Letters

To the Editor: Perusing your long-needed issue on men’s health,1 I was struck by the absence of any mention of obstructive sleep apnoea. As an anaesthetist in private practice, I see three or four middle-aged men with previously undiagnosed obstructive sleep apnoea each week. Usually, I also see at least one man who has had the diagnosis confirmed, but has not persisted with treatment because his wife has become used to his snoring or has moved to another bedroom. Advising the undiagnosed men of the importance of a sleep test, I refer them back to their general practitioner for follow-up, and suggest a couple of respiratory physicians who could perform the test. On a somewhat random follow-up, I have been disappointed with the results, as the following comments were reported back after men’s GP consultations: “Most blokes over 50 snore”; “Your wife will get used to it”; and “Surgery doesn’t work”. Men who have been diagnosed but haven’t persisted with treatment (together with their wives) are often totally unaware of the health risks; they believe that they are only managing the unacceptable noise of their snore! I would have thought that some of the articles in the issue would have mentioned the contribution of obstructive sleep apnoea to hypertension, atrial fibrillation, erectile dysfunction and sleep disturbances, with resulting poor performance during the day, particularly in the workplace. This is an extremely important health issue (and not only in men) that appears to be sadly neglected, still.

Kenneth W Sleeman

In reply: We thank Sleeman for his astute comment. In the men’s health issue,1 our intention was to highlight several major areas relevant to men’s health rather than attempt comprehensive coverage of the field. Sleep apnoea was indeed one of the potential topics we identified when we planned the issue. We anticipated that sleep apnoea would be discussed within some of the key contributions to the issue. Although this did not eventuate, we acknowledge the importance of sleep apnoea in general medical practice, and plan to revisit the topic in future issues of the Journal.

Ann T Gregory

To the Editor: With the proposed formation of the Australia New Zealand Therapeutic Products Authority (ANZTPA), the recent viewpoint article1 and accompanying editorial2 on systems of evaluating medicines were timely. Both reports provided interesting comments on existing systems and proposals for improving these in the future. However, I would like to comment on some omissions and errors in these articles. In their viewpoint article, Kelman et al stated that “there are as yet no overseas examples of ‘routine’ medicines monitoring”.1 This is not correct. The New Zealand Intensive Medicines Monitoring Programme (IMMP) has been undertaking routine monitoring of selected medicines since 1977. The IMMP collects nationwide prescription data to form cohorts of patients who are subsequently monitored for adverse events.3 These patient cohorts provide accurate denominator populations, which, as noted by Kelman et al,1 is important for risk quantification by measurement of incidence. The IMMP uses prescription-event monitoring (PEM) methods to perform active postmarketing surveillance of new medicines in New Zealand, and has been successful in identifying numerous new signals of adverse drug reactions and in quantifying risk.4 The IMMP has developed ways of enhancing PEM methodology by linking records with national morbidity and mortality databases.3 This methodology was recently successfully applied in a study of the safety and usage of atypical antipsychotic medicines in a nationwide paediatric population.5 In their editorial, Stanley and Meslin commented that none of the health care data linkage systems in England, Scotland, the United States or Canada “are nationwide or have the routine ability to link health care records with drug prescription data”.2 As described above, the IMMP has both these abilities. It was somewhat surprising that, although discussions regarding pharmacovigilance in the ANZTPA are now well underway, current systems in New Zealand were not mentioned in either of these Journal articles. I would encourage Australia to develop pharmacovigilance systems similar to those established in New Zealand. Of course, these will need to be adequately funded to achieve the expected outcomes. The formation of the ANZTPA is a great opportunity to improve pharmacovigilance in both countries.

Mira L Harrison-Woolrych

To the Editor: In his article on research misconduct,1 Marcovitch cited my article on institutional corruption in medicine, which was published in the BMJ in 2002.2 He states: Readers of the MJA will have to find the paper version in their libraries, as the electronic version has been replaced on the BMJ’s website . . . with the bald statement that it has been removed for legal reasons. In case any of your readers are concerned that the article has been retracted, I would like to point out that the article was removed from the website on 10 June 2004, when Dr Richard Smith was editor of the BMJ. Dr Smith cited my article in his own article on research misconduct in 2006.3 He would not have done so if the article had been retracted. Neither would Marcovitch.1 My article described how some senior individuals in British academic medicine had concealed misconduct for a decade. The article had an editorial footnote stating: “Documentary evidence corroborating this article was made available by Dr Wilmshurst to the BMJ.” It was cleared for publication by the BMJ’s lawyers. An “Editor’s Choice” column entitled Corruption in medicine accompanied my article online.4 That column has also been removed from the website. It stated: “The article by Wilmshurst has its origins in a seminar he gave to the BMJ in 1996. For years he had been informing us of misdemeanours. Fear of libel stopped us from publishing.”4 Ironically, it was fear of libel actions that caused the BMJ to remove the article from the website. Soon after publication, the BMJ received threats of libel actions from academics and their institutions. Dr Smith and I spent considerable time working with lawyers to counter these challenges. None came to court, but the legal costs for the BMJ’s insurers mounted. It was pointed out that a libel action must be started within 1 year of publication. Because the article was on the website it was constantly being republished. If it was removed from the website there could be no more threats of litigation after 1 year. Therefore, the insurance company that covers the BMJ against libel insisted that the article be removed from the website. If readers are unable to get a copy, they can email me and I will send a PDF version.

