Volume 192 Issue 11

The worldwide availability of preventive genetic health information will benefit millions of families In Australia, it has been estimated that around a million people are affected directly or indirectly by inherited disease. An audit of admissions to a major paediatric hospital in the United States showed that, in 71% of admitted children, their condition had a significant genetic component and, of these, 10% had an inherited disease.1 However, inherited diseases have received little attention in health budgets and research grants. One of the reasons is that each of the thousands of different inherited diseases caused by gene mutations is extremely rare and, as a consequence, affected families and clinicians in the field have little voice. Understanding and developing care for people with inherited disease depends on setting up and maintaining databases with information on the incidence, phenotype, penetrance, treatment strategies, and prognosis of these conditions. Gene mutation databases are labour intensive to develop, populate and maintain, but are essential if we are to realise the benefits of the vast amount of genetic data on individuals and populations, both healthy and unhealthy, embedded in the human genome. At present, there is a lack of funds for critical inherited disease registries or databases in Australia and around the world. Without adequate and sustained funding for database set-up and curation, these databases will inevitably harbour data deficiencies and even inaccuracies, which may have serious health consequences. So, what is being done, and what more can be done, to address this deficiency. Several specific databases already exist: Online Mendelian Inheritance in Man (http://www.ncbi.nlm.nih.gov/omim) is a public database of bibliographic information about human genes and genetic disorders;2 the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/ac/index.php) collects data on published germline mutations in nuclear genes underlying human inherited disease;3 the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/) provides access to biomedical and genomic information;4 and there are over a thousand genes in locus-specific databases (http://www.hgvs.org/dblist/glsdb.html).5 However, all these excellent activities are insufficient to meet the rapidly emerging need to document all mutations in all genes, which would allow interpretation of the human genomic sequences available from diagnostic, research and, increasingly, commercial sources. At a gathering of experts in human genetics in 2006, the Human Variome Project (www.humanvariomeproject.org) was created to fulfil this need.6-8 This project aims to facilitate “the establishment and maintenance of standards, systems and infrastructure for the worldwide collection and sharing of all genetic variations effecting human disease”. It is working towards the comprehensive collection of genetic information from all sources, ensuring data accuracy, making the information freely available and, at the same time, developing standards to achieve these goals. Critical collaborative projects are underway to define protocols that can be readily extended to all genes and to all countries. The Human Variome Project has initiated two pilot studies that will act as models for global collection of all gene mutations and their effects. The first involves the International Society for Gastrointestinal Hereditary Tumours (InSiGHT; http://www.insight-group.org), the peak international body of health care professionals caring for families with inherited gastrointestinal cancer. InSiGHT maintains a database of mutations in the mismatch repair genes responsible for Lynch syndrome (hereditary non-polyposis colorectal cancer syndrome). InSiGHT has established governance, curation, interpretation, phenotype, functional assay, and histopathology subcommittees to support its database, aiding in ensuring integrity of the data, controlling access for bona fide use, and encouraging submissions of variants from individual laboratories and national data collections. Since engaging with the Human Variome Project, and learning of its experience in locus-specific database management, InSiGHT has increased its variant submissions from 550 to over 11 000, and attracts over 20 000 website “hits” per month, strongly affirming its value to the scientific community. Obtaining funding for this critically important database has been difficult, but full credit needs to go to the Cancer Council Victoria, the Victorian Cancer Agency and, most importantly, to the George Hicks Foundation, for grasping an important leadership opportunity. The second pilot study is being conducted by the Australian Node of the Human Variome Project, which is developing a country-specific system as a model for other countries, where possible using freely available software and data management systems.9 While several countries have collected mutation data for their population, there are no unified collection standards and no links to other international efforts. This project, funded by the Australian Government’s National eResearch Architecture Taskforce (NeAT) (https://www.pfc.org.au/bin/view/Main/NeAT), will address this deficiency. It is in the early- to mid-phase of its work, and trials in two laboratories are expected to take place by the end of 2010. Examples of the potential future uses of a complete list of mutations causing human disease are given in the Box. In brief, the possibilities for preventing or otherwise reducing suffering from disease opened up by the Human Variome Project will benefit individuals, as well as reduce the burden of global health care budgets. The main limitations to achieving the aims of the Human Variome Project are the speed of development and the spread of systems for countries, genes and disease groups; capitalising on these developments is, and will be, dependent on funding. Funding is needed for efforts to collect disease- or gene-specific data and data for individual countries, but the benefits for each country’s health care budget should more than offset the necessary initial outlay. The fact that genetic data are not in a single repository means that expensive professional time is spent “surfing” the web to look for previous examples of a particular mutation, or proper care cannot be given because vital data are buried in hospital files. Funding and recognition of the global Human Variome Project’s key coordinating role has been problematic due to it “falling through the cracks” of existing funding mechanisms. However, this situation is changing, with recognition by the World Health Organization in 2006, and UNESCO in 2010, which hosted the third Human Variome Project meeting at its headquarters in Paris, 10–14 May 2010. The pilot studies and the clear clinical need support the case for funding. It should be remembered that genetics has allowed medical testing to predict outcomes for patients and families contributing to prevention. Past, current and future support will ensure cost-effective, translational and preventive personal genetic health care worldwide, which will benefit millions of families. Future uses of a complete list of mutations causing human disease, as envisaged by the Human Variome Project Individuals (or their advisers) will be able to search their genome sequence for variations. If a variation is found, it can be compared with the complete catalogue of mutations to determine whether it is harmful. Examples include: a variation in a colon cancer gene — if harmful, preventive screening can be instituted; or a variation in the glaucoma gene in a person whose grandfather went blind at age 57 — preventive therapy can be instituted. When two individuals are planning to have children, they will be able to compare their genome sequences with the complete catalogue of mutations and their effects. They might be told that they both have a serious defect in, for example, the gene locus responsible for maple syrup urine disease, and advised to consult a genetic counsellor. This type of use has precedents in the premarital testing for the globin gene causing thalassaemia in the Mediterranean area, particularly in Cyprus. This has resulted in almost complete elimination of this disease through family planning. The ethnic-specific mutations in the Ashkenazi Jewish population are well known. When an individual has a specific disease, defining the mutation in a number of specific genes costs around $50, compared with several thousand dollars when the whole gene in question has to be sequenced. Lists of mutations in genes in all ethnic groups will allow definition of the most common mutations in each group.

