Child health

To the Editor: Isoniazid is used extensively for the treatment of active and latent tuberculosis (TB). It is generally well tolerated by children, and hypersensitivity reactions resulting in skin rash and requiring cessation of treatment are rarely reported in this age group.1,2 We report a case of isoniazid hypersensitivity in a 21-month-old boy potentially exposed to TB in a childcare setting. He was one of over 80 children screened after contact with a childcare worker who showed a positive smear result. His initial tuberculin skin test (TST) was negative and, in line with New South Wales guidelines,3 he was commenced on isoniazid 150 mg daily (10mg/kg/day) while awaiting a repeat TST. After 3 days of treatment, he developed a small number of round vesicular lesions on his tongue. They were associated with mild discomfort but his appetite was not affected. There were three small maculopapular lesions on his legs and back that reportedly looked like mosquito bites before blistering. The child remained afebrile and was systemically well. The family general practitioner considered that this presentation was possibly an allergic reaction and isoniazid was discontinued. Population health staff were consulted, and the risks and benefits of further isoniazid treatment were discussed with paediatric TB specialists. It was recommended that, after the rash had resolved, isoniazid be reintroduced at half the dosage and with close supervision. Two days after isoniazid 75 mg daily was recommenced, the rash recurred. The child’s mother described lesions appearing as “burns all over his tongue” and reported further sores around his lips and six welt-like lesions on his legs. Isoniazid was immediately discontinued, the skin lesions resolved within 5 days and no further antituberculous therapy was administered. His repeat TST 12 weeks after the initial test was negative and he remains well. No other potential triggers for a hypersensitivity reaction were identified. In particular, no other medications were administered during this period or for the week before commencing isoniazid. According to his mother, the child had experienced a similar reaction within 1 hour of a single dose of ibuprofen when he was 8 months old. Several tongue blisters were accompanied by a generalised fine maculopapular rash lasting several days. We concluded that the child most likely had a hypersensitivity reaction to isoniazid that required discontinuation of treatment. We reported this to the Therapeutic Goods Administration, which advised that it had received seven other reports since 1991 of suspected hypersensitivity, but none were for children under 10 years of age.

Tony D Merritt · Peter D Massey

To the Editor: Accidental asphyxia in very young children is an ongoing problem caused by hazardous sleeping environments and toddlers’ inability to understand dangers or to physically extricate themselves once entrapped. Two common problems involve children becoming wedged between mattresses and cot sides or walls, and hanging from clothing caught on projections inside cots.1 Autopsy in such cases requires careful death scene evaluation to prevent confusion with sudden infant death syndrome and to identify any evidence of inflicted injury, if present. National legislation requiring both new and second-hand cots to meet Australian safety standards has reduced the numbers of unsafe cots on the market. I report a case of another continuing, albeit less common, circumstance that is also resulting in lethal outcomes for toddlers — about one child dies every 1–2 years in Australia in this manner.2 A healthy 13-month-old boy was placed in his cot next to a window with blinds from which a cord was hanging. A loop of the cord measuring about 10 cm was hanging inside the cot. When checked later, the boy was found unresponsive, hanging from the cord. Resuscitation attempts were to no avail. At autopsy, a parchmented ligature mark was present around the neck, with facial and conjunctival petechiae. There were no other injuries or significant illnesses present. Death was therefore attributed to accidental hanging. (Further information on this case is available in the Finding of Inquest.3) Prevention of such tragic fatalities requires ongoing public awareness campaigns, using pamphlets such as the Australian Government’s blind and curtain cords safety alert brochure,2 to advise parents and child carers to keep cots and furniture that can be climbed on away from windows that have curtain or blind cords, to use cleats and cord wind-ups to keep cords at least 1.6 m above the floor, to cut loops, and to keep cords that must be looped under tension with tie-down devices. A safety tassel is also available that clips the two ends of a cord together but that easily separates when put under pressure.4 In addition, national legislation similar to that currently enacted in New South Wales and other states would provide uniform guidelines for managing these devices that would include warning labels and written safety information for parents.4

Roger W Byard

Pediatric respiratory medicine. 2nd ed. Lynn M Taussig, Louis I Landau, editors. Philadelphia: Mosby, 2008 (xxiii + 1118 pp). ISBN 978 0323 04048 8. If you are looking for an up-to-date encyclopaedia of paediatric chest disease, then this is it. As expected, this second edition is a substantial improvement over the first. Most of the 75 chapters are short and user friendly. The text is broken up with numerous coloured diagrams, figures, tables, x-ray images and boxed sections highlighting key points, teaching points, pitfalls and controversies. For those who want teaching resources, all images can be captured with ease directly into Powerpoint presentations via electronic access. This edition is slightly less hefty than the previous edition, largely because the references are not included in the book — however, they are accessible electronically, with direct links to MEDLINE abstracts. Most chapters are very heavily referenced (eg, Chapter 3 has over 300 references) and remarkably up to date for a multi-author textbook, including a few references from as late as 2007. Since the editors are from Western Australia and the United States, it is understandable that the majority of the expert authors are also from WA and the US. Nevertheless, all are clearly national and international authorities on their specific topics. Because there are over 130 separate authors, the style and format vary considerably. It is disappointing to see some very user “unfriendly” chapters. For example, in Chapter 35 (bacterial pneumonia) there are over 30 pages of continuous, dense text with only occasional subheadings, and illustrated with a total of only four small x-ray images. To check both content and ease of access, I tested for several of my pet topics — including “plastic bronchitis” and “genetic surfactant deficiency mimicking interstitial lung disease”. Both were readily found, comprehensively covered, and with key references included. At $190.00, the book represents outstanding value for money, given the quality of the content, the outstanding diagrams and figures, and the huge number of electronic references.

Craig M Mellis

To the Editor: The incidence of type 1 diabetes mellitus (T1DM) is increasing in Australia.1,2 There is also general consensus that the incidence of diabetic ketoacidosis (DKA) is increasing in children, as noted in an Australian study.3 We conducted a retrospective audit of the referral pattern of patients with newly diagnosed T1DM presenting to the Children’s Hospital at Westmead, a tertiary referral centre serving the population of western Sydney. Referral data were available for 191 of 204 patients with newly diagnosed T1DM admitted to the hospital between January 2003 and December 2004. Most patients (150; 79%) had presented to their general practitioner before admission to hospital, and the remainder had initially presented to an emergency department. In the former group, the diagnosis of diabetes was indicated in referral letters or admission notes for 128 patients (85%), while a diagnosis other than diabetes (eg, gastroenteritis, urinary tract infection, sepsis) was made for 22 patients (15%). DKA was less common among patients whose referral letter indicated a diagnosis of diabetes compared with those with an alternative or no diagnosis or without a referral letter (27% v 47%; P < 0.001). Most patients (105; 70%) were referred to an emergency department within 24 hours of presentation to the GP, and their rate of DKA was lower than in those referred after 24 hours (31% v 51%; P = 0.03). These data suggest that better understanding by primary carers of the symptoms of new-onset T1DM and earlier referral are significantly associated with reduced risk of DKA. Most patients who first saw a GP (125; 83%) had initial investigations arranged; bedside urinalysis and/or measurement of fingerprick blood glucose levels were performed in 66%, while 31% were sent for formal blood tests. Patients who had bedside investigations performed had a significantly lower rate of DKA than those who had only formal blood tests or no investigations performed (26% v 52%; P = 0.002). It is noteworthy that, among patients who first saw a GP, 23 (15%) were diagnosed with diabetes but were not referred to an emergency department within 24 hours. The reasons for this are unclear but may be due to the GP waiting for confirmatory blood test results. The Australasian Paediatric Endocrine Group and International Society for Pediatric and Adolescent Diabetes guidelines recommend immediate referral for suspected new-onset T1DM, as DKA is fatal if left untreated.4 A public awareness campaign conducted in Italy in the 1990s was successful in reducing the incidence of DKA in children with newly diagnosed T1DM.5 Australian communities might benefit from a similar campaign to encourage prompt identification of symptoms of diabetes in childhood, prompt bedside investigations, and immediate referral to hospital for definitive care.

