Letters

In reply: The commitment of Russell and Abraham to their own program has distracted them from accurate reporting and sound epidemiological principles. They say that the majority of patients that we studied received no treatment. Not so. We clearly stated that only 34 of the 220 patients studied received no treatment.1 They then draw a range of inferences from the fact that "3/95 (3.2%)" patients with anorexia nervosa died. In fact, only 2 of 95 patients with anorexia nervosa died as a consequence of that disorder during the five years of our study. At 2.1%, this is similar to the crude death rate of 1/61 (1.6%) that they describe in their own study. However, it is only acceptable to use a rare outcome as a measure of the efficacy of a treatment program if the clinical characteristics that put patients at risk for such an outcome are known and accounted for. We do not know the specific factors that put people at particular risk of dying from anorexia nervosa. Without such knowledge, small differences in crude death rates can not of themselves inform us whether treatment programs diminish or accentuate such risks. Unfortunately, there are no other studies against which to compare the outcomes of the patients with "eating disorders not otherwise specified" in our study. We have dealt with issues such as the representative nature of our study elsewhere.2 I stand by our work and the conclusions we draw from it.

David I Ben-Tovim PhD FRANZCP

To the Editor: A 27-year-old hospital medical officer received a penetrating needlestick injury to her left hand, drawing blood, after using a 22-gauge needle to deroof a vesicle for diagnosis in a two-year-old patient with orolabial herpes simplex virus type 1 (HSV-1). The medical officer had no significant medical history, took no regular medication, and had no previous history of oral or genital herpes. On Day 4, a vesicle appeared at the site of inoculation, with surrounding erythema. The medical officer first presented on Day 6, by which time the vesicle was crusting over, with several satellite lesions (see Figure). She described mild pain in her left axilla, but no fevers or sweats. A 10-day course of oral famciclovir (250 mg, three times daily) was prescribed and she was restricted from work until the lesions had completely healed (Day 16). During 12 months of follow-up there has been no clinical recurrence. Specimens from the two-year-old child were positive for HSV-1 by direct immunofluorescence, and HSV-1 DNA was detected by polymerase chain reaction (PCR). Specimens from the medical officer on Day 6 were negative for HSV-1 by direct immunofluorescence, but positive by PCR. There was no evidence of HSV-2 or varicella zoster virus in either specimen. To our knowledge this is the first reported transmission of HSV-1 after needlestick injury. Herpetic whitlow (HSV of the hands), a well-recognised occupational hazard for dentists and anaesthetists, is frequently misdiagnosed, resulting in unnecessary surgical procedures and delayed healing. In healthcare workers, pain and also work restrictions to limit cross-infection reduce productivity. Horizontal transmission can occur in the absence of clinical lesions, but latex gloves are an effective barrier.1 There are few guidelines available for postexposure prophylaxis for HSV-1, and no controlled clinical trials in humans. The short incubation period and early establishment of latency in HSV infection remain obstacles for effective delivery of postexposure prophylaxis. HSV can establish latent infection of neurones in the absence of peripheral replication.2 In an animal model, postexposure treatment with famciclovir or valaciclovir inhibited peripheral replication of HSV, reducing latent infection but not preventing it altogether.2 In one case report, a patient who started taking famciclovir within one hour of a needlestick injury did not develop whitlow and remained seronegative for HSV.4 Famciclovir and valaciclovir have high oral bioavailability, minimal toxicity and proven efficacy in treating HSV. Available data suggest that treatment with these drugs after documented exposure to HSV reduces the severity of acute disease, limits the number of neurones infected and may reduce the frequency of subsequent recurrences. If started early enough, postexposure prophylaxis may prevent latent infection altogether.

Mark W Douglas FRACP, BScMed(Hons) · Jane L Walters MB BS(Hons), MSc, DTM · Bart J Currie FRACP

To the Editor: We report two episodes of serotonin toxicity (or serotonin syndrome) caused by drug interaction in one individual chronically treated with dexamphetamine. The interacting drugs were venlafaxine, then later citalopram. We are not aware of any previous reports of serotonin toxicity caused by dexamphetamine in combination with either venlafaxine or any selective serotonin reuptake inhibitor (SSRI). A 32-year-old man presented after two days of marked agitation, anxiety, shivering and tremor. He was being treated with dexamphetamine, 5 mg three times daily, for adult attention deficit hyperactivity disorder. He had started venlafaxine (75 mg daily) two weeks previously, and this had been increased to 150 mg daily after a week. On examination, he was alert and oriented, but diaphoretic, shivering and had fine motor tremor. His heart rate was 140 bpm, blood pressure was 142/93 mmHg and temperature 37.3°C. Pupils were 3 mm diameter and reactive, with no nystagmus or ocular clonus. There was generalised hypertonia, hyperreflexia, 1–2 beats of inducible ankle clonus, frequent myoclonic jerking and tonic spasm of the right side of his orbicularis oris muscle. His abdomen was tense, but non-tender, with normal bowel sounds. An electrocardiogram showed sinus tachycardia with a baseline tremor, but no other abnormality. Therapy with dexamphetamine and venlafaxine was ceased, and cyproheptadine (8 mg doses up to a total of 32 mg over three hours) was given. The patient had a stepwise reduction in heart rate, with complete resolution of his symptoms, and was discharged the next morning. Dexamphetamine therapy was restarted three days later and citalopram therapy was commenced one week after discharge. Two weeks after discharge, he reported similar symptoms, and ceased citalopram. Three days later he was still agitated, with nausea, diarrhoea and teeth clenching. There was no rigidity, tremor or diaphoresis, and his heart rate was 76 bpm. He was given two 8 mg doses of cyproheptadine and was asymptomatic two days later. Some of this patient's symptoms could be attributed to noradrenaline excess. However, the combination of neuromuscular and autonomic features is more consistent with serotonin toxicity. The fact the symptoms resolved after administration of cyproheptadine (a 5-HT2-receptor antagonist) supports this hypothesis. There is no theoretical reason why the interaction of citalopram (a pure SSRI) and dexamphetamine should cause catecholamine excess, and again the more likely explanation is serotonin toxicity. Dexamphetamine causes psychostimulation and increased peripheral sympathomimetic activity. Centrally it causes presynaptic release of serotonin,1 and dopamine and catecholamine release.2 Venlafaxine and its metabolite, O-desmethylvenlafaxine, inhibit both neuronal 5-HT reuptake and noradrenaline reuptake,3 whereas citalopram, an SSRI, has little effect on noradrenaline reuptake.4 The combination of serotonin reuptake blockade and either presynaptic release of serotonin or monoamine oxidase inhibition by dexamphetamine will cause increased serotonin levels in the central nervous system, and is the likely mechanism of toxicity in this patient. This is consistent with the mechanism for other reports of serotonin toxicity.5 Increased awareness and cautious monitoring is advised when using a combination of dexamphetamine and either venlafaxine or an SSRI. This is particularly important in people using amphetamines recreationally and in children taking dexamphetamine for attention deficit hyperactivity disorder.

