Volume 181 Issue 5

It all depends on which studies you emphasise Four years ago in the Journal we posed the question of whether active and passive exposure to cigarette smoke could cause breast cancer. We concluded, at the time, that biological plausibility had been established, but that the epidemiological evidence was inconclusive.1 This was consistent with a 1997 report2 of the California Environmental Protection Agency (Cal/EPA), which found that the link between environmental tobacco smoke (ETS) and breast cancer was inconclusive. However, in a recent draft review of the health effects of ETS,3 the Cal/EPA stated that the evidence for a causal association between ETS and breast cancer is now conclusive. Its latest report was based on a systematic review of 15 studies, 11 of which had been published since the 1997 report. Is this new conclusion justified? Until the 1990s, most case–control and cohort studies examining the association between cigarette smoke exposure and breast cancer focused on active smoking. These studies did not adequately ascertain the whole-of-life ETS exposure of the participants.1,4,5 Notably, childhood exposure was usually ignored.6 This is of particular relevance, as chemical carcinogenesis studies of breast cancer in experimental animals, and other studies on the development of the mammalian breast, indicate that breast ductal cells would be most susceptible to chemical carcinogenesis during puberty and first pregnancy.5 Thus, it is possible that childhood, adolescent and adult exposure to cigarette smoke up until the delivery of a woman’s first child is a crucial component of lifetime exposure. If an association with ETS did exist, case–control and cohort studies on active smoking and breast cancer could have underestimated the effects by inadequate assessment of ETS exposure.1,4-6 The conclusion of the Cal/EPA report on ETS and breast cancer3 is based on a systematic review that gives prominence to the recent studies in which several sources of ETS exposure have been ascertained and to the clear dose–risk relationships seen in some studies. The meta-analysis used in the Cal/EPA’s review yielded a relative risk of 1.40 (95% CI, 1.17–1.68) — a significantly increased risk. However, a closer look at the studies reviewed in the latest Cal/EPA report raises some questions about its conclusion. Of the 15 studies in the review, five were cohort studies, of which none showed a statistically significant increase in breast cancer risk with ETS exposure. Several of these cohort studies had a very limited assessment of ETS — for example, defining exposure as simply being married to a smoker. However, one of the five cohort studies, which prospectively assessed childhood, adult and occupational ETS among US nurses,7 also showed no association. Moreover, another major cohort study8 published since the Cal/EPA review supports the conclusion of the US nurses’ study in regard to ETS. In this report of a 5-year follow-up of a cohort of 116 564 Californian teachers, 1150 new cases of invasive breast cancer were diagnosed among the 76 189 never-smoking women who provided data on ETS.8 The study aimed to ascertain total lifetime ETS exposure, although the published analysis is limited to household exposure throughout life. No significant association between ETS exposure and breast cancer was found for any age range of exposure or by menopausal status. However, a significant association was found between active smoking and breast cancer. The relative risks of acquiring breast cancer after ETS exposure in childhood, adulthood, or both childhood and adulthood, were 0.92, 0.93 and 0.93, respectively. Adding this new study to the Cal/EPA’s meta-analysis, the overall relative risk, based on the six cohort studies, is 1.01 (95% CI, 0.92–1.12) — that is, there is no significant effect. The strong association between ETS exposure and breast cancer emphasised in the Cal/EPA report3 is based on five case–control studies regarded as “unlikely to have missed important ETS exposures”. The summary odds ratio for these studies was 1.92 (95% CI, 1.54–2.39). The association was stronger in premenopausal women (summary odds ratio, 2.20; 95% CI, 1.70–2.85). However, if a true association exists, it is difficult to see why the two high-quality US cohort studies of nurses and teachers7,8 showed no association. In both studies, data on ETS exposure were collected before the diagnosis of breast cancer, thus avoiding recall bias, and both groups are likely to have given reasonably complete and valid information, including data on childhood exposures. Other research results add to the complexity of the issue. A 2002 systematic review, based largely on the same case–control studies as the Cal/EPA review,3 concluded that the strength of the association with breast cancer is similar for passive as for active smoking9 — a conclusion that others find implausible.7 One possible explanation for this seeming paradox could be that the association is linked mainly or exclusively to ETS exposure in childhood or early adolescence, as has also been suggested for active smoking, perhaps through hormonal mechanisms as well as the direct effects of carcinogens.10 The fact that p53-gene mutations in breast tumours are increased in smokers compared with non-smokers or ex-smokers suggests a genotoxic effect of smoking on breast tissue.11 Further complexities related to genotype may emerge: one case–control study12 showed that the association between passive smoking and breast cancer was stronger in rapid acetylators (ie, women who, owing to their specific NAT2 genotype, more rapidly metabolise carcinogenic compounds, such as aromative amines, in tobacco smoke). However, with regard to active smoking, slow acetylators were more at risk.12 Although many genotypes have been reported to affect the association between active or passive smoking and breast cancer,13 the results are inconsistent and do not explain the variable epidemiological results. Is a causal association between ETS exposure and breast cancer now certain, as the Cal/EPA draft report proposes? The jury would be wise to stay out on this one. If the emphasis is put on cohort studies, there appears to be no association between ETS exposure and breast cancer. If the emphasis is put on case–control studies with more detailed information on ETS exposure — but the possibility of recall bias — there appears to be an increased risk, especially in premenopausal women. An analysis focusing on childhood and adolescent ETS exposure may be the key to solving the current confusion. Such an analysis could be based on a pooled analysis of available studies with access to the original data, or on further assessment and follow-up of the ongoing cohort studies. In the interim, it is prudent to accept the possibility of an association, while also accepting the limitations of the available evidence. The International Agency for Research on Cancer has just released a major report on smoking, in which it states that the evidence does not support a causal link between either active or passive smoking and breast cancer.14 However, the report confirms a causal link between ETS and lung cancer, which, in itself, justifies efforts to restrict ETS.

J Mark Elwood MD, DSc · Robert C Burton MD, PhD

High-quality primary evidence from an Australian and New Zealand study provides a definitive answer The 1998 report of a meta-analysis by the Cochrane Injuries Group Albumin Reviewers presented an important public health issue and questioned the practices of many doctors in Australian intensive care units (ICUs).1 Using data from 24 studies involving 1419 patients, the meta-analysis reported that the administration of albumin-containing fluids to critically ill patients increased the absolute risk of death by 6%, suggesting one extra death for every 17 patients given albumin. The authors recommended that albumin should not be administered to critically ill patients outside the context of rigorously conducted, randomised trials. A subsequent meta-analysis did not resolve the issue of albumin’s safety in the critically ill.2,3 Due to its ready availability, albumin has been widely used in Australian ICUs. Even after the publication of the Cochrane review, half of all patients in surveyed ICUs in Australia received albumin during their ICU stay (R Bellomo, S Finfer, unpublished data). Extrapolating these results would mean that 50 000 patients received albumin in Australian ICUs each year and, if the Cochrane meta-analysis was correct, this would result in an additional 3000 deaths annually. Thus, the issue of albumin’s safety was of particular importance in Australia. The recent publication of the SAFE (Saline versus Albumin Fluid Evaluation) study in the New England Journal of Medicine4 not only brings certainty to the issue of albumin’s safety in a heterogeneous population of adult ICU patients, it also marks the coming of age of clinical research in Australian and New Zealand ICUs. The SAFE Study, a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian Red Cross Blood Service, and The George Institute for International Health, was a double-blind, randomised controlled trial of albumin versus saline for fluid resuscitation involving 6997 patients. Conducted in 14 ICUs in Australia and two in New Zealand, it was funded by the National Health and Medical Research Council and the Health Research Council of New Zealand, and by direct grants from the Australian federal, state and territory governments, the two New Zealand hospitals and CSL Ltd. Internationally, the SAFE Study is the largest randomised controlled trial conducted in intensive care or transfusion medicine to date. An accompanying editorial acknowledged that the SAFE Study heralded a new era in critical care marked by the large, simple randomised trial.5 The design of the study reflected the SAFE collaborators’ desire to conduct a definitive trial that would answer an important clinical question and provide results that would be widely applicable in ICUs around the world. As a result, the trial sought to include as many adult patients admitted to participating ICUs as possible by using broad, simple inclusion criteria and few exclusion criteria. The main inclusion criterion was that the treating clinician believed that fluid administration was indicated for the treatment of intravascular volume depletion. The primary outcome measure was all-cause mortality 28 days after randomisation. The only broad patient groups excluded were those admitted to the ICU after liver transplantation, burns or cardiac surgery. The study enrolled 6997 patients in 69 weeks, an average recruitment rate of 101 patients per week. The rapid recruitment rate was made possible by the commitment of the clinical staff in the participating ICUs, the provision for delayed consent, and web-based randomisation and fluid distribution. The blinded study design was possible as both study fluids were manufactured by CSL Ltd and packaged in specially designed blinding materials6 before distribution by the Australian Red Cross Blood Service, New Zealand Blood Service and participating centres’ blood banks. What did the study find? The primary outcome was available for 99.1% of the 6997 patients randomised; of these, 726 assigned albumin (20.9%) and 729 assigned saline (21.1%) had died by Day 28. The relative risk of death for patients assigned albumin compared with patients assigned saline was 0.99 (95% CI, 0.91–1.09; P = 0.87). There were no differences in secondary outcomes, with patients assigned albumin and saline having similar incidences of new organ failure, similar durations of mechanical ventilation and renal replacement therapies, and similar ICU and hospital lengths of stay. Key findings of the study are shown in the Box. The study identified six predefined subgroups: patients with and without trauma, with and without severe sepsis, and with and without acute respiratory distress syndrome (ARDS). As a previous meta-analysis had suggested that trauma patients resuscitated with colloid solutions had higher mortality than those resuscitated with crystalloid solutions,7 trauma was a stratification variable in the study. Patients with severe sepsis and ARDS were identified at baseline to determine whether the increased capillary permeability to albumin seen in those conditions8,9 resulted in a treatment effect that differed from that seen in the study patients without those conditions. Within the predefined subgroups there was limited evidence of a treatment effect favouring saline in patients with trauma, and favouring albumin in patients with severe sepsis. The possibly detrimental effect of albumin in patients with trauma was limited to patients with evidence of traumatic brain injury, namely those patients admitted to the ICU as a result of trauma who had a documented unsedated Glasgow Coma Scale score less than 14 and evidence of brain injury on cerebral computed tomography. The investigators cautioned readers that such subgroup differences frequently occur by chance, and the accompanying editorial advised cautious interpretation of the subgroup findings.5 Thus, the study demonstrated that, in this heterogeneous population of adult ICU patients, albumin can be considered safe, without demonstrating any clear efficacy advantage over saline. The SAFE Study achieved its goal of providing a definitive answer to an important clinical question. The result is widely applicable in those ICUs around the world where purified albumin is available. In addition, the study has demonstrated that investigators in Australian and New Zealand ICUs are capable of conducting large-scale collaborative trials on modest budgets and in a realistic timeframe. The SAFE Study has been described as a landmark study that heralds a new era in critical care.5 We hope that it will be only the first of many such studies. Key findings of the SAFE Study4 6997 patients were randomised to receive either albumin (3497) or saline (3500). The primary outcome (alive or dead at 28 days) was available for 6933 patients (99.1%). No significant difference was seen between the albumin and saline groups in: 28-day all-cause mortality (20.9% v 21.1%; P = 0.87) days in the intensive care unit (6.5 [SD, 6.6] v 6.2 [SD, 6.2]; P = 0.44) days in hospital (15.3 [SD, 9.6] v 15.6 [SD, 9.6]; P = 0.30) days of mechanical ventilation (4.5 [SD, 6.1] v 4.3 [SD, 5.7]; P = 0.74) days of renal replacement therapy (0.5 [SD, 2.3] v 0.4 [SD, 2.0; P = 0.41)

