Volume 185 Issue 6

It is in doctors’ and the drug industry’s best interests that their interactions be openly declared There is no such thing as a free lunch. Pharmaceutical companies lavish meals, five-star travel, cash and gifts on doctors for one reason: to encourage them to prescribe their drugs. The standard retort from the medical profession is that doctors have sufficient clinical objectivity — and personal integrity — not to be so crudely swayed. Perhaps so.1 The interaction between doctors and the pharmaceutical industry was recently catapulted into the public domain by a piece of investigative journalism published in The Australian, detailing the wining and dining of doctors by the pharmaceutical giant, Roche, at an educational meeting in Sydney.2 What surprised many observers was not the revelations regarding the extent of hospitality provided by pharmaceutical companies to doctors, but the response of the Australian Medical Association (AMA). The AMA’s public stance was that pharmaceutical industry sponsorship of accommodation and restaurant meals is perfectly acceptable, that drug company sponsorship serves to “oil the wheels” of medical education, and that industry-sponsored events provide valuable opportunities for doctors “to critically question the companies’ products” and that “no patient harm comes from this practice”.2 A review of the literature, however, suggests that this is not true.3,4 The Australian Competition and Consumer Commission (ACCC) had a differing view. Following the recent release of the ACCC’s revised guidelines for disclosure of industry support, the Chairman of the ACCC noted that “Consumers should be able to have confidence that decisions made by their doctors are made solely having regard to their best interest without any potential for influence by benefits or perks”.5 Stated in these terms, the issue is not so much the pharmaceutical industry itself, but the prevention, assessment and management of conflict of interest and, more fundamentally, the importance of public trust in doctors. The moral core of medicine and the therapeutic relationship has always been expressed in terms of the possession and expression of values such as honesty, integrity, benevolence, respect, compassion, courage and trustworthiness. Trust, which in relation to health care may denote faith, commitment, respect, belief and confidence, has been the focus of extensive academic exploration by a broad range of writers.6-10 All have pointed to the centrality of trust in therapeutic relationships, the “non-legal” expression of trust, the specific and contextual nature of trust and the manner in which trust can be threatened, diminished or destroyed by actions or behaviour including professional incompetence, abuses of power, boundary violations, experience of harm or the lack of care or respect, deception and manifest conflicts of interest.11 Of those things that may damage trust in doctors, much of the attention in recent years has been on recognising and managing conflict of interest. What then constitutes a conflict of interest and how may we avoid it occurring? Although medical codes of ethics and statements of medical professionalism often give the impression that doctors have a single higher duty to care for the sick, in reality, the relationships that doctors have with their patients are determined by multiple interests, many of which may influence care or decision making. Doctors may hold patient care as their highest professional ideal, but they may also be concerned with community welfare, participation in research, career advancement, student teaching, continued employment, public or professional recognition, and the obligations they have to their care for themselves and their families. While it is inevitable that doctors will have multiple interests, true conflicts of interest (a set of conditions in which professional judgement concerning a primary interest, such as a patient’s welfare, is unduly influenced by a secondary interest, such as financial gain) are neither inevitable nor common.12 But distinguishing where there are no conflicts between these interests from where there is a genuine conflict of interest is sometimes difficult, as any assessment of behaviour must take into account the ethical standards of the profession, the nature of the relationship in question, and the values of the community within which it occurs. What makes this assessment even more difficult is that standards of doctors’ behaviour may change as a consequence of deeper sociocultural changes, and according to changes in professional interests, and changes in public or patient needs and expectations. This means that the only way to establish that a conflict of interest exists is to have all the relevant facts available for scrutiny by the participants in the relationship, and by the community or an independent third party. This is only possible if there is a genuine commitment to disclosure and transparency in all areas of medical practice. Unfortunately, a review of the history of medicine suggests that the medical profession has, until recently, generally been reluctant to be exposed to public scrutiny, either out of fear of legal or social repercussions that may result from such disclosure, or on the grounds that that there is no need for it or no public desire for it. Although such concerns may be understandable, for the most part they are unfounded. Transparency and honest disclosure may actually reduce loss of trust, formal and informal complaints and litigation, and it is the culture of secrecy and sense of moral superiority that sometimes runs through the health professions, rather than “unnecessary” exposure to a disinterested public, that threatens public trust and undermines the doctor–patient or researcher–patient relationship. In this regard, it is of note that a recent randomised trial in the United States of disclosing doctors’ financial incentives to patients found that patients’ trust in their doctors was unharmed, and their loyalty to their doctor’s practice was strengthened.13 Therefore, it is hard to disagree with the ACCC that there is merit in increasing the degree to which the relationships between doctors and the pharmaceutical industry are transparent. It may, as has been claimed, ultimately prove to be the case that these relationships do not give rise to conflicts of interest and that the ACCC’s new reporting requirements are excessive or unreasonable, but at this stage we do not know that this is true, and we have ample evidence that interaction with industry can create complex and dependent relationships and influence decision making, prescribing, formulary requests, attitudes and knowledge regarding pharmaceuticals and therapeutics, and the design and interpretation of research.14 In light of this, it is in doctors’ and the industry’s best interests that their interactions be openly declared in the relevant context. This will enable informed public and professional consideration of the legitimacy of each group’s interest and determination of whether a conflict of interest exists and what measures should be taken to deal with it. There are many means for encouraging transparency, responsibility and accountability in health care, including the incorporation of ethics in medical education; support for inquiries into professionalism and trust; introduction of templates for disclosure of secondary interests in the research and clinical setting;15 development and compliance with codes of ethics by the major medical colleges and industry groups; incorporation of patients’ representatives and conflict of interest committees into hospitals; and establishment of health care complaints commissions by government. All are deserving of support, even though currently there are insufficient data to evaluate the effect of most such interventions. Given what we know about the fragility of trust in medicine and the interaction between doctors and the pharmaceutical industry, the profession should support moves to increase disclosure. Even though disclosure may not, in itself, reduce the frequency of unethical behaviour or relationships, and may have no effect on public awareness, it is impossible to adequately identify, manage or prevent conflicts of interest if doctors, the peak bodies that represent them, and the industry groups with which they deal are not completely open about their interactions. Claims that the medical profession is not subject to influence, that the possibility of conflicts of interest arising in relationships between doctors and the pharmaceutical industry does not exist, and that disclosure requirements will lead to the collapse of continuing medical education are naïve, unfounded, inappropriate, and counterproductive. Doctors occupy a unique position of trust in society. They should act solely in the best interests of the patient — as many do. But drug companies spend billions of dollars on promotions because they work. The medical profession cannot have it both ways. If doctors want to be seen to be beyond influence, the remedy is simple. Be willing to say thanks, but no.1

