Volume 180 Issue 4

If we can learn from this, it will have made a contribution to the pursuit of integrity in research On beginning his recent sabbatical at the Mayo Clinic, Professor Michael O’Rourke, a renowned academic from the University of New South Wales, was handed a slim volume entitled Honor in science. First published in 1984, it is recommended reading for research trainees as a guide to ethics and the values of research. Significantly, there are now more than 50 000 copies in circulation.1 Activities such as the dissemination of this booklet are central to ensuring society’s trust in the integrity of research. More than 20 years ago, Al Gore Jr (then a United States congressman, and later Vice President in the Clinton administration), as chairman of the first congressional hearing into scientific misconduct, noted: “At the base of our involvement in research lies the trust of American people and the integrity of the scientific exercise.”2 There is no reason to believe that this would be any different in Australia. Allegations of research impropriety affect the careers of both the accused and the accusers and . . . can divide an institution and damage its reputation. But trust in our research enterprise has recently been shaken by the “Hall affair” at the University of New South Wales (UNSW). At the end of 2001, complaints of research misconduct were levelled at Professor Bruce Hall, a Professor of Medicine at UNSW, and an internationally acclaimed scientist in immunology. The complainants were members of Hall’s research laboratory and it has taken more than 2 years to resolve their allegations. During this time, there were four different inquiries and reports, which reached different conclusions (see Box). From the beginning of the affair, all the allegations have been vigorously denied by Hall. Sadly, as it unfolded, the Hall affair illustrated the reality that allegations of research impropriety affect the careers of both the accused and the accusers and, in the process, can divide an institution and damage its reputation.11 Most importantly, such allegations jeopardise public trust in the integrity of research. Further, they provide fuel for a media that feeds on human discord, and, dealing in perceptions and innuendo, accelerate this corrosion. The Hall affair was first publicly dramatically exposed on the Australian Broadcasting Corporation (ABC) Radio National’s Science Show,4 and then clinically dissected by ABC television’s Four Corners9 (see Box). The media also covered the investigation as it progressed and, on the release of the UNSW Vice-Chancellor’s Report on the affair,8 one journalist commented, “Let me get this straight. Plucking data from thin air, recycling old research in new papers and telling porkies in a grant application is OK. Funny, I thought such doings were serious no-nos, construed at best as scientific misconduct, or at worst scientific fraud. Apparently not . . .”12 Looking back over the Hall affair, we are forced to ask ourselves how we can move forward. Are there any lessons to be learned? Scientific misconduct and fraud may well be seen as an illness, requiring not only diagnosis but also treatment. The diagnosis involves a fast and fair inquiry which, at the same time, must assure the public of its propriety. Unhappily, the Hall affair dragged on for more than 2 years and involved at least four inquiries (see Box). The initial inquiry by the UNSW’s Dean of Medicine should not have moved beyond a prompt and preliminary process to establish whether there was a case to be answered. In any event, it went on, patently crippled by perceptions of conflicts of interest — including an institution investigating allegations of improprieties carried out in its own backyard! Herein lies lesson number one — once allegations of scientific misconduct and fraud have been made, these should be addressed from the beginning by an external and independent inquiry. The external inquiry must establish the evidence for misconduct. From the publicly available details of the Brennan Inquiry,7 it appears the inquiry had its hands tied in testing the evidence. Herein lies lesson number two — the external inquiry should have statutory power to investigate and inquire. Defining this power will not be straightforward, as the inquiry should not be hijacked by obfuscating and delaying legal tactics. The Brennan Inquiry was made up of legal and scientific experts, with the latter in the majority. Despite the fact that the framework of research conduct is generic, professional criticisms surfaced in the Four Corners program9 and elsewhere about the inquiry panel’s lack of expertise in immunology.10,13 To allay public concerns about the lack of relevant “expertness” — inquiries into allegations of scientific misconduct and fraud should consider having on the panel of inquiry at least one expert from the same scientific discipline as the scientists under investigation — lesson number three! In the 2002 Reith Lectures for the British Broadcasting Corporation, Onora O’Neill stated that “. . . ‘Loss of trust’ is, in short, a cliché of our times.”14 Mistrust of professionals, politicians and public servants and their institutions permeates our society. The antidotes to this “culture of suspicion” are supposedly higher standards of accountability and greater transparency.14 As it progressed, the Hall affair was not the epitome of transparency and, to date, the details of its four inquiries remain cloistered within academia. Herein lies lesson number four — to preserve public confidence, inquiries into scientific misconduct should aim for the highest degree of transparency and accessibility of final reports. Finally the Vice-Chancellor’s Report (see Box) makes judgements on the outcomes of the Brennan Inquiry, and also conveys opinions on the relative value of scientific abstracts and the nature of data in research-funding applications that are at odds with conventional scientific wisdom. Even more intriguing is the rationale behind the action of the Vice-Chancellor in judging the findings of the Brennan Inquiry, yet not consulting its panel. Why bother with an external inquiry if its outcomes are to be subsequently interpreted and judged by an individual calling on his own wisdom along with the views of another battery of experts? Such action may be in accordance with and required by the UNSW enterprise agreement, but surely the integrity of research transcends any industrial agreement! Herein lies lesson number five — universities, research institutions, research societies, societies and funding bodies need to collectively define uniform processes and procedures for addressing and adjudicating on scientific research and fraud.15 But what about treatment? The emphasis in healthcare today has shifted from the management of diseases to their prevention, and herein lies lesson number six — there is a need to shift the emphasis from managing scientific misconduct and fraud to preventing them. This shift is thoroughly summarised in the recent report of the United States Institute of Medicine (IOM), Integrity in scientific research: creating an environment that promotes responsible conduct.16 Its central theme is the need to foster responsible research conduct, and it identifies the individual scientist as the most unpredictable variable in the equation. But it also throws back to institutions the responsibility of creating a culture that values research integrity through comprehensive and effective education, self-assessment and self-improvement, aimed at both the individual and the institutional level. In short, the IOM report moves the prevention of research misconduct from focusing on what we should do in the conduct of research, as prescribed in guidelines, codes of conduct and other affirmations or declarations, to determining what we actually do through individual and institutional self-assessment, and moving to best practice through education and continuous improvement underpinned by a reward system. The IOM report lists desirable goals for both individuals and institutions in maintaining scientific integrity, but, ultimately, research is an intense and complex human exercise — one which sees young investigators and their mentors working in a “pressure-cooker” environment, where the only safety valves are open communication, mutual respect and mentors prepared to be actively involved. In his 1982 Presidential Address to the American Society for Clinical Investigation, Phillip Majerus (Professor of Medicine, Biochemistry, and Molecular Biophysics at Washington University, and past editor of the Journal of Clinical Investigation) describes this ideal environment: “Students, postdoctoral fellows and junior colleagues are the future of medical research. They are our most valuable resource and should be treated as such. Senior investigators have a solemn responsibility to guide trainees to allow them to express their full potential. If because of clinical, administrative or other constraints, an investigator does not have time to participate in the ongoing progress of an investigation on a day-to-day basis, then he should dissociate himself from it . . . Work in progress should be discussed openly and the data should be reviewed, frequently, not just by the laboratory chief but also by disinterested parties. Group meetings of large laboratories where there is evaluation of data of individuals are important. Even better are presentations to departmental or other groups, where investigators not directly connected with the work, evaluate the data. These exercises require heavy applications of skepticism, the most important ingredient in scientific creativity.”17 Good advice then and good advice now. The Hall affair has wreaked untold havoc, but, despite this, can be viewed in a detached, scientific sense as experiments in processes and procedures. The results of experiments need to be mulled over and interpreted to determine future directions. In this vein, the Hall affair should make a contribution to the pursuit of research integrity. Ultimately, integrity in research requires leadership. If, in the wake of the Hall affair, our universities cannot ensure an enlightened and responsible ethos in their research enterprises they risk a loss of public confidence. The ball is in their court. The “Hall affair” — investigations of complaints against Bruce Hall, Professor of Medicine at the University of New South Wales September 2001 – January 2002 Complaints received by the University of New South Wales (UNSW) from three members of Professor Hall’s laboratory, which, among other things, raised allegations of scientific misconduct and fraud, as well as deficiencies in workplace relationships and procedures.3 13 April 2002 Dr Norman Swan revealed details of the complaints against Professor Hall, and discussed these with the complainants on the Australian Broadcasting Commission Radio National’s Science Show.4 Hall, at all times, fiercely denied these allegations. 17 April 2003 The UNSW released the outcomes of two parallel internal inquiries by Professor Bruce Dowton, Dean of the Faculty of Medicine, who carried out the initial investigation of the complaints, and Professor Elspeth McLachlan, Pro-Vice-Chancellor (Research), who focused on complaints that had been raised with the National Health and Medical Research Council. Both inquiries found no overwhelming evidence to sustain the complaints. Both were unable to report conclusively on some matter of alleged scientific misconduct and fraud.3 As to the workplace complaints, the inquiries found there were unsatisfactory working relationships and an unsatisfactory working environment in Hall’s laboratory.3 UNSW Vice-Chancellor John Niland announced the setting up of an external inquiry to address the allegations of scientific misconduct and fraud as defined by the National Health and Medical Research Council and the Australian Vice-Chancellors Committee (NHMRC/AVCC) Joint Statement and Guidelines on Research Practice.5 June 2002 The UNSW announced the members of the external independent inquiry, who were: Sir Gerard Brennan, previous Chief Justice of the High Court (chair); Professor John Chalmers of the University of Sydney; Sir David Weatherall of Oxford University; and Professor Judith Whitworth of the Australian National University.6 Subsequently, it become known as the Brennan Inquiry. January 2003 The UNSW received the final report of the Brennan Inquiry, after which the Hall Affair proceeded along two pathways: (a) matters related to the release of the Brennan Inquiry report; and (b) processes required to comply with the University Enterprise Agreement in dealing with allegations of research misconduct. Events were as follows: (a) On 14 February 2003, the UNSW Council resolved not to release the Brennan Inquiry report, and also considered a submission by Professor Hall as to why its release should not occur. Ten days later, the Council reversed its position and sanctioned limited release. The following day (24 February), lawyers for Hall obtained a temporary injunction against its release. In August 2003, Justice McLennan lifted the injunction.7 (b) To satisfy the provisions of the UNSW Enterprise Agreement for pursuing alleged research misconduct, the Brennan Report was referred to Professor Stephen Deane, Professor of Surgery at Liverpool Hospital, acting as Hall’s academic supervisor at Liverpool Hospital. The UNSW Enterprise Agreement sets out a detailed process to be followed in cases of alleged research misconduct, so that the UNSW may only discipline an academic if the Enterprise Agreement process has been complied with. Professor Deane’s remit was to determine whether the Brennan Inquiry report gave rise to any allegations of misconduct or serious misconduct as defined by the Enterprise Agreement and, if so, whether such allegations could be “resolved through guidance, counselling, conciliation or other appropriate action.”8 Professor Deane provided a report (the Deane Report) on 17 March to UNSW Deputy Vice-Chancellor, Professor Mark Wainwright. Based on the Deane and the Brennan Inquiry reports, Professor Wainwright identified 12 outstanding allegations against Hall which warranted further investigation. Professor Hall was given the opportunity to respond to these allegations. Ultimately, Professor Wainwright determined that, in relation to six allegations, there was no misconduct or serious misconduct. However, for the remaining six he was unable to determine whether or not serious misconduct had occurred. Hall was notified of these allegations, which he denied, but he elected to have the matter referred directly to the Vice-Chancellor. 6 October 2003 An ABC Four Corners program presents the central concerns and provides real-life insights into the key players in the Hall Affair.9 23 December 2003 UNSW releases the report by the Vice Chancellor, Rory Hume, on findings of allegations of misconduct.8 In reaching his decision, Hume considered the Brennan Inquiry report and the views of two experts, along with a written response from Hall, which included reports by six experts in immunology. Professor Hume considered the allegations only in the terms of the Enterprise Agreement and, where indicated, the NHMRC/ACVV statement and guidelines.5 His findings are shown below. Allegation 1: A paper that was submitted or authorised to be submitted contained data and statements for which there were no supporting experiments. Finding: Professor Hall was not guilty under the Enterprise Agreement. Rather he had committed an error of omission reflecting the pressure of mitigating circumstances.* Allegation 2: A grant application by Professor Hall contained a figure with a conclusion “all differences are significant at P < 0.05”, but omitted relevant facts. Finding: Guilty of misconduct, but, given the mitigating circumstances* and the Vice-Chancellor’s belief that grant proposals are preliminary data yet to be validated and that there was no intention to deliberately deceive, he deemed the transgression to be minor and warranting no further action. Allegation 3: A grant application by Professor Hall contained a statement when no experiments to support the statement were ever done in Hall’s laboratory or in the laboratory of any other author of the grant application. Finding: Guilty of misconduct despite the mitigating circumstances.* Hall was censured. Allegation 4: Failure to notify the granting body of the details once the absence of the experiments outlined in Allegation 3 became apparent. Finding: Guilty of misconduct warranting censure. However, Professor Hall’s lack of action did not demonstrate an intention to deceive. Allegation 5: The publication of an abstract which contained a statement for which no experiments were performed in Hall’s laboratory. Finding: Guilty of misconduct in failing to take reasonable steps to ensure that the abstract was accurate, but, in view of mitigating circumstances,* including the Vice-Chancellor’s view that “abstracts have very little potential to damage the fabric of science,” along with the premise that individuals’ interpretations of the abstracts differ, no further action was taken. Allegation 6: That Professor Hall must accept the main responsibility for allowing a substantial degree of procedural laxity in his laboratory at Liverpool Hospital. Here, there were mitigating circumstances* against a background of a complex research laboratory and Hall’s need to supervise a busy clinical service and a teaching program. Finding: Guilty of misconduct. Hall was advised of his error of judgement, but, given the circumstances, no further action was taken. In summary, the Vice-Chancellor did not believe that Professor Hall was guilty of scientific misconduct. Rather, he committed errors of judgement sufficiently serious in two instances to warrant censure. None of the Vice-Chancellor’s findings warranted Hall’s dismissal. With the release of the Vice-Chancellor’s findings, one prominent immunologist was quoted as saying that the allegations against Hall were “much ado about nothing”.10 * During the period when some of the alleged misconduct occurred, Hall was afflicted by a debilitating illness, his laptop and disks containing grant proposals were stolen, and he was subject to the pressure of tight deadlines.