Richard G H Cotton AM, BAgSc, PhD, DSc · Finlay A Macrae MB BS(Hons), MD, FRACP

New data bring to a close Australia’s most intensive cancer cluster investigation Though only a small proportion of cancer clusters are reported in the peer-reviewed literature, a consistent picture emerges from those reports. The term “cancer cluster” refers to health authorities being alerted to a perceived increased incidence of cancer, involving 15 cases or fewer in the first instance, within a particular community or group. Aware of the anxiety generated by the prospect of a cancer cluster, cluster investigators focus on local circumstances that might account for increased risk, and if they fail to identify any such factors, the matter rests.1 The report by Sitas and colleagues in this issue 2 is a rare example of the implications of a cluster investigation being rigorously pursued. In this case, the implication was that a cluster among staff of the Australian Broadcasting Corporation (ABC) studios in Toowong, Brisbane, might reflect a higher-than-average risk of breast cancer among female employees of the ABC throughout Australia, due to some common cause.3 In terms of identifying causative agents, notification of an individual cluster can be likened to a case report. Nothing can be immediately proved; everything depends on a subsequent, more broadly based study. Cancer clusters, and their investigation, are distinguished from infectious disease clusters by, among other things, the longer time frame involved and the fact that cancer is the most feared disease in Australia and similar countries. Demands made in respect of cancer cluster investigations centre on whether the cluster is explicable by chance and, if not, what caused it. The Toowong cluster came to national attention via a television program entitled “One in a million”, an epithet derived from the cluster investigators’ initial assessment of the likelihood that the increased incidence of breast cancer might be attributable to chance.4 Calculation of the probability that a cluster is attributable to chance is limited, if not precluded, by a posteriori definition of the study population — often illustrated by reference to the Texas sharpshooter who was in the habit of firing at the side of a barn, locating the bullet hole and painting a target round it.5 But the community wants answers, not technicalities. In the case of Toowong, the difficulty inherent in making such a determination is illustrated by revision of the initial estimate, specified in the summary of the final report as follows: [T]he likelihood of this event occurring by chance is about one in a million. This, however, may oversimplify the situation and, when further analyses are performed, adjustment of the P-value for implied multiple comparisons increased its estimated value to 0.04. That potentially increases the likelihood of the cluster occurring by chance to one in 25.3 Whether cluster investigations have ever revealed a new carcinogen is debated. Though vinyl chloride and diethylstilboestrol are sometimes cited in this context, the carcinogenicity of these compounds was implicated from multiple case reports involving alert physicians rather than from the perceptions of people in the affected group. Indeed, diethylstilboestrol was initially investigated because a lift malfunction in Boston resulted in a gynaecologist and a pathologist exchanging experiences.6 Otherwise, increased numbers of cancer cases within communities located adjacent to point-source pollution may implicate particular carcinogens. However, assessments of lung cancer near steelworks or smelting operations, mesothelioma near asbestos mines, thyroid cancer near a failed reactor, or haematopoietic malignancy in the vicinity of toxic waste dumps7 are readily distinguished from cluster studies, the latter being prompted by increased incidence rather than any attempt to determine whether an increase exists in light of a specific exposure. Novel exposure to carcinogens may also be investigated following spatial aggregation studies, which typically involve hundreds or thousands of cases — for example, the investigation of exposure to pesticides or other agents in relation to increased breast cancer incidence on Long Island, New York.8 Once cluster investigations are distinguished from case reports, point-source pollution investigations and spatial aggregation studies, it is arguable that clusters have rarely, if ever, resulted in the discovery of a specific cause of cancer, much less revealed a new carcinogen. Accordingly, the result of the Toowong cluster investigation was typical. In Toowong, all plausible causes of the cluster, including radiofrequency and extremely low frequency electromagnetic fields, ionising radiation and chemical contamination of the site or its water supply, were excluded.3 The findings of Sitas and colleagues2 are a good outcome for women employed by the ABC, and for those who worked in Toowong specifically. The absence of increased risk of breast cancer among ABC employees Australia-wide, together with a failure to identify any agent that could account for increased risk in Toowong and the 1 in 25 probability that the situation may have arisen by chance,3 mean the case is closed. However frustrating it may be, chance emerges as the most likely explanation. ABC staff at Toowong and elsewhere have no reason to be apprehensive about being at increased risk. There are no reasonable medical or scientific grounds for such women to undergo more rigorous clinical examination or more frequent mammographic screening than is recommended for women in Australia generally. These considerations critically depend on the findings of Sitas et al.2 Likewise, any notion that the building or site at Toowong presents a toxic hazard is now little short of absurd. Hopefully, ABC staff will be so advised. Beyond that, however, this good news might be shouted from the top of Uluru for all the likelihood it has of reaching the wider community, whose perceptions about cancer causation now include the “one in a million” scenario. The media in Australia respond to an insatiable demand for news of unsuspected exposure to carcinogens. Overwhelmingly, reports about possible cancer causation refer to consumer products and food contamination.9 Apart from a correct appreciation of carcinogens in tobacco, perceived causes of cancer range from pesticide residues in food to deodorants, from artificial sweeteners to mobile phones.7 For each such agent, there exists evidence of potential harm — but the relevant risks are either vanishingly small or simply not established. Maintaining speculation about Toowong comes a recent report of another breast cancer case and related matters connected with Toowong (Box). In point of fact, more and more cases of breast cancer will occur among women who once worked at ABC Toowong, in the same way that more and more cases of breast cancer will occur among any cohort of Australian women initially identified as aged 30–50 years. Tragically, one Australian woman in nine will develop breast cancer by the age of 85 years.10 About 60 cases must be anticipated within the Toowong cohort of 550, taking account of no other risk factor than being a woman in Australia. The prospect, however, is that each such case will be reported as involving another Toowong employee, fuelling anxiety about a common cause of harm, with no mention being made of the work of Sitas et al.2 Reference to a lack of risk hardly contributes to the momentum of a great story. But there is a price. People who misunderstand cancer causation are less likely to engage in practices known to reduce the risk of disease.11 Any unwarranted anxiety about insidious exposure to carcinogens seems likely to impede adoption of evidence-based measures to prevent cancer. That, together with any needless burden of anxiety, is bad news. Headlines from the Brisbane Courier Mail, 22 and 26 February 2010

Bernard W Stewart PhD, FRACI, DipLaw

A simple-to-use, inexpensive, low-risk tool that is not about ticking boxes but about keeping patients safe — it encourages surgeons, anaesthetists and perioperative nurses to work as a team, communicate and engage fully in safety processes Following pilot implementation of the World Health Organization’s Surgical Safety Checklist (the Checklist), a 30% reduction in surgery-related death and complications was achieved — a great result from a simple and affordable intervention!1 The Checklist2 was launched in Australia by the Hon Nicola Roxon MP, Federal Minister for Health and Ageing, on 19 August 2009, and a week later in New Zealand by the Hon Tony Ryall MP, Minister of Health. Similar launches have occurred around the world. The Checklist, produced by the WHO’s Second Global Challenge of the World Alliance for Patient Safety, was evaluated in a pilot study involving almost 8000 patients in eight centres, including one in our region, in countries with health systems of varying sophistication.1 This study showed that the Checklist was simple to use, and was associated with a worthwhile improvement in outcomes attributable to improved adherence to a number of predefined safety processes. For example, combined results from the sites showed reductions in: deaths, from 1.5% to 0.8% (P = 0.003); complications, from 11% to 7% (P = 0.001); and unplanned re-operations, from 2.4% to 1.8% (P = 0.047). This was a quality improvement study, not a randomised controlled trial, but the Checklist is a well thought-out, inexpensive, low-risk initiative that makes sense and works. The problem of iatrogenic harm has been characterised and quantified in a number of studies internationally,3,4 including widely cited work in our own region.5,6 These studies show that too many patients are harmed by the health care intended to help them,7 and that this harm is often the result of preventable failures in process.8 The Checklist is a cognitive aid to assist in the processes of caring for patients during anaesthesia and surgery but, more importantly, it is also designed to promote teamwork and communication within the operating room. Therefore, it was appropriate that the launches of the Checklist were collaborative affairs, with wide representation from nursing and medical organisations, including the Royal Australasian College of Surgeons, Australian and New Zealand College of Anaesthetists and Australian College of Operating Room Nurses, among others. The value of checklists in process management has been recognised in high-stakes activities other than medicine since at least the 1930s, and it is now time for surgeons, anaesthetists and perioperative nurses to increase their use of checklists for process control. Various methods of checking have been used by nurses, anaesthetists and surgeons for many years, but unacceptable errors continue to occur. For example, of the serious and sentinel adverse events reported in New Zealand in 2008, 19 cases involved the wrong site, wrong patient or wrong procedure, and six involved retained surgical swabs or other paraphernalia.9 This distressing situation is not far out of line with experiences in similarly sized Australian states or other countries. In New South Wales, in the second half of 2007, there were 10 wrong patient, wrong site or wrong procedure incidents in operating rooms; 61 incidents involving imaging and nuclear medicine; two in radiology services; and 13 in wards and other areas.10 The Checklist is applied in three phases: “Sign In”, when key issues are checked before induction of anaesthesia in the operating room; “Time Out”, which includes introducing all staff in the operating room, a briefing of the team and a final check of key issues before incision; and “Sign Out”, which is a clear handover to postoperative staff of important issues for ongoing patient management. It is relevant that the Checklist was developed through a highly evidence-based process, in which an international interprofessional group of experts reviewed the available literature, identified aspects of the perioperative process which typically fail, and consulted widely in designing a solution. Ticking the boxes is not the objective — getting people to engage in the key processes of perioperative care is. Local modification is encouraged, and an Australian and New Zealand version has been developed and launched,11 which includes prophylaxis of venous thromboembolism as one of the key issues checked during “Time Out”. Change management is hard work and worldwide experience indicates the need for active implementation programs led by clinical champions. The Checklist will not eliminate mistakes, but it has good potential to reduce them. All who practise surgery, anaesthesia and perioperative nursing are asked to adopt the Checklist in an engaged and constructive manner and make it work. The importance of instigating the use of the WHO Surgical Safety Checklist as an operating room routine cannot be overstressed. Preventable iatrogenic harm continues to be a major problem internationally, including in surgery and anaesthesia. The Checklist is an inexpensive, low-risk, adaptable initiative based on commonsense that has been shown to be workable and to significantly reduce harm in surgery and anaesthesia. The Checklist has the support of many local and international medical and nursing organisations.

