Volume 190 Issue 8

A national study of eating disorders highlights potential underdiagnosis and high rates of complications in 5–13-year-olds In this issue of the Journal, Madden and colleagues report their prospective investigation of eating disorders in children across Australia (Madden et al).1 This study is an important “first” and investigates the putative increasing problem of early-onset eating disorders (EOEDs) in children aged 5–13 years. Over 3 years, detailed data were collected by the Australian Paediatric Surveillance Unit for 101 children who were managed either as outpatients or in hospital for EOEDs — mainly from paediatricians, but also from child psychiatrists. Most children were hospitalised for treatment. The study raises interesting issues and unanswered questions about eating disorders. Although there are no earlier data for comparison (ie, conclusions cannot be drawn about whether or not the incidence of eating disorders in younger children is increasing), the annual incidence rate for EOEDs of 1.4 per 100 000 children aged 5–13 years accords with international figures. This is especially true of the even higher incidence rate in New South Wales, where there may have been more comprehensive reporting. Of particular concern were the high rates of severe, life-threatening medical complications (hypothermia, hypotension and bradycardia) in inpatients, suggesting under-referral or under-recognition of the problem, and thus delays in active specialist care. Further, most of the children received nasogastric feeding, and a third received psychotropic medication — treatments that may not have been required with earlier, more active intervention. Turning to specific issues, there was a relatively high proportion of boys in this study — a quarter of the total. In contrast, men account for about one in 10 adult cases of anorexia nervosa and bulimia nervosa. When broader diagnostic groups, such as binge eating disorder, are considered, rates are higher, particularly in community samples,2 albeit men account for a minority (around 30%) of patients.3 However, the types of eating disorder reported in higher numbers in men (such as binge eating disorder) differ from the EOEDs reported in Madden and colleagues’ study. EOED was characterised by “determined food avoidance plus weight loss or a failure to gain weight during a period of growth, in the absence of any identifiable organic cause”1 — a variant of anorexia nervosa, if not full-spectrum anorexia nervosa. Nevertheless, the finding that one in four EOED cases affected boys is consistent with results of other studies. For example, a Danish study found males to be younger than females at first presentation and more likely to re-present with psychotic disorder.4 In addition, a large recent study of United States high school students found that binge-eating symptoms were reported by 11.0% of girls and 3.3% of boys, and that recurrent serious purging behaviour (eg, vomiting, laxative use or excessive exercise) was reported by 9.4% of girls and 13.5% of boys.5 How EOEDs in children relate to the eating disorders that emerge later, in adolescence and adult years, is unknown. A 10-year follow-up of a community cohort of 1943 Australian 14–15-year-old adolescents found that partial anorexia nervosa and bulimia nervosa occurred in nearly one in 10 girls aged 15–17 years, and that these girls appeared to be psychologically vulnerable, with poorer functional outcomes and psychiatric morbidity. However, there was little evidence of progression to full anorexia nervosa or bulimia nervosa.6 In contrast, prepubertal children with eating disorders are thought to have a particularly poor prognosis, with high levels of physical and psychiatric morbidity.7 Madden and colleagues’ data support a hypothesis that EOEDs may differ in important ways — including sex distribution and course — from eating disorders with onset in adolescence and adulthood. Whether they have a differing outcome is unknown, and follow-up is imperative. It is also important that an evidence base for treatments for prepubertal children is developed, despite the well known challenges of conducting controlled trials in an uncommon disorder in children. Notwithstanding this, the high (71%) rate of response to treatment reported by Madden and colleagues accords with other research that has demonstrated more positive treatment outcomes in older children and adolescents when compared with adults, particularly for anorexia nervosa.7 Madden and colleagues report that comorbidities, particularly anxiety disorders and depression, were common in the patients with EOEDs; they also found that around one in five patients were prescribed antidepressants, and one in 10 were prescribed antipsychotics. Given the concerns about the effects of these medications on the developing brain and the risks of antidepressant prescribing in youth, this level of use seems high. It is likely to reflect the severity of illness (especially anorexia nervosa), and the small evidence base supporting use of second-generation antipsychotics, such as olanzapine, in adults with anorexia nervosa.8 Lastly, these results highlight the dilemma of how to address concerns about the epidemic of obesity, while also avoiding contributing to the problems of the much smaller number of children with EOEDs that involve severe dietary restriction and weight loss. Although there is no similar “epidemic of eating disorders”,9 a recent South Australian study indicated that disordered eating in adults is increasing, mostly in the overweight population.10 This supports closer integration of prevention strategies and treatments for disordered eating and obesity, such as the promotion of healthy eating patterns and foods, rather than severe dietary restriction. Extreme weight control behaviour and weight disorders are both important health problems in young people, and Hippocrates’ aphorism that “a diet brought to the extreme point of attenuation is dangerous; and repletion, when in the extreme, is also dangerous”11 remains relevant today. In conclusion, Madden and colleagues address an important and potentially increasing problem in prepubertal children. It is imperative that research attention is now directed towards understanding why such young children are developing severe eating disorders and how effective identification and treatment can be targeted earlier.

Phillipa J Hay MD, DPhil, FRANZCP

An appropriate strategy is to test patients with symptoms and signs attributable to coeliac disease In recent years, knowledge about coeliac disease (CD) has improved significantly, and we now have a better understanding of the diagnosis and pathogenesis of the disease. In this issue of the Journal Chin and colleagues report the largest community study of CD undertaken in Australia.1 The study found a prevalence of CD of between 0.56% and 0.96%,1 similar to prevalences found in European population studies. A recent population-based serological study (without biopsy) in the United States found a prevalence of 0.95%.2 The screening strategy used by Chin and colleagues involved IgA and IgG anti-tissue transglutaminase (anti-tTG) antibody assays, HLA-DQ2 and HLA-DQ8 haplotyping, and, where appropriate, gastroscopy and duodenal biopsy.1 We believe that the data do not justify population-based screening for CD in Australia, but the diagnostic approach developed by Chin et al is appropriate for diagnosing patients in whom CD is suspected. Genetic and environmental factors are important in the genesis of the disease. The role of the HLA-DQ2 and -DQ8 haplotypes is yet to be fully understood. One or other haplotype is present in nearly all CD patients, yet they are also present in 20%–40% of subjects without CD. The “gold standard” for diagnosis has long been histological findings from a duodenal biopsy, despite the discordance between clinical symptoms and these findings. CD is caused by an immune response to antigens in gluten proteins. Wheat, barley and rye, but not corn or rice, contain gluten proteins. Ingested gluten is partially digested to peptides, some of which are absorbed into the lamina propria of the small intestine. The enzyme, tissue transglutaminase, deamidates certain glutamine residues in the peptides to glutamic acid. In patients with CD, this results in enhanced binding to HLA-DQ2 or -DQ8 cells. Within the lamina propria, T cell recognition of the amino acid sequences presented by the DQ2 or DQ8 cells produces a series of inflammatory changes, with the release of cytokines and the activation of lymphocytes. This leads to the characteristic histological findings in the proximal duodenum — lymphocytic infiltration, villous damage or loss, and crypt hyperplasia.3 Increases in transglutaminases in the lamina propria produce several effects: they catalyse the crosslinking of gluten peptide residues to lysine residues in various local proteins, including in transglutaminase itself, creating an immunogenic gluten–peptide–protein complex. This becomes an autoantigen, producing the characteristic IgA/IgG anti-tTG antibody of CD, which is best detected by an enzyme-linked immunosorbent assay. The mainstay of diagnosis of CD remains the anti-tTG assay, followed by duodenal biopsy, with the patient on a gluten-containing diet (equivalent to four slices of wheat bread a day) for several weeks. It is important to recognise that false-negative test results do occur, an underappreciated cause being IgA deficiency, which occurs in one in 40 people and can be identified using a combined IgG/IgA anti-tTG assay. Recent evidence suggests that the IgA/IgG anti-tTG antibody test has superior performance (sensitivity of about 90%, specificity of about 80%) to the anti-endomysial antibody (EMA) test, is less expensive, and overcomes the potential problem of IgA deficiency.4 If doubt persists, HLA haplotyping is useful, and a negative test for both DQ2 and DQ8 effectively excludes the diagnosis.5 Several factors should raise suspicion of the presence of CD and prompt testing: first-degree relatives of CD patients; adult type 1 diabetes mellitus; osteoporosis; ill-defined abdominal symptoms (eg, irritable bowel syndrome); iron or other nutritional deficiency; unexplained transaminase elevations; or Down syndrome. In patients in whom testing points to CD, the benefits of a gluten-free diet should be considered. Given that a gluten-free diet is arduous, we need to be assured that the risk–benefit ratio is appropriate. The benefits in those with florid symptoms are life-transforming (“Doctor, I never knew what it was like to be well before the diet”), but for the symptomless patient the gains in quality or quantity of life are less clear.2 Recent studies show a mild increase in risk of death from malignancy, which appears to diminish with time from diagnosis. Future research needs to quantify the benefits, if any, of lifelong treatment of people with asymptomatic and currently undiagnosed CD. What, then, is the role of screening for CD? To be justified, population screening must be effective, acceptable and cost-effective, and these conditions are not met for CD.6 Focused screening is preferable, as shown by a number of primary care studies. A study from nine surgeries in central England screened 1000 sequential patients with an anti-EMA test and found 30 patients in whom CD was confirmed by small-bowel biopsy. Half of these 30 patients presented with anaemia.7 Another study from five general practices in Yorkshire reported positive serological results in 12 of 1200 subjects, a prevalence of 1%. In patients with irritable bowel syndrome, the figure was 3.3%; in those with iron-deficiency anaemia, 4.7%; and in those complaining of fatigue, it was 3.3%.8 In a more recent US study in primary care, all individuals with symptoms or conditions known to be associated with CD were tested: 30 of 976 patients had positive results of an anti-tTG test and 22 (2.25%) were diagnosed with CD. These studies support our recommendation of a low threshold for serological testing of patients with coeliac-associated conditions. In summary, CD is now recognised as a common disorder, with a population prevalence of nearly one in 100 people. In most people, its manifestations are mild or non-existent. In others, it is associated with symptoms such as fatigue, iron-deficiency anaemia, and vague abdominal complaints. Rarely, CD is associated with more significant problems, such as strange neurological symptoms, hyper- or hypothyroidism and hepatic dysfunction. The most appropriate strategy for general practitioners is to have a high level of suspicion when patients present with symptoms and signs that may be attributable to CD and to test these patients.