Martin B Van Der Weyden MD, FRACP, FRCPA

Improving global health requires foreign policy reform and more aid Health and foreign affairs are inextricably linked. No day goes by without news reports on health and its global dimensions, whether focused around HIV/AIDS, the rise of non-communicable diseases, the implications of ageing populations, bioterrorism, or other topics. While global population health indices have improved considerably, many countries — both rich and poor — are experiencing health crises, and, in a globalised world, proactive policies are essential in all regions to protect and promote public health. In a number of countries discussion is under way about how best to respond;1 Australia is adding its voice to these debates. What are the links between health and foreign policies? How consistent and coherent are they? What are the benefits or dangers of improving these links? In this special issue of the Journal, we present a selection of papers presented at a symposium entitled “Health and foreign policy: scope for Australian engagement”, held in Sydney in September 2003. The Symposium was a collaboration between the School of Public Health and Community Medicine (University of New South Wales), the Institute for International Health (University of Sydney) and the Nuffield Trust, a leading health charity and research organisation in the United Kingdom.2 What is Australia’s contribution to overseas aid?Australia’s geography provides a particular focus on the Asia–Pacific region. The total Australian aid program for 2003–04 is budgeted at $1.894 billion,3 representing 0.25% of gross national income (GNI). Although this is above the donor average in 2002 (0.23%), this proportion has declined from close to 0.5% in the early 1970s,3 and remains well below the target of 0.7% of GNI set internationally several years ago.4 AusAID, the agency charged with implementing Australia’s overseas aid policy and delivering the Government’s overseas aid program, has highlighted five key themes for its activities: governance — “promoting democratic and accountable government and effective public administration”; globalisation — “assisting developing countries to access and maximise the benefits from trade and new information technologies”; human capital — “supporting stability and government legitimacy through improved delivery of basic services”; security — “strengthening regional security by enhancing partner governments’ capacity to prevent conflict, enhance stability and manage trans-boundary challenges”; and sustainable resource management — “promoting sustainable approaches to the management of the environment and the use of scarce natural resources”.3 The overarching objective of AusAID’s program remains “to advance Australia’s national interest by assisting developing countries to reduce poverty and achieve sustainable development”,5 elements of which are the focus of ongoing debate and critique.6,7 A particularly fundamental challenge is to take account of the new focus on global security, terrorism and governance, while still addressing fundamental health and development concerns, as expressed, for example, in the Millennium Development Goals.8 Alexander Downer, the Australian Foreign Minister, also draws attention to the need for greater involvement of recipient countries in determining what is done with foreign assistance resources; greater emphasis on building developing country capacity to achieve development objectives; greater coordination among development partners; and less reliance on standalone projects.9 Within this broader context, AusAID itself is currently reviewing its health strategy and approach, although this process is at an early stage. Development assistance for health has increased globally from 3.8% of total overseas development assistance to 6.8% in 2002. AusAID anticipates devoting 13% of its 2003–04 budget allocation to health sector support.3 AusAID has previously directed such funding to health sector reform, mental health and non-communicable diseases, and promoting primary healthcare with a focus on the Asia–Pacific region. Australia has devoted particular attention to action on HIV/AIDS, one of the key success areas for the Millennium Development Goals, and HIV/AIDS consumes an ever-increasing share of the health aid budget. Moving beyond aidGlobal health inequality is mirrored by global patterns in health research — less than 10% of health research concerns the major health problems affecting 90% of the world’s population.10 This is now the focus of concerted international action, and Australian research contributions, many of which have great potential, could be greatly facilitated by more extensive support and engagement by AusAID, the National Health and Medical Research Council and the Australian Research Council. It is notable that increasing aid alone will not solve global health problems; reform of broader policies on trade, debt and globalisation are needed if global health is to be promoted and protected. Direct foreign investment is four times greater than the transfer of aid from wealthy to developing countries, and is likely to have a major impact on health.5 The complexity of global governance means that diverse international linkages and structures are needed. Australia’s active membership and involvement in a reforming United Nations, as well as in the Commonwealth of Nations, and regional Asia–Pacific structures, all present avenues for strengthening multilateral commitment to global health and ensuring that it endures as a global priority beyond the current window of opportunity. The debateThe global health and foreign policy articles presented here reflect concern with a number of the major issues of the debate. What is the nature of globalisation and who benefits from it (Lee, page 156)? How do changes in the global trade environment affect health (Labonte, page 159)? What are the challenges and impediments to ensuring that those responsible for forging our foreign policy include health issues on their agenda (Harris, page 171)? What are the dangers of seeking a closer relationship between health and foreign policy, given that security and national interest inevitably are higher on the agenda than concerns for development or poverty reduction (McInnes, page 168)? How does the growing acknowledgement of health as a human right affect health-related foreign and development policies (Reid, page 163). The debate in Australia is at an early stage. The articles that follow highlight many of the key challenges and constraints, but also the promise and potential, of fostering a more inclusive and humane globalisation. Promoting intercountry and intracountry equity, alongside tackling poverty, is consistent with Australian values of a “fair go” and should contribute to multiple desirable and integrally related objectives — promoting health, economic growth, development, poverty reduction, and regional stability (see workshop recommendations, page 166). Read on . . .

