(Aust Prescr 1995;18:27-9)
Letters, which may not necessarily be published in full, should be restricted to not more than 250 words. When relevant, comment on the letter is sought from the author. Due to production schedules, it is normally not possible to publish letters received in response to material appearing in a particular issue earlier than the second or third subsequent issue.
Wall chart commonly prescribed medications
Editor, I read with interest the recent issue of Australian Prescriber and the wall chart contained within it (insert to Aust Prescr Vol. 17 No. 3 1994).It surprised me no end to see no mention at all of renal impairment in relation to ACE inhibitors but frusemide rated such a mention.
There is abundant evidence in the literature on the effects of ACE inhibitors on renal function, and we at this hospital have at least two patients on longterm haemodialysis because of uncritical use of them in patients with renal artery stenosis.
A.Z. Gyory
Professor of Medicine
Royal North Shore Hospital
St. Leonards, N.S.W.
The Editor comments:
The wall chart was based on the Australian Pharmaceutical Formulary. This contains the requirements of the Pharmaceutical Society of Australia on the labelling and counselling which should be given when drugs are dispensed. Clearly, doctors have additional factors to consider when they are prescribing. The 'Other comments' column was intended to include a few of those considerations, but it was not intended to be a complete list of prescribing instructions. The column contains enough space for additional information to be included, so practitioners can add Professor Gyory's warning and any other advice they choose.
I have also been advised that the labelling for doxycycline differs slightly from the other tetracyclines. Doxycycline can cause oesophageal or gastric irritation, so it should be taken with fluids or food. The advice on the wall chart for doxycycline should be '4 (delete milk) B,D'.
Editor, Associate Professor Hector Maclean's article on 'Eye infections' (Aust Prescr 1994;17:66-8) has a misleading synopsis. It states 'although a chalazion will eventually settle spontaneously, a recurrence is an indication for a biopsy to exclude malignancy.' Infection in a chalazion may well resolve, most do not. Thechalazion itself will not resolve until it is curetted and, unless adequate treatment is carried out, will almost certainly recur. So the synopsis should read: a recurrence following adequate treatment is an indication for biopsy
to exclude malignancy.
Brian Ancell
Ophthalmologist
Adelaide, S.A.
Editor, Associate Professor Maclean points out in his article regarding eye infections that blepharitis is probably the most common external eye infection.
Whilst the treatment that he recommends cannot be criticised, by far the most common cause of severe blepharitis is in association with acne rosacea. This condition and its associated corneal ulceration is exquisitely sensitive to a prolonged course of doxycycline. This needs to be given as 100 mg per day for 4-6 weeks and provides longlasting symptomatic relief of this recurring problem.
Patrick Lockie
Ophthalmologist
Geelong, Vic.
Associate Professor H. Maclean, the author of the article, comments:
I agree with Dr Ancell's revision of the infelicitous wording in the synopsis. I hope it is clear from the full text that I agree with him.
Dr Lockie does well to remind us that blepharitis can be associated with many skin conditions, including acne rosacea. Acne rosacea seems much less common in Australia than in northern Europe and there is remarkably little about its association with blepharitis in recent literature.1 I hope DrLockie will be moved to put his experiences into print, and to include information as to whether he finds the same rather gloomy risk of relapse after withdrawal of tetracyclines that earlier authors have noted.
Reference
1. HuberSpitzy V, Baumgartner I, BohlerSommeregger K, Grabner G. Blepharitis a diagnostic and therapeutic challenge. A report on 407 consecutive cases. Graefes Arch Clin Exp Ophthalmol 1991;229:224-7.
I believe, however, that Professor Fletcher's hope that all new technology will be backed by outcome studies is probably unrealistic. For example, to study the cardiovascular outcomes of an intervention procedure would cost a minimum of $30-$40 million. Governments are unlikely to make this money available. The real cost of new technology is, of course, not in its development in teaching hospitals, but in its proliferation elsewhere, particularly in the private sector, where restriction may be an unpalatable political decision.
Colin I. Johnston
Chairman
Division of Medicine
University of Melbourne, Vic.
Professor P.J. Fletcher, the author of the editorial, comments:
I believe Professor Johnston's pessimism concerning the financial viability of appropriate evaluation of expensive technology is unwarranted.
Let us make the assumption that a procedure costs the government $1000. If 10 000 procedures are performed each year, the annual cost to the taxpayer is $10 million. Even on Professor Johnston's rather generous estimate, this will pay for a formal evaluation in 3-4 years.
This is surely a compelling argument that it will be costeffective for the government to insist on proper evaluation of new technology and to fund that evaluation before uncontrolled proliferation contributes to escalating health care costs.
Editor, Professor Fletcher raises important points in his editorial 'Expensive medical technology we can, but should we?' (Aust Prescr 1994;17:54-5). His concern is shared by the Australian and New Zealand Association of Physicians in Nuclear Medicine which believes that quality assurance and technology assessment are essential to the rational use of these procedures.1 However, I wish to take issue with several points in his editorial.He refers to a study2 that is said to use 'the most modern methods of thallium scanning', which shows that 'only age and definite evidence of coronary disease were identified as statistically significant predictors of postoperative cardiac adverse events'. But 'definitive evidence of coronary disease' and the most common 'cardiac adverse event', perioperative ischaemia, were defined using clinical or ECG criteria, and therefore a correlation is not unexpected. Furthermore, the method of analysis of scans was not that usually applied and is likely to lead to false positive and false negative results.
