ABSTRACT
Precision oncology is a rapidly evolving interdisciplinary medical specialty. Comprehensive cancer panels are becoming increasingly available at pathology departments worldwide, creating the urgent need for scalable cancer variant annotation and molecularly informed treatment recommendations. A wealth of mainly academia-driven knowledge bases calls for software tools supporting the multi-step diagnostic process. We derive a comprehensive list of knowledge bases relevant for variant interpretation by a review of existing literature followed by a survey among medical experts from university hospitals in Germany. In addition, we review cancer variant interpretation tools, which integrate multiple knowledge bases. We categorize the knowledge bases along the diagnostic process in precision oncology and analyze programmatic access options as well as the integration of knowledge bases into software tools. The most commonly used knowledge bases provide good programmatic access options and have been integrated into a range of software tools. For the wider set of knowledge bases, access options vary across different parts of the diagnostic process. Programmatic access is limited for information regarding clinical classifications of variants and for therapy recommendations. The main issue for databases used for biological classification of pathogenic variants and pathway context information is the lack of standardized interfaces. There is no single cancer variant interpretation tool that integrates all identified knowledge bases. Specialized tools are available and need to be further developed for different steps in the diagnostic process.
Subject(s)
Databases, Genetic , Knowledge Bases , Neoplasms , Precision Medicine , Software , Humans , Neoplasms/genetics , Neoplasms/metabolismABSTRACT
Approaches to integrating mixed methods into medical research are gaining popularity. To get a holistic understanding of the effects of behavioural interventions, we investigated religious fasting using a triangulation of quantitative, qualitative, and natural language analysis. We analysed an observational study of Bahá'í fasting in Germany using a between-method triangulation that is based on links between qualitative and quantitative analyses. Individual interviews show an increase in the mindfulness and well-being categories. Sentiment scores, extracted from the interviews through natural language processing, positively correlate with questionnaire outcomes on quality of life (WHO-5: Spearman correlation r = 0.486, p = 0.048). Five questionnaires contribute to the first principal component capturing the spectrum of mood states (50.1% explained variance). Integrating the findings of the between-method triangulation enabled us to converge on the underlying effects of this kind of intermittent fasting. TRIAL REGISTRATION: NCT03443739.
ABSTRACT
Large amounts of important medical information are captured in free-text documents in biomedical research and within healthcare systems, which can be made accessible through natural language processing (NLP). A key component in most biomedical NLP pipelines is entity linking, i.e. grounding textual mentions of named entities to a reference of medical concepts, usually derived from a terminology system, such as the Systematized Nomenclature of Medicine Clinical Terms. However, complex entity mentions, spanning multiple tokens, are notoriously hard to normalize due to the difficulty of finding appropriate candidate concepts. In this work, we propose an approach to preprocess such mentions for candidate generation, building upon recent advances in text simplification with generative large language models. We evaluate the feasibility of our method in the context of the entity linking track of the BioCreative VIII SympTEMIST shared task. We find that instructing the latest Generative Pre-trained Transformer model with a few-shot prompt for text simplification results in mention spans that are easier to normalize. Thus, we can improve recall during candidate generation by 2.9 percentage points compared to our baseline system, which achieved the best score in the original shared task evaluation. Furthermore, we show that this improvement in recall can be fully translated into top-1 accuracy through careful initialization of a subsequent reranking model. Our best system achieves an accuracy of 63.6% on the SympTEMIST test set. The proposed approach has been integrated into the open-source xMEN toolkit, which is available online via https://github.com/hpi-dhc/xmen.
