessments13 and are well positioned to provide carer health education, service referral and coordination. A counsellor or carer-support worker attached to a general practice can assist with identifying carer needs and making referrals, as well as helping the carer to develop skills and to work through emotional or relationship issues.6 The Better Outcomes in Mental Health Initiative14 is relevant to assisting carers who are experiencing severe stress, anxiety or depression. The initiative provides incentive payments for mental health needs assessment, planning and review activities to doctors who register interest with their local Division of General Practice and receive training. We believe that including educational material on carer mental health issues in training packages would enhance this initiative. Given the absence of clear strategies and leadership on this issue over the past four years, the development of clinical practice guidelines and policy positions by governments and peak practitioner bodies is needed. The evolving Commonwealth-funded Primary Health Care Research Evaluation and Development Strategy15 provides an ideal opportunity to prioritise collaborative research in this area. The demonstration of the benefits to carers, those they care for, and the community generally, of an overtly aware and interventionist clinical approach is well overdue. What carers would like general practitioners to do6-8 Recognise their carer status and care responsibilities and include them in care planning and decision-making. Avoid assumptions about carer's capacity, confidence and willingness to provide home care. Provide plain-language information to the carer on the patient's condition, prognosis, treatment, care needs and management (including behaviour management). Provide information and referrals relevant to carers (eg, in-home and residential respite care options, counselling, peer support groups, financial entitlements, self-care and coping strategies). Give referrals to carer associations and state-wide condition-specific bodies as a starting point. Discuss and, where appropriate, assess the carer's own physical and psychosocial health needs. Engage other family members in understanding and sharing care responsibilities. Recognise grief and loss on cessation of caring.

Julie M Nankervis MSW MAPS · Peter J Waxman MB BS FRACGP · Denise A O'Hara MB BS MPH FAFPHM · Mary Burbidge MB BS

Trial evidence best informs real-world medicine when it is relevant to the clinical problem Controlled clinical trials provide the most reliable evidence of whether treatments are effective, particularly when the effects of treatment are moderate. Without such trials, ineffective treatments or, even worse, harmful interventions may be accepted in medical practice. Yet medical practice is often not based on clinical trial evidence, because the evidence is considered not relevant or does not exist. Real-world medicine must not only consider the effectiveness of specific treatments, but must do so in the context of patients who have multiple problems and who are often already receiving many different treatments in a setting different from that tested in the trial.1 Throughout the history of medicine, many treatments have been considered effective until well-controlled trials demonstrated otherwise.2 Some recent treatments based on observational data that have been discredited by randomised controlled trials include hormone replacement therapy to prevent coronary heart disease events,3 vitamin supplements to prevent lung cancer4 or cardiovascular disease events,5 and arthroscopic surgery for osteoarthritis of the knee.6 Although data from observational studies may be of value,7 these data may sometimes suggest a harmful outcome for treatments that are known, from controlled trials, to be effective, such as blood pressure treatment.7 Applying trial results to individual patientsAlthough clinical trial evidence for the introduction and use of new drugs is widely accepted, the "real-world" uptake is often erratic. For patients with coronary heart disease, the merits of statins, angiotensin-converting enzyme (ACE) inhibitors, β-blockers and aspirin are well recognised from clinical trial evidence, yet these treatments are still significantly underused.8 The gap between evidence and practice is even wider in other areas. Evidence is an essential part of good medical practice, but it is not the only information needed for clinical decision-making. Real-world medicine may ignore clinical trial evidence if it does not seem relevant to the clinical problem at hand or if the benefit is uncertain. A drug that shrinks a cancer is not necessarily useful unless it also improves the patient's quality of life or prolongs survival. A treatment that lowers blood pressure or cholesterol has value only if these outcomes are translated into meaningfully fewer cardiovascular events, without a penalty of increased adverse effects. Hence, evidence from trials is most applicable in practice when the design and the outcomes chosen are directly relevant to real patients, the trials are undertaken against a background of standard medical care, patients in trials are broadly representative of patients in the real world, and evidence from trials is integrated with individual patient characteristics for meaningful risk–benefit assessment. Absolute differences in risk (or numbers needed to treat) are recognised as most relevant to decision making; yet clinical trial results are often reported as changes in relative risk. For example, recent clinical trial results of breast cancer risk in women taking hormone replacement therapy appeared exaggerated if the increased risks were considered in relative rather than absolute terms. Treatment resulted in a 26% relative increase in breast cancer, which equated to an absolute increase of just 0.08% per year.3 Nevertheless, the relative treatment effect is of value if applied appropriately (by combining it with the individual's baseline risk), providing a better guide to the absolute effect of treatment in specific patient groups.1 ParticipationDespite the need for high-quality clinical trials, few patients participate in them, even in areas where trials are common. For example, less than 5% of eligible patients participate in most cancer trials9 and less than 10% in many cardiovascular trials.10 Low participation rates raise concerns that the results from trials apply only to select groups of patients. Scant participation is not necessarily a problem if patients are representative, but patients in trials are often narrowly selected because of the eligibility criteria, the setting, or the patients agreeing to participate. Strategies such as public access to ongoing trials through registers and more pragmatic trial designs are needed to maximise participation and ensure treatments are assessed in a variety of settings. The need for wider use of clinical trialsWhenever a new drug treatment is discovered that has the potential to help many patients, prevailing systems support well-controlled trials addressing effectiveness and safety. Systems to assess new technologies or interventions other than drugs are equally important, yet more challenging and much less developed. Also lacking are sufficient trials of new devices, health service management decisions, and trials in community or Third World settings. It has been suggested that clinical trials are too expensive, and funding outside the pharmaceutical industry is limited. A randomised clinical trial, evaluating a moderate treatment effect on important clinical outcomes, may cost from $1 million to more than $50 million. However, this cost needs to be put in the context of healthcare generally (more than $50 billion in Australia each year11) and the cost of not undertaking trials before deciding which treatments to support. The Australian government has recognised the importance of basing funding decisions for new health technologies (through the Pharmaceutical Benefits Advisory Committee and the Medicare Services Advisory Committee) on the best evidence of the effectiveness, safety and cost-effectiveness of each treatment. But funding more research on the cost-effectiveness of new technologies is also warranted. Specific clinical trials in this context may be much more cost-effective than using funds to introduce therapies on the basis of less reliable evidence.12 Consequently, a more proactive funding strategy for trials should be considered, extending the model proposed by Glasziou: 13 up to 1% of the national healthcare budget could be used to test new and existing health technologies for which there is inadequate evidence, but potentially large benefits or cost savings.14 One approach to monitor and implement some of these strategies is through the use of a comprehensive national trials register to aid the planning of new trials, ensure all trials are identified when evaluating trial evidence, and maximise participation of patients and doctors in ongoing trials.15 Many clinical trials already play a central role in everyday clinical practice. However, if we seriously address each of the above issues, health outcomes could be further improved through clinical trials assessing new health technologies and existing treatments in the real world of modern medicine. It is time for us to look at how to make this more of a reality.

R John Simes

Objective: To determine the prevalence of psychiatric disorders among Vietnamese children and adolescents living in Perth, Western Australia.Design, participants and setting: A list of Vietnamese households was drawn from Perth telephone directories. A computer program generated a systematic probability sample of households. All children and adolescents aged 9–17 in these households were invited to participate in the study. Children and their parents were interviewed in their home using the Diagnostic Interview Schedule for Children, version 2.3 (DISC-2.3). The child version (DISC-C) was used for children and the parent version (DISC-P) for adults. The study was conducted between July and December 1997.Main outcome measures: The prevalence of psychiatric disorders in children and adolescents, based on DISC-C and DISC-P data.Results: Results were based on the 519 children (89.2%) for whom complete data were available. Twenty-three parents (4.4%) reported that their child had one or more disorders on the DISC-P, 82 children (15.8%) reported one or more disorders on the DISC-C, and 18.3% of children were reported to have a disorder on either the DISC-C or the DISC-P. Parent–child concordance on specific diagnoses was very low (0.6%). The great majority of disorders reported were anxiety disorders, especially simple and social phobias.Conclusions: The combined prevalence of psychiatric disorders among Vietnamese children aged 9–17 was similar to that found among children in Western Australia's general population. Vietnamese children in our study were much more likely to report symptoms of a psychiatric disorder than were their parents.

Robert S McKelvey MD, FRANZCP · David L Sang PhD · Loretta Baldassar PhD · Lisa Davies PhD · Lynne Roberts PhD · Neil Cutler BA

Objective: To describe the frequency, cause and potential cost of prevention of hollow-bore dirty needlestick injury (NSI) sustained by healthcare workers.Design and participants: Ten-year prospective surveillance study, 1990–1999, with triennial anonymous questionnaire surveys of nursing staff.Setting: 800-bed university tertiary referral hospital in Brisbane, Australia.Main outcome measures: Rates and circumstances of NSI in medical, nursing and non-clinical staff; knowledge of NSI consequences in nurses; and minimum costs of safety devices.Results: Between 1990 and 1999, there was a significant increase (P < 0.001) in the trend of the reported rate of NSI. Of the 1836 "dirty" NSIs reported, most were sustained in nursing (66.2%) and medical (16.8%) staff, with 62.7% sustained before disposal. Hollow-bore injuries from hypodermic needles (83.3%) and winged butterfly needles (9.8%) were over-represented. Knowledge among nursing staff of some of the risks and outcomes of NSI improved over the decade. A trend (χ2 = 9.89; df = 9; P = 0.0016) with increasing rate of reported injuries in this group was detected. The estimated cost of consumables only, associated with the introduction of self-retracting safety syringes with concomitant elimination of butterfly needles, where practicable, would be about $365 000 per year. Conclusion: More than one NSI occurs for every two days of hospital operation. Introduction of self-retracting safety syringes and elimination of butterfly needles should reduce the current hollow-bore NSI by more than 70% and almost halve the total incidence of NSI.

