Letters

To the Editor: Awareness about atypical and malignant modes of presentation of a clinical condition can avoid catastrophic outcomes, assist in correct diagnosis in the appropriate clinical setting and, as typified by the following case, offer complete cure. A 39-year-old woman presented with a 5-year history of intermittent, recurrent brief syncopal episodes. During an episode at presentation, telemetry showed torsade de pointes with ventricular fibrillation (Box), and external defibrillation was required to restore sinus rhythm. Amiodarone infusion was initiated at a local hospital before the patient was referred to our institution for further investigation and management. On presentation, her heart rate was 50 beats/min and her blood pressure was 170/95 mmHg. No other abnormalities were detected on examination. A resting electrocardiogram (ECG) showed prominent U waves, with a long QT interval (QTc of 540 ms). As the patient had mild hypokalaemia (serum potassium level, 3.1 mmol/L), mild hypocalcaemia (serum calcium level, 2.10 mmol/L) and a prolonged QT interval, the amiodarone infusion was discontinued, and supplementation with potassium and calcium was initiated. In view of the hypertension and hypokalaemia, primary aldosteronism was suspected. Serum cortisol, 24-hour urinary cortisol and 24-hour urinary catecholamine levels were normal. The plasma aldosterone/renin ratio was markedly elevated (1920/1.2 = 1595; normal, < 99). Failure of aldosterone suppression after acute saline loading was also noted. Computed tomography of the abdomen showed a right adrenal ovoid mass (1.9 × 1.2 cm). Adrenal vein sampling confirmed right lateralisation (right to left ratio, 40 : 1; aldosterone level in the right vein was 224 000 pmol/L while that in the left vein was 5570 pmol/L). Despite initial potassium supplementation, the hypokalaemia persisted and only improved after initiating diuretic therapy with amiloride. Two weeks later, laparoscopic right adrenalectomy was performed, and adrenocortical adenoma was confirmed histologically. After surgery, plasma aldosterone and renin levels normalised to 106 pmol/L and 8.9 mU/L, respectively. Nine months later, the patient was normotensive (without treatment) and had a normal ECG with no further recurrence of arrhythmias. This was a case of primary aldosteronism presenting as aborted sudden cardiac death and malignant syncope secondary to hypokalaemia-induced torsade de pointes. Most patients with primary aldosteronism are either asymptomatic or have symptoms related to hypertension or hypokalaemia (eg, polyuria, cramps, paraesthesia or muscle weakness); the diagnosis is often missed because of the non-specific clinical features. Primary aldosteronism presenting with cardiovascular collapse caused by hypokalaemic torsade de pointes and recurrent ventricular fibrillation is extremely rare, as is presentation as sudden cardiac death secondary to ventricular fibrillation.1 A prolonged QT interval has been reported in cases of primary aldosteronism,2 with values normalising after adrenalectomy.3 Torsade de pointes noted on telemetry in a 39-year-old woman

Aditya Kapoor · Timothy A Wells · Daniel Wong · John P O’Shea

To the Editor: Childhood overweight and obesity have become a major public health concern in Australia. Between July 2003 and December 2004, we conducted the Australian National Iodine Nutrition Study (NINS) among schoolchildren.1 While visiting primary schools across Australia, we observed that many children were overweight or obese. The NINS data allowed us to estimate the prevalence of overweight and obesity among 8–10-year-old Australian schoolchildren, and to determine whether the prevalence was associated with socioeconomic background. The study population comprised a one-stage random-cluster sample from all Year 4 school classes in 92 government and non-government schools.1 Children were aged 8–10 years (mean, 9.3 years). Height and weight were measured by standard techniques and were used to calculate body mass index. Overweight and obesity were identified using international standard definitions.2 Socioeconomic status was defined by the Index of Relative Socio-Economic Advantage/Disadvantage of the Census of Population and Housing’s Socio-Economic Indexes for Areas (postal areas).3 This index is a continuum of advantage to disadvantage. A higher score indicates that an area has a relatively higher proportion of people with higher incomes or a skilled workforce. The prevalence of overweight and obesity in 8–10-year-old schoolchildren was 18.5% and 6.5%, respectively. There was no significant sex difference in prevalence and no significant evidence of an association between socioeconomic status and overweight or obesity (Box). The prevalence of overweight and obesity combined and of obesity alone was similar to previously reported prevalence,4,5 although the age range of the participants was more limited than in other studies. We minimised measurement error bias by using the same equipment throughout, in the same setting. Furthermore, most measurements were taken by the same person. We could not demonstrate an association between socioeconomic status and the prevalence of overweight and obesity combined, or of obesity alone. This suggests that childhood overweight and obesity is common to all Australian communities, irrespective of socioeconomic background. Preventing overweight and obesity in children may reduce the risk of adult overweight and obesity and related diseases. Regular monitoring and surveillance of the situation is needed. Australia is one of the first countries in the world to develop a national strategy for overweight and obesity.6 However, the strategy needs to be communicated to the wider community and turned into action to combat this public health problem. Proportion (number) of boys and girls categorised as overweight or obese by index of advantage/disadvantage* SEIFA percentile Not overweight or obese Overweight Obese n Overall Boys Girls Overall Boys Girls Overall Boys Girls Lowest 10 130 79% (102) 77% (56) 82% (46) 12% (16) 12% (9) 13% (7) 9% (11) 11% (8) 5% (3) 10–25 286 72% (207) 72% (103) 73% (103) 22% (64) 22% (31) 23% (33) 5% (15) 6% (9) 4% (6) 25–50 210 74% (156) 72% (72) 76% (84) 17% (35) 18% (18) 16% (17) 9% (19) 10% (10) 8% (9) 50–75 505 75% (379) 72% (183) 79% (195) 19% (98) 21% (53) 18% (45) 6% (28) 8% (20) 3% (8) 75–90 427 75% (319) 78% (179) 71% (140) 18% (78) 17% (39) 20% (39) 7% (30) 6% (13) 9% (17) Highest 10 225 77% (174) 79% (84) 76% (89) 17% (39) 16% (17) 19% (22) 5% (12) 6% (6) 5% (6) Total 1782 75.0% (1337) 74.4% (677) 75.6% (657) 18.5% (330) 18.4% (167) 18.8% (163) 6.5% (115) 7.3% (66) 5.6% (49) * Overall χ2 = 11.42, P = 0.33; Boys χ2 = 8.73, P = 0.56; Girls χ2 = 12.36, P = 0.26. SEIFA = Socio-Economic Indexes for Areas (a higher score corresponds to higher socioeconomic status).