Peter T Wilmshurst

To the Editor: A further reason for the differences in antenatal Down syndrome screening rates between urban and rural women, reported by Coory and colleagues,1 is likely to be the relative difficulties many Queensland women face in accessing abortion services. We are aware of several Queensland public hospitals that provide excellent antenatal screening services — testing for chromosomal abnormalities as well as providing the 18–20-week ultrasound scan for structural abnormalities. However, these hospitals do not offer subsequent counselling or abortion for women who make the difficult decision to terminate a pregnancy at this gestation, instead directing them to the private system. Some of these women are undoubtedly among the many Queensland women who travel interstate for abortions each year.2-5 First-trimester abortion is difficult to access for women in rural areas throughout Queensland. This is probably an important factor in women making the decision not to have early screening and/or chorionic villus biopsy, and possibly also a factor in doctors not offering it. Having to travel several hundred kilometres for the test, with the possibility of a further journey for an abortion, is beyond the resources of many rural women. We are in agreement with Coory et al that a majority of the population would support equity of access to services and equal choices for all women in the matter of antenatal screening for fetal abnormality. In fact, amniocentesis for chromosomal abnormalities has been available, with little controversy, for more than 30 years. If early antenatal screening is made available to all women, then it is reasonable to expect that appropriate counselling and access to safe, affordable abortion is also provided.

Caroline M De Costa · Cait Calcutt

To the Editor: Women of the remote Indian Ocean Territories (Christmas Island and the Cocos Islands [see map]) regularly question why their comprehensive obstetric service, allowing deliveries on the Islands, ceased in 1998. A study in 20051 aimed to provide answers for these women. There is one general practitioner on the Cocos Islands and two on Christmas Island. Previously, procedural GPs attended to most deliveries. Now, pregnant women must leave the Islands 4 weeks before their expected delivery. The financial, physical, emotional, and cultural costs of this are substantial. Reports published in 20022 and 20043 identified community concerns, but resisted recommendations to resume on-Island birthing, because of perceived low birth numbers and difficulty sustaining the skills of clinicians. Both studies relied on external birthing data, as the Indian Ocean Territories Health Service (IOTHS; administered by the Department of Transport and Regional Services) had not documented numbers of deliveries. The Alberton Report,3 extrapolating from Australian Bureau of Statistics (ABS) data, assumed that the population of children aged less than 1 year in a census year equalled the number of deliveries the year before. The ABS has a system to protect the confidentiality of small isolated populations and purposely does not report these numbers. The Bath Report2 relied on data from the Western Australian Midwife Notification System (MNS). The MNS reported 136 births to Island women from 1995 to 2004, while our study (Western Australian Centre for Remote and Rural Medicine)1 recorded 326 births. Thus, the MNS attributed only 41% of known births to Island women during 1995–2004, and only 23% during the period considered by the Bath Report. We believe that the MNS data shortfall occurred for two reasons. Firstly, women frequently provide their temporary mainland address on the MNS form for practical reasons. Secondly, one in seven women leaving the Islands to deliver their babies choose to give birth in a state other than Western Australia to be closer to family, and these births are not attributed to women from the Islands. The methods used by the Alberton Report, the MNS and the Bath Report result in underestimations of the number of confinements for Island women by up to 77%. It is regrettable that this situation has not been previously recognised or acknowledged, and that recommendations for the resumption of obstetric services by the IOTHS have repeatedly been based on incomplete data. If records of the numbers of births for Island women had been collected and considered by the IOTHS, Island families might again enjoy a comprehensive on-Island delivery service for low-risk pregnancies.

Susan Downes · Sally M Roach

To the Editor: We report an exceptional case of a woman who underwent emergency “finger fracture valvuloplasty” (FFV) in 1954 to treat rheumatic mitral stenosis and required no further surgical intervention for 51 years. The woman presented in 1954 with pulmonary oedema due to mitral stenosis during the first trimester of her second pregnancy. She underwent FFV at Lewisham Hospital in Sydney. She had a prolonged convalescent period, was discharged after 5 months, and delivered a healthy child. She was one of two pregnant patients reported in the Medical Journal of Australia by Hall and Windsor.1 She remained well and active until 2005, when she presented with New York Heart Association Class III symptoms of dyspnoea on exertion, and ultimately underwent mitral valve replacement that year. She made a good recovery postoperatively and remains well. In the 1920s, 10 patients with mitral valve stenosis were treated surgically.2 In 1923, Cutler and associates from Boston operated on seven patients using a cardiovalvulotome (through the left ventricle) and, in the same year, Duff and Evarts from Washington used a cardioscope (through the left atrium) on one patient. In 1925, Soutter from London and Pribram from Germany used a “finger fracture method” and a valvulotome, respectively, on one patient each. However, of the 10 patients, only two survived, one of Soutter’s and one of Cutler’s. The procedure was subsequently successfully revived in 1948 by Harken in Boston, Bailey in Philadelphia, Blalock in Baltimore, Brock in London, and others, who performed various procedures including valvuloplasty and commissurotomy. However, the so-called FFV (Harken) became the favoured procedure. It evolved from using the forefinger, to using the little finger, to eventually using a knife. Most surgeons had difficulty in using the mitral knife to divide the medial commissure and thus developed their own instrument.2 There are few successful case reports of FFV in pregnancy. In the United Kingdom, Brock reported three, Logan and Turner, six, and Marshall and Pantridge, 18.3 Hall and Windsor in Sydney performed FFV in two of seven pregnant women who were being considered for FFV, including our patient. One of the other five, who were managed conservatively, died.1 In 1963, Windsor said, “Eleven years’ experience in the surgery of the mitral valve has brought with it a great respect for the ability of the mitral commissures to resist finger, knife and dilator”. He reported follow-up of 90 patients who underwent FFV. No more than 40 patients (45%) obtained good results. Sixteen patients in this group have since been reoperated upon by the more effective transventricular route using a mechanical expanding dilator.4 It should be noted that mitral stenosis in young women is rarely accompanied by calcification, and this may allow a more complete and successful valvuloplasty. All the procedures mentioned above occurred before the development of cardiopulmonary bypass and open heart surgery in 1954. Early pioneers in surgery faced many challenges and disappointments, as well as condemnation, criticism and ridicule from colleagues. Some, like Soutter and Bailey (the latter nicknamed the “butcher of Hahnemann Hospital [Philadelphia]” after his first four FFV patients died) lost their practices.5 We would like to pay homage to all surgical pioneers and conclude with a comment from Harken: “He who would not learn from the past is condemned to relive it”. Finger fracture mitral valvuloplasty technique (Hall and Windsor1)