Simon R Finfer FRCA, FRCP, FJFICM · Neil W Boyce FRACP, PhD · Robyn N Norton PhD, MPH

An Australian model could be used to get better “evidence” into legal decision-making The UK government is reviewing 258 cases in which a parent was convicted of murder, manslaughter or infanticide. This review follows the overturning of the conviction of one mother for the murder of two of her children, and the collapse of the prosecution case against another mother accused of murdering three of her children. In addition, the cases of thousands of children spirited into care, as they were deemed to be at risk of child abuse, may also be revisited. One of the key issues in these events has been the incorrectness of evidence advanced by an expert medical witness whose estimates of the probability of the occurrence of more than one sudden infant death occurring in a family were grossly incorrect. Both in the UK and Australia, primary care is not particularly well placed to detect cases of child abuse As a consequence of all these developments, UK doctors are now apparently reluctant to sit on child protection committees. A news item in the BMJ reporting this eventually generated 38 rapid online responses, reflecting varied but always strong views on the difficulty of getting the appropriate balance between protecting the child and destroying the family. The foregoing events raise two issues — how do we get better “evidence” into legal decision-making and, realising that we may never get it completely correct, should we have a system that is inclined to accept false positives or false negatives in attribution of guilt in cases of possible child abuse? Taking the issue of evidence first, one of Australia’s better-kept secrets is its excellent system of applying evidence to compensation claims of military veterans — a model which could be adopted elsewhere. The crux of the system is an independent panel that uses sound medical–scientific evidence to determine the causation of injury, disease or death in relation to exposure to military service. Although this does not relate to individual cases, but to the generality of exposure, the success of the program and the principles by which it operates provide a model that may be adapted in other jurisdictions. The independent panel arose from a request in 1994 by the Australian government to the Repatriation Commission. The Commission was asked to prepare, in consultation with veterans’ organisations, legislation to reform the process of decision-making about the causation of disease. The purpose of the reform was to create a more equitable and consistent system for dealing with claims for disability pensions received from Australian veterans and their dependants. One of the outcomes of the legislative reform was the formation of the Repatriation Medical Authority (RMA), an independent statutory authority responsible to the Minister for Veterans’ Affairs (see <www.rma.gov.au/>). The RMA consists of a panel of five practitioners eminent in fields of medical science. Their role is to determine “statements of principles” for any disease, injury or death that could be related to military service, based on sound medical–scientific evidence. The statements of principles state the factors that “must” or “must as a minimum” exist to cause a particular kind of disease, injury or death. The statements of principles also identify what constitutes “sound medical–scientific evidence” for the purpose of applying the relevant standards of proof relating to particular kinds of injury, disease or death affecting veterans: the “reasonable hypothesis” standard and the “reasonable satisfaction” (or “balance of probabilities”) standard. In its modern guise, epidemiology makes attribution of causation a rigorous process, with clear principles to be followed, and there can even be different levels of proof required for decisions from the same database. Acquiring these skills is quite different from the experience of clinical practice and significantly changes the definition of the traditional “expert witness”. The RMA has been externally reviewed and shown to make consistent decisions at its prescribed standards of proof. With such consistency in establishing causal decisions, all plaintiffs can be assured of a standardised level of judgement that does not vary from one expert witness to another. Such a system would not have allowed the error in assigning probabilities that occurred after the deaths of children in the UK. Having mentioned epidemiology, let’s move to the question of false positives or false negatives. Set the bar of suspicion too high, and child abuse will go unpunished. Set it too low, and there will be false accusations, imprisonment and family break-ups. What would be the epidemiological approach to this? First, there is a pressing need for better diagnostic tests. Are social workers and paediatricians trained well enough to identify and differentiate between real and alleged child abuse? Does this training identify the importance of pretest probability (the prevalence) and its influence on false positives and false negatives? While the training should include the relevant clinical, psychosocial, ethical and legal domains, there needs to be some good old-fashioned clinical epidemiology thrown in, to demonstrate that, in situations of low prevalence (as is usually the case with child abuse), the predictive value of a “positive” test is low. Paediatricians, social workers and primary care teams should receive more formal training and undergo some kind of accreditation and review process. Both in the UK and Australia, primary care is not particularly well placed to detect cases of child abuse or early warning signs of infanticide, and there are lost opportunities. Second, can we improve systems for reporting or our monitoring and evaluating services? An overhaul of current processes, development of less cumbersome reporting procedures, and better resourcing, as well as incentives for people to do this work, would be a start. In all this, the role of the media and various lobby groups in whipping up public concern cannot be forgotten — objectivity is difficult enough to achieve without these pressures. There is an obsession with identification and demonisation of paedophilia in Britain, fuelled by the tabloid press with its unhelpful, brutalising effect on complex social issues. But is child abuse less common in Australia? Are the media more, or less, responsible? Are paediatricians and social workers better trained? The Repatriation Medical Authority certainly sets a good example, which could be followed both within Australia and elsewhere for reducing the variability of expert opinion in possible child abuse and other medicolegal cases. Adopting this model in the UK may reduce the uncertainty surrounding child abuse that has transfixed the medical and general community here.

