Volume 179 Issue 2

The recently released PREVENT trial provides some answers Venous thromboembolism (VTE) affects 1–2 people per 1000 in the general population each year.1 It most commonly manifests as deep vein thrombosis of the leg, or as pulmonary embolism. There are many acute provoking factors or triggers (eg, major trauma, recent surgery), and many chronic predisposing factors, both genetic (eg, factor V Leiden) and acquired (eg, cancer). Most patients with provoked VTE have a low risk of recurrence (0–4% per year without anticoagulation), presumably because most have no major predisposing factors for VTE.2 Treatment for provoked VTE is short term and consists of giving intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin (LMWH) for at least 5 days, followed by warfarin (target international normalised ratio [INR], 2.0–3.0) for 3 months.3 Further antithrombotic therapy is usually not required unless patients are re-exposed to known triggers for VTE. Standard-intensity therapy with warfarin remains the treatment of choice for the long-term prevention of recurrent VTE in patients who are at highest risk of recurrence Most patients with unprovoked VTE, however, have a higher risk of recurrence (≥ 5% per year without anticoagulation) over many years.4,5 This is because they are chronically exposed to one or more underlying genetic or acquired predisposing factors for VTE, which may be identifiable from the clinical history or through laboratory testing. Furthermore, the absence of a provoking factor or trigger for VTE is the most important predictor of recurrence in these patients. They require longer-term or indefinite treatment, which consists of giving intravenous unfractionated heparin or subcutaneous LMWH for at least 5 days, followed by warfarin (target INR 2.0–3.0).3 This is standard-intensity anticoagulation therapy, and is highly effective in preventing recurrent episodes of VTE for as long as it is continued. In trials in which patients were treated for a median of 4–6 months, it reduced the absolute risk by 7.6%, which is equivalent to preventing one event for every 13 patients treated (odds ratio [OR], 0.15; 95% CI, 0.10–0.23).6 In patients considered at highest risk of recurrent unprovoked VTE (eg, > 10% per year; see Box), warfarin therapy is continued indefinitely, whereas in most patients, it is discontinued after 6–12 months.3 This is because long-term anticoagulation is associated with a cumulative risk of bleeding, which is perceived to outweigh its benefits in preventing recurrent VTE. Standard-intensity therapy with warfarin causes minor "nuisance" bleeding in 5%–15%, major bleeding in 2%–3%, and fatal bleeding in 0.2%–0.6% of patients each year.7 A hitherto burning question for patients with unprovoked VTE is whether there are other anticoagulant treatment regimens with a more acceptable benefit-to-harm ratio, such as lower-intensity oral anticoagulation therapy. The recently reported Prevention of Recurrent Venous Thromboembolism (PREVENT) trial was initiated in July 1998 to test the hypothesis that long-term, low-intensity warfarin therapy (target INR, 1.5–2.0) might provide a safe and effective method of reducing the risk of recurrent VTE among patients who had a previous idiopathic (unprovoked) venous thrombosis.8 After completing at least 3 months of standard-intensity warfarin therapy (target INR, 2.0–3.0), 508 patients were randomly allocated to receive low-intensity warfarin therapy or placebo in a double-blinded fashion. The trial was terminated after a mean follow-up duration of 2.1 years because there was strong evidence of efficacy of warfarin. Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), compared with 14 of 255 patients assigned to low-intensity warfarin therapy (2.6 per 100 person-years). This represents a relative risk reduction of 64% (hazard ratio [HR], 0.36; 95% CI, 0.19–0.67; P < 0.001), and an absolute risk reduction of 4.6%, equivalent to one event prevented for every 22 patients treated for 1 year. Bleeding episodes necessitating hospitalisation occurred in two patients in the placebo group (0.4 per 100 person-years), and five patients in the warfarin group (0.9 per 100 person-years); this difference was non-significant (P = 0.25).8 Although the PREVENT trial showed no significant excess of major bleeding with low-intensity warfarin therapy compared with placebo, event rates were low (5 v 2), and the 95% confidence intervals do not reliably exclude even a 13-fold increase in risk of major bleeding (HR, 2.53; 95% CI, 0.49–13.03). Yet, there is no doubt that low-intensity warfarin causes bleeding. In the PREVENT trial, "minor" bleeding was significantly increased in the warfarin group compared with the placebo group (12.8% v 6.7%; HR, 1.92; 95% CI, 1.26–2.93), with an increase in absolute risk of 6.1%, equivalent to one minor bleed caused for every 16 patients treated for 1 year. The results of the PREVENT trial indicate that low-intensity warfarin therapy is effective for long-term prevention of recurrent VTE. However, it was not shown to be sufficiently superior to placebo for low-intensity warfarin to be adopted for this indication. Standard-intensity warfarin is also superior to placebo when continued for up to 4 years after an initial thrombotic event.6,9-11 Indeed, it almost eliminates the risk of recurrent VTE in patients who continue the therapy, but is not routinely used because of the bleeding risks. Mini-dose warfarin therapy (fixed-dose, 1–2 mg daily) has never been shown to be effective for this indication, while low-intensity warfarin therapy is unlikely to offer any advantages over standard-intensity therapy in terms of convenience, and would only be a viable alternative if it were significantly safer. Indirect comparisons of the relative effectiveness and safety of low-intensity and standard-intensity therapy with warfarin, compared with placebo, are unreliable.8-11 For example, the apparently lower rates of bleeding in the PREVENT trial when indirectly compared with previous trials of warfarin might simply be explained by differences in patient selection. The PREVENT trial randomly allocated patients to treatment or placebo after they had completed a median of 6.5 months of warfarin treatment, and also included a 28-day run-in phase. It is thus likely that patients at increased risk of bleeding were excluded from the long-term phase of the study. By contrast, in most previous trials of long-term standard-intensity therapy with warfarin, patients were randomly allocated after no more than 3 months of treatment. This is as unreliable as comparing two sporting teams by their respective performances against another team rather than having them oppose each other directly. Indeed, the results of a recent direct head-to-head randomised comparison showed that low-intensity warfarin therapy was not only less effective than standard-intensity therapy for preventing recurrent VTE (absolute risk increase of 1.3% per patient year, equivalent to one event caused for every 77 patients treated for 1 year), but provided no advantage in terms of major bleeding (1.0% v 0.9% per patient-year; HR, 1.0; 95% CI, 0.4–2.7) or minor bleeding (4.9% v 3.6% per patient-year; HR, 1.3; 95% CI, 0.8–2.1).12 Taken together, these results indicate that standard-intensity therapy with warfarin is more effective for preventing recurrent VTE than low-intensity warfarin therapy, which, in turn, is more effective than placebo. However, because low-intensity warfarin therapy does not appear to be any safer in terms of bleeding and still requires close laboratory monitoring, it is difficult to justify this approach as an alternative to standard-intensity therapy for the long-term prevention of VTE, irrespective of a patient's baseline risk of recurrence or bleeding. The implications of these results for clinicians are that standard-intensity therapy with warfarin (target INR, 2.0–3.0) remains the treatment of choice for the long-term prevention of recurrent VTE in patients who are at highest risk of recurrence (eg, history of recurrent unprovoked VTE, major predisposing factor such as cancer; see Box) or with an initial life-threatening event (eg, major pulmonary embolism), and low risk of haemorrhagic complications. For patients with a first episode of unprovoked VTE or at increased risk of haemorrhagic complications, to decide about long-term treatment, doctors need to weigh the absolute risks of recurrent VTE and bleeding complications with and without warfarin treatment in each patient. In most cases, this is likely to result in the discontinuation of treatment after 6–12 months. The implications of these results for researchers are that more data are required to improve the reliability of clinical and laboratory predictors of recurrent VTE and haemorrhagic complications in individual patients, and that randomised controlled trials are required to evaluate the effectiveness and safety of alternative long-term antithrombotic therapies (eg, ximelagatran,13 antiplatelet agents) that are likely to be more convenient or have a more favourable benefit-to-risk profile than either standard-intensity or low-intensity warfarin therapy. Major determinants of the risk of recurrent venous thromboembolism Low risk (0–4% per year) Provoked event* Isolated distal deep vein thrombosis Intermediate risk (5%–10% per year) First unprovoked event Major predisposing factor(s)† Highest risk (> 10% per year) More than one unprovoked event First unprovoked event plus major predisposing factor(s)† Active cancer * Provoking factors include, in the last 3 months: hospitalisation, major surgery, trauma, leg fracture, plaster cast, puerperium. †Major predisposing factors include: prolonged immobility, neurological disease with paresis, homozygosity for factor V Leiden, combined (multiple) thrombophilic abnormalities, antiphospholipid antibody syndrome, inferior vena caval filter. Cancer is also a major predisposing factor but is mentioned separately because it is such a strong predisposing factor in its own right.

John W Eikelboom FRACP, FRCPA · Graeme J Hankey MD, FRACP

The multisector approach to reducing smoking may be a good model for tackling physical activity Over the past year, the signals that physical activity is a critical community issue in Australia have become overwhelming. The increasing obesity of Australians has attracted the attention of our politicians and spawned obesity summits in New South Wales and Victoria; these both recognised that the energy expenditure imbalance (physical activity versus diet) is key to the obesity epidemic.1 Related to obesity is an inexorable increase in the prevalence of type 2 diabetes. The recent seminal Diabetes Prevention Program trial demonstrated that physical activity and dietary modification are effective lifestyle strategies for curbing this problem.2 In the area of cancer control, a notable event in the past year was the Eat and Run Conference hosted by the New South Wales Cancer Council, where evidence was presented that regular physical activity contributes to preventing colon and breast cancer.3 The past year has also seen reports that reinforce the benefits of regular physical activity in preventing coronary heart disease4 and falls in the elderly,5 and in reducing depression.6 Thus, physical activity is a pivotal public health issue, contributing to the prevention and management of at least six of Australia's seven current national health priorities: cardiovascular disease, cancer, mental health, diabetes, injury and musculoskeletal problems. However, the prevalence of inactivity in our communities is high and increasing. In 2000, 42% of Australian men and 44% of women did not partake in the levels of physical activity recommended by the National Physical Activity Guidelines (30 minutes of moderate-intensity activity, accumulated in bouts as short as 10 minutes, on most days of the week, or 20 minutes of vigorous-intensity activity on at least three days).7 These data revealed an increase in the prevalence of inactivity from 1997, when it was 37% among men and 39% among women.7 Over the past decade, there have been numerous calls for general practitioners to address physical activity and other behavioural risk factors. Along with these calls have come an increasing number of studies evaluating physical-activity interventions delivered in primary care. The National Institute of Clinical Studies (NICS) in Australia funded a systematic review of published studies, which was completed late in 2002 and included 20 studies.8 While most interventions entailed verbal advice and written information materials, they differed in scope (some targeting physical activity only, others addressing multiple risk factors); intensity (brief advice through to more intensive counselling with multiple contacts); method of delivery (physicians, nurses, health educators or exercise scientists); and target audience (all adults, older people only, interested volunteers or whole patient populations). The review concluded that there is evidence that interventions in primary care can increase physical activity in the short term. Notably, brief interventions appeared to be as likely to succeed as intensive interventions, although there was insufficient evidence to identify other attributes of successful interventions. The NICS review is one of several recent reviews that support the contribution that GP interventions can make to promoting physical activity.9,10 A notable dissenting opinion came from the recent United States Preventive Services Task Force review of clinician counselling to promote physical activity,11 but this review included only eight studies published since 1994. Overall, the level of supporting evidence for GP interventions offers encouragement. However, much still needs to be done to promote greater attention to physical activity in general practice, given that lack of time and a perceived lack of patient interest are major barriers reported by GPs.12 The NICS review offers a practical way forward in light of these barriers. It recommended brief physical-activity interventions specifically for patients with risk factors or health conditions that could be modified by increased activity. This approach should not require a major investment of time from already busy GPs and, by directing interventions to patients with current health problems that could be alleviated by physical activity, is more likely to be well received by patients. Despite the growing evidence about general practice-based physical-activity counselling, until recently there had been no efforts to disseminate intervention materials or protocols for GPs to use. However, agencies like the National Heart Foundation and the Victorian Council on Physical Activity and Health have been working with health authorities in several states to develop tools to help GPs to promote physical activity. An example of these is the Active Prescription protocol disseminated by the National Heart Foundation in NSW.13 It provides a format for delivering brief advice to patients about physical activity and also serves as a written record of this advice for doctors and patients. An electronic version has been included in the latest version of the Medical Director clinical management software (Health Communication Network, Sydney, NSW). These efforts are promising and require continued support, together with continued research on the effectiveness of the interventions, as well as dissemination strategies. Numerous social and environmental factors lead to physical inactivity in Australia. Thus, addressing this public health priority will require the sustained involvement of a range of sectors in addition to primary healthcare (eg, transport, urban development, education, sport and recreation). We can look to the past three decades of efforts to reduce smoking as an example of an integrated, multisector approach that has significantly reduced population levels of smoking. As with smoking, GPs — the preferred source of health information for most Australians — have a key role to play in promoting physical activity.

