Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

High prevalence of potential biases threatens the interpretation of trials in patients with chronic disease

BACKGROUND: The complexity of chronic diseases is a challenge for investigators conducting randomized trials. The causes for this include the often difficult control for confounding, the selection of outcomes from many potentially important outcomes, the risk of missing data with long follow-up and the detection of heterogeneity of treatment effects. Our aim was to assess such aspects of trial design and analysis for four prevalent chronic diseases. METHODS: We included 161 randomized trials on drug and non-drug treatments for chronic obstructive pulmonary disease, type 2 diabetes mellitus, stroke and heart failure, which were included in current Cochrane reviews. We assessed whether these trials defined a single outcome or several primary outcomes, statistically compared baseline characteristics to assess comparability of treatment groups, reported on between-group comparisons, and we also assessed how they handled missing data and whether appropriate methods for subgroups effects were used. RESULTS: We found that only 21% of all chronic disease trials had a single primary outcome, whereas 33% reported one or more primary outcomes. Two of the fifty-one trials that tested for statistical significance of baseline characteristics adjusted the comparison for a characteristic that was significantly different. Of the 161 trials, 10% reported a within-group comparison only; 17% (n = 28) of trials reported how missing data were handled (50% (n = 14) carried forward last values, 27% (n = 8) performed a complete case analysis, 13% (n = 4) used a fixed value imputation and 10% (n = 3) used more advanced methods); and 27% of trials performed a subgroup analysis but only 23% of them (n = 10) reported an interaction test. Drug trials, trials published after wide adoption of the CONSORT (CONsolidated Standards of Reporting Trials) statement (2001 or later) and trials in journals with higher impact factors were more likely to report on some of these aspects of trial design and analysis. CONCLUSION: Our survey showed that an alarmingly large proportion of chronic disease trials do not define a primary outcome, do not use appropriate methods for subgroup analyses, or use naïve methods to handle missing data, if at all. As a consequence, biases are likely to be introduced in many trials on widely prescribed treatments for patients with chronic disease

Outcome following patent ductus arteriosus ligation in premature infants:A retrospective cohort analysis

BACKGROUND: The patent ductus arteriosus (PDA) is an important problem in premature infants. Surgical PDA ligation is usually only be considered when medical treatment has either failed or was contraindicated. The aims of our study were to determine the mortality and morbidity following patent ductus arteriosus ligation in premature infants, and whether prostaglandin synthetase inhibitor (PSI) use prior to ligation affects outcome. METHODS: A retrospective case note review study to determine the outcome of premature infants undergoing patent ductus arteriosus ligation in one tertiary neonatal intensive care unit and two paediatric cardiothoracic centres. RESULTS: We had follow-up data on 87 infants. Cumulative mortality rates at 7 days, 30 days and at hospital discharge were 2%, 8% and 20% respectively. The incidence of chronic lung disease, intraventricular haemorrhage, necrotising enterocolitis and retinopathy of prematurity were 77%, 39%, 26% and 28% respectively. There was no difference in mortality, incidence of chronic lung disease or duration of oxygen dependence between those who had and those who had not received a PSI prior to surgical ligation. In those who had received 2 or more courses of PSI prior to surgical ligation, there was a trend to increase in the duration of oxygen therapy and chronic lung disease, but no difference in mortality. CONCLUSION: This study shows that patent ductus arteriosus ligation is a relatively safe procedure (30 day survival 92%) but there is substantial late mortality and a high incidence of morbidity in the survivors. 2 or more courses of PSI prior to surgical ligation trends to increased oxygen dependence and chronic lung disease. This high risk population requires careful follow-up. A definitive prospective cohort study is lacking

What is the probability of detecting poorly performing hospitals using funnel plots?

Recent high profile cases in the UK have highlighted the impact that the reporting of clinical outcomes can have for healthcare providers and patients. Great importance has been placed on the use of statistical methods to identify healthcare providers with observed poor performance. Such providers are highlighted as potential outliers and the possible causes investigated. It is crucial, therefore, that the methods used for identifying outliers are correctly understood and interpreted. While patients, funders, managers and clinical teams really want to know the true underlying performance of the provider, this true performance generally cannot be known directly and must be estimated using observed outcomes. However, differences between the true and observed performance are likely to arise due to chance variation. Clinical outcomes are often reported through the standardised mortality ratio (SMR), displayed using funnel plots. Providers whose observed SMR falls outside the funnel plot control limits will be identified as potential outliers. However, while it is obviously desirable that a healthcare provider with a true underlying performance different from that expected should be identified, the actual probability that it will be identified from observed SMRs has not previously been described. Here we show that funnel plots for the SMR should be used with caution when the expected number of events is small as the probability of identifying providers with true poor performance is likely to be small. On the other hand, when the expected number of events is large, care must be taken as a provider may be identified as an outlier even when its divergence is of little or no clinical importance