Letters

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

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

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

Hasantha Gunasekera

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

Claire Hewat

To the Editor: Trans fats are produced by partial hydrogenation of liquid vegetable oils to produce oils which are more solid at room temperature and have better physical properties for food processing, such as increased shelf-life. Trans fats represent a major dietary cardiovascular disease risk, with as little as 5 g daily increasing the risk of ischaemic heart disease by 25%.1 A recently published survey of the trans-fat content of French fries and chicken nuggets purchased from two international fast food chains in 20 countries emphasises the wide variability of trans fats in different countries.2 This work highlights the potential health risks imposed by the industrially generated trans fats in these food products. Of the sampled French fries and nuggets, 20 of 39 samples from 19 different countries yielded trans-fat levels in excess of 5 g for an average serve. Interestingly, the report included no data from Australia. We have evidence that similar fast foods have substantial quantities of trans fats (putting Australia in the mid-range of the league table). The only available published results are those reported by the Australian Consumers Association (ACA) in 2005.3 The ACA tested 55 foods and found 18 had trans-fat levels greater than 2% of total fat. The interesting issue is that the ACA data show a variation in trans-fat levels of greater than 22-fold (0.8%–22.5% of total fat) in popular fast foods. Data on trans-fat levels should be available on all foods in this country, whether sold in supermarkets or to the food service industry. However, at present, there is no requirement to include trans-fat content on nutrient information panels, except when the manufacturer wishes to make a nutritional claim about cholesterol, saturated, unsaturated or trans-fatty acids.4 Many countries, including the United States, Canada and some European countries, have either placed limits on the permissions for trans fat in processed foods, or, more commonly, mandated labelling requirements. The most notable is Denmark, where legislation restricts maximal industrially produced trans fats to less than 2%.5 Not surprisingly, that country reported markedly lower trans-fat contents in fries and nuggets than those sold in Australia.2 Despite review of the “Australia New Zealand Food Standards Code”, labelling of the trans-fat content of food has not been mandated,4 and consumers and health professionals wishing to reduce their trans-fats intake remain unable to make informed choices.

David Cameron-Smith · Andrew J Sinclair

To the Editor: With obesity reaching epidemic proportions in Australia, professional education needs to reflect this increase in prevalence. Research has shown that health professionals’ lack of knowledge is a common barrier to providing care for overweight and obese individuals.1-3 We investigated the coverage of obesity education in university medical, dietetic and nursing curricula (partially replicating the earlier study in the Journal by Campbell and Welborn4), and also the extent to which obesity was covered in the curricula of selected professional specialist colleges in Australia. Contact hours for obesity were compared against two “control diseases”, diabetes and depression. Surveys were sent to 15 medical schools, and administrators of six dietetic courses and six nursing courses in Australia. The survey asked questions including the total number of contact hours in the course for each topic, and if additional teaching was needed. Most college curricula were publicly available, as were the Continuing Medical Education events and topics. Nine of the 15 medical schools and three of the six dietetic and nursing courses returned the questionnaire. Because of the nature of the data and the very small sample sizes, no statistical analysis was conducted. In the medicine curriculum, while variation in mean contact hours between obesity, diabetes and depression was small, the range was quite large (Box). There was also wide variation in the contact hours for obesity education in the nursing curriculum. The median contact hours for obesity education were half that of both depression and diabetes, and one university reported zero contact hours for obesity education. With the exception of the Royal Australian College of General Practitioners, the colleges surveyed did not include obesity in the prescribed teaching curriculum. Several professional education topics were available on obesity, but considerably more were available relating to diabetes and depression. Our findings indicate that most of the universities appear to provide undergraduate students with adequate contact hours for education about obesity. The professional training provided by the individual specialist medical colleges is not as comprehensive, and lacks specific obesity education. Based on these findings, more systematic research is needed to examine the details of training and to develop programs which better equip health professionals to deal with the growing burden of obesity and related diseases. Future research should not be limited to measuring contact hours — the focus should extend to investigating the content of courses and professional development programs, and to examining the barriers to including obesity education. Summary of median, mean, standard deviation and range for contact hours of teaching about obesity, diabetes and depression in undergraduate courses Course and disease Number reporting contact hours Contact hours Median Mean ± SD Range Medicine Obesity 8 7 13 ± 11 5–30 Diabetes 8 13 20 ± 20 6–64 Depression 6 13 13 ± 5 4–20 Nursing Obesity 3 6 8 ± 10 0–19 Diabetes 3 13 18 ± 8 10–25 Depression 3 13 16 ± 10 8–28 Dietetics Obesity 3 15 14 ± 8 6–22 Diabetes 3 20 17 ± 8 8–23 SD = standard deviation.

Melissa J Hayden · Leon Piterman · John B Dixon · Paul E O'Brien

To the Editor: The discussion of fibrinolysis in the recently published guidelines for the management of acute coronary syndromes 20061 is interesting. The recommendations clearly indicate that second-generation agents should be preferred to streptokinase in all circumstances. The guidelines reference the GUSTO-I trial data2 as the primary support for those recommendations. These data are, at best, debatable in terms of showing any benefit of front-loaded tissue plasminogen activator over streptokinase, and then only in limited circumstances (ie, patients aged less than 75 years with anterior infarcts and within 4 hours of the onset of symptoms).3,4 To my knowledge, there have been no head-to-head trials of this size of the other fibrinolytic agents discussed against streptokinase. Thus there is no justification for the blanket superiority that is accredited to these agents, both by implication and explicitly, in the guidelines. It is a matter of some concern that guidelines from such respected groups should make statements that will be used broadly by clinicians, but that go beyond the evidence base to which they refer. On the balance of information available there is no compelling case to relegate streptokinase from the front line.

