A major new initiative to improve treatment for children.
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Child↗
Biomedical subjects
R L Smyth
Publications and source records attributed to R L Smyth.
Trends in deaths from respiratory illness in children in England and Wales from 1968 to 2000.
BACKGROUND: Childhood mortality has decreased markedly over the last three decades. A study was undertaken to determine trends in deaths from respiratory illness in children in England and Wales. METHODS: Mortality data collected by the Office for National Statistics were analysed. The data included all deaths registered from all causes in children aged between 28 days and 16 years in England and Wales from 1 January 1968 to 31 December 2000. The main outcome measures were overall and age-specific mortality rates due to all respiratory disorders and specific rates for pneumonia, asthma, cystic fibrosis (CF), and bronchiolitis. RESULTS: In children aged 1-16 years the overall mortality rate (per 100,000 children) declined from 49.9 in 1968 to 16.3 in 2000, and rates due to respiratory illness fell from 8.6 to 1.3. The proportion of all deaths caused by respiratory illness in children aged 28 days to 16 years fell from 30.8% in 1968 to 9.9% in 2000. In post-neonatal infants (aged 28-364 days), the "all cause" mortality rate fell from 592.8 in 1968 to 176 in 2000 and the rates due to respiratory illness fell from 280 to 22.8. In 2000, pneumonia, asthma and CF together accounted for 73% of all respiratory deaths in 1-16 year olds. In this age group, mortality rates per 100,000 for pneumonia fell from 4.22 to 0.57, for asthma from 0.83 to 0.25, and for CF from 0.66 to 0.12 between 1968 and 2000. Over the same period mortality rates for pneumonia in post-neonatal infants fell from 165 to 6.78 per 100,000 and for CF from 4.88 to 0.33. Bronchiolitis mortality rates per 100,000 in post-neonatal infants fell from 21.47 in 1979 to 1.82 in 2000. CONCLUSIONS: Mortality rates due to all respiratory illnesses in children have fallen markedly in the last three decades. This decline has been more rapid than the overall decline in childhood mortality and respiratory diseases are now responsible for a smaller proportion of deaths in children. These data could provide a foundation for assessing the impact on mortality of future health initiatives such as the introduction of a universal pneumococcal vaccination programme in England and Wales.
Adolescent↗
Reliability of calculating body mass index centile.
OBJECTIVE: Body mass index (BMI) centile is recommended for assessing body fatness in children. We compared the reliability of two methods of deriving BMI centile. METHOD: A total of 42 dietitians calculated the BMI centiles of six children, half using the Cole Calculator (a slide rule) and half calculating by hand and plotting on the BMI centile chart. RESULTS: The centile chart method was more reliable than the Cole Calculator, probably due to its greater familiarity.
Adolescent↗
Evidence-based treatment of haemophilia.
Haemophilia care is effective but therapy is expensive. Despite concentrates being available in some areas for more than 30 years, many scientific questions concerning the management of haemophilia, such as what doses and duration of factor are required for different bleeding episodes or for surgical procedures, remain inadequately answered. Modern rigorous methods of assessment of the evidence both assist in determining what facts are available, how reliable the evidence is, and also help to define what studies need to be done. Cochrane methodology can be applied to haemophilia, and an assessment of prophylaxis provides an example. International collaborative studies would be valuable and require enthusiastic participants.
Biomedical Research↗
Intravenous immunoglobulin for cystic fibrosis lung disease.
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Cystic Fibrosis↗
Validity and reliability of acoustic analysis of respiratory sounds in infants.