Mu Li · Karen Byth · Creswell J Eastman

To the Editor: Obesity in adults presents significant issues for health care providers, including practical problems in transporting and accommodating large individuals, and in performing standard tests and investigations.1 However, this issue has been little addressed in the mortuary setting, although a recent media report detailed the need for larger crematorium furnaces to accommodate oversized coffins, as well as larger graves for burials.2 We reviewed the body mass index (BMI) of individuals who had undergone coronial autopsies in South Australia in the first 3 months of 2007. Weight and height of all bodies were measured using standardised equipment and were used to calculate BMI by the usual formula.3 A total of 255 individuals aged over 17 years were included in the study (male to female ratio, 2 : 1; age range, 17–97 years). A third of individuals were classified as obese (BMI ≥ 30 kg/m2), and 6% as morbidly obese (BMI ≥ 40 kg/m2). The highest BMIs were: 132.3 kg/m2 (175 kg, 115 cm); 109.0 kg/m2 (315 kg, 170 cm); 82.8 kg/m2 (220 kg, 163 cm); and 79.5 kg/m2 (201 kg, 159 cm). In comparison, over a similar time period at the same institution in 1986, 17% of individuals were obese, and 3% were morbidly obese, with the four highest BMIs being: 55.2 kg/m2 (137 kg, 157.5 cm); 48.3 kg/m2 (148 kg, 175 cm); 44.7 kg/m2 (137 kg, 175 cm); and 41.9 kg/m2 (104 kg, 157.5 cm). This study demonstrates that forensic facilities are now dealing with individuals of considerable body mass. Despite government and industry guidelines for manual handling practices,4 these bodies are difficult to lift, move and store, and present major logistical problems for pathologists and technicians attempting to perform standard examinations. Mechanical lifting hoists, x-ray tables and trolleys are often not designed to cope with such weights. Putrefaction is hastened in morbidly obese individuals, and associated skin slippage and purging makes the bodies even more difficult to handle. Given that autopsies are often required in such individuals to determine the cause of death, consideration must be given to the significant occupational health and safety issues they create for staff in facilities with substandard equipment (ie, designed for normal-sized bodies). The construction of specially designed mortuaries will be required if this trend continues, with larger storage and dissection rooms, and more robust equipment engineered to cope with increasing numbers of individuals with BMIs sometimes considerably greater than 30 kg/m2. Failure to provide these may compromise the postmortem evaluation of markedly obese individuals, in addition to potentially jeopardising the health of mortuary staff.

Roger W Byard · Maria Bellis

To the Editor: The increase in medical graduates expected over the next decade presents a huge challenge to the many stakeholders involved in providing their prevocational and vocational medical training.1 Increased numbers will add significantly to the teaching and supervision workload for registrars and consultants, while specialist training and access to advanced training positions may be compromised. However, this predicament may also provide opportunities for innovation in the way internships are delivered. Although facing these same challenges, regional and rural hospitals could use this situation to enhance their workforce by creating opportunities for interns and junior doctors to acquire valuable experience in non-metropolitan settings. We surveyed a representative sample (n = 147; 52% of total cohort) of Year 3 Bachelor of Medicine and Bachelor of Surgery students at the University of Queensland about their perceptions and expectations of their impending internship and the importance of its location (ie, urban/metropolitan versus regional/rural teaching hospitals) to their future training and career plans. Most students (n = 127; 86%) reported a high degree of contemplation about their internship choice. Issues relating to career progression and support ranked highest in their expectations. Most perceived internships in urban/metropolitan hospitals as more beneficial to their future career prospects compared with regional/rural hospitals, but, interestingly, felt that they would have more patient responsibility and greater contact with and supervision by senior staff in a regional setting (Box). Regional and rural hospitals should try to harness these positive perceptions and act to address any real or perceived shortcomings in order to enhance their future workforce.2 They could look to establish partnerships with rural clinical schools3 to enhance recruitment of interns as early as Year 3. To maximise competitiveness with their urban counterparts, regional and rural hospitals need to offer innovative training and career progression pathways to junior doctors, to combat the perception that internships in urban hospitals are more beneficial to future career prospects. Partnerships between hospitals, medical schools and vocational colleges, with input from postgraduate medical councils, should provide vertical integration4 in the important period between student and doctor. Work is underway to more closely evaluate and compare the intern experience across regional/rural and urban/metropolitan hospitals, and track student experiences and career choices longitudinally. This information may benefit teaching hospitals and help identify the optimal combination of resources necessary to provide quality teaching and a clear career pathway for the expected influx of new interns. Year 3 medical students’ perceptions of internship in a regional/rural hospital versus an urban/metropolitan hospital Perception Strongly disagree Disagree Not sure Agree Strongly agree My acceptance onto a training program will be influenced by the reputation of the hospital in which I do my internship 4% (5) 18% (24) 28% (38) 43% (59) 8% (11) I would have less responsibility for my patients in a regional/rural hospital 21% (29) 67% (92) 12% (17) 0 0 There would be more contact with senior staff in an urban/metropolitan hospital than in a regional/rural hospital 11% (15) 48% (66) 29% (39) 11% (15) 2% (2) I would have more clinical supervision in an urban/metropolitan hospital than in a regional/rural hospital 11% (15) 47% (64) 25% (34) 15% (20) 2% (3) I would feel more part of a team in an urban/metropolitan hospital than in a regional/rural hospital 11% (15) 60% (83) 27% (38) 2% (3) 0 Numbers are percentage of respondents (number of respondents). Denominators vary due to missing responses.

Diann S Eley · David K Morrissey

To the Editor: We report that the internship location choices of the second cohort of medical students to graduate from James Cook University (JCU) are very similar to those of the first cohort.1 Of the 75 students who graduated in the second cohort in 2006, 65 (87%) are working in Queensland; 42 (56%) in North Queensland (roughly the area north of Mackay). Fifty-three (71%) are in non-metropolitan hospitals, including three of the 10 graduates who moved or returned interstate. These proportions reflect the cohort’s geographic origins. As in the first cohort, a small number of students (13; 17%) of North Queensland origin moved away and a similar number (14; 19%) from elsewhere stayed in North Queensland. Further, a majority of the first cohort have remained where they undertook internship: 24 of 29 (83%) have remained in North Queensland and one commenced remote practice, consistent with the group’s stated intentions to work in regional locations.2 Hence, JCU’s first two graduating cohorts had a combined effect of strong recruitment to non-metropolitan hospitals, particularly in Queensland, some of which have experienced difficulty in recruiting junior staff. These results have two implications. First, they contribute to the debate on selection into medicine.3 JCU gives weight to rural schooling, with about two-thirds of each cohort having a rural background, and a similar proportion coming from North Queensland.4 Second, there are workforce policy implications. The growth in medical school numbers over the past 3 years has not evenly reflected workforce needs or availability of postgraduate training places. As some urban areas become oversupplied with junior doctors, it will be important not to neglect areas of maldistribution that are drivers of growth. Regional training pathways for specialist and generalist careers need urgent definition; graduates in Queensland are expected to increase from 300 in 2007 to 727 in 2014, so vocational training places will need to more than double.5 An impact on the Australian medical workforce shortage will only be felt when a number of cohorts have graduated from JCU and other regional schools, and bottlenecks to subsequent training are removed. It will take another decade to obtain a clear picture of postgraduate career outcomes for this group, but the investment in regional medical education in North Queensland appears at this stage to be having the desired effect. If this effect is sustained and replicated in other new regional medical schools, Australia may soon have an adequate supply of medical graduates who both understand and choose to live and work in regional Australia.

