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TP53 mutation predicts the poor prognosis of non-Hodgkin lymphomas: Evidence from a meta-analysis
No full textThe effect of early versus late initiation of renal replacement therapy in patients with acute kidney injury: A meta-analysis with trial sequential analysis of randomized controlled trials
No full textThe optimal timing for initiating renal replacement therapy (RRT) in patients with acute kidney injury (AKI) remains controversial.We conducted a meta-analysis with trial sequential analysis (TSA) of randomized controlled trials (RCTs) using PUBMED, Cochrane Library databases, and Web of Science (from January 1, 1985, to August 21, 2016). Adult patients with AKI who received RRT with different timing were included. The primary outcome was mortality. The secondary outcomes were intensive care unit (ICU) length of stay (LOS) and hospital LOS.We included 9 RCTs with a total of 1636 participants. No differences between the early RRT group and the late RRT group were found with respect to mortality (38% vs 41.4%; relative risk, 0.93; 95% confidence interval [CI], 0.74–1.18). However, TSA showed that the cumulative Z-curve did not cross either the conventional boundary for benefit or the trial sequential monitoring boundary, indicating insufficient evidence. Similarity, there were no findings of benefits in terms of reduction in the ICU LOS (standard difference in the means, −0.32 days; 95% CI, −0.71 to 0.07 days) and hospital LOS (standard difference in the means, −1.11 days; 95% CI, −2.28 to 0.06 days). Meanwhile, the results of TSA did not confirm this conclusion.Although conventional meta-analysis showed that early initiation of RRT in patients with AKI was not associated with decreased mortality, ICU LOS and hospital LOS, TSA indicated that the data were far too sparse to make any conclusions. Therefore, well-designed, large RCTs are needed
The signal peptide-like segment of hpaXm is required for its association to the cell wall in transgenic tobacco plants
No full textRehabilitation for people living with dementia: A practical framework of positive support
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Interrater agreement of two adverse drug reaction causality assessment methods: A randomised comparison of the Liverpool Adverse Drug Reaction Causality Assessment Tool and the World Health Organization-Uppsala Monitoring Centre system
No full textA new method to assess causality of suspected adverse drug reactions, the Liverpool Adverse Drug Reaction Causality Assessment Tool (LCAT), showed high interrater agreement when used by its developers. Our aim was to compare the interrater agreement achieved by LCAT to that achieved by another causality assessment method, the World Health Organization-Uppsala Monitoring Centre system for standardised case causality assessment (WHO-UMC system), in our setting.Four raters independently assessed adverse drug reaction causality of 48 drug-event pairs, identified during a hospital-based survey. A randomised design ensured that no washout period was required between assessments with the two methods. We compared the methods’ interrater agreement by calculating agreement proportions, kappa statistics, and the intraclass correlation coefficient. We identified potentially problematic questions in the LCAT by comparing raters’ responses to individual questions.Overall unweighted kappa was 0.61 (95% CI 0.43 to 0.80) on the WHO-UMC system and 0.27 (95% CI 0.074 to 0.46) on the LCAT. Pairwise unweighted Cohen kappa ranged from 0.33 to 1.0 on the WHO-UMC system and from 0.094 to 0.71 on the LCAT. The intraclass correlation coefficient was 0.86 (95% CI 0.74 to 0.92) on the WHO-UMC system and 0.61 (95% CI 0.39 to 0.77) on the LCAT. Two LCAT questions were identified as significant points of disagreement.We were unable to replicate the high interrater agreement achieved by the LCAT developers and instead found its interrater agreement to be lower than that achieved when using the WHO-UMC system. We identified potential reasons for this and recommend priority areas for improving the LCAT
Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted
No full textIn 2014–2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations.). There was no significant relationship between favipiravir concentrations and EBOV viral kinetics or mortality.Favipiravir plasma concentrations in the JIKI trial failed to achieve the target exposure defined before the trial. Furthermore, the drug concentration experienced an unanticipated drop between Day-2 and Day-4. The origin of this drop could be due to severe sepsis conditions and/or to intrinsic properties of favipiravir metabolism. Dose-ranging studies should be performed in healthy volunteers to assess the concentrations and the tolerance that could be achieved with high doses
Stress indicator gene expression profiles, colony dynamics and tissue development of honey bees exposed to sub-lethal doses of imidacloprid in laboratory and field experiments
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