Letters

To the Editor: Figures from the Australian Bureau of Statistics show that Australians make about 3.3 million overseas departures each year.1 Few data are published on the extent to which Australian travellers seek pre-travel health advice, what vaccinations they receive, and what risks they are exposed to during travel. A series of surveys of travellers examining these questions has been conducted under the auspices of the Travel Health Advisory Group, a coalition of Australian travel and medical organisations. Surveys were conducted in 1996, 1997, 2000, 2001 and 2002. On each occasion, a market research company telephoned people from mainland capitals using numbers randomly selected from the telephone directory. This process continued until 500 people aged 18 or over who had travelled overseas in the previous two years had been interviewed. In the 2002 survey, about 10 000 calls were made to complete the interviews. The questions on vaccinations focused on hepatitis A and B, two of the most common vaccine-preventable diseases associated with travel.2 Results from the 2002 survey are shown in the Box. A minority of people (31%) reported seeing a doctor or travel clinic for pre-travel health advice. Of those who saw a doctor or travel clinic, 31% did so two weeks or less before departure. Over the series of surveys, there has been an increase in travel to destinations with high- or intermediate-risk for hepatitis A infection, from 40% of travellers in 1996 to 58% in 2002. Despite this increase, only a minority of travellers could recall ever being vaccinated for this illness. Travellers were informed about how they might be exposed to hepatitis A and B and asked if they believed that they could have been at risk during their most recent overseas trip. Substantial numbers recalled a risk (34% and 16% for hepatitis A and B, respectively) and some of these could not recall being vaccinated (18% and 7%, respectively) (Box). These surveys have methodological limitations, including lack of information on the consent rate and potential recall bias. However, the results suggest that substantial numbers of travellers do not seek pre-travel health advice and are at risk of vaccine-preventable diseases during travel. Not only does this have implications for individual travellers, it also creates public health risks, as travellers can introduce hepatitis A and B into their home communities. These results suggest more public education is needed about the importance of pre-travel health advice and appropriate vaccination. Results of 2002 survey of Australian travellers overseas Variable No. of travellers (n = 500) Age (years) 18–29 156 (31%) 30–49 188 (38%) ≥ 50 153 (31%) Not stated 3 (0.6%) Male sex 205 (41%) Hepatitis A risk in country visited* High 226 (45%) Intermediate 62 (12%) Low 212 (42%) Sought pre-travel health advice from doctor or travel clinic Doctor 135 (27%) Travel clinic 20 (4%) No professional advice 345 (69%) Believed could have been at risk of hepatitis on most recent trip Hepatitis A 168 (34%) Hepatitis B 79 (16%) Vaccinated against hepatitis Hepatitis A 195 (39%) Hepatitis B 197 (39%) Believed at risk of hepatitis on most recent trip and not vaccinated or unsure Hepatitis A 91 (18%) Hepatitis B 36 (7%) Hepatitis A risk in country visited* among those not vaccinated for hepatitis A or unsure High 123 (25%) Intermediate 40 (8%) Low 142 (28%) * As defined by the United States Centers for Disease Control and Prevention, 2000.3 Destinations for the cohort of 500 were Asia (45%), northern Europe (28%), southern Europe (14%), North America (15%), Oceania (14%), eastern Europe (3%), Africa (3%), Middle East (2%), South America (1%) and Central America (1%), with some having more than one destination.

Nicholas A Zwar

To the Editor: I would like to comment on a recent article by Young and Dobson on the decline of bulk-billing and the increase in out-of-pocket expenses.1 It is true, as the authors state, that "Australia has no legislation restricting how much a general practitioner can charge for a consultation". It is a shame that they did not take equal time to point out that there is no binding requirement on governments to ensure that Medicare rebates remain within striking distance of the real cost of service provision. Policy change is required — with as much political and moral urgency as Young and Dobson advocate for patient access reform — to enable doctors to provide affordable healthcare under a fee-for-service system without being penalised for accepting a substantial number of elderly or socially disadvantaged patients. Primary healthcare policy needs to be adjusted to maintain rebate justice for low-income patients by linking patients' rebates to their doctors' real-life market costs (or even to relative value studies), not budget "bottom lines". Is the patient to be out of pocket, or the doctor? Surely, both positions are equally unfair, and equally unlikely to bring about an equitable system.

Warwick H Ruse

To the Editor: Young and Dobson1 have confirmed what has been long suspected by many rural doctors and patients — that women (and patients in general) in rural areas are paying higher out-of-pocket costs for general practice consultations than those in urban areas. I wonder whether the authors have considered analysing the data by State and Territory, as the structure of a State healthcare system often has a significant impact on healthcare costs to individuals. I am also interested to know whether total costs of healthcare (including on-costs, referrals, specialist fees, hospital and investigative care) were analysed. There is a long held view that rural doctors have a more holistic approach to patient care than their urban colleagues, who are more inclined to recommend unnecessary investigations and specialist referrals. It would be fascinating to know whether urban women would actually be more "out-of-pocket" than rural women if total contact with the healthcare system (not just general practice consultations) was taken into account.

