Letters

Peter A Frith Head of Southern Respiratory Services, Respiratory Unit, Flinders Medical Centre, Bedford Drive, Bedford Park, SA 5042. Peter.frithATrgh.sa.gov.au To the Editor: The informative study by Simons and colleagues1 has highlighted a major concern. Chronic obstructive pulmonary disease (COPD) is one of Australia’s top four causes of death and burden of illness,2 yet the authors have made no mention of COPD. Failure to recognise the importance of this disease is an endemic attitude in Australia and globally3-5 that results in under-representation of COPD in epidemiological surveys and in inadequate funding for effective treatments and research. The study found that peak expiratory flow (PEF) provides the highest hazard ratios for predicting time to death in women (and the second highest in men). There is even a “dose–response” effect. Using the term “impaired PEF” is a bit like saying “impaired ECG” without attributing a diagnosis. PEF is a measure of airway calibre, and impairment of PEF indicates airway disease — largely COPD in this population. Smoking accounts for about 85% of the risk of COPD, and about 50% of smokers develop airflow limitation,4-6 so it is not surprising that the interaction between PEF and smoking was the most important predictor of reduced survival in this large cohort. It’s time to stop hiding our heads in the ashtray! Smoking combined with low PEF is COPD. We must demand that our medical and epidemiological professions uncover people with undiagnosed COPD. Early diagnosis is simple.5 It’s not normal to be unable to keep up with friends at work or during recreation because of breathlessness, and a daily cough is really an airway disease. If symptoms are acknowledged, spirometry will confirm the diagnosis. We should help our patients to enunciate these hidden symptoms so their condition can be diagnosed accurately, and effective management begun, as highlighted in the “COPDX management guidelines”.5 Primary and secondary prevention must focus on reducing smoking among young people. Smoking cessation, the use of effective drugs, and pulmonary rehabilitation are the cornerstones of COPD therapy that lead to better quality survival. COPD is common and under-diagnosed. Simons et al have partly exposed this deadly condition. Their data, added to other Australian data,7 should trigger actions that facilitate earlier diagnosis throughout Australia and support delivery of effective treatment to the thousands “dying a slow death” from COPD. Australia’s illness burden from COPD is high. Its prevalence and burden in Australia are rising, especially in women. Globally, the World Health Organization expects COPD to rise from 12th to 5th as a cause of illness burden by 2020. We must acknowledge that PEF impairment is not simply a mysterious risk factor for early “all-cause mortality”, but is indicative of COPD being a major contributor to death in this population.

Peter A Frith

Leon A Simons,* Judith Simons† * Director, Dubbo Study of the elderly, † Data Manager, Lipid Department, St Vincent’s Hospital, Darlinghurst, NSW 2010. L. SimonsATnotes.med.unsw.edu.au In reply: The prospective Dubbo Study of the elderly has produced a series of publications in which reduced peak expiratory flow (PEF) has been shown to be associated with increased risk of death,1,2 as well as increased risk of heart attack,3 ischaemic stroke4 and admission to a nursing home. 5 We have employed a purely statistical definition of impaired PEF, namely the lowest third of our sex-specific population distribution. We agree that many subjects so defined with impaired PEF, and who are smokers, will have underlying and potentially undiagnosed chronic obstructive pulmonary disease (COPD). Epidemiological studies have highlighted the importance of impaired PEF. It is now time for health professionals to implement the COPDX management guidelines referred to by Frith6 in a still more effective manner and to devise better prevention programs.

Leon A Simons · Judith Simons

Bernard M Bourke Vascular Surgeon, Gosford Hospital, 4/213 Albany Street North, Gosford, NSW 2250. Dr. BourkeATgvs.com.au To the Editor: Up and coming surgical registrar, Ken Wong, presents a revolutionary plan to allow him to look after surgical patients in the operating theatre.1 The use of the telephone for communication has merit, but he won’t feel so smug when he gets to the chapter entitled “The management of surgical patients in NSW public hospitals in winter”. There will be nowhere for Dr Wong to “hide” when he realises our operating theatres are, in fact, solar powered and that, when the sun goes down in winter, the theatres conk out. Surely now, with the statewide mergers of health services, there will be enough excess “committee people” to form a collaboration with the western NSW farmers so that the mice plague can be harnessed and trained to run on the cogs and at least provide lighting during power shortages. I’m sure my daughter could lend a few cats to chase the mice. In the absence of the provision of more hospital beds, the substitution of cat-and-mouse power for solar power is the best “winter strategy” I’ve heard in the last 10 years. This concept will feature in our next chapter, “How to train surgeons without patients or operating time”.

