Intricate decision making: ambivalences and barriers when fulfilling an advance directive.

Background: Despite a recent statutory ruling stating the binding nature of advance directives (ADs), only a minority of the population has signed one. Yet, a majority deem it of utmost importance to ensure their wishes are followed through in case they are no longer able to decide. The reasons for this discrepancy have not yet been investigated sufficiently.

Public health relevance of Graves' orbitopathy.

Context: Disfiguring proptosis and functional impairment in patients with Graves' orbitopathy (GO) may lead to impaired earning capacity and to considerable indirect/direct costs.

Objective: The aim of the study was to investigate the public health relevance of GO.

Design And Setting: This cross-sectional study was performed between 2005 and 2009 at a multidisciplinary university orbital center.

Quality of life in a german graves orbitopathy population.

Purpose: To evaluate the validity and responsiveness of a German-language version of the disease-specific Graves orbitopathy quality-of-life questionnaire (GO-QOL).

Design: Prospective cross-sectional study.

Methods: At a multidisciplinary university orbital center, 310 consecutive unselected Graves orbitopathy outpatients answered the GO-QOL before undergoing complete ophthalmic and endocrine assessment.

Multiple hypotheses testing based on ordered p values--a historical survey with applications to medical research.

Global tests and multiple test procedures are often based on ordered p values. Such procedures are available for arbitrary dependence structures as well as for specific dependence assumptions of the test statistics. Most of these procedures have been considered as global tests.

Survival analysis: part 15 of a series on evaluation of scientific publications.

Background: Survival times are often used to compare treatments. Survival data are a special type of data, and therefore have to be analyzed with special methods.

Methods: We illustrate special techniques for analyzing survival times by applying them to a publication on the treatment of patients with brain tumors.

Test and power considerations for multiple endpoint analyses using sequentially rejective graphical procedures.

A variety of powerful test procedures are available for the analysis of clinical trials addressing multiple objectives, such as comparing several treatments with a control, assessing the benefit of a new drug for more than one endpoint, etc. However, some of these procedures have reached a level of complexity that makes it difficult to communicate the underlying test strategies to clinical teams. Graphical approaches have been proposed instead that facilitate the derivation and communication of Bonferroni-based closed test procedures.

Multiple testing in candidate gene situations: a comparison of classical, discrete, and resampling-based procedures.

In candidate gene association studies, usually several elementary hypotheses are tested simultaneously using one particular set of data. The data normally consist of partly correlated SNP information. Every SNP can be tested for association with the disease, e.

Linear regression analysis: part 14 of a series on evaluation of scientific publications.

Background: Regression analysis is an important statistical method for the analysis of medical data. It enables the identification and characterization of relationships among multiple factors. It also enables the identification of prognostically relevant risk factors and the calculation of risk scores for individual prognostication.

Choosing statistical tests: part 12 of a series on evaluation of scientific publications.

Background: The interpretation of scientific articles often requires an understanding of the methods of inferential statistics. This article informs the reader about frequently used statistical tests and their correct application.

Methods: The most commonly used statistical tests were identified through a selective literature search on the methodology of medical research publications.

Judging a plethora of p-values: how to contend with the problem of multiple testing--part 10 of a series on evaluation of scientific publications.

Background: When reading reports of medical research findings, one is usually confronted with p-values. Publications typically contain not just one p-value, but an abundance of them, mostly accompanied by the word "significant." This article is intended to help readers understand the problem of multiple p-values and how to deal with it.

Confidence interval or p-value?: part 4 of a series on evaluation of scientific publications.

Background: An understanding of p-values and confidence intervals is necessary for the evaluation of scientific articles. This article will inform the reader of the meaning and interpretation of these two statistical concepts.

Methods: The uses of these two statistical concepts and the differences between them are discussed on the basis of a selective literature search concerning the methods employed in scientific articles.

Quality of life and occupational disability in endocrine orbitopathy.

Background: In endocrine orbitopathy (EO), disfiguring proptosis and diplopia impair patients' quality of life both at home and at work.

Methods: From late 2006 to the beginning of 2008, 250 outpatients in an interdisciplinary thyroid and eye clinic filled out a questionnaire about their quality of life, occupational disability, and use of psychotherapy. 400 physicians who referred their EO patients to the clinic also participated in a survey on these issues.

Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.

Adaptive designs with correlated test statistics.

