Child health

Research into adolescent health issues is hampered by absolute requirements for parental consent. Society’s recognition of adolescents’ autonomy and decision-making capacity has been embodied in the legal recognition of the mature minor’s right to make decisions on matters affecting his or her life. Psychological research indicates that young people from 14 years have decision-making capacity. US and UK research ethics guidelines acknowledge the mature-minor principle, but Australian guidelines are out of step with international practice. An absolute requirement for parental consent in Australian research ethics guidelines is potentially unethical if it denies mature adolescents’ autonomy and is a barrier to participation, study validity and improved health outcomes through research findings. There are grounds for considering a mature-minor clause in the National Health and Medical Research Council research ethics guidelines, particularly in the context of youth participation in minimal-risk research.

Lena A Sanci MB BS, PhD, FRACGP · Susan M Sawyer MB BS, MD, FRACP · Penny J Weller BA/LLB, MA, PhD · Lyndal M Bond BA(Hons), MA, PhD · George C Patton MB BS, MD, FRANZCP

Clinical records Patient 1 A 5-month-old girl presented with biphasic stridor (ie, stridor present during inspiration and expiration) and feeding difficulties since birth. The stridor was not related to her position or to her level of wakefulness. Asthma treatment with bronchodilators, inhaled corticosteroids (up to 500 μg/day fluticasone propionate) and courses of oral steroids were prescribed by several doctors from 6 weeks of age for her “noisy breathing”. These treatments did not alter her symptoms. No investigations were undertaken. There was no significant perinatal or other medical history. The child appeared well; she was thriving and her development was appropriate for her age. The biphasic stridor was not associated with wheeze or tachypnoea. She had mild tracheal tug and chest wall recession. Her chest was clear, and the findings from the remainder of the examination were normal. A chest x-ray (CXR) showed a right aortic arch and reduced air–tissue interface at the carina, consistent with tracheomalacia. A barium swallow showed a posterior indentation of the mid-oesophagus, suggestive of a vascular ring (extrinsic compression of the oesophagus and trachea by aberrantly sited blood vessels [Box 1]). Bronchoscopy confirmed these findings and showed significant reflux oesophagitis. A magnetic resonance angiogram confirmed the presence of a vascular ring formed by a double aortic arch, with each arch giving rise to its own common carotid and subclavian arteries. Surgical correction of the compressive vascular band on the trachea 3 days later was uneventful. The proton pump inhibitor omeprazole was prescribed for the reflux oesophagitis, but this proved insufficient. After further hospitalisations for pulmonary aspiration, a fundoplication was performed and a gastrostomy tube inserted. Twelve months later, she remains asymptomatic with normal growth. Patient 2 A 9-week-old girl presented with biphasic stridor and a 3-week history of intermittent central cyanosis associated with feeding. She was noted to have had “noisy breathing” from birth. At age 6 weeks, she had been admitted to another hospital with cough and more prominent biphasic stridor. Her respiratory difficulties were attributed to bronchiolitis caused by respiratory syncytial virus. She required supportive treatment including oxygen for 5 days in hospital. On discharge, she improved, but continued to have very noisy breathing, which was worse when she was active or feeding. She was bottle fed with infant formula and noted to have occasional episodes of transient cyanosis during feeding. On examination, she appeared well and was thriving. She had a moist cough, moderate subcostal recession and audible biphasic stridor. A CXR showed a left, normally sited aortic arch and poor delineation of the distal tracheal air column suggestive of tracheomalacia. A barium swallow (Box 2A) showed significant oesophageal compression anteriorly and posteriorly, consistent with a double aortic arch. A magnetic resonance angiogram (Box 2B) confirmed the presence of the double aortic arch, as well as extrinsic, anterior compression of the distal trachea. Bronchoscopy, performed before surgery to divide the vascular ring, showed mild tracheomalacia. The infant was discharged a week later with reduced stridor and recession. No further episodes of central cyanosis with feeding occurred during the 6-month follow-up period after surgery. Biphasic stridor from birth or early infancy suggests fixed proximal airway obstruction, which may be intra- or extrathoracic. Conversely, variable inspiratory stridor suggests a less severe, extrathoracic, dynamic obstruction. Patients with biphasic stridor (such as that caused by a vascular ring) are often initially misdiagnosed as having asthma because of noisy respirations, although stridor is never a sign of asthma, but rather of proximal airway compromise. Stridor differs from wheeze in that it has a different pitch and harsher sound than the more musical pitch of a wheeze. Stridor is heard predominantly during inspiration. Children with a vascular ring usually present in infancy with non-specific symptoms of dyspnoea, cough, inspiratory or biphasic stridor, and sometimes an expiratory “wheeze” (presumably related to downstream obstruction of the intrathoracic trachea) as well as feeding problems.3-5 A vascular ring occurs when one or more aortic arch abnormalities, with or without a patent ductus arteriosus or ligamentum, produce a ring that completely encircles the trachea and oesophagus, leading to symptoms of tracheal or oesophageal compression6 (Box 1). Differential diagnosesThe differential diagnosis of persistent biphasic stridor in an infant includes severe laryngomalacia, tracheomalacia and, less commonly, vocal cord paresis (causing a hoarse cry), subglottic haemangioma (causing rapidly progressing stridor, sometimes associated with a facial haemangioma) and vascular ring. Laryngomalacia is the most common cause of neonatal inspiratory stridor, but is an unlikely cause of biphasic stridor from birth, unless it is very severe. Stridor in laryngomalacia more commonly occurs after several weeks of age, is usually limited to inspiration and varies with posture and airflow (eg, it is louder with crying). Signs usually gradually resolve without treatment by 12 to 18 months of age.7 Tracheomalacia, a condition characterised by weakness of the tracheal walls and supporting cartilage (localised to the region of external compression by blood vessels), commonly occurs in association with lesions such as a vascular ring and persists for several years until the tracheal cartilage firms. The formation of the ring depends on the preservation or deletion of specific segments of the rudimentary aortic arch complex, or the presence of major arteries with anomalous origins or remnants (eg, ligamentum arteriosum) compressing the trachea and oesophagus. The double aortic arch is the most common form of vascular ring,4 and is characterised by persistence of both embryonic aortic arches, with separate carotid and subclavian arteries originating from each arch. The ascending aorta bifurcates anterior to the trachea to form the aortic arches, and each courses either right or left of the trachea and the oesophagus. The larger of the two arches usually crosses posterior to the oesophagus and unites with the other arch in the posterior mediastinum to form the single descending aorta. This can be seen as a posterior indentation on the mid-oesophagus on a barium swallow (Box 2A). When biphasic stridor is detected in an infant, a chest x-ray (CXR) and a barium swallow are simple initial investigations that together will usually confirm or exclude a vascular ring as the underlying cause.8-10 The CXR may show a right-sided aortic arch, a poorly visualised distal trachea, or another cause for tracheal compression or deviation (eg, a mediastinal mass). A barium swallow may show abnormal indentations on the posterior oesophageal wall. If these abnormalities are detected, referral for more detailed investigations (including bronchoscopy and magnetic resonance angiography) and treatment is appropriate.11,12 Tracheomalacia may occur in isolation, and the diagnosis often relies on the bronchoscopist’s interpretation of the airway calibre and shape at bronchoscopy. ManagementAfter surgical treatment for a vascular ring, it is essential that the child’s parents receive ongoing management advice, as tracheomalacia will persist, and there is therefore an increased risk of severe croup. The child may continue to display noisy breathing for a period of a few months to several years13 and should be followed up until school age. In school-age children, any residual inspiratory flow limitation can be quantified using inspiratory flow volume loops with spirometry. Residual tracheomalacia commonly results in difficulty clearing airway secretions (impaired mucociliary clearance) through the functionally narrowed section of trachea at the site of the previous extrinsic wall compression. This may manifest as a brassy, rattly cough that persists longer than expected after a viral infection. It would be appropriate to consider influenza and pneumococcal vaccination in these children. Lessons from practice Stridor is never a feature of asthma and can be differentiated from wheezing by its predominance during inspiration, its harsher sound and different pitch. Biphasic stridor suggests fixed intra- or extrathoracic proximal airway obstruction. Any infant with biphasic stridor should have a chest x-ray and a barium swallow to detect the presence of a rare congenital anomaly in which aortic arch or large blood vessel abnormalities produce a ring encircling and compressing the trachea and oesophagus. Management of patients with vascular ring must include postoperative advice concerning the ongoing tracheomalacia and the associated risk of croup, as well as possible continuation of noisy breathing and impaired mucociliary clearance, which may prolong a viral-induced, rattly cough. 1: A double aortic arch (as in Patient 1) The simplified anatomy of a double aortic arch, which produces a vascular ring encircling the trachea and oesophagus, causing symptoms of tracheal or oesophageal compression. 2: Investigations for biphasic stridor (Patient 2) 2A: Barium swallow, showing anterior (arrow A) and posterior (arrow B) compression of the oesophagus, together with a posterior bulge (arrow C) caused by a double aortic arch. 2B: Magnetic resonance image, showing the double aortic arch — superior vena cava (A), brachiocephalic vein (B), pulmonary arteries (C, D), prominent left aortic arch (E), and smaller right aortic arch (F).