John S Murala · Hugh D Wolfenden · George S Youssef · Daniel Friedman

To the Editor: Systemic ototoxicity secondary to the use of aminoglycosides is well known in clinical medicine, and appropriate monitoring measures to prevent vestibulo-cochlear ototoxicity are routinely performed. Less well known is the potential for topical ear drops, particularly the aminoglycoside group, to cause both vestibular and cochlear damage when introduced through a patent grommet or tympanic membrane perforation for the treatment of infection.1 Although the incidence of aminoglycoside ototoxicity with ear drops is uncommon (for cochlear toxicity, in the order of one in 10 000 patients treated2), individual susceptibility and patient compliance problems may lead to inner ear damage. Concerns with the potential ototoxicity of aminoglycoside ear drops has led to American,3 British4 and Canadian5 expert committees providing guidelines on the use of potentially ototoxic ear drops in patients with tympanic membrane perforations or patent grommets. The Consensus Panel of the Australian Society of Otolaryngology Head and Neck Surgery (ASOHNS) unanimously agreed on the recommendations shown in the Box, which are based on the American guidelines. Broadly speaking, the Consensus Panel recommends avoiding the use of ototoxic ear drops in patients with perforated tympanic membranes where possible. The Australian National Aboriginal Community Controlled Health Organisation study showed that the non-ototoxic fluoroquinolone drops were more effective than commonly used ototoxic ear drops.1 An application to the Therapeutic Goods Administration for introduction of ciprofloxacin drops to the ear has recently been approved, and has been placed on the Pharmaceutical Benefits Scheme as an authority prescription for Aboriginal and Torres Strait Islander children with chronic suppurative otitis media as of February 2007. However, clinical circumstance may dictate that potentially ototoxic agents need to be used if culture/sensitivity testing suggests that fluoroquinolone drops would not be appropriate, are unavailable, or if previous treatment with fluoroquinolone ear drops failed. The Consensus Panel did not believe routine auditory/vestibular monitoring was warranted by the risks of ototoxicity, provided the treatment was short (5–10 days). The full document outlining the Consensus Panel’s recommendations is available from ASOHNS. Recommendations of the Consensus Panel of the Australian Society of Otolaryngology Head and Neck Surgery on ototoxic ear drops and tympanic membrane perforation Non-ototoxic eardrops are preferable in the presence of tympanic membrane perforations or grommets. If potentially ototoxic antibiotic ear drops are used, they should only be used in infected ears and discontinued immediately the infection has resolved. If potentially ototoxic antibiotic ear drops are prescribed for use in the open middle ear or mastoid, the reason for their use and a warning to the patient/parent of the risk of ototoxicity should be given and documented. If potentially ototoxic antibiotics are prescribed, the patient should be specifically instructed to return to the doctor if he or she develops vertigo, hearing loss or tinnitus. If the tympanic membrane is known to be intact and the middle ear and mastoid are closed, then the use of potentially ototoxic preparations presents no risk of ototoxic injury.

Robert J Black · Vince C Cousins · Peter Chapman · Zoran Becvarovski · Harvey L C Coates · Stephen J O’Leary · Christopher F Perry · Brian J Williams

To the Editor: Coiera accurately described some lessons from the United Kingdom’s experience with health information technology1 that should be noted by potential “fast followers”, such as Australia’s National E-Health Transition Authority (http://www.nehta.gov.au). The debate about the merits of the “opt-in” versus the “opt-out” approach highlights a need for further discussion about the optimum consent model to achieve the aims of a shared electronic health record (EHR), combining patient-controlled health records with a tool for clinical decision making, and research and planning.2 Informed consent and ethical approval are vital for publication of evaluation findings. The 2007 National statement on ethical conduct in human research3 recognises that consent processes do vary, depending on the context and type of research. Opt-in is an active process and is believed to build consumer confidence and reinforce a strong privacy message.2 Opt-out is more passive, assuming that most people are willing to share their health information for clinical and/or research purposes. Our own experience with opt-in is that less than 0.4% of patients approached decline to participate in data extraction projects.4 With opt-out, there is little evidence to show that it is in any way harmful for initial patient contact. On the other hand, opt-in has been associated with a poor response rate and a biased study population in medical record research,5 in research in screening clinics,6 and in a pilot study of patients with angina.7 Because recruiting unbiased patient samples with high response rates is essential for scientific rigour, opt-out should be the default recruitment strategy for studies with a low risk for participants. The most appropriate consent model for all situations, in an ethical and secure electronic environment, is one that allows patients and providers to make their own decisions about giving expressed or implied consent within an opt-in or opt-out approach. The participants in the process must be sure that consent has in fact been granted. The health record (paper or electronic) must demonstrate that the consent process has taken place and document the outcome. We have developed software to enable use of this flexible consent protocol, permitting context-sensitive and ethical access to personal health information if patients, clinicians and researchers have given their consent. The literature and our experience suggest that this flexible approach, based on the choices of patients and providers, should lead to good participation rates and allow the objectives of a shared EHR to be achieved in a cost-efficient manner.