John M Duggan AM, MD, FRACP · Anne E Duggan MHP, PhD, FRACP

A key issue is to recognise when a duality of interest has become a conflict of interest In Australia, provision of specialised product information and promotion by the pharmaceutical industry of drugs approved by the Therapeutic Goods Administration is an integral part of the health care environment. The pharmaceutical industry provides information and training to health professionals about new products; funding for conferences; support for professional and social activities secondary to medical education; support for the conduct of research and information about its outcomes; and opportunities to meet with peers. However, the primary goals of the pharmaceutical industry and health professionals differ: the pharmaceutical industry has a financial responsibility to shareholders, while health professionals have a moral responsibility to their patients. The challenge for both is to manage their responsibilities when interacting with one another. The pharmaceutical industry’s code of conduct1 upholds the principles of Australia’s Quality Use of Medicines program and National Medicines Policy. However, an interaction between pharmaceutical representatives and hospital employees will ultimately have a promotional intent. In itself, an indirect promotional activity is not a problem. However, the interaction will often influence prescribing.2 Many health professionals deny that such activity influences their behaviour, although, paradoxically, they believe their peers may be more easily swayed.3 Appropriate provision of patient care requires health professionals to understand these influences and keep them in mind in order to maintain independence of judgement. Ethics relating to promotional activities of pharmaceutical companies and managing conflicts of interest have been recently reviewed.4-10 Some researchers have argued that contact with the pharmaceutical industry should be more restricted and certain activities prohibited. In the United States, steps have been taken to prohibit all gifts (including meals) and to institute central management of product samples.8 A US report commented that “bias, either by appearance or reality, has been woven into the very fabric of continuing education” and called for cessation of commercial support from pharmaceutical and medical device companies.11 In Australia, while the move to state and federal funding and other non-commercial sources for educational and drug information activities is currently being debated, it is unrealistic to prohibit contact between health professionals and the pharmaceutical industry. It may be argued that industry plays an important role in health education — indeed, constructive engagement between industry and health professionals may be in the interests of patients. Severing all contact between industry and health care providers could limit open dialogue, hamper innovation and create a huge gap in educational support for health professionals. Initiatives to bridge the gap have been suggested.4-6 In the meantime, hospital staff must analyse the nature of their current interactions with the pharmaceutical industry and aim to improve it to optimise benefit to the patient. Codes of practice have been developed by professional bodies, societies, hospitals, government and the pharmaceutical industry in an attempt to ensure that interactions between hospital-based health professionals and the pharmaceutical industry are ethical and in the interests of the patient. However, a more practical framework is required to evaluate these interactions and to work towards achieving the highest standards of patient care and quality use of medicines. At the request of its members, the New South Wales Therapeutic Advisory Group (NSW TAG) recently updated its existing position statement on liaison between hospital staff in NSW and the pharmaceutical industry. The position statement provides evidence-based guidelines to help hospital staff recognise the activities that enhance clinical practice and those that potentially damage the relationship between health professionals and patients.12 It suggests steps to minimise potential conflicts of interest and ways to support ethical interaction, including making full use of independent sources of evidence-based medicine. It proposes that all health professionals adopt the approach of the Royal Australasian College of Physicians with regard to identifying and managing dualities and conflicts of interest.13 A duality of interest (where two or more interests coexist) is not unethical, but the key issue is to recognise when one interest is compromising the other (ie, when a conflict of interest is present). It is not enough to voluntarily disclose a duality of interest and then feel justified in proceeding regardless. Members of NSW TAG have discussed establishing a system of review and authorisation, deciding whether steps are necessary to separate or prohibit the conflicting activities and how open communication contributes to the transparency of the process. Our intention has been to ensure that the primary objective of professional interactions with pharmaceutical companies is to advance the health and wellbeing of patients. A recent article called for a set of guidelines for academic medical centres and opinion leaders.4 Extension of practical guidelines to all health professionals is a necessary next step. The pharmaceutical industry has established a system of self-regulation.1 In authorising the Medicines Australia code of conduct, currently under review, the Australian Competition and Consumer Commission requires details to be published of educational events provided or sponsored by member companies. All events have been reviewed by an independent auditor, and the first of these 6-monthly reports is now available.14 The audit had limitations with regard to investigation of high-cost activities and verification of data supplied. Nevertheless, such measures from industry to increase transparency support the intentions of NSW TAG’s position statement.12 The issues discussed in the position statement extend well beyond the pharmaceutical industry. They also include providers of medical devices, chemicals in pathology laboratories, and machines and consumables in radiology departments. Understanding the differences between the role of the health professional and that of the pharmaceutical industry is fundamental to understanding how to handle the interaction between the two groups. This process is evolving and the NSW TAG position statement is considered a “work in progress” to provide guidance within existing codes. The pharmaceutical industry and health professionals need to continue to foster a process of introspective challenge and regulation. Ongoing discussion by all stakeholders to find solutions that benefit patients is paramount.

Diana H Shipp BPharm, MRPharmS · Gordon Mallarkey BSc(Hons), PhD

Transparency and open communication are key to a healthy relationship Medical practice these days is influenced to a large extent by clinical practice guidelines. Usually sponsored by professional bodies, these compendia of advice should be produced by groups of experts with broad representation and credibility. These experts are expected to follow clearly defined processes1 to arrive at recommendations that are based on evidence, and which are unadulterated by other influences, such as commercial considerations. Strict adherence to this framework underpins the authority and acceptability of the guideline. But these standards are sometimes not met, and there have been calls for reform to ensure reliability of guidelines, and thereby offer patients protection from treatment based on guidelines whose content may be affected by extraneous influences.2-4 In this issue of the Journal, Millar5 adds to the disquiet regarding guideline formulation with his critique of the Prevention of venous thromboembolism: best practice guidelines for Australia and New Zealand, fourth edition,6 produced by a Working Party of Australian and New Zealand experts. The Guidelines were published in booklet form by a company part-owned by a member of the Working Party, and were supported by a grant from a pharmaceutical company that manufactures enoxaparin, a low molecular weight heparin recommended in the Guidelines for prophylaxis and treatment of venous thromboembolism. In Australia, the National Health and Medical Research Council (NHMRC) has published criteria for developing guidelines,1 and in doing so has set high standards, including standards for commercial sponsorship. In light of the NHMRC criteria, the overall process involved in the Guidelines can be criticised for the: apparent lack of independent peer review, as best exemplified by publication in a recognised medical journal; lack of comprehensive declarations of conflicts of interests in a setting where at least a perception of pecuniary interest is possible; failure to provide levels of evidence or costing for the recommendations; failure to include a full and readily available list of the references on which the evidence for the recommendations are based; failure to divulge the precise writing process and the details of the relationships between the publisher, the Working Party in general, and individual Working Party members and the sponsoring pharmaceutical company; and publication as a booklet that was initially distributed only by the sponsor, and thus not easily or independently accessible. Millar’s article implicitly raises the question of tolerance by the medical profession in general of the involvement of the pharmaceutical industry with these and other guidelines. At the core of this issue lie the opposing aims and philosophies of the pharmaceutical industry and medicine — namely that, although both groups ostensibly work for the benefit of patients, the industry does so to make a return on capital, whereas doctors generally do so altruistically. As stated in a recent commentary in JAMA: By favoring . . . one therapy over another, guidelines often create commercial winners and losers, who cannot be disinterested in the results and who therefore must be separated from the process.2 Nevertheless, it is natural that the pharmaceutical industry has a keen interest in guideline development. Commenting on the interaction of industry and medicine, Sir Iain Chalmers of the James Lind Initiative in the United Kingdom was recently quoted as saying: I do not blame industry for trying to get away with anything that is normally considered to be its primary purpose, which is to make profits and look after its stakeholders’ interests.7 Sponsorship and marketing behaviour is not unlawful (nor should it be), and indeed is at the centre of company philosophy and statute in a capitalist economy. Therefore, the restraint on unbridled marketing effort that can compromise patient care lies squarely with the medical profession. The profession’s individual members are obliged to maintain a respectful distance from the pharmaceutical industry and show some disdain for the apparent benefits of pharmaceutical sponsorship — to avoid being stabbed, one should not waltz too closely with the porcupines! Two senior editors of JAMA recently wrote: The profession of medicine, in every aspect — clinical, education, and research — has been inundated with profound influence from the pharmaceutical and medical device industries. This has occurred because physicians have allowed it to happen, and it is time to stop.9 In Australia, there is no overarching national policy for interactions of Australian doctors and the pharmaceutical industry. We should consider the lead of our colleagues in the UK, where the Royal College of Physicians of London (RCP) recently published a report entitled Innovating for health: patients, physicians, the pharmaceutical industry and the NHS, which extensively defines a framework for proper interaction.10 The Royal Australasian College of Physicians has also commented on this topic.11 There have also been recent multinational calls for the cessation of industry support for continuous medical education directed to individual doctors and institutions.10,12-14 However, the President of the RCP counsels that there is no need to destroy the bridges between industry and the profession. What is required is that the culture between these sectors should be transparent, and governed by open communication and agreed-upon national policy.15 This is sound wisdom to guide national policy deliberations in Australia.

Martin B Van Der Weyden MD, FRACP, FRCPA

Objective: To collect nationally representative epidemiological data on early-onset eating disorders (EOEDs) in children.Design: Prospective, active surveillance using the Australian Paediatric Surveillance Unit with key informant design.Setting: Child health specialists in Australia (July 2002 to June 2005).Patients: Incident cases of EOEDs in children aged 5–13 years.Main outcome measures: Disease rates, demographic characteristics, clinical features and complications, hospitalisation, psychological comorbidity, and concordance of clinical features with Diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV) criteria.Results: We identified 101 children aged 5–13 years with EOEDs (median age, 12.2 years; range, 5.5–13.9 years), of whom one in four were boys. Most were hospitalised (78%), and the mean duration of hospitalisation was 24.7 days (range, 1–75 days). More than 70% of inpatients were admitted to specialised eating disorder units in paediatric teaching hospitals. Among inpatients, 37% met DSM-IV diagnostic criteria for anorexia nervosa; although 61% had life-threatening complications of malnutrition, only 51% met weight criteria. Psychological symptoms were similar to those in adults with anorexia nervosa: 67% of inpatients met both psychological diagnostic criteria for anorexia nervosa (fear of weight gain/fatness and misperception of body shape). Of 19 postmenarchal girls, 18 had secondary amenorrhoea. Nasogastric feeding was used in 58% of inpatients, and 34% received psychotropic medications.Conclusions: This is the first prospective national study of EOEDs. It demonstrates the limitations of applying DSM-IV diagnostic criteria for anorexia nervosa to young children; the high proportion of boys affected by EOEDs; and the significant psychological comorbidity and high frequency of hospitalisation associated with EOEDs. Potentially life-threatening medical complications are common at presentation, suggesting possible missed diagnoses and a need for education of health professionals. The study underlines the severity of EOEDs and the need for joint medical and psychiatric specialist management.

