3,136 research outputs found

    Understanding and improving the applicability of randomised controlled trials: subgroup reporting and the statistical calibration of trials to real-world populations

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    Context and objective Randomised controlled trials (hereafter, trials) are widely regarded as the gold standard for evaluating treatment efficacy in medical interventions. They employ strict study designs, rigorous eligibility criteria, standardised protocols, and close participant monitoring under controlled conditions, contributing to high internal validity. However, these stringent criteria and procedures may limit the generalisability of trial findings to real-world situations, which often involve diverse patient populations such as multimorbidity and frailty patients. Consequently, there is growing interest in the applicability of trials to real-world clinical practice. In this thesis I will 1) evaluate how well major trials report on variation in treatment effects and 2) examine the use of trial calibration methods to test trial applicability. Methods 1) A comprehensive and consistent subgroup reporting description was presented, which contributes to the exploration of subgroup effects and treatment heterogeneity for informed decision-making in tailored subgroup populations within routine practice. The study evaluated 2,235 trials from clinicaltrial.gov that involve multiple chronic medical conditions, assessing the presence of subgroup reporting in corresponding publications and extracting subgroup terms. These terms were then standardised and summarised using Medical Subject Headings and WHO Anatomical Therapeutic Chemical codes. Logistic and Poisson regression models were employed to identify independent predictors of subgroup reporting patterns. 2) Two calibration models, namely the regression-based model and inverse odds of sampling weights (IOSW) were implemented. These models were utilised to apply the findings from two influential heart failure (HF) trials - COMET and DIG - to a real-world HF registry in Scotland consisting of 8,012 HF patients mainly with reduced ejection fraction, using individual participant data (IPD) from both datasets. Additionally, calibration was conducted within the subgroup population (lowest and highest risk group) of the real-world Scottish HF registry for exploratory analyses. The study provided comparisons of baseline characteristics and calibrated and uncalibrated results between the trial and registry. Furthermore, it assessed the impact of calibration on the results with the focus on overall effects and precision. Results The subgroup reporting study showed that among 2,235 eligible trials, 48% (1,082 trials) reported overall results and 23% (524 trials) reported subgroups. Age (51%), gender (45%), racial group (28%) and geographical locations (17%) were the most frequently reported subgroups among 524 trials. Characteristics related to the index condition (severity/duration/types, etc.) were somewhat commonly reported. However, reporting on metrics of comorbidity or frailty and mental health were rare. Follow-up time, enrolment size, trial starting year and specific index conditions (e.g., hypercholesterolemia, hypertension etc.) were significant predictors for any subgroup reporting after adjusting for enrolment size and index conditions while funding source and number of arms were not associated with subgroup reporting. The trial calibration study showed that registry patients were, on average, older, had poorer renal function and received higher-doses of loop diuretics than trial participants. The key findings from two HF trials remained consistent after calibration in the registry, with a tolerable decrease in precision (larger confidence intervals) for the effect estimates. Treatment-effect estimates were also similar when trials were calibrated to high-risk and low-risk registry patients, albeit with a greater reduction in precision. Conclusion Variations in subgroup reporting among different trials limited the feasibility to evaluate subgroup effects and examine heterogeneity of treatment effects. If IPD or IPD alternative summarised data is available from trials and the registry, trial applicability can be assessed by performing calibration

    UMSL Bulletin 2023-2024

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    The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp

    UMSL Bulletin 2022-2023

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    The 2022-2023 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1087/thumbnail.jp

    Advances and Applications of DSmT for Information Fusion. Collected Works, Volume 5