Variation in the use of thallium scanning relates to many factors including access and the understanding of its role by referring practitioners. In general, it is not a selfreferred procedure.
When examining the efficacy of a diagnostic test, outcome measures such as mortality and infarction rates may not always be appropriate as many factors can intervene between test result and outcome, including what the referring practitioner does with the information, patient preferences and the quality and nature of subsequent procedures. The use of intermediate outcomes is preferred, but they must be specific to each context.
R. McLean
President
Australian and New Zealand Association
of Physicians in Nuclear Medicine
Sydney, N.S.W.
References
1. McLean RG. Diagnostic imaging: reversing the focus [editorial]. Med J Aust 1994;161:460-1.
2. Baron JF, Mundler O, Bertrand M, Vicaut E, Barre E, Godet G, et al. Dipyridamolethallium scintigraphy and gated radionuclide angiography to assess cardiac risk before abdominal aortic surgery. N Engl J Med 1994;330:663-9.
Professor P.J. Fletcher, the author of the editorial, comments:
I am delighted to have assurances from Dr McLean that the Australian and New Zealand Association of Physicians in Nuclear Medicine supports the formal assessment of new technology.
He criticises the method of analysis of the scans in the study of Baron et al.; however, this was the largest and best designed study evaluating thallium scanning in this context, and still provided a negative result. Moreover, all the previous 'positive' studies used even more primitive methods of thallium scanning, yet he has not criticised these studies.
The use of intermediate outcomes is often necessary, but carries grave dangers if the intermediate outcome and the more important longerterm outcome are not closely linked. Dr Dawson has referred to this in his editorial.
Editor, In the article 'Testing for drug allergy' (Aust Prescr 1994;17:62-5) I believe the wrong impression is provided under recommendations concerning vaccines in eggsensitive patients in that it is stated 'small amounts of egg protein may be found in vaccines for influenza, measlesmumpsrubella and yellow fever'. In the subsequent recommendation concerning skin testing, no distinction is made between these vaccines. As influenza and yellow fever vaccine are grown in eggs, there may be small amounts of egg protein present and caution is required in eggsensitive individuals. In contrast, measlesmumpsrubella is produced on chicken fibroblasts and does not contain any egg protein. There have been suggestions of crossreacting proteins1; however, the likelihood of significant immediate hypersensitivity reaction in eggsensitive individuals is of a different order to that with vaccines grown in eggs. It is important to make the distinction between the two types of vaccine.The requirement for skin prick testing and intradermal testing with vaccine in eggsensitive children, prior to the administration of measles vaccine, has no firm scientific basis. We have demonstrated in a recent publication that a positive reaction on either intradermal or prick tests with vaccine does not predict a significant adverse reaction to vaccination.2 We and other authorities1-4 have questioned the scientific validity of skin prick testing in eggsensitive children prior to administration of measles vaccine. It is important to distinguish between those vaccines which are grown in eggs and may be contaminated with egg protein and the measlesmumpsrubella vaccine when discussing the requirements for skin testing in eggsensitive subjects.
Andrew Kemp
Director of Clinical Immunology
Consultant Paediatrician
Royal Children's Hospital
Melbourne, Vic.
References
1. Fasano MB, Wood RA, Cooke SK, Sampson HA. Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine. J Pediatr 1992;120:878-81.
2. Aickin R, Hill D, Kemp A. Measles immunisation in children with allergy to egg. Br Med J 1994;309:223-5.
3. Kemp A, Van Asperen P, Mukhi A. Measles immunization in children with clinical reactions to egg protein [see comments]. Am J Dis Child 1990;144:33-5. Comment in: Am J Dis Child 1990;144:32
4. David TJ. Food and food additive intolerance in childhood. Oxford: Blackwell Scientific Publications, 1993:126-33.
There is a relationship between the observed increase in QT interval and the circulating level of terfenadine, but little or no relationship with levels of the acid metabolite. The impression given by Professor Moulds' article is that the metabolite is potentially cardiotoxic. All data currently available point to the metabolite being devoid of cardiotoxic effects. In individuals who are using Teldane at the recommended dose, the parent compound is essentially undetectable in plasma, due to the extensive first pass metabolism. The metabolite is responsible for the antihistamine activity. According to the article, the metabolite has been implicated in causing arrhythmias and in the development of torsades de pointes, which is incorrect.
In the interest of concerned practitioners, I wish to have this error corrected.
Errol Kaplan
Associate Medical Director
Marion Merrell Dow Australia Pty Ltd
Frenchs Forest, N.S.W.
Associate Professor R.F.W. Moulds, the author of the article, comments:
Dr Kaplan is correct that the most recent evidence, whilst not absolutely conclusive, suggests that it is the native terfenadine, rather than the active metabolite, which is responsible for the potentially fatal arrhythmias documented when erythromycin is coadministered with terfenadine.
My report was based on studies which showed that the concentration of the metabolite increased markedly when terfenadine was administered to normal volunteers in the presence of erythromycin, and the accumulation of the metabolite was associated with ECG changes thought to
be a marker for the development of more severe arrhythmias.
However, more recent information, including in vitro testing of terfenadine and its metabolite on isolated cardiac cells, suggests it is more likely to be increased concentrations of terfenadine itself, caused by delayed conversion of terfenadine to its metabolite, rather than the accumulation of the metabolite, which is responsible for the arrhythmias.
As a separate issue, it should also be noted that large doses of erythromycin can themselves cause cardiac arrhythmias, so it is possible that the arrhythmias caused by the combination of terfenadine and erythromycin have a multifactorial basis.
