Letters

In reply: We welcome Brown's observations. However, with regard to orthopaedic surgeons, we are unaware of any correlation between affability and ability.

Lachlan Brown MB BS, FRACGP

To the Editor: The recent article by Chapman et al1 and a case report published some years previously in the Journal2 indicated that hyponatraemia may occur during indapamide therapy. However, it should be noted that the data came from spontaneous adverse drug reaction reporting, and therefore can give no indication of the incidence or relative risk of hyponatraemia compared with other diuretics. Nor can it give the incidence of hyponatraemia as a proportion of side effects occurring during indapamide therapy. The presentation of these data appears to cause some confusion, including an interpretation that hyponatraemia was more common with indapamide therapy than other diuretics.3 However, adverse events may be more likely to be reported for drugs which are usually well tolerated. Hyponatraemia led to discontinuation of therapy in only eight out of 3000 patients in the PROGRESS study.3,4 Previous controlled studies of indapamide (2.5 mg or sustained-release 1.5 mg daily) have found no significant overall changes in serum sodium levels.3 Hyponatraemia associated with indapamide therapy may occur with a recommended dose of 2.5 mg, which does not have a significant diuretic effect. Indapamide appears to be useful for treating central diabetes insipidus, raising the possibility that hyponatraemia occurs because of an inappropriate antidiuretic hormone secretion syndrome.6 Indapamide-related hyponatraemia may be more common in elderly women,1 as is the case for hyponatraemia associated with selective serotonin reuptake inhibitors. Hyponatraemia associated with indapamide therapy appears to be sporadic and uncommon and may be avoided by appropriate monitoring of serum electrolyte levels.

Laurence G Howes · John McEwen · John E Marley

To the Editor: I was impressed by the article on the seven deadly genes in a recent issue of the Journal.1 Your readers may also be interested to learn that we have recently discovered an entire family of antisocial recessive genes in colleagues and patients. 2 These include the stalk-r gene (not only in patients who stalk doctors, but also in doctors who molest their patients3) and the hum-r gene for socially inappropriate comicality, which clearly invites correlation with the dub (formerly cyn) gene for cynicism and medical humour.1 I cordially wish Fitzgerald and Isaacs the Best of British (and Irish) luck with the lofty ambitions expressed in the penultimate paragraph of their discussion; and, together with Arthur Koestler, we speculate that "in lieu of abolishing language the only way to curb human destructiveness would be to retool the brain", and that "advances in genetic engineering might encourage evolution along its path".4

Lachlan Brown

In reply: Howes writes that previous studies have not shown significant hyponatraemia with indapamide. Our article highlighted that hyponatraemia was reported in a much larger proportion of all types of adverse drug reactions to indapamide than to chlorothiazide in Australia. As we clearly acknowledged, "Voluntary reporting systems do not provide a basis for calculating incidence or robust risk estimates". In the PROGRESS study, 1770, and not 3000, participants were exposed to 2–2.5 mg of indapamide.1 The mean age of participants given active therapy in that study was 64 years and 30% were women. Details of the eight patients withdrawn because of hyponatraemia were not published. Importantly for indapamide, chlorothiazide and the other comparator (hydrochlorothiazide with amiloride), more than 80% of the patients with hyponatraemia in our study of Australian adverse reaction reports were aged 65 years or older (mean age for indapamide, 69.3 years, unpublished data), and at least 78% were female. Given that indapamide formulations have been promoted as a replacement for chlorothiazide notwithstanding the acknowledged limitations of the data, our article was appropriate in alerting practitioners to the possibility of hyponatraemia, particularly in elderly women.

Laurence G Howes MB BS, PhD, FRACP · John McEwen MB BS, MSc, MPS · John E Marley MD, MB ChB

To the Editor: Your editorial comment1 about the fact that the "Death and Dying" issue of the Journal [19 November 2001] contained no obituaries because "the obituary tray was empty" prompts me to make a suggestion. Having, over the years, written obituaries for colleagues, including one for my own father, I have always believed we would do colleagues a great favour if each of us wrote our own obituary and left it in the keeping of a colleague, to be dealt with at the appropriate time. Not only would it ensure that the obituary included services for which the departed would like to be remembered, but it would also save the writer of the obituary a great deal of time in research. PS. Now in my own 91st year, I've not yet written my own obituary.

H Stuart Patterson

To the Editor: Although treatment with vitamin D has been shown to reduce hip fracture risk in elderly institutionalised people,1 there has been a perception that vitamin D deficiency is generally uncommon in countries with high sunlight exposure such as Australia. We studied the prevalence of vitamin D deficiency in older people in residential aged-care facilities (hostels and nursing homes) in the northern Sydney area as part of the FREE study (Fracture Risk Epidemiology in the Elderly), a prospective study of fracture incidence in more than 2000 participants. Here, we report baseline serum 25(OH) vitamin D concentrations in the first 386 participants, determined in partially purified lipid extracts using a competitive protein binding assay.2 The sample comprised 252 women and 134 men (mean ± SE age, 86.7 ± 0.6 v 81.2 ± 0.7 years, respectively; P < 0.001). The mean serum 25(OH)D level was 17 nmol/L (SD, 12) and median serum 25(OH)D level was 15 nmol/L (interquartile range, 9 to 22). Vitamin D deficiency (defined as a serum 25(OH)D concentration < 28 nmol/L) was present in 86% of women and 68% of men. There was no significant difference in serum vitamin D levels between women in nursing homes versus women in hostels, nor between men in nursing homes versus those in hostels. Although serum vitamin D levels were low throughout the year, a small rise was observed in summer (P < 0.01). Length of stay in the residential facility was not a predictor of serum vitamin D level. Mean parathyroid hormone levels were 93 pg/mL (normal range, 12–72 pg/mL) and rose when vitamin D levels dropped below 21 nmol/L, indicating secondary hyperparathyroidism. A number of previous studies have suggested a high prevalence of vitamin D deficiency in older institutionalised Australians in southern States,2-4 but we are unaware of any published studies in Sydney (latitude 33°S). However, as the prevalence of vitamin D deficiency in older people living in the community in Geelong is low,5 our study suggests that factors like confinement indoors is more important than latitude. Given the relationship between vitamin D status and fracture, with more than 72 500 nursing home residents and 60 200 hostel residents in Australia in 1997, our findings indicate that vitamin D deficiency represents a significant public health problem in elderly institutionalised Australians regardless of geographical location. Importantly, this problem could be solved relatively simply by measures such as a short period of daily sunlight exposure or giving moderate doses of vitamin D annually to nursing home and hostel residents.