Maria E Craig · Catherine H Wong · Joanna Alexander · Ann M Maguire · Martin Silink

A 5-month-old boy with known congenital varicella syndrome presented to our hospital emergency department with generalised herpes zoster (shingles). The child was born in Australia. His Sri Lankan-born mother had developed chickenpox in the second trimester of pregnancy. Examination and investigation of the child at birth for complications of congenital varicella syndrome had revealed only skin changes on the left thigh (Box, A). A new vesicular rash had evolved over 3 days, initially involving right T8 (Box, B) and L4–5 (Box, C) dermatomes, then progressing to cover the entire body. There was no clinical evidence of visceral involvement. Cicatricial scarring had replaced the congenital skin changes (Box, D). Varicella zoster virus was isolated from vesicular fluid. Oral valaciclovir was prescribed for 7 days because the generalised nature of the rash demonstrated an insufficient immune response to varicella reactivation. The symptoms rapidly resolved, with no new scarring. A maternal chickenpox infection during pregnancy can be severe and life-threatening, and can also cause in-utero infection, which may be fatal or result in congenital abnormalities.1 Important features of congenital varicella syndrome include: dermatomal cicatricial scarring (highlighted by this patient); limb defects; intrauterine growth restriction; ophthalmological defects (chorioretinitis, optic atrophy, cataract); gastrointestinal or genitourinary abnormalities; neurological defects (developmental delay, seizures, deafness, limb paralysis, microcephaly).1 Shingles is caused by reactivation of varicella zoster virus. Childhood shingles is uncommon (incidence, 0.05%/year), rarely indicates primary immunodeficiency,2 and occurs more frequently following congenital infection (4.4%/year)2 or chickenpox infection during infancy (0.4%/year).2 Antiviral treatment of shingles in immunocompetent young children is not usually recommended, as complications (including post-herpetic neuralgia) are rare.3 Chickenpox has been mainly a childhood disease in Australia, but in many tropical countries it predominantly affects adults. Immigrants to Australia from these regions (including the mother of our patient) may remain susceptible to varicella infection.4 At least 5% of Australian women of childbearing age were born in tropical countries.5 Varicella vaccine is highly effective and is listed on the National Immunisation Program Schedule6 for childhood immunisation. Lowering the community prevalence of varicella infection by routine childhood immunisation can help protect non-immune adults and immunocompromised patients.1 Opportunistic, proactive identification and immunisation of non-immune adults, particularly for both prospective parents before pregnancy, could help prevent serious consequences. Cicatricial scarring and shingles in a 5-month-old infant with congenital varicella syndrome

Elizabeth K Nairn · Joshua Wolf · Jim P Buttery

Australia needs to develop its own guidelines based on local data New guidelines for testing and treating lipid abnormalities in children have recently been published by the American Academy of Pediatrics and the American Heart Association (Box).1,2 These recommendations, made partly in response to the high prevalence of obesity in children in the United States, provoke consideration of whether they should also be adopted in Australia. The previous US recommendations,3 which targeted cholesterol testing to children with a family history of premature cardiovascular disease or high cholesterol levels, had focused on a population-based approach to treatment through a fat- and cholesterol-restricted diet. Drug therapy was reserved for children with more persistent and extreme elevations in cholesterol level. In contrast, the recent guidelines recommend that testing be broadened to include all overweight or obese children, with the first cholesterol assessment to be done between the ages of 2 and 10 years. The new guidelines further recommend that initiation of drug therapy be considered at a younger age (from 8 years) and with a lower low-density lipoprotein cholesterol (LDL-C) level target for children with multiple cardiovascular risk factors. Indirect evidence suggests that childhood lipid abnormalities are important in the development of cardiovascular disease in adults. For example, autopsy studies indicate that atherosclerosis begins in the young and that the extent of lesions correlates with traditional cardiovascular risk factors, including lipid levels.4 However, advanced atherosclerosis rarely occurs in children and adolescents. Arterial wall thickness in adults, as assessed by carotid artery ultrasonography, is associated with childhood lipid levels, and children with lipid abnormalities display altered arterial structure and function.5,6 However, direct evidence for an association between childhood lipid levels and adult cardiovascular outcomes, such as myocardial infarction and stroke, is not available. Why, then, test children and adolescents at all? Would it be equally effective to test young adults? One important potential rationale for cholesterol testing in children is that lipoprotein levels tend to track from childhood into adult life.7,8 Detection of lipid abnormalities in young children could prompt changes in diet and physical activity that would be required through the whole of life. It is important to note, however, that both universal and targeted lipid testing in children result in a high false-positive rate for adult dyslipidaemia.8,9 Moreover, the predictive value of childhood lipid levels depends on the threshold values used to define dyslipidaemia. Threshold values derived from populations of US children may not be sensitive to trends in childhood lipid levels and overweight and obesity in Australia. The prevalence of childhood overweight and obesity is high and increasing in both Australia and the US.10,11 Moreover, in both countries, lipid abnormalities are common in overweight and obese children,12,13 with low high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels particularly prevalent. Importantly, targeting overweight and obese children for LDL-C testing does not improve the specificity for detecting elevated LDL-C levels in adults.8 Although most overweight and obese children with low HDL-C levels become adults with low HDL-C levels, targeting overweight and obese children for HDL-C testing will not identify the majority of adults with low HDL-C levels.8 Overweight and obese children, whether or not they have high triglyceride and low HDL-C levels, require weight management through changes in diet and physical activity levels. But it is uncertain, particularly in the case of young children, whether knowledge of their lipid status will lead to greater motivation to implement such changes. Improved diet and increased physical activity are both safe and effective ways of reducing cardiovascular risk factors in children, and should be promoted across the whole paediatric population.14-17 Most overweight and obese children could be encouraged to adopt these lifestyle changes without testing their lipid status. Testing for lipid abnormalities could be reserved for older, obese children (> 10 years of age) in the context of an overall assessment of their risk for future cardiovascular disease. Screening based on family history may be hampered by inaccurate or incomplete information and the need for adult family members to have their cholesterol levels measured. However, obtaining an accurate family history, combined with testing of adults to detect those with significant elevation in LDL-C levels, may help identify children with inherited dyslipidaemias (eg, familial hypercholesterolaemia). Such children have the highest risk of premature cardiovascular disease and may benefit most from drug therapy at a young age. The new US recommendations also raise questions about which children should be considered for drug therapy for lipid abnormalities. A number of randomised clinical trials have demonstrated the short-term safety and efficacy of HMG-CoA reductase inhibitors (statins) in children.18 Statins are currently the first-line drug treatment for elevated cholesterol levels in children. However, there is a lack of evidence for their long-term safety, and animal studies have shown they may be toxic to the developing fetus.19 Although there have been no controlled epidemiological studies relating gestational exposure to statins with adverse human pregnancy outcomes, case reports of structural anomalies and the biological plausibility of a teratogenic effect mean that statins are contraindicated in pregnancy.20 Thus, a case can be made for reserving statin therapy for older children at high risk of future cardiovascular disease. In girls, it may be appropriate to delay statin therapy until an age when discussions about reproduction and contraception can occur. A strong family history of premature cardiovascular disease or a rapid progression in surrogate measures of atherosclerosis (eg, carotid arterial wall thickness, measured by ultrasound) may lower the age threshold for statin therapy. In Australia, we should be taking action to address the increasing prevalence of childhood cardiovascular risk factors. However, guidelines from the US may not be appropriate for Australian children, and it is imperative that we formulate new local recommendations based on recent local data. Guidelines for lipid assessment and management in Australia should also propose strategies for reducing cardiovascular risk factors in childhood more generally. This will require discussion and collaboration between clinicians, researchers, and governmental and non-governmental organisations, such as Diabetes Australia, the National Heart Foundation, the Paediatric Cardiac Council of the Cardiac Society of Australia and New Zealand, and the Royal Australasian College of Physicians. In the interim, a careful assessment of the risk of future cardiovascular disease is required for all paediatric patients. This will be based on ascertainment of an accurate family history of premature cardiovascular disease, information on diet and physical activity, anthropometric and blood pressure measurements made at routine paediatric health checks, and the targeted assessment of blood lipid levels in older children with a family history of premature cardiovascular disease or hyperlipidaemia and/or multiple other cardiovascular risk factors, including obesity. Summary of recent changes to recommendations in the United States for cholesterol testing and treatment in children1,2 Stronger recommendations for cholesterol testing in children who have cardiovascular risk factors other than lipid abnormalities — particularly overweight and obesity, but also hypertension, cigarette smoking or diabetes. A stronger recommendation on the timing of initial cholesterol testing: between the ages of 2 and 10 years. A recommendation to consider commencing drug therapy in children aged over 8 years (rather than 10 years), with a target low-density lipoprotein cholesterol level of < 3.3 mmol/L (rather than < 4.1 mmol/L).