Felicity H Prior BPharm, GradDipEpi · Geoffrey K Isbister BSc, MB BS · Andrew H Dawson MB BS, FRCP, FRACP · Ian M Whyte MB BS, FRACP FRCP

To the Editor: We report a case of bilateral acute angle closure glaucoma associated with venlafaxine. A 45-year-old woman with a history of bipolar affective disorder and borderline personality traits was admitted with increasing depression and suicidal ideation. She was taking sodium valproate (1500 mg/day) and slow-release lithium (450 mg/day). She had also taken dothiepin (50 mg nightly) for seven days, but this therapy was ceased on admission. Her only previous ophthalmological history was hypermetropia, and she had been taking low-potency neuroleptic medications and selective serotonin reuptake inhibitors in the past with no significant adverse effects. She was treated with chlorpromazine (up to 150 mg daily), and venlafaxine therapy (extended release, 75 mg/day) was commenced. After three days of taking venlafaxine, she developed left retro-orbital pain associated with nausea and vomiting, with subsequent swelling and drooping of the left upper lid and a dilated and fixed pupil. The eye was congested and visual acuity was reduced to counting fingers. She was diagnosed with acute angle closure glaucoma, treated with timolol, and transferred to a tertiary referral hospital. During this period, she sustained an injury to her right eye following an assault by a third party. A computed tomography scan revealed a right blow-out fracture with inferior rectus muscle entrapment. On admission, intraocular pressures were 16 mmHg in the right and 50 mmHg in the left eye, and gonioscopy revealed closed angles (grade 1–2). Ninety minutes after being given intravenous mannitol, topical apraclonidine hydrochloride, latanoprost and pilocarpine eye drops, the intraocular pressure dropped to 35 mmHg in the left eye. Initial laser iridotomy was unsuccessful because of a hazy cornea. Laser iridotomy was repeated several times after topical steroid therapy until it was successful. The right orbital floor fracture was repaired with a Medpor implant (Porex Surgical Products Group, Atlanta, Georgia). Eight days after starting venlafaxine therapy, she developed similar symptoms in her right eye, despite prophylactic treatment with pilocarpine eye drops four times a day. Venlafaxine was discontinued, and three days later a successful right laser iridotomy was performed. Her visual acuity was 6/5 in her right and 6/18 in her left eye. After eight weeks she was receiving no ophthalmic treatment and her intraocular pressures were well controlled. In a MEDLINE search, we found no published reports of venlafaxine associated with acute angle closure glaucoma. The manufacturers report it as a rare adverse event (fewer than 1/1000; data on file; Wyeth-Ayerst Laboratories). There has been one previous report of increased intraocular pressures in two patients with known narrow-angle glaucoma who began taking venlafaxine.2 Glaucoma has also been reported with paroxetine.3-4 Our patient had no associated family history of glaucoma, but her eyes were predisposed to angle closure glaucoma owing to hypermetropia. Patients with acute angle closure glaucoma usually have a structural defect that produces a narrow drainage angle, and thus moderate dilation of the pupil may precipitate an attack. Drugs like tricyclic antidepressants cause mydriasis and may cause the narrow angles to close as a result of anticholinergic effects. Venlafaxine, however, is a serotonin and noradrenaline reuptake inhibitor without anticholinergic activity. This fact and the time course suggest that a combination drug interaction may have occurred in this patient, perhaps by the hepatic inhibition of chlorpromazine metabolism by venlafaxine, increasing anticholinergic activity, or by a direct effect of venlafaxine on the eye unrelated to mydriasis.

Bradley Ng MB ChB · G Mark C Sanbrook MB BS, FRANZCP · Anthony J Malouf · Smita A Agarwal

To the Editor: Akathisia is a clinical syndrome that manifests as the subjective sense of unease or restlessness, or observable motor manifestations such as shuffling or tramping movements of the legs and feet, or both.1 The marked distress associated with akathisia can lead to impulsive suicide attempts.2 It is commonly associated with antipsychotic medications, as well as various antidepressants, including tricyclics and selective serotonin reuptake inhibitors (SSRIs). Mirtazapine is a novel antidepressant. It acts centrally to increase both noradrenergic and serotonergic neurotransmission. Common side effects include sedation, weight gain and increased appetite. Tremor is listed as an adverse reaction, but this does not represent akathisia. A MEDLINE database search (up to September 2001), using the words "akathisia" and "mirtazapine", did not reveal any reports of an association. However, as of mid-November 2001, the Adverse Drug Reactions Advisory Committee (ADRAC) had received five reports of "hyperkinesia (probably equivalent to akathisia)" associated with mirtazapine. We would like to report two cases of acute akathisia associated with mirtazapine. A 52-year-old man was referred by his psychiatrist for inpatient management of his depressive illness. He had previously tried multiple antidepressants, including various tricyclics and SSRIs. However, because of the sexual side effect anorgasmia, adherence to antidepressant treatment was poor. He was prescribed mirtazapine (30 mg at night). Within an hour of taking the first dose, he complained of feeling restless and unable to keep his legs still. He was given 1 mg of clonazepam, which settled his symptoms after 30 minutes. He was also observed to jiggle his legs and feet while at rest. His symptoms recurred the next day, necessitating further successful treatment with clonazepam. Mirtazapine therapy was continued, and the patient's depression improved significantly over the next few days, and the akathisia gradually resolved with regular use of clonazepam. A 73-year-old woman with chronic depression was admitted after an overdose. Her medications on admission were omeprazole, amiodarone, bendrofluazide and fluvoxamine (50 mg). The fluvoxamine was changed to mirtazapine (15 mg/day initially, increased to 30 mg/day after three days). After the first 30 mg dose, she described intense restlessness in her legs lasting up to two hours. The distress necessitated reintroducing the fluvoxamine in place of the mirtazapine. Within three weeks the patient was readmitted with depressed mood and suicidal ideation. Mirtazapine (30 mg at night) was re-introduced, with consequent acute return of restless legs. The patient's akathisia settled when the mirtazapine was reduced to 15 mg at night. No additional treatment was required. The neurobiological basis for akathisia remains unclear. Involvement of central serotonergic and adrenergic neurotransmitter systems has been postulated. One of mirtazapine's main actions is blockade of α2-adrenoreceptors. Clonidine, an α2-agonist, is effective in treating akathisia.3 We suggest that mirtazapine's adrenoceptor action might be the basis for the occurrence of akathisia in these patients.