Bernard M Bourke

Craig A Aboltins,* John R Daffy,† Penny Allen‡ * Infectious Diseases Registrar, † Infectious Diseases Physician, St Vincent’s Hospital, Victoria Parade, Fitzroy, VIC 3065; ‡ Ophthalmologist, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC. craigaboltinsATnetspace.net.au To the Editor: Within the last 12 months, four injecting drug users (IDUs) who had been injecting buprenorphine presented to the Royal Victorian Eye and Ear Hospital with endogenous fungal endophthalmitis (EFE) involving Candida species. All four patients admitted that they had diverted or obtained diverted sublingual buprenorphine from the oral cavity after it was dispensed. They had dissolved the remaining drug in water and injected it intravenously. We present an illustrative case. A 28-year-old woman presented with a 4-week history of left eye pain and erythema. She had a 10-year history of intravenous drug use. Over the previous 6 months, she had been regularly injecting buprenorphine that was prescribed to a friend. The friend had been removing the partially dissolved buprenorphine from his mouth before giving it to our patient. On examination, the patient could only detect hand movement with her left eye. Fundoscopy showed vitritis with a “snow ball appearance” consistent with EFE. Treatment involved vitrectomy, intravitreal amphotericin and oral fluconazole. Candida albicans was cultured from vitreal specimens. Her visual acuity had improved to 1/60 at the time of discharge. Intravenous drug use is known to be a risk factor for EFE. Candida species are the usual causative organisms, but Aspergillus species have also been reported.1 In the 1980s, there were many reports of candida endophthalmitis in injecting drug users associated with the use of “brown” (or Iranian) heroin. The “brown” heroin required an acidic substance, often lemon juice, as a solvent. Lemon juice was shown to be the source of the candida.2 However, over the past 10 years, the heroin available in Australia has been water soluble, and sterile or tap water is usually used to dissolve the heroin before injection. None of the cases we report in this letter involved lemon juice to dissolve heroin or buprenorphine before injection. Buprenorphine has been available in Australia since 2001 for the treatment of opiate addiction. It is usually dispensed daily by pharmacies in a crushed tablet form. Pharmacists are required to watch patients place and dissolve the medication under the tongue before they leave the pharmacy. Contamination of injected buprenorphine with orally derived Candida species presents a recently recognised cause of fungal endophthalmitis in injecting drug users.3 Doctors, pharmacists and drug users need to be aware of the risk of this sight-threatening complication.

Craig A Aboltins · John R Daffy · Penny Allen

Ariella Glaser,* Dwight Arakaki,† Gar Ming Chan,‡ Robert S Hoffman§ * Resident, Mount Sinai Medical Center, New York City, NY, USA; † Resident, Beth Israel Medical Center, New York City, NY, USA; ‡ Fellow (and corresponding author), § Director, New York City Poison Control Center, New York City, NY, USA. garchanATpol.net To the Editor: Two aspects of the recent article by Kelly et al comparing intranasal with intramuscular naloxone in suspected opioid overdose1 make their study difficult to interpret. The methods allowed for a great deal of bias. There was no attempt to blind evaluators to therapy, and knowing which therapy is to be used a priori may influence both therapy selection and perceived outcome. The second flaw we noted was the use of the Glascow Coma Scale (GCS) in a non-trauma patient.2 An improvement in GCS score may represent increased wakefulness or even withdrawal. The use of the GCS does not make it possible to determine what degree of improvement or worsening the therapy resulted in. In the opioid-intoxicated patient, the “alert/verbal/pain/unresponsive” (AVPU) scale is more appropriate. We agree that the use of needles in a high-risk patient is dangerous. However, if these patients do not respond to painful stimuli, there should be no danger at all.

Ariella Glaser · Dwight Arakaki · Gar Ming Chan · Robert S Hoffman

Anne-Maree Kelly,* Debra Kerr,† Paul Dietze‡ * Director, † Deputy Director, Joseph Epstein Centre for Emergency Medicine Research, Western Hospital, Private Bag, Footscray, VIC 3011. ‡ Research Fellow, Turning Point Alcohol and Drug Centre, Fitzroy, VIC. Anne-Maree. KellyATwh.org.au In reply: The prehospital setting for research poses challenges that require some flexibility in study design. While it would have been preferable to have used blinded naloxone and placebo solutions for both routes of administration in our study, financial and operational constraints made this impossible, so some bias in evaluations is possible. However, this is not necessarily in favour of the intranasal route, as before the study many paramedics were very sceptical about the intranasal naloxone preparation. Therapy selection was by random allocation in sealed envelopes as described in our article. The Glasgow Coma Scale score was chosen as an outcome measure because it was the parameter used operationally for treatment and disposition decisions in the ambulance service within which our study was conducted. We acknowledge its limitations in non-trauma patients. The potential for needlestick injury in this situation is real. Patients with opioid intoxication may be in cramped locations and may be irritable on waking, increasing the risks involved with handling a “sharp”. Given the prevalence of blood-borne viruses in the injecting drug user population, strategies to reduce the risk of needlestick injury are highly desirable. Additionally, a strategy that has been suggested for preventing opioid-overdose-related deaths is to make naloxone more widely available in the community. 1 The intranasal formulation of naloxone may be appropriate for this, as it has significant advantages including reducing risks of blood-borne virus transmission and minimising the requirement for training and the secure storage of syringes and needles. 2

Anne-Maree Kelly · Debra Kerr · Paul Dietze

Roslyn G Poulos,* Anthony B Zwi† * Lecturer, † Professor and Head, School of Public Health and Community Medicine, University of New South Wales, Sydney, NSW 2052. r.poulosATunsw.edu.au To the Editor: With increasing attention focused on the need for evidence-based policy making in recent years, researchers have come to the realisation that research has, in fact, little impact on policy making. The literature abounds with theories on how to improve the appropriate use of research evidence in policy decisions. Researchers must shoulder a large proportion of the responsibility, having spent too much energy generating evidence and insufficient time “translating” this knowledge into a useful product for decision makers.1 Further, the failure of the two communities to communicate has allowed researchers to follow their own agendas, rather than those of the potential users of their research.2 Improved two-way communication between researchers and policy makers may improve the uptake of research evidence.3 This is best achieved by supporting policy makers to utilise evidence and researchers to become more policy-sensitive. However, even when evidence has been “translated” and acknowledged, it is still subject to other forces. There are numerous barriers to evidence-based policy making, not the least of which is politics. For example, Stevenson recently highlighted the fact that young drivers are disproportionately represented in road trauma statistics.4 He presented data on a number of interventions that have successfully reduced fatal and injurious crashes involving young drivers. Similar data were presented by the NSW Government in its options paper on improving safety for young drivers, which was put out for community consultation in late 2004.5 So far, a policy decision has been made on only two out of 11 options. One decision, which prohibits provisional (P1) licence holders from driving high-performance cars, has, by the Government’s own admission, no supporting evidence of effectiveness.5 The other decision places a limit of one passenger for 12 months for drivers who lose their provisional (P1 or P2) licence. However, this decision is a variant of a strategy that is supported by evidence, and consequently may have little or no effect. Researchers need to be aware that social, electoral, ethical, cultural and economic factors have a powerful influence on policy.6 While the literature on evidence-based policy exhorts researchers and policy makers to work on bridging the gap between evidence and policy, the role of other key players (such as the public) has tended to be overlooked.7 As part of a National Health and Medical Research Council capacity-building grant in population health research, a consortium of academic institutions is working on enhancing the interface between injury research and policy and on promoting evidence-informed policy in injury prevention. (Members of the consortium are the NSW Injury Risk Management Research Centre, the School of Public Health and Community Medicine, and the Prince of Wales Medical Research Institute [all of the University of NSW]; and the Rehabilitation Studies Unit and George Institute for International Health [of the University of Sydney]). The role of the public as an audience with which researchers might profitably interact to improve dissemination and uptake of evidence will be explored, as will the role of health journalists in facilitating this.