Andrew J Bezzina

In reply: As Bezzina states, the GUSTO-I trial is the main source of evidence for the superiority of front-loaded alteplase (rt-PA) over streptokinase, showing a 1% absolute and 15% relative benefit.1 Subgroup analysis suggested that only certain groups benefited, but this is an inappropriate use of subgroups, and the result should be applied overall. A clear mechanistic reason for the advantage of rt-PA — greater 90-minute full coronary patency — has also been demonstrated.2 Meta-analyses of the percutaneous coronary intervention (PCI) trials in acute myocardial infarction have all shown benefit over fibrinolysis. However, the benefit of PCI is greater compared with streptokinase than with plasminogen activators.3 Although not providing a head-to-head comparison, these data also support the superiority of plasminogen activators over streptokinase. The second generation plasminogen activator studies have all compared these with the “gold standard” front-loaded rt-PA. These agents have been shown to not be inferior in relation to mortality,4,5 and tenecteplase showed a decrease in systemic bleeding.5 Administration as a bolus without the adverse reactions commonly seen with streptokinase (such as hypotension) make them much more convenient and safe, particularly in smaller institutions. In addition, streptokinase is an inappropriate choice in Indigenous patients because many have high levels of anti-streptokinase IgG and streptokinase resistance.6

Philip Aylward · Constantine N Aroney · Ken Hossack · Andrew M Tonkin

To the Editor: We are delighted at the attention which the editorial by Hickie and Blashki1 has drawn to our clinical update on the management of bipolar disorder in general practice.2 However, we are bemused by a number of the sentiments, criticisms and statements of fact included in that robustly expressed editorial. We will focus only on a few of the major issues raised. Hickie and Blashki argue that there are too many “worthy” guidelines promulgated to general practitioners by “specialist colleagues” across the range of medical conditions, and that extrapolation from specialist centre studies “may particularly annoy GPs”. On the other hand, they bemoan the fact that “few [guidelines] have targeted general practice”. We are surprised by this insinuation that such issues pertain to our clinical update. Three of the authors of our article are GPs in either clinical or academic practice, and the document has been formally endorsed by the Royal Australian College of General Practitioners. Our article focuses on the practical issues concerning the role of the GP in the management of patients with bipolar disorder, and deals frankly with the respective contributions of the GP, psychiatrist, and psychologist. It is our experience that GPs are enthusiastic in enhancing their skills in the management of mental illnesses such as bipolar disorder in the primary care setting. Therefore, we have little doubt that updates such as ours will be viewed as helpful aids for GPs, who are often the main “port of call” for people with this condition. We strongly contend the statement that we ignore practice-based issues and thereby risk “an overall negative rating from the target audience”. Hickie and Blashki state that “the most useful mental health guidelines tackle the tough issues”, such as sources of self-help, self-monitoring, detailed illness descriptions, family education, quality e-health resources, and guidance when patients become a danger to themselves and others. We fail to understand the implication that our update does not address such issues, as these very practical matters are clearly highlighted in detail in our article. Finally, we are surprised at the negative tone concerning guidance for the management of mental illness in general practice by authors who have argued strongly for the value of evidence-based guidelines in specialist psychiatric practice.3 Although (as we clearly acknowledge) there is currently a limited evidence base for managing such conditions in primary care, there is still a major need for practical guidance for the practitioner in this setting.

Philip B Mitchell · James A Best · Bronwyn M Gould · Ian G Wilson

To the Editor: Hickie and Blashki are to be commended for their view that clinical practice guidelines in mental health should be relevant to a primary care setting.1 Unfortunately, such guidelines have little effect on clinical outcomes, as most general practitioners have not been taught how to use them to their best advantage.2 There is also little known about the best way to implement guidelines in mental health, let alone in primary care mental health settings.3 As a result, more guidelines, even those more attuned to the primary care environment, will be of little benefit to our community. The Royal Australian and New Zealand College of Psychiatrists (RANZCP) is actively promoting the use of clinical practice guidelines4 as a quality improvement tool that will allow mental health practitioners (including GPs) to assess their practice more carefully and measure and analyse variance. The next step is to fund research into how best to implement mental health guidelines at the coalface. It is only through practice-based research that the barriers to successful implementation of evidence-based practice can be identified and overcome. Such research could be funded via a National Health and Medical Research Council (NHMRC) or Australian Research Council (ARC) grant program and coordinated by groups such as the RANZCP or the National Mental Health Working Group Safety and Quality Partnership Group. Mental health has already been identified as a grant funding priority by the ARC.5 Once this has been achieved, then training and mentoring to help practitioners review their practice as part of a quality improvement framework is required, rather than more guidelines per se. Providing well researched, up-to-date and accessible information for GPs on “self-help, self-monitoring, [and] detailed illness descriptions”, as suggested by Hickie and Blashki, is commendable, but is not what is required for guidelines to truly improve the safety and quality of mental health care in Australia.

Andrew J Wilson · David Barton

To the Editor: With Australia’s rapidly ageing population and an explosion in the number of retirement villages and nursing homes, Finn and associates are to be congratulated for ventilating the subject of the interface between residential aged care facilities and emergency departments.1 My experience of emergency department (ED) and aged care facility relations spans over 50 years and I have been involved in both sides of the equation. Firstly as a surgeon, then as director of an ED, and finally, as a resident of a retirement village for over 20 years (including, for my wife, 5 years in the affiliated nursing home), and during that time my wife and I have had at least eight episodes as patients in an ED. Retirement villages and nursing homes are not equipped or organised to handle medical or surgical emergencies. Problems of “disposal” arise after ED assessment and treatment in a public hospital. The hospital may not have an empty bed. The patient’s condition may not be serious enough to require a hospital bed, but the patient may not be well enough to return to his or her retirement village. Privately insured patients may have the option of transferring to a private hospital but usually spend an unnecessarily long time in the ED awaiting such transfer. Matters that need attention are: a standing arrangement between public and neighbouring private hospitals to facilitate quick transfer of suitable patients. the removal of long delays in EDs that occur while waiting for the results of investigations and even longer periods awaiting “higher opinions” after receiving these results. a speedier and more detailed hospital summary addressed to the general practitioner (if known) as well as to the aged care facility concerned.

