Letters

Grant A Mackenzie Paediatrician and Postgraduate Student, Ear Health and Education Unit, Menzies School of Health Research, PO Box 41096, Darwin, NT 0811. grantmacATmenzies.edu.au To the Editor: Funding of universal varicella zoster vaccine (VZV) at ages 18 months and 10–13 years was recently announced in Australia. Health professionals should be aware of a number of related issues. Varicella vaccination was recommended in the United States from 1996 for all children aged 12–18 months, with catch-up vaccination to age 13 years. US surveillance shows: Decreased varicella mortality in all age groups except those aged ≥ 50 years (average varicella deaths per year: 145 in 1990–1994 versus 66 in 1999–2001).1 Decreased varicella cases in all age groups, with a non-significant reduction in hospitalisations (average annual hospitalisations in three surveillance regions: 40 before vaccination versus 14 after vaccination).2 US data on herpes zoster have not yet been published. There are concerns that, in the longer term, universal varicella vaccination may increase the incidence of adult varicella and herpes zoster, similar to the effect of pertussis vaccination on adult pertussis. Modelling in the United Kingdom predicted that universal infant vaccination would initially reduce varicella, but would result in increases in herpes zoster 5–10 years later and adult varicella 20–40 years later.3 In contrast, modelling of adolescent vaccination predicted a small decrease in varicella, but no increase in later adult varicella.3 Varicella is generally perceived as a mild illness, while vaccination is largely valued for preventing serious, life-threatening conditions. Anecdotal reports of low levels of private purchase of VZV in Australia suggest it may not be a priority for some families. With 36% of general practitioners concerned about unknown side effects of VZV,4 and public concern about vaccine adverse events in the face of low disease rates, the level of acceptance of universal varicella vaccination by providers and consumers is uncertain. Alternatives to universal varicella vaccination were a high-risk strategy (vaccination of children with chronic illness and family members of high-risk individuals) or waiting until US disease patterns were established. These were real options as: A high-risk strategy may prevent up to 45% of paediatric hospitalisations.5 Hospitalisation and herpes zoster contribute more to health costs than treatment in the community or acute varicella.5 Natural infection, at the cost of disease, immunises most of the population. Any increase in adult varicella and herpes zoster caused by varicella vaccination may be alleviated by booster doses, but the added cost, difficulty in reaching the target population, and potential impact on community confidence in vaccination may be significant problems. The universal varicella vaccination program will test providers’ and consumers’ acceptance of vaccination against what is perceived as a mild illness.

Grant A Mackenzie

Kristine Macartney,* Peter McIntyre† * Senior Research Fellow, † Director, National Centre for Immunisation Research, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145. petermATchw.edu.au Comment: Recently published data have added considerably to the evidence about the impact of varicella vaccination programs, and address many of the concerns raised by Mackenzie. First, in the United States where universal varicella vaccination was recommended a decade ago, recent data show that — despite much slower implementation than is expected in Australia — varicella-related disease has declined by up to 90%, and hospitalisation rates and deaths from varicella by more than two-thirds, due to herd immunity.1,2 Second, data have now been published on the incidence of herpes zoster in areas of sentinel surveillance in the US, showing no change in age-specific rates to 2002.3 Along with the success of a recent trial of high-dose varicella vaccine in reducing herpes zoster in older adults,4 these data add to confidence that any increase in herpes zoster — as predicted in some models — will be detected and effectively combated by vaccinating people aged over 60 years. A substantial allowance for surveillance of both varicella and herpes zoster was included in the 2005 federal budget, to accompany the introduction of universal varicella vaccination in Australia. Mackenzie is correct that varicella is perceived by some as a mild illness, but it is important for general practitioners to emphasise to patients that this is incorrect.5 Each year in Australia, varicella causes around seven to eight deaths and more than 1500 hospitalisations,6 many associated with serious complications, such as invasive bacterial infection, pneumonia, and encephalitis. Although complications are more likely in adults and immunocompromised patients, 42% of hospitalisations are in children aged 0–4 years,6 most of whom are otherwise healthy.7 Patients can also be reassured about the safety of varicella vaccines, as clinical trials now date back 30 years, and more than 40 million doses of vaccine have been distributed in the US. Mackenzie suggests alternatives to universal childhood varicella vaccination, such as vaccination of “high risk” patients and their families, or of adolescents alone. However, these programs would not prevent morbidity among otherwise healthy young children and older age groups, as they would be insufficient to generate herd immunity. Moreover, age-based vaccination strategies have been shown to be easier to implement than more targeted programs. In the absence of a publicly funded universal program, the private market could sustain modest varicella vaccination rates of around 40%–50% in Australia.8 This would increase the number of adolescents and adults susceptible to varicella, because of reduced exposure to the virus and lack of vaccination; these groups also experience greater morbidity with infection than children. A universal program vaccinating young children and adolescents against varicella offers the best current option to reduce morbidity and mortality from this disease in Australia. Ongoing surveillance of varicella and herpes zoster in Australia and elsewhere will reveal whether there is a need for further interventions, such as a second dose of varicella vaccine in children and high-dose varicella vaccine to prevent herpes zoster in older adults.

Kristine Macartney · Peter McIntyre

Adam P Morton Physician, Department of Medicine, Mater Adult Hospital, Raymond Terrace, South Brisbane, QLD 4101. AmortonATmater.org.au To the Editor: The excellent report by Harding et al in the Diagnostic Dilemmas article in the Journal highlighted medications and conditions that may cause false positive results of biochemical tests for phaeochromocytoma.1 Another group of patients, those with obstructive sleep apnoea (OSA), may have raised urine noradrenaline levels in the absence of a phaeochromocytoma. Of about 170 patients seen at a hypertension screening service at the Mater Adult Hospital between 1998 and 2000, six had elevated levels of urine noradrenaline and normetadrenaline up to twice the upper limit of the normal range on repeated testing. Five were obese and were proven to have significant OSA. All required at least three antihypertensive drugs for reasonable control of their blood pressure, and had normal suppression of catecholamines with clonidine. A recent report described a series of five patients with OSA presenting as pseudophaeochromocytoma who had consistently elevated levels of noradrenaline on measurement of 24-hour urinary catecholamine levels; normetadrenaline levels were not measured.2 Noradrenaline levels became normal in all five patients after treatment with continuous positive airway pressure, and blood pressure levels improved significantly. Excess urinary noradrenaline, rather than being adrenal in origin, was thought most likely to be due to increased neuronal release of noradrenaline from small arteries and arterioles as a result of sympathetic nerve activity and synaptic overflow. In conclusion, OSA is an important reversible cause of elevated urine noradrenaline and normetadrenaline levels in patients with resistant hypertension.