Alan F Merry MB ChB, FANZCA, FFPMANZCA · Bruce H Barraclough FRACS, DDU, FACS

Objective: To compare changes in the costs of statins following patent expiry in Australia and England, and to estimate projected savings for Australia based on the government and consumers paying prices equivalent to those in England and increased use of generics.Design: Review of administrative data and predictive models based on recent trends.Setting: Administrative price and quantity data for the Pharmaceutical Benefits Scheme between January 2002 and October 2009, and comparable information from England.Main outcome measures: Total government and consumer expenditure on statins whose patent has expired, and projected expenditure on all statins from January 2009 to December 2019 under various scenarios regarding pricing and prescribing trends.Results: From January 2005 to October 2009, the cumulative loss to the Australian community from paying more than the English price for generic statins was more than $900 million. Expenditure could have been reduced by a further $1087 million if Australia had increased the proportion of generic medications prescribed to match trends in England. Future savings depend on the proportion of statin prescriptions that are subject to lower generic pricing. From January 2009 to December 2019, potential savings from paying English prices could be as high as $3.21 billion, and savings of up to $9.31 billion could be made by paying English prices and using generic statins only.Conclusion: The current arrangement for pricing statins places a considerable burden on the Australian community. Alternative pricing arrangements that provide incentives to lower statin prices and increase the proportion of generic prescriptions could be highly advantageous.

Philip M Clarke PhD · Edmund M Fitzgerald BSc, BCom

Objective: To audit and describe the effects of participation in the Dose Adjustment for Normal Eating (DAFNE) course on clinical outcomes in people with type 1 diabetes mellitus (T1DM).Design, setting and participants: Audit of clinical outcomes before and 1 year after DAFNE training for 145 people with T1DM who participated in courses at seven Australian diabetes centres between February 2005 and March 2007. Participants had been diagnosed with T1DM at least 1 year before and were beyond the “honeymoon phase”, with glycated haemoglobin (HbA1c) < 12% and no severe diabetes complications. They were aged over 17 years and able to understand written and spoken English.Intervention: A 5-day structured education program covering T1DM management with an emphasis on unrestricted diet, precise carbohydrate estimation and prandial insulin dosing using insulin-to-carbohydrate ratios.Main outcome measures: Glycaemic control (HbA1c levels), weight, severe hypoglycaemia, and quality of life scores on general (Hospital Anxiety and Depression) and diabetes-specific (Problem Areas in Diabetes) scales.Results: Mean HbA1c fell from 8.2% to 7.8% (95% CI for change, − 0.5% to − 0.2%; P < 0.0001) and weight from 75.1 to 74.2 kg (95% CI for change, − 1.6 to − 0.2 kg; P = 0.012). Severe hypoglycaemia was less frequent after DAFNE training (P = 0.0001). Quality of life improved (P < 0.0001 for both scales).Conclusions: One year after participation in the DAFNE program of structured education, people with T1DM showed improved glycaemic control, reduced incidence of severe hypoglycaemia, slightly reduced weight and improved quality of life. The DAFNE course offers one means of improving clinical outcomes in T1DM.

H David McIntyre MB BS, FRACP · Brigid A Knight BSc, GradDipNutrDiet · Dianne M Harvey BSc, GradDipDietetics · Marina N Noud MNurs, DipEd, CDE · Virginia L Hagger MPH, RN-CDE, GradDipVet · Kristen S Gilshenan BMaths(Hons), BInfoTech

Objectives: To assess the prevalence of and risk factors for claudication and its association with subsequent cardiovascular events.Design, setting and participants: Observational cohort study of 12 203 Western Australian men aged 65 years and over, recruited from 1996 to 1999, and followed up from 2001 to 2004.Main outcome measures: Prevalence of claudication and incidence of peripheral arterial disease (PAD); risk factors for claudication and its association with subsequent cardiovascular events.Results: The prevalence of claudication was 5.3% (638 of 11 970 men). At follow-up, after exclusion of 148 men with claudication at baseline and 76 with missing data at follow-up, the crude average annual incidence of new PAD (claudication or procedure for PAD) was 0.85% (95% CI, 0.72%–0.96%). The risk factors for prevalent claudication and incident PAD were similar, with age, smoking, hypertension, diabetes and history of cardiovascular disease dominating. Of the men with claudication at baseline, nearly half (47.5%; 303 of 638) were not taking aspirin. At follow-up, 42.5% (82 of 193) of the men with incident PAD were not taking aspirin. Claudication at baseline was associated with twice the risk of cardiovascular death (hazard ratio, 2.00; 95% CI, 1.52–2.64). There was a J-shaped relationship between aortic diameter, and both prevalent claudication and subsequent cardiovascular events.Conclusions: Among older men, claudication is prevalent and is associated with factors that can still be modified in older age, including smoking, exercise and diet. Relatively few men with claudication or at risk of PAD use aspirin. Claudication is a significant predictor of cardiovascular outcome.

Rahul Lakshmanan MB BS · Zoë Hyde BSc, PGradDipHlthProm, MPH · Konrad Jamrozik MB BS, DPhil · Graeme J Hankey MD, FRACP, FRCP · Paul E Norman BSc(Hons), DS, FRACP

Objective: To assess how much Australian research is available to inform reform of hospital services.Design: Bibliographic analysis using a MEDLINE search to locate all research publications focused on the organisation and delivery of Australian hospital services for the period 1996 through 2007.Main outcome measures: Number of peer-reviewed articles published by year and categorised by: study design (descriptive, methodological, intervention); type of intervention; clinical focus; and funding source.Results: 679 articles on the organisation and delivery of Australian hospital services were published in peer-reviewed journals from 1 January 1996 to 31 December 2007. Of these, 57% were empirical research reports and 43% were commentaries. There were, on average, 32 empirical research articles per annum. Of the empirical research articles, 70% were descriptive, 23% tested an intervention, and 7% were methodological. Research output increased over time with increases in commentary and descriptive research being the main contributors to this trend. The main funding bodies for this research were universities and government departments.Conclusion: A small but growing amount of local research is available to support reform of Australian hospital services. To boost the amount of relevant research evidence, we need to: build formal partnerships between researchers, policymakers, clinicians and health service managers; make targeted investment in health systems and services research; and increase the use of routinely collected data for research.

Mary Haines PhD · Sally Redman PhD · Louisa R Jorm PhD · Teresa M Wozniak PhD · Sanja Lujic MBiostats

Objective: To determine whether there is an excess risk of breast cancer among female employees of the Australian Broadcasting Corporation (ABC), especially outside Queensland, compared with women in the general populations of the states and territories.Design, setting and participants: We used an occupational cohort design. Information from ABC staff records was linked with data from state and territory cancer registries to identify female employees of the ABC with an incident, histologically confirmed breast cancer. Data linkage was complemented by a self-report method. We included a cohort of ABC female employees who had developed breast cancer at any time between 1994 and 2005, during their employment or after cessation of employment with the ABC. The standardised incidence ratio (SIR) was calculated as the number of women at the ABC observed with breast cancer divided by the expected number based on population rates in each state and territory. Tests for heterogeneity were performed to examine the variation of breast cancer risk between states and territories.Results: Out of 5969 women who were permanently employed either part-time or full-time at the ABC between 1994 and 2005, 48 eligible women with breast cancer were identified. An excess risk of breast cancer among ABC female employees in Queensland (identified in an earlier study) was reconfirmed. No excess risk of breast cancer was observed among ABC staff diagnosed in states outside Queensland (SIR, 1.01 [95% CI, 0.72–1.38]), or in Australia as a whole (including Queensland) (SIR, 1.12 [95% CI, 0.83–1.49]). There was no significant heterogeneity in breast cancer risk among states and territories once Queensland was excluded from the analysis (P = 0.39).Conclusion: No statistically significant excess risk of breast cancer in ABC female employees was found across the Australian states and territories as a whole compared with their respective population incidences. A statistically significant increased risk of breast cancer was found among ABC female employees in Queensland, consistent with the findings in an earlier report.