Philip N Sambrook · Ian D Cameron · Robert G Cumming · Stephen R Lord · Jennifer M Schwarz · Angelika Trube · Lynnette M March

To the Editor: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients with cardiovascular disease, including those taking perhexiline for severe ischaemic heart disease. Elevated serum perhexiline concentrations have been observed during therapy with the SSRIs fluoxetine and paroxetine, which are known to be strong inhibitors of cytochrome P450 2D6, the enzyme system responsible for the hepatic metabolism of perhexiline.1 The Adverse Drug Reactions Advisory Committee has received five reports of a possible interaction between perhexiline and SSRIs, but none of these involved the SSRIs citalopram or fluvoxamine, which are generally considered to be weak inhibitors of cytochrome P450 2D6. I describe here a case of perhexiline toxicity that occurred within 10 days of starting citalopram therapy. An 82-year-old man was admitted to hospital for drainage of a femoral abscess. His medical history included bilateral hip replacements, ischaemic heart disease, hypertension, renal artery stenosis, renal calculi, gout, gastroesophageal reflux disease and prostate cancer. His medications included (daily) aspirin 100 mg, isosorbide mononitrate 120 mg, pravastatin 40 mg, allopurinol 300 mg, celecoxib 200 mg, lorazepam 2 mg, nitrazepam 10 mg; (twice daily) perhexiline 100 mg; and paracetamol and tramadol as needed. On Day 51 after admission the patient underwent first-stage revision of an infected hip implant under general anaesthesia, and on Day 60 citalopram was commenced (10 mg daily for four days, then 20 mg daily). On Day 70, the patient complained of diarrhoea, nausea and dizziness. Citalopram was discontinued but the nausea was slow to settle. After a perhexiline assay on Day 75 revealed a high serum concentration (see Box), the perhexiline dose was reduced to 100 mg daily and the patient's nausea settled. Previous perhexiline concentrations on a dose of 100 mg twice daily had ranged from 0.29 to 0.34 mg/L over a two-year period. Tests of renal and hepatic function were normal throughout the patient's hospital stay. While in hospital, the patient was given celecoxib (a cytochrome P450 2D6 inhibitor) at a constant dose between Days 1 and 95, and meropenem (not a documented cytochrome P450 2D6 inhibitor) between Days 51 and 95. These patterns of administration suggest that neither of these drugs had a significant effect on perhexiline concentration. On the other hand, the laboratory evidence of a marked inhibition of perhexiline metabolism during treatment with citalopram suggests that caution is required when prescribing citalopram (or any other SSRI) for a patient taking perhexiline.2 Serum concentrations (mg/L) of perhexiline and perhexiline metabolite Day 48 Day 75 Day 95 Perhexiline (therapeutic range, 0.15–0.60 mg/L) 0.37 0.82 0.27 Perhexiline metabolite 3.53 0.37 2.22 Ratio of perhexiline to perhexiline metabolite 0.10 2.22 0.12

Karin Nyfort-Hansen

To the Editor: Hydroxymethylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (or statins) are widely prescribed, and any class-specific side effect has the potential to affect many thousands of patients. The statin drugs are well recognised as a cause of mild and usually transient hepatitis.1-3 Cholestatic liver injury has been reported with simvastatin4 and atorvastatin,5 but pravastatin has only been implicated as a cause in one report.6 We report a 64-year-old woman who was twice treated with pravastatin sodium and who, on both occasions, demonstrated cholestasis, which, at its peak, was associated with minimal hepatocellular injury. Our patient presented to the liver clinic of the John Hunter Hospital in 2001 for investigation of abnormal liver function test results. She was taking diltiazem, aspirin, irbesartan plus hydrochlorothiazide, and pravastatin as therapy for hypertension and hyperlipidaemia. She consumed less than 10 g alcohol per week. Liver function tests showed a predominant elevation of alkaline phosphatase and γ-glutamyltransferase, with a minimal rise in alanine and aspartate aminotransferases, a picture consistent with cholestasis rather than hepatocellular disease (see Box). She had started taking pravastatin in the three months preceding her referral, and commented that when she was taking the drug in the previous year she had also had abnormal liver test results. Her liver function test results in 1998 were normal. Two ultrasound examinations of the liver, performed after five months of taking pravastatin in the first period and two months after beginning her second period of therapy, showed normal liver size and echogenicity, and no sign of obstructive liver disease. Tissue antibodies, viral studies for hepatitis viruses, α1-antitrypsin and iron studies were all either normal or negative. Renal function was normal throughout. She had no biochemical evidence of impaired hepatocellular function, and for this reason liver biopsy and endoscopic retrograde cholangiopancreatography were not undertaken. In view of the association the patient made between previously ceasing therapy with the drug (because she felt unwell) and improving liver function, therapy (which was recommenced by the cardiologist for hyperlipidaemia) was again suspended and within two months liver test results improved markedly. We believe that in the absence of other markers of liver disease and with improvement of liver function on both occasions that therapy with pravastatin was suspended, it is likely that this patient has twice developed a cholestatic response to pravastatin. Patient's liver function test results during and after two periods of pravastatin therapy Initial period Second period* Normal range Pravastatin No pravastatin Pravastatin No pravastatin Test Month 0 Month 4 Month 5 Month 6 Month 10 Month 0 Month 1 Month 2 Month 3 Bilirubin (µmol/L) < 20 7 13 5 7 10 11 11 7 9 Alkaline phosphatase (U/L) < 115 230 362 220 213 242 291 347 186 171 γ-Glutamyltransferase (U/L) < 25 259 625 353 231 195 297 463 167 126 Alanine aminotransferase (U/L) < 40 26 85 31 25 28 25 49 16 18 * Commenced seven months after initial episode. Patient's results were normal two years before the initial period.