OBJECTIVE: To investigate the validity and reliability of computerised acoustic analysis in the detection of abnormal respiratory noises in infants. METHODS: Blinded, prospective comparison of acoustic analysis with stethoscope examination. Validity and reliability of acoustic analysis were assessed by calculating the degree of observer agreement using the kappa statistic with 95% confidence intervals (CI). RESULTS: 102 infants under 18 months were recruited. Convergent validity for agreement between stethoscope examination and acoustic analysis was poor for wheeze (kappa = 0.07 (95% CI, -0.13 to 0.26)) and rattles (kappa = 0.11 (-0.05 to 0.27)) and fair for crackles (kappa = 0.36 (0.18 to 0.54)). Both the stethoscope and acoustic analysis distinguished well between sounds (discriminant validity). Agreement between observers for the presence of wheeze was poor for both stethoscope examination and acoustic analysis. Agreement for rattles was moderate for the stethoscope but poor for acoustic analysis. Agreement for crackles was moderate using both techniques. Within-observer reliability for all sounds using acoustic analysis was moderate to good. CONCLUSIONS: The stethoscope is unreliable for assessing respiratory sounds in infants. This has important implications for its use as a diagnostic tool for lung disorders in infants, and confirms that it cannot be used as a gold standard. Because of the unreliability of the stethoscope, the validity of acoustic analysis could not be demonstrated, although it could discriminate between sounds well and showed good within-observer reliability. For acoustic analysis, targeted training and the development of computerised pattern recognition systems may improve reliability so that it can be used in clinical practice.
Acoustics↗
Pro- and anti-inflammatory responses in respiratory syncytial virus bronchiolitis.
Respiratory syncytial virus (RSV) bronchiolitis is an important cause of severe respiratory disease in infants. This study aimed to characterise changes in pulmonary pro- and anti-inflammatory responses in infants with RSV bronchiolitis over the course of the illness. On the day of intubation (Day 1) and the day of extubation (Day X), nonbronchoscopic bronchoalveolar lavage was performed on term and preterm infants ventilated for RSV bronchiolitis and on control infants on Day 1. Tumour necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR) and interleukin (IL)-6 messenger ribonucleic acid (mRNA) and protein were measured. Twenty-four infants, born at term and 23 infants born preterm with RSV bronchiolitis and 10 controls were recruited. TNF-alpha and IL-6 mRNA and protein in infants with bronchiolitis were greater than the control group on Day 1. In preterm infants, who were ventilated for longer than term infants, TNF-alpha and IL-6 proteins decreased between Day 1 and Day X. Concentrations of sTNFRs differed between groups on Day 1, but levels did not change between Day 1 and Day X. Large amounts of tumour necrosis factor-alpha and interleukin-6 in the respiratory syncytial virus-infected lung suggest important roles for these cytokines in the pathogenesis of respiratory syncytial virus bronchiolitis. The decrease in tumour necrosis factor-alpha and interleukin-6 protein in preterm infants may reflect the prolonged clinical course seen in these infants.
Bronchiolitis, Viral↗
Reversible bronchial dilatation in children: comparison of serial high-resolution computer tomography scans of the lungs.
INTRODUCTION: Bronchiectasis is generally considered irreversible in the adult population, largely based on studies employing bronchography in cases with a significant clinical history. It is assumed, that the same is true for children. Few studies have examined the natural history of bronchiectasis in children and diagnostic criteria on high-resolution computer tomography of the lungs are derived from studies on adults. Frequently, bronchiectasis is reported in children in cases where localised bronchial dilatation is present, incorrectly labelling these children with an irreversible life-long condition. OBJECTIVE: to evaluate changes in appearance of bronchial dilatation, unrelated to cystic fibrosis in children, as assessed by sequential high-resolution computer tomography (HRCT) of the lungs. METHODS: The scans of 22 children with a radiological diagnosis of bronchiectasis, seen at Alder Hey Children's Hospital between 1994 and 2000, who had at least two CT scans of the lungs were reviewed by a single radiologist, who was blinded to the original report. RESULTS: Following a median scan interval of 21 months (range 2-43), bronchial dilatation resolved completely in six children and there was improvement in appearances in a further eight, with medical treatment alone. DISCUSSION: A radiological diagnosis of bronchiectasis should be considered with caution in children as diagnostic criteria derived from studies in adults have not been validated in children and the condition is generally considered irreversible.
Adolescent↗
Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis.