Siaw-Teng Liaw · Douglas I R Boyle

To the Editor: The editorial by Coiera and Westbrook1 and indeed the letter by Fox2 tended to use the term “clinical software” in a broad sense. In Australia, doctors who use clinical applications are in fact using electronic medical records. The major functionality provided is one of information storage, with the ability to produce a range of documents that were previously handwritten. To accept that the currently available applications offer decision support is a very generous, and possibly naïve, interpretation. The common example of decision-support tools used in Australia is the humble prescription writer. Current vendors offer a variety of prescription writers and, as Coiera and Westbrook1 assert, they check for drug–drug interactions and dosage errors and provide various alerts. Coeira and Westbrook go on to question whether appropriate testing is being performed on the large number of applications available. At first glance this question may seem to be somewhat invalid, as most of the software packages in Australia use either the AZDex (a proprietary internal drug database used by Medical Director) or MIMS (a pharmaceutical database of products currently available in Australia by CMPMedica Australia) drug databases. These two highly regarded sources of drug information provide the developer with an easy-to-implement set of tools that effectively ensures “quality” information is provided to the doctor preparing the prescription. The problem is that, although we have quality databases, there is little or no compliance testing to ensure that the applications that use them are developed to an equally high standard. For example, there is no mechanism to inform end-users which parts of the database have been used, and there is no testing to ensure the end-user is presented with accurate information. While many Australian doctors have moved to computerised clinical records, their ability to use these data for improving clinical care is being curtailed by a lack of standards and coding of conditions. Computers are not efficient in dealing with the free text that is traditionally used in clinical notes, and even data such as drug prescriptions are difficult to analyse because of the lack of a standard method of drug naming or coding. I look to a future when true clinical support tools are available. To this end, the development, coordination, and facilitation of a series of standards by the National E-Health Transition Authority should be supported.

Ian D Williams

In reply: At the heart of much debate on patient consent for access to electronic data are two conflicting desires — many consumers wish to minimise access to their record, and many clinicians have genuine concerns that such restriction may lead to patient harm. In some cases, privacy is paramount (eg, psychiatric or sexual health history). In others, such as emergency presentations, patient wellbeing may override such concerns. This has led many to conclude that there is no “one size fits all” model for e-consent.1 The current debate between the boundary cases of “opt-in” and “opt-out” is misleading because many specialist services of necessity will have local consent processes, crafted to meet the need of their patients and their clinicians. Yet, many health information technology initiatives do not seem prepared to consider this complexity, and opt-in or opt-out are all that is on offer. Liaw and Boyle’s concerns about dropout rates under an opt-in system affecting secondary use of patient data for research purposes are no doubt real, but it is hard to draw too strong a comparison between patient recruitment for research and patient permission to store data for their own care. Williams correctly points out in his letter that decision support remains a small component of the software to support clinical practice that most Australian general practitioners now use. However, anyone using a prescription program that suggests doses, checks interactions, or generates alerts is using decision support. We can say so confidently because research repeatedly shows that such functions change clinical decisions. Indeed, something as simple as accessing research articles and guidelines using the Internet is a form of decision support, because it changes clinical decisions significantly, and sometimes negatively.2 Consequently, it is perhaps naïve to await “true” decision support using artificial intelligence before we worry about how software affects clinical behaviour. If the intervention was a drug and serious patient harm resulted from infrequent side effects, everyone would quickly agree some controls might be needed. Somehow, we still don’t seem to get as excited about the harm that may come from using bread-and-butter clinical software, but we should.

Enrico W Coiera

To the Editor: Whatever the method used to select medical students (whether academic, psychometric, or interview), the basic problem in assessing the method’s predictive capability is that only candidates who perform at the higher levels in the assessment will be admitted. The only way to test the predictive validity of an assessment is to admit candidates from a much wider band of performance, creating a much less compressed score range for comparison. By definition, candidates with lower scores are excluded, thus making this analysis impossible. The study by Groves et al had an overall response rate of 13.6%,1 a rate at which no conclusions could, or should, be drawn. Entry to medicine remains a highly charged and emotional subject. It is unfortunate that the press has drawn conclusions from a study from which conclusions cannot be drawn.

John E Marley

In reply: Marley makes an important point about the conclusions that can be drawn from our study on the effectiveness of medical school admissions tests. As acknowledged in our article, the size of the study and the restriction of range to which he refers do limit the strength of the findings. Nevertheless, it is precisely because admissions tests elicit such an emotional response from the general community, as well as being costly and stressful for both aspiring students and medical schools, that there is an urgent need for a large-scale multi-institutional evaluation of the process — a need that our results highlight. It is reassuring that the Australian Council for Educational Research, the developers of the Graduate Australian Medical School Admissions Test (GAMSAT), is currently conducting one such study in conjunction with several Australian graduate-entry medical schools. We hope that our study serves to stimulate still more discussion and analysis of medical student selection processes.

Michele A Groves

To the Editor: We welcome your recent focus on rural and remote health. Kamien and Cameron’s editorial addressed medical workforce supply issues,1 and the accompanying article ranged across not only workforce supply issues, but also broader systemic issues, including the roles of different levels of government.2 Coincidentally, the Australian Institute of Health and Welfare released its latest medical workforce report, which reported a rise in the number of doctors per head of population overall, particularly specialists, and particularly in urban areas, but decreased numbers of doctors in the bush, particularly in remote areas.3 Most of the media response ignored the contemporaneous nursing workforce report,4 which described a much more even geographical distribution of the nursing workforce — the largest health professional group. We agree that access to health care is more than a workforce supply issue.2 While we acknowledge the critical importance of general practice, perhaps part of the problem in improving access has been an almost exclusive policy focus on medical workforce supply issues, and not the broader consideration of a range of factors that will improve access to effective primary health care services for the 30% of Australians living in rural and remote areas. Our recent systematic review of models of rural and remote primary health care service delivery in Australia identified a number of essential requirements of successful primary health care models.5 These inter-related requirements are adequate workforce supply; appropriate workforce organisation; adequate funding and appropriate financing; leadership, good management and governance; adequate infrastructure; and strong linkages — both internal and external. Successful models also exhibited an appropriate level of community participation. There are a number of demonstrably successful rural and remote models, such as the Katherine West Health Board, an exemplary remote comprehensive primary health care service.5 To generalise these successful models and improve access, we need a rural and remote primary health care policy framework for Australia that coordinates national, state and territory resources to ensure that all of these essential requirements are systematically addressed. We agree with Kamien and Cameron1 that a solution will not be forthcoming until governments take a courageous stance in overcoming the implementation gap associated with translating research evidence into policies and programs. The time has never been riper for Commonwealth, state and territory governments to assume leadership and agree on an evidence-informed implementation strategy to assure rural and remote communities of accessible, high quality health care. Our systematic review5 provides a solid base to underpin such a response.

