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Integrating biomedical research and electronic health records to create knowledge-based biologically meaningful machine-readable embeddings.
In order to advance precision medicine, detailed clinical features ought to be described in a way that leverages current knowledge. Although data collected from biomedical research is expanding at an almost exponential rate, our ability to transform that information into patient care has not kept at pace. A major barrier preventing this transformation is that multi-dimensional data collection and analysis is usually carried out without much understanding of the underlying knowledge structure. Here, in an effort to bridge this gap, Electronic Health Records (EHRs) of individual patients are connected to a heterogeneous knowledge network called Scalable Precision Medicine Oriented Knowledge Engine (SPOKE). Then an unsupervised machine-learning algorithm creates Propagated SPOKE Entry Vectors (PSEVs) that encode the importance of each SPOKE node for any code in the EHRs. We argue that these results, alongside the natural integration of PSEVs into any EHR machine-learning platform, provide a key step toward precision medicine
Enhance Representation Learning of Clinical Narrative with Neural Networks for Clinical Predictive Modeling
Medicine is undergoing a technological revolution. Understanding human health from clinical data has major challenges from technical and practical perspectives, thus prompting methods that understand large, complex, and noisy data. These methods are particularly necessary for natural language data from clinical narratives/notes, which contain some of the richest information on a patient. Meanwhile, deep neural networks have achieved superior performance in a wide variety of natural language processing (NLP) tasks because of their capacity to encode meaningful but abstract representations and learn the entire task end-to-end. In this thesis, I investigate representation learning of clinical narratives with deep neural networks through a number of tasks ranging from clinical concept extraction, clinical note modeling, and patient-level language representation. I present methods utilizing representation learning with neural networks to support understanding of clinical text documents.
I first introduce the notion of representation learning from natural language processing and patient data modeling. Then, I investigate word-level representation learning to improve clinical concept extraction from clinical notes. I present two works on learning word representations and evaluate them to extract important concepts from clinical notes. The first study focuses on cancer-related information, and the second study evaluates shared-task data. The aims of these two studies are to automatically extract important entities from clinical notes. Next, I present a series of deep neural networks to encode hierarchical, longitudinal, and contextual information for modeling a series of clinical notes. I also evaluate the models by predicting clinical outcomes of interest, including mortality, length of stay, and phenotype predictions. Finally, I propose a novel representation learning architecture to develop a generalized and transferable language representation at the patient level. I also identify pre-training tasks appropriate for constructing a generalizable language representation. The main focus is to improve predictive performance of phenotypes with limited data, a challenging task due to a lack of data.
Overall, this dissertation addresses issues in natural language processing for medicine, including clinical text classification and modeling. These studies show major barriers to understanding large-scale clinical notes. It is believed that developing deep representation learning methods for distilling enormous amounts of heterogeneous data into patient-level language representations will improve evidence-based clinical understanding. The approach to solving these issues by learning representations could be used across clinical applications despite noisy data. I conclude that considering different linguistic components in natural language and sequential information between clinical events is important. Such results have implications beyond the immediate context of predictions and further suggest future directions for clinical machine learning research to improve clinical outcomes. This could be a starting point for future phenotyping methods based on natural language processing that construct patient-level language representations to improve clinical predictions. While significant progress has been made, many open questions remain, so I will highlight a few works to demonstrate promising directions
Secondary use of Structured Electronic Health Records Data: From Observational Studies to Deep Learning-based Predictive Modeling