Adam P Morton

Stan B Sidhu In reply: We thank Morton for his letter which highlights another group of patients in whom raised urinary noradrenaline levels exist in the absence of a phaeochromocytoma. His experience and our group of patients1 should serve as a note of caution when making the diagnosis of phaeochromocytoma. A combination of positive results of biochemical tests, along with results of anatomical and functional imaging, should serve to minimise false positive diagnoses.

Stan B Sidhu

Raymond W Cook Retired anaesthetist, PO Box 6135, O’Connor, ACT 2602. dcookATactonline.com.au To the Editor: A great deal has been said and written in recent years about inadequate numbers in the medical workforce. As a result, many scientific and political articles about the need to increase the number of medical students and how to train them for the workforce have been written.1,2 Yet there has been little discussion of how those already trained and in the workforce should be retained, or of the rate of attrition of those in the workforce. After 30 years as an anaesthetist, I can recall only one positive change in my conditions of work — the introduction of exhaust gas scavenging. All other changes have been negative: longer hours, greater stress (from multiple factors, such as increased complexity, day surgery and admission on day of surgery) and higher public expectations. My motives in suggesting the need for such research are purely selfish — having recently retired, and enjoying the lack of stress, I wish to be sure there is an adequate workforce in my old age.

Raymond W Cook

Rebecca J Guy,* David E Leslie,† Kleete Simpson,‡ Beth Hatch§ Jennie Leydon,¶ Margaret E Hellard,** Heath A Kelly†† * Epidemiologist, ** Head, Centre for Epidemiology and Population Health Research, Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne, VIC 3001; † Microbiologist, ¶ Senior Serologist, †† Head, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC; ‡ Surveillance Manager, § Partner Notification Officer, Blood Borne Viruses and Sexually Transmissible Infections Program, Department of Human Services, Melbourne, VIC. Rebecca. GuyATburnet.edu.au To the Editor: In Victoria, notifications of infectious syphilis infection (primary, secondary and early latent [< 2 years’ duration]), reported by the Department of Human Services, have increased more than fivefold in the past decade, from 16 in 1995 to 85 in 2004 (Box). An increase in notifications has also been observed in Sydney.1 Whereas previously in Victoria, very few infectious syphilis notifications were reported among men who have sex with men (1 of 16 cases in 1995), in 2004, 63 of a total of 85 cases (74%) were in this group (68% of these were acquired in Victoria). The Victorian Infectious Diseases Reference Laboratory (VIDRL) conducts testing for sexually transmitted infections (STI) and HIV for three Melbourne sexual health clinics with a high proportion of patients who are men who have sex with men. In 2004, 62 male patients tested positive for infectious syphilis, and 40% of these were HIV-positive. This is similar to the situation in Sydney, where in 2003, 54% of infectious syphilis cases were reported among HIV-positive men who have sex with men.1 Syphilis outbreaks among men who have sex with men have been reported elsewhere in recent years. There was an outbreak of syphilis in this group in Greater Manchester; between 1999 and 2002, and 37% of cases were in HIV-positive men.2 In this population, syphilis infection was associated with unprotected oral sex with high numbers of partners, seeking sexual partners at venues (darkrooms, cruising areas and saunas) and use of drugs (GHB [gamma hydroxybutyrate] and poppers [amyl nitrate]).3 A San Fransisco study in 2000, performed in response to a syphilis outbreak among men who have sex with men, reported that meeting sexual partners through use of the Internet was a factor significantly associated with syphilis infection.4 It is likely that some or all of the factors reported in these outbreaks overseas are contributing to the sustained increased in infectious syphilis notifications in Victoria, but it is important to have local data to ensure interventions are targeted appropriately and cost effectively. In Victoria, responses to the increase in syphilis notifications have already included an alert to general practitioners to encourage men who have sex with men to have syphilis testing and individual counselling, and syphilis testing of men who have sex with men at a popular sex-on-premises venue over a 4-week period. Depending on further studies in this population in Victoria, other responses could include enhancing outreach at Internet chat rooms, intensive counselling of HIV-positive men who have sex with men, and education interventions such as peer-led community-based strategies for countering unsafe sex and substance-use behaviours. Finally, it is vital that interventions are multidisciplinary, collaborative and evidence-based. Infectious syphilis notifications by year, Victoria Data from the Notifiable Infectious Diseases Surveillance System Database, Communicable Diseases Section, Victorian Department of Human Services.

Rebecca J Guy · David E Leslie · Kleete Simpson · Beth Hatch · Jennie Leydon · Margaret E Hellard · Heath A Kelly

To the Editor: Lymphogranuloma venereum (LGV) is an uncommon sexually transmitted infection caused by Chlamydia trachomatis serovars L1–3. LGV is not endemic in Australia, and rare Australian cases of LGV have been seen in patients who have either acquired the infection while travelling overseas in an endemic area, or have had local contact with an imported case. Currently, there is an outbreak of LGV in western Europe (in particular, The Netherlands) and the United States.1-4 A case of LGV in an Australian man with no history of overseas travel was managed recently. A 42-year-old bisexual man with previously treated early syphilis and hepatitis C infection presented to a Melbourne hospital in August 2004 complaining of 3 months of tender right inguinal lymphadenopathy. An excisional biopsy showed the formation of necrotising granuloma indicative of LGV. He had no history of penile ulceration, urethritis or proctitis. The surgical wound healed normally. The patient gave a history of attending sex-on-venue premises (“gay saunas”) and “beats”. He reported having oral sex with men, and recently having non-insertive sex involving masturbation with an unknown casual male contact who was apparently an overseas visitor. The patient had a female sexual partner with whom he had irregular, unprotected vaginal intercourse. The diagnosis of LGV was confirmed by polymerase chain reaction (PCR), which detected C. trachomatis, identified as serovar L2 by nucleotide sequencing, from the excised lymph gland. IgG and IgA antibodies to C. trachomatis were demonstrated by enzyme-immunoassay. Tests for other active sexually transmitted infections were negative. The patient was treated with doxycycline (100 mg twice daily for 3 weeks). His asymptomatic female partner was also treated. LGV is endemic in developing countries in our region, but occurs only sporadically in industrialised countries. The first stage of disease consists of a papule or ulcer that may occur on the penis, urethra or cervix. Proctocolitis may also be present, mimicking inflammatory bowel disease. Regional lymphadenopathy develops in the secondary stage of disease when there may be systemic symptoms. Fistula formation at these sites can be prevented by early recognition and treatment. Late, severe genital ulceration is rarely seen. Confirmation of a diagnosis of LGV requires showing C. trachomatis serovars L1–3 by serological tests or PCR on genitourinary specimens. Lymph node resection is not favoured because of the possibility of sinus formation. Prolonged treatment with doxycycline or roxithromycin for 3 weeks is required for affected patients. Asymptomatic contacts are treated with doxycycline for 1 week or a single dose of azithromycin. This case of locally acquired LGV highlights the features of this progressive disease that may now be recognised more frequently in Australian men who have sex with European or North American men. Histological section of the lymph node showing the thickened node capsule and necrotising granuloma Image courtesy of Dr Malcolm Buchanan, Department of Anatomical Pathology, Royal Melbourne Hospital.

