Biomedical subjects
Publications and source records attributed to R L Smyth.
AIMS: To assess the reliability of percentage ideal weight for height (%WFH) as a measure in children. METHODS: Forty two dietitians calculated %WFH of six children. Eleven of the 42 repeated the calculations. RESULTS: Interexaminer estimates varied by 16.5 to 40 percentage points (mean 27.8). Intraexaminer variability was also large. CONCLUSIONS: %WFH is an unreliable measure of nutritional status.
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Cystic fibrosis (CF) is one of the commonest lethal inherited conditions among Caucasians. It affects multiple organ systems and exhibits a range of clinical problems of varying severity. Life expectancy has improved in recent years as treatment regimes have become more intensive, but current treatments are expensive, often time consuming and may affect quality of life. This review summarises the treatments currently used in the management of patients with CF, and the evidence for these.
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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 conscientious clinicians have always sought to achieve, but an evidence-based approach applies a systematic and rigorous methodology to this process to ensure that the evidence applied is relevant and of high quality. Because of the volume of potentially relevant information that needs to be accessed from the medical literature, many clinicians rely on reviews of the evidence. Systematic reviews provide summaries of the results of evidence-based healthcare, which can be made available to clinicians, healthcare administrators, and patients. The use of explicit, systematic methods in reviews limits bias (systematic errors) and reduces random errors (simple mistakes), thus providing reliable results on which to draw conclusions and make decisions. Meta-analysis is the use of statistical methods to summarize the results of independent studies. When used appropriately, meta-analysis can provide more precise estimates of the effects of healthcare than those derived from the individual studies included in a review. Childhood respiratory diseases can be a challenging area in which to undertake clinical research. These challenges include diagnostic uncertainty, lack of objective endpoints, and aspects of generalizability of randomized controlled trials. Despite these difficulties, there are now many examples of systematic reviews and evidence-based approaches in pediatric pulmonology. If applied appropriately, they can ensure that management of patients is based on clinically useful diagnostic tests and treatments that have been shown to be effective and not harmful.
OBJECTIVES: To determine 1) what proportion of abstracts of randomized controlled trials (RCTs) presented at international conferences on cystic fibrosis (CF) are published as full reports, 2) time to publication, and 3) factors that might delay or prevent publication. METHODS: At the end of 1995, the Cochrane CF Group's register of RCTs contained 199 abstracts describing 180 RCTs. Abstracts were identified by handsearching 44 abstract books of three international CF conferences over a 30-year period. We searched the register for subsequent full reports of these RCTs and used survival analysis to investigate time to publication. Using the log-rank test, we examined 1) whether there is a difference in time to publication between reports where the investigators concluded that the test treatment was as effective as or better than the control treatment, and reports where it was not, and 2) whether there is a difference in time to publication according to sample size. RESULTS: Thirty-two percent of the 178 abstracts analyzed were subsequently published in full. Survival analysis indicated that the proportions published before 12 months, 2 years, and 5 years were 8.1%, 29%, and 40% respectively. No difference in time to publication was identified when the abstracts were stratified according to conclusions or sample size; no significant association (P > 0.05) existed between time to publication and both sample size and conclusions together. CONCLUSION: Only a small proportion of abstracts of RCTs presented at international conferences on CF are followed by full publication, and usually only after several years. Therefore, many potentially valuable studies do not reach a wide audience. However, we found no consistent factors which might delay or prevent publication.
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OBJECTIVES: To determine whether there is evidence of immunological responses in infants with respiratory syncytial virus (RSV) bronchiolitis by measuring inflammatory mediators in peripheral blood and, if found, whether these related to the severity of illness. PATIENTS AND METHODS: Blood was taken from 94 children with RSV infection during the acute episode and 10 or more days later when the child was well. Control serum samples were obtained from well children of similar ages. Serum samples were assayed for mediators of lymphocyte activity (interleukin-4 (IL-4), soluble interleukin-2 receptor (sCD25), soluble intercellular adhesion molecule-1 (sICAM-1), eosinophil activity (eosinophil cationic protein) and neutrophil activity (myeloperoxidase). Symptoms were assessed as very mild (coryza only), mild (symptoms of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: IL-4 concentrations were at the lower limits of detection of the assay. The concentrations of sCD-25 were greater in samples from patients with acute illness than from convalescent patients and both were greater than in control samples. sICAM-1 concentrations were similar in samples from patients with acute illness and convalescent patients, but both were greater than in samples from controls. Eosinophil cationic protein concentrations were lower in samples from patients with acute illness than in those from convalescent patients; there was no difference between samples from convalescent and control patients. Myeloperoxidase concentrations were similar in all samples. There was no correlation between the severity of infection and the concentrations of any inflammatory mediators. CONCLUSIONS: There is evidence of an inflammatory response in the peripheral blood of infants with acute bronchiolitis which may affect lymphocytes and eosinophils, but an association between this response and the severity of illness was not shown here.