Keith S Jones

To the Editor: A nationwide colorectal cancer (CRC) screening program will commence in 2006. It has been shown that general practitioners can influence their patients in the decision to have CRC screening.1,2 There are several screening test options in Australia, and the relative geographical isolation of rural centres may influence attitudes and participation. We sought to determine the attitudes of GPs towards CRC screening and test preferences. Between January and September 2005, all GPs in Western Australia (n = 1837; 1298 metropolitan, 539 rural) were sent a questionnaire, which was completed by 801 (43.6%). Overall, 62.8% of respondents believed that asymptomatic average-risk subjects should have CRC screening (67.1% of metropolitan GPs v 54.2% of rural GPs; P = 0.003). The questionnaire revealed major differences between which test GPs would recommend for their patients and which test they preferred for their own personal screening (Box). These differences were related to the factors GPs believed were most likely to influence choice of screening test. For colonoscopy, accuracy and speed of result were considered most important; for faecal occult blood testing, no need for bowel preparation or time off work and no discomfort were considered the strongest determinants. Previous studies that included patients’ views have found that physicians may incorrectly perceive certain factors in screening to be important to their patients.3 There were no significant differences in choice of test between rural and metropolitan GPs. Although the target age group for the Australian pilot study and the national screening program is 55–74 years,4,5 two thirds of GP respondents felt screening should be offered from the age of 50 years, and a quarter believed it should continue beyond 80 years. Many GPs (65%) indicated they would like further education on CRC screening. In summary, there is good support for CRC screening among Western Australian GPs, but the availability of different screening tests and variations in GPs’ opinions are likely to significantly influence clinical practice. Colorectal cancer screening methods and general practitioners’ recommendations and attitudes Test recommended by GP for patients GPs’ perception of patients’ choice of test GPs’ preferred test for their own screening Faecal occult blood testing 430 (53.7%) 396 (49.4%) 236 (29.5%)* Colonoscopy 285 (35.6%) 278 (34.7%) 479 (59.8%)* Flexible sigmoidoscopy 37 (4.6%) 20 (2.5%) 20 (2.5%) Computed tomography colonography 18 (2.2%) 69 (8.6%) 32 (4.0%) Barium enema 0 2 (0.25%) 3 (0.4%) * P = 0.004 (χ2)

Graham B Turner · Marcus W Chin · Noellene M Foster · Jon Emery · Geoff M Forbes

To the Editor: Australia’s imminent bowel cancer screening program will revolve around the general practitioner,1-3 whereas, in the United Kingdom, the GP will have virtually nothing to do with the national screening program now underway.4 It is curious that two programs with the same evidence base regarding effectiveness should be so fundamentally different. One explanation could be the differing health care systems in each nation. However, they are more alike than not, so the true explanation for the Australian methodology could rest with the outcome of the Australian pilot studies. If that is the case, then perhaps one should be both alert and alarmed. Given the inequity in access to GPs in Australia, it is not surprising that the Final Evaluation Report5 of the pilot national screening program stated that: Some GPs interviewed in Woolcott’s Qualitative Research focus groups . . . expressed concern over access to FOBTs [Faecal Occult Blood Tests] for people without a fixed address. It was mentioned that this group, particularly Aboriginal and Torres Strait Islander people and people in low socioeconomic groups, particularly homeless people, did not receive invitations to participate in the Pilot. Some GPs commented that the information packs, in both English and the translated versions, were too complicated for people with low literacy and those from culturally and linguistically diverse backgrounds.5 The same report noted that 38% of people overall (men, 42%; women, 34%) and 52% of non-English speakers did not visit their GP after a positive FOBT. Nevertheless, the report favours the continued central role of the GP.5 This is not the case in the UK screening program, which has a more direct approach, with program hubs and associated screening centres — all with defined accountabilities. The Australian approach is to simply add to the workload of GPs — a more pragmatic approach in the short term, but less imaginative. Our program will undoubtedly be a step forward in colorectal cancer prevention. The question is how large that step will be. Reliance on the existing system threatens to reinforce existing health care inequities.

Allan D Spigelman

To the Editor: The recent report by the Multicentre Australian Colorectal-neoplasia Screening (MACS) Group1 offered some intriguing findings. Participation in bowel cancer screening was lower than expected, despite a range of tests being offered. In addition, people offered a choice of different faecal occult blood tests (FOBTs) were less likely to participate than those not offered this choice. The accompanying editorial by Salkeld and colleagues concluded that “Informed consumers making smart choices about screening . . . would be a public health success”.2 We believe the available evidence indicates otherwise. As the MACS Group study showed, participation in FOBTs was lower than in the Australian Government FOBT pilot program,3 and participation in screening by colonoscopy was lower than for other studies, including our recent Australian study.4 They suggested this may be because local general practitioners were not engaged in the project. Our study was designed to address this issue, and concluded that involvement of GPs had a small, non-significant effect on participation rates and no effect on response to invitation.4 This is not to say that involvement of GPs is undesirable. The MACS Group study found participation in FOBTs of 27.4% when only an FOBT kit was provided and a significantly lower participation when a choice of four screening modalities was offered, with an FOBT kit provided (18.6%, P = 0.03). These data confirm the findings of a large multicentre study from the SCORE2 Working Group.5 In that study, participation in FOBT was 30.1%, while participation in either FOBT or flexible sigmoidoscopy, when a choice of the two was offered, was 27.1%. The authors did not offer this analysis, but the difference was again significant (P = 0.015, two-tailed Fisher’s exact test). The editorial by Salkeld et al suggested that the Australian bowel cancer screening program should incorporate decision-support systems to allow informed choice of screening options. The “choice paradox” reported by the MACS and SCORE2 studies argues against this. Further, there is no evidence that decision support improves rates of participation in screening, and some explicit evidence that it has no effect.6 This should not be troubling. At this time, most colon cancer screening is still performed after consultation between patient and doctor, and in this setting informed choice is possible and desirable. Decisionmakers such as the Australian Government Department of Health and Ageing use a different process, which is explicit and quantitative,7 in determining screening policy. With the evidence available, the Australian mass-screening program should offer and evaluate a single test modality.