Robert G Batey · Michelle Harvey

To the Editor: A potentially important, if somewhat crude, means of suicide prevention involves restricting the availability of commonly used methods. In 1967, for example, restrictions on barbiturate prescribing in Australia led to declines in its use for suicide and in overall suicides.1 A crucial concern with this approach is that distressed individuals might use alternative, more lethal, methods. In Britain, there is just such a concern in relation to recent legislation restricting the availability of paracetamol.2 Analysis of the natural experiment investigated by Balit and colleagues3 does not, however, provide useful insights into the impact of paracetamol sales restrictions. Their most consistent finding was that, despite restricted availability for the period studied, paracetamol accounted for about 10% of all contacts with the two poisons information centres in both time periods. In Britain, in 1998, paracetamol purchases from chemists and supermarkets were restricted rather than banned.4 Up to 16 g (32 tablets) may be purchased from pharmacies and 8 g from supermarkets. The aim was not to prevent overdose but to reduce its severity. Presumably, over the periods studied by Balit et al, paracetamol was simply unavailable. As their analysis is based on calls to poisons information centres rather than on the clinical records of people presenting to hospital, they could not assess whether changes in paracetamol availability influenced indicators of severe poisoning — death and liver damage. A decline in the number of severe paracetamol poisonings, without a change in total episodes of paracetamol overdose, might be considered the most important end-point. Attention is drawn to statistically significant rises in calls concerning ibuprofen in one centre and aspirin in the other. The clinical significance of these observations is questionable. Overdoses of ibuprofen are less harmful than paracetamol,5 and the significant rise in aspirin overdose represents an increase from two calls per year to five per year — an increase of only three calls. Of note is the fact that the largest absolute decline in calls related to paracetamol (from 423 per year in 1997–1999 to 370 per year in 2000). Furthermore, as only two time points are compared, it is impossible to determine whether the increases reflect year-on-year changes in use of particular drugs for overdose, as might occur with increased ibuprofen sales. Legislation seeking to influence patterns of harm through changing the availability of drugs which are beneficial when used safely should be monitored carefully.4 Balit et al do not provide convincing evidence concerning the effects of paracetamol sales restrictions on population health.

Corrine R Balit BPharm · Geoffrey K Isbister BSc, MB BS · Andrew H Dawson FRCP(Ed), FRACP · Ian M Whyte MB BS, FRACP

To the Editor: In their recent article,1 Balit et al concluded "restriction of paracetamol-containing products may inadvertently increase poisoning with potentially more toxic agents". As manufacturers of one brand of ibuprofen tablets and the only brand of ibuprofen suspension in Australia, we would like to comment on the article and its conclusion. We understand that the objective of the audit was to determine whether the occurrence of paracetamol and non-paracetamol analgesic deliberate self-poisoning and accidental paediatric poisoning was affected by two periods of recall of paracetamol products. However, our concern is that the article's conclusion — "may inadvertently increase poisoning with potentially more toxic agents" — is not linked to any long term outcomes nor any follow-up regarding ongoing sequelae. This conclusion might give the impression that ibuprofen is more toxic than paracetamol when taken in an overdose situation, whether deliberate or accidental. It might also give the impression that overdoses of ibuprofen leave the patient with ongoing morbidity. In addition, we note that the percentage change in deliberate self-poisonings at both the NSW Poisons Information Centre (PIC) and the Hunter Area Toxicology Service for the periods when paracetamol was restricted, although seemingly large and statistically significant for the PIC, both came from a very low base (0.9% and 0.8% of all calls, respectively).

David Gunnell · Anthea Steans

In reply: There appears to be some misunderstanding about both the conclusions and the methodology of our study.1 We showed that when the availability of one analgesic (paracetamol) decreased, the use of the next most available analgesic increased in deliberate and accidental self-poisonings. We did not look at the relative toxicity of the analgesics, but referred to the published literature on acute paracetamol and ibuprofen overdoses in children, noting that serious complications of acute overdose in children have only been reported with ibuprofen.2-4 Data reported in the study not only included a poisons information centre, but also included data from hospital presentations. The Hunter Area Toxicology Service (HATS) manages all patients with poisoning in the Newcastle region and is based at the Newcastle Mater Misericordiae Hospital. The limitation of the small sample size in the HATS data was discussed in the article, highlighting the fact that, as this was an opportunistic study, it was not possible to increase the sample size. However, the conclusions drawn were based on two different data sets, with a much larger sample size for the NSW Poisons Information Centre data. Overdose is a significant public health problem that requires appropriate post-marketing vigilance. For drugs that are commonly taken in overdose, it is important to take advantage of opportunities to assess the potential effect of any change in availability.