Anthony B Zwi MB BCh, P hD, FFPHM · John Wyn Owen CB, MA(Camb) · Alan Ingram MA, PhD

The term “globalisation” tends to be misused and overused. We need greater clarity in our understanding of the globalisation process, including the distinct changes involved and their relation to human health. The health impacts of globalisation are simultaneously positive and negative, varying according to factors such as geographical location, sex, age, ethnic origin, education level, and socioeconomic status. Globalisation is not an unstoppable force. Our key challenge is to create socially and environmentally sustainable forms of globalisation that provide the greatest benefits and least costs, shared more equitably than is currently the case. The health community must engage more directly in current research and policy debates on globalisation and encourage values that promote human health. At the same time, those at the helm of globalisation processes must recognise that attending to health impacts will strengthen the long-term sustainability of globalisation.

Kelley Lee MPA, MA, DPhil

Foreign policy, especially trade policy, can have dramatic but rarely considered effects on public health. International human rights covenants oblige governments to scrutinise their foreign policy, including trade policy, for its impact on the progressive realisation of the right to health. Health is both a means and an end of development policy, but government investments in health are inadequate to reduce health disparities within and between nations. Few donor countries provide the agreed target of 0.7% of gross national income for development aid or toward reaching the Millennium Development Goals. The progressive liberalisation requirement of the General Agreement on Trade in Services (GATS), if applied to commitments in health care, education, and water and sanitation services, may conflict with the progressive realisation obligation of the right to health. Alternatives to regulating trade in such essential services are proposed in this article.

Ronald Labonte PhD

International human rights law affirms that everyone has a right to the enjoyment of the highest attainable standard of physical and mental health. States that are parties to human rights treaties are obliged under international law to observe these rights. Australia has ratified all international human rights law instruments in which the right to health is enshrined, and so is obliged to ensure that its foreign policy, including its development assistance program, contributes towards the progressive realisation of the right to health. International trade regulation should be consonant with the progressive realisation of the right to health globally.

Elizabeth A Reid AO, FASSA

Conference delegates participated in five thematic workshops with the aim of discussing and making practical recommendations for action. The themes and recommendations of these workshops were as follows: Globalisation and healthEncourage political advocacy for Australia’s commitment to the Millennium Development Goals (<www.developmentgoals.org/>) and recognition of the links between and inequities in health, security and economic development. This should occur at the highest political levels — the Prime Minister’s Department, the Department of Foreign Affairs and Trade (which could devote part of its website to these issues <www.dfat.gov.au/>), and the Australian Agency for International Development (AusAID <www.ausaid.gov.au/>). Galvanise non-government organisations (NGOs) to advocate issues of health and economic development. Such NGOs could include the Australian Council for Overseas Aid, as well as others with little international involvement at present (eg, the National Heart Foundation and the Cancer Council) which could be encouraged to work in the Asia Pacific region. Urge the Confederation of Australian Industry and the Business Council of Australia to consider health and economic development issues in their overseas ventures. Subject all treaties, covenants and agreements ratified by the Australian Government and by private sector agencies to health impact assessments. Encourage the transfer of quality, relevant Australian health research (eg, on tobacco, injury prevention) to developing countries. Develop the small pool of international health expertise by providing more training opportunities in the Asia Pacific region and a career structure with Australian and multi-national organisations involved in international health. Anthony I Adams Retired Professor of Public Health and Medical Administrator Avoca Beach, NSW AarrATnetspeed.com Emergence of global health strategiesRegard global health strategies as an opportunity to begin to redress the inequitable distribution of global resources, which can threaten social and economic stability and the health of people in all countries. Use many different discussion forums (eg, World Health Organisation, national medical associations, learned colleges) to prepare policy options for implementing these strategies. Mobilise multiple constituencies (eg, citizens’ groups, medical associations) to work with governments, organisations such as the UN, and international NGOs to influence the development and implementation of their global health strategies. Strengthen the role of civil society (ie, non-government elements of society) to determine the goals, priorities, and resource distribution of such global organisations. Peter E Baume Honorary Emeritus Professor, and Chancellor Australian National University, Canberra, ACT chancellorATanu.edu.au Marilyn J Wise Executive Director, Australian Centre for Health Promotion School of Public Health, University of Sydney, Sydney, NSW Human security, conflict and healthInvite the Australian Government to create a standing committee of relevant government departments and civil society representatives to consider global health issues in developing public policy (including foreign policy). Encourage the Australian Government to introduce the concept of human security into official foreign policy (as Japan, Canada and Norway have done). Form a coalition of academics and development practitioners to conduct a dialogue on health and development and to promote evidence-based policies. Develop a media strategy to improve public understanding of the issues and interests around global health. Build the study of global health and conflict into relevant undergraduate curricula and invite university schools of public health or health sciences to create opportunities for students to gain overseas experience by, for example, accrediting overseas units and placements, and facilitating internships with multilateral organisations, such as the World Health Organization and the World Bank. Undertake research and advocacy on conflict-related issues critical to public health, such as arms control. Sue Ingram Senior Policy Fellow, Policy and Practice Division Institute for International Health, Sydney, NSW singramATiih.usyd.edu.au Development and humanitarian aidCreate a "Coalition for global health" to:engage in dialogue on future policy formulation within AusAID. (This could influence a health issues and trends paper presently being developed as the basis for a new AusAID health policy.) form a strategy group that meets quarterly and would drive the global health agenda forward. develop a public information strategy that is based on policy goals, addresses public opinion, uses multimedia channels of communication, and identifies advocating champions. develop a mechanism for supporting public discussion that also identifies funding opportunities and targets the next generation of health and other relevant professionals. conduct an annual symposium on global health that continually evaluates progress and identifies ways forward. Heather B Macdonald Health Adviser, AusAID, Canberra, ACT heather_macdonaldAtausaid.gov.au Human rights and equity in health policyStrengthen ethical and human rights awareness in AustraliaThrough evidence-based advocacy, strengthening of organisations and public discussion. This could include an Australian Bill of Rights enshrining social, cultural and economic rights, so that society collectively thinks about and acts on these issues; and ethical considerations are taken into account in political and policy formulation processes. Strengthen Australian awareness of the ethical and human rights aspects of global healthThrough the development of such awareness in health, development and foreign policy professionals; support for the appointment of clinical ethicists in teaching hospitals; commitment to equity and diversity in health representation, employment and practice; and honouring Australia’s international human rights obligations, so that equity in health is realised, both nationally and globally. Seek to achieve an aspirational element to Australia’s foreign policy and international assistanceThrough influencing political and policy development processes, so that Australia acts to achieve the common good, globally as well as domestically. Elizabeth A Reid Visiting Fellow, Gender Relation Centre RSPAS Australian National University, Canberra, ACT elizabeth.reidATrunbox.com

The Global Health and Foreign Policy articles in this issue of the Journal leave us in no doubt that the answer to the question posed in the Symposium title is an emphatic “Yes”! There is a great deal of scope for Australian engagement. Symposium participants outlined some practical steps to strengthen the links between health and foreign policy by: broadening the public policy agenda; engaging civil society more closely in the policy debate; and improving public understanding of global health issues. What is needed to develop and advance this agenda? There was overwhelming support from Symposium participants for the creation of an Australian Coalition for Global Health (name yet to be determined). The broad purpose of such a Coalition would be to advocate for (i) considering health implications in developing Australian foreign policy and trade agreements, and (ii) reducing global health inequalities. It was agreed during the Symposium that, to achieve this goal, a small coordination group should be formed, which would comprise participants from non-government organisations, academia, the private sector and interested individuals. Nominations have been sought for this coordination group, the purpose of which would be to advise on the creation of the Coalition and the organisational arrangements underpinning it, as well as to examine possible funding options, agree on an appropriate name, develop terms of reference, and formulate a work program. The coordination group will meet over the next few months, with a potential launching of the Coalition by mid 2004. The strategic pathway the Coalition adopts to argue the case for increased importance of health in foreign policy will be critical. As articles in this issue highlight, there are many ways of viewing the prism. One current strategy promotes national self-interest, with a particular focus on topical issues such as controlling the international spread of infectious diseases and bioterrorism. Such a strategy may resonate with governments; however, there is a risk that broader global health considerations would be constrained by this limited agenda. Conversely, while a strong humanitarian and human rights-based approach might be more in tune with the beliefs of many of those advocating greater consideration of health in foreign policy, such arguments have not held much sway in the Australian political context in recent years. A promising pathway is proposed by McInnes (page 168).1 He argues that, in an environment in which national boundaries are of decreasing importance, “narrow conceptions of the national interest have become less relevant, and a more internationalist and communitarian perspective is required”. This strategy treads a fine line by arguing that Australia’s national interest is best served if our Asian and Pacific neighbours enjoy good health, robust economies, and good security. What is evident is that, unless a strong, active and broad-based advocacy group is formed in Australia, the considerable enthusiasm and desire for action evident at the September 2003 Global Health and Foreign Policy Symposium will dissipate.

