Letters

To the Editor: Australia and the other member nations of the World Health Organization’s Western Pacific Region were declared free of circulating endemic poliovirus in 2000, although the last case of endemic polio in Australia occurred in the 1970s.1 Nevertheless, the low risk of vaccine-associated paralytic poliomyelitis (VAPP) persisted through the continued use of the Sabin live attenuated oral polio vaccine (OPV) until it was replaced by the Salk inactivated polio vaccine in the National Immunisation Program from 1 November 2005.2 Despite the eradication of indigenous wild poliovirus and the removal of the risk of VAPP, Australia cannot afford to be complacent with surveillance for cases of poliomyelitis. Polio is a highly infectious disease and is quickly spread through international travel. All countries risk importation of wild poliovirus from the four remaining endemic countries (Afghanistan, India, Nigeria and Pakistan) — as occurred in Indonesia and 11 other countries during 2005.3 Until the latest outbreak, involving over 300 cases, Indonesia had not reported a single case of poliomyelitis since 1995. Genetic sequencing of the wild polioviruses from Indonesia determined that they originated in Nigeria and were related to strains isolated in Sudan, Saudi Arabia and Yemen. Australia is also at risk from imported vaccine-related strains of poliovirus, as indicated by two reports from the United States in 2005. The first was a case of imported VAPP in an unimmunised adult, who had been in close contact with an infant recently immunised with OPV, while in Costa Rica.4 The second report described isolation of OPV poliovirus type 1 with a significant number of mutations (referred to as vaccine-derived poliovirus [VDPV]) from unvaccinated members of a religious community.5 Given that OPV has not been used in the USA since 2000, the source of the virus is unknown. VDPVs have been associated with paralytic polio worldwide. It is imperative that the Australian community maintains the current high rate of polio vaccination coverage, especially for travellers, which remains the best defence against all forms of imported polio. A surveillance scheme for investigation of children with acute flaccid paralysis, the major clinical presentation of poliomyelitis, was established in Australia in 1995. It is coordinated by the National Poliovirus Reference Laboratory and the Australian Paediatric Surveillance Unit (Box). While the scheme focuses on children, specimens from patients of all ages are tested. Notification of all cases with a clinical suspicion of poliomyelitis is essential for the detection of imported polio. Surveillance for acute flaccid paralysis (AFP) within Australia Paediatricians notify cases of AFP via a monthly report card to the Australian Paediatric Surveillance Unit and submit a clinical questionnaire to the National Poliovirus Reference Laboratory (NPRL). Stool specimens from AFP cases are tested at the NPRL for isolation of poliovirus. The Australian Polio Expert Committee reviews the clinical and laboratory data to determine whether the case is compatible with poliomyelitis. The Committee reports to the Australian Government Department of Health and Ageing and the World Health Organization. Protocol for investigation of suspected polio cases Clinicians should phone the NPRL to notify the case and arrange for two stool specimens to be collected 24 hours apart (due to intermittent virus shedding) and within 14 days of onset of symptoms, for testing at the NPRL. Polio antibody testing requires acute and convalescent serum, and is only performed when there is a clinical suspicion of poliomyelitis. Contacts National Poliovirus Reference Laboratory, Victorian Infectious Diseases Reference Laboratory Phone: (03) 9342 2607; fax: (03) 9342 2665; email: polioATmh.org.au; website: http://www.vidrl.org.au/labsandunits/polio/polio_activity.htm Australian Paediatric Surveillance Unit, Children’s Hospital at Westmead Phone: (02) 9845 3005/ 9845 2200; fax: (02) 9845 3082; email: apsuATchw.edu.au; website: http://www.apsu.org.au

Bruce Thorley PhD · Kerri Anne Brussen BAppSc · Elizabeth J Elliott MD, FRACP, FRCPCH · Heath A Kelly MB BS, MPH, FAFPHM

To the Editor: Rickettsia typhi is an endemic cause of atypical pyrexial illness worldwide.1 Its non-specific presentation can lead to misdiagnoses, with overseas reports of unwarranted laparotomies in affected patients.2,3 We describe a patient with R. typhi infection presenting as cholecystitis, in whom a cholecystectomy was avoided by vigilance for R. typhi. A 51-year-old businessman presented to a general practitioner with a 5-day history of fever, sore throat, headaches and myalgia. The illness had begun a week after his return to Sydney from a business trip to major cities in Asia, his last stop being Hong Kong. Investigations revealed mild lymphopenia and thrombocytopenia, negative results on screening for malaria, and normal results on chest x-ray. A non-specific viral illness was provisionally diagnosed. A week later, the patient presented again to a GP with fever, abdominal pain, cough, dehydration and confusion. Investigations revealed lymphopenia (0.7 × 109/L; reference range [RR], 1.5–4 × 109/L], thrombocytopenia (93 × 109/L; RR, 150–400 × 109/L), and raised serum levels of bilirubin (25 μmol/L; RR, 0–17 μmol/L) and hepatic enzymes (alanine aminotransferase, 307 U/L [RR, 5–40 U/L]; alkaline phosphatase, 381 U/L [RR, 30–115 U/L]; aspartate aminotransferase, 389 U/L [RR, 5–40 U/L]; and γ-glutamyl transferase, 364 U/L [RR, < 66 U/L]. Serological tests were negative for hepatitis viruses A, B and C, and dengue and Epstein–Barr viruses. The patient was referred to an emergency department. On presentation to the hospital, the patient was febrile, with severe right upper quadrant abdominal tenderness, and a slight truncal macular rash. Abdominal computed tomography and ultrasound examination indicated cholecystitis (Box). Acute cholecystitis was diagnosed, and treatment begun with intravenous fluids, ampicillin, gentamicin and metronidazole. Following clinical improvement, the patient was discharged on Day 8 with plans for an elective cholecystectomy. In view of the atypical symptom complex, serological testing for leptospirosis, syphilis, and rickettsial, amoebic and HIV infection had been requested during his admission. Results received after discharge indicated a R. typhi antibody titre of 1:1024 (RR, < 1:128). Results of the remaining serological tests were negative. The patient was contacted, and the cholecystectomy cancelled. He has remained well. Murine typhus is a zoonosis caused by R. typhi, and is acquired from rodent flea faeces, either by bite inoculation or inhalation. Hepatobiliary involvement occurs in up to 34% of cases. Histopathology specimens show neutrophilic sinusoidal infiltrates and cloudy swelling of hepatocytes,2 but hepatocyte injury and cholestasis are transient, resolving over 1–3 weeks. Diagnosis is by serological testing: a single indirect immunofluorescent antibody (IFA) titre against R. typhi of at least 1:400; or a fourfold rise in IFA titre from the acute to the convalescent phase (2 weeks apart). The treatment of choice is doxycycline. Although the clinical course is usually benign, the mortality rate can reach 4%.1 Rickettsial diseases remain an under-reported cause of febrile illness.4 As R. typhi has now been described throughout Australasia,1,5 it is important that murine typhus is excluded in patients with atypical pyrexial illnesses and abnormal liver function results. Computed tomography and ultrasound examination in a patient with murine typhus Computed tomography on admission showed pericholecystic inflammation, suggesting acute cholecystitis, and a possible gallstone at the lower pole (arrow), which was later noted to be a fibrous septum on ultrasound examination. Ultrasound examination also showed a thickened gall bladder wall and pericholecystic fluid.

Vidyut P Suttor MB BS, BSc(Med) · Robert B Feller MB BS, PhD, FRACP

To the Editor: Routine school vision screening has been discontinued in many regions.1 Since 2000, children around Newcastle and Lake Macquarie in New South Wales only have their vision checked at school if their parents request it. I am particularly concerned that this may disadvantage young children with diabetes, who may also have undetected amblyopia. These children are already at risk of diabetes-related vision impairment, and simple screening could prevent further disability related to amblyopia. Amblyopia, commonly known as “lazy eye”, is an asymptomatic, potentially treatable condition of poor vision in a “normal” eye. It is caused by the brain suppressing an unclear image from the affected eye. Amblyopia occurs in 2.5%–3.2% of the population.2 The condition needs to be detected early, and treatment needs to be instituted before the end of practical vision development at about 7–8 years of age, otherwise even intensive treatment is unlikely to restore normal vision.3 This is especially important because people with untreated amblyopia have an increased lifetime risk of loss or impairment of vision in their good eye,4 as well as the poor vision in their amblyopic eye. The current Australian screening guidelines for children with diabetes recommend screening for retinopathy after 5 years of diabetes in those who are prepubertal, and annually in adolescents after 2 years of diabetes.5 The International Society for Pediatric and Adolescent Diabetes recommends retinopathy screening in children with diabetes of prepubertal onset at 5 years after the onset of diabetes, or 11 years of age, or at puberty, whichever is earlier.6 Neither document specifies other visual screening (although the National Health and Medical Research Council guidelines do recommend a clinical examination of the eyes for cataract soon after diagnosis). Thus, a 6-year-old child with diabetes would not have his or her vision screened until 11 years of age. An eye with significant amblyopia detected at this age will not achieve normal vision, and the child would be reliant on only one eye for his or her lifetime. Even a 3-year-old child with diabetes would not have visual screening until 8 years of age, the end of practical vision development. The case has been made recently for biennial retinopathy screening for children with diabetes.7 I propose that diabetic children under 9 years of age have their vision fully assessed soon after the diagnosis of diabetes. Should amblyopia be detected then, treatment could commence before the end of active vision development.

