Adverse Drug Reaction Classification With Deep Neural Networks

We study the problem of detecting sentences describing adverse drug reactions (ADRs) and frame the problem as binary classification. We investigate different neural network (NN) architectures for ADR classification. In particular, we propose two new neural network models, Convolutional Recurrent Neural Network (CRNN) by concatenating convolutional neural networks with recurrent neural networks, and Convolutional Neural Network with Attention (CNNA) by adding attention weights into convolutional neural networks. We evaluate various NN architectures on a Twitter dataset containing informal language and an Adverse Drug Effects (ADE) dataset constructed by sampling from MEDLINE case reports. Experimental results show that all the NN architectures outperform the traditional maximum entropy classifiers trained from n-grams with different weighting strategies considerably on both datasets. On the Twitter dataset, all the NN architectures perform similarly. But on the ADE dataset, CNN performs better than other more complex CNN variants. Nevertheless, CNNA allows the visualisation of attention weights of words when making classification decisions and hence is more appropriate for the extraction of word subsequences describing ADRs

Effective Feature Representation for Clinical Text Concept Extraction

Crucial information about the practice of healthcare is recorded only in free-form text, which creates an enormous opportunity for high-impact NLP. However, annotated healthcare datasets tend to be small and expensive to obtain, which raises the question of how to make maximally efficient uses of the available data. To this end, we develop an LSTM-CRF model for combining unsupervised word representations and hand-built feature representations derived from publicly available healthcare ontologies. We show that this combined model yields superior performance on five datasets of diverse kinds of healthcare text (clinical, social, scientific, commercial). Each involves the labeling of complex, multi-word spans that pick out different healthcare concepts. We also introduce a new labeled dataset for identifying the treatment relations between drugs and diseases

A Neural Attention Model for Categorizing Patient Safety Events

Medical errors are leading causes of death in the US and as such, prevention of these errors is paramount to promoting health care. Patient Safety Event reports are narratives describing potential adverse events to the patients and are important in identifying and preventing medical errors. We present a neural network architecture for identifying the type of safety events which is the first step in understanding these narratives. Our proposed model is based on a soft neural attention model to improve the effectiveness of encoding long sequences. Empirical results on two large-scale real-world datasets of patient safety reports demonstrate the effectiveness of our method with significant improvements over existing methods.Comment: ECIR 201

Named Entity Recognition in Electronic Health Records Using Transfer Learning Bootstrapped Neural Networks

Neural networks (NNs) have become the state of the art in many machine learning applications, especially in image and sound processing [1]. The same, although to a lesser extent [2,3], could be said in natural language processing (NLP) tasks, such as named entity recognition. However, the success of NNs remains dependent on the availability of large labelled datasets, which is a significant hurdle in many important applications. One such case are electronic health records (EHRs), which are arguably the largest source of medical data, most of which lies hidden in natural text [4,5]. Data access is difficult due to data privacy concerns, and therefore annotated datasets are scarce. With scarce data, NNs will likely not be able to extract this hidden information with practical accuracy. In our study, we develop an approach that solves these problems for named entity recognition, obtaining 94.6 F1 score in I2B2 2009 Medical Extraction Challenge [6], 4.3 above the architecture that won the competition. Beyond the official I2B2 challenge, we further achieve 82.4 F1 on extracting relationships between medical terms. To reach this state-of-the-art accuracy, our approach applies transfer learning to leverage on datasets annotated for other I2B2 tasks, and designs and trains embeddings that specially benefit from such transfer.Comment: 11 pages, 4 figures, 8 table