David Gunnell

To the Editor: We read with interest the case report of Ward and colleagues, describing methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in a patient being treated for lower-limb ischaemia.1 We conclude that this antibiotic resistance may not have developed if the patient had been treated with conventional vascular therapy. The patient had diabetes, was haemodialysis-dependent and continued to smoke. Bilateral lower-limb ischaemia in such a patient is an indication for early vascular assessment, including angiography, debridement of non-viable tissue and, if possible, revascularisation. The option of early below-knee amputation should always be considered for such a patient. Broad-spectrum antibiotics administered over a long period to patients with ischaemic tissue can provide the ideal medium for development of multiresistant organisms. In this patient, 41 days of chronic infection, combined with the decreasing nutritional status typical of haemodialysis patients, contributed to the breakdown of both below-knee amputation sites and the ongoing sepsis. The difficult decision to preserve or amputate an ischaemic limb is best made by a vascular surgeon in consultation with the patient. Amputation should not be seen as treatment failure but as another stage of vascular disease. Early amputation preserves the physical condition and nutrition of patients and allows earlier transfer to rehabilitation units, with an improved result.2

Anthony J Grabs · Reginald SA Lord

To the Editor: The Lipid management guidelines — 2001 supplement1 is no doubt full of cardiovascular wisdom. Unfortunately, the authors appear oblivious to the fact that people are more than just cardiovascular systems. I found no mention of the risks of violent deaths associated with low cholesterol levels, which in some studies have been found to offset the decreased cardiovascular mortality benefits.2 In 1995, Engstrom et al neatly reviewed the relevant issues for those interested in populations of whole people. They cite studies which found low cholesterol levels to be associated with homicidal offenders with habitual violent tendencies when under the influence of alcohol, boys with aggressive conduct disorder, and criminals with antisocial personality, as well as with increased depressive symptoms in men aged 50–89 years. Further, an evaluation of six primary prevention trials found a significant increase in violent deaths in groups receiving interventions to reduce serum cholesterol levels.2 Engstrom et al also reviewed studies which found increased aggression in cynomolgus monkeys fed a low-fat diet. This appeared related to reduced serotonin activity, as serotonin is widely known to reduce aggression. In fairness, Engstrom and colleagues also cited studies which have not found an association between low cholesterol levels and aggression. If the increase in violent deaths associated with changing the dietary habits of whole populations turns out to be more than a red herring, the ethical and financial implications will be staggering. This evidence is not so conclusive as to have made me change my own relatively low-fat diet, but they do make me wonder if my irritation about the oversight in the Lipid management guidelines — 20011 might have something to do with my low fat intake!

Christopher H Cantor

To the Editor: The Australian Defence Force (ADF) has sustained many cases of malaria following service in East Timor.1 To reliably prevent relapse of malaria caused by the Chesson strain of Plasmodium vivax present in this region, larger doses of primaquine are required2 (up to 6 mg/kg total dose,3 compared with > 3.5 mg/kg to prevent relapse of sub-Saharan vivax malaria4). The ADF uses 1500 mg chloroquine (total base) followed by 315 mg primaquine (total base) for the treatment of vivax malaria, which, in Australia, is commonly treated either without primaquine or with inadequate dosages of either chloroquine or primaquine.5 A fit, 65 kg male soldier who deployed to East Timor from October 1999 to May 2000 experienced one episode of vivax malaria during his deployment and a further four episodes on return to Australia (Box). Having had malaria in East Timor, he complied closely with postexposure prophylaxis with primaquine and tolerated his dose (7.5 mg three times daily with meals) well for the required 14 days (315 mg total). He was seronegative for HIV, hepatitis C, and dengue IgG and IgM, and was not glucose-6-phosphate dehydrogenase deficient. The Table shows that our patient had a parasite that was apparently responsive to chloroquine, although it did not respond as readily in the last episode. In his first episodes of malaria on return from East Timor, he received the recommended dose of primaquine, but developed recurrences in the absence of further exposure to malaria. These relapses presumably indicate an inadequate response to the primaquine. The total dose of primaquine used for postexposure prophylaxis and treatment of the first episodes in Australia was about 4.8 mg/kg. He has subsequently received a treatment of 6 mg/kg total primaquine (see Table, Episode 5). This follows extended suppression with chloroquine before and doxycycline during a three-month deployment to Malaysia. There has been no further relapse six months after treatment. Chesson-strain vivax malaria is known to be difficult to treat and in which to prevent further relapse. Adequate primaquine to treat vivax malaria from other areas is not adequate for that contracted to the immediate north of Australia. Relapsing vivax malaria from East Timor may require a dose of 6 mg/kg of primaquine to prevent further relapse. Parasite density and treatment during the patient's episodes of malaria Episode Date of diagnosis Parasite density Treatment 1 1 April 2000 Positive on immunochromatographic test* Chloroquine 1500 mg, continued doxycycline 100 mg daily, primaquine 315 mg from 2 May 2 17 July 2000 23 000/µL Chloroquine 1500 mg, then primaquine 315 mg 20 July 2000 No parasites seen 3 26 Sep. 2000 8607/µL Chloroquine 1500 mg, then primaquine 315 mg 29 Sep. 2000 No parasites seen 4 11 Dec. 2000 11 400/µL Chloroquine 1500 mg, then weekly for two months† 14 Dec. 2000 No parasites seen 5 3 April 2001 Occasional trophozoites on thick and thin film Chloroquine 1500 mg, then weekly for one month; doxycycline for three months, then primaquine 420 mg 6 April 2001 Occasional trophozoites only on thick film * Immunochromatographic test used in the field. † Patient ceased treatment.

