Volume 178 Issue 8

Formal risk-based protocols and clinical audits of process indicators and outcomes are needed "Missed" myocardial infarction occurs when a patient with an unrecognised acute coronary syndrome is discharged from hospital prematurely. The correct diagnosis becomes apparent only when the patient has an infarct or cardiac arrest, or is later found to have biochemical evidence of myocardial injury. There has been a paradigm shift in management of patients with chest pain over the past decade, with the focus moving from establishing a diagnosis towards ensuring the safety of the management strategy. This change was heralded by the publication of Australian guidelines in 1996 that recommended: Initial risk stratification of patients using clinical variables; Admission of intermediate- and high-risk patients for 48 hours of clinical observation to identify those with recurrent ischaemia at rest or evidence of myocardial damage (raised levels of cardiac biomarkers or electrocardiogram [ECG] changes); and If these features are absent, stress testing to exclude exercise-induced ischaemia in all remaining patients before discharge.1 Studies in the United States showed that the period of observation can be shortened to eight hours without affecting patient outcomes.2,3 Management guidelines were updated accordingly.4 Missed myocardial infarction usually results from a breakdown in the system of care — the patient's risk has been underestimated or formal protocols have not been fully implemented. Two studies in this issue of the Journal provide excellent examples of hospital strategies to improve the safety of chest pain triage. Aroney and colleagues (page 370) demonstrate that implementation of a protocol adhering to current Australian guidelines4 minimises missed myocardial infarction.5 They provide a benchmark for other hospitals to compare their practice. Boufous and colleagues (page 375) show that local implementation strategies can reduce medical error which contributes to missed myocardial infarction.6 A new "gold standard" for care. Aroney et al describe an "accelerated chest pain assessment protocol" that minimised hospital stay without jeopardising patient safety.5 After identifying intermediate-risk patients, they implemented a rapid, two-step process to ultimately identify those who were low risk and suitable for early discharge. They shortened the period of observation to a minimum of six hours. The absence of a single infarct in the 409 patients classified as low risk is an excellent outcome, clearly confirming the safety of the protocol. Of interest, 11% of the study population had diabetes but were safely triaged by the protocol. Thus, the recent recommendation to classify all patients with diabetes as high risk may not be necessary. Validation of new markers of increased risk, such as C-reactive protein, may allow risk-stratification algorithms to be further refined.7,8 Aroney et al achieved their outcomes in a large teaching hospital where coronary care nurses and "on-call" cardiology registrars were used to implement weekend stress testing, the final step in risk stratification before discharge. As many Australian hospitals have fewer resources, it is worth identifying non-essential elements of the protocol. The study data allow limited assessment of the incremental value of each step in the protocol, excluding the 78 patients who were unable to perform an exercise test. Most of the remaining 142 at-risk patients were identified by clinical, ECG or cardiac biomarker findings. Continuous ST-segment monitoring detected less than 2% of at-risk patients. As this monitoring is expensive, its use is difficult to justify in smaller hospitals. On the other hand, 42 at-risk patients (30%) were identified by an exercise ECG. Thus, this test should not be omitted. Coronary angiography was recommended in high-risk patients, but was performed in only 41%, as many were frail or had significant comorbidities. It is interesting to speculate whether outcomes in this group could have been improved by attention to optimal medical therapy and routine stress imaging. Are patients selected appropriately? Aroney et al do not report the numbers and outcomes of patients who were classified as low risk at initial clinical assessment and who were therefore not included in the study. Some at-risk patients may have been misclassified and discharged prematurely, predisposing them to missed myocardial infarction. Boufous et al audited this phenomenon.6 Their method was imperfect, as the reviewing cardiologist had to rely on the original clinical records. Despite this reservation, it is reassuring that formal adoption and use of a risk-stratification algorithm by clinical staff halved the rate of inappropriate discharge from 20% to 10%. Nevertheless, some potentially at-risk patients were discharged against current guidelines. The study was too small to detect an impact on their outcomes, and, to my knowledge, there are no published data on outcome in this group. However, the value of such a study is illustrated by an eight-month audit of emergency chest pain triage performed at my institution five years ago. Using a risk-stratification algorithm, we identified 136 intermediate-risk patients who were discharged contrary to guidelines. In most cases, patients were observed for at least eight hours, and serial biomarkers were measured. The guideline violation was primarily a failure to perform exercise stress testing, either because it was not available or because there was no in-patient bed to hold the patient until the test could be performed. Outcome was determined in all patients at one month. One death (documented ventricular fibrillation after recurrent chest pain) and five myocardial infarctions occurred during this period: three of these events, including the death, occurred within 24 hours of discharge. While the outcome for this group of patients was not statistically different from the outcome in 116 patients managed appropriately and discharged within 24 hours (one missed myocardial infarction), the clinical significance of the data persuaded our hospital managers to fund exercise stress testing on weekends. Coupled with an education program and a protocol similar to that described by Aroney et al, we subsequently reduced our underadmission rate substantially. How can hospitals improve triage of chest pain? It is unlikely that there will ever be high-level evidence to guide chest pain triage. As outlined above, poor outcomes such as missed myocardial infarction arise through medical error or inadequate resources, and the changes required to conduct a randomised trial would reduce the likelihood of the former and, by ethical necessity, ensure the latter. In the absence of high level evidence, hospitals should adopt methods to improve clinical practice,9,10 such as strategies similar to those described by Aroney and Boufous. Risk stratification and standardised protocols can reduce medical error, as shown by Boufous et al.6 To optimise bed use, all hospitals should adopt accelerated chest pain assessment protocols similar to that described by Aroney et al.5 Lack of stress testing, particularly at weekends, is the major impediment to their widespread adoption. To inform local resource allocation, hospitals should audit indicators of process, such as appropriate risk stratification and underadmission of at-risk patients. They should also measure patient outcomes, and, if these outcomes do not match those of Aroney et al, then hospitals should revise their current management strategies.