Michael A Reid

Current international instability has promoted health to the foreign and security policy agenda; however, health is narrowly conceived in terms of promoting the national interest and defending the state, particularly from the risks of infectious disease and bioterrorism. This development involves the risk of global health being co-opted into an international agenda that focuses narrowly on security concerns rather than on broader global health issues. An alternative construction places greater emphasis on shared humanitarian values in a globalised world. This offers a more equal relationship between health and foreign policy and allows a broader range of issues (eg, trade in goods and services affecting health) to be considered in bringing together global health and foreign and security policy.

Colin J McInnes PhD

Although there appears to be no Australian foreign policy statement on health, much of our existing foreign policy has health implications, ranging across security, economic, political and humanitarian objectives. Humanitarian motives have influenced Australia’s foreign-aid policy, but our aid program, like our wider foreign policy, has a large national interest component. A generalised approach to health and foreign policy activities is difficult given the disparate direct and indirect links between foreign policy and global health issues, and the various official and unofficial interests and responsibilities involved. The greatest benefit may come from the health community making its own judgements on health priorities and seeking to engage in specific terms with foreign policy makers.

Stuart Harris BEc (Syd), PhD

Recruitment by wealthy countries of health personnel from developing countries is threatening the viability of crucial health programs in poor countries, especially in sub-Saharan Africa. Australia has participated in this “brain drain”, although the extent and impact of this on different countries has not been adequately assessed. Australia depends on overseas-trained doctors to fill vacancies in public hospitals and private practice, particularly in rural and outer suburban areas where locally trained professionals are reluctant to work. Australia should adopt national strategies to minimise harm and maximise benefits of skills migration; concerted international action will also be required.

Mark L Scott BA · Anna Whelan PhD, AFCHSE · John Dewdney MD, SM, DPH · Anthony B Zwi MB ChB, PhD, AFPHM

Although infectiousness is a feature of Creutzfeldt–Jakob disease (CJD), only a small proportion of cases are linked to transmission through healthcare provision. As of January 2003, over 120 cases of CJD associated with use of human cadaveric dura mater had been recognised worldwide; almost all were associated with the commercial product Lyodura. Most cases (97) have occurred in Japan, giving an overall risk estimate of around 1 per 2268 patients treated with Lyodura (0.04%) in that country. In Australia, five cases of CJD have so far been linked to Lyodura, but, given the protracted tails of previous epidemics of transmissible spongiform encephalopathies, further cases are possible. Results of surveys of Lyodura use in Australia are incomplete, but information from the manufacturer suggests that 2208–2478 sheets of Lyodura may have been used here. This use translates to a relatively high incidence of Lyodura-associated CJD, with current overall rates appearing around five times higher than those reported in Japan; reasons for this difference are unclear.

Fiona J Brooke BA(Hons) · Alison Boyd PostGradDipGenCoun · Genevieve M Klug BSc(Hons), PostGradDipEpiBiostat · Colin L Masters FRCPA · Steven J Collins FRACP

Clinical records Patient 1 A 77-year-old woman was referred to us for an urgent surgical opinion regarding an abdominal mass. Fifteen months previously, she had been referred to a major metropolitan hospital with symptomatic iron deficiency anaemia, and weight loss of 5 kg in 6 months. Gastroscopy, colonoscopy and abdominal CT scan were unremarkable. There were no clinical features to suggest malabsorption, nutritional deficiency or inflammatory bowel disease. A diagnosis of angiodysplasia was considered, although there was no direct evidence of this. The patient received a 5-unit blood transfusion and iron supplements. During the 7 months after initial presentation, she was seen in medical outpatient clinics six times. Over the next 8 months, she was admitted six times, transfused 13 units of red cells, and given two iron infusions. A labelled red cell scan showed no gastrointestinal bleeding. An abdominal ultrasound was unremarkable. Results of investigations for coeliac disease and pernicious anaemia were normal. A bone marrow biopsy was consistent with iron deficiency anaemia. On one occasion, the admitting registrar considered a small bowel follow-through, but this was not performed. Paroxysmal nocturnal haemoglobinuria was excluded. During the last of these admissions, a firm abdominal mass was palpated. A computed tomography (CT) scan revealed an 8 cm heterogeneously enhancing soft tissue mass in the proximal jejunum. Lymphoma was considered the most likely diagnosis, and the patient was referred to our department. Push enteroscopy revealed an ulcerated adenocarcinoma in the proximal jejunum (A). A 10 cm, poorly differentiated jejunal adenocarcinoma was resected. Eleven months after surgery, the patient has shown no further symptoms of anaemia, and no evidence of recurrence. Patient 2 A 68-year-old man was admitted to our department for laparotomy for a small bowel tumour. The patient had a past history of an open cholecystectomy. Twenty-eight months before admission, he had been referred to a gastroenterologist with symptoms of gastro-oesophageal reflux disease; he underwent gastroscopy, which showed reflux oesophagitis, and was treated with proton pump inhibitors. Eleven months later, he was referred to a gastroenterologist again with persistent symptoms. He was seen several times in the next 9 months, and was then admitted to a general surgical service of a metropolitan hospital with abdominal pain. A provisional diagnosis of small bowel obstruction was made, and the patient was discharged the following day once his pain had settled. Twice during the next 5 months, he presented to the emergency department with abdominal pain, nausea and vomiting. His symptoms settled with analgesia and fluids. Persistent retrosternal pain had not been helped by a variety of H2 antagonists, proton pump inhibitors or prokinetic agents. He was admitted to our surgical service after presenting on two successive days with severe epigastric pain. Upper gastrointestinal endoscopy showed severe reflux oesophagitis. The first and second parts of the duodenum were normal. Abdominal CT showed a circumferential mass in the proximal jejunum with dilation of proximal bowel (B). Small bowel follow-through then showed an annular, stenosing lesion in the region of the duodenojejunal flexure. At laparotomy, a localised adenocarcinoma was resected (C). The patient had adjuvant chemotherapy and 12 months after surgery was asymptomatic, taking no medication, and had no evidence of recurrence. A: Small bowel carcinoma detected on push enteroscopy (Patient 1). B: Abdominal CT scan showing a large dilated small bowel loop in the left upper quadrant (Patient 2). C: Operative specimen showing a localised, constricting cancer (Patient 2). Small bowel carcinoma is rare compared with gastric and colorectal cancer. Fifty-eight cases were reported in Victoria in 2001.1 Although the small bowel comprises 75% of the gastrointestinal tract length, less than 2% of gastrointestinal malignancies arise there.2-6 Adenocarcinoma accounts for 40% of small bowel malignancies; others include carcinoids, lymphomas and gastrointestinal stromal tumours, as well as metastases from melanoma, breast, lung and renal cancer.3,5,6 Small bowel tumours are rarely considered as a differential diagnosis, and their discovery is usually greeted with surprise. They are much more common in patients with coeliac disease (risk of lymphoma) and in hereditary bowel cancer syndromes (hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, and Peutz–Jegher syndrome).2,4,6 Thus, small bowel tumours must be considered in patients with a family history of bowel cancer. A low index of suspicion for small bowel tumours is a result of their relative rarity, but delayed diagnosis may reduce the chance of successful treatment. Reasons for diagnostic delay include the non-specific presentation, the lack of awareness of the diagnosis and the inaccessibility of the small bowel to investigation. In one analysis of 77 consecutive patients with primary small bowel malignancy over 22 years, average delays were 2 months before presentation to primary care physicians, 8 months from presentation until appropriate investigation, and 12 months from presentation until definitive diagnosis.7 Our first patient represents a common scenario. A patient with iron deficiency anaemia had investigations to exclude gastroduodenal, colonic, and extra-intestinal sources of blood loss. The inaccessibility of the small bowel to investigation resulted in a 15-month delay to diagnosis of a small bowel adenocarcinoma. An abdominal computed tomography (CT) scan performed early in the investigation of anaemia failed to show any disease, and the patient’s symptoms were attributed to intestinal angiodysplasia, a diagnosis that is difficult to confirm. The failure to perform small bowel follow-through, despite its low sensitivity, may have contributed to the delay in diagnosis. Our second patient highlights the non-specific way in which small bowel adenocarcinoma can present. The patient presented with symptoms of reflux oesophagitis refractory to treatment. The abdominal CT scan was the pivotal investigation that alerted clinicians to a lesion in the jejunum. CT is frequently used to assess the abdominal cavity. The accuracy of abdominal CT in detecting primary small bowel tumours is poor — reported as 57% in one study of 85 patients.5 It is a useful staging procedure, but, given the poor sensitivity for small bowel pathology, abdominal CT should be used in concert with other imaging modalities. Barium contrast studies are the standard test for intraluminal or mucosal abnormalities beyond the duodenojejunal flexure, but have limited sensitivity.3-5 Small bowel enteroclysis is more sensitive than small bowel follow-through,8 and involves delivery of barium to the small bowel via an intestinal tube. Push enteroscopy, using a paediatric colonoscope, is an alternative, but does not visualise the entire small bowel. Video capsule endoscopy has shown promise in the diagnosis of small bowel disorders.9,10 It is not yet widely available, and further trials are required before its role is defined. It is contraindicated when small bowel strictures are suspected, so should be preceded by small bowel follow-through in these cases.9,10 Early studies show that it is more accurate than small bowel follow-through,9,10 so, when there is a strong clinical suspicion of small bowel pathology, patients should be referred to a specialist centre. Occasionally, exploratory surgery is appropriate, particularly when anaemia and abdominal pain coexist and the results of all other investigations have been negative. ConclusionThis report highlights the difficulties in diagnosing small bowel tumours. The diagnosis requires a high index of suspicion and early investigation. Iron deficiency anaemia in an older patient with normal results of endoscopic studies is not an uncommon clinical scenario. Small bowel malignancy should be considered when more common causes have been excluded, especially if there are general features suggestive of malignancy, such as anorexia, abdominal pain or weight loss. Abdominal CT scan coupled with small bowel follow-through is the minimum requirement. If this is negative, further investigation in a specialist centre should be considered. Lessons from practice Small bowel malignancy should be considered in cases of unexplained gastrointestinal bleeding, anaemia or obscure abdominal symptoms. Abdominal computed tomography scan and small bowel barium studies are minimum requirements for investigation, but have limited sensitivity. Capsule enteroscopy appears to be more accurate than barium studies and may have an increasing role in these cases as it becomes available.