Martin H N Tattersall FRCP, FRACP, MB BChir · Ian H Kerridge FRACP, FRCPA, MPhil

Strategies to close the gap between development and implementation of guidelines In the past decade, evidence-based clinical guidelines have become a major feature of health care. Researchers and clinicians in many countries have established programs to summarise the evidence for managing specific health problems and to disseminate practice guidelines. However, clinical use of guideline recommendations does not necessarily follow. Numerous studies show that recommendations are frequently not applied in practice and that many patients do not profit from evidence-based insights.1 Large variations in performance between clinicians, practices and institutions are commonly observed. Two reports in this issue of the Journal (Bryant et al and Irving et al) illustrate this well.2,3 In the first, an audit in a hospital outpatient clinic showed that large numbers of patients with diabetes do not achieve recommended treatment targets for control of glycaemia, blood pressure and lipid levels, despite evidence that control of these risk factors produces better outcomes.2 The second, a study of six Australian dialysis units, showed that, despite high levels of awareness of iron guideline recommendations in participating units, there is considerable variation in achievement of targets and widely differing practices in unit processes for iron management.3 Guidelines are expensive — the cost of producing a single guideline may range from US$50 to US$500 000, not to mention the substantial donated time from many contributors.4 Given the lack of practical impact of many clinical guidelines, a critical observer might well ask, “Why spend so much money and effort on something that is so poorly adhered to in practice?” However, the question should really be, “What can we do to increase the use of best evidence guideline recommendations?” Guideline developers, research funders, health care managers and policymakers may need to consider a few key strategies: the need for greater focus on producing guidelines in formats that promote their use; the requirement for planned (and funded) implementation programs that take into account the complexity of change in health care; and the need to improve our knowledge about cost-effective methods of achieving sustained practice changes. Worldwide, many guideline developers give little consideration to the use of their products in the real world. The reality is that guidelines are too often “lost in translation”.5 Many current programs for guideline development seem to be “science-driven”, rather than scientifically based but “customer-driven”. Guideline developers would do a far better job if they focused on the needs of the end user and provided clear statements, decision aids, patient education materials and practical tools to manage difficult problems in practice. More guidelines need to identify specific evidence-based indicators and criteria for clinical performance (as the guidelines discussed in this issue of the Journal do). These provide the capacity to monitor performance and give feedback to clinicians. Public reporting of significant aspects of care quality would help meet the urgent need in society for more transparency about important aspects of health care provision, and would provide a clear imperative to improve implementation and ensure guideline recommendations are feasible and do not become outdated. There is also a need to seek a better balance between the resources devoted to summarising evidence and developing guidelines and those spent on finding the most effective ways to improve patient care. Evidence-based guideline development reflects just one specific approach to improving care — it assumes that professionals are rational decisionmakers who will act on convincing information about the pros and cons of specific routines. Most of the time, effective change in health care demands other models, ranging from those that emphasise patient involvement in decision making to those that focus on organisational development.6 Sadly, good evidence for the cost-effectiveness of many of these strategies aiming to change practice is lacking.6-8 Greater investment by research funders in studies that would improve this knowledge base would help direct implementation resources and effort to where they could be of most use. Policymakers who seek to change health care practices need to understand that some current expectations about the impact of clinical guidelines are unrealistic. A belief that developing and disseminating systematic reviews and guidelines will improve patient care ignores the complexity of change in health care. Guidelines do not implement themselves — most need well developed, well executed and sustained implementation programs,7 and even such programs usually have only a moderate effect on performance in terms of care improvement (around 8%–10%).8 Many factors play crucial roles in blocking or stimulating relevant changes in performance. These are not only related to professional decision making, but also to patient behaviour, interaction with colleagues, team functioning, organisational conditions for change, resources, and economic or legal conditions.7,9,10 This aspect was clearly demonstrated in the renal impairment study.3 For most complex changes in health care, we need to build bridges between the different approaches to better care — guidelines, performance indicators and feedback; patient empowerment; quality management; organisational change; improving culture, teamwork and leadership in the workplace; and creating the necessary financial incentives.6 So, with a change of focus in current guideline development and more realistic expectations of the role of guidelines in improving patient care, with better knowledge about costs and effects of change strategies, and with clinical guidelines embedded in comprehensive programs for change, evidence-based guidelines for clinical practice may become more relevant in the future.

Richard Grol PhD · Heather Buchan MB ChB, MSc, FAFPHM

There is a desperate need for effective mental health services for prisoners and ex-prisoners Deinstitutionalisation in Australia has seen the number of public and private psychiatric hospital beds fall from 30 000 in the early 1960s to 8000 today. The population of Australia doubled during this time. There is no doubt that many people with serious mental illness are not being managed well in the community.1 Some mental health researchers,2-4 as well as the popular press, argue that there has been a recent related transmigration of people from psychiatric beds to remand centres (which house prisoners who have been charged with an offence but not yet convicted) and prisons. Australian remand centres often contain more seriously mentally ill people than general hospital mental health inpatient units. However, it is unclear whether the apparent rise in prevalence of mental illness among prisoners reflects a genuine increase or an improvement in detection rates. Statistical modelling of the effect of deinstitutionalisation on the number of prisoners with mental health problems is fraught with methodological challenges and the absence of longitudinal data.5 This debate has tended to overshadow other major areas of concern about mental illness among prisoners.6 As Herrman et al pointed out 15 years ago, whatever the cause, services for people with mental illness in Australian prisons are inadequate and in need of urgent reform.6 On 30 June 2005, there were 25 353 people in prisons in Australia. This represents an overall imprisonment rate of 163 per 100 000 adults, although there was considerable variation between states. The average age was 34.5 years (with 20.2% aged under 25 years); 6.8% were women; 22.2% were Indigenous people (the Indigenous imprisonment rate was 2021 per 100 000); and 60.4% had been in prison previously. In Queensland, the Department of Corrective Services estimates that the custodial population will increase by 90% over the next 10 years. Australian and New Zealand studies have shown that many people involved in the criminal justice system have had psychiatric contact before entering the system. Prevalence rates for all psychiatric morbidities in the prison population are markedly higher than rates in community samples.6-14 This is particularly evident for substance misuse, with up to 80% of remandees and prisoners dependent on alcohol, cannabis or amphetamines before entering prison.6,7,12,14 However, few published studies allow direct comparison with rates of psychiatric morbidity in community populations. Butler et al9 compared the 12-month prevalence rate for prisoners in their survey to the results of the National Survey of Mental Health and Well-Being, a community-based survey. Prevalences of psychiatric disorders in prisoners were more than double those among people living in the community (Box). Studies in remandees have found prevalences of psychotic illness, such as schizophrenia, ranging from 5.1% to 9.6%.10,13 By comparison, in the general community, the 1-month prevalence is 0.5% for psychosis and 0.3% for schizophrenia.15 Other Australian and New Zealand studies of prisoners have found prevalence rates of between 25% and 50% for non-psychotic disorders such as major depression, anxiety disorders and post-traumatic stress disorder.6,8-10,12 Ex-prisoners also have an increased relative risk of mortality. Death from all causes in some groups was found to be 17 times higher than in the general population in the 2 weeks following release.16 The main causes of excess death are associated with drug and alcohol misuse. These deaths have been cited as an indicator of the poor mental health of prisoners. The experience of release may present an additional challenge to prisoners’ mental health and wellbeing, particularly in the absence of ongoing support. Despite these high morbidity and mortality rates, treatment services for prisoners and ex-prisoners are very limited and often ineffectual. This makes little sense, even from a criminal justice perspective, as comprehensive services can delay or prevent recidivism in mentally ill offenders.17 In February 2006, the Council of Australian Governments (COAG) announced a major reform of mental health services in Australia.18 In April 2006, the Prime Minister announced the Australian Government would commit $1.8 billion over 5 years to this reform. In July 2006, COAG released a National Action Plan on Mental Health, to be supported by a total federal, state and territory government commitment of almost $4 billion over 5 years.19 While only some of the funding announced at COAG by the states and territories is new funding, there is a clear commitment by governments to improve the state of mental health services in Australia. As COAG reforms bind all government agencies, they bring with them the opportunity to improve services in all the relevant government departments in order to provide the range of health, housing and community services needed by people with mental illness. This must include improved and expanded prison mental health services, court diversion programs, and well resourced inpatient and community forensic services that link mental health, judicial and correctional services and provide specialist pre-release assessment, consultation and liaison for clinical managers. Diversion from the criminal justice system of mentally ill people who have committed minor offences is one of the few opportunities for community-based prevention. Access to stable housing and to appropriate vocational rehabilitation services is essential for functional recovery. All of these programs will need specially trained and supported mental health and custodial personnel, including psychologists, psychiatrists and specialist case managers. Adequate training of other personnel involved, such as court and police staff, is also necessary. Thus, crucial to the success of the COAG package will be necessary workforce reforms. Forensic and prison mental health services are target areas for the COAG National Action Plan. However, drafting and funding an action plan is one thing; turning good intentions and money into better services is another, much harder task. To know whether services are improving, we will need public reporting of specific performance indicators, which are currently being developed. In time, the data may be able to tell us whether the historical deficiencies in care for people disadvantaged by both mental illness and involvement in the criminal justice system are at last being addressed. Comparative prevalence of psychiatric disorders in prisoners and in people living in the community9 Prevalence Disorder In prisoners In community Any psychiatric disorder 80% 31% Psychosis 7% 0.7% Affective disorder 23% 9% Anxiety disorder 38% 11% Substance abuse disorder 66% 18% Personality disorder 43% 9%