M Andrew Fitzpatrick MD FRACP

Careful assessment of car accident risk in patients with sleep disorders should guide advice Alcohol and excessive speed, often combined with inexperience and youthfulness, are the most widely recognised causes of motor vehicle accidents (MVAs). There is, however, increasing recognition that fall-asleep MVAs contribute significantly to road accident statistics.1-5 The typical fall-asleep accident involves a sole driver driving at night or in the early afternoon "siesta" period at relatively high speed.1 As with other causes of MVAs, fall-asleep accidents are more common in men under 30 years.1,3,5 In this issue (page 396), Desai and colleagues6 describe seven cases of fall-asleep fatal MVAs, and highlight the inconsistent way in which the New South Wales legal system dealt with these cases. They also draw attention to the role of sleepiness and sleep disorders in these cases, five of which involved under-treated or unrecognised obstructive sleep apnoea. These case studies are, by any measure, tragic, involving as they do serious injury, loss of life and, in several instances, imprisonment of the driver. They raise the question as to what role the medical profession might have in the prevention of such accidents. Obstructive sleep apnoea is the most common clinical sleep disorder leading to daytime sleepiness. About 26% and 10% of the Australian adult male population have ≥ 5 and ≥ 10 sleep apnoeas or hypopnoeas per hour, respectively.7 However, it is important to maintain perspective when thinking about this issue. First, while obstructive sleep apnoea is very common, most people with sleep apnoea will never have an accident due to sleepiness or be at significant risk for an accident.8 The relative risk for MVAs among all people with obstructive sleep apnoea is about 2–7 compared with the general population. This seems high, but is similar to the increased risk associated with driving at night,1 or for young drivers compared with older drivers. Second, sleep restriction (lack of sleep) is at least as common and is possibly of greater concern with respect to fall-asleep MVAs.5 The drivers with sleep apnoea described by Desai and colleagues all had mild-to-moderate obstructive sleep apnoea, which normally would not be associated with a high risk of an MVA,9 but, as acknowledged by the authors, the commercial drivers in particular were probably also sleep-deprived. In one case, prior sleep deprivation appeared to be the sole cause of the fall-asleep MVA. Nevertheless, there are patients with obstructive sleep apnoea who constitute a real and immediate risk to other road users. How does a medical practitioner identify and advise these patients, to try to prevent the tragedies so graphically described by Desai et al? The approach I would advise is as follows. First, establish good rapport with your patient and his or her family. A confrontational approach or immediately raising the possibility of revoking the driver's licence will lose you the patient. The emphasis should be on maintaining doctor–patient confidentiality, appealing to the patient's social responsibility, and the fact that, with appropriate diagnosis and treatment, most patients with sleep disorders can drive unrestricted. Assessing the effect of a patient's sleepiness on their driving Ask about instances of falling asleep while driving (eg, wheels on the verge or hitting the "cats eyes", lane drifting, previous fall-asleep crash) Seek corroborative history from the spouse or partner Ask patient to fill out the Epworth Sleepiness Scale questionnaire,10 which takes about five minutes. It requires patients to rate their chance of dozing in eight specific situations. The normal value is < 10 out of a maximum possible score of 24. A score > 15 indicates severe sleepiness and has been associated with substantially increased risk of fall-asleep MVAs.3 Consider additional causes of daytime sleepiness. Sleep restriction is very common and sleeping for less than five or six hours for even one night significantly increases the risk of a fall-asleep MVA.3,5 Second, make an assessment about the level of sleepiness and its possible impact on driving risk in your patient (Box). It would be unreasonable and totally impractical to send all patients with obstructive sleep apnoea for daytime sleep latency tests to determine level of sleepiness. Third, consider your patient to be in a "high-risk" category if there is a history of (1) a recent fall-asleep accident, (2) repeated "near-miss" fall asleep episodes while driving, (3) repeatedly falling asleep in other active situations (eg, during conversation, at meal table), or if your patient has a very high score on the Epworth Sleepiness Scale.10 Current Australian guidelines for healthcare professionals11 indicate that such "high-risk" patients should be instructed to stop driving immediately while referral to a sleep specialist and further investigation and treatment is arranged. If you consider that your patient is sleepy but does not fit the above "high-risk" categories, it may nevertheless be wise to advise him or her to reduce the risk of an MVA by avoiding night or country driving and by abstaining from all alcohol before driving. Fourth, keep careful notes. Ideally, all patients with obstructive sleep apnoea should be informed verbally, and in writing (eg, a pamphlet) if possible, about the increased risk of fall-asleep MVAs and the need to exercise care while driving. Special provisions apply if your patient wishes to apply for or renew a commercial or heavy vehicle driver's licence. Current Australian guidelines for healthcare professionals12 recommend that the licence be withheld if obstructive sleep apnoea (of any severity) is diagnosed, unless and until it is successfully treated. A conditional licence should be recommended (ie, restrictions imposed) if the driver has sleep apnoea symptoms of any severity until these symptoms are investigated. Thus, the burden of proof of driver safety has been deliberately increased for commercial drivers who have or are suspected of having obstructive sleep apnoea. Current uniform national driver licensing laws in Australia place the legal responsibility on drivers to notify their State/Territory licensing authority that they have a medical condition likely to affect their driving. If effective treatment for obstructive sleep apnoea (or any other sleep disorder) cannot be instituted within a reasonable time frame, and if your patient refuses to restrict driving as advised, you should remind him or her of this obligation. Finally, what is your ethical and legal responsibility if you have reason to believe that, against your advice, your patient is continuing to drive while seriously impaired? I believe at this point public safety takes precedence over patient confidentiality. Also, you could be found liable in the case of serious injury or death in the event of a fall-asleep accident should you fail to take reasonable steps to prevent your patient driving in a dangerous manner. You should advise the patient that, in the interests of public safety, you must inform the licensing authority. This action can and will annoy some patients, but legislation in all Australian States and Territories (Western Australian legislation is under review) provides medical practitioners with legal indemnity under these circumstances. The National Road Transport Commission will soon release new medical standards for drivers of all vehicle types. These will provide specific advice for medical practitioners relevant to licensing and driver safety across a wide range of medical conditions, including obstructive sleep apnoea.