Roslyn G Poulos · Anthony B Zwi

Simon J Foote Professor, Senior Principal Research Fellow, and Joint Head, Genetics and Bioinformatics Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, VIC 3050. footeATwehi.edu.au To the Editor: I am amazed by your assertion in your recent column in the Journal that many clinicians fail to equate advances in basic research to advances in clinical medicine. 1 I would therefore like to make some small contribution to your understanding of the work of Richard Axel and Linda Buck, 2004 Nobel laureates in Physiology or Medicine, 2 and why this was considered worthy of the Nobel Prize. Our understanding of the nervous system is still very primitive, and their almost complete description of the functioning of the odorant system — a small part of the nervous system — has laid down many of the principles pertinent to the more complex fundamentals for understanding neuronal signalling and signal processing. This is essential to an understanding of neurological and psychiatric diseases. The odorant receptors are also G-coupled protein kinases, and this is one of the most frequently targeted groups of compounds for novel small-molecular therapies. If anyone still believes that Nobel Prize-winning science, such as understanding neuronal circuitry, is irrelevant to clinical medicine, they might look at the 2003 recipients for the Nobel Prize in Physiology or Medicine, Paul Lauterbur and Peter Mansfield. They received the award for the discovery of magnetic resonance imaging, which clearly plays a role in “mainstream” medicine.

Simon J Foote

Martin B Van Der Weyden Editor, The Medical Journal of Australia, Locked Bag 3030, Strawberry Hills, NSW 2012. medjaustATampco.com.au In reply: I welcome Foote’s comments, but, to the contrary, I find it entirely credible that many clinicians “fail to equate advances in basic research to advances in clinical medicine.” The reasons are many, but include not only the tortuous language of research,1,2 but also the scepticism that inevitably follows research announcements of “cures” and “breakthroughs”, which prove to be patently premature or just peter out.3 However, I am amazed that Foote appears to have missed the point of my column — the “narrowness of the Nobel awards for physiology or medicine” with their recent predominance of basic research.4 While it must be admitted that the Nobel Prize is increasingly awarded for what is undoubtedly outstanding basic research that has the potential to be of “greatest benefit for mankind”, much of this potential remains unrealised. Indeed, it was the need for recognition of clinical and epidemiological research in the Nobel awards that moved the Lancet, in its Paper of the year 2004, to seek sponsorship for the clinical equivalent of the Lasker and Nobel awards.5 In summary, it is research’s exclusivity, the rise of its false prophets, and the irrelevance of most recent Nobel Awards to everyday practice that fuel disinterest among clinicians.

Martin B Van Der Weyden

Kevin L Forbes Head, Years 3 & 4 MB BS Program, School of Medicine, University of Queensland, Mayne Medical School, Herston, QLD 4006. k.forbesATuq.edu.au To the Editor: The personal perspective on continuous improvement outlined by Kilham succinctly documents the concerns surrounding the application of management tools to the practice of medicine.1 As Kilham says, continuous improvement has been around for a long time and “flowed from a particular attitude . . . [that of] a mind open enough to recognise better ways of doing things, or ways of doing better things”.1 However, I would argue that even history-taking does need to continually improve to include various communication skills appropriate to individual patients. Continuous improvement in history-taking skills, to enable each patient to express their major concerns and to feel more in control of the consultation, has significantly reduced my feelings of frustration provoked by previous patients. Adherence to the strict script of history-taking taught to me in my undergraduate training seemed to provoke a rejection of the expert advice I was giving them. Management does need to understand the importance of recognising good work already done and the current high achievements of medical practitioners. On the other hand, even the busiest of clinicians should understand the professional advantage of participation in a project to further improve or develop new ways of solving their patients’ problems. There are multiple strategies needed for the effective “change from the existing entrenched structure and culture of patient care to one based on patient- centred, evidence-based care”.2 However, management certainly needs to support the busy clinicians during the project. It is also better to avoid jargon and the constant renaming of programs. I would argue that the learning principle underlying the range of continuous improvement programs is the same. That principle is to question, accept challenges, explain, justify and seek further information as a continuous process.3 One essential feature of continuous improvement (whatever it is called) is that the practitioner needs to participate in the selection of the project for continuous improvement and the objective outcome measures that will prove the change to be advantageous or not advantageous. It is also important to recognise that successful continuous improvement programs in one context do not necessarily translate to another context. I agree that management must accept the same standards and accountability demanded of clinicians. In addition, all clinicians should participate in continuous improvement projects as well as being assured that we currently practise medicine at a high standard.

