Presentation of continuous outcomes in randomised trials: an observational study.

OBJECTIVE: To characterise the percentage of available outcome data being presented in reports of randomised clinical trials with continuous outcome measures, thereby determining the potential for incomplete reporting bias. DESIGN: Descriptive cross sectional study. DATA SOURCES: A random sample of 200 randomised trials from issues of 20 medical journals in a variety of specialties during 2007-09. MAIN OUTCOME MEASURES: For each paper's best reported primary outcome, we calculated the fraction of data reported using explicit scoring rules. For example, a two arm trial with 100 patients per limb that reported 2 sample sizes, 2 means, and 2 standard deviations reported 6/200 data elements (1.5%), but if that paper included a scatterplot with 200 points it would score 200/200 (100%). We also assessed compliance with 2001 CONSORT items about the reporting of results. RESULTS: The median percentage of data reported for the best reported continuous outcome was 9% (interquartile range 3-26%) but only 3.5% (3-7%) when we adjusted studies to 100 patients per arm to control for varying study size; 17% of articles showed 100% of the data. Tables were the predominant means of presenting the most data (59% of articles), but papers that used figures reported a higher proportion of data. There was substantial heterogeneity among journals with respect to our primary outcome and CONSORT compliance. LIMITATIONS: We studied continuous outcomes of randomised trials in higher impact journals. Results may not apply to categorical outcomes, other study designs, or other journals. CONCLUSIONS: Trialists present only a small fraction of available data. This paucity of data may increase the potential for incomplete reporting bias, a failure to present all relevant information about a study's findings.

Triazoles as γ-secretase modulators.

Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs. 1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of γ-secretase activity, excellent pharmacokinetics and good central lowering of Aß42 in Sprague-Dawley rats.

Molecular determinants of dihydrouridine synthase activity.

Dihydrouridine is one of the most abundant modified bases in tRNA. However, little is known concerning the biochemistry of dihydrouridine synthase (DUS) enzymes. To identify molecular determinants that are necessary for DUS activity, we have developed a DUS-complementation assay in Escherichia coli. Using this assay, we have identified amino-acid residues that are critical for the activity of YjbN, an E. coli DUS. We also show that the aq1598 gene product, a putative DUS from Aquifex aeolicus, catalyzes dihydrouridine formation, providing the first biochemical demonstration that A. aeolicus encodes an active DUS.