Ben J Smith PhD · Elizabeth G Eakin PhD · Adrian E Bauman PhD, FAFPHM

Risk factors and diseases in developing countries are becoming "westernised" Cardiovascular disease is usually considered to be the scourge of wealthy countries. However, the recent World health report1 draws attention to the increasing importance of cardiovascular disease in developing countries. The report identifies principal risk factors and diseases in regions of the world divided into three categories: developed countries, developing countries with low mortality rates, and developing countries with high mortality rates. It is no surprise that the leading risk factors contributing to disease, disability and death in developed countries are tobacco consumption, high blood pressure, high cholesterol level, overweight, low fruit and vegetable intake, and physical inactivity (Box 1). Coronary heart disease is the leading cause of death and disability, and stroke ranks third. In developing countries with high mortality rates (eg, Nepal, Myanmar, the Maldives and numerous African countries), factors such as underweight and unsafe sexual practice are more important than risk factors for non-communicable diseases. Nevertheless, tobacco consumption, high blood pressure and high cholesterol levels are still responsible for substantial morbidity and mortality (Box 1). The five leading causes of death and disability in these countries are HIV/AIDS, lower respiratory tract infections, diarrhoeal diseases, childhood diseases and low birthweight — coronary heart disease ranks eighth. Countries between these two extremes have rapidly changing profiles. In these low-mortality developing countries (eg, Cambodia, China, and Fiji), "developed country" factors have already outstripped traditional "developing country" factors in terms of importance for overall disease, disability and death (Box 1). In these countries, the juxtaposition of underweight with overweight as the fourth and fifth leading risk factors, respectively, starkly exemplifies the "double burden of disease" they carry. Following an upsurge in "developed country" risk factors in these countries, stroke is now the second most important cause of disability and death, and coronary heart disease the sixth. Unfortunately, the health services of low-mortality developing countries have not been able to adjust quickly enough to these changing disease profiles. The lack of epidemiological data on diseases and risk factors has hampered appropriate health service development and responses. A number of Australian organisations, including the Institute for International Health (IIH) at the University of Sydney,2 are trying to address these issues, with a focus on our neighbours in Asia and the Pacific region. The IIH has recently introduced initiatives, involving data collection and analysis, as well as technology transfer and capacity development, with partners in China, India and Thailand.3,4 The IIH has also worked with Asia–Pacific partners in multicentre trials and epidemiological studies, including the Asia Pacific Cohort Studies Collaboration (APCSC). The APCSC is a collaborative project that seeks to pool data from existing longitudinal studies with information on cardiovascular disease in the region. The project database now has data on 659 000 adults in eight countries (Box 2), making it one of the largest medical studies ever, and certainly the largest in the Asia–Pacific region. The collaboration aims to produce reliable regional estimates of the excess risks for coronary heart disease, stroke, total cardiovascular disease and all-cause mortality associated with a number of risk factors, and to accurately compare risk-factor associations between ethnic groups, age-specific groups and the sexes. After several years of compiling data, obtaining cooperation of key individuals and devising appropriate methodology, initial reports from the APCSC have begun to appear.5-7 These reports underline the increasing importance of cardiovascular disease in the less developed parts of the region, and show that the risk factors applicable in Australia are just as important elsewhere. This is a crucial finding that has not previously been established with large numbers. For instance, the analyses show that people with diabetes are about twice as likely to die from heart disease or stroke, regardless of whether they live in Asia or Australasia.5 Increasing levels of obesity across the region will lead to a considerable increase in diabetes and its sequelae, such as cardiovascular disease. Further, the research shows that younger people with diabetes have much larger excess risks for cardiovascular disease than older people. Asia, with its predominantly young population, can thus expect an even greater increase in cardiovascular disease than that anticipated in Australia. The challenge now is to use the results from the APCSC, and other relevant studies, as a starting point for tackling the global problem of cardiovascular disease highlighted by the World health report.1 In developing countries, substantial health gains can be made for relatively modest expenditures. In human terms, this means that much ill-health and millions of premature deaths can be avoided. As far as cardiovascular disease is concerned, a necessary step will be to develop accurate risk algorithms, specific to local situations.8 These algorithms would help in developing treatment and prevention strategies to target overall risk. For example, strategies to reduce salt intake and lower cholesterol level have been shown to be very cost-effective.1 Blood-pressure-lowering drugs are likely to benefit not only people with hypertension, but also normotensive people at high risk of cardiovascular disease.9 The ultimate aim will be to develop strategies with maximum benefit for minimum cost. This is especially the case in developing countries, where the conflicting demands on a meagre pool of resources make the need for cheap, finely-targeted strategies absolutely crucial. 1: The 10 leading selected risk factors for death and disability, by type of country1 High-mortality developing countries Low-mortality developing countries Developed countries 1 Underweight Alcohol consumption Tobacco consumption 2 Unsafe sexual practices High blood pressure High blood pressure 3 Unsafe water, poor sanitation and poor hygiene Tobacco consumption Alcohol consumption 4 Indoor smoke from solid fuels Underweight High cholesterol level 5 Zinc deficiency Overweight Overweight 6 Iron deficiency High cholesterol level Low fruit and vegetable intake 7 Vitamin A deficiency Low fruit and vegetable intake Physical inactivity 8 High blood pressure Indoor smoke from solid fuels Illicit drug use 9 Tobacco consumption Iron deficiency Unsafe sexual practices 10 High cholesterol level Unsafe water, poor sanitation and poor hygiene Iron deficiency 2: Geographical distribution of studies presently included in the Asia Pacific Cohort Studies Collaboration

Mark Woodward · Michael A Reid

Objective: To determine the factors associated with general practitioners' current practice location, with particular emphasis on rural location.Design: Observational, retrospective, case–control study using a self-administered questionnaire.Setting: Australian general practices in December 2000.Participants: 2414 Australian-trained rural and urban GPs.Main outcome measure: Current urban or rural practice location.Results: For Australia as a whole, rural GPs were more likely to be male (odds ratio [OR], 1.42; 95% CI, 1.17–1.73), Australian-born (OR, 1.95; 95% CI, 1.55–2.45), and to report attending a rural primary school for "some" (OR, 2.21; 95% CI, 1.69–2.89) or "all" (OR, 2.79; 95% CI, 1.94–4.00) of their primary schooling. Rural GPs' partners or spouses were also more likely to report "some" (OR, 2.75; 95% CI, 2.07–3.66) or "all" (OR, 2.86; 95% CI, 2.02–4.05) rural primary schooling. A rural background in both GP and partner produced the highest likelihood of rural practice (OR, 6.28; 95% CI, 4.26–9.25). For individual jurisdictions, a trend towards more rural GPs being men was only significant in Tasmania. In all jurisdictions except Tasmania and the Northern Territory, rural GPs were more likely to be Australian-born.Conclusions: GPs' and their partners' rural background (residence and primary and secondary schooling) influences choice of practice location, with partners' background appearing to exert more influence.

Gillian A Laven BHSc · Justin J Beilby MB BS, MD · Heather J McElroy BSc(Hons) · David Wilkinson MB ChB, MD, PhD

Objective: To audit the appropriateness of use of a troponin I assay in three hospitals.Design: Cross-sectional survey of use of a troponin assay.Setting: Three hospitals in Melbourne, Victoria, each with an emergency department and a coronary care unit.Participants: Patients for whom a troponin I assay was requested between 1 and 7 May 2002, 27–42 months after introduction of the assay.Interventions: User-focused dissemination of relevant information, including protocols for use, from opinion leaders when the assay was introduced; continuous reinforcement of information in pathology reports.Main outcome measures: Adherence to protocol for assay use.Results: Troponin assays were requested for 333 patients during 351 symptom episodes. A single assay was used in 194 symptom episodes (55%), and serial assays in 157 (45%); proportions were statistically indistinguishable across all three hospitals (χ2; P = 0.71). Of the 194 single assays, 13 (7%) diagnosed a myocardial infarction. Serial troponin testing in all three hospitals followed the suggested protocol, with mean time between serial assays being more than 6 hours at all hospitals.Conclusions: Adherence to the protocol for serial troponin assay intervals was adequate, but single troponin assays were used extensively and probably inappropriately.

Richard X Davey FRCPA, FACB

Objectives: To describe the clinical features, antecedents and impact of chronic pain.Design: Telephone survey of randomly selected household respondents.Setting: Northern Sydney Health Area, metropolitan Sydney, July to September 1998.Participants: 2092 English-speaking residents aged 18 years or over.Main outcome measures: Age- and sex-adjusted prevalence of chronic pain (pain experienced every day for 3 months in the previous 6 months), pain-related disability, and use of health services and analgesic medications.Results: Chronic pain affected 474/2092 respondents (22.1%; 95% CI, 20.2%–24.0%), with high levels of pain-related disability in 129/439 (27%). Nominated causes of chronic pain were injury in 173 (38%), most commonly sports injury (54; 13%), and a health problem in 132 (29%). Pain was work-related in 62 (14%). A musculoskeletal condition was the leading diagnosis (127; 26%). Of the 474 with chronic pain, 374 (78%) had consulted at least one health practitioner for pain in the previous 6 months, comprising medical practitioners (consulted by 292 [60%] and including general practitioners [55%]), allied health professionals (245; 50%), and alternative practitioners (99; 21%). Current or recent use of oral analgesic medications (often over-the-counter preparations) was common (339; 70%). Higher levels of pain-related disability were associated with greater use of medications and health services.Conclusions: Our study shows that chronic pain is common and often results from injury. It highlights the importance of timely interventions to prevent progression from acute to chronic pain and the need for a coordinated approach to managing pain-related disability.