Sloane Madden MB BS(Hons), FRANZCP, CAPCert · Anne Morris MB BS, MPH, FRACP · Yvonne A Zurynski BAppSc, MAppSc, PhD · Michael Kohn MB BS, FRACP · Elizabeth J Elliot MD, FRACP, FRCPCH

Objective: To describe the pattern of perinatal HIV exposure and outcomes among children born in Australia, 1982–2006.Design and setting: National surveillance for perinatal HIV exposure.Participants: Women with HIV infection and their perinatally exposed children.Main outcome measures: Trends in the age-standardised rate of perinatal exposure, uptake of interventions by women with an antenatal HIV diagnosis, and rate of mother-to-child transmission.Results: Between 1982 and 2006, there were 354 reported cases of perinatal HIV exposure among children born in Australia. The age-standardised rate of perinatal exposure per 100 000 live births increased from 2.3 (1982–1986) to 5.1 (1991–1998), 9.9 (1999–2002) and 8.3 (2003–2006). Among children whose mother was diagnosed antenatally, the mother-to-child transmission rate declined significantly, from 25% (4/16; 95% CI, 7%–52%) in 1987–1990 to 5% (4/82; 95% CI, 1%–12%) in 2003–2006 (P < 0.001). The rate declined from 8% (4/51; 95% CI, 2%–19%) in 1987–1998 to 1% (2/151; 95% CI, 0.2%–5%) in 1999–2006 among children whose mother used at least two interventions. Mother-to-child transmission remained high among children born to women diagnosed postnatally (39/87, 45%; 95% CI, 34%–56%) and to women diagnosed antenatally who used no interventions (7/15, 47%; 95% CI, 21%–73%).Conclusion: The increasing rate of perinatal exposure and the decreasing rate of mother-to-child transmission among children whose mothers’ HIV infection was diagnosed antenatally were temporally associated with use of interventions for minimising mother-to-child transmission. Mother-to-child transmission remained high when the mother’s HIV infection was not known during pregnancy.

Ann M McDonald BSc, MPH · Yvonne A Zurynski PhD · Handan C Wand PhD · Michelle L Giles MB BS(Hons), FRACP · Elizabeth J Elliott MD, FRCP, FRCPCH · John B Ziegler MD, FRACP, FRCPCH · John M Kaldor PhD

About 13 000 refugees are currently accepted for migration into Australia each year, many of whom have spent protracted periods living in extremely disadvantaged circumstances. As a result, medical practitioners are increasingly managing recently arrived refugees with acute and chronic infectious diseases. The Australasian Society for Infectious Diseases has formulated guidelines for the diagnosis, management and prevention of infection in newly arrived refugees. This article is an abridged version of the guidelines, which are available in full at <http://www.asid.net.au>. All refugees should be offered a comprehensive health assessment, ideally within 1 month of arrival in Australia, that includes screening for and treatment of tuberculosis, malaria, blood-borne viral infections, schistosomiasis, helminth infection, sexually transmitted infections, and other infections (eg, Helicobacter pylori) as indicated by clinical assessment; and assessment of immunisation status, and catch-up immunisations where appropriate. The assessment can be undertaken by a general practitioner or within a multidisciplinary refugee health clinic, with use of an appropriate interpreter when required. The initial assessment should take place over at least two visits: the first for initial assessment and investigation and the second for review of results and treatment or referral.

on behalf of the Australasian Society for Infectious Diseases Refugee Health Guidelines Writing Group

Objective: To describe the natural history of vitamin D deficiency in an at-risk population of African migrants living in Sydney.Design, setting and participants: Opportunistic study of 25-hydroxyvitamin D [25(OH)D] concentrations over time in a community-based cohort of North African refugee families living in south-western Sydney. As part of a health-screening program, serum concentrations of 25(OH)D, parathyroid hormone (PTH), calcium, phosphate (PO4) and alkaline phosphatase (ALP) were measured in September 2006 (end of winter, T1). Results for 25(OH)D were made available, and treatment was recommended as appropriate. In February–March 2007 (end of summer, T2), in the setting of a separate study of high-dose vitamin D (stoss) therapy, the same cohort was contacted, and measurements were repeated.Main outcome measures: Changes in 25(OH)D, PTH, ALP and PO4 concentrations between T1 and T2 in those who had not received vitamin D supplementation in the intervening period.Results: We collected data from 149 participants at T1; by T2, 58 participants (39%) had been excluded or lost to follow-up. Data from 91 participants (46% female), all of whom had Type VI (very dark) skin pigmentation, were included in the analysis. All 91 were 25(OH)D deficient at T1. Between T1 and T2, mean 25(OH)D serum concentration increased from 19 nmol/L (SD, 5.6 nmol/L) to 36 nmol/L (SD, 12.4 nmol/L) (P < 0.001). Of the 91 participants, 79 (87%) remained vitamin D deficient at T2. Serum PTH and ALP activity decreased between T1 and T2 (P < 0.05).Conclusion: Despite a significant increase in 25(OH)D serum concentration over the study period, most participants (87%) remained 25(OH)D deficient at the end of summer. Our results support the current consensus that recommends annual screening for vitamin D deficiency and routine vitamin D supplementation in at-risk populations, such as dark-skinned or veiled groups.

Paul Z Benitez-Aguirre MB BS, BSc, MPH · Nicholas J Wood MB BS, FRACP · Cornelis Biesheuvel PhD · Conrad Moreira MB BS, MPH, FAFPHM · Craig F Munns MBBS, PhD, FRACP

Objectives: To determine (i) the prevalence of positive results of anti-tissue transglutaminase (anti-tTG) antibody assays and coeliac disease (CD) in a rural Australian community; and (ii) whether confirmatory testing of a positive assay result with an alternative anti-tTG assay improved the positive predictive value of the test in population screening for CD.Design: Retrospective analysis in December 2004 of stored serum samples taken in 1994–1995 from 3011 subjects in the Busselton Health Study follow-up. Assays for IgA and IgG anti-tTG antibodies were performed, and positive or equivocal samples were retested with a different commercial anti-tTG assay. Available subjects with one or more positive assay results were interviewed, had serum collected for repeat anti-tTG assays and for HLA-DQ2 and HLA-DQ8 haplotyping and, if appropriate, gastroscopy and duodenal biopsy were performed. In unavailable subjects, HLA-DQ2 and -DQ8 haplotyping was performed on stored sera. Total serum IgA levels were assessed in subjects with initially negative assay results.Main outcome measure: Prevalence of anti-tTG positivity and biopsy-proven CD.Results: In 47 of 3011 serum samples (1.56%), at least one anti-tTG assay gave positive results: 31 of the subjects who provided these sera were available for clinical review, and 21 were able to have a gastroscopy. Seventeen subjects (0.56%) were diagnosed with definite CD (14 were confirmed at gastroscopy, and three unavailable subjects had three positive results of anti-tTG assays and an HLA haplotype consistent with CD); in a further 12 unavailable subjects, CD status was considered equivocal, with one or more positive anti-tTG assay results and an HLA haplotype consistent with CD. If these subjects were regarded as having CD, the prevalence of CD would be 0.96%. The positive predictive value when all three anti-tTG assays gave positive results was 94%, but fell to 45.2% with only one positive result.Conclusions: The prevalence of anti-tTG antibodies in this population is 1.56%; the prevalence of CD is at least 0.56%. The utility of a single, positive result of an anti-tTG assay in screening for CD in the community is poor, and repeat and/or collateral assessment with different assays may decrease the need for gastroscopy and distal duodenal biopsy.

Marcus W Chin MB BS, FRACP · Dominic F Mallon MB BS, FRACP, FRCPA · Digby J Cullen MB BS, FRACP · John K Olynyk MB BS, FRACP, MD · Lindsay C Mollison MB BS, MPH, FRACP · Callum B Pearce MD, MRCPI, FRACP

Successful transition of students to competent work-ready health professionals requires an ability to work in health care teams. Poor communication and teamwork practice has been implicated as a contributing source of error affecting patient safety. Traditional university curriculum structures severely limit the time that students from different professions can spend together, learning about and from each other (interprofessional education [IPE]). IPE initiatives need to focus on whole-of-system impacts and organisational sustainability. The Health Care Team Challenge (HCTC) is a high-profile leadership strategy that engages students, academic staff, practising professionals, policymakers and industry in a whole-of-system approach to IPE and interprofessional practice. Interprofessional student teams compete at a live public event for a cash prize for the best management plan centred on a complex clinical case study. National and international HCTCs are planned for future years.