Paul White MB BS, FRANZCP · Harvey Whiteford MB BS, MPH, FRANZCP

Current data are encouraging, but no reason for complacency Since 1997, when the number of Australians committing suicide peaked at 2720, there has been a sustained reduction in the number of suicides each year. The most recently available figure — 2098 suicides in 20041 — represents an age-standardised suicide rate of 10.4 per 100 000 population, 29% lower than the rate of 14.7 per 100 000 in 1997. The figures are even more striking for people aged 15–24 years, for whom there was a reduction in suicide rates of about 50% — from 19.3 to 9.6 per 100 000 between 1997 and 2004.1 These figures have not achieved the media publicity that they warrant. Although suicide accounts for only 1.6% of all deaths in Australia, it comprises more than 20% of deaths for men aged between 20 and 39 years, and men remain four times more likely than women to die by suicide, with overall age-standardised rates of 16.8 and 4.3 per 100 000, respectively.1 The reduction in male and female suicide rates has been similar: 28.8% for males and 30.6% for females between 1997 and 2004.1 Remarkably, there was a reduction in all 5-year age groups for men and women between 1997 and 2004, except for women in the 45–49-years age group, for whom the rates were 7.0 and 7.1 per 100 000, respectively.1 The highest suicide rates in 1997 were for men aged 15–34 years, and in 2004 the peak was in that same group of men, now aged 25–44 years. This is consistent with a “cohort effect”, with that group carrying forward their increased propensity to suicide, a phenomenon noted previously in Australia in 1983.2 Methods of suicide have changed between 1997 and 2004, with the proportion using firearms reducing from 12.1% to 8.1%. This has been a continuing trend over the past 25 years, although it appeared to accelerate following the enactment of stricter firearms legislation after the Port Arthur massacre in 1996.3 In contrast, hanging has increased from 36.3% to 47.6%. This is of particular concern, as legislating against hanging is difficult, and it probably requires an education program to bring the dangerousness of hanging to the attention of the community. Poisoning by drugs has remained relatively constant (11.4% of suicides in 1997 compared with 10.9% in 2004). This is reassuring and is consistent with recent data, which have allayed previous concerns that use of antidepressants could be associated with suicidal behaviour.4 Naturally, there are always reservations in interpreting data of this nature. The figures are for deaths registered in each calendar year rather than the year they occurred, and about 7% of suicides over the past decade have not been registered until the year after they occurred.1 It is also possible that coronial practices and medical certification of cause of death may have changed. Notwithstanding such caveats, these most recent figures are gratifying, particularly in view of Australia-wide initiatives in the past decade to reduce suicide.5 The question arises of what may have been the reason or reasons for this reduction. The problem in determining this is that there is no clear-cut cause of suicide. Furthermore, even though suicide may seem all too frequent when it occurs, and retrospective analysis may suggest a plausible precipitant, the low base rate of suicide and ethical constraints preclude randomised controlled trials to assess the effectiveness of any one prevention program.6 Nevertheless, it can reasonably be assumed that the causes are several: better community awareness of both the antecedents of suicide and the fact that suicide prevention is possible has probably played a role, along with the provision of more accessible services. More specifically, it is likely that programs promoting better recognition and treatment of depression (the mental disorder most commonly associated with suicide) are paying dividends. That this is so is suggested by the research of Hall et al,7 who found an inverse relationship between antidepressant prescribing and suicide, and concluded: The increase in antidepressant prescribing may be a proxy marker for improved overall management of depression. If so, increased prescribing of selective serotonin reuptake inhibitors in general practice may have produced a quantifiable benefit in population mental health.7 This observation is consistent with the recent report by Ludwig and Marcotte,8 who, after analysing antidepressant use and suicide rates in 27 different countries, calculated that the rate of suicide for those 27 countries would have been 17% higher in 1999 than in 1990, but for the introduction of newer antidepressants. Although these latest Australian Bureau of Statistics data are gratifying, they are no reason for complacency, as illustrated by the increase in suicide in the Northern Territory reported by Measey et al (page 315).9 Furthermore, the general reduction in suicide rates does not negate its tragedy for the individuals and families affected. Continuing vigilance is required, with ongoing acknowledgement and acceptance of the unique role and responsibility that medical professionals, particularly general practitioners, have in identifying and treating the mental disorders, particularly depression, that are associated with suicide.