Tarun Sen Gupta · Richard B Hays · Richard B Murray

To the Editor: The Transition Care Program (TCP) is a joint federal and state government program that provides short-term (8–12 weeks) support and therapy to improve functioning for older people who are hospitalised (either in public or private hospitals) and would otherwise require admission to a residential aged care facility.1 Participants are provided with a care package that assists with activities of daily living, and provides limited allied health, nursing and medical input, with the aim of improving functional status, if possible. The TCP is currently being implemented across Australia. We selected and audited three transition care services that commenced operation early in the program (2005 and early 2006), with the aim of describing the outcomes of these services, and determining whether the older people participating in the various services were similar. Approval was obtained from the relevant ethics committees. Three services were purposefully sampled: two services in Adelaide (Service A providing packages in a community setting, and Service B providing packages in a high-level care, residential aged care setting); and one service in Sydney (Service C providing packages in a community setting). The residential package allocates temporary residential placements for patients with defined rehabilitation goals, and thus also frees up acute care hospital beds. These services supplied de-identified audit data about the first 30 participants, who were in the program between June and December 2006. A summary of the data is given in the Box. The participants in the residential program tended to be older, more likely to be male, and less likely to have “fracture or fall” as their primary diagnosis. These older people also had more severe disability that generally does not improve, and were significantly less likely to return to community living. The two community-based programs were generally similar. The data suggest that there is considerable variation between the TCP services, with the residential service providing packages to older people with severe disability who generally remain in a residential aged care program, although some may improve from high- to low-level aged care services. By contrast, the outcome of the community-based services is generally maintenance in the community and is associated with an improvement in functioning. This profile is similar to that of a community-based rehabilitation service for older people. It is not clear from the TCP guidelines whether this level of variation in program implementation was anticipated.1 This limited audit suggests that the Australian TCP is not homogeneous and is substituting for other forms of treatment and care. Thus, there is provision of high-level residential care as a substitute for waiting for residential aged care in a hospital bed, and community rehabilitation as a substitute for rehabilitation services provided by state health departments. This situation is potentially beneficial to older people who previously did not have access to these services, but it also could mean that state governments may not establish rehabilitation services for older people, or may even cease providing these services. Comparison of background, status and outcomes for participants in three Transition Care Program (TCP) services Service A (community) (n = 30) Service B (residential) (n = 30) Service C (community) (n = 29) Statistical significance* Mean age (SD) in years 80.9 (7.9) 84.5 (5.1) 80.4 (8.0) ns Female 60% 47% 59% ns Living alone 40% 47% 62% ns Primary diagnosis — trauma (fractures and falls) 43% 20% 41% ns Barthel Index On admission to the TCP — mean (SD) 66.9 (13.8) 55.2 (26.8) 69.2 (19.1) F = 3.85; P = 0.025 On discharge from the TCP — mean (SD) 72.8 (17.6) 56.4 (34.2) 82.8 (22.0) F = 7.69; P = 0.001 Mean change (SD) 5.9 (21.3) 1.5 (19.0) 11.6 (13.3) ns Discharge status — in the community† 60% 20% 76% χ2 = 35.6; P = 0.000 * Based on a comparison between the three groups (χ2 test for categorical data, and analysis of variance [F test] for continuous data). † Patients were in the Program for 12 weeks unless they left early because of admission to hospital or permanent admission to a residential care facility. ns = not significant.

Ian D Cameron · Owen Davies

To the Editor: In an ironic clinician–academic dichotomy, in the same month that the Royal Australian and New Zealand College of Psychiatrists published a survey showing that 79% of Australian psychiatrists combine antidepressants and 75% of psychiatrists believe that general practitioners should be given information on this topic,1 Keks et al chose a non-psychiatric journal to “mandate that combinations be used as a last resort, and only in specialist settings”.2 Specialists have voted with their prescription pads. That a large majority of Australian psychiatrists feel ethically and clinically obliged to use combination antidepressants speaks volumes about the poor results from the suggestions outlined by Keks et al. The multiple clinical reports and reviews of the benefits of combination antidepressants,3 the suffering and death from depression, and the very low rate of complications reported to the Adverse Drug Reactions Advisory Committee from combination antidepressants do not allow the luxury of awaiting combination therapy research which may never happen. Many combinations of antihypertensives or anti-asthma medications similarly lack such rigorous proof, but are widely used. Isolated case reports of medication complications must be seen as such. Access to psychiatrists for combination antidepressant therapy is a well intentioned but currently impractical suggestion. Most psychiatrists have massive waiting lists, and research confirms treatment resistance and progressive cell death in the hippocampus of depressed patients while awaiting effective treatment. Australian GPs are just as capable of using combination antidepressant therapy as their international colleagues, if given the same simple information and training. Canadian GPs read in their journals advice about using combination antidepressants. Anecdotally, many Australian GPs combine antidepressants, but express the wish that the issue could be discussed openly, without them feeling intimidated. Even textbooks of psychiatry, drafted some years ago, teach about combination antidepressants. In the United States, the National Institute of Mental Health STAR*D study of 4000 patients approved combination antidepressants such as venlafaxine with mirtazapine years ago, with no safety concerns.4 Keks et al refer to treatments that today are unacceptable to many, ranging from electroconvulsive therapy to tricyclic antidepressants, despite GPs and psychiatry trainees having been warned for years by academics that tricyclics are outdated, “dirty” and dangerous. Informed consent requires that patients be informed of all therapies that are relevant to their care and survival, and 88% of psychiatrists believe patients should be informed of combination antidepressants.1 Recent results from the STAR*D study demonstrate the superiority of modern combination antidepressants, with no statistically based evidence that they should not be used.5

David P Horgan

To the Editor: Keks et al make a number of important points about the place of combination antidepressant strategies in the pharmacotherapy of depression.1 However, it is important for readers to note that the vigorous repudiation of combination treatments is a peculiarly Australian preoccupation. Our colleagues in Europe and North America are not nearly so troubled. Combination antidepressant treatments are widely used by specialists. A recent survey of Australian doctors working in psychiatry reported that 79% of respondents had used combination antidepressants and that 75% believed that general practitioners should be given information on their use.2 There is emerging evidence for the use of combination antidepressant strategies — from case series, open clinical trials, and randomised controlled trials (RCTs). The largest summation of the data is a meta-analysis which found that combination antidepressant treatment produced a 62% response rate when monotherapy had failed.3 Although this finding alone cannot be convincing because of the acknowledged lack of large sample RCTs, it is quite another matter to decry combination prescribing as clinically unsound based only on the history of augmentation treatments such as lithium and, to a lesser extent, thyroid hormone treatment when, anecdotally, they provide such clinically disappointing results. It is not unreasonable to assert the primacy of good clinical reasoning, including sensible prescribing of combination antidepressants, over rigid adherence to evidenced-based algorithms. This sort of thinking is allowable because the evidence base for the treatment of depression is poor. Meaningful guidelines cannot be produced while the evidence is predicated on the flawed proposition that depression is an “it” (a homogenous construct).4 GPs might well be puzzled by the zeal in academic psychiatry for monotherapy. They are advised to “optimise” monotherapy, but not told what this means. They are very familiar with models of staged polypharmacy for common chronic illnesses such as hypertension, epilepsy, diabetes, and asthma, but in psychiatric pharmacotherapy this is apparently unwise or too risky. The way such admonishments are usually framed is by reference to serious but rare adverse reactions (like the serotonin syndrome), without proper attention to the equally serious and probably more common problems with the current “simple” psychotropic drug options already used by GPs. Failure to contextualise these risks leads to a distortion of risk–benefit prescribing decisions and an unnecessary restriction of treatment choices. We must have a commonsense approach to the treatment of depression that recognises the proper context of our knowledge base. Combination antidepressant treatments may be “beyond the evidence”, but this alone is not a sufficient justification to stop using them.

Murray J Walters · Alston M Unwin · Sean B Gills

In reply: The letters by Horgan and Walters et al underline our motive for reviewing antidepressant combinations. The conclusions of the survey are at least questionable, given that the response rate was only 36%, 18% of respondents were not psychiatrists, and affirmative responders may have only used combination antidepressants once.1 In any case, should clinical popularity substitute for evidence? If so, once popular but now research-discredited treatments such as insulin coma therapy would still be used. Equating combination antidepressants to combination drugs for asthma and hypertension is misleading. How often are two β-blockers given together in maintenance treatment? Major depression causes severe suffering, but this does not justify the use of unproven treatments ahead of those supported by evidence. General practitioners should be informed about antidepressant combinations, but the information must be evidence-based. We described the process of dose optimisation, and stand by our advice that complex cases that require unproven treatment (such as combination antidepressants) be referred to a psychiatrist. Patients should also be informed about combination antidepressants, including the paucity of evidence concerning efficacy and safety, the absence of information about consequences of long-term treatment, and that some combinations are lethal and others frequently unsafe. Published data from the STAR*D study provide equivocal support for the combination of citalopram and bupropion, as we noted. Evidence of modest effectiveness (remission rate, 13.7%) for the combination of mirtazapine and venlafaxine has appeared.2 Our conclusion was that some antidepressant combinations could be used in certain clinical situations where evidence-based treatments have failed, with safeguards. Given that 17% of respondents to the survey1 observed serious complications with combination antidepressants, this is good advice.