Chris A Harrison

To the Editor: Do the data in Young and Dobson's study of general practice consultation fees1 support their conclusion that women in rural and remote areas lack access to affordable healthcare services? The declining prevalence of bulk-billing by general practitioners suggests that healthcare may be becoming increasingly unaffordable for people on lower incomes. But affordability is not only income-related — it depends also on choices regarding discretionary expenditure. Considering median levels of disposable weekly income, together with the prices of basic daily commodities such as milk or bread (not to mention a $10 pack of cigarettes!), how "unaffordable" is an occasional $5–$10 out-of-pocket fee for a GP consultation? As Young and Dobson concede, a further complicating factor in their study was that "the consenters . . . tended to have higher socioeconomic status and so may be less likely to be bulk-billed". It would have been helpful if the authors had defined affordability of GP care in relation to family income (perhaps analogous to advice that rental or mortgage repayments should not exceed a third of household disposable income) and identified just how much their frequent attenders' GP costs exceeded a specified limit of affordability. Services free at point of delivery are overused, both by patients and doctors, as evidenced by the Commonwealth's implementation of the Professional Services Review Scheme and the States' legislating to curb the costs of workers compensation and third-party motor vehicle insurance claims. There is probably an optimal price range that would facilitate affordable access without penalising the less affluent or encouraging "inappropriate practice". Closer attention to the affordability of GP services for individual households would help target resources to people who truly need the services but cannot afford them. This may be a better alternative to the authors' suggestion of simply making policy changes (taxpayer-funded?) to lower the price of GP services for all women in rural and remote Australia.

Peter C Arnold

In reply: We thank the authors of these letters for raising many of the complex issues that underlie the current geographical inequities in costs of general practice consultations. Ruse is concerned that we did not point out the inadequacy of the current Medicare rebates to practitioners. An appraisal of the adequacy of Medicare Benefits Schedule fees was beyond the scope of our study. We presented data on the out-of-pocket costs of general practice consultations, according to demographic and health-related characteristics of consumers, for consideration by all interested parties — practitioners and patients. As suggested by Harrison, we could also look at differences in bulk-billing and costs by State and Territory. However, as Medicare rebates are a Commonwealth issue, looking at national data seemed a sensible first step. We cannot examine total costs of healthcare, as the Medicare data do not include all costs related to care. Arnold argues that "affordability" should be better defined by us and questions, "how unaffordable is an occasional $5–$10 out-of-pocket fee for a GP consultation?". We have three responses. Firstly, many medical practices require an "up-front" payment. As written by one older respondent living in a rural area, "Small country town medical clinics do not give bulk-billing to aged pensioners and insist on cash payment on the day of the visit . . . many pensioners would not seek medical help when needed if at the time no cash was available". Our second response is that, regardless of how "affordability" is defined, the issue is one of equity. Is it reasonable that a major factor identified in our study as influencing access to bulk-billing is whether you consult a practitioner in an urban area or a rural area? Finally, "affordability" can only be assessed in relation to income and other expenditure and commitments. In our surveys we ask women how satisfied they are with the costs of GP care and, while the responses are subjective, they are likely to take into account these contextual issues. These data have not yet been fully analysed.

Anne F Young · Annette J Dobson

To the Editor: I note with interest the case study of experimental Ancylostoma caninum infection in a 22-year-old student.1 In his accompanying editorial, Van Der Weyden highlights the courage of these researchers, as well as some of the risks and discomforts associated with their participation,2 including in two studies in which he was a co-author. However, it is also worth highlighting some of the ethical issues associated with such experimentation. Larry Altman, who provided many of the quoted examples of self-experimentation, also reflects on Walter Reed's experiments with yellow fever vectors in Cuba. Although later credited with the use of written consent forms, on an earlier occasion Altman alleges that Reed withdrew at the last moment from inoculation experiments in which one of his colleagues died.3 Although not mentioned in the published work, the A. caninum experiment was initiated and undertaken by Landmann under the supervision of Prociv, who has himself self-experimented with both A. caninum and Necator americanus (human hookworm) in previous work (Juergen Landmann, Student; Paul Prociv, Senior Lecturer, Department of Microbiology and Parasitology, University of Queensland, personal communication). In this case, the study was wholly initiated by the student so consent was not an issue, but other such studies raise the potential problem of consent in situations of an unequal power relationship. Students under supervision constitute a "vulnerable" group in that consent may be given under a form of duress.4 Just as special protection is needed for populations for whom research is combined with care, protection is required for students who may feel obliged to participate in such research. There have been recent calls for a fuller discussion of ethical issues in published experimental studies,5 where ethical justification should be accorded the same weight as statistical considerations. The unusual study by Landmann and Prociv highlights the need for such discussion in potentially controversial research protocols.

Allen C Cheng MB BS, FRACP

To the Editor: The most recent newsletter of the New South Wales Medical Board1 opens with a plea by the president for better understanding of the Board's initiatives, inspired by the "public interest". We hope that the board recognises the gulf between legitimate public interest and unrealistic, illegitimate public expectation. The newsletter goes on to justify the Board's policy against doctors self-prescribing, with six examples (hardly significant from a register of 25 000). The first, Dr A, aged 70 (the only one whose age was given) was referred to the Board by colleagues for mental impairment, and was not self-prescribing. He was prescribed warfarin by his cardiologist, but also took aspirin. The other five were all involved with drugs of addiction, earning whatever sanctions the Board applied. The newsletter then states that these were "ordinary doctors providing ordinary services in the community" (p. 3).1 They were certainly not, and it is this patronising assessment of the behaviour of ordinary doctors that is objectionable. We are next told that "these dramatic examples represent the tip of an alarming iceberg" (p. 3).1 The Board has enough to do without plumbing the depths for imagined "icebergs", and should reconsider their policy on the alleged dangers of self-prescribing, a policy both unwarranted and unwanted. The mocking adage that "doctors who treat themselves have a fool for a physician" is not made correct by repetitive quotation. There are not many fools in our profession, and sanctions applied to them should not affect the Board's assessment of the whole profession. Although not mentioned in this newsletter, similar motives are apparent in the Board's disapproval of self-referral, where we are not credited with sufficient wit to discover for ourselves appropriate specialists for clinical referral. All medical boards are currently seized with similar agenda. The Victorian Medical Board ponders the "problem" of retired doctors, with the comment in their newsletter on doctors affected by "increasing age and commensurate reduction in cognitive ability", another gratuitous observation without supporting evidence. They could as correctly, and more kindly, have referred to the accretion of clinical wisdom commensurate with age, but respect for seniors seems to have declining value in current professional ethics.