Rosalie A Boyce BSc, MBus, PhD · Monica C Moran MPhil(OT), GCertED, DSocSc · Lisa M Nissen BPharm, PhD, FSHP · Helen J Chenery BSpTher, MSpTher, PhD · Peter M Brooks MD, FRACP

The Australian Government's “alcopops” tax legislation will soon be voted on by the Senate. This is the first time in memory that an alcohol taxation measure has been informed principally by public health concerns. Much debate surrounds the utility of alcohol taxation as a measure to reduce alcohol-related harm. However, the harms resulting from alcohol misuse in Australia are at unacceptable levels and action to reduce them is overdue. There is good evidence from Australia and internationally that taxation and price measures are among the most effective and cost-effective in reducing alcohol consumption and related harms. Recent alcohol sales data give an early indication that the alcopops tax is being effective in reducing consumption. Current alcohol tax policy is unwieldy and not well directed towards improving public health. A proportion of tax revenues dedicated to alcohol programs would assist public acceptance of the measures. A broad review of alcohol taxation policy is needed as part of a comprehensive approach to alcohol problems in Australia.

for the Royal Australasian College of Physicians Alcohol Advisory Group

Objective: To evaluate current evidence in support of therapies for preventing and treating cardiogenic shock (CS) after acute myocardial infarction that can be initiated in hospitals without invasive cardiac facilities.Study design: Systematic review.Data sources: MEDLINE and PubMed were searched from January 1985 to May 2008 using the MeSH terms “myocardial infarction”, “thrombolytic therapy”, “shock, cardiogenic”, “angioplasty, transluminal, percutaneous coronary”, “intra-aortic balloon pumping” and “platelet aggregation inhibitors”. Additional keyword and reference list searches were performed. Articles in English relating to adults were included.Study selection: Meta-analyses and comparative studies were included if they reported mortality or prevention of CS as an endpoint. In total, 35 articles were analysed (four meta-analyses, eight randomised controlled trials and 23 cohort studies).Data extraction: Studies were summarised by the first author and the level of evidence graded. Each study was checked by the second author and consensus was reached about inclusion and levels of evidence.Data synthesis: In the management and prevention of CS, the following are supported by high-level evidence: prehospital thrombolysis, transfer for emergency revascularisation (patients aged < 75 years) and thrombolysis for older patients (patients aged ≥ 75 years). In established CS, evidence supporting inhospital thrombolysis and intra-aortic balloon pump use in patients aged < 75 years and emergency revascularisation in older patients is limited to subgroup analyses and observational studies.Conclusions: In regional centres, prevention of CS is achieved with early fibrinolysis, preferably before hospital arrival. Patients of all ages should be considered for thrombolysis, early transfer for coronary revascularisation, and intra-aortic balloon pump insertion unless contraindicated. Glycoprotein inhibitors have no role in the management of CS in non-tertiary hospitals.

Enda O’Connor MRCPI, FJFICM · John F Fraser FRCA, FFARCSI, FJFICM

Clinical guidelines are recommendations based on systematic identification and synthesis of the best available scientific evidence. The National Health and Medical Research Council (NHMRC) has published standards for guideline development. According to the NHMRC standards, guideline development must be a transparent and independent process, with full disclosure of any potential competing interests. Australian guidelines for prevention of venous thromboembolism have been published by an autonomous group. Several features of the processes used to produce and distribute these guidelines, such as pharmaceutical sponsorship, do not meet NHMRC endorsement standards. The guidelines may overstate the need for thrombo-prophylaxis in medical patients, and thus expose some patients to an unnecessary risk of bleeding complications. Despite this, these guidelines have been taken up avidly by national and state bodies responsible for safety and quality in health care, and mandated national application has been proposed.

J Alasdair Millar PhD, FRACP, FRCP

Comment on Millar: The application of appropriate prophylaxis for venous thromboembolism (VTE) is recognised as an important patient safety measure. In a systematic review ranking 79 safety interventions, the Agency for Healthcare Research and Quality in the United States found that, based on the strength of overwhelming evidence that thromboprophylaxis reduces adverse patient outcomes and decreases overall costs, the highest-ranked safety practice was the appropriate use of prophylaxis to prevent VTE.1 However, it has been shown that, worldwide, the application of appropriate VTE prophylaxis is underutilised.2 The Australia and New Zealand Working Party on the Management and Prevention of Venous Thromboembolism first convened in 1997. It comprises a group of specialists from medical and surgical disciplines actively involved in VTE management and representing all Australian states and New Zealand. Its objective was to produce a practical, pocket-sized booklet summarising published evidence-based guidelines, drawing on those of the American College of Chest Physicians (ACCP)3 and the International Consensus Statement.4 The Working Party has never attempted to produce a new set of guidelines. The first edition of the Guidelines was published in 1998, with subsequent editions published in 2001, 2006 and 2008. Support from various companies in the medical industry was accepted to allay the cost of bringing Australian and New Zealand representatives to a meeting venue, usually an airport hotel meeting room on a Saturday. Members of the Working Party willingly gave of their time for these meetings, and none received payment. In return for their support and their assistance in distribution of the Guidelines, it was agreed that the companies could place their logo on the back cover of the booklets. It is erroneous to state that “the Guidelines are sponsored by a global pharmaceutical company and are professionally marketed”. The statement that “the current (fourth) edition of the Guidelines acknowledges commercial sponsorship by a ‘non directed’ grant from Sanofi-Aventis, the manufacturer of the LMWH enoxaparin” is incorrect. It is clearly stated in the Guidelines that “The Working Party members wish to acknowledge the support of the medical industry through their provision of non-directed educational grants. The opinions expressed in this booklet are entirely those of the expert clinicians on the Working Party”. The concern expressed in the article that “the Guidelines overstate the need for pharmacological prophylaxis in medical patients, and that patients at low risk of VTE will be exposed unnecessarily to the risk of bleeding complications” is at variance with the recommendation from the latest ACCP guidelines, which advocate low molecular weight heparin (Grade 1A recommendation), low-dose unfractionated heparin (Grade 1A), or fondaparinux (Grade 1A) for acutely ill medical patients admitted to hospital.5 The Working Party advocates that VTE risk assessment should become standard practice for all surgical and medical patients on admission to hospital. From experience since publication of the first edition of the Guidelines, it is anticipated that there will be an ongoing demand for a pocket-sized booklet that summarises current best practice in VTE prevention, and we will endeavour to continue to meet this need.

John P Fletcher

A 49-year-old health care worker received varicella vaccine in accordance with current Australian guidelines. She developed streptococcal toxic shock syndrome, complicated by acute atraumatic dislocation of the right wrist secondary to poststreptococcal reactive arthritis — to our knowledge, the first report of spontaneous wrist dislocation as a complication in this condition. Vaccination was accompanied by prolonged viraemia with the varicella vaccine strain — also, we believe, the first report of this in an immunocompetent patient. Clinical recordA 49-year-old female hospital employee received varicella vaccination, in accordance with the guidelines of New South Wales Health for varicella-seronegative health care workers.1 She presented 17 days after the second vaccine dose (38 days after the first dose) with a 12-day history of joint pain and swelling, predominantly affecting the upper limbs and knees, along with myalgia and lethargy. These symptoms had worsened over the preceding 48 hours. There were no noticeable skin lesions, and no local reaction at the vaccination site. The patient’s past medical history was unremarkable except for depression treated with venlafaxine, the only medication she was taking at the time of admission. At presentation, she was afebrile, with a blood pressure of 95/60 mmHg, and pulse rate of 96 beats/min. The dominant clinical finding was gross peripheral oedema of the upper limbs, including the hands (Box 1). Initial investigations showed raised total white cell count (13.1 × 109/L; reference range [RR], 3.9–11.1 × 109/L) and neutrophil count (12.1 × 109/L; RR, 2.0–8.0 × 109/L) and abnormal liver function (bilirubin, 51 μmol/L [RR, < 21 μmol/L]; concentration of alanine aminotransferase [ALT], 152 U/L [RR, < 33 U/L]; aspartate aminotransferase [AST], 112 U/L [RR, < 45 U/L]; γ-glutamyltransferase [GGT], 112 U/L [RR, < 30 U/L]; alkaline phosphatase [ALP], 308 U/L [RR, 30–115 U/L]; and albumin, 32 g/L [RR, 35–53 g/L]). The possibility of varicella hepatitis complicating vaccination was considered. Forty-eight hours after admission, the patient became confused and hypotensive, with a systolic blood pressure of 70 mmHg. Streptococcus pyogenes was isolated from blood cultures. Her blood pressure did not increase in response to intravenous resuscitation with normal saline (1 L) and colloid (2 L). She was transferred to the intensive care unit, where she received inotropic support with noradrenaline for 22 hours. She developed streptococcal toxic shock syndrome, with renal impairment (concentration of sodium, 126 mmol/L [RR, 135–145 mmol/L]; potassium, 4.3 mmol/L [RR, 3.2–5.0 mmol/L]; urea, 23.4 mmol/L [RR, 2.5–6.1 mmol/L]; creatinine, 195 μmol/L [RR, 50–110 μmol/L]), thrombocytopenia (platelet count, 86 × 109/L [RR, 150–400 × 109/L]) and continuing impairment of liver function (bilirubin, 76 μmol/L; ALT, 78 U/L; AST, 58 U/L; GGT, 72 U/L; ALP, 237 U/L; and albumin, 22 g/L). After 4 days, the serum albumin concentration had dropped to 17 g/L, and gross oedema persisted. The source of the S. pyogenes infection was not established, but the organism was cultured from a small skin lesion in the right cubital fossa. The isolate was subsequently identified as S. pyogenes serotype M11. Varicella zoster virus (VZV) genotyping of serum showed the presence of the Oka vaccine strain of VZV.2 Nucleic acid testing by quantitative polymerase chain reaction (PCR) using primers that target VZV open reading frame 62 revealed a serum load of 480 000 VZV DNA copies/mL 2 days after admission and 19 days after the last varicella vaccination. Tests on admission for VZV-specific IgG were positive. The patient was treated with high-dose intravenous benzylpenicillin (1.8 g 4-hourly) for 10 days and aciclovir (10 mg/kg 8-hourly) for 7 days. Ten days after admission, serum albumin levels had risen to more than 30 g/L. Although the peripheral oedema resolved gradually, both wrists and the left knee remained swollen. The patient had no fever and no clinical features of septic arthritis. Ultrasound examination of the joints and a technetium-labelled bone scan did not suggest joint fluid or adjacent osteomyelitis. Nineteen days after admission, the patient showed signs of bilateral median nerve compression. The right wrist appeared clinically deformed, with palpable synovitis (Box 2A ). Imaging showed disruption of the right wrist and carpus to a degree usually associated with high-energy trauma (in the absence of any history of trauma), with dislocation of the distal radioulnar joint (DRUJ), and wide diastasis of the scapholunate interval (Box 2B). The left wrist and carpus showed lesser disruption. The following day, the patient underwent aspiration of the left knee effusion, and bilateral carpal tunnel decompression and flexor synovectomy. Extensive synovitis was observed around the flexor tendons of both wrists (Box 2C), with rupture of the right lunotriquetral ligament. The right DRUJ was reduced and held in a supination splint, avoiding the insertion of metalware until infection had been excluded. Fluid from the knee contained 85 000 polymorphonuclear cells/mL, but no organisms were seen. Fluid and synovial tissue from the right wrist and left knee showed no bacterial growth on culture, and were negative for VZV by quantitative PCR (although the patient had received no antimicrobials in the 21 days before surgery). Histological examination of synovial tissue showed an acute and chronic inflammatory cell response and granulation tissue-type reaction, consistent with poststreptococcal reactive arthritis. The patient was negative for HLA-B27 antigen. The supination splint did not adequately control the right DRUJ. K-wiring of the joint was required, with subsequent fusion of the wrist joint and stabilisation with a tendon graft. Symptoms were initially treated with non-steroidal anti-inflammatory drugs, with the later addition of systemic corticosteroids. Quantitative varicella PCR was performed weekly for 4 weeks. A decrease in varicella DNA concentration in serum from 480 000 to 3400 copies/mL was shown 5 days after admission to hospital. Levels stabilised at 9600 ± 2100 copies/mL, and had decreased to 800 copies/mL before discharge. The Oka vaccine strain of VZV was still detectable by quantitative PCR in the blood 54 days after vaccination, but had become undetectable just over 2 months after vaccination. The timeline of events is outlined in Box 3. DiscussionThis is the first report, to our knowledge, of prolonged viraemia after varicella vaccination in an immunocompetent patient, and also of spontaneous wrist dislocation as a complication of poststreptococcal reactive arthritis. Varicella vaccine contains live attenuated virus (Oka/Merck strains), and has been used in Australia since 2000.3 Although the Oka vaccine strain has been detected in patients with varicella or zoster-like rashes after VZV vaccination,4 its persistence and load in blood after vaccination of immunocompetent adults has not been established. In a study of primary varicella infection, wild-type virus was not detected more than 8 days after the onset of rash, nor in any patient who received aciclovir.5 Another study was unable to detect virus more than 14 days after onset of illness.6 In contrast, in our patient, viraemia persisted for 54 days and the Oka VZV strain was detectable after aciclovir treatment. S. pyogenes infection has long been recognised as a sequelae of chickenpox.7-9 A study found that up to 50% of cases of invasive group A streptococcal infections in children were associated with recent VZV infection.7 However, in previous cases, varicella infection was clearly apparent, and skin lesions were present from which secondary bacterial infection was presumed to arise. Our patient had no clinically apparent chickenpox-like skin lesions, and, in her case, the association between the varicella vaccination and streptococcal infection cannot be clearly defined. The frequency of poststreptococcal reactive arthritis complicating streptococcal septicaemia is difficult to determine because of the heterogeneity of the condition and lack of well accepted diagnostic criteria.10 Although palmar flexor tenosynovitis is described,11 acute atraumatic wrist dislocation has not been documented previously as a complication of poststreptococcal reactive arthritis. Occasional reports of atraumatic dislocation of the wrist have been in the setting of a pre-existing connective tissue disorder or had unknown aetiology.12,13 The M11 serotype of S. pyogenes isolated from our patient has been reported previously in invasive streptococcal disease, although M1 and M3 are the most commonly isolated serotypes.8 However, we believe this is the first report of the M11 serotype as a cause of poststreptococcal reactive arthritis,14 possibly reflecting a more virulent strain. This case highlights the possibility of prolonged high-level viraemia following varicella vaccination and the possible association with invasive S. pyogenes disease. However, this must be considered in the context of the benefits of varicella vaccination in preventing transmission of disease to health care workers15 and susceptible individuals. 1 Gross oedema of the patient’s hands at presentation 2 The patient’s wrist 19 days after admission A: Clinical deformity of right wrist. B: Posteroanterior and lateral x-rays showed carpal disruption, dislocation of the distal radioulnar joint and wide diastasis of the scapholunate interval. C: At surgery, synovitis was apparent around the flexor tendons. 3 Timeline of events Day Event 0 First dose of varicella vaccine 21 Second dose of varicella vaccine 26 Onset of symptoms 38 Admission to hospital 40 Serum VZV DNA level 480 000 copies/mL Admission to intensive care unit with streptococcal toxic shock syndrome 57 Bilateral median nerve compression 68 Median nerve decompression, flexor synovectomy, and knee aspiration. No evidence of infection, clinical picture suggestive of reactive arthritis 75 Serum VZV 800 copies/mL by quantitative PCR 89 Serum negative for VZV by quantitative PCR VZV = varicella zoster virus. PCR = polymerase chain reaction.