R Doug McEvoy MD, FRACP

Infarct angioplasty has the potential to increase the disparity in outcomes between rural and urban patients with myocardial infarction The need for rapid treatment of coronary syndromes has been recognised for many years. Despite recent emphasis on the benefits of rapid thrombolysis, the main advantage of early presentation remains resuscitation from ventricular fibrillation. Defibrillation has been estimated to save about six times as many lives as thrombolytic treatment,1 but patients must reach medical assistance in time for it to be effective. On average, patients delay more than an hour before seeking help for symptoms of acute myocardial infarction, and about another hour elapses before they arrive at hospital.2-4 Attempts to shorten patient delay by education campaigns have been generally ineffective5 and, in recent years, efforts have been mainly directed towards expediting transport and hospital treatment of patients with myocardial infarction.2,3,6 In Australia, these efforts include fast-track pathways and delivering thrombolysis in emergency departments, before cardiological review.2,7 Significant improvements in call-to-needle times have been achieved,6 but, as Kelly and colleagues document in this issue of the Journal (page 381),2 not all patients are treated as rapidly as is desirable. The study by Kelly et al is particularly useful because it includes many of the patients treated with thrombolysis in Victoria over their study period of 30 months, and includes patients from rural and urban regions. Their data show that patients from rural areas delay longer before seeking attention and are slower to receive treatment than patients from large urban areas. While the association between delay in treatment and increased mortality in this study is likely to be partly confounded by unmeasured variables, few would dispute that these delays increase infarct size and the likelihood of dying during and after hospitalisation. Delayed treatment of myocardial infarction is one more manifestation of the geographic gradient in healthcare and outcomes in Australia.8 Controlled trials have shown that prehospital thrombo-lysis reduces mortality by about 20%.9 Prehospital thrombolysis is particularly suitable for remote regions with long ambulance transport times, and has been successfully implemented overseas without the use of mobile intensive care units.10 Even in urban areas, significant reductions in treatment delay have been achieved (between 30 and 60 minutes9), perhaps partly because a diagnosis is established before patients arrive at hospital and the hospital assessment process is circumvented. Yet, in Australia, prehospital thrombolysis has not been implemented in a systematic way. Kelly et al identify many of the barriers to the use of prehospital thrombolysis, including lack of appropriate ambulance equipment and failure to train and empower paramedics and nurses to give thrombolysis.2 They argue for a "bottom up" approach where individual healthcare ser-vices develop and own their strategies. Unfortunately, by itself, this is unlikely to effect change because of the complex funding mix of healthcare services in Australia and the parlous financial state of many rural health services. While rural and regional centres struggle to treat patients expeditiously with limited resources, metropolitan hospitals with cardiac catheterisation laboratories are moving steadily towards infarct angioplasty instead of thrombolysis.11 Whether this proceeds on a 24-hour basis depends mainly on the ability of individual cardiology departments to corral the necessary resources from their hospitals and the willingness of their staff to work nights and weekends. There is a strong body of evidence showing that infarct angioplasty is a better treatment than thrombolysis,12 but it is certainly more expensive to institute upfront. Proponents argue that it is cost effective compared with thrombolysis as it reduces hospital stay, but experience has taught hospital administrators to be wary of these claims as they rarely result in real cost savings. However, there is little doubt that infarct angioplasty is here to stay and that it will improve outcomes from myocardial infarction in patients fortunate enough to have access to it. If current trends continue, it has the potential to further increase the disparity in outcomes between rural and urban patients with myocardial infarction. How then should we respond to the data provided by Kelly and colleagues? Time delays in administering thrombolysis need to be seen in the context of the emergence of widespread use of infarct angioplasty and the particular geographic difficulties imposed by the Australian setting. In areas with transport times of more than 20 minutes, systematic use of prehospital thrombolysis could substantially improve outcomes at a modest cost. In urban areas, rapid transit to a facility with the ability to perform percutaneous transluminal coronary angioplasty (PTCA) is likely to become the standard. A combination of the two strategies could also be trialed in patients from areas without rapid access to PTCA (so called facilitated infarct angioplasty). Finally, in the debate about how best to achieve early revascularisation, it should not be forgotten that most of the delay occurs before the patient contacts the ambulance service and that, in this period, death is usually the result of ventricular fibrillation. As no strategy has been identified that encourages patients to present earlier, research should be directed towards improving the treatment of cardiac arrest with interventions such as prehospital thrombolysis13 and public access defibrillators.14

James W Leitch MB BS, FRACP

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months.Design: Prospective clinical audit.Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features.Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines — 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand.Main outcome measure: Adverse cardiac events during six-month follow-up.Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%).Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.

Con N Aroney MD, FRACP · Heather L Dunlevie BHlthScN · JH Nicholas Bett FRACP

Objective: To evaluate the impact of a chest-pain guideline on clinical decision-making and medium-term outcomes of patients presenting to a hospital emergency department (ED) with non-traumatic chest pain.Design: Before-and-after guideline implementation study.Setting: Bankstown–Lidcombe Hospital, Sydney, NSW (454-bed metropolitan teaching hospital), in the six-month periods before and after guideline implementation in February 2001.Participants: Patients presenting to the ED with non-traumatic chest pain who had chest-pain assessment forms completed by ED doctors, comprising 422/768 (54.9%) of those presenting before and 461/691 (66.7%) after guideline implementation.Main outcome measures: Appropriateness of admission/discharge decisions compared with decision of senior cardiologist based on guideline; death, recurrent chest pain, ED re-presentation and hospital readmission in the ensuing three months.Results: After guideline implementation, appropriate admission/discharge decisions increased significantly from 180/265 (68%) to 261/324 (81%) (difference, 13%; 95% CI, 6%–20%). The largest increase was for patients at moderate risk of death or acute myocardial infarction within six months, from 39/96 (38%) to 57/103 (55%) (difference, 18%; 95% CI, 4%–31%). Increases were seen for both junior doctors (interns and resident medical officers) (18%; 95% CI, 7%–30%) and senior doctors (11%; 95% CI, 2%–19%). Logistic regression showed that implementation of the guideline, seniority of assessing doctor and patient history of coronary disease were independent predictors of appropriate decisions. There was a significant decline in re-presentations to ED with recurrent chest pain in patients previously presenting with cardiac or possibly cardiac pain, from 46/201 (23%) before implementation to 32/247 (13%) after (difference, 210%; 95% CI, 217% to 23%).Conclusions: The chest-pain guideline resulted in a significant improvement in clinical decision-making in the ED and reduced re-presentations with cardiac/possibly cardiac chest pain.