R Michael Whitby FRACP, FRCPA · Mary-Louise McLaws MPH, PhD

Objectives: To investigate whether pantoprazole (20 mg/d) produces significantly greater symptom control than ranitidine (300 mg/d) in patients with gastro-oesophageal reflux disease (GORD).Design: Multicentre, randomised, double-blind, parallel-group comparison.Setting: 76 general practices in north-west Sydney and Newcastle, New South Wales (Australia), from 19 January 1999 to 22 September 2000.Patients: 307 patients aged 18 years or over presenting with symptomatic GORD.Interventions: Pantoprazole (20 mg once daily) or ranitidine (150 mg twice daily).Main outcome measures: Patient-assessed frequency and severity of heartburn using the Gastrointestinal Symptom Rating Scale (GSRS) and a patient heartburn diary.Results: Pantoprazole was associated with significantly higher rates of complete control of GORD symptoms than ranitidine at four weeks (40% v 19%; P < 0.001), eight weeks (55% v 33%; P < 0.001), six months (71% v 56%; P = 0.007) and 12 months (77% v 59%; P = 0.001).Conclusions: Low-dose pantoprazole is an effective alternative to standard-dose ranitidine for initial and maintenance treatment of patients with symptomatic GORD.

Nicholas J Talley MD, FRACP · Michael G Moore FRACGP, GradDipPublicHealth · Arn Sprogis MB BS, FRACGP, GradDipClinEpid · Peter Katelaris MD, FRACP

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels.Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo.Patients and setting: 9014 patients aged 35–75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992.Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life.Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%–4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626–$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%).Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Paul P Glasziou FRACGP, PhD · Simon D Eckermann BEc(Hons), BSc(Ma · Sarah E Mulray BA · R John Simes FRACP, MD · Andrew J Martin MA, PhD · Adrienne C Kirby BSc(Hons), MSc · Susan Caleo BPharm, GradDipSci · Jane P Hall BA, PhD · Harvey D White DSc, FRACP · Andrew M Tonkin MD, FRACP

In response to difficulties meeting the demand for hospital services ("access block") at Royal Melbourne Hospital, a major metropolitan tertiary referral hospital, an audit of patient needs revealed a shortage of aged-care beds and a need for post-acute care. A multidisciplinary Care Coordination Team (CCT) was formed at the end of July 2000 to ensure that emergency department patients were provided with services that would facilitate their return to, or maintenance in, the community. The target population included the frail elderly, those living alone, the homeless, frequent emergency department attenders, and those with complex medical or drug and alcohol problems. As part of routine emergency department care, a risk screen was implemented to determine referral to the CCT. In the first 12 months, the CCT saw 2532 patients (5.8% of all emergency department attendances). Nearly half of these patients were discharged home with referrals to community service providers. The rate of hospital admission from the emergency department fell significantly compared with the 12-month period before implementation of the CCT (13 420 patients, 30.9% [95% CI, 30.5–31.3] v 14 217 patients, 32.6% [95% CI, 32.2–33.0]; P < 0.001). Surveys of staff, patients and carers, as well as community service providers, showed a high level of satisfaction with the CCT.

Joanne E Moss MNurs(Melb), BNurs · Liza M Houghton BAppSci(Nurs), GradDipNurseEd · Carolyn L Flower BOccThy, Occupational Therapist, Emergency Department Care Coordination Team · Danielle L Moss BA, BSW · David A Nielsen BAppSci(Nurs), GradDipGeronNurs · David McD Taylor MD, FACEM