Claire M Italiano MB BS · Cheryl S Toi PhD · Simon P Chan MB BS, FRACS(ORTH) · Dominic E Dwyer MD, FRACP, FRCPA

Clinical record A 68-year-old man presented to our general district hospital in December 2006 with the chief complaint of sore throat, which had started abruptly 2 hours earlier. The pain was described as intense with a stabbing character. He reported minimal improvement after being given 10 mg of morphine subcutaneously. The patient did not report experiencing any cardiac or pulmonary discomfort, and he had no pertinent past medical history. His family history included one sister who had died of a ruptured aortic aneurysm. The patient was a non-smoker and denied any recent medication use. Physical examination showed that the patient’s vital signs were stable, with a normal level of consciousness, a regular pulse of 61 beats/min, and a blood pressure equal at both arms of around 115/70 mmHg. He was slightly tachypnoeic and diaphoretic. An ear, nose and throat examination did not provide any diagnostic clues as to the cause of the pharyngeal pain. Findings of a cardiovascular examination were normal apart from an audible right carotid artery bruit. No other physical abnormalities were detected. Results of laboratory tests were unremarkable, except for a markedly elevated d-dimer level (8.41 mg/L; upper limit of normal, 0.50 mg/L). Routine chest radiography was suggestive of mediastinal widening (Figure A). On the basis of these findings, a thoracic computed tomography scan was performed, which showed a 5.4 cm dissecting ascending aortic aneurysm (Figure B). The dissection involved the aortic root, ascending part of the aorta and aortic arch, and propagated into the right brachiocephalic trunk and left common carotid artery (Figure C). Transthoracic echocardiography additionally showed the presence of a bicuspid aortic valve with moderate grade 2/4 aortic insufficiency. Thoracic aortic dissection was diagnosed, classified as a Stanford type A dissection, given the involvement of the ascending aorta. A congenital bicuspid aortic valve and an ascending aortic aneurysm were predisposing factors for aortic dissection. The patient successfully underwent emergency surgery with graft replacement of the aortic valve and the dissected aortic segment. A: Chest x-ray showing mediastinal widening. The upper normal mediastinal width is defined as a mediastinum to chest-width ratio of over 0.25, measured at the level of the aortic arch (illustrated by the length of the solid line); this is noticeably exceeded in our patient (dashed line). B: Computed tomography scan showing an aneurysmatic dilatation of the ascending aorta with a classical dissection flap (black arrowhead) separating a true and false lumen. C: Propagation of the dissection process into the supra-aortic vessels (white arrows). The clinical presentation in our case was rather trivial, but the combined results from two basic investigations — an elevated d-dimer level and an abnormal chest x-ray — heightened our clinical suspicion for aortic dissection and led us to perform aortic imaging. Thoracic aortic dissection generally results from a laceration of the intimal lining of the aorta. This allows blood leakage into the aortic wall resulting in a propagating separation of the aortic media, thereby creating a false blood-filled lumen.1 Hence, the major criterion for definitive diagnosis of aortic dissection includes visualisation of a so-called intimomedial flap that divides the aorta into a true and a false lumen. Several aortic imaging techniques can be used for this purpose, of which contrast-enhanced computed tomography (CT) and transoesophageal echocardiography (TOE) are the most feasible to perform in an emergency department setting.1,2 Moreover, these investigations help to localise the dissection, thereby allowing appropriate classification. Currently, the Stanford classification of aortic dissection is the most widely adopted system.1,2 This system has the virtue of merely dividing aortic dissection into two subtypes, depending on whether the ascending aorta is involved (type A) or not (type B).1,2 While the definitive diagnosis of aortic dissection is usually straightforward, making the initial clinical diagnosis can be extremely challenging. Aortic dissection is associated with a dramatic rate of misdiagnosis and delayed recognition.3 This is no doubt partially explained by the highly variable clinical presentation of the condition. Our case is a striking illustration of why acute aortic dissection is colourfully called a “clinical chameleon”.1 Although most patients with aortic dissection present with severe chest or back pain (Box 1), the pain can be variably localised to the neck, jaw or throat.4 Throat pain occurs most often in cases of a dissection of the aortic arch, particularly when the supra-aortic vessels are involved. Our patient complained only of a sore throat, and denied having thoracic pain. Only two similar cases have been previously reported.5,6 Moreover, findings on physical examination can be very subtle.1 Classical signs consistent with the diagnosis of thoracic aortic dissection, such as an aortic insufficiency murmur or decreased femoral arterial pulsation, were not present in our patient. According to the International Registry of Acute Aortic Dissection,7 these so-called typical findings are infrequently detected during physical examination (Box 1). In our case, the only notable features of the physical examination were diaphoresis and a right carotid artery murmur. The latter was presumably the result of propagation of the dissection into the right brachiocephalic trunk. Because symptoms and signs of aortic dissection can be diverse and sometimes treacherously trivial, the initial diagnostic suspicion might rely on abnormalities observed during the basal diagnostic work-up. This routinely consists of laboratory testing with d-dimer analysis and chest radiography. d-dimer analysis has only recently come to the fore, with several studies focusing on the stringent association between the d-dimer level and aortic dissection.3,8,9 The pathophysiological mechanism for this relationship is well explained by the release of tissue factor from the dissected aortic wall. This sets off a cascade of events — activation of the extrinsic coagulation system, generation of fibrin, and secondary fibrinolysis with d-dimer formation.8 The d-dimer assay is reported to have an excellent sensitivity and negative predictive value for aortic dissection (Box 1). The quoted sensitivity is equal for both types of dissection, although absolute d-dimer values tend to be higher in type A aortic dissections as they are usually more extended.10 Given its high sensitivity and negative predictive value, d-dimer testing is an attractive tool for the diagnostic work-up of aortic dissection, particularly in the setting of a low pretest probability for aortic dissection. In such cases, a normal d-dimer result can reliably exclude the presence of aortic dissection, hence obviating the need for further investigations.9,10 Besides elevation of the d-dimer level, the clinical suspicion for aortic dissection should also be heightened if the chest radiograph is abnormal (Box 1). Mediastinal widening (relative mediastinum to chest-width ratio > 0.25;11 Figure A) is the most common radiographic finding in aortic dissection.7 Of note, absolute estimations of the mediastinal width are practically inaccurate, as these measurements are influenced by the distance between the roentgenographic source and the thorax.12 It is worth mentioning that one in three patients with aortic dissection has a normal chest x-ray.11 Thus, relying on chest radiography alone as the initial diagnostic modality is inefficient as it clearly carries a high risk of misdiagnosis. When readily available, contrast-enhanced CT and TOE are the preferred imaging modalities in an acute care setting. Both investigations have a comparable diagnostic accuracy and allow a definitive diagnosis of aortic dissection to be established.1,2 However, the diagnosis must first be suspected before it can be confirmed — this case serves as a reminder of this life-threatening condition’s wide variability in clinical presentation, and the need to maintain continuing vigilance. 1 Clinical and basic diagnostic features of thoracic aortic dissection, and percentages of patients presenting with these features who are subsequently diagnosed with Stanford type A or B aortic dissection1,2 Stanford classification Features Type A* Type B† Clinical symptoms and signs7 Presence of any pain 94% > 95% Retrosternal pain 71% 44% Interscapular pain 33% 41% Back pain 47% 64% Abdominal pain 22% 43% Blood pressure Hypotension or shock/tamponade < 25% < 5% Hypertension 35% 70% Aortic insufficiency murmur < 45% < 15% Decreased or absent peripheral pulsations < 20% < 10% Laboratory analysis8,9 d-dimer sensitivity (cutoff, 0.50 mg/L) > 95% > 95% d-dimer negative predictive value (cutoff, 0.10 mg/L) 100% Not reported Chest radiography7 Mediastinal widening 63% 56% Abnormal or blurred aortic contour 47% 53% Other radiographic features‡ < 25% < 25% * Dissection with involvement of the ascending aorta. † Dissection of the descending aorta without involvement of the ascending aorta. ‡ Such as displaced aorta, aortic calcification, tracheal displacement, pleural effusion. Lessons from practice Thoracic aortic dissection is characterised by a highly variable clinical picture, which has led to the condition being called a “clinical chameleon”. d-dimer testing can be of value in excluding aortic dissection. A normal chest x-ray does not rule out the possibility of aortic dissection. Advanced aortic imaging should be performed early in patients who have symptoms suggestive of aortic dissection in order to prevent misdiagnosis.