Sami Spencer · Belinda H Yeoh MB BS · Peter P Van Asperen MD, FRACP · Dominic A Fitzgerald MB BS, PhD, FRACP

Can we solve a riddle by burying an illusion? Over the past 40 years, the prevalence of asthma appeared to rise inexorably in both the developed and the developing world. So the report by Robertson and colleagues in this issue of the Journal (page 273), showing a decline in reported symptoms in children since 1993,1 is to be warmly welcomed. It comes with supporting evidence, in the form of reduced hospital admissions for asthma in Victoria, but also with a catch. The prevalence of reported hay fever and eczema has increased over the same period. Why the prevalence of asthma increased and why it may now be stabilising or declining is baffling. Robertson et al suggest one possibility may be the increased use of daycare facilities. The “hygiene hypothesis” — the inverse relationship between microbial or infection exposure and allergic disease — was first suggested by Gerrard et al while studying allergic disease in the Metis Indian community in Canada.2 Strachan refined this observation from large UK cohorts, in which he found an inverse relation between the number of older siblings and the prevalence of hay fever, but not asthma.3 He emphasised that the link was through atopy to allergic disease. Several studies have subsequently shown reduced asthma prevalence in school-aged children with early daycare attendance. These children tend to show more early wheezing, but less asthma later on. The proposed explanation is that they contract more upper respiratory tract infections from close contact with children, and this leads them to have more early wheezing, but, in turn, protects them from later developing atopy and atopic disease. This explanation seems less likely in the study by Robertson et al, given that the prevalence of hay fever and eczema increased while asthma prevalence decreased. However, one would need to know the atopic status of the children to clarify the issue. The 26% reduction in current wheeze prevalence in Melbourne, while significant, is within the range found in Australia in phase 1 of the International Study of Asthma and Allergies in Childhood (ISAAC) study. For example, in the four Australian centres that took part, there was a 19% difference between the highest and lowest prevalence. For sleep disturbance and speech limitation, this was 40%.4 There is even greater variation in large cities. In Mumbai (Bombay), for example, reported current wheeze varied by more than 100% in different parts of the city. Large cities are not homogeneous, with large variations in many factors that may affect wheezing, such as housing conditions, smoking prevalence, diet and variable access to healthcare. Over time, with gentrification and changes in zoning, factors may vary even in the same narrow geographic location. Robertson et al also note that awareness of asthma in the community is a determinant of the prevalence of reported symptoms. The pool of individuals with a history of symptoms in any population will be larger than the proportion who report symptoms in a defined period. In a resurvey of 700 young adults, all of whom had 4 years previously responded positively to at least one of three asthma questions, only two-thirds reported symptoms. In the first survey, 28% had responded positively to all three questions, and in the second, 29%. However, only 60% were the same individuals.5 Just how large this pool is has recently been clarified, at least in New Zealand. In a 26-year follow-up of a birth cohort in Dunedin, 73% reported wheezing on at least one occasion and 51% on at least two.6 Given that there is likely to be some loss to recall, wheezing at some time between birth and adulthood appears virtually universal. Clearly, most of this wheezing is occasional, trivial, inconsequential, and a normal phenomenon. It is now easy to see how a change in diagnostic and hence societal emphasis on wheezing, as opposed to bronchitis, with attendant changes in treatment, can enhance recall for asthma in cross-sectional surveys. Perhaps this emphasis is now stabilising and the diagnostic label “asthma” is being applied slightly less frequently in Melbourne. The strengths of the ISAAC approach — simple questionnaires requiring minimal funding — allow large-scale international comparisons of children (in fact, this is the only way that such large population studies can be conducted), but interpreting relatively small changes over time in a very asthma-“savvy” environment like Australia is more difficult. Although the ISAAC approach clearly shows that reported asthma symptoms are far more frequent in Australia, New Zealand and the United Kingdom compared with, say, Albania or India (more than 10-fold), smaller differences over relatively short time intervals in individual countries are harder to interpret. In the past 30 years there have been many cross-sectional studies reporting an increase in the prevalence of asthma symptoms over time. In only two has this been accompanied by measures of airway hyperresponsiveness. In the first, in the United Kingdom, Burr et al showed that current asthma symptom reporting had doubled over a 15-year period, but exercise-induced fall in peak expiratory flow rate had not changed.7 In the second, Peat et al showed a doubling of current symptoms and airway hyperresponsiveness, predominantly among atopic children, suggesting an increase in asthma relating to greater allergen exposure.8 There is a real need for the measurement of objective markers over time in similar populations. The advent of easily obtainable markers of airway inflammation, such as exhaled nitric oxide or constituents of breath condensate, may allow population studies of airway inflammation to be quantified and tracked over time. Perhaps it is time to abandon our inconvenient population model of asthma as a disease, just as doctors did for essential hypertension in the 1950s.9 Nature provides no obvious support for asthma and we can neither define nor measure it accurately; indeed, it remains a mystery because it is largely an illusion. The late Geoffrey Rose (Professor of Epidemiology at the London School of Hygiene and Tropical Medicine) suggested that we should seek the answers to “disease” by exploring populations rather than atypical minorities.10 We need to consider applying this concept to airway inflammation. Now that appropriate tools are becoming available, we should measure airway inflammation and airway responses in large populations and explore the environmental and genetic factors that affect the airway at a population level. This might reveal that it is not just the upper end of the distribution of airway inflammation (which we arbitrarily and inconsistently call asthma) that varies by environment, and over time, but the whole distribution. In the meantime, Robertson and colleagues have shown that parent-reported asthma symptoms of young Melbourne children have declined in the past decade. This may or may not be an early signal for a real decline in asthma prevalence. What it does suggest is that asthma prevalence has not increased, which in itself is a welcome observation.

Julian Crane MB BS, FRCP, FRACP

Objective: To determine the change in prevalence of asthma, eczema and allergic rhinitis in Australian schoolchildren between 1993 and 2002.Design: Questionnaire based survey, using the protocol of the International Study of Asthma and Allergy in Childhood.Setting: Metropolitan Melbourne primary schools within a 20 km radius of the GPO in 1993 and 2002.Subjects: All children in school years 1 and 2 (ages 6 and 7) attending a random sample of 84 schools in 1993 and 63 schools in 2002.Main outcome measures: Parent-reported symptoms of atopic disease; treatment for asthma; country of birth.Results: There was a 26% reduction in the 12-month period prevalence of reported wheeze, from 27.2% in 1993 to 20.0% in 2002. The magnitude of reduction was similar for boys (27%) and girls (25%). The 12-month period prevalence of reported eczema increased from 11.1% in 1993 to 17.2% in 2002, and rhinitis increased from 9.7% to 12.7%. There were reductions in the proportion of children attending an emergency department for asthma in the previous year (3.6% to 2.3%), the proportion admitted to hospital (1.7% to 1.1%) and the proportion taking asthma medication (18.5% to 13.4%). Of those who reported frequent wheeze, there was an increase in the proportion taking regular inhaled steroids (34.5% to 40.9%).Conclusion: There has been a significant reduction in the prevalence of reported asthma in Melbourne schoolchildren, whereas the prevalence of eczema and allergic rhinitis has continued to increase.

Colin F Robertson MD, FRACP · Mary F Roberts BAppSci · Johanna H Kappers BNursSci

Objectives: (i) To evaluate the benefits and adverse effects of a Diabetes Day Care Program (DDCP); and (ii) to compare outcomes in two cohorts diagnosed before and after implementing the DDCP (“pre-DDCP” and “post-DDCP”).Design: Outcomes from the pre-DDCP cohort were compared with those of the post-DDCP cohort.Setting: The study was conducted from March 2001 to October 2002 at the Children’s Hospital at Westmead.Participants: The pre-DDCP cohort comprised all children newly diagnosed with type 1 diabetes from March 2000 to November 2000 (n = 49). The post-DDCP cohort were those diagnosed from November 2000 to August 2001 (n = 61).Main outcome measures: Length of stay, adverse events, insulin requirement and glycohaemoglobin (HbA1c) level over the first year after diagnosis were ascertained from medical records. Questionnaires to measure parents’ knowledge of diabetes, emotional adjustment to diabetes, and responsibility for and conflict over specific diabetes management tasks were completed by parents at 6-monthly intervals.Results: Median length of hospital stay decreased from 5.14 days (range, 2–10) to 1.70 days (range, 0–10) (P < 0.001). There were no differences between the two cohorts in insulin requirement at 12 months (pre-DDCP: 0.9 U/kg [95% CI, 0.8–1.0]; post-DDCP: 0.8 U/kg [95% CI, 0.7–0.9]; P = 0.22), HbA1c level at 12 months (pre-DDCP: 8.4% [95% CI, 8.0%–8.9%]; post-DDCP: 8.2% [95% CI, 7.9%–8.5%]; P = 0.37) and adverse events over the first year after diagnosis. Both groups reported similar scores for the parental questionnaires.Conclusions: Ambulatory stabilisation of children with type 1 diabetes provides similar metabolic outcomes for the child, and comparable levels of diabetes knowledge and similar psychosocial outcomes for the family, to inpatient stabilisation programs.