Six patients presented with clinical, biochemical and histological evidence of severe hepatitis after taking herbal remedies. One patient required urgent liver transplantation for fulminant hepatic failure after the brief use of black cohosh. Five patients took a combination of herbs and presented with jaundice, fatigue and pruritus. Healthcare providers and members of the public should be aware of the potential adverse effects of these remedies. (MJA 2002; 177: 432-435) There has been a steady rise in the use of complementary medicine throughout the world. In 1997 it was estimated that 57% of Australians used complementary medicines, with an annual expenditure of $621 million.1,2 Self-medication is common, with 62%–72% of patients not disclosing the use of herbal preparations to their family doctors.3 This reluctance may be due to a perceived conflict between practitioners of conventional and alternative medicine. Although there have been trials on the efficacy of several herbal remedies, most information is based on anecdotal evidence and reputation. Information documenting adverse reactions is based on case reports and literature reviews, as there have been few prospective trials to date.4-7 As a result, the data available may not highlight potential adverse effects. In 1999 the Office of Complementary Medicine was created as part of the Therapeutic Goods Administration (TGA) in an attempt to regulate alternative medicine in Australia. The constituents of a herbal remedy must undergo pre-market evaluation for safety and quality before being listed on the Australian Register of Therapeutic Goods. Manufacturers of herbal products must now be licensed and need to adhere to the Therapeutic Goods Advertising Code. If a complementary medicine claims to "cure/manage or prevent" a disorder it requires high-level evidence to be registered, but if it claims to be for "symptom relief/health maintenance or health enhancement" then the product does not need formal evaluation. With the expanding use of these remedies, the risk of serious drug interactions increases. There is some information available on common interactions,7,8 but continued vigilance is required with the introduction of new medications. We describe six patients with hepatotoxicity from a variety of herbal remedies. The patients were reviewed by a gastroenterologist in Queensland (P K) between 1996 and 2001. Data were collected when the patient presented and subsequent telephone inquiry clarified any other details. The individual herbal products were not analysed for their constituents. Clinical recordsClinical records for the six patients are summarised in Box 1. One woman used black cohosh (Cimicifuga racemosa) alone for one week, and the other five patients were taking various combinations of herbs for 6–18 weeks before the onset of symptoms. Four patients disclosed the use of the herbal product to their general practitioner before referral. Patient 1 was taking the herbal remedy for relief of symptoms of menopause, Patient 5 as a "liver tonic", and Patient 6 to lose weight. The others took the remedies for general health promotion. The doses varied and were not reported to exceed the dosage recommended on the package. None of the patients had a history of excessive alcohol intake, injecting drug use, prior blood transfusion, family history of liver disease, or past history of liver or biliary tract disease. Patient 3 was taking temazepam, and Patient 4 had been taking long term low dose aspirin. No other concurrent medication was reported. Two patients had notable comorbidities: Patient 3 suffered from Huntington's chorea, and Patient 2 was diagnosed with ovarian adenocarcinoma shortly after presenting with hepatitis, but had no evidence of metastatic involvement of the liver on biopsy, computed tomography scan or at laparotomy. All patients developed jaundice, and the pattern of liver enzyme abnormality was predominantly hepatocellular (serum alanine aminotransferase level > 1000 U/L in each), with moderate elevations in the cholestatic enzymes. Pruritus was present in three patients. The international normalised ratio [INR] was elevated in two subjects (Patient 1: INR, 4.6; Patient 2: INR, 2.4). Peripheral blood eosino-philia was not present in any of the patients. No causes for liver disease other than the herbal remedies were found. Serology for hepatitis A (IgM, anti-HAV), hepatitis B (HBsAg) and hepatitis C (anti-HCV) was negative in each of the patients. The antinuclear antibody was positive in a titre of 1: 40 in Patients 2 and 3. The smooth-muscle antibody and antimitochondrial antibody titres were negative for all patients tested (1–3, 5, 6). The iron and copper profiles were in keeping with an acute phase response. The alpha-1-antitrypsin level was normal in all patients. An endoscopic retrograde cholangiopancreatogram demonstrated a normal biliary tree in two patients with jaundice and cholestatic features. All patients had normal imaging of the liver by upper abdominal ultrasound or computed tomography examination. Percutaneous liver biopsy was performed in five subjects with severe hepatitis, and the liver removed at transplantation (Patient 1) was available for study (Box 2). The biopsies were processed routinely, three sections were stained with haematoxylin–eosin, and additional sections were stained with haematoxylin–van Gieson. In all biopsies there was moderate to marked portal and lobular hepatitis. The limiting plates showed moderate to severe interface hepatitis (piecemeal necrosis). In addition, there was confluent zone 3 dropout and linkage of portal tracts and central veins. Eosinophils were present in five of the six cases but were not a conspicuous feature. All the biopsies were typical of acute hepatitis such as that seen in severe viral hepatitis. These changes are typically found in severe immunological reactions and are not the changes of direct toxic injury. Three patients with persistent jaundice and severe pruritus were treated with oral prednisone, resulting in immediate improvement in the symptoms of pruritus and jaundice. DiscussionHerbal remedies, like conventional medications, carry a risk of adverse reactions. There are many factors contributing to the potential toxicity of herbs. These include misidentification of the plant, variability in the time and place of collecting the plant, use of the wrong part of the plant, incorrect storage, contamination during preparation, and inconsistency in nomenclature and labelling of the final product.10 Adulterants such as corticosteroids have been added to some preparations.11 The remedies may have multiple ingredients, creating difficulty determining the causative agent and possible mechanism of injury. The identification of a herbal remedy as being responsible for hepatotoxicity often depends on demonstrating a temporal relationship between consumption of the product and development of the illness and improvement after discontinuation, after excluding other causes of liver disease. Some herbal agents used as medicinal products which are known to cause liver disease are listed in Box 3. We have identified six patients who developed abnormal liver function tests after taking herbal remedies. Other causes of liver disease were excluded. One patient required urgent liver transplantation, and the others recovered after stopping the herbal remedy. For ethical reasons, challenge experiments were not performed. Liver biopsies were characteristic of an idiosyncratic, immunological reaction24,25 and were very similar to the changes seen in acute viral hepatitis. In particular, there was prominent hepatocyte apoptosis, acinar zone 3 dropout, and at least focal bridging "necrosis" in all cases. This pattern of injury has been noted with skullcap and valerian,19 but differs from the liver injury described with chaparral12 and germander,14 where true coagulative necrosis rather than apoptosis is observed (suggesting toxic injury and not an immunological reaction). The most serious illness occurred in a 47-year-old woman (Patient 1) who was taking black cohosh for symptoms related to the menopause. Histological examination of her explant liver confirmed severe hepatitis and multiacinar dropout. The large number of synonyms for black cohosh highlights the problems with nomenclature, with up to 20 names used in North Carolina and South Carolina alone.11 It is widely used, particularly in Europe, for its putative beneficial influence on perimenopausal symptoms.26 In the United States, the Food and Drug Administration (FDA) lists it as a "herb of undefined safety".27 There are no restrictions on the use of black cohosh in Australia. It contains a mixture of alkaloids, tannins and terpenoids, and has not previously been reported to have hepatotoxic effects. Diterpenoids have been shown in animal models to result in liver injury, either by reactive metabolites or by an auto-immune mechanism.7 Previous studies have incriminated mixtures of skullcap and valerian as causing hepatitis,13,19 with jaundice and marked elevation in serum bilirubin and alanine amino-transferase levels being features. In our series, two patients (2 and 3) were using this combination and a further patient (4) used skullcap without valerian. In addition, the mixture Patient 2 took also contained black cohosh. Patient 5 was taking a combination of herbs that included chaparral. Chaparral, when taken in capsule or tablet form, can cause subacute hepatitis, but no deaths have been reported.12 In 1992, the FDA issued a warning about the potential danger of its use. There are no reported cases of the other herbs being hepatotoxic. Patient 6 was taking a preparation containing a mixture of herbs advertised as a fat metaboliser and a fluid retention remedy. Greater celandine (Chelidonium majus) has been associated with acute hepatitis characterised by marked cholestasis.15 Buchus leaf contains pulegone, a volatile oil also found in pennyroyal oil. Pulegone has been reported to be hepatotoxic,28 either directly or via a reactive intermediate.29 The true incidence of hepatic damage caused by herbal medications remains unknown owing to a lack of prospective studies. The incidence of hepatotoxicity from Chinese herbal remedies has been estimated at between 0.2% and 1%.30 With the increasing use of herbal remedies, medical practitioners need to be aware of the potential adverse effects and should routinely ask patients about all medications, including herbal mixtures. Labelling and advertising should include the known adverse effects, and a public education program is needed so that consumers are more aware of potential risks. The establishment of the Office of Complementary Medicine should address some of these issues. Finally, toxicity testing for plants and herbs used therapeutically should be undertaken as for manufactured drugs. 1: Summary of clinical and laboratory data for six patients who developed hepatitis after taking herbal remedies Patient (sex, age) Herbal remedy Time on herbs (weeks) Time to symptoms (weeks) Symptoms Peak value Time from diagnosis to normal laboratory results (weeks) Treatment Symptom Duration(weeks) Bilirubin† (μmol/L) ALP‡ (U/L) AST§ (U/L) ALT¶ (U/L) GGT** (U/L) 1(F, 47) Black cohosh 1 1 Jaundice 2 335 158 3182 2295 163 Not applicable Liver transplant 2(F, 43) Skullcap;* valerian;* black cohosh; passionflower; Angelicia sinensis; hops; Avema sativa; chasteberry N/A N/A Jaundice; nausea; vomiting; diarrhoea 18 284 80 1140 1500 N/A N/A Nil 3(F, 75) Skullcap; valerian;* hops 6 6 Jaundice 4 169 219 933 1470 330 20 Nil 4(M, 55) Skullcap; Ginkgo biloba 14 18 Jaundice; pruritus 5 181 150 1018 1293 373 7 Prednisone 5(M, 25) Chaparral;* dandelion; Withania somnifera; horsetail; echinacea 6 8 Jaundice; pruritus; fatigue 4 684 159 3910 3104 318 7 Prednisone 6(F, 23) Greater celandine;* buchus leaf; Uva ursi; juniper; parsley piert; choline bitartrate; dandelion 12 12 Jaundice; pruritus; fatigue 5 1073 134 2092 3764 81 25 Prednisone * Herbal remedies reported as hepatotoxic (see Box 3). † Bilirubin normal range < 20 μmol/L. ‡ Alkaline phosphatase (ALP) normal range 40–250 U/L. § Aspartate aminotransferase (AST) normal range < 35 U/L. ¶ Alanine aminotransferase (ALT) normal range < 40 U/L. ** Gamma glutamyltransferase (GGT) normal range < 50 U/L. N/A = not available. Botanical names: Black cohosh, Cimicifuga racemosa; Skullcap, Scutellaria lateriflora; Valerian, Valeriana officinalis; Passionflower, Passiflora incarnata; Hops, Humulus lupulus; Chasteberry, Vitex agnus-castus; Chaparral, Larrea tridentata; Dandelion, Taraxacum officinale; Horsetail, Equisetum arvense; Greater celandine, Chelidonium majus; Juniper, Juniperus communis. 2: Liver histology for the six patients* Patient Interface hepatitis (0–4) Portal inflammation (0–4) Zone 3 hepatocyte loss (0–4) Bridging necrosis (0–2) Lobular inflammation (0–4) Eosinophils (0–2) Bile duct damage Fibrosis (0–6) 1 ++ ++ ++++ ++ ++ ++ 0 Early 2 ++++ ++++ +++ focal ++++ ++ 0 0 3 +++ ++ ++++ + ++++ + 0 Early 4 +++ ++ +++ focal +++ 0 0 0 5 +++ +++ +++ focal ++++ ++ 0 0 6 +++ +++ ++++ + ++++ + 0 0 * Scoring system adapted from Ishak et al.9 Eosinophils 0 = none; 1 = 1–4 per portal tract; 2 = > 4 per portal tract. 3: Common herbal remedies suspected of being hepatotoxic Common name Botanical name Potential toxic constituents Indications Hepatic disease References Chaparral Larrea tridentata Nordihydroguaiaretic acid Free radical scavengerDelays aging Hepatitis Gordon et al (1995)12 Comfrey Symphytum officinale Pyrrolizidine alkaloids Herbal teaPoultice Veno-occlusive diseaseHepatic adenomas Miskelly et al (1992)13 Germander Teucrium chamaedrys Furano neoclerodaneFlavonoids Antipyretic Weight control Hepatitis Larrey et al (1992)14 Greater celandine Chelidonium majus Unknown Gallstones Dyspepsia Hepatitis Benninger et al (1999)15 Jin Bu Huan Lycopodium serratum Unknown Sedative Analgesic Hepatitis Graham-Brown (1992)16 Kombucha tea Kombucha "mushroom" Unknown Arthritis Cancer cure Hepatitis Perran et al (1995)17 Mistletoe Viscum album Unknown Antihypertensive Sedative Hepatitis Harvey and Colin-Jones (1981)18 Mixtures of valerian and skullcap Valeriana officinalis Scutellaria lateriflora Alkylating agents Crystalline glycoside and a volatile oil Sedative Sedative Hepatitis Hepatitis MacGregor et al (1989)19 Miskelly et al (1992)13 Pennyroyal oil (squawmint oil) Labiatae spp. Pulegone Abortifacient Menstrual complaints Hepatic necrosis Anderson et al (1996)20 Sassafras Sassafras albidum Safrole Arthritis Hepatitis Hepatocarcinogen Segelman et al (1976)21 Senna Cassia angustfolia Sennosides Laxative Hepatitis Beuers et al (1991)22 White chameleon Atractylis gummifera Potassium atractylate Gummiferin Antipyretic Purgative Hepatitis Georgiou et al (1988)23

Peter W Whiting MB BCh, BAO, FRACP · Andrew Clouston MB BS, PhD, FRCPA · Paul Kerlin BA, MD, FRACP