Damon P Eisen

To the Editor: A 47-year-old woman presented with a 1-week history of spontaneous prominent and painful bruising and haematomata, 5–6 weeks after commencing meloxicam 15 mg daily for osteoarthritis and plantar fasciitis. The bruises varied in size from 2 cm × 2 cm to 3 cm × 4 cm. She had a past history of acne rosacea, for which she was taking clonidine 100 μg daily, and reflux oesophagitis, for which she was taking pantoprazole 40 mg daily. Meloxicam, being the only new drug taken by the patient, was suspected as the causative agent and was therefore discontinued. Activated partial thromboplastin time (APTT) at presentation was 58 s (reference range, 22 s –38 s). A week after stopping meloxicam, it had fallen to 37 s. All other haematological parameters, including platelet count and international normalised ratio, were normal, as were renal and liver function. New bruises and haematomata stopped appearing 2 days after the patient stopped taking meloxicam. She continued taking clonidine and pantoprazole. Meloxicam is a selective nonsteroidal anti-inflammatory drug (NSAID) (a cyclo-oxygenase 2 [COX-2] inhibitor). It was chosen for this patient in view of her reflux oesophagitis and because she had already been unresponsive clinically to one of the other COX-2 inhibitors. Unlike non-selective NSAIDs, meloxicam has been shown to have negligible effect on platelet function as measured by bleeding time.1-3 Rinder et al4 reported no prolongation of APTT or prothrombin time after 8 days of regular administration of meloxicam at 7.5 mg, 15 mg or 30 mg. In spite of these contrary findings, I believe the prolongation of APTT and spontaneous bruising and haematomata in this patient were directly attributable to meloxicam, as the bruises disappeared 2–3 days after stopping the drug (with no other changes in the patient’s existing medication) and a repeat APTT a week after cessation of the drug was normal.

Anil M Kurien

Diane A Longstreet,* Deanne L Heath,† Robert Vink‡ * Dietitian, † Research Scientist, Townsville Aboriginal and Islander Health Services, 57–59 Gorden Street, Garbutt, QLD 4814; ‡ Head, Department of Pathology, University of Adelaide, SA. dlongstreetATtaihs.net.au To the Editor: Diabetes in Indigenous Australians occurs at a younger age and at almost four times the rate in non-Indigenous Australians. The age-adjusted prevalence of diabetes among Indigenous people is 16% in remote areas and 9% in non-remote areas, with the actual prevalence estimated to be between 20% and 25%, and possibly higher than 30% in some remote areas.1 The cause for this disparity in diabetes incidence is multifactorial, and recent evidence suggests that nutrition — particularly magnesium intake — may play a role. Although central obesity remains a major risk factor, magnesium deficit has been posited to be an underlying common mechanism for the insulin resistance found in type 2 diabetes, as well as in metabolic syndrome, hypertension, and impaired glucose tolerance.2 The clinical correlations between low magnesium and diabetes have been well documented,3 with serum magnesium deficits being reported in 25%–39% of diabetic outpatients in the United States and Switzerland, and up to 73% of diabetic outpatients in Mexico. With magnesium deficits being observed in diabetes, studies examining the effects of magnesium-rich foods on diabetes risk become relevant. The Nurses’ Health Study and the Health Professionals’ Follow-up Study, which included 85 060 women (18 years follow-up) and 42 872 men (12 years follow-up), demonstrated that, after adjusting for confounding variables, a magnesium-rich diet reduced the relative risk of developing diabetes by 34% in women and 33% in men.4 A similar inverse correlation between magnesium intake and diabetes risk was shown in the Iowa Women’s Health Study with a cohort of 35 988 older women,5 and in the Honolulu Heart Program and the Women’s Health Study with cohorts of 8006 men and 39 345 women, respectively.6,7 Despite this growing body of evidence supporting the involvement of magnesium in diabetes, consideration of magnesium status has not been integrated into Australian medical care for diabetes, and more specifically, for Indigenous Australians. It is known that the traditional diet of hunter-gathers such as Indigenous Australians was much more nutrient- and magnesium-rich than the current estimated Australian intake.8 Nonetheless, there remains a lack of information about current magnesium status, including dietary intake, in Indigenous Australians. It is possible that dietary magnesium intake may be too low to maintain normal serum magnesium homoeostasis, and that this might contribute to the development of type 2 diabetes. Further research into this issue may provide this information.

Diane A Longstreet · Deanne L Heath · Robert Vink

To the Editor: The clinical update on venous thromboembolism by Lee and colleagues advises that “Ventilation perfusion (V/Q) isotope scanning reliably establishes the diagnosis of PE [pulmonary embolism] if the V/Q features suggest a high probability of PE . . .”.1 Although this is probably true for patients with intermediate or high pretest probability, a discordant result (low pretest probability and high probability V/Q) should be regarded with suspicion. From the original PIOPED data, high probability V/Q was predictive of angiographically confirmed PE in 80% of patients,2 which drops to 56% by Bayesian analysis if the pretest probability is low. False positive results may be due to previous PE or unrelated parenchymal lung disease. There is significant potential morbidity associated with a false positive result for PE, both from the acute anticoagulation and for future presentations with PE-type symptoms, where PE will be accorded a higher probability because of the previous documented diagnosis. As Lee and colleagues also state, D-dimer testing must be combined with an estimate of pretest probability to be useful. They advocate excluding PE on the basis of low pretest probability and negative D-dimer result. However, a negative D-dimer result (rapid enzyme-linked immunosorbent assay [ELISA] type) may be used to exclude PE in intermediate as well as low probability patients.3 This is dependent on the type of assay available as well as the local PE prevalence, and local guidelines should therefore be developed.