Shubha Srinivasan MB BS, FRACP · Maria E Craig FRACP, PhD · Linda Beeney PhD · Rachel Hayes MND · Nuala Harkin RSCN, APN · Geoffrey R Ambler FRACP, MD · Kim C Donaghue FRACP, PhD · Christopher T Cowell MB, FRACP

Objective: To determine changes in morbidity and management of disease in children in Australian general practice.Design and setting: A comparative study of general practice consultations in children under 15 years, using data from cross-sectional general practice surveys (1990–91 and 2000–01), and a descriptive comparison with a similar study from 1971.Main outcome measures: Relative rates of management (rate/100 general practice encounters) of the most common children’s problems and treatments.Results: Problems with significantly higher management rates in 2000–01 compared with 1990–91 included vaccination (11.1 v 7.6 per 100 encounters in 1990–91) and contact/allergic dermatitis (3.1 v 2.5). Those managed significantly less often in 2000–01 v 1990–91 included acute otitis media (7.7 v 9.4), asthma (5.4 v 8.8), tonsillitis (4.4 v 6.0), acute bronchitis (3.8 v 5.3) and gastroenteritis (1.7 v 2.7). Asthma management rates rose from 2.4% of all problems managed in 1971 to 7.2% in 1990–91, then fell in 2000–01 to 4.6%. More frequent rates of counselling and advice in 2000–01 (28.4% of encounters v 22.9% in 1990–91) were associated with a decrease in rates of prescribing and supply of medication (56.6% of encounters v 64.3% in 1990–91). Antibiotic prescribing declined significantly (from 33.8 per 100 encounters in 1990–91 to 25.2 in 2000–01), as did prescribing of respiratory medications (from 15.5 to 9.9 per 100 encounters), while prescribing of vaccines and systemic corticosteroids doubled (from 9.6 to 18.8 per 100 encounters, and from 0.6 to 1.2, respectively). (All comparisons between 1990–91 and 2000–01 are significant at P < 0.01.)Conclusions: These findings point to the emergence of a generation of Australian children who are generally well vaccinated and are less likely to present to GPs with “traditional” childhood illnesses.

Janice Charles BA, MSc(Med) · Ying Pan MCH · Helena Britt BA, PhD

Paul Walker Paediatric Otolaryngologist, John Hunter Children’s Hospital, PO Box 293, New Lambton, NSW 2305; and Conjoint Associate Professor, Disciplines of Surgery and Paediatrics, University of Newcastle. walkerpATtpgi.com.au To the Editor: The study by Paradise et al on tympanostomy tubes for persistent otitis media,1 which was expertly reviewed by Morris and Leach in the Journal recently,2 has since been updated.3 The findings of both studies from Pittsburgh should only be applied with caution in Australia. Indications for inserting ventilating tubes (VTs) can be divided into three: bilateral hearing loss of more than 25–30 dB continuously for 3 months after failed non-operative management; structural damage to the tympanic membrane (TM) which may lead to irreversible hearing loss or cholesteatoma; and a miscellany which includes under-lying sensorineural hearing loss or learning difficulties or similar conditions with deterioration associated with bilateral middle ear effusion (MEE), and recurrent middle ear infections with use of VTs as an alternative to antibiotic prophylaxis, among others. The conclusion of the more recent article by Paradise et al3 — that there was no difference in expressive or receptive speech or cognition between children in whom VTs were inserted early or late — is valuable, but may not readily be extended to Australian practice. Although 6350 children were enrolled, only 397 were actually randomly allocated into the early or late treatment groups. Thus, the numbers are not large. Of more concern is that only 18% of those analysed had bilateral continuous MEE (40 in the early and 32 in the late treatment group), with the remaining 82% having unilateral (continuous or discontinuous) or bilateral discontinuous MEE. Only the 18% with bilateral continuous MEE would ordinarily be candidates for VTs in Australia, as Paradise et al underline the fact that intermittent and/or unilateral MEE is not associated with speech and language difficulties in the absence of other handicaps to learning. An abnormal hearing test result was identified by the study as a 15 dB loss. This could well fall in the normal range for the Australian Hearing Service for children wearing headphones, and a minimum threshold of 25-30 dB should typically be required for considering VTs in Australia. As Morris and Leach2 pointed out for the earlier study,1 the later study also excludes children “not otherwise healthy”,3 and the results cannot be generalised to such children, or to those with moderate rather than mild hearing loss. Pointing to studies such as that of Paradise et al can be very helpful in reassuring parents who want VTs for their child with unilateral or intermittent hearing loss that not having VTs does not place the child’s speech and language development at risk.

Paul Walker

Communicating with vulnerable children: A guide for practitioners. David P H Jones. London: Gaskell, 2003 ($72.00, xvi + 188 pp). ISBN 1 901242 91 9. David Jones is well recognised for his research into the reliability of child testimony. This text provides a primer on good professional practice for interviewing children, based on current scientific evidence. This is an essential area of competence for the ever-increasing range of professionals working with children who have experienced adversity or abuse. This book provides a comprehensive and well-organised summary of the area, and is relevant to all those who may communicate with vulnerable children, including professionals from health, education, welfare and the law. It describes the process of enabling children to communicate freely and honestly, and to impart reliable and accurate information. The book is based on relevant research and clinical experience. As well, it has been carefully edited by an advisory board from the Department of Health and the Family Division of the High Court of Justice in the United Kingdom, with the aim of improving practice and reducing the amount of malpractice in communication with children. The first section covers the knowledge base of influences on childhood communication and interviewing style. It includes developmental limitations and considerations, especially regarding memory and language, and the influence of social context, including disability and culture. Childhood reliability in providing information is a small, though important, part of the problem of “erroneous concerns” in the system of child protection and notification, and the chapter about these issues helps refocus on the practitioner’s responsibility for unreliability. The second section guides practice at the different stages of communication, including response to first concerns, initial assessment and in-depth interviews. It also contains helpful chapters on the problems of using communication aids such as anatomically correct dolls, and advice on coping for parents. Medicolegal sensitivity means that this book is not always light reading and more case examples and diagrams would help improve accessibility. While full of useful details for even the most experienced clinicians, problems of development and mental health require more knowledge and expertise than is provided here. On the whole, a wide range of detailed information and practical advice is clearly presented, and we would recommend this as a comprehensive and common sense introductory text for all those who understand children, and essential reading for those who don’t. Emma HartwellPsychologist David R DossetorDirector of Mental Health Children’s Hospital at Westmead, Sydney, NSW