Ronil V Chandra MB BS · Julie A Miller MD, FRACS · Ian T Jones MB BS, FRACS · Brett Manley MB BS · G Bruce Mann MB BS, PhD, FRACS

The most common cause of hyperthyroidism in Australia is Graves disease, caused by a defect in immunoregulation in genetically predisposed individuals, leading to production of thyroid-stimulating antibodies. Each of the three modalities of therapy for Graves disease — thionamide drugs, subtotal or total thyroidectomy, and radioactive iodine ablation — can render the patient euthyroid, but all have potential adverse effects and may not eliminate recurrences. Hypothyroidism occurs in about 5% of the adult population; most present with “subclinical” hypothyroidism (mild thyroid failure), characterised by raised levels of serum thyroid stimulating hormone (TSH) but normal free thyroxine (T4). The most common cause of hypothyroidism in Australia is autoimmune chronic lymphocytic thyroiditis, characterised by raised circulating levels of thyroid peroxidase antibody. Symptoms and signs of hypothyroidism are often mild or subtle and, when there is clinical suspicion, thyroid function tests are needed; if serum TSH level is raised, free T4 and thyroid peroxidase antibody should be measured. Replacement therapy with thyroxine is the cornerstone of therapy (1.6 μg/kg lean body weight daily, taken on an empty stomach); combination therapy with thyroxine and liothyronine (T3) is promoted, but there is little evidence of its clinical benefit. Despite the development of highly sensitive laboratory tests, clinical assessment and judgement remain paramount

Duncan J Topliss MD, FRACP, FACE · Creswell J Eastman AM, MD, FRACP, FRCPA

Stacey L Emmett,* Adam J O’Brien,† Joseph E Ibrahim† * Research Officer, † Consultant Physician, Clinical Liaison Service, Victorian Institute of Forensic Medicine and the State Coroner’s Office, 57-83 Kavanagh St, Southbank, VIC 3006. staceyeATvifm.org To the Editor: Root-cause analysis is an established, retrospective, structured investigative technique1 that was first introduced into wide clinical practice in public hospitals in Victoria in 2001.2 It is usually reserved for investigating infrequent and significant adverse events and explores the nature and causes of organisational systems failures.1 It is important for all healthcare professionals to understand this technique, as it is used increasingly by healthcare organisations. Cooper and Blamey’s Lesson from Practice described the outcome of an investigation using root-cause analysis of an occupational exposure to HIV from a needlestick injury.3 We commend the analyses that identified multiple failures of the system for reporting and responding to occupational exposures to hazardous material. The practice changes that ensued at Southern Health demonstrate the value of root-cause analysis. However, more information and analysis is required about the mistaken use of the stored serum samples. As the authors explain, the initial information was that the source patient tested negative for HIV antibodies. Some time later, it was discovered that the specimen tested was not from the source patient but from a patient of the same surname in the same ward. This caused a 3-day delay between the initial test and the Infectious Diseases Unit being notified that the source patient had twice tested positive for HIV antibodies. We contend this is an important and common systems failure that usually makes headlines of the form “Wrong site, wrong procedure, wrong person surgery”. The Joint Commission on Accreditation of Healthcare Organisations developed a universal protocol with the intention of highlighting the causative systems failures and minimising the frequency of recurrences of wrong-site surgery.4 The information given by Cooper and Blamey does not clearly explain why (ie, the root cause) the incorrect specimen was tested initially. The pathology department’s review identified the presence of unacceptable “informal norms” in the practice of blood collection and labelling. The suggested remedy that “all serum should be collected with strict adherence to blood collection and labelling protocols” is unlikely to prevent a recurrence. Exhortation to do better rarely solves the underlying problem. It is therefore important to understand why health professionals violate procedures and protocols.5 The experiences of Cooper and Blamey demonstrate that some of the limitations and benefits of root-cause analysis depend on the depth of the investigation. The early and unquestioning acceptance that strict adherence to an existing protocol will prevent another “wrong person” error is not convincing. This contrasts with the well-conducted inquiry and subsequent management of occupational exposure to needlestick injuries.

Stacey L Emmett · Adam J O’Brien · Joseph E Ibrahim

Elizabeth E Cooper,* Stephen L Blamey† * Sterilisation and Infection Control Coordinator, Southern Health Infection Control and Epidemiology, Southern Health, Locked Bag 29, Clayton, VIC 3168; † Head, Department of GastrointestinaI Surgery, Monash Medical Centre, Melbourne, VIC. elizabeth.cooperATsouthernhealth.org.au In reply: Emmett and colleagues request more information and analysis about the mistaken use of stored serum samples. The pathology staff member correctly labelled the specimen of the patient being bled but did not follow the protocol in identifying that the patient was the same as on the request slip. It had not been highlighted that there were two patients with the same surname (but different first names) in the ward, and blood was collected from one patient with a request slip labelled for another. At specimen reception, the protocols were again not followed, as the staff did not check that the minimum identifiers on the specimen label and request form matched. It is recognised that violations of procedures are not root causes and are not directly manageable. The cause of the procedural violation must be managed.1 The collection and labelling of blood protocols were reviewed after this incident and found to be appropriate. The root-cause analysis identified that the protocols were not followed and that unacceptable “informal norms” had become practice in the collection and labelling of specimens. Staff training was examined and revised to ensure that staff were aware of the content of the protocols and that they followed them accordingly. All staff members were counselled about the importance of following correct procedures and the consequences of not doing so. Up to 1000 specimens are received at specimen reception each weekday. New “front end processing” technology is to be introduced at the end of 2003. This electronically scans the specimen and request slip to ensure details match. In the interim, in recognition that mislabelling will occur, all specimens relating to occupational exposures are collected at the time of the incident. Previously available results and serum stored in the laboratory are not relied on.

Elizabeth E Cooper · Stephen L Blamey

Nicola Magnavita Researcher, Italian Study Group on Hazardous Workers and Institute of Occupational Medicine, Catholic University School of Medicine, Largo Gemelli 8, Rome, 00168, Italy. magnavitaATrm.unicatt.it To the Editor: The article by Charles and colleagues1 is an interesting contribution to the development of Australian protocols for healthcare workers infected with hepatitis C virus (HCV). To date, most European countries have no national policy for HCV-infected healthcare workers, and existing guidelines are advisory in nature and poorly enforced. A panel of European and American experts recently failed to reach consensus on management of HCV-infected healthcare workers who perform exposure-prone procedures, and concluded that screening for HCV infection and restricting infected healthcare workers is not justified, based on current published data.2 Today, the effectiveness of guidelines relies solely on self-assessment of HCV status from healthcare workers. However, collaboration of healthcare workers might be problematic if management criteria are not defined, and workers’ rights are not guaranteed. Issues such as practice restriction, disclosure of serological status to patients, privacy and discrimination need to be resolved. Given the risk of HCV transmission from healthcare workers to patients is not clear, the burden of uncertainty rests entirely with healthcare workers. Because of the fear of discrimination, needlestick injuries may be under-reported, and infected workers may not seek diagnosis and treatment because they have greater legal protection if they can honestly say that they did not know their serological status.3 Moreover, the largely asymptomatic nature of HCV infection may leave healthcare workers unaware of their infective status. The results of Charles and colleagues suggest up to tenfold underreporting of occupational injuries with blood exposure in Australian healthcare workers.1 With this number of unreported exposures, there may be two or three new cases of HCV infection in healthcare workers in metropolitan hospitals in Melbourne each year — a figure similar to the prevalence of occupational HCV infection from notified injuries. Paradoxically, the prevalence of HCV infection in healthcare workers and the transmission risk for patients cannot be assessed without compulsory testing of healthcare workers, but without risk assessment there is no reason for this compulsory testing. Overcoming this Catch-22 with well-targeted epidemiological studies may help create broad consensus about policies for HCV-infected workers.