Matthew J Bragg

To the Editor: I read with interest the article by Lee et al regarding the investigation and treatment of pulmonary embolism (PE).1 The investigation of patients presenting with PE as a diagnostic possibility is of great interest to emergency physicians, and such presentations are a daily occurrence in emergency departments around the country. Unfortunately, only a small amount of text is devoted to describing the relative merits of ventilation perfusion (V/Q) scanning and computed tomography pulmonary angiography (CTPA), and no guidance is provided as to which is the test of choice when both are available. The British Thoracic Society has recommended CTPA as the lung imaging modality of first choice for patients presenting with non-massive PE.2 There is a large and increasing body of evidence that CTPA provides superior specificity to V/Q scanning in the detection of PE. CTPA also provides the opportunity of establishing diagnoses other than PE and, in addition, a negative multi-slice CTPA is of sufficient sensitivity to enable the withholding of anticoagulation.3 It is also my experience that CTPA is easier to obtain out of hours, compared with V/Q scanning. The authors state that V/Q scanning “reliably establishes the diagnosis of PE if the V/Q scan features suggest a high probability of PE . . .”.1 Unfortunately, this statement is incorrect. It is essential that V/Q scan results be interpreted in the light of the patient’s clinical probability for PE. In the PIOPED study, only 56% of patients with high probability V/Q scan reports had pulmonary embolism if the pretest probability was low.4 No mention is made of the special situation of pregnant women presenting with pleuritic pain, or which lung imaging test is considered “safest” for both mother and baby. Although the risks of PE are generally agreed to be increased in pregnancy, it is my experience that pregnant women are extremely reluctant to undergo any form of diagnostic investigation that exposes the fetus to radiation. The Wells criteria have been validated for the assessment of PE in emergency department patients only, and provide a means for clinicians with little experience to make an accurate assessment of an individual patient’s clinical probability of PE.5 Once initiated, clinical assessment of the patient with possible PE is straightforward. The key question facing emergency physicians is this: is there a group of patients that have such low probability for PE that no investigation at all is required?

Paul M Bailey

John W Eikelboom,* Graeme J Hankey,† Wai Khoon Ho,‡ Cindy H Lee§ * Haematologist, Thrombosis Service, McMaster University, HHS General Divison, 237 Barton Street East, Hamilton, ON L8L2X2, Canada; † Neurologist, ‡ Fellow in Haematology, § Senior Registrar in Haematology, Royal Perth Hospital, Perth, WA. eikelbj@mcmaster.ca In reply: Pulmonary embolism (PE) remains a complex diagnosis despite the availability of validated prediction models and D-dimer testing to direct the need for diagnostic imaging. We agree with Bailey that the ability to exclude the diagnosis of PE on clinical grounds in patients with a low pretest probability is highly desirable. Unfortunately, clinical features lack sensitivity and specificity for the diagnosis of PE, and clinical prediction models, laboratory investigations, and diagnostic imaging are likely to remain an integral part of the clinical work-up. As suggested by Bragg, it may be possible to simplify the diagnostic approach by using a highly sensitive D-dimer assay, and simplified pretest probability models have been proposed. However, this may come at a cost of reduced specificity,1 which leads to unnecessary diagnostic imaging studies and thus limits the clinical utility of these approaches. Further improvements in the diagnostic approach to PE are clearly needed. There are emerging data demonstrating the accuracy of computed tomography pulmonary angiography (CTPA) for the diagnosis of PE. However, CTPA has limitations (a large contrast load, high radiation dose, and lack of sensitivity of first generation scanners for small thrombi2), some of which are evident in the recently published validation study referred to by Bailey:3 25% of screened patients with suspected PE were not eligible for this study because of renal impairment, a contraindication to CT, or other reasons. The diagnostic algorithm that we provided in our review suggests that either ventilation perfusion (V/Q) scanning or CTPA can be used for patients with suspected PE who require diagnostic imaging,2 with the choice determined by patient factors and availability. The diagnosis of PE during pregnancy is challenging because of concerns about radiation exposure and uncertainty about whether CTPA or V/Q delivers more radiation to the fetus.4 Furthermore, clinical decision rules have not been validated in pregnancy. However, recommendations from experts and professional bodies suggest that V/Q scanning can be used in combination with compression ultrasound to establish or exclude the diagnosis of PE during pregnancy in most cases with minimal fetal radiation exposure.5,6 The comments by Bailey and Bragg concerning the interpretation of high probability V/Q scan results highlight the pitfalls of performing diagnostic imaging without considering the patient’s pretest probability of PE. Although a high probability V/Q scan is diagnostic in patients with a moderate or high pretest probability of PE (prevalence of disease ≥ 90%), the prevalence of disease is only about 50% in those with a low pretest probability.7,8 Therefore, V/Q scanning should not be performed in patients with a low pretest probability unless the D-dimer test is positive. In this situation the algorithm for moderate or high pretest probability should be followed,2 and a high probability scan reliably establishes the diagnosis.

John W Eikelboom · Graeme J Hankey · Wai Khoon Ho · Cindy H Lee

Richard F O’Reilly,* Ian A Burgess,† Bernard Zicat‡ * Physician, † Radiologist, ‡ Orthopaedic Surgeon, Mater Misericordiae Hospital, Rocklands Road, North Sydney, NSW 2060. roreillyATbigpond.net.au To the Editor: In a recent editorial, Gallus estimates the cost of doing ultrasonography in all patients after unilateral hip or knee replacement, with further testing in the 9% or 26% of patients, respectively, found to have deep vein thrombosis (DVT), to be about $200 000 per 1000 patients.1 We agree. He then states, “Many would argue that extended prophylaxis is likely to be the simplest, cheapest and perhaps safest solution”. However, prophylaxis is also expensive. Subcutaneous enoxaparin 40 mg administered daily for 30 days costs $170, or $170 000 per 1000 patients.2 In our study, we found DVTs in 1086 of 5999 patients (18.1%) before discharge,3 so that extended prophylaxis would involve 81.9% of patients receiving prophylactic doses of anticoagulants, with the risk of unwanted bleeding, despite the absence of DVT on ultrasound at Day 7 postoperatively. In addition, if an ultrasound scan was not done before discharge, the 18.1% of patients with a DVT would receive only prophylactic (not therapeutic) doses of anticoagulant for their DVT. We plan a further study to check the prevalence of post-discharge DVT by repeating ultrasonography at 90 days postoperatively in patients without DVT on ultrasound at Day 7. We suspect the prevalence is lower than suggested in the literature, as the data on late presentation of DVTs have been obtained by retrospective study of the number of patients re-admitted to hospital with DVT. Finally, on the question of whether performing ultrasonography on all patients has clinical benefit, we concur with Gallus when he writes that “Logic suggests it should . . .”.

