Point estimation and p-values in phase II adaptive two-stage designs with a binary endpoint.

Clinical trials in phase II of drug development are frequently conducted as single-arm two-stage studies with a binary endpoint. Recently, adaptive designs have been proposed for this setting that enable a midcourse modification of the sample size. While these designs are elaborated with respect to hypothesis testing by assuring control of the type I error rate, the topic of point estimation has up to now not been addressed. For adaptive designs with a prespecified sample size recalculation rule, we propose a new point estimator that both assures compatibility of estimation and test decision and minimizes average mean squared error. This estimator can be interpreted as a constrained posterior mean estimate based on the non-informative Jeffreys prior. A comparative investigation of the operating characteristics demonstrates the favorable properties of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.

Lower prevalence of chronic itch in haemodialysis patients on loop diuretics: results from GEHIS (German Epidemiological Hemodialysis Itch Study).

BACKGROUND: Chronic itch (CI) is a very tormenting symptom in haemodialysis (HD) patients. GEHIS (German Epidemiological Hemodialysis Itch Study) is a representative cross-sectional study showing that current chronic itch (CI) affects 25.2% of haemodialysis (HD) patients. OBJECTIVE: We investigated drug intake and possible associations between CI and medications of HD patients. METHODS: Eight hundred and sixty HD patients from a randomly selected cluster sample of 25 dialysis units (GEHIS) in Germany were investigated. Statistical analyses were performed using R (version 3.3.0) for Windows. Logistic regression was used to identify influential covariates for prevalence of chronic itch and intensity of itch. RESULTS: Taking loop diuretics (furosemide, torasemide) was significantly negatively associated with the occurrence of CI in HD patients meaning that those who had received any type of loop diuretics were significantly less likely to suffer from less CI compared to those who had not taken them. There were no associations of CI with other medications. No correlation was detected between the intensity of itch and the intake of loop diuretics or any other medication. CONCLUSION: Loop diuretics may have an impact on the development of CI in HD patients. As it is most likely that a multifactorial origin may explain CI in HD, future research should also focus on the role of loop diuretics in CI, both on a clinical as well as on a molecular level.

CCL-2 as a possible early marker for remission after traumatic spinal cord injury.

STUDY DESIGN: Prospective observational study. OBJECTIVES: To describe the correlation between CCL-2, CCL-3, CCL-4 and CXCL-5 serum levels and remission after traumatic spinal cord injury (SCI) in a human protocol compared with animal studies. SETTING: Germany, Rhineland-Palatinate (Rheinland-Pfalz). METHODS: We examined the serum levels of CCL-2, CCL-3, CCL-4 and CXCL-5 over a 12-week period; in particular, at admission and 4, 9 and 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. According to our study design, we matched 10 patients with TSCI and neurological remission with 10 patients with an initial ASIA A grade and no neurological remission. In all, 10 patients with vertebral fracture without neurological deficits served as control. Our analysis was performed using a Luminex Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value with respect to neurological remission vs no neurological remission. RESULTS: The results of our study showed differences in the serum expression patterns of CCL-2 in association with the neurological remission (CCL-2 at admission P=0.013). Serum levels of CCL-2 and CCL-4 were significantly different in patients with and without neurological remission. The favored predictive model resulted in an area under the curve (AUC) of 93.1% in the receiver operating characteristic (ROC) analysis. CONCLUSIONS: Our results indicate that peripheral serum analysis is a suitable concept for predicting the patient's potential for neurological remission after TSCI. Furthermore, the initial CCL-2 concentration provides an additional predictive value compared with the NLI (neurological level of injury). Therefore, the present study introduces a promising approach for future monitoring concepts and tracking techniques for current therapies. The results indicate that future investigations with an enlarged sample size are needed in order to develop monitoring, prognostic and scoring systems.

Determination of quantitative leucite content in pressable ceramics compared to conventional dental porcelains.

In the present study, the leucite content of two different veneering porcelains and one pressable ceramic have been determined by X-ray diffraction after establishing a standard, using artificial leucite. The results are directly linked to the microstructure and mechanical properties of the materials. The most homogeneous glass-ceramic exhibits the highest relative leucite content and the highest fracture strength.

The pattern of urbanization in Western Europe.

This report "presents major trends and changes in the urban system in Europe over the last thirty years (1960-1990). It examines the present state of urbanization and considers the cycles and dynamics of urban development, urban growth and urban decline and describes current and future issues of urban development in the twelve countries of the European Community, including the united Germany, and in Austria and Switzerland."