Scott J Kitchener · Isaac Seidl

To the Editor: We were disappointed with the article by Bailie and Runcie on household infrastructure in Aboriginal communities.1 It has major methodological and ethical problems that, in our view, should have precluded its publication. The data were not collected by a process which allows meaningful scientific analysis. In determining the state of health hardware, the authors did not outline the testing methods or how functioning of different items was assessed. No standardised procedure is evident within the process, no formalised training of those conducting the assessment is indicated, and there is no evidence that supervision or auditing of consistency was performed. In fact, these problems are acknowledged by the authors in a publication on the same project, in which they state: "There was no protocol for a number of steps in the data collection process. There was no protocol for what type of information was gathered by interviewing residents, nor for which resident was the most appropriate interviewee. "The way data was collected varied between field officers, and the way an individual officer collected data varied between houses. Firstly, the items might be observed. Secondly, but not always, items may be tested for functionality (eg, by turning a tap on). Whether items were physically tested sometimes depended on how "clean" the house was. If it was clean, then the items were sometimes assumed to be functioning . . .".2 No amount of analysis can correct for such inadequacy in primary data. The authors dismiss this problem by referring to consistent patterns of data across different communities. This in no way addresses the problem of identifying the true level of hardware functioning. It simply suggests that measurement omission or error was widespread. Even if the items tested did not require maintenance, this does not indicate that they were functioning adequately, as no defined and standardised tests were applied (see Appendix B, page 38, in reference 2).2 The article's ethical problems are masked by discussion about community confidentiality. The authors described an audit and assessment of health hardware without any attempt at intervention and improvement. This is in a setting where a method that links assessment and intervention has not only been established, but is now performed by different groups across a wide range of communities. In fact, this process is referenced by the authors.3 The article by Bailie and Runcie reinforces what is widely known — that Aboriginal housing is generally poor. There can be only two reasons for trying to assess the actual state of Aboriginal housing and health hardware. The first is to enable intervention to rectify the problem at the same time. The second is to enable future housing and infrastructure programs conducted by government to be technically targeted and subsequently assessed to determine whether improvement really is occurring. Unless the baseline status is accurately and reproducibly determined, then we will have no way of knowing whether such programs are actually making a difference.

Paul J Torzillo · Paul Pholeros

In reply: A primary objective of our evaluation1 was to identify methodological deficiencies for the purpose of improving data quality in subsequent surveys. These deficiencies, described in detail in our evaluation report and referred to by Torzillo and Pholeros, are also described in our Medical Journal of Australia article.2 Our assessment (reinforced by reference to subsequent survey findings) was that the data were of sufficient quality to be useful for the purpose for which they were collected — to guide and monitor a substantial maintenance and building program. Torzillo and Pholeros appear to have missed this point. Their analogy with a clinical therapeutic trial where the survey is equated with a placebo is absurd, all the more so for the reference to the HealthHabitat work as being "an effective agent [that] is already licensed". This "effective agent" has, to my knowledge, never been subjected to external evaluation or peer review — some licensing process! With regard to ethics, a fundamental aim of the survey was to identify areas of greatest need, and allow the allocation of resources on an equitable basis to improve Aboriginal housing standards across the Northern Territory. In an environment of massive need and limited resources, this is arguably a more ethical approach than that of HealthHabitat, where, in 2001, intensive input was delivered to only four out of hundreds of Aboriginal communities in the NT. Runcie M, Bailie R. Evaluation of environmental health survey data – Indigenous housing. Darwin, Northern Territory: Menzies School of Health Research, July 2000. Bailie RS, Runcie MJ. Household infrastructure in Aboriginal communities and the implications for health improvement. Med J Aust 2001; 175: 363-366. <eMJA Full text> <PubMed> (Received 21 Mar, accepted 25 Mar 2002)

Ross S Bailie

To the Editor: Cunningham has shown that in Australian public hospitals patients identified as Indigenous are significantly less likely than other patients to have a principal procedure recorded.1 This finding is based on data collected by the Australian Institute of Health and Welfare using the coding scheme of the International classification of diseases, 9th revision, clinical modification (ICD-9-CM). No information was available about the clinical indications for conducting a principal procedure. Despite this crucial omission, Cunningham speculates about the reasons for the disparity in the rate of procedures between Indigenous and non-Indigenous patients. These speculations include alarming suggestions such as the possibility of systematic discrimination against Indigenous patients of both an institutional and personal nature. She then concludes that "Work is urgently needed to characterise more fully the nature, level, sources and consequences of institutional and interpersonal discrimination so that we can reduce unfair treatment, ensure equitable care and improve outcomes for the most disadvantaged Australians". These speculations and conclusions are simply unjustified by the data. In addition, such comments may cause more harm than good — Indigenous people have become extremely sensitive about medical and social research and may reject future investigations that are essential to their welfare. There are reasons other than adverse discrimination which may explain the data. These include the common rejection by Indigenous patients of medical advice to have a procedure (they may well be adopting the wisest action), and their more frequent admission to hospital (rather than outpatient care), as they may have travelled from remote communities (ie, there are social criteria for admission without the need for medical procedures). Furthermore, the quality of the data must be questioned, as many Indigenous patients are admitted to hospitals where the data forms are completed by unskilled personnel who do not understand the meaning of a "principal procedure". Cunningham J. Diagnostic and therapeutic procedures among Australian hospital patients identified as Indigenous. Med J Aust 2002; 176: 58-62. <eMJA Full text> <PubMed> (Received 1 Mar 2002, accepted 25 Mar 2002)