Catherine Dunlop

To the Editor: I agree with Jones1 that the body surface area (BSA) formula printed in the position statement on reporting of estimated glomerular filtration rate (eGFR)2 is wrong, even though the authors say that he is mistaken.3 As stated by Jones, the correct formula4 for BSA in m2, for a body weight W kg and height H cm is: (i) BSA = W0.425 × H0.725 × 0.007184. However, the position statement2 gave the following formulas: (ii) BSA = W0.425 × H0.725 × 0.007184/1.73; and (iii) Uncorrected eGFR = GFR estimate (mL/min/1.73m2) × BSA. It appears that the denominator “1.73” has migrated from formula (iii) to formula (ii), so in fact both of these formulas are incorrect. This is potentially misleading for doctors and others who may want to calculate the eGFR for someone who is unusually big or small. Formula (iii) should in fact be: (iii) Uncorrected eGFR = GFR estimate (mL/min/1.73m2) × BSA/1.73. It is interesting that the same two errors in BSA calculations are present on the US National Kidney Disease Education Program website,5 which was presumably the source of the formulas used by the Australian Creatinine Consensus Working Group.

Alan McNeil PhD, FRACP, FRCPA

In reply: McNeil draws attention to the detail in the correction factor we published in an attempt to assist users to “uncorrect” the eGFR derived from the MDRD (Modification of Diet in Renal Disease) equation used in calculating GFR from a serum creatinine concentration. Recalculating the eGFR to remove the adjustment for body surface area (BSA) in an individual is unnecessary except at extremes of body size.1 Readers can be reassured that the formulas published in the position statement,2 if used as directed, will not lead to any error. However, it would have been clearer if we had labelled the “BSA” equation as “correction factor” instead of “BSA”. In the position statement2 it can be misinterpreted that the BSA formula has a denominator, whereas, when used primarily to calculate BSA, it of course does not. Both versions of the formulas (ours in the position statement and McNeil’s) therefore lead to identical answers. The reader can choose which one to use.

Timothy H Mathew MB BS, MRACP, FRACP · Graham Jones MB BS, DPhil, FRCPA · David Johnson MB BS, FRACP, PhD

To the Editor: This question was recently posed by Massie and colleagues in an editorial in the Journal.1 We have experience in providing cystic fibrosis (CF) carrier testing in pregnancy and in those planning pregnancy. In 1998, we ran a 12-month pilot program, the Double Testing Program, offering ΔF508 carrier testing to couples attending the John Hunter Hospital, Newcastle, NSW, for nuchal translucency screening. Of 491 participants, 84% chose CF carrier testing; 23 carrier–non-carrier couples were identified, and no carrier–carrier couples. A postnatal questionnaire compared knowledge of CF, anxiety levels and perceptions of the service between non-carrier couples and couples in which one partner was a carrier.2 Both groups were very satisfied with the service, with no increased levels of anxiety. The second initiative has been to offer CF carrier testing to clients attending the “drop-in” clinic at Hunter Genetics, Newcastle. This clinic has been available for 10 years and provides genetic counselling for clients referred by their general practitioners for pre-pregnancy or pregnancy counselling. Over the past 3 years, there have been 560 occasions of service with CF carrier testing in 499 individuals. Indications for testing include pregnancy screening or a family history of CF. With couples, both are tested for ΔF508, and, if one partner is identified as a carrier, the other partner is tested for 28 other mutations. The area health service, Hunter New England Health, meets the cost of the service and testing — $100 per couple for the ΔF508 test, and $250 for the full mutation screen. Of the 499 individuals, 65 (13%) were found to be CF carriers; after excluding those with a family history of CF, the carrier rate was 5.8%. Twenty carrier–non-carrier couples and one carrier–carrier couple with a family history of CF were identified. Benefits included enabling the carrier–carrier couple to know their 1 in 4 risk of having a child with CF. Most women who have a child with CF want to avoid having further affected children, and most who have a subsequent pregnancy choose prenatal diagnosis.3 Cascade testing can be offered to carrier families. Non-carrier couples can be reassured that they have a low risk. The uptake of CF couple screening is low, given that there are over 3500 births annually at the John Hunter Hospital. The main obstacles are lack of awareness and costs. CF tests are not covered by public health funding or by private health insurance, and this issue needs urgent attention. We believe that GPs are best placed to offer CF couple testing. Testing could be incorporated into routine first trimester pregnancy care. We can provide a distance CF learning package, pamphlets and informed consent material to those interested.

Louise M Christie · Elvira M Zilliacus · Angela J Ingrey · Gillian Turner

To the Editor: We were interested to note that the evolution of morning handover at Launceston General Hospital, as described by Fassett and Bollipo,1 closely parallels our own experience at the Canberra Hospital, and we endorse their points about running a successful meeting. Our hospital has a large Geriatric Unit and all subspecialties are covered, but we do not have a general medicine unit. In 2002, we began a formal morning handover meeting from 08:00 to 08:30 for junior medical officers (JMOs) in the Department of Medicine, with the initial intention of providing an opportunity for Royal Australasian College of Physicians (RACP) basic trainees to present cases they had seen overnight. Scrutiny of the individual’s clinical approach by consultants, in preparation for the RACP examination, was the main emphasis, and “interesting” cases were chosen. The meeting was also used for case presentations by specialty units. Attendance was variable, and many junior staff reported feeling somewhat threatened by having their patient management approach examined in a public forum. Handover of most newly admitted patients did not occur during this meeting. The format was incrementally modified over the following 3 years so that, by 2005, the meeting had become a formal handover of all patients admitted during the previous evening and overnight. Attendance is now compulsory (except for staff attending medical emergencies), and breakfast of brewed coffee and tea with fruit and muffins is provided (funded by the Canberra Hospital). We have over 40 daily attendees (comprising registrars, residents, interns, medical students and 5–10 consultants). We have minimised the number of specialty presentations: these now usually take the form of “red flag” sessions, in which a specialist unit highlights areas of common and/or life-threatening importance (eg, a patient with unstable angina needs admission, regardless of their troponin level; recurrent rigors in a middle-aged person usually signal a bacterial infection). A survey of 57 of the attendees this year revealed that over 90% thought the format and duration of meetings and attendance by consultants was appropriate; 54% and 39%, respectively, said they learned new information every day or every week. Over the past 4 years, the handover has become embedded in the clinical culture of the hospital. The long-term commitment of a small group of consultants has demonstrated that this is a safe and encouraging environment for clinical teaching, and the level of discomfort of the JMOs appears to have receded. The morning handover has been an important means of ensuring that young doctors are exposed to a broad perspective on patient care and that their after-hours patient care can be supervised.

Francis J Bowden MB BS, FRACP, MD · Christian Lueck FRCP, FRACP, PhD · Mark Hurwitz MB BCh, FCCO, FRACP · Karina Kennedy MB BS, FRACP