Soufiane Boufous MPH(Hons) · Bin B Jalaludin PhD, FAFPHM · Charles H Pain FAFHPM · Susan Ieraci FACEM · Anne-Louise Gray BAppSc, PGCertMgt · Susan E Harris B Phty, MPH · Craig P Juergens FRACP · Peter W Kelleher FRACP · Linda M Dann FANZCA, FACEM

Objective: To determine the proportion of patients in Victoria treated within the British Heart Foundation 90-minute call-to-needle (CTN) time benchmark for thrombolysis of ST-elevation myocardial infarction (STEMI), and to validate the British Heart Foundation 90-minute benchmark with respect to mortality.Design: Cohort study.Setting: 20 hospitals and two ambulance services in the State of Victoria, Australia.Participants: 1147 patients with STEMI transported to hospital by ambulance and eligible for thrombolysis.Main outcome measures: CTN time, and in-hospital mortality.Results: Median CTN time was 83 minutes (mean, 93.2 min; range, 29–894 min). Median door-to-needle (DTN) time was 37 minutes (mean, 46.5 min; range, 0–853 min). 61% of patients received thrombolysis within the 90-minute benchmark. Patients with CTN times > 90 minutes had an increased risk of dying (relative risk, 1.8; 95% CI, 1.3–2.7). Factors associated with CTN time < 90 minutes were lower DTN time, prior notification of the receiving hospital and transport time less than 20 minutes.Conclusion: The British Heart Foundation CTN time benchmark is being met for 61% of eligible STEMI patients in Victoria. Strategies to reduce CTN time should be region-specific, and should include attempts to reduce DTN and to enhance ambulance–hospital communication. Prehospital thrombolysis may be appropriate for some regions.

Anne-Maree Kelly MD, FACEM · Debra Kerr BN, MBL · Ian Patrick BParamedStud, MICAcert · Tony Walker BParamedStud, GDipEd

Objective: To achieve sustained improvement in use of cefotaxime and ceftriaxone (CEFX) in a major teaching hospital, as measured against national antibiotic guidelines.Design and setting: Pre- and post-intervention survey of CEFX use in the Royal Melbourne Hospital, a tertiary hospital in Melbourne, Victoria.Intervention: Web-based antimicrobial approval system linked to national antibiotic guidelines was developed by a multidisciplinary team and implemented in March 2001.Main outcome measures: Change in rate of CEFX use (defined daily doses [DDDs] per 1000 acute occupied bed days) over 8 months pre- and 15 months post-intervention; concordance of indication for CEFX with national antibiotic guidelines pre- and post-intervention.Results: CEFX use decreased from a mean of 38.3 DDDs/1000 bed days pre-intervention to 15.9, 18.7 and 21.2 DDDs/1000 bed days at 1, 4 and 15 months post-intervention. Concordance with national antibiotic guidelines rose from 25% of courses pre-intervention to 51% within 5 months post-intervention (P < 0.002). Gentamicin use also increased, from a mean of 30.0 to 48.3 DDDs/1000 bed days (P = 0.0001).Conclusion: The web-based antimicrobial approval system achieved a sustained reduction in CEFX use over 15 months as well as increased prescribing concordance with antibiotic guidelines. It has potential for linking to electronic prescribing and for wider use for other drugs, as well as for research into the epidemiology of antibiotic use.

Michael J Richards FRACP · Lyn-Li Lim MB BS · Marion B Robertson BPharm, MSc · Nicholas R Jones BPharm, Grad Dip Clinical Pharmacy · Simone E Taylor PharmD, Grad Cert CRM · Margarida M Duarte BA (CompSci), BEng (partial) · Dale A Kerr BBus (Information Systems) · Graham J Stanton · Peter D Ritchie MPubHlth, FACEM · Jonathan G A Dartnell BPharm, PhD

Community-based surveys indicate that about a fifth of women have significant vulval symptoms lasting over three months at some time in their lives. Common causes of itch or pain are dermatitis, recurrent candidiasis and the recently recognised pain syndromes — vulvar vestibular syndrome and dysaesthetic vulvodynia. Diagnosis is usually apparent after a thorough history and examination, although conditions commonly coexist and are complicated by prior treatment. Skin lesions not responding to treatment require biopsy. Treatment aims to control symptoms rather than to cure; avoiding soaps and other irritants is central to management. An early, accurate diagnosis should enhance management of vulval conditions, particularly pain syndromes.

Belinda M Welsh FACD · Karen N Berzins DRANZCOG, Dip Ven · Kathy A Cook FRACOG · Christopher K Fairley FRACP, PhD

Obstructive sleep apnoea is associated with an increased risk of sleep-related motor vehicle accidents. Seven recent legal cases of fatal motor vehicle accidents on NSW roads are presented, where the driver who caused the accident was suffering from an unrecognised or under-treated sleep disorder. The legal outcomes in these cases were variable: some of the drivers have been acquitted and others have been jailed. All remained licensed to drive immediately after their accidents. In some of the cases, the driver was cleared of any culpable driving offence because of a defence of sleepiness or a sleep attack without warning ("Jiminez defence"). This appears at odds with current medical research and legal opinion in other countries. More research is needed to understand the relation between sleep disorders and awareness of sleepiness. Medical practitioners need to be aware of current advice and guidelines with respect to obstructive sleep apnoea and driving.