Subject(s)
Natural Language Processing , HumansABSTRACT
The availability of high-throughput molecular diagnostics builds the foundation for Molecular Tumor Boards (MTBs). Although more fine-grained data is expected to support decision making of oncologists, assessment of data is complex and time-consuming slowing down the implementation of MTBs, e.g., due to retrieval of the latest medical publications, assessment of clinical evidence, or linkage to the latest clinical guidelines. We share our findings from analysis of existing tumor board processes and defininion of clinical processes for the adoption of MTBs. Building on our findings, we have developed a real-world software prototype together with oncologists and medical professionals, which supports the preparation and conduct of MTBs and enables collaboration between medical experts by sharing medical knowledge even across the hospital locations. We worked in interdisciplinary teams of clinicians, oncologists, medical experts, medical informaticians, and software engineers using design thinking methodology. With their input, we identified challenges and limitations of the current MTB approaches, derived clinical process models using Business Process and Modeling Notation (BMPN), and defined personas, functional and non-functional requirements for software tool support. Based on it, we developed software prototypes and evaluated them with clinical experts from major university hospitals across Germany. We extended the Kanban methodology enabling holistic tracking of patient cases from "backlog" to "follow-up" in our app. The feedback from interviewed medical professionals showed that our clinical process models and software prototype provide suitable process support for the preparation and conduction of molecular tumor boards. The combination of oncology knowledge across hospitals and the documentation of treatment decision can be used to form a unique medical knowledge base by oncologists for oncologists. Due to the high heterogeneity of tumor diseases and the spread of the latest medical knowledge, a cooperative decision-making process including insights from similar patient cases was considered as a very valuable feature. The ability to transform prepared case data into a screen presentation was recognized as an essential feature speeding up the preparation process. Oncologists require special software tool support to incorporate and assess molecular data for the decision-making process. In particular, the need for linkage to the latest medical knowledge, clinical evidence, and collaborative tools to discuss individual cases were named to be of importance. With the experiences from the COVID-19 pandemic, the acceptance of online tools and collaborative working is expected to grow. Our virtual multi-site approach proved to allow a collaborative decision-making process for the first time, which we consider to have a positive impact on the overall treatment quality.
ABSTRACT
BACKGROUND: Extraction of medical terms and their corresponding values from semi-structured and unstructured texts of medical reports can be a time-consuming and error-prone process. Methods of natural language processing (NLP) can help define an extraction pipeline for accomplishing a structured format transformation strategy. OBJECTIVES: In this paper, we build an NLP pipeline to extract values of the classification of malignant tumors (TNM) from unstructured and semi-structured pathology reports and import them further to a structured data source for a clinical study. Our research interest is not focused on standard performance metrics like precision, recall, and F-measure on the test and validation data. We discuss how with the help of software programming techniques the readability of rule-based (RB) information extraction (IE) pipelines can be improved, and therefore minimize the time to correct or update the rules, and efficiently import them to another programming language. METHODS: The extract rules were manually programmed with training data of TNM classification and tested in two separate pipelines based on design specifications from domain experts and data curators. Firstly we implemented each rule directly in one line for each extraction item. Secondly, we reprogrammed them in a readable fashion through decomposition and intention-revealing names for the variable declaration. To measure the impact of both methods we measure the time for the fine-tuning and programming of the extractions through test data of semi-structured and unstructured texts. RESULTS: We analyze the benefits of improving through readability of the writing of rules, through parallel programming with regular expressions (REGEX), and the Apache Uima Ruta language (AURL). The time for correcting the readable rules in AURL and REGEX was significantly reduced. Complicated rules in REGEX are decomposed and intention-revealing declarations were reprogrammed in AURL in 5 min. CONCLUSION: We discuss the importance of factor readability and how can it be improved when programming RB text IE pipelines. Independent of the features of the programming language and the tools applied, a readable coding strategy can be proven beneficial for future maintenance and offer an interpretable solution for understanding the extraction and for transferring the rules to other domains and NLP pipelines.
Subject(s)
Electronic Health Records , Natural Language Processing , Humans , Comprehension , Algorithms , Information Storage and RetrievalABSTRACT
We present CARDIO:DE, the first freely available and distributable large German clinical corpus from the cardiovascular domain. CARDIO:DE encompasses 500 clinical routine German doctor's letters from Heidelberg University Hospital, which were manually annotated. Our prospective study design complies well with current data protection regulations and allows us to keep the original structure of clinical documents consistent. In order to ease access to our corpus, we manually de-identified all letters. To enable various information extraction tasks the temporal information in the documents was preserved. We added two high-quality manual annotation layers to CARDIO:DE, (1) medication information and (2) CDA-compliant section classes. To the best of our knowledge, CARDIO:DE is the first freely available and distributable German clinical corpus in the cardiovascular domain. In summary, our corpus offers unique opportunities for collaborative and reproducible research on natural language processing models for German clinical texts.
ABSTRACT
Clinical guidelines integrate latest evidence to support clinical decision-making. As new research findings are published at an increasing rate, it would be helpful to detect when such results disagree with current guideline recommendations. In this work, we describe a software system for the automatic identification of disagreement between clinical guidelines and published research. A critical feature of the system is the extraction and cross-lingual normalization of information through natural language processing. The initial version focuses on the detection of cancer treatments in clinical trial reports that are not addressed in oncology guidelines. We evaluate the relevance of trials retrieved by our system retrospectively by comparison with historic guideline updates and also prospectively through manual evaluation by guideline experts. The system improves precision over state-of-the-art literature research strategies while maintaining near-total recall. Detailed error analysis highlights challenges for fine-grained clinical information extraction, in particular when extracting population definitions for tumor-agnostic therapies.