Freddy Sitas MSc(Med), MSc(Epidemiol), DPhil · Dianne L O’Connell BMaths(Hons), PhD · Cathelijne H van Kemenade MSc, MPH · Mark W Short BSc(Hons), PhD · Kun Zhao BEcon, BPsych(Hons)

Good medical practice: a code of conduct for doctors in Australia provides uniform standards to be applied in relation to complaints about doctors to the new Medical Board of Australia. The draft Code was criticised for being prescriptive. The final Code employs apparently less authoritative wording than the draft Code, but the implicit obligations it contains are no less prescriptive. Although the draft Code was thought to potentially undermine trust in doctors, and stifle professional judgement in relation to individual patients, its general obligations always allowed for flexibility of application, depending on the circumstances of individual patients. Professional codes may contain some aspirational statements, but they always contain authoritative ones, and they share this feature with legal codes. In successfully diluting the apparent prescriptivity of the draft Code, the profession has lost an opportunity to demonstrate its commitment to the raison d’etre of self-regulation — the protection of patients. Professional codes are not opportunities for reflection, consideration and debate, but are outcomes of these activities.

Malcolm H Parker MB BS, MLitt, MHthMedLaw

The negative consequences of alcoholism are well established.1 Although there have been recent improvements in interventions, some of them acknowledging that abstinence may be rejected by problem drinkers,2 most treatments focus on readiness to change.3 This may be problematic for people with advanced dependence, as alcoholism is associated with: (a) psychological issues4 and memory loss,5 which may reduce motivation for treatment compliance; and (b) damage to the frontal lobes,6 which can reduce risk appreciation and forward planning. In other words, the disease itself serves to reduce readiness to change. This is further complicated for people with concomitant alcohol-related health problems such as hepatitis, cardiovascular illness, gastrointestinal disease, pancreatic cancer or stomach cancer, which typically require treatment with several, often carefully titrated, medications. Not only do these medications often interact with alcohol, but also managing them can be difficult for a person with chronic alcoholism. Support from family and friends can be critical. Unfortunately, these essential relationships are put under strain by the drinker’s behaviour.4 Moreover, doctors can have negative perceptions of dealing with people with alcohol-related issues.7 In other words, the disease itself serves to reduce support for change and treatment compliance. Recently, this became all too clear for me while caring for my father Mervyn. Despite my training in psychology, there were serious challenges in securing good quality care for him. I imagine it may be even more difficult for carers without any medical or psychological background. Case studyMervyn was a highly educated 58-year-old man who had retired from his profession to care for his wife. She had died of cancer 2 years before Mervyn first presented to hospital with alcohol-related symptoms. He had a history of smoking and alcohol use, drinking only at night for most of his adult life in a pattern consistent with heavy dependence, while maintaining a successful career. After the death of his wife, his drinking escalated, with binges lasting for weeks at a time. He became reclusive. He presented to hospital with confusion, disorientation, memory loss and hallucinations. He was unable to identify himself and began to have seizures and lose consciousness. He was clearly under the influence of alcohol, as confirmed by blood alcohol content analysis. Consistent with this, examination revealed dehydration, high fever, vitamin deficiency (particularly thiamine deficiency), and compromised liver function. Further tests revealed damage to the heart from septicaemia. After intravenous antibiotic treatment, detoxification and stabilisation, he underwent an aortic valve replacement. After the surgery, he was required to take warfarin daily and had weekly or fortnightly blood tests to check and adjust the dosage. He spent several months in hospital and then several weeks in a physical rehabilitation facility before returning home. Over the next 5 years, Mervyn returned to hospital every 1–4 months with alcohol-related illnesses that included recurring septicaemia, falls resulting in head injuries, hip injuries, burns, liver failure, kidney failure, heart attack, stroke, seizures, pancreatitis, gastric polyps, pancreatic cancer and stomach cancer. His hospital stays lasted between 2 weeks and several months at a time. Nearly all hospital visits were associated with correcting coagulation issues resulting from the interaction between warfarin and changes in alcohol intake, which frequently caused severe and protracted bruising and bleeding from the nose, ears and any areas of damaged skin (eg, head wounds from falls). Neuropsychological assessments, conducted twice during this period, revealed frontal lobe damage consistent with difficulty in risk evaluation and planning, and damage affecting language and balance. Together, this resulted in severely compromised social functioning, and activities that he could engage in for enjoyment were reduced. He became unable to live independently. Most of his time was spent in hospital or recuperating in physical rehabilitation or residential or community care. However, my family had extreme difficulty finding appropriate support for a severely physically and cognitively compromised person with chronic alcohol dependence. In particular, after an alcohol-related fall, he was “strongly encouraged” to leave one residential care home. It is important to acknowledge that this home was not necessarily the most appropriate place for him. Nonetheless, available alcohol rehabilitation programs and support groups required a certain level of self-awareness and a willingness to change that was arguably no longer possible for him. Treatment with naltrexone, which has demonstrated efficacy in reducing dependence,2 resulted in some transient positive change. After several years of decline in my father’s condition, my brother and I took on primary caregiver responsibilities, including medical and financial power of attorney. We sought new avenues of health care. With assistance, particularly from a thorough general practitioner and dedicated social workers, we managed to have Mervyn placed in community care accommodation with home nursing. Overall, he was able to access: increased family support; a non-judgemental and friendly living environment; and a multidisciplinary team, including his GP, nurses, social workers, physiotherapists, specialists and surgeons. This stabilised and minimised Mervyn’s drinking and improved his medication management. Unfortunately, by this time, he had developed fatal pancreatic cancer and died a short time later from a gastric obstruction. ReflectionA non-judgemental attitude is required.4 For many individuals, alcohol abuse can at least partially be explained by genetic factors;8 childhood exposure to alcohol and parental attitudes and drinking behaviours;9 and/or an unpleasant or traumatic triggering event.4 Certainly, it was clear that the loss of his wife triggered an extreme escalation in alcoholism for Mervyn. Moreover, once individuals begin down a path of alcohol abuse, the disease itself attacks cognition, motivation and support structures. Nevertheless, blame and negative judgement of individuals with alcohol problems persist. There is absolutely nothing to be gained by these attitudes, and everything to lose, for the patient and for their families. Outcomes are dependent on the person’s readiness to change.3,4 However, after a certain point, cognitive and social impairment makes this extremely difficult, if not impossible, for patients. What do we do then? Abstinence will not be the goal for everyone, and relapse is common.2,4 When managing treatment of concurrent, and often related, chronic illness, interactions between medications and alcohol as well as changes in alcohol intake must be considered, and we cannot assume abstinence. Lifestyle adjustments and psychosocial support are necessary.4 Indeed, when adequate psychosocial support was made available for Mervyn, the problems were stabilised, albeit at a significantly lower level of functioning and quality of life. The GP and social workers, in particular, played a critical role. This raises questions about why this type of support was not accessed earlier. Each time Mervyn was hospitalised, he was either intoxicated or experiencing withdrawal symptoms. Yet, especially early on, alcoholism was not addressed in his treatment plan. While medical staff were cognisant of his alcohol problem, we are uncertain whether he was assessed by a physician with specific expertise in diagnosing and managing alcoholism. Certainly, his acute physical problems were severe, and thus the attention of health care professionals was tunnelled toward immediate, life-threatening issues. Did the doctors’ focus on repairing physical damage result in a tendency to overlook the psychological component of the addiction? As all of the health problems stemmed from alcoholism, were they treating the symptoms rather than the disease? Further, was the alcoholism just another symptom of a more fundamental problem? The situation can be characterised by a hierarchical symptomatology model in which diseases, or disease clusters, represent symptoms of an underlying issue. Indeed, it could be argued that all of Mervyn’s health issues stemmed from deep grief over the loss of his wife. Thus, grief led to accelerated alcohol abuse, which in turn led to a spectrum of physical problems. If psychosocial support had been accessed earlier, would it have been possible to prevent or reduce the cognitive and psychological damage that led to the inability of the patient to engage and to be ready to change? This suggests that routine screening for problem alcohol use in middle-aged and older men, particularly following bereavement, would be beneficial. Certainly, patients displaying clear indications of a problem, as in this case, should be referred early to alcohol and drug services. It’s too late for Mervyn — but maybe in telling his story I can help save the life of another person.

