A confidence interval approach for difference and ratio of normal means in self-designing clinical trials

In self-designing clinical trials, confidence intervals are derived for the difference and the ratio of normal means, where the results of the independent study stages are combined using the weighted inverse normal method. The confidence intervals always hold the predefined nominal confidence level. During the course of the Self-designing trial, the sample sizes as well as the number of study stages can be determined simultaneously in a completely adaptive way. Self-designing may be considered as the limit case of adaptive group sequential designing of O'Brien and Fleming type when the full significance level is shifted to the last stage. We consider the effect measures difference and ratio of normal means, where the latter has not yet been considered in group sequential trials so far. Concrete rules are derived for updating sample sizes and assigning weights to the stages of the trial. The clinical trial may be originally designed either to show non-inferiority or superiority. But, in each interim analysis, it is possible to change the planning from showing non-inferiority to showing superiority or vice versa. The performance of the Self-designing and the resulting confidence intervals are demonstrated in real-data examples for both considered effect measures showing both kinds of switching during an ongoing trial

Asymptotic tests for general linear hypotheses on variance components in models of commutative quadratic type

In this paper we derive asymptotic x^2 -tests for general linear hypotheses on variance components using repeated variance components models. In two examples, the two-way nested classification model and the two-way crossed classification model with interaction, we explicitly investigate the properties of the asymptotic tests in small sample sizes

Short term and intermediate term comparison of endarterectomy versus stenting for carotid artery stenosis: systematic review and meta-analysis of randomised controlled clinical trials

Objective To evaluate the relative short term safety and intermediate term efficacy of carotid endarterectomy versus carotid artery stenting

The impact of the coronary collateral circulation on mortality: a meta-analysis

Aims The coronary collateral circulation as an alternative source of blood supply has shown benefits regarding several clinical endpoints in patients with myocardial infarction (MI) such as infarct size and left ventricular remodelling. However, its impact on hard endpoints such as mortality and its impact in patients with stable coronary artery disease (CAD) is more controversial. The purpose of this systematic review and meta-analysis was to explore the impact of collateral circulation on all-cause mortality. Methods and results We searched MEDLINE, EMBASE, ISI Web of Science (2001 to 25 April 2011), and conference proceedings for studies evaluating the effect of coronary collaterals on mortality. Random-effect models were used to calculate summary risk ratios (RR). A total of 12 studies enrolling 6529 participants were included in this analysis. Patients with high collateralization showed a reduced mortality compared with those with low collateralization [RR 0.64 (95% confidence interval 0.45-0.91); P= 0.012]. The RR for ‘high collateralization' in patients with stable CAD was 0.59 [0.39-0.89], P= 0.012, in patients with subacute MI it was 0.53 [0.15-1.92]; P= 0.335, and for patients with acute MI it was 0.63 [0.29-1.39]; P= 0.257. Conclusions In patients with CAD, the coronary collateralization has a relevant protective effect. Patients with a high collateralization have a 36% reduced mortality risk compared with patients with low collateralizatio

Effects of exercise on the resting heart rate

Resting heart rate (RHR) is positively related with mortality. Regular exercise causes a reduction in RHR. The aim of the systematic review was to assess whether regular exercise or sports have an impact on the RHR in healthy subjects by taking different types of sports into account. A systematic literature research was conducted in six databases for the identification of controlled trials dealing with the effects of exercise or sports on the RHR in healthy subjects was performed. The studies were summarized by meta-analyses. The literature search analyzed 191 studies presenting 215 samples fitting the eligibility criteria. 121 trials examined the effects of endurance training, 43 strength training, 15 combined endurance and strength training, 5 additional school sport programs. 21 yoga, 5 tai chi, 3 qigong, and 2 unspecified types of sports. All types of sports decreased the RHR. However, only endurance training and yoga significantly decreased the RHR in both sexes. The exercise-induced decreases of RHR were positively related with the pre-interventional RHR and negatively with the average age of the participants. From this, we can conclude that exercise—especially endurance training and yoga—decreases RHR. This effect may contribute to a reduction in all-cause mortality due to regular exercise or sports

Physical Activity and Outdoor Play of Children in Public Playground : Do Gender and Social Environment Matter?