Kevin L Forbes

Bill Coote Medical Practitioner, 20 Ryrie St, Campbell, ACT 2612. billcooteATnetspeed.com.au To the Editor: Gordon, Director of the Centre for Medical Humanities at the University of Sydney, suggests that “the separation of clinical care from the ‘human sciences’ is a professional and social mistake”, and that “the arts, humanities and social sciences act as a counterbalance to the relentless reductionism of the biomedical sciences”. 1 Her university now offers a Masters in Medical Humanities and the opportunity to study subjects such as Medicine and war and Medicine and music. Gordon suggests that study of the medical humanities could result in “a more insightful view of the patient, the doctor and the health care system, and an enhanced capacity to cure, relieve and comfort”, and that “history, philosophy and sociology warn that the person with the disease is all too easily reduced to the non-hygienic, non-rational, disordered ‘other’ ”, while “the growth of medicine as an economic and rational profession has paradoxically contributed to the social diminution of the body, the very object of its focus”. 1 This warrants a response more elegant than the earthy Australian expletives that come to mind. That master of teasing irony, Jane Austen, makes gentle fun in Emma of educational establishments “which professed, in long sentences of refined nonsense, to combine liberal acquirements with elegant morality upon new principles and new systems”.2 In an article entitled Medicine and literature, UK medical historian Neve argues “there are numerous difficulties tracing the connections between two vast areas of human effort that may not be easily twinned” and that “the desire to twin them may be an ambition more attractive to medical practitioners than to writers and artists”.3 Doctors may yearn to counter a modern perception that they are mere technicians, some by seeking to reclaim a lost identity as the last of the humanists. Neve provocatively suggests that for many modern practitioners, often “their cases are routine, unglamorous, and socially explicable in matter-of-fact terms”.3 Maybe the best approach to the humanities for anyone, including doctors, lies somewhere between the sermonising of Gordon and the temptations of escapist fantasy, such as those offered by the master of ceremonies in the movie Cabaret with his excuse that “life is disappointing, forget it”.4

Bill Coote

Jill Gordon Director, Centre for Medical Humanities, University of Sydney, NSW 2006. jill.gordonATarts.usyd.edu.au In reply: It may be possible to identify an approach that lies “somewhere between the sermonising of Gordon”, as Coote puts it, and the world-weariness of the master of ceremonies at the Kit Kat Club. Research in the social sciences suggests that we derive more personal happiness from positive experiences, including our social and intellectual pursuits, than from material possessions. These findings are probably due to the fact that positive experiences generate pleasant memories and a richer sense of personal identity. Positive experiences also have greater social value than possessions, being more easily shared with others. Thinking and talking about new ideas provides a great deal of pleasure and satisfaction for students in the medical humanities. While mere “cases” may be, as Coote quotes, “routine, unglamorous, and socially explicable in matter-of-fact terms”, the doctor–patient relationship is not. Medicine provides a resource which can be used, as philosopher Martyn Evans has pointed out, to reflect on ourselves, express ourselves, develop ourselves, criticise ourselves and encounter ourselves.1 To do these things, we need tools constructed by the arts and humanities, as well as the sciences. Coote’s choice of reading material — the Companion encyclopedia of the history of medicine2 — is a great place to begin.

Jill Gordon

To the Editor: The disastrous events of Boxing Day, 2004 left hundreds of thousands dead, injured or homeless across large parts of Asia. Many aid teams dispatched to affected areas are grappling with the aftermath of this catastrophe. Here, I present one of many clinical observations of what we encountered in the field. It is a clinical anecdote, but one worth sharing, as it may guide future teams in similar situations. A 62-year-old woman was admitted to hospital with a history of vague ill-health for 12 months, and a subacute illness over the 4 weeks since immersion in the tsunami, with persistant cough, dyspnoea and weakness to the point of being largely bed-bound. She was cachectic, had a fever of 37.5°C and scattered crackles in both lower lung fields. Radiology facilities were not available and she was not producing sputum. She was treated empirically with antituberculous chemotherapy, as well as broad-spectrum antibiotics in the form of amoxycillin and ciprofloxacin orally, but her condition did not improve. X-ray facilities became available soon thereafter, and a chest x-ray showed changes more in keeping with a necrotising pneumonia than tuberculosis ( [a]). Her treatment was changed to intravenous meropenem (1 g every 8 hours) and her condition was slowly improving when we left. During our 2-week posting in Banda Aceh, we saw about 6–10 patients at three hospitals presenting about a month after their immersion, with fluctuating fever; chronic, non-productive cough; and radiological evidence of bilateral, asymmetric, necrotising pneumonia with cavitation. Some patients developed empyemas and pneumothoraces ( [b]). They failed to respond to broad-spectrum antibiotics including ampicillin/gentamicin/metronidazole and ticarcillin–clavulanate/cotrimoxazole. Burkholderia pseudomallei was cultured from the pleural fluid of two of these patients, and Nocardia sp. from the sputum of another. A notable feature of these patients was their subacute presentation weeks after immersion in the tsunami, the persistence of symptoms despite other broad spectrum antibiotic therapy, and the development of radiological and clinical manifestations of necrosis with pleural involvement. Many of our patients described the wave as being “black”. In view of the immersion in muddy water in a tropical environment, B. pseudomallei is likely to have been one of the causative organisms in many of these cases. However, it has not been possible to culture B. pseudomallei from all patients, and it is likely that their infections were polymicrobial given the circumstances of their injuries. A variety of bacterial organisms, as well as fungi, have been recognised in other such situations.1-3 When we were there, Fakinah hospital provided one of the few laboratory services in Banda Aceh, and the availability of these facilities were limited as they were focused on public health surveillance. Thus, collection of specimens for culture was not routine. Furthermore, when we arrived there were no nurses, no medical records and no medication or observation charts. While the situation improved rapidly during our stay, these limitations meant that recognition of emerging clinical patterns was important. Many of the antibiotics initially used for patients with immersion injuries were ineffective in this setting, and the use of carbapenems became our first-line, or early second-line, antibiotic in post-immersion respiratory infections in Banda Aceh. Chest x-rays of patients with subacute necrotising pneumonia (a) Bilateral consolidation with scarring and early cavitation in the lower lung fields (b) Bilateral necrotising pneumonia complicated by right pneumothorax