Anup V Desai MB BS, FRACP · Ronald R Grunstein PhD, FRACP · Elizabeth Ellis PhD, MHL · John R Wheatley PhD, FRACP

John Simpson Kirkpatrick, generally known as "Simpson", is one of the most famous Anzacs of the Gallipoli campaign.1-3 From the Gallipoli landing on 25 April 1915 until his death 25 days later, Simpson and his donkey retrieved perhaps 300 casualties from the battlefield. He did this work independently, sometimes in disregard of orders, and frequently with a disregard for danger that kept the onlooking soldiers in the trenches enthralled as they watched him moving calmly to rescue wounded soldiers while under direct fire from the enemy. He is often thought of as the quintessential larrikin Anzac, although he was born in England and only spent four years in Australia before enlisting in the Australian Army Medical Corps in 1914. Simpson's childhood was spent in Tyneside, United Kingdom, where his selfless military service is also well remembered. Early childhood John Kirkpatrick was born on 6 July 1892 in a newly-built4 three-roomed terrace tenement at 10 South Eldon Street, in the Tyne Dock area of South Shields.5 He was the son of Robert Kirkpatrick (c.1845–1909), a merchant navy seaman, and a domestic housekeeper, Sarah Simpson (c.1856–1933).6 Kirkpatrick had three surviving elder sisters and one elder brother. Census records reveal that their mother was sometimes away, and help with the care of the children in 1892 was provided by a domestic live-in servant, Ettie Crozier, aged 15 years.5 His younger sister Annie (born 10 November 1884) wrote to John and sent him cigarettes when he was working as a ship's stoker on Australian coastal traders and subsequently at Gallipoli.2 It is known from Kirkpatrick's surviving letters that food was not plentiful in his family, and the neighbourhood was poor.2 There was no social welfare. In one letter dated 31 May 1911 he replies to his mother's plan to become a shopkeeper in Edward Street, South Shields: A short life of Simpson 1892 John Simpson Kirkpatrick ("Simpson") born at 10 Eldon Street, Tyne Dock, South Shields, UK. 1898–1905 Attended school. 1906–1908 Worked as a milk-float boy. 1908–1909 Volunteer coastal-defence gunner with the 4th Durham (Howitzer) Battery of the 4th Northumbrian County of Durham Brigade, Royal Field Artillery. 1909–1914 Went to sea. Worked as a stoker and engine room greaser, mostly on Australian coastal shipping vessels. 1914 Enlisted in the Australian Army Medical Corps on 24 August, 20 days after Britain declared war on Germany. 1915 Landed at Anzac Cove on 25 April as a stretcher bearer with 3 Australian Field Ambulance. An undisciplined soldier, Simpson worked alone with donkeys he found in camp. He retrieved 200–300 men before he was killed by machinegun fire on 19 May — his 25th day of active service. I am very much afraid that you are in the wrong district ... for the people round there would rob "Old Nick" himself if he gave "Tick" [ie, credit] and I suppose you will know that there is no hope unless you give the good old "Tick". I wasn't four years going round with the milk without finding out a little of there [sic] weak points. Robert Kirkpatrick and his family moved frequently, perhaps because of difficulties paying the rent. John Kirkpatrick lived in at least five homes, and possibly six or more, during the first 16 years of his life. His father was frequently at sea, until he was injured in 1904, thereafter remaining at home as an invalid until his death in 1909 when John was 17 years old.2 The boy's entire childhood was spent in working-class streets. Census data from 1891 lists the occupation of the Kirkpatricks' neighbours as sailor, boilersmith, dressmaker, blacksmith, steam-engine fitter and iron moulder;5 in 1901 the neighbours were a shipyard plater, shipyard labourer, boilersmith and draper's assistant.7 The local society in which he grew up was dominated by shipbuilding and its industries, the Tyne River and the sea beyond. Schooling Kirkpatrick began school, aged six years, at the Barnes Road Infants' School in 1898. Surviving archives record that the school was crowded; in 1904 (four years after Kirkpatrick had left) it was closed for some weeks because 40 of the 509 pupils had measles, mumps, whooping cough or diphtheria. Kirkpatrick's initial two years of education included a curriculum of "reading, recitation, writing, arithmetic, singing and drawing".8 In July 1900, about the time of his eighth birthday, Kirkpatrick transferred to the South Shields Barnes Road Boys' School, where he remained a pupil until 19 June 1903.9 His attendance was exemplary, and he was absent for only one day throughout the school year of 1900–1901.10 He learned to read and write fluently at school. He was a prolific letter-writer in his later teenage years, although his punctuation and spelling were somewhat deficient. In 1903 he transferred to Mortimer Road Council School, where he completed his formal education in 1905 immediately before his thirteenth birthday. Tyneside children, contemporaries of John Simpson Kirkpatrick, playing in the street at the beginning of the 20th century. Epidemics of diphtheria, measles, scarlet fever, whooping cough and mumps swept through the Tyneside estates. (Photograph courtesy of the Ward Philipson Group, Gateshead, UK.) After Kirkpatrick's death at Anzac Cove, two memorial bursaries were instituted at Mortimer Road School, but these were abandoned in the 1960s. A building at the school was also named the Kirkpatrick House Block. The building was subsequently demolished in 1990. Of Kirkpatrick's surviving correspondence, nothing remains that refers to his childhood. Information from his sister Annie suggests that he had a typical Tyneside boyhood.2 The young Jack "played cricket using wickets chalked on a brick wall". He kept rabbits and "was an ordinary boy with little relish for scholarship but delighted in pranks and games and an occasional escapade". He played in the environs of the Gutt leading to Tyne Dock. The "Gutt" was an inlet with stone paving sloping down into the water to facilitate coal-loading. It was a scene of constant activity between people, animals, goods and the water of the Tyne. He attended weekly Sunday School at St Mary's Church (now demolished). Teenage years The terrace of John Williamson Street, Tyne Dock, South Shields, UK, built about 1889. Simpson lived briefly at number 360, far right. Kirkpatrick left school before his 13th birthday, and was employed as a milk-float boy. His sister Annie wrote later: 2 Jack had a dappled grey pony [which pulled the milk float] with which he became close friends. His devotion to "Andrew", to whom he talked like a human, was known to everybody on the milk rounds. Like many local teenage boys, Kirkpatrick volunteered to train at weekends as a coastal defence gunner in the Royal Field Artillery.11 He served in the Howitzer Battery at South Shields and trained nearby at Trow Lea and attended annual Volunteer Camp at Fleetwood in Lancashire, with his volunteer colleagues. It is probable that this was the first time, at 17 years of age, that he had journeyed beyond Tyneside. After his father's death in 1909, Kirkpatrick left Tyneside to go to sea. His second ship, the SS Yeddo, brought him to Australia via South America. He then worked for four years, mostly at sea, as a stoker and as an engine-room greaser on Australian coastal shipping vessels. He tried cane cutting and horse-mounted stock work in north Queensland, each for a period of about one week, but found the overwhelming heat and humidity intolerable. Life-saving influences? John Kirkpatrick spent the first 16 years of his life in South Shields, Tyneside. It was here that the life boat was invented by Greathead and Wouldhave in 1789. A second lifeboat, the "Tyne", managed by the Tyne Lifeboat Institution, was said to have saved 1028 lives between 1833 and 1894. It was then placed on public display in Ocean Road, South Shields, close to where Simpson grew up. The painting, "A wreck off the South Pier, South Shields, 1861", by John Scott, shows the "Tyne" in action. The painting has been on display in the South Shields Museum and Art Gallery since the late 19th century. (Reproduced courtesy of Tyne and Wear Museums.) During this time Kirkpatrick was leading a knockabout life. He jumped ship when it suited him, and, as his letters to his mother showed,2 enjoyed a drunken brawl with his fellows. This medallion showing Simpson and his donkey is presented annually by the Returned and Services League to an outstanding Australian "for exceptional service to the Australian community demonstrating compassion, endurance and dedication". (Photograph courtesy of Dr Robert Pearce.) At the outbreak of war in 1914, he was one of the first to enlist (on 25 August 1914) at Perth, in 3 Australian Field Ambulance. His physical strength and fitness (of which he was very proud) were ideally suited to his Anzac duties as a stretcher-bearer in the Australian Army Medical Corps. On a number of occasions he rescued two wounded soldiers simultaneously. His gregarious "Geordie" personality stamped him as a "character" among his fellow soldiers at Gallipoli. He has been described variously as "original, forthright, fearless, ingenious and generous hearted"; and as "witty, cracking jokes, happily lazy at times, careless of dress, a friendly chap and one who was a 'handful' to ... his Section Sergeant".2 Simpson's lasting fame arises from just 25 days of active service. What made him such a hero? The record we have cannot quite unfold the enigmatic "incalculable personal factor" which Lord Moran felt was "the essence of courage".12 "Simpson" on the web Simpson and his donkey (John Simpson Kirkpatrick). Australian War Memorial. <http://www.awm.gov.au/encyclopedia/simpson.htm> Simpson and his donkey. Convict Creations. Com — The hidden story of Australia's missing links. <http://www.convictcreations.com/history/simpson.htm> John Simpson Kirkpatrick. July 6, 1892 – May 19, 1915. Anzac House Youth Hostel. <http://www.anzachouse.com/simpson.shtml> Stretcher bearers. Digger history: an unofficial history of the Australian Armed Services. <http://www.diggerhistory.info/pages-nurses/stretcher.htm>