AIM: To examine over time, the cellular response within the lungs of infants ventilated with respiratory syncytial virus (RSV) bronchiolitis and to compare this response in infants born at term with those born preterm. METHODS: Non-bronchoscopic bronchoalveolar lavage (BAL) samples were taken from 47 infants (24 born at term and 23 born preterm) who were ventilated for RSV positive bronchiolitis and 10 control infants. BAL cellularity and differential cell counts were calculated using standard techniques. RESULTS: Total cellularity in BAL over the first four days of ventilation in infants with RSV bronchiolitis was greater in term infants (median 2.2 (IQR 4.27) x 10(6) cells/ml) compared with preterm infants (0.58 (1.28) x 10(6) cells/ml). The magnitude of the cellular response in preterm infants with bronchiolitis was similar to that in the control group measured on day 1 (0.62 (0.77) x 10(6) cells/ml). BAL cellularity decreased progressively from the time of intubation in term infants, but remained relatively constant in preterm infants up to seven days after intubation. CONCLUSIONS: There are differences in the magnitude and type of pulmonary cellular response in term and preterm infants ventilated with RSV bronchiolitis. The cellular response in term infants with bronchiolitis differs from that in a control group of infants. These differences may reflect variations in cellular recruitment in the lung and/or variations in airway calibre.
Bronchiolitis, Viral↗
Meta-analysis of method comparison studies.
Methods for the meta-analysis of results from randomized controlled trials are well established. However, there are currently no methods for the meta-analysis of method comparison studies. Here the combination of results from studies comparing two methods of measurement on the same unit of observation is required. We compare standard methods for the pooling of k samples from the same Normal population to those for pooling parameter estimates, in order to estimate the pooled mean difference and 95 per cent limits of agreement. Methods for investigating heterogeneity across studies and for calculating random effects estimates are proposed. We postulate that for published studies either the estimated mean or variance of the difference between measurements will tend to be smaller than for unpublished studies and investigate the evidence for the existence of such publication bias. The methods are illustrated with an example evaluating the accuracy of temperature measured at the axilla compared to the rectum in children.
Axilla↗
Creon 10,000 Minimicrospheres vs. Creon 8,000 microspheres--an open randomised crossover preference study.
Creon 10,000 Minimicrospherestrade mark (Creon) 10,000 MMS) is a pancreatic enzyme formulation that contains smaller spheres of pancreatin in a 50% smaller capsule than conventional microspheres (Creon) 8,000). This three-centre study investigated the preference of cystic fibrosis (CF) patients for these products. In one centre, 72 h stool fat excretion and coefficient of fat absorption (CFA) were also compared. Fifty-nine patients with a mean age 10 years (range 3-17) took Creon 8,000 ms for 14 days and were then randomised to 28 days of Creon 8,000 ms followed by 28 days of Creon 10,000 MMS, or vice versa. Dosing was lipase for lipase according to the labelled declaration. At the end of the second treatment period, 51 of 54 patients who completed the study expressed a preference, with a statistically significant preference in favour of Creon 10,000 MMS (47/51; 87%) vs. Creon 8,000 ms (4/51; 7.4%; P<0.0001). Stool fat (g/day) and CFA (%) were measured in 24 patients at the end of each treatment period: the products were therapeutically equivalent (Creon 10,000: 8.4 g/day, 91.3% CFA; Creon 8,000: 6.7 g/day, 93.5% CFA). Both products were well tolerated. In conclusion, in CF children we found a clear preference for Creon 10,000 MMS compared with Creon 8,000 ms with no difference in fat absorption between the two products. Creon 10,000s smaller capsules are easier to take and should aid patient compliance.
Administration, Oral↗
The promise of and problems with evidence-based medicine for paediatric asthma management.