Julian G Ayer BSc(Med), MB BS, FRACP · David R Sullivan MB BS, FRACP, FRCPA · Gary F Sholler MB BS, FRACP

Objective: To document haemopoietic stem cell transplantation (HSCT) activity and trends among paediatric patients in Australia and New Zealand.Design, setting and participants: A retrospective analysis of data reported to the Australasian Bone Marrow Transplant Recipient Registry by the seven paediatric HSCT institutions in Australia and New Zealand over the 9-year period 1998–2006, with particular focus on the most recent years (2002–2006).Main outcome measures: Types of HSCT performed; transplant-related mortality (TRM); stem cell sources; indications for HSCT; causes of death after HSCT.Results: Over the period 1998–2006, 522 autologous HSCT procedures (41%) and 737 allogeneic procedures (59%) were performed. About 60% of allogeneic transplants involved alternative donors (donors other than a human leukocyte antigen-matched sibling). The use of umbilical cord blood as a source of haemopoietic stem cells has doubled since 1998, with 34% of allogeneic transplants in 2006 using cord blood. Over the period 2002–2006, the median age of patients receiving transplants was 7 years (range, 0–19 years). The most common indications for allogeneic HSCT were acute lymphoblastic leukaemia (33%) and acute myeloid leukaemia (24%). The most common indications for autologous HSCT were neuroblastoma (23%), medulloblastoma (21%) and Ewing sarcoma (10%). TRM at 1 year after transplant was 22% for alternative donor transplants, 7% for matched-sibling transplants and 5% for autologous transplants. Relapse or persistence of a child’s underlying condition accounted for 54% of all deaths within 1 year after transplant.Conclusions: HSCT is an important procedure for children with a range of life-threatening illnesses. Local trends in the indications for HSCT, donor selection and TRM reflect contemporary international practice.

Andrew S Moore MB BS · Peter J Shaw MB BS, MRCP, FRACP · Andrew R Hallahan BSc(Med), MB BS(Hons), FRACP · Tina L Carter MB BS, FRACP, PhD · Tatjana Kilo MD · Ian Nivison-Smith BSc, MAppStat · Tracey A O’Brien MB ChB, FRACP, MHL · Heather Tapp MB BS, FRACP, FRCPA · Lochie Teague MB ChB, FRACP, FRCPA · Shaun R Wilson MB ChB, DCH, MRPCH · Karin Tiedemann OAM, MB BS, FRACP

Severe childhood obesity and its associated comorbidities are increasing in prevalence. Extreme childhood obesity may be viewed as a mirror image of severe non-organic failure to thrive. Parental neglect may be a causative factor in both circumstances. When suspicion of parental neglect arises, health care professionals may have both an ethical obligation and a statutory duty to notify child protection services. Guidelines on the point at which medical practitioners should seek state assistance in cases of severe childhood obesity would be helpful, not only for medical practitioners, but also for child protection services.

Shirley M Alexander MB ChB, MRCPCH, FRACP · Louise A Baur BSc(Med), PhD, FRACP · Roger Magnusson BA, LLB(Hons), PhD · Bernadette Tobin MA, MEd, PhD

Objective: To explore the experiences of families with a baby with Down syndrome at the time of diagnosis, and their preferences for information and support in the early period after diagnosis.Design, setting and participants: A qualitative, interview-based study of 18 families living in Victoria with a child with Down syndrome born between 2002 and 2004 who had not been diagnosed with the syndrome before birth. Interviews were transcribed verbatim and interpretive content analysis was undertaken.Results: Parental coping with the unexpected diagnosis of Down syndrome in their infant was influenced by the time interval between birth and disclosure of clinical suspicion of Down syndrome, the level of certainty of the attending physician at the time of disclosure, and the time interval between disclosure of clinical suspicion and confirmation of karyotype. Initial uncertainty and a delay in the diagnosis were detrimental to parental coping, as was premature communication of the news. Perinatal complications increased parental anxiety regarding their child’s condition and future. Individual communication style of midwives and physicians was a powerful predictor of parental adaptation. Parental needs for support and information were facilitated through normalising postnatal care, ensuring privacy, and providing early access to peer support and up-to-date written information. Many parents would have appreciated access to a liaison worker.Conclusion: The experiences of parents in this study provide practice points for improving postnatal care with minimal changes to formal service systems.

Evelyne E Muggli MPH · Veronica R Collins PhD · Catherine Marraffa FRACP, FRCPCH

To the Editor: Accidental ingestion of foreign bodies is common in children. Most pass through the gastrointestinal tract spontaneously,1 but some, such as magnets and batteries, can cause serious problems. We treated three children, aged 4–11 years, who ingested magnets that caused multiple bowel perforations. All three children presented with abdominal pain and vomiting, and were initially treated for gastroenteritis as the history of ingestion was not available. Plain abdominal films were subsequently used to make the diagnosis of foreign body ingestion. The ingested objects were later found to be pieces from magnetic construction toy sets. The first patient was an 11-year-old child with autism. An initial laparoscopy revealed marked dilatation of the small bowel and interloop adhesions. Subsequent laparotomy revealed several magnets (rods, rings and balls) in adjacent loops of the small bowel (Box, A), as well as necrosis and 13 perforations of the small bowel. Segmental resection was performed with a defunctioning ileostomy. During surgery, radiography was performed to ensure that all foreign bodies were removed before closure of the abdomen. The child made a good recovery, and the ileostomy was closed 3 weeks later. The second patient was 4 years of age. An abdominal x-ray revealed a cluster of foreign bodies in the right lower quadrant of the abdomen, with a small gap between the fourth and fifth foreign bodies. A laparoscopy revealed a cluster of magnetic rings (Box, B) perforating the small bowel and the caecum. Two of the rings were on the caecal side and four were on the small bowel side, with an intervening fold of mesentery — the gap on the x-ray. The magnets were retrieved through a minilaparotomy, and the caecal perforation was oversewn. The third patient was a 5-year-old who presented with similar symptoms and x-ray findings. Laparotomy revealed an area of pressure necrosis underlying the magnet and causing perforation of the jejunum, which was repaired by segmental resection and primary anastomosis. As ingestion of foreign bodies is usually not witnessed, a high index of suspicion is required for correct diagnosis.2 Of confirmed cases, 50% of patients remain asymptomatic.3 Fewer than 10% of cases require intervention, and about 1% require surgery.4,5 Ingestion of multiple magnetic objects in children is particularly serious, because of their tendency to aggregate in the bowel and compress intervening tissue, and should be treated aggressively. These cases demonstrate the harmful consequences of magnets in toys. More stringent regulations on the use of magnets in toys — especially in toys for children younger than 5 years — and measures to increase public awareness of this issue are needed. Clusters of ingested magnets in children A: Magnets in loops of the small bowel. B: Magnetic rings perforating the small bowel and caecum, showing intervening fold of mesentery and bowel wall (arrow).

