Confirmatory Adaptive Designs for Clinical Trials With Multiple Time-to-Event Outcomes in Multi-state Markov Models.

The analysis of multiple time-to-event outcomes in a randomized controlled clinical trial can be accomplished with existing methods. However, depending on the characteristics of the disease under investigation and the circumstances in which the study is planned, it may be of interest to conduct interim analyses and adapt the study design if necessary. Due to the expected dependency of the endpoints, the full available information on the involved endpoints may not be used for this purpose.

Adaption of neurosurgical resection patterns for pediatric low-grade glioma spanning two decades-Report from the German LGG-studies 1996-2018.

Introduction: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies.

Two-sample survival tests based on control arm summary statistics.

The one-sample log-rank test is the preferred method for analysing the outcome of single-arm survival trials. It compares the survival distribution of patients with a prefixed reference survival curve that usually represents the expected outcome under standard of care. However, classical one-sample log-rank tests assume that the reference curve is known, ignoring that it is frequently estimated from historical data and therefore susceptible to sampling error.

Reference curve sampling variability in one-sample log-rank tests.

The one-sample log-rank test is the method of choice for single-arm Phase II trials with time-to-event endpoint. It allows to compare the survival of patients to a reference survival curve that typically represents the expected survival under standard of care. The one-sample log-rank test, however, assumes that the reference survival curve is known.

Confirmatory adaptive group sequential designs for single-arm phase II studies with multiple time-to-event endpoints.

Existing methods concerning the assessment of long-term survival outcomes in one-armed trials are commonly restricted to one primary endpoint. Corresponding adaptive designs suffer from limitations regarding the use of information from other endpoints in interim design changes. Here we provide adaptive group sequential one-sample tests for testing hypotheses on the multivariate survival distribution derived from multi-state models, while making provision for data-dependent design modifications based on all involved time-to-event endpoints.

Pseudoprogression Is Frequent After Front-Line Radiation Therapy in Pediatric Low-Grade Glioma: Results From the German Low-Grade Glioma Cohort.

Purpose: Expansion of magnetic resonance imaging T2- or T1-tumor lesion volume after radiation therapy (RT) may indicate pseudoprogression (PsPD). The differentiation between true progression and PsPD is a clinical challenge and underinvestigated in pediatric low-grade glioma (LGG). We evaluated radiologic criteria for PsPD after front-line RT and investigated the frequency and duration of PsPD after 3 RT-modalities within the framework of the German pediatric multicenter LGG-studies.

Second trimester fetal thymus size in association to preterm birth.

Objectives: The aim of this study was to compare the second trimester thymus-thorax-ratio (TTR) between fetuses born preterm (study group) and those born after 37 weeks of gestation were completed (control group).

Methods: This study was conducted as a retrospective evaluation of the ultrasound images of 492 fetuses in the three vessel view. The TTR was defined as the quotient of a.

Adaptive group sequential survival comparisons based on log-rank and pointwise test statistics.

Whereas the theory of confirmatory adaptive designs is well understood for uncensored data, implementation of adaptive designs in the context of survival trials remains challenging. Commonly used adaptive survival tests are based on the independent increments structure of the log-rank statistic. This implies some relevant limitations: On the one hand, essentially only the interim log-rank statistic may be used for design modifications (such as data-dependent sample size recalculation).

Doubling Recruitment of Pediatric Low-grade Glioma within Two Decades does not change Outcome - Report from the German LGG Studies.

Background: Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival.

Methods And Results: Participating centers reported 4634 patients with the radiologic/histologic diagnosis of LGG (1996-2018), rising from 109 to 278/year.

Monitoring the Structural Health of Glass Fibre-Reinforced Hybrid Laminates Using Novel Piezoceramic Film.

This work investigates a new generation structural health monitoring (SHM) system for fibre metal laminates (FML) based on an embedded thermoplastic film with compounded piezoceramics, termed piezo-active fibre metal laminate (PFML). The PFML is manufactured using near-series processes and its potential as a passive SHM system is being investigated. A commercial Polyvinylidene fluoride (PVDF) sensor film is used for comparative evaluation of the sensor signals.

Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II-Report from the German/Swiss SIOP-LGG 2004 cohort.

Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.

An improved one-sample log-rank test.

The one-sample log-rank test allows to compare the survival of a single sample with a prefixed reference survival curve. It naturally applies in single-arm phase IIa trials with time-to-event endpoint. Several authors have described that the original one-sample log-rank test is conservative when sample size is small and have proposed strategies to correct the conservativeness.

[Treatment of a necrotizing soft tissue infection].

The surgical procedure for the life-threatening course of a necrotizing soft tissue infection of the leg after minor trauma is described. The necessary consistent resection of extensive fascial and muscular necroses required the reconstruction of soft tissue defects of the knee, the ankle joint and peroneal tendons exposed over a long distance. The functional outcome is presented 1 year after use of MatriDerm® and a split-thickness skin graft for defect coverage.

Treatment of children under 4 years of age with medulloblastoma and ependymoma in the HIT2000/HIT-REZ 2005 trials: Neuropsychological outcome 5 years after treatment.

Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005.

Correction: Fast Tac Metabolizers at Risk-It is Time for a C/D Ratio Calculation. 2019, , 587.

The authors wish to make the following corrections to this paper [...

A new risk score for patients after first recurrence of stage 4 neuroblastoma aged ≥18 months at first diagnosis.

Background: The prognosis of patients with recurrences from stage 4 neuroblastoma is not uniformly dismal. The evaluation of new therapies therefore needs to consider the individual risks of the treated patients. This study aims to define clinically useful risk criteria.

Favorable prognosis in pediatric brainstem low-grade glioma: Report from the German SIOP-LGG 2004 cohort.

Reports on pediatric low-grade glioma (LGG) of the caudal brainstem are retrospective with heterogeneous cohorts, variable treatments and inconsistent outcome data. We analyzed their natural history and asked whether brainstem location proved unfavorable for survival within the framework of the comprehensive SIOP-LGG 2004 management strategy. Within the prospectively registered, population-based German SIOP-LGG 2004 cohort 116 patients (age 0.

Procedure related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study.

Background The aim of this study was to compare transabdominal and transcervical chorionic villus sampling (CVS) as well as amniocentesis (AC) with respect to their rates of premature delivery and fetal growth restriction. Methods We retrospectively evaluated the mentioned procedures of invasive prenatal testing performed in a single center between 2001 and 2016. Seven hundred and ninety-nine cases of AC and 719 cases of CVS were included, of which 400 were performed transvaginally.

Effects of system response delays on elderly humans' cognitive performance in a virtual training scenario.

Observed influences of system response delay in spoken human-machine dialogues are rather ambiguous and mainly focus on perceived system quality. Studies that systematically inspect effects on cognitive performance are still lacking, and effects of individual characteristics are also often neglected. Building on benefits of cognitive training for decelerating cognitive decline, this Wizard-of-Oz study addresses both issues by testing 62 elderly participants in a dialogue-based memory training with a virtual agent.

Fast Tac Metabolizers at Risk ⁻ It is Time for a C/D Ratio Calculation.

Tacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with inferior renal function after RTx.