In clinical trials, the collected observations such as clustered data or repeated measurements are often correlated. As a consequence, test statistics in a multistage design are correlated. Adaptive designs were originally developed for independent test statistics.

Aesthetics and power considerations in multiple testing--a contradiction?

In this paper we discuss aesthetical concepts and requirements for reasonable multiple test procedures. Aesthetical considerations lead to logical decision patterns which are conceivable and, if possible, simple to use and to communicate. Such considerations are sometimes contradictory to the ubiquitous requirement of maximizing power for a multiple test procedure.

Long term follow up after percutaneous closure of PFO in 357 patients with paradoxical embolism: Difference in occlusion systems and influence of atrial septum aneurysm.

Background: Percutaneous transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA is an alternative to medical therapy especially in patients with atrial septal aneurysm (ASA). The differences in time to complete occlusion for various closure devices in PFO alone and PFO plus ASA are of natural interest.

Methods And Results: Between January, 1st 1998 and November, 30th 2006 percutaneous PFO closure was performed in 357 patients with a history of > or =1 paradoxical embolism using three different devices: Amplatzer PFO-(n=199), Starflex-(n=48) and Helex Occluder (n=110).

Mean maternal second-trimester hemoglobin concentration and outcome of pregnancy: a population-based study.

Both anemia and the lack of physiological maternal plasma volume expansion during the second trimester are associated with higher maternal morbidity and poor fetal outcome. Mean hemoglobin levels between the 14th and 30th gestational weeks were calculated in 4985 consecutive pregnant women and were correlated with outcome data of pregnancy. It was found that 9.

Strategies for including patients recruited during interim analysis of clinical trials.

In clinical trials a periodical check of safety and efficacy data is often needed. For organizational reasons it is rarely desirable to stop a trial during such an interim analysis. Therefore, new study patients are included in the trial while the interim analysis is ongoing.

[Decompression surgery for endocrine orbitopathy].

Background: Endocrine orbitopathy is a common feature of autoimmune thyroid disease. The increase of pressure within the eye socket leads to proptosis and compression of the optic nerve. This results in cosmetic impairment as well as loss of vision.

Powerful short-cuts for multiple testing procedures with special reference to gatekeeping strategies.

In this paper we present a general testing principle for a class of multiple testing problems based on weighted hypotheses. Under moderate conditions, this principle leads to powerful consonant multiple testing procedures. Furthermore, short-cut versions can be derived, which simplify substantially the implementation and interpretation of the related test procedures.

Combining adaptive designs with control of the false discovery rate--a generalized definition for a global p-value.

When combining adaptive designs with control of the False Discovery Rate one has to keep in mind that the most frequently used procedure for controlling the False Discovery Rate--the explorative Simes procedure--is a stepwise multiple testing procedure. At the interim analysis of an adaptive design it is however not yet known what the boundaries for rejection of hypotheses in the final analysis will be as these boundaries depend on the size of the final p-values. Therefore classical adaptive designs with a predefined stopping criterion for early rejection of hypotheses are not well suited.

Performance of adaptive sample size adjustment with respect to stopping criteria and time of interim analysis.

The benefit of adjusting the sample size in clinical trials on the basis of treatment effects observed in interim analysis has been the subject of several recent papers. Different conclusions were drawn about the usefulness of this approach for gaining power or saving sample size, because of differences in trial design and setting. We examined the benefit of sample size adjustment in relation to trial design parameters such as 'time of interim analysis' and 'choice of stopping criteria'.

Tests for differentiation in gene expression using a data-driven order or weights for hypotheses.

In the analysis of gene expression by microarrays there are usually few subjects, but high-dimensional data. By means of techniques, such as the theory of spherical tests or with suitable permutation tests, it is possible to sort the endpoints or to give weights to them according to specific criteria determined by the data while controlling the multiple type I error rate. The procedures developed so far are based on a sequential analysis of weighted p-values (corresponding to the endpoints), including the most extreme situation of weighting leading to a complete order of p-values.

Two-stage adaptive designs with correlated test statistics.

When performing a trial using an adaptive sequential design, it is usually assumed that the data for each stage come from different units; for example, patients. However, sometimes it is not possible to satisfy this condition or to check whether it is satisfied. In these cases, the test statistics and p-values of each stage may be dependent.

Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

Context: Glucocorticoids are effective for severe Graves' orbitopathy (GO), which causes substantial morbidity. The question at issue is how best to use them.

Objective: The objective of this study was to optimize glucocorticoid application in GO.