John H Pearn MD, PhD, FRACP · David Gardner-Medwin MD, FRCP

Clinical question"Is sunlight an effective treatment for jaundice in term infants?" A women's health educator at Southern Health wanted to know if there was any evidence that sunlight helps to reduce physiological jaundice in healthy term infants. Search question Definition of physiological jaundice1 Physiological jaundice is a diagnosis of exclusion. It should not fill any of the following criteria: Clinical jaundice in the first 24 hours of life; Total serum bilirubin level > 300 μmol/L in a term infant or > 255 μmol/L in a preterm infant; Direct reacting serum bilirubin level > 30 μmol/L, persisting more than 10 days in a term infant or 14 days in a preterm infant. The formulated search question followed a standard patients/interventions/comparisons/outcomes (PICO) format. Patients were term newborn infants with physiological jaundice (see Box), and the intervention was exposure to sunlight. Clinical outcomes of interest were primarily a reduction of jaundice. A randomised controlled trial comparing sunlight exposure to no treatment or another treatment would be the most appropriate study design to answer this clinical question. Search The search terms "neonatal jaundice", "hyperbilirubin(a)emia" or "icterus" were combined with the treatment search terms "sunlight", "heliotherapy" or "phototherapy". We searched the following electronic databases: the Cochrane Library, Best Evidence, MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Current Contents and Biological Abstracts. MEDLINE indexes articles published since 1966, but a widely cited and historically important article that provided the first English-language report of an association between light and a reduction in neonatal jaundice was published in 1958.2 In light of this, we hand-searched the print versions of Index Medicus and Science Citation Index from 1958 to 1966. We also searched the websites of a number of organisations: Bandolier, University of Michigan Department of Pediatrics (Evidence-Based Pediatrics), US National Guidelines Clearinghouse, National Health and Medical Research Council of Australia (Publications Catalogue), Scottish Intercollegiate Guidelines Network, and UK National Health Service (Institute of Health Sciences Guideline Project). Summary of findingsOur extensive search identified only the one, original study that examined sunlight exposure as a treatment for neonatal jaundice.2 This was a case series reporting the effect of sunlight in jaundiced preterm, rather than term, infants. The same authors then reported a case series of artificial light therapy for jaundiced preterm infants, which stimulated the subsequent considerable volume of research articles on the effectiveness of phototherapy for neonatal jaundice in both term and preterm infants. Current recommendations for artificial phototherapy are summarised elsewhere.3 We found no controlled trials comparing sunlight against either no treatment or artificial light treatment for jaundice. The use of sunlight appears to have resulted from anecdotal reports of its effectiveness4 rather than from rigorous medical evidence. And if the effectiveness of sunlight exposure for jaundice is unknown, so too is the incidence of potential risks to the neonate — for example, sunburn or photosensitivity. OutcomeThere is insufficient evidence to support exposure to sunlight for the treatment of jaundice. The persistence of this practice 40 years after publication of a report on a single case series raises questions about the influence of evidence on the beliefs of professional healthcare workers. Based on our search results, a recommendation against using sunlight exposure to treat jaundice was distributed to Southern Health staff and used in an education program for midwives.