Manjunath B Siddaiah-Subramanya · Peter Borzi

Objective: To document general baseline data on the patterns of childhood malignant tumours at a teaching hospital in south-western Nigeria.Design, setting and participants: A retrospective study of childhood malignancy at Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria, during an 11-year period, from January 1996 to December 2006.Results: 77 children were diagnosed with malignant tumours (an average of seven diagnoses per year); 46 were boys (60%), giving a male-to-female ratio of 1.5 : 1. The age distribution of patients was 1–18 years. There were 42 diagnoses (55%) in the 1–5-year age group and 68 malignancies (88%) were diagnosed at ages of 12 years or younger. Lymphomas were the most prevalent malignancy identified, accounting for 31 diagnoses (40%). Burkitt’s lymphoma constituted the majority of malignancies (28 cases; 36%), followed by retinoblastoma (16 cases; 21%) and nephroblastoma (11 cases; 14%). Other malignancies included germ cell tumours (6), neuroblastomas (4), osteosarcomas (3), rhabdomyosarcomas (3) and non-Hodgkin’s lymphomas (3). One case each of medullary thyroid carcinoma, adenocarcinoma of the rectum, invasive mucinous carcinoma of the colon were also identified.Conclusion: These data suggest that Burkitt’s lymphoma is the most common childhood malignant tumour in our geographic area of south-western Nigeria. With the rising incidence of childhood malignancy in resource-poor countries, measuring the baseline occurrence of such tumours is imperative to provide much-needed resource allocation.

Ayodeji O J Agboola MB ChB, MSc · Folashade A Adekanmbi MB BS, FWACP · Adewale A Musa MB BS, FWACS · Adetoun S Sotimehin MB BS, FWACP · Anotu M Deji-Agboola BSc, MSc, PhD · Aderibigbe M O Shonubi MB BS, FWACS · Temitope Y Oyebadejo MB BS, FMCPath · Adekunbi A F Banjo MB BS, FMCPath

The time has arrived to sort out the decades-long ADHD debate The Royal Australasian College of Physicians is currently revising the 1997 National Health and Medical Research Council (NHMRC) guidelines on attention deficit hyperactivity disorder (ADHD).1 Also, the American Psychiatric Association is working towards the fifth edition of the Diagnostic and statistical manual of mental disorders (DSM), with an expected publication date of 2012. These are valuable opportunities to review existing diagnostic criteria for ADHD and consider alternatives. Recent refinements in psychiatric classification and advances in neuroscience research have jointly contributed to a clearer understanding of some childhood psychiatric disorders. Paradoxically, these developments also raise doubts about the diagnostic validity of ADHD — the most common psychiatric clinical presentation in childhood. These doubts arise from difficulties in conceptualising ADHD as a “disorder”. They also exemplify the growing turmoil that is part of the larger disillusionment with psychiatry,2 reflecting fundamental changes both within and beyond the profession in many Western countries, including Australia. A central concern is the increasing tendency of psychiatry to transform what many regard as normal emotional responses to life’s stresses and traumas into psychiatric disorders. The nosological conundrum of ADHD was highlighted in the United States National Institutes of Health’s ADHD consensus statement; it concluded that there is evidence supporting the validity of the disorder, but did not provide a consensus regarding which ADHD patients should be treated with psychostimulants.3 A response to the statement noted that: ... [the] “unproven” status of the disorder should give pause to both researchers and clinicians who may have reified ADHD as a “thing” or “true entity” (rather than a working hypothesis that serves scientific, communication, and clinical decision-making purposes).4 In addition, it has been noted that discussion of the diagnostic validity of ADHD is far from stale or easily dismissed, and that a renewed sense of urgency arises when a: ... diagnostic concept is listed in an official nomenclature and provided with a precise, complex definition [which] tends to encourage ... insidious reification.5 Such unintentional reification by DSM-IV6 — where so-called core symptoms of ADHD (poor impulse control and lack of sustained attention) are construed as a disorder — is illustrated by tracing the DSM’s successive revisions of ADHD as a diagnostic entity. Antecedents for ADHD range from “motoric disinhibition” in DSM-II (categorised as hyperkinetic reaction) and “inattention” in DSM-III (categorised as attention deficit disorder) to attention deficit hyperactivity disorder (ADHD) in both DSM-III-R and DSM-IV.7 The fact that such conceptual changes are part of the DSM’s stated aim (ie, to identify clinical conditions that can be considered as genuine medical disorders and to distinguish them from problems of living) results in a catch-22 error that has been noted in relation to major depressive disorder.8 This flaw in logic also applies to ADHD. Beyond this flawed logic, Russell Barkley — a respected American authority on ADHD — reviewed the criteria for ADHD and concluded that “what is clear is that the current DSM-IV approach has little clinical or research merit”.9 Further disenchantment with the disease entity assumptions of the DSM revisions has arisen from the serial increase in numbers of diagnostic categories: from 60 in 1952 (DSM) to 145 in 1968 (DSM-II) and 410 in 1994 (DSM-III). This led one author to comment: ... particularly badly affected by this constantly creeping diagnostic expansion have been children, whose least oddity or not quite normal (frequently confused with average) quirk is now assigned to some syndrome or other and treated with behaviour therapy and drugs. The ethics of all this is rarely called into question.10 At the ideological level, some see a process of “psychotherapeutic revisionism” in mental health care in the US.11 I have discussed how such a revisionist ideology views ADHD in detail elsewhere.12 In summary, it fails to distinguish between psychology as “science” and as “scientism”. As a consequence, the former holds that ADHD symptoms arise from the interaction of genetic and developmental influences during pregnancy through childhood, whereas the latter focuses on symptoms as utilitarian targets for treatment. The DSM’s atheoretical approach, which perpetuates the continuing absence of a “developmentally sensitive, interactive or longitudinal perspective in the DSM system”,13 sits within such revisionist ideology. These contrasting conceptual and ideological views have resulted in divergent perspectives on the conceptualisation of ADHD, reliability and validity of ADHD diagnosis, and treatment options for behaviour labelled as ADHD.14,15 Ethical dimensions and other subjects for consideration in the ADHD debate include: diagnostic decision making; inappropriate (over- or under-) medication; “performance enhancement” arguments; the relationship between the psychiatric profession and the pharmaceutical industry, raising possible conflicts of interest; third-party reimbursement for ADHD as a disability; the lack of childhood safety and efficacy data leading children to be termed “therapeutic orphans”; and purported aetiologies based on genetics versus “toxic environments”.16 Importantly, these purported aetiologies have been recast into integrative models that include both genetics and environmental factors,17 a new direction that has immediate implications for clinicians and researchers. Global expenditure on drugs to treat ADHD rose ninefold to US$2.4 billion in the decade to 2003.18 It would be naïve to think that market pressure does not influence evidence-based protocols in resource-starved health services. The revised practice parameters from the American Psychiatric Association relied on the DSM-IV text revision definition of ADHD. The limitations of their recommendations were explicit: These parameters are not intended to define the standard of care, nor should they be deemed inclusive of all proper methods of care or exclusive of other methods of care directed at obtaining the desired results.19 Let us hope that the committee created by the Royal Australasian College of Physicians to define and describe the current conceptualisation of ADHD will have the scientific rigour, maturity and wisdom as they undertake the revision of the 1997 NHMRC guidelines on ADHD1 to emphasise the distinction between ADHD as a set of symptoms and a disease concept. As we approach the critical crossroads between the fourth and fifth revisions of the DSM’s ADHD criteria, a glimmer of hope has emerged, signalling that the time has arrived to sort out the decades-long ADHD debate. The Psychodynamic diagnostic manual (PDM)7 offers an alternative to the DSM construct of ADHD — a relief to what I believe to be shortcomings of the current DSM.9 The PDM’s inclusive approach to diagnosis integrates the subjective experiences of patients with their neuropsychological capacities for regulation of relationships, intimacy and emotional experiences, as well as attention and behaviour. Ideally, such an approach will enable the next generation of children to be spared prescription medications in the current quantities and combinations, based on dubious diagnostic criteria for behaviour labelled ADHD.