Trial: Hurskainen R, Teperi J, Rissanen P, et al. Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. Lancet 2001; 357: 273-277. QuestionWhat is the effectiveness of the levonorgestrel-releasing intrauterine system (IUS) compared with hysterectomy for the management of women with menorrhagia? Trial details Design: Randomised controlled trial, double-blind. Setting: Five university hospitals in Finland. Patients: Premenopausal women aged 35–49 years, with menorrhagia and no major gynaecological abnormalities were recruited to the study. Exclusion criteria were submucous fibroids, endometrial polyps, ovarian tumours or masses greater than 5 cm, cervical disease, urinary and bowel symptoms or pain resulting from large fibroids, lack of indication for hysterectomy, history of cancer, menopause, severe depression, metrorrhagia as a main complaint, previous treatment failure with levonorgestrel-releasing intrauterine system (IUS), severe acne, and uterine malformation. Interventions: 119 patients were allocated to the IUS group and 117 were allocated to the hysterectomy (any method) group. Hysteroscopy was performed before randomisation only if clinically indicated. Main outcome measures: Quality-of-life measures (including health-related, measured on a scale of 0–1 with the EuroQuol [EQ-5D] instrument), anxiety measures, resource use, menstrual blood loss, haematological indices. Main results: In the IUS group, 24 women (20%) had had a hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation (5 cancelled before surgery and 5 withdrew from the study group). Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change in EQ-5D, 0.10 [95% CI, 0.06–0.14] in both groups), as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that the hysterectomy group had less pain than the IUS group at 12 months. Overall costs were about three times higher for the hysterectomy group than for the IUS group. Conclusion: The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy for treating this disorder. CommentaryRationale for the trialInternational hysterectomy rates vary considerably; by the age of 60 years, a third of women in the United States will have undergone a hysterectomy and menorrhagia is one of the most common indications.1 Satisfaction rates with hysterectomy have been consistently reported as 95% or higher.2 Quality-of-life measures have also been reported to improve following hysterectomy.3 It is perceived as a permanent solution to the problem of menorrhagia. However, short-term complications following hysterectomy are not uncommon; recent studies report rates of moderately severe complications of 16% while in hospital.4 The IUS is an intrauterine system that can be sited during a clinic visit and its duration of action is five years. The IUS contains 52 mg of levonorgestrel which is released through a rate-limiting membrane (20 μg/24 h), resulting in endometrial shrinkage and a reduction in menstrual bleeding. As the IUS has been proposed as an alternative to hysterectomy, it was important to establish if improvements in quality of life are reported with the IUS. Trial methodsThe trial was well conducted and reported according to published guidelines.5 Patients were allocated to the two treatment groups without the prior knowledge of the investigators, although blinding of patients and investigators was not possible in the follow-up period. An instrument measuring disease-specific QOL may have made QOL differences between the two groups more apparent; however, no disease-specific QOL measure exists. The completeness of follow-up was 97% (228/236), and an intention-to-treat analysis was done. In the IUS group, a third of devices were removed and 20% of the women underwent hysterectomy during the first year of follow-up. Reasons for removal included spotting and other bleeding disorders. This removal rate is higher than the two smaller trials comparing IUS with endometrial resection, which report a 20% removal rate, possibly reflecting the severity of symptoms among women who seek hysterectomy instead of endometrial resection.6,7 The use of health-related quality of life (EuroQol) and other measures of psychological wellbeing was appropriate, and the measures had been validated in the population before the study. Not all women referred for menorrhagia were included. Most of those not participating either did not want to take part or did not meet the eligibility criteria for either of the two treatments. Therefore, it is likely that the study group was representative of women who were candidates for both treatments, and the results can be generalised to the population of women with menorrhagia. The planned five-year follow-up will be welcome. New informationTwo small trials had previously reported that the IUS was an alternative to hysterectomy.8 However, this large randomised trial has improved on those studies, as it included a wider range of outcomes, and shows that, after a year, no statistically significant differences were present between the treatment groups in terms of health status, health-related quality of life, and psychological wellbeing. Cost-effectiveness data favour the IUS. Implications for clinical practiceThis study has shown that, in women with menorrhagia, there were no statistically significant differences between IUS and hysterectomy for the outcomes of quality of life and psychological wellbeing. The quality-of-life data show that the IUS scored as well at 12 months as hysterectomy in seven of the eight areas assessed, with the only difference between the groups being pain scores, despite a 66% reduction in the IUS group. The IUS is by no means the final answer to the problem of menorrhagia — a third of women had the device removed by one year because of bleeding problems. Costs to both the healthcare system and the patient were reduced with the use of the IUS, although these cost differences may reduce with time. The costs of hysterectomy may be higher because of the 30% complication rate reported in this study — similar rates have been reported by others.4,9 This study provides convincing evidence that the IUS is an effective alternative for women with uncomplicated menorrhagia, and should be offered as a treatment choice.

Cynthia M Farquhar MD, FRANZCOG, CREI

In planning clinical trials, it is common to find that the calculated sample size1 (Item 7 of the CONSORT checklist; Box 1) is too large for available resources. Strategies to determine whether the trial question(s) can be answered with fewer subjects are needed. These include: focusing on higher-risk subjects; using a run-in phase before randomisation; "expanding" the primary study endpoint; or running the trial for a longer period, with an event-based, rather than a calendar-based, stopping rule. Choosing subjects with higher riskIf the subjects in a trial have a very low risk of the condition that the intervention is hypothesised to prevent, the trial, regardless of sample size, will not prove the value or otherwise of the intervention. For example, in the "Finnish Businessmen's Study", the efficacy of a multifactorial risk-factor intervention to prevent cardiovascular death among middle-aged men could not be proven, as only five such deaths had accrued at the end of the scheduled follow-up.2 The proof required from trials relies on demonstrable differences in event counts between the intervention and control groups, and whether this difference could reasonably have occurred by chance alone. It matters little how many subjects produced these event counts — the evidence rests in the main with the event counts themselves and the size of the difference between them. Consequently, if the calculated sample size of a proposed clinical trial is larger than feasible, limiting the subjects to those in a higher-risk category should be considered. In the Finnish Businessmen's Study, it might have been better to recruit only men with prior heart disease, with four to eight times the risk of those in the primary prevention category. Similarly, in trials to prevent cancer recurrence after initial therapy, focusing on individuals with above-average risk of recurrence would require a smaller sample size. At times, however, the cost and feasibility advantage of using a lower sample size might be outweighed by the extra time and effort needed to identify high-risk individuals. This might occur especially where the features determining higher risk are not clinical characteristics, but are based on medical testing. In Box 2, a comparison of two possible trials shows that Trial B, with a similar study power, is more feasible and presumably less costly than Trial A. Maximising study power through better compliance — use of a "run-in" design In a clinical trial design, a "run-in" phase can reduce the required sample size.3 Subjects who are entering a long-term trial are asked to take the study medication(s) for a period before randomisation. Individuals who lose interest early on (potential "drop-outs") can then be excluded before random allocation. Similarly, any subjects who feel they may have an indication to receive the intervention treatment (potential "drop-ins") can also withdraw before randomisation. This potentially lowers rates of anticipated non-compliance to allocated treatment during a trial, resulting in a smaller required sample size. As the calculated sample size is exquisitely sensitive to compliance, this procedure can be of major benefit (Box 3). (Once randomised, these participants would generally be included in an intention-to-treat analysis4 and only dilute the apparent effect of the intervention, boosting the sample size needed and/or follow-up duration.) Run-in phases can use either placebo or active therapy, and are usually single blind (ie, only the study staff are aware of the nature of the medication). A placebo run-in allows trial staff to be sure that reported side effects are not caused by treatment (colouring agents and excipients in placebos can occasionally cause reactions), whereas an active run-in can identify and exclude individuals who may be unable to tolerate the medication being tested in a long-term trial. In the US Physicians Study (testing the value of aspirin to prevent coronary death and β-carotene to prevent cancer), a placebo run-in phase allowed a trial of 22 000 doctors to deliver comparable results to a trial requiring 33 000 doctors, assuming that doctors who withdrew during the run-in period would otherwise have stopped taking the study medication soon after randomisation.3,5 Whether excluding any potential trial subjects in this way will reduce the generalisability of the ultimate trial results needs to be carefully considered. Choosing a different endpoint to limit the sample sizeIf a more frequently occurring endpoint can be substituted, with the same biologically anticipated effects of treatment, then the required sample size will fall accordingly. For example, while trials of lowering cholesterol level to reduce total mortality over 5 years may require, say, 12 000 patients, similar trials to reduce coronary mortality only (which cause a fall in total mortality) may only need 8000 patients, depending on the proportion of deaths due to coronary causes. Furthermore, trials designed to reduce the combined endpoint of coronary death plus non-fatal myocardial infarction may require perhaps 4000 patients, with even fewer required for trials designed to reduce all vascular events (all cardiovascular deaths plus non-fatal myocardial infarction plus non-fatal stroke plus any revascularisation procedure). Of course, in the above example, as the endpoint becomes broader, "softer" clinical outcomes are included (ie, some outcomes, such as a decision to send a patient for a revascularisation procedure, may be more subjectively based, and even influenced by a patient's treatment, including the study treatment, if blinding has failed). The decision as to the choice of the primary endpoint in trials should be made in consultation with the clinicians who will ultimately use the trial's outcomes in practice. Selection of the endpoint must ensure that sufficient information is available to determine whether the new treatment should be applied in clinical practice.1 In any case, tracking (which is blinded to study treatment) of the risk profile of subjects randomised into a clinical trial should occur during recruitment, as well as monitoring during follow-up (also blinded) of the event rates in the entire cohort to allow consideration of a possible increase (or, rarely, decrease) in the target sample size before the end of recruitment; a change in the primary outcome of the study; and extending the scheduled follow-up period to yield more events. Whenever possible, it is important to specify a stopping rule in the study protocol, based on accrued numbers of events rather than a calendar date, to allow a trial to continue without major disruption when trial outcome risks are lower than expected. Buying extra science for little extra cost — substudies in large clinical trialsOnce a study outline has been finalised, formal consideration should be given to substudies nested within the larger trial. The use of surrogate outcomes offers the opportunity to answer questions of related interest, or to explore the mechanism of the treatment effect6 in ways which might otherwise be prohibitively costly (ie, setting up substudies as separate enterprises). For example, in a study of the effects of lipid-lowering therapy on coronary death and stroke in many thousands of subjects with prior cardiovascular disease, substudies exploring the effects of treatment on (i) the measured progression of coronary atherosclerosis (using serial coronary angiography), (ii) the progression of carotid intima media thickness, (iii) the change in brachial vascular reactivity (using serial ultrasound examinations), or (iv) endothelial vasoactive peptide levels, may have sufficient power with only several hundred subjects each. For each substudy, the resources needed for subject identification and recruitment, running trial clinics and follow-up are already largely covered by the main trial infrastructure, resulting in extremely cost-effective research opportunities. ConclusionA number of strategies can help to ensure that clinical trials research can be done within limited budgets and by smaller-scale collaborations (Box 4). Care must be taken, however, to deliver results that are still meaningful to clinicians, and have a low risk of false-negative conclusions. As always, seeking professional advice can help to ensure success. 1: CONSORT checklist of items to include when reporting a trial1 Section and topic Item no. Descriptor Methods Sample size 7 How sample size was determined and, when applicable, explanation of any interim analyses and stopping rules 2: Comparison of two possible trials — Trial A, with lower-risk subjects, and Trial B, with higher-risk subjects — to determine the value of the same treatment hypothesised to reduce events by 25% (ie, relative risk [RR] = 0.75) during follow-up* Trial A – lower risk (n = 2000) Trial B – higher risk (n = 1000) Treatment group Control Active Control Active Number of subjects 1000 1000 500 500 Proposed RR with treatment 0.75 0.75 Expected event rate 20% 15% 40% 30% Expected number of events 200 150 200 150 Study power at 2P = 0.05 82% 90% * The number of events, rather than the number of subjects, principally determines the power of the study, although the number of subjects determines in part the reliability of each event count and of the difference. 3: Possible effect of a "run-in" design on the sample size of a randomised trial Trial scenario Required sample size A: 100% compliance in both trial arms 400 B: Average of 80% compliance in active arm (ie, 20% drop-outs at study mid-point) 625 C: Half (10%) of the average long-term non-compliers (drop-outs) instead withdraw during run-in phase before randomisation 494 D: Average of 80% compliance in both study arms (ie, 20% drop-ins plus 20% drop-outs) 1110 E: Half the average long-term non-compliers (10% drop-outs plus 10% drop-ins) instead withdraw during run-in phase before randomisation 625 4: Checklist for managing sample size demands in clinical trials Determine the risk profile of the intended population of interest. Can a subpopulation at higher risk readily be found? Determine whether the study design will accommodate either a placebo or an active run-in phase? Establish clear guidelines on whether to randomise potentially non-compliant subjects. Determine the clinically justifiable power for the particular trial. Adjust the calculated sample size for the expected level of non-compliance with treatment. If the event rates are small, identify potential outcomes which may provide alternative endpoint(s) for which the event rate is much larger. Ensure that the risk profile of subjects is monitored blinded during recruitment as well as the event rate during follow-up. Where possible, base stopping rules on the number of events rather than the duration of follow-up. Identify related questions which may be investigated using surrogate outcomes on a subpopulation of randomised subjects.