Sébastien Anguille MD · Aurélie M Derweduwen MD · Jeroen Lenz MD · Luc Vanuytsel MD, PhD · Frank J Cools MD

To the Editor: The National Heart Foundation of Australia believes the study by Vitry and Zhang on the quality of Australian clinical guidelines1 is useful and raises two important questions: Are guidelines approved by the National Health and Medical Research Council (NHMRC) of a superior quality, as the study suggests? and, Why doesn’t Australia have a robust, focused approach to the funding, development and implementation of clinical guidelines? Vitry and Zhang assessed various guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. This instrument, developed by an international collaborative process,2,3 defines “quality” by two definitions: potential for bias; and content validity. The process to determine validity, however, does not test a guideline’s potential to change practice or improve health outcomes. This limitation needs to be acknowledged to avoid over-interpretation of the AGREE instrument’s ability to assess quality. Vitry and Zhang acknowledge that the AGREE instrument is not able to distinguish between “actual poor process” and “poor reporting of the methods”, recognising that some criteria for assessment involve a subjective appraisal with definitions of “effectiveness” still open to debate. Including resources developed essentially as a practice tool or quick-reference guide4 with those that received full NHMRC support5 in this study diminishes the usefulness of its conclusions from using the AGREE instrument to evaluate clinical guidelines. It’s a pity that this important study of clinical guidelines failed to account for the range of activities and resources that support the implementation of individual guidelines, including companion patient resources. These shortcomings, however, should not diminish a further key message from this study: Australia needs to abandon its laissez-faire approach to guidelines. The National Heart Foundation of Australia goes further and calls for a strong and robust national framework for the funding, prioritisation, development and implementation of guidelines. There is, as yet, no such centralised or strategic approach to guidelines development, no national register or central database for guidelines, and a poor and uncoordinated approach to guideline implementation and evaluation. In contrast, the United Kingdom has adopted a comprehensive approach through the National Institute for Health and Clinical Excellence (www.nice.org.uk), the United States has its National Guideline Clearinghouse (http://www.guideline.gov), while New Zealand has its government-funded Guidelines Group (http://www.nzgg. org.nz). The Australian Government should adopt a similar approach as part of its national health reform agenda to ensure that the best possible guidelines are developed, that they are regularly updated, that developers are well resourced to undertake this increasingly complex task and that implementation and evaluation is rigorous. The NHMRC and its National Institute of Clinical Studies (http://www.nhmrc.gov.au/nics) are obvious candidates to take this work forward, but they will need additional federal resources to enable them to do so.

James Tatoulis · Nancy P Huang · Andrew N Boyden

To the Editor: Two articles in the 19 January issue of the Journal1,2 and an article on the involvement of pharmaceutical companies in studies of their own products published in The Australian on the same day3 impel me to relate my own experience of attempting to influence my colleagues’ attitudes toward transparency in relationships with the pharmaceutical industry, and my good fortune to be working in a 21st century oncology clinical trials unit. The relationship between the science of pharmaceutical development and the science of oncology is robust and fruitful. While intending to be only mildly controversial, I caused great offence in my opening address to the Australian and New Zealand Children’s Haematology and Oncology Group annual meeting in 2008 by suggesting that it is no longer acceptable for any of us at the coalface of oncology to deal directly with pharmaceutical salespeople or for medical education to be directly funded by industry. I note the view of Tattersall and colleagues that “... sponsoring doctors to attend independent conferences is recognised as facilitating continuing medical education ...”.1 In my view, financial support for medical education should come from unaffiliated sources — perhaps competitive grants from the government, who may in turn raise funds from industry. Similarly, we must be able to deny (not just declare) a conflict of interest in our activities in clinical trials and practice, and teach the difference between clinical trials (phase III cooperative group randomised controlled trials of multidrug treatment, with wide eligibility criteria to benefit as many patients as possible) and drug trials (phase I or II single-agent trials with narrow eligibility criteria, such that adverse effects of new drugs are found quickly). Both groups of trials are essential for the benefit of patients with cancer and leukaemia, as is the need for clinicians to be — and to be seen to be — at arm’s length from industry. I have been fortunate to work in a clinical trials unit that is supported by a wise medical administration and an ethics committee devoted to the practice of clinical trials as the best evidence-based medicine for patients. Our unit has clinical research associates on staff, is an active member of the United States-based Children’s Oncology Group, and does not partake in trials directly sponsored by industry. Indeed, after 20 years in the field, I know the trade names of less than 10% of the drugs I prescribe. I decline invitations to see pharmaceutical representatives or to attend industry-sponsored events. I followed the leadership of my mentors and senior clinicians. Can I convince today’s trainees to follow suit?

Catherine H Cole

To the Editor: We support the findings of Tattersall and colleagues relating to the disclosure of competing interests by general practitioners to their patients, and we agree that greater transparency in general is required with physician–industry relationships.1 Such relationships have the potential to enhance patient outcomes through quality use of medicines. However, in the interests of a balanced perspective, several points regarding Tattersall et al’s article warrant attention. First, the 2007–08 BEACH (Bettering the Evaluation And Care of Health) survey suggests that the mean length of GP consultations in Australia is 15.1 minutes.2 Considering this, an adequate discussion or disclosure of industry links to each and every patient is simply not practical. Furthermore, the frequency with which GPs see industry representatives can vary greatly. Given these complexities, perhaps clinics could consider having a simple sign in the waiting room that states “We do/do not see pharmaceutical industry representatives”. Disclosures would be most valuable if interested parties agreed on definitions for categories of relationships and payments, uniform approaches to calculating amounts, and standards for information to be made public. Inconsistent practices could create the impression that some practices are being hidden.3 Second, we want to highlight the potential benefits of physician–industry collaborations. We recently organised a panel of Australian physicians to advise a pharmaceutical company on research initiatives that need to be undertaken in a highly specialised area of medicine. An Advisory Group Charter, describing the purpose of the group, desired outcomes, and remuneration, was developed and agreed upon by all members. In this case, physicians received remuneration for time spent reviewing documents and collecting information for the meeting, and to cover costs associated with non-attendance at clinic. The aim of the Charter and two-way confidentiality agreements was to ensure transparency. After reviewing the published literature, each physician shared information about treatment practices and outcomes. The physicians identified several areas that require further research and have the potential to enhance patient outcomes in the immediate future. However, they suggested that these initiatives could be undertaken without industry support. They advised the company to direct its research funding towards large, population-based research initiatives. This is just one example of how transparent collaborations can result in enhanced patient outcomes and a redirection of funding into areas of greatest need. While we agree that increased transparency is important for physician–industry relationships, and improvements can be made through such avenues as disclosure, a retreat from physician–industry collaborations is not in the interests of improved patient outcomes or enhanced quality use of medicines.

Brad S Dalton · Deborah J Richards

In reply: We thank Cole for her suggestions. We note the Royal Australasian College of Physicians Guidelines for ethical relationships between physicians and industry state: “Industry sponsorship to attend conferences ... should usually be restricted to those in which the professional anticipates active engagement ... and when attendance without support is not possible”.1 With regard to Dalton and Richards’ first point, our survey asked patients for their views about doctors in general and not specifically about general practitioners.2 We do agree that disclosure would be most valuable if definitions for categories of relationships and payments were agreed on. Unfortunately, the options we presented to patients in our survey did not include disclosure being presented on a website, a method that has recently been launched by the Cleveland Clinic in the United States.3 A US Senate Bill, if enacted, would require health companies to report all their financial links with doctors on a government website.4 The potential benefits of physician–industry collaboration were not presented in our survey. Obviously, having doctors advise the pharmaceutical industry is likely to be beneficial, but is it appropriate to continue relationships where industry is advising or educating doctors? Notable among the 41 recommendations of a report from a Royal College of Physicians working party in the United Kingdom, chaired by the Editor-in-Chief of the Lancet, are: the promotion of standards for prescribing at postgraduate level; a method for gradually ending the support of the pharmaceutical industry in the education of doctors in training; and any honorarium and fee, commercial or otherwise, paid to a doctor should be declared on a publicly accessible website.5 We strongly support any interventions that enhance the quality use of medicines.