Emma Hartwell

Adolescents and young adults fare worse than children, yet do not have the same access to clinical trial therapy In almost half a century of clinical trials in children with cancer, survival rates have increased from less than 20% to over 80%. The national and international cooperation for such results has been an enormous feat of organisation. However, older adolescents and young adults, while having a higher and increasing incidence of cancer, have not fared so well.1 As shown by Mitchell and colleagues in this issue of the Journal (page 59), few are recruited into clinical trials, and improvement in survival has lagged behind that in younger patients.2 Some cancers that affect adolescents have a good prognosis (eg, Hodgkin’s disease and gonadal tumours), and little difference in survival is seen between patients who are treated in trials and those who are not. Yet clinical trials are still necessary to find the least toxic therapy while maintaining excellent survival. On the other hand, other cancers common in adolescents, such as acute myeloid leukaemia, acute lymphoblastic leukaemia, rhabdomyosarcoma, osteogenic sarcoma and Ewing’s sarcoma, are associated with considerably lower 5-year disease-free survival rates in adolescents than in younger patients.3 With increasing intensity of therapy, the importance of supportive care and a multidisciplinary approach cannot be over-emphasised. Outcomes of adolescents with acute lymphoblastic leukaemia have been reported to be markedly better with paediatric-based, high-risk (intensive) therapy performed in large teaching hospitals with appropriate support and a commitment to multidisciplinary coordinated care. In Children’s Cancer Group trials between 1989 and 1995, older adolescents had a 6-year event-free survival of 64%, compared with 38% for similar patients on (adult) Cancer and Leukemia Group B trials.4 Cooperation between paediatric and adult groups is essential to encourage entry into clinical trials. In France in 1993 and 1994, 15–20-year-old patients with acute lymphoblastic leukaemia treated within the paediatric FRALLE-93 study had a 5-year event-free survival of 67%, compared with 41% for 15–20-year-olds treated within the adult LALA-94 study.5 How can the lessons learnt in the large, multi-institutional, national and international paediatric cooperative groups be translated into better outcomes for adolescents and young adults with cancer? The Children’s Oncology Group (United States, Canada, Australia, New Zealand) and adult cooperative groups sponsored by the National Cancer Institute have identified four initiatives to improve the accrual of adolescents and young adults with cancer into clinical trials:2 Improving access to care through understanding barriers to participation. These barriers remain largely unstudied, but might include the time, cost and effort of being involved in a clinical trial, which may deter both physician and patient. Oncologists in private practice may retain these patients rather than referring them to a tertiary-care facility or cooperative group member institution. Also, clinicians and patients may not be aware of opportunities for clinical trials, the age policies of hospitals may prevent access to clinical trials for eligible patients, eligibility criteria may exclude some adolescent and adult patients, or there may be no available clinical trial for a patient. Developing a cancer resource network to provide information about clinical trials to patients, families, healthcare professionals and the public. Enhancing adherence to protocol therapy among adolescents. Although compliance was not found to be poor in the study by Mitchell et al,1 adolescent and young adult patients are often perceived as having difficulty in complying with treatment while keeping up their normal lives. Ancillary medical, psychological and educational support should be directed towards their specific needs.6 Increasing adolescent and adult participation in sarcoma trials specifically designed for patients in this age group. Just as paediatric oncologists have little experience with epithelial tumours, some adult oncologists have limited experience managing rare sarcomas.7 Cooperation between paediatric and adult groups is essential to encourage entry into clinical trials. For example, many Children’s Oncology Group trials will admit patients up to 30 years of age. It is imperative that alliances are formed to enable haematologists and oncologists who treat adults to enrol their younger patients in these trials. Although institutions that are members of the Children’s Oncology Group undergo rigorous performance monitoring to maintain high quality of care and data, this should not be a hindrance to such associations. Managing cancer patients in clinical trials requires significant financial support for administration and data management, but the benefit in improved survival will prove to be highly cost effective. Current funding models for research in Australia may not be suitable for the funding of clinical research such as cancer trials. National Health and Medical Research Council funding is tied strongly to researchers’ previously published research. Clinical research as part of a large cooperative group will not lead to numerous publications for individual clinicians. Nevertheless, commitment to such trials must be acknowledged by funding groups so that appropriate financial support to treat patients in trials is forthcoming. Only in this way will Australians of all ages with cancer have the benefit of the best evidence-based treatment within randomised controlled clinical trials in centres of excellence.

Catherine H Cole FRACP, FRCPA

Amanda J Caswell Managing Editor, MIMS Australia, Locked Bag 3000, St Leonards, NSW 1590. amanda.caswellATmims.com.au To the Editor: Tan et al outline deficiencies in product information documents (PIs) as published in MIMS.1 It needs to be clarified that MIMS Australia is not responsible for the content of PIs — this is specified and approved by the Therapeutic Goods Administration in consultation with the sponsoring company. The conclusion by the authors that the “PIs for many prescription products listed . . . do not adequately detail paediatric doses” should not be specifically attributed to MIMS, as all published medicines information that relies on approved PIs will suffer from the same deficiencies.

Amanda J Caswell

We should do all we can to ensure that every baby benefits from this important preventive activity Newborn screening is a wonderful example of preventive medicine. Pioneered by Dr Robert Guthrie in the early 1960s, the blood-testing of newborns for treatable disorders has become almost universal in developed countries. From the first programs for phenylketonuria testing, the scope has widened to include disorders such as hypothyroidism and cystic fibrosis. More recently, analysis by tandem mass spectrometry, which can detect over 30 rare inborn errors of protein and fatty-acid metabolism, has been introduced.1 Soon all babies in Australia will be able to be tested by tandem mass spectrometry. A simple heelprick is all that is needed. More than one baby in every 1000 (over 250 babies a year in Australia) will have a detectable disorder needing treatment. Without early detection, some of these babies would develop intellectual disability, some would develop acute life-threatening illness, and a few avoidable deaths would result. Screening for phenylketonuria alone, with subsequent treatment, has saved over 700 Australian children from moderate to severe disability since screening began. The consequences of not having a screening test might seem trivial to an individual family — only about one chance in 1000 that anything threatening would be missed. But, for every 1% of babies in Australia that are not tested, two or three babies per year with a treatable disorder could die or suffer permanent damage. In this issue of the Journal, Metz and colleagues (page 412) report the results of a systematic investigation of the coverage of newborn screening in South Australia for the year 1999.2 The team not only examined coverage, but carefully analysed who it was that missed out on screening. Some of the results are not surprising, but some are. Being Aboriginal, having a home birth, being in hospital for less than three days, or suffering neonatal death were all risk factors for missed screening, as were having a gestational age of less than 32 weeks, being in intensive care, having a congenital anomaly, or having a mother who normally lived in another state. (Being a twin or triplet, however, was protective — they rarely missed being screened.) Metz and colleagues concluded that, overall, about 2% of babies did not get a screening test. The methodology used was thorough, matching newborn screening data with the SA perinatal data collection using sophisticated software. Of course, data matching is never perfect. Baby’s-surname changes are common soon after birth (even the mother’s indicated surname can change), and babies are sometimes transferred from one hospital to another. In the end, there were 413 births to which Guthrie screening cards could not be matched, and 44 unmatched cards. Even if the unmatched cards represented babies who were born interstate then transferred to South Australia, as was suspected, this would not have materially altered the finding that about 1 in every 50 babies born was not screened in 1999. This should sound a warning note to those who oversee other screening programs, many of whom have assumed a greater than 99% coverage without adequate supporting data. There has indeed been little published on newborn screening coverage, although a recent survey from London did suggest an enviable coverage of 99.9%.3 Newborns are an ideal population to screen, being “captive” for the crucial time, but the problem of early discharge is threatening this, just as screening is poised to expand into new fields. Newborn hearing screening is becoming universal in Australia, and for this, too, it will be important to ensure a very high coverage.4 Biochemical screening by means of the routine dried blood spot is also very likely to expand as new possibilities, supported by new technology, are being explored.5 The lessons from the SA study are clear. To achieve close to 100% coverage, strategies must especially target groups at high risk of not being screened, and healthcare providers need to be reminded and re-reminded about the importance of the test. In relation to the SA study, it would have been interesting to know whether some birth units had particularly high rates of missed tests — if that were the case, such units could be targeted for kindly reminders. As the authors point out, it is also important to collect a sample from newborns who die. Now that expanded testing by tandem mass spectrometry is available, firm diagnoses can sometimes be made from dried blood samples of babies who have died. In New South Wales, over a 4-year period, we have diagnosed fatty-acid-oxidation disorders in this way in three children who died 2–3 days after birth. Achieving a diagnosis makes possible either prenatal diagnosis in a future pregnancy, if desired, or early management of a subsequent baby to avoid clinical problems. For better coverage, perhaps screening should become mandatory in Australia, as it largely is in the United States. In Australia, we have felt that parents have a right to refuse neonatal screening on behalf of their baby. But should parents be able to refuse a procedure that carries such a tiny risk and has an obvious potential benefit, and would this not infringe on the baby’s right to have what ethicists call an “open future”?6 This is a difficult question, but one that is growing in importance as the potential for well targeted newborn screening increases. At present, in our experience, only a very small number of parents refuse newborn screening, for a variety of reasons. If we feel that newborn screening tests are valuable, then we need to ensure that every baby has a chance to benefit. Few preventive medicine programs are so effective.

Bridget M Wilcken AM, FRACP

Objective: To determine the biochemical screening rate of newborns in South Australia and the factors associated with babies not being screened.Design: Matching of data in the SA Newborn Screening Centre database (acquired from Guthrie cards) with the SA perinatal data collection (compiled from supplementary birth records) to determine how many newborns missed screening. Risk factors for missed screening were identified from sociodemographic and clinical variables recorded in the perinatal data collection and analysed by multivariable unconditional logistic regression analysis.Patients and setting: All live births (n = 18 426) in South Australia in 1999, in the 63 hospitals assisting deliveries or in the home.Main outcome measures: Rates of biochemical screening and missed screening in all newborns and among various subgroups; adjusted odds ratios (after multivariable logistic regression analysis) for risk factors for missed screening.Results: The newborn screening rate in South Australia in 1999 was 97.8%. Babies born at home, born to an Aboriginal mother, or born to a mother who normally resided in another state were at higher risk of missed screening. Other factors associated with missed screening were having fewer than seven antenatal visits, prematurity (gestational age at birth < 32 weeks), congenital abnormality in the baby, use of paediatric intensive care, early discharge from hospital before 3 days (but especially after less than 1 day), and death of the baby during the neonatal period.Conclusion: In South Australia, while 2.2% of all newborns missed screening in 1999, in certain high-risk groups the proportions of unscreened babies were significantly higher. With a 2% missed screening rate, one might expect one newborn with a screening-detectable disorder to elude detection every other year in South Australia.