Fiona M Blyth PhD, FAFPHM · Michael J Cousins MD, FANZCA · Lyn M March PhD, FRACP

Objective: To determine the spectrum of severity and early diagnostic predictors of redback spider bites (Latrodectus hasselti ), and to examine the effect of intramuscular redback antivenom.Design and setting: Prospective cohort study of calls to New South Wales, Queensland and Western Australian poisons information centres and presentations to Royal Prince Alfred Hospital and Royal Darwin Hospital emergency departments.Patients: 68 people with definite redback spider bites in which the spider was immediately collected and expertly identified (1 February 1999 to 30 April 2002).Interventions: Intramuscular redback spider antivenom in a smaller cohort of hospitalised patients.Main outcome measures: Pain severity and duration, local effects and systemic envenomation (effects, prevalence, and persistence > 24 hours).Results: The median duration of effects was 48 hours (interquartile range, 24–96 hours). Pain occurred after all bites and was severe in 42 (62%). Forty-five patients (66%) had pain lasting longer than 24 hours, and 22 (32%) were unable to sleep because of pain. Systemic effects occurred in 24 (35%). Increasing pain over one hour occurred in 37 cases (54%), and local/regional diaphoresis in 23 (34%); both these features were highly predictive of L. hasselti bites compared with bites of other spiders. One of six patients treated with intramuscular antivenom (17%) had no pain at 24 hours, compared with two of 17 untreated patients (12%) (difference, 5%; 95% CI, –36% to +64%; P = 0.95). There was no difference in duration of systemic effects with antivenom administration.Conclusions: Most redback spider bites cause severe and persistent effects. Intramuscular antivenom appears to be less effective than previously thought and its use by this route needs review.

Geoffrey K Isbister BSc, MB BS, FACEM · Michael R Gray MSc, PhD

In Victoria, decisions regarding late termination of pregnancy no longer involve just pregnant women and their clinicians. At two major women's hospitals, committees now govern the decision-making process for approval of a late termination of pregnancy. The legal and ethical implications of clinical decision-making by committee need to be widely debated. decision-making processes for termination of pregnancy after 20 weeks' gestation have recently changed in Victoria. Most late terminations of pregnancy are conducted in the public sector at two major centres for obstetrics and gynaecology: the Royal Women's Hospital, and Monash Medical Centre. Before June 2000, in response to a request for a late termination of pregnancy, the clinicians managing the woman's pregnancy would meet and attempt to reach a consensus as to the appropriateness of a termination in her circumstances. Following the reporting of a late termination of pregnancy to the Victorian Coroner,1 Monash Medical Centre and the Royal Women's Hospital each decided to create a termination review committee (TRC) to deal with the decision-making (Box). The role of each committee is to receive referrals from obstetricians regarding requests for late termination of pregnancy from pregnant women, and to decide whether the request should be approved. Clinical decision-making by committeeThere is a growing belief in the medical community that doctors can no longer make important clinical decisions in isolation. This is particularly evident where clinicians have diverse views about the appropriateness of a late termination. The major dilemmas are whether a clinician views the status of the fetus as secondary to the mother's interests, or whether the fetus is a separate entity with rights that can be in conflict with the rights of the pregnant woman. Clinical decision-making by committee can perform several roles, and these depend on whose interests the committee is intended to serve. Expert ethical and legal guidanceA committee may provide expert guidance in areas in which clinicians need assistance, predominantly in clinical ethics and the law, where clinical requests would be assessed in line with current standards. By obtaining appropriate expert guidance, a TRC may protect the community against possible poor ethical or legal decisions by clinicians. LiabilityA committee may accept the bureaucratic responsibility for the care of the patient, including liability. The clinicians become absolved of legal liability for the decision about a late termination. This would serve the interests of doctors, who give up their clinical autonomy to the committee, and are not responsible for the decisions made by the committee in patient care. An attempt has been made by the Royal Women's Hospital TRC to recognise this role (Guidelines for the termination of pregnancy. Royal Women's Hospital, Melbourne, intramural communication). The Royal Women's Hospital guidelines for termination of pregnancy state that "staff will be strongly supported by the Hospital in patient care which is in accordance with these guidelines." However, "staff will be strongly supported" is a weak legal statement to take on legal liability. It is doubtful whether a doctor can absolve himself or herself from legal responsibility. Nevertheless, many clinicians feel supported by ethics committees in making these difficult decisions. They feel it is helpful if a TRC shares with them the responsibility for the decision-making. Avenue of appealA committee may act as an avenue of appeal for the pregnant woman. That is, if the clinician disagreed with the woman's position, she could seek another opinion. In this case, the committee would be set up to serve the interests of the pregnant woman. If the committee came to a different conclusion, it would be required to facilitate a second opinion — either within the hospital, in another hospital, privately or interstate. However, the Victorian TRCs do not act as an avenue of appeal for pregnant women in their current structure. It is the decision of the obstetrician to put forward her case; the pregnant woman has no right to do so herself. In the case of pregnant women denied a termination by a TRC, it is unclear how to offer a second opinion. Obtaining a second opinion outside the major teaching hospitals is not necessarily straightforward. The pregnant woman may have to request the second opinion of her own volition. Although not impossible, it is unlikely that a doctor in Victoria (or perhaps even interstate) would proceed against the decision of a TRC, even if he or she thought the woman had an ethical and legal reason for a late termination. It may be in the pregnant woman's best interests to inform her of this before the case is put before a TRC. Pregnant women can then exercise their autonomy to pursue private or interstate options before these become "closed". Public accountabilityA committee may act to provide public accountability as well as an educative role for clinicians. Public accountability would require that the committee have appropriate representation from the community. The committee would need to publish its cases or make them accessible to clinicians for general examination. Clinical decision-making, whether by a committee or by clinicians, should be publicly accountable. Clearly, this is not the current role of the Victorian TRCs. Ethical considerations of clinical decision-making by committeeInterestsWhose interests does a TRC serve? The major concerns that have been expressed about ethics committees can be levelled at TRCs.2 If a committee is set up to serve the interests of the hospital, then it tends to err on the side of "conservative" decision-making. In late terminations, where the law is unclear, this is to be expected, but this may not be in the interests of pregnant women. A committee could also come under the influence of a particular constituency or lobby group, which might not serve the best interests of either pregnant women or clinicians. This would depend on how members (and their delegates) are co-opted on to the committee, and whether any external process assesses the committee. The pregnant woman's autonomy and a TRCWho is ultimately responsible for a decision? In Victoria, a pregnant woman has no explicit right to demand a review by a TRC, even if she is aware of the inside workings of the process. She cannot attend personally to put her case forward, nor is she able to send a patient advocate, or even a clinician of her choice, to review the process. It must also be remembered that the obstetrician presenting the case may not agree with the woman's decision for a termination, but may bring the case to a TRC anyway. This raises several issues about patient autonomy and informed consent. All the woman's preferences and circumstances are heard second-hand. How strongly her preferences are advanced will depend on the communication from the obstetrician. Should an obstetrician who disagrees with the patient's preference inform the woman before he or she attends a TRC? As a legal question, this may be extending the disclosure principle to its limit, as patients have no right to demand that a procedure should be provided. However, from an ethical viewpoint, a lack of disclosure may restrict a pregnant woman's autonomy to seek other options. Most members of a TRC do not meet the pregnant woman who is making the request for a termination. This "arm's length" approach may undermine the autonomy of the pregnant woman to argue her case. Anonymity of the membersThe Royal Women's Hospital TRC insists on anonymity for its members. The hospital administration is concerned that if names of the members of the TRC were available outside the hospital, members risked being victimised and stalked, as occurred with a former senior consultant in the 1970s (Review of Royal Women's Hospital TOP [termination of pregnancy] Working Party. Notes of meeting number 1. 17 October 2000, intramural communication). The inconsistency in this defence of anonymity is that the doctor performing the termination of pregnancy is not anonymous, nor are the doctors counselling the pregnant woman. It could be argued that the people most at risk of a political act of violence are the clinicians, not the members of the Royal Women's Hospital TRC. The ethical difficulty is who takes the responsibility for the decision-making if committee members are anonymous. An attempt is made to offer support to the clinician by the Chairman of the Royal Women's Hospital TRC "signing off" on the patient's chart. Third-party considerations The Royal Women's Hospital TRC considers the "desires of the father, other children and familial circumstances" in evaluating the appropriateness of a termination. Third-party considerations for termination of pregnancy have no standing in Australian law. The countries which do have "third-party authorisation" for terminations of pregnancy (eg, Morocco, which requires a husband to authorise his wife's abortion) are considered to have the most restrictive laws on abortion.3 How can a TRC consider the desires of the father or other children without asking them for their opinion? Does this contravene our privacy laws and our commitment to our patient's privacy? The intention of this clause is unclear, but I have reservations that our care for pregnant women may be harmed by third-party considerations. ConclusionWhile we are waiting for a legal solution, women will continue to attend clinicians requesting late termination of pregnancy. Further research needs to be performed on the impact that clinical decision-making by committees has on the effective care of pregnant women. In particular, we need to review the psychological effects on women who were denied a termination by a TRC. Clinicians need support in making controversial and difficult ethical decisions. Clinical ethics committees can provide support and advice, particularly in clinical ethics and the law, but should they take over clinical decision-making? This alienates both the pregnant woman and the clinicians, and may lead to inappropriate clinical care. The committee must not erode the doctor–patient relationship, which provides a framework for mutual decision-making. It is the setting where patients make many of their difficult quality-of-life decisions. Each case is unique and there is no right answer when a pregnant woman asks, "Doctor, what would you do?". We live in a pluralistic society with diverse views on abortion. Why should the decision of a committee, which bears no long-term responsibility for the unborn child, prevail over an informed, conscientious, pregnant woman, especially when there is no sound legal basis for the committee's decision-making? Termination review committees in Melbourne, Victoria Why were they formed? The Royal Women's Hospital Executive created a termination review committee in June 2000, following widespread publicity of a controversial late termination of pregnancy. The hospital created a set of guidelines for late termination to be referred to the TRC as "hospital policy". The TRC was formed to ensure that hospital administration approved all late terminations performed within the hospital. The hospital administration believed that this was the best way to protect itself, clinicians and patients from possible poor decision-making by doctors. A TRC was also formed at Monash Medical Centre in July 2000. The initiative came from clinicians who wished to formalise the process that was already in place for approving a late termination of pregnancy. The clinicians believed that a formal process would improve communication with the hospital administration and lawyers, and ensure all options were explored before a late termination was performed. What are the terms of reference of the committees? The committees deal with the decision-making for approval of all terminations of pregnancy at or after "viability" (22–24 weeks' gestation) to be performed within the hospital. Their role is to assess a request for a termination in line with their interpretation of current Victorian law. The committees are also responsible for ensuring adequate consultation, counselling and documentation before the approval of a late termination. Who are the members? Royal Women's Hospital: A member of the executive (eg, Chief Executive Officer, Executive Director [medical or nursing]), a neonatal paediatrician, two medical divisional directors, one nursing divisional director, and the obstetrician managing the pregnancy. Delegates may be used in some cases. The committee may co-opt non-voting members with relevant clinical, legal and ethical skills. Monash Medical Centre: The clinicians involved in the woman's care (obstetrician, ultrasonologist, geneticist, paediatrician, labour ward midwives, resident staff) and a general practitioner practising outside the hospital. Opinion may be sought from a member of the hospital executive and the hospital lawyer. How do the committees make decisions? Initially, the pregnant woman has a consultation with her clinicians. After comprehensive counselling, she may request a termination of pregnancy. Requests for termination may be in the setting of an obstetric complication, a medical or psychiatric illness, or a fetal abnormality. The clinicians meet to decide if they believe that the request should be upheld and if this requires approval from a TRC. The referral to a TRC comes from the obstetrician, not from the pregnant woman. In arriving at a decision, the TRC needs to compare the consequences for the pregnant woman if she has a termination, if she continues the pregnancy and cares for the child, or if she gives up the child for adoption. Other considerations include the extent and severity of a fetal abnormality, and the physical, psychological and social circumstances of the pregnant woman. At the TRC, an attempt is made at consensus, but if necessary, decisions are made by majority vote. The clinician is bound by the decision of the committee. The Monash Medical Centre model differs from the Royal Women's Hospital model in that opinion from the hospital executive and lawyer is consultative rather than prescriptive in nature. The final decision is made by the pregnant woman, her clinicians and an independent GP. Both committees can be convened and decisions made within days of a request being put forward.