Anthony C Keech FRACP, MScEpid · Val Gebski MStat

The 1997 NHMRC clinical practice guidelines for depression in young people included recommendations for treatment that need to be modified in light of more recent research. Changes to the guidelines should include the findings that selective serotonin reuptake inhibitors and some forms of psychotherapy are effective in treating adolescent depression. It is increasingly recognised that depression in adolescents often recurs and that prevention of recurrences should be a priority for research and practice.

Raphael T W Chan MB BS, FRANZCP · Joseph M Rey PhD, FRANZCP · Philip L Hazell PhD, FRANZCP

Stroke is the third highest cause of death and the leading cause of chronic disability in adults in Australia. Studies show clear advantages of treatment of patients in the acute phase of stroke in a dedicated stroke unit. Rehabilitation after stroke is a continuum, starting within days of stroke onset and ending only when it no longer produces any positive effect. More than half the 75% of patients who survive the first month after a stroke will require specialised rehabilitation. Effective rehabilitation relies on a coordinated, multidisciplinary team approach. Regular team meetings, as well as meetings with the patient, his or her family and carers, are essential. Improvements in function after stroke are the result of recovery within the ischaemic penumbra, resolution of cerebral oedema, neuroplasticity, and compensatory strategies learnt by the patient. Evidence supporting rehabilitation programs is based on evaluation of the multidisciplinary approach, or on the effect of a particular discipline (eg, speech therapy), rather than on individual components of treatment. When the patient is discharged from a formal rehabilitation program, the general practitioner's role becomes paramount. GPs can help patients deal with the consequences of stroke, such as depression, and any comorbidities. GPs may also provide counselling on issues ranging from interpersonal and sexual relationships, through ability to drive again, and vocational and recreational activities.

Michael R P Pollack FAFRM, MMedSci(ClinEpi) · Peter B Disler PhD, FAFRM, FRACP

To the Editor: A 63-year-old woman presented with polyuria, polydipsia, lethargy and vomiting. Two weeks previously, she had been diagnosed as having diffuse scleroderma with possible interstitial lung disease, and had started taking 50 mg prednisolone daily. Her past history included diabetes, hypertension, hypercholesterolaemia and β-thalassemia trait, and her other medications were metformin, glibenclamide, quinapril and amlodipine. Examination revealed blood pressure 150/60 mmHg, a loud second heart sound with no murmurs, and late inspiratory crepitations at lung bases. Her serum creatinine concentration was 270 μmol/L (compared with 100 μmol/L two weeks previously) and serum glucose concentration was 26.5 mmol/L. Treatment by the admitting doctor included insulin, rehydration, and cessation of prednisolone (given hyperglycaemia) and quinapril (secondary to acute renal impairment). She developed a fever and cough, with bilateral pneumonia, which was treated with intravenous ceftriaxone. Despite normotension, concern regarding scleroderma renal crisis (SRC) was raised. On Day 12 of admission, when renal failure had developed to the dialysis-dependent level (serum creatinine level, 690 μmol/L), quinapril was recommenced for its proposed renoprotective effect and haemodialysis was initiated. Microangiopathic haemolytic anaemia (haemoglobin, 7.2 g/L) was diagnosed, with fragmented red blood cells (Box). Several months later, she continues on haemodialysis three times a week. Renal biopsy was not performed given the clinical picture of diffuse scleroderma and recent corticosteroid use with rapid development of renal failure — consistent with SRC. SRC is defined as rapidly progressive renal failure and/or new onset of malignant hypertension during the course of scleroderma, occurring in 15%–20% of patients with the diffuse variety.1 Risk factors include male sex, black race, and early diffuse scleroderma with rapidly progressive skin thickening.2 Precipitation of SRC by corticosteroid use, especially in normotensive patients, is well described, particularly with high-dose (>15 mg/day) treatment.2 Early diagnosis is critical because treatment may preserve renal function.3 Outcomes have improved with use of angiotensin-converting enzyme (ACE) inhibitors,2 which are thought to improve renal function by controlling the high renin levels seen in patients with SRC. About 61% of patients have a good outcome, with no or temporary dialysis.3 Predictors of poor outcome, despite ACE inhibitor use, include older age, male sex, higher initial serum creatinine level, and scleroderma myocardial disease.1 Eleven per cent of SRC patients remain normotensive and have significantly reduced 12-month survival rates.4 This may relate to delay in diagnosis of SRC. The use of high dose corticosteroids in patients with early diffuse scleroderma should be strongly discouraged, and intensive monitoring for SRC is recommended if low dose corticosteroids are required. Peripheral blood film, magnification x40 Changes of thalassaemia (microcytosis and hypochromasia) and microangiopathic haemolysis (fragmented red cells and spherocytes). 1. Spherocytes. 2. Fragmented red blood cells.

Anita T Y Lee · Simon Burnet

To the Editor: Comprehensive care has been shown to improve outcome in asthma management when it has four components — asthma education, self-monitoring, written self-management plans, and regular medical review.1,2 A recent Cochrane Review has explored the role of one of these components — written self-management plans — and concluded that there is "no consistent evidence that written plans produced better patient outcomes".3 Should this cause us to change our management strategies in Australian general practice? Does this mean that our patients are not able to care for their own asthma without our intensive assistance? These findings update a 1998 review of the role of written asthma management plans as part of comprehensive care in 1998: "In five studies which compared subjects who managed their asthma by self-adjustment according to individualised written plan with those whose medications were adjusted by the doctor, lung function data (FEV1 [forced expiratory volume in one second] and PEF [peak expiratory flow]) were significantly higher in the self-managed group."1 In Australian general practice, between 30% and 50% of patients are given a written asthma management plan.4 These plans form part of known beneficial comprehensive asthma care plans, such as the Six-Step Asthma Management Plan5 or the Asthma 3+ Visit Plan.4 The small number of available high quality trials for this most recent review led the authors to say, "Available trials are too small and the results too inconsistent to form any firm conclusions", and suggests that more trials are needed to produce a conclusive result.3 We should be careful not to lose the positive effects of improved chronic disease management in asthma by over-responding to this one review of one component of comprehensive care.