John Wakerman · John S Humphreys · Robert W Wells · Pim Kuipers · Philip Entwistle · Judith Jones

To the Editor: The report by See and colleagues on an accidental death from acute selenium poisoning1 draws attention to a misconception among some health-conscious consumers that, because selenium is obtainable without a prescription, it is safe to take in high doses. Selenium is available over the counter in tablets containing as much as 200 μg. The only advice printed on packs is not to exceed the recommended daily intake, which is not specified (the current Australian values are 70 μg and 60 μg per day for men and women, respectively). There is no mention of the upper limit of 400 μg, beyond which there is risk of toxicity. Selenium supplements are consumed by many people worldwide. Up to 9% of adults in the United States use these supplements.2 Consumption is much the same elsewhere in the Western world. They are used by many in the belief that their dietary intake of selenium is inadequate, and that the supplement will protect them against a variety of illnesses. Consumers get information from several sources, not least the general media and the Internet. These sources can seriously mislead, especially when they misinterpret the results of clinical trials and make exaggerated claims of health benefits. Those who rely on such popular, but simplistic, information can reach false and sometimes dangerous conclusions. Health advisors who become aware that patients are self-medicating with selenium need to point out the dangers. Unfortunately, after years of teaching students of medicine and other health-related fields about trace elements, I know that many graduates do not have enough knowledge in this area to provide accurate guidance. Even if they want to learn more by consulting current literature, the sheer volume of articles can deter them. It is for this reason that I wrote the book Selenium in food and health3 — to provide an up-to-date, scientifically based review of the nature and role of selenium in human health and metabolism. I hope that the book’s readable and user-friendly style will make it easy for overburdened professionals to learn enough about this element to help prevent the sort of tragedy described by See and colleagues.

Conor S Reilly

To the Editor: It is of great concern to me that the recent case report Accidental death from acute selenium poisoning by See and colleagues1 inappropriately cast doubts on the safety of complementary and alternative medicines (CAM). This incident should be placed in its correct context. The guidelines are clear for listed complementary medicines (ie, compounds or formulas registered and approved by the Australian Register of Therapeutic Goods for distribution in Australia).2 As a trace element, selenium is required in microgram amounts. The Therapeutic Goods Administration stringently regulates its use in nutritional supplements in Australia, with an allowed limit of 26 μg per daily dose (as selenomethionine) in unrestricted products, and 50 μg per daily dose (as selenite) in restricted, pharmacy-only supplements. This is considerably less than the “no observed adverse effects level” for selenium, which is as high as 400 μg per day,3 as noted by See and colleagues. Furthermore, even at these low doses, CAM products that contain selenium must carry substantial “red flag” label warnings. Bulk sodium selenite powder — the form which led to this fatality — is definitely not dispensed as a complementary medicine. Nevertheless, the authors of the case report conclude that “adverse outcomes of complementary and alternative medicines should be better publicised and more stringently reported to the Adverse Drug Reactions Advisory Committee (ADRAC)”. While this may be a commendable recommendation, it is inappropriate and incongruous with the findings presented in this case report. Furthermore, the sodium selenite used by nutritional doctors is administered as a liquid at a dose of 50 μg per drop, and is a restricted S4 prescription-only product. To achieve a dose of 10 g of sodium selenite, as taken by the reported patient, would require ingestion of 115 bottles of the registered S4 supplement or, even less plausibly, 400 000 doses of a listed CAM supplement. Neither of these preparations was implicated in the reported case. So why then are the authors of this case report asking for increased vigilance for complementary medicines? It is surely the interchange between the pharmacist and the customer that lies at the heart of this matter. Had a listed selenium product been dispensed, this poisoning would not have occurred.

Ian Brighthope

To the Editor: I wish to address a statement made in a recent case report in the Journal entitled Accidental death from acute selenium poisoning.1 The authors claim that the death of a 75-year-old man after ingesting 10 g of sodium selenite “exposes the myth that natural therapies are inherently safe”. The patient actually purchased sodium selenite powder and tablets. This is a restricted substance and an industrial chemical which would certainly have been labelled a poison. It should be noted that the maximum recommended daily dose of selenium in complementary medicines in Australia is 52 μg.2 The authors of the case report do point out that the patient took more than 10 000 times the recommended dose of selenium which would be available from a medicine. (My calculations put this closer to 20 000 times.) An individual drinking more than 10 000 times even the daily recommended amount of water would probably not end up in much better shape. Is this evidence of an underlying agenda to discredit natural products? The Complementary Healthcare Council of Australia recommends that consumers take steps to thoroughly inform themselves about products, preferably by asking their health care practitioner. We also urge them to inform their health care practitioner of which medicines, complementary or otherwise, they are taking. The incident involving the sodium selenite is regrettable, but for the authors to link the product and this case of fatal ingestion to exposing the myth that natural therapies are safe is, at best, ridiculous, with no foundation. They also state that adverse reactions to complementary and alternative medicines should be better publicised and more stringently reported to the Adverse Drug Reactions Advisory Committee. Adverse reactions are routinely reported and publicised for all medicines, and have been for some time, as any check of the website of the Therapeutic Goods Administration will show.3,4 I agree with the authors that the case highlights the dangers of consumers’ reliance on the Internet. Local Internet sites that advertise therapeutic goods must conform to the requirements of the Therapeutic Goods Advertising Code, as well as the Therapeutic Goods Act 1989 (Cwlth) and Regulations. However, overseas sites are not necessarily regulated or policed, and may provide inappropriate and misleading information. While our industry’s products are low risk, they should be taken, like other medicines, with due care.