Michael P Metz MD, MAACB · Enzo Ranieri BSc(Hons), MSc · Rosemarie L Gerace BSc · Kevin R Priest BSc · Colin G Luke MPH, FAFPHM · Annabelle Chan DPH, FAFPHM

QuestionIs early surgical referral for children with persistent otitis media with effusion (OME) appropriate? Trial details Design: Randomised, assessor-blinded, controlled trial. Setting: Two hospitals and six private paediatric group practices from the Pittsburgh region in the United States. Participants: 429 children aged less than 3 years who had otitis media with effusion (OME) that had persisted despite treatment with antimicrobial drugs for the equivalent of: 90 days in the case of bilateral effusion; or 135 days in the case of unilateral effusion. Interventions: Children assigned to the early treatment group were scheduled to have ventilation tubes (grommets) inserted as soon as possible. Children assigned to the late treatment group were scheduled to undergo the operation 6 months later if bilateral effusion persisted (or 9 months later if unilateral effusion persisted). Children in the late treatment group could receive grommets earlier if their parents requested the operation. Main outcome measures: Standardised assessment of cognitive ability, receptive language ability, expressive language ability, parenting stress, and child behaviour at 3 years of age. Main results: 169 children in the early treatment group (82%) and 66 children in the late treatment group (34%) had had ventilation tubes (grommets) inserted by 3 years of age. There were no significant differences (mean ± standard deviation) for early treatment versus late treatment in the General Cognitive Index of McCarthy's Scales of Children's Abilities (99 ± 14 v 101 ± 13); Peabody Picture Vocabulary Test–Revised (92 ± 13 v 92 ± 14), Number of Different Words Test (124 ± 32 v 126 ± 30), Percentage of Consonants Correct–Revised Test (85 ± 7 v 86 ± 7), Total Parenting Stress Index, Short-form–Total Stress (66 ± 18 v 68 ± 21), and Child Behaviour Checklist–Total Problems (50 ± 10 v 49 ± 10). Conclusion: In young children with persistent OME, prompt insertion of ventilation tubes (grommets) does not measurably improve developmental outcomes by 3 years of age. CommentaryRationale for the trialOtitis media with effusion (OME) is the most prevalent form of middle ear disease in young children. It is defined as the presence of fluid behind the tympanic membrane without the symptoms or signs of acute otitis media (AOM).1 It is usually associated with some hearing loss. OME with persistent hearing loss may contribute to delays in speech and language development.2 Recommended interventions include the use of antibiotics and the insertion of ventilation tubes (grommets).2-4 There have been concerns about the overuse of grommet surgery. Substantial variation in rates of this procedure have been documented.5,6 Clinical practice guidelines have recommended that grommets are an option for children who have bilateral OME associated with a hearing loss of > 20 decibels for at least 3 months.2-4 The intervention is most likely to benefit younger children (during the most critical phase of language development) and those with most hearing loss. Trial methodsThis trial was part of the largest otitis media cohort study ever conducted.7 The study was generally well designed and well reported.8,9 A total of 6350 healthy infants were enrolled in their first 2 months of life and were evaluated monthly for otitis media; 588 of these children had persistent or very frequent OME. They were regarded as typical of children who might receive surgery in the United States. The aim of the study was to determine the benefits of early referral for surgery compared with delayed referral (where “watchful waiting” continued for an additional 6 months). Random assignment was made by designated non-clinical staff using separate, computer-generated lists of random numbers. Children were stratified according to site, age (in 6-month categories), and whether the eligibility criteria were met on the basis of bilateral or unilateral effusion. Assignment within each of the predetermined strata occurred in permuted blocks of four. This ensured that the allocation was balanced after every four new children (in a stratum) were randomly allocated. Children underwent developmental assessment as soon as possible after their third birthday (and always within 2 months). Standardised assessment tools were used. Assessors were unaware of the child’s medical history, health insurance status, and mother’s level of education. The investigators proposed that a difference of 0.33 standard deviations between groups on any outcome measure could be clinically important. Follow-up of participants over a prolonged period was reasonably good (95% and 92% of the early- and late-treatment groups, respectively). All analyses were based on the intention-to-treat principle (although children who were not assessed could not be included in the analysis). Any weaknesses in the methods and the quality of reporting were relatively minor. Ideally, the authors should have also described (i) how random allocation was concealed from the investigators, (ii) how block size was concealed from investigators (so they couldn’t guess which intervention would be allocated next), (iii) the adequacy of blinding, (iv) the primary outcome for the study, and (v) an assessment of adverse outcomes. The choice of a 0.33-standard- deviation difference between the groups in any of the assessments as the minimal clinically important difference was controversial. While this approach should be able to identify reasonably small statistical differences attributable to the intervention, the clinical importance of such a difference is not easily understood. In the end, because there were no statistically significant differences in any of the outcome measures, this issue did not arise. New informationThis is the largest randomised trial to evaluate ventilation tubes in children with persistent OME. Previous studies had shown that surgery improved hearing by around 12 dB at 6 months and 6 dB at 12 months.5 Most of these studies involved older children and did not include an assessment of speech and language (which is generally regarded as the most important outcome). The results of this study are consistent with those of previous studies in demonstrating that grommet surgery will substantially reduce the amount of time that a child has OME, and modestly improve hearing. However, by 3 years of age, early referral for surgery had no beneficial effect on development or behaviour. The consistent lack of effect for a range of outcome measurements was striking. These findings were not changed by the subsequent subgroup analyses.10 The results of this study are unlikely to be explained by a biased estimate of effect or by chance. Similar results have also been documented in other recent well designed studies in different populations.11-13 Implications for clinical practiceIdentifying young children with persistent OME is a common problem for general practitioners in Australia. For children who are otherwise well, this study shows that early referral for surgery does not improve developmental outcomes at 3 years of age. For individual families affected by long waiting times or preferring to avoid an operation, parents can be reassured that the child will not be disadvantaged by delaying the decision about surgery. The duration of “watchful waiting” can be extended to 9–12 months without serious consequences. Although hearing loss will persist longer, many episodes of persistent OME will resolve and potential complications of surgery (otorrhoea, chronic perforation) will be avoided. It is still possible that the insertion of ventilation tubes will improve developmental outcomes in some children. The results of this study are not applicable to: children with established speech and language delay (or conditions known to be associated with speech and language delay); children with bilateral OME that persists longer than 9–12 months; and children with more substantial conductive hearing loss. Parents of these more severely affected children can be advised that this simple and safe operation will improve their child’s hearing. However, whether it will improve their speech and language development is still uncertain. Further trials targeting these specific subgroups should be supported.

Peter S Morris FRACP, PhD · Amanda J Leach PhD

Objective: To determine the prevalence of iodine deficiency in primary school children in an Australian urban population.Design and setting: A cross-sectional survey of school children aged 5–13 years attending a public school on the Central Coast of New South Wales in November 2000.Participants: 324 (70%) of the 465 children enrolled in the school (180 boys; 144 girls).Main outcome measures: Thyroid volumes compared with World Health Organization/International Council for the Control of Iodine Deficiency Disorders (WHO/ICCIDD) thyroid volume reference values. Iodine status based on WHO/ICCIDD urinary iodine concentration (UIC) categories (normal, ≥ 100 μg per litre of urine [μg/L]; mild iodine deficiency, 50–99 μg/L; moderate deficiency, 20–49 μg/L; severe deficiency, < 20 μg/L); not more than 20% of the population should have a UIC below 50 μg/L.Results: Median UIC for school children was 82 μg/L, and 14% of children had UICs below 50 μg/L. Thyroid volume reference values indicated a prevalence of goitre of zero. In girls, only four (3%) and one (1%) had thyroid volumes above the WHO/ICCIDD medians by age and body surface area (BSA), respectively (P < 0.001). In boys, three (2%) and one (1%) had thyroid volumes above WHO/ICCIDD medians by age and BSA, respectively (P < 0.001).Conclusion: Despite the median UIC being less than ideal, most children were not goitrous. This underscores the importance of using physiological outcome measures in areas where iodine deficiency is marginal before concluding the need for iodine supplementation based purely on median UIC. We call for a systematic national survey to determine iodine status using a combination of iodine deficiency indicators.

Kamala Guttikonda MB BS, FRACP · Steven Boyages FRACP, PhD · Cheryl A Travers BSc · Peter R Lewis MB BS, FAFPHM

Croup affects about 2% of preschool-aged children every year. Most children have mild croup and are managed at home, often after review by a general practitioner, who may decide that a single dose of oral corticosteroid is indicated (eg, if a risk factor for hospital admission exists). A minority of children develop moderate or severe croup. They should be reviewed in an emergency department and may need hospital admission. More liberal use of systemic corticosteroids for croup (in both primary care and emergency department settings) has been associated with reduced rates of hospital admission, reduced admissions to the intensive care unit and a reduced need for endotracheal intubation. We discuss the assessment and evidence-based management of a child with mild croup presenting to a GP and a child with moderately severe croup presenting to an emergency department. We present a flow chart summarising an approach to assessing and treating croup in the emergency department.