Andrew M Thornett · Jonathan W Newbury · Andre J Duszynski

Comment: A Cochrane systematic review identified the beneficial effects of planned asthma management and education that includes a written action plan.1 These findings have now been adapted for primary care and implemented as the Asthma 3+ Visit Plan. This involves a systematic assessment of asthma symptoms, lung function, and current treatment at each visit. Treatment and management skills are optimised and the patient is given written instructions on how and when to increase treatment when asthma deteriorates (a written action plan). A recent Cochrane review asked whether one can get the same benefits by doing less — by simply supplying a patient with a written action plan.2 The review found that the literature was inconclusive. This doesn't mean that written action plans are not effective; it means that there is not enough evidence to be able to answer the question. The result of "no evidence of effect" is completely different to "evidence of no effect".3,4 This is a crucial distinction, as many systematic reviews find insufficient evidence to be able to assess a treatment. This is a statement about our ignorance rather than a statement about whether a treatment works or not. The review also highlights the need to carefully evaluate the control intervention. For example, the control groups in two studies in the systematic review2 received regular medical review, with assessment of severity and optimisation of inhaled steroid therapy. It is not surprising that these studies found it difficult to identify any additional effect of an action plan. Cochrane systematic reviews conclude with recommendations for clinical practice that highlight effective treatments,1 and with recommendations for research that indicate where more information is needed.2 The review looking at just supplying patients with written action plans2 exemplifies the latter.

Peter G Gibson

To the Editor: I read with great interest the article by Byard et al,1 as well as the previous work by these authors on paramethoxyamphetamine (PMA)-related fatalities in South Australia.2 In 2001, I encountered a similar fatal "outbreak" in Belgium: six fatal cases, four of them in the Antwerp metropolitan area.3,4 Striking similarities between the Belgian and Australian fatalities include the clinical symptoms, the autopsy findings and the history of alleged "ecstasy" intake. Pure PMA tablets were found on a victim with an "xTc" logo pressed onto the surface of the tablets.3 I agree with Byard et al1 that the sudden "outbreaks" of death from PMA intoxication probably do not result from contamination during the synthesis of 3,4-methylene-dioxymethamphetamine (MDMA). In Belgium, there are strong indications that the resurgence of PMA resulted from a legal loophole. Early in 2001, PMA was encountered for the first time in the blood sample of a young girl who presented to an emergency department for alleged ecstasy intoxication. A few weeks later, the first fatal case was reported, and over a period of a few months five other fatal cases were seen. After the first two deaths, PMA captured a lot of media attention and even evoked some political disturbance. By the end of 2001, PMA and its precursor molecule, p-methoxyphenylacetone, were placed on the list of regulated and restricted substances (and hence the unauthorised possession of these products became a criminal offence). Afterwards, no more fatalities were reported. I therefore hypothesise that illicit amphetamine manufacturers were aware of the (temporary) legal vacuum in Belgian law before the deaths occurred and substituted PMA for MDMA because PMA precursors were easier to obtain and less strictly controlled by legislation. It has been suggested in the Australian illicit drug report 1994,5 as well as by Byard et al,1 that manufacturers of PMA may have been deliberately marketing it as another drug (eg, MDMA) or may have promoted it specifically as a drug to augment the effects of MDMA. If this is the case, there may be serious implications for criminal liability, as we now know that PMA intoxication has a significantly worse clinical outcome than MDMA intoxication (including a greater likelihood of QRS-interval prolongation, extreme hyperthermia, seizures and a significantly lower score on the Glasgow Coma Scale).6

Werner Jacobs

To the Editor: I read with interest the MJA supplement The student and junior doctor in distress — "our duty of care".1 It is encouraging to see the time, effort and research currently being devoted to the health and mental wellbeing of our colleagues. One aspect of the medical workforce that was not discussed is that of locum doctors, who, in metropolitan and rural New South Wales, are increasingly called upon to staff public hospitals. Under this system, a doctor registers with a locum agency, hospitals advise the agency (often multiple agencies) of the shifts they need filled, and the agency then sends to all the doctors on their books a list of shifts available. Doctors then choose which shift(s) they would like to work and the agencies supply their names to the hospitals. They are paid by the hospital — the current rate for all doctors, Post Graduate Year (PGY) 1 and upwards, being a minimum of $70–$80 an hour — and the agency receives a 10%–15% commission. In contrast, the base hourly rate for a full-time PGY 1 doctor is $23.11, with a loading of 75% on Sundays and 100% for any hours worked beyond a 10-hour shift. The only barrier to locum work is that a doctor is unable to have two rates of pay within the one Area Health Service. There is thus a strong incentive for full-time employees to refuse extra overtime work at their own hospital and do locum work at other hospitals. The number of shifts needing to be filled by hospitals increases as Junior Medical Officers choose this option. The current restrictions on access to provider numbers, rather than serving as an incentive to remain in the hospital system, have encouraged many junior doctors to seek locum work. It is also relevant that, as more graduate students come through the system, more doctors are older and have financial obligations. Many have had good incomes prior to studying medicine and wish to maximise their earnings once they graduate. Wilhelm2 and Mouret3 both observe that financial concerns are a major stressor for Junior Medical Officers. There are significant disadvantages for the locum doctor (eg, lack of ongoing education from patient follow-up, feedback about mistakes, mentor and peer support; inadequate supervision of "safe working hours") and for the healthcare system (eg, lack of continuity of care; locums' unfamiliarity with the hospital and its procedures; variable skill levels of locums; resentment by regular staff of pay rate discrepancies; cost). While there is no doubt a role for locum doctors within the healthcare system, there is no overall control of the situation. Locum agencies are businesses that exist to make money for their owners. The hospitals see themselves as paying top dollar for locum doctors and therefore see no obligation to provide training and counselling. The doctors are in the middle. To protect the doctors and also the hospitals, changes must be considered. Representatives of the NSW Medical Board, Postgraduate Medical Council and Area Health Services need to discuss this issue.

Elizabeth Swinburn

To the Editor: It was most enlightening to read the articles on cosmetic surgery in the 17 June 2002 issue of the Journal. In particular, the Clinical Update by Castle et al on psychosocial wellbeing and cosmetic surgery1 is pertinent to everyday practice. The warning given that cosmetic specialists should be concerned about patients who have had numerous procedures, in particular patients who have previously sued physicians, is a poignant one. Psychological testing of patients who wish to have plastic and cosmetic surgery is not routine, and plastic or cosmetic surgeons cannot be expected to carry out such testing. Liaison with psychologists and psychiatrists can be conducted on a case-specific basis, but not routinely. The aim is to screen for body dysmorphic disorder, but this can be quite difficult, as the presentation is often obscure.2 In reality we live in a world where appearance is very important, and self-esteem is related to appearance. Age discrimination is a reality, and cosmetic surgery has been shown to improve a patient's psychosocial wellbeing.3 The issue of advertising of cosmetic surgery services is a vexed one, as is the issue of where cosmetic surgery should be performed. As it is usually not performed in public hospitals, it has been relegated to the private sector in Australia, and private hospital appointments that might include cosmetic surgery have been vigorously protected by special-interest craft groups in Australia. Misconceptions by the general medical community are rife, due to both the lack of exposure to cosmetic surgical procedures and the lack of information on the subject. The assistance of the general practitioner, together with a thorough patient history, is very valuable in determining whether cosmetic surgery is likely to have a positive psychosocial outcome. Unfortunately, the generally poor attitude of the Australian medical community towards cosmetic surgery has led to patients being afraid of a negative response when asking their GPs about cosmetic surgery. Often referrals are either not made or are made by an anonymous practitioner, which is not an ideal situation. Liaison with surgeons who have previously treated a patient is ideal, but cooperation in this area is not always forthcoming, as some surgeons fear litigation from former patients. With most cosmetic surgeons being shut out of the medical mainstream, access to potential patients comes through normal commercial means, such as advertising in the Yellow Pages and in magazines. It is to be hoped that in future there will be more contact between cosmetic surgeons and other medical practitioners so that the true benefits and risks of the procedures can be understood by the general medical community, who, in turn, can counsel their patients in a sympathetic manner as to whether cosmetic surgery is advisable.