Renea V Johnston PhD · Jeremy N Anderson MSc MD FRANZCP · Cheryl Prentice

Clinical record Day 1: A 32-year-old man who was HIV positive presented to a specialist HIV clinic with a one-month history of rectal discharge. Serological tests for syphilis performed five months earlier were unreactive. There were no genitourinary symptoms at this visit. Swabs to test for gonorrhoeal and chlamydial infection were obtained from the throat, urethra and rectum, and the patient was referred for serological tests for syphilis at a follow-up visit one week later (he was immune for hepatitis A and B). He had no penicillin allergy. He was given empirical treatment for chlamydia and gonorrhoea (a single dose of azithromycin 1 g orally and ceftriaxone 250 mg intramuscularly). His contacts were unknown. Six hours later the patient developed severe fever, chills, rigors, headache, severe myalgia and photophobia and was prostrate in bed overnight. Self-administered paracetamol did not relieve the symptoms, which largely subsided spontaneously after 8 hours. Day 2: The patient noticed a rash on the soles of his feet, and myalgia persisted, but his other systemic symptoms resolved. He contacted the clinic and was advised to return immediately for syphilis serological tests, as the acute symptoms suggested a Jarisch–Herxheimer reaction. On examination, the patient had bilateral non-tender inguinal lymphadenopathy. No chancres (ulcers of primary syphilis) were visible, including in the oral cavity and the perianal and genital areas. There was a non-pruritic, macular, symmetrical rash on the soles of both feet. His ankle joints were tender on passive movement. Day 3: Neisseria gonorrhoeae was isolated from the rectal culture. The serological tests for syphilis showed a rapid plasma reagin titre of 1:8 and a reactive Treponema pallidum haemagglutination assay. The patient's presentation was consistent with a Jarisch–Herxheimer reaction unmasking secondary syphilis (ie, systemic, cutaneous and nodal involvement, without a primary chancre). Subsequently, the patient was given 1.5 g procaine penicillin intramuscularly for 14 days. His sexual contacts were unknown. With continued treatment, his plantar rash became desquamating, and a new symmetrical macular rash appeared on his arms and trunk, but not on his palms. Follow-up: Over the next few weeks, the patient's symptoms resolved completely. Three months after treatment, his rapid plasma reagin titre had fallen to 1:4 and by 6 months it had fallen to 1:1. Classic presentation of secondary syphilis: macular, symmetrical rash on the back, palms, and soles. (NB: These photographs are not of the patient reported, who did not have a rash on his hands. However, the rashes he had on his back and feet were very similar to those shown.) In this patient, syphilis was unmasked by the Jarisch–Herxheimer reaction after ceftriaxone therapy for rectal gonorrhoea. The Jarisch–Herxheimer reaction is a self-limiting febrile reaction occurring 4–8 hours after penicillin treatment in 95% of early (primary and secondary) syphilis cases. The pathogenesis is unknown although lysis of the spirochaete, releasing endotoxin, probably contributes to the systemic illness. As the patient had no laboratory confirmation of syphilis at the time of presentation, we made this diagnosis based on (i) the acute onset and systemic nature of the symptoms of fever, malaise, chills, rigors, myalgia, and headache, occurring 6 hours after ceftriaxone injection; and (ii) the complete resolution of symptoms within 24 hours — all characteristic features of this reaction. Secondary syphilis occurs as the spirochaete disseminates from the site of infection (chancre) via blood and lymph nodes. A characteristic symmetrical macular rash (often on palms and soles) occurs 4–10 weeks after the appearance of the chancre. Less common symptoms include malaise, myalgia, pharyngitis, headache, lymphadenopathy, condylomata lata (which may mimic genital warts), oropharyngeal snail-track ulcers and, rarely, generalised pruritis. However, the diagnosis of secondary syphilis in this patient was clinical and based on (i) the Jarisch–Herxheimer reaction; and (ii) the appearance of the characteristic body and plantar rash (see Box), which intensified during treatment and desquamated before disappearing with successful treatment. Primary syphilis was excluded as there were no chancres. Because the systemic symptoms of the Jarisch–Herxheimer reaction and those of secondary syphilis are similar and overlap, delineating where the former "ends" and where the latter "starts" is not always clear-cut. The symptoms of secondary syphilis may increase during the Jarisch–Herxheimer reaction. The recommended treatment for early syphilis is 1 g procaine penicillin intramuscularly for 10 days.1 In our patient, the attending physician decided on a longer course and higher dose because the patient's HIV viral load was > 100 000 copies/mL and the CD4 count (350 × 106/L) was low. The efficacy of ceftriaxone in primary and secondary syphilis is comparable with that of intramuscular penicillin,2,3 and ceftriaxone is used in treating penicillin-allergic patients in the United States4 and Europe.5 One case of Jarisch–Herxheimer reaction after ceftriaxone therapy for primary syphilis has been reported;6 however, to the best of our knowledge, this adverse reaction to ceftriaxone has not previously been reported in Australia. The incidence of syphilis is increasing among homosexually active men in some large cities overseas (eg, Los Angeles).7 In south-eastern Sydney in 2002, 20 of the 119 notifications of syphilis received to August were classified as new infectious cases, compared with a total of 19 infectious syphilis cases notified for the whole of 2001.8 Local guidelines for sexual health testing have been established in response to concurrent gonorrhoea and hepatitis A epidemics in south-eastern Sydney.9 Screening for sexually transmitted infections is recommended at least annually among homosexually active men. All patients receiving intramuscular antibiotic treatment for early syphilis should be forewarned about the Jarisch–Herxheimer reaction. Without this reaction, syphilis may have been missed in this patient, had he not returned for serological tests a week later, as prearranged. Ideally, in this high-risk, symptomatic patient, serological tests for syphilis should also have been done at his initial presentation. In conclusion, the main lesson from this case is the need for full screening for sexually transmitted infections in all high-risk patients presenting with anogenital symptoms. Lessons from practice A thorough sexual history should be obtained from sexually active individuals at each visit to enable screening for sexually transmitted infections (STIs) and education to occur. Patients presenting with new symptoms suggestive of STIs should be screened for other STIs. Current guidelines recommend screening for syphilis and other STIs in sexually active individuals at least annually. In high-risk patients, more frequent screening should be considered. In Australia, intramuscular penicillin is recommended as first-line treatment for syphilis. All patients receiving intramuscular penicillin for early syphilis should be forewarned about the Jarisch–Herxheimer reaction.