Nicole L Woodrow FRACOG

Critical care encompasses elements of emergency medicine, anaesthesia, intensive care, acute internal medicine, postsurgical care, trauma management, and retrieval. In metropolitan teaching hospitals these elements are often distinct, with individual specialists providing discrete services. This may not be possible in rural centres, where specialist numbers are smaller and recruitment and retention more difficult. Multidisciplinary integrated critical care, using existing resources, has developed in some rural centres as a more relevant approach in this setting. The concept of developing a specialty of integrated critical-care medicine is worthy of further exploration. In Australia, "rural" centres have been defined statistically as local areas where most of the population resides in centres of 10 000–99 999 people, and "remote" centres where the population is less than 10 000 people.1 It has been claimed that a two-tiered system of hospitals has developed, one tier composed of "centres of excellence", and the other of hospitals more limited in their range of expertise and technology.2 The first tier is predominantly hospitals in the heart of capital cities, while rural hospitals fall into the second tier. In this hierarchical system, metropolitan teaching hospitals are often perceived as setting the standards for practice, but this perception can be challenged. Standards are sometimes based as much on opinion as evidence and are not necessarily universally applicable.3 It has been questioned whether a resource-intensive intervention should become a standard of care if it produces a small benefit in clinical outcome in trials in large institutions, when a greater benefit may be gained by giving a greater number of patients a more basic minimum standard of care that is sustainable across the entire healthcare system.4 Metropolitan tertiary hospitals provide a super-specialised level of care that is essential for some patients, but not sustainable outside resource-concentrated centres. On the other hand, rural base hospitals and metropolitan district hospitals provide a broad spectrum of hospital and community medicine, and therefore training opportunities, that may no longer be available in major tertiary hospitals.5 With respect to hospital practice, then, it could be argued that it is the second-tier hospitals that currently deliver the generic standard of care. Part of the problem with rural healthcare systems is that models of care applied to super-specialised metropolitan practice are assumed to be relevant to rural practice. A different level of care does not necessarily equate with a lower standard of care. Indeed, structuring resources to match the specific rural milieu may well lead to more appropriate care for this setting and therefore better care. Wakerman and Humphreys6 suggest that a distinctive "rural health" approach is needed because rural Australia is sociologically, culturally, economically and spiritually different from metropolitan areas, and that a hallmark of rural and remote healthcare is innovation generated by local need and community action.6 This approach has been successfully applied in a number of rural centres to the problem of providing critical-care services in the face of limited numbers of medical specialists. Medical specialist involvement in rural intensive care in Australia — the status quoRecent reviews of intensive-care activity in Australia found that 37% of Australian public-sector intensive-care units7 and 34.5% of medical specialists working in public-sector intensive care8 were in rural and remote centres. The nature of the work in these units differs from that in metropolitan centres. Many are combined with high-dependency and coronary care, with over half the patients admitted being in these categories.7 The medical specialists involved also differ in their qualifications and background from specialists in major metropolitan hospitals, as training, recruitment and retention difficulties limit the number and type of specialists available in rural centres. Of the specialists currently involved in rural intensive care in Australia, only a small number have qualifications endorsed by the Joint Specialist Advisory Committee in Intensive Care (JSAC-IC).8 Instead, the majority have backgrounds in anaesthesia, emergency medicine, general medicine and/or general surgery and have acquired expertise in intensive-care medicine through specific training, clinical practice, or both. In addition to their base discipline, many specialists are also involved in other phases of critical care. Traditionally, this multiskilling has developed out of necessity. Increasingly, however, it is occurring by choice, as it can result in efficient use of skills and afford a unique and interesting casemix for specialist medical staff, while at the same time providing benefits to critically ill rural patients and rural communities. Models of integrated critical careTrunkey9 proposes that physicians and surgeons are evolving towards three types of practice: ambulatory care, hospital-based practice and intensive care. We suggest that the third branch is actually critical care. Critical-care medicine is the multidisciplinary healthcare specialty that incorporates the knowledge, skills, attitudes and problem-solving abilities required for the recognition and early management of patients with acute life-threatening illnesses and/or injuries.10,11 It encompasses elements of emergency medicine, anaesthesia, intensive care, acute internal medicine, postsurgical care, trauma management and retrieval medicine. Clearly, critical care is a continuum that begins at the onset of critical illness or injury, and continues through the transportation process and the acute hospital care process.12,13 The principles for managing critical illness and injury are similar, regardless of patient location or diagnosis. The aim is to keep alive those patients who have a reasonable chance of survival.14 In rural Australia, this may require organisation of resources in a fashion that is different from that undertaken in metropolitan centres. In metropolitan hospitals, subspecialists would be involved in each phase of the management process, but this may not be possible in rural centres, where specialist numbers are smaller. This is where a multidisciplinary critical-care physician becomes particularly valuable. This specialist has many of the characteristics that have recently been attributed to those of a "hospitalist".2,15 Through local innovation and necessity, models for effectively delivering critical care using existing resources have been developed in several sites in rural Australia, including Tamworth Base Hospital and Port Macquarie Base Hospital in New South Wales. These models of integrated critical care (see Box) involve a hospital-wide approach, acknowledging that care of critically ill patients is a collaborative endeavour, not the exclusive domain of an intensive-care unit. The critical-care facilities are located nearby and share specialist medical staff, resident medical staff, career medical officers and nursing staff. Integration has resulted in a more seamless interface between the various phases of critical care and between the respective disciplines. Although multidisciplinary and multiskilled, individuals are not required to perform multiple tasks at any given time — for example, when on duty in the critical-care unit, they are not given other responsibilities. Rather than being partisan about individual specialty groups, the focus has been on providing the most appropriate services to meet the needs of critically ill patients and their rural communities, using the most appropriate resources. Thus, these successful models are based on cooperation rather than competition or duplication. This was recognised in the 2001 NSW Government Action Plan for intensive-care services.16 The Plan recommended that, in rural hospitals, a formal working relationship be developed between staff of the intensive-care unit and anaesthetic or emergency-department consultants to provide appropriate senior medical cover for the unit.16 A collaborative approach for the future?Currently, there is no formal program for training specialists for multidisciplinary rural critical-care practice. Training in many of the relevant base specialties remains metropolitan-based with a metropolitan focus. For example, of the registrars working in Australian public-sector intensive-care units identified in a recent survey, only 3.7% were in rural and remote areas, and the majority of these were not JSAC-IC trainee registrars.7 To address this disparity, a fresh approach may be required. In rural and non-tertiary metropolitan centres, critical-care practice has characteristics that distinguish it from tertiary metropolitan practice. Integrated critical-care medicine could therefore be defined as "the practice of critical-care medicine that occurs in non-metropolitan Australia" and developed as a distinct specialty, with appropriate input from existing specialty Colleges and societies. Specialist training could be provided at appropriate rural sites rather than concentrated in tertiary metropolitan centres. Alternatively, strong subspecialty groups could be developed within existing Colleges, with a unifying cross-College standing committee and joint training. Approaches to critical care vary throughout the world,12,17-19 and a number of approaches tried elsewere may provide suitable models for integrated critical-care medicine in Australian rural areas. Whatever model is adopted, given the backgrounds of the majority of specialists currently involved in critical care in rural Australia, the specialties of emergency medicine, anaesthesia and intensive-care medicine will need to lead the process. Like anaesthesia, emergency medicine and intensive-care medicine have significant clinical links, and these need to be encouraged and strengthened.12,13,19 ConclusionTo ensure high standards of critical care for rural patients, it is vital that realistic solutions continue to be developed that match the existing realities of rural practice. The integrated critical-care model has successfully provided quality services in a number of hospitals and offers potential for wider implementation in rural areas. The concept of developing a specialty of integrated critical care is worthy of further exploration. This will require collaboration and cooperation between all stakeholders. Features of integrated critical care Multiskilled critical-care specialists trained and experienced in the various aspects of critical care in rural hospitals. Multidisciplinary critical-care teams that provide: a more seamless interface between the various phases of critical care and between its respective disciplines; a rapid response to, and a continuum of care for, critically ill and injured patients; clinical leadership in evaluating and managing critically ill and injured patients, both in the hospital (including the emergency department, critical-care unit and hospital wards) and in the community (including retrievals, and support for ambulance crews, peripheral hospitals and general practitioners); and training of medical students, medical staff, nursing staff and allied health professionals to recognise and provide a systematic approach to critical illness and injury. Team members who are empowered to work beyond perceived traditional boundaries, but within the realms of their clinical expertise and credentials, to enable the best use of available resources.

Craig T Hore MB BS, FACEM · William Lancashire FRACGP, CCFP · John B Roberts MB BS, FACEM · Rob Fassett MB BS, FRACP

Heart failure Digoxin therapy has no effect on mortality in heart failure. Digoxin may be useful for maintaining clinical stability and exercise capacity in patients with symptomatic heart failure. Digoxin appears to be of most benefit in patients with severe heart failure, cardiomegaly and a third heart sound. Digoxin should be used as a second-line drug after diuretics, angiotensin-converting enzyme inhibitors and β-blockers in patients with congestive heart failure who are in sinus rhythm. Digoxin should be used as a first-line drug in patients with congestive heart failure who are in atrial fibrillation. Arrhythmias Digoxin has a limited, but useful, role, either alone or in combination with other agents such as β-blockers, diltiazem or verapamil, in achieving satisfactory resting ventricular rate control in patients with chronic atrial fibrillation. In patients who lead a predominantly sedentary lifestyle (perhaps particularly in those who are elderly), digoxin alone may be the agent of choice.