Nicola Magnavita

Patrick G P Charles,* M Lindsay Grayson,† Peter W Angus,‡ Joseph J Sasadeusz§ * Registrar, Department of Infectious Diseases, † Director, Infectious Diseases and Clinical Epidemiology, ‡ Director, Gastroenterology and Hepatology, Austin and Repatriation Medical Centre, Studley Road, Heidelberg, VIC 3084; § Director, and Infectious Diseases Physician, Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, VIC. patrick.charlesATmh.org.au In reply: Magnavita correctly points out the need for a national policy on the management of healthcare workers who are either infected with or occupationally exposed to hepatitis C virus (HCV). Compulsory testing of healthcare workers is neither practical, logical nor fair in the current Australian healthcare environment. Firstly, most healthcare institutions do not currently have adequate staff health systems in place to ensure that staff are appropriately vaccinated against readily preventable diseases, such as hepatitis B, measles and varicella, let alone to test all staff for a disease such as hepatitis C, for which there is no vaccine. Secondly, awareness about important issues, such as healthcare worker transmission-risk assessment is embryonic (at best) in most institutions. The risk of HCV transmission from infected healthcare workers to their patients is generally considered to be extremely low, but probably depends on a number of factors, including the nature of the patient’s procedure and the healthcare worker’s injury and level of viraemia at the time. Simplistic legal opinions about such matters rarely help. Finally, we agree that the rights of healthcare workers are often neglected in this era of litigation-driven medicine. If these rights are not considered, and infected or exposed healthcare workers are simply excluded from all types of work without any appropriate risk assessment or compensation, then compliance with any form of postinjury testing is unlikely. However, rather than ignoring this important workplace issue, as we believe many Australian institutions currently do, a logical assessment of potential transmission risk is possible that is both fair to the patient and the infected worker. Stratification of healthcare workers according to their level of HCV viraemia and whether they are involved in exposure-prone procedures is a logical start — this we have attempted in our proposed guidelines.1 Some healthcare workers may avoid being tested so that they can have the protection of not knowing their serological status.2 However, recent studies suggesting the efficacy of early treatment of acute HCV infection3 mean that it will actually be in healthcare workers’ interest to know if they have recently acquired HCV infection — as long as they are treated in a manner that protects their health and workplace rights, while also protecting the rights of their patients.

Patrick G P Charles · M Lindsay Grayson · Peter W Angus · Joseph J Sasadeusz

Caroline M de Costa Obstetrician and Gynaecologist, Cairns Base Hospital, Cairns, QLD 4870. carolinedecAThotkey.net.au To the Editor: As a “grand multip” myself, I turned with interest to Humphrey’s recently published study of grand multiparity and pregnancy risk at Cairns Base Hospital.1 However, I cannot support his conclusions. Throughout the period of the study, most grand multiparous women giving birth at this hospital were actively managed in the third stage of labour with a regimen designed to prevent postpartum haemorrhage (intravenous ergometrine/oxytocin). Women of lesser parity were also given preventive therapy, but generally in lower doses and less consistently. This is a major confounding factor not addressed in Humphrey’s study. Clearly, an unknown, but probably significant, number of haemorrhages were prevented by this treatment. Given that 9.2% of grand multiparous women still had a postpartum haemorrhage, any prospective randomised controlled trial that allowed some of these women not to have active management of the third stage would be unethical. Numerous other studies have shown an association between grand multiparity and postpartum haemorrhage. 2-4 These include the study of Babinszki and colleagues, which limited study subjects to upper-class, private patients and thereby eliminated many confounding variables.4 Humphrey’s study does not report the severity of the postpartum haemorrhages that did occur; even a small number of life-threatening haemorrhages could justify continuing very active preventive measures in grand multiparous women. The incidences of anaemia and previous postpartum haemorrhage, not recorded in the study, would also be of interest; both are independent reasons to actively manage the third stage in women of any parity, and there are good reasons to believe that both may be more common in grand multiparous women. Humphrey also states that grand multiparous women did not have higher perinatal mortality rates or poorer maternal outcomes than women of lower parity. However, whenever possible throughout the period of the study, grand multiparous women were identified on booking into antenatal care and treated by senior obstetricians. Many had conditions such as diabetes, hypertension, anaemia and heart disease managed carefully to ensure as good a pregnancy outcome as possible. This focused obstetric care could well have counteracted any natural tendency of grand multiparous women towards poorer outcomes, and thus it is not possible to draw any conclusions about perinatal results from the data provided. What is clear from these data is that grand multiparous women in far north Queensland are often economically and socially disadvantaged compared with women of lower parity. This is a common finding in almost all studies of grand multiparity. 2,3,5 We should remember that these women are taking home a new baby to conditions that may already be quite compromised. They deserve the best obstetric care we can offer them, and we should be very cautious when reviewing protocols that we do not increase risks to these women or their babies.

Caroline M de Costa

Michael D Humphrey Director, Obstetrics and Gynaecology, Women's and Children's Health Service, King Edward Memorial Hospital, PO Box 134, Subiaco, WA 6904. Michael. HumphreyAThealth.wa.gov.au In reply: I thank de Costa for her interest in the debate about excessive medicalisation of normal childbirth in women with significant parity. The obstetric protocol manual of Cairns Base Hospital did not, at any time, discriminate in the details of management of the third stage of labour between grand multiparous and non-grand multiparous women. The statistical analysis in my report shows that, once confounding factors are accounted for, grand multiparous women who labour spontaneously are twice as likely as their less parous counterparts to have a spontaneous vaginal birth, with no statistically greater risk of a postpartum haemorrhage requiring transfusion.1 The purpose of multivariate analysis is to remove, as far as possible, the influences of the confounding factors that de Costa’s appraisal relies on. The recommendation from my study is not that grand multiparous women be ignored, but that, if labour occurs spontaneously at the end of an uncomplicated pregnancy, they be treated no differently to their less parous sisters in terms of venous cannulation and blood cross-matching. I am on record as strongly recommending sensible, routine oxytocin-based management of the third stage of labour in all pregnancies.2 In the end, the question is whether or not evidence wins out over an individual’s historically influenced clinical beliefs.

Michael D Humphrey

Neil H Cradick General Practitioner, PO Box 1127, Buderim, QLD 4556. cradwhitAToptusnet.com.au To the Editor: On opening the MJA Focus document “Prevention of cardiovascular disease: an evidence-based clinical aid”,1 I expected to find useful and contemporary guidelines for general practice. However, I was surprised to read two of the recommendations — for the use of antihypertensive and antiplatelet drugs in “low risk” patients (those without risk-associated clinical conditions or end-organ damage). The document recommends drug treatment only if systolic blood pressure is > 180 mmHg or diastolic blood pressure is > 100 mmHg in people under 60 years, or systolic blood pressure is > 160 mmHg in people over 60 years. While Fulcher et al1 volunteered that this was at odds with clinical practice, they supported the recommendations by stating that they were in accordance with published guidelines. The data for these conservative hypertension parameters were published nearly 10 years ago,2 or derived from textbooks,3 and are at odds with the 1999 WHO/ISH guidelines,4 and even more at odds with the excellent Joint National Committee (JNC 7) report.5 The latter publication recommends, after lifestyle recommendations, drug treatment for a blood pressure of 140–159/90–99 mmHg for those without end-organ damage. Furthermore, the focus document recommends primary prevention with aspirin in those with a calculated annual cardiovascular event risk > 3%. Hayden et al6 suggest antiplatelet treatment should be offered to those with a 5-year cardiovascular event risk > 3%, which equates to a > 0.6% annual risk. The benefit to harm ratio needs to be explained to the individual, and therapy should only be initiated once blood pressure is controlled. As an interested general practitioner and user of evidence-based guidelines, I usually check the funding of publications, and, with the heavy emphasis on the use of ACE inhibitors (in particular ramipril) and statins (which are produced by Aventis Pharma), it is difficult to rely on the evidence as presented. I would hope that independent bodies such as the National Prescribing Service or Australian Prescriber could take the pharmaceutical lead and produce desktop references with a more unbiased opinion on the latest collection of evidence that is shaking us up in primary care medicine. I would again refer readers to the excellent hypertension guidelines mentioned above4,5 (in particular the JNC 7 reference card available on the Internet at www.nhlbi.nih.gov/guidelines/hypertension/jnc7card.htm), and caution them to remain wary of easy-reference desktop items funded by pharmaceutical companies.