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

Harm-reduction approaches are more easily embedded in policy when drugs are legally regulated “Harm reduction” in relation to drugs refers to policies and practices intended primarily to reduce the health, social and economic costs of mood-altering drugs without necessarily restricting their consumption. The recognition of AIDS in 1981, and the subsequent realisation of the magnitude of the threat of HIV spread among and from injecting drug users, has given increasing prominence to harm-reduction approaches. The 15th International Conference on the Reduction of Drug Related Harm was held in Melbourne from 20 to 24 April 2004. This is the third time this conference has been held in Australia, an indication of Australia’s leadership position in this field for nearly two decades. The goal of the conference is to bring together people representing the diverse aspects of harm reduction, and the conference’s theme was “Minimising the harm: maximising the impact”. As a reflection of the growing strength of the harm-reduction movement worldwide, the conference attracted over 1100 delegates from more than 40 countries. Delegates included researchers, clinicians, policy makers, law-enforcement officers, politicians, past and present drug users and private industry representatives. Cross-sectoral and interdisciplinary discussions and networking were a major feature of the conference. The 875 papers presented (including 450 posters) covered a diverse range of topics (see Box) and encompassed a wide range of approaches, including sophisticated science, complex policy analysis and activism. Research methods varied from quantitative epidemiology, qualitative ethnography, randomised clinical trials to economic analyses. Round-table discussion and other interactive forums were common, and the conference included the first international festival of films about drugs and harm reduction. Legal drugs (alcohol and tobacco), which account for 4% of the global burden of illness, were the subject of only 10% of papers, compared with illicit drugs, which account for 0.8% of the global burden of illness, but to which almost 90% of papers were devoted. This reflects the reality that harm-reduction approaches are much more easily embedded in policy when drugs are legally regulated. Public health and human rightsPublic health was the major framework for many conference speakers, who saw harm-reduction approaches as essential for improving the health status of drug users and their communities. Other speakers emphasised the important links between human rights and public health. This aspect dominated many discussions of HIV prevention among injecting drug users in countries where this population is savagely discriminated against and driven underground, reducing substantially the effectiveness of health and social interventions. Harm-reduction tensionsA fertile debate centred on the relationship between harm reduction and demand reduction. For some speakers, preventing drug use sat uncomfortably with harm reduction, while many others saw no conflict in simultaneous efforts to reduce both demand and harm. The observation that “what works in drug policy is unpopular and what’s popular doesn’t work” struck a chord with delegates from many countries familiar with official denigration of evidence-based interventions, such as needle and syringe and methadone programs, and the zealous promotion of law-enforcement efforts to restrict drug supply, notwithstanding limited evidence of benefit. A second area of controversy is in the relationship between harm-reduction and law-enforcement approaches. An important paper by Peter Reuter (School of Public Affairs and Department of Criminology, University of Maryland, USA), a world expert on organised crime and the impact of drug policy, concluded that there was “no evidence to support law enforcement efforts” to curtail the availability of illicit drugs. Two senior Russian law-enforcement representatives demonstrated for delegates — somewhat unintentionally — the conflict around harm reduction within conservative law-enforcement ranks in Russia, and the difficulties of establishing effective drug policy and HIV prevention in environments where authorities rely almost entirely on harsh law-enforcement measures to control illicit drugs. The first representative called for tougher measures against drug traffickers, and said that, although Russia needed harm reduction, its introduction was impossible because it was illegal. His colleague counselled “methadone is a therapy of despair . . . like a death sentence”. Attending delegates strongly refuted the claims, with representatives from the Central Eastern European harm-reduction network pointing to the lawful establishment of needle and syringe programs in Russia. Other papers emphasised the now extensive research evidence supporting methadone maintenance and needle and syringe programs as highly effective harm-reduction strategies. For example, new data were presented at the conference based on evidence that needle and syringe programs in Australia had meant 25 000 fewer cases of HIV and saved up to $7 billion.1 Collateral damageCollateral damage from the “War against drugs” was a popular theme, with numerous illustrations of the severe counterproductive effects of current prohibition policies. Some speakers provided ample grounds for pessimism: thousands of drug users and traffickers mysteriously murdered in Thailand in recent years after a government-inspired campaign; five million new cases of HIV infection globally in 2003; widespread and active discrimination against illicit drug users; entrenched negative attitudes opposing harm reduction among some UN organisations and in some countries and regions; and an epidemic of incarceration of drug users in many countries. Ernie Drucker (Director, Division of Public Health and Policy Research, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, USA) estimated that the introduction of the draconian Rockefeller drug laws in New York State in 1973, requiring harsh prison terms for the possession or sale of relatively small quantities of drugs, had resulted in more years of life lost than had the 2900 deaths in the attack on the World Trade Center on 11 September 2001. Positive progressSome speakers saw abundant grounds for optimism: the growing strength of the evidence base for harm reduction and rational drug policy; revolutionary recent shifts in attitudes in Central and Eastern Europe; the success of the recent decriminalisation of use and possession of all drugs in Portugal; the remarkable adoption and implementation of harm reduction in Iran; and the active involvement of law-enforcement participants in the conference, and their growing involvement in harm reduction worldwide. The scientific and policy aspects of the conference were balanced by more personal views: some speakers referred to immense personal loss from drugs, while others argued from their individual perspective for more humane attitudes towards drug users. Conference highlightsThe 2004 Annual National Rolleston Award is granted at each conference to an individual from the host country who has contributed outstandingly to harm reduction. The award perpetuates the memory of an influential English physician who, in 1926, supported the lawful provision of morphine or heroin to selected drug-dependent people if this would assist their leading “a fairly normal and useful life”. It was awarded to Mr Tony Trimingham, founder and coordinator of Family Drug Support, Sydney, for his work in support of families and friends of those affected by heroin-related deaths. There was a strong presence of Indigenous Australians and Indigenous culture throughout the conference. This reflected the enormous toll, initially from licit and more recently also from illicit, drugs on the health and wellbeing of Indigenous Australians. A presentation by Tony McCartney (Chair of the National Aboriginal Community Controlled Health Organisation) highlighted the ineffectiveness of policy, attracting considerable attention and concern from national and international delegates. However, numerous delegates praised many other aspects of Australia’s response to illicit drugs in recent decades. Another of the conference highlights was the annual Rolleston Oration. Former Australian Minister for Health, Neal Blewett (currently President of the Alcohol and Other Drugs Council of Australia), delivered the 2004 Oration. He presented a magisterial review of the almost two decades since he, as the responsible minister, oversaw the introduction of harm reduction in Australia in 1985. This shifted the emphasis of drug policy from intent to consequences, enabling the rapid introduction and vigorous expansion of measures that successfully controlled HIV infection among injecting drug users, and allowed policy makers to encompass legal as well as illegal drugs in a pragmatic policy framework. The current Indonesian Minister for Health, Dr Achmad Sujudi, made a strong call for the wide-scale introduction of harm-reduction measures in his country to stem the tide of HIV infection. Ms Marina Mahathir, President of the Malaysian AIDS Council, echoed this call, urging the adoption of effective and pragmatic, human-rights-based measures to combat AIDS in Asia. ConclusionJudging by the breadth and confidence of the discussions and presentations at the conference, harm reduction now seems to be leaving behind a phase of marginalisation and conflict and entering an era of mainstream acceptance and understanding. The conference disseminated new evidence of the effectiveness of harm-reduction approaches to drug problems, stimulated collaboration between participants from diverse backgrounds, gave new energy and confidence to harm-reduction practitioners from far and wide, and helped focus attention on how much more needs to be accomplished, especially in the global battle to contain the AIDS epidemic. Distribution of the topics of the verbal presentations at the 15th International Conference on the Reduction of Drug Related Harm.

Alison J Ritter PhD, MA(ClinPsych), MAPS · Alex D Wodak FRACP, FAFPHM, FChAM · J Nick Crofts MB BS, FAFPHM, MPH

Objective: To determine risk factors for ischaemic stroke recurrence among patients admitted to hospital for a first-ever occurrence of ischaemic stroke.Design, setting and patients: Retrospective study involving linked hospitalisation and death records. The cohort comprised 7816 people who were hospitalised for first-ever ischaemic stroke between July 1995 and December 1999 in Western Australia. Cox’s proportional hazards model was used to identify risk factors for stroke recurrence.Main outcome measures: Time to first recurrence; cumulative recurrence risk; risk factors for recurrence.Results: The median time to first stroke recurrence was 255 days. The cumulative probability of first recurrence was 5.1% (95% CI, 4.6%–5.7%) at 6 months, 8.4% (95% CI, 7.6%–9.1%) at 1 year and 19.8% (95% CI, 18.1%–21.4%) at 4 years. The risk of first recurrence was increased by advancing age (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04), Aboriginality (HR, 1.50; 95% CI, 1.02–2.22), diabetes (HR, 1.27; 95% CI, 1.07–1.51), a history of cardiac conditions (HR, 1.18; 95% CI, 1.01–1.38), post-stroke urinary incontinence (HR, 1.27; 95% CI, 1.03–1.57) and transfer to another hospital on index admission (HR, 1.26; 95% CI, 1.08–1.46). Admission at first stroke occurrence to a hospital maintaining a stroke unit reduced the risk of recurrence (HR, 0.84; 95% CI, 0.72–0.99).Conclusion: The risk factors identified in our study have implications for planning secondary prevention strategies. In particular, Aboriginality and transfer to another hospital upon admission for first-ever ischaemic stroke were important risk factors. Research into the level of compliance and access to stroke treatment by Aboriginal patients to prevent further strokes is required.

Andy H Lee PhD · Peter J Somerford BSc · Kelvin K W Yau PhD, AStat

Objectives: To investigate complementary and alternative medicine (CAM) use by patients with chronic obstructive pulmonary disease (COPD) and to explore their beliefs about CAM.Design and participants: Cross-sectional study of 173 patients with moderate to severe COPD, and indepth interviews with a purposive sample of 28 patients.Setting: Ambulatory care.Main outcome measures: Use of CAM; beliefs about the value of CAM.Results: 71 patients (41%) claimed to be using some form of CAM. Most commonly used were multivitamins and minerals, and garlic was the most commonly used herbal preparation. Patients reported that advertisements and people with prior experience of using CAM were their major sources of information. Extent of knowledge about CAM, degree of faith in CAM and personal attitudes influenced decisions to try CAM. Patients used CAM to promote general wellbeing, to counteract drug side effects, to compensate for dietary deficiencies and to ameliorate their disease. Efficacy appeared less important to users than safety. CAM practitioners were regarded as more convincing, informative, considerate and available compared with mainstream health professionals.Conclusions: Communication between patients and mainstream health professionals about CAM use could be improved by health professionals being more accepting of CAM use and having some basic knowledge about commonly used CAM preparations.