Jillian Dorrian PhD(Psych)

Clinical record We report anoxic convulsions occurring in two medical students competing in a breath-hold dive competition in shallow water. The seizure-like activity occurred during a competition called the “Dolphin Dive”, which was part of a university medical school swimming function. The goal set for the competitors was to swim as far as possible underwater in a swimming pool without taking a breath. Three students participated in the event and two students had convulsions. In both cases, the students hyperventilated before the dive. Student 1 A 27-year-old man, with a past medical history of asthma, had been involved in underwater hockey and spear fishing, and was previously able to underwater breath-hold for 2 minutes while keeping still. During the competition, he swam about 60 metres and spent 40 seconds underwater. After the dive, he stood up in the water, lost consciousness and was witnessed to have multifocal myoclonic jerks lasting about 1 minute. He recalled some jerking of the limbs when asked afterward. Student 2 A 27-year-old man, with no significant past medical history, had previously swum at national championship level and had worked as a surf lifesaver. He reported swimming about 85 metres for the competition and spending 90 seconds underwater. At the end of his dive, he became unconscious, floated to the surface of the pool and had multifocal myoclonic jerks lasting less than 1 minute. He had no recollection of the convulsive movements. Many people were observing the race and so the students were rapidly retrieved from the pool; they regained consciousness and did not experience any long-term consequences. The seizure-like activity that occurred in the two university students was probably convulsions secondary to cerebral hypoxia induced by breath-holding. Anoxic convulsions result from interruption of the oxygen supply to metabolically active neurones, particularly in the cerebral cortex.1 They may be regarded as a brainstem-release phenomenon in which primitive movements can occur, particularly multifocal arrhythmic myoclonic jerks.1,2 They can result from voluntary breath-holding, such as cyanotic breath-holding of early childhood.1 Swimmers often hyperventilate before breath-holding to reduce the urge to breathe from hypercapnia. This may result in prolonged breath-holds with consequent hypoxaemia. Loss of consciousness may ensue without forewarning because the respiratory stimulus from hypoxaemia is weak and easily overridden.3 Vigorous exercise, such as underwater swimming, may exacerbate hypoxia by increasing oxygen consumption. These factors are likely to result in syncope occurring late in the dive, as in our two cases. Hyperventilation-induced hypocapnia is known to constrict cerebral vasculature and may contribute to syncope.2 In addition, the Valsalva manoeuvre can cause syncope during the early stages of a breath-hold dive,4 probably by reducing cerebral blood perfusion further as a result of decreased cardiac output from reduced thoracic venous return. This may be a cause of early syncope before hypoxia and hypercapnia have occurred, but the Valsalva effects may still be operative late in the dive. When Student 1 stood up at the end of his dive, the change in posture would have impaired venous return even more, and may have triggered the anoxic convulsions. Breath-hold practitioners are often skilled male swimmers who are not closely watched by lifeguards. Loss of consciousness underwater can lead to drowning. A report of 58 cases of syncope during underwater swimming and diving found that all victims were known to be good swimmers or divers and the victims were almost exclusively men (56 cases).5 Victims were often involved in a competition in which they wanted to “beat” someone else’s or their own underwater distance record. The number of fatalities in that particular medical case series was high (23 cases). Anecdotal observations suggest that underwater breath-holding is a relatively common practice in Australia. The practice is particularly dangerous if coupled with prior hyperventilation. This report provides further evidence that hyperventilating before breath-holding should be discouraged. Swimming pool authorities should be made aware of the potentially dangerous consequences, as should, arguably, children and adults undergoing basic swimming training. Lessons from practice Syncope can manifest as seizure-like activity. Hypercapnic respiratory drive is important in breath-hold diving and swimming. Hyperventilation before breath-hold diving reduces hypercapnic respiratory drive and can result in anoxic loss of consciousness. Hyperventilation is the main causative factor in the development of hypoxia and syncope in underwater breath-holding. Loss of consciousness underwater can lead to drowning — the danger of underwater breath-holding is an important public health and safety issue that warrants increased awareness among the general public.

Kishore R Kumar MB BS, FRACP · Karl Ng MB BS(Hons I), FRACP

To the Editor: Treatment of critically ill pregnant women is challenging, and information on medication use during pregnancy is scant. We describe the case of a pregnant woman who required extracorporeal membrane oxygenation (ECMO), prolonged sedation and paralysis to treat acute respiratory distress syndrome secondary to pandemic (H1N1) 2009 influenza. A 34-year-old pregnant woman (G2P1) at 21 weeks’ gestation presented to a metropolitan hospital with level 1 intensive care unit facilities. She had known Grade 2 placenta praevia, a 5-day history of influenza-like symptoms, and no history of asthma, chronic disease or recent travel. On examination, she was severely hypoxic (PaO2, 27 mmHg on 15 L/min O2), conscious, tachypnoeic and speaking in single words. A chest x-ray showed extensive bilateral infiltrates (Box). She needed urgent endotracheal intubation but remained hypoxic despite maximal intensive mechanical ventilation. The patient was transferred to St Vincent’s Hospital, Sydney, where venovenous ECMO was commenced on arrival. Her oxygenation status improved and remained satisfactory. Mechanical ventilation was reduced (tidal volume, < 6 mL/kg; peak pressure, < 30 cm H2O) to avoid ventilator-induced lung injury. The patient required very high doses of morphine, fentanyl, midazolam, propofol, dexmedetomidine, cisatracurium and heparin during ventilation and ECMO. In addition, empirical treatment with oseltamivir (150 mg twice a day, Days 1–8), azithromycin and ceftriaxone was started on admission, before a bronchoalveolar lavage specimen tested positive for influenza A and pandemic influenza. Furthermore, a multiresistant Escherichia coli caused ventilator-associated pneumonia, which was treated with meropenem (1 g three times a day, Days 17–30). ECMO was discontinued on Day 19, when lung function had improved. No other organ failure developed. On Day 21, a tracheostomy was performed for severe weakness and weaning failure. The patient was weaned from the ventilator on Day 35 and was discharged home 2 weeks later, after making a full recovery. She gave birth by caesarean section at 35 weeks’ gestation. The baby was in good health and the patient recovered well — both left hospital 3 days after the birth. Information on the use of medication in pregnant women who require intensive care is limited, especially the use of neuraminidase inhibitors.1 We found little evidence on the safety of long-term use of neuromuscular blockers and sedation in pregnancy, with or without ECMO.2 Most literature on this topic describes short-term use of neuromuscular blockers and sedation. Dexmedetomidine has a short postmarketing history, and has therefore had limited use. Data from Australia and New Zealand indicate that 9% of patients admitted to an intensive care unit with pandemic influenza are pregnant. An estimated inhospital mortality rate of more than 16% in this population indicates the severity of the infection.3,4 Single-organ lung failure is a common feature of complicated pandemic influenza, and venovenous ECMO should be considered in these circumstances.2,4,5 Our case demonstrates that ECMO and the drugs necessary for its use can be used during pregnancy in a patient with influenza-associated acute respiratory distress syndrome, and that survival of the patient and fetus is possible. Chest x-ray of a pregnant woman with influenza-associated acute respiratory distress syndrome showing extensive bilateral infiltrates

