Do guidelines for treating chest disease in children use Cochrane Reviews effectively?: a systematic review

Cochrane Reviews summarise best evidence and should inform guidelines. We assessed the use of Cochrane Reviews in the UK guidelines for paediatric respiratory disease. We found 21 guidelines which made 1025 recommendations, of which 96 could be informed by a Cochrane Review. In 38/96 recommendations (40%), some or all of the relevant Cochrane Reviews were not cited. We linked recommendations to 140 Cochrane Reviews. In 37/140 (26%) cases, the guideline recommendation did not fully agree with the Cochrane Review. Guideline developers may fail to use Cochrane Reviews or may make recommendations which are not in line with best evidence

The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis:A randomised comparison

AbstractBackgroundCircadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity.AimTo investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission.MethodsChildren (age 5–18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin.ResultsEighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%).ConclusionsRenal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245)

Do guidelines for treating chest disease in children use Cochrane Reviews effectively?: a systematic review

Cochrane Reviews summarise best evidence and should inform guidelines. We assessed the use of Cochrane Reviews in the UK guidelines for paediatric respiratory disease. We found 21 guidelines which made 1025 recommendations, of which 96 could be informed by a Cochrane Review. In 38/96 recommendations (40%), some or all of the relevant Cochrane Reviews were not cited. We linked recommendations to 140 Cochrane Reviews. In 37/140 (26%) cases, the guideline recommendation did not fully agree with the Cochrane Review. Guideline developers may fail to use Cochrane Reviews or may make recommendations which are not in line with best evidence

Assessing the impact of posture on diaphragm morphology and function using an open upright MRI system – a pilot study

PurposeThe diaphragm is the most important muscle of respiration. Disorders of the diaphragm can have a deleterious impact on respiratory function. We aimed to evaluate the use of an open-configuration upright low-field MRI system to assess diaphragm morphology and function in patients with bilateral diaphragm weakness (BDW) and chronic obstructive pulmonary disease (COPD) with hyperinflation.MethodThe study was approved by the National Research Ethics Committee, and written consent was obtained. We recruited 20 healthy adult volunteers, six subjects with BDW, and five subjects with COPD with hyperinflation. We measured their vital capacity in the upright and supine position, after which they were scanned on the 0.5 T MRI system during 10-second breath-holds at end-expiration and end-inspiration in both positions. We developed and applied image analysis methods to measure the volume under the dome, maximum excursion of hemidiaphragms, and anterior-posterior and left-right extension of the diaphragm.ResultsAll participants were able to complete the scanning protocol. The patients found scanning in the upright position more comfortable than the supine position. All differences in the supine inspiratory-expiratory parameters, excluding left-right extension, were significantly smaller in the BDW and COPD groups compared with healthy volunteers. No significant correlation was found between the postural change in diaphragm morphology and vital capacity in either group.ConclusionOur combined upright-supine MR imaging approach facilitates the assessment of the impact of posture on diaphragm morphology and function in patients with BDW and those with COPD with hyperinflation

Are citations from clinical trials evidence of higher impact research? An analysis of ClinicalTrials.gov

An important way in which medical research can translate into improved health outcomes is by motivating or influencing clinical trials that eventually lead to changes in clinical practice. Citations from clinical trials records to academic research may therefore serve as an early warning of the likely future influence of the cited articles. This paper partially assesses this hypothesis by testing whether prior articles referenced in ClinicalTrials.gov records are more highly cited than average for the publishing journal. The results from four high profile general medical journals support the hypothesis, although there may not be a cause-and effect relationship. Nevertheless, it is reasonable for researchers to use citations to their work from clinical trials records as partial evidence of the possible long-term impact of their research

Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions : A Systematic Review

BACKGROUND: We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events. METHODS AND FINDINGS: Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published. CONCLUSIONS: There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events