Dominic A Fitzgerald MB BS, PhD, FRACP · Henry A Kilham MB BS, FRACP

Of children needing palliative care, less than half have a malignancy. Most families will elect to care for their child at home if this is offered as a realistic option. The often protracted and unpredictable nature of the many illness trajectories encountered in paediatric palliative care requires an approach that integrates palliative care with curative care. Children bring added dimensions to the physical, psychosocial and ethical aspects of palliative care. Health professionals from both paediatric and palliative care sectors have skills and knowledge to bring to palliative care of the child.

Jenny L Hynson MB BS, FRACP · Jonathon Gillis MB BS, FRACP · John J Collins FRACP, FAChPM · Helen Irving MB BS, FRACP · Susan J Trethewie FRACP, FAChPM

Objective: To determine whether high maternal parity has any effect on pregnancy outcome independent of other maternal characteristics.Design and setting: Retrospective observational study using the database of a referral obstetric unit in a 280-bed regional hospital in far north Queensland.Participants: All 15 908 women who had singleton births between 1992 and 2001, comprising 653 women with grand multiparity (≥ 5 previous births at gestation ≥ 20 weeks) and 15 255 women with lower parity.Main outcome measures: Spontaneous vaginal birth, postpartum haemorrhage (estimated blood loss > 500 mL), placental retention requiring manual removal, blood transfusion associated with the birth, and perinatal death.Results: Women with grand multiparity were significantly older than those with lower parity, more likely to be Indigenous, not to have had antenatal care, to have smoked during pregnancy and to have had one or more previous caesarean sections. On univariate analysis, women with grand multiparity were more likely to have a postpartum haemorrhage (9.2% v 5.3%) and blood transfusion (2.8% v 1.5%). However, multivariate logistic regression analysis of women who began labour (ie, did not have an elective caesarean section) showed that grand multiparity was not significantly associated with postpartum haemorrhage or blood transfusion when other maternal characteristics were included in the model (regression coefficients [95% CI], 1.36 [0.99–1.87] and 1.09 [0.59–2.02], respectively). However, they remained more likely to have a spontaneous vaginal birth (regression coefficient [95% CI], 2.10 [1.56–2.74]).Conclusions: Women with grand multiparity do not have an increased likelihood of poor pregnancy outcomes. Birth-suite protocols which dictate extra interventions as routine during labour in these women should be revised.

Michael D Humphrey PhD, FRANZCOG, FRCOG

Donna B Mak,* Alastair MacKendrick,† Max K Bulsara,‡ Sharon Weeks,§ Lewis Leidwinger,¶ Harvey Coates,** Francis J Lannigan,** Deborah Lehmann†† * Public Health Physician, ¶ Audiologist, Kimberley Public Health Unit, Derby, WA; † Ear, Nose and Throat Surgeon, Southern Corridor ENT Services, South Fremantle, WA; ‡ Biostatistician, Biostatistical Consulting Service, School of Population Health, University of Western Australia, Crawley, WA; § Audiologist, Disability Services Commission, West Perth, WA; ** Ear, Nose and Throat Surgeon, Department of Otorhinolaryngology – Head and Neck Surgery, Princess Margaret Hospital for Children, Subiaco, WA; †† Senior Research Fellow, Centre for Child Health Research, University of Western Australia, Telethon Institute for Child Health Research, Subiaco, WA. Correspondence: Dr Donna B Mak, 189 Royal Street, East Perth, WA 6000. makhoATbigpond.com To the Editor: Chronic suppurative otitis media is very common among Australian Aboriginal children, resulting in hearing loss and educational and social disadvantage.1 Reconstructive middle-ear surgery has been part of the accepted treatment for decades. However, there are no publications about long-term outcomes in Aboriginal populations.2 We report here the results of a study of long-term postoperative outcomes in Aboriginal children following reconstructive middle-ear surgery. We studied all Aboriginal children aged ≤ 15 years who underwent middle-ear surgery for a tympanic membrane perforation (excluding cholesteatoma) in the Kimberley region of Western Australia between 1 October 1986 and 31 December 1995. Data had been collected prospectively during a previous study, and long-term follow-up was undertaken as part of a recent study of middle-ear surgery outcomes.2,3 Ethical approval was obtained from the WA Aboriginal Health Information and Ethics Committee. The study population consisted of 93 children (57 girls, 36 boys), aged 5–15 years (mean, 10 years; median, 10 years) at the time of operation. Preoperative air–bone gap (ABG) measurements ranged from 8.75 to 58.75 dB (mean, 36.7 dB; median, 36.25 dB). The operations were performed by nine surgeons at three hospitals and included tympanoplasty using temporalis fascia (73%), dura (13%), and other graft materials (8%), and mastoidectomy (6%). Sixty-four children (69%) underwent early postoperative review (median follow-up interval, 11 months) and 73 children (78%) underwent late postoperative review (median follow-up interval, 103 months). More of the patients had a late review because, at the time, additional resources were available to actively locate the patients for follow-up. At late postoperative review, 56/93 (60%) patients had a successful outcome (intact tympanic membrane and normal hearing) and 17/93 (18%) did not (20/93 [22%] did not undergo late postoperative review). Of the 32 patients who had a successful outcome at the early postoperative review (median follow-up interval, 5 months), 26 (81%) underwent late postoperative review; 24/26 (92%) still had an intact tympanic membrane and ABG ≤ 25 dB at late postoperative review (median follow-up interval, 109 months) (Box). These findings indicate that successful tympanic membrane closure with hearing improvement after middle-ear surgery in Aboriginal children is probably longlasting. The major limitation of our study is the absence of clinical information in the time period (mean, 8 years) between the early and late postoperative reviews. An unknown (but likely to be small) number of patients may have had further operations and/or conservative management, which may have influenced their ear health status at late postoperative review. Collection of these data would have been extremely difficult given the nomadic lifestyle of many patients and the logistical realities of remote-area healthcare. Our findings support the current recommendation of the Office of Aboriginal and Torres Strait Islander Health that Aboriginal children should be offered tympanoplasty if conservative management of chronic suppurative otitis media is unsuccessful.4 Postoperative review status of 93 Aboriginal children who underwent middle-ear surgery for a tympanic membrane (TM) perforation* in the Kimberley region of Western Australia between 1 October 1986 and 31 December 1995† * Excluding cholesteatoma. † If a patient had more than one operation, the first ear operated on during this time period was included in the analysis. If a patient had operations on both ears on the same date, the ear with the largest preoperative hearing loss was included. If hearing loss was the same on both sides, the right ear was chosen.

Donna B Mak · Alastair MacKendrick · Max K Bulsara · Sharon Weeks · Lewis Leidwinger · Harvey Coates · Francis J Lannigan · Deborah Lehmann