Robert D Goldney MD, FRANZCP, FRCPsych

Objective: To review the management of glycaemia, blood pressure and serum lipids in a hospital outpatient diabetes clinic, the director of which co-authored the current national diabetes management guidelines.Design: Retrospective audit.Setting: Outpatient diabetes clinic in a tertiary referral teaching hospital, Sydney, NSW.Study population: 96 patients with type 1 diabetes (mean age, 44.4 [SD, 12.8] years) and 509 patients with type 2 diabetes (mean age, 64.4 [SD, 12.0] years) attending the clinic in 2003, who had undergone formal review of complications.Main outcome measures: Weight, height, control and treatment of glycaemia, blood pressure and serum lipids, and prevalence of diabetic microvascular complications.Results: Glycated haemoglobin (HbA1c) was < 7% in 13% of type 1 and 30% of type 2 diabetes patients, and > 8% in 47% and 34%, respectively. 35% of patients with type 1 diabetes and 71% of patients with type 2 diabetes were treated with antihypertensive agents. Of these patients, 29% and 24%, respectively, had blood pressure readings ≤ 130/80 mmHg. Among patients not treated with hypertensive agents, blood pressure readings were ≤ 130/80 mmHg in 60% of type 1 and 38% of type 2 diabetes patients. About 30% of patients with type 1 diabetes and 50% of those with type 2 diabetes were being treated with lipid-lowering agents; of these, about 60% had low-density lipoprotein (LDL) cholesterol levels < 2.6 mmol/L. Among patients not treated with lipid-lowering agents, about 40% had LDL cholesterol levels < 2.6 mmol/L. Retinopathy was documented in 52% and 18%, and nephropathy in 9% and 36% of type 1 and type 2 diabetes patients, respectively.Conclusions: Despite the demonstrated benefits of tight glucose, blood pressure and lipid control in reducing the risk of macrovascular and microvascular complications in type 1 and type 2 diabetes, our results suggest that treatment targets are not being met in a large proportion of patients attending a tertiary referral hospital. Responsible practice suggests that treatment targets and the current means to achieve them should both be examined.

Wendy Bryant,* RN, CDE, GradDipDiabetesEdManagement · Jerry R Greenfield,* PhD, FRACP · Donald J Chisholm FRACP · Lesley V Campbell FRCP, FRACP

Objective: To evaluate the outcomes of and barriers to implementing standard guidelines (Caring for Australasians with renal impairment [CARI]), using iron management in patients having dialysis as an example.Design and setting: On-site review of iron management processes at six Australian dialysis units varying in size and locality. Patients’ iron indices and haemoglobin levels were obtained from the Australian and New Zealand Dialysis and Transplant Registry.Participants: Patients with chronic kidney disease who were dependent on dialysis.Main outcome measures: Processes for assessing indices of iron stores and iron supplementation; comparison with target indices in the CARI guidelines.Results: There was considerable variability among the units in achievement of haemoglobin and iron targets, with 25%–32% of patients achieving haemoglobin targets of 110–120 g/L, 30%–68% achieving ferritin targets of 300–800 μg/L, and 65%–73% achieving transferrin saturation targets of 20%–50%. Implementation barriers included lack of knowledge, lack of awareness of or trust in the CARI guideline, inability to implement the guideline, and inability to agree on a uniform unit protocol. Factors associated with achieving the CARI guideline targets included nurse-driven iron management protocols, use of an iron management decision aid, fewer nephrologists per dialysis unit, and a “proactive” (actively keeping iron levels within target range) rather than “reactive” (only reacting if iron levels are out of the range) protocol.Conclusions: Variability in achievement of iron targets, despite the availability of a clinical practice guideline, may be explained by variability in processes of care for achieving and maintaining adequate iron parameters.

Michelle J Irving MHSciEd · Jonathan C Craig MMed, PhD, FRACP · Martin Gallagher MB BS, MMEpi, FRACP · Stephen McDonald MB BS(Hons), PhD, FRACP · Kevan R Polkinghorne MB ChB, FRACP, MClinEpi · Rowan G Walker MD, MB BS, FRACP · Simon D Roger MD, FRACP

Objective: To examine trends in suicide in the Northern Territory between 1981 and 2002, and demographic and other characteristics of people completing suicide in the Top End region in 2000–2002.Design: Retrospective descriptive analysis of Australian Bureau of Statistics death registration data and data from the NT Coroner’s Office.Setting and participants: All residents of the NT who completed suicide between 1981 and 2002.Main outcome measures: Changes in the age-adjusted and age- and sex-specific rates of suicide in Indigenous and non-Indigenous NT residents over time; prior diagnosis of mental illness and use of alcohol or other drugs by those completing suicide.Results: The age-adjusted suicide rate in the NT increased significantly between 1981 and 2002 (P < 0.001). Over this period, the rates among the Indigenous and non-Indigenous male populations increased by 800% (P < 0.05) and 30% (P > 0.05), respectively. Indigenous males aged under 45 years and non-Indigenous males aged 65 years and over were most at risk. In the Top End, a history of diagnosed mental illness was present in 49% of suicide cases, and misuse of alcohol or other drugs around the time of death was associated with 72% of suicide cases.Conclusion: Our study highlights the rising rate of suicide in the NT and suggests that suicide prevention initiatives need to specifically target Indigenous and non-Indigenous males in the age groups most at risk.

Mary-Anne L Measey MPH · Shu Qin Li MPH · Robert Parker FRANZCP · Zhiqiang Wang PhD

Australia is largely self-sufficient in its supply of safe, fresh blood products because of the goodwill of non-remunerated, volunteer donors, plus rigorous testing and processing standards. CSL Limited is the sole provider of plasma fractionation services in Australia, enjoying exclusive rights under the Plasma Fractionation Agreement with the Australian Government. In the Australia–United States Free Trade Agreement (AUSFTA), Australia agreed to review its current contract with CSL Limited, and to recommend to the states and territories that the process be opened up to overseas tender. Overseas tenders for off-shore fractionation services are likely to be highly competitive due to their low manufacturing costs and accumulated expertise. Off-shore fractionation could compromise the safety of Australia’s blood supply through delays in processing and transportation, issues related to quality control, and even the siphoning of stock to overseas markets. This could compromise the long-term care of Australian patients and create a serious national security risk in the event of a terrorist attack or natural disaster. Australia’s AUSFTA obligation to recommend changes does not equate to an obligation to actually proceed. The states and territories should carefully consider whether such changes would be in our national interest. The long-term security of the Australian people in the current security environment is dependent on continuance of an on-shore fractionation plant and appropriate back-up facilities.

Hilary J Bambrick BSc, BA(Hons), PhD · Thomas A Faunce LLB(Hons), BMed, PhD · Kellie Johnston BSc(Hons), LLB(Hons)

BCG vaccination is no longer routinely offered to all medical students in Victoria. Practices in Australia’s 15 medical schools vary widely with respect to BCG vaccination and surveillance for tuberculosis (TB) infection during the medical course. Health care workers can be exposed to TB in Australian hospitals, but the risk is much higher if they undertake work in countries with a high prevalence of TB, such as during student electives. BCG vaccination is safe, cheap and protects 50% or more of recipients from active TB, including multidrug-resistant TB. Protection is long-lasting, requires only a single dose, and there is new evidence that BCG may prevent primary infections, not just active disease. Although BCG vaccination interferes with the interpretation of the tuberculin skin test (TST), newer tests (QuantiFERON-TB Gold, T-SPOT.TB) are unaffected by BCG vaccination. We propose a standard approach for all Australian medical students that includes screening with TST and QuantiFERON-TB Gold/T-SPOT.TB at course entry, and recommending BCG vaccination for students who test negative, provided they have not previously received BCG vaccine.