To the Editor: Healthy ageing is listed as a National Research Priority by the Australian Government. The higher prevalence of sensory, cognitive and mobility impairments in older people presents a major challenge in achieving this goal. The effects of single impairments are recognised,1,2 but the cumulative effects of multiple impairments have not been reported from population-based samples. We aimed to assess the impact of multiple impairments (vision, hearing, cognitive, mobility) on health-related quality of life (HRQOL), hospitalisation, and aged-care service use in an older Australian population. In the second cross-sectional Blue Mountains Eye Study,3 HRQOL was measured by means of the self-administered Short Form 36-item Health Survey (SF-36)4 (n = 3509; mean age, 66.7 years; 57% women). Visual impairment was defined as best-corrected visual acuity (after refraction) of less than 6/12 (better eye). Hearing impairment was defined as average hearing threshold (pure-tone air conduction, frequencies 500–4000 Hz) over 25 decibels (better ear). Possible cognitive impairment was defined as Mini Mental State Examination scores less than 24/30. Mobility impairment was recorded. General linear regression was used to calculate age-adjusted SF-36 mean scores,5 and logistic regression was used to estimate likelihood ratios for use of health and aged-care services. Models were age-adjusted to eliminate confounding. For 2873 participants who had completed the SF-36 (90.9%), the mean physical component score (PCS) was 44.9 (95% CI, 44.5–45.3) and the mean mental component score (MCS) was 51.9 (95% CI, 51.5–52.2). Age was significantly associated with the prevalence of these impairments (P < 0.001). After adjusting for age, people with any of the impairments had poorer mean PCS and MCS than those without the impairment (Box 1). Hospitalisation within the last year was reported by 743 participants (23.5%; 58.3% women), and 97 (3.1%; 65.0% women) reported regular use of community support services. Use of community support services was reported more frequently by people with any impairment, except possible cognitive impairment (Box 1). The presence of two or more impairments was associated with a cumulative, linear decline in HRQOL (Box 2). The successive addition of each impairment was associated with a decrease of 4.0 in mean PCS and 2.1 in mean MCS, and with greatly increased reporting of regular community support service use. The likelihood of participating in or completing the SF-36 decreased with increasing number of impairments. Hence, the prevalence of impairments and the extent of detrimental impacts on HRQOL may be underestimated. Nevertheless, our data highlight a linear increasing pattern of cumulative effects from multiple impairments on HRQOL, hospitalisation, and use of aged-care services. Preventing and reducing these impairments is crucial in maximising healthy ageing. 1 Prevalence, mean SF-36 physical and mental component scores, and use of services by impairment Impairments Prevalence (%) Age-adjusted mean SF-36 scores (95% CI) Use of services: %, age-adjusted and sex-adjusted odds ratio (95% CI) Physical component score Mental component score Hospitalisation in past 12 months Regular use of community services Visual impairment 2.7 42.8 (39.9–45.7) 47.6 (44.8–50.3)* 34.9%, 1.3 (0.8–2.2) 24.2%, 2.9 (1.4–6.0) Hearing impairment 33.4 43.8 (43.0–44.7)* 51.1 (50.3–51.9)* 27.5%, 1.1 (0.9–1.3) 7.4%, 2.7 (1.4–5.0) Cognitive impairment 2.2 42.2 (39.5–44.8)* 46.0 (43.4–48.5)* 28.2%, 1.0 (0.6–1.6) 14.1%, 1.7 (0.8–3.7) Mobility impairment 7.6 32.3 (30.8–33.7)* 48.1 (46.7–49.5)* 41.0%, 2.0 (1.5–2.7) 21.3%, 6.8 (4.2–11.0) All mean values adjusted to 66.7 years, the overall sample mean age. SF-36 = Short Form 36-item Health Survey.4 * Significantly lower than without disability. 2 Mean physical and mental component scores and use of services by increasing number of impairments No. of impairments* Age-adjusted mean SF-36 scores (95% CI) Use of services: %, age-adjusted and sex-adjusted odds ratio (95% CI) Physical component score Mental component score Hospitalisation in past 12 months Regular use of community services 0 (n = 1031) 46.6 (45.9–47.2) 52.8 (52.6–53.8) 22.0%, 1.0 0.4%, 1.0 1 (n = 616) 42.6 (41.8–43.3) 51.0 (50.3–51.7) 25.3%, 1.1 (0.8–1.3) 4.2%, 7.4 (2.7–19.8) 2 (n = 121) 38.6 (37.1–40.0) 48.8 (47.4–50.2) 35.5%, 1.5 (1.0–2.3) 19.0%, 24.9 (8.5–73.2) ≥ 3 (n = 31) 34.5 (32.2–36.8) 46.6 (44.5–48.8) 45.2%, 2.0 (0.9–4.1) 41.9%, 47.4 (13.1–171.4) SF-36 = Short Form 36-item Health Survey.4 * Includes vision, hearing, cognitive and mobility impairments.

Ee-Munn Chia · Jie Jin Wang · Elena Rochtchina · Paul Mitchell

To the Editor: Despite a new survey with some interesting results, the MJA’s Medicine and the Media special failed overall to advance the topic. Van der Weyden and Armstrong enthusiastically cite Schwartz and Woloshin: “don’t report preliminary findings”.1 (In fact, they wrote, “In general, don’t report preliminary findings”,2 but let’s allow this journalistic context tweak.) In their article, Schwartz and Woloshin contend that this is because “what is new may turn out to be wrong”. Many things reported in newspapers are subject to subsequent change. So, to be on the safe side, let’s exclude them all. No more Cabinet leaks: let’s wait till everything is resolved and perfect-bound by the government stationery office. An end to covering murder trials: what if the accused is found not guilty? Forget about half-time match scores, and definitely no celebrity weddings because they’ll be divorced within the year. A moratorium on discussing preliminary findings would put off-limits highly respected annual meetings such as those of the American Society of Clinical Oncology and the American Society for Reproductive Medicine, which set the treatment agenda annually for clinicians and patients in the fastest-paced medical specialties. It is nonsense to suggest the media should censor early results, a point that has been made previously.3 The world has moved on. News is no longer a series of monolithic reports, each entirely true and complete. Like life, news is a work in progress — a rolling tide of updates, each modifying the last. Everyone loves a winner, and it is gratifying to note the Sydney Morning Herald is currently top of the Media Doctor league table.4 This website is a useful focal point, and Smith and colleagues’ suggestion that researchers take some responsibility for how their results are presented to the public is helpful.5 But of the three solicited commentaries,6-8 not one was from a newsroom health reporter, or — better still — a daily news editor or producer who decides, amid the controlled chaos of breaking and evolving stories, which reports should run and how prominently. Was this because they were not approached? Imagine a five-article package on immunisation practice without a view from a general practitioner, or one on appendicectomy without the insight of a surgeon. It is a serious omission that undermines the credibility of the MJA’s package and calls its motivation into question. Genuine rapprochement might threaten the sport of media sniping that has become a lively sideline for some medical journals.

Julie Robotham BA (Oxon)

In reply: Would that we could convince newspaper editors not to publish inaccurate stories, cabinet leaks, sensational and one-sided details of trials in progress, hope-raising interim football scores or the details of celebrity weddings. However, our media package was not that ambitious! In the context of medical reporting, we stand by our advice against publishing interim results. The reason that clinical trials have protocols, power calculations and stopping rules is that (just as football is a game of two halves) the results are really not relevant or reliable until all the data have been collected and analysed. Our media package included contributions from two highly respected medical writers1,2 and a representative of Australian journalism’s peak body.3 Robotham is correct in surmising that we did not approach a newsroom health reporter or a news editor, but the immunisation analogy seems spurious. If we published a research paper that identified, for instance, deficiencies in general practitioners’ delivery of vaccinations, we would not necessarily accompany it with a commentary from a GP. Whatever their discipline, we would assign the task to someone who could point the way towards best practice. Nevertheless, we are grateful for Robotham’s interest and acknowledge the responsibilities shared by both journalists and medical journal editors, albeit with differing emphasis — the dissemination of accurate and timely information.