G Douglas Tracy

In reply: Tracy's letter seems to focus on age. The Board's policy about treating family members is not about age, but about the wisdom or otherwise of this practice for medical practitioners at any stage of their career. The policy is not mandatory, but reflects what the Board considers to be prudent practice. The policy does not prohibit writing referrals or repeat prescriptions, but emphasises the importance of having an independent treating practitioner responsible for initiation of treatment and ongoing management. The New South Wales Medical Board is not alone in having such a policy, with similar views being expressed by UK's General Medical Council, the Medical Council of New Zealand, and Canadian, American and other Australian medical boards. The Australian Medical Association position statement on the "Health of medical practitioners" emphasises the importance of medical practitioners and their families having their own general practitioners. The case studies were published following a request from members of the profession for the Board to provide examples of problems arising through treating themselves or family members. Sadly, there are many more instances than the five referred to in the article. The doctors were certainly not ordinary once their attempts to treat family members went astray, but the point is that they had been ordinary doctors who got into difficulties because they crossed the professional–personal boundary.

Brian C McCaughan

To the Editor: This is the first report of the use of magnesium sulfate to treat Irukandji syndrome. A previously well 26-year-old commercial diver was stung on the neck by a jellyfish while collecting sea cucumbers in Barrier Reef waters off Townsville in February 2003. As is typical for an Irukandji syndrome, he was asymptomatic for about 30 minutes, after which he developed back and abdominal pain, nausea and headache. He was retrieved from the scene by helicopter and arrived in the emergency department (ED) two hours after the onset of symptoms. On retrieval he had a blood pressure of 150/90 mmHg, agitation, marked diaphoresis, piloerection and some dyspnoea. A typical carybdeid jellyfish sting mark was present on the neck. The cardiac troponin I level was elevated from the time of admission. En route and in the ED he was treated with intravenous morphine and diazepam. Skin scrapings were taken for nematocyst identification. After he had received 27.5 mg of morphine and 15 mg of diazepam, his pain settled somewhat, but abdominal discomfort, agitation and profuse diaphoresis persisted. Despite the dyspnoea, he showed no other overt clinical signs of cardiac failure. Concern with the patient's increasing hypertension (170/100 mmHg five hours after envenomation) led to his being transferred to the high dependency unit (HDU) six hours after envenomation. It was decided to try a therapeutic trial of magnesium sulfate for this patient in an attempt to control the hypertension. This decision was taken on the basis of: the unsatisfactory results of measures taken thus far, the postulated hyperadrenergic basis of hypertension in Irukandji syndrome, the known 20%–30% fall in systemic vascular resistance associated with magnesium administration in hyperadrenergic states,1 and considerable experience within the HDU with managing severe pre-eclampsia. Intravenous magnesium sulfate was administered as a loading dose of 10 mmol followed by an infusion of 5 mmol per hour. Sympathetic features and agitation resolved, and pain nearly completely resolved towards the end of the loading dose. Of note, an early reduction in the rate of magnesium sulfate infusion resulted in recrudescence of hypertension, back pain and piloerection. The infusion was uneventfully reduced to 3 mmol per hour at 11 hours after envenomation, and discontinued at 20 hours after envenomation. No adverse effects related to the magnesium infusion were noted. The patient subsequently remained well. The troponin I level rose to a peak of 6.4 μg/L, and an echocardiogram was normal at 20 hours after envenomation. Irukandji syndrome is produced by carybdeid jellyfish envenomation2 and has been shown (in animals) to be associated with dramatically elevated serum noradrenaline levels.3 Severe hypertension in Irukandji syndrome can be difficult to treat and has been associated with two deaths from intracranial haemorrhage. The origin of the extensive, severe pain associated with the syndrome is unknown. Postulated mechanisms include ischaemia from widespread small vessel vasoconstriction resulting from a hyperadrenergic state, and sodium channel opening in afferent pain fibres. Other mechanisms are equally likely. Induced catecholamine release or direct toxicity have been proposed as the cause of myocardial injury. This may produce overt, and occasionally severe, cardiac failure. Magnesium decreases both catecholamine release and sympathetic terminal receptivity to catecholamines1 via multiple sites of action, including most calcium channel subtypes (both at the cell membrane and intracellularly), as well as modifying other cation fluxes. It reduces catecholamine-induced myocardial necrosis in phaeochromocytoma (Professor M James, Department of Anaesthesia, University of Cape Town, personal communication) and is widely used in other hyperadrenergic states, such as phaeochromocytoma and pre-eclampsia.1 The apparent efficacy of intravenous magnesium in our patient suggests the need to further investigate this therapy. A larger case series, a multicentre randomised trial of magnesium sulfate administration in Irukandji syndrome and a dose-finding study are under way.