Susan A Welch · Leone N Snowden · Hergen Buscher

To the Editor: Hydroxychloroquine is used infrequently (in less than 0.1% of Australians) for the long-term management of chronic conditions (eg, rheumatoid arthritis).1 Hydroxychloroquine retinopathy is a rare but sight-threatening side effect that is usually not reversible.2-5 Various eye screening recommendations for hydroxychloroquine toxicity have been proposed overseas,3-5 but there is no recommended consensus for eye screening in Australia. As a result, screening is currently not uniform or universal, and this sometimes leads to significant consequences. A 36-year-old woman with a longer than 10-year history of hydroxychloroquine therapy (400 mg/day; body weight, 62–67 kg) for rheumatoid arthritis presented to her general practitioner after a year of central visual disturbance and photopsias (a sensation of flashes of light). She was referred to the Medical Retinal Clinic at the Royal Victorian Eye and Ear Hospital in August 2009 with suspected hydroxychloroquine toxicity. She had undergone screening by her optometrist for an initial period, but had not been screened within the past 4 years because she failed to attend; she appeared unaware of the potential serious side effect of the medication on her vision. On examination, her visual acuity was 6/9 in the right eye and 6/12 + 2 letters in the left. Her colour vision (assessed by Ishihara plates for colour blindness) was normal. She had left vortex keratopathy (a whorl-like corneal epithelial deposit) and examination of her fundus revealed subtle macular pigment change and retinal arteriolar attenuation (Box, A). Fundus autofluorescence showed significant changes at the level of the retinal pigment epithelium (Box, B). Dense bilateral paracentral field defects were detected on visual field testing. The rheumatologist was notified of the hydroxychloroquine retinal toxicity, and therapy with the drug was ceased. At 6-month eye review, the patient’s vision was stable. Recommendations on the timing of eye screening vary.3 The manufacturer’s product information recommends quarterly ophthalmological examinations, but this is impractical and not cost-effective.3,5 The Royal College of Ophthalmologists (RCO) in the United Kingdom found no evidence-based justification for a systematic screening program.4 They recommend ophthalmological referral only when there are visual symptoms (eg, distorted or patchy central vision, reading difficulties), or eye disease is detected at baseline and confirmed by an optometrist. In contrast, the American Academy of Ophthalmology (AAO) suggests a systematic approach, determined by risk status, that is based on factors such as hydroxychloroquine dose and duration of intake.5 Despite their differences, these protocols both aim to detect toxicity early and minimise the degree of visual loss, rather than to prevent visual loss. This is because there are currently no established criteria to identify toxicity at a reversible stage.4 We recommend adoption of the AAO or RCO protocols and alerting patients to the symptoms of toxicity. Careful counselling of patients at commencement of hydroxychloroquine treatment and on an ongoing basis is essential to promote early presentation and minimise toxicity. Hydroxychloroquine toxicity, although rare, can lead to severe loss of vision if therapy is not stopped. By stopping treatment, the condition may stabilise, and further irreversible vision loss can potentially be avoided. Hydroxychloroquine retinopathy in a 36-year-old woman A: Subtle macular pigment change (black arrows) and some arteriolar narrowing (white arrows). B: Autofluorescence imaging showing symmetrical changes at the level of the retinal pigment epithelium. Mottled loss of autofluorescence (black arrows) indicates loss of retinal pigment epithelium cells, and the adjacent increased autoflourescence (white arrows) indicates cell abnormality.

Elvis Ojaimi · Robyn H Guymer · Tien Y Wong · C Alex Harper

To the Editor: In their letter in the 1 February 2010 issue of the Journal, Rashid and Grant reported the first Australian case of hepatotoxicity associated with the weight-loss product Hydroxycut.1 They noted that, in May 2009, the United States Food and Drug Administration (FDA) advised consumers to stop using Hydroxycut products on the basis of 23 reports linking them to serious injury, including one fatal case of liver failure. In response, the Australian sponsor, Export Corporation (Australia) Pty Ltd told the Therapeutic Goods Administration (TGA) that there were differences between the US and Australian formulations of Hydroxycut products. As the TGA had received no reports of adverse reactions similar to those reported in the US, they allowed local marketing to continue. The TGA website advised consumers to exercise caution when using Australian Hydroxycut products;2 however, no such warnings appeared in local promotional material. In contrast, despite also being told that products marketed in the United Kingdom had different formulations, the UK Food Standards Agency (FSA) said: The specific ingredient or dosage which might be causing health problems has not yet been identified. However, as a precautionary measure, the FSA is warning people not to take them. There are no reported illnesses in the UK related to these products. . . . Hydroxycut products have been withdrawn from sale in the USA, Finland and Canada. Ireland has also advised retailers to withdraw the product and consumers to discontinue use of the products.3 Meanwhile, there have been three complaints upheld about the promotion of Australian Hydroxycut products, with another in progress.4 In 2008, the Complaints Resolution Panel (CRP) requested that the sponsor, retailers and website publishers withdraw any representations that the advertised product(s) has benefits in relation to fat-burning, weight loss, or weight management. Regardless, these claims continue to be made by numerous Australian internet pharmacies, and supplement and health food sites. This highlights the impotence of the CRP (which lacks the power to impose sanctions), the ineffectiveness of the TGA (which can impose sanctions, but apparently declines to do so) and the need for regulatory reform.5 A reformulated Hydroxycut is back on the shelves in the US. An FDA spokesperson said: “The only ingredient left in from the original formulation is caffeine. We do not have any evidence that caffeine causes liver toxicity.”6 However, on 14 February 2010, I had no difficulty in purchasing Hydroxycut (AUST L 154243) from a local pharmacy. This product has a similar formulation to products withdrawn overseas. Rashid and Grant called on the TGA to re-examine the continued availability of these products in Australia.1 I reiterate their call. Why is the TGA out of step with other regulators? Why are these products still on the Australian market if their benefits are negligible or absent, if unethical promotion continues despite CRP determinations, and when the risks are clear?

Ken J Harvey

To the Editor: In the December 2009 issue of the MJA, I came across an interesting article by Dr Paul Zimmet, “A lifetime pursuit of diabetes through chance”.1 This is an account of his impressive achievements in medicine. However, I disagree with the statement that describes his father’s situation in 1930s Poland: “He returned to an unpaid position in the Tarnopol Hospital — unpaid because Jewish doctors could not be ‘officially’ employed in Poland.” I argue that, in Poland at that time, there was no discrimination against national minorities, and this applied to the Jewish minority as well.2 I have done some research on the subject. There were 3.5 million Jewish people in Poland before the war — 10% of the population. According to numerous historical sources, Jewish doctors represented 34% of doctors in Poland in 1938. In the Polish capital, Warszawa, this percentage was 66%. The same sources quote the percentage of lawyers of Jewish origin as 55%.3,4 These numbers are a tribute to the talents and assertiveness of Polish Jews; however, they do not support the statement by Zimmet that I am disputing. In Polish archives, I have discovered statistical documents containing alphabetical lists of all doctors registered in Poland between 1936 and 1938.5 According to these documents, there were two hospitals in Tarnopol at that time: the General Hospital and a Jewish hospital. In the official register of all Polish doctors practising between 1936 and 1938, I have not found the name of Dr Jacob Zimmet. He was not registered as a doctor, and therefore could not legally be employed as a doctor in Tarnopol or any other Polish hospital.

Wladyslaw W Smolilo

In reply: Dr Smolilo has challenged my claim that my father, the late Dr Jacob Zimmet, worked in a hospital in Tarnopol, Poland, and without salary, in the pre-World War II period.1 I am pleased to refute Smolilo’s inaccurate claims. Smolilo argues that “. . . in Poland at that time, there was no discrimination against national minorities, and this applied to the Jewish minority as well”. I accept his statement that there was not an official policy as such. There are, however, ample historical records of discrimination against Jews in many areas.2 Smolilo questions the specific instance relating to my late father. I have a letter in Polish from the Director of the Government Hospital in Tarnopol and its 1939 official translation by the Polish Consul-General in Sydney, copies of which I have provided to the Editor of the Journal. This letter not only confirms my father’s employment from 1935 to 1938, but also the fact that he was not paid. The very fact that Smolilo could not find my father in the official records also stands as confirmation! Clearly, there were many Jewish doctors and other professionals employed in Poland from earlier years who retained their positions during the period from 1935 to 1939. However, even before that time, a quota was imposed on Jewish students and many had to go overseas for medical training.3 On return, like my father, they were unable to find gainful employment and eventually left Poland, many emigrating to Australia. My father provided loving care to many Polish immigrants in his medical practice in South Australia.