Ruth M Armstrong BMed · Martin B Van Der Weyden MD, FRACP, PhD

To the Editor: During a national multicentre study of snake bites — the Australian Snakebite Project (ASP), involving over 40 hospitals — we have recently noted a high rate of early allergic reactions following the administration of tiger snake antivenom in Australia. People with suspected or definite snake envenoming are recruited to ASP, and laboratory and clinical data and serial blood samples are collected to measure venom and antivenom concentrations. From 1 November 2005 to 31 January 2006, 14 patients who had been given tiger snake antivenom (CSL Limited, Parkville, VIC) were recruited. These patients are briefly described in the Box, and include bites from several different groups of snakes. Of the 14 patients, 11 exhibited immediate systemic hypersensitivity reactions to antivenom infusion. Reactions were mild in five patients, moderate in three, and severe in three, according to the grading system by Brown.1 The six patients in the moderate and severe groups fulfilled the criteria for anaphylaxis according to a recent consensus definition.2 All patients required specific treatment in addition to ceasing antivenom therapy, and nine were treated with adrenalin. Antivenom was recommenced in all patients at a slower rate, although an adrenalin infusion was required in four of these and repeat doses of intramuscular or subcutaneous adrenalin in another four while the antivenom infusion continued. Over the same period, there were seven administrations of brown snake antivenom (over 30 vials of antivenom) reported to ASP without any hypersensitivity reactions. There has been a previous report of allergic reactions to tiger snake antivenom in a single hospital,3 and we are concerned that there may be a particular problem with tiger snake antivenom. The reaction rate in this series is similar to reported rates in parts of the world where high reaction rates have been attributed to relatively impure antivenom preparations.4,5 The reactions here were traced to at least four different batches of tiger snake antivenom. We have informed CSL of this high rate of reactions and the antivenom batch numbers, and we have encouraged the treating doctors to make formal reports of each adverse reaction to CSL and the Adverse Drug Reactions Advisory Committee. Health care professionals treating patients with tiger snake antivenom need to be aware of the possible higher risk of anaphylaxis with tiger snake antivenom and be prepared to treat with adrenalin. Recommendations for the diagnosis and treatment of anaphylaxis have recently been reviewed.6 However, this current problem with CSL tiger snake antivenom should not cause health professionals to reduce or cease its use. In all patients described here, control of the adverse reaction and continuation of antivenom was possible. The rapid identification of this problem over a short period was only possible because of our large multicentre collaborative study, and supports such studies for recognising uncommon envenoming syndromes. Fourteen patients administered tiger snake antivenom for snake envenoming Age/sex Previous antivenom Snake Clinical features Grading Treatment of reaction 47 M No; SH BHS No reaction Nil Nil 13 M No TSG No reaction Nil Nil 17 M No TSG Nil Nil Nil 20 M No TSG Generalised erythema, urticaria, tachycardia Mild IM adrenalin (0.5 mg), then IV adrenalin infusion 12 M No RBBS Generalised erythema Mild IM adrenalin (0.2 mg × 3) 12 M No RBBS Generalised erythema, urticaria Mild IM adrenalin (0.25 mg 3 2) 28 F No TSG Pruritus, erythema and moist cough (no wheeze) Mild Promethazine (10 mg) 53 M No TSG Generalised pruritus Mild Promethazine (25 mg) 32 M No TSG Dizziness, chest tightness, tachycardia, vomiting Mod. SC adrenalin (0.3 mg) 21 M Yes; SH SBS Generalised rash and pruritus, vomiting Mod. IV adrenalin infusion for 1 hour 9 M No SBS Urticarial rash, chest tightness Mod. IV adrenalin infusion 55 M No; SH PHS Generalised pruritus, diaphoresis, confusion, hypotension Severe SC adrenalin (0.5 + 0.5 + 1 mg), IV fluid, IV hydrocortisone (100 mg) M No RBBS Rash, wheeze and hypotension Severe Adrenalin, IV fluid, antihistamines, steroids 45 F No TSG Hypotension, sweaty and unwell appearance Severe IV adrenalin infusion BHS = Broad-headed snake (Hoplocephalus bungaroides); IM = intramuscular; IV = intravenous; Mod. = moderate; PHS = Pale-headed snake (H. bitorquatus); RBBS = Red-bellied black snake (Pseudechis porphyriacus); SBS = Stephens’ banded snake (H. stephensii); SC = subcutaneous; SH = snake handler; TSG = Tiger snake group (any snake from the Notechis, Hoplocephalus, Tropidechis, and Austrelaps genera).

Geoffrey K Isbister · Alan Tankel · Julian White · Mark Little · Simon G Brown · David J Spain · Chris F Gavaghan · Bart J Currie

Comment: Thank you for the opportunity to comment on the letter by Isbister et al regarding hypersensitivity reactions to tiger snake antivenom. CSL has been notified about the cases of hypersensitivity reactions to tiger snake antivenom in general, but has only received two individual case reports. We have been in contact with the study investigators and have requested more detailed information on the other patients so that we can further our investigations. A thorough check of product manufacturing records revealed no deviations from approved specifications for tiger snake antivenom. It is important to note Isbister et al have advised health professionals not to reduce or cease the use of tiger snake antivenom. We would like to draw physicians’ attention to the approved Product Information before use of the product. The tiger snake (and other antivenom) Product Information lists the possibility of both anaphylactic and anaphylactoid reactions. Hypersensitivity and skin reactions (including urticaria, rash, hypotension, bronchospasm, anaphylaxis and delayed serum sickness) are listed as common, and are more likely to occur in people who have had previous exposure to equine-based products. In addition, the Product Information describes an anaphylactoid reaction which can occur because the antivenom has the ability to bind complement. The risk of this reaction can be minimised by adequate dilution of the antivenom (1 : 10 for adults and 1 : 5 in small children) before infusion. Further, the Product Information states that a syringe already loaded with 1 : 1000 adrenalin must be available during antivenom therapy. CSL is continuing to monitor this situation closely and is awaiting further details on the patients from the reporting physicians. In the meantime, we encourage users of all antivenom products to report any untoward reaction to CSL so that these can be fully evaluated.

Jane Leong

To the Editor: Community strains of methicillin-resistant Staphylococcus aureus (MRSA) are increasingly seen in Australia, particularly in certain population subgroups, such as Pacific Islander1 and Aboriginal2 people. We report the case of an African with community MRSA to highlight its existence in yet another subgroup. Given the increase in people arriving in Australia from Africa under the Humanitarian Program (with around 8500 arrivals from Africa in 2004–2005)3 and their wide dispersal around the country, it is possible that African community MRSA will be seen increasingly in Australia. A 53-year-old Burundi refugee presented with an infected wound overlying the left lateral malleolus after laceration 6 weeks previously in a Tanzanian refugee camp. An unknown antibiotic was given for 2 weeks before travel to Australia. On the patient’s arrival in this country, the wound appeared purulent, erythrocyte sedimentation rate was 82 mm/h (reference range [RR] < 10 mm/h), and C-reactive protein level was 9 IU/L (RR < 5 IU/L). Plain x-rays and bone scans suggested osteomyelitis. A wound swab grew S. aureus, Streptococcus pyogenes and Pseudomonas species. The patient was initially given intravenous cefazolin, and then definitive therapy (for MRSA and S. pyogenes, ignoring the colonising pseudomonad) with oral clindamycin (450 mg three times daily). Clinical resolution was complete, and levels of acute-phase reactants returned to normal. The antibiotic sensitivity pattern of the S. aureus isolate raised suspicion that it might be an unusual strain: it was resistant to methicillin, tetracycline and trimethoprim–sulfamethoxazole, but sensitive to erythromycin, clindamycin, ciprofloxacin, gentamicin, vancomycin, linezolid, mupirocin, rifampicin, fusidic acid and chloramphenicol. The mecA gene was detected by polymerase chain reaction testing, confirming methicillin resistance. The organism possessed staphylococcal cassette chromosome mec (SCCmec) element type IV. The Panton–Valentine leukocidin gene, staphylococcal enterotoxins A to E and toxic shock syndrome toxin-1 were not detected. As DNA fingerprinting with standard pulsed-field gel electrophoresis showed a novel banding pattern, the “gold standard” of multilocus sequence typing was used for identification. This confirmed an ST140 allelic profile, which has not been seen previously in Australia.4 On the balance of probabilities, the isolate represents an African community MRSA strain, not previously detected in Australia. Non-multiresistant community MRSA is not widely recognised in African countries. Hospital MRSA rates vary widely in Africa (eg, between 21% and 30% of all S. aureus isolates in Nigeria, Kenya and Cameroon, and fewer than 10% in Tunisia and Algeria5), but most are multiresistant. Medical practitioners in Australia who treat African refugees need to be aware that pyogenic soft tissue infections could be caused by community MRSA, and these MRSA strains may have a different antibiotic sensitivity profile to Australian community MRSA strains. It is essential to take appropriate specimens for microbiological analysis (wound swabs and possibly blood cultures and/or tissue samples), as antibiotic susceptibility profiles are increasingly unpredictable.

Annabelle Donaldson MB ChB · Iain B Gosbell MD, FRACP, FRCPA

To the Editor: We recently treated two patients with invasive meningococcal disease presenting with cellulitis. This presentation contributed to a delay in diagnosis and appropriate antibiotic treatment. The first patient was a 33-year-old woman, recently diagnosed with nephrotic syndrome, who had been unwell for a week with mild upper respiratory tract symptoms. During this time, her nephrologist began treating her with prednisolone (15 mg daily). The day before presentation, she developed abdominal pain, vomiting, chills, myalgia and headache. A rash developed on the day she presented to hospital. The temperature was 39.2°C, heart rate 148 beats per min, and blood pressure 146/57 mmHg. She had an area, measuring 20 cm × 20 cm, of tender cellulitic rash on the right thigh (Box) and mild neck stiffness. The diagnosis was initially unclear, leading to a delay of several hours before ceftriaxone was administered, and a lumbar puncture performed. Cerebrospinal fluid (CSF) examination revealed a leukocyte count of 4500 × 106/L (98% polymorphs) (reference range [RR], < 5 × 106/L), gram-negative diplococci, and protein concentration of 2073 mg/L (RR, 150–450 mg/L). The patient subsequently required intensive care admission for non-invasive ventilation and inotropic support. Neisseria meningitidis serotype C was detected in the CSF by polymerase chain reaction testing. The patient was discharged well except for mild headache and lethargy after 6 days. At 1-week review, she remained lethargic but was otherwise well. The rash was slowly resolving. The second patient was a 51-year-old woman with fever and a 2-day history of progressive pain, swelling and erythema of the anterolateral area of the neck. The temperature was 38.5°C, heart rate 115 beats per min, and blood pressure 134/86 mmHg. There was no evidence of upper airway involvement. The anterior area of the neck and upper chest wall were swollen, erythematous, tender and warm. No fluid collections or masses were detected on ultrasound examination. The patient was admitted to hospital with a diagnosis of cellulitis, and treatment was begun with intravenous flucloxacillin and metronidazole. After 17 hours, culture of blood taken on admission showed N. meningitidis serotype W135. Antibiotic treament was changed to ceftriaxone. After 5 days, the patient had mild residual inflammation and tenderness of the neck. She completed another week of treatment with oral amoxycillin. Only 14 cases of N. meningitidis cellulitis have been published.1-3 Seven cases involved children with periorbital cellulitis. In adults, three cases involved the face and neck, and four the limbs. N. meningitidis was isolated from blood (eight patients), conjunctival swabs (three), aspirates of the cellulitic areas (two) or CSF (one). There was one death: an elderly woman with bacteraemia and cellulitis of the face and neck.2 As illustrated by our cases, the many guises of meningococcal disease continue to challenge clinicians. Cellulitis in Patient 1 Cellulitic area on the right thigh of a 33-year-old woman with Neisseria meningitidis meningitis.