Michael A Corkeron

To the Editor: We wish to comment on the article by Whiting and colleagues1 on the proposed causal relationship between herbal remedies and severe acute hepatitis. Investigators have found that reported adverse effects of herbal medicines are not, in fact, caused by herbs alleged to be in the product, but result from substitution or contamination of the declared ingredients, intentionally or by accident, with a more toxic herb, a poisonous metal or even a pharmaceutical compound.2,3 In reports of adverse effects, there is often no effort to establish a positive identification of the herb involved or any adulterants. The attribution of toxicity to the wrong plant leads to inaccurate information being provided to patients, practitioners and regulators.4 A significant problem is the use of common names. As mentioned by Whiting and colleagues,1 Cimicifuga racemosa (black cohosh) has at least 20 different common names, which can be very confusing. The most tragic example of such confusion is the fatal substitution of Stephania tetrandra by the toxic herb Aristolochia fangchi owing to the similarity of the common names of the two herbs.5 In recording and responding to adverse events involving herbs, certain key questions need to be asked by those reporting the event and, more crucially, by those subsequently citing the report. No details regarding verification of the herbal products taken by the individual patients were supplied by Whiting and colleagues.1 Because of this failure to authenticate the plant compounds in the preparations, one cannot establish that the herbs were the cause of the hepatotoxicity. No information about plant parts used, solvent, concentration, manufacturing process or chemical analysis was supplied. Although Whiting et al exclude other causes for hepatitis, external factors may have contributed to the reported liver reactions. Hepatitis for which no cause can be identified is not uncommon.6 In addition, absence of hepatitis B surface antigen does not exclude the possibility of hepatitis B virus infection.7 The correlation of the liver diseases with preparations of Cimicifuga racemosa is speculative, as viral causes were not definitively ruled out. Without further pathophysiological or biochemical investigation, no conclusion can be made as to the exact mechanism. In a review of eight human studies on the effectiveness of an extract of black cohosh for alleviating menopausal symptoms, the authors concluded that black cohosh appears to be a safe, effective alternative to oestrogen replacement therapy for patients in whom oestrogen replacement therapy is refused or contraindicated.8

Luis Vitetta · Michael Thomsen · Avni Sali

To the Editor: We urge caution about the recently published findings of Durna and colleagues on use of hormone replacement therapy (HRT) by breast cancer patients.1 They found no increase in risk of breast cancer recurrence or reduction in life expectancy in women using HRT after treatment for primary breast cancer, leading them to conclude that HRT seems a safe treatment for women with a history of breast cancer. We believe that their study has many limitations and consequently their conclusions are unfounded Durna's group conducted a retrospective, observational study using unmatched patient groups. The HRT group was statistically younger, with smaller tumours and fewer positive nodes, and thus had better prognosis. The authors discussed regression analyses for age of diagnosis and stage to reduce potential bias, but did not include these data. The omission of tumour grade and receptor status in the analysis is an obvious flaw. The mean duration of HRT use was short compared with many previous studies (mean, 1 year). This is particularly important, as any risk is likely to be cumulative.2 There were also statistically more women in the HRT group who had received HRT before diagnosis, and for a longer duration (mean, 6.5 years v 3 years). This too may bias results, as breast cancer that develops after HRT has been suggested to carry a better prognosis.3 There was also no subgroup analysis of those who took concomitant tamoxifen. Durna and colleagues also do not address the concerns raised by the Women's Health Initiative study, which showed an excess of cardiovascular and thromboembolic events in "healthy" women taking HRT.4 Many of these events occurred in the first years of HRT use, the time assessed in Durna's study. The risks of short-term HRT in breast cancer patients may be not only tumour-related, but may also include cardiac and thrombotic events, which were not specifically considered by Durna and colleagues. Of additional concern is the extensive portrayal in some sections of the media that this study is conclusive regarding the risks of HRT use by women with breast cancer. The importance of correct media interpretation of studies is discussed in the accompaning editorial by Patel and colleagues.5 Despite this editorial and the inadequacies of Durna's study, the results of this study, released through the media, inaccurately suggested safety and even a possible benefit of HRT.6 This simply adds to the "HRT furore". All studies addressing this issue to date have been small and non-randomised, often with no control group or unmatched groups.2 Because of these limitations, no clear recommendation can be made about the safety of HRT in women with breast cancer. Until results are available from rigorous randomised controlled trials, such as the ongoing HABITS (Hormone Replacement Therapy After Breast Cancer — Is It Safe?) study (IBCSG 17-98), we should not be "advocating" HRT to breast cancer patients. For Durna's group to suggest otherwise is very premature. In addition, there are well studied, effective alternatives to HRT for treating menopausal symptoms in breast cancer patients (eg, venlafaxine),7 and these would seem the current safer option.

Theresa M Hayes · Craig R Underhill · Kerrie Clarke · Martin HN Tattersall

In reply: We feel that Hayes and colleagues repeat the editorial comments of Dixon1 that accompanied our article.2 Our investigation, being retrospective, had biases and limitations normally associated with that type of study. In the third and fourth paragraphs of the discussion section of our article, we examined further the sources of bias and their impact. Hayes and colleagues state that the omission of tumour grade and receptor status from our analysis is a flaw. We agree that including these variables would have made our study more complete, even if we doubt that this would have altered the conclusions. So many of these data were missing that statistical analysis would have been unreliable. As was stated in the methods section, the analysis was adjusted for the covariate HRT use before diagnosis. Tamoxifen use was very similar among HRT users and non-users (58% and 60%, respectively), and any bias introduced by this difference would be insignificant. The scope of our article, as suggested by its title, was limited to the issue of cancer recurrence and mortality. We did not specifically investigate the impact of HRT on cardiovascular and thromboembolic events. Nonetheless, if car-diovascular disease had increased mortality, this would have been apparent as an increase in all-cause mortality. We agree with Hayes and colleagues that it is vital that the media interpret studies correctly for the general public. We are disappointed that Hayes and colleagues have misinterpreted our conclusion. Our article does not advocate HRT use by women with breast cancer. We explicitly stated that "These results need to be confirmed in a randomised trial before HRT can be advocated for all women who have had breast cancer." Furthermore, ". . . the observed association between HRT use and [reduced] risks of breast cancer recurrence and death cannot be inferred to be causal". We believe that we are justified in our conclusion that HRT use in women diagnosed with breast cancer is not associated with an increased risk of recurrence of breast cancer or a shortened life span. It is our clinical practice to use HRT only when alternative therapy fails.