Boregowda G Girishchandra MB BS, DPM, DipNB · Liana Johnson BPharm, MPS · Rebecca M Cresp MB BS · Kenneth G D Orr MB BS, FRANZCP

To the Editor: In a recent editorial, Mason and Diamond state that ergocalciferol (vitamin D2) is bioequivalent to cholecalciferol (vitamin D3) and that 1000 IU/day of ergocalciferol is sufficient for the treatment of vitamin D deficiency.1 Both statements are contentious. Although ergocalciferol (vitamin D2) is the only single prohormonal form of vitamin D available on prescription in Australia, there are three reasons to be cautious about the use and dose equivalence of ergocalciferol (vitamin D2) compared with cholecalciferol (vitamin D3). Cholecalciferol (and not ergocalciferol) has been shown in two randomised trials to reduce fracture rates when administered concomitantly with calcium to elderly patients.2,3 Furthermore, all recently studied agents for treating postmenopausal osteoporosis (alendronate, risedronate, raloxifene and parathyroid hormone 1-34 [the first 34 amino acids of the hormone]) were shown to lower fracture rates, but study participants were routinely given supplementary calcium and vitamin D when deficiency was established. At least two studies specified the use of cholecalciferol. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are probably not bioequivalent.4,5 Ergocalciferol administration to vitamin-D-replete premenopausal women reduced the amount of circulating 25-hydroxyvitamin D3 (25OHD3) while only modestly increasing 25OHD2 levels, with a resultant marginal effect on the total 25OHD level.4 In contrast, the equivalent dose of cholecalciferol increased the circulating level of 25OHD3 significantly.4 Lastly, while radioimmunoassays (RIAs), such as the INCSTAR/DioSorin assay (Stillwater, Minnesota, USA), used in both studies of vitamin D levels published recently in the MJA6,7 are able to measure 25OHD levels, they are incapable of differentiating between 25OHD2 and 25OHD3. Furthermore, neither of the commercially available RIAs (the other one is made by IDS Ltd, Tyne and Wear, UK) is able to measure both vitamin D metabolites with equivalent accuracy. In a study comparing RIAs for the measurement of 25OHD against high performance liquid chromatography (the gold standard method) both assays did not recognise 25OHD2 as well as 25OHD3, with r2 of 0.74 and 0.58, respectively, for 25OHD2.8 Until further research is available, using more patients and a greater number with vitamin D deficiency, caution must be exercised in the interpretation of 25OHD levels measured with RIAs. This applies especially to individuals taking ergocalciferol (vitamin D2) for the treatment of vitamin D deficiency. Thus, it would appear that cholecalciferol (vitamin D3 ) has a role to play in the reduction of osteoporotic fractures, but only when administered with calcium. If administering ergocalciferol (vitamin D2), a far greater dose than 1000 IU/day may be needed, and the use of commercial RIAs to determine the therapeutic response may be misleading.

Paul Glendenning PhD, FRACP · Rebecca S Mason · Terrence H Diamond

In reply: Glendenning raises a number of interesting points, which require some clarification. Are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) biologically equivalent? The statement that ergocalciferol and cholecalciferol are bioequivalent in humans is made by most authoritative textbooks, based mainly on evidence from early studies of the antirachitic efficacy of ergocalciferol and cholecalciferol compounds, and contrasts with reduced efficacy of ergocalciferol in birds and monkeys.1 Recent studies using more precise measurements have raised some doubts as to the absolute equivalency of ergo- and cholecalciferol, but the differences are marginal2 and not universally found.3 There are few recent data on relevant biological endpoints. Serum concentrations of the active hormone, 1,25-dihydroxyvitamin D, were not different after administration of ergo- or cholecalciferol,2 and increases in bone mineral density were greater after ergocalciferol therapy than after cholecalciferol in patients taking anticonvulsants.1 In short, on current evidence, differences in biological activity between ergocalciferol and cholecalciferol are likely to be relatively minor. Are there problems monitoring therapy? 25-Hydroxyvitamin D values may be used for monitoring treatment. The possibilities of impaired detection of the 25-hydroxy metabolite of ergocalciferol by some assays,2 and perhaps a smaller rise in total 25-hydroxyvitamin D concentrations after low doses of ergocalciferol, should be borne in mind when monitoring therapy. What is the current recommendation for vitamin D supplementation? While the availability of larger dose sizes and/or cholecalciferol preparations would be helpful, 800 IU of ergocalciferol and 1 g of calcium for six months was shown to reduce secondary hyperparathyroidism in older patients,1 and 600 IU/day (same for ergo- and cholecalciferol) is the new recommended adequate intake for older patients with limited sun exposure.1

Paul Glendenning

To the Editor: A recent editorial in the Journal focused on the "blurring of research ideals and corporate interests".1 But there are other funding and commissioning bodies, including government, whose wants or needs also have the potential to blur research ideals and exert control over what can be published. In recent times, those who pay the piper increasingly want to call the tune. Understandably, this is also an issue for research into Aboriginal ill health.2,3 Van Der Weyden's plea for the development of national guidelines on institutional conflict of interest should therefore be broadened to include all funding bodies. One suggestion for inclusion in these guidelines, to enhance public interest in research, is an obligation for authors to state not only their sources of funding, but "the origin of the research question they are attempting to answer"4 and the person or group who initiated the funding of the project.