Maryza Graham MB BS · Tanya M Howley MB BS · Robert J Pierce MD, FRACP, FCCP · Paul D Johnson PhD, FRACP

Early adolescence is associated with high rates of experimental inhalant misuse, but only a minority continue to inhale on a regular basis. Inhalant misuse is associated with a range of adverse outcomes, including reports of increased morbidity and mortality. Research into inhalant use among adolescents is lacking, with limited data available on long-term outcomes or evidence-based approaches to treatment. Legislative and supply-reduction strategies have been introduced by a number of states and territories over recent years, but direct funding for specific targeted interventions is lacking. Investment and commitment to a national research framework, as well as coordination of local services, is urgently required.

Dan I Lubman PhD, FRANZCP, FAChAM · Leanne Hides BBehSc(Hons), PhD(Clin) · Murat Yücel BA(Hons), ClinPhD(Npsych)

Clinical record A 22-year-old male kitchen-hand presented with a 4-week history of extensive bruising and petechiae on his legs (Figure). He had no history of any medical conditions, except for several episodes of epistaxis in the past few months. He was not taking any medication, and there was no known familial bleeding tendency. On review, he had a large tense haematoma on his left leg that was restricting his mobility, and several smaller bruises in various stages of resolving, along with a palpable petechial rash on both legs (Figure inset). He was unable to recall any trauma that may have precipitated most of the bruises, but, on further questioning, believed that the rash may have been present for up to 2 years. He had no bruising elsewhere. His gums were swollen and bleeding, and oral hygiene was poor. Further examination was unremarkable. Systematic questioning revealed a long history of a poor diet comprised mainly of carbohydrates, with no vegetable or fruit intake. He smoked 10–15 cigarettes daily and episodically drank large amounts of alcohol. He lived with his girlfriend. A review of other systems showed no abnormalities. The results of initial investigations, including haemoglobin level, white cell count, and platelet count, were normal, but a blood film showed hypochromic, microcytic red cells. Liver function tests showed no abnormality; and levels of urea, electrolytes and creatinine were normal, as was prothrombin time. Activated partial thromboplastin time was increased at 39 s (reference range [RR], 26–34 s), with full correction on addition of normal plasma. Further investigations included a repeat measurement of activated partial thromboplastin time (34 s); and a test for levels of factors IX, XI and XII, which gave normal results, whereas the level of factor VIII was raised (249% [RR, 50%–150%]). A screen for lupus anticoagulant was negative, and assays for von Willebrand factor antigen and ristocetin cofactor gave normal results. The results of iron studies showed: iron, 6 μmol/L (RR, 9–27 μmol/L); transferrin, 3 g/L (RR, 2–3.6 g/L); transferrin saturation, 9% (RR, 20%–50%); and ferritin, 83 μg/L (RR, 50–150 μg/L). Finally, the level of vitamin B12 was within the normal range, serum folate level was > 45 nmol/L (RR, 12–32.7 nmol/L); and complement assays (C3, C4) gave normal results. On review 2 weeks later, a repeat blood test showed a low haemoglobin level at 72 g/L (RR, 130–185 g/L). There was no history of altered bowel habit or melaena, and the patient refused a rectal examination. Haptoglobin and lactate dehydrogenase levels were normal. Because of his iron deficiency and the possibility of significant occult blood loss, he was given a transfusion of packed red cells. The haemoglobin level remained stable after the transfusion. Further testing revealed a low level of vitamin C (3 μmol/L [RR, 26–85 μmol/L]), and he was prescribed oral vitamin C and iron supplements. Within a week, the condition of his legs was starting to improve. On review 1 month later, their appearance was almost back to normal. Patient’s left leg at presentation: extensive bruising and petechiae. Inset: perifollicular haemorrhages. Humans are one of the few mammals that cannot synthesise vitamin C (ascorbic acid). Stores are readily depleted, with studies showing clinical manifestations after about a month on a vitamin C-free diet.1 Vitamin C is absorbed by an energy-dependent, saturable transport system throughout the length of the small intestine, with any excess excreted by the kidneys. Ascorbic acid promotes the hydroxylation of proline and lysine residues in procollagen, helping to stabilise the collagen triple helix. It is the defect in collagen synthesis that produces most of the clinical manifestations. Vitamin C is particularly abundant in citrus fruit and many green vegetables. Scurvy is usually seen in mentally ill patients, people on “fad” diets, people who misuse alcohol, and, occasionally, elderly patients who live alone.2 Initial symptoms are non-specific, including weakness, anorexia, depression and lethargy. Subsequent dermatological features include broken and coiled hairs (due to abnormal keratin formation) and perifollicular haemorrhages and hyperkeratosis. Bleeding tends to be a late feature and affects spongy, friable gums as well as muscles, joints and skin. This is thought to be due to breakdown of the connective tissue within and supporting the vessel walls, rather than a platelet or clotting factor defect.3 Many patients with scurvy are anaemic, with contributing causes likely to be bleeding, altered absorption and metabolism of iron and folate,3 and other dietary deficiencies. Lessons from practice Scurvy can occur in apparently well-nourished populations, as a result of severely restricted food choices (eg, avoiding fruit and vegetables). It may be associated with other vitamin and mineral deficiencies. Bleeding is a late manifestation of scurvy. Our patient is interesting in that he does not seem to fit into the usual groups with a tendency to develop vitamin C deficiency. A full dietary history revealed a diet entirely comprised of Vegemite spread, cheese, bread, dry biscuits, chocolate and a cola drink, with no fruit or vegetables. The patient conceded that he had not tried any new foods for over 10 years, and, despite the recent diagnosis, was reluctant to initiate dietary change. Although such a limited food intake is probably uncommon, recent trends towards consumption of pre-prepared carbohydrate-rich food mean that scurvy or subclinical vitamin C deficiency and other vitamin and trace metal deficiencies should not be forgotten.

Sally J Mapp MB BS, FRACP, FRCPA · Paul B Coughlin FRACP, PhD

A 58-year-old man presented with a 1-month history of persistent nausea, vomiting, diarrhoea and fevers. He also reported worsening shortness of breath, lower extremity swelling, and a 4.5 kg weight loss. He was febrile and hypotensive, with pedal oedema and a soft diastolic murmur over the mitral area. A white cell count and chest x-ray were normal. A transthoracic echocardiogram, performed to assess cardiac function, showed a large, highly mobile left atrial mass prolapsing into the left ventricle (Box, A [arrowed]). At urgent surgery, an 8 cm left atrial myxoma arising from the interatrial septum was resected (Box, B). Histopathological examination showed dense colonies of yeast. Histoplasma capsulatum was grown from blood cultures and cultures of the surgical specimen (Box, C). HIV testing was negative. The patient made a full recovery after completing antifungal therapy. Infected left atrial myxoma is rare. We know of only one other reported case in which Histoplasma was the infective agent.1 A: Transthoracic echocardiogram B: Surgical specimen C: Microscopic view of Histoplasma capsulatum (Gomori methenamine silver stain)

Ahmed Awab MD · Mehdi Hamadani MD · Bhanu Sud MD · Gene W Voskuhl MD

Most drug reactions are pharmacological reactions rather than hypersensitivity reactions. In assessing drug reactions, a detailed clinical history and careful documentation of reactions are most important. Elucidating the nature and time course (first versus subsequent exposure, immediate versus non-immediate) of a reaction can help to distinguish immune from non-immune hypersensitivity, as well as IgE-mediated from T cell-mediated allergy. Skin testing and in-vitro tests are of predictive value for only a limited group of IgE-mediated drug allergic reactions. Drug provocation challenges can be used to eliminate suspicion of a low-probability drug reaction, find a safe alternative to a proven or probable drug reaction, or as a means of desensitisation. If a patient taking an angiotensin-converting enzyme (ACE) inhibitor develops angioedema, the cause must be assumed to be the ACE inhibitor until proven otherwise.