Darryl J Hodgkinson

To the Editor: According to the article by Kennedy in the Journal,1 we failed to address the objections to the RARE SALAMI trial (the Royal North Shore and Ambulance Regional Study of a Stenting Strategy as an Alternative to Lytic/Medical Therapy in Acute Myocardial Infarction) in our account of the fate of this trial.2 Allegedly, we contravened standard advice regarding emergency cardiac care ("to attend the nearest hospital emergency department as quickly as possible").1 However, the standard advice is to call an ambulance,3 not to go to hospital by private transport. Kennedy also claimed that the trial would interfere with " . . . established therapeutic networks and ongoing therapeutic relationships, including relationships with hospitals".1 The reason we ignored such objections was that the wellbeing of networks seemed unimportant in comparison with the welfare of patients with life-threatening illness. The issue of the risk to patients of transport time and treatment delays with the new strategy was also raised,1 but Kennedy did not challenge the actual measured delays or other published evidence we referred to.2 These suggested that mortality was likely to be reduced with the RARE SALAMI strategy. Without reference to published data, he quoted the opinions of clinicians and a municipal council to support the opposite conclusion. The northern suburbs of Sydney are not so remote or exotic that opinion based on knowledge of the "local practicalities" he referred to1 would outweigh the evidence of published data. We argued that complexities of treatments, patients' condition and the pressure of time precluded fully informed consent.2 Allegedly, established guidelines were breached.1 However, the ethics committee, well aware of these, waived conventional informed consent after careful deliberation. A new area ethics committee, constituted subsequently,2 concurred with this decision. Now, in the light of new evidence, the RARE SALAMI trial, as originally proposed five years ago, can no longer be done. The recently presented DANAMI II study4 randomised 1129 patients to treatment with fibrinolysis at local hospitals or to transportation to angioplasty centres up to 153 km away. Transport was found to be safe, and angioplasty was associated with a 40% reduction in adverse outcomes. Field triage was not tested. However, we believe the results of the DANAMI II study now preclude randomisation of 50% of patients with suspected acute myocardial infarction presenting to the Ambulance Service (and eligible for the RARE SALAMI trial) to treatment at district hospitals. Ironically, in northern Sydney, status quo reigns and 100% of trial-eligible patients are taken to district hospitals and delays in achieving reperfusion persist! Thiemann, in a recent editorial, concluded that accrued evidence now favours treatment of patients with acute myocardial infarction in a few high-volume centralised angioplasty centres,5 and that field triage and direct transport to such centres holds great promise. He also deplored the lack of research into system changes and the economic self-interest that, he believed, had stymied change in the United States. Opposition to the RARE SALAMI trial was altruistic.6 However, it nevertheless stopped much needed research and hence may have compromised patients' rights to optimal care.

Helge H Rasmussen · Peter S Hansen · Gregory I C Nelson

In reply: Rasmussen, Hansen and Nelson have missed the entire thrust of my article.1 When an individual calls a health professional for help, we can assume he or she agrees to standard treatment, but not to be placed into an experiment. Failure to inform patients that they are being placed into an experiment is a denial of basic human rights. I outlined a mechanism by which it would be possible to conduct an experiment such as RARE SALAMI that would comply with the appropriate guidelines and avoid denial of informed consent. It is worth noting that failure to inform patients that they have been placed in a clinical experiment could also worsen our present medical indemnity crisis and lower the standing of medical research. It has been shown how institutional ethics committees can be subjected to local pressures.2 As a result, it is possible some may adopt pseudolegalistic interpretations of accepted guidelines and approve studies that would be rejected elsewhere. This is another reason why informed consent is so important. Without it some studies simply can't be done.

Michael C Kennedy

To the Editor: I thought it most appropriate that you juxtaposed the articles by Kilmartin et al1 and Fitzgerald2 in your General Practice issue (15 July). Missing from each article is a key aspect from the patient's point of view. As a patient, I value, above all else, continuity of care by my general practitioner. In this age of increasing sessional work (by both female and male doctors) and of increasing employment of doctors on a sessional basis by corporations, this feature of general practice is threatened. As a former GP, I am increasingly being asked to comment by lawyers (for both plaintiffs and defendants) on cases where patients have fallen through the cracks that are an inevitable aspect of sessional care. Patients are being seriously harmed because of poor communication and poor or no handover between sessional doctors. What is most disturbing is the absence of failsafe mechanisms to ensure that communication, both verbal and, more importantly, written, between the sessional GPs in a practice comes as close as possible to providing the continuity of care offered by the now nearly obsolete five- or six-day-a-week and after-hours family doctor.

Peter C Arnold

To the Editor: I offer the following additions to the growing list of favourite books with a medical flavour.1,2 The house of God, by pseudo-intern Samuel Shem, is an irreverent, bawdy, cult classic ("Catch-22 with stethoscopes"). I was particularly intrigued by the "laws of the house of God", including "placement comes first" and "if you don't take a temperature, you can't find a fever." The woman who walked into doors, by Dubliner Roddy Doyle, is a heartrending narrative of emotional and physical abuse of a woman by her partner, and of neglect by her health professionals. "A nurse . . . She'd seen me before . . . I waited to be asked. Ask me. Ask me. Ask me. I'd tell them everything. Look at the burn. Ask me about it. Ask. No. . . Her boyfriend was waiting." "The doctor never looked at me. He studied part of me but he never saw all of me." Another is The plague, by French novelist Albert Camus and translated by Stuart Gilbert. " 'Please, doctor, what is it?' 'It might be — almost anything. There's nothing definite as yet.' . . . On returning to his flat [Dr Bernard] Rieux rang his colleague Richard, one of the leading practitioners in the town. "'No,' Richard said, 'I can't say I've noticed anything exceptional.' 'No cases of fever with local inflammation?' 'Wait a bit! I have two cases with inflamed glands.' 'Abnormally so?' 'Well,' Richard said, 'that depends on what you mean by "normal".' "

C Ross Philpot

To the Editor: In their recent article, Makdissi and Brukner stated that resumption of play should follow the "30/30" rule.1 In the article, the authors cited three references, each of which relates to position statements rather than to any scientific reference that "blue skies and lack of rainfall are not adequate reason to breach the 30 minute return to play rule".2-4 Unless there are reasonable scientific explanations why lightning should strike someone in the presence of blue skies, I would think that this policy needs some reconsideration. It seems logical that if a storm is moving away, the skies should become blue, and the time between lightning and thunder should increase. I would have thought that if there was a weather watcher around, he or she could monitor the situation, and ascertain that the storm was moving away, and this would allow for earlier resumption of sport. Can you imagine a weather watcher preventing play in an AFL game, or even a minor suburban game of football, because of the threat of lightning if the skies were indeed blue? If I am to take this recommendation to my local football club, I would like to see evidence that this has some credible scientific backing.

David Vivian

In reply: The "30/30" rule is a simple and easy-to-remember rule designed to reduce the probability of lightning strikes. Two important studies over recent years have led to its development. First, in 1993, Holle et al analysed the number of casualties relative to flash rates during thunderstorms and found that most casualties occur at the beginning and end of storms.1 They concluded that individuals typically wait too long to seek safe shelter and often resume too soon. Secondly, in 1999, Lopez and Holle examined the distribution of successive flashes for large numbers of different types of storms, and found that, although most were separated by less than 8 km, a significant number of successive flashes occurred up to 13 km apart.2 This was noted to be more likely with larger, more complex storms. Given that lightning can strike kilometres forwards or backwards from the storm front, being within 10 km of lightning activity (as estimated by a "flash-to-bang" count of 30 seconds) reflects a risk that the next flash might conceivably be at the observer's location, irrespective of whether there are blue skies overhead. This is why blue sky alone is not enough reason to break the 30/30 rule.

Michael Makdissi

To the Editor: I enjoyed reading Makdissi and Brukner's "Recommendations for lightning protection in sport",1 but I feel that in addressing an audience of renowned golf hacks the authors have made a glaring omission. It is well known in golfing circles that the first rule of lightning self-protection on the golf course is to always carry a 1-iron in the bag and in appropriate conditions to reach for it — because not even God can hit a 1-iron!

Michael Gullquist

A 35-year-old woman presented with symptoms suggestive of gallstones. These were confirmed on a computed tomography cholangiogram (see picture), the contrast clearly defining their outline. However, their unique "jack-o'-lantern" configuration also serves as a seasonal reminder that, like the present-day association with Halloween, the word "gall" derives from an Old English word meaning "something unpleasant to experience"!

Andrew D Wills MB ChB BSc MRCS

Joe Correy, an outstanding contributor to the field of obstetrics and gynaecology in Tasmania, died on 18 April 2002 of severe Parkinson's disease. Joe was born in Manilla, New South Wales, on 17 June 1925, and moved to Sydney in 1930. Although his family was not well off, he won scholarships that enabled him to study medicine at the University of Sydney, from which he graduated in 1947. After completing his residency at Sydney Hospital, he began training in obstetrics at the Royal Hobart Hospital. He married Lucy Denne in 1950 and went to Oxford, UK, in 1951. He obtained his Membership of the Royal College of Obstetricians and Gynaecologists in 1952 and returned home in the following year. With his great personality, energy and ability, Joe built up a very successful private practice in Hobart over the next 15 years. In 1966, he received a William Morton Lemon scholarship to study ovulation induction in Melbourne, and returned to establish the Gynaecological Endocrinology and Infertility Clinics in Hobart and Launceston later that year. In 1969, accepting an appointment as Director of Obstetrics and Gynaecology at the University of Tasmania's medical school, Joe began a remarkable transition from private practitioner to full-time academic, involving research work, training to run a university department, study and teaching. By 1977 he had been promoted to the position of Professor, which he held until his retirement in 1990. With boundless energy and enthusiasm, he continued to take on new challenges throughout his academic career. In 1972, under a Brown Craig Travelling Fellowship, he studied ultrasound in the United Kingdom and returned to set up and run the first ultrasound service for pregnant women in Tasmania. In 1973–1974, he trained to acquire proficiency in pelvic cancer treatment. In 1981, he organised the IVF Clinic in Hobart, which he ran successfully for many years. He also initiated the collection of statistics for all public and private obstetric procedures in Tasmania. Joe was an active member of many medical committees, including (at various times) secretary and president of the Tasmanian branch of the Australian Medical Association, president of the Royal Australian College of Obstetricians and Gynaecologists, an examiner with the RACOG and the Royal College of Obstetricians and Gynaecologists, and president of the Tasmanian Medical Council and the Australian Medical Council. Joe's enthusiasm for life encompassed car trials, great parties, trips with his travellers' group, bridge and lawn bowls. Integrity, honesty and wit were inherent in his character. He was made a Member of the Order of Australia in 1986 for services to medicine. He also became an Honorary Fellow of the Royal Australasian College of Surgeons in 1975 and received an Advance Australia Award in 1994. Joe is survived by his second wife, Pam, and his three children and their families.

