Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia

Background and purpose Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. Methods: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). Results: Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 €/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. Conclusions: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness

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Peer Reviewe

DASC-PM v1.0 : ein Vorgehensmodell für Data-Science-Projekte

Das Thema Data Science hat in den letzten Jahren in vielen Organisationen stark an Aufmerksamkeit gewonnen. Häufig herrscht jedoch weiterhin große Unklarheit darüber, wie diese Disziplin von anderen abzugrenzen ist, welche Besonderheiten der Ablauf eines Data-Science-Projekts besitzt und welche Kompetenzen vorhanden sein müssen, um ein solches Projekt durchzuführen. In der Hoffnung, einen kleinen Beitrag zur Beseitigung dieser Unklarheiten leisten zu können, haben wir von April 2019 bis Februar 2020 in einer offenen und virtuellen Arbeitsgruppe mit Vertretern aus Theorie und Praxis das vorliegende Dokument erarbeitet, in dem ein Vorgehensmodell für Data-Science-Projekte beschrieben wird – das Data Science Process Model (DASC-PM). Ziel war es dabei nicht, neue Herangehensweisen zu entwickeln, sondern viel-mehr, vorhandenes Wissen zusammenzutragen und in geeigneter Form zu strukturieren. Die Ausarbeitung ist als Zusammenführung der Erfahrung sämtlicher Teilnehmerinnen und Teilnehmer dieser Arbeitsgruppe zu verstehen

Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted. (C) 2022 by American Society of Clinical Oncolog

Examination of the Intrinsic Strain State of Silicon Wafers with Oxygen Precipitates via Energy Dispersive X-ray Diffraction

Czochralski-Silizium-Wafer (Cz-Si-Wafer) sind das mit Abstand am häufigsten eingesetzte Substratmaterial bei der Produktion von Computerchips. Das Material beinhaltet produktionsbedingt einen Sauerstoffgehalt in der Größenordnung von einigen 1017 Atomen/cm3. Durch geeignete Temperprozesse können Sauerstoffpräzipitate im Cz-Si-Wafer generiert werden. Diese binden (metallische) Verunreinigungsatome (internal Gettering, IG), welche während der Waferprozessierung ins Material gelangen. Hierdurch wird es erst ermöglicht, wirtschaftliche Produktionsausbeuten in der Chipherstellung zu erzielen. Die fortschreitende Miniaturisierung der Chipgeometrien bei gleichzeitiger Erhöhung der Zuchtkristalldurchmesser stellt neue Herausforderungen an die Charakterisierbarkeit des Sauerstoffpräzipitatinventars in Cz-Si-Wafern. Im Rahmen der hier vorgestellten Arbeit wurde eine Methode basierend auf energiedispersiver Röntgenbeugung (Energy Dispersive Strain Field Diffraction, eSFD) zur Charakterisierung der durch die Sauerstoffpräzipitation induzierten Verspannung in Si-Wafern entwickelt. Hiermit gelingt es, die Reflektivität ausgewählter Bragg-Reflexe der untersuchten Wafer auf absoluter Skala zu ermitteln und daraus den intrinsischen Verspannungszustand der Wafer mit zuvor unerreichter Genauigkeit zu quantifizieren. Die Korrelation der eSFD-Ergebnisse mit Präzipitatdichten und -größen, die mit Transmissions-Elektronen-Mikroskopie (TEM) bestimmt wurden, zeigt, dass die induzierte Verspannung von der Entwicklungsphase der Präzipitate abhängt, und legt einen Zusammenhang mit Temperbedingungen und der Bor-Dotierstoffkonzentration nahe. Diese Resultate werden mit Punktdefektwechselwirkungen am Präzipitat als auch einem möglichen Einbau von Boratomen ins Präzipitat interpretiert.Czochralski silicon wafers (Cz-Si wafers) are by far the most used substrate material in the field of computer chip production today. Due to the growth conditions Cz-Si always contains a fraction of oxygen in the order of magnitude of some 1017 atoms/cm3. This allows for the generation of oxygen precipitates in the material through appropriate annealing. These are used to bind (metallic) impurities (internal Gettering, IG), which are brought into the material during wafer processing. The IG is essential for obtaining economic yields in chip production. Both the onward miniaturization of chip geometries and the simultaneous trend towards larger crystal diameters during the growth process result in increased demands on the characterization methods of precipitate inventory in Cz-Si wafers. A new method for the characterization of the precipitate induced strain in Cz-Si wafers based on energy dispersive X-ray diffraction (energy dispersive strain field diffraction, eSFD) has been developed in the present work. Within this the internal strain states of the wafers are quantitatively deduced with an unprecedented precision from the reflectivities of Bragg reflexions determined on an absolute scale. The correlation of the eSFD results with precipitate densities and diameters (determined with transmission electron microscopy) shows that the induced strain depends on the growth state of the precipitates. Further it suggests a dependence of the strain on the boron doping concentration of the material as well as on the annealing conditions, which are sample geometry and process atmosphere. These findings are interpreted in terms of point defect interactions at the precipitates as well as a possible incorporation of boron atoms into the precipitates