Johnson George MPharm · David C M Kong MPharm PhD · Kay Stewart BPharm(Hons), PhD · Lisa L Ioannides-Demos BPharm, PhD · Nick M Santamaria RN, PhD

Objective: To estimate Pharmaceutical Benefits Scheme (PBS) subsidies for drugs to treat smoking-related cardiovascular disease (CVD) in 2001–02, and over the period of the government’s Intergenerational Report (IGR), assuming current smoking prevalence rates and a 5% absolute reduction.Design and setting: An Australian epidemiological study, using prescribing data, aetiological fraction methodology, and IGR trends.Main outcome measures: Estimated smoking-related PBS subsidy costs in 2001–02 and predicted cumulative subsidies until 2041–42, under current and reduced smoking prevalence assumptions.Results: The PBS costs of smoking-related CVD in 2001–02 were $126 million, 9.77% of the cost of drugs for CVD and 2.96% of total PBS subsidies. The cumulative difference in these costs over the 40-year period with a 5% drop in smoking prevalence was predicted to be $4.5 billion, a 17% reduction. The saving would be $1.14 billion discounting future costs at 5% per year.Conclusions: Further investment in tobacco control interventions could curb the increasing cost of the PBS and contribute to government efforts to ensure the viability of Australia’s healthcare-financing programs. The net present value of a campaign to reduce smoking prevalence was estimated at $1 billion, with an internal rate of return of 33%.

Susan F Hurley MS, PhD · Michelle M Scollo BSc, GradDipCommHlth, CertHlthEcs · Sandra J Younie PostgradDipHealthEc · Dallas R English PhD · Maurice G Swanson BSc, MPH

The Australia–United States Free Trade Agreement (AUSFTA) contains major concessions to the US pharmaceutical industry that may undermine the egalitarian principles and operation of the Pharmaceutical Benefits Scheme (PBS) and substantially increase the costs of medicinal drugs to Australian consumers. AUSFTA’s approach to the PBS excessively emphasises the need to reward manufacturers of “innovative” new pharmaceuticals, instead of emphasising consumers’ need for equitable and ...

Ken J Harvey MB BS, FRCPA · Thomas A Faunce LLB(Hons), BMed, PhD · Buddhima Lokuge MB BS, MPH · Peter Drahos GDLP, LLM, PhD

Paget’s disease of bone is common, affecting up to 4% of Australians over the age of 55 years. The incidence of the disease and the severity of newly diagnosed cases appear to be falling, for unknown reasons. The cause of Paget’s disease is unknown, but there is a strong genetic influence. Recently, mutations in the sequestosome 1/p62 gene have been identified as a cause of familial Paget’s disease and of some apparently sporadic cases of the disease. The disease is often asymptomatic, but can cause bone pain, deformity, fracture and other complications. Paget’s disease is eminently treatable. Potent bisphosphonates such as pamidronate, alendronate and risedronate relieve symptoms and may reduce the risk of complications. The Pharmaceutical Benefits Scheme subsidises treatment only for patients with symptomatic disease. A strong case be made for also treating asymptomatic patients with involvement of long bones, vertebrae or base of skull, patients with significant osteolytic lesions, and perhaps all younger patients.

John P Walsh FRACP, PhD

The United Kingdom is currently introducing public reporting of performance information for individual cardiac surgeons. The reports will indicate whether a surgeon has an acceptable level of performance, measured by in-hospital mortality. In the United States, surgeon-specific performance data have been available for over a decade. Arguments from both safety and accountability perspectives provide strong justifications for public reporting of such data. Were Australia to adopt similar public reporting processes, we should learn from overseas experiences. Surgical associations should be actively involved in developing data standards and processes for data collection, validation, analysis and publication. Any Australian policy initiative for public reporting of individual surgeon data should be backed by a political commitment to adequate funding.

David A Neil PhD · Justin G Oakley PhD · Steve Clarke PhD

Clinical record A 32-year-old woman presented to the Royal Brisbane Hospital immediately on disembarking from a flight from Bangkok. She had a 5-day history of gastrointestinal symptoms, fever and altered mental state. She was a university graduate and had travelled for 2 months across south-east Asia before becoming unwell in Phnom Penh, Cambodia. Her illness began with mood elevation, hallucinations, muscle spasms and paraesthesiae, shortly after ingestion of a “herbal pizza”. Within 24 hours, nausea, vomiting and profuse watery diarrhoea ensued. Despite empirical treatment for bacterial gastroenteritis, symptoms progressed to lethargy with altered mental state. The patient had been taking doxycycline for malaria prophylaxis, and had been vaccinated against viral hepatitis, tetanus, poliomyelitis and typhoid. She was aware of the availability of a Japanese encephalitis vaccine, but had been advised that it was not essential. On presentation, the patient was drowsy and dehydrated, with a temperature of 38°C and tachycardia. There was peripheral leukocytosis (white cell count, 17.9 x 109 cells/L; reference range [RR], 4.0–11.0 x 109 cells/L) with dominant neutrophilia, as well as hyponatraemia, but renal function was preserved. Fever and lethargy persisted over 48 hours despite rehydration and regular paracetamol. Increasing obtundation and a fine tremor were observed. The patient complained of persistent headache, mild photophobia and neck discomfort. Her partner commented on her slow mentation, reduced concentration and personality change. Investigations for malaria, typhoid, rickettsial disease and infectious diarrhoea were all negative. Magnetic resonance imaging of the brain detected no abnormalities. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis (white cell count, 12 x 106 cells/L; 92% mononuclear cells [RR, < 5 x 106 mononuclears/L]), with mild elevation of protein level (0.62 g/L [RR, <0.45 g/L]), but was negative for herpes simplex virus by polymerase chain reaction. Flavivirus-specific IgM was detected in CSF and subsequently blood. The diagnosis of Japanese encephalitis was confirmed by a rise in titre of specific IgG in blood, from 80 (8 days after onset of illness) to 1280 (4 weeks after onset). The fever resolved spontaneously by Day 4 after presentation, and the patient was discharged after 10 days. At the time of discharge, her level of alertness had improved, but global impairment of higher cognitive functioning and tremor persisted. After a period of convalescence of approximately 5 months, during which she was cared for by her partner, the patient was able to return to work. Japanese encephalitis is the leading cause of viral encephalitis in Asia, with recent epidemics in India, Malaysia and Nepal.1 An outbreak of Japanese encephalitis in the Torres Strait Islands and the northern extremity of Cape York in March 19952 raised concern that this arbovirus may become established in feral pigs in northern Australia. Although the overwhelming majority of infections are asymptomatic, the case-fatality rate of symptomatic infection is 25%–30%, with neuropsychiatric sequelae seen in 30%–50% of survivors.3 The incubation period ranges from 4 to 21 days. The earliest symptoms are lethargy, high fever, headache and gastrointestinal symptoms.4 Japanese encephalitis should therefore be considered among unwell travellers returning from endemic areas, including those with undifferentiated fever.4 Blood and CSF are positive for flavivirus antibodies by 10 days after symptom onset. Specific IgM antibody may appear earlier in the CSF. Treatment is symptomatic. A vaccine is available for Japanese encephalitis and is administered as three doses over 30 days, at a material cost of over $300. Vaccination is recommended for: Travellers spending at least one month in rural areas of Asia or the Western Province of Papua New Guinea, particularly during the wet season, or if there is considerable outdoor activity, or suboptimal accommodation. It is possible that this recommendation will be expanded to include all areas of Papua New Guinea.5,6 Travellers spending a year or longer in Asia (except Singapore), even if lifestyle is predominantly urban.7 All permanent residents of the outer Torres Strait Islands over the age of 1 year and all non-residents who will be living in the region for 30 or more days during the wet season (December–May). Vaccine uptake among travellers in whom it should be considered has been hindered by the cost of the vaccine, and by occasional reports of delayed and (rarely) life-threatening adverse reactions.8 Overall, local injection-site reactions occur in about 20% of recipients. Systemic reactions, such as fever, rash, myalgia and gastrointestinal symptoms, are seen in about half that number.9 A new live, attenuated vaccine that allows a simpler administration regimen and is likely to produce fewer of these adverse reactions than the current vaccine is undergoing Phase II testing.10 Statistics on vaccine use include military personnel and residents of northern Cape York and the Torres Strait Islands, who receive free vaccinations under the Queensland Government Vaccination Programme. Separate statistics on vaccine use by travellers are unavailable. Adventure travel is popular among Australians. Uncertainty about disease risks and the financial burden of vaccination and antimalarial prophylaxis combine to make pre-travel counselling a challenge. This case of a rare vaccine-preventable infection with a potentially devastating outcome exemplifies these issues. As an efficacious vaccine for Japanese encephalitis is available, it should be considered for all at-risk travellers. This case also highlights the need to emphasise mosquito avoidance in pre-travel counselling, and to consider a broad differential diagnosis in unwell returning travellers. Lessons from practice Japanese encephalitis is a potentially devastating illness; it can be fatal and can have permanent neurological effects in survivors. Vaccination is indicated for many Australians who seek pre-travel counselling; they should be counselled about their risk of contracting Japanese encephalitis and the benefits of the vaccine. Mosquito avoidance is a key message in pre-travel counselling. Japanese encephalitis may present as an undifferentiated fever; gastrointestinal symptoms may be prominent.