The Australian Institute of Health and Welfare, using the definition “a disability which restricts a child’s ability to perform tasks associated with daily living”,1 reported that in 2002 almost 300 000 Australian children (7.5%) had a disabling chronic illness. The disability was primarily physical in 54% of children, and intellectual/developmental/behavioural in 46%. Asthma comprised 31% of the physical conditions, the rest being other respiratory diseases and diseases of the ears and nervous system.1 It is estimated that, at any given time, 23% of Australian children have recent asthma, 10% have eczema, and 15% have emotional/behavioural problems. For comparison, 0.5%–1% of the whole population has epilepsy, of which about 60% begins in childhood; about two per 1000 schoolchildren have juvenile-onset diabetes mellitus; and the incidence of childhood cancer is about 14 per 100 000, with a 75% survival rate.1 Although advances in technology have greatly improved survival for many children (eg, those born prematurely, or those with cancer or cyanotic heart disease), they have also created a population of children living with disabilities. Without belittling these technological achievements, it is important that the quality of life of survivors also be considered. For example, over 50% of extremely low birthweight babies (500–999 g) now survive to discharge, but 15%–20% of survivors have a major disability (cerebral palsy; visual, auditory or intellectual impairment), and at least half the remainder have significant learning difficulties.2 For all children with disabilities, limitations to schooling, mobility and communication constitute the most significant restrictions of daily activity.1,3 Psychosocial impact of chronic conditions. Chronic conditions put increased stress on the child and the child’s parents and siblings. Children with any chronic condition have twice the risk of developing mental health disorders of healthy children, and three times the risk if they have an accompanying disability.3 The clinical “severity” of the condition is not necessarily the major psychosocial prognostic factor. For example, the stress on a family of caring for a child with moderate or severe eczema exceeds the stress related to insulin-dependent diabetes mellitus.4 Conditions that disrupt sleep for the child and the parents are possibly the most stressful. A child’s view of his or her quality of life may differ from the views of parents and others.2 Children born with chronic conditions may be more accepting of handicap, even while recognising their difference from other children,5 and they often adjust better to visible handicaps than to hidden ones.3 It is important to emphasise what disabled children can do, rather than what they cannot do. One positive approach to chronic illness is to consider the factors that enable most children and families with chronic illness to cope as well as they do. It has been advocated that we should focus on interventions to improve this resilience, although there is a dearth of supportive research.3 Robert Louis Stevenson, who had pulmonary tuberculosis, said that “life is not a matter of holding good cards, but of playing a poor hand well”. The prognosis for a child with chronic illness is highly dependent on how the family functions. The illness places stress on parents and siblings, who may themselves become exhausted and develop psychological problems such as anger and depression. It is vital to communicate well with the parents or carers of chronically ill children, and not to forget the siblings, whose needs are easily neglected if parents focus too much on the sick or disabled child. Avoidable risk factors for psychosocial problems include prolonged ambiguity about the diagnosis and poor communication to parents and siblings. Other risk factors include stressors such as moving house or changing schools, as well as the known underlying risks of low socioeconomic status, marital discord and parental mental health problems.3 Warning signs of distress in children include problems at school or in social relationships; low self-esteem, manifested as self-blame, helplessness or hopelessness; and denial, including poor compliance with treatment. Psychological problems may manifest as anxiety, depression, oppositional behaviour, suicidality or disorders of eating, conduct or sleep.3 Interventions that have been shown to be beneficial include family therapy, supportive counselling of children and parents, and the use of supportive protocols such as those blending advocacy and liaison work.3 Overall adjustment is better with family-centred interventions and when needs are met in the home.3 Prevention. Disruptive influences in early infancy can be particularly damaging to later emotional and psychological development. Studies are under way to see if strategies to improve the early childhood environment (eg, parenting support and universal early childhood programs) can effectively optimise development and prevent chronic mental health problems. Recommendations. Consensus guidelines, developed by an expert panel and based on best available evidence,3 include the following recommendations: Practical support. Families need clear communication, with healthcare professionals and with each other; opportunities for choice of supports; and practical assistance with finances, transport, respite care and recreation. Additional support may be needed for staff and peers at school. Many parents report benefits from involvement in self-help groups. Multidisciplinary teams. Assessments by well qualified teams can identify areas of immediate and future need and can improve communication between professionals, children and families. Self-determination. Young people with chronic conditions should be allowed to decide which professionals coordinate their care, what form of treatment they want, and what part they wish to play in their own treatment.

David Isaacs MD, FRACP, FRCPCH · Jill R Sewell MB BS, FRACP

Thirty years ago, Pless and Pinkerton1 highlighted the fact that, although children and adolescents experience a diverse range of illnesses, those with chronic conditions have great similarities in their life experiences and in the preventive and rehabilitative aspects of their lives. Since then, the intensity of treatment programs recommended for managing adolescent chronic illnesses has increased greatly. As a result, the daily lives of adolescents with chronic illness are often very different from those of their healthy peers. Adolescents with a chronic illness have usually lived with the illness for much of their lives. Although there is generally no prospect of a cure, they have to complete time-consuming and inconvenient treatment tasks every day. Treatment regimens now recommended for managing chronic illnesses are intensive and often tedious, but there is evidence that they can lessen the impact of some disorders (eg, in adolescents with diabetes, good metabolic control is associated with better quality of life).2 As adolescents take over management of their illness from their parents, they have to decide to what extent they will comply with treatment. Young people who develop a chronic illness during adolescence often have difficulty accepting their illness, and treating them can be quite a challenge for physicians. In a recent two-year prospective study of chronic illness conducted by our group,3 we found that adolescents with diabetes did not consider the restrictions on their regular food or drink intake a large inconvenience. However, managing their illness (including injecting insulin and monitoring blood glucose levels) took them an hour a day, on average. Adolescents with cystic fibrosis spent even longer (1.5 hours a day) managing their illness: typically, they began each day by consuming a large quantity of tablets, followed by other tasks including physiotherapy, the use of inhalers and nebulisers, and possibly overnight feeding. Managing chronic illness can be particularly difficult for adolescents while at school. Secondary schools find it hard to be flexible in accommodating students’ healthcare needs and doing so in a way that protects their privacy and dignity. Adolescents and their families feel frustrated when they have to explain their needs repeatedly to new staff or in new situations such as camps and excursions. These problems can be exacerbated when young people need the support of a visiting nursing service. Nursing roster changes may put adolescents in the position of having to explain their treatment needs more than once to an unfamiliar nurse in a school setting that is not designed to provide healthcare. The combined impact of their health support needs and increasing academic demands increases the risk that adolescents with chronic illness will leave school early and not fulfil their vocational potential. Chronic illnesses adversely affect adolescents in a range of ways. For example, the impact of recurrent asthma symptoms is widespread, with exercise-induced dyspnoea often limiting participation in sport and daily exercise. For those with diabetes, adolescence is perhaps the most challenging time for illness management: the physiological insulin resistance of puberty is exaggerated in adolescents with diabetes, and the first subclinical signs of microvascular complications are starting to appear. Adolescents with cystic fibrosis are more likely to be shorter and thinner than their peers and to have more difficulty with issues of intimacy and sexuality. Although most are socially competent, they tend to take less part in social activities outside the home.4 Epidemiological studies have shown that adolescents with chronic illness have twice the rate of mental disorders as their healthy peers.5 While there is evidence that intensive therapy improves the wellbeing of adolescents with chronic illness, careful organisation of daily activities is necessary to complete all the treatment tasks. This requirement conflicts with adolescents’ desire to participate in spontaneous activities being enjoyed by healthy peers and to experiment with new autonomy and freedom from parental control. A major challenge for those responsible for developing new treatment regimens is to achieve a partnership with adolescents to ensure that new programs are both effective and acceptable to the adolescents who will be responsible for implementing them.

Michael G Sawyer MB BS, PhD, FRANZCP · Jennifer J Couper MB ChB, MD, FRACP · A James Martin MB ChB, MRCP, FRACP · J Declan Kennedy MD, FRCP, DCH

Children in the new millennium. Environmental impact on health Geneva: World Health Organization, 2002 (vi + 141 pp). ISBN 92 807 2065 1. On World Health Day 2003, the World Health Organization called for “concerted action to protect three of our greatest assets: children, the environment and health”1. Dr Gro Harlem Brundtland, stated: “The biggest threats to children’s health lurk in the places that should be safest — home, school and community. Every year, over 5 million children aged 0–14 die, mainly in the developing world, from diseases related to their environments”. Children in the new millennium. Environmental impact on health presents these issues with disturbing clarity. The volume can be downloaded free from www.who.int and this site also contains a link to the Healthy Environments for Children Alliance (www.who.int/heca/en/). In just 141 pages we are presented with a depressingly pervasive summary of the key environment issues of our day, and children, especially poor children, suffer a disproportionate burden of this litany: Unsafe drinking water — two thirds of the world will live in “water-stressed” conditions by 2025. Poor hygiene and sanitation — diarrhoeal diseases have killed more children in 10 years than has armed conflict in 50 years. Catastrophic degradation of lands and fisheries — nearly 1 billion of us depend on fish for protein. Indoor and outdoor air pollution. Toxic chemicals — lifelong exposure to pesticides often starts in the womb. Warming habitats that favour insect vectors of killers such as malaria and dengue. This compendium of facts will be useful to teachers of public or environmental health. For each environmental threat the authors summarise proven remedies that can be applied at household, community, national and international levels. I would have liked more detail on the nitty gritty of negotiating multilateral environmental agreements, which must represent our best hope for their implementation. Most sobering is the realisation that nearly all of these harmful legacies bestowed on our children have their origins in human society — conflict, inequality, or our excessive and wasteful consumption. Christopher J MorganCentre for International Health Macfarlane Burnet Institute for Medical Research and Public HealthMelbourne, VIC 1. www.who.int/mediacentre/statements/2003/statement6/en/ accessed Apr 2003.

Christopher J Morgan

Objectives: To compare the effectiveness of ototopical ciprofloxacin (0.3%; CIP) with framycetin (0.5%), gramicidin, dexamethasone (FGD) eardrops (5 drops twice daily for 9 days) together with povidone-iodine (0.5%) ear cleaning as treatments for chronic suppurative otitis media (CSOM) in Aboriginal children.Design and participants: Aboriginal community-controlled, community-based, multicentre, double-blind, randomised controlled trial in eight Aboriginal Community Controlled Health Services across northern Australia, involving 147 Aboriginal children with CSOM.Main outcome measures: Resolution of otorrhoea (clinical cure), proportion of children with healed perforated tympanic membrane (TM) and improved hearing, 10–21 days after starting treatment.Results: 111 children aged 1–14 years (CIP, 55; FGD, 56) completed treatment. CSOM cures occurred in 64% (CIP, 76.4%; FGD, 51.8%), with a significantly higher rate in the ciprofloxacin group (P = 0.009, absolute difference of 24.6% [95% CI, 15.8%–33.4%]). TM perforation size and the level of hearing impairment did not change. Pseudomonas aeruginosa was the most common bacterial pathogen (in 47.6%), while respiratory pathogens were rare (in 5.7%).Conclusions: Twice-daily ear cleaning and topical ciprofloxacin is effective at community-level in achieving cure for CSOM. Healthcare providers to Aboriginal children with CSOM should be given special access to provide ototopical ciprofloxacin as first-line treatment.