Terence J Campbell MD, FRACP, FACC · Peter S MacDonald FRACP, PhD

QuestionDoes indomethacin given prophylactically after birth improve long-term outcome for babies with extremely low birth weight? Trial details Design: Randomised, double-blind, controlled trial. Setting: 32 intensive care nurseries in Australia, Canada, Hong Kong, New Zealand and the United States. Participants: 1202 babies of 500–999 g birthweight; groups were similar in demographic and perinatal characteristics. Exclusions included major anomalies and inability to give indomethacin before 6 hours of life. Interventions: Indomethacin (0.1 mg/kg, intravenously) once daily for 3 days, or equivalent volume of saline placebo. Main outcome measures: Composite outcome of mortality, cerebral palsy, developmental delay, deafness or blindness at 18 months of age, corrected for prematurity. Main results: There was no substantial difference in the primary composite outcome between the indomethacin (47% [261/574]) and placebo (46% [261/569]) groups (odds ratio [OR], 1.1; 95% CI, 0.8–1.4; P = 0.61). However, the indomethacin group had a lower rate of patent ductus arteriosus (PDA), including cases requiring medical or surgical treatment, and severe (grade 3 or 4) cerebroventricular haemorrhage (CVH). Conclusion: In infants with extremely low birthweight, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite reducing the frequency of PDA and severe CVH. CommentaryRationale for the trialPersistent patent ductus arteriosus (PDA) is a problem after birth for very tiny or preterm infants, many of whom require either medical or surgical intervention to close the ductus in the newborn period. Indomethacin is often successful in closing the ductus when used therapeutically, but is associated with many short-term side effects. Before this trial, prophylactic use of indomethacin was known to reduce the frequency of symptomatic PDA and severe cerebroventricular haemorrhage (CVH) in these babies.1 Reducing severe CVH might be expected to improve long-term neurological outcome. However, the mechanism for reducing severe CVH may be diminishing cerebral blood flow, which in turn may cause long-term neurological problems. Therefore, whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in cerebral blood flow, as well as reduced blood flow to other organs, is not certain. Trial methodsInfants were stratified by birthweight (< 750 g or ≥ 750 g) and individual study centre. This stratification was sensible, as the rate of the major adverse outcomes in the study was much higher in those of < 750 g birthweight (62% [298/481]) than in those of birthweight ≥ 750 g (35% [234/662]), and was bound to differ between individual centres (although individual centre data were not reported). Most infants (86%) received their allocated treatment within 6 hours of birth, and most (81%) received all three doses; there were no differences in drug administration (compliance) between the treatment groups. Other aspects of care followed an individual unit's protocol. Blinding was achieved by having a placebo that looked identical to the indomethacin. Although unblinding was theoretically possible through observing urine output, only 7% in the indomethacin group and 4% in the placebo group had treatment withdrawn because of oliguria. Significantly more babies in the placebo group (46%) subsequently received open-label indomethacin to treat a PDA than did babies in the treated group (17%). The follow-up rates to 18 months corrected age were very high (95%) in each group, which is important methodologically, as babies who are difficult to follow-up have more adverse outcomes than those who are followed up more easily.2 All analyses were by intention to treat. New informationIn infants of extremely low birthweight, prophylaxis with indomethacin did not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of PDA and severe CVH. Before this study, it would have been assumed that because prophylactic indomethacin reduces severe CVH, it should improve long-term outcome. This study highlights the problem of relying on changes in surrogate (or intermediate) endpoints, or in risk factors, to determine the effectiveness of therapies. For any therapy to be introduced into clinical practice, the endpoints in trials must be clinically meaningful. Implications for clinical practiceThe types of babies included in this study are typically found in intensive care nurseries in the developed world, and hence the results of the study are widely applicable to infants of birthweight < 1000 g, including those cared for in Australian intensive care nurseries. The study has been incorporated into an update of the Cochrane review of prophylactic indomethacin.3 There are now 19 trials with a total of 2872 babies enrolled. The study by Schmidt et al4 is the largest in the review, with 42% of the total babies enrolled. Its results dominate the review, especially those for long-term neurosensory outcomes, where the study contributes more than two-thirds of all babies in the review. The Cochrane review confirms that prophylactic indomethacin confers no important long-term benefit (or harm) on survival free of neurosensory impairment, despite significantly reducing the rate of severe CVH (relative risk [RR], 0.66; 95% CI, 0.53–0.82). However, the duration of follow-up in most studies is short, and important long-term neurological effects may not be manifest until school-age or later. Hence, it is still not certain that indomethacin imparts no long-term harm. Prophylactic indomethacin reduces the incidence of symptomatic PDA (RR, 0.44; 95% CI, 0.38–0.50), and the need for ductal ligation (RR, 0.51; 95% CI, 0.37–0.71). The absolute reduction in the rate of surgical ligation is 5%, which means that prophylaxis would need to be given to 20 babies to prevent one surgical ligation. For neonatal units where surgical ligation is not an option and where the need for surgical ligation is relatively frequent, giving 20 babies indomethacin to prevent one operation might be a reasonable option. However, this should be undertaken in the full knowledge that indomethacin prophylaxis does not impart any other important short-term benefits, such as a reduction in oxygen requirements, and that there remains the unknown issue of potential longer-term harm. There is no evidence of substantial differences in rates of necrotising enterocolitis, gut perforation, excessive clinical bleeding, or sepsis.

Lex W Doyle MD, FRACP

Although reporting baseline data seems simple, it is crucial information for readers in judging the validity of a trial. Knowing the baseline characteristics of the trial participants allows readers to assess how closely these match patients seen in their own clinical practice, and therefore how generalisable the results of the trial will be (so-called external validity). Baseline characteristics also allow the success of randomisation to be assessed. In studies where important baseline factors appear well balanced, it is likely that any differences in outcome between the intervention and control groups are a real effect of treatment (one component of internal validity). For these reasons, the reporting of baseline demographic and clinical characteristics of each group is a requirement of the CONSORT statement.1 The item and its descriptor as they appear in the CONSORT checklist are shown in Box 1, and a checklist for baseline data is provided in Box 2. ContentBaseline data should adequately describe the population in the trial. This means including demographic variables, known factors that influence the outcome (including medications being taken by participants), factors that are likely to modify any benefit of treatment, and those that may predict adverse reactions. These factors are called potential "confounders", because, if they are imbalanced between the treatment groups at baseline, they may result in an apparent treatment effect when none exists, or mask an effect that does exist. Baseline data should also include any factors (especially known potential confounders) that have been used as strata for randomisation. Stratified randomisation, described in detail earlier,2 is used when a baseline characteristic, such as tumour stage, is known to affect outcome risk; the characteristic is therefore included in the randomisation algorithm to minimise imbalances between treatment groups. This is particularly useful in small studies. If the study population contains subgroups of particular interest, the characteristics defining these subgroups, and numbers or proportion in each group, should be stated. For example, in a long-term trial of a new medication for preventing heart attack, diabetes mellitus would be a potential confounder (as people with diabetes have a much higher risk of heart attack than similar people without diabetes). Those with diabetes in this study would also be an interesting subgroup in whom the effects of the intervention might be different. Similarly, concurrent therapy with aspirin (which would substantially reduce the risk of heart attack) could confound the trial results if there was an imbalance between trial groups in the proportions of patients taking aspirin; aspirin therapy might also influence the likelihood of adverse reactions to study therapy. Baseline factors can be determined from interviews, physical examination, laboratory measures or imaging studies. MeasurementBaseline data are measured as close as possible to the time that participants are randomly allocated to study groups, and in all cases, should be measured before the allocated treatment commences (information collected after the commencement of trial treatment may have been altered by the treatment itself, and is generally not regarded as baseline data). Ideally, baseline data should be collected on all patients screened for eligibility, as this would provide further information about the generalisability of the trial population. However, this is not always practicable or affordable, so some variables (eg, tissue biopsy, measurement of genetic markers, expensive imaging tests) are measured only in actual participants randomly allocated to a trial group. For factors that are not constant, the conditions under which the baseline data are collected should be stated in the methods section of the study report. For example, it should be clear whether blood pressure recordings were measured sitting or supine, or after a specified rest period; also whether a single reading, the average of several readings, the highest of two, or the first of two or more, was used. Baseline data as entry criteriaIn some circumstances, threshold levels of one or more baseline variables will form part of the entry criteria for the study. In this case, if an extreme value of a baseline factor, such as high blood pressure, is required to qualify a person for entry into a study, potential participants whose value on the day of screening is more extreme (higher) than their usual level will be more likely to qualify for entry. A second baseline reading of the average blood pressure for this group will be lower and more accurately reflect their usual blood pressure; this is known as regression towards the mean.3 For this reason, remeasuring factors required for entry is desirable, to establish a more realistic group average value of the characteristic at baseline. PresentationThe baseline characteristics are usually presented in the first table in a report. Care should be taken to include the necessary descriptive information without overwhelming readers with unnecessary details. For example, in the recent AFFIRM trial comparing rate control with rhythm control of atrial fibrillation, the published first table has 16 baseline characteristics, each with a mean and percentage value for the overall group, and for both treatment groups separately, together with P values.4 The resulting table of 107 values and four footnotes may make it difficult for some readers to extract the key information.5 A simpler presentation appears in the FRISC II study of invasive compared with non-invasive treatments for unstable coronary artery disease.6 This presents more baseline characteristics (20), but by minimising detail (omitting overall group and P values), allows a more rapid comparison of the characteristics between groups. Comparability between groupsIf randomisation has been performed correctly, the groups should be similar in baseline characteristics, except for the play of chance. Stratification in the randomisation process further restricts the extent of chance imbalances.2 For continuous variables (such as blood pressure, age, cholesterol level), the similarity of the treatment groups should be assessed by comparing relevant summary measures (mean and standard deviation, or median and range). For categorical factors (such as sex, disease stage), the numbers and proportions in each category level should be shown for each treatment group. The more similar the treatment groups, the more credible are the trial results as reflecting a true result of treatment, especially if unadjusted analyses are presented.5,7 Use of P values to assess randomisationUse of statistical tests to compare the balance and/or values of baseline characteristics between the study groups and the presentation of P values are not uncommon. However, many authors assert that this is inappropriate.3,5,8-10 If randomisation has been performed correctly, chance is the only explanation for any observed difference between groups at the outset of the study, in which case statistical tests become superfluous. Consequently, only if it is suspected that the randomisation process has failed or was flawed, can performing significance tests on the baseline data be readily justified.8 It is worth remembering that, if 20 baseline characteristics are presented from a trial using simple randomisation, it is more likely than not that at least one characteristic will show a significant imbalance between groups at two-sided P < 0.05 by chance alone (actual likelihood, 64%). In any case, providing P values is not a substitute for carefully describing, in the results section, any imbalances between study groups that may be clinically important. For example, in a trial of a thrombolytic drug, a 1% baseline difference in history of previous intracranial haemorrhage may not be statistically significant, but could still affect haemorrhagic stroke rates after treatment (an outcome of the study), and hence could be regarded as potentially clinically significant. If there are imbalances that are considered important to the final study results, they should be accounted for by an adjusted analysis of the data, not simply noted with a P value in the first table.7 Other uses of baseline dataA longer-term benefit of collecting comprehensive baseline data is that, after outcome data become available, it allows the estimation of risk of the outcome in the control group, related to various baseline characteristics. This effectively uses the control group as an epidemiological cohort study, providing contemporary information about predictors of disease outcomes. In summary, careful planning and collection of baseline data enables performance of a high-quality trial and allows readers to clearly see the internal and external validity of the study. 1: CONSORT checklist of items to report when reporting a trial 1 Section and topic Item no. Descriptor Baseline data 15 Baseline demographic and clinical characteristics of each group 2: Checklist for baseline data Measurement Consider all important baseline variables to be measured and how they are to be measured before treatment starts: Demographic characteristics (age, sex, height, weight, etc) Known factors that predict the outcome (potential confounders) Factors that predict or alter the risk of adverse reactions Stratification factors Pre-specified subgroups. Reporting Tabulate relevant summary measures (eg, mean and standard deviation). Include all important baseline characteristics while keeping the table readable. Wherever possible, avoid displaying P values. Analysis In the results section, discuss the similarity of the two groups, highlighting any clinically important differences that may influence the outcome. Discussion Discuss the effect of the baseline data balance on the internal validity of the study and the comparability of the study population to patients seen in wider clinical practice.