Karina J Kennedy MB BS · Jhumur Roy MB BS, FRCPA · Paul Lamberth MB BS, FACEM

To the Editor: The CanMEDS 2000 report1 and its 2005 revision2 have emphasised that effectiveness as a medical specialist requires competencies in addition to clinical and medical expertise. These include being a communicator, collaborator, manager, health advocate, scholar and professional. Building the non-clinical skills of doctors has been the focus of a professional development project in Australia that is targeting registrars. Junior doctors usually step up to the role of registrar in the 3rd year of their prevocational training. A national workshop convened by the Postgraduate Medical Council of Victoria in March 2004 agreed on a framework for the professional development of registrars, comprising the following 10 competencies: leadership; communication skills; supervision; mentoring; teamwork; self-awareness and empathy; time management; problem solving; professionalism and ethics; and safety and quality.3 To provide content for these competencies, a job-shadowing exercise involving two registrars at two different Victorian hospitals was undertaken in April 2005 to get a first-hand understanding of the roles of medical registrars as managers. The registrars were voluntary participants, and permission was obtained from all participants. I shadowed the two registrars during their entire 9-hour shifts. No major issues arose in relation to the shadowing process itself, and the consultants overseeing the two registrars were extremely accommodating in this process. The two observed registrars authenticated the veracity of the recorded observations. The observations from the job-shadowing exercise were clustered into competencies using the framework developed for the professional development of registrars discussed above. The Box summarises these observations and highlights the range of registrar interactions that are influenced by non-clinical competencies. While the small number of registrars is an obvious limitation of the study, this job-shadowing exercise did demonstrate that managerial skills, knowledge and behaviour represent a significant component of the work of clinicians, especially as they move up the medical hierarchy. This assertion should not be misconstrued as suggesting that the clinical skills and knowledge become any less important. As noted in the 2005 CanMEDS framework, the medical expert role is the central role for doctors. It is also worth noting here that some pilot professional development programs conducted recently as part of the registrar project show that registrars welcome training that enhances their non-clinical skills, especially when provided professionally in an environment conducive to learning. Observations during job-shadowing of two registrars at two Victorian hospitals Competency Observed interactions Supervision Reviewing patient treatment plans and test results and prescribing a course of action Ensuring that procedures are followed Coaching intern on test procedures, completion of patient records, etc Giving ongoing feedback to intern Delegating tasks to intern Coordinating patient treatment with other units Leadership Dealing with other health professionals, some of whom take directions from the registrar, as well others over whom there is no formal authority Providing advice to intern and role modelling desired behaviour Demonstrating the ability to respond quickly and with confidence Involving subordinates and providing opportunities for them to participate in decision making Using networking skills with other departments Using negotiating skills in dealing with other departments, hospitals, etc Communication skills Using communication skills with patients, intern, medical colleagues, other health care professionals, and service departments Dealing with cross-cultural diversity issues with patients, their families, and staff Using negotiating skills in dealing with other departments, hospitals, patients, and family members Using recording skills to ensure treatment plans properly documented for others Time management Prioritising patient list for ward rounds The constant need to re-assess priorities during ward rounds, in light of time constraints The ability to deal with constant interruptions from other colleagues, to provide necessary clarifications Problem solving Making decisions on patients’ continued treatment or discharge, and stipulating any follow-up action Task contingency management skills to deal with patient treatment plans not proceeding as planned Dealing with information gaps in patient historical records Involving intern and other staff to assist in the decision-making process and raising issues with consultant Professionalism and ethics Dealing with demarcation issues with other doctors and professionals Role modelling professional behaviour to patients, staff, and the public Balancing the interests of patients with hospital needs, without sacrificing patient trust Obtaining patient consent for procedures Teamwork Coordinating treatment plans with other doctors and health professionals Sharing information and agreeing on treatment plans with allied health staff Joint meeting with other colleagues to advise a patient and family members on surgical procedures and associated risks Ability to work in both collaborative and individual modes during the day Mentoring Providing advice to intern to be more assertive and confident when dealing with consultant Self-awareness and empathy Patience and empathy in giving bad news to family Dealing with patients who are aged or mentally or physically challenged Safety and quality Knowledge and application of safe practices in relation to patient management Ensuring that procedures are followed, such as obtaining consent, ordering of tests, etc Reviewing records before dispensing treatment Recording treatment plans and medications

Jagdishwar Singh PhD

To the Editor: We were pleased to read Turnbull and Parisi’s short piece on the effectiveness of shade structures, highlighting the challenges of ensuring adequate and effective shade protection, particularly in children’s settings.1 Cancer councils in various states have long recognised these challenges and provided assistance to those who design or manage facilities for children, in the form of training workshops, resources and guidelines. Epidemiological evidence indicates that childhood exposure to ultraviolet (UV) radiation is a strong determinant of risk of melanoma but there is also evidence of its contribution to the development of non-melanocytic skin cancer.2,3 It is estimated that living in Australia for the first 15 years of life contributes about two-thirds of the lifetime risk of melanoma of a lifelong resident.4 Sun exposure in childhood, especially that leading to sunburn, is the main environmental determinant of the number of melanocytic naevi. An individual’s number of naevi is the strongest measurable predictor (after age and ethnicity) of risk of melanoma.5 Our publication, Under Cover, referred to by Turnbull and Parisi, is one such resource, developed as a comprehensive reference tool for anyone involved in shade planning and design in New South Wales and has been adapted for use in other states by state cancer councils.6 Turnbull and Parisi comment that Under Cover provides inappropriate advice regarding the use of deciduous trees, as solar UV radiation levels can be hazardous during winter in subtropical Queensland. As might be expected, the NSW edition of Under Cover does not address winter solar protection issues in northern Queensland. We note that the “requirements for effective shade” cited by Turnbull and Parisi are identical to those prescribed in Under Cover. For those interested in determining when UV protection is required throughout the year in different locations, an interactive shade planning software program will be available shortly at <www.webshade.com.au>. In it, ShadeCalendar recommends what type of shade would be most appropriate for comfort and solar protection in different months of the year. The Bureau of Meteorology now issues the SunSmart UV Alert when the UV Index is forecast to reach 3 or above, highlighting when sun protection is required (www.bom.gov.au/products/uvindex_national.shtml). The SunSmart UV Alert is reported in most newspaper, television and radio weather forecasts across Australia. Shade is only one of a range of sun protection strategies recommended by the Cancer Council. With Australia having the highest skin cancer rates in the world, general practitioners play a pivotal role in providing sun protection counselling advice to parents of children aged 1–13 years.7 The Cancer Council NSW recommends a range of sun protection measures including UV avoidance during the peak UV times (10:00–14:00 or 11:00–15:00 during daylight saving time), shade, clothing, hats, sunglasses and use of sun protection factor 30+ broad spectrum, water resistant sunscreen.