Anthony M Allworth

To the Editor: When discussing causes of childhood leukaemia, Ziegler et al stated, “Exposure to electromagnetic fields has been ruled out as playing any significant role”. 1 They cited one large study2 in support of this statement, but overlooked two independent pooled analyses that showed the opposite. Greenland et al analysed 12 studies involving 2656 patients and 7084 controls, 3 and Ahlbom et al analysed nine studies involving 3247 patients and 10 400 controls.4 Each analysis found an association with a doubling of risk of childhood leukaemia at levels of household exposure at and over 0.4 microtesla (4 milligauss). Confounders and sources of bias to explain these findings have been sought without success. Consequently, in 2002, the International Agency for Research on Cancer classified 50 and 60 Hz magnetic fields as a “possible carcinogen” (Group 2b)5 even though the mechanism of an effect is not clear. The role of magnetic fields in childhood leukaemia cannot be “ruled out”, given the substantial epidemiological evidence, the international classification of magnetic fields as a possible carcinogen, and the subtlety of gene–environment interactions. Moreover, although exposures to magnetic fields are low within most households, there is opportunity to easily prevent or treat the uncommon situations where household exposures exceed 0.4 microtesla by means of electrical engineering, household wiring and town planning.

Bruce Hocking

In reply: Hocking states that electromagnetic fields cannot be ruled out as a cause of childhood leukaemia. However, several large studies have all failed to find any association between childhood exposure to electromagnetic radiation and leukaemia.1-4 The two pooled meta-analyses Hocking refers to both found no increased incidence of leukaemia with exposure to electromagnetic fields of < 0.4 microtesla.5,6 Although there was an increased risk of leukaemia with exposure to ≥ 0.4 microtesla, 99.2% of children with leukaemia had not received such a high level of exposure. 5 In addition, both studies acknowledged the potential for selection bias. As such, for the overwhelming majority of children with leukaemia, exposure to electromagnetic fields does not play any significant causative role. Although we agree its effect cannot be ruled out for the remaining < 1% of patients, it should not be given undue epidemiological weight.

David S Ziegler · Luciano Dalla Pozza · Keith D Waters · Glenn M Marshall

To the Editor: The recent position statement by the Warfarin Reversal Consensus Group provides clear and concise guidelines for a number of clinical scenarios related to the use of warfarin. 1 Unfortunately, it makes the general statement about the periprocedural management of warfarin in patients with atrial fibrillation (AF), “clinical experience suggests that bridging therapy is not required” [page 496]. Clinicians caring for patients with large ischaemic stroke in these circumstances may beg to differ. Although studies of bridging therapy in patients with AF in the periprocedural period are lacking, there are data which suggest that there is a considerably higher risk of thromboembolism during this period than would be expected by simply calculating the risk for several days off anticoagulation therapy.2-4 My own study of such patients undergoing endoscopy found a stroke risk of up to 3% in those at high risk.2 Many of these strokes were severe. The prothrombotic periprocedural environment may be a factor here, although advanced age and vascular risk factors may also contribute. The outstanding risk factor, however, is a previous history of stroke,2 and this is also a major risk factor for perioperative stroke in patients without AF.5 I would suggest careful, individualised assessment of all patients, and judicious bridging therapy where possible for patients with AF who have a past history of stroke.

David J Blacker

To the Editor: The recent position statement from the Warfarin Reversal Consensus Group provides a comprehensive, coherent and practical approach to warfarin reversal management. 1 In reviewing the position statement, and with particular reference to the paragraph about modifiers of warfarin response, we noted that the contribution of cytochrome P450 2C9 (CYP2C9) genotype to the response to warfarin was not addressed. There is debate in the current literature about the clinical utility of evaluating CYP 2C9 genotype in patients already taking or about to start warfarin therapy. Nonetheless, a significant body of evidence supports the contribution of CYP2C9 genetic variants as modifiers of response to warfarin therapy. CYP2C9 is the enzyme principally involved in metabolising warfarin.2 Several studies have identified the presence of single nucleotide polymorphisms in the CYP2C9 gene resulting in the expression of two allelic variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) that are associated with reduced enzymatic activity, impaired metabolism of and increased sensitivity to standard warfarin doses.2,3 The allelic frequency of the mutant genotypes is in excess of 21% in the white population2 (they occur at reduced frequencies in African American populations and are rare in Asian populations4). The presence of allelic variants (CYP2C9*2 and CYP2C9*3) with reduced enzymatic activity is closely correlated with increased bleeding complications.2,3 Thus, there is potential for a considerable clinical impact given the large number of patients taking warfarin. We have identified an allelic frequency of CYP2C9*2 and CYP2C9*3 genotypes in an Australian population of patients attending an anticoagulant clinic comparable to that reported in the literature.2,3 We also identified international normalised ratios in excess of the target range in patients with the CYP2C9*2 or CYP2C9*3 genotype undergoing induction warfarin therapy with standard dosing regimens, relative to those who did not have these genotypes (personal, unpublished data, presented as: Cytochrome P450 CYP2C9 genotyping and warfarin induction therapy, presented at the 2004 Annual Scientific Meeting of the Haematology Society of Australia and New Zealand [Oct 17–20, Melbourne, Australia]). Recent reports suggest that CYP2C9 genotyping before inducing warfarin therapy may avert bleeding complications.5 However, CYP2C9 genotyping is currently only available within research institutes and larger corporations with research and development facilities and does not attract a Medicare rebate. While simple and inexpensive, genetic CYP2C9 screening has yet to be proven cost effective. However, genotyping may be of benefit in averting over-anticoagulation in certain clinical scenarios. These include commencing warfarin therapy in “high risk” elderly patients; those in whom low-dose, long-term, low-testing-frequency warfarin regimens are being contemplated; and in other “high risk” patients, such as those with conditions affecting warfarin metabolism, including liver disease, and in those taking medications known to interact with the hepatic metabolism of warfarin.