George Halasz MRCPsych, FRANZCP

After several years suffering from Parkinson disease, Ian Reid, a paediatric surgeon, died on 20 March 2008. Ian was born on 5 July 1926 at Port Vila, New Hebrides (now Vanuatu). The family returned to Australia in his early childhood. After service in the Royal Australian Air Force, Ian graduated in medicine from the University of Melbourne in 1953. Three years later, he returned to the New Hebrides as Mission Doctor on the island of Tanna. During his years in Tanna, Ian observed at close hand the infamous “cargo cult”. A rather dramatised account of his part in stopping the intrusion of cult members into his hospital was written by David Attenborough in his book The quest for paradise. And his ways are ways of gentleness and all his paths are peace In 1959, Ian went to Papua New Guinea (PNG) to work as a Medical Officer at the Port Moresby General Hospital. He became Foundation Dean of the Papuan Medical College, where he lectured from 1961 to 1969. In 1968, he was awarded a World Health Organization travelling fellowship in paediatric surgery, which took him to Philadelphia Children’s Hospital and other children’s hospitals throughout the United States. During his time in Philadelphia, he worked with “Chick” (C Everett) Koop, one of the first surgeons to successfully separate Siamese twins. On his return from PNG to Australia, Ian worked at the Royal Children’s Hospital, Melbourne, from 1970 to 1971. The following year, he became a James Fairfax Surgical Research Fellow at the Children’s Medical Research Foundation and a Consultant Surgeon at the Royal Alexandra Hospital for Children, Sydney. The award of a Sir Denis Browne Memorial Travelling Fellowship in Paediatric Surgery in 1975 took him to Great Ormond Street Hospital for Children, London, and to other hospitals in the United Kingdom and Ireland. In 1980, Ian was invited to take up a lectureship at the newly established Medical School at the University of Newcastle (New South Wales), where he would help plan the surgical contribution to the paediatric curriculum. In Newcastle he was involved with neonatal work and with children requiring particularly difficult surgical procedures. He also helped to establish neonatal paediatric surgery at the Newcastle Mater Misericordiae Hospital and had the distinction of performing the first neonatal operation at the John Hunter Hospital. Ian’s gentle sense of humour, matched by his courage, invariably won the day. In the somewhat stormy days during the establishment of the Medical School in Newcastle, he quietly retired from the academic arena, citing his reason as “preferring to deal with premature babies than immature professors”. After retirement, he helped in a voluntary capacity with the Hunter Orthopaedic School and the Tingira Centre for blind and deaf children.

Thirty years ago, when general practice surgeries were attached to doctors’ houses, there was generally someone around to help in emergencies, even at awkward times. One Saturday morning, when I was working alone, a boy aged about 7 was brought in to the surgery by his mother. He needed a penicillin injection, and when I asked his mother if she could hold him, she said “The last time he had a needle it took three people to hold him, so I’ll wait outside”. I went upstairs to the house and enlisted the help of my veterinarian son, who was home for the weekend. “I’ll show you how to hold him”, I said. “We learnt how to hold all animals,” he replied. So I left him to it. In keeping with the fashion favoured by vets at the time, my son had long ginger brown hair, a beard and a bushy moustache. He pinned the child to the examination couch with two ginger-haired hands and grinned at him through his beard. Hypnotised by this spectacle, the boy didn’t move, breathe or make a sound. When it was all over, I took him back out to his mother, who had not seen my son enter the consulting room from upstairs. The boy said to her “Was that a bear?”. I didn’t disillusion them. Doubtless, they still tell the story about the odd assistants employed by the funny woman doctor in Brisbane.

Alison Miller MB BS

Objectives: To ascertain changes in: women’s knowledge of the role of folic acid in the prevention of neural tube defects (NTDs); intake of folic acid among pregnant women; and prevalence of NTDs in South Australia.Design, setting and participants: Computer-assisted telephone interviews of South Australian households from 1994 to 2007 over a period encompassing a statewide folate promotion campaign (1994–1995), continuing folate promotion, as well as the introduction of voluntary folate fortification of foods (1996); ascertainment of the total prevalence of NTDs from births and terminations of pregnancy from 1966 to 2007.Main outcome measures: Changes in women’s knowledge of the role of folic acid in the prevention of NTDs; changes in the prevalence of NTDs.Results: From 1994 to 2006 and 2007, knowledge about the role of folic acid increased from 25% to 77% (P < 0.001) and knowledge that folic acid needs to be taken in the periconceptional period increased from 12% to 39% (P < 0.001). The proportion of pregnant women who increased their periconceptional intake of folate rose from 61% in 1998 to 81% in 2006 and 2007 (P < 0.001), with significant increases in the consumption of fortified cereals (from 15% to 29%) and folic acid tablets (from 37% to 64%). The total prevalence of NTDs fell from 2.06 per 1000 births in 1986–1990 to 1.23 per 1000 births in 2002–2007 (relative risk, 0.60; 95% CI, 0.48–0.74; P < 0.001).Conclusions: Folate promotion and voluntary fortification of certain foods with folic acid were associated with increased awareness of the role of periconceptional folic acid, increased folate consumption and a reduction in the prevalence of NTDs in South Australia by 40% (95% CI, 26%–52%).

Annabelle C Chan DPH, DCCH, FAFPHM · Phillipa van Essen BHSc, MPH · Heather Scott · Eric A Haan BMedSc, MB BS(Hons), FRACP · Leonie Sage RN, RM · Joan Scott RN, RM · Tiffany K Gill MAppSc, CertHealthEc, PostGradDipHlthSc · Anh-Minh T Nguyen BSc(Hons)

Objective: To describe the prevalence of neural tube defects (NTDs) in Victoria, and to evaluate women’s knowledge and awareness of the importance of folate after the introduction of voluntary food fortification.Design and setting: Descriptive study, set in Victoria, Australia, based on routinely collected data from the Victorian Birth Defects Register (VBDR) for 1998–2006, and responses by women aged 18–50 years to five questions relating to folate on the 2005 and 2006 Victorian Population Health Surveys (2314 and 2488 women, respectively). Main outcome measures: Prevalence of NTDs, and extent of women’s knowledge of the importance of folate in NTD prevention, comparing the period before and since voluntary food fortification and a folate awareness campaign.Results: The total prevalence of pregnancies affected by NTDs declined from approximately 17 to 14 per 10 000 births from 1997 to 1999 (coinciding with the period when voluntary food fortification was introduced, and a 1-year folate awareness campaign was held). It has since remained static. Over the 9-year study period, the termination of pregnancy rate was 79%, resulting in three NTD-affected babies per 10 000 livebirths. Compared with women aged 30–34 years (the reference group), those aged 20–24 years had the greatest likelihood of having a baby with an NTD (adjusted odds ratio, 1.70; 95% CI, 1.33–2.18; P < 0.001). Women aged 18–24 years had the lowest rate of folate supplement use (15.9% in 2006), while women aged 30–34 years had the highest rate (30.3% in 2006).Conclusions: There has been no further reduction in prevalence of NTDs in Victoria since 1999, and this prevalence remains well above that achievable through adequate folate intake. Accurate knowledge of folate consumption, population-based NTD prevalence data and folate awareness data are essential in monitoring the effectiveness of the mandatory fortification program to be implemented in Australia in the next 2 years.

Louise du Plessis BSc(Hons), MB ChB, FRACP · Rod W Hunt BM BS, MMed, PhD · Ashley S Fletcher BSc, MEpi · Merilyn M Riley BApplSc, GradDipEpi, Biostat · Jane L Halliday BSc, PhD

Chronic neonatal lung disease (CNLD) is defined as a supplemental oxygen requirement beyond 36 weeks’ postmenstrual age, with more severely affected infants requiring oxygen beyond a full-term-equivalent age. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who develop hypoxia in air. There is a lack of data on the most appropriate minimum mean target oxygen saturation (Spo2) level. Reflecting a variety of clinical practices and infant comorbidities (frequency of oxygen desaturation, presence of pulmonary hypertension, retinopathy of prematurity, and adequacy of growth), the minimum mean target range for Spo2 during overnight oximetry should be 93%–95%. The effect of supplemental oxygen on carbon dioxide retention should be considered before deciding on an oxygen flow. Most infants with CNLD are not ready for discharge until their supplemental oxygen requirement is ≤ 0.5 litres per minute delivered through a nasal cannula. The safety of short-term disconnection from supplemental oxygen should be assessed before discharge. Assessment of oxygenation during sleep with continuous overnight oximetry or polysomnography is recommended when weaning infants from supplemental oxygen. Discontinuation of oxygen therapy is based on clinical assessments and documentation of adequate oxygenation in room air. There is limited objective evidence on which to base recommendations.