David C Burgess BMed · Val J Gebski BA, MStat · Anthony C Keech MSc(Epid), FRACP

GPs are involved in long term care of patients and families with complex conditions. They juggle the need for medical expertise, the relationships between family members, the cost of expertise, limitations of access, and the medicolegal environment. With this background, the GP is ideally placed to play an active role in the "new genetics". GP consultations involving the new genetics will include diagnostic testing for patients with clinical problems, preconception and prenatal testing for couples in relation to pregnancy, predictive testing for families with some genetic conditions, and community genetic screening in some circumstances. GPs will need to understand the language of the new genetics, undergo continuing education, and receive ongoing support to enable them to communicate effectively with patients and their families. Different models of care incorporating GPs, specialists and allied health professionals can be developed to provide maximum delivery of relevant genetic data for both genetic and common multifactorial disorders.

Linda Mann DipRACOG, FRACGP

Peter J Collignon*, Dianne E Dreimanis† and Wendy D Beckingham† *Director, Infectious Diseases Unit and Microbiology Department; †Clinical Nurse Consultants, Infection Control; The Canberra Hospital, PO Box 11, Woden, ACT 2606. peter.collignonATact.gov.au To the Editor: Single-use devices (SUDs) are in common use, and many are reprocessed.1-7 When examined, these devices are frequently not clean and have residual biological material on or within them.2-4,6 This material may contain viruses or other infectious agents. SUDs are usually made from plastics or other heat-sensitive materials resulting in less effective means being used for sterilisation than can be used for more robust materials — chemical disinfectants can be ineffective in the presence of organic material, and have poor penetration compared with heat (eg, an autoclave). In 1994 we found that, of 168 Australian hospitals reviewed, 68% were reprocessing SUDs used in sterile sites.1 We repeated this survey (using a similar questionnaire) in 2001, in acute-care hospitals with more than 45 beds. The questionnaire was sent to 461 hospitals — 181 private hospitals (117 with fewer than 100 beds, 59 with 100–300 beds, and five with more than 300 beds) and 286 public hospitals (115 with fewer than 100 beds, 116 with 100–300 beds and 55 with more than 300 beds). Responses were received from 189 (see Box 1). Not all respondents answered all questions and many responded anonymously. Reuse of SUDs still occurred in all states and territories, but compared with 1994 the rate had dropped to 15% (28 hospitals). Large hospitals reused more often than smaller hospitals (see Box 1). Reuse was slightly lower in private hospitals than in public hospitals (13% v 16%). Rural hospitals reused SUDs less often than metropolitan hospitals (12% v 16%). The commonest SUDs reused were diathermy pencils. Given their low cost ($5), the labour costs of reprocessing would exceed the cost of replacement. Diathermy pencils (Box 2) have spring-loaded buttons, which inevitably become contaminated with blood during surgical procedures. Thus, the potential exists to contaminate the surgeon's fingers during subsequent procedures. We believe that reusing such relatively inexpensive items is inappropriate from both financial and infection control perspectives. An Australian National Health and Medical Research Council (NHMRC) report stated that, after reprocessing and packaging in hospitals, almost all SUDs were contaminated with foreign material (including blood), and several pacing electrodes had damaged insulation.6 Other studies have shown that blood persists on cardiac ablation catheters when structural abnormalities (which occurr frequently and early) are present.3 The reuse of these devices has been reviewed by the NHMRC and important changes have been recommended.6 Reuse of SUDs has been common in many countries. In the United States, reprocessing is frequent (eg, 2.5 million devices by one commercial reprocesser).5 In 2000, the US Food and Drug Administration issued a policy that, for practical purposes, should abolish the practice of reprocessing SUDs in hospitals.4 In Australia, the Therapeutic Goods Administration recently announced that reprocessing of SUDs will be regulated.7 This should have a similar effect. As the methods and response rates of our two surveys were similar, we believe that the reuse rate has decreased. However, proportionately, fewer large public hospitals responded (only 13 of 55, or 24%, compared with 41% overall), even though they have the highest reuse rate (54%). Therefore, we are likely to have underestimated the actual rate of reuse. Also, those who are reusing may be less likely to admit to this practice, and thus less likely to respond. Reuse of SUDs in sterile sites remains common practice in Australian hospitals (although the rate is lower than it was in 1994). Most SUDs appear to be unsuitable for reuse as they cannot be adequately cleaned and sterilised. We strongly advise against further reuse of these items. 1: Number and types of hospitals reusing single-use medical devices Number reusing devices / Number respondents Bed numbers Type of hospital Unknown < 100 100–300 > 300 Total respondents Unknown 0/1 0/2 1/4 1/1 2/8 (25%) Public 0/1 5/41 4/44 7/13 16/99 (16%) Private 4/40 6/36 0/2 10/78 (13%) Combined public and private 0/2 0/2 0/4 Total respondents 0/2 9/85 (11%) 11/86 (13%) 8/16 (50%) 28/189 (15%) 2: A diathermy pencil

Peter J Collignon · Dianne E Dreimanis · Wendy D Beckingham

Clifford F Hughes Head, Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Suite 304, 100 Carillon Avenue, Newtown, NSW 2042 clifford.hughesATemail.cs.nsw.gov.au Comment: The letter by Collignon, Dreimanis and Beckingham about reuse of single-use medical devices (SUDs) in Australian hospitals again brings in to stark contrast the issue of safety and quality of medical devices and the pressing need to provide affordable services to the Australian public. Seven years ago, Collignon and colleagues showed an unacceptably high reuse of SUDs in Australia, especially in public healthcare institutions.1 Since then, the National Health and Medical Research Council (NHMRC) has produced an expert panel report on these devices2 and the Therapeutic Goods Administration has promulgated detailed device regulations.3 There has been continued debate in both the scientific literature and lay press, and the United States Food and Drug Administration has had extensive comments published on this matter.4,5 Given the intensity of this debate, it is surprising that so few hospitals completed the questionnaire. It is also surprising that, despite the overall reduction in the reuse of SUDs, there has been no apparent reduction in their use in large public institutions, 50% of which continue the practice. Collignon and colleagues have not investigated the quality control mechanisms in place in these hospitals. That could well be a subject for further research. Not so obvious to the casual user is the effect of resterilisation on the materials of the device. The authors allude to the potential for degradation during sterilisation. There is inevitable pressure to use less effective (chemical) means for re-sterilisation. On the other hand, the waste of an enormous resource that, if safe, could be readily reused must be recognised. The costs of devices are easy to quantify. The costs of resterilisation, not to mention quality control, less so. Collignon et al suggest one example of false economy in the reuse of a low budget but commonly used item — diathermy pencils. They make a strong case for mandated reporting of resterilisation protocols for all single-use items. Informed consent must be a prerequisite. Tracking systems could well provide beneficial information on the safety and efficacy of procedures for particular devices. Furthermore, clinical audit would provide an early warning mechanism should resterilisation prove inadequate. These are among the main recommendations of the Report of the NHMRC Panel.2 Extensive regulations and controls have been applied to the use of biological products such as dura mater, heterograft and cardiac valves, among others. There is, however, reluctance to apply similar stringent controls to devices which may be contaminated by more pervasive but less obvious biological hazards. There are only three options: cease this practice wherever a viable alternative is available until there is incontrovertible proof of the safety of reuse; mandate detailed protocols which include audit and surveillance mechanisms coupled with appropriate informed consent whenever SUDs are reused;2 and develop a research and evidence base for improvements in design and materi-al technology so that the "cost efficiencies" of single-use devices could be translated to "nondisposable items". All three must be adopted.

Clifford F Hughes

Graeme H Johnson*, Donna B Mak†; *Acting Public Health Medical Officer; †Former Public Health Medical Officer, Kimberley Population Health Unit, Derby, WA 6728. graeme.johnson@health.wa.gov.au To the Editor: In their study of a SAFE-style trachoma control program (which included Antibiotic treatment, Facial cleanliness, and Environmental improvement, but not Surgery) in a remote Australian community, Ewald et al suggest that no systematic SAFE trachoma control program exists in Australia.1 In the Kimberley region of Western Australia, the Kimberley Public Health Unit (KPHU) has coordinated a trachoma control program since 1989. The World Health Organization SAFE strategy has been implemented since 1996, as described in the Kimberley regional trachoma control guidelines and a peer-reviewed publication.2,3 The trachoma control program in the Kimberley has been delivered by a variety of environmental health, health promotion, community and clinical health professionals employed by State and local governments, and by community-controlled and other non-government organisations. We believe a coordinated regional approach is mandatory, because of the numerous organisations involved in program delivery. The trachoma control program in the Kimberley continues to achieve good results. The prevalences of follicular trachoma during annual screening of school-aged children in the Kimberley have been published annually in the KPHU Bulletin.4 Since 1996, in accordance with the WHO SAFE strategy, communities with trachoma prevalences of less than 5% were not screened in subsequent years and did not contribute to regional prevalence data. Thus, the observed decrease in trachoma prevalence between 1996 and 2001 is likely to be greater than that shown in the Box. We believe the Kimberley region is well placed to achieve the WHO aim of eradicating blinding trachoma by 2020.5 However, it is a concern that other regions of Australia with endemic trachoma infection may not conduct disease control activities in a coordinated manner because of lack of leadership in trachoma control or insufficient resources, or both. The community described by Ewald et al borders the Kimberley region and has strong cultural links with several Kimberley groups. The achievements in trachoma control in the Kimberley cannot be sustained in the long term without a nationally coordinated approach. We believe that it falls within the statutory responsibilities of State and Territory departments of health to ensure that environmental and clinical health services are coordinated to achieve trachoma control in Australia. Trachoma in Kimberley children Point prevalence of follicular trachoma among children in the Kimberley region aged 5–15 years at annual trachoma screening, 1991–2002

Graeme H Johnson · Donna B Mak

Andrew C Laming,* Bart J Currie† * Advisor, Federal Minister for Health and Ageing, Parliament House, MG 48, Canberra, ACT 2600; † Professor in Medicine, Northern Territory Clinical School and Menzies School of Health Research, Darwin, NT. andrew.lamingAThealth.gov.au To the Editor: The important article by Ewald et al shows that offering azithromycin treatment to 70% of a remote community may be inadequate to control hyperendemic trachoma, even when combined with a health promotion campaign.1 Yet, significant short-term gains in similar locations have been achieved with as little as 20% of the population receiving azithromycin, where administration to children with trachoma and their household contacts was directly observed by health staff.2 In that study,2 we reported a 6-month follicle resolution rate in schoolchildren of 72%, followed, however, by a return of trachoma prevalence towards baseline levels over 12 months. The critical factors for short-term success with azithromycin appear to be appropriate selection of cases and contacts, plus, where possible, directly observed therapy to minimise reinfection from untreated cases. Sustainability of initial reduction in trachoma prevalence is problematic, and issues of how extensively and how often to screen and/or treat need to be determined in the Australian context. Similar sustainability considerations have arisen in community scabies programs.3 Ewald et al are correct to identify population mobility as a major issue, with trachoma likely to be reintroduced by untreated children entering a community where a treatment program has occurred. Hence the need for a coordinated regional approach. However, a regional approach to trachoma control does not necessarily mean a uniform approach, and it is vital to tailor programs to suit the capacity of communities and their degree of commitment to labour-intensive treatment and health promotion. Our study suggested that directly observed twice-yearly azithromycin therapy, with a health promotional component, is likely to be preferable to an annual program.2 Mathematical modelling supports this more frequent dosing and, unlike in Africa, the cost of azithromycin should not be a constraining factor in Australia.4 Regardless of the strategy selected, if, after treatment, the prevalence remains hyperendemic (> 20%), then the outcomes from concurrent health promotion are compromised. Appropriately targeted and directly observed azithromycin therapy can help create conditions favourable for health promotion campaigns, which in turn prolong those gains by reducing trachoma transmission.5 Major issues for trachoma control in Australia are (i) who to screen and treat (with directly observed azithromycin therapy); (ii) how often to screen and treat; (iii) how to plan trachoma programs as regional initiatives; and (iv) who will fund, coordinate and implement trachoma programs.