Nicholas A Keks · Graham D Burrows · David L Copolov · Richard Newton · Nick Paoletti · Isaac Schweitzer · John W G Tiller

To the Editor: In his “Personal perspective” piece, Allen1 reminded us all of how medicine can at times truly be the noblest of professions. Writing to the next of kin after the death of a patient is occasionally a difficult task, but more usually provides an appropriate form of closure, not only to the relationship with the deceased patient, but also to relationships with the person’s partner, family members and friends whom you may have met during the treatment episode and whom you may not see again. Since I began practice as a consultant 20 years ago (a practice that involves a substantial number of patients who require surgery for cancer), I have tried to write to the next of kin or significant other of every patient who has died while under my care. The letter allows me the opportunity to say perhaps how brave the patient had been in the face of adversity or to acknowledge the support the next of kin had provided. A simple expression of condolence and an indication of how much a loved one may be missed seems to be the best way to “sign off”. Such letters are only a small gesture, but I have often been gratified by how much comfort they seem to provide to those who receive them, and in all this time I have never had a response that could even remotely be considered “negative”. In this current day, when practising clinicians appear to have a diminished role in our medical schools, may I suggest that Allen’s article — which I think is a great example of what is meant by the “art of medicine” — be distributed to our universities and colleges to be considered for inclusion in their teaching material and curricula.

Ian T Jones

To the Editor: Human normal immunoglobulin (NIG) has historically been used to provide passive immunity against hepatitis A infection for susceptible travellers to areas where the virus is endemic.1 The introduction of effective hepatitis A vaccines in recent years (which result in active, long-term immunity to the virus) should have largely replaced the use of NIG for travel prophylaxis.2 However, the Australian Red Cross Blood Service still receives requests to supply NIG for travellers, even though the intended recipients have no contraindications to vaccination. Requests for use of NIG for this purpose appear in many cases to be a consequence of the “out-of-pocket” cost to the patient of the hepatitis A vaccine, which is about $70–$100 (depending on the formulation used and the private dispensing fee charged). In contrast, NIG is provided free of charge to the recipient, but the community still incurs substantial costs related to blood collection and fractionation of plasma products. There is also the concern of unnecessary exposure of a healthy traveller to a pooled plasma product, which, despite blood donor screening, dedicated viral inactivation steps, and an excellent safety record in Australia, may theoretically transmit infectious agents. In addition, even if a small amount of NIG is used for this purpose, the plasma source would be better used for production of greater amounts of other scarce plasma-derived products (such as intravenous immunoglobulin). While NIG can effectively prevent hepatitis A infection from developing in susceptible contacts, immunity is short-lived and likely to be inferior to the results of active vaccination.1-3 Accordingly, NIG is only indicated for at-risk people who have a contraindication to vaccination, or in whom there is insufficient time to mount an endogenous antibody response (active immunity develops within 7–10 days of vaccination,3 and vaccination may also prevent hepatitis A infection even when the vaccine has been administered up to a week after exposure4). Use of NIG is also appropriate where at-risk contacts may be unable to mount a protective antibody response because they have a congenital or acquired immune deficiency. Although the extent of NIG use for travellers appears to be limited, we wish to highlight that, in the absence of contraindications to vaccination, it can no longer be advocated as best practice, and it is certainly not an appropriate cost-saving measure.

Jake Shortt · Denis Spelman · Erica M Wood

To the Editor: Rabies vaccine is recommended for pre-exposure prophylaxis in travellers over 1 year old who intend to travel to predominantly developing countries where canine rabies is endemic. The incidence of dog bites in such countries is relatively high, being more common among travellers than typhoid fever.1 Postexposure rabies treatment of pre-immunised travellers is simpler, cheaper and safer than treatment of those who have not been immunised. Rabies vaccines currently available in Australia are given intramuscularly as three doses of 1.0 mL on Days 0, 7, and 21–28, but are relatively expensive at more than $100 per dose. Some travellers will choose not to be vaccinated because of this cost. For at-risk travellers who might choose to decline vaccination because of the cost, and to facilitate use of pre-exposure vaccination in poorer countries, the World Health Organization approves the intradermal route of vaccination, where 0.1 mL of vaccine is administered, also on Days 0, 7 and 21–28.2 However, the intradermal technique is technically more difficult, may result in lower antibody levels that decline more quickly, and may be interfered with by concurrent administration of chloroquine or immunosuppressants. The Australian immunisation handbook therefore recommends that this technique be performed by vaccinators experienced in the technique, and that satisfactory antibody production is confirmed after vaccination.3 Antibody levels of at least 0.5 IU/mL are considered protective, and the commercial enzyme immunoassay, available under Medicare, has been shown to correlate well with the gold-standard virus neutralisation test.4 We have been using the intradermal method for over 10 years for travellers considered at high risk, but who decline vaccine on cost alone; we use imported human diploid cell vaccine of potency of at least 2.5 IU/mL. As several travellers can be vaccinated from the same vial, costs are $30–$40 per dose, and vials can be stored and reused within 7 days under aseptic conditions. However, travellers must be vaccinated 7–8 weeks before departure to enable antibody testing and a booster vaccination if required. Recent analysis of 1532 non-immunosuppressed travellers (aged between 9 and 77 years; 55% female) who received three intradermal doses of 0.1 mL rabies vaccine on Days 0, 7, and 21–28 in our Melbourne clinic showed that only seven (0.46%) failed to reach the protective antibody level of 0.5 IU/mL on testing 2–4 weeks after the third dose, with readings of 0.4 IU/mL (in four), 0.3 IU/mL (in two) and 0.2 IU/mL (in one). None had undetectable antibody levels. All seven were advised to receive an intramuscular booster dose of 1.0 mL. These data support the contention that the intradermal method is appropriate for use in travellers who may otherwise decline pre-exposure rabies vaccination, when the vaccine is administered by vaccinators with relevant experience.5 Recipients of intradermal rabies vaccine who have satisfactory antibody levels may be considered fully vaccinated in the postexposure situation and managed accordingly.

Anthony Gherardin · Sonny Lau

To the Editor: We report a patient with spontaneous intracranial hypotension (SIH), which is now an increasingly recognised syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the keys to diagnosis. When correctly diagnosed, SIH management is easy and highly effective in most cases. A 38-year-old woman presented to our hospital after having daily headaches for 3 weeks. The acute onset of severe headache occurred initially when she bent down and tried to lift her 16-month-old child. The headache began as a sharp pain over the right side of her occiput and rapidly spread to her frontal area. The headache was particularly bad in the morning and while standing, and was relieved by assuming a recumbent posture. Apart from nausea, she had no other associated symptoms. General and systemic examination findings were normal. MRI of the brain showed diffuse dural enhancement and smooth thickening of the dura (Box, A) and a total spinal magnetic resonance image showed fluid in the posterior soft tissues at C1/C2 level (Box, B). These findings confirmed the leak of cerebrospinal fluid that accounted for the intracranial hypotension and orthostatic headache. Initial treatment with bed rest, increased fluid intake and non-steroidal anti-inflammatory drugs relieved her symptoms marginally. After a failed lumbar epidural blood patch, 10 mL of autologous blood was injected at the site of the cervical level leak. The patient’s symptoms resolved, and she was asymptomatic and had had no recurrence at follow-up at 4 months. Also known as Schaltenbrand syndrome, SIH is very rare, with a prevalence of about 1 in 50 000 population, and a female preponderance of 3:1.1 Patients with connective tissue diseases2 or Chiari malformation may be more susceptible to SIH. Orthostatic headache is the cardinal feature of this syndrome. Headache is usually holocranial, although it might be localised to the frontal or occipital regions. Patients may have other symptoms such as diplopia and photophobia. MRI with gadolinium is critical in diagnosing this syndrome. The condition of most patients improves with conservative therapy (bed rest, increased fluid intake and caffeine). Epidural autologous blood patch is effective in relieving low intracranial pressure headaches.3 Surgical repair of the leak is rarely used and should be used only if medical therapy fails.4 Magnetic resonance images of the patient’s brain and cervical spine A: Diffuse dural enhancement and smooth thickening of the pachymeninges. B: Fluid in the posterior soft tissues at C1/C2 level.