Max Kamien

To the Editor: We report the appearance of erythromycin and inducible clindamycin resistance in the south-west Pacific strain of non-multiresistant methicillin-resistant Staphylococcus aureus, which has recently appeared in eastern Australia. Infections occur predominantly in Polynesian people and are usually community-acquired. Most strains belong to Western Samoan phage patterns (WSPP1 or WSPP2) and pulsotype A when typed by pulsed-field gel electrophoresis.1,2 These strains are resistant to all β-lactams, but are usually susceptible to erythromycin, clindamycin, gentamicin, tetracycline, trimethoprim–sulfamethoxazole and ciprofloxacin. Although most of these antibiotics would not be recommended for therapy,3 clindamycin has been recommended for non-parenteral treatment of soft-tissue and bone infections, as it is efficacious in treating similar infections caused by methicillin-susceptible S. aureus.4 Twenty isolates of community-acquired, non-multiresistant pulsotype A MRSA were collected from patients from southern Brisbane and Logan in 1997 and 1998.2 A further 16 isolates were obtained from Ipswich patients between December 1998 and February 2001. We found that all 36 isolates were susceptible in vitro to gentamicin, tetracycline, trimethoprim–sulfamethoxazole, ciprofloxacin, rifampicin, fusidic acid and vancomycin. However, two of the Ipswich isolates had erythromycin and inducible clindamycin resistance. When susceptibility testing was performed using standard disc methods, both isolates appeared resistant to erythromycin but susceptible to clindamycin. However, on testing for inducible macrolide resistance (MLSB phenotype) using a disc-approximation method, both showed inducible clindamycin resistance.5 These isolates were from superficial abscesses in Polynesian people with community-acquired infection. They were indistinguishable by pulsed-field gel electrophoresis, but there were no epidemiological links. As yet, we have found no community-acquired pulsotype A strains of MRSA with erythromycin resistance and constitutive (ie, non-inducible) clindamycin resistance. Two other recent Australian studies found erythromycin resistance in 13 of 153 and three of 29 isolates of non-multiresistant MRSA, respectively.3,6 These studies did not report clindamycin susceptibilities, and it was not clear what proportion of the isolates belonged to phage patterns WSPP1 or WSPP2, or were community-acquired. As clindamycin has been recommended as a therapeutic option for soft-tissue and bone infections caused by non-multiresistant MRSA, this finding of inducible clindamycin resistance has important implications. Microbiology laboratories should screen for inducible clindamycin resistance in erythromycin-resistant strains, and, if found, an alternative antibiotic should be used for treatment.7 Alternatively, rather than assessing inducible clindamycin resistance with a disc-approximation test, some laboratories may prefer to report all erythromycin-resistant strains as clindamycin-resistant. Also, given the increasing incidence of community-acquired MRSA infection in Australia, all suspected staphylococcal infections that are not responding to empiric therapy with β-lactam antibiotics should be swabbed for culture.

Wendy J Munckhof MB BS, FRACP FRCPA, PhD · Jacqueline Harper BSci (Hons), PhD · Jacqueline Schooneveldt BAppSci, MAppSci, GCM · Graeme R Nimmo MB BS, MSc MPH, FRCPA

To the Editor: We strongly support the proposal1 that it is time to create a special grant category for curiosity-based research proposals. Having been in biomedical research for over 50 years, we have experienced a period when most research was curiosity based. We can thus compare with the present situation — research aiming for a rapid, practical and commercial outcome has become almost a necessity for survival because of the increasingly severe reduction in government funding for universities and research institutes. We would like to illustrate the value of curiosity-based research with a few Australian examples from our own fields. In 1946, one of us (F F) was working on the experimental epidemiology of the causative agent of infectious ectromelia of mice (related to vaccinia virus). A chance observation — that the mice which survived the infection developed a skin rash — led to further study of the virus as a model for smallpox, measles and chickenpox infections. Thus, unexpected discoveries were made about the way the virus spreads through the body during the incubation period of these diseases.2 In 1951, myxomatosis spread in rabbits in the Murray–Darling basin of south-eastern Australia. The virus was initially extremely virulent (99% fatal), but the rabbits slowly developed genetic resistance. One of us (F F) studied the virus for 15 years, and this work was acknowledged as the best example of the co-evolution of viral virulence and host resistance.3 In 1957, Macfarlane Burnet proposed the clonal selection theory of antibody formation — that individual B lymphocytes made antibody of a single specificity.4 This was one of the most original concepts ever proposed in biology and it took 10 years to be widely accepted. It has since led to the production of monoclonal antibodies, which are used as basic reagents in research and diagnostic laboratories, and are now being used in immunotherapy. In the 1970s, Peter Doherty and Rolf Zinkernagel studied the role of the newly discovered cytotoxic T cells (which could lyse virus-infected cells) to find out how T cells recognised the infected cells. They showed that killing was restricted by the major histocompatibility complex (MHC) and that its role was to signal "altered self" to the T cell.5 These studies led to the award of the Nobel Prize in 1996. Cytotoxic T cell activity has since been shown to be the main immune mechanism for controlling and clearing many intracellular infections. Induction of a strong cytotoxic T cell response is the mechanism of candidate vaccines currently being trialled against HIV-1. In the late 1960s, one of us (G A), together with Chris Parish, showed that a bacterial protein, flagellin, induced antibody tolerance over a wide dose range. Parish was the first to show the inverse relationship between antibody and cell-mediated immune responses, which led others to describe two classes of helper T lymphocytes.6 These have been shown to be important in the development of allergy in infants, and offer the opportunity for immunotherapy to reduce the later incidence of allergy. None of these research programs was initiated with a commercial goal in mind. Benjamin Franklin, when asked about the importance of some research, replied "Of what use is a baby?".

Gordon L Ada AO, DSc, FAA · Frank Fenner MB BS, MD

To the Editor: There is much conflicting evidence that increased intake of vitamin C enhances the natural protective mechanisms of the body and decreases both the incidence and severity of the common cold.1 It is regrettable that the study by Audera and colleagues failed to show a significant therapeutic effect of megadose vitamin C in treatment of the common cold.2 The groups compared had, on average, similar composition after randomisation. However, the viral infections that cause the common cold and its progression to ill health, as evidenced by multiple symptoms, are affected by many factors, while symptom severity is well known to vary greatly. Therefore, the study's reliance on respondents' self-diagnosis of symptom severity and onset is a significant weakness in design. Randomisation of participants to the treatment groups may have been insufficient to override this design deficit, thereby significantly biasing the outcome. A better design might have combined patient self-report of symptom severity with physical examination, thus allowing independent and professional assessment of severity. Also, proper assessment of previous history of severity of cold symptoms is crucial for proper randomisation to treatment groups. If Audera and colleagues' study failed to control for this history, then randomisation may have also failed to balance its effect equally between treatment groups, significantly compromising the study's validity to detect any therapeutic benefit of vitamin C. Cold symptoms also vary diurnally, while severity varies with alcohol use and smoking status,3,4 which also affect vitamin C absorption.5,6 No information was provided on study participants' alcohol consumption and smoking status. Finally, the study did not assess stress, which may constitute a further, important uncontrolled bias. A recent cohort study of stress and the common cold concluded that all four dimensions of stress investigated — stressful life events, negative affects, positive affects and perceived stress — were significantly related to occurrence of the common cold.7 Stress may also have significantly affected symptom severity and participants' perception of their symptoms. Certainly, the trend observed in the placebo group of shorter duration of some symptoms and lower mean severity could have been due to less severe symptom history, compounded by a lower degree of overall stress.