David J Blacker · Faye Gray · Keith Byron

To the Editor: The article by Baker et al was a timely review of managing anticoagulation therapy and balancing the risks of thrombosis and bleeding.1 However, in managing anticoagulation therapy before non-cardiac surgery in patients with mechanical cardiac valve prostheses, the suggested 5-day cessation of warfarin therapy, with only subcutaneous heparin cover, is not appropriate. I have had three patients with mechanical bileaflet mitral prostheses develop valve thrombosis while under this protocol, two with a fatal outcome. I have also had one patient with a mechanical bileaflet aortic valve develop a popliteal arterial embolus requiring thrombectomy, despite being treated according to the protocol. The consequences of valve thrombosis and thromboembolism far outweigh the lesser complications of increased bruising or bleeding associated with non-cardiac surgery. To avoid the potentially devastating complications of valve thromboembolism associated with the routine cessation of warfarin therapy 5 days before surgery, warfarin ought to be continued to maintain an INR (international normalised ratio) of around 2.0, supplemented with subcutaneous heparin. Alternatively, full intravenous heparinisation can be used while ceasing warfarin treatment, and continued postoperatively until the INR is restored to the therapeutic level. Warfarin should never be reversed with vitamin K, except in cases of life-threatening haemorrhage. Apropos of the therapeutic INR ranges generally recommended for mechanical cardiac valve replacements, the current generation of prostheses does not require the anticoagulation intensity of the older style prostheses.2,3 Lower intensity anticoagulation is sufficient to prevent thromboembolism at decreased risk of haemorrhagic complications.4 My personal practice for patients with bileaflet mechanical prostheses is to maintain an INR of 2.0–2.5 for aortic valves, and 2.5–3.0 for mitral valves. The higher intensity for mitral prostheses relates to potential increased thrombogenicity because of lower leaflet opening pressures, as well as the common association of left atrial dilatation and atrial fibrillation.

Serge Lubicz

To the Editor: A middle-aged woman with atrial fibrillation had her warfarin therapy stopped for 2 days before dental extraction. She had a catastrophic stroke and is now a plaintiff. I was asked if her medical management accorded with common practice. At the October 2004 Annual Conference of the Royal Australian College of General Practitioners, I conducted a straw poll of 20 experienced GPs, of whom 18 said they would stop warfarin for between 2 and 4 days before a dental extraction. Some of these GPs regarded a dental extraction as elective surgery and pointed me to authoritative (but slightly ambiguous) sources to back up their view. 1,2 However, a review of the medical and dental literature shows that this is an example of common practice lagging behind clinical evidence. The first controlled trial of dental extraction in patients on warfarin therapy was conducted in 1983.3 It showed that it was not necessary to cease warfarin prophylaxis for patients whose international normalised ratio (INR) was within the normal therapeutic range. Since then, two major literature reviews have confirmed these conclusions.4,5 A recent Australian review on warfarin reversal expresses a similar point of view.6 The incidence of a serious embolic complication from stopping therapy with warfarin is 1%, and this is three times more likely to occur than bleeding complications in patients whose warfarin therapy was continued.4 Furthermore, a stroke is a catastrophic event, while a bleeding tooth socket is simply messy and usually easily controlled. An authoritative review and position statement on warfarin therapy and dental procedures from the Australasian Society of Thrombosis and Haemostasis may be the catalyst required to align common practice with clinical evidence.

Max Kamien

In reply: We thank Blacker for his constructive and helpful comments. Our recommendations on bridging therapy in patients with atrial fibrillation were for patients with chronic atrial fibrillation who had not previously had a thromboembolic event.1 We do agree with Blacker that extreme care needs to be exercised in patients with atrial fibrillation and a previous thromboembolism. These patients should be managed along the same lines as patients who are at relatively high risk of recurrent thromboembolism. We also wish to emphasise that it is extremely important to assess each individual patient carefully, and to use the consensus guidelines as guiding principles, and not apply them blindly. Dear and his colleagues correctly point out that there are several published studies that have confirmed increased warfarin sensitivity in allelic variants of the cytochrome P450 2C9 (CYP2C9) enzyme. Polymorphisms associated with reduced enzymatic activity have been reported to be associated with increased warfarin sensitivity. They suggest that determining the genotype of individuals before commencing warfarin therapy may be of benefit in reducing the incidence of over-anticoagulation in a select group of patients. We do not believe that this approach is currently practical or possible. From a practical point of view we recognise several reasons why patients become over-anticoagulated when treated with warfarin. In our article we discussed several important modifiers that contribute to an individual’s sensitivity to warfarin. While we agree that polymorphisms of the CYP2C9 gene on its own have been linked with increased sensitivity to warfarin, we are not aware of any studies showing a synergistic interaction of the polymorphism with other clinically recognised causes of increased warfarin sensitivity. Furthermore, we are not aware of any properly conducted studies that have attempted to address the clinical or economic viability of screening for CYP2C9 polymorphisms in patients for whom warfarin therapy is planned. Finally, the time required to obtain the results of this investigation would preclude its application in the routine management of patients who require warfarin therapy. The letter by Lubicz highlights the difficulties encountered in bridging anticoagulant therapy in patients with prosthetic valves. As pointed out in our article, the management of these patients is controversial and mostly anecdotal.1 We believe that the recommendations in our article are useful for most patients, but would like to emphasise the need to consult with the relevant experts in order to avoid bleeding or thrombosis. We would not recommend routine full therapeutic anticoagulation therapy with heparin immediately after surgery, or the combined use of warfarin at any international normalised ratio (INR) with subcutaneous heparin before surgery. Such approaches are more likely to cause confusion and predispose the patients to either bleeding or the risk of thrombosis. Patients with prosthetic valves require careful handling, and involving experts in their management is critical. Kamien’s comments are important and illustrate the difficulties in changing entrenched practices. We hope that our recommendations will go some way to improving the way we manage patients on warfarin therapy who are about to undergo surgery.