Tony Lewis

In reply: The myth we referred to is the commonly held misperception by a significant percentage of the population that natural therapies are inherently safe. As Lewis and Brighthope very correctly point out, the dose ingested by our patient was hugely in excess of any recommended maximum. We believe this is evidence of the misperception, as most patients would not dream of taking 10 or 20 thousand times the maximum dose of “non-natural” remedies, because they recognise that all such remedies have side effects. Our patient’s confidence that he could safely take such a huge dose was, we consider, at least partly a consequence of his belief in the myth that natural therapies are safe. The fact that the dosage of selenium in nutritional supplements is strictly regulated does not prevent problems such as this — where patients obtain information of variable quality on the Internet, make their own arrangements to obtain the product, and then ingest a toxic amount. Our article was in no way part of “an underlying agenda to discredit natural products”; it merely highlighted the risks inherent in self-medication based on information of variable quality obtained from the Internet, coupled with the impression that natural therapies are inherently safe. We hope that our call for adverse outcomes of complementary and alternative medicines to be better publicised will go some way to preventing such a tragic error occurring again.

Peter S Lavercombe

To the Editor: We read with great interest the article by Bambrick et al relating to the potential impact of the Australia–United States Free Trade Agreement (AUSFTA) on supply of blood products in Australia.1 Our recent experience with Octagam (Octapharma Australia, Sydney, NSW), an intravenous immunoglobulin (IVIg) product produced overseas, highlights some of the quality concerns raised in their article. Routine practice in our bone marrow transplant unit is to administer IVIg weekly for 100 days after allogeneic stem cell transplantation. Until December 2004, locally produced IVIg, Intragam-P (CSL, Melbourne, Vic), was used exclusively as the IVIg product for these patients. From October 2005, because of limitations in the supply of Intragam-P, the Australian Red Cross Blood Service (ARCBS) also provided Octagam for IVIg replacement therapy in transplant recipients. It has also been routine practice within our transplant unit to repeat serological tests for a variety of transfusion-transmitted viral infections, including human T-lymphotropic virus type I and type II (HTLV-I and HTLV-II), in all transplant patients 100 days after transplantation. Until 2006, none of our patients had ever tested positive for HTLV-I or HTLV-II antibodies. After the introduction of Octagam, the first two transplant patients who received this product for IVIg replacement tested positive for HTLV-I/HTLV-II antibodies at 100 days after transplant (signal to cut-off [S/CO] ratios, 4.36 and 6.33, respectively). Subsequent investigation revealed that these results were probably secondary to passive transfer of HTLV antibodies from the IVIg product used. Both patients received Octagam from the same batch, and subsequent testing of this batch was positive for the presence of HTLV-I/HTLV-II antibodies. Of note, both patients tested negative for HTLV-I/HTLV-II antibodies before transplantation (S/CO ratio < 1.00). Their stem cell donors were also negative for HTLV on testing immediately before stem cell donation, and the only other blood product shared between the two patients (platelets from a common donor) also tested negative for HTLV. Follow-up testing for HTLV-I/HTLV-II antibodies at about 12 months after transplantation gave a negative result in both patients (S/CO ratio < 1.00). Given that Octagam is a plasma (acellular) product processed with appropriate viral inactivation steps,2 we believed it to be extremely unlikely that direct transfer of HTLV virus had occurred. The most likely explanation was the passive transfer of HTLV antibodies. It followed that Octagam must have been sourced from HTLV-positive plasma donors — a practice that is in direct conflict with current ARCBS policy, which specifies that all blood and plasma donors must be screened for HTLV-I and HTLV-II, and that any donors testing positive should be excluded from blood or plasma donation.3 The HTLV-I/HTLV-II serostatus of donors used to source plasma for Octagam are not reported on the product information sheet.2 Testing of one patient sample at the National Serology Reference Laboratory (Melbourne, Vic) suggested the positive serological results in our patients were due to the presence of HTLV-II antibodies. In collaboration with Octapharma, it was subsequently determined that plasma for Octagam was sourced from paid donors from the southern United States, an area where HTLV-I and HTLV-II seropositivity is known to be prevalent among blood donors.4 The clinical implications of our findings are unclear. Our results were reported rapidly to the ARCBS and subsequently to the Therapeutic Goods Administration. Our main concerns are that Octagam plasma is sourced from donors who would normally be excluded from plasma donation within Australia,3 and that there appears to be no current mechanism for addressing this issue. Some of the quality concerns raised by Bambrick et al appear to be not so theoretical after all.