Richard F O’Reilly · Ian A Burgess · Bernard Zicat

In reply: O’Reilly and colleagues belatedly address the need to consider bleeding risk and costs when choosing between management routines designed to prevent venous thrombosis and pulmonary embolism. Their otherwise valuable article1 failed to record bleeding rates when patients (almost 17%) with subclinical calf-vein thrombosis were exposed to therapeutic (not prophylactic) anticoagulant dosages. Nor did they evaluate the dollar and manpower costs of their complex management routines. Present evidence-based international guidelines from the Seventh ACCP (American College of Chest Physicians) Conference on Antithrombotic and Thrombolytic Therapy recommend effective prophylaxis for at least 10 days in all patients having hip or knee replacement, extending to 28–35 days after hip replacement.2 The ACCP guidelines also recommend against routine use of ultrasound screening because it is “neither clinically effective nor cost effective”.2 This is a Grade 1A recommendation from the ACCP (“Grade 1” implies certainty “that the benefits do, or do not, outweigh the risks, burdens, and costs”; “Grade A” refers to recommendations based on “randomized clinical trials with consistent results [that] provide evidence with a low likelihood of bias”).3 To reverse this recommendation would require randomised comparisons between routine prophylaxis alone or routine prophylaxis supplemented by screening ultrasonography — powered to permit meaningful measures, in both groups, of thromboembolism rates, bleeding rates and costs. Routinely screening for subclinical thrombosis after major joint surgery should not be done outside suitably designed clinical trials until such evidence is available. The role of logic in medicine is to generate hypotheses, which must then be tested by clinical trial. Unfortunately, evidence derived from uncontrolled cohort studies remains limited to Grade C (based on “observational studies or [on] generalization from one group of patients included in randomized trials to a different, but somewhat similar, group of patients”).3

Alexander S Gallus

Ian Hamilton-Craig Chairman, MEDPED-FH Australia, North Adelaide Heart Centre, 80 Brougham Place, North Adelaide SA 5006. IhcATsahc.com.au To the Editor: In their editorial, Burnett and colleagues correctly emphasise the importance and cost-effectiveness of cascade family screening in the early diagnosis of familial hypercholesterolaemia (FH) among relatives of known cases. They point out that Australia does not have “a national program for detecting the vast majority of patients with FH in our community . . .”.1 Such an approach has been advocated since the 1980s by the international MEDPED-FH project, initiated in Utah to raise public and professional awareness of the need to detect and treat FH at an early age (MEDPED-FH stands for Make Early Diagnosis to Prevent Early Deaths in Familial Hypercholesterolaemia).2 Since then, the project has spread to over 30 countries, including Australia, and has over 25 000 patients with FH registered worldwide.3 In Australia, the MEDPED-FH program has registered about 700 patients with FH, about 2% of the estimated 33 000 patients overall.4 This proportion is similar to registrations in many other countries (including the US). Only the Netherlands, Denmark and Finland, where government-financed screening programs are in place, have higher proportions of registrations, with 10%–50% of patients with FH registered with MEDPED-FH. Also, in these countries, DNA detection of low-density lipoprotein cholesterol receptor gene mutations is used routinely for the diagnosis of FH. At present in Australia, nurse practitioners are performing FH cascade screening in collaboration with MEDPED-FH physicians in each capital city, supported by Pfizer Australia. Further work on FH is being carried out by Associate Professor David Sullivan and colleagues in Sydney, supported by the Western and Central Sydney Area Health Services. In addition, the Cardiac Society of Australia and New Zealand has established a working party to investigate cardiac genetic disorders, including FH, and is involved in further education among cardiologists regarding screening, diagnosis and treatment of FH. But these efforts are not enough. I support Burnett and colleagues in recommending the establishment of a nationwide screening program for FH, and also recommend that DNA diagnosis be incorporated as an essential component. There is a definite cost benefit of early detection and treatment with statins of patients with FH.

Ian Hamilton-Craig

John R Burnett,* David Ravine,† Frank M van Bockxmeer,‡ Gerald F Watts§ * Medical Biochemist, Department of Core Clinical Pathology and Biochemistry [corresponding author]; † Medical Geneticist, Medical Genetics Unit; ‡ Director, Cardiovascular Genetics Laboratory; § Physician, Department of Internal Medicine, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847. john.burnettAThealth.wa.gov.au In reply: The international MEDPED-FH project has made a major contribution towards introducing family-based cascade screening into the Australian health care system. Although these achievements are important, we agree with Hamilton-Craig’s view that they are dwarfed by the magnitude of what now has to be done to deliver to all at-risk relatives the health gains that can be achieved by a proactive program of population screening. The risk of familial hypercholesterolaemia (FH) for a first-degree relative of an affected index case is 250 times greater than the risk for a member of the general population. The relative cost-efficiency of family-based cascade genetic screening is high, compared with population-wide screening for a dominantly inherited disorder.1,2 We disagree with Hamilton-Craig that DNA diagnosis is an essential component of an effective screening program. Among FH-affected families, biochemical testing has a sensitivity of 95%, and a specificity of 96%.3 The additional diagnostic gain from DNA testing in the context of screening relatives at 50% prior risk is marginal, although of use in determining with certainty whether or not a relative has inherited the family-specific trait. FH offers a paradigm of best clinical practice for improving health care outcomes for a widening range of “monogenic” disorders with complications that can be avoided or reduced by focused health care provision. The time has come when physicians, cardiologists, paediatricians, biochemists, geneticists, public health physicians, general practitioners and those administering the funding of health care delivery in Australia come together and formulate the changes necessary to allow cascade genetic screening for FH to become part of routine health care.