James S Lawson

In reply: Lawson suggests that my conclusions1 are not justified, and that they may "cause more harm than good". I strongly disagree. He suggests a number of alternative explanations, including "social" admissions for remote patients, and poor coding, but these do not account for the differences observed. Over half of the separations identified as Indigenous were of urban (19%) or rural (33%), rather than remote, area residents. Disparities in procedures for Indigenous and other patients were evident for each area. Almost half (46%) the separations identified as Indigenous were in principal referral or major hospitals, where coding should be of a high standard. Indigenous–non-Indigenous disparities existed within each hospital category. The results presented in my report1 were adjusted for area of residence, hospital category, as well as several other factors, and large differences in procedures remained. Lawson also suggests that rejection of medical advice by Indigenous patients may play an important role. Rejection of advice certainly occurs on occasion, by both Indigenous and non-Indigenous patients. I question whether it is "common", as Lawson suggests, but that is not really the point. It would be far more productive to ask why and how this occurs, and how interactions between healthcare providers and Indigenous patients can be improved. Lawson takes exception to my raising the possibility of systematic discrimination in the Australian healthcare system, referring to it as "alarming". In that we are in complete agreement. I, too, find it alarming. However, unlike Lawson, I choose not to deny it, but to accept it as an important challenge. My aim is not to make medical practitioners defensive, but to invite them to participate in finding ways to reduce disparities. Systematic discrimination can occur even when well-meaning people are trying to do the right thing. The systems in which we work can defeat our best intentions, even when we don't realise it. The reasons why a procedure was not performed on a particular patient may be perfectly sound given the circumstances. What we must ask ourselves is how those circumstances came to be, and what we can do to change them. I agree with Lawson that some Indigenous people are sensitive about research, but I do not accept that they will "reject future investigations that are essential to their welfare". On the contrary, I expect that many Indigenous people would be happy to participate with healthcare providers in the development and implementation of creative solutions to improve the healthcare system. Cunningham J. Diagnostic and therapeutic procedures among Australian hospital patients identified as Indigenous. Med J Aust 2002; 176: 58-62. <eMJA full text> <PubMed> (Received 21 Mar 2002, accepted 25 Mar 2002)

Joan Cunningham

To the Editor: It is possible to diminish bias, especially in litigation concerning general practitioners.1 First, request all the defendant's clinical notes about the patient, not merely the records of the incident. Then, before reading the allegations or the history following the incident, read the entire history of the patient's contacts with the doctor or the practice: frequency of attendances, nature of complaints, details of history and examination, referrals for tests or second opinions — all give insight into the nature of that patient–doctor relationship. Reading the notes from the beginning allows the expert to approach, anterospectively, the consultation(s) at which things went awry. If the relevant consultation cannot be identified, the expert has to correlate the patient's story, as presented by the solicitor, with the doctor's records. As he or she progresses through the records, the expert can assess whether or not the doctor's recorded acts accorded with responsible practice. Unrecorded omissions can also be identified, based on what is written in the records: why didn't the doctor ask about X, examine for Y, request a test for Z or refer to a specialist? Of course, these things might have been done, but not recorded. One would hope that barristers for both parties would frame their questions based on a similarly anterospective approach, and that judges would focus their attention and that of a jury (if there is one) on the appropriateness of process rather than on the unfortunate outcome. I cannot conclude without mentioning one solicitor's claim that the doctor had failed to use a retrospectoscope. Competing interests: P C A, at the request of both plaintiffs and defendants, provides expert opinions for the courts. Hugh TB, Tracy GD. Hindsight bias in medicolegal expert reports. Med J Aust 2002; 176: 277-278. <eMJA Full text> <PubMed> (Received 19 Mar 2002, accepted 11 Apr 2002)

Peter C Arnold

To the Editor: I read with interest the recent article by Hugh and Tracy on hindsight bias in medicolegal expert reports.1 As they themselves admit, "the very seeking of an expert opinion usually indicates that there has been an adverse outcome". In my experience, the unfortunate outcome can usually be predicted within reading the first few paragraphs of the brief. I do not think withholding information on outcome would prevent the occasional use of the "retrospectoscope". I wondered whether the views of the authors might have been slightly biased on the basis of the particular cases they had reviewed as Chairmen of the Australian Cases Committee of the Medical Defence Union. Did these cases range across all specialties and subspecialties? The problem of hindsight bias is, in my view, greater when there are no clearly accepted guidelines for diagnosis and management, or where the case is unusual and falls outside the exposure of experienced clinicians. They mention clinical practice guidelines as a way to improve the objectivity of experts, but then seem to exclude them on the basis of the expense and time involved in their development. In cardiology, there are now internationally accepted guidelines developed by the American College of Cardiology and the American Heart Association for the diagnosis and management of all common clinical situations.2 These are regularly updated and have been sometimes modified for Australian use by the Quality of Health Care Committee of the National Health and Medical Research Council (NHMRC) or the Cardiac Society of Australia and New Zealand.3 These guidelines provide an important baseline for any expert opinion in this specialty. More universal clinical guidelines will educate reviewers. It will reduce the problems of hindsight and the overzealous expert. It will also allow the expert to be tested by the well-prepared barrister. Human nature being fallible, it will not eliminate personal bias. Hugh TB, Tracy GD. Hindsight bias in medicolegal expert reports. Med J Aust 2002; 176: 277-278. <eMJA full text> <PubMed> American College of Cardiology/American Heart Association guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. Circulation 2001; 104: 2996-3007. <PubMed> Clinical exercise stress testing. Safety and performance guidelines. The Cardiac Society of Australia and New Zealand. Med J Aust 1996; 164: 282-284. <PubMed> (Received 19 Mar 2002, accepted 11 Apr 2002)