Luis Vitetta · Avni Sali · Bill Paspaliaris · Nicola J Reavley

In reply: Precisely because of the temporal variation in symptom severity described by Vitetta and colleagues, we judged that medical professionals are not as well able, in a variably timed interview, to quantify patients' cold symptoms as the patients themselves can do on a continuing basis. Therefore, we consider that our study1 would have been no more valid if the detailed symptom severity cards had been supplemented by one or more physical examinations. In that respect, we are in good company with others who have studied the common cold over many years.2 We agree that double-blind randomisation does not necessarily distribute all relevant variables equally. That is why, in Box 2 of our study report, we presented four variables — age, sex, mean number of colds in the previous year, and mean number of days unwell with colds in the previous year.1 The likelihood that stress, smoking and alcohol status would have been sufficiently maldistributed in this large group to mask a significantly beneficial effect in even one of the three groups which received high-dose vitamin C seems vanishingly small. Nevertheless, we acknowledge that the study would have been stronger if we could have reported the distribution of these three potential confounders. We contest the view of Vitetta and colleagues that the evidence from randomised controlled trials of vitamin C in treating the common cold conflicts significantly (see Box 1 of our article1). The overview finding — that mega-doses of vitamin C for prophylaxis produce a relatively trivial reduction in cold severity but no reduction in incidence3 — was the stimulus for our own study. No community studies of this issue have been flawless, but the mounting collective evidence suggests that we should look elsewhere for a cold panacea.

Carmen Audera · Roger V Patulny · Beate H Sander · Robert M Douglas

To the Editor: A whole issue of the Journal devoted to Death and Dying [19 November 2001 issue] and not a single obituary!

Paul B Harris MB BS FRACR

In reply: I am reminded of a line from the American poet Edwin Arlington Robinson: "I shall have more to say when I am dead." Nowadays, the opportunity to be the voice commemorating the life of a colleague through an obituary in the Journal seems to be of low priority for members of Australia's medical profession. The decade 1991–2000 saw the lowest number of obituaries published by the Journal in the five decades since 1951.1 We did not include an obituary in the "Death and Dying" issue because, fortunately or unfortunately, the obituary tray was empty.

Martin B Van Der Weyden

To the Editor: We wish to report the identification of a novel virus causing lower respiratory tract disease in Australian children. The presence of this virus was recently described in Dutch children and tentatively called human metapneumovirus (hMPV).1 Clinical symptoms of infection are reported to resemble those of human respiratory syncytial virus (hRSV) infection. We therefore investigated whether the virus was present in Australian children. Three isolates were identified from a random selection of 200 nasopharyngeal aspirate (NPA) specimens collected throughout 2001 from children presenting to the Royal Children's Hospital, Brisbane, or the Logan Hospital, a public hospital to the south of Brisbane, with clinical respiratory tract disease. All NPA specimens were initially negative for hRSV, influenza A and B, parainfluenza 1, 2 and 3 and adenovirus by direct fluorescent antigen testing and subsequent viral culture. These negative NPA specimens were then screened by polymerase chain reaction (PCR) for hMPV, based on the known sequence of the virus.2 Sequencing of the PCR product in all three positive samples was 100% homologous with the known hMPV sequence. Viral growth was subsequently detected in culture from two of these samples, and confirmed as hMPV, using the method of van den Hoogen et al.1 Co-existent infection with coronavirus, rhinovirus, Bordetella pertussis, Chlamydia pneumoniae and Mycoplasma pneumoniae was excluded by PCR screening of the three hMPV isolates using validated in-house methods based on established protocols. Clinical features of the infected children are summarised in the Box. This is the first report of the presence of hMPV infection in Australian children and describes a new viral respiratory syndrome. It also adds to the clinical spectrum and understanding of respiratory viruses causing acute bronchiolitis in children. Only 25%–33% of NPA specimens collected from our population with suspected respiratory tract disease yield a positive result for a known viral or bacterial pathogen. Clinical features in this small cohort are difficult to separate retrospectively from hRSV. Based on the findings of this limited preliminary study of children presenting to hospital with respiratory tract symptoms, we would predict that hMPV is also relatively common in the Australian community. We are currently undertaking further characterisation of the hMPV isolates, a more detailed study of the epidemiology of hMPV disease, as well as developing improved diagnostic assays to rapidly identify clinical cases and assess seroprevalence of immunity to hMPV. Clinical features of human metapneumovirus in three Australian children Case 1 (Girl, 12 months) Case 2 (Boy, 5 years 11 months) Case 3 (Boy, 20 months) Date of nasopharyngeal aspirate collection 17/2/01 21/3/01 11/5/01 Presenting symptoms Rhinorrhoea, cough, tachypnoea, wheeze, vomiting Rhinorrhoea, cough, pharyngitis, conjunctivitis Rhinorrhoea, cough, fever Symptom duration before presentation (days) 4 3 4 Clinical signs Respiratory distress with hypoxia, rhinorrhoea, pharyngitis, chest wheeze with crackles Pharyngitis, chest wheeze Rhinorrhoea, pharyngitis, chest wheeze, cervical lymphadenopathy Chest X-ray Not performed Bilateral parahilar pneumonic infiltrates Bilateral parahilar pneumonic infiltrates Clinical diagnosis Bronchiolitis Viral lower respiratory tract infection Viral lower respiratory tract infection Outcome Admitted for oxygen therapy and nasal suctioning for three days Symptomatic treatment at home Symptomatic treatment at home

Michael D Nissen · Ian M Mackay · Stephen J Withers · David J Siebert · Theo P Sloots

To the Editor: I write to offer a re-analysis of the data presented by Whitby and colleagues.1 They reported a meta-analysis of crude estimates and relative risk of death derived from nine published studies for Staphylococcus aureus bacteraemia. They concluded that bacteraemia caused by methicillin-resistant S. aureus (MRSA) is associated with a "real increase in risk of death" compared with bacteraemia caused by methicillin-sensitive S. aureus (MSSA), with a relative risk of 2.12. However, they failed to explore fully the possible confounding effect of the patients' underlying diseases and treatment in their analysis. With this in mind, I offer a re-analysis of their data using regression analysis. Mortality rates versus median length of stay in hospital before bacteraemia (LOS) are shown in the Box (next page) for the five studies for which these data were presented by Whitby et al (in Boxes 1 and 2). The four studies without LOS data were combined, using the median LOS from the other five studies in the figure and the regression model. The regression analysis was performed with and without the weights provided by Whitby et al (Box 2), and also with and without the four studies for which LOS data were not available. Regression analysis revealed a significant association between mortality rate and LOS (P < 0.005). However, the addition of group status (MRSA or MSSA) failed to achieve significance in any iteration of the regression, while LOS remained a significant predictor of mortality risk. This suggests that, with S. aureus bacteraemia, mortality rate increases with length of time in hospital before the bacteraemia. The likely explanation is that patients residing in hospital for longer periods are sicker. Moreover, they are more likely to have been exposed to antibiotics, leading to increased risk of acquiring an S. aureus strain that is methicillin-resistant. The mortality risk is no different for MRSA versus MSSA bacteraemia if LOS, a surrogate marker for severity of patient illness, is taken into account. The difference that Whitby et al observed between the groups of patients with MRSA and MSSA bacteraemia could be accounted for by the difference in LOS between these groups. Mortality rate versus hospital length of stay before bacteraemia (LOS) in patients with MRSA or MSSA bacteraemia