Glen A Kennedy · Judy Cummings · Simon T Durrant

In reply: I would like to respond to the letter by Kennedy et al regarding the passive transfer of human T-lymphotropic virus (HTLV) antibodies following Octagam (intravenous immunoglobulin [IVIg]) administration. Octapharma does not routinely test Octagam for HTLV antibodies — this is in line with Australian regulatory requirements.1 Furthermore, in accordance with global regulatory requirements (including those defined by the Australian Therapeutic Goods Administration), plasma from sources in Europe and the United States is also not routinely tested for HTLV antibodies.2,3 It is important to note that the patients described by Kennedy et al tested positive for HTLV antibodies rather than the HTLV virus, and that the presence of antibodies in the finished product does not pose an infection risk. As noted by the authors, the manufacturing process for Octagam includes viral inactivation. There are two dedicated viral inactivation and removal steps: Solvent/detergent treatment, which is a highly effective step for inactivating lipid-enveloped viruses; Incubation at pH 4 and 37°C for 24 hours. The combination of these two processes ensures that lipid-enveloped and several non-lipid-enveloped viruses are inactivated. Since the initial launch of Octagam in Europe in 1993, more than 33 million grams of the product have been infused, corresponding to more than 2.5 million infusions. During this time, there have been no documented cases of viral transmission resulting from the use of Octagam. Since the launch of Octagam in Australia in 2005, Octapharma has supplied over 600 kg of IVIg, representing about 40 000 infusions to Australian patients. Therefore, taking into account the steps used to remove and/or inactivate lipid- and non-lipid-enveloped viruses, the fact that there have been no documented cases of transmission of any virus since the launch of Octagam, and that plasma sources and testing meet both Australian and global regulatory requirements, the positive HTLV antibody results reported by Kennedy et al have no bearing on either the quality or safety of Octagam.

Wolfgang Frenzel

To the Editor: Bambrick et al1 suggest that the importation of overseas plasma products or the processing of Australian plasma overseas may pose a threat to the safety and security of Australia’s supply of plasma products. The National Blood Authority (NBA) and the Therapeutic Goods Administration (TGA) would like to respond to these issues to ensure that clinicians have confidence in the safety of products currently available in Australia and a better understanding of current blood processing and supply arrangements. Australia is largely self-sufficient in plasma products, a position supported by all Australian governments.2 The governments also agree to the supply arrangements for imported plasma products when demand exceeds domestic supply (as in the case of intravenous immunoglobulin [IVIg]), and for products not supplied by Australian manufacturers (eg, fibrin sealant and other coagulation products). All these products are purchased by the NBA on behalf of Australian governments. Standards applied in Australia ensure that all products on the Australian market are derived from sources — in Europe, the United States and Australia — approved by the relevant authorities. The TGA regulates all plasma products to ensure that they meet international standards of safety, quality and efficacy, irrespective of their source.3 No centres sourcing blood from countries in the developing world, as cited by Bambrick et al, are used. National health systems around the world strive to attain degrees of self-sufficiency that suit their particular economic and policy objectives. However, as the US supplies 60%–70% of global plasma (while consuming only 40% of products sourced from this plasma4), many patients outside the US are dependent on the system of both compensated and uncompensated donors operating in the US. It is worth noting that definitions of “remuneration” vary across countries. The Commission of the European Communities reported in 2006 that “the principle of voluntary and unpaid donations does not exclude compensation for donors, if it is limited to making good the expenses and inconveniences related to the donation”.5 Examples of compensation that this article cites include tax relief of up to €70 per annum in the Czech Republic, an expense allowance of up to €25 for a whole blood donation in Germany, and up to €50 for an apheresis donation in Austria. Thus, the boundary between compensated and non-compensated donors is not distinct globally. Bambrick and colleagues’ contention that products manufactured from paid donors may be less safe is not supported by evidence. The history of blood safety clearly demonstrates that there were major safety issues with both fresh blood and blood products in the 1980s. These problems were more a result of pathogen epidemiology and governments’ blood safety policies than whether donors were paid or unpaid. For example, the Canadian and French blood systems relied entirely on volunteer donors, but the delayed implementation of safety measures and good governance measures led to pathogen risks that exceeded those of the US.6,7 In Australia, the incidence of HIV/AIDS in people with haemophilia exposed to only one type of product in the 1980s approached that of the same patient group in the US, despite the product being sourced entirely from domestic voluntary donors.8 Currently, robust plasma product safety measures in the US have proved to be effective in minimising contamination from both known and emerging pathogens, such as West Nile virus. This virus did not infect the recipients of plasma products from compensated donors, but did infect the recipients of (uncompensated) fresh blood transfusions.9 The equivalence in safety between plasma products sourced from compensated and uncompensated donors has been confirmed by the European Medicines Agency.10 Ensuring the security of supply is central to Australia’s plasma fractionation arrangements. The NBA’s contracts include provisions to ensure product supply security and product safety, including compliance with TGA requirements. Under Australia’s emergency response plans, plasma could be supplied from fresh stock, while the inventory of product in the system and the national reserve of products (funded by the NBA to cover contingencies) could provide fractionated products. A range of other supply security measures is implemented by the NBA on behalf of Australian governments, including secondary suppliers for critical products. These measures take into account the fact that Australian plasma used to manufacture fractionated products is not produced in sufficient quantities to permit storage of excess. Thus, Bambrick and colleagues’ concern that geographical factors may restrict access to Australian plasma has limited relevance in an emergency situation. In summary, Australia has a comprehensive system that draws on international best practice and national jurisdictional arrangements to ensure the supply of high-quality, safe, efficacious plasma products, irrespective of their source.

Alison Turner · Albert Farrugia

In reply: Turner and Farrugia highlight important issues about the safety and supply of Australia’s blood and plasma that constituted key findings of the recent Australian Government review of Australia’s plasma fractionation arrangements.1 These included the desirability of self-sufficiency and the need for a viable contingency plan in the event of local supply failing to meet demand, in the context of probable increased uncertainty in relevant security and supply circumstances. The authors note the importance of a rapid regulatory response to new risks, and rightly emphasise the important role of our National Blood Authority and the Therapeutic Goods Administration in relevant safety assurance processes. However, a crucial issue highlighted in the review that they fail to address is the difficulty of relying on the application and enforcement of regulatory standards if the bulk of Australia’s fractionation occurs offshore.1 After an exhaustive study of arrangements in Europe and the United States, the review concluded that overseas fractionation of Australian plasma would involve significant costs in moving away from the current local arrangements ($75 million) and, because of yield considerations, there would be the potential for an ongoing shortfall in the supply of intravenous immunoglobulin (IVIg) and other plasma-derived products. The review also found that overseas fractionation was potentially associated with major risks to the supply chain, with increased distance and handling providing more opportunities for loss and error, while a doubling or tripling of the turnaround period would have implications for continuity of supply. The review recommended that the federal government maintain the reservation exempting plasma fractionation services from the government procurement provisions of Chapter 15 of the Australia–United States Free Trade Agreement.1 The review confirmed that volunteering for blood donation should be institutionally reinforced as an important exemplar and means of sustaining Australia’s national culture, and that donor payment endorsed a very different set of values and was unlikely to assure sustainability of supply.2 It did, however, suggest initiatives such as tax relief or other institutional ways to encourage donation.1 We fully endorse the summary assessment of the review that: [T]he current structural arrangements, whereby domestically collected plasma is fractionated by CSL Bioplasma, are, subject to careful monitoring of prices, in Australia’s best interests. The present system is well entrenched in the “hearts and minds” of the Australian population and of the Australian medical community and, particularly, in the strategy, thinking and reliance of all end user groups.1