Kay R Coppa MPH · John S Greenwood

To the Editor: Investigators in the recent Canberra Heart Study1 highlighted the importance of improving the detection of heart failure in the community, given the high proportion of people with preclinical disease. The accompanying editorial2 expressed concern about the lack of major Australian initiatives that focus on the prevention and treatment of this disease. We fully endorse the authors’ view that under-recognition and under-treatment of heart failure is an important national issue. While we support their call for sustained and adequately funded programs, we feel it is important to note that there are initiatives under way to attempt to improve the situation. The National Prescribing Service, the National Heart Foundation of Australia and the National Institute of Clinical Studies joined forces in 2004 to improve the diagnosis and management of heart failure in primary care. A national program, undertaken in partnership with 45 divisions of general practice, began in October 2004 and will conclude in early 2006. Nationally, the program provided newsletter materials to all general practitioners, pharmacists and physicians.4 In participating divisions, educational outreach visits and interactive small group meetings involved over 1600 GPs and local specialists in discussions of the role of echocardiography in diagnosis, and pharmacological and lifestyle management issues. Patient education materials were also widely disseminated.5 Outcomes of this large-scale quality improvement program are currently being evaluated, and results are expected to be available in early 2007. Other groups have also recognised heart failure as an important issue — for example, it is one of the featured conditions in the Department of Veterans’ Affairs Medicines Advice and Therapeutics Education Services program.6

Heather H Buchan MBChB, MSc, FAFPHM · Susan M Phillips DPhil · Lynn M Weekes BPharm, MSc, PhD · Judith M Mackson BPharm, MMedSci(ClinEpi) · Andrew N Boyden MB BS(Hons), MPH, FRACGP · Andrew M Tonkin MB BS, MD, FRACP

To the Editor: Q fever is a serious disease caused by Coxiella burnetii, and usually occurs in people exposed to livestock. In Australia, acute Q fever generally manifests as nonspecific febrile illness. We report a case of spontaneous splenic rupture as a complication of acute Q fever acquired in Australia. A 29-year-old, previously well man presented in March 2005, with 5 days of fever, rigors and severe headache. On examination he had a temperature of 40°C, was tachycardic at 100 beats per minute, but normotensive. There were no focal examination findings. Investigations revealed thrombocytopenia at 123 × 109/L, a normal white cell count, and clear chest x-ray. The patient worked at a factory that processed animal placentas and fetal products. A provisional diagnosis of Q fever was made based on the illness and this exposure. The man was admitted and treated with empiric doxycycline, penicillin, and ceftriaxone. On Day 1 of the admission, he developed sudden, severe, left upper quadrant abdominal pain with shoulder tip radiation, diaphoresis and hypotension. An urgent computed tomography scan of the abdomen revealed splenomegaly with a diameter of 14 cm, and a crescentic, subcapsular splenic haematoma with rupture into the peritoneal space (Box). There was no history of trauma. He was admitted to the high dependency unit for monitoring. His haemoglobin level dropped from 151 g/L to 102 g/L, but he was managed conservatively and discharged from the high dependency unit 24 hours later. Acute Q fever was confirmed by polymerase chain reaction on Day 2, and antibiotic therapy was simplified to doxycycline 100 mg twice daily for 14 days. He was discharged from hospital on Day 5, and recovered fully. Seroconversion to Q fever was subsequently confirmed. His workplace now practices Q fever prevention policies, including pre-employment vaccination. Common presentations of Q fever include nonspecific febrile illness, pneumonia and hepatitis. There are five reported cases of Q fever associated with spontaneous splenic rupture, but this is the first Australian case.1-5 The other patients presented with flu-like symptoms and abdominal pain of 2–14 days’ duration, and required splenectomy between Day 1 and 4 of admission. Clinicians should be aware of splenic rupture as a potential complication of Q fever in Australia. Abdominal computed tomography scan A crescentic, subcapsular splenic haematoma is visible (arrow).

Amanda J Wade MB BS · Tim Walker MB BS · Eugene Athan MB BS, FRACP · Andrew J Hughes MB BS, FRACP

To the Editor: Current Australian guidelines for urgent warfarin reversal recommend withholding warfarin, and giving vitamin K as well as factor replacement (Prothrombinex HT; PTX) with or without fresh frozen plasma (FFP).1 PTX administration without FFP is recommended only when FFP is unavailable, as PTX factor VII levels are low and unquantified.2 Transfusion of 25–50 IU/kg PTX and 150–300 mL of FFP is advised. We examined the effectiveness of warfarin reversal using PTX alone or combined with FFP. One hundred and fifty-five patients given PTX were identified from the transfusion medicine unit’s computer records. Fifty patients were excluded — no warfarin (19), non-hospital patients (11), no record of PTX administration (14), no monitoring (5), normal international normalised ratio (INR) (1). One hundred and five patients who had received warfarin were reviewed. The reasons for anticoagulation were atrial fibrillation (45 patients), venous thromboembolism (22 patients), cardiac valve replacement (21 patients), myocardial infarction (9 patients), and other (8 patients). PTX was administered for bleeding in 51 patients (32 had major bleeds), suspected bleeding in eight patients, high INR in 11 patients, and before a procedure in 35 patients. Bleeding severity was graded using published criteria.3 Post-treatment INR and patient details were used to determine clinically significant INR lowering and haemostasis. The patients were divided into two groups — patients administered PTX without FFP (n = 74) and patients administered PTX and FFP (n = 31) (Box 1). Seventy-four patients (71% receiving PTX; 67.7% PTX + FFP) were given vitamin K (71 intravenously) to ensure ongoing correction of coagulopathy. This was administered within 2 hours of PTX (77%), with doses 1–2.5 mg (44 patients), 3–6 mg (13 patients), and 10 mg (17 patients). The mean PTX dose used was 862 IU or 12.9 IU/kg. Slightly higher PTX doses were administered to patients in the PTX group (913 IU or 13.1 IU/kg) than to patients receiving PTX and FFP (742 IU or 12.3 IU/kg) (Box 1). Seven of 89 patients (7.9%) received the published recommended PTX dose.1 The remaining patients received < 25 IU/kg. Neither the degree of warfarin coagulopathy nor FFP transfusion appeared to influence PTX doses administered. One patient in the PTX group with end-stage renal impairment failed to show any reduction in INR, but did achieve haemostasis. All patients with bleeding achieved haemostasis after PTX. The degree of INR correction after PTX varied considerably, with the percentage reduction in INR after PTX ranging from 0 to > 90% per vial of PTX transfused (Box 2). Achievement of haemostasis did not require normalisation of INR (Box 2). The INR is designed for monitoring therapeutic warfarin levels and its accuracy declines with excessively prolonged clotting times. As PTX is more likely to produce correction of coagulopathy through increased thrombin rather than through factor VII replacement, INR may not be the best test for monitoring haemostatic changes after PTX. Our data suggest that FFP may be unnecessary when PTX is used to reverse warfarin coagulopathy. We have also shown that doses of PTX under 25 IU/kg are effective. Administration of low-dose PTX will produce cost savings and may reduce PTX-associated adverse events (including infusional reactions, thrombocytopenia [secondary to heparin], and thrombosis). The risks associated with FFP transfusion (including allergic reaction, transfusion-related acute lung injury, fluid overload, and infection transmission) would be eliminated. A prospective study is necessary to confirm our findings and assess the efficacy of lower PTX doses, so that, if our results are confirmed, warfarin reversal guidelines can be reviewed. 1 International normalised ratio (INR) before transfusion of Prothrombinex HT (PTX) and dose of PTX in patients in the two groups (PTX and PTX + fresh frozen plasma [FFP]) at increasing levels of anticoagulation INR before PTX PTX group (n = 74) PTX + FFP group (n = 31) No. of patients PTX dose IU (range) PTX IU/kg* (range) No. of patients PTX dose IU (range) PTX IU/kg† (range) FFP units (range) < 2.0 8 556 7.69 1 500 9.09 2 (500–1000) (5.32–11.1) — — — 2.0–3.9 22 929 12.81 16 562 8.48 2.2 (500–2000) (4.85–31.25) (500–1000) (5.1–17.54) (1–10) 4.0–5.9 12 1083 16.2 7 1000 15.51 4 (500–3000) (6.67–34.8) (500–2000) (7.14–44.4) (2–6) 6.0 + 32 1187 14.17 7 929 12.65 4.7 (500–2000) (4.17–27.03) (500–1000) (7.69–19.23) (2–10) * PTX doses calculated for the 89% of patients in the PTX group whose weight was recorded in notes. † Doses calculated for the 77% of patients in the PTX + FFP group whose weight was recorded in notes. 2 Absolute and percentage reduction in international normalised ratio (INR) per vial of Prothrombinex HT (PTX) transfused for the 74 patients in the PTX group (treated with PTX without fresh frozen plasma) INR after PTX INR before PTX < 1.5 1.5–1.9 2.0–2.9 3.0–3.9 4.0–5.9 6.0 + < 2.0 No. of patients (no. with bleeding) 5 (0) 3 (1) — — — — Mean percentage reduction in INR (range) 18.6% (7.1%–31.3%) 9.3% (0–16.7%) — — — — 2.0–3.9 No. of patients (no. with bleeding) 7 (4) 9 (2) 6 (1) — — — Mean percentage reduction in INR (range) 35.9% (21.4%–53.6%) 23.5% (9.1%–44.4%) 30.5% (9.6%–40.0%) — — — 4.0–5.9 No. of patients (no. with bleeding) 1 (1) 7 (5) 3 (3) 1 (1) — — Mean percentage reduction in INR (range) 33.8% 34.4% (9.9%–65.5%) 31.7% (25.5%–39.5%) 21.8% — — 6.0 + No. of patients (no. with bleeding) 8 (4) 4 (1) 8 (5) 8 (2) 2 (1) 2 (0) Mean percentage reduction in INR (range) 52.8% (19.4%–86.4%) 66.9% (44.5%–90.1%) 55.7% (33.6%–82.5%) 37.8% (19.9%–40.2%) 39.6% (35.7%–43.5%) 26.7% (19.0%–34.4%)