John R Burnett · David Ravine · Frank M van Bockxmeer · Gerald F Watts

Caroline F Finch Director, New South Wales Injury Risk Management Research Centre, University of New South Wales, Level 8, Applied Science Building, Sydney, NSW 2052. c.finchATunsw.edu.au To the Editor: I am prompted to write to you in response to a recent MJA editorial.1 It amazes me that the health sector in Australia, as I think the editorial did, continues to largely ignore the magnitude of the problem of injury in our children. This is despite clear evidence of the excess ill-health burden that injury places on our children, according to the Australian Institute of Health and Welfare (AIHW) report (the subject of the editorial)2 and other reports.3-5 Having said this, the editorial did highlight a very pleasing trend — there has been a steady decline in injury deaths in later childhood. Unfortunately, however, this was the only mention of injury in the editorial, and readers could be forgiven for thinking that this is the end of the story: the injury death rate is declining; therefore, we are doing all we can, and injuries are not a major issue. Nothing could be further from the truth. Our children continue to die from road and drowning accidents and will do so until injury prevention is recognised as paramount. The AIHW report clearly states that the single highest cause of death in children remains injury and poisoning.2 Accordingly, trauma is the single highest contributor to premature mortality and years of potential life lost of any health condition in Australia. If we don’t develop new approaches to reducing the incidence of drownings and road deaths, in particular, we will not see further declines in injury-related death rates, and injury will continue to rate highly as a killer of young people. Importantly, injuries do not only kill young people — they also hospitalise and maim them. The second most common reason for hospitalisation in Australian children is injury.2 Unlike injury deaths, there has been no trend in the rate of hospitalisation for injury. Across age groups, there appears to be a shift from fatalities to an increasing number of people with a high lifetime burden of significant disability, including brain and spinal cord damage. Imagine what this does to the quality of life and life expectancy of a child. How many of these children will be able to lead physically active lives? It is time for the health sector, particularly public health agencies, to properly recognise injury as a critical issue for the ongoing health of Australian children and to formally commit to appropriate preventive actions, commensurate with the priority ranking of childhood injuries.

Caroline F Finch

George C Patton,* Sharon R Goldfeld,† Indrani Pieris-Caldwell,‡ Meredith Bryant,§ Graham V Vimpani¶ * VicHealth Professor of Adolescent Health Research, Centre for Adolescent Health, Murdoch Childrens Research Institute, Flemington Road, Parkville, Melbourne, VIC 3052; † Paediatrician and Research Fellow, Royal Children’s Hospital, Melbourne; ‡ Senior Analyst, § Project Officer, Australian Institute of Health and Welfare, Canberra; ¶ Clinical Chair in Paediatrics, University of Newcastle, NSW. george.pattonATrch.org.au In reply: There is little to disagree with in this excellent summary of injury morbidity and mortality in Australian children. However, the principal point of our editorial1 was to highlight important problems where adequate data are currently unavailable. The Australian Institute of Health and Welfare report was able to give extensive coverage to injuries and accidents in children.2 Indeed, seven indicators specifically addressed aspects of childhood injury, with a range of others (eg, child abuse and neglect, neighbourhood safety) addressing relevant aspects of the family and social context. This emphasis reflected not only the importance of childhood injury, but the extent to which reasonably good data are available. We agree that, despite some favourable mortality trends, the burden of childhood injury remains high, as are associated health care costs. However, childhood injury is an area where advocacy has translated into action.3 One of the reasons for the success of that advocacy has been the availability of sound data, both to make the case and to ensure an appropriate focus in policy responses.4 While there is undeniably much more to do, we can learn much from injury prevention about how to tackle the newly emerging problems of childhood.

George C Patton · Sharon R Goldfeld · Indrani Pieris-Caldwell · Meredith Bryant · Graham V Vimpani

Sandy L A Reid Professor, School of Rural Health, University of New South Wales, PO Box 5695, Wagga Wagga, NSW 2650. s.reidATunsw.edu.au To the Editor: Reilly et al draw attention to the lack of research on the impact of the findings of physical examination on patient care, and state that, in the United States, many doctors “do not know how to do it, and do not see why they should”.1 Should we continue to teach these skills in Australia? Experience tells us, even if research does not, that the presence or absence of one or more physical findings may make a crucial difference to patient care. The important thing for teachers is that, while students learn the rituals, we should encourage them to think critically about what they are doing. They focus on passing the next objective structured clinical examination (OSCE), which often requires them to carry out a ritual. They are vaguely aware they will be required to think selectively about real patients and the necessity to make a diagnosis, but have little practice in selecting appropriate physical examination. We who teach them should formally recognise the distinction between ability to perform and ability to choose and interpret physical signs. I learned an inductive process: take a history and perform a complete examination, and then engage the brain. Research would not tolerate such a “fishing trip”! The inductive method has been replaced by a hypothetico-deductive approach. This is criticised, but all doctors take intelligently selected short cuts. We should acknowledge this and critically examine the skill. Students must learn systematic examination. This is the repertoire from which they choose when faced with a clinical problem. OSCEs early in the undergraduate course should assess their competence in this, and students should know exactly what they are to do. Our bedside clinical teaching and later OSCEs should explicitly challenge students to consider the selection of relevant clinical examination required in the light of the history, just as they should consider the value of all other tests, rather than using a blunderbuss approach. Together, history and physical examination have two objectives. One is diagnosis; the other defines or excludes comorbidity. Without them, medical care cannot begin to function effectively or economically. Neither I nor your authors are bewitched; their anecdotes make this clear, and they define the reasons for the lack of research. A focus on considering what can, and cannot, be gained by selective physical examination should reduce our own and our students’ bother and bewilderment.

