19 research outputs found

    A New Hierarchy of Research Evidence for Tumor Pathology: A Delphi Study to Define Levels of Evidence in Tumor Pathology

    Get PDF
    Copyright \ua9 2023 The Authors. Published by Elsevier Inc. All rights reserved. The hierarchy of evidence is a fundamental concept in evidence-based medicine, but existing models can be challenging to apply in laboratory-based health care disciplines, such as pathology, where the types of evidence and contexts are significantly different from interventional medicine. This project aimed to define a comprehensive and complementary framework of new levels of evidence for evaluating research in tumor pathology-introducing a novel Hierarchy of Research Evidence for Tumor Pathology collaboratively designed by pathologists with help from epidemiologists, public health professionals, oncologists, and scientists, specifically tailored for use by pathologists-and to aid in the production of the World Health Organization Classification of Tumors (WCT) evidence gap maps. To achieve this, we adopted a modified Delphi approach, encompassing iterative online surveys, expert oversight, and external peer review, to establish the criteria for evidence in tumor pathology, determine the optimal structure for the new hierarchy, and ascertain the levels of confidence for each type of evidence. Over a span of 4 months and 3 survey rounds, we collected 1104 survey responses, culminating in a 3-day hybrid meeting in 2023, where a new hierarchy was unanimously agreed upon. The hierarchy is organized into 5 research theme groupings closely aligned with the subheadings of the WCT, and it consists of 5 levels of evidence-level P1 representing evidence types that merit the greatest level of confidence and level P5 reflecting the greatest risk of bias. For the first time, an international collaboration of pathology experts, supported by the International Agency for Research on Cancer, has successfully united to establish a standardized approach for evaluating evidence in tumor pathology. We intend to implement this novel Hierarchy of Research Evidence for Tumor Pathology to map the available evidence, thereby enriching and informing the WCT effectively

    Systematic analysis of gene properties influencing organ system phenotypes in mammalian perturbations.

    No full text
    MOTIVATION: Diseases and adverse drug reactions are frequently caused by disruptions in gene functionality. Gaining insight into the global system properties governing the relationships between genotype and phenotype is thus crucial to understand and interfere with perturbations in complex organisms such as diseases states. RESULTS: We present a systematic analysis of phenotypic information of 5,047 perturbations of single genes in mice, 4,766 human diseases, and 1,666 drugs that examines the relationships between different gene properties and the phenotypic impact at the organ system level in mammalian organisms. We observe that while single gene perturbations and alterations of nonessential, tissue-specific genes or those with low betweenness centrality in protein-protein interaction networks often show organ specific effects, multiple gene alterations resulting e.g. from complex disorders and drug treatments have a more widespread impact. Interestingly, certain cellular localizations are distinctly associated to systemic effects in monogenic disease genes and mouse gene perturbations, such as the lumen of intracellular organelles and transcription factor complexes, respectively. In summary, we show that the broadness of the phenotypic effect is clearly related to certain gene properties and is an indicator of the severity of perturbations. This work contributes to the understanding of gene properties influencing the systemic effects of diseases and drugs

    Potential savings through single-dose intravenous Dalbavancin in long-term MRSA infection treatment - a health economic analysis using German DRG data

    No full text
    Complicated infections such as osteomyelitis, skin and soft tissue infections or endocarditis often require antibiotic therapies that can last up to several weeks. The prolonged hospital length of stay (LOS) leads to a dramatic increase in costs. Single-dose intravenous Dalbavancin is a novel antimicrobial agent for the treatment of acute bacterial skin, skin structure and soft tissue infections (ABSSSI) that allows an earlier discharge of patients, resulting in potential savings. Joint, bone and prostheses infections (JBPI) are also related with long LOS. The aim of this study is to determine the economic effects of single-dose intravenous Dalbavancin in suitable patients with Methicillin-resistant Staphylococcus aureus infections in Germany. For this purpose, an analysis with real-world patient treatment data was performed, which was subsequently validated in a large German hospital. In total, ABSSSI patients with MRSA infections could stay 6.45 days shorter and 2,865 Euro could be saved while JBPI patients could be discharged eventually 10.6 days earlier and 3,909 Euro could be saved. Single-dose intravenous Dalbavancin is thus an option for patients with ABSSSI and JBPI who are eligible for discharge
    corecore