Andrew C Laming · Bart J Currie

Dan P Ewald,* Gillian V Hall,† Christine C Franks‡ * Senior Research Fellow, Centre for Remote Health, Flinders University, PO Box 4066, Alice Springs, NT; † Lecturer, National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT; ‡ Educator, Health Development, Health and Community Services, Alice Springs, NT. dan.ewaldATflinders.edu.au In reply: These letters reinforce a number of important points about control of trachoma (and other endemic infections) in Australia. The questions of whom and how often to treat need refining through Australian experience. Long-term control needs multifaceted, intersectoral collaboration to alter environmental and behavioural conditions against disease transmission. Strategies should be sustained, regional (large as practicable); acknowledging, and guided by, Aboriginal kinship networks; and recommend observed drug treatment (which was negotiated for the final treatment in our study). A non-uniform approach could include more frequent treatment in hyperendemic communities, probably leading to less net use of antibiotic treatment. Reports from the Kimberley Population Health Unit show a very mixed picture, with wide year-to-year fluctuations in prevalence in many communities. While hyperendemic communities remain in a region, the prevalence of trachoma may increase unnoticed in communities no longer screened because their prevalence has dropped below 5%. If not looked for, it is unlikely to be noticed. Further analysis, such as the graph provided by Johnson and Mak, is to be applauded in the context of a thorough analysis. When this happens, it will greatly strengthen the case for active trachoma control in other regions. For trachoma prevention, and for many other reasons, we believe environmental health interventions are critical. These remain difficult to evaluate given the high mobility of people in Aboriginal communities. Reliable, long-term, regional environmental health and mobility data are needed as part of this broad issue.

Dan P Ewald · Gillian V Hall · Christine C Franks

Richard X Davey Chemical Pathologist, Melbourne Health Shared Pathology Service, Pathology Department, Western Hospital, Footscray, VIC, 3011. richard.daveyATwh.org.au To the Editor: Stone and colleagues must be complimented for their study of gestational diabetes mellitus (GDM) published recently in the Journal.1 Although the study was comprehensive, in that it linked two pertinent records for 99.3% of the women delivering in Victoria in 1996, their analysis was necessarily limited to the parameters recorded in those two data sets. Stone et al do not refer to relevant recent work from Toronto, Ontario,2 and Sunshine, Victoria,3 which has already determined the maternal risk factors for GDM: increasing age, racial origin, family history of diabetes mellitus, and pre-pregnancy body mass index. Data on the latter two of these four factors were specifically noted as not available to Stone's group, but could have been mentioned as established risk factors to consider in patient management. The findings of Stone et al regarding age are similar to those previously reported. However, the relative risk for GDM in the Sunshine cohort increased from 25 years of age (odds ratio, 1.9; 95% CI, 1.3–2.7).3 Recasting the all-Victorian data1 with "< 25 years" as the reference datum would most likely produce a similarly significant result to that found in the Sunshine study. Again, the Victorian data on racial origin are but the Sunshine data writ large. Stone and colleagues had to choose a reference datum for this parameter, but have not avoided a problem that bedevils all such work in the "New World": there is as yet no definitive Australian reference datum available for racial origin. For example, the designation "Australian" may be used, but parents who are themselves second or third generation Australian-born may have, say, pure Maltese ancestry, giving them a high risk of GDM and thus distorting the reference datum. I have argued this case in more detail elsewhere,4 and took measures to circumvent the problem in the Sunshine study.3 Among their findings, Stone et al confirm that there is a significantly increased incidence of macrosomia in GDM-affected infants. I agree. Their work is unquestionably the definitive statement of Victoria's GDM-related macrosomia status (as at 1996), but it lacks one vital ingredient: it defines macrosomia, but does not cite the source of the data used as the study's benchmark. To enable comparisons with their work in future years, could we please have that benchmark referenced so that others may use it too?

Richard X Davey

Christine A Stone,* Kylie A McLachlan,† Jane L Halliday,‡ Peter Wein,§ Christine Tippett¶ * Epidemiologist, Prevention and National Health Priorities, ‡ Epidemiologist, Birth Defect Registry, Perinatal Data Collection Unit, Public Health Division, Department of Human Services, 17th Floor, 120 Spencer Street, Melbourne, VIC 3001; † Research Fellow in Endocrinology, Department of Endocrinology and Diabetes, St Vincent's Hospital, Fitzroy, VIC; § Senior Lecturer, Department of Obstetrics and Gynaecology, University of Melbourne, East Melbourne, VIC; ¶ Director, Maternal Fetal Medicine, Monash Medical Centre, Clayton, VIC. christine.stoneATdhs.vic.gov.au In reply: We thank Davey for his comments, which provide us with the opportunity to highlight the benefits and limitations of reports using population-based data. The value of population-based data is that the reported incidence, risk factors and outcomes reflect current practice in the whole of Victoria and are not subject to bias introduced by local referral patterns or clinical practice. Our study1 shows that, in addition to established risk factors for gestational diabetes mellitus (GDM), the reported incidence varies according to hospital size and geographic location, demonstrating the type of bias that can occur. In addition, the large number of subjects in our study (over 60 000) enables more accurate analysis of subgroups. A limitation, already highlighted in our discussion, is that we are restricted to the parameters available within the data sources used. Davey and Hamblin's article2 demonstrates the difficulty of obtaining individual patient data on body mass index, racial grouping, and family history of diabetes. Even working at the hospital level, they had to extrapolate from population-level data to derive an estimate of these risk factors among the control subjects.2 Given that their study population is a subgroup of ours,1 it is no surprise that the two studies showed similar results. An important implication for providers of health services is that, with increases in the age at which mothers give birth and in the number of births to Asian-born mothers,3 we predict that the prevalence of GDM in Victoria will rise. Davey correctly points out that our article does not refer to a relevant 1997 study by the Toronto group.4 However, we do actually refer to a later publication by the same group.5 The problem of ethnicity and migration arises in studies of conditions that are not only polygenic but also a result of complex interactions between a person's genes and his or her environment. Lastly, the source of information on macrosomia was 1996 population data. We have since produced a percentile chart of weight (g) for gestational age (weeks) based on 15 years of Victorian data.6

Christine A Stone · Kylie A McLachlan · Jane L Halliday · Peter Wein · Christine Tippett

Michael Copeman Paediatrician, Department of Paediatrics, Manly and Mona Vale Hospitals, Darley Road, Manly, NSW 2095. mcopeman@bigpond.net.au To the Editor: Law and Batey1 rely on a flawed study for their conclusion that needle/syringe programs (NSPs) have saved lives and money. The study in question2 compared the incidence of HIV and hepatitis C virus (HCV) infections in cities round the world and concluded that cities with NSPs had achieved reductions in HIV incidence that were not seen in cities without NSPs. However, interestingly, no similar reduction in HCV incidence was reported. Detailed reading of the study shows that a third of the cities (22/67) without NSPs were in Thailand — a country in which, unfortunately, there are many other reasons why HIV incidence is increasing rapidly. Given the large proportion of Thai cities included in the study, it is plausible that the rapid rise in HIV incidence in these cities biased the overall results of the study, leading to an erroneous conclusion that NSPs themselves were associated with a reduction in HIV incidence in cities worldwide. Further reading of the study shows that HCV incidence was not measured in any studies in Thailand. So, the reported lack of effect of NSPs on HCV incidence depends on comparisons between cities with and without NSPs from other parts of the world, perhaps less affected by some of the problems in Thailand. In conclusion, if Thai cities had been excluded from the study, it seems likely that no change in the incidence of either HCV or HIV might have been found in association with NSPs. The original study needs urgent re-analysis to see if this is in fact the case.

Michael Copeman

Matthew G Law,* Robert G Batey† Statistician, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, 376 Victoria Street, Darlinghurst, NSW 2010; † Clinical Chair, Division of Medicine, John Hunter Hospital, Newcastle, NSW. mlawATnchecr.unsw.edu.au In reply: Copeman's criticism of the report Return on investment in needle and syringe programs in Australia1 is essentially that the comparison of the effectiveness of needle/syringe programs (NSPs) is confounded by other factors. This point, and its implications for the results, was extensively discussed in that report. Copeman suggests that the estimated reduction in HIV due to NSPs might largely be attributable to the inclusion of data from many cities in Thailand that do not have NSPs. This criticism is not supported by the data. A sensitivity analysis including only cities from developed countries was performed at the time of the report (see Methods, Section 3.1.2, page 131), but was not included among the report's results because of space constraints and because it didn't alter the main findings. The analysis of cities in developed countries showed an overall mean reduction in the annual rate of change in HIV seroprevalence of –30.0%, compared with –24.7% based on all cities, albeit with lower statistical significance (P = 0.105 v P = 0.057), reflecting the loss in power through exclusion of cities. Copeman's assertion that the report indicated that NSPs had no effect on rates of hepatitis C virus (HCV) infection is incorrect. The report estimated that, following the introduction of NSPs, HCV prevalence among injecting drug users declined by 2% per annum, compared with no introduction of NSPs (P < 0.001). The report is freely available on the Internet,1 and we encourage readers to look at it for themselves.

Matthew G Law · Robert G Batey

Peter J Goadsby Professor of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen's Square, London, WC 1N 3BG, United Kingdom To the Editor: Gebski and Keech describe with clarity and accuracy the important basic concepts of statistical analysis for physicians.1 I would like to draw attention to two issues. Firstly, the authors refer to common measurement scales that are used in medicine. It is crucial to understand the limits of a measurement to begin to appreciate results from any study. They describe the continuous scale and offer blood pressure and temperature measurements as examples. This scale refers to data determined such that the distance between any two points is known and measureable. Siegel used the term "ratio scale" if there was a true zero point to the measurement.2 This contrasts to an ordinal categorical scale, in which the intervals are not constant. The scale referred to can be transformed, and is anchored with respect to the measurements to some reproducible point. The term "ratio" for this scale seems preferable, as the world is, in essence, discrete when measured, in the quantum sense. Certainly, the measured world is not continuous, at least as far as we can determine it. Secondly, the authors do not mention resampling methods.3 These can be very powerful and are attractive in biomedical research when the distribution may not be defined. While I realise these methods are relatively new, they do seem unreasonably ignored in undergraduate medical education.