Douglas R Taupin · Mike Corbett

In reply: Taupin and Corbett contend that the “choice paradox” reported by the MACS Group study argues against decision-support systems to allow informed choice of screening options. That would be true if the purpose of informed choice was simply to increase participation in screening.1 Our point is that the purpose of informed choice is to support an ethical basis for individuals’ decisions about screening.2,3 This can occur within the single-test modality (faecal occult blood tests) of the national screening program. It would be desirable to have decision-support systems embedded in a doctor–patient consultation. But this may not be feasible in terms of screenee access to a general practitioner, nor affordable for the Australian Government — hence our call for a self-directed decision-support system as an adjunct to a doctor-guided system. This is one way of applying the principle that patients should be given unbiased information on the benefits and harms of screening that enables them to make an informed choice about their own participation in screening.4

Glenn P Salkeld · Jane M Young · Michael J Solomon

To the Editor: We read with alarm the skin cancer clinic profile published recently in the Journal.1 This article publicly states what has been privately suggested for some time — that doctors in skin cancer clinics provide a service no better than the average Australian general practitioner. Surely, if these doctors are calling themselves skin cancer “experts”, the aim of their practice should be to reduce the skin biopsy rate. This is obviously not the case. They report a consultation to biopsy ratio of 1.79. Thus, 56% of all their consultations result in a skin biopsy. The biopsy to treatment ratio of 3.1 is also very high. In addition, they report that only 32% of all biopsies yield a non-melanoma skin cancer. This figure indicates either no additional diagnostic ability on the part of the skin cancer clinic doctors compared with the average Australian GP (who, according to a recent retrospective study, can clinically diagnose a basal cell carcinoma 34% of the time2) or an effort to maximise income. Similarly, the article describes a number needed to treat (NNT) of 28.6. This means that for every 29 benign lesions excised and sent for histological examination to exclude melanoma, only one melanoma is detected. The authors concede that this figure is equivalent to that observed in mainstream general practice. We therefore question the motives of doctors at these clinics in presenting themselves as skin cancer “experts”. However, perhaps the greatest indicator of their seeming intent to maximise financial gain can be demonstrated by an analysis of skin flap item numbers. The article indicates that the total number of excisions was 8055, of which 116 were melanomas and 4709 were non-melanoma skin cancers (ie, 4825 cancers were excised). If one assumes that a suspicious or benign mole biopsy is never closed with a skin flap repair (standard clinical practice), then, of the 4825 skin cancers excised, 2651 (55%) were closed with a flap procedure, and of these, 55% were either “complicated” or “site-specific” flap repairs. There were only 111 skin grafts performed out of the 4825 cancers excised (2.3%). Thus, more than half of the skin cancers excised were closed with a flap repair! Moreover, more than half of the flaps used were “complicated” or “site-specific” flaps, with 24 flaps performed for every skin graft! Surely, no one can argue that these figures are reasonable or consistent with good clinical practice. In comparison, current Australian Medicare data indicate that dermatologists and specialist surgeons close large skin cancer excisions (lesions > 2 cm on the trunk [item number 31290]) with skin flaps at rates of 15% and 17%, respectively (Andrew Miller, Australian Medical Association Skin Representative Group, personal communication). Large lesions normally require a higher skin flap closure rate than smaller lesions. Hence, a flap repair rate of 55% — for lesions of all sizes and sites — reported by the skin cancer clinic doctors is all the more extraordinary. We believe that the above suggests that many skin cancer clinic practitioners are more concerned with maximising income than improving patient care.

Alvin L K Chia · Stephen Shumack

In reply: Our previous publications1,2 should calm Chia and Shumack’s “alarm”. We have urged for the development of education, standards, accreditation, research and audit for skin cancer clinics.1 Over the past 12 months, the Skin Cancer Society of Australia has been formed (http://www.skincancersociety.com.au), standards have been developed, a process of skin cancer practice accreditation has been established, and a masters-level degree in primary care skin cancer medicine has been created (http://www.som.uq.edu.au/skincancer/masters.htm). Our results described activities of a single network of skin cancer clinics.2 They should not be viewed as a benchmark, and caution must be exercised in making any generalisations from them. They are simply the first such data to be presented for public scrutiny. It will be important to see results from other skin cancer clinics. Regarding flap repairs, we were unable to confirm the findings alluded to by Chia and Shumack based on a personal communication. However, we are currently undertaking a detailed analysis of relevant Medicare Benefits Schedule data for general practitioners and specialists and we look forward to presenting this for rigorous peer review and publication shortly. Skin cancer medicine is an established component of primary care. Whether this occurs in mainstream general practice, “special interest services” or skin cancer clinics, the same standards apply to all.