Paul Z Zimmet

To the Editor: In your recent column, you drew attention to the “limitations of psychiatry’s scientific foundations for disorders of the mind”.1 This was despite psychiatry’s recent high profile, and the very large sums of money being thrown at the problem. The limiting factor for a scientific psychiatry is that there isn’t one. Extensive research has shown that orthodox psychiatry does not yet have a formal, articulated model of mental disorder to guide its practice, its teaching and its research.2,3 Moreover, not one of the models used today, including the biological approach, can be developed to the point where it would meet the minimum criteria for a scientific model. Confections such as the “biopsychosocial model” do nothing but conceal the problem under yet another layer of jargon. Releasing another Diagnostic and statistical manual of mental disorders (DSM) will achieve nothing because it does not address mental disorder within the framework of an agreed model. In the absence of science, there is scope for non-scientific pressures (such as politics and finance) to have an inordinate influence on the many DSM committees. Needless to say, this conclusion is most unpopular among many in the psychiatric establishment but, sooner or later, they will have to come to grips with the problem; otherwise, psychiatry as a profession will cease to exist.4

Niall McLaren

To the Editor: We read the article by Gibson and colleagues on the assessment and management of cough1 with some concern, specifically regarding the authors’ classification of levels of evidence for current therapies for allergic rhinitis. We would agree that a trial of antihistamines, intranasal corticosteroids and allergen immunotherapy is unlikely to help non-specific cough in the absence of allergic rhinitis. This consensus should be distinguished from the beneficial impact of these modalities on symptoms of allergic rhinitis, for which the authors misquote their main source of information2 and suggest that evidence of benefit from these is “weak”. Although evidence of benefit from allergen avoidance to help manage allergic respiratory disease is controversial,3 a large number of double-blind placebo-controlled trials of all other modalities show Level I evidence of benefit and category A strength of recommendation specifically for treatment of allergic rhinitis, as recently reviewed2,4-6 — evidence consistent with “strong” recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.7 We do our patients and colleagues a disservice to suggest otherwise.

Raymond J Mullins · Constance H Katelaris · Janet Rimmer

To the Editor: We read with interest the Australian Cough Guidelines summary statement by the CICADA multidisciplinary group.1 However, we feel that the role of direct examination of the upper aerodigestive tract in assessing cough was underemphasised. Flexible nasal endoscopy (FNE) is a quick, relatively straightforward examination performed under topical anaesthesia as part of an ear, nose and throat (ENT) consultation. It allows direct visualisation of the nasal cavities, postnasal space, oropharynx and larynx, and can be performed on adults and older children and also some younger children.2 Nasal causes of cough, and hence the potential role of FNE, appear to have received more emphasis in previous chronic cough management strategies, including those proposed by the American College of Chest Physicians in 20063 and the European Respiratory Society task force in 2004.4 The diagnosis of chronic rhinosinusitis or upper airway cough syndrome (postnasal drip syndrome) is enhanced by direct examination. The presence of mucopus in the middle meatus of the nasal cavity is associated with a positive diagnosis of chronic rhinosinusitis.1 FNE can also provide direct evidence of the presence of gastro-oesophageal reflux affecting the larynx (laryngopharyngeal reflux), and plays a significant role in the clinical diagnosis of laryngopharyngeal reflux.5 FNE should be used in patients with alarm symptoms for serious underlying disease (as suggested by the CICADA group1), particularly those potentially related to laryngeal causes (hoarseness, haemoptysis, feeding difficulties, stridor or smoking). As part of a complete examination, FNE can help in targeting therapy for two of the three most common causes of cough in adults (gastro-oesophageal reflux and rhinosinusitis), and in excluding some of the significant causes of cough in both adults and children. It is particularly recommended in patients with a suspected nasal or laryngeal cause, in those with alarm symptoms, and in those for whom initial therapy fails.

Nicholas J Potter · Eduard I Pudel

In reply: The recently published CICADA cough guidelines1 draw attention to the important role of systematic assessment of chronic cough in children and adults, and provide an appraisal of the evidence that treating specific conditions will improve cough. Mullins and colleagues raise a key point that requires emphasis, and is relevant beyond the instance of allergic rhinitis that they cite. Chronic cough is associated with several common conditions, such as allergic rhinitis, asthma, gastro-oesophageal reflux disease and sleep apnoea. For each of these conditions, there are well established treatment guidelines that describe the effectiveness of treating that primary condition. However, in developing the CICADA guidelines we were considering the effect of the treatments on the symptom of cough, not on the primary condition. It was stated at the bottom of Box 1 (page 2661) that “The final GRADE recommendations were based on [the] votes [of committee members] and considered cough in the context of the respective conditions”. We agree that the evidence for treating symptoms of allergic rhinitis per se is strong, as published.2 But in the case of a patient presenting with cough and associated rhinitis, the CICADA group determined that the evidence that treating allergic rhinitis would resolve the cough was weak. It is often not possible to determine from successful trials of immunotherapy for rhinitis the outcome for cough. For example, trials of injectable or sublingual immunotherapy both mention cough only once, and it is not possible to determine the effect of the treatment on this symptom.3,4 We welcome the comments by Potter and Pudel giving more specific details of the role of FNE in assessing the upper airway in people with chronic cough. We agree that this is a quick and useful examination. We believe we have placed greater emphasis on upper airway disorders compared with other cough guidelines. Specifically, we have identified vocal cord dysfunction and sleep apnoea as relevant upper airway disorders that are associated with chronic cough. These conditions are not featured in previous guidelines, yet they respond well to specific therapy. We also devote comparatively more space to upper airway disorders that to lower airway disorders.

Peter G Gibson · Anne B Chang · Andrew S Kemp

A 61-year-old woman presented for management of a large, toxic multinodular goitre. A decision about therapeutic modality (radioiodine ablation or total thyroidectomy) was facilitated by an incidental finding, on computed tomography, of a large, anterior mediastinal thymoma (Figure, A), confirmed by core biopsy. The patient had no symptoms of tumour compression or paraneoplastic phenomena such as myasthenia gravis. She underwent a total thyroidectomy and resection of the thymoma by median sternotomy. Histopathological examination revealed a completely encapsulated and resected thymoma (stage 1, World Health Organization type B2 [mixed epithelial and lymphoid cells]) measuring 140 × 80 × 45 mm (Figure, B), and a benign multinodular goitre. A: Sagittal view of a computed tomography scan of the neck and chest showing a large multinodular goitre (black arrow) and a large incidental anterior mediastinal thymoma (white arrows). B: Resected thymoma.

Jimmy Z Shen · Jui T Ho

Konrad Jamrozik was born on 2 May 1955 in Leigh Creek, South Australia. He undertook basic medical training in Adelaide and Hobart, graduating from the University of Tasmania in 1977. After a year as an intern in Hobart, he won a Nuffield Dominion Trust scholarship to study at Oxford University from 1979 to 1982. There, he worked with Sir Richard Peto and the late Sir Richard Doll and produced a doctoral thesis examining strategies for promoting smoking cessation in general practice. In 1983, Konrad lectured in Community Medicine at the University of Papua New Guinea in Port Moresby, where he was also a clinical assistant in the leprosy service. He took up a research fellowship in epidemiology at the University of Western Australia in mid 1984, and was promoted to Professor of Public Health in early 2000. From December that year until September 2004, he held the Chair in Primary Care Epidemiology at Imperial College London. Later in 2004, he moved to Brisbane as Professor of Evidence-based Health Care and Head of the Division of Health Systems, Policy and Practice at the University of Queensland, then in 2007 became Head of the School of Population Health and Clinical Practice at the University of Adelaide. He also held short-term posts at the World Health Organization in Geneva, Harvard Medical School, the National Public Health Institute in Helsinki, Finland, and Jagiellonian University in Krakow, Poland. Konrad had wide research interests including health promotion, the epidemiology and prevention of vascular disease, the design and conduct of randomised-controlled trials, and the translation of evidence into everyday practice. He had a natural talent for teaching and mentorship, helping to produce the next generation of health leaders. He also earned an international profile in the area of tobacco control as a researcher and advocate, and maintained a clinical commitment in medical oncology. He was a prominent life member of the Australian Council on Smoking and Health and a Fellow of the Public Health Association of Australia. In 2009, he was awarded the Nigel Gray Award for his outstanding contribution to tobacco control. Konrad was a dedicated cyclist and a keen rower who competed for Oxford and rowed for pleasure in rivers around Australia and the world. He was an unforgettable, extraordinary, dedicated man, and a loyal and caring friend and colleague with a commitment to excellence and justice. One colleague wrote, “It feels like public health in Australia has lost a limb”. Konrad was diagnosed with advanced sarcoma in 2009 and remarked, in light of his work on cancer, that this placed him within “a tradition of doctors who fall victim to their disease of special interest”. He died in Adelaide on 24 March 2010 and is survived by his wife Lesley and children Euzebiusz, Harriet, Magnus and Aleksander, and his parents Adam and Ruth.