Catherine M Geraghty MB BS · James S McCarthy FRACP, MD

Patients want doctors who are competent, respectful, honest and able to communicate with them. That is patient-centred professionalism. Professional self-regulation, as practised hitherto, has failed to achieve this for all patients. In the United Kingdom, a new way of looking at professional regulation has been developed — as a partnership between public and doctors. At its heart is a code of good practice, agreed between public and profession, in which doctors’ licence to practise is conditional on regularly demonstrating continuing compliance. That means revalidation–relicensure.

Donald H Irvine CBE, MD, FRCGP

Some knowledge of complementary and alternative medicine is essential if we are to support patients in making healthcare choices Complementary medicine use is increasing in Australia and other developed countries, with nearly 50% of Australians taking a complementary therapy in any one year and an increasing number of doctors prescribing these forms of treatment.1 With this widespread use, it seems rational for the medical practitioners of tomorrow to be provided with some knowledge of complementary therapies, particularly from an evidence-based perspective.2 There is also significant interest from students and recent graduates in training in this topic.3 The article by Owen and Lewith in this issue of the Journal (page 276) outlines experience in CAM teaching within one of the newer medical schools in the United Kingdom (Southampton).4 It points out that CAM familiarisation courses are relatively new, but do provide students with a knowledge of complementary therapies and the ability to discuss these with their patients. The use of specific learning objectives provides a rational approach to learning and gives students a benchmark for what they need to know. It would seem that the teaching of CAM familiarisation in Australian medical schools is still varied. A recent review conducted specifically for this series suggests that there are few dedicated CAM familiarisation courses in Australian medical schools (Associate Professor Alan Bensoussan, Director, Centre for Complementary Medicine Research, University of Western Sydney, personal communication). Some Australian medical schools are in the process of revising their curricula, with several considering the addition of a CAM component. CAM may be taught as an independent elective, within another unit such as “society, health and health psychology”, or in the teaching of ethics. Major training programs for complementary medicine practitioners in Australia are run by universities which do not have medical schools, so expertise in CAM usually has to be brought into the medical schools from outside their universities. The Australian Medical Council (AMC) produced a position statement, endorsed in July 2000, which reviewed the status of CAM courses in Australia.5 It reported that at least 16 degree courses in “unorthodox” practices were offered at a university level, in addition to courses at colleges of technical and further education and through independent training providers. It is unfortunate that, in the title of the position statement, the term “unorthodox” was used rather than the more commonly accepted term “complementary”. The position statement actually goes to great lengths to justify its use of this word, saying that it is non-mainstream health practices that should be referred to as “unorthodox”. Given that “mainstream,” according to the , refers to “the prevailing trend of opinion, fashion, etc”, the fact that over 50% of the population use alternative treatments suggests that the AMC has taken the viewpoint of the profession rather than the patient. Not surprising, perhaps, but we should remember that the healthcare system is supposed to work for patients as well as doctors. The AMC document does, however, provide a list of objectives relating to knowledge and understanding of complementary therapies and encourages medical schools to devise teaching and learning strategies that address these.5 It points out that “unorthodox practices that can be demonstrated by the methodology of evidence-based medicine to be efficacious become orthodox by definition, even if the scientific basis of their efficacy is not understood”, and that medical graduates “need to have some knowledge of the range of unorthodox practices, the needs they meet, their effectiveness and safety, the extent of their use and their costs”.5 It also points out that Medical Board “guidelines” encourage doctors to present all the information available to allow patients to make informed choices about their management. In terms of skills that should be gained by medical students, the position paper focuses on the importance of history taking, which should include any use of complementary therapies. It should be appreciated that the Cochrane electronic library currently houses more than 80 CAM-related full-text systematic reviews and about 5000 CAM-related clinical trials and that these should be used as a teaching resource.6 Of singular importance in teaching students about CAM is that they are given a broad view of the strengths and weaknesses of CAM therapies, and how to assess their efficacy. These principles are no different to those of the approach to medicine in general. Practitioners of today and tomorrow must appreciate that patients may choose to use CAM therapies and that we are there to assist them in making those choices.

Peter M Brooks MD, FRACP

As the use of CAM grows, CAM familiarisation offers educational opportunities for undergraduates to understand CAM, their attitudes to medical change and the process of evidence-based medicine. Such courses also offer the opportunity to integrate patient care and improve the relationship between medical and CAM practitioners. CAM familiarisation courses are available in many medical schools in the United States and the United Kingdom. The multiprofessional model which we have developed at the University of Southampton (UK) offers valuable experience to those thinking of establishing such courses.

David Owen MRCS, LRCP, FFHOM · George T Lewith DM, FRCP

A 28-year-old woman presented with a 3-month history of wrist and ankle pain, lethargy and weight loss. She had clubbing of the fingers (Box 1) and toes. A bone scan (Box 2) and chest x-ray (Box 3) revealed periostosis in the wrists and pulmonary metastases, respectively. Two years earlier she had been diagnosed with a malignant phyllodes tumour of the left breast (Box 4), which was treated by mastectomy and axillary dissection. Hypertrophic osteoarthropathy (HOA) secondary to pulmonary metastatic phyllodes tumour was diagnosed. HOA is a paraneoplastic syndrome characterised by digital clubbing, polyarthralgia and periostosis.1 The joint pain, resistant to non-opiate and opiate analgesia, responded to intravenous pamidronate. There was no tumour response to chemotherapy with adriamycin and ifosfamide. Phyllodes tumours are fibroepithelial lesions arising from intralobular breast stroma. They account for less than 1% of breast neoplasms. Treatment is by surgical resection. About 20% of patients with phyllodes tumours develop distant metastases, and long-term survival in these women is rare.2 1 Digital clubbing The distal portions of the fingers show characteristic thickening. 2 Wrist views from whole-body bone scan Note the symmetrical increased radioisotope uptake (arrows) in the periosteum of the distal radius and ulna. 3 Chest x-ray Multiple “cannon ball” pulmonary metastases are present (arrows). 4 Histopathological specimen from mastectomy A malignant phyllodes tumour with a sarcomatous stromal component is present (arrows) (haematoxylin – eosin stain, x 12.5)

Fiona J Collinson MB ChB, MRCP · A Michael Bilous MA, MB ChB, FRCPA · Richard F Kefford MB BS, FRACP, PhD

First used in 1967, the drug levodopa has rescued many patients with Parkinson’s disease from silence, rigidity and tremor. Parkinson’s disease is called an extrapyramidal disorder. It results from damage to black brain cells aggregated beside the pyramid-shaped tracts of motor nerves. Stephen Leeder, 26 February 2004

Stephen R Leeder AO PhD, FRACP

Joshua P Hanson,* Carmel T Taylor,† Ann R Richards,‡ Ina L Smith,§ Craig S Boutlis¶ *Registrar, ¶ Physician, Cairns Base Hospital, PO Box 902, Cairns, QLD 4870; † Scientist, § Research and Development Coordinator, Public Health Virology, Queensland Health Scientific Services; ‡ Public Health Nurse, Tropical Public Health Unit, Cairns, QLD. joshua_hansonAThealth.qld.gov.au To the Editor: The Japanese encephalitis flavivirus is the most common cause of encephalitis in Asia. Death occurs in 25% of clinical cases, and permanent neurological deficits occur in up to 50% of survivors.1 Infection is transmitted from amplifying hosts (primarily waterbirds and pigs) by Culex mosquitoes. Although the virus has been isolated in the Western Province of Papua New Guinea,2 and clinical cases have been described in the Western Province and suspected in the Milne Bay region,3 to our knowledge cases have not been reported from around Port Moresby. In January 2004, a 66-year-old man of European background was evacuated to our hospital with a 7-day history of fever and confusion. On examination, he had generalised upper motor neurone signs and a Glasgow coma score fluctuating between 6 and 10. Computed tomography and magnetic resonance imaging showed multiple non-specific white-matter lesions bilaterally. An electroencephalogram (EEG) demonstrated diffuse slowing in the delta to theta range in both hemispheres, with preserved response to painful stimulation. Lumbar puncture showed clear cerebrospinal fluid (CSF), with a leukocyte count of 65 × 106 cells/L (81% mononuclear) (reference range [RR], < 5 × 106 cells/L), normal erythrocyte count, raised protein level of 0.79 g/L (RR, 150–500 mg/L); glucose level of 4.3 mmol/L (RR, 2.8–4.0 mmol/L) and negative bacterial and fungal cultures. The CSF was also negative for cryptococcal antigen and by polymerase chain reaction (PCR) testing for enterovirus and herpes simplex, Japanese encephalitis, Murray Valley encephalitis and Kunjin viruses. Serological tests were negative for syphilis and human immunodeficiency virus infection. Paired sera from Days 2 and 19 of admission were tested in parallel against a panel of flaviviruses using a haemagglutination inhibition assay.4 This showed fourfold rises in antibody titre against dengue virus serotypes 1, 3 and 4, and Japanese encephalitis, Murray Valley encephalitis, Kunjin, Alfuy and Kokobera viruses, and twofold rises in titre against dengue virus serotype 2 and Stratford virus. Overall, these results were diagnostic of recent flavivirus infection but were non-specific. IgM antibody responses to the same flaviviruses were measured in sera and CSF using an in-house enzyme-linked immunosorbent assay (ELISA), with strongest reactivity demonstrated to Japanese encephalitis virus (Box). The patient had lived in Papua New Guinea since 1970, predominantly on a church-run farm at Bootless Bay, about 20 km from Port Moresby. He had not travelled outside this region in the month before his illness, and had no history of Japanese encephalitis vaccination or of dengue fever. The farm was situated about 150 metres from a piggery. The patient had no direct contact with this piggery. His accommodation was poorly screened against mosquitoes. After 3 weeks of primarily supportive intensive care, the patient was discharged to a general ward. His neurological recovery was slow. After 5 months, he was able to walk with assistance and required a tracheostomy to protect his airway. He was judged likely to experience permanent neurological deficits. The clinical, epidemiological, radiological, EEG and serological features of this case strongly support a diagnosis of Japanese encephalitis. Japanese encephalitis virus is difficult to detect in CSF by isolation or PCR because of neutralising antibodies and the limited duration of viraemia, which may have accounted for the negative PCR result in this case, despite the use of a highly sensitive method.5 This case highlights the desirability of further defining the epidemiology of Japanese encephalitis in the Port Moresby region, as well as reconsidering the current recommendation to vaccinate Australians only if they intend travelling to the Western Province of Papua New Guinea.1 IgM antibody levels, measured against a panel of flaviviruses by enzyme-linked immunosorbent assay (ELISA) JE = Japanese encephalitis. MVE = Murray Valley encephalitis. * IgM levels were measured as the P/N (positive/negative) ratio (ratio of the absorbance of the test sample to the absorbance of a negative control sample tested against the same antigen).