Mohamed Asif Chinnaratha · Ronald A Criddle · Paul J Graziotti

To the Editor: Recent studies provide evidence that having a low serum vitamin D level is a risk factor for autoimmune disease, including type 1 diabetes mellitus (T1DM).1,2 Available data come from northern hemisphere countries where sunlight exposure levels and the genetic background of the population are different from those in Australia. We compared vitamin D levels in stored serum from Brisbane children and adolescents with T1DM who attended the Mater Children’s Hospital clinic with local historical control data from a previous study.3 Levels of 25-hydroxyvitamin D (25-OHD; the major circulating form of vitamin D) were lower in those with T1DM than in the control group, with no difference in levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D; the biologically active form). Children and adolescents with T1DM were more than three times as likely to have vitamin D deficiency4 as those in the control group. There was a trend towards seasonal variation in 25-OHD levels, with mean levels (95% CI) being 53.8 nmol/L (47.0–60.6 nmol/L) in summer, 61.4 nmol/L (54.9–67.9 nmol/L) in autumn, 56.4 nmol/L (51.7–61.0 nmol/L) in winter and 64.7 nmol/L (58.8–70.6 nmol/L) in spring (P = 0.06), but no difference in seasonal variation between T1DM and control groups (P = 0.73). There was no difference in the ages or proportions of males and females in the two groups (Box). There were no differences in vitamin D levels between the sexes in either T1DM or control groups, nor any correlation with duration of diabetes. These observations support previous reports. One found low 25-OHD levels in 459 Swedish patients aged between 15 and 34 years who were newly diagnosed with T1DM compared with age-matched and place-matched controls.1 Another found low 25-OHD levels in 88 newly diagnosed children and adolescents.2 Understanding the nature of low vitamin D levels in people with diabetes is important because it potentially clarifies the mechanisms of autoimmune β-cell destruction, and may lead to interventions for preventing or delaying insulin dependence by using vitamin D or its analogues. Vitamin D probably acts by modifying the autoimmune response, as 1,25-(OH)2D modulates dendritic cell function to promote tolerogenic T cells. It may be relevant that we have recently found low blood dendritic cell counts in children and adolescents with T1DM.5 Vitamin D levels in our Queensland sample of children and adolescents were lower overall than those found in the subjects of the Swedish study, (mean 25-OHD levels [± SEM] were 96.7 ± 2.7 nmol/L for the control group and 82.5 ± 1.3 nmol/L for those with T1DM); this is unexpected given Brisbane’s latitude (29°S) compared with that of Sweden (about 55–65°N). These differences might be explained by differences in dietary intake, sun avoidance behaviours promoted in Queensland, or differences in the assays used, as the Swedish group used the Nichols chemiluminescence assay (Nichols Institute, San Juan Capistrano, Calif, USA) and we used the DiaSorin radioimmunoassay (DiaSorin Inc, Stillwater, Minn, USA). The observation in the Swedish study that the deficit in 25-OHD level did not resolve over time after diagnosis concurs with our finding of low levels in children and adolescents several years after diagnosis. While our pilot data cannot support causal inference, and is limited by being retrospective and our lack of information about history of sunlight exposure, dietary vitamin D intake, cultural factors such as sun avoidance or veiling, skin tone, and not having contemporaneous controls, it strongly supports the case for prospective clinical studies of vitamin D in T1DM. Comparison of clinical characteristics and vitamin D levels in healthy children and adolescents and those with type 1 diabetes mellitus Variable Control group Type 1 diabetes mellitus group P No. of children and adolescents 94 47 Age (range) 13.2 years (12.5–13.8 years) 13.6 years (12.6–14.6 years) 0.47* No. of males/females 44/50 21/26 0.81† Mean duration of diabetes (95% CI) — 4.7 years (3.9–5.5 years) Sample collection period July 2000 – December 2001 June 2001 – July 2006 Mean 25-OHD level (95%CI)‡ 64.6 nmol/L (61.3–67.9 nmol/L) 54.7 nmol/L (50.3–58.9 nmol/L) 0.0005* Mean 1,25-(OH)2D level (95% CI)‡ 126.7 pmol/L (115.8–137.6 pmol/L)§ 127.6 pmol/L (114.8–140.4 pmol/L) 0.92* Proportion 25-OHD-deficient (≤ 50 nmol/L) 18% (17/94) 43% (20/47) 0.002† (OR,¶ 3.4; 95% CI, 1.5–7.3) Proportion with 1,25-(OH)2D level below reference range (40–150 pmol/L) 0 (0/84) 4% (2/47) 0.13** (OR,¶ 9.3; 95% CI, 0.4–197.6) * t test. † χ2 test. ‡ DiaSorin radioimmunoassay double antibody assay (DiaSorin Inc, Stillwater, Minn, USA), performed by Queensland Health Pathology Services. § 84 controls; insufficient serum for analysis in 10. ¶ Odds ratio for deficiency in type 1 diabetes mellitus. ** Fisher’s exact test. 25-OHD = 25-hydroxyvitamin D. 1,25-(OH)2D = 1,25-dihydroxyvitamin D.

Ristan M Greer · Meredith A Rogers · Francis G Bowling · Helen M Buntain · Mark Harris · Gary M Leong · Andrew M Cotterill

To the Editor: I read with interest the excellent review article on the metabolic syndrome by Chew et al in the 16 October 2006 issue of the Journal.1 In their article the authors claim there is a lack of data about the relationship between hyperinsulinaemia and changes in free testosterone levels. As part of the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study, an ongoing prospective epidemiological study of 2682 middle-aged Finnish men investigating risk factors for chronic disease, our research group has shown an association between the presence of metabolic syndrome at baseline and a change in sex hormone levels at follow-up after 11 years.2 In our study, men who met the World Health Organization criteria for metabolic syndrome both at baseline and at 11-year follow-up were at 2.6-fold increased risk of developing hypogonadism (serum total testosterone concentration < 11 nmol/L) during the study period compared with men who did not have metabolic syndrome. There was also a non-significant trend for men with metabolic syndrome to develop hypogonadism as defined by calculated free testosterone levels of < 225 pmol/L at 11-year follow-up.2 In the same cohort, we also reported a reverse association — that is, hypogonadism predicting metabolic syndrome.3,4 However, as the question posed by Chew et al was whether hyperinsulinaemia affects free testosterone levels, I examined the KIHD data further for evidence of such an association. I found that subjects grouped in ascending baseline fasting serum insulin quartiles had baseline mean free testosterone levels of 316 pmol/L (SD, 72 pmol/L), 312 pmol/L (SD, 77 pmol/L), 299 pmol/L (SD, 74 pmol/L) and 271 pmol/L (SD, 79 pmol/L), respectively (P < 0.001 for trend). At 11-year follow-up, mean free testosterone levels for subjects in each quartile were 248 pmol/L (SD, 64 pmol/L), 242 pmol/L (SD, 68 pmol/L), 229 pmol/L (SD, 70 pmol/L) and 216 pmol/L (SD, 67 pmol/L), respectively (P < 0.001 for trend). The proportional drop in free testosterone levels over 11 years was approximately the same in each quartile, ranging from 20% to 23%. On the basis of these data, it seems that hyperinsulinaemia is associated not only with a fall in serum total testosterone levels but also with a fall in free testosterone levels in a general population.