Francis C K Thien MD, FRACP

Latex allergy (LA) is an IgE-mediated reaction to latex proteins. It is a relatively new phenomenon, first described convincingly in 1979 and increasingly recognised in subsequent years.1 Much has been achieved from years of research into the problem, including: an understanding of the causes and mechanism of sensitisation; implementation of effective public health measures to reduce the incidence of sensitisation; identification of the major allergens of natural rubber latex; and delineation of cross-reactive allergens. Who is at risk? LA is primarily an occupational disease, with health care workers and other highly exposed workers at greatest risk of becoming sensitised. Other at-risk groups include children with spina bifida and people who have had multiple surgical procedures.1 Clinical signs of LA occur in less than 1% of the general population.2 Screening sera from blood donors shows that about 7% of samples contain latex-specific IgE antibodies,2 but this observation can be explained by cross-reactivity between latex and certain plant food and pollen allergens. Risk factors. Atopy is a risk factor for developing LA: a hospital worker who is atopic has a 17% greater chance of developing LA than a non-atopic worker. Australian and other studies have demonstrated that pre-existing hand dermatitis is also a major risk factor for occupational sensitisation. But the greatest risk factor for developing LA is high exposure to powdered latex gloves. Routes of sensitisation and clinical features. Exposure may occur by cutaneous contact, in which case urticaria is the most common clinical manifestation. Sensitisation via the respiratory route occurs when there is airborne allergen in the environment, most commonly caused by airborne powder particles carrying latex allergen. This exposure may produce systemic reactions, but more often produces symptoms of acute rhinoconjunctivitis. Occupational asthma secondary to LA results from inhalation of airborne latex protein-bearing particles. This explains why cases of asthma caused by LA are almost only seen in people with occupational exposure. Contact with latex proteins via the mucosal route, such as occurs during surgical or dental procedures, is most likely to result in systemic allergic reactions such as bronchospasm, hypotension and shock. Rubber glove use may also lead to problems with hand dermatitis, which may be due to chronic irritation or may be secondary to delayed type hypersensitivity reactions to preservative agents in the rubber. Both types of dermatitis are more common than LA. Diagnosis. Diagnosis of LA depends on a high level of suspicion in the correct clinical setting. Confirmation is sought by performing skin prick tests and/or in-vitro assays for specific IgE. However, there is still no uniformly satisfactory diagnostic test reagent available. Several manufacturers have produced extracts for skin testing and in-vitro reagents, but these lack the high degree of efficiency desirable for a diagnostic test. The major allergens of latex have been identified, and many are now cloned and sequenced. Hopefully this will lead to the development of improved diagnostic assays and new immunotherapy vaccines in the future.1 Clinically important cross-reactivity exists between latex and various plant-derived foods, including nuts, kiwifruit, avocado, banana, potato and tomato. This is due to structural and biological similarities between the various protein allergens. Fact or fiction — true or false? People with latex allergy must avoid all rubber products (T/F) False. The greatest risk to a person with latex allergy is contact with “dipped” rubber products (eg, gloves, condoms, balloons). Some hard or black rubber products may not pose a risk. Patients should seek specialist advice on which products to avoid. Management. Keeping sensitised individuals safe from allergic reactions on exposure to latex proteins depends on making a correct diagnosis, notifying relevant medical and dental personnel of the allergy, and being prepared to treat an acute reaction. People with LA should wear a MedicAlert bracelet (Australia MedicAlert Foundation, Adelaide, SA) and, if necessary, carry an adrenaline auto-injector. Education about the possibility of cross-reacting allergens and advice about alternative, safe, non-latex products (including polyurethane condoms) are important. Small studies of immunotherapy for LA have shown encouraging results, but further work needs to be done before this strategy can be recommended.1 Workplace measures. With the correct measures in place, there is no reason why a health care worker sensitised to LA cannot work in health care facilities. Sensitised individuals should wear non-latex gloves. If others working in the facility continue to use latex gloves, these should be powder-free with a low protein content. Universal adoption in the workplace of low-protein, non-powdered gloves and avoidance of latex gloves in non-clinical areas (eg, for kitchen and cleaning personnel) can dramatically reduce exposure and risk of sensitisation.3 Workers should be educated about the early manifestations of LA and the need for early consultation with an appropriate specialist if LA is suspected. Good hand-care education is essential in workplaces where there is frequent washing and gloving. Evidence is emerging that continuing avoidance may reduce sensitisation to LA, at least in some individuals.

Constance H Katelaris MB BS, PhD, FRACP

To the Editor: Since my article on medical abortion was published in the Journal,1 I have received some information from colleagues, and from women who have undergone abortions, about the current practice of medical abortion in Australia. I believe this may be of interest to readers of the MJA. More than a dozen practitioners have informed me that they have used misoprostol or methotrexate/misoprostol combinations to induce early abortion (before 9 weeks’ gestation) outside of hospitals, and a number of women have reported undergoing such abortions. The number of cases involved in this anecdotal sample is at least several hundred annually. Induced abortion using methotrexate/misoprostol was practised in the United States up until the introduction there of mifepristone/misoprostol regimens in 2000.2,3 There is wide experience of this drug combination reported in the medical literature, and the consensus is that, in the short term at least, it is safe and effective, although less effective than the mifepristone/misoprostol combination.2-4 Both drugs are licensed for purposes other than abortion in Australia, as elsewhere (misoprostol for treatment of gastric ulceration; methotrexate as a cytotoxic agent, and for psoriasis and rheumatoid arthritis), but the use of drugs “off-label” is an acknowledged medical practice.5 Misoprostol in particular is widely used in obstetrics for cervical ripening and treatment of postpartum haemorrhage.5 These early abortions take place “under the radar” in the sense that there is no specific Medicare item number; the administration of the drugs occurs in the course of a standard consultation. There is nothing irregular about this, but it does mean that the inaccurate data we currently have on the number of abortions performed in Australia are even more inaccurate than initially thought. It should be noted also that misoprostol alone or in combination with other prostaglandins is being used in Australian hospitals, as overseas, in a more evident manner for the induction of late abortion in cases of severe fetal abnormality detected after 13 weeks’ gestation.5 As well, methotrexate is commonly used in the treatment of early, unruptured ectopic pregnancy, in doses well below those used in oncology. The communications I have received on the subject lead me to believe that medical abortion is currently extensively practised in Australia.