Joshua P Hanson · Carmel T Taylor · Ann R Richards · Ina L Smith · Craig S Boutlis

To the Editor: The Australian Technical Advisory Group on Immunisation (ATAGI) is responsible for maintaining and updating the Australian immunisation handbook, on behalf of the National Health and Medical Research Council (NHMRC).1 At its 25th meeting, in April 2004, ATAGI discussed data (then unpublished) presented by Hanson and colleagues on evidence for the spread of Japanese encephalitis virus beyond the Western Province of Papua New Guinea to the Port Moresby region.2 ATAGI believes it is probable the virus has spread to other parts of Papua New Guinea. The current (8th) edition of The Australian immunisation handbook states on page 179: “Current understanding of the ecology of the JE [Japanese encephalitis] virus elsewhere in Papua New Guinea is fragmentary and unsubstantiated. Therefore no definitive recommendations about JE vaccination for travellers to other parts of Papua New Guinea can be made at the current time.” ATAGI agreed that the evidence provided by Hanson and colleagues was compelling, and sufficient to warrant expanding the current recommendation for Japanese encephalitis vaccination. ATAGI is proposing the recommendation be changed to include travellers staying more than one month in all parts of Papua New Guinea, not just those planning to stay in the Western Province. A public consultation process to change this recommendation is being conducted as part of the requirements of the NHMRC Act 1992. A public consultation paper is available from the Immunise Australia Program website (www.immunise.health.gov.au). Submissions close on 17 September and can be directed to Ms Letitia Toms, Assistant Director, Immunisation Section, Department of Health and Ageing, MDP 14, GPO Box 9848, Canberra, ACT 2601 (letitia.tomsAThealth.gov.au).

on behalf of the Australian Technical Advisory Group on Immunisation (ATAGI)

Darryl J Hodgkinson Director, Cosmetic and Restorative Surgery Clinic, Double Bay Day Surgery, 20 Manning Road, Double Bay, Sydney, NSW 2028. dr_hodgkinsonATbigpond.com To the Editor: I would like to congratulate Peters et al on their strong stance against elective surgery in patients who smoke.1 The plastic surgery community became aware in the last two decades of the problems of healing in smokers. When patients claimed that they gave up cigarette smoking before surgery, we often found that the serum cotinine levels on testing were elevated, indicating that they had not given up smoking. Patients who are smokers and who develop a healing complication, in breast reduction, mastopexy, abdominoplasty or a facelift, often attribute the complication to the surgical technique rather than their own habit. Many of these patients have gone on to litigate successfully. Voracious plaintiff lawyers attribute only a small amount of blame to the patient whose smoking has, in fact, contributed significantly to their complication. In our plastic surgery practice, we have a non-smoking policy, and my malpractice insurer will not cover me for patients on whom I operate and who develop a complication associated with smoking. Hence, all patients who are smokers who wish to have elective surgery are referred to a smoking-cessation program and have to have given up smoking for at least 2 to 4 weeks before surgery. I prefer not to operate on smokers at all, as serum cotinine tests often confirm that their cessation attempt has been incomplete. In the United States, where patients pay for their own health insurance, their premiums are adjusted for lifestyle. In Virginia, in the 1990s, a “Healthy Virginian policy” existed where premiums were reduced for non-smokers. My suggestion would be that the Medicare levy also be either reduced for individuals who do not smoke or increased for those who do.

Darryl J Hodgkinson

Nicholas A Tonti-Filippini Medical Ethicist, 15 Alburnum Crescent, Lower Templestowe, VIC 3107. ntf-dslATkeypoint.com.au To the Editor: Some time ago, I was approached by a general practitioner who had been trying for more than 12 months to arrange surgery for a patient who was suffering from intermittent claudication. The indications for surgery seemed compelling. The man was in great pain and disabled by the condition. The vascular unit at a major metropolitan hospital refused to operate on him while he remained a smoker. The man had been an alcoholic, but had managed to beat that addiction and had been “dry” for the entire 12 months. With the patient’s permission, and at the request of the GP, I contacted the surgeon. The surgeon explained to me that his refusal to provide elective surgery was on the grounds that the patient smoked, which would increase recovery time and the risk of complications. After discussion of the ethical and legal situation, an early appointment for surgery was arranged with the patient. Peters and colleagues, authors of a recent editorial on smoking cessation and elective surgery,1 would do well to attend to the terms of the Commonwealth Disability Discrimination Act 1992. It is unlawful for a person who provides services, or makes facilities available, to discriminate against another person on the grounds of the other person’s disability. It seems legitimate to consider the effects of smoking on success rates as part of deciding whether elective surgery is likely to be safe and effective for an individual patient. However, the editorial suggests that patients be denied surgery, such as joint reconstruction, as a resource-allocation decision, even if the surgery would be in their interests. It is important that smoking is recognised as an addiction. Some groups, such as the mentally ill, are particularly prone to it. A study by the Harvard medical school found that people with mental illness are twice as likely to be smokers, and nearly 45% of all smokers in the United States are people with a “mental disorder”.2 To the extent that it is an addiction, smoking needs to be considered as a medical condition in much the same way as alcoholism is referred to as a medical condition. A doctor who did not provide a needed treatment to a smoker on the grounds that the patient was a smoker would be in violation of that person’s fundamental human right to healthcare and his or her right not to be discriminated against because of a disability. In fact, the doctor would be in breach not only of the Hippocratic oath, but of the Australian Medical Association’s Code of Ethics 2004,3 which states “. . . refrain from denying treatment to your patient because of a judgement based on discrimination”.

Nicholas A Tonti-Filippini

Matthew J Peters,* Lucy C Morgan,† Laurence Gluch‡ *Head, Department of Thoracic Medicine, †Thoracic Physician, ‡ Surgeon, Department of Breast and Endocrine Surgery, Concord Repatriation General Hospital, Hospital Road, Concord, NSW 2137. matthew.petersATcs.nsw.gov.au In reply: The rigid way in which Hodgkinson has addressed risk reduction in plastic surgery seems reasonable, as long as there is open disclosure and access to smoking-cessation services is assured. It is an unfortunate fact that our healthcare system cannot provide everyone with what they want, or need, in a clinically appropriate timeframe. Resources are finite. In his own case example, and without considering the legal or ethical basis of his intervention, once Tonti-Filippini arranged for a patient at high risk of complications to have surgery, someone else was immediately prevented from having hospital care that was necessary for them. If complications developed, extending hospital stay, more than one patient might have been adversely affected. Let me extend Tonti-Filippini’s case a little and imagine that a similar patient with peripheral vascular disease who was moved further down the vascular surgery waiting list as a result of the smoker’s surgery being expedited was an ex-smoker who had taken advice and ceased smoking to reduce risks and improve the surgical outcome. Then, in the period of surgical delay, the affected leg became acutely ischaemic and amputation (rather than vascular reconstruction) was required. Are there not ethical implications that follow? Reading more deeply into the Australian Medical Association’s Code of Ethics, one finds that we should work to increase standards and the quality of and access to medical services in the community, and make available our special knowledge and skills to assist those responsible for allocating healthcare resources. These are important obligations. Most smokers are addicted, and this is a medical problem that needs to be consistently identified and addressed; the issue of smokers with mental illness was highlighted in the editorial. If a clinical decision is made not to perform surgery in the context of continued smoking, it is not made because the person is a smoker, or because they have an addiction, but because the ongoing smoking has major, adverse consequences that we are unwise to ignore. The distinction is subtle but important.