Tomi-Pekka Tuomainen

In reply: We thank Tuomainen for his interest in our review article, and for sharing with us his data showing an inverse association between fasting serum insulin levels and calculated serum free testosterone levels. We were cautious in our statement about the relationship between hyperinsulinaemia and free testosterone levels, as there are conflicting data in the literature regarding this,1,2 and few studies that directly measure free or bioavailable testosterone. Moreover, there is ongoing controversy about the calculation of free testosterone levels using total testosterone and sex hormone-binding globulin concentrations, with the validity and assumptions of some of these widely used estimation equations being called into question.3,4 We also echo the concerns of Allan et al5 about the potential pitfalls of diagnosing hypogonadism based on testosterone levels only. As the presence of low total (and even calculated free) testosterone in obese men may not necessarily reflect deficient androgen action, the diagnosis of androgen deficiency should only be made in the context of supportive clinical features. Furthermore, in abdominally obese men with the metabolic syndrome, levels of sex hormone-binding globulin and both total and calculated free testosterone can increase following weight loss,6 thereby obviating the inappropriate use of testosterone supplementation in such patients.

Gerard T Chew · Seng Khee Gan · Gerald F Watts

To the Editor: The recent article by Miller and colleagues regarding adverse drug events (ADEs) in general practice highlights the high frequency and considerable morbidity associated with ADEs in the general community.1 The authors identified recognised side effects, drug sensitivity, and allergy as responsible for most ADEs. The contribution of the patient’s genotype to drug response, via altered metabolism or responsiveness to pharmaceuticals, is increasingly recognised as potentially responsible for a significant proportion of ADEs. The science of determination of the genetic contribution to an individual’s response to drug action is referred to as pharmacogenomics,2 and represents a potentially beneficial diagnostic tool to aid in the prevention of ADEs. Treatment with warfarin, one of the most frequently prescribed drugs in Australia, has been estimated to account for up to15.1% of all severe ADEs, manifest as minor and major bleeding.3 We have recently determined the presence, frequency and laboratory sequelae of genetic variants (single nucleotide polymorphisms) in two genes responsible for the metabolism (cytochrome P450 2C9 [CYP2C9]) and potency (vitamin K epoxide reductase complex, subunit 1 [VKORC1]) of warfarin4 in an Australian population. In our study of 120 patients in an anticoagulation clinic, the frequencies of allelic variants of the CYP2C9 and VKORC1 genes responsible for altered warfarin activity were 31%5 and 59% (unpublished data), respectively, in keeping with previously published studies.4 Detection of these variants was associated with increased induction international normalised ratio (INR) readings compared with controls, and reduced overall warfarin requirements.6 These findings support previous studies,7 and suggest that genotype determination may be of benefit in identification of patients with increased sensitivity to empiric induction phase warfarin dosing schedules. This may allow for a reduction of induction doses of warfarin, decreasing the risk of excessive INR and bleeding sequelae, commonly observed with induction of warfarin treatment. Furthermore these benefits may aid in reduced time to stabilisation. Additional cost–benefit analysis8,9 will enable determination of the economic viability of genotype determination as an adjunct to management of warfarin dosing. The high population frequency of genetic variants associated with warfarin response emphasises the significant contribution genetic factors can play in patient reaction to drugs and highlights their involvement as potential causes of ADEs.

Keith A Byron · Anthony E Dear

To the Editor: V-shaped pillows (“tri-pillows”) may cause suffocation of an infant left to sleep between the two arms of the pillow when he or she slips into the crevice between the arms, or beneath the pillow. The deaths of two infants who died in this manner were reported in South Australia in 1997, and a third death was the subject of a coronial inquiry.1,2 In 1998, the SA State Coroner recommended that “a public warning be issued against the use of tri- or U-shaped pillows by infants under two years of age for sleeping”.2 This message has also been issued in subsequent safe-sleeping campaigns, with a statement in the SIDS and Kids national “Safe sleeping” brochure that “tri-pillows are too soft and can cover baby’s face”, and a statement on the SA Child and Youth Health website that “. . . babies should not be left in these pillows while they are sleeping”.4 Despite these clear messages, deaths continue to occur in SA,5 and V-shaped pillows are still being sold in the foyer of a local obstetric hospital. Although the pillows are being promoted to assist breastfeeding, infants who have been left to sleep on them will be exposed to the risk of suffocation. Deaths of infants in shared sleeping situations may also occur due to suffocation from “overlaying”. However, parents are still being advised by health advice telephone enquiry services to sleep in the same bed with their children. This was the unequivocal message given to one of the authors (G C) when she recently telephoned for advice following the birth of her first child. No mention was made of the potential danger of suffocation if parents are physically large, intoxicated, sedated, or simply exhausted, or if the infant is placed between the parents under bedcovers. It appears, despite clear evidence that certain sleeping situations are potentially dangerous for infants, as well as the widespread dissemination of this information in safe-sleeping literature, that certain organisations or individuals continue to give a contrary message. What hope do parents have of understanding these issues and making informed decisions to optimise the safety of their infant’s sleeping environment if they are exposed to such conflicting messages and advice? Perhaps another question to ask is, “What responsibility do organisations and employees bear if an infant dies as a result of parents following such advice or purchasing equipment such as a V-shaped pillow?”

Roger W Byard · Glenda Cains · Helen Noblet · Maxine Weber

To the editor: Bairnsdale ulcer is known by the eponyms Buruli in Uganda, Kakerifu in Zaire, Kumusi in New Guinea, and was formerly referred to as Searls’ ulcer in Australia. In the original 1948 article describing the causative organism,1 MacCallum and colleagues acknowledged assistance from Drs Alsop, Clay and Searls, in that (alphabetical) order. In sending material to Melbourne for examination, these doctors of the Bairnsdale Clinic described the ulcers, and also commented on the similarity of their appearance in the first three patients. J R Searls, after whom the ulcer was originally named, was regarded as an excellent general practitioner. He died in 1971.