on behalf of the Warfarin Reversal Consensus Group

To the Editor: Incidents involving assaults on staff by medical equipment are uncommon, but have been reported in this Journal before. 1 We report another “attack”, involving an x-ray machine and an anaesthetist. A woman was scheduled for endoscopic retrograde cholangiopancreatography in the radiology suite. During induction of general anaesthesia, the patient’s foot moved against an x-ray table control knob (Box). This triggered slow, downward movement of an x-ray “C-arm”, which was positioned above the head of the unsuspecting anaesthetist. Tracheal intubation was rudely interrupted when the C-arm met the anaesthetist’s head and pushed it towards the patient’s face. However, the radiographer in attendance quickly reversed the movement just before the anaesthetist and patient collided. The radiology suite is often regarded as an unfriendly environment for anaesthetists.2 This incident reminds us that, in some cases, it may be frankly hostile! A patient’s foot activates a control knob on an x-ray table

Richard H Riley · Leigh J Coombs

Robert J Menz General Practitioner, East Adelaide Healthcare, 296 Payneham Road, Payneham, SA 5070. robert.menzATeahc.com.au To the Editor: “Texting” tendinitis (resulting from excessive sending of text messages via mobile phone) has not been reported in Australia, although a recent article in the Adelaide Advertiser reported a case in Italy. 1 A 13-year-old girl presented to me in mid-January with an acutely tender swelling in the mid-radial aspect of her right forearm. It had been present for about 2 days. There was no history of trauma, or recalled change of activity. Further enquiry revealed that she had been given a mobile phone in December and that the associated plan allowed $100 credit that had to be used between 5 January and 4 February. This equates to nearly 300 SMS messages, or 10 a day, if all available credit were used for sending text messages (although, in this case, some of the credit had been used in making calls). The phone and plan also allowed up to 760 characters per message, instead of the usual 160. The patient had been using only her right thumb to press the keypad, and was using “traditional” rather than “predictive” text input (ie, creating the message one letter at a time, rather than using the mobile’s interpretative software to reduce the number of keystrokes). Examination of the patient’s forearm revealed a firm, tender swelling in the dorsi-radial aspect of the mid-forearm (presumably involving the abductor or extensor pollicis longus muscle). There was pain with resisted thumb and wrist dorsiflexion. A presumptive diagnosis of “texting” tendinitis was made. The condition settled rapidly with explanation and reassurance, rest, application of naproxen gel twice daily for 2 days, and use of both hands to operate the keypad. To my knowledge, this is the first report of this condition in Australia, although other unusual overuse injuries of the hand have been described with Nintendo playing. 2 Perhaps the manufacturers of mobile phones should include health warnings of the risk of overuse injury as part of product labelling.

Robert J Menz

Lourdes I St George,* Daniel Lin† * Obstetrician and Gynaecologist, Suite 4, 36 Belmore Street, Burwood, NSW 2134. † Paediatrician, Westmead Private Hospital, Westmead, NSW. lourdesstgeorgeATbigpond.com To the Editor: A 33-year-old woman, who had borne five children and had had previous caesarean sections, presented in her eighth pregnancy with worsening malabsorption after biliopancreatic diversion for morbid obesity, performed 3 years earlier. Before surgery, she had weighed about 130 kg (height,161 cm; body mass index [BMI], 46 kg/m2); she had gradually reduced her weight to 67 kg. Her surgery had created intestinal malabsorption resulting from the intestinal bypass and from dietary restriction because of gastroplasty. The physiological stress associated with pregnancy worsened her anaemia from protein and vitamin deficiencies, especially fat-soluble vitamins and calcium. She required frequent hospitalisation for intravenous fluids to compensate for dehydration from vomiting and diarrhoea. She was taking oral iron, folate, vitamin D, a calcium supplement, vitamin B12, and having vitamin K injections. Her total weight gain in pregnancy was poor (from 71 kg to 74 kg). At 32 weeks she presented with premature labour and a persistent low fetal baseline heart rate of 90 beats per minute and an unstable lie. She had an emergency caesarean section and delivered a baby boy with a birth weight of 2095 g (average for gestational age). Apgar scores were 7 and 8 at 1 and 5 minutes, respectively; the baby required ventilation for hyaline membrane disease and phototherapy for jaundice, although his blood profile was normal. His clinical course thereafter was uneventful. Obesity (BMI > 30 kg/m2), has become the epidemic of the 21st century, with one in two Australian women being overweight or obese. 1 Morbid obesity (BMI > 40kg/m2) is associated with a 6–12-fold increase in mortality.2 A multifaceted approach is essential for treatment in all patients with obesity, but unfortunately, medical treatment mostly produces short-term weight loss. Thus, bariatric surgery is being performed more frequently. Biliopancreatic diversion has two components: a limited gastrectomy results in reduction of oral intake, inducing weight loss, especially during the first postoperative year; and the construction of a long limb Roux-en-Y anastomosis with a short common “alimentary” channel of 50 cm length, which maintains weight loss long term. Scopinaro, who pioneered this technique, has published long-term results reporting 72% excess body weight loss maintained for 18 years.3 He documented 239 pregnancies in 1136 patients who had undergone biliopancreatic diversion, 25% of whom had been infertile before the operation. During pregnancy, 20% required parenteral nutrition and had fetuses that were small for gestation age. The women had a mean weight gain of 6 kg during their pregnancies, and 80 % delivered babies at term with a mean birth weight of 2.8 kg. 4 From the patient’s perspective, the great advantage of biliopancreatic diversion is the ability to eat a normal diet and still achieve excellent, long-term weight loss. The most serious potential complication is protein malnutrition, with a need to take supplemental calcium and vitamins, particularly vitamin D, lifelong. Because of this potential for significant complications, patients who have had biliopancreatic diversion require lifelong follow-up and pregnancy should be avoided. Ideally this operation should be performed in women who have completed their childbearing.