Matthew J Peters · Lucy C Morgan · Laurence Gluch

Jessica H Ford,* Annette J Dobson† * Research Assistant, † Professor of Biostatistics, School of Population Health, University of Queensland, Herston Road, Herston, QLD 4006. A. DobsonATsph.uq.edu.au To the Editor: Helping pregnant women to stop smoking and not to resume after their baby is born is a key target for smoking prevention. Pregnancy (or trying to become pregnant) is a time when women are motivated to stop smoking for the sake of the baby and they are in contact with healthcare professionals who can help them do so. We have calculated the impact of smoking during pregnancy in terms of deaths, hospital separations and costs to the healthcare system, and estimated the extent to which these effects could be reduced through interventions initiated by healthcare professionals as part of routine clinical contact. We considered the following conditions: pre-eclampsia (which is less common among smokers), low birthweight (including hospital costs for the mother and the baby, and infant deaths), premature rupture of membrane, spontaneous abortion, ectopic pregnancy, placenta praevia (including infant death), and sudden infant death syndrome (SIDS). We used estimates of relative risks (RRs) for these conditions for women who smoke during pregnancy (or, for ectopic pregnancy, for women who might become pregnant) from meta-analyses.1-3 We obtained data on deaths,4 hospital separations,5 and costs to the healthcare system6 for 2001–02. The prevalence of smoking among pregnant women of all ages in New South Wales since 1994 has been in the range 17% to 22%.7 The prevalence of smoking among all women of child-bearing age in 2001 was about 28%.8 From these data, we calculated attributable fractions1,2,9 for average values (using point estimates for RRs and 20% for prevalence of smoking in pregnancy) and extreme values (using the 95% confidence limits for RRs and 17% and 22% for smoking prevalence). In summary, the average number of adverse events attributable to smoking each year in Australia are: infant deaths, 78 (extreme values, 66–87); hospital separations, 6890 (extreme values, 4130–9450); costs to the healthcare system, $23 million (extreme values, $16–$29 million). A Cochrane review of behavioural (not pharmacological) interventions for stopping smoking in pregnancy showed an absolute reduction of 6% (95% CI, 4%–8%).10 Thus, if the prevalence of smoking during pregnancy were reduced from 20% to 14%, we calculate that there would be 20 fewer infant deaths, 1600 fewer hospital separations, and a saving of $5 million to the Australian healthcare system per year. (Details of the calculations can be obtained from the authors.) These gains could be realised by increasing community awareness of the risks of smoking in pregnancy and helping health professionals to use smoking prevention strategies in their routine encounters with pregnant women.

Jessica H Ford · Annette J Dobson

Adam P Morton* * Endocrinologist, Mater Hospital, South Brisbane, QLD 4101. AmortonATmater.org.au To the Editor: I appreciated the recent comprehensive review of androgen deficiency and replacement therapy in men by Handelsman and Zajac.1 I ask their opinion of the importance of obstructive sleep apnoea as a cause of secondary hypogonadism, and also of the safety of androgen replacement in men with hypogonadism who have obstructive sleep apnoea but are intolerant of continuous positive airway pressure (CPAP) treatment. In my practice, obstructive sleep apnoea is one of the most common associations, if not indeed causes, of hypogonadotropic hypogonadism. Several studies have shown that obstructive sleep apnoea is associated with secondary hypogonadism, which is partly or completely reversed by both CPAP treatment and uvulopalatopharyngoplasty.2-4 Secondary hypogonadism is also a feature of several conditions in which there is a high prevalence of obstructive sleep apnoea, including chronic spinal cord injury and cardiac failure. Of concern, studies have shown that androgen replacement may precipitate or worsen obstructive sleep apnoea.5,6 Similarly, a study of women with endogenous androgen excess caused by polycystic ovary syndrome found they were 30 times more likely to suffer from sleep-disordered breathing than control women.7 A single case report describes resolution of obstructive sleep apnoea in a non-obese woman after removal of a benign testosterone-producing ovarian tumour.8 Thus, I would value Handelsman and Zajac’s comments as to whether they consider obstructive sleep apnoea to be an important cause of secondary hypogonadism, and whether symptoms of this condition should be sought before initiating androgen replacement therapy.

Adam P Morton

David J Handelsman,* Jeffrey D Zajac† * Director, ANZAC Research Institute, Concord Hospital, Hospital Road, Concord, NSW 2139; † Head, Department of Medicine, Austin Hospital, Melbourne, VIC. djhATanzac.edu.au In reply: We thank Morton for his thoughtful comment that, in addition to monitoring for obstructive sleep apnoea precipitated by testosterone therapy, it may be worthwhile screening for this condition before starting treatment. Symptoms to be sought include daytime sleepiness and partner reports of loud and irregular snoring, especially among overweight men with large collar size. Obstructive sleep apnoea rises steeply in prevalence with age and causes mild hypogonadotropic hypogonadism, which is rectified by effective continuous positive airway pressure (CPAP) treatment.1 Obesity, depression, cardiovascular disease and other conditions that become more common with age have similar effects. Together, they contribute to the lower blood testosterone levels found in unselected older men, in whom testosterone remains an unproven treatment.2 This condition differs from classical hypogonadotropic hypogonadism caused by hypothalamic or pituitary disorders, which routinely requires lifelong testosterone replacement, and (occurring in a younger population) is rarely associated with obstructive sleep apnoea. The prevalence of obstructive sleep apnoea precipitated by testosterone treatment remains unclear. A case precipitated by injectable testosterone has been reported,3 while testosterone has potential adverse effects on sleep in older men.4 Clinical experience suggests that, among younger hypogonadal men, obstructive sleep apnoea is a rare idiosyncratic reaction to testosterone, which, like polycythaemia, may be particularly related to supraphysiological blood testosterone levels. However, the prevalence may be higher among older men. Hence, we agree that pretreatment screening is wise (rather than proven) for older men starting testosterone treatment, but is not routinely necessary for young men with classical hypogonadism.

David J Handelsman · Jeffrey D Zajac

B E Christopher Nordin,* Allan G Need† * Physician, Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA; † Head, Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, SA. christopher.nordinATimvs.sa.gov.au To the Editor: The article by Seeman and Eisman on treatment of osteoporosis1 not only neglects the pathogenesis and prevention of this condition, but also fails to appreciate the profound differences between the three main types of fragility fracture (peripheral non-hip, hip and spine). To say that adults lose bone with age because the “volume of bone resorbed is greater than the volume replaced” is a spectacular but common tautology which simply describes what would be expected from an external negative calcium balance. The common postmenopausal bone loss can generally be accounted for by the rise in calcium requirement due to a fall in calcium absorption and rise in obligatory calcium excretion.2-4 This can be corrected with hormones or compensated for with a calcium supplement, which is known to suppress bone resorption.5 In 20 trials of calcium therapy completed up to 1997, the loss of bone in 855 postmenopausal women treated with calcium was 0.3% per annum, compared with 1.0% per annum in 635 untreated control women (P < 0.001).6 In older women, this relative calcium deficiency is complicated by a decline in vitamin D status caused by reduced exposure to sunlight and progressive thinning of the skin. It has been known for 30 years that vitamin D deficiency is common in patients with hip fracture,7 for 20 years that this was also true in Australia,8 and for 12 years that vitamin D with calcium can reduce the hip fracture rate by 43% in 18 months in women in residential care.9 When it comes to established osteoporosis (the combination of low bone density with fracture), treatment needs to distinguish between the three main types of fracture referred to above. In hip fractures, surely the first priority must be to give adequate vitamin D and calcium. Most non-hip peripheral fractures occur in women with bone densities in the normal range,10 so the need for treatment is debatable unless bone turnover is very high. Vertebral fractures are a different matter. Unlike peripheral fractures, they do not “heal” in the usual sense — the deformity remains and often causes local pain and mechanical dysfunction. The recurrence rate is very high, because all the vertebrae have much the same bone density, and the osteoporotic collapse of one indicates that the others are ready to follow. This condition is notoriously difficult to manage and should almost be regarded as a medical emergency that requires full investigation — not least to exclude myeloma — and rapid, effective treatment. It is in the secondary prevention of these fractures that the remedies advocated by Seeman and Eisman probably have their main role and are most cost-effective. In fact, although the authors place great emphasis on prevalent fracture as a risk factor for further fracture, the reference they quote deals with prevalent vertebral fracture, not with prevalent non-hip peripheral fracture, where the evidence of benefit from bisphosphonates and raloxifene is very much weaker. We are arguing for much greater emphasis on the prevention of osteoporosis with adequate calcium after the menopause and adequate vitamin D in the elderly, and the use of appropriate investigation and selective treatment in the management of the condition when it is established.