The concept of 'evidence-based medicine' has now been in widespread use in clinical practice for over a decade. There are different types of clinical study, which may provide evidence on which to base clinical decisions, but some are much less robust than others. In making decisions about treatment, one of the highest levels of evidence in primary research is the randomized controlled trial. This study design has been used in clinical research for over 50 years. Systematic reviews of randomized controlled trial are scientific studies that review, critically appraise and, where appropriate, aggregate results from a number of different randomized controlled trials. They are increasingly being used throughout health care to provide guidance about treatment. Under the auspices of The Cochrane Collaboration, systematic reviews of randomized controlled trials are being conducted across the whole of health care. One of the most active areas for this work is within the field of asthma and clinicians are now able to access a large number of different systematic reviews on The Cochrane Library. If used appropriately, they can aid the clinician in making decisions about individual patients and provide a sound evidence base from which clinical guidelines can be developed.
Asthma↗
Research with children. Paediatric practice needs better evidence--gained in collaboration with parents and children.
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Child↗
Temperature measured at the axilla compared with rectum in children and young people: systematic review.
OBJECTIVE: To evaluate the agreement between temperature measured at the axilla and rectum in children and young people. DESIGN: A systematic review of studies comparing temperature measured at the axilla (test site) with temperature measured at the rectum (reference site) using the same type of measuring device at both sites in each patient. Devices were mercury or electronic thermometers or indwelling thermocouple probes. STUDIES REVIEWED: 40 studies including 5528 children and young people from birth to 18 years. DATA EXTRACTION: Difference in temperature readings at the axilla and rectum. RESULTS: 20 studies (n=3201 (58%) participants) had sufficient data to be included in a meta-analysis. There was significant residual heterogeneity in both mean differences and sample standard deviations within the groups using different devices and within age groups. The pooled (random effects) mean temperature difference (rectal minus axillary temperature) for mercury thermometers was 0.25 degrees C (95% limits of agreement -0.15 degrees C to 0.65 degrees C) and for electronic thermometers was 0. 85 degrees C (-0.19 degrees C to 1.90 degrees C). The pooled (random effects) mean temperature difference (rectal minus axillary temperature) for neonates was 0.17 degrees C (-0.15 degrees C to 0. 50 degrees C) and for older children and young people was 0.92 degrees C (-0.15 degrees C to 1.98 degrees C). CONCLUSIONS: The difference between temperature readings at the axilla and rectum using either mercury or electronic thermometers showed wide variation across studies. This has implications for clinical situations where temperature needs to be measured with precision.
Adolescent↗
Randomized controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention.
The improved prognosis of cystic fibrosis (CF) over the last three decades has been associated with an increased use of a range of treatments, but it is important that the use of an individual treatment is based on evidence. Well-designed randomized controlled trials (RCTs) are a robust method for evaluating the effectiveness of such treatments. We have developed a register of RCTs in CF and have studied when they were performed, their design, and what interventions were investigated. We identified 506 RCTs; 37.5% were identified solely as abstract reports in conference proceedings. There has been about a 30-fold increase in the number of RCTs in CF since 1966. A high proportion of the RCTs (72.7%) had a sample size of 30 or less, and only 8.7% were multicenter trials. Reporting of study design was poor: in 51.4% the report did not state whether there was any blinding in the trial design; 53.6% of studies were of crossover design. The most common interventions studied were antibiotic treatments and physiotherapy, but a number of commonly used therapies had been evaluated only in a small number of patients. Although the number of RCTs of interventions in CF patients has increased over the last 25 years, the sample sizes of these trials are generally too small to indicate whether the intervention was effective, and very few were multicenter. Future RCTs in CF are more likely to provide clinically useful answers if higher numbers of patients are recruited into large, well-designed multicenter trials. This should be a priority of the organization of future research in CF.
Cystic Fibrosis↗
Oral protein calorie supplementation for children with chronic disease.