Eva M Durna · Barry G Wren · Gillian Z Heller · Leo R Leader · Peter Sjoblom · John A Eden

To the Editor: McBride reports that there were four deaths from cancer before the age of 40 years in a group of 480 thalidomide-affected people in the United Kingdom, an approximate cumulative mortality rate of 0.83%.1 He compares this with the annual death rate in the under-40-years age group, and concludes that the rate is increased almost 100 times in those affected by thalidomide. The correct comparison is with the cumulative mortality rate in the general population from birth to age 40. From 1999 UK statistics,2 this is about 0.31% — that is, we would expect 1.48 deaths among 480 people. While the observed number of four is greater than this, it is only slightly greater, and the difference is not statistically significant (the mortality ratio is 2.7, with exact 95% confidence limits of 0.7 to 6.9, based on a Poisson distribution). McBride's conclusion is based on an inappropriate comparison. A full analysis would use population death rates over the 40-year period and take account of censoring, but that is unlikely to affect the result substantially.

J Mark Elwood

To the Editor: In a valuable review of low-molecular-weight heparins (LMWH), Eikelboom and Hankey1 stray off the beaten path into the unwelcoming area of obstetric therapeutics — a notoriously hostile environment replete with traps and hazards. Their statement that "low-molecular-weight heparins are being used increasingly in pregnant women with prosthetic heart valves and for the prevention and treatment of venous thromboembolism" is contentious and requires considerable qualification. The Journal has already published a position statement concerning the use of these heparins in pregnancy.2 It clearly stated that the initial treatment for pulmonary embolism in pregnancy remains intravenous unfractionated heparin, because so far there are no trials of LMWH in pulmonary embolism in pregnancy. The guidelines of the American College of Chest Physicians do endorse the use of LMWH for this indication,3 but base that view on data in non-pregnant patients. We believe that, as yet, there is insufficient evidence to recommend LMWH for the initial management of pulmonary embolism in pregnancy, although, on theoretical grounds, the treatment seems attractive. In anticoagulation therapy for artificial heart valves in pregnancy, there are serious problems. Unfortunately, the conscientious adviser must be very circumspect in counselling women with these prostheses. Pregnancy for these women presents significant risks. None of the heparins, unfractionated or low molecular weight, has been shown to protect reliably against embolism from, or thrombosis of, these valves in pregnancy. Whether LMWH is better than unfractionated heparin has not been established and awaits appropriate trials. Warfarin, which crosses the placenta, remains a valid, but worrying, choice in pregnancy for antico-agulation in patients with prosthetic heart valves. This drug provides optimal protection from valve thrombosis, but with the potential for teratogenicity in the first trimester and fetal (and maternal) haemorrhage later in pregnancy. Many experts use heparin and warfarin sequentially in this situation.3 Thus, anticoagulation therapy for pregnant women with serious medical problems remains, as always, perplexing, difficult and dangerous. While LMWH offer considerable promise and have undoubted utility in several areas, there are very compelling caveats about their current use for pulmonary embolism and prosthetic heart valves in pregnant women. For these reasons and others, women with prosthetic heart valves planning pregnancy, as well as those already pregnant, should be counselled about these problems by a physician experienced in managing medical problems in pregnancy.

Barry NJ Walters · Dorothy Graham

To the Editor: The recent "New Drugs, Old Drugs" review of low molecular weight heparins (LMWH) and heparinoids1 provides a timely reminder of the limitations of studies that support the use of these agents in preventing venous thromboembolism (VTE), particularly in orthopaedic surgery. A new class of anticoagulants has recently been released in Australia and is being promoted as being more effective than LMWH in preventing VTE. However, while several randomised controlled trials suggest that fondaparinux reduces the risk of asymptomatic deep vein thrombosis (DVT) in patients undergoing hip and knee replacement surgery,2,3 there is currently no evidence to suggest that it reduces the risk of symptomatic VTE. Fondaparinux is a synthetic penta-saccharide that selectively binds to antithrombin III, enhancing the neutralisation of factor Xa and inhibiting generation of thrombin and subsequent clot formation.2 Unlike LMWH, fondaparinux does not appear to affect platelet function, thus potentially reducing bleeding tendencies and avoiding the risk of immune-mediated thrombocytopenia. The main problem facing researchers who study VTE prophylaxis in patients undergoing orthopaedic surgery is that, while asymptomatic DVT is common, symptomatic VTE is rare. The rate of fatal pulmonary embolism in patients undergoing hip replacement surgery is 0.1%–0.2% in those who receive no prophylaxis.4 Trials to demonstrate a reduction in symptomatic VTE are not performed because huge sample sizes are required to show a statistically significant difference in outcome (50 000 patients would need to be enrolled in a trial to show a reduction in the rate of fatal pulmonary embolism from 0.2% to 0.1% with 80% power). If such a difference could be shown, it would probably be clinically irrelevant to an orthopaedic surgeon performing 50 joint replacements a year. Although asymptomatic DVT is used as a surrogate endpoint for trials that support VTE prophylaxis, the natural history of asymptomatic DVT is poorly documented. There is some evidence to suggest that asymptomatic DVT is not associated with an increased risk of subsequent chronic venous insufficiency,5 and the association between asymptomatic DVT and subsequent clot propagation and embolisation is not well established. Further information on the natural history of asymptomatic DVT must be obtained before the clinical relevance of results from current studies of VTE prophylaxis can be determined. Until then, the clinical relevance of studies comparing the use of "new drugs" with "old drugs" in preventing VTE in orthopaedic surgery cannot be assessed.