David Wilkinson · Deborah A Askew

To the Editor: Food, medication or insect stings are the major causes of systemic allergic reactions.1 That topical agents can mimic such reactions is not commonly appreciated. I report here a systemic allergic reaction to a topical medication (initially attributed to food). A 7-year-old boy experienced generalised urticaria and facial swelling within an hour of eating a peanut-containing slice. His father recalled applying a topical antiseptic (Medi Creme [Pharmacare]) to a graze over the boy’s right elbow at about the same time. There were no respiratory or cardiovascular symptoms, and the urticaria settled within 2 hours of taking oral promethazine. Six months later, the same cream applied to a graze over the boy’s right chest resulted in a localised 15 cm urticarial welt. Intercurrent problems included atopic dermatitis but no known food or drug hypersensitivity. The active ingredients of Medi Creme are hexamidine isethionate, chlorhexidine acetate, cetrimide and lignocaine hydrochloride. With the assistance of the manufacturer, skin prick tests using a 10% weight/volume suspension of Medi Creme or a 10% suspension of hexamidine isethionate in normal saline produced 5 mm itchy weals at 15 minutes in the patient (but not controls). By contrast, skin prick tests to the other active ingredients, inert vehicles and relevant foods (including peanut, almond, brazil nut, cashew, hazelnut, pecan, walnut, sunflower seed and sesame seed) were negative. Avoidance of hexamidine was advised. The child has eaten peanut products before and since without any adverse reaction. Hexamidine is an aromatic diamidine antiseptic (other members of the group include pentamidine and dibrompropamidine). These drugs have broad antibacterial and antifungal properties and are also used topically to treat corneal infections and some skin infections.2 In Australia, hexamidine is an ingredient of one topical local anaesthetic/antiseptic cream (Medi Creme) and one nappy rash cream, as well as some tinea treatment creams, medicated shampoos, sunscreens and cosmetic facial wipes in other countries. Adverse reactions (such as contact allergic dermatitis and photodermatitis3) are rare — only four reports of localised dermatitis have been reported to Australia’s Adverse Drug Reactions Advisory Committee (ADRAC) in the past 6 years (Dr K Mackay, Acting Director, ADRAC, Adverse Drug Reactions Unit, Therapeutic Goods Administration, personal communication). There have been more reports of systemic allergic reactions (including anaphylaxis) triggered by chlorhexidine or cetrimide,4 with one description of anaphylaxis to hexamidine after patch testing, but none with clinical use.3 Underlying dermatitis is a risk factor for sensitisation to topical agents.5 This case emphasises the importance of documenting exposure to potential allergenic triggers in the setting of a short-lived episode of urticaria (where the search for an avoidable trigger is more likely to be productive) or anaphylaxis. Exposure to stinging insects is usually obvious, whereas exposure to particular foods or medications is often poorly recalled. That topical allergens can also trigger systemic reactions should be considered.

Raymond J Mullins PhD, FRACP, FRCPA

To the Editor: Extended-wear silicone hydrogel contact lenses allow the convenience of 24-hour correction of refractive error and freedom from cleaning solutions and storage containers. However, they are associated with an increase in the risk of microbial keratitis when worn overnight compared with daily wear.1-5 The following cases from a single ophthalmology practice illustrate the risk to contact lens wearers when they use silicone hydrogel contact lenses overnight. A 36-year-old woman presented 11 days after sleeping with her silicone hydrogel contact lenses in overnight. She had increasing right ocular pain and photophobia over the preceding 9 days, which had not resolved with chloramphenicol drops. On examination, visual acuity was 6/18 right and 6/6 left. Corneal cultures grew Acanthamoeba, which responded to polyhexamethylene biguanide and brolene drops hourly. Her final best corrected visual acuity was 6/9 right, 5 weeks later. A 24-year-old woman presented with 2 days of left ocular pain, conjunctival injection, and epiphora following continuous silicone hydrogel contact lens use over the preceding week. On examination, visual acuity was 6/6 right and 6/18 left. A central corneal ulcer with stromal infiltrate and significant anterior chamber activity was present in her left eye (Box). Corneal cultures grew Pseudomonas aeruginosa, which responded to topical gentamicin 1% drops hourly. Her final best corrected visual acuity was 6/5 left, 3 weeks after diagnosis. An 8-year-old girl was seen 2 months after commencing continuous wear of her silicone hydrogel contact lenses for uniocular myopia. She had worn the same lenses for 4 weeks continuously when she presented with a 2-day history of right ocular irritation, photophobia, and conjunctival injection. On examination, visual acuity was 6/36 right and 6/6 left. She was commenced empirically on cephalothin 5% and gentamicin 1% drops hourly. Corneal cultures did not grow any causative organism, and her clinical condition improved significantly over the following 7 days. Her final best corrected visual acuity was 6/9 right. Although microbial keratitis may only affect a small proportion of individuals1,2,5 and our patients did not experience significant reduction in vision following treatment, microbial keratitis is potentially blinding and should not be trivialised. Silicone hydrogel contact lenses have a lower risk of associated microbial keratitis than other lens types, but they do not remove it completely. In view of this, contact lenses should not be worn overnight or for an extended period. Furthermore, a painful red eye in a contact lens wearer should be considered microbial keratitis until proven otherwise, and needs a prompt ophthalmologist referral. Microbial keratitis in a 24-year-old woman