James C Hurley MB BS, PhD, FRACP

In Reply: We thank Hurley for his comments on our meta-analysis.1 However, we strongly dispute that our analytical technique is flawed, and argue that we have been extremely cautious in drawing our conclusions. Hurley's contention is that hospital length of stay before bacteraemia (LOS) is a surrogate for severity of underlying disease and risk for colonisation with methicillin-resistant Staphylococcus aureus (MRSA), and that these factors explain the higher mortality in patients with MRSA. We agree that LOS may be a confounder. It may be an effect modifier, whereby patients in hospital for longer may be more ill, and therefore more susceptible to infection with and death from MRSA. Both are intuitive and biologically plausible conclusions. In fact, we referred to these possibilities in our Discussion, writing that "patients who ultimately become infected with MRSA are more seriously ill than those who become infected with MSSA [methicillin-sensitive S. aureus]" and "separating the effect of the bacteraemia per se from the effects of patients' underlying disease and treatment is a major problem when comparing outcomes". We also cautioned readers that available published data on mortality made it impossible for us to adjust for numerous potential confounders, including LOS, as the information given did not link these potential confounders with the outcome in individual patients. Hurley has not, as he suggests, undertaken an analysis that would allow him to control correctly for the potential confounder, LOS. He, like us, used "group-as-a-unit" data, but, although the groups are homogeneous for MRSA or MSSA, they are heterogeneous for LOS. Adequate examination of and control for potential confounders requires either individual patient data or data from homogeneous groups. Hurley has attempted to use analysis normally reserved for individual data.4 His analysis was analogous to treating the data as though from an ecological study, a design in which control of confounding is difficult,5 and thus does not permit him to draw his conclusions. Our analysis (not presented in our original article) of only those studies where the authors attributed mortality to bacteraemia6-8 found that the magnitude of effect remained (fixed-effect relative risk, 2.27; 95% CI, 1.75–2.96; P < 0.001; test for heterogeneity, χ2 = 6.14, df = 4, P = 0.19). As MRSA bacteraemia is a rare event and published studies are small, the statistical ability to control for confounding and effect modification is limited. Until sufficient suitable data for individual patients are available for analysis, we have remained restrained in our assessment. Mindful that MRSA bacteraemia is associated with increased mortality, regardless of the cause, we hold with our original conclusion that "our findings justify ongoing surveillance and proactive management of MRSA in healthcare facilities".

Michael Whitby · Mary-Louise McLaws · Geoffrey Berry

To the Editor: The article by Nelson et al1 estimates Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme (PBS/RPBS) savings if hypertensive patients on monotherapy were prescribed the agents recommended in guidelines; however, the analysis contains algebraic errors and insufficient sensitivity analyses. The question of excessive costs through the use of expensive agents for which there is no evidence of increased benefit for most patients is an important one, but the estimates of extent of overuse should be methodologically sound. The three main concerns we have with the paper's estimates are as follows: The total number of patients on monotherapy in Box 3 of the article adds to 1.1 million, whereas elsewhere the authors state that 60% of all 1.2 million Australian patients treated for hypertension are on monotherapy, giving an estimate of 0.72 million. (These estimates of 60% and 1.2 million are not referenced in the article.) One reason for this discrepancy is that the authors have treated the sum of column 4 in Box 2 as patients, not patient-years of treatment (some patients are on dual or triple therapy), leading to a 40% overestimate of numbers of patients on monotherapy reported in Box 3. Utilisation of prescription drugs is recorded by PBS/RPBS only if the cost to patient is subsidised. Therefore, PBS/RPBS expenditure divided by total patient numbers (Box 2) underestimates consumer cost for diuretics and β-blockers, both of which cost less than the non-concessional co-payment. Of total PBS/RPBS scripts, 16% are for non-cardholders,2 and the cost per script to these patients is about three to four times the prevailing 1998 cardholder co-payment. As a rough estimate, total consumer cost for these agents may need to be doubled, and their omission is therefore material. Although non-concessional patients still have a saving, it is less than that estimated in the article. Sensitivity analysis should have been performed on the following critical assumptions: (1) proportion of use for hypertension for each class of drugs, (2) the number of unsubsidised users of diuretics and β-blockers, and (3) the proportion of patients on each agent who are on monotherapy. It is vital that the current scrutiny by all stakeholders of PBS/RPBS expenditure be informed by reasonable estimates of inappropriate utilisation. The contribution made by the authors in developing a technique to estimate appropriate use for this group of drugs is valuable. However, use of unreferenced estimates of key variables, insufficient application of sensitivity analyses, algebraic errors and inappropriately combining PBS with non-PBS data may cloud rather than shed light on this issue.

Ben D Ewald · Brita A Pekarsky

In reply: We thank Pekarsky and Ewald for their comments. It is difficult to estimate the percentage of patients on monotherapy from any source. We used data from IMS Health (http: //www.ims-global.com/) to determine the number of person-years of exposure to drugs prescribed with a principal indication of hypertension. Some of these drugs were prescribed as a sole agent if the script was for this single drug alone. Exposure for such agents was expressed as a percentage of the total exposure of this drug. For example, angiotensin-converting enzyme (ACE) inhibitors were sole agents in 63.9%. In the other 36.1%, the co-prescribed drugs may have been another antihypertensive drug or another type of drug altogether. Corresponding figures for calcium-channel blockers were 61.3%, for diuretics 53.6%, and for β-blockers 60.0%. As an approximation, we used the estimation that 60% of patients were likely to have been on monotherapy for hypertension. Adding the number on monotherapy for each drug gives an estimate of 1.2 million for the total population on monotherapy for hypertension. Therefore, the total number on drugs is likely to be greater than the 1.2 million as estimated in our article. However, the essential figure is that of 1.2 million for monotherapy, which we stand by. It is true that a minority of prescriptions (16%) are written for people without a concession card and that these are more likely to pay the full cost of a cheaper drug. Our economic perspective was that of the PBS/RPBS. Hence, consumer costs were only included where the government made a copayment. It is acknowledged in the Methods section that "with some drugs, the patient copayment covers the total cost; in these instances the Commonwealth makes no contribution to the cost and these prescriptions are not recorded in the PBS/RPBS data" (page 566). It is also stated in the Discussion that the PBS/RPBS captures "much more of the cost of the newer, more expensive agents than thiazide diuretics or β-blockers" (page 567). We chose to limit our sensitivity analysis to the key issue of redistribution of agents after initiation of monotherapy. The data we presented allow interested parties to conduct their own further sensitivity analyses, such as those suggested by Pekarsky and Ewald.