Derek H Meyers

“What’s in a name? That which we call a rose By any other name would smell as sweet.” — William Shakespeare, Romeo and Juliet; II, ii, 1-2; circa 1595 Comment: In 1948, MacCallum and colleagues published an article reporting a new mycobacterial infection in man,1 and later named the causative organism Mycobacterium ulcerans. In their article, they described six patients, five of whom came from the Bairnsdale district in Gippsland, Victoria. Three Bairnsdale general practitioners, Drs Alsop, Clay and Searls, had initially recognised a novel disease in their region and submitted pathological specimens to Melbourne University for diagnosis.2 Subsequently, the same disease was described in many different areas, mostly in Africa (“Buruli ulcer”). Each new outbreak tended to give rise to a new name; of all these, perhaps the most colourful is “Sik belong Sepik”, describing the infection as it occurs along the Sepik River in Papua New Guinea. In Victoria, where most Australian cases of M. ulcerans infection occur,3 we have continued to use the term “Bairnsdale ulcer” even though the main endemic areas are now the Bellarine and Mornington Peninsulas near Melbourne.3 Medical eponyms have a place for diseases that are poorly understood or have unknown causes, but it could be argued that the terms “Bairnsdale ulcer” and “Buruli ulcer” now belong in the annals of medical history. However, there are other considerations. In 1998, the World Health Organization launched the Global Buruli Ulcer Initiative.4 This successful advocacy raised the profile of this neglected disease and facilitated major improvements in diagnosis and treatment. For better or worse, “Buruli ulcer” has become the internationally recognised term for M. ulcerans infection, and we propose that we should now also adopt this name in Australia. While this should come as a relief to the good citizens of Bairnsdale and the Bellarine peninsula, what about those of Buruli in Uganda? Fortunately, their county has been renamed and is now known as the Nakasongola District.5

Paul D R Johnson · John A Hayman

To the Editor: Recent articles in the Journal referred to clinical characteristics of lesions caused by Mycobacterium ulcerans in Australia, and to recommendations and challenges in their management.1-3 Brazil may also be an endemic area of this devastating neglected but treatable disease. In developing countries, cases of Bairnsdale or Buruli ulcer (BU) can be misdiagnosed or underreported because neither the general public nor health care workers have sufficient knowledge about the disease, and because affected people usually have little contact with the health care system, or do not seek prompt treatment.4 Expensive tests like the polymerase chain reaction are not available to confirm all suspicious cases, and smears can give a low diagnostic yield; there are often minimal histopathological changes and absence of bacilli, particularly in patients with long-standing lesions previously treated with effective antimicrobial drugs.4 We report the case of a 65-year-old Brazilian woman with a 2-year history of BU in her extremities coexistent with osteomyelitis in the fourth cervical vertebra (Figure 1), and evidence of inadequate nutrition. Although she had received BCG vaccine as an infant, mycobacteria osteomyelitis developed in the site of an arthrodesis performed in 1998 to treat an accidental fracture.4,5 This patient had lived in a poor riverside rural area with a humid, hot climate. As in descriptions of Australian cases, our patient was much older than the age (5–15 years) at which most cases of M. ulcerans infection are reported in tropical and subtropical regions.1,2,4 Before her disease was characterised through positive cultures for M. ulcerans in samples from skin and bone lesions, the main differential diagnosis was ulcers resulting from fungal infection and leishmaniasis,4 conditions that are frequently seen in the region where she lived. The earlier skin lesions had appeared in May 2004 as papules and nodules, and evolved as painless, chronic, indolent ulcers with undermined edges.2,4 Despite treatment in another hospital that included surgery as well as medical therapy with rifamycin, aminoglycoside and quinolone antibiotics, the disease recurred. On admission to our hospital in August 2006, she had an extensive ulcer on her left arm in addition to scars on the right inner thigh (Figure 2). After nearly 2 months of hospitalisation, the patient was discharged to continue antimicrobial therapy with outpatient follow-up. Despite this, the lesions are healing very slowly. 1: X-ray image of osteomyelitis (arrows) affecting the body of the fourth cervical vertebra. 2: Extensive ulcer on the left arm (arrows; A) and brown pigmented scars on the inner right thigh (B).

Vitorino M dos Santos · Flávio L Noronha · Érica C Vicentina · Camila C Lima

To the Editor: In 2000, the United Nations Millennium Summit produced an agenda for reducing global poverty. It listed eight Millennium Development Goals (MDGs) and was signed by 189 countries. Improving maternal health (with the aim of reducing the maternal mortality ratio by three-quarters between 1990 and 2015) is the fifth and perhaps the core health-related MDG if we consider the centrality of mothers in social development and health.1,2 Globally, the number of maternal deaths remains high at 529 000 per annum.2 Ensuring maternal survival demands functional health care systems with skilled health care workers. However, migration of health care workers (mostly to wealthier English-speaking countries) is a major threat to achieving the MDGs.3-5 Here, I estimate the associations between maternal health and physician migration and human resources for health. I used recently updated physician migration3 and global health workforce data4 to look at correlations between physician migration and two core maternal health indicators — the maternal mortality ratio, and the percentage of births attended by skilled personnel.1,2 I also explored the associations between these maternal health indicators and human health care resources. Migration was measured as the number of physician émigrés working in Australia, the United Kingdom, Canada, and the United States during 1999–2002, per 1000 population of their source countries.5 Physician migration density values for all four countries combined, and for each country individually, were determined (Box). Human health care resources included current densities of health care workers remaining in the source countries (Box). I calculated the Pearson’s correlation coefficients between these variables and the two core maternal MDG indicators. The Box shows that countries with better maternal health are likely to have higher physician migration and more human resources for health care. For example, higher migration to Australia is seen from countries with lower maternal mortality (r = − 0.29; P = 0.011) and more births attended by skilled staff (r = 0.25; P = 0.037). I acknowledge that, like most health system and global health analyses, these correlations are based on an ecological (cross-country) design which does not lend itself to causal inference. These findings are therefore descriptive and require further exploration. Furthermore, the two maternal health indicators used here (which are the core maternal health MDG indicators used by the United Nations) could be viewed as indicators of health system and population health progress. Although physicians and other health care workers play major roles in maternal survival, especially in pregnancy, they cannot be seen as the only requirements for better maternal health. Physicians’ roles can also be substituted by other health care workers in many situations in resource-poor settings. However, less-poor source countries often have higher capacities than poor nations to turn out skilled workers who subsequently migrate. Contrary to conventional wisdom, Australia, the UK, Canada, and the US draw substantially more migrant physicians from countries with higher health care worker capacities. Many countries may be losing physicians just when they should be reaping the benefits of their improving fortune. Given the patchy progress towards achieving the MDGs,1 health care worker shortages may impede many countries’ progress in improving health standards if migration rates exceed workforce replacement in the face of changing but increasingly complex health care needs.1,2,4 Physician migration must be taken seriously if the global target of reducing maternal mortality by three-quarters between 1990 and 2015 is to be realised and sustained. Australia and other Western countries must partner with source countries to develop strong political commitment and scaled-up investments in human resources for health. Correlations between source countries’ core maternal Millennium Development Goal indicators and (A) physician migration to Australia, the United Kingdom, Canada and the United States and (B) human health care resources* Maternal Millennium Development Goal indicators in source countries (A) Physician migration to Australia, the UK, Canada and the US No. of source countries† Mean physician migration density‡ (SD) Maternal mortality ratio¶ P Births attended by skilled health care staff** P Total migration 141 0.094 (0.224) − 0.45 < 0.001 0.34 < 0.001 Migration to Australia 75 0.007 (0.040) − 0.29 0.011 0.25 0.037 Migration to the UK 117 0.017 (0.072) − 0.27 0.003 0.17 0.072 Migration to Canada 116 0.008 (0.027) − 0.47 < 0.001 0.45 < 0.001 Migration to the US 124 0.061 (0.158) − 0.55 < 0.001 0.43 < 0.001 (B) Human health care resources Mean density of health care workers§ (SD) Physicians 141 1.655 (1.426) − 0.84 < 0.001 0.67 < 0.001 Nurses 141 3.636 (3.544) − 0.81 < 0.001 0.72 < 0.001 Public and environmental health care workers 64 0.114 (0.169) − 0.56 < 0.001 0.54 < 0.001 Health management and support workers 71 1.488 (2.222) − 0.73 < 0.001 0.51 < 0.001 * Data are those available for 1999–2002, and each variable was transformed into its natural logarithmic form for analysis. † Top 10 source countries losing physicians (per 1000 population) to the four destinations combined (in decreasing order): Ireland, Saint Lucia, Lebanon, New Zealand, Jamaica, Iceland, Malta, Dominican Republic, Israel, and Cook Islands. Top 10 source countries for Australia: New Zealand, Ireland, Singapore, Fiji, Malta, Sri Lanka, South Africa, Slovakia, Bahrain, and Hungary. Top 10 source countries for the UK: Ireland, Malta, Barbados, Jamaica, New Zealand, Sri Lanka, Libya, Greece, Iraq, and Iceland. Top 10 source countries for Canada: Ireland, Jamaica, Kuwait, Lebanon, South Africa, New Zealand, Barbados, Bahrain, Saudi Arabia, and Iceland. Top 10 source countries for the US: Saint Lucia, Lebanon, Ireland, Iceland, Dominican Republic, Jamaica, Cook Islands, Israel, Belize, and the Philippines. ‡ Number of source country’s physicians working in Australia, the UK, Canada and the US per 1000 source country’s population (based on average year-2000 population). § Number of health care workers remaining in home/source country per 1000 population. ¶ Correlations between the number of maternal deaths per 100 000 live births and (A) physician migration density and (B) human health care resources. ** Correlations between the percentage of births attended by skilled health care staff and (A) physician migration density and (B) human health care resources.