Caroline M de Costa

To the Editor: The Australian Fracture Prevention Summit held in 2002 recognised osteoporosis as a major public health issue. Despite this, several Australian studies have found that a majority of patients with osteoporosis-related fractures do not receive appropriate evaluation and treatment as recommended by the clinical guidelines.1-4 In 2003, the Queen Elizabeth Hospital, a tertiary referral hospital which services the north-western suburbs of metropolitan Adelaide, implemented a novel approach to improve the secondary prevention management of patients admitted to the orthopaedic unit with fragility fractures. The strategy was based on the “plan-do-study-action” principle of medical quality improvement, with the primary goal of enhancing performance.5 Before commencing, a retrospective case-note review of 40 consecutive patients who had been admitted to the orthopaedic unit with osteoporotic fractures revealed that, at discharge, none were receiving any medication for osteoporosis. Patients over the age of 50 years who had been admitted with fragility fractures were identified from computer records. With the support of a physician and junior medical staff, a clinical pharmacist provided individual counselling, written materials and osteoporosis therapy. The rate of medication prescription was initially assessed at discharge. In a follow-up telephone interview, participants were queried about the continuation of osteoporosis therapy, performance of investigations by general practitioners, and history of falls. Over a 10-month period, of 259 patients admitted with fragility fractures, 228 patients (88%) were prescribed osteoporosis therapy (calcium, vitamin D and risedronate) on discharge. Of those eligible, 65 patients participated in the follow-up audit. Forty-eight patients (74%) continued to take medications for osteoporosis as initially prescribed; only 28% had had laboratory investigations for osteoporosis and 31% a bone mineral density test. In addition, three patients had experienced recurrent falls complicated by further fragility fractures. The appointment of an allied health champion with clinical backup from a general physician appeared to have achieved a high level of initiation and continuation of osteoporosis pharmacotherapy in at-risk patients during hospital admission. The low rate of follow-up investigations is consistent with previously published data suggesting poor community-based follow-up after hospital discharge of patients admitted for osteoporotic fractures. The major limitation of this clinical pathway is the low rate of patient participation in the follow-up audit. Therefore, the results of follow-up data cannot be said to be representative of the cohort. This study highlights the importance of the participation of GPs in maintaining patient compliance with hospital-initiated programs, especially those involving chronic illnesses.

Tim Yu-Ting Lu · Jennifer A Pink · Lauren E Whitten · Catherine L Hill · Robert J Adams · Catherine Gibb

To the Editor: The Experimental Drugs Section (EDS) of the Drug Safety and Evaluation Branch of the Therapeutic Goods Administration (TGA) administers the clinical trial notification (CTN) and clinical trial exemption (CTX) arrangements for unapproved medicines used in clinical trials. These arrangements provide an avenue of “exemption”, whereby medicines that have not been approved for marketing in Australia are able to be supplied to patients within the context of a clinical trial approved by a human research ethics committee working under the guidelines of the Australian Health Ethics Committee (a subcommittee of the National Health and Medical Research Council). Although these arrangements cover only clinical trials in which unapproved medicines are used, a substantial number of such trials are carried out in Australia each year. (Clinical trials using unapproved medical devices that also use the CTN/CTX arrangements are administered by the TGA’s Office of Blood, Devices and Tissues and are not included in these statistics.) The EDS often receives queries from stakeholders requesting some form of basic statistical data with respect to clinical trial activity in Australia. The EDS intends to begin use of a new database in 2007 for recording CTNs and CTXs notified to the TGA. It is hoped that this will enable us to publish a basic statistical subset of clinical trial information on an annual basis. As a prelude to this capability, we have manually compiled a few simple statistics on clinical trials notified within the financial year 2004–05. Box 1 breaks down the trials conducted into various body systems or treatment areas. There were 739 separate clinical trials of unapproved medicines commenced over the 1-year period. As many of these are multicentre trials, there are a much greater number of actual trial sites involved. (A good measure of the number of trial sites is simply the raw CTN notification figures, numbering 2776 for the same period.) Box 2 breaks down the trial numbers into the various phases of drug development. Although this is not relevant to all trials, these figures give an indication of the main areas of drug development research currently being conducted in Australia. Given the number of multicentre trials being carried out, we did not think it useful to break down trial numbers by state and territory. We trust that these data convey some idea of current clinical trial activity with respect to unapproved medicines in Australia. 1 Clinical trials of unapproved medicines, by body system and therapeutic area, July 2004 to June 2005* Body system/therapeutic area Number of trials Neoplastic disorders 252 Cardiovascular system 78 Central nervous system 71 Immunology 64 Endocrine and metabolic disorders 60 Infections and infestations 42 Musculoskeletal system 36 Genitourinary system 28 Analgesia 20 Respiratory system 16 Alimentary system 15 Skin 13 Eye 7 Surgical preparations 5 Nutrition 3 Ear 2 Unspecified† 27 Total 739 * Based on clinical trial notification and clinical trial exemption data. † “Unspecified” refers either to trials that were not directed toward a body system or trials in which the system could not be determined from the information on the clinical trial notification form. 2 Clinical trials of unapproved medicines, by trial phase, July 2004 to June 2005* Trial phase Number of trials Phase 1 87 Phase 2 259 Phase 3 277 Phase 4 53 Other† 63 Total 739 * Based on clinical trial notification and clinical trial exemption data. † “Other” denotes trials that were not nominated in a particular phase or to which these designations were not relevant.

Jonathon Rankin · Jenny Mason · Neil Kottege · Natasha Y Andersson

The recent viewpoint by Kamien1 is timely, given Food Standards Australia New Zealand is currently advocating for the mandatory fortification of all bread-making flour with folic acid (80–180 μg per 100 g of bread). The proposal is now before the Australia and New Zealand Food Regulation Ministerial Council, and a decision is imminent. In 1991, the Medical Research Council Vitamin Study Research Group reported a randomised double-blind trial conducted at 33 centres in seven countries. Periconceptual folic acid supplementation had a 72% protective effect against neural tube defects (relative risk, 0.28; 95% CI, 0.12–0.71).2 Because folic acid supplementation is ineffective when started after the pregnancy is confirmed, fortification of staple foods such as bread remains best practice. The United States started mandatory fortification of enriched cereal-grain products a decade ago. As expected, there has been an increase in the population geometric mean concentrations of serum folate and red blood cell folate,3 and a corresponding reduction in the number of babies born with debilitating neural tube defects.4 The benefits are clear and the risks are vague. Historical concerns that folic acid supplementation could mask pernicious anaemia and cause cancer have not been substantiated by international experience in more than 50 countries. Australian health professionals have a brief window of opportunity to join Maberly and Stanley5 and advocate for mandatory fortification in spite of commercial objections, which are based on market-share concerns for existing “designer” products. If we educate and inform our patients and the community at large, the decisionmakers should finally get the message and this cheap, safe and effective public health policy would be implemented — a decade overdue.