Mark R Nelson MFM, FRACGP · John J McNeil PhD, FRACP · Anna Peeters BSc(Hons), PhD · Henry Krum PhD, FRACP · Christopher M Reid MSc, PhD

To the Editor: In his recent Commentary on hastening death in terminally ill patients,1 Hunt may not have fully appreciated a very cogent point made in the research by Douglas and colleagues.2 The surgeons surveyed clearly reported the intent of their prescribing. This is contrary to Hunt's assertion that "Intention is inherently subjective . . . complex [and] ambiguous". Some surgeons gave a dose appropriate to the symptoms, others deliberately increased the dose beyond direct symptomatic control, and a few deliberately ended life, at times with no explicit request. As Douglas points out, the dose of a medication given will be an important clue in this. Good clinical practice is about minimum effective dose (MED), not maximum administrable dose (MAD). This is the case for all patients, whether they are near the end of life or not. Hunt also states that "The duty of doctors is to strive to satisfy the wishes and interests of their patients and their patients' loved ones".1 This is a disturbing comment if left unqualified. There is a broader accountability for doctors to the community through the registration process, quality assurance and continuing education, and the criminal code. If the article by Douglas et al highlights nothing else, it should be clear that there are certain members of the medical profession who believe that they are above the law and have control over the life and death of their patients, with no external review.2 It is frightening that such paternalism still exists. Unfortunately, the Dutch experience of tolerating euthanasia does not appear to have decreased unilateral decision-making on the part of some doctors.3,4 If the premise that the interests of the patients' loved ones is a consideration in the duty of care,1 then we are risking the loss of patient autonomy in an unprecedented way. As a practising clinician, the majority of requests that I receive to hasten death are from relatives, not patients. These relatives ask that they be put out of their own misery by ending the patient's life prematurely. To do something to a patient for a third party, however concerned or distressed, is an unacceptable action for clinicians. For the profession to credibly engage in the debate about end-of-life care, we must accept that we are part of the community and hence governed by its laws. There are reference points external to the profession by which we will be judged.

David C Currow

In reply: The survey by Douglas et al1 indicated that, under the current criminal code, about one in three Australian general surgeons are at risk of prosecution for murder because of the way they treat their dying patients. It is likely that many other Australian doctors are similarly at risk of prosecution. This is a serious problem that raises important questions: Why are so many doctors breaking the law? Should these practices be kept covert or brought out into the open for audit and discussion? Is the law serving the needs and interests of dying patients, those who care for them, and the wider community? Rather than argue that doctors are above the law, I have argued that the practice of medicine should be congruent with the law.2 Laws have been established and refined over time so doctors can help their patients (eg, with procedures and the administration of drugs) in ways that are illegal for others. An integral part of the medical role involves the negotiation of life–death decisions. I believe murder laws should be refined to reflect the reality that some terminally ill patients want death as a release from suffering and seek the help of their doctor to provide this. Just as there are differences between rape and making love, I see obvious differences between common murder and the hastening of death that doctors provide for terminally ill patients out of compassion, mercy, and respect for their wishes. Unfortunately, the ethics of current practices are difficult to elucidate because the existing law makes investigations problematic. The current crude law does not reflect community values — Morgan Gallup polls indicate about 80% of Australians are in favour of allowing voluntary euthanasia in certain circumstances.3 As Currow observes, these widely held values are sometimes expressed by the relatives of dying patients. In my experience, however, these relatives are usually advocating for the patient's wishes and interests, rather than undermining patient autonomy. I support the established hospice tenet that "the family is the unit of care" and there is a duty to address the concerns not only of patients but also of their loved ones. I think it is only a matter of time before politicians introduce the reforms that render the legal framework for terminal care more congruent with community values, the wishes of patients and their families, and current medical practices. These reforms should enable research, audit and the better regulation of end-of-life care.

Roger W Hunt BM BS, GDPH, FAChPM

To the Editor: Australia has been successful so far in maintaining a low prevalence of HIV infection among injecting drug users (IDUs). This has been achieved by adopting a harm-reduction approach to the prevention of bloodborne virus transmission, including needle and syringe programs, methadone maintenance and peer-education. Sharing of needles and syringes has declined markedly: cross-sectional surveys among users of needle and syringe programs across Australia have shown a decrease in the prevalence of reported sharing from 31% in 1995 to 15% in 1997.1 However, there is evidence that among some subpopulations, especially those of Indo-Chinese origin, unsafe injecting practices remain common. In a survey of Indo-Chinese IDUs in Sydney and Melbourne, Maher et al reported that 22% of those surveyed had shared needles and syringes in the preceding month.1 Although the Indo-Chinese community is becoming increasingly aware of issues related to drug use, IDUs are under-represented in drug treatment programs.3 There is also evidence that parents send their children back to their country of origin to escape the Australian heroin scene. In a Melbourne survey of Vietnamese IDUs, Kelsall et al reported that 19% of their sample (38 of 200) had returned to Vietnam during the previous five years for drug-related reasons. Of these, 24 reported using heroin in Vietnam, a disturbing finding given that HIV prevalence among IDUs in parts of Vietnam is greater than 50%.4 We analysed HIV surveillance data in Victoria to investigate whether there was an over-representation of Indo-Chinese-born IDUs. Country of birth has been collected as part of HIV notification in Victoria since January 1996. Since then, there have been 38 notifications of HIV infection in individuals reporting intravenous drug use as a risk factor. Of these 38, 11 (29%; 95% CI, 15%–46%) reported an Indo-Chinese country of birth — a higher proportion than expected given the 1996 census finding that 1.5% of Victoria's population was born in an Indo-Chinese country.5 These 11, all men, were significantly younger than other IDUs notified in this time (mean, 23.3 years v 31.3 years, respectively; P < 0.05). Although these numbers are small, they highlight a group at increased risk of HIV who are not currently being effectively reached by prevention services. These data also suggest a hidden route for spread of HIV from Asia into the Australian community. There is an urgent need to provide culturally relevant education and harm-reduction programs to prevent transmission of HIV within this group. The Victorian Department of Human Services is allocating additional resources to working with culturally and linguistically diverse communities on prevention activities to address this issue.