Hilary J Bambrick · Thomas A Faunce

To the Editor: Gleason et al describe the continued tendency of hospitals to allow prevocational, newly graduated doctors to flounder as they provide the cannon fodder to keep those hospitals running.1 For about 5 years, I coordinated an education program for junior medical staff. It is a model that other areas could consider. The Northern Sydney Area Health Service — as it was then — had two primary allocation centres for junior staff, and three local secondment hospitals. During their time in Sydney, all interns at those five hospitals were required to attend a 3-hour program of education provided for them, off site, each fortnight. In the first week, half of the interns attended; the program was repeated the following week to allow the other half to attend. A separate program was developed for Postgraduate Year 2 doctors that provided day-long programs centred on a particular topic (eg, renal disease or paediatrics). Each hospital put half of their Postgraduate Medical Council of New South Wales (now NSW Institute of Medical Education and Training) funding towards the cost. The teaching was provided by clinical staff within the area health service. The size of the area health service meant that there was an enormous pool of expertise to call on. The very size of that pool meant that we did not over-use the same keen teachers. The quality of the teaching was regularly rated as high by the doctors who attended. The off-site venue meant that time was truly quarantined. The provision of breakfast and morning tea meant an opportunity for junior medical staff to spend time with their cohort, compare experiences, complain, commiserate, and congratulate, in an informal atmosphere. Of course senior staff — administrative and medical — would complain. However, they gradually grew used to the format, and learned to time rounds, to make allowances and to value their happier, better educated staff. Of course there were problems of all sorts, and the system was not perfect, but it signalled to junior staff that they were valuable and valued. As Gleason et al noted: Hospitals must meet their training responsibilities and should not continue to place service demands above the training needs of doctors. Teaching time needs to be a regular, protected, paid part of every junior doctor’s day. In 2007, it is completely unacceptable to continue to see junior medical staff as “workforce”. It shames us all as senior clinicians that we have not ensured that all hospitals meet their educational and training responsibilities to these valuable members of our profession.

Lilon G Bandler

To the Editor: Medical education faces a number of significant challenges in the coming years. The most concerning problem is that there are insufficient medical educators. To compound this problem further, clinicians with an interest in teaching lack academic recognition, funding, time for medical education, and institutional support.1 While this is already creating problems for training of medical students and junior doctors, the situation will only become worse as the number of graduates increases to meet workforce shortages. A greater number of medical students and graduates will put further pressure on an already over-stretched health system to deliver adequate medical education. Therefore, we need to consider new ways of creating effective clinical teachers and learning materials that are educationally sound and supported by research. One way to address some of these deficits is to create specific training positions for doctors interested in pursuing a career in medical education, perhaps called “medical education registrars”. These positions could be jointly funded by hospital networks, universities and other interested groups, such as the postgraduate medical councils, and could be aimed at doctors with a strong interest in medical education, especially those at an early stage in their career, such as postgraduate year (PGY) 3 and PGY4. This joint funding would support hospitals and universities working collaboratively, and taking responsibility for making medical education “a priority, rather than an add-on”.2 The hospital appointment would maintain the registrars’ clinical knowledge, and the university appointment would allow opportunities for further study in medical education theory and research methods. Both environments would allow for academic mentoring. These registrars would then be ideally placed to assist in the development, implementation and evaluation of education materials using the newly released Australian Curriculum Framework for Junior Doctors as a guide. While agreeing that the Framework provides a “unique opportunity to improve the quality of medical training in Australia”, Gleason et al expressed concerns about how the Framework would be implemented.3 Medical education registrars could play a pivotal role in this process, and would be strong advocates for junior doctors. Medical education registrar positions are a simple, cost-effective way to encourage clinicians, especially those early in their careers, to pursue medical education as a serious and satisfying career path. Urgent action is required now to avert certain disaster in a few years, when hospitals are full of medical students and junior doctors, and there is no one to supervise and train them.

Andrew M Foote

In reply: A teaching registrar position is a great idea. It could foster development of knowledge and skills in interested clinicians, and perhaps higher degrees in learning and teaching, as well as serving as the start of a career pathway.1 The United Kingdom allows specialist trainees to take a year out to develop skills in education or research. Here, however, it is doomed to fail, unless there is a receptive environment for these registrars to work in or a career path that is attractive. What kind of educational environment is needed? We need leaders with vision, knowledge, new ideas and resources to lead the development of programs and assessment. We need teachers whose main focus is to teach and implement programs. And we need to support all clinicians to continue to supervise and teach. Not all these roles need to be performed by a medical practitioner.2 Without all of this, someone who is “interested in teaching” may be burdened with an unsustainable level of teaching and administration. Better integration at a local level across undergraduate and prevocational training3 (not to mention linking with other professional groups) and a culture of teaching are needed. Importantly, we need coherent and visionary leadership at national and state levels to underpin these endeavours.3,4

Fiona R Lake