Peter J Goadsby

Val J Gebski,* Anthony C Keech† * Principal Research Fellow, † Deputy Director, NHMRC Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450. valATctc.usyd.edu.au In reply: While one can view the world as being "discrete", the assumptions underpinning most common statistical methods in analysis of clinical studies are "continuous" distributions. In fact, statisticians go to enormous lengths to approximate discrete systems as continuous ones (lifetime analysis, normal approximations, etc). The measurement scale by which study outcomes are assessed needs careful consideration (to ensure consistent precision and units of measurement). However, both practical and statistical considerations allow for the more common definitions of continuous and discrete measurements to be just as effective for statistical comparisons. Indeed, there is frequently little loss of statistical efficiency when "continuous" variables are appropriately categorised into ordinal groups.1 Resampling methods randomly sample the data repeatedly to estimate the underlying population distribution parameters (eg, mean, standard deviation, etc). They can be very useful in solving specific problems in which the underlying properties of the data used to make treatment comparisons are unknown and using other statistical approximations is deemed to be inappropriate. However, these are specialised computer-intensive techniques for use by trained biostatisticians, rather than commonly used analysis methods. Problems arise with resampling techniques (eg, obtaining confidence intervals), which require specialised statistical expertise.

Val J Gebski · Anthony C Keech

John H T Ellard Psychiatrist, Medical Specialist Centre, 710 Military Road, Mosman, NSW. To the Editor: I read with interest the article in the Journal on ranking medical journals and the fallacies to be found therein.1 I have a simpler method. I subscribe to two classes of journals: those specialising in psychiatry, and more general journals. The psychiatry journals I keep entire. However, as my house is of modest size I cannot do that with the general journals, so I tear out and file the articles that I find interesting and informative. You will be interested to know that in the past month I have filed away one article from the Lancet, one from the New England Journal of Medicine and three from the Medical Journal of Australia. What better measure of merit could there be?

John H T Ellard

A 39-year-old woman with AIDS (CD4 count, 30 cells/mL) had a 4-day history of nausea, vomiting and profuse watery diarrhoea. The patient was afebrile and had a distended abdomen with diffuse guarding without rebound tenderness. Abdominal x-rays (Box 1) and computed tomography scans (Box 2) were performed. The white blood cell count was within normal limits and stool cultures were negative. Colonoscopy revealed yellow plaques throughout the colon. The patient improved clinically after taking oral metronidazole. Bowel wall "thumbprinting" (the appearance of "thumbprint"-shaped projections) is a radiological sign of thickening of the colonic wall. It occurs secondary to submucosal haemorrhage and oedema from capillary leakage.1 It can result from any process that leads to oedema of the bowel wall, including pseudomembranous colitis (as shown here), ischaemic colitis, non-infective inflammatory bowel disease, other infective bowel diseases, submucosal/intramural haemorrhage and other conditions.2 The mucosal damage and inflammation seen in pseudomembranous colitis are caused by Clostridium difficile toxin.3

Moishe Liberman MD · Chris Labos · Jeff Wiseman MD

Cries unheard. A new look at attention deficit hyperactivity disorder. George Halasz, Gil Anaf, Peter Ellingsen, Anne Manne, Frances T Salo. Alton, VIC: Common Ground, 2002 (x+91pp). ISBN 1 86335 497 2. There have been controversies about the existence and nature of attention deficit hyperactivity disorder (ADHD) since George Still first described it in 1902. The “new look” presented here is the notion that the diagnosis is used as a quick fix to deal with complex situations, allowing one to write a prescription rather than attempt to understand a complex psychodynamic problem. There can be no objection to this approach as our profession has some expertise in producing epidemics which disappear as rapidly as they have appeared — consider the rise and fall of repetitive strain injury (RSI). This book argues that there are many pressures in modern society urging us to find a quick fix, ranging from the activities of the pharmaceutical companies, to the DSM-IV-driven push to confine human distress within categorical boundaries. This is true, however one must examine the total situation, and this is where the authors’ bias shows. Being psychodynamically oriented, they see it as likely that wisdom is to be found in that direction. So it may be, but it is not many years since their antecedents proclaimed that schizophrenia was due to the activities of “schizophrenic” mothers, autism to cold-hearted parents, and the “psychosomatic” disorders to psychodynamic mechanisms. For example, Alexander regarded ulcerative colitis as a regression to the anal stage of psychosexual development, while Szasz and Cushing emphasised the orality of the disease. There were descriptions of the “typical conflict situation” associated with peptic ulcer and asthma. No theoretical position has a mortgage on wisdom. There are some facts about ADHD which will not go away. They emerge most clearly when one deals with adults who are able to give a good account of themselves. It has a firm correlation with dyslexia and anomalies of motor dominance, such as being left-handed and right-footed. Recent work suggests that chromosome 6p may be involved. There are well-established neuroimaging anomalies and there is the paradox that the hyperactivity calms with stimulants instead of being exacerbated. By all means let us look carefully, but let us look in all possible directions. John H T EllardPsychiatrist Balmoral Beach, NSW

John H T Ellard

Guides casebook. Cases to accompany Guides to the evaluation of permanent impairment, 5th edition. Christopher R Brigham, Leon H Ensalada, James B Talmange. Chicago: AMA Press, 2002 (xi + 384 pp). ISBN 1 57947 264 8. Impairment evaluation using the American Medical Association (AMA) Guides is an important requirement in the medico-legal arena, but correct application can be a daunting process given the Guides’ complexity. This casebook highlights the need for a good understanding of how to apply the Guides correctly and for a thorough objective assessment. For clinicians involved in impairment assessment, this book provides an insight into the methods of evaluation as well as some of the shortcomings of these methods. Sixty-eight cases are presented, most of them relating to musculoskeletal disorders. There is a broad spread of clinical cases; ranging from the more severe and catastrophic injuries, to more common conditions. The more controversial and ill-defined conditions, such as complex regional pain syndrome, fibromyalgia and the curiously termed "elusive cumulative trauma disorder", are discussed in detail. Each case is presented with a history and physical examination followed by a discussion of the rating according to the 4th and 5th edition of the Guides. After each case, there is a useful explanation of the differences between the ratings as well as relevant discussion on the difficulties of evaluating impairment. In most cases, there is little difference between the rating according to the 4th and 5th editions, one exception being impairment of the spine. The other differences are mostly with regard to musculoskeletal disorders. Given the current preponderance of claims for loss of sexual function following spinal injury, and cognitive loss following relatively mild traumatic head injury, the detailed discussion of these cases is particularly relevant. Problems associated with impairment evaluation in the presence of pain behaviour and in patients with poor credibility are also discussed. This book is topical, user friendly and essential for clinicians who carry out independent impairment evaluations. Although many insurance companies require clinicians to complete a certified course before undertaking evaluations, this casebook illustrates that being certified in the use of the Guides is not sufficient. Thorough and objective clinical examination remains a necessity for impairment evaluation, particularly in musculoskeletal injury. My experience in reading medico-legal reports is that while ratings according to the AMA Guides are frequently quoted, the clinical findings of the examiner often do not stand up to close scrutiny, and incorrect impairment ratings are sometimes provided. Hopefully, this casebook will assist both doctors and lawyers in their quest to provide objective and accurate evaluation of impairment. The book is value for money and essential reading for those who are called upon to provide an assessment of impairment. Seamus E DaltonOrthopaedic Surgeon Crows Nest, NSW Order this book See also:• Guides to the evaluation of permanent impairment (5th edition) • Special package prices

Seamus E Dalton

Sorting out SARS The global effort to understand SARS continues, with researchers in Frankfurt suggesting that a component found in liquorice roots, glycyrrhizin, may be effective in treating the condition. Glycyrrhizin was the most active of five compounds, including ribavirin, assessed for antiviral activity against clinical isolates of SARS-associated coronaviruses.1 Closer to the crisis, Hong Kong authors say WHO criteria for suspected SARS were only met by one in four cases of the disease admitted via a screening clinic early in the outbreak.2 They studied the onset of symptoms in 141 patients admitted after screening to Hong Kong's Prince of Wales Hospital; of this group, 97 patients had SARS subsequently confirmed by anti-coronavirus IgG antibody detection in saved serum samples. In the early stages of SARS, the main discriminatory symptoms were systemic — fever, chills, malaise, myalgia and rigors — rather than respiratory ones; but a documented fever of more than 38oC occurred in only about one-in-four cases. Radiological evidence of pneumonic change often preceded fever and the authors stated that chest radiography should be mandatory for all patients being screened for SARS. Hong Kong researchers also reported haematological findings in 157 patients with SARS.3 Lymphopenia and a transient prolonged activated partial thromboblastin time occurred commonly. Advanced age, high lactate dehydrogenase levels and an early, notable drop in CD4 and CD8 lymphocyte counts were associated with a poorer outcome. 1. Lancet 2003; 361: 2045-2046 2. BMJ 2003; 326: 1354-1358 3. BMJ 2003; 326: 1358-1362 Out of Africa Human monkeypox, a smallpox-like virus, has hit North America for the first time. It has similar but less severe manifestations than smallpox. The 50 non-fatal cases of the disease reported in the USA ranged in age from four to 48 years and all had contact with sick prairie dogs purchased as pets from exotic pet stores. Some of the dogs have died from the disease. Previously, sporadic cases had been reported in remote African villages, although an outbreak, with a case-fatality rate of about 10%, occurred in the Congo in the late 1990s. Smallpox vaccination appears to be able to prevent monkeypox; the CDC is looking at its potential role post-exposure. CMAJ 2003;169: 44-45. Fun down under Western Australian researchers report that the Funhaler — a low-volume spacer device that self-reinforces effective technique in young patients by using incentive toys, like a spinner and a whistle — can improve compliance in parents as well as children. They also found that, compared with a conventional spacer, this innovative device did not compromise the aerosol output of the two drugs tested, salbutamol and beclomethasone dipropionate. They hypothesise that use of the Funhaler may lead to improved clinical outcome measures. Arch Dis Child 2003; 88: 579-581 Screening smoking An expert commentator says cigarette smoking portrayed in a movie should automatically garner the film an adult content or "R" rating.1 Hopefully, this would have the effect of encouraging studios to stop putting smoking in movies aimed at teenagers. The recommendation followed a New England study of 2603 mainly white, rural adolescents, which found that viewing smoking in movies promoted smoking initiation in this group.2 The researchers did point out that not all initiates will go on to become established smokers. 1. http://image.thelancet.com/extras/03cmt159web.pdf 2. http://image.thelancet.com/extras/03cmt1353web.pdf Use it or lose it? Seniors should be encouraged to read, play board games and musical instruments, and go ballroom dancing, says a US author.1 These activities may do more than enhance quality of life; they may also provide protection against dementia. The Bronx Aging Study found that participation in leisure activities requiring mental effort was associated with a reduced risk of dementia in a cohort of elderly subjects who resided in the community.2 Mere physical activity, such as climbing stairs, was not linked to reduced risk. 1. N Engl J Med 2003; 348: 2489-2490 2. N Engl J Med 2003; 348: 2508-2516