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    This fifth volume on Advances and Applications of DSmT for Information Fusion collects theoretical and applied contributions of researchers working in different fields of applications and in mathematics, and is available in open-access. The collected contributions of this volume have either been published or presented after disseminating the fourth volume in 2015 in international conferences, seminars, workshops and journals, or they are new. The contributions of each part of this volume are chronologically ordered. First Part of this book presents some theoretical advances on DSmT, dealing mainly with modified Proportional Conflict Redistribution Rules (PCR) of combination with degree of intersection, coarsening techniques, interval calculus for PCR thanks to set inversion via interval analysis (SIVIA), rough set classifiers, canonical decomposition of dichotomous belief functions, fast PCR fusion, fast inter-criteria analysis with PCR, and improved PCR5 and PCR6 rules preserving the (quasi-)neutrality of (quasi-)vacuous belief assignment in the fusion of sources of evidence with their Matlab codes. Because more applications of DSmT have emerged in the past years since the apparition of the fourth book of DSmT in 2015, the second part of this volume is about selected applications of DSmT mainly in building change detection, object recognition, quality of data association in tracking, perception in robotics, risk assessment for torrent protection and multi-criteria decision-making, multi-modal image fusion, coarsening techniques, recommender system, levee characterization and assessment, human heading perception, trust assessment, robotics, biometrics, failure detection, GPS systems, inter-criteria analysis, group decision, human activity recognition, storm prediction, data association for autonomous vehicles, identification of maritime vessels, fusion of support vector machines (SVM), Silx-Furtif RUST code library for information fusion including PCR rules, and network for ship classification. Finally, the third part presents interesting contributions related to belief functions in general published or presented along the years since 2015. These contributions are related with decision-making under uncertainty, belief approximations, probability transformations, new distances between belief functions, non-classical multi-criteria decision-making problems with belief functions, generalization of Bayes theorem, image processing, data association, entropy and cross-entropy measures, fuzzy evidence numbers, negator of belief mass, human activity recognition, information fusion for breast cancer therapy, imbalanced data classification, and hybrid techniques mixing deep learning with belief functions as well

    Taylor University Catalog 2023-2024

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    The 2023-2024 academic catalog of Taylor University in Upland, Indiana.https://pillars.taylor.edu/catalogs/1128/thumbnail.jp

    Modern meat: the next generation of meat from cells

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    Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

    A web-based platform promoting family communication and cascade genetic testing for families with hereditary breast and ovarian cancer (DIALOGUE study)

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    The overall aim of this dissertation is to develop an eHealth intervention to promote family communication and cascade genetic testing among families concerned with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Within this context an international, multi-centre scientific project entitled "DIALOGUE" was designed that aims to develop (Phase A), and test the feasibility (Phase B) of an intervention within various genetic clinics across Switzerland and South Korea. This dissertation describes only the Phase A, the adaptation of an intervention, a web-based platform designed for families with HBOC to share genetic test results, including usability testing in a sample from Switzerland. Chapter 1 provides a general introduction to the current field of hereditary cancer and cascade genetic testing, including the current state of eHealth technologies in science. The chapter also includes a short introduction to the prototype developed in the U.S.—as well as a description of the DIALOGUE study. In addition, the chapter summarises the main conceptual models, i.e. the Ottawa Decision Support Framework (ODSF) and the Medical Research Council (MRC) framework. These models are commonly implemented in the development and evaluation of complex interventions. The rational of this dissertation is guided by all of these elements. Chapter 2 provides a detailed description of the dissertation’s specific aims, including the three studies conducted. The articles presented in Chapter 3 describe the methodology and findings of the dissertation. Study I comprises a systematic literature review of previous studies, with a particular focus on HBOC and Lynch syndromes. The literature review identified and synthesised evidence from psychoeducational interventions designed to facilitate family communication of genetic testing results and/or cancer predisposition and to promote cascade genetic testing. A meta-analysis was also conducted to assess intervention efficacy in relation to these two research aims. Our findings highlight the need to develop new interventions and approaches to family communication and cascade testing for cancer susceptibility. Study II describes the state-of-the-art text mining techniques used to detect and classify valuable information from interviews with study participants concerning determinants of open intrafamilial communication regarding genetic cancer risk. This study had two major aims: 1) to quantify openness of communication about HBOC cancer risk, and 2) to examine the role of sentiment in predicting openness of communication. Our findings showed that the overall expressed sentiment was associated with the communication of genetic risk among HBOC families. This analysis identified additional factors that affect openness to communicate genetic risk. These were defined as “high-risk” factors and integrated into the design and development of the intervention. Study III describes the development of the intervention, a web-based platform designed for families with HBOC to share genetic test results. The platform was developed in line with the quality criteria set by the MRC framework. Being web-based, the platform could be accessed via a laptop, smartphone or tablet. Usability testing was applied to evaluate the prototype intervention which received high ratings on a satisfaction scale. Chapter 4 synthesises and discusses the key findings of all the studies presented in the previous chapter, and addresses study limitations and implications for future research
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