Owen D Williamson · Alison M. Street

In reply: Walters and Graham question the role of low-molecular-weight heparin (LMWH) as a replacement for unfractionated heparin during pregnancy, and cite the lack of randomised comparisons to support their view that the standard initial treatment for pulmonary embolism during pregnancy remains intravenous unfractionated heparin. We do not deny the lack of clinical trials of LMWH in pregnancy; we were simply referring to the increased use of LMWH.1,2 However, the lack of evidence of effectiveness does not equate with evidence of lack of effectiveness of LMWH in pregnancy. Clinical trials are needed to determine optimal anticoagulant strategies during pregnancy, particularly in patients with prosthetic heart valves. While awaiting the results of these trials, we believe that the major pharmaco-kinetic and safety advantages of LMWH over unfractionated heparin, coupled with an extensive body of evidence demonstrating their efficacy and safety in non-pregnant patients, should not be ignored in our pursuit of optimal anticoagulation therapies. Williamson and Street question the validity of asymptomatic deep vein thrombosis as a surrogate for symptomatic venous thromboembolism in patients undergoing major orthopaedic surgery. Further, they cite a 0.1%–0.2% incidence of pulmonary embolism in patients undergoing hip replacement surgery without prophylaxis3 to support the conclusion that any effect of thromboprophylaxis on reducing symptomatic events is likely to be irrelevant for individual orthopaedic surgeons. We believe that their argument is seriously flawed. Firstly, the "meta-analysis" they cite3 had major methodological limitations, as elegantly highlighted by "Sherlock Holmes" in his critical appraisal of systematic reviews of surgical thromboprophylaxis.4 Secondly, rigorously conducted randomised trials and meta-analyses of randomised trials have demonstrated the efficacy of antithrombotic therapy for the prevention of both symptomatic and fatal venous thromboembolism in high-risk surgical patients, including lower-limb orthopaedic surgery.5,6 Thirdly, the clear correlation between reduction in asymptomatic and symptomatic venous thromboembolism in patients undergoing elective joint replacement surgery7 suggests that asymptomatic thrombosis detected by screening venography is a valid surrogate for symptomatic events. Fourthly, we agree that an individual orthopaedic surgeon performing 50 joint replacements per year may remain unaware of a small reduction in fatal pulmonary emboli in his or her own practice (eg, a 0.1% absolute risk reduction would be equivalent to preventing one death in 20 years of practice). Yet, on a population basis, even a 0.1% absolute reduction (which is likely to be an underestimate — the PEP study showed a 0.3% absolute reduction in fatal pulmonary embolism with aspirin5) equates to 50 preventable deaths per year in Australia alone8 and many thousands worldwide. There is now overwhelming evidence of the efficacy of thromboprophylaxis for preventing venous thromboembolism, including symptomatic and fatal pulmonary embolism, in high-risk surgical patients. With the rapid ageing of the Australian population and the expected increase in joint replacement surgery in coming years,9 the failure to use effective thromboprophylaxis in orthopaedic patients will likely result in a growing burden of preventable morbidity and mortality from venous thromboembolism.

John W Eikelboom · Graeme J Hankey

To the Editor: Koenig's rebuttal of some of the conclusions I drew in my recent article was perhaps more vigorous than can be justified given recent changes in Australian culture and the paucity of practice-oriented research.1,2 I accept that religious patients may be healthier in many respects, and being religious may help some patients cope with illness. However, it does not follow that having doctors in Australia enquire into their patients' religious beliefs almost as a matter of routine would be a cost-effective use of their time. In hospitals, doctors are part of a team, and do not themselves have to identify religious concerns and mobilise spiritual resources. Nurses commonly ascertain whether patients are religious, identify concerns, and liaise with chaplains and pastoral workers. Chaplains themselves are highly regarded by all members of the healthcare team; they counsel and help patients cope with illness as part of their role, and are effective.3 For most Australians, religious affiliation is largely nominal. Consequently, only a minority of patients presenting to general practitioners are likely to have religious beliefs affecting their care. Rather than take a religious history routinely, it might be better if GPs were to enquire into religious beliefs when a patient or the family is known to be particularly religious or if the clinical situation warrants it. Urging doctors to take a religious history ignores those patients who are not religious but who might have a spirituality that helps them cope with illness and their particular needs.4 It also ignores changes which have occurred in Australian culture since the mid-1970s.5 Organised religion has declined, while spirituality has surged.5 Moreover, whereas Christians understand spirituality in terms of their relationship with God, in the wider community, spirituality needs no God association. It is often seen as a previously ignored aspect of being human, alongside physical, emotional and social aspects.5 It is increasingly regarded as the integrating holistic factor in life, associated with healing, therapy and well-being. The healthcare system as a whole will need to consider the relevance of these cultural shifts and how it is going to respond. Medical professionals should keep this in mind when discussing the relevance for medical practice and how they will respond. Spirituality has already assumed greater prominence in the practice and education of nurses, psychologists and social workers, and medical professionals should take account of the skills and experience of these groups.

Hedley G Peach

In reply: Despite recent changes in Australian culture, Peach underestimates the importance of religious beliefs to older Australians likely to see physicians today.1-3 As people age and experience negative life events, such as medical illness, longitudinal studies show that they become more and more religious.4 Given the potential impact that spiritual issues have on treatment decisions, the physician–patient relationship and medical outcomes, physicians cannot simply defer these issues to nurses or chaplains, nor do many physicians wish to do so.5 Deferring such issues could, in fact, be more costly than the few additional minutes necessary to take a spiritual history, particularly in patients with serious or chronic medical illness. For patients who are not religious, the doctor should enquire about secular beliefs that could influence medical decisions or that give the patient's life meaning and purpose in the context of their illness. I do agree with Peach that physicians should always phrase enquiries in terms of "spirituality", allowing patients to determine for themselves what this involves — whether it be God, church, or the random forces of nature. Keeping the spiritual history "patient-centred" in this way ensures that no one is excluded and provides many additional safeguards.