Sandy L A Reid

To the Editor: One of the great privileges in practising obstetric medicine is to support a couple through a successful confinement when they have previously been advised against attempting pregnancy because of pre-existing maternal disease. However, in some cases, pregnancy carries a substantial risk of morbidity and mortality to both the mother and infant. Indeed, many maternal deaths in Australia are still preventable,1 and underlying cardiac disease is an important cause.2 Recently, I was consulted for preconception counselling by a young woman with dilated cardiomyopathy. Based on the limited evidence in the literature, her risk of dying as a result of pregnancy would be greater than 25%.3 Similarly, I was recently involved in the care of a young woman with Eisenmenger syndrome who elected to terminate her pregnancy due to the 50% mortality associated with pregnancy with this condition.4 Pregnancy in young women with moderate renal failure carries a significant risk of permanent decline in renal function, along with a high risk of intrauterine growth retardation and prematurity for the baby.5 Organ transplantation offers the best hope for women in this situation, as pregnancy outcomes are excellent after solid organ transplantation (with the exception of lung transplantation). However, many women have organ dysfunction severe enough to compromise pregnancy outcome, but not to warrant transplantation.6 Pregnancy in the presence of maternal disease may also pose a substantial cost to the community. A 2001 study in the United Kingdom estimated the mean cost of pregnancy care for five mothers with severe cardiac disease to be £23 000, not including the cost of neonatal care.7 One mother and one baby died. Options for couples with pre-existing maternal disease are limited. In Queensland, they are excluded from adopting a child because they are not infertile and because of the mother’s medical condition. Altruistic surrogacy would allow them to have a child that is genetically their own without risking the mother’s and infant’s health. However, legislation on surrogacy varies significantly between Australian jurisdictions (Box),8 and, in Queensland, all surrogacy arrangements — both commercial and altruistic — are illegal. Thus, my patient with dilated cardiomyopathy faces prosecution if she were to attempt surrogacy anywhere in Australia while a Queensland resident, whereas it would be freely available to her if she moved 80 km south and became a New South Wales resident. I believe altruistic surrogacy should be available for women in whom underlying medical conditions result in a significant risk of morbidity or mortality associated with pregnancy. Legislation on surrogacy arrangements in Australia* Queensland: The Surrogate Parenthood Act 1988 (Qld) makes all arrangements relating to surrogacy illegal in Queensland, imposing criminal penalties on all parties involved in both altruistic and commercial surrogacy arrangements. Tasmania: The Surrogacy Contracts Act 1993 (Tas) makes it an offence to make or receive a payment or to publish any advertisement in relation to a surrogacy contract. All surrogacy contracts are void and unenforceable. South Australia: The Family Relationships Act 1975 (SA) makes it an offence to enter into a surrogacy contract for valuable consideration, and contracts are illegal and void. Australian Capital Territory: The Parentage Act 2004 (ACT) does not prohibit non-commercial surrogacy, provided no advertising or intermediaries are involved, and payments to cover expenses are allowed. Victoria: The Infertility Treatment Act 1995 (Vic) prohibits commercial surrogacy, and has complex criteria regarding eligibility of surrogate mothers. * New South Wales, Western Australia and the Northern Territory do not have surrogacy legislation.

Adam P Morton

Comment: Morton feels that women for whom pregnancy poses a substantial risk should be offered altruistic surrogacy, so that they can still have a child that is genetically their own. The suggestion is commendable but opens a hornets’ nest. First, “genetic ownership” is a bit of a fiction at best, given that the only item genetically owned by the mother is an egg with 23 chromosomes and some cytoplasm. Admittedly, Morton refers to couples rather than to women, but few are the men who have incontrovertible evidence of any genetic stake in their alleged offspring,1 and, given the rate with which partnerships change, thousands willingly care for children in whom they know they have no genetic stake at all. After implantation of the fertilised embryo, the carrier of the pregnancy owns whatever there is to be owned, irrespective of where some of the genes came from. At birth, genetic ownership changes again, and the child becomes its own “genetic owner”. So, how much “genetic ownership” of a child can there be? Second, who would qualify for altruistic surrogacy? It seems reasonable that women with Eisenmenger syndrome should not embark on a pregnancy given the high mortality associated with it. But how do we know that collecting ova and all it entails, and the subsequent years caring for a baby/toddler/child/teenager, would not be an even greater challenge to the woman’s health than pregnancy? Third, where will these surrogates come from (especially for women without sisters or other suitable family volunteers), and how do we ensure that they will be happy to hand back the child to its “genetic owners”? How will we protect these altruistic women in subsequent years against potential law suits for alleged failures in duty of care to the child that they carried (for example, by exposure to toxins during the pregnancy)? Fourth, is there not a far easier and more logical solution to this problem, provided that egg collection does not endanger the woman’s health? Why not preserve the woman and her partner’s frozen embryos until the woman’s medical condition is sufficiently stable to both sustain a pregnancy and care for the child that hopefully results from it? If the woman’s health cannot be restored sufficiently to achieve this, these couples could then show some altruism of their own by donating the embryos to infertile couples who desperately want a child irrespective of whether they can claim “genetic ownership”. Thus far, there is little evidence that altruistic donation and genetic ownership are even half way to meeting each other.2 However, Morton should be commended for drawing attention to a national problem in women’s health. The disparities and discrepancies between the Australian states and territories in almost anything that relates to reproduction2-5 is an utter disgrace. Reproductive health should be equitable among all Australians.

Marc J N C Keirse

To the Editor: Osteonecrosis of the jaw, recently reported in patients treated with bisphosphonates, may be analogous to the historic occupational disease “phossy jaw”.1,2 Phossy jaw was osteonecrosis of the jaw caused by exposure to white phosphorus during the manufacture of matches. “Lucifer” strike-anywhere matches were first produced in 1833. They were made by dipping the match ends into a mixture containing white phosphorus.3 Workers were exposed to fumes from the white phosphorus during mixing and spreading of the dip material, and dipping, drying and boxing of the matches.3,4 The first case series, comprising 22 cases, was reported in Vienna in 1845.5 About 11% of those exposed developed the disease.5 The average period from first exposure to diagnosis was 5 years.4,5 Occasionally, this period was as short as a few months.5 The mandible and maxilla could be affected, the mandible in 60% of cases (Box).3 Dental decay was considered a prerequisite, and preventive measures included dental surveillance and treatment within the factories.4 In that pre-antibiotic era, phossy jaw was fatal in about 20% of cases, usually because of septicaemia or meningitis.5 Donald Hunter, British doyen of occupational medicine, commented: “It was the most distressing of all the occupational diseases because it was very painful and was accompanied by a foul fetid discharge that made its victims almost unendurable to others. It was obstinate and chronic, the treatment was agonising and the final result was a distressing disfigurement. It was this disfiguring effect plain to every observer that made phosphorus poisoning so notorious and led to determined efforts for its abolition in every civilised land.”5 In 1906, several European countries banned the manufacture and importation of white phosphorus matches at the Berne Convention.4,5 A safe substitute, sesquisulfide, had been discovered by a French chemist and successfully used for manufacture of strike-anywhere matches in 1898.4,6 In the United States, John Andrews published a report in 1910 of 150 cases of phossy jaw from 15 of 16 match factories then in operation.4,6 The Diamond Match Company, which held the American patent rights for sesquisulfide, waived their rights, thereby allowing the entire US match industry to use this alternative.6 Congress then passed the Esch law, which imposed a prohibitive tax on white phosphorus matches and banned their import and export.4,6 Eventually safety matches were developed that used amorphous red phosphorus, which did not have the toxic properties of white phosphorus.5 Phosphorus necrosis of the jaw A Deformity resulting from excision of entire lower jaw in a case of phosphorus necrosis. (Case of Dr John P. Andrews, The Occupational Diseases, W Gilman Thompson, D Appleton & Co, New York, 1914). B Phosphorus necrosis of entire lower jaw excised by Mr McCarthy in 1884 (London Hospital Medical College Museum).