John B Hickie

In reply: We agree with Arnold that, ideally, expert witnesses should attempt to assess management decisions before acquainting themselves with the outcome and allegations in negligence cases. In practice, we suspect this is rarely done. In any case, the mere seeking of an expert opinion conveys the information that there has been an adverse outcome and, as we noted, there is evidence that, even if experts attempt to guard against it, hindsight bias is unavoidable in such circumstances. The central problem is that the expert is, as it were, looking back down one fork in the pathway of events, whereas the treating doctor was looking forwards at many possible and often uncertain forks.1 Hickie's statement "in my experience the unfortunate outcome can usually be predicted within reading the first few paragraphs of the brief" epitomises the very problem we address. Such retrospective snap judgements are characteristic of hindsight bias and are often accompanied by the telltale phrase, known to be a marker for hindsight bias,1 "it should have been obvious". We are unable to understand Hickie's statement that our "views . . . might have been slightly biased on the basis of . . . cases . . . reviewed as Chairmen of the Australian Cases Committee of the Medical Defence Union". The Committee contained representatives from the major specialties, including two consultant physicians, and the cases ranged over all specialties and subspecialties. Experts from subspecialties, including cardiology, were co-opted when appropriate. We agree with Hickie that clinical practice guidelines are useful. We did not recommend that they be excluded, but we did draw attention to their difficulties and limitations. We acknowledge the admirable work done by the American College of Cardiology in developing an impressive range of guidelines, but our view remains unaltered that they are costly in terms of time and effort to produce, cannot cover all clinical contingencies, and have limitations when applied to negligence cases. The guidelines for heart failure referred to by Hickie took more than three years to prepare, involved numerous committee members and no fewer than 26 reviewers, and were not subsequently updated for six years. Relatively few guidelines have been modified for Australian use and some are obviously deficient. For example, the current National Health and Medical Research Council (NHMRC) guidelines relating to the common problem of chest pain2 are six years old, and have been criticised on the grounds that they have not been rigorously tested to ensure clinical usefulness and do not include appropriate management strategies for patients with non-cardiac chest pain.3 We adhere to our view that these problems make it likely that clinical practice guidelines will have a limited role in negligence cases. Cook RI, Woods DD. Operating at the sharp end: the complexity of human error. In: Bogner MS, editor. Human error in medicine. New Jersey: Lawrence Erlbaum, 1994; 255-310. Working party of the NHMRC Standing Committee on quality of care and health outcomes. Clinical practice guidelines: diagnosis and management of unstable angina. Canberra: National Health and Medical Research Council, 1996. Eslick GD, Talley NJ. Non-cardiac chest pain: squeezing the life out of the Australian healthcare system? Med J Aust 2000; 173: 233-234. <PubMed> (Received 9 Apr 2002, accepted 11 Apr 2002)

Thomas B Hugh · G Douglas Tracy

To the Editor: Comments made by Parker et al1 in response to Leeder and Rychetnik's article on evidence-based medicine (EBM)2 do not reflect the reality of the dilemmas clinicians face in practice — arguably, because of political misuse of the concept of EBM, which Leeder and Rychetnik warned against. Parker et al take issue with the "worry that EBM might be misused in public policy . . . where evidence is difficult to obtain", and argue that this is not the case. However, the previous Health Minister, Dr Wooldridge, was a great admirer of the Cochrane Collaboration, and, based on a perceived lack of evidence, he cut Medicare rebates in 1996 (by 50%) for patients needing long-term intensive psychiatric outpatient treatment. Although, after much protest, this decision was amended somewhat, Item 319 of the Medical Benefits Schedule remains today as a stark reminder of how some patients cannot access fully the treatment they desperately need. There is abundant evidence (international and local) as to the efficacy of this form of intensive treatment.3 There is also abundant and clear evidence that all who seek this treatment are traumatised by previous failed shorter treatments, often have comorbid disorders, and have established DSM-IV diagnoses of long standing.4 All this evidence was made available to the Minister — but Item 319 remains, with its exclusionary and discriminatory criteria to ration access, in my opinion due in large part to political misuse of the concept of EBM. Contrary to the assertion of Parker et al, there is a great deal to worry about. In addition, Parker and colleagues make the claim that mental health is attracting government attention and funding. Again, in reality, a great deal of money is being spent on promoting education and awareness — and certain kinds of treatment. There is no evidence that short-term treatments (which are heavily promoted) actually help the group excluded by Item 319 regulations. Yet public policy is being pushed along the lines of "one size fits all". It does not. All this is evidence of misuse of the idea of EBM reflected in public policy, and patients are suffering as a result. To make matters worse, cuts in one area are mindlessly used to push agendas that in clinical reality will be unworkable in other areas — all of which devalues professional expertise and judgement. Parker MH, Del Mar CB, Glasziou PP. Ethics and evidence-based medicine [letter]. Med J Aust 2001; 176: 138. <eMJA full text> Leeder SR, Rychetnik L. Ethics and evidence-based medicine. Med J Aust 2001; 175: 161-164. <PubMed> Doidge N. In: Cameron PM, Ennis J, Deadman JC, editors. Standards and guidelines for the psychotherapies. Toronto: University of Toronto Press, 1998. Doidge N, Simon B, Gillies LA, Ruskin R. Characteristics of psychoanalytic patients under a nationalised health plan: DSM-III-R diagnoses, previous treatment and childhood trauma. Am J Psych 1994; 151: 586-590. (Received 7 Feb 2002, accepted 25 Mar 2002)