John A Landers · John L Crompton

To the Editor: Uveitis is an intraocular inflammation which potentially leads to permanent loss of vision.1,2 Tuberculosis is considered to be an infrequent infectious cause of uveitis in the developed world. However, its recurrence as a major public health problem raises the possibility that the incidence of tuberculosis-related uveitis in the developed world may rise.3,4 Uveitis in tuberculosis is presumed to result from either direct invasion or a hypersensitivity reaction. At the ophthalmology departments of the Erasmus Medical Center and the Eye Hospital in Rotterdam, The Netherlands, all patients presenting with refractory uveitis undergo investigation for a systemic cause, including tuberculin skin testing. When ocular findings are consistent with intraocular tuberculosis, and the tuberculin skin test is positive, while no other cause of uveitis is suggested by symptoms, signs or ancillary testing, then a diagnosis of presumed intraocular tuberculosis is made. Using these criteria, eight cases of presumed intraocular tuberculosis were identified among 89 people referred with refractory uveitis between January 2002 and January 2004. Characteristics of the eight patients are shown in the Box. One patient (F) withdrew from clinical care, and another (A) later had a positive culture result for tuberculosis on lymph node biopsy. This patient had complete remission of uveitis after tuberculostatic treatment, but was excluded from this study as the aim was to assess whether antituberculosis treatment is warranted based solely on a positive tuberculin skin test. We treated the patients with a complete tuberculostatic regimen (2 months of isoniazid, rifampicin, ethambutol and pyrazinamide, followed by 4 months of isoniazid, rifampicin and ethambutol). All had been previously treated for more than 3 years with immunosuppressive drugs (mainly corticosteroids), either local or systemic, or both, without adequate response. Main outcome measures were visual acuity and degree of intraocular inflammation seen on ophthalmological examination before and on completion of antituberculosis therapy. The predominant clinical finding was blurred vision. Five patients exhibited decreased intraocular inflammation and an increase in visual acuity after antituberculosis treatment, allowing tapering of the corticosteroid treatment. One patient had no response. Improvement as part of the natural history was regarded unlikely. As our department is a tertiary referral centre for patients with uveitis, our patient population is not a representative sample of all patients with uveitis in The Netherlands. Nevertheless, our findings suggest that intraocular tuberculosis should be considered in the differential diagnois of uveitis, even in developed countries. We believe that, given our results, antituberculosis therapy is justified in patients with uveitis even when a positive tuberculin skin test is the only argument for tuberculosis as the cause of the eye disease. An additional argument for antituberculosis treatment is that many patients with uveitis refractory to immunosuppressive therapy can be adequately treated with tumour necrosis factor-α (TNF-α) blocking drugs.5 However, as severe tuberculosis infection has been described after use of these agents, antituberculosis therapy is warranted in any patient with a positive tuberculin skin test who is a candidate for TNF-α blocking therapy. Details of eight patients with presumed intraocular tuberculosis Affected eye Place of birth Visual acuity Uveitis treatment Antituberculosis treatment Patient Sex Age Uveitis Before* After* Response A M 25 Left Anterior Congo NR† NR† NR† NR† NR† B F 40 Both Posterior Cape Verde 1.8/6 (R), 1.2/6 (L) 4.8/6 (both) Local steroids HRZE, HRE Partial response, local steroids continued C F 69 Left Posterior Netherlands‡ 4.8/6 4.8/6 Local steroids HRZE, HRE Complete response, local steroids stopped D M 49 Right Posterior Surinam 0.6/6 0.8/6 Vitrectomy, local steroids HRZE, HRE No response E F 36 Both Anterior Morocco 2.4/6 (R), 3/6 (L) 4.8/6 (R), 6/6 (L) Local steroids HRZE, HRE Complete response, local steroids stopped F F 62 Both Posterior Morocco 0.6/6 (R), 0.6/6 (L) Local steroids — Lost to follow up before treatment G M 54 Right Posterior Surinam 2.4/6 5.5/6 Local and systemic steroids HRZE, HRE Partial response, systemic steroids stopped H F 19 Both Intermediate Netherlands‡ 4.3/6 (R), 1.2/6 (L) 6/6 (R), 6/6 (L) Local steroids HRZE, HRE Complete response, local steroids stopped * Before and after antituberculosis therapy. † NR = no result as patient excluded from the study. ‡ Patient C’s parents were born in The Netherlands, but Patient H’s parents were from Morocco. M = male. F = female. H = isoniazid. R = rifampicin. Z = pyrazinamide. E = ethambutol.

Paul L A van Daele · Marleen Bakker · P Martin van Hagen · G Seerp Baarsma · Robert W A M Kuijpers