Terry Slevin · Euzebiusz Jamrozik

Incorrect revenue amount: In “Cost-effectiveness of volumetric alcohol taxation in Australia” in the 19 April 2010 issue of the Journal (Med J Aust 2010; 192: 439-443), there was an error in the taxation revenue amount specified in the Abstract and Results section. In the Abstract (fourth sentence of Results paragraph), the wording should be “a tax on all alcohol at a spirits rate would reduce consumption by 23.85% and increase revenue by $3094 million”. In the text of the article (first paragraph of Results section), the wording should be “A volumetric tax set equal to the current spirits tax rate provided a substantially greater reduction (23.85%) in consumption of alcohol and an increase in taxation revenue of $3094 million”.

Joshua M Byrnes · Linda J Cobiac · Christopher M Doran · Theo Vos

Incorrect formula and number of trial subjects in Box: In “It’s time to depolarise the unhelpful PSA-testing debate and put into practice lessons from the two major international screening trials” in the 5 April 2010 issue of the Journal (Med J Aust 2010; 192: 393-396), in the Box, there was an error in the total number of prostate cancers detected in the screening arm of the ERSPC trial and in the formula used to calculate differences between the two arms. The Box, with corrected figures in the last two columns and a replacement formula in a footnote, is reproduced here. Staging and prostate cancer deaths among men participating in the PLCO and ERSPC trials5,6 Control arm Screening arm STAGE OF CANCER AT DIAGNOSIS PLCO Trial n = 2940 n = 3437 RD (%)* Stage 1 15 (0.5%) 18 (0.5%) + 2.6% Stage 2 2790 (94.9%) 3297 (95.9%) + 1.1% Stage 3 56 (1.9%) 49 (1.4%) – 25.2% Stage 4 79 (2.7%) 73 (2.1%) – 21.0% ERSPC n = 4611 n = 6169 RD (%)* Stage T1a,b 277 (6.0%) 212 (3.4%) – 42.8% Stage T1c 1805 (39.1%) 3477 (56.4%) + 44.0% Stage T2 1320 (28.6%) 1755 (28.4%) – 0.6% Stage T3 749 (16.2%) 509 (8.3%) – 49.2% Stage T4 156 (3.4%) 67 (1.1%) – 67.9% Stage M1 304 (6.6%) 149 (2.4%) – 63.4% CAUSE OF DEATH (in men diagnosed with prostate cancer) PLCO Trial Rate ratio† Prostate cancer 82 92 1.11 Other causes‡ 225 312 — ERSPC Prostate cancer 326 214 0.80 Other causes ns ns ns ERSPC = European Randomized Study of Screening for Prostate Cancer. ns = not specified. PLCO = Prostate, Lung, Colon and Ovarian. RD = relative difference. * The relative difference is the percentage increase or decrease in cases of a given stage of prostate cancer detected by screening, using the formula RD = {[(proportion in screened arm ÷ proportion in control arm) × 100] – 100}%. eg, for the PLCO Trial, Stage 3, RD = {[(49/3437 ÷ 56/2940) × 100] – 100}% = –25.2%. † Rate ratio = adjusted value given by the authors.5,6 ‡ Men with prostate cancer dying of other causes.

James W Denham · Ron Bender · William E J Paradice

Omission of potential competing interests: In “Managing residual risk in patients receiving statin therapy” in the 5 April 2010 issue of the Journal (Med J Aust 2010; 192: 366-367), potential competing interests were omitted. The author, Ian Hamilton-Craig, has received financial support to attend and give presentations at scientific meetings from AstraZeneca, Merck Sharp & Dohme, Schering-Plough, Pfizer, Bristol-Myers Squibb, Solvay, Sanofi-Aventis, Novartis and Abbott Australasia. He is a member of the Lipid Advisory Board of Merck Sharp & Dohme/Schering-Plough, AstraZeneca and Solvay, the Familial Hypercholesterolaemia Committee of the Australian Atherosclerosis Society, and the Council on Genetic Cardiovascular Diseases of the Cardiac Society of Australia and New Zealand.

Ian R Hamilton-Craig

The right stuff We’re all used to having bar codes of various types scanned at some point in our lives, from checking in our tickets at sporting grounds to checking out our groceries at the local supermarket. Now, bar-code verification technology is being used to check that patients are getting the right medicines at the right time in a 735-bed tertiary academic medical centre in the US — Boston’s Brigham and Women’s Hospital. Unit nurses are required to scan the bar codes on a patient’s wristband and on their medication before it is administered. If the dose does not correspond to a valid pharmacist-approved medication order, the application issues a warning. Previously, nurses manually verified the dose and the patient’s identity before medication was given. Over a 9-month period of observation, it was found that this bar-code technology significantly reduced, but did not eliminate, errors in medication administration. The bar-code medication-verification technology is embedded within a broader, integrated electronic medication-administration system. N Engl J Med 2010; 362: 1698-1707 Pets aboard Cats and small dogs are permitted to travel in the cabin of many Air Canada flights. Each animal needs to be small enough to fit and stay comfortably in a carrier-cage under the seat in front of the owner for the duration of the flight. This your-animals-are-welcome-to-fly-with-you policy has got the CMAJ editor’s and colleagues’ dander up, because they believe that the preferences of pet owners should not supersede the wellbeing of fellow passengers. In particular, they are concerned about passengers with allergies to animals, as pet dander has been shown to remain on seats long after the pet and its owner have gone. They say about one in 10 people have allergies to animals. Would you want to manage a patient having a severe allergic reaction on an aeroplane, at high altitude and isolated from emergency medical care? CMAJ 2010; 182: 421 After-death experiences If a patient’s loved one died in tragic circumstances, would you advise them to view or not to view the body? UK researchers interviewed 80 mainly white British people bereaved because of suicide or other traumatic modes of death, including by murder, fire, and bomb explosion. Most had seen the body of their deceased loved one. Although seeing a damaged body was distressing, it was rarely regretted. Those who had regretted or who had mixed feelings about seeing the body felt they had lacked either choice about it or preparation, in that they had not been warned how different their loved one might look to them. The researchers said that clinicians should not assume that relatives will necessarily be harmed by seeing a bruised or damaged body; and that within a family there may be different attitudes and preferences that need to be taken into account. BMJ 2010; 340: c2032 doi:10.1136/bmj.c2032 Drugs and sport Growth hormone supplementation can increase sprint capacity, according to Australian research. The researchers conducted a randomised controlled trial involving 63 men and 33 women, all of whom were healthy recreational athletes. After 8 weeks of treatment, a modest dose of growth hormone had no effect on the subjects’ aerobic capacity or on measures of their strength and power. However, there was an effect on sprint capacity; an effect that was nearly doubled in the men who had received testosterone as well as growth hormone supplementation. The researchers did state that the athletic significance of their finding was unknown; however, they did also speculate that the approximately 4% increase in sprint capacity could translate to an improvement of 0.4 seconds in a 10-second sprint over 100 metres or 1.2 seconds in a 50-metre swim. Ann Intern Med 2010; 152: 568-577 Worldwide healthmap The integration of new with traditional approaches to surveillance offers the greatest promise for future surveillance of influenza and other emerging diseases, say the authors of a special report in the New England Journal of Medicine. Brownstein and colleagues highlighted HealthMap (http://healthmap.org), a new effort in transparent, global, public health surveillance. The HealthMap system combines automated 24/7 data collection from diverse sources, including online news media, blogs, Twitter and Facebook, with expert review and analysis to provide not only comprehensive but also contemporaneous reports by type of disease and geographic location. N Engl J Med 2010; 362: 1731-1735

Ann T Gregory

Med J Aust 2010; 192 (11 Suppl).