B E Christopher Nordin · Allan G Need

Ego Seeman,* John A Eisman† * Professor of Medicine and Endocrinologist, Austin Hospital, Studley Road, Heidelberg, VIC 3084. † Professor of Medicine, and Director, Bone and Mineral Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, NSW. egosATunimelb.edu.au In reply: Our article concerned a discussion of evidence-based treatment for the prevention of osteoporotic fractures. Prevention of osteoporosis per se is important, but the approaches chosen must be evidence- based. Calcium supplementation may diminish, but not abolish, bone loss by reducing remodelling rate.1 Any association of a lifelong diet high in calcium appears to be with peak bone mass, not rates of bone loss,2 and may be attributable to differences in protein intake or physical activity. Despite opinion, meta-analysis of prospective, randomised, double-blind, placebo-controlled studies does not support a role for calcium supplementation in reducing fractures.3 Later rather than earlier intervention avoids needless exposure to treatment for large numbers of individuals at low absolute risk of fracture (ie, those who are unlikely to sustain a fracture even without treatment).4 Vitamin D is of course indicated in vitamin D deficiency. However, there is no evidence for anti-fracture efficacy of vitamin D in ambulant community dwellers.5

Ego Seeman · John A Eisman

John M N Hilton Associate Professor, Department of Pathology, University of Sydney; and Consultant in Forensic Medicine, PO Box 45, Katoomba, NSW 2780. kornhilATiinet.net.au To the Editor: Byard’s succinct dissertation on the Clark case1 omits one crucial aspect in redressing this miscarriage of justice. Without the vigorous and persistent efforts of a vocal and well directed support group, which included Mrs Clark’s legal team, their scientific and medical advisors, the Law Society of England, and her family, she would still be serving a life sentence in jail. An Australian example of the effectiveness of such a support group in combating injustice is afforded by the Lindy Chamberlain case.2 Historically, Sir Arthur Conan Doyle spearheaded the efforts — sustained over nearly 20 years — to exonerate Oscar Slater,3 an unfortunate German–Jewish immigrant to Glasgow who was condemned to death after a conviction for murder based largely on identification evidence given by one of the probable perpetrators. Slater was granted a reprieve from the death sentence at the last moment, only to serve some 17 years in a grim Scottish penitentiary. Less fortunate was Timothy Evans,4 who was convicted and hanged for murdering his wife and daughter on the evidence of one of London’s infamous mass murderers, John Christie. Evans was eventually pardoned — unfortunately, too late to save his life — largely thanks to a very active support group headed by the journalist Ludovic Kennedy. In contrast, those who lack such a support group are exemplified by Ziggy Pohl,5 who was convicted, despite rather than because of the evidence, of killing his wife in Queanbeyan, NSW. He served more than a decade in prison, only to have the true perpetrator confess after Pohl was released on parole. Byard highlights evidentiary shortcomings in one recent English case. How many other people have suffered the ignominy, distress and dire consequences of unjust convictions because they lacked the support of an individual or a group prepared to question the propriety of the conviction process?

John M N Hilton

Sukhi Chand was born on 5 May 1938 in Fiji. He came to Australia in 1957 to study medicine at the University of Sydney, and graduated in 1963. After a 2-year residency at St Vincent’s Hospital, Darlinghurst, Sukhi was a tutor in anatomy for 3 years at the University of Queensland. From 1968 to 1969, he worked at Townsville General Hospital as an orthopaedic registrar and then a general surgical registrar. In 1970, after marrying Jenny, a nursing sister at Townsville General Hospital, Sukhi went to Launceston to continue his surgical training. He gained a Fellowship of the Royal College of Surgeons, Edinburgh, in 1973 and Fellowship of the Royal Australian College of Surgeons in the following year. Sukhi returned to Townsville in 1973 and entered general surgical practice. At that time he was appointed Consultant Surgeon to the Ayr District Hospital. He continued to serve the Burdekin community in Ayr until forced to retire because of ill health. He was a member of the Rotary Club of Mundingburra, in Townsville, for many years. Sukhi was a quietly spoken, patient and thoughtful man who devoted his life to his patients and their problems. Many of them became personal friends. His skill and proficiency, bonhomie and sense of humour were greatly appreciated by his colleagues. Outside his work commitments, Sukhi enjoyed spending time with his wife and four children. He also had a keen interest in the stockmarket — after some spectacular investment successes, his advice on shares was eagerly sought by colleagues and friends. His other great love was his farm. He hand-planted a large mango farm at Crystal Creek, just north of Townsville. He delighted in watching it grow to be a productive and successful venture. A cerebral complication after cardiac stenting left Sukhi markedly restricted, and forced his retirement from practice in 1997. During his prolonged and relentless illness, Jenny cared for Sukhi at home. He died on 7 April 2004. He is survived by Jenny, Anita, Andrew, Sunita and Sonya. A Denis Campbell

A Denis Campbell

Understanding health. A determinants approach. Helen Keleher, Berni Murphy (editors). Melbourne : Oxford University Press, 2004 (xx + 361 pp). ISBN 0 19 551661 3. Most doctors in practice today graduated at a time when there were few universities, fewer medical schools and only one School of Public Health. I was looking forward to reading what academics at the “newer” Deakin University in Victoria were going to say about public health, and I was delighted to discover that their views confirmed my own. Gone is the stuffy epidemiology of defined disease, to be replaced by discussion (and analysis) of the social and health issues that trouble our community and give angst to politicians. There are case studies of individuals and populations, which challenge the intellect and ethics and which, in turn, become the wellspring for wanting to know and understand more. Good health results from intersecting systems involving individuals and populations, and their beliefs and values. So while health status has to be measured objectively, there are perspectives from other disciplines such as anthropology, psychology and sociology that can be brought together with the clinical disciplines, to understand the many predicaments in health. These range from physical illness and disablement and the effects of ageing, to the massive burdens of substance use, mental illness and suicide risk, and the evolving threats from the environment — all of which can be better understood if the data and information are up-to-date. How this is all put together and evaluated is the next challenge. The framework used in this book is health promotion, an approach that could be easily dismissed as mere health education. But the authors show that this is the only way to construct a reasoned public health response in modern societies. This demands new forms of evidence and evaluation, which must span education, criminal justice and social policy as well as care — evidence not so readily found in the application of evidence-based medicine. The authors have done an excellent job of encapsulating these issues and more within contemporary Australian and international data. This book is only a first step for exploration, and throughout there are pointers to websites and current data sources for the reader and student to follow-up. If this is the “new public health”, it makes a lot of sense to me. Ian W WebsterEmeritus Professor of Public Health and Community Medicine Sydney, NSW

Ian W Webster

Power of one more How many doctors does a two-doctor town need? The answer isn’t two, but three — one more than an "efficient" health service might dictate. So says Dr Paul Worley, an Australian rural medicine expert, who believes that perpetually "lean" systems can only end up in crisis, for both town and doctors alike. Further, important matters like preventive medicine cannot be attended to because they are deemed "non-urgent", and the consequences of this coping strategy will come home to haunt future generations. Dr Worley believes the solution to the rural workforce problem lies in setting higher workforce targets and to meeting these not by continuing the "intellectual pillage" of other nations but rather by training more of our own health professionals. Rural and Remote Health 4 (online) 2004: 317 Available from http://rrh.deakin.edu.au How did I get it, doctor? The exact mode of spread of Helicobacter pylori is still unknown. Now, French researchers provide another piece to help complete the puzzle of this organism’s transmission. Over a one-year period, they monitored H. pylori infection status in 112 young people living in an institution for the neurologically handicapped. Using a non-invasive stool antigen test, the researchers detected that seven of the 65 residents who were initially H. pylori-negative had converted during follow-up. All seven either lived in the section of the institution, or associated with residents living in that section. This section had experienced peaks of potentially infective diarrhoea during outbreaks of gastroenteritis; in all cases, conversion occurred 3 to 11 weeks after a peak of diarrhoea. BMJ 2004; 329: 204-205 Looking for breast cancer In women at high risk of breast cancer, screening with magnetic resonance imaging (MRI) may help to pick up some cancers earlier, according to the Dutch MRI Screening Study Group. The Group conducted six-monthly clinical breast examination and yearly mammography and MRI in 1909 women with a familial or genetic predisposition to breast cancer. In an average follow up period of 2.9 years, 44 invasive cancers were detected. Compared with mammography, screening MRI was more sensitive (79.5% v 33.3%) but less specific (89.8% v 95%) in detecting invasive breast cancer. The role of ultrasound was not addressed. N Engl J Med 2004; 351: 427-437 A rash of ecstasy . . . A young man at a rave party scored more than a "high" when he took a tablet of ecstasy for the first time, according to the Australian authors of a case report. Four days later he got an itchy rash, which developed into typical guttate psoriasis. The rash cleared after 14 sessions of narrowband UVB treatment. Although the main ingredient of ecstasy is a phenylethylamine (3,4-methylenedioxymethamphetamine, [MDMA]), various other drugs are also mixed into the tablet and impurities are common, making rechallenge (to prove causation) impractical as well as illegal. Australas J Dermatol 2004; 45: 167-169 Death by 1000 arrows Although NZ doctors have benefited from a largely "no fault" medical misadventure compensation system, they may have suffered unduly as a result of their current complaints process. The process is jokingly referred to as "death by a thousand arrows", as complaints can be made and handled via multiple pathways and disciplinary processes. According to a series of surveys of doctors' opinions, this process is flawed and may have had a largely negative impact on doctors and doctor-patient relationships, without necessarily improving patient care.1 In an accompanying editorial, the NZ Health and Disability Commissioner (HDC) says that from 18 September 2004, the HDC will become the single point of entry for all complaints about patient care (except those regarding confidentiality).2 1. www.nzma.org.nz/journal/117-1198/968/ 2. www.nzma.org.nz/journal/117-1198/970/ Smoke gets in our hearts Exposure to passive smoking increases the risk of coronary artery disease (CAD), according to new results from 1978-1980 British regional heart study. In 2001-2002, stored serum samples from more than 2000 men who were non-smokers at the time of the original study were thawed, allowing their serum cotinine concentration to be assayed. Cotinine, a nicotine metabolite, is a biomarker of passive exposure to smoking. The men in the quarter with the highest concentrations of cotinine were 50%-60% more likely to have developed CAD during 20 years of follow-up than those in the lowest quarter. Study researchers said their results added to the weight of evidence suggesting that exposure to passive smoking is a public health hazard and should be minimised. BMJ 2004; 329: 200-204 Dr Ann Gregory, MJA

Ann Gregory