Dominic A Fitzgerald MB BS, PhD, FRACP · R John H Massie MB BS, PhD, FRACP · Gillian M Nixon MB ChB, MD, FRACP · Adam Jaffe MD, FRCPCH, FRACP · Andrew Wilson MB BS, PhD, FRACP · Louis I Landau MD, FRACP · Jacob Twiss MB ChB, FRACP · Greg Smith MB ChB, FRACP · Claire Wainwright MB BS, MD, FRACP · Margaret Harris MB ChB, FRACP

To the Editor: Despite expert recommendation, Australian states have yet to enact legislation requiring use of child restraints beyond the age of 12 months. Our analysis of police crash records and linked hospital separation data for the period July 2000 to June 2001 in New South Wales found that a large proportion of children who were hospitalised following motor vehicle accidents were reported by police as having used adult (standard) seatbelts at the time of injury (Box). It is of particular concern that over 80% of 5–8-year-olds in this cohort were using standard seatbelts rather than child restraints (eg, booster seats). This pattern of premature “graduation” to seatbelts has also been reported in general populations of child motor vehicle passengers both overseas1 and in Australia,2 and also in presentations of child motor vehicle passengers after a crash to a NSW hospital’s emergency department.3 Child restraints are specifically designed to provide crash protection for children’s anthropometrical dimensions. Standard seatbelts are not designed to accommodate children, so they are unlikely to achieve the good fit to rigid body parts required for safety. Consequently, use of standard seatbelts by young children allows more head excursion during a crash, thereby negating their primary goal of protecting against central nervous system injury, and potentially causing Chance fractures and abdominal injuries.4 Our results provide further evidence that such seatbelt use may not protect, or may even cause injuries, during a crash. Child road trauma is largely preventable or controllable with the use of appropriate child restraints, including booster seats. A cost–benefit analysis showed that the use of booster seats produced a benefit–cost ratio for road trauma prevention of 9.4 (US$1854/US$197).5 To prevent child road trauma in Australia, all child motor vehicle passengers should use appropriate child restraints. Australian child road safety stakeholders recommend that child motor vehicle passengers use appropriate restraint systems according to their height, weight and age when travelling on road. Our findings provide further justification for proposed legislative changes that would require the compulsory use of appropriate child restraints for child motor vehicle passengers. Child restraint use among children (0–8 years) hospitalised for injury after a motor vehicle accident, compared with that of the general population, New South Wales Hospitalised children* General population† Restraint use 0–4 years 5–8 years Total 0–4 years 5–8 years Total Child restraint 9 (22%) 0 9 (10%) 295 (94%) 70 (31%) 365 (68%) Adult seatbelt 11 (27%) 42 (82%) 53 (58%) 12 (4%) 153 (67%) 165 (31%) Unknown/ no restraint 21 (51%) 9 (18%) 30 (33%) 6 (2%) 4 (2%) 10 (2%) Total 41 (100%) 51 (100%) 92 (100%) 313 (100%) 227 (100%) 540 (100%) * Linked hospital and police data from July 2000 – June 2001 were accessed from the NSW Injury Risk Management Research Centre. Case selection is based on corresponding codes in the International Classification of Diseases, 10th revision, Australian modification, 2nd edition. † Based on a telephone survey conducted in NSW during 2005–2006.

Wei Du · Caroline F Finch · Lynne E Bilston

Consensus recommendations for managing bronchiectasis in Indigenous children and adults living in rural and remote regions were developed during a multidisciplinary workshop and were based on available systematic reviews. Successful diagnosis, management and prevention of bronchiectasis in Indigenous Australians requires access to comprehensive health care services, as well as improved housing, education and employment and reduced poverty levels. Diagnosis of bronchiectasis requires a chest high-resolution computed tomography scan. Children who have bronchiectasis symptoms but non-diagnostic scans are described as having chronic suppurative lung disease (CSLD), rather than bronchiectasis. Untreated CSLD may progress to bronchiectasis. Chronic wet cough (> 4 weeks) or recurrent wet cough (> 2 episodes/year) are important but often under-reported symptoms. Bronchiectasis is suspected when chronic cough is excessively prolonged (> 12 weeks) or if a chest radiographic abnormality persists despite appropriate therapy. Intensive treatment aims to improve symptom control and quality of life while preserving lung function and reducing acute exacerbation frequency. Antibiotics should be prescribed for acute infective episodes according to culture results of respiratory secretions, local susceptibility patterns and clinical severity. Patients not responding promptly to oral antibiotics should be hospitalised for more intensive treatment. Ongoing care requires regular primary health care and specialist review, including monitoring for complications and comorbidities. Corticosteroids, bronchodilators and mucoactive agents may be used in individual cases, but routine use is not recommended. Physiotherapy and exercise should be encouraged, nutrition optimised, environmental pollutants (including tobacco smoke) avoided, and immunisations maintained.

Anne B Chang MPHTM, PhD, FRACP · Keith Grimwood MB ChB, FRACP, MD · Graeme Maguire MB BS, FRACP · Paul T King MB BS, FRACP, PhD · Peter S Morris MB BS, FRACP, PhD · Paul J Torzillo MB BS, FRACP

Objective: To determine whether a 5-day course of oral prednisolone is superior to a 3-day course in reducing the 2-week morbidity of children with asthma exacerbations who are not hospitalised.Design, setting and participants: Double-blind randomised controlled trial of asthma outcomes following a 5-day course of oral prednisolone (1 mg/kg) compared with a 3-day course of prednisolone plus placebo for 2 days. Participants were children aged 2–15 years who presented to the emergency departments of three Queensland hospitals between March 2004 and February 2007 with an acute exacerbation of asthma, but were not hospitalised. Sample size was defined a priori for a study power of 90%.Main outcome measures: Difference in proportion of children who were symptom-free at Day 7, as measured by intention-to-treat (ITT) and per-protocol analysis; quality of life (QOL) on Days 7 and 14.Results: 201 children were enrolled, and there was an 82% completion rate. There was no difference between groups in the proportion of children who were symptom-free (observed difference, 0.04 [95% CI, − 0.09 to 0.18] by ITT analysis; 0.04 [95% CI, − 0.17 to 0.09] by per-protocol analysis). There was also no difference between groups in QOL (P = 0.42). The difference between groups for the primary outcome was within the equivalence range calculated post priori.Conclusion: A 5-day course of oral prednisolone confers no advantage over a 3-day course for children with asthma exacerbations who are not hospitalised.Trial registration: Australian Clinical Trials Registry ACTRN012605000305628.

Anne B Chang MPHTM, PhD, FRACP · Ronald Clark PhD, FRACP · Theo P Sloots BSc, PhD · David G Stone FRACP · Helen L Petsky BN · Donna Thearle BN · Anita A Champion BPharm · Coralie Wheeler BN · Jason P Acworth FRACP