Gerard Gartlan FRANZGOG FRCOG

There were many facets to Peter Ryan's busy life. He was a family man, surgeon, scientist, teacher and serviceman. Born on 25 November 1925 in Dookie, Victoria, to farming parents, he was the eldest of four boys. He was dux of Assumption College, Kilmore, and studied medicine at Melbourne University. He graduated in 1948 and was a Resident Medical Officer at St Vincent's Hospital. In 1950, he married Margery Manly, an Arts graduate. Peter served as a Major in the Royal Australian Army Medical Corps in Japan and Korea (1953–1954), then worked for a number of years in England. After obtaining his Fellowship of the Royal College of Surgeons, he spent three years at the Leicester General Hospital. Upon his return to Australia in 1960 he joined the surgical staff at St Vincent's Hospital, Melbourne. In 1972, the Ryan Unit was established, with Peter as the Inpatient Surgeon. It later became the Department of Colon and Rectal Surgery, with Peter as its first Director. He retired from St Vincent's in 1990. Peter had a keen intellect and an inquiring, even restless, mind. His laboratory work included studies of the effects of a proximal colostomy on bowel anastomoses. In 1986, his Hunterian address to the Royal College of Surgeons was on diverticular disease. He was the first to advocate immediate resection (with anastomosis) in selected cases of diverticular perforation. Peter was keen to share Australian surgical expertise with medical colleagues in Asia. In 1965–1966, he led a St Vincent's surgical team to Long Xuyen, in Vietnam. He also established a program of visiting Fellows from Japan and Indonesia, and lectured in Kuala Lumpur and Jakarta. He was the first Honorary Fellow of the Indonesian Surgical Association. Peter was President of the International Society of University Colon and Rectal Surgeons (1986–1988) and an original member of the Royal Australasian College of Surgeons' Road Trauma Committee, which was responsible for the introduction of compulsory car seatbelts. His knowledge of anatomy and ability to sketch clearly made him a popular teacher. He was proud of his small red book entitled A very short textbook of surgery, which ran to several editions and was translated and widely used in China. He was an author of over 50 journal articles. Peter and Margery raised 10 children and, despite his busy professional and academic schedule, he instilled in them his love of literature and music. Three of his children — Rowena, Jeremy and Roderick — followed him into medicine. Peter was a pioneer in colorectal surgery and was awarded the Medal of the Order of Australia in 2002, shortly before his death on 3 June 2002.

Brian T Collopy

Hepatitis C, other liver disorders and liver health. A practical guide. Geoffrey C Farrell. Sydney: MacLennan and Petty, 2002 ($71.50, xi + 324 pp). ISBN 0 86433 157 6. As this book claims to be aimed at general practitioners and “a broader readership”, including laypeople, I felt that, as a specialist hepatologist, I was not necessarily the best person to review it. I asked a layperson and an experienced general practitioner for their opinions. From the layperson: The book is clearly written and the language and concepts are accessible to a non-medical reader. I particularly liked the style of writing and the tone, which was non-dogmatic when discussing alternative therapies, yet able to convey warnings when necessary. Geoffrey Farrell also shows cultural awareness. The book is easily followed as a reference text. If I had liver disease, I would want to have this book.– Colleen VaughanSecondary School English teacher, Essendon, VIC From the general practitioner: The book is comprehensive and informative. It will answer all your questions — if you can find what you are looking for. Finding information was a problem, as there is so much information packed into the 320 pages. For example, in the chapter “Diet and liver disease — is there a liver cleansing diet?” I had to wade through three recipes, four tables and 18 pages to find the answer — no! I also thought that starting each chapter with case studies, but not presenting the commentaries until the chapter’s end, was confusing. I would have preferred much of the information found in tables and charts to have been placed in appendices so that the book flowed more smoothly.– Robert BensonGeneral Practitioner, Footscray, VIC From the specialist: Does this book add to the cornucopia of print and electronic resources on hepatitis C? Yes, it does! For the health care worker it gives a sensitive, yet scientific, approach to issues which often deeply concern our patients, but are sometimes trivialised by health professionals (eg, diet, complementary therapies). Geoffrey Farrell is courageous enough to debunk the so-called “liver cleansing diet”, even if it did take him 18 pages (see above). On the other hand, the book gives the layperson information on hepatitis C and other liver disorders which is otherwise difficult to access. The style is idiosyncratic and may not appeal to all, but overall it has achieved its goal. It is trustworthy and novel and I’ll be recommending the book both to patients and health professionals. Katrina J R WatsonHepatologist, Fitzroy, VIC

Katrina J R Watson

Time to heal While research published in this issue of the MJA reveals largely good mental health among Vietnamese children living in Perth, a Sydney-based study has found that their adult counterparts are also faring well. Interviews with 1161 Vietnamese migrants who had lived in Australia for a mean of 11.2 years revealed that most (60%) had suffered some kind of pre-migration exposure to traumatic events, such as a lack of food or water, life-threatening situations, imprisonment or violence. Overall, only 95 participants (8%) had mental disorders as defined by ICD-10 and 75 participants (7%) had mental disorders according to a psychiatric scale developed specifically for use with Vietnamese people. Post-traumatic stress was the most common diagnosis (4%), followed by major depression (3%). The length of time since the most significant traumatic event and the total number of traumatic events both played a role in current psychiatric illness. Thus, for one to two traumatic events, only those affected less than four years ago were at increased risk (OR 6.3, compared with no trauma), while those reporting three or more traumatic events were still at increased risk 10 years later (OR 4.7). Lancet: published online Sept 17 2002. http://image.thelancet.com/extras/01art9374web.pdf A problem shared . . . Researchers in Bangladesh say “well switching” is a short-term solution to the problem of arsenic contamination of drinking water, thought to affect 30–36 million Bangladeshis. Drinking from wells has been encouraged in Bangladesh because of bacterial contamination of surface water, but the groundwater has high levels of naturally occurring arsenic. Global Positioning System receivers were used to map the locations of 4997 contiguous tube wells serving 55 000 people, and the water in each well was examined for arsenic content. Only 48% of the wells met the current Bangladeshi standard for drinking water of < 50 mg/L (current WHO recommendation is 10 mg/L). However, the researchers determined that almost 90% of the area’s inhabitants lived within 100 m of a safe well. They recommended that safe wells be identified and shared. Bull World Health Organ 2002; 80: 732-737 Perilous pairings A British study has found that, for several common disease states, having a spouse with the condition is a risk factor in itself! Researchers used the Trent Focus Collaborative Research Network to access data on 8386 married couples from 10 general practices. After adjusting for age, smoking, obesity and the practice attended, they found increased risks of asthma (OR 1.69), depression (OR 2.08), hypertension (OR 1.32), hyperlipidaemia (OR 1.44) and peptic ulcer disease (OR 2.01) in people whose spouses had these conditions compared with those whose spouses did not. Shared environmental factors and health-seeking behaviours were postulated as possible causes for this phenomenon. BMJ 2002; 325: 636-640 Bogus breast boast? The belief that being breastfed will reduce your likelihood of atopy and asthma is being questioned by researchers from New Zealand. Their study followed a birth cohort of 1037 subjects to age 26 years, revealing that the 504 subjects who were breastfed for four or more weeks actually had higher rates of atopy (from age 13 years) and asthma (from age 9 years) than those who were not breastfed. The researchers believe that the conflicting findings of studies examining the links between breastfeeding and allergic disease are due to differing durations of follow-up, with shorter-term studies showing protection and longer-term studies showing increased susceptibility. Lancet 2002; 360: 901-907 Bread and behaviour If you’re wondering why your local bakery is displaying signs about the preservative content of its bread, it may relate to research from Darwin, which links the preservative calcium propionate with behavioural problems in children. Twenty-seven children with behavioural problems (defined by scores in the 85th centile or more on the Rowe Behaviour Rating Inventory) consumed an elimination diet (excluding 50 additives, and natural salicylates, amines and glutamates) for three weeks. The mean RBRI percentile of the group decreased from 95% to 31% on the diet. They then participated in a double-blind, placebo-controlled, crossover trial in which each child consumed four pieces of bread, with or without the preservative, daily for three days. Mean RBRI scores after preservative-free and preservative-containing bread did not differ significantly. However, the researchers drew attention to the fact that the scores of 14 children worsened after the preservative, while eight were unchanged and five improved. J Paediatr Child Health 2002; 38: 373-376