Lourdes I St George · Daniel Lin

Alexandra A Bennett,* Jo-anne E Brien,† Peter S Macdonald‡ * PhD Candidate, † Professor of Clinical Pharmacy, University of Sydney, Sydney, NSW (address for correspondence: Therapeutics Centre, St Vincent's Hospital, Darlinghurst, NSW 2010); ‡ Associate Professor of Medicine, and Cardiologist, St Vincent's Hospital, Sydney, NSW. sashabATpharm.usyd.edu.au To the Editor: We wish to add our perspective to the article by Phillips et al. 1 Needs identified by GPs included education about the effectiveness and target dosing of angiotensin-converting enzyme (ACE) inhibitors and β-blockers, and improved communication. We wish to highlight the potential roles hospital and community pharmacists have in supporting GPs caring for patients with heart failure. It is expected that by 2010 there will be at least 25 patients with heart failure per GP and 100 per community pharmacy in Australia. A recent review of 100 patients with heart failure discharged from St Vincent’s Hospital (SVH) in New South Wales showed they were taking an average of 9.5 regular medications, two-thirds of which were cardiac medications. 2 Their average age was 70.5 years. They had an average of 7.3 diagnoses, including ischaemic heart disease, atrial fibrillation and osteoarthritis. They were commonly taking amiodarone, warfarin and digoxin. Six per cent of patients had taken cyclooxygenase-2 (COX-2) inhibitors before they were admitted to hospital. 2 While rates of ACE inhibitor (or angiotensin-II-receptor antagonist) and β-blocker use at discharge were high in patients with systolic dysfunction (84% and 65%, respectively), only a minority of patients were taking target doses (27% and 15%, respectively). This highlights the need for good communication between healthcare providers. Discharge letters are often illegible and do not necessarily prioritise issues or detail future management, such as stating whose responsibility it is to up-titrate the dose of ACE inhibitor or β-blocker. Electronic entry of medical information, including e-prescribing (currently being trialled in some hospitals), may assist. Some patients have typed medication cards from a pharmacist on discharge. However, this is not routine practice. Ideally, all patients should receive such cards with supporting information. Copies of this information should be provided for the GP and pharmacist. Such a system would support Australian Pharmaceutical Advisory Council guidelines for continuity of care. Since 2002, a pharmacist has consulted with patients in the SVH Heart Failure Clinic regarding medication and lifestyle issues. Problems identified are referred to the treating cardiologist. A pilot study of this service showed high patient satisfaction (T Hargraves, Pharmacist, St Vincent’s Hospital, personal communication). Such a service could also be provided by community pharmacists, perhaps linked to home medicines review. A pharmacist is also employed by the community multidisciplinary heart failure service based at SVH. These positions support patients and their carers as well as healthcare providers, including GPs, community and hospital pharmacists and nurses. Evidence for such roles for pharmacists is supported by US and UK data. 3 We propose that designs for future models of care for patients with heart failure should incorporate pharmacists.

Alexandra A Bennett · Jo-anne E Brien · Peter S Macdonald

Matthew J Bragg,* Paul Middleton* * Emergency Physician, Prince of Wales Hospital, Barker St, Randwick, NSW 2031. braggmATsesahs.nsw.gov.au To the Editor: We read with interest the case reported by Williamson and colleagues of an adult survivor of near-drowning complicated by cardiorespiratory arrest. 1 This is a remarkable account of survival with near-intact neurological recovery from what was a very bleak initial clinical scenario, and the pre-hospital and hospital personnel responsible for his resuscitation should be congratulated for their efforts. However, the authors’ use of therapeutic hypothermia in this case does not necessarily support their contention that “controlled hypothermia . . . should be used in near-drowned patients who have spontaneous circulation but remain comatose”. As presented, the case illustrates the benefit of supportive care in general, and the use of appropriate controlled ventilation in particular. As the authors noted, “gentle hyperventilation to ‘blow off’ excess CO2” corrected the hypercapnia and acidosis. The graphs of arterial pH, lactate level and Pco2 presented in the report show a linear improvement in all three indices after controlled ventilation, before hypothermia measures were begun. Indeed, the commencement of hypothermia had no discernible impact on these trends. While there is some evidence in the literature for the use of controlled hypothermia after cardiac arrest,2 there is no direct evidence of its benefit for victims of near-drowning. We do not feel that controlled hypothermia can currently be recommended as standard of care for near-drowning on the basis of this single case report.

Matthew J Bragg · Paul Middleton