To the Editor: Spriggs and Gillam1 recently evaluated the updated guidance on ethical conduct in human research from the National Health and Medical Research Council (NHMRC),2 with particular reference to paediatric consent. The introduction in 2007 of the National Ethics Application Form (NEAF; http://www.neaf.gov.au) represented an attempt to streamline the process of obtaining ethics approval from multiple human research ethics committees (HRECs) for multicentre research. In 2007, just prior to mandatory introduction of the NEAF, we submitted identical NEAFs to 13 HRECs, covering all Australian states and territories, for an epidemiological study into childhood empyema. All but one HREC accepted the NEAF, but, despite use of the same form by the majority, we identified a variety of inconsistencies. With regard to child consent or assent, 11 HRECs required a single child information sheet and consent form; one required two separate age-appropriate forms; and one questioned the planned involvement of children in the consent/assent process and did not require a child’s consent. This latter response arguably contravenes the United Nations Convention on the Rights of the Child, which provides for a child’s right to information in a form they can comprehend, whether or not they have the ability to make decisions.3 Other inconsistencies included the time taken to obtain approval, which ranged from 1 day to 197 days (median, 31 days). One HREC defined a child as being aged less than 18 years; the others used a cut-off of 16 years. One HREC responded that the application did not specifically address local Aboriginal and Torres Strait Islander peoples’ issues, which suggests that the NEAF may not be sufficient to cover such site-specific requirements. One HREC required plain-language translation of consent and information sheets, and another required Aboriginal translation. Also of concern, the NEAF requires justification for the inclusion of Aboriginal or Torres Strait Islander children and other groups where ethical considerations may be different, such as children with intellectual impairment or mental illness. This approach places the wrong emphasis on the desired outcome, which is to give due consideration to cultural, social, health, psychological and local issues that may introduce ethical concerns that are not the same for all children, and it risks exclusion of some children from research that is relevant to them. We suggest the NEAF should instead include a justification for exclusion of any children as a result of cultural or religious background or social or psychological problems. This would provide an alternative way of gathering information about ethically relevant issues, to ensure best practice in ethical conduct or research. Clearly, there is a lack of consistency across Australia in engaging children in research, including the consent/assent process. We believe that use of the NEAF alone is insufficient to rectify these inconsistencies, and now is the time to consider a single national ethics committee for Australia, similar to the National Research Ethics Service recently introduced in the United Kingdom (http://www.nres.npsa.nhs.uk).

Adam Jaffe · Roxanne E Strachan · Katrina J Williams

To the Editor: We read with interest Rey’s interpretation of the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (MTA).1 The MTA was a large randomised study comparing the impact of stimulant medication, behavioural treatment, a combination of the two, and standard community care on attention deficit hyperactivity disorder (ADHD).2 The treatment phase lasted 14 months, during which the children taking medication showed more improvement than the other groups. Participants were then allowed to change their treatment and, at 36-month follow-up, the outcomes in all groups were similar. Rey concluded that, if stimulant medication is not associated with sustained improvement, its place in the treatment of ADHD is limited. This conclusion overlooks two important points. First, the greater initial improvement in symptoms of ADHD associated with stimulant medication might be important both clinically and socially. The second point is the expected impact of a relatively brief intervention: is it really plausible that an independent effect of 14 months of controlled treatment will be detectable after a further 22 months of self-selected management? The observation that the 14-month treatment phase becomes progressively less relevant as time passes is perhaps not altogether unexpected. In the unmedicated group, the 23% non-compliance rate during the 14-month treatment phase indicated greater dissatisfaction with treatment than the 10% non-compliance in the medication groups (P < 0.005, χ2 test). This could imply a parental preference for more immediate relief of symptoms, even if it involves their child taking medication. Parental preference can be accommodated if the family and treating physician discuss and agree on a treatment plan, adjusted to optimise functioning. Far from indicating a diminished role for medication, the evidence from the MTA study suggests that the clinical approach would involve most individuals with ADHD being treated with stimulant medication at some stage. Stimulant medication treats symptoms; it is not curative. It is likely that the role of stimulant medication in the treatment of ADHD decreases as children mature. However, temporary relief of symptoms can be highly valuable for affected children and their families.

Alison Poulton · Ralph K H Nanan

In reply: Poulton and Nanan question my statement that the role of psychostimulant medication in attention deficit hyperactivity disorder (ADHD) becomes less prominent when the 3-year results of the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (MTA) are taken into account.1 Studies such as the MTA that report dramatic short- to medium-term improvement have, in my experience, increased practitioners’ expectations and reliance on these medications. Their clinical use has gradually widened to preschool-aged children and to the, so far, poorly validated inattentive and impulsive–hyperactive subtypes of ADHD. I observe this increasing the pressure on parents — not necessarily from clinicians — to use stimulants through an emphasis on the consequences of non-treatment, such as underachievement and conduct problems. The 3-year follow-up of the MTA brings the early findings into perspective: a carefully titrated medication regimen produces no better results 3 years later than behavioural treatment and standard community care.2 In that sense, the role of stimulants versus other interventions has shrunk, and conscientious practitioners will inform parents and children of these findings when examining treatment options. My editorial did not query the many short-term benefits of stimulants but raised questions about when, and for how long, they should be used. Poulton and Nanan rightly emphasise that stimulants are a “symptomatic” treatment. Further, stimulants increase the ability to concentrate and be on task whether or not individuals meet criteria for ADHD.3 This is further compounded because ADHD, like intellectual disability in the case of intelligence, represents the extreme of a dimension of behaviour.4 The boundary between illness and non-illness depends on where you draw the line, not on qualitative differences. However, there is no good tool to measure ADHD, unlike intelligence, and asessment depends on clinicians’ thoroughness and skill, and on informants, who may or may not be reliable. The situation with ADHD is also similar to that for nocturnal enuresis, another disorder that lessens with increasing age, although it may persist. While behavioural treatment (the bell and pad alarm) is effective for enuresis, families and clinicians prefer using medication, even though the latter is “symptomatic” treatment and potentially harmful.5 This may be an alternative explanation for the higher non-compliance rate in the non-medicated group: behavioural treatments place more demands on parents, children and schools than a pill.