Martin H N Tattersall · Aneta Dimoska

To the Editor: The timely article by Olver and Haines on industry-led versus investigator-led studies in cancer clearly outlines the importance of appropriate trial design.1 However, perhaps one aspect of this critical issue was underemphasised. In cancer trials, overall survival is typically seen as the primary endpoint. In fact, at time of relapse or disease progression, patients are generally treated in a non-uniform manner. In this scenario, treatment is frequently tailored depending on whether the aim of therapy is curative or palliative. Ad-hoc or experimental approaches are used for some patients with relapsed or refractory cancer. Thus, although survival is undoubtedly the most clinically relevant endpoint, the lack of standardisation of treatment at relapse inevitably confounds assessment of the impact of the study drug on survival. Furthermore, for many tumour types, full evaluation of time-to-event outcomes, such as event-free and overall survival, requires prolonged follow-up, resulting in studies taking many years to be completed. For these reasons, biomarkers that accurately serve as early surrogate endpoints to predict for clinical outcome are urgently needed. Yet a striking feature of much industry-led trial design is the paucity of correlative laboratory studies and tissue banking to identify and validate new biomolecular endpoints. Such studies are frequently seen as unnecessary and burdensome. By contrast, although investigator-led laboratory studies of novel biomarkers generate much interest from the clinical and scientific community, their resource and cost implications (chiefly data manager support) prevent many centres from participating. Lucrative company-sponsored trials will always take precedence unless state and/or federal initiatives to support investigator-led studies are enacted. Funding research nurses and data managers to help oncology units conduct non-industry trials that are well designed and incorporate laboratory-based biomolecular research would be an important beginning.

Maher K Gandhi

In reply: We support Gandhi’s contention about the value that can be added to clinical trials by performing correlative laboratory studies. The investigation of biomarkers as potential surrogate endpoints that may indicate efficacy, or lack thereof, earlier than the prolonged time sometimes required to reach a survival endpoint, is one such example. Such studies are often not funded by industry and the importance of funding these, which yield greater clinical benefit, should be recognised by government and non-government agencies. It is possible, but very unlikely, that a survival endpoint may be compromised by the lack of a standardised approach to second-line therapies. We believe that if a new first-line agent is associated with a clinically significant improvement in survival, this will be evident irrespective of subsequent therapies used, which will usually yield inferior results to first-line therapies and will most likely be distributed randomly across the treatment arms. The need for tissue banks as a resource required across trials in all tumours is something that governments could address by funding them as vital clinical research infrastructure. The same applies to data managers for non-industry sponsored trials that are well designed and incorporate laboratory-based research, as Gandhi suggests.

Ian N Olver · Ian E Haines

To the Editor: Parker and Wilkinson raised the issue of medical students who behave inappropriately.1 It is likely that the major way medical students cause distress to others is through deliberate, inappropriate behaviour, representing a deficiency in empathy, rather than through laziness or other mental or social problems. In identifying the problem in these individuals, we need to consider whether the impairment is to the cognitive aspects of empathy — knowing how to behave — or to the emotional aspects — caring about the feelings of other people.2 Inappropriate behaviour can result from differing degrees of impairment in either of these domains, and different courses of action need to be considered for those at the extremes of either type of impairment. An extreme lack of the cognitive components of empathy might be seen in those with developmental disabilities, such as autism spectrum disorders. In these cases, intensive tutoring in professional skills and appropriate career guidance can produce competent and sympathetic doctors.3 At the other extreme, a severe deficiency in the emotional aspects of empathy — not caring about other people’s feelings — may be difficult to correct. Individuals with these psychopathic traits are thought to exist at high levels in many organisations.4 They — especially those with Machiavellian and narcissistic tendencies — may alter their behaviour to become competent medical students. However, their true lack of empathy may become apparent when their careers are secure, and they are in positions of real power. At that stage, they might put patient health and the psychological state of their colleagues at much greater risk. It is likely that some of the most dangerous doctors, such as Harold Shipman in the United Kingdom, represent extreme examples of this pattern. Medical schools need to be certain that any behaviour problems are truly correctable, and consider a thorough personality and cognitive assessment for students who present with inappropriate behaviour, to determine a course of action that will ensure the safety of future patients and colleagues of these students.

Sarah J Abrahamson

To the Editor: Controlled breathing is a fundamental principle of marksmanship. I describe an effect of viral lower respiratory tract infection on small arms training that was unexpectedly prolonged. The patient (myself) had abrupt onset of respiratory infection, 1 day after a marksmanship training session on an electronic firing range. During the session, I obtained satisfactory scores from several firing positions (best score, 66 mm grouping for five shots and 126 mm grouping for 20 shots, at 200 m, prone firing position). The illness progressed rapidly from a non-specific prodrome to a flu-like illness with fever, malaise, muscle aches, lethargy, slowed cognition, cough, sore throat, rhinorrhoea, persistent lacrimation and a 24-hour period of prostration. Recovery began after 48 hours, allowing a return to light work at 72 hours and full working duties by Day 7. On Day 14, during another marksmanship training session, my accuracy was severely decreased. I failed to obtain satisfactory scores in any position because of persistent erratic breathing and occasional involuntary coughing (best score, 235 mm grouping for 20 shots at 200 m). Spirometry later that day showed a reduced peak flow rate (310 L/min) (see Box). Serological tests were negative for IgG and IgA for all respiratory agents assessed. Nasal swabs were positive for parainfluenza virus type 3 by polymerase chain reaction testing. Involuntary coughing, particularly towards the end of the day, and decreased exercise tolerance persisted for a further 2 weeks, by which time peak flow had increased to 500 L/min. A third marksmanship session the week afterwards showed an improvement in scores, but they were still worse than those obtained pre-infection. Notably, grouping deteriorated rapidly after the first series of 20 shots, and could not be regained even after short rests. Replay of the recorded laser beam pattern for the session indicated that the breathing pattern remained erratic, although peak flow had risen further to 550 L/min. In the aftermath of the First World War, the joint head of Germany’s forces, Ludendorff, claimed that the failure of his 1918 spring offensive was ultimately caused by epidemic influenza.1 The epidemic affected German troops later than the allied forces, in June 1918. By July 1918, there were an estimated 500 000 German influenza casualties. Ludendorff’s initial successes were a result of new, highly mobile type infantry tactics — the forerunner of today’s “fire and movement” — which require physical fitness, stealth and accuracy of rifle fire. My case demonstrates that the tactical consequences of a viral lower respiratory infection can last much longer than medically explicit morbidity. Prolonged effects in my case included persistent involuntary cough, loss of exercise tolerance and loss of marksmanship, weeks after the initial acute illness. Ludendorff’s claim may be not so far off the mark. Marksmanship scores* and peak flow rates over time after onset of a respiratory tract infection * Lower scores for shot grouping indicate better marksmanship (shots are more closely grouped).

Timothy J J Inglis

To the Editor: I read with interest the research article by O’Connor and colleagues, which concluded that the medical and retrieval costs of road crashes in rural and remote northern Queensland represent “a considerable economic burden”.1 Although the authors noted that the broader Rural and Remote Road Safety Study aimed to also gain an understanding of the social costs of such crashes, they focused on the monetary costs in this report. As we all know, road crashes not only cost money but have enormous personal impact, in both the short and long term, on the patients and their families. This impact is likely to be even greater for patients from rural and remote areas who are unable to be cared for in their local hospital. Remember that for almost all patients transferred, there are families who must also find their way to, and temporary accommodation (sometimes for months) in, an unfamiliar large town or city. Close family members, in addition to the patient, also suffer loss of income, disruption of schooling, and loss of personal network support due to the geographic dislocation. Thank you to the authors of this study, which reinforces the desperate need to continue to improve local health services in rural and remote Australia, including “more efficient trauma management”,1 to contain costs and to lessen patient and family suffering.

Susan M Gorton

In reply: We can only agree with Gorton about the high level of costs to families and communities caused by road trauma. While our report attempted to provide estimates of the immediate, direct costs to the medical system,1 we were well aware of the additional costs to families, particularly those from rural and remote areas, as they attempted to support their injured family member. These costs, unfortunately, are difficult to quantify, and have a long-term impact on families and communities. Although our study was able to estimate some of the costs associated with road trauma, there is a need for prospective studies with specially formulated costing tools to capture the costs more fully. An associated study describing the impact of road trauma on the work of general practitioners in rural and remote areas2 outlined the problems that GPs have in managing chronic vehicle-related trauma without access to specialist rehabilitation services. Improving local health services may reduce some costs to families, but many of the patients retrieved from rural road crashes initially require specialist care in tertiary-level facilities. Changing the behaviour of drivers who take risks on roads will also reduce the costs of road trauma. Unfortunately, this is a difficult process.

Teresa M O’Connor · Heather A Hanks · Mark S Elcock · Richard C Turner · P Craig Veitch

To the Editor: More than 1000 sunscreen products are marketed in Australia, and an increasing proportion (about one-third) incorporate engineered nanoparticles (ENPs). Defined as manufactured particles having one or more dimensions less than 100 nm (0.00001 cm), ENPs exploit the altered chemical reactivity and other changes that reduction to nanosize elicits. ENPs in sunscreen, such as titanium dioxide (TiO2) and zinc oxides, constitute effective broad-spectrum ultraviolet radiation (UVR) blocking agents with enhanced cosmetic transparency. The Australian Therapeutic Goods Administration (TGA), in approving such products, has stated that “there is no evidence that sunscreens containing these materials pose any risk to the people using them”.1 Similarly, authors of a recent article (written in collaboration with representatives of a cosmetic company) interpret the evidence as confirming that ENPs do not penetrate below the stratum corneum, or only in small amounts, producing limited cellular toxicity.2 Information on sunscreen packaging is not required to disclose the presence of ENPs. Yet, when TiO2 nanoparticles are incorporated into human cells in vitro, mobilisation of electrons by absorption of ultraviolet A (UVA) light produces reactive oxygen species and causes DNA damage (strand breakage and base modification). In fact, TiO2 has been used in this way to kill cancer cells in vitro.3 In sunscreens and cosmetic preparations, TiO2 is often coated to reduce this photocatalytic activity because over 90% of ambient UVR is UVA. However, evidence has now emerged that TiO2 in uncoated anatase form has been added to a marketed but as yet undivulged Australian sunscreen — in this form, TiO2 is capable of producing damaging photocatalytic free-radical reactions on particular steel roofing materials.4 Likewise, zinc oxide ENPs manufactured for use in sunscreens are potent biocides and subject to disposal restrictions in most countries. Despite the TGA’s stance, existing research does not comprehensively ensure the safety of all ENPs in sunscreens, particularly ENPs less than 40 nm in size applied long term to human skin that is immature, aged, diseased, damaged, hairy or covering flexural creases.5 The non-government organisation Friends of the Earth has compiled a list of sunscreens available in Australia that are claimed by the manufacturers to be free of nanoparticles.6 A New South Wales Government committee has recommended that, for regulatory purposes, ENPs be considered new chemical entities that require increased safety data.7 Policymakers should increase funding for objective research in this area (such as that by Macquarie University and the flagship project in nanotechnology of the CSIRO [Commonwealth Science and Industry Research Organisation]). Until such safety data are available, the TGA should apply the “precautionary principle”5 and, at a minimum, increase packaging information about nanoparticles in sunscreens.