To the Editor: Mycobacterium ulcerans is an environmental pathogen with a global geographic distribution and focal disease clusters. The World Health Organization considers M. ulcerans infection to be of increasing global importance, particularly in West Africa. In Australia, the clinical and pathological features were fully described in 1948, when the disease was named Bairnsdale ulcer.1 Since then, the number of cases has increased, and new focal areas continue to emerge around southern coastal Victoria.2 In Queensland, the disease is most frequently reported in the Mossman area (north of Cairns in north Queensland), where it is known as Daintree ulcer.3 However, the organism is probably more widely distributed. We describe four patients recently diagnosed with proven M. ulcerans infection in the Capricorn coast region of central Queensland (Box). The suspected epicentre of infection is around Yeppoon, approximately 1000 km south of Mossman. None of the patients had significant contact with recognised endemic areas in north Queensland or Victoria. Patient 1 had visited Townsville in July 2000, but had minimal contact with the natural environment. She undertook extensive gardening at her home in North Rockhampton, using sugar cane bagasse mulch from north Queensland. The previous occupants of her house had lived in north Queensland and left behind at her home numerous potted plants originally from that area. However, investigation of soil from potted plants, gardens and roses at the home using polymerase chain reaction (PCR) failed to detect any evidence of M. ulcerans. Patient 2 lived near a coffee plantation originally planted with seeds transported from north Queensland. Sampling of plants and soil in the area by PCR revealed no atypical mycobacteria. M. ulcerans is an environmental organism associated with bodies of water, but its specific ecological niche is unknown.4 The organism is difficult to culture from the environment but has been identified by PCR in water, biofilms, aquatic insects, snails and fish. The mode of transmission to humans remains unknown. It has shown a marked propensity for causing intense focal outbreaks in Victoria (Phillip Island and Point Lonsdale) and Queensland (Daintree region). The recognition that M. ulcerans occurs in coastal central Queensland is important, as early diagnosis of M. ulcerans infection minimises the extent of tissue debridement necessary and improves outcomes. The patients we describe had complicated disease requiring multiple debridements and, in one case, amputation. Awareness of the possibility of M. ulcerans infection is critical, as diagnosis by PCR is straightforward once the infection is considered in the differential diagnosis. In 1942, Cilento described possible M. ulcerans infections from around Rockhampton.5 Four other culture-confirmed cases were reported between 1957 and 1962 from the Glass House Mountains (Sunshine Coast)3 and Maryborough (Fraser Coast)6-8 regions in Queensland. Our four cases occurred within a small geographic area centred on Yeppoon and the suburbs of Rockhampton. If the cases previously described by Cilento were truly related to M. ulcerans, then there appears to have been a five-decade gap in identification of M. ulcerans infection in the Capricorn Coast region of central Queensland. Possible explanations for this include low organism numbers resulting in sporadic infection, focal concentrations of the organism with environmental changes, such as development, land clearing and cultivation modifying human contact, or failure to diagnose the condition. Patients who acquired the infection in central Queensland may also have been diagnosed outside the area. The increase in cases in Victoria raises the possibility of a potentially similar dramatic increase in cases in central Queensland. Consideration should be given to making M. ulcerans infection a reportable disease to enable monitoring. Four patients with Mycobacterium ulcerans infection in central Queensland Age/sex Location Presentation Site Clinical features Diagnosis Treatment 47 F North Rockhampton Sep 2000 Fifth finger (left hand) Nodule Histology, PCR Debridement, antimycobacterial antibiotics, amputation 33 F Yeppoon Jun 2003 Left knee Ulcer Histology, culture Debridement 64 M Bungundarra Aug 2004 Right elbow Ulcer Histology, PCR Multiple debridements 18 M Keppel Sands Nov 2004 Right knee Ulcer Histology, culture Multiple debridements, antimycobacterial antibiotics PCR = polymerase chain reaction. F= female. M = male.

Glenn D Francis · Michael Whitby · Marion Woods

To the Editor: “... what a difference can be made and how bureaucracies can stuff things up”. “... systematic testing and treatment of people with high blood pressure and kidney disease dramatically improved blood pressure and resulted in a 50% reduction of deaths”. “... excellent results were achieved by good management and they were lost when intensity of management was relaxed”. The above quotes are from an episode of The health report broadcast late last year on Radio National.1 The episode, which described a deterioration in the health of an Indigenous community after a chronic disease treatment program was handed over to a community health board, caused me to take a closer look at the articles in the Journal by Hoy and colleagues on which the claims were based.2,3 I found several issues of concern. The small numbers of deaths each year in the study community and the analysis and presentation of the death data mean that the conclusions about trends in mortality over time are tenuous. This is highlighted by the discrepancies between the two articles in the terminology used to classify deaths, in the numbers of deaths reported, and in the trends over time. Discrepancies in terminology or numbers of reported deaths are not explained. The declining trend in the number of “natural” deaths described in the 2000 article is not apparent in the “non-renal” deaths in the 2005 article. The rate of “non-renal” death for the period 1996–97 to 1998–99 reported in the 2005 article appears to be increasing rather than declining, as described in the 2000 article (rates for earlier years are not presented in either article). It is clear that, with these small numbers, the reclassification or misclassification of a single death can affect the trends in “renal death” or end-stage renal disease over time, and that the use of “rolling averages” hides the year-to-year variability that would be expected in these data. The trend over time in the key intermediate outcome indicator of blood pressure control does not support the conclusion regarding impact of the “handover” on the program. The data presented in the 2005 article show a decline in control commencing in the third year. An earlier analysis of the same data showed the decline in blood pressure control began as early as the second year after entry into the program.4 Neither analysis shows any clear change in the declining trend in blood pressure control around the time of “handover” of the program. While the discussion of the findings of the 2005 article is circumspect, at the time of interview, Hoy conspicuously did not deny the statement of The health report host that the primary cause of the apparent loss of the early impact of the program was the bureaucracy “stuffing up”. The article makes some important points about the operation of chronic disease programs, but makes no mention of the commonly experienced difficulties of sustaining health programs,5,6 or the research requirements for understanding sustainability.7 These issues raise serious questions about the validity of the conclusions and the simplistic claims arising from the articles.