Neil H Cradick

Gregory R Fulcher,* John V Amerena,† Greg W Conner‡ * Director, Department of Diabetes, Endocrinology and Metabolic Medicine, Level 3, Main Block, Royal North Shore Hospital, St Leonards, NSW 2065; † Cardiologist, Department of Clinical and BioMedical Sciences, University of Melbourne, Melbourne, VIC; ‡ Vascular Physician, Cardiovascular Diagnostic Services, Sydney, NSW. gfulcherATmed.usyd.edu.au In reply: We thank Cradick for his critical review of our publication.1 His interesting points illustrate some of the reasons we were keen to publish this work. Firstly, the average practitioner is confused about which guidelines (both national and international) to follow. Cradick refers to the JNC 7 report and WHO/ISH guidelines (the committee is familiar with these), but which to follow? The committee decided a priori that Australian national guidelines, if they existed, would be referenced in preference to overseas ones. We mentioned that current Australian hypertension guidelines should be revised, and that clinical practice was probably at odds with these recommendations. Secondly, guidelines quickly become dated. Cradick cites the recommendation of Hayden et al that aspirin should be introduced if the annual risk of a cardiovascular event is > 0.6%.2 The latest Australian guidelines3 recommending a > 1% annual risk as the treatment threshold were published just after we received Cradick’s letter. The Hayden article is thus (for some patients) at odds with current local recommendations. Consistent with our approach, we will include the Australian recommendations in the first update of our document (July 2004). Cradick’s comments imply bias in the presentation of the data; yet he fails to substantiate this. Neither the clinical trials quoted (nearly all of which are funded by the pharmaceutical industry) nor the conclusions or inferences drawn have been challenged. He refers to the “heavy” emphasis on the use of ACE inhibitors and statins, implying that this is inappropriate. We would argue that, given the strength of the evidence, this emphasis is appropriate, and reflects current specialist practice in tertiary centres. Careful reading of the National Prescribing Service publications will show that “heavy” reference is made to the 4S,4 LIPID,5 CARE,6 and WOSCOPS7 studies (for example, NPS News 20 February 20028), as well as to the prescribing information for Lipitor (Pfizer), Pravachol (Bristol-Myers Squibb) and Zocor (Merck Sharp & Dohme). We must caution against “throwing the baby out with the bathwater”. The HPS, CARE, LIPID, WOSCOPS, HOPE, PROGRESS, 4S, CURE, and CREDO studies represent substantial and widely acclaimed clinical trials that have had a positive impact on clinical care. They have all been funded by the pharmaceutical industry. Finally, about 130 GPs in clinical practice had some input in compiling and formatting this document. The document was tested before publication in over 30 000 patients, and was peer reviewed by several clinicians. It is a pity that Cradick was not a participant in any of these processes.

Gregory R Fulcher · John V Amerena · Greg W Conner

Michael Thomsen,* Luis Vitetta,† Mathias Schmidt,‡ Avni Sali§ * Research Associate, † Director of Research, § Head, Graduate School of Integrative Medicine, Swinburne University, 9 Frederick Street, Hawthorne, VIC 3122; ‡ Head of Toxicology, Society of Nutritional Medicine and Dietetics, Harsewinkel, Germany. lvitettaATmedicine.swin.edu.au To the Editor: Gow and colleagues recently attributed fulminant hepatic failure in an Australian patient to an over-the-counter herbal product containing kava (Piper methysticum) that is extensively used in the community.1 We are not convinced that kava caused this patient’s liver failure. The hepatotoxicity could have been due to other unidentified contaminants of the herbal preparation or to chromium (from the mineral supplements also taken by the patient). We tested a sample of the product Kava 1800 Plus (Eagle Pharmaceuticals, Batch No. 10711) by thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC) methods, and assessed it against defined standards. Kavalactones were identified and quantified by normal-phase HPLC. Kava was positively identified, with a content of about 47 mg of kavalactones per tablet (the product label specifies 60 mg per tablet). However, flavonoids from Scutellaria lateriflora, analysed by reverse-phase HPLC, could not be found. Passiflora incarnata, analysed by TLC, was also not found, with none of the typical flavonoid bands being detectable. The absence of two ingredients listed on the product label, P. incarnata and S. lateriflora, raises a new concern that there may be batch variations, as well as the possibility of unknown adulterants or contaminants being present. The possibilities of contaminants and batch variation were not excluded in the case report by Gow and colleagues.1 The Therapeutic Goods Administration established that Kava 1800 Plus did not contain common germander (Teucrium chaemaedrys), a known adulterant for S. lateriflora. However, Teucrium species are known to have hepatotoxic effects and there are about 100 species, any one of which could have been a contaminant. Gow et al refer to 68 international case reports of suspected hepatotoxicity with the use of kava.1 An independent analysis of these 68 cases concluded that only two were probable kava-associated hepatotoxicities.2 An incidence calculation from these case reports indicates that hepatotoxicity from kava occurs in 0.008 cases per million daily doses,2 which represents an extremely low risk of adverse reactions associated with kava. Recently, a study on the potential hepatotoxicity of kava found that the aqueous extract of kava does not affect results of liver function tests in rats. Extracts were administered in daily dosages of 200 or 500 mg of active kavalactones per kilogram of bodyweight for 2 or 4 weeks. Sera were assayed for four enzymes that are markers of liver toxicity, and liver homogenates were assayed for malondialdehyde formation, which indicates changes in lipid peroxidation. Kava did not elevate malondialdehyde or the enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase or lactate dehydrogenase. In fact, in certain instances, these enzymes were significantly reduced, suggesting a lack of toxic effect of kava on the liver.3 TLC analyses have shown that there is no qualitative difference between aqueous, acetone or ethanol extracts of kava.4 We propose, given that patients can consume other over-the-counter products such as chromium (shown to have hepatotoxicity at high concentrations),5 that all products consumed by patients must be evaluated before causality can be attributed to a particular herb. Reports of case records associated with hepatic failure due to kava require proper verification and documentation of all the findings.

Michael Thomsen · Luis Vitetta · Mathias Schmidt · Avni Sali

Paul J Gow,* Nathan J Connelly,† Richard L Hill,‡ Peter Crowley,§ Peter W Angus¶ * Gastroenterologist, † Gastroenterology Registrar, ¶ Director, Department of Gastroenterology and Liver Transplantation, § Pathologist, Department of Anatomical Pathology, Austin and Repatriation Medical Centre, Studley Road, Heidelberg, VIC 3084; ‡ Medical Officer, Adverse Drug Reactions Unit, Therapeutic Goods Administration, Canberra. paul.gowATarmc.org.au In reply: Thomsen et al raise several points regarding our recent report of a death following ingestion of a preparation containing kava.1 The first is that the results of their analysis of the herbal preparation differ from those of the Therapeutic Goods Administration (TGA). The TGA found Passiflora incarnata in the tablets, whereas Thomsen and colleagues did not. The explanation for this lies in the fact that different batches of the product were analysed by the two laboratories. The analysis we reported relates to batch 13861, which was the source of the patient’s tablets. Thomsen and colleagues have analysed material from a different batch that may have contained different components. Thomsen et al also raise the possibility that Teucrium, a known adulterant of Scutellaria, may have been present in the preparation. With respect to this issue, the TGA tested for both T. chamaedrys and T. canadensis and found none present. They also tested for the presence of the chemicals teucreoside and verbascoside, both of which are found in many Teucrium species. Neither was present. The raw materials used to make the tablets were also analysed, and no evidence of Teucrium substitution or contamination could be found. The next point raised is whether the association between kava use and hepatotoxicity is causal, and they quote an analysis published in the journal Phytomedicine, in which the authors claimed that kava was the probable cause in only two of 68 reviewed cases. In marked contrast, the Journal of Hepatology, in July 2003, published an analysis of 36 cases of hepatitis associated with the use of kava.2 The review concluded that kava was the certain or probable cause of the hepatitis in 24 of the 36 cases. Worryingly, eight of these patients required liver transplantation. Thomsen and colleagues then point to a lack of evidence of hepatotoxicity in studies in rats administered kavalactones.3 We believe it is inappropriate and misleading to suggest that a study of this kind could rule out the possibility that kava preparations cause life-threatening but uncommon idiosyncratic hepatotoxic reactions in humans. Finally, Thomsen et al wonder whether the patient’s illness may have been due to chromium toxicity. However, the illness was not suggestive of chromium poisoning.4 There is no reason to believe that chromium was present at other than normal background levels.

Paul J Gow · Nathan J Connelly · Richard L Hill · Peter Crowley · Peter W Angus

Colin L Crawford Retired physician, 23 Grafton Road, London, W3 6PB, UK clcraw13AThotmail.com To the Editor: The Australian Drug Evaluation Committee (ADEC) has recommended that thalidomide be approved for the management of erythema nodosum leprosum. This recommendation has now been accepted by the Therapeutic Goods Administration. Was ADEC unaware that the World Health Organization no longer recommends thalidomide in the management of this complication of lepromatous leprosy?1,2