Julie H Crawford MB BS · Bradley M Augustson FRACP, FRCPA

To the Editor: Obesity-related glomerulopathy (ORG) is a condition that is partially reversible by weight loss. A 48-year-old morbidly obese man presented with massive proteinuria (8.4 g/day; reference range[RR], < 0.03 g/day). His medical history included hypertension of 4 years, morbid obesity, gout and impaired fasting glycaemia. His hypertension had been relatively well controlled, with no known end-organ complication until the current review. His urinary protein excretion rate measured 6 months earlier had been 0.13 g/day. Longstanding medications included aspirin, lisinopril and allopurinol. The patient weighed 125 kg and was 1.77 m in height (body mass index, 40 kg/m2 [class III obesity]). His blood pressure was 130/70 mmHg, with no postural hypotension. The fundi were normal, with no evidence of hypertensive retinopathy. There was no peripheral pitting oedema and there were no tendon xanthomata. A repeat urinary protein measurement showed an excretion rate of 7.9 g/day, confirming the earlier result. Renal and liver function tests were normal. Other laboratory tests produced the following results: fasting cholesterol, 5.5 mmol/L (RR, < 4.0 mmol/L); triglycerides, 2.4 mmol/L (RR, < 1.8 mmol/L); serum creatinine, 92 μmol/L (RR, 60–110 μmol/L); albumin, 38 g/L (RR, 35–45 g/L); fasting glucose, 6.8 mmol/L (RR, < 5.5 mmol/L); serum insulin, 66 mU/L (RR, 5–25 mU/L); and C-peptide, 6.8 nmol/L (RR, 0.2–0.6 nmol/L). All relevant tests for glomerulonephritis, including serum antinuclear antibodies, antinuclear cytoplasmic antibodies, C3 and C4 levels, protein electrophoretic studies, and hepatitis B and C serology were negative, making a diagnosis of glomerulonephritis unlikely. While awaiting the renal biopsy, the patient decided to attempt rapid weight loss. He began consuming mostly one meal a day of about 5000 kJ (which included about 2000 kJ of protein). Six weeks later, his weight had fallen to 118 kg and his blood pressure was 130/80, with no oedema. His urinary protein excretion rate was 7.6 g/day. After 18 weeks, the patient weighed 110 kg and his urinary protein excretion rate had fallen to 2.1 g/day. At 6 months, his weight loss had plateaued at 102 kg and urinary protein excretion was 0.85 g/day. The renal biopsy showed features consistent with ORG1 (Box). No other abnormality was detected. A concomitant minimal change lesion with spontaneous remission would be a possible explanation, but such a lesion is exceedingly rare and difficult to exclude in the absence of electron microscopy. It is also unlikely given the patient’s age and abnormal light microscopy finding. It is apparent that class III obesity, through unknown mechanisms,2 is a major contributing factor in causing ORG and massive proteinuria — conditions that can be readily improved by weight loss. It remains to be seen in this case whether further weight reduction will further reduce the proteinuria, which, on the other hand, may also be confounded by the hypertension. Impaired fasting glycaemia is not a cause of proteinuria.3 This clinical vignette reinforces the need to check vigilantly for proteinuria and rigorously advise obese patients to attempt weight reduction, especially now that obesity has been confirmed to be an independent risk factor for end-stage renal disease.4 Histopathology of a representative glomerulus There is prominent vascular pole/perihilar sclerosis (broken circular line) and mild fibrosis of the Bowman capsule (arrow) (haematoxylin–eosin stain; original magnification, 3 40). No evidence of hypertensive diabetic nephropathy or tubular disease was detected. Other histological findings (not shown here) included glomerulomegaly, peripheral hyalinosis and mild basement membrane thickening.1 Morphologically, obesity-related glomerulopathy can be difficult to separate from idiopathic focal and segmental glomerulosclerosis.1

Huy A Tran FRACP, FRCPA

To the Editor: Motor neurone disease (MND) is a relentlessly progressive neurodegenerative disease with a median survival of 1–3 years. It results in the death of nearly 400 Australians per year.1 The management of MND remains problematic, tending to be offered in a heterogeneous and ad-hoc fashion across Australia. This heterogeneity arises in part from a lack of understanding of the aetiology of the disease and its progression in different patients,2 the absence of established guidelines for standard care,3 and a lack of concentrated experience among medical practitioners, nursing and allied health care workers in treating patients with MND. With new diagnostic techniques, treatments and interventions for MND undergoing trials, there is a clear need for more baseline information on MND management and outcomes and a method for monitoring any changes on a population basis.4 To facilitate this, the Australian Motor Neurone Disease Registry (AMNDR) has been developed. The Registry is governed by a steering committee comprising specialist physicians from each state and territory around Australia, neuroscientists, an epidemiologist and patient representatives. AMNDR was launched in Sydney in June 2004 to coincide with Motor Neurone Disease Global Awareness Day and, to November 2005, had enrolled 351 patients from 67 study locations, with 88% of registrations coming from 10 major sites. As of September 2005, 90 patients had undergone at least one further follow-up assessment. A copy of the registration, assessment and completion case report forms can be viewed on the AMNDR website (http://ww.amndr.org.au). From the patient information collected in the registration data, three distinct clinical phenotypes have emerged (Box). Patients with the “global” MND phenotype (combined upper and lower motor neurone signs in at least two regions) tended to have the shortest survival time. AMNDR was designed to obtain information that will increase the understanding of MND and its progression in different patients. Through the process of registry establishment, those involved in care, management and scientific research related to MND have been galvanised into a more effective and cooperative working unit. Ownership of the database has been retained by all who have contributed to data collection, and the information has been increasingly used to promote research into the causes and treatment of MND, locally and internationally.5 Through participation, it is expected that treating doctors will be able to evaluate their current management and associated patient outcomes relative to other centres around Australia. Demographic data for 351 patients with motor neurone disease enrolled in the Australian Motor Neurone Disease Registry to November 2005, by phenotype Phenotype, site of symptom onset Percentage of all registrations* Mean age at onset in years (SD) Sex ratio (F : M) Mean survival time in months (SD; range)† Deaths (%) Global† Bulbar 27% 64 (13) 1.5 : 1 27 (10; 20–48) 24% Cervical 25% 55 (19) 0.4 : 1 20 (10; 7–33) 13% Lumbar 19% 61 (10) 1.1 : 1 36 (16; 14–63) 24% Flail limb§ Arm 10% 63 (13) 0.07 : 1 95 (85; 30–238) 27% Leg 10% 58 (10) 2 : 1 59 (28; 33–100) 7% Primary lateral sclerosis¶ All regions 11% 54 (9) 0.9 : 1 103 (55; 24–259) 0 * Sum > 100% because of rounding. † Censored at November 2005. ‡ Global phenotype = combined upper and lower motor neurone signs in at least two spinal regions. § Flail limb variants = predominantly lower motor involvement of arms or legs, with prolonged disease duration. ¶ Primary lateral sclerosis = characterised by pure upper motor neurone involvement.

