To evaluate the results of large clinical trials vs the pooled results of smaller trials.
Meta-analyses with at least 1 "large" study were identified from the Cochrane Pregnancy and Childbirth ...Database and from MEDLINE (1966-1995).
We used a sample size approach to select 79 meta-analyses with at least 1 large study of 1000 or more patients. We used a statistical power approach to select 61 meta-analyses with at least 1 large study based on statistical power considerations.
The outcome of interest for each meta-analysis was the primary one stated in the original publication or, when not clearly specified, was decided on clinically.
By random effects calculations, we found agreement between large and smaller trials in 90% of the meta-analyses selected by the sample size approach and in 82% of the meta-analyses selected by the statistical power approach. Twice as many disagreements appeared when the variability among large studies and among smaller studies was not considered (ie, fixed effects calculations). Of the 15 disagreements between results of large and smaller trials using the random effects model, plausible explanations were identified in 10 meta-analyses: 5 with differences in the control rate of events between large and smaller trials, 4 with specific protocol or study differences, and 1 with potential publication bias. Two other disagreements were not clinically important, and tentative reasons could be identified for 2 of the remaining 3 disagreements.
Results of smaller studies are usually compatible with the results of large studies, but discrepancies do occur even when the diversity among both large studies and smaller studies is considered. Clinically important differences without a potential explanation are extremely uncommon. Future research should further examine sources of heterogeneity between the results of large and smaller trials.
It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary bypass (LF), deep hypothermic circulatory arrest ...(CA), or both.
In a database review of a prospective trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were randomly assigned to predominantly LF or CA, glucose was measured after induction (T1), 5 min after cardiopulmonary bypass onset (T2), at the onset of CA or LF (T3), 5 min after CPB resumption (T4), at rewarming to 32 degrees C (T5), 10 min after cardiopulmonary bypass weaning (T6), and 90 min after CA or LF (T7). Outcomes included seizures, electroencephalographic findings, and neurodevelopmental evaluation at 1, 4, and 8 yr.
Glucose concentrations were affected by support strategy and age at surgery. Lower glucose in the entire group at T6-T7 tended to predict electroencephalographic seizures (P = 0.06 and P = 0.007) but was not related to clinical seizures. Within the predominantly CA group, higher glucose did not correlate with worse outcomes. Rather, it was associated with more rapid electroencephalographic normalization of "close burst" and "relative continuous" activity at all times except T2 (P < or = 0.03), a finding more pronounced in infants aged 7 days old or younger. Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1, 4, and 8 yr.
Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery, independent of CA duration. High glucose concentrations were not associated with worse neurodevelopmental outcomes. Avoiding hypoglycemia may be preferable to restricting glucose in infants undergoing heart surgery.
The initial and primary treatment of abnormal lipid levels (Table 13-1) in children is to change diet and activity levels. Pharmacological treatment of lipid disorders is used according to guidelines ...published in 1992 (Table 13-2). In adults, treatment cutpoints and goals for therapy are adjusted based on high-risk populations and in the presence of other cardiovascular (CV) risk factors; a similar approach is being taken in pediatrics (Table 13-3). New pediatric lipid guidelines are being developed and will likely reflect this type of thinking. Although atherosclerosis is known to begin in childhood, extensive outcome data are lacking in pediatrics, and parental and/or patient preferences are usually included in the decisionmaking process.
...this trial should be the main evidence on which general practitioners should base their practice-that antibiotics have no effect in adults with acute sinusitus-like complaints-until other studies ...in similar situations show otherwise.
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