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Andexanet alfa: trials just leave us with more questions.

Res Pract Thromb Haemost

January 2025

Department of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom.

Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4).

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Introduction: As a hallmark feature of amyotrophic lateral sclerosis (ALS), bulbar involvement significantly impacts psychosocial, emotional, and physical health. A validated objective marker is however lacking to characterize and phenotype bulbar involvement, positing a major barrier to early detection, progress monitoring, and tailored care. This study aimed to bridge this gap by constructing a multiplex functional mandibular muscle network to provide a novel objective measurement tool of bulbar involvement.

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AI-assisted data analysis can help risk analysts better understand exposure-response relationships by making it relatively easy to apply advanced statistical and machine learning methods, check their assumptions, and interpret their results. This paper demonstrates the potential of large language models (LLMs), such as ChatGPT, to facilitate statistical analyses, including survival data analyses, for health risk assessments. Through AI-guided analyses using relatively recent and advanced methods such as Individual Conditional Expectation (ICE) plots using Random Survival Forests and Heterogeneous Treatment Effects (HTEs) estimated using Causal Survival Forests, population-level exposure-response functions can be disaggregated into individual-level exposure-response functions.

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Objective: This study constructed a new conditional generative adversarial network (CGAN) model to predict changes in lateral appearance following orthodontic treatment.

Methods: Lateral cephalometric radiographs of adult patients were obtained before (T1) and after (T2) orthodontic treatment. The expanded dataset was divided into training, validation, and test sets by random sampling in a ratio of 8:1:1.

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The classical meta-analytical random effects model (REM) has some weaknesses when applied to the standardized mean difference, g. Essentially, the variance of the studies involved is taken as the conditional variance, given a δ value, instead of the unconditional variance. As a consequence, the estimators of the variances involve a dependency between the g values and their variances that distorts the estimates.

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