Harold G Koenig

To the Editor: The recent articles about spirituality and health1,2 provide a welcome discussion about the very soul of medicine as well as the soul of the individual healthcare practitioner. If spirituality is "whatever is left over when the doctor, social worker, psychologist, community education officer or psychiatrist have had a go",3 then indeed spiritual questions should be left to the particular expert on that fragment of the person. However, if spirituality is the integration of every aspect of the person, the plumbing of depth, the search and discovery of meaning and purpose, the exercise of compassion and love often in relation to the divine,4 then our whole practice of medicine needs to be spiritually conceived and executed, both for our patients and for ourselves. We need to pause and reflect on the quality of our care of ourselves as well as of our patients.5 We need to rescue healthcare delivery from the reductionism of a mere science of "fixing bits" according to economic criteria. We need to deliver healthcare with humanity, compassion and wisdom. Some would include godliness. This is not an optional extra, but the core of true healthcare, in which each of us will need to freely contribute, without imperialism, from the depths of our own spiritual journey.

Alan J Gijsbers

To the Editor: I am happy to inform Whiteman and colleagues1 that, should they wish to undertake a project in Australian general practices, the Royal Australian College of General Practitioners (RACGP) has one ethics committee which covers the whole of Australia. As a researcher, I have participated in many multicentre trials under the aegis of this committee over the past 8 years. Details of the RACGP national ethics committee may be found at <http://www.racgp.org.au/document.asp?id=523>.

Christopher D Hogan

To the Editor: It was estimated in 1989 that cervical screening in Australia was preventing only 46% of squamous malignancies, against a theoretical capacity of 90%.1 This suboptimal achievement after almost 25 years of cervical screening led to a major reorganisation of the program. The 1989 analysis has been repeated, using the most recent year (1998) for which incidence rates have been published (Box). The more recent figures suggest that cervical screening in Australia is now preventing 70% of squamous carcinoma of the cervix. This remarkable improvement can probably be attributed to the improved participation by women in regular screening, improved standards within laboratories, and better follow-up of cytological abnormalities. While there is still scope for improvement, there is clear evidence of a substantially better gain from cervical screening. Continued efforts to increase the participation rate among women aged 60–69 years is appropriate given that the prevented proportion appears to be lower in this age range. Percentage of squamous carcinoma of the cervix prevented, by age group, Australia 1998 Age group Number of women (estimated number with a cervix*) in Australia2 Expected rate (per 100 000 women) of squamous carcinoma without screening† Expected number of squamous carcinomas‡ Estimated number of squamous carcinomas observed in 1998§ Percentage prevented 20–24 665 691 (665 025) 5 33.3 9.6 71.1% 25–29 733 145 (732 412) 15 109.9 34.8 68.3% 30–34 706 925 (687 838) 25 172.0 62.9 63.4% 35–39 748 913 (728 692) 45 327.9 74.7 77.2% 40–44 702 629 (608 477) 45 273.8 76.2 72.2% 45–49 649 539 (562 501) 45 253.1 81.4 67.8% 50–54 570 287 (410 607) 45 184.8 48.1 74.0% 55–59 431 183 (310 452) 45 139.7 40.7 70.9% 60–64 370 123 (251 314) 45 113.1 40.7 64.0% 65–69 348 707 (236 772) 45 106.6 44.4 58.3% Total 5 927 142 (5 194 090) 1714 514 70.0% * Calculated by multiplying the number of women in Australia by the estimated age-specific hysterectomy fractions.3 † Methodology as for the study by the International Agency for Research on Cancer,4 using incidence in Norway at a time when the rates would have been little affected by screening. ‡ Calculated by multiplying the estimated number of women in Australia with a cervix by the expected rate of squamous carcinoma of the cervix in the absence of screening.4 § Calculated by multiplying the number of cases of cervical cancer observed in 1998 by 0.74, which was the proportion of all cervical cancers that were squamous.5

Heather S Mitchell

To the Editor: The recent article by Scott and colleagues1 described a retrospective analysis by postal questionnaire of the attitudes of family members to participation (about a year earlier) in a face-to-face interview about their child's diagnosis of Ewing's sarcoma. This was accompanied by an editorial exposing the complexities of research participation, including the potential risks of interviews as well as the role of altruism.2 Although results derived from the questionnaire have only recently been published (November 2002), the questionnaire was distributed in November 1997, before introduction of the National statement on the ethical conduct of research involving humans.3 Some ethical uncertainties and questions of historical interest arise. First, what was the nature of the original consent obtained for the initial interviews? Presumably it involved written informed consent in which the risks of participation were clearly mentioned, including the possibility of distress associated with the interview. Did it mention a procedure for aborting or complaining about the interview? Second, did the patients (aged up to about 35 years) and their families give permission to be contacted again by the same research group? Third, for the follow-up on research participation, was consent implied simply by return of the questionnaire? Finally, how would the conduct of the initial interviews and the follow-up questionnaire differ in the light of recent developments in the ethics of research involving humans? Importantly, the respondents (84% of those surveyed) indicated that participation in the original study had not "upset them".1 While the attitude of non-responders is unknown, this would seem to confirm that the original process had been sensitive and appropriate. This is supported by the finding that families whose child had died after the initial interview were more likely to respond to the questionnaire. As a long-time member of a university human research ethics committee, I have often been required to evaluate research protocols that involve potentially threatening or distressing interviews. This has occurred more frequently since introduction of the National statement, as much qualitative research previously conducted under different jurisdictions (such as quality control or clinical audit) has been submitted for formal ethical review. The risk of harm to participants in qualitative research cannot be trivialised. Its impact can be minimised by wording the consent form to warn of possible adverse psychological reactions to interviews and questionnaires, using trained interviewers and providing counselling support if needed.