Ross S Bailie MD, FAFPHM

In reply: I appreciate the feedback on the 2000 and 2005 articles describing the dynamics and outcomes of the “Tiwi treatment program”.1,2 Thorough and timely identification and enumeration of deaths is a problem, especially for people not enrolled in the treatment program. Without a register of such people, systematic checking of their fate was not possible. The additional “non-renal” deaths in the community-at-large presented in our 2005 article, compared with previous articles, seem to have been captured largely by the broad net spread by the Tiwi Health Board when it assumed responsibility for its primary care services, in an attempt to identify all its potential clients. This process identified several hundred more people than expected and captured additional deaths, several dating back years. The precise definition of a community member is also a problem, especially for people living permanently or intermittently elsewhere (eg, in Darwin or other communities). The broadened definition of “renal deaths” in the 2005 article,2 which accommodates people who died with renal failure but did not begin dialysis, more fully represents the impact of renal disease. Conversely, recording only those who began dialysis allows estimates of the impact on health services and potential savings from better management.3 Both approaches have their place. Rolling averages, which indeed have limits, were used in view of the overall small and erratically spaced number of terminal events in any year. The figures we reported in our 2005 article did not show a deterioration in blood pressure at Year 2, either in the treatment group as a whole, or in the smaller cohort followed for a full 6 years.2 An earlier analysis, which largely embraced the active years of the program, also showed that blood pressure at Year 3 was not significantly different from that at Year 2 (systolic blood pressure, P = 0.68) (Box). With time, the number of people who had moved through 3 years of treatment increased, and the timing of their 3-year blood pressure measurements moved from a mix of 1998–1999 to 1999–2002, when, as program dynamics suggest, intensity of management was relaxed, and mean values deteriorated, as we reported in 2005. The blood pressure measurements in the report by Bailie’s group5 were compiled from a review of paper-based medical records, the clinic’s newly implemented Coordinated Care Trial Information System, and the Territory’s Information System (Systematic Health Information Logically Organised), as well our from our treatment program database. Those blood pressures were allocated time definitions in a different way, and the summary data were derived from adjusted predictions from cross-sectional time series modelling, rather than from factual recordings at the stated intervals.5 I did not solicit the interview for The health report, nor determine its directions nor the resulting headlines. However, the under-resourcing of primary care relative to needs in remote Aboriginal settings, and the lack of stability in the organisations in which it is delivered, are very detrimental. I regret that, once the Tiwi Health Board was constituted, it was not mentored and supported through its difficulties. More recently, the fledgling community-controlled Gulf Health Service in the Borroloola region of the Northern Territory met a similar fate. Chronic disease remains underserviced in both these regions, where the people are among the sickest in Australia. Blood pressure measurements (mm Hg) over 3 years of follow-up after enrolment in 123 people who had observations at every interval4 Baseline 6 months 1 year 2 years 3 years Mean systolic BP (SD) 136.2 (21.6) 125.4 (21.6) 123.6 (20.3) 120.6 (21.6) 121.7 (21.5) Mean diastolic BP (SD) 81.9 (13.2) 75.5 (13.7) 76.3 (12.9) 74.5 (13.7) 74.0 (11.0)

Wendy E Hoy

To the Editor: As I have said elsewhere, “The last thing the majority wants is that the tyranny of the majority be applied to it. It is much easier to apply the tyranny of the majority to a minority. In a properly functioning democratic society minorities are not subjected to, but are protected against, the tyranny of the majority. Is the tyranny of the majority being applied through the medium of the Howard government onto the Aboriginal communities of Australia in this matter of ‘shared responsibility agreements’?”1 I note with interest recent articles by Collard and colleagues2 and by Kowal,3 debating “shared responsibility agreements”. The expressions “shared responsibility agreement”3 and “mutual obligation” are variations of the expression “social contract”. The concept of “social contract” underlies the concept of democracy originating in the writings of Thomas Hobbes, John Locke and Jean-Jacques Rousseau. Present-day political scientists discuss social-contract theory in their writings about democracy, and may mention “mutual obligation” or “shared responsibility”. While it is commonplace for aspects of the social contract to apply to subgroups in the population, it is discriminatory to make arrangements that apply only to a particular racial or ethnic group. Even though the agreements are declared to be voluntary, it is likely that Aboriginal communities are under pressure to do as they are told to achieve social contracts with the Australian Government. If Indigenous people must comply with certain conditions before they can achieve social contracts, how might similar conditions be applied to the rest of the Australian population? The “ticking time bombs” of Australian public health are smoking and obesity. If non-Indigenous Australians refuse to stop smoking and refuse to eat less and take more exercise, should access to public hospitals and pharmaceutical benefits be denied them? Should they be denied petrol to force them to walk and to use public transport? Obviously not. These services are not subject to social-contract agreements as thiswould be a clear violation of Australian law. Australian members of parliament in particular, and Australians in general, for the sake of themselves, their families and of Australian health care costs, would benefit from negotiating “shared responsibility agreements” with themselves to stop smoking and to lose weight. In current circumstances, “shared responsibility agreements” with Aboriginal communities represent inequality of sharing the responsibility for health.

John N Burry

To the Editor: Where is the evidence for the claim by Joyce, McNeil and Stoelwinder1 that there was a boom in medical workforce supply in the 1970s? They are perpetuating the accepted macroeconomic myth of there having been a surplus at that time. The microeconomic, marketplace truth was that there was a shortage of general practitioners throughout the 1970s.2 This was so severe that, after battling for some years after 1974 to find a partner for my suburban Sydney practice, I resorted to advertising overseas, finally importing an overseas-trained graduate. It is time for this myth to be laid to rest. There has been a marketplace shortage of GPs since the early 1970s. The truth is that federal governments have baulked at the expansion of payments through Medibank/Medicare. Rather than apply any controls on demand, they have obstinately rationed supply, repeatedly citing dubious statistics and invalid international comparisons to justify a diminution in the supply of GPs.

Peter C Arnold

In reply: Our reference to a boom in medical workforce supply during the 1970s was based on the marked increase in medical workforce entries in that decade. The number of Australian medical graduates rose from 851 in 1970 to 1278 in 1980.1,2 In contrast — and as a result of a shift to a policy of constraint — graduate numbers remained quite static during the 1980s and 1990s, at around 1200–1300 per year (Commonwealth Department of Education, Science and Training custom datasets RFI 03-312, RFI 04-360, 2004). Although the policy shift in the 1980s was based on a perception of surplus, judgements about workforce adequacy were contentious at that time and remain so. We did not intend to imply necessarily that there was a surplus in the medical workforce (or the general practice workforce specifically) during the 1970s. Rather, our historical reference was intended to show the parallels with the large influx that will result from current expansion in medical school intakes, and to highlight the cyclic nature of both medical workforce policy and perceptions of adequacy. We agree with Arnold’s implication that policies which attempt simply to adjust gross supply (up or down) are insufficient to ensure an adequate medical workforce.

Catherine M Joyce · John J McNeil · Johannes U Stoelwinder