Gil M Anaf

In reply: Anaf seems to have missed our point that the choice by Leeder and Rychetnik1 of mental health as an area relatively devoid of good quality evidence was a poor one — quality research has revealed mental health as an area of considerable need, and mental illness as a significant component of the global burden of disease. Despite the fact that evidence is often more difficult to obtain within the mental health area, much evidence exists — for example, the Cochrane Collaboration Depression, Anxiety and Neurosis Group has 11 500 controlled trials in its registry, and the Drugs and Alcohol Group has 3314. Anaf would agree with us here (on the basis of his assertions about the quality of the particular evidence he alludes to). On the narrower issue of the evidence base for long-term intensive psychiatric treatment, Anaf implies that this was ignored or distorted by the then Health Minister in deciding to amend the Medicare Benefits Schedule. We agree that EBM (and sound research) can be politically misused (as can any product of science), but that is no basis for rejecting EBM. Political misuse is a political mischief, not a failing in the particular instrument being misused. EBM itself is frequently blamed for all sorts of problems in health service, whereas, to use Anaf's example, the relative quality of the evidence for short or long term psychiatric treatment is a contingent matter for development and deliberation within and outside the psychiatric research community. Leeder SR, Rychetnik L. Ethics and evidence-based medicine. Med J Aust 2001; 175: 161-164. <PubMed> (Received 22 Mar 2002, accepted 25 Mar 2002)

Malcolm H Parker · Chris B Del Mar · Paul P Glasziou

To the Editor: The Australian Red Cross Blood Service (ARCBS) introduced a national policy for therapeutic venesection in December 1999 which allows the collection of blood from people with haemochromatosis. There is no charge for this service. The policy outlines the principles under which ARCBS provides a therapeutic venesection service, conditions of management of the donors and the acceptability of the donations for clinical use.1 These conditions are: The patient's condition benefits from regular venesection and the patient does not have a transfusion-transmissible disease. The blood donation will be used in clinical or derivative products only if the donors fully meet the donor selection guidelines for clinical use. Responsibility for patient management remains with the referring physician. ARCBS is responsible for the collection and for ensuring donor safety during the procedure. We will liaise with referring physicians about the venesection protocol if necessary, and reserve the right to refuse to venesect if there is a concern for donor safety. A diagnosis of hereditary haemochromatosis (evidence of iron overload together with appropriate genetic studies2) is required before patients are accepted into the therapeutic venesection program. Contact your local ARCBS for copies of the therapeutic request form. Completion of this will facilitate the entry of people to the ARCBS therapeutic program. The full policy can be obtained from our website <www.arcbs.redcross.org.au>.

Margaret L Buring

To the Editor: Consensus exists that the provision of medical advice must be based on the correct interpretation of the evidence base. It is logical to assume that consideration should also apply to the provision of medical opinion in cases of medical litigation. The recent article on Sharp v Port Kembla RSL Club1 raises concerns which require wider debate. It is not our purpose to discuss legal niceties nor to contest the epidemiological evidence of an increased incidence, in active smokers, of cancers at several sites, including the head and neck. Rather, we wish to concentrate on a central conclusion in the report, namely the assertion that ". . . a relationship between exposure to ETS [environmental tobacco smoke] and an increased risk of head and neck cancer . . . is supported by the available epidemiology". The larger2 of the two studies quoted showed a crude odds ratio of 2.4 (95% CI, 0.9–6.8). This result is statistically non-significant. The authors also claimed a dose response between "moderate" and "heavy" exposure of 1.8 (95% CI, 0.5–7.3) and 4.3 (95% CI, 0.8–23.5) for non-smokers and 2.5 (95% CI, 0.9–6.9) and 5.3 (95% CI, 1.8–16.1) for smokers. Statistical interpretation of these results leads to a conclusion of no evidence of an increased risk compared with people who were "never" exposed to ETS. Leaving aside our considerable reservations regarding the overall design and analysis of this case–control study, the data as presented are at best suggestive. Significant doubt must remain regarding the role of ETS in head and neck cancer. That being so, two disturbing issues emerge which merit further debate. Firstly, there is an ethical issue as to whether the requirements for the correct interpretation of the evidence base for medical opinion should be any different in the clinic or the courtroom. Secondly, the judgment in this case highlights a dilemma in clinical practice. A clinician is not expected to practise according to non-significant differences in outcome. But, in the event of litigation, will the courts decide, as in this case, that bigger is better?

Allan O Langlands FRACR, FRACS · Val J Gebski BA, MStat