Simon C Gandevia

To the Editor: The article by Mant et al1 and the letters following its publication focus attention on a long-standing problem that, despite concerted efforts by governments, healthcare providers and other stakeholders to address it, remains a major obstacle to effective and appropriate continuity of pharmacotherapy following discharge from hospital. There is little doubt that many of the difficulties arise as a result of poor communication between hospitals and general practitioners. This is further exacerbated by a lack of standard protocols for the preparation and dissemination of discharge summaries. Nowhere is this more evident than in the case of residents of aged-care facilities returning from hospital with radically changed medication regimens. To establish appropriate communication channels, Mant et al mention hospital GP liaison officers.1 New canvasses the potential problems and suggests sensible solutions, including the involvement of community pharmacists.2 However, every hospital has a readymade resource that requires only a set of formal protocols and procedures to make it function — clinical pharmacists. Clinical pharmacists view every patient's chart at least once every day. The chart not only provides information for dispensing, but also gives pharmacists an opportunity to monitor Quality Use of Medicines and communicate with hospital doctors regarding existing or potential problems. By the time the "prescription" is processed and the medication dispensed, quality issues have been addressed and a detailed record created. From the dispensing record, a "medication profile" could be generated. This can provide the patient with consumer information regarding each drug, its dose, frequency of administration and mode of action, and can act as an accurate and up-to-date discharge summary. In addition, a clear, legible copy can be faxed, mailed or electronically transmitted to the patient's GP, pharmacist, specialist, allied healthcare professional, rehabilitation hospital or aged-care facility. Our organisation provides medication management services to a large number of aged-care facilities as well as to public and private hospitals, and correctional facilities. Quality Use of Medicines monitoring constitutes a vital part of our clinical pharmacists' duties. It provides an effective, accurate and timely method of communicating detailed discharge summaries (which have undergone thorough Quality Use of Medicines screening) to GPs and other interested parties. By including hospital clinical pharmacists in the Quality Use of Medicines monitoring and evaluation process, meaningful information can be obtained, appropriate judgements made, effective communication conducted and optimum pharmacotherapy outcomes achieved.

Joseph J Gelb

In reply: Gelb points out that clinical pharmacists can, and in some cases do, provide useful communication to general practitioners following hospitalisation, as well as for their patients in aged care facilities. Regrettably, clinical pharmacists are in short supply, even in teaching hospitals; thus, in practice, their expertise often cannot be fully utilised.1 Attention to this shortage is clearly warranted to safeguard patient care. We agree that clinical pharmacists (hospital and community based) should be included in the Quality Use of Medicines monitoring and evaluation process. In addition, we urge all healthcare providers to take responsibility for careful and timely communication to ensure continuity of patient care.

Karen I Kaye · Andrea Mant · Linda Kehoe · Wendy C Rotem

To the Editor: We would like to comment on a recent article by Chan et al on clinical practice guidelines for depression in young people.1 We disagree with their proposal to amend National Health and Medical Research Council (NHMRC) guidelines2 to include a statement that "SSRIs [selective serotonin reuptake inhibitors], particularly fluoxetine and paroxetine, should also be considered as a first-line treatment" for major depression in young people. We believe that there is insufficient evidence to assign a grade of "E1"2 to this statement. Chan et al1 quote three randomised controlled trials (RCTs) and one systematic review in support of their argument, but as yet the results of only two of the three RCTs have been published.3,4 Unfortunately, Chan et al do not include a critical appraisal of the significant methodological and analytical problems with each of the studies. Nor is any comment made about risk–benefit ratios, or the fact that even if the results were sound the clinical relevance of such small differences between active drug and placebo is questionable.5 The following brief commentary on the two studies highlights the dangers of carrying out sophisticated procedures such as meta-analysis without sufficient attention to the quality of the trials included in the analysis. The very high dropout rates (46% of 48 for placebo; 29% of 48 for fluoxetine) in the study by Emslie et al3 raise questions about the reliability of the results. Other interpretations of the findings are plausible. For example, in their study, significant advantage to fluoxetine over placebo on the Clinical Global Impressions improvement rating (a primary outcome measure) was lost when only patients completing the trial were counted (P = 0.2). More worrying is that Chan and colleagues do not seem to have noticed the dangerously distorted reporting in the study by Keller et al.4 On neither of the two designated primary outcome measures (change from baseline in Hamilton Rating Scale for Depression [HAM-D], and response, set as "fall in HAM-D to ≤ 8 or by ≥ 50%") did paroxetine differ significantly from placebo. But Keller and colleagues never report this negative finding. Instead, the criteria for response are covertly altered (to "fall in HAM-D to ≤ 8", which does achieve significance). The authors then erroneously claim significance on this (altered) primary outcome measure, ignoring the lack of significant change. Thus, a study that showed no significant improvement on either of two primary outcome measures is reported as demonstrating unqualified efficacy. Similar problems can be found in a more recent article by Emslie and colleagues6 (published after the review by Chan et al1), in which the authors openly acknowledge that the difference between fluoxetine and placebo on their prospectively defined primary outcome measure did not reach statistical significance, yet claim to have demonstrated the drug's efficacy. Another worry is that Chan and colleagues, in their list of proposed changes to NHMRC recommendations,1 suggest that the availability of SSRIs obviates the need for more expert and thoughtful assessment and management of depression. We are uncomfortable that the prescribing and management of psychotropic medication is portrayed as requiring relatively few skills and resources, to be carried out by those general practitioners who lack training in mental health and/or access to expert mental health services. We urge the NHMRC to maintain a conservative approach to the use of psychotropic drugs in children with depression unless more convincing evidence is forthcoming.

Jon N Jureidini · Anne L Tonkin