Thomas A Faunce

Sed quis custodiet ipsos custodes? (Who guards the guardians?) To the Editor: Adler and Constantinou raised a concern about the ageing doctor1 that also worried me when I was practising as an anaesthetist. The same concern was raised recently in the Australian and New Zealand College of Anaesthetists Bulletin.2 In anaesthesia, decisions and actions have to be made in seconds and minutes, rather than days and weeks, and maintenance of standards is very important. Doctors practise largely in isolation, and may not be aware of their standard failing against the general standard. Operating theatres offer both an opportunity to observe the practice of others and a conduit for information on colleagues — nursing and medical. I used this opportunity in private and public practice by asking younger colleagues, one in each, to be my “buddy”, as in diving safety. They were asked to keep watch for any rumour of my declining standards and to report it to me. We would then discuss what to do: retrain or retire. The latter became more of an option the older I grew. This strategy opened up pathways. One was that the buddy was given the authority to approach me on the topic. Another was that I was open to the idea that my ability could diminish, while a third was that the hostility, so often seen in this setting, was abolished. I would rather be tapped on the shoulder by a sympathetic colleague than a medical board, a hostile coroner or a vindictive prosecution lawyer. In the end, there was no tap on the shoulder, and I went because I had had an enjoyable and rewarding career and could afford to retire. This allowed succession planning in both areas, public and private, and a younger colleague could embark on a similar path.

David G Fenwick

Incorrect name of author: In the Notable Case “Clinical, electrophysiological and genetic features of a large Australian family with paramyotonia congenita” in the 16 March 2009 issue of the Journal (Med J Aust 2009; 190: 334-336), an incorrect author name was printed. The fourth author’s name was given as Thyagarajan E Dominic. It should have been Dominic E Thyagarajan.

Sharavanan Parasivam · Malgorzata Krupa · Mark Slee · Dominic E Thyagarajan

A 45-year-old man presented with marked, progressive bulging of the right tonsil (Figure, A) and slight swelling of the right submandibular region. Gadolinium-enhanced magnetic resonance imaging of the head and neck showed a large (5 × 4 × 3 cm) neoplasm, occupying the right parapharyngeal space, extending from the deep parotid lobe to the ipsilateral tonsillar region (Figure, B). The neoplasm was removed via an incision in the neck and identified, by histological examination, as a pleomorphic adenoma. In many cases, the first clinical sign of a deep-lobe parotid neoplasm is enlargement of the tonsillar region. Other differential diagnoses of tonsillar swelling include peritonsillar abscess, tonsillar neoplasm and internal carotid aneurysm.

Matteo Alicandri-Ciufelli · Gabriele Molteni · Domenico Villari · Francesco Mattioli · Livio Presutti

Ten questions you must ask your doctor. Ray Moynihan, Melissa Sweet. Sydney: Allen & Unwin, 2008 (xvii + 238 pp). ISBN 978 1 74175 145 1. Ten questions you must ask your doctor, by Ray Moynihan and Melissa Sweet, is a timely contribution to issues involving the patient–doctor relationship. The basis of any such relationship should be trust. Trust is not a given; it relies on good communication. Yet, communication does not always work out well in these relationships (as complaints to my office testify), as much because of patients and their state of mind as because of busy general practitioners themselves. We know patients want to participate in decisions about their health, but they are not always in a position to know how to get the information they need. Will this book assist patients and doctors to communicate better and, if so, how? The authors are leading health writers, and this book is written with the consumer in mind: “This book will help you and your loved ones”. Questioning that is aggressive or overly assertive has the potential to undermine the relationship between doctors and patients. Moynihan and Sweet explain that questions framed constructively have the potential to assist patient and doctor by encouraging relevance, and could promote efficiency. Useful questions include “How long will it take for this treatment to have a useful effect?” and “Are there other treatment options, which don’t involve taking pills?” There are helpful tips, for example, “be sceptical about medical promotion” and “headlines can be misleading”. The questions on page 164 about evidence for particular health information are particularly useful. Chapter nine is dedicated to “Who else is profiting here?” The question, “What are your links with drug companies (or device companies, or complementary medicine companies)?” is not likely to be helpful in a therapeutic setting. In any event, many doctors would not have the answer. The authors of this book are no newcomers to examining difficult and complex issues within health and our health systems. At $24.95, this is a useful book with the potential to be of assistance to doctors and patients.

Beth A Wilson

Fixing sex. Intersex, medical authority, and lived experience. Katrina Karkazis. New York: Duke University Press, 2008 (xiii + 364 pp). ISBN 978 0 8223 4318 9. Currently, there is an intense ethical debate about genital surgery for infants born with ambiguous genitalia. The controversy rose to a new level of intensity in Australia in 2008 with the involvement of the Australian Human Rights Commission and the Victorian Government Department of Justice. Doctors in Europe and North America are facing the same dilemmas. This new book, possibly the best contribution to the debate yet published, is very welcome, not only because it is timely but because it is deeply thoughtful, thoroughly researched and very respectful of all points of view. The author, Katrina Karkazis, PhD, MPH, is a Senior Research Scholar with the Center for Biomedical Ethics at Stanford University in the United States. In addressing the historical basis for current understanding of sex and gender, Karkazis discusses the contribution to the understanding of sex development made by John Money (a psychologist at Johns Hopkins University) in depth, in a way that is refreshingly generous. She traces the development of what became the traditional treatment model, the scepticism that emerged, and the origins of Internet-based patient advocacy groups in the mid 1990s. Her exploration of what is posted on discussion boards is balanced by her careful study of what scientific long-term outcome studies have, and have not, delivered. She has also conducted hundreds of interviews with doctors, parents and adult patients. Her book concludes with the following:

Garry L Warne

Melamine in milk The recent epidemic of urinary tract stones in young children in China has been formally linked to melamine contamination of infant formula, according to the results of a clinical study. Over 500 children aged 36 months or younger were screened in the study, which set out to determine the level of exposure to melamine, and symptoms of and predisposing factors for urinary tract stones. Clinical tests included urinalysis, tests for glomerular dysfunction, ultrasound, and biochemical markers. High melamine content in formula was significantly associated with urolithiasis — children fed high-melamine formula were seven times more likely to develop stones than those fed no-melamine formula. Most children with melamine-associated urinary stones did not have classic symptoms and signs, such as haematuria and white cells in urine. The authors advise that screening for urolithiasis should be based on the history of exposure to melamine, as symptoms may be non-specific or absent. N Engl J Med 2009; 360: 1067-1074 Maternal migraine Women who experience migraine in late pregnancy appear to be at higher risk of cardiovascular events, say US researchers. In a population-based sample of almost 34 000 post-partum women, diagnoses jointly associated with migraine at hospital discharge were assessed. Stroke, myocardial infarction, pulmonary embolus, hypertension, smoking, and diabetes were found to be related to migraine. In particular, peri-partum migraine was associated with a 17-fold increase in the risk of pregnancy-related stroke. The authors comment that the link between migraine and vascular disease in pregnancy is most likely due to the existence of overlapping pathophysiological mechanisms, combined with the physiological alterations of pregnancy. BMJ 2009; 338: b664 Folate in pregnancy Taking folic acid supplements during pregnancy may be associated with a slightly increased risk of wheeze and lower respiratory tract infection in infants, according to US and Norwegian researchers. In a study involving over 32 000 children born between 2000 and 2005, data were collected on the timing of folate and other vitamin supplementation in pregnancy, and wheezing and respiratory tract infection in children up to 18 months of age. Over 79% of mothers took folate supplements at some point during pregnancy. Women who took folate supplements were likely to be more educated, breastfeed for longer, and less likely to smoke. Wheeze and lower respiratory tract infections were most strongly associated with exposure to folic acid supplements in the first trimester of pregnancy. The authors postulate that the action of folate as a methyl donor may affect the fetus by epigenetic mechanisms influencing gene expression and phenotypes. They also caution that the effect measured was small, and that unmeasured confounding factors may be acting to influence this association. Arch Dis Child 2009; 94: 180-184 Legacy of Wittenoom Of the almost 3000 women and girls who lived at the blue asbestos mining and milling town of Wittenoom in Western Australia, 40 had died of malignant mesothelioma by the end of 2004. Australian researchers studying the outcomes for those living in the area between 1943 and 1992 have gone a step further and calculated the predicted mortality from mesothelioma for these women, who were either mine or mill workers, or residents. In the cohort of 2402 women remaining, the authors predict between 66 and 87 deaths up to 2030, with no decline in the number of deaths each year. The model that the researchers used to estimate future mortality included risks from other causes, time since first exposure, lag periods, and rates of clearance of crocidolite from the lungs. They comment that using rate of fibre clearance in the model avoids over-estimation of the predicted number of malignant mesotheliomas, a problem encountered in other studies. Occup Environ Med 2009; 66: 169-174 Absorbable stents The use of metallic drug-eluting coronary stents has been controversial because of the association with late stent thrombosis and difficulties with subsequent surgical revascularisation. Bioabsorbable everolimus-eluting stents may be a viable alternative, according to the results of a 2-year clinical follow-up of 29 patients treated with the stents. All participants had a single de-novo coronary artery lesion and were assessed using multiple imaging methods. After 2- years, the biodegradable stent had been absorbed and was incorporated into the vessel wall in all patients. No stent thrombosis occurred and the device appeared safe, with no cardiac deaths and one myocardial infarction in participants. The authors of the small study, which was funded by the stent manufacturers, admit that, although promising, the research has limitations and that results should be interpreted as preliminary findings only. Lancet 2009; 373: 897-910

Tanya Grassi