Sophie Couzos FRACGP, FACRRM, FAFPHM · Traven Lea MAEIH, DipPHTM · Margaret Culbong · Reinhold Mueller MSc, PhD · Richard Murray FRACGP, MPH

Objective: To assess the reported rate of local reactions after administration of acellular pertussis vaccine (DTPa) according to dose number and type of pertussis vaccine (whole-cell or acellular) used for the primary course, and to document the severity and outcome of fourth-dose local reactions.Design and setting: Retrospective review. Reports of adverse events after vaccination in South Australia between 1 January 1997 and 31 December 2000 were reviewed, and a questionnaire administered to all parents who reported a local reaction after the fourth dose of DTPa.Main outcome measures: The number, and rate per 100 000 administered doses, of local reactions following the primary and booster doses of DTPa, and of local reactions after the fourth-dose in cohorts of children whose primary vaccinations were with either DTPw or DTPa. Redness and/or swelling at the injection site as reported by parents.Results: Of 581 reported adverse events after vaccination, 138 were local reactions after a pertussis-containing vaccine. Primary vaccinations with DTPa was a significant risk factor for a fourth-dose local reaction (relative risk, 6.7; 95% CI, 2.4–18.5). Parental questionnaires were completed for 45 of the 71 children (63%) with reported local reactions after the fourth dose of DTPa; extensive limb swelling was reported in 8 children (18%) and all except one child had recovered by the time of review.Conclusions: Parents should be informed that children receiving booster doses of DTPa vaccine, after primary doses with DTPa, are at increased risk of local reactions (which tend to resolve spontaneously) but not of systemic effects. Studies should be initiated to investigate the pathogenesis and the risk of recurrence of local reactions to further improve vaccination schedules.

Michael S Gold MD, FRACP · Sara Noonan RN · Maggi Osbourn RN · Stella Precepa RN · Ann E Kempe RN, MPH, BSc

Objectives: To review the approved product information (PI) of prescription medicines to determine the extent and nature of information available on paediatric dosing and the availability of paediatric dosage formulations in Australia.Methods: The PIs for all prescription medicines listed in the Australian Monthly Index of Medical Specialties (MIMS) were reviewed. Dosing information for each PI was categorised according to age groupings. PIs claiming suitability for use in paediatric patients were reviewed for information on the availability of paediatric dosage forms.Main outcome measures: Proportion of PIs providing paediatric dosing information; availability of dosage forms suitable for children.Results: A total of 1497 PIs were reviewed. The proportions, for each age group, of PIs with inadequate paediatric dosing information were: < 1 month (80.5%), 1–3 months (79.1%), 3 months–2 years (77.5%), 2–6 years (73.2%), and 6–12 years (71.6%). The proportions, for each age group, of PIs that gave specific paediatric dosing information but did not provide a paediatric dosage form were: < 1 month (26.5%), 1–3 months (25.1%), 3 months–2 years (23.3%), 2–6 years (21.9%), and 6–12 years (24.0%).Conclusions: The PIs for many prescription products listed in MIMS do not adequately detail paediatric doses. Many medicines for which specific paediatric dosing information is given are not available in dosage forms appropriate for children.

Elaine Tan BPharm, BPharmSc(Hons) · Craig R Rayner BPharm, BPharmSc(Hons), PharmD · Colin B Chapman BPharm, PhD, FPS · Noel E Cranswick MB BS, FRACP

QuestionDoes indomethacin given prophylactically after birth improve long-term outcome for babies with extremely low birth weight? Trial details Design: Randomised, double-blind, controlled trial. Setting: 32 intensive care nurseries in Australia, Canada, Hong Kong, New Zealand and the United States. Participants: 1202 babies of 500–999 g birthweight; groups were similar in demographic and perinatal characteristics. Exclusions included major anomalies and inability to give indomethacin before 6 hours of life. Interventions: Indomethacin (0.1 mg/kg, intravenously) once daily for 3 days, or equivalent volume of saline placebo. Main outcome measures: Composite outcome of mortality, cerebral palsy, developmental delay, deafness or blindness at 18 months of age, corrected for prematurity. Main results: There was no substantial difference in the primary composite outcome between the indomethacin (47% [261/574]) and placebo (46% [261/569]) groups (odds ratio [OR], 1.1; 95% CI, 0.8–1.4; P = 0.61). However, the indomethacin group had a lower rate of patent ductus arteriosus (PDA), including cases requiring medical or surgical treatment, and severe (grade 3 or 4) cerebroventricular haemorrhage (CVH). Conclusion: In infants with extremely low birthweight, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite reducing the frequency of PDA and severe CVH. CommentaryRationale for the trialPersistent patent ductus arteriosus (PDA) is a problem after birth for very tiny or preterm infants, many of whom require either medical or surgical intervention to close the ductus in the newborn period. Indomethacin is often successful in closing the ductus when used therapeutically, but is associated with many short-term side effects. Before this trial, prophylactic use of indomethacin was known to reduce the frequency of symptomatic PDA and severe cerebroventricular haemorrhage (CVH) in these babies.1 Reducing severe CVH might be expected to improve long-term neurological outcome. However, the mechanism for reducing severe CVH may be diminishing cerebral blood flow, which in turn may cause long-term neurological problems. Therefore, whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in cerebral blood flow, as well as reduced blood flow to other organs, is not certain. Trial methodsInfants were stratified by birthweight (< 750 g or ≥ 750 g) and individual study centre. This stratification was sensible, as the rate of the major adverse outcomes in the study was much higher in those of < 750 g birthweight (62% [298/481]) than in those of birthweight ≥ 750 g (35% [234/662]), and was bound to differ between individual centres (although individual centre data were not reported). Most infants (86%) received their allocated treatment within 6 hours of birth, and most (81%) received all three doses; there were no differences in drug administration (compliance) between the treatment groups. Other aspects of care followed an individual unit's protocol. Blinding was achieved by having a placebo that looked identical to the indomethacin. Although unblinding was theoretically possible through observing urine output, only 7% in the indomethacin group and 4% in the placebo group had treatment withdrawn because of oliguria. Significantly more babies in the placebo group (46%) subsequently received open-label indomethacin to treat a PDA than did babies in the treated group (17%). The follow-up rates to 18 months corrected age were very high (95%) in each group, which is important methodologically, as babies who are difficult to follow-up have more adverse outcomes than those who are followed up more easily.2 All analyses were by intention to treat. New informationIn infants of extremely low birthweight, prophylaxis with indomethacin did not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of PDA and severe CVH. Before this study, it would have been assumed that because prophylactic indomethacin reduces severe CVH, it should improve long-term outcome. This study highlights the problem of relying on changes in surrogate (or intermediate) endpoints, or in risk factors, to determine the effectiveness of therapies. For any therapy to be introduced into clinical practice, the endpoints in trials must be clinically meaningful. Implications for clinical practiceThe types of babies included in this study are typically found in intensive care nurseries in the developed world, and hence the results of the study are widely applicable to infants of birthweight < 1000 g, including those cared for in Australian intensive care nurseries. The study has been incorporated into an update of the Cochrane review of prophylactic indomethacin.3 There are now 19 trials with a total of 2872 babies enrolled. The study by Schmidt et al4 is the largest in the review, with 42% of the total babies enrolled. Its results dominate the review, especially those for long-term neurosensory outcomes, where the study contributes more than two-thirds of all babies in the review. The Cochrane review confirms that prophylactic indomethacin confers no important long-term benefit (or harm) on survival free of neurosensory impairment, despite significantly reducing the rate of severe CVH (relative risk [RR], 0.66; 95% CI, 0.53–0.82). However, the duration of follow-up in most studies is short, and important long-term neurological effects may not be manifest until school-age or later. Hence, it is still not certain that indomethacin imparts no long-term harm. Prophylactic indomethacin reduces the incidence of symptomatic PDA (RR, 0.44; 95% CI, 0.38–0.50), and the need for ductal ligation (RR, 0.51; 95% CI, 0.37–0.71). The absolute reduction in the rate of surgical ligation is 5%, which means that prophylaxis would need to be given to 20 babies to prevent one surgical ligation. For neonatal units where surgical ligation is not an option and where the need for surgical ligation is relatively frequent, giving 20 babies indomethacin to prevent one operation might be a reasonable option. However, this should be undertaken in the full knowledge that indomethacin prophylaxis does not impart any other important short-term benefits, such as a reduction in oxygen requirements, and that there remains the unknown issue of potential longer-term harm. There is no evidence of substantial differences in rates of necrotising enterocolitis, gut perforation, excessive clinical bleeding, or sepsis.

Lex W Doyle MD, FRACP