BACKGROUND: Growth failure and poor nutritional status are common features in children with chronic diseases due to reduced appetite, malabsorption and increased nutritional requirements associated with some diseases. The provision of oral protein calorie supplements is one of a number of interventions used to improve nutritional status in these children. The use of these products, which are expensive, may be associated with a number of adverse effects, for example, they may effect development of normal eating behaviour patterns or lead to unpleasant symptoms such as vomiting and diarrhoea. OBJECTIVES: To examine the evidence that in children with chronic disease, oral protein calorie supplements alter daily nutrient intake, nutritional indices, survival and quality of life and are associated with adverse effects, for example diarrhoea, vomiting, reduced appetite, glucose intolerance, bloating and eating behaviour problems. SEARCH STRATEGY: All publications describing RCTs of the use of oral protein calorie supplements in children with chronic diseases were identified through comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. The companies which market oral protein calorie supplements were also contacted. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing use of oral protein calorie supplements for at least one month to increase calorie intake with existing conventional therapy, which may include nutritional advice on how to improve nutritional intake from food or no specific intervention, in children with chronic disease. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: indices of nutrition and growth, anthropometric measures of body composition, calorie and nutrient intake (total, from oral protein calorie supplements and from food), eating behaviour, compliance, quality of life, specific adverse effects and disease severity scores, and mortality. MAIN RESULTS: Three trials have been identified as being suitable for inclusion in the review and we are awaiting further data from one of these trials. All of these trials were carried out in children with cystic fibrosis. Few statistical differences could be found between the treatment and control groups apart from change in total fat intake at three months (weighted mean difference 69.20 [95% CI 11.05, 127.35]). However, this was based on the results of only one, small study. No trials have been identified which assess the effectiveness of oral protein calorie supplements in children with other chronic diseases. REVIEWER'S CONCLUSIONS: Oral protein calorie supplements are widely used to improve the nutritional status of children with a number of chronic diseases. We have only been able to identify a small number of trials assessing these products in children with cystic fibrosis and have been unable to draw any conclusions based on the limited data extracted from these. We therefore recommend that a series of large, randomised controlled trials are undertaken investigating the use of these products in children with different chronic diseases. Until further data are available, we would suggest that these products are only used with caution.
Adolescent↗
Evidence-based medicine.
Evidence-based medicine aims to identify, critically appraise and apply the best available evidence in making decisions about the care of patients. These aims are similar to those which conscientious clinicians have always tried to achieve. An evidence-based approach applies a systematic and rigorous methodology to this process to ensure that the evidence which is applied is relevant and of high quality. The use of this methodology limits bias (systematic errors) and reduces random errors (simple mistakes), thus providing reliable results on which to draw conclusions and make decisions. Meta-analysis, when used appropriately, can provide more precise estimates of the effects of healthcare than those derived from the individual studies included in a review. Systematic reviews also provide summaries of the results of evidence-based healthcare. These are available to all interested individuals, including clinicians, healthcare administrators and patients.
Decision Support Techniques↗
Intestinal inflammation in cystic fibrosis.
BACKGROUND: There is controversy about whether the inflammatory response observed in the cystic fibrosis (CF) lung occurs secondary to bacterial infection or is caused by a dysregulation of the inflammatory response associated with the basic cellular defect of CF. AIMS: To study the inflammatory response in the gastrointestinal tract of children with CF; and to investigate whether there is increased inflammation in the gastrointestinal tract of CF children with fibrosing colonopathy. METHODS: Whole gut lavage was performed on 21 pancreatic insufficient children with CF, who were clinically well, five children with CF and fibrosing colonopathy, and 12 controls. Intestinal outputs of plasma derived proteins (albumin, alpha(1) antitrypsin, IgG), secretory immunoglobulins (IgA and IgM), cellular constituents (eosinophil cationic protein and neutrophil elastase), and cytokines (interleukin 8 and interleukin 1beta) were measured. RESULTS: Compared to controls, the 21 CF patients, with no intestinal complications, had increased intestinal outputs of albumin, IgG, IgM, eosinophil cationic protein, neutrophil elastase, interleukin 1beta, and interleukin 8. Similar values were obtained for the CF patients with fibrosing colonopathy. CONCLUSIONS: These data suggest that there is immune activation in the gastrointestinal mucosa of children with cystic fibrosis, which may result from the basic cellular defect. Fibrosing colonopathy does not appear to be associated with increased inflammation.
Adolescent↗