Joseph M Rey

Two children with advanced lung disease underwent successful cadaveric bilateral lobar lung transplantation, using lungs “cut down” from deceased adult donors — the first reported use of the technique in Australia. This approach, while it cannot address the lack of donor organs, may enable us to redress any size bias limiting paediatric lung transplantation. Clinical recordsPatient 1A previously healthy 9-year-old girl presented in early 2007 with an upper respiratory tract infection that progressed over 10 days to respiratory failure, requiring intubation and ventilation with high inspiratory pressures. Subsequent tracheal aspirates were positive for Mycoplasma (by polymerase chain reaction), with consistent serological results (antibody titres, 1 : 640). Computed tomography of the chest demonstrated widespread bronchiectasis (Box 1, A). Although she was extubated 6 weeks after initial presentation, she remained in hypercapnic respiratory failure (Pco2, 80 mmHg), requiring continuous oxygen supplementation (5 L/min) and bilevel non-invasive positive-pressure ventilation (BiPAP). She was listed for lung transplantation in May 2007, but, given the severity of her lung disease and in the absence of appropriately matched donor organs, the transplant team gave early consideration to cadaveric bilateral lobar transplantation using an adult “oversized” donor. This was performed in August 2007. Patient 2A 13-year-old girl with cystic fibrosis was referred for consideration of lung transplantation. She had been diagnosed with cystic fibrosis at birth (Δ508 homozygous, without liver, sinus or diabetic sequelae), and over the preceding 2 years developed progressive bronchiectasis (Box 1, B), necessitating supplemental oxygen and initiation of nocturnal BiPAP. She was initially listed for either lung transplantation or heart–lung transplantation; however, after 9 months of progressive respiratory failure (Pco2 increased to 46 mmHg; forced expiratory flow in 1 second [FEV1], 16%; forced vital capacity [FVC], 28% predicted), the transplant team considered cadaveric bilateral lobar transplantation, which was performed in September 2007. Surgical procedure and clinical courseBoth children underwent cadaveric bilateral lobar transplantation as described by Starnes and colleagues1 for living-related lung transplantation. Briefly, the donor right lower lobe was resected, and the right upper and middle lobes were implanted, the anastomosis being performed at the right main bronchus. On the left, the inferior pulmonary vein, interlobar artery distal to its lingular branch, and bronchus were transected, and the lower lobe removed. Size mismatch was compensated for by seating the donor bronchus inside the recipient bronchus, while pulmonary vessel mismatch was taken up in the suture lines. Neither patient required cardiopulmonary bypass, and resected lobes were not used further. Following surgery, both children were established on an internationally standardised immunosuppression regime, comprising prednisolone, tacrolimus and mycophenolate mofetil.2 Both patients made a good postoperative recovery, with short intensive care unit stays. Patient 1 required a longer inpatient stay for treatment of pneumonia. Neither patient developed allograft rejection, and lung function gradually improved (Box 2). Both patients were discharged to their respective tertiary hospitals for continuing follow-up. Both patients were well and without complication at follow-up 10 and 9 months postoperatively, respectively. DiscussionTo our knowledge, these are the first reported cases of cadaveric bilateral lobar transplantation in Australia. They demonstrate its efficacy as a means of reducing waiting-list mortality for paediatric lung transplantation recipients. Lung transplantation is now an established treatment for patients with severe end-stage lung or pulmonary vascular disease. Despite attempts to increase organ donation worldwide, the number of patients requiring lung transplantation far exceeds the availability of donor lungs. In Australia, this is of particular concern for children awaiting appropriate size-matched donor organs.3 Review of the Australian and New Zealand Organ Donation Registry between 2002 and 2006 revealed that very few lungs are retrieved from paediatric donors younger than 14 years (26/497 lung donors).4 The number of children with severe lung disease warranting consideration of lung transplantation, both globally and in Australia, is, fortunately, very small. The most recent data from the International Society for Heart and Lung Transplantation show that only 65 paediatric lung transplantations were performed worldwide in 2005.2 However, of concern is that waiting-list mortality is greater for children than for adults — a worrying trend as fewer paediatric lung transplantations have been performed per annum, while adult lung transplantation numbers have increased.5 In Australia during 2006, 181 donor lungs were offered for lung transplantation, with only seven paediatric donors contributing, all of whom were aged 6–14 years (Ross Pettersson, Australian and New Zealand Cardiothoracic Organ Transplant Registry and Heart Transplant Data Manager, St Vincent’s Hospital, Sydney, NSW, personal communication). Despite an active policy of utilising “extended” donor organs (eg, from older donors or donors with previous cancer, smoking or aspiration history) wherever possible, only 30%–50% of available lungs are actually suitable for transplantation,6 further diminishing the number of available donor lungs, which is low by international standards.7 In the absence of appropriately size-matched organs, children from our institution have died while on the waiting list (2/9 listed in 2000–2007); after reviewing the 2007 donor referrals, it became apparent that the children described here would most likely have died while waiting. Minimising paediatric waiting-list mortality requires consideration of non-traditional donor sources, such as live donors, who have been used in small numbers in the United States and Japan.8 The technique involves a bilateral lobar transplantation, typically taking one lobe from each of two larger, usually related, adult donors. Outcomes for living-donor bilateral lobar transplantation are similar to cadaveric lung transplantation, but there are significant ethical and technical issues with such an approach, and a potential 300% mortality rate. The number of these procedures being performed is declining.5 To our knowledge, no centre presently offers this service in Australia. In adults, cadaveric lungs have been cut down to facilitate lung transplantation where size mismatch between donor and recipient could prevent transplant.9 Typically, this involves non-anatomical “lung shaving” or anatomical lobar resection. Rarely is this a bilateral extensive procedure, given the potential complications, including persistent air leaks, airway stenoses and stump dehiscence. Lobar transplantation is not specific to lung transplantation and has become common practice in liver transplantation; lessons may be learned from these experiences.10 Paediatric lobar transplantation has not been widely performed outside of the living-related scenario, but despite the additional surgical complexity, outcomes have proven comparable to cadaveric lung transplantation.8,9 Starnes and colleagues’ work suggests our two patients can be expected to ultimately achieve near-normal lung function,11 and their total lung capacity will increase as they grow.12 Cutting down cadaveric adult donor lungs for use in paediatric recipients raises ethical and practical issues about removing donor lungs from an already insufficient adult pool. Should lungs that might “perfectly” match an adult be cut down for a paediatric patient? Is a child more deserving than an adult? Our approach to reducing waiting-list mortality is to perform transplantation on recipients with the most severe lung disease at the first opportunity, and both these children satisfied that criterion. In conclusion, our cases illustrate the difficulty experienced by many centres in acquiring an adequate number of donor lungs to service the needs of the paediatric lung transplantation waiting list. Using cut-down adult donor lungs had a good outcome in both our patients. Such an approach is likely to expand the donor pool available for children needing lung transplantation, thereby reducing the high waiting-list mortality experienced by this age group. 1 Computed tomography scans of the two patients’ lungs before transplantation A: Patient 1 had cysts and lung destruction after Mycoplasma infection (arrows). B: Patient 2 had severe cystic fibrosis-related bronchiectasis (arrows). 2 Clinical course after cadaveric bilateral lobar transplantation in two children Patient ICU days Hospital days Respiratory infection in first 3 months Biopsy (ISHLT grade) 30 days 90 days 180 days FEV1 (% pred) FVC (% pred) FEV1 (% pred) FVC (% pred) FEV1 (% pred) FVC (% pred) 1 2 27 Pseudomonas, Staphylococcus A0 0.89 (40%) 0.90 (37%) 1.02 (46%) 1.33 (54%) 1.26 (55%) 1.81 (78%) 2 2 11 Staphylococcus A0 1.12 (72%) 1.27 (71%) 1.17 (75%) 1.45 (81%) 1.11 (63%) 1.66 (94%) ICU = intensive care unit. ISHLT = International Society for Heart and Lung Transplantation. FEV1 = forced expiratory flow in 1 second. pred = predicted. FVC = forced vital capacity.

Dominic T Keating MD, MRCPI · Glen P Westall FRACP, PhD · Silvana F Marasco MS, FRACS · Jacquie H Burton DipAppSci(Nursing), BN, GradDipPaed · Mark R Buckland MB BS, FANZCA · Colin F Robertson MSc(Epi), MD, FRACP · Trevor J Williams MB BS, FRACP, MD · Gregory I Snell MB BS, FRACP, MD

To the Editor: Australian consensus guidelines for selecting formulas for infants with cows milk protein allergy (CMPA) have recently been published.1 We reviewed formula choices and outcomes for 51 children with immediate allergic reactions to cows milk protein who were referred to one of us (S S M) in a tertiary specialist clinic over a 2-year period before the guidelines were published. The formula was selected by the referring specialist medical practitioner in 44 cases (and by S S M in the other seven). Of the 51 children (mean age at initial reaction to cows milk protein, 7.8 months), 42 had skin and/or gastrointestinal features, and nine had an anaphylactic reaction with respiratory and/or cardiac features. Forty-six children had a positive skin prick test to cows milk protein, and one had a positive radioallergosorbent test. Four children with immediate (< 30 min) reactions of generalised erythema and/or angioedema (3) or vomiting (1), but a negative skin prick test, were also included. Soy was the most common formula used, followed by extensively hydrolysed formula (EHF) (Box). Three of eight children commenced on EHF had allergic reactions, with urticaria and angioedema, and one child also had a transient (60 s) cough. Three children were given partially hydrolysed formula (PHF), with one experiencing an immediate cutaneous reaction. These observations suggest that, in clinical practice, soy is frequently a satisfactory first choice for children with CMPA, as suggested in the guidelines.1 Some children with CMPA will also react to EHF, providing a rationale for choosing amino acid-based formula as a first-line treatment prior to allergy evaluation in children with anaphylaxis to cows milk protein. As about 5% of infants with CMPA also react to EHF,2 some allergists advocate the introduction of EHF under medical supervision in either all children with immediate CMPA3 or only those who have had severe life-threatening reactions.4 Although PHF is tolerated by a significant proportion of children (70%) with immediate CMPA,3 it is not recommended for the treatment of CMPA1 due to its high content of potentially allergenic cows milk protein. The fact that three children with CMPA were given PHF suggests there is confusion in the prescribing community, and that the availability of the new guidelines may help in achieving a more appropriate choice of formula. Feeding choice for 51 children referred with cows milk protein allergy Type of feeding selected No. of children Mean age at initial reaction to cows milk (months) No. who reacted to selected feeding Soy 29 9.5* 0 Extensively hydrolysed formula (EHF) 8 5.3 3 Amino acid-based formula (AAF) 6 4.2 0 Partially hydrolysed formula (PHF) 3 6.0 1 Breastfeeding 5 6.0 0 * P < 0.05 for soy versus PHF, EHF, AAF or continuing to breastfeed (t test).

Sam S Mehr · Andrew S Kemp