Jane S Hocking · Peter G Higgs · Cathy M Keenan · Nick Crofts

To the Editor: On reviewing the results of the Wimmera clinical risk management program,1 we are prompted to ask whether the model can be generalised to a tertiary hospital. The program outlined by Wolff and colleagues is a good model for local quality improvement and provides a foundation for developing a model for tertiary hospitals. However, in considering its applicability to tertiary hospitals, a number of issues must be addressed. The number of separations and emergency department presentations at tertiary hospitals does not lend itself to review of all medical records. Such review is time- and resource-intensive and probably unrealistic in a tertiary setting. A sampling strategy might be more suitable, but would introduce the possibility of sampling error and missing adverse events. The availability of medical staff to review records is also limited, with clinicians often having public, private and teaching commitments. It would also not be feasible for a medical director to be involved regularly in the day-to-day tasks of the process. Nevertheless, these issues could be addressed by allocating the review process to a dedicated, trained team. Development of a review pathway would ensure participation of senior medical or management staff when necessary. The interface between tertiary hospitals and local general practitioners is broader and less defined than in rural areas, making the involvement of GPs difficult. The clinical mix and complexity of patients requiring tertiary care differ significantly from those at a rural base hospital, and restricting screening criteria for adverse events to eight items, as in the Wimmera program, would likely result in adverse events being missed. In addition, the clinical structure of tertiary hospitals is not uniform, and specific criteria may need to be developed to address the clinical specialties of the hospital. Lastly, in this era of cost containment in healthcare, Wolff et al did not address the cost of its clinical risk management program. While this is not a fault in the study, cost would be an essential consideration in generalising the program to a tertiary hospital. The model used in the Wimmera program has limitations when considering adaptability to tertiary hospitals, because of issues of scale and day-to-day practicalities. Further examination of the costs involved in ongoing operation of the program and a cost–benefit analysis are required. In addition, investigation is needed into feasible options that deliver useful results in a tertiary setting before a quality improvement model can be developed that is relevant, appropriate and cost-effective for tertiary hospitals.

Kathy M Brown · Humsha Naidoo · Arona E Offenberger

In reply: The model developed in the Wimmera hospital for clinical quality improvement has formed the basis for quality improvement systems in several regional and tertiary hospitals in Australia. The resources required to implement the model have been costed, and the Victorian Department of Human Services has allocated $4.8 million to establish clinical risk management programs based on the Wimmera model in every Victorian public hospital in 2001–2002.1 Whichever programs are implemented, some adverse events will be missed. However, not all medical records need to be reviewed, nor all adverse events found. Regular identification of some events provides significant opportunities to improve care. As clinician time is limited, some hospitals that have implemented the Wimmera model have paid clinicians with existing appointments for extra hours to participate in risk-management programs. Although feedback to general practitioners is logistically more difficult in a tertiary centre, it can still provide valuable information if limited to only a sample of inpatients. We agree that some departments in tertiary hospitals, because of their specialised nature, would need to develop additional screening criteria. The actual cost of running a clinical risk-management program based on the Wimmera model depends on how many components of the model are implemented, but in our experience should not exceed 0.5% of a hospital's total budget. Cost–benefit analyses are difficult to undertake, as some adverse events arise through underuse of available evidence, and additional resources would be needed for full implementation of the evidence (eg, giving prophylactic antibiotics immediately before surgery to prevent postoperative infection,2 or low molecular weight heparin postoperatively to prevent thromboembolism3). We believe that in any institution, whatever its size, the initiation of effective programs for clinical quality improvement needs both enthusiastic support from the highest level of management and champions at the "coalface" of patient care. If these two elements are present, adequate resources will often be found. However, providing resources without appropriate clinical and administrative support is unlikely to improve patient care.

Alan M Wolff · Jo Bourke · lan A Campbell · David W Leembruggen

To the Editor: The recent supplement by Hickie et al looking at the mental health of Australians attending general practice1 would have us believe that we are quite a mentally unwell nation indeed! The authors propose a broad concept of "mental disorder" which they found in 49% of general practice attenders based on 12 questionnaire items (the SPHERE-12). These 12 items include six relating to psychiatric symptoms (PSYCH-6) and six relating to somatic symptoms (SOMA-6).2 The SOMA-6 items are muscle pain after activity, needing to sleep longer, prolonged tiredness after activity, poor sleep, poor concentration, and tired muscles after activity. Patients with a total score of two or more in PSYCH-6 and/or three or more on SOMA-6 were classified as having a "mental disorder". Firstly, the SPHERE-12 is grossly oversensitive, as the six somatic items detect many medical conditions, glandular fever being just one example. Other validity issues include the two-week cut-off for symptoms (further adding to the overinclusiveness because of temporary distress and minor illnesses), and the lack of discussion regarding transcultural and inter-rater reliability, particularly with so many general practitioners involved. Secondly, the authors' interchangeable use of neurasthenia and chronic fatigue syndrome and somatisation needs discussion. Ten years ago, Hickie and several New South Wales physicians were dismissive of an article linking chronic fatigue syndrome and neurasthenia: "We have demonstrated immunological abnormalities in patients with chronic fatigue syndrome as compared with both normal controls and patients with major depression. Further, the demonstration of abnormal cytokine production in patients with chronic fatigue syndrome may underpin 'acquired neurasthenia'."3 All the SOMA-6 items are key symptoms of chronic fatigue syndrome. With the overwhelming amount of biological data now available, purely psychological theories about chronic fatigue syndrome (as opposed to chronic fatigue) are totally untenable, as is the use of the term neurasthenia, introduced into medicine in 1869 and discarded by the American Psychiatric Association's Diagnostic and statistical manual of mental disorders4 as invalid.5 A recent study from the Fatigue Clinic, King's College Hospital, UK,6 found that an astonishing 68% of patients had been inappropriately misdiagnosed with a psychiatric illness. This is surely a warning for overzealous psychiatrists. Thirdly, treatment implications are a concern. The authors comment that "only 27% of patients with Level 1 disorders received pharmacological interventions" (Level 1 implying positivity for PSYCH and SOMA items). They say that general practitioners mostly used "relatively ineffective non-pharmacological strategies", and that they had responded to missing all this "unmet need" by "criticising the oversensitivity of the screening instrument and inappropriateness of diagnostic systems used", implying an underprescribing of antidepressants. The recent National Survey of Mental Health and Well-being7 showed that somewhere between two-thirds and a half of the 23% of the population diagnosed with psychiatric disorders did not visit their general practitioner. How does this fit in with the 49% found by Hickie et al? In summary, the authors' broad and idiosyncratic conceptualisation of "mental disorder" and their use of a screening tool which labels many physically ill people with or without concurrent distress as cases of "mental disorder" implies that general practitioners need to prescribe more antidepressants — at what cost and for whose benefit?

Nicole Phillips MB ChB, FRANZCP · Michael J Oldmeadow MB BS, FRACP · Natalie Krapivensky MB BS, FRANZCP