Derek J Chan MB ChB, MM, MPH · Harry M Michelmore MB BS, DipVen, FACSHP · Julian Gold FACHSE, FAFPHM, MD

A "new genetics" has emerged driven by knowledge gained at the DNA level. In clinical practice, a practical application of the new genetics is DNA testing, which can be expected to expand with the completion of the Human Genome Project as the functions of new genes are discovered. Genetic DNA testing scenarios include diagnostic DNA testing, prenatal DNA testing, predictive (presymptomatic) DNA testing and screening DNA testing. The challenge for genetic DNA testing and clinical practice will be to define the roles to be played by the general practitioner, the specialist, and other healthcare professionals. From the patients' and families' perspective, the new genetics will best be implemented if a planned approach is adopted in the ordering of DNA tests and the associated counselling and support processes.

Ronald J A Trent FRACP, FRCPA · Robert Williamson FRS, FAA · Grant R Sutherland FRS, FAA

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

A 71-year-old man with a past history of right-sided, renal cell carcinoma presented with a recurrent, right upper eyelid lesion (Box, Figure A). The initial biopsy showed Bowen's disease, but review after Mohs micrographic surgery revealed focal sebaceous differentiation suggestive of in-situ sebaceous carcinoma. A diagnosis of Muir–Torre syndrome was suspected, and the patient was referred for genetic counselling and targeted cancer surveillance. This led to the discovery of multiple dysplastic colonic adenomas and a left renal cell carcinoma (Box, Figure B). Muir–Torre syndrome is an autosomal-dominant genodermatosis characterised by cutaneous sebaceous neoplasia and one or more visceral malignancies. Diagnostic criteria include at least one sebaceous gland adenoma, epithelioma, or carcinoma, and at least one internal malignancy. The diagnosis of sebaceous carcinoma can be difficult, particularly in the periocular region, where it often masquerades clinically as blepharoconjunctivitis or recurrent chalazia. Furthermore, sebaceous carcinoma often displays only focal differentiation and, as seen in our patient, may be histologically misdiagnosed as squamous-cell or basal-cell carcinoma. A history of internal malignancy in patients presenting with sebaceous gland carcinoma should raise the possibility of Muir–Torre syndrome. Correct diagnosis in this case enabled early detection of dysplastic colonic polyps and renal cell carcinoma. A: Clinical photograph showing induration and ulceration of the central right upper eyelid margin. B: Computerised tomography scan showing a left renal mass (arrow) confined to the capsule.

Celia S Chen MB BS · Lindy Loweinstein · Shyamala C Huilgol FACD · Dinesh Selva FRANZCO · Craig James FACPA

In January 2002, 12 European Union countries introduced a new common currency, the euro, which soon afterwards displaced the national currencies of the member states. With that historical act, along with the loss of monetary individuality, we lost an unusual "document" of medical history: the Greek 10 000-drachma note. The front of this banknote shows George Papanicolaou, the "father" of exfoliative cytology (Box, A). Born in Kymi, Greece, in 1883, he studied medicine in Athens and graduated with honours. After emigration to the United States in 1913, he began to study the ovarian cycle in animals (and later in humans), using vaginal smears. He identified the female sexual cycle and, in 1928, presented his results of "possible diagnosis of certain conditions, especially malignancy" by vaginal smear. Through his studies, he became aware that "carcinoma of the fundus and carcinoma of the cervix are to some extent exfoliative lesions, in the sense that cells at the free surface of the growth tend to be dislodged and subsequently find their way into the vagina". In 1941, he presented the method of taking and staining vaginal smears and described the cellular appearance in carcinoma of the uterus. His method was validated and adopted worldwide as the "Papanicolaou test". Papanicolaou died in Miami, Florida, in 1962. Nowadays, cervical cancer, once the most lethal of gynaecological carcinomas, is rare in Western countries, but still the first cause of death among women in most developing countries, where few women receive Pap smears. The reverse side of the banknote shows the god of healing, Asklepios (also called Asclepius or Aesculapius), who lived around 1200 BC in Thessaly, Greece (Box, B). In Greek mythology he was the son of Apollo and the nymph Koronis (Coronis, Cronis). Apollo entrusted the education of Asklepios to the centaur Chiron, who taught him how to treat wounds and how to use herbs for healing. Zeus, who was afraid that Asklepios's great healing powers might render all men immortal and thus challenge the power of the gods, killed Asklepios with a thunderbolt. (Another version of the myth relates that Asklepios was made immortal.) The symbol of Asklepios is the staff with a serpent coiled around it. Besides being mystical and symbolic animals, sacred snakes played an important role in healing rituals. Current biological knowledge suggests that growth factors, which are present in the saliva of certain snakes, may have stimulated healing processes at the site of wounds. The historic 10 000-drachma note A. The front of the 10 000-drachma note, showing George Papanicolaou (1883–1962), with his microscope and famous Atlas of exfoliative cytology, published in 1954. B. The reverse side of the 10 000-drachma note, showing Asklepios, the god of healing, with his symbol, the staff with a serpent coiled around it. Beside him, a healing scene depicts a sacred snake licking or biting the right shoulder of a sleeping patient.

Theodor Tirilomis MD FETCS · Stella Malliarou MD