PLoS medicine
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Review Meta Analysis
Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy.
Despite guidelines establishing the need to perform comprehensive paediatric drug development programs, pivotal trials in children with epilepsy have been completed mostly in Phase IV as a postapproval replication of adult data. However, it has been shown that the treatment response in children can differ from that in adults. It has not been investigated whether differences in drug effect between adults and children might occur in the treatment of drug-resistant partial epilepsy, although such differences may have a substantial impact on the design and results of paediatric randomised controlled trials (RCTs). ⋯ Children with drug-resistant partial epilepsy receiving placebo in double-blind RCTs demonstrated significantly greater 50% responder rate than adults, probably reflecting increased placebo and regression to the mean effects. Paediatric clinical trial designs should account for these age-dependent variations of the response to placebo to reduce the risk of an underestimated sample size that could result in falsely negative trials.
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Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. ⋯ Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP.
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Traumatic brain injury (TBI) is a leading cause of death and disability. A reliable prediction of outcome on admission is of great clinical relevance. We aimed to develop prognostic models with readily available traditional and novel predictors. ⋯ Prognostic models using baseline characteristics provide adequate discrimination between patients with good and poor 6 mo outcomes after TBI, especially if CT and laboratory findings are considered in addition to traditional predictors. The model predictions may support clinical practice and research, including the design and analysis of randomized controlled trials.