The effect of cystic fibrosis on caffeine metabolism was studied in young children using the caffeine breath test. Eight children with cystic fibrosis aged 2-6 years and nine age matched controls were studied on a single occasion, and the cumulative percentage of labelled caffeine exhaled as carbon dioxide measured over two hours. This was significantly higher in the patients with cystic fibrosis than in controls, suggesting an increase in the CYP1A2 metabolic pathway in the former. The fact that these were young children with minimal lung and liver disease suggests that enhanced drug metabolism in children with cystic fibrosis is hereditary rather than secondary to lung and liver damage.
OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.
BACKGROUND: Pseudomonas aeruginosa colonisation of the airways of patients with cystic fibrosis (CF) is associated with considerable respiratory morbidity. Although segregation of colonised patients from non-colonised patients to prevent cross-infection has been recommended, there is little evidence that such cross-infection is widespread. We observed that a high proportion of children attending our CF clinic were colonised with P aeruginosa that was resistant to ceftazidime and other beta-lactam antibiotics. We used two genomic fingerprinting techniques to see whether this may have arisen from epidemic spread of a single strain. METHODS: The prevalence of P aeruginosa colonisation and the antibiotic susceptibility of the organisms was determined from review of laboratory reports in the case-notes of 120 children with CF. Isolates were cultured from the sputum of 65 children colonised with ceftazidime-resistant P aeruginosa. Polymorphisms in total bacterial DNA from 92 isolates were analysed with two molecular fingerprinting techniques--pulsed-field gel electrophoresis after restriction enzyme digestion and assessment of flagellin gene polymorphisms by amplification of the whole gene and restriction enzyme digestion. RESULTS: 92 (76.7%) of 120 children were colonised with P aeruginosa, and 65 of the 92 harboured isolates that were resistant to ceftazidime. Only three of the 92 children had never been treated with ceftazidime. The results of the two molecular-fingerprinting techniques were concordant and showed that 55 of 65 children harboured the same epidemic strain. This strain was resistant to ceftazidime, azlocillin, and imipenem, and sensitive to tobramycin and ciprofloxacin. INTERPRETATION: This study provides the first molecular evidence of a long-term outbreak of P aeruginosa in a CF centre. We suggest that careful surveillance of the prevalence of antibiotic resistance in CF centres should be instituted with measures to prevent cross-infection. We believe that antipseudomonal monotherapy should be considered with caution.
Spirometry was performed before operation, soon after recovery ("early") and the day after ("late") general anaesthesia for elective surgery in 20 children with asthma and 20 matched children without asthma. Pulse oximetry was recorded on the first postoperative night. The mean early peak expiratory flow rate (PEFR) decreased in the asthmatics by 19.91 (95% confidence intervals (CI) 10.84-28.97)% and in the controls by 19.25 (10.70-27.80)%. The mean early FEV1 decreased in the asthmatics by 16.02 (9.29-22.75)% and in the controls by 11.03 (2.86-19.19)%. The mean late decrease from baseline PEFR for the asthmatics was 18.55 (11.23-25.87)% but only 14.93 (7.89-21.97)% for the controls. The mean late FEV1 was 8.2 (0.83-15.56)% below baseline in the asthmatics but only 6.82 (-0.79 to 14.42)% in the controls. There were no differences in overnight pulse oximetry. We conclude that healthy children exhibited a decrease in FEV1 and PEFR after general anaesthesia for elective surgery, but this decline did not appear to be any greater in well controlled asthmatic children compared with children who did not have asthma.
The introduction of enteric coated pancreatic enzyme supplements in the early 1980s was undoubtedly one of the major advances in the care of children with cystic fibrosis. Further refinements in the presentation of these preparations inevitably followed, to improve patient acceptability and compliance. The emergence of fibrosing colonopathy took clinicians dealing with cystic fibrosis completely by surprise, and in the last two years there has been a gradual appreciation that as far as pancreatic enzyme products are concerned 'More is not necessarily better'. However, it is encouraging that, in the UK, there have been no histologically confirmed cases in children receiving high strength pancreatic enzyme preparations since July 1994. Hopefully this trend will continue and the causal factors will be defined, ensuring that this serious complication can be effectively prevented in the future.
A large series of patients is reported in whom the laryngeal mask airway was used to perform fibreoptic bronchoscopy. It allows direct visualisation of the airways during spontaneous respiration. It has enabled bronchoalveolar lavage and bronchography to be performed in children as young as 6 months and transbronchial biopsies in children as young as 4 years.
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