Hasantha Gunasekera

To the Editor: Tan et al1 found that patients value key elements of successful weight management, including advice on healthy eating and exercise and regular follow-up. Accredited practising dietitians (APDs) provide all of these things and have the qualifications, skills and time to work with people to effectively manage weight. APDs use the Obesity Best Practice Guidelines of the Dietitians Association of Australia, providing evidence-based dietary therapy. By working alongside general practitioners to provide individual advice, APDs ensure the best outcomes for patients. A considerable number of patients surveyed said that referral to a dietitian would be useful and that they would be likely to follow their GP’s advice if referral was recommended. The weight management roles of GPs and APDs are complementary and, by addressing any patient concerns and providing a referral to an APD, GPs can help their patients achieve their weight management goals.

Claire Hewat

Stem cells. Controversy at the frontiers of science. Elizabeth Finkel. Sydney: ABC Books, 2005 (vi + 282 pp). ISBN 0 7333 1248 9. There has been no more controversial area in medical science in recent years than the discovery that embryonic and adult stem cells have the potential to generate a range of different tissues, possibly even organ repair and regeneration. As the field has evolved at a blistering pace, several important strands can be discerned. Firstly, the science, while complex, is of great interest to the lay reader. For the public to adequately understand and appraise the importance and potential of these new developments, it is crucial that the current state of scientific development be explained in readily understandable terms. Secondly, the area of stem cell therapy, especially embryonic stem cells and their development, raises many complex ethical issues divisive in our society. Thirdly, Australian scientists have played a major role both in the development of in-vitro fertilisation, the precursor to the embryonic stem cell age, and in the development of embryonic and adult stem cells as potential treatments of the future. Elizabeth Finkel, a distinguished science journalist with a strong background in embryology, has written an intriguing account of the stem cell story. She has brought together all three strands into a very readable account of the field. On one level, for those interested in human stories in science, this is a very good read with great human achievement and political drama. It is also one of the best accounts of the scientific achievements with stem cells to date and of the basis for arising ethical issues. Finkel makes no secret that she is an enthusiast for developing stem cell science as a viable treatment, with both embryonic and adult stem cell research. In some of the examples she covers, most notably Parkinson’s disease, she may overstate the current state of success of stem cell therapies just a little, but does so in an attempt to give a balanced story. One of her key conclusions, that scientific facts must be presented and discussed dispassionately, and that ethical considerations and viewpoints should not be allowed to bias interpretation and presentation of the science to the general public, is a pivotal one in all aspects of science. Stem cell therapy, whether derived from embryonic or adult stem cells, has a great way to go before we will know for sure whether it will be a viable treatment in a major sense for human illness. Elizabeth Finkel’s book makes clear that it is an area of very considerable promise, and I commend this riveting account to all who have an interest in the area. Edward ByrneDean of Medicine, Nursing and Health Sciences, Monash University, VIC Competing interests: Professor Byrne is the current Dean of Medicine at Monash University, where much of the stem cell work in this book was carried out. “Stem cells” won the Science Writer’s Award in the 2005 Queensland Premier’s Literary Awards

Edward Byrne

Recycling asbestos In the 1950s, five Western Australian children helped out their parents on the family farm by shaking out hessian superphosphate bags before they were returned to a fertiliser supplier for recycling. Today, three of these children, now adults, have asbestos-related disease (calcified pleural plaques); one has no history of any other exposure to asbestos. Musk and colleagues suggest that before the hessian bags got to the fertiliser industry and the farm, some may have been used, contrary to regulations, to transport asbestos from the mine to the coast. They say this family’s experience highlights the potential results of the insidious dissemination of asbestos throughout the Western Australian community in past years. Aust N Z J Public Health 2006; 30: 312-313 Educating Rita Last year’s hurricane season in the United States was followed by much criticism of government response. Now, one unheralded success has been reported which may assist future disaster management. When Hurricane Rita headed for Alexandria, Louisiana, in September 2005, the Louisiana Office of Public Health led a pro-active, cooperative and flexible response to enable effective care for hundreds of evacuees, including bedridden and oxygen-dependent residents of chronic care facilities. One key to their success was solving logistical problems before they happened, for example, by deploying resources before the hurricane hit, such as alternate sources of oxygen, electricity and water. They also relied on multiple communication facilities — not only mobile phones, landlines and computers but also walkie-talkies, fax machines and digital cameras — this deliberately redundant infrastructure increased reliability. A joint command with state, local and volunteer partners avoided unnecessary duplication; rather, it enabled multiple coordinated, simultaneous interventions. Ann Intern Med Online, 15 August 2006 Changing China’s children Many younger women in urban areas of China are now expressing a preference for having a baby girl, according to a 2001 survey of nearly 40 000 Chinese women aged 15 to 49 years. This was a surprise finding among more expected results — a decreased birth rate and an imbalance in the sex ratio of children, favouring boys. BMJ 2006; 333: 371-373 Home-grown doctors States or territories that are short of doctors might do well to train up students from within their own borders or from a rural background, suggest Canadian researchers.1 As doctors aren’t conveniently radio-tagged like sea turtles, the researchers trawled through alumni lists and medical registers to determine where 1322 doctors from a single Newfoundland medical school had ended up in 2004.1,2 Just over 85% were working in Canada; about 30% were still in Newfoundland — especially those originally from Newfoundland, who had done some or all of their residency training in Newfoundland, or who had a rural background. Students from rural communities were also, in general, more loyal to Canada, the country that trained them, even if their contribution was not necessarily rural. 1. CMAJ 2006; 175: 357-360 2. CMAJ 2006; 175: 371 Heat shock protein promise Chaperonin 10, also known as heat shock protein 10, may be effective in treating rheumatoid arthritis, according to Australian research. Vanags and colleagues conducted an exploratory proof-of-principle investigation of chaperonin 10 in 23 patients with moderate to severe active rheumatoid arthritis. The patients, who were also receiving disease-modifying anti-rheumatic drugs, received 5-10 mg intravenous chaperonin twice daily for 12 weeks. Symptoms improved from as early as a fortnight into the trial; and in vitro inhibition of cytokine production was detected. Some adverse events were reported but there were no toxicity or tolerability issues. Chaperonin 10 is thought to exert anti-inflammatory activity by inhibiting a range of cytokines, including tumour necrosis factor-α, and interleukins 1 and 6. Lancet Online, 23 August 2006 Opt-in v opt-out research New privacy laws on recruitment for research may lead to increased costs and reduced generalisability, say Australian researchers. Trevena and colleagues recruited two-thirds of 60 of a larger group of randomly selected patients into the pilot phase of a general practice-based randomised trial using an opt-out protocol. To opt out, patients needed to respond to an introductory letter from their doctor, indicating they did not wish to be contacted by researchers. However, an opt-in protocol was used after privacy legislation had been enacted, with just less than half of the remaining 92 randomly selected patients recruited into the main trial. To opt in, patients needed to respond to the introductory letter. As a result, to obtain a similar recruited sample size to that of the pilot phase, the researchers needed to increase the number of eligible participants by 50%. Further, they found that opt-in recruits were more likely to include active, preventive health-seeking participants with a personal motivation to be involved in the trial. J Med Ethics 2006; 32: 473-477 Dr Ann Gregory, MJA

Ann Gregory