Background: Few studies have delved into the relationship of the social environment with children’s physical activity and outdoor play in public playgrounds by considering gender differences. The aim of the present study was to examine gender differences and the relationship of the social environment with children’s physical activity and outdoor play in public playgrounds. Methods: A quantitative, observational study was conducted at ten playgrounds in one district of a middle-sized town in Germany. The social environment, physical activity levels, and outdoor play were measured using a modified version of the System for Observing Play and Leisure Activity in Youth. Results: In total, 266 observations of children (117 girls/149 boys) between four and 12 years old were used in this analysis. Significant gender differences were found in relation to activity types, but not in moderate-to-vigorous physical activity (MVPA). The presence of active children was the main explanatory variable for MVPA. In the models stratified by gender, the presence of opposite-sex children was a significant negative predictor of MVPA in girls but not in boys. Conclusions: The presence of active children contributes to children’s physical activity levels in public playgrounds. Girls’ physical activity seems to be suppressed in the presence of boys

Methods to estimate the between-study variance and its uncertainty in meta-analysis

Meta‐analyses are typically used to estimate the overall/mean of an outcome of interest. However, inference about between‐study variability, which is typically modelled using a between‐study variance parameter, is usually an additional aim. The DerSimonian and Laird method, currently widely used by default to estimate the between‐study variance, has been long challenged. Our aim is to identify known methods for estimation of the between‐study variance and its corresponding uncertainty, and to summarise the simulation and empirical evidence that compares them. We identified 16 estimators for the between‐study variance, seven methods to calculate confidence intervals, and several comparative studies. Simulation studies suggest that for both dichotomous and continuous data the estimator proposed by Paule and Mandel and for continuous data the restricted maximum likelihood estimator are better alternatives to estimate the between‐study variance. Based on the scenarios and results presented in the published studies, we recommend the Q‐profile method and the alternative approach based on a ‘generalised Cochran between‐study variance statistic’ to compute corresponding confidence intervals around the resulting estimates. Our recommendations are based on a qualitative evaluation of the existing literature and expert consensus. Evidence‐based recommendations require an extensive simulation study where all methods would be compared under the same scenarios. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd

Methods to calculate uncertainty in the estimated overall effect size from a random-effects meta-analysis

Meta-analyses are an important tool within systematic reviews to estimate the overall effect size and its confidence interval for an outcome of interest. If heterogeneity between the results of the relevant studies is anticipated, then a random-effects model is often preferred for analysis. In this model, a prediction interval for the true effect in a new study also provides additional useful information. However, the DerSimonian and Laird method - frequently used as the default method for meta-analyses with random effects - has been long challenged due to its unfavourable statistical properties. Several alternative methods have been proposed that may have better statistical properties in specific scenarios. In this paper, we aim to provide a comprehensive overview of available methods for calculating point estimates, confidence intervals and prediction intervals for the overall effect size under the random-effects model. We indicate whether some methods are preferable than others by considering the results of comparative simulation and real-life data studies

First Light LBT AO Images of HR 8799 bcde at 1.65 and 3.3 Microns: New Discrepancies between Young Planets and Old Brown Dwarfs

As the only directly imaged multiple planet system, HR 8799 provides a unique opportunity to study the physical properties of several planets in parallel. In this paper, we image all four of the HR 8799 planets at H-band and 3.3 microns with the new LBT adaptive optics system, PISCES, and LBTI/LMIRCam. Our images offer an unprecedented view of the system, allowing us to obtain H and 3.3$ micron photometry of the innermost planet (for the first time) and put strong upper-limits on the presence of a hypothetical fifth companion. We find that all four planets are unexpectedly bright at 3.3 microns compared to the equilibrium chemistry models used for field brown dwarfs, which predict that planets should be faint at 3.3 microns due to CH4 opacity. We attempt to model the planets with thick-cloudy, non-equilibrium chemistry atmospheres, but find that removing CH4 to fit the 3.3 micron photometry increases the predicted L' (3.8 microns) flux enough that it is inconsistent with observations. In an effort to fit the SED of the HR 8799 planets, we construct mixtures of cloudy atmospheres, which are intended to represent planets covered by clouds of varying opacity. In this scenario, regions with low opacity look hot and bright, while regions with high opacity look faint, similar to the patchy cloud structures on Jupiter and L/T transition brown-dwarfs. Our mixed cloud models reproduce all of the available data, but self-consistent models are still necessary to demonstrate their viability.Comment: Accepted to Ap