Colin L Crawford

Martin H N Tattersall Chairman, Australian Drug Evaluation Committee; and Professor of Cancer Medicine, Blackburn Building D06, University of Sydney, Sydney, NSW 2006 mtattATmed.usyd.edu.au In reply: When it considered thalidomide for registration for management of erythema nodosum leprosum (ENL) and another indication (myeloma), the Australian Drug Evaluation Committee (ADEC) was not aware that the World Health Organization (WHO) does not recommend the drug for this indication. ADEC bases its recommendations on review of the scientific and clinical evidence submitted concerning the efficacy and safety of products submitted for registration. In the case of thalidomide in the management of ENL, ADEC reviewed the results of several randomised studies, together with additional published reports. Data from the US Public Health Service analysing the entire experience of thalidomide use in ENL in the United States from 1978 to 1994 were also reviewed. The committee concluded that the efficacy of thalidomide in acute ENL is beyond dispute. Moreover, thalidomide was also shown to be useful in patients with ENL already treated with corticosteroids and dapsone. ADEC discussed the side-effect profile of thalidomide in the ENL studies and concluded that skin rashes, sometimes with eosinophilia, were somewhat more common than in the myeloma studies that were also reviewed. In regard to safety concerns relating to thalidomide’s teratogenicity, the committee was informed of the sponsor’s proposed risk management program, which is based on mandatory registration of prescribing doctors, patients and dispensing pharmacists. This program is based on an effective program in the US, where the Food and Drug Administration has registered thalidomide for treatment of ENL. ADEC felt that the risk–benefit ratio favoured registration for ENL (and myeloma). However, the committee resolved that a boxed warning should be included stating: Thalidomide has caused severe birth defects when taken during pregnancy. Thalidomide should never be used by women who are pregnant or who could become pregnant whilst taking the drug, or could become pregnant within four weeks after stopping the drug. Even a single dose can cause severe birth defects. I have reviewed the WHO documents referred to by Crawford,1,2 and consulted Medline. I have also had access to a review article in press in the Lancet.3 I believe the evidence indicates that thalidomide is superior to steroids in controlling ENL. Britton and Lockwood state that thalidomide is the drug of choice for men with ENL;3 however, they comment that using thalidomide in women with ENL is a difficult decision for a woman and her doctor. The WHO documents emphasise that any benefit from thalidomide must be balanced against its known toxicity, and conclude that experience has shown that it is virtually impossible to develop and implement a foolproof surveillance mechanism to combat thalidomide toxicity. ADEC concludes that thalidomide is an effective and useful drug in the management of ENL, and that the risk management program which is to be established in Australia, together with the inclusion of a boxed warning, will ensure that the risk–benefit profile of thalidomide use in ENL is favourable.

Martin H N Tattersall

Trevor (“Jim”) Dinning was born in Adelaide on 16 February 1919 and died on 22 September 2003 after a long illness terminating in renal failure. He was the chief architect of neurosurgical services in South Australia and the creator of a very successful research foundation. After graduating in medicine from the University of Adelaide in 1942, Jim served as an army medical officer in several units, including the North Australian Observer Unit, charged with detecting Japanese landings. However, he developed pulmonary tuberculosis and was incapacitated for some 2 years. After his recovery, he took an appointment as lecturer in anatomy at the University of Adelaide. He decided to make a career in neurosurgery, and in 1951 he went to Guy’s Hospital in London to undergo specialist training. From the outset he had the qualities of a good neurosurgeon: an unhurried and meticulous operative technique and a total commitment to the welfare of patients. Jim returned to Australia in 1953 to take up an appointment, initially as Honorary Assistant Neurosurgeon, at the Royal Adelaide Hospital (RAH), where he remained for the next 30 years under various titles. From 1953 to 1971 he was also Chief of Neurosurgery in what is now the Women’s and Children’s Hospital. In 1971 he became full-time Director of Neurosurgery at the RAH. In both hospitals he established modern neurosurgical units, with rigorous attention to quality control and case audits. The development of an integrated state-wide neurosurgical service was very largely Jim’s achievement. He gave special attention to the needs of Australians living in rural areas and was ahead of his time in planning how to manage head injuries in remote locations. On a national level, Jim was a major force in creating neurosurgical training systems in Australia, beginning around 1970, when he was president of the Neurosurgical Society of Australasia. He helped to place promising trainees in overseas units with good research facilities, where they learned skills that have since helped to make Adelaide a leading centre for head-injury research. In 1964 he created what is now the Neurosurgical Research Foundation. As NRF President, Jim initiated fundraising for an academic chair in neuroscience. His vision was realised in 1992 with the establishment of a chair of neurosurgery research at the University of Adelaide. Jim was liked and trusted by his colleagues, and admired as a superb diagnostician, teacher and scholar. He was warm and compassionate towards his patients, and had a long and fulfilling life with his wife Beatrice and his four children. After official retirement, he continued to treat patients with intractable pain at the Memorial Hospital. His other retirement activities included bee keeping and sheep breeding. The many memorials to Jim’s achievements include the RAH’s Dinning Neuroscience Library, the Neurosurgical Research Foundation, and the legacy of his practice and teaching, which are now part of the fabric of Australian neurosurgery. Donald Simpson

Donald Simpson

Global public health: a new era. Robert Beaglehole (editor). Oxford: Oxford University Press, 2003 (xx + 284 pp). ISBN 0 19851529 4. Those of us trained as "curative" practitioners should pause to take note of this book, which gives an account of many awesome phenomena. These include: the terrible inequalities and worsening health figures in many countries; the importance of non-medical factors (such as schooling for girls) in achieving better health outcomes; a disgraceful rise in tobacco marketing and in the incidence of tobacco-related disease in developing countries; unipolar depression as the greatest cause of chronic disability in developed countries; the destruction of our fragile biosphere; health outcomes in Canada consistently outperforming those in the United States; and the political nature of many of our problems. Many of us practise some preventive medicine, such as vaccination and providing lifestyle advice — but as adjunctive activities. This is a book for those interested in the next steps in public health. It is not, nor does it pretend to be, a first book. It does not study the rudiments of public health. It points to new and different world problems. It identifies important influences in our previous "golden" century of progress and other influences that will be important this century. However, the text lacks a discussion of the possible consequences for local and international economies of acting on some of the strategies advocated by public health practitioners. Thus, if universal immunisation was achieved, avoidable child mortality would drop and nations would then have to provide more schools, more teachers, more roads, more hospitals, more clean water, more food, more social services and so on. None of these downstream consequences is developed adequately. Peter E Baume AOHonorary Research AssistantSocial Policy Research Centre University of New South Wales Chancellor, Australian National University

Spinning out The patient with the first probable case of variant Creutzfeldt-Jakob disease (vCJD) contracted after a blood transfusion has died. The death has prompted an editorialist to outline the expensive, intrusive but necessary steps in preventing further human-to-human transmission in the UK. Many people who were caught up in the surgical web spun out from recipients of "at vCJD risk" blood and blood products will need to be managed as if vCJD had been diagnosed. They may also need to accept restrictions on what they can do until we know more, so as not to expose others to potential risk. BMJ 2004; 328: 118-119 Wet markets whet viruses According to a US expert, permanent live-animal markets (known as "wet markets") provide optimal conditions for the zoonotic transfer and evolution of infectious disease agents. The markets allow intermediate hosts for influenza (poultry, pigs), and possibly SARS, to commingle with human contacts. The author said that while wet markets will eventually be phased out — when younger generations no longer prefer live animals for fresh produce — to ban them now would probably drive the wet-market system "underground", where monitoring would be impossible. Rather, we need to reduce the viral burden in wet markets (eg, by using pandemic vaccines, improving hygiene and sanitation and discouraging the sale of animals caught in the wild). Lancet 2004; 363: 234-236 Malaria mistreatment A group of international experts, writing in their personal capacity, have decried the difference between policy and reality when it comes to funding malaria treatment in Africa. They say that although artemisinin-class combination therapies (ACT) are WHO’s stated preferred first therapy for malaria wherever Plasmodium falciparum is the predominating infective species, WHO representatives are approving funding for other treatments which are often ineffective because of drug resistance. Attaran and colleagues say that such funding decisions, the result of pressure from aid donors, are indefensible: at the very least, they waste precious international aid money and, at worst, they kill patients who have malaria. The authors call for WHO to produce malaria treatment guidelines and to convene a Green Light Committee of independent malaria treatment experts to oversee the financing and supply of drugs — without delay. Lancet 2004; 363: 237-240 Extreme medicine The health and human rights implications of non-lethal weapons, of being a prisoner-of-war, of famine relief and of child labour in India are among 28 various topics addressed in essay form in a special supplement, Extreme Medicine, published by the Lancet. The foreword acknowledges that war, plague and political turmoil inevitably end in individual suffering, which the medical profession attempts to address. Lancet 2003; 362: S1-S57 Sign language A road sign depicting a pair of "John Lennon-style" glasses indicates blind people are in the vicinity — if you're driving in the former Eastern Bloc, that is. The equivalent Bangladeshi road sign portrays a stick, while many other countries do not seem to have any such sign, according to UK authors. They engaged the services of British diplomats and consuls stationed around the world to explore how road signs worldwide illustrate the physically disabled and the elderly. Only a few countries (30 of 118) were reported to have signs featuring one or more of the elderly, blind, deaf or disabled categories, and the signs used would not always be clear or familiar to drivers. If signage does improve the road safety of these pedestrians, perhaps an international agreement on the content and style of these signs is needed, the authors said. BMJ 2003; 327: 1456-1457 Tarred with the same brush Smoking filtered, very low tar (≤ 7 mg) cigarettes carries a similar risk of dying of lung cancer as does smoking filtered, low tar (8–14 mg) and medium tar (15–21 mg) cigarettes, according to US researchers. Their finding comes from the American Cancer Society-initiated Cancer Prevention Study II, which followed more than 940 000 people, of whom about 25% were cigarette smokers, for six years (1982–1988). People smoking non-filter, high tar (≥ 22 mg) cigarettes were, however, at greatest risk. The researchers said their findings were consistent with evidence of "compensatory smoking", in which addicted smokers maintain their nicotine intake by increasing the "puff volume", or the time during which smoke is retained in the lungs, and by smoking more cigarettes. Further, even as tar yields of cigarettes have declined, changes in tobacco curing and blending have increased the delivery of carcinogenic tobacco-specific nitrosamines (TSNAs). BMJ 2004; 328: 72-75 — Dr Ann Gregory, MJA

Ann Gregory