Onyebuchi A Arah

To the Editor: In reference to the letter by Kennedy et al, reporting two patients who tested positive to human T-lymphotropic virus I/II (HTLV-I/HTLV-II) antibodies after administration of the intravenous immunoglobulin, Octagam (Octapharma Australia, Sydney, NSW),1 the Therapeutic Goods Administration (TGA) would submit that: This product was accepted for review by the TGA at a time when plasma products sourced from overseas had to demonstrate superiority over the local product. This requirement was fulfilled by Octagam on grounds that included pathogen safety issues. HTLV-I and HTLV-II are entirely cell-associated viruses and are thus irrelevant to the safety of plasma derivatives. They are in a group of pathogens for which risks, implied by epidemiological factors, apply to cellular but not to plasma products. Another common example is malaria. The Australian plasma pool includes donations from individuals who are at risk of transmitting malaria, so their cells are not used but their plasma is used for fractionation. This situation is well understood and managed by regulators, none of whose standards internationally include the need to test plasma donors for HTLV-I/HTLV-II infection. As the bulk of Australia’s fractionation pool is derived as a by-product of whole blood, blood is tested for HTLV-I/HTLV-II in this country, but it is not a mandatory requirement in Australia or anywhere else. The exclusion of antibody from the plasma pool, as occurs for HTLV-I/HTLV-II in Australia, may actually lead to the loss of potentially protective antibodies, which may well have a therapeutic effect in protecting patients from HTLV-I/HTLV-II infection.2 Such considerations apply, for example, in the requirements of the Food and Drug Administration in the United States for source plasma for fractionation. The requirements take care to allow the inclusion of antibody-positive units for some viruses that would be excluded from blood transfusion. The incident referred to by Kennedy et al was appropriately reported to the TGA’s Adverse Drug Reactions Unit, which concluded that this was not an adverse event. A Northern Territory Government document on HTLV reports: “In Central Australia the prevalence of HTLV-I is estimated to be up to 14%, compared to 4.7% in the Northern Territory cattle country . . .”3 The residual risk of transmission of HTLV-I/HTLV-II infection, while low,4 clearly varies across the potential donor population, and comparisons that are irrelevant in relation to the safety of specific products would appear to be unwise. It is recommended that practitioners seeking to assess causality in putative infectious disease transmission by plasma products follow rigorous scientific processes, such as those recommended by the German regulatory authority.5

Albert Farrugia

To the Editor: Growth charts are important tools in assessing the physical development of infants and children. Understanding and comparing the derivation and applicability of the new World Health Organization Child Growth Standards1 and the Centers for Disease Control and Prevention (CDC) growth charts2 is essential. Arguments for and against the standard use of the new WHO growth charts are being discussed on the basis of differences in study designs used and growth patterns found.3,4 The WHO charts show the growth of breastfed infants on the basis of data from about 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the United States); these children were from selected populations in which no health, environmental or economic constraints on growth existed.1 In contrast, the CDC charts represent the combined growth pattern of artificial-formula-fed and breastfed infants in the United States, where about 50% of infants are never breastfed and only around 33% are breastfed for 3 months or longer.2 Is it possible to misdiagnose breastfed infants who are growing normally as failing to thrive if the CDC growth charts are used? The simplest common definitions used for failure to thrive are a drop below the 3rd or 5th percentile for weight, or when growth deviates from an established growth curve for 3 consecutive months.5 By the CDC growth charts, the normal growth pattern described by the WHO Child Growth Standards for a 15th percentile, breastfed, female infant at 18 months would meet all three definitions of failure to thrive. The clinical response to this perceived failure to thrive may be to provide additional energy in the form of energy-dense foods or supplements (eg, artificial formula). This would at best be unnecessary, and at worst might contribute to the development of overweight and obesity. So, where to from here? We recommend that all health professionals who use growth charts be cognisant of which chart they are using and its application, especially for breastfed infants. There is also a need for Australian national and state governments to debate which growth charts should be used and in what contexts. Finally, irrespective of the choice of growth charts, it must be recognised by practitioners and the general public that these charts are guides only, and should be used as part of a holistic approach to infant growth assessment and management.

Barbara Radcliffe · Jan E Payne · Helen Porteous · Simone G Johnston

To the Editor: Single case reports of “meth mouth”, similar to that recently published in the Journal,1 exaggerate the dental problems surrounding the use of methamphetamines. Evidence that methamphetamines cause grinding and wear of teeth,2 xerostomia,3 and cravings for sweet drinks is weak. The drug use reported by Shetty was intravenous or intranasal, not oral. While systemic effects may contribute to dental problems, local oral effects associated with acidity of methamphetamines would be minimal with intravenous or intranasal drug use. A more plausible explanation for dental disease may be the years of neglect, trauma and poor diet experienced by many people who use drugs.4 Many drug users begin using as early as 14 years of age and consume multiple illegal psychoactive and legal antipsychotic and antidepressant medications associated with xerostomia. A comprehensive drug-use history is required before dental problems are attributed to one drug. Advising treating dentists to avoid the use of analgesics is misinformed and potentially leaves patients in severe pain unnecessarily. People affected by methamphetamines are unlikely to seek dental or medical treatment. A more likely scenario is presentation because of pain between methamphetamine binges, or presentation when they are taking stock of their health problems. At such times, they are unlikely to be affected by methamphetamines, which generally have short half-lives. At these times, non-steroidal anti-inflammatory drugs, nitrous oxides, narcotics (including codeine) or increases in methadone dose may be needed to manage pain. Analgesic depressants are not contraindicated unless other illicit or licit depressants are being used concurrently, as depressants work on different receptors and areas of the brain than amphetamine-type stimulants. Careful discussion with the patient and the patient’s general practitioner or alcohol and drug specialist is critical in balancing the need for pain relief with the potential for drug interactions and even overdose, if the patient is taking other depressants (legal or otherwise). Practitioners can contact a 24-hour drug information line for health professionals for information of this kind in most Australian states and territories (Box). Drug information contact numbers Service Contact number DACAS (VIC) 1800 812 804 DACAS (TAS) 1800 630 093 DACAS (NT) 1800 111 092 DASAS (NSW) 1800 023 687 or (02) 9361 8006 ADIS (SA) 1300 131 340* CAS (WA) 1800 688 847 or (08) 9442 5042 ADIS = Alcohol and Drug Information Service. CAS = Clinical Advisory Service. DACAS = Drug and Alcohol Clinical Advisory Service. DASAS = Drug and Alcohol Specialist Advisory Service. * Clinicians should ask to be put through to the duty doctor service.

Anne-Marie L Laslett · John N Crofts