A Michael Donoghue

Peter W Holmes,* David Armstrong,† Nicholas Freezer‡ * Deputy Director, Adult Respiratory Medicine, † Director, Paediatric Cystic Fibrosis Unit, ‡ Director, Adult and Paediatric Respiratory Medicine, Department of Respiratory and Sleep Medicine, Monash Medical Centre, Locked Bag 29, Clayton, VIC 3168. peter.holmesATsouthernhealth.org.au To the Editor: We congratulate Lam et al1 for identifying the major problems in transferring adolescents from the Royal Children’s Hospital, Melbourne, to adult care. The article and the accompanying editorial2 address a difficult problem relating to the transfer of adolescent patients from a stand-alone paediatric hospital to adult services. Lam et al conclude that there needs to be a change of attitude among adult physicians, and recommend the provision of additional resources to enhance the smooth transition to adult care. As long as paediatric services remain geographically separated from their adult counterparts in stand-alone hospitals, these problems will continue, regardless of any increase in resources. In New South Wales, tertiary paediatric services have now been incorporated onto the same campus as tertiary adult hospitals in shared-site arrangements. This facilitates the transition process, as adult physicians are more closely linked to their paediatric colleagues via shared clinical and research infrastructures. Such close cooperation allows paediatric and adult physicians to share their care during transition and provides the adult physicians with full access to the patients’ medical records and radiology, microbiology, laboratory and pulmonary function data. At Monash Medical Centre, we have taken this further by totally incorporating our adult and paediatric services into one single Department of Respiratory and Sleep Medicine. This arrangement allows an integrated approach to childhood, adolescent and adult care. The combination of services generates trust between all members of staff (an issue raised in the editorial2) and gives adult physicians a greater understanding of the needs of adolescents with complex health problems. One solution to the difficult problem of transition to adult care is to phase out stand-alone paediatric services with their own costly management infrastructure. A shared campus arrangement allows greater integration of the full range of tertiary paediatric and adult services and offers many advantages in providing a seamless transition to adult care.

Peter W Holmes · David Armstrong · Nicholas Freezer

Robert D Henderson,* Pamela A McCombe* * Neurologist, Royal Brisbane and Women’s Hospital, Herston Road, Herston, QLD 4029. Robert_HendersonAThealth.qld.gov.au To the Editor: We read with interest the recent article by Kiernan.1 Many patients with motor neurone disease (MND) are also taking complementary therapies, with the potential for drug interaction with riluzole. A recent patient highlighted this. A man in his 50s with progressive MND commenced riluzole at the time of diagnosis. Initial liver function tests performed after starting the drug gave normal results. Eight months later, with disease progression, he began taking low-dose naltrexone 50 mg dissolved in 50 mL of water, of which he took 4 mL a day. Three months later, he began to feel nauseous, with debilitating lethargy, and developed jaundice. Liver function tests showed: alanine aminotransferase level, 3030 U/L; and asparate aminotransferase level, 2074 U/L. On stopping taking both drugs, his symptoms resolved and the liver function test results gradually became normal. No other contributing cause for the hepatotoxicity was found. From the temporal profile, the hepatotoxicity in our patient was possibly due to the combination of riluzole and naltrexone, although either drug alone could be implicated, or there may have been another mechanism. Riluzole is predominantly metabolised by cytochrome P450 enzymes (CYP1A2), but there is considerable patient variability, and the hepatotoxicity mechanism is largely unknown2 (see also MIMS Online: http://www.mims.hcn.net.au). In recent months, low-dose naltrexone has become popular with patients who have MND, although there are no published data of efficacy. Hepatotoxicity caused by naltrexone is dose-dependent and uncommon.3 Naltrexone is metabolised by glucuronidation in the liver to an active metabolite, but a direct interaction with riluzole through cytochrome P450 enzymes appears unlikely.4 There have been no clinical studies to evaluate interactions with other drugs of either riluzole or naltrexone (apart from opiates).3 This case highlighted for us that patients may be taking other therapies for MND, and that clinicians should be aware of the possibility of serious drug interactions when riluzole is prescribed.

Robert D Henderson · Pamela A McCombe

In reply: Henderson and McCombe describe a patient to highlight an issue raised in a recent editorial:1 that patients with motor neurone disease (MND) may develop abnormal liver function tests for reasons other than riluzole therapy. In their patient, riluzole was prescribed for a year and liver function test results remained stable. Deterioration in liver function coincided with the introduction of naltrexone. Ultimately, riluzole, an established MND therapy, had to be ceased. Naltrexone is an authority medication, prescribed in the setting of alcohol or opioid dependence. MEDLINE searches failed to find any study or indication for naltrexone in the treatment of MND. An internet search, however, revealed a number of personal anecdotes, with a curiously Australian emphasis, suggesting an immuno-modulatory role for naltrexone in MND. A few further clicks of the mouse and the naltrexone ordering site with costings appeared. Patients with incurable diseases commonly seek “alternative” treatments2 at great personal financial cost, calculated at thousands of dollars per patient with MND.3 Often there is insufficient, or, as with naltrexone, no evidence that these treatments are effective.4 Most patients with MND will consider alternative therapy, irrespective of their educational background5 or understanding of disease pathophysiology. How each physician approaches the use of complementary and alternative therapies by their patients may develop into an important issue in the therapeutic relationship. Certainly, being aware of the possibility may prove critical. In the patient described by Henderson and McCombe, an unfortunate outcome of irreversible liver failure in a patient with NMD was averted through conventional monitoring of liver function.

Matthew C Kiernan