Matthew C Kiernan PhD, FRACP · Paul Talman FRACP · Robert D Henderson FRACP · Rodney Harris BA, GradDipBusStud, MAICD · on behalf of the Australian Motor Neurone Disease Registry Steering Committee

Noel McK Bennett Infectious Diseases Physician, Victorian Department of Human Services, 14A Marquis Street, Ashburton, VIC 3147. bennettnATbigpond.net.au To the Editor: In a recent issue of the Journal, Chew et al described a woman from Vietnam with skin nodules that, on histological examination, showed lobular panniculitis with granulomatous inflammation.1 No mycobacteria were visible and a polymerase chain reaction test for Mycobacterium tuberculosis was negative. Two months after starting quadruple antituberculous therapy (including rifampicin), her lesions had resolved. Erythema induratum (ostensibly due to hypersensitivity to M. tuberculosis) was diagnosed, despite the absence of evidence of tuberculosis. Other possible diagnoses were considered, but leprosy was not mentioned. In regions of Australia where leprosy is not endemic, the disease is frequently overlooked.2 Birrell3 described a man from Malta with recurring skin lumps. Biopsy showed panniculitis with giant cells, and the man was initially misdiagnosed as having “Weber–Christian syndrome” or “relapsing febrile non-suppurative nodular panniculitis”. Soon after, another Maltese patient presented similarly. This time, leprosy was suggested, and a biopsy revealed the presence of Mycobacterium leprae.4 Re-examination of slides from the first case showed similar organisms, confirming leprosy.5 The patients described by Chew et al and Birrell had migrated from countries in which leprosy was endemic, and biopsies revealed granulomatous panniculitis. Weber–Christian syndrome and erythema induratum are rare, ill-defined conditions with confused aetiologies, and both lack a specific diagnostic test. Therefore, cases of leprosy can be easily misdiagnosed as one of these conditions. That the biopsy in this patient did not show visible M. leprae is against a diagnosis of leprosy. But in my experience, even in lepromatous (multibacillary) disease, occasionally a skin smear of a lesion or (more rarely) a biopsy specimen may fail to reveal bacilli. Of course, this would be likely if the patient had received specific treatment for leprosy previously. Respectfully, I suggest that Chew et al should attempt to exclude lepromatous leprosy in their patient by looking for possible missed stigmata of leprosy, enquiring whether she has ever been treated for leprosy, asking whether any close acquaintances have had the infection or a chronic skin condition, and following up the patient in the long term.

Noel McK Bennett

James B Muir Dermatologist, Southeast Dermatology, 1202 Creek Road, Carina Heights, QLD 4152. arnoldmuirAToptusnet.com.au To the Editor: One of the Journal’s recent Lessons from Practice illustrates common errors in the approach to dermatological conditions.1 As in all areas of medicine, an accurate diagnosis is crucial to the management of any skin disease. This is especially so if a medical practitioner institutes treatments, such as oral steroids, that have considerable potential for causing morbidity. The lessons I would draw from the case of erythema induratum described are as follows. If you suspect an unusual presentation of a common condition, perform investigations to confirm your suspicions. Although erythema nodosum classically occurs on the anterior lower leg, lesions above the knee may occasionally be seen. To make a diagnosis, investigations need to be appropriate. The battery of blood tests ordered in the case described would not have shed light on the pathological process occurring in the skin. There is a reluctance among the general medical community to perform skin biopsies. These procedures cause little morbidity, have a high diagnostic yield, and should be within the skill set of any medical graduate. Concern over causing a scar is often cited as a reason for not doing a biopsy. But, in my experience, patients are rarely worried about such a prospect. Missing the diagnosis is surely of much greater concern. Taking a simple biopsy, including fat, at the initial presentation would have saved the patient in question a lot of trouble and risk. If there is no response to your treatment, it may well be that the initial diagnosis was incorrect. For example, it is common to see “steroid-resistant eczema” that is actually intraepidermal carcinoma. Erythema nodosum will usually show at least some response to non-steroidal anti-inflammatory treatment. Lack of response to a treatment that usually works should lead to a re-evaluation of the diagnosis. Systemic steroids should not be used for a dermatological condition without a firm diagnosis. Firstly, they can suppress many of the clinical and histological changes that allow a diagnosis to be made. Appropriate investigations need to be done before starting steroids. Secondly, a drug like prednisolone may well make matters worse, especially if, as here, there is an infectious aetiology. Patients from areas in which tuberculosis is endemic should have this condition excluded before being given systemic steroids. A lack of obvious exposure to or symptoms of tuberculosis is not unusual in patients from such areas who are subsequently shown to harbour this infection. The authors state that, as erythema induratum can resolve with corticosteroid treatment, this can lead to an erroneous diagnosis of erythema nodosum. Using response to treatment as a quasi-diagnostic test is dangerous indeed. Steroids will cause many conditions associated with significant inflammation to improve or even appear to resolve. But this does not mean that there is no infectious or malignant aetiology.

James B Muir

Gary Y Chew,* Christopher Henderson,† John W Quin‡ * Registrar, ‡ Director of Clinical Immunology, Department of Immunology, Liverpool Hospital, Bigge Park Centre, PO Box 103, Liverpool, NSW 2170; † Anatomical Pathologist, South Western Sydney Area Health Service, Liverpool, NSW. john.quinATswsahs.nsw.gov.au In reply: We thank Bennett and Muir for their pertinent comments. Our patient did not have any history or clinical evidence of lepromatous leprosy. The skin biopsy did not reveal any dermal granulomatous involvement, and there were definitely no organisms seen on an auramine stain of the biopsy specimen. Subcutaneous involvement in leprosy is uncommon except in erythema nodosum leprosum or as a neurotropic phenomenon. When present, it tends to be a neutrophil-rich hypersensitivity necrotising vasculitis — no features of which were seen in this case. Neither the woman’s partner nor child had a chronic skin condition or clinical history of leprosy or tuberculosis. Furthermore, the patient has been followed up for 12 months, with no recurrence of the rash. We agree with Muir that an accurate diagnosis is crucial to managing any skin disease and that there were many lessons to be gathered from this case apart from the five points we listed. It is our usual practice not to begin definitive treatment until we have examined a skin biopsy of any suspicious lesion and made a diagnosis. As this patient was very concerned about getting a scar, we did not perform a skin biopsy initially, but informed her that we may need to do so if the condition did not respond to treatment. We agree that patients from areas where tuberculosis is endemic should have tuberculosis excluded before instituting systemic steroid treatment. In this case, the patient was given a chest x-ray by the appropriate authorities before her migration to Australia. She has not returned to Vietnam since then. Furthermore, the patient had failed a trial of a non-steroidal anti-inflammatory drug and found the lesions cosmetically distressing. Consequently corticosteroids were instituted.

Gary Y Chew · Christopher Henderson · John W Quin

Mu Li,* Kay V Waite,† Gary Ma,‡ Creswell J Eastman§ * Senior Lecturer, School of Public Health, University of Sydney, Sydney, NSW 2006; † Technical Officer, ‡ Principal Scientist, § Director, Australian Centre for Control of Iodine Deficiency Disorders, ICPMR, Westmead Hospital, Sydney. muliAThealth.usyd.edu.au To the Editor: Iodine is essential for production of thyroid hormone. The recommended daily intake is 100 μg for children, 150 μg for adults and 250 μg for pregnant and lactating women.1 Sporadic surveys of population iodine intake in Sydney, New South Wales, between 1985 and 1992 showed median levels of urinary iodine excretion (UIE) > 200 μg/L, indicating iodine sufficiency.2 However, a recent national study demonstrated mild iodine deficiency (median UIE < 100 μg/L) in New South Wales and Victoria, borderline levels in South Australia and adequate intake in Queensland and Western Australia.3 The major sources of dietary iodine are dairy milk and dairy products, seafood and iodised salt. In Australia, few people purchase iodised salt, and, except in Tasmania, the food industry does not use iodised salt in the production and preparation of food.4 For decades, milk contaminated with iodine residues from sanitising solutions (iodophors) used in the dairy industry has probably been the largest source of iodine in the Australian diet. We undertook a survey of the iodine content of milk samples from supermarkets around metropolitan Sydney in 2001 and 2004. In each year, iodine levels were measured in 13 samples, comprising a range of milk types (including whole, full cream, lite and skim) and brands (including Dairy Farmers, Devondale, Farmdale, Farmland, Perfection, Pura and Woolworths). Iodine concentrations were highly variable. Median concentrations were 140 μg/L in 2001 (range, 60–220 μg/L) and 195 μg/L in 2004 (range, 66–412 μg/L). Iodine concentrations varied between samples of the same brand and type by up to 100 μg/L. Many samples contained less than 200 μg/L (10/13 in 2001 and 7/13 in 2004). A 1975 survey of iodine concentration in milk conducted by the Australian Consumers’ Association found mean concentrations of 593.5 μg/L and 583 μg/L in NSW and Victoria, respectively.5 Because of concerns about iodine toxicity, Food Standards Australia and New Zealand specified an iodine limit of 500 μg/L in the Food Standards Code 1982. The replacement of iodophors by other sanitisers in the dairy industry appears to be the reason for the decrease in iodine content of Sydney milk. The perception that milk is a rich source of iodine is no longer true. A cup (250 mL) of milk a day would provide at most 50–60 μg iodine, approximating a third of the daily requirement for an adult. We suggest that the reduced amount of iodine in milk is likely to be one of the explanations for the re-emergence of iodine deficiency in Sydney and perhaps elsewhere in Australia. Despite these changes, dairy milk remains an important source of dietary iodine. The iodine content in milk should be monitored.

Mu Li · Kay V Waite · Gary Ma · Creswell J Eastman