With the wide adoption of electronic health records (EHRs), researchers, as well as large healthcare organizations, governmental institutions, insurance, and pharmaceutical companies have been interested in leveraging this rich clinical data source to extract clinical evidence and develop predictive algorithms. Large vendors have been able to compile structured EHR data from sites all over the United States, de-identify these data, and make them available to data science researchers in a more usable format. For this dissertation, we leveraged one of the earliest and largest secondary EHR data sources and conducted three studies of increasing scope. In the first study, which was of limited scope, we conducted a retrospective observational study to compare the effect of three drugs on a specific population of approximately 3,000 patients. Using a novel statistical method, we found evidence that the selection of phenylephrine as the primary vasopressor to induce hypertension for the management of nontraumatic subarachnoid hemorrhage is associated with better outcomes as compared to selecting norepinephrine or dopamine. In the second study, we widened our scope, using a cohort of more than 100,000 patients to train generalizable models for the risk prediction of specific clinical events, such as heart failure in diabetes patients or pancreatic cancer. In this study, we found that recurrent neural network-based predictive models trained on expressive terminologies, which preserve a high level of granularity, are associated with better prediction performance as compared with other baseline methods, such as logistic regression. Finally, we widened our scope again, to train Med-BERT, a foundation model, on more than 20 million patients’ diagnosis data. Med-BERT was found to improve the prediction performance of downstream tasks that have a small sample size, which otherwise would limit the ability of the model to learn good representation. In conclusion, we found that we can extract useful information and train helpful deep learning-based predictive models. Given the limitations of secondary EHR data and taking into consideration that the data were originally collected for administrative and not research purposes, however, the findings need clinical validation. Therefore, clinical trials are warranted to further validate any new evidence extracted from such data sources before updating clinical practice guidelines. The implementability of the developed predictive models, which are in an early development phase, also warrants further evaluation
Automated Coding of Under-Studied Medical Concept Domains: Linking Physical Activity Reports to the International Classification of Functioning, Disability, and Health
Linking clinical narratives to standardized vocabularies and coding systems
is a key component of unlocking the information in medical text for analysis.
However, many domains of medical concepts lack well-developed terminologies
that can support effective coding of medical text. We present a framework for
developing natural language processing (NLP) technologies for automated coding
of under-studied types of medical information, and demonstrate its
applicability via a case study on physical mobility function. Mobility is a
component of many health measures, from post-acute care and surgical outcomes
to chronic frailty and disability, and is coded in the International
Classification of Functioning, Disability, and Health (ICF). However, mobility
and other types of functional activity remain under-studied in medical
informatics, and neither the ICF nor commonly-used medical terminologies
capture functional status terminology in practice. We investigated two
data-driven paradigms, classification and candidate selection, to link
narrative observations of mobility to standardized ICF codes, using a dataset
of clinical narratives from physical therapy encounters. Recent advances in
language modeling and word embedding were used as features for established
machine learning models and a novel deep learning approach, achieving a macro
F-1 score of 84% on linking mobility activity reports to ICF codes. Both
classification and candidate selection approaches present distinct strengths
for automated coding in under-studied domains, and we highlight that the
combination of (i) a small annotated data set; (ii) expert definitions of codes
of interest; and (iii) a representative text corpus is sufficient to produce
high-performing automated coding systems. This study has implications for the
ongoing growth of NLP tools for a variety of specialized applications in
clinical care and research.Comment: Updated final version, published in Frontiers in Digital Health,
https://doi.org/10.3389/fdgth.2021.620828. 34 pages (23 text + 11
references); 9 figures, 2 table
Multi-domain clinical natural language processing with MedCAT: The Medical Concept Annotation Toolkit
Electronic health records (EHR) contain large volumes of unstructured text, requiring the application of information extraction (IE) technologies to enable clinical analysis. We present the open source Medical Concept Annotation Toolkit (MedCAT) that provides: (a) a novel self-supervised machine learning algorithm for extracting concepts using any concept vocabulary including UMLS/SNOMED-CT; (b) a feature-rich annotation interface for customizing and training IE models; and (c) integrations to the broader CogStack ecosystem for vendor-agnostic health system deployment. We show improved performance in extracting UMLS concepts from open datasets (F1:0.448-0.738 vs 0.429-0.650). Further real-world validation demonstrates SNOMED-CT extraction at 3 large London hospitals with self-supervised training over ∼8.8B words from ∼17M clinical records and further fine-tuning with ∼6K clinician annotated examples. We show strong transferability (F1 > 0.94) between hospitals, datasets and concept types indicating cross-domain EHR-agnostic utility for accelerated clinical and research use cases
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