딥 뉴럴 네트워크를 활용한 의학 개념 및 환자 표현 학습과 의료 문제에의 응용

학위논문(박사) -- 서울대학교대학원 : 공과대학 전기·정보공학부, 2022. 8. 정교민.본 학위 논문은 전국민 의료 보험데이터인 표본코호트DB를 활용하여 딥 뉴럴 네트워크 기반의 의학 개념 및 환자 표현 학습 방법과 의료 문제 해결 방법을 제안한다. 먼저 순차적인 환자 의료 기록과 개인 프로파일 정보를 기반으로 환자 표현을 학습하고 향후 질병 진단 가능성을 예측하는 재귀신경망 모델을 제안하였다. 우리는 다양한 성격의 환자 정보를 효율적으로 혼합하는 구조를 도입하여 큰 성능 향상을 얻었다. 또한 환자의 의료 기록을 이루는 의료 코드들을 분산 표현으로 나타내 추가 성능 개선을 이루었다. 이를 통해 의료 코드의 분산 표현이 중요한 시간적 정보를 담고 있음을 확인하였고, 이어지는 연구에서는 이러한 시간적 정보가 강화될 수 있도록 그래프 구조를 도입하였다. 우리는 의료 코드의 분산 표현 간의 유사도와 통계적 정보를 가지고 그래프를 구축하였고 그래프 뉴럴 네트워크를 활용, 시간/통계적 정보가 강화된 의료 코드의 표현 벡터를 얻었다. 획득한 의료 코드 벡터를 통해 시판 약물의 잠재적인 부작용 신호를 탐지하는 모델을 제안한 결과, 기존의 부작용 데이터베이스에 존재하지 않는 사례까지도 예측할 수 있음을 보였다. 마지막으로 분량에 비해 주요 정보가 희소하다는 의료 기록의 한계를 극복하기 위해 지식그래프를 활용하여 사전 의학 지식을 보강하였다. 이때 환자의 의료 기록을 구성하는 지식그래프의 부분만을 추출하여 개인화된 지식그래프를 만들고 그래프 뉴럴 네트워크를 통해 그래프의 표현 벡터를 획득하였다. 최종적으로 순차적인 의료 기록을 함축한 환자 표현과 더불어 개인화된 의학 지식을 함축한 표현을 함께 사용하여 향후 질병 및 진단 예측 문제에 활용하였다.This dissertation proposes a deep neural network-based medical concept and patient representation learning methods using medical claims data to solve two healthcare tasks, i.e., clinical outcome prediction and post-marketing adverse drug reaction (ADR) signal detection. First, we propose SAF-RNN, a Recurrent Neural Network (RNN)-based model that learns a deep patient representation based on the clinical sequences and patient characteristics. Our proposed model fuses different types of patient records using feature-based gating and self-attention. We demonstrate that high-level associations between two heterogeneous records are effectively extracted by our model, thus achieving state-of-the-art performances for predicting the risk probability of cardiovascular disease. Secondly, based on the observation that the distributed medical code embeddings represent temporal proximity between the medical codes, we introduce a graph structure to enhance the code embeddings with such temporal information. We construct a graph using the distributed code embeddings and the statistical information from the claims data. We then propose the Graph Neural Network(GNN)-based representation learning for post-marketing ADR detection. Our model shows competitive performances and provides valid ADR candidates. Finally, rather than using patient records alone, we utilize a knowledge graph to augment the patient representation with prior medical knowledge. Using SAF-RNN and GNN, the deep patient representation is learned from the clinical sequences and the personalized medical knowledge. It is then used to predict clinical outcomes, i.e., next diagnosis prediction and CVD risk prediction, resulting in state-of-the-art performances.1 Introduction 1 2 Background 8 2.1 Medical Concept Embedding 8 2.2 Encoding Sequential Information in Clinical Records 11 3 Deep Patient Representation with Heterogeneous Information 14 3.1 Related Work 16 3.2 Problem Statement 19 3.3 Method 20 3.3.1 RNN-based Disease Prediction Model 20 3.3.2 Self-Attentive Fusion (SAF) Encoder 23 3.4 Dataset and Experimental Setup 24 3.4.1 Dataset 24 3.4.2 Experimental Design 26 ii 3.4.3 Implementation Details 27 3.5 Experimental Results 28 3.5.1 Evaluation of CVD Prediction 28 3.5.2 Sensitivity Analysis 28 3.5.3 Ablation Studies 31 3.6 Further Investigation 32 3.6.1 Case Study: Patient-Centered Analysis 32 3.6.2 Data-Driven CVD Risk Factors 32 3.7 Conclusion 33 4 Graph-Enhanced Medical Concept Embedding 40 4.1 Related Work 42 4.2 Problem Statement 43 4.3 Method 44 4.3.1 Code Embedding Learning with Skip-gram Model 44 4.3.2 Drug-disease Graph Construction 45 4.3.3 A GNN-based Method for Learning Graph Structure 47 4.4 Dataset and Experimental Setup 49 4.4.1 Dataset 49 4.4.2 Experimental Design 50 4.4.3 Implementation Details 52 4.5 Experimental Results 53 4.5.1 Evaluation of ADR Detection 53 4.5.2 Newly-Described ADR Candidates 54 4.6 Conclusion 55 5 Knowledge-Augmented Deep Patient Representation 57 5.1 Related Work 60 5.1.1 Incorporating Prior Medical Knowledge for Clinical Outcome Prediction 60 5.1.2 Inductive KGC based on Subgraph Learning 61 5.2 Method 61 5.2.1 Extracting Personalized KG 61 5.2.2 KA-SAF: Knowledge-Augmented Self-Attentive Fusion Encoder 64 5.2.3 KGC as a Pre-training Task 68 5.2.4 Subgraph Infomax: SGI 69 5.3 Dataset and Experimental Setup 72 5.3.1 Clinical Outcome Prediction 72 5.3.2 Next Diagnosis Prediction 72 5.4 Experimental Results 73 5.4.1 Cardiovascular Disease Prediction 73 5.4.2 Next Diagnosis Prediction 73 5.4.3 KGC on SemMed KG 73 5.5 Conclusion 74 6 Conclusion 77 Abstract (In Korean) 90 Acknowlegement 92박

Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning

BACKGROUND: Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. OBJECTIVE: To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. METHODS: We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. RESULTS: Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. CONCLUSIONS: It shows that classical learning models (SVM) remains advantageous over deep learning models (RNN variants) for clinical relation identification, especially for long-distance intersentential relations. However, RNNs demonstrate a great potential of significant improvement if more training data become available. Our work is an important step toward mining EHRs to improve the efficacy of drug safety surveillance. Most importantly, the annotated data used in this study will be made publicly available, which will further promote drug safety research in the community

Improving RNN with atention and embedding for adverse drug reactions

Electronic Health Records (EHR) narratives are a rich source of information, embedding high-resolution information of value to secondary research use. However, because the EHRs are mostly in natural language free-text and highly ambiguity-ridden, many natural language processing algorithms have been devised around them to extract meaningful structured information about clinical entities. The performance of the algorithms however, largely varies depending on the training dataset as well as the effectiveness of the use of background knowledge to steer the learning process. In this paper we study the impact of initializing the training of a neural network natural language processing algorithm with pre-defined clinical word embeddings to improve feature extraction and relationship classification between entities. We add our embedding framework to a bi-directional long short-term memory (Bi-LSTM) neural network, and further study the effect of using attention weights in neural networks for sequence labelling tasks to extract knowledge of Adverse Drug Reactions (ADRs). We incorporate unsupervised word embeddings using Word2Vec and GloVe from widely available medical resources such as Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) II corpora, Unified Medical Language System (UMLS) as well as embed pharmaco lexicon from available EHRs. Our algorithm, implemented using two datasets, shows that our architecture outperforms baseline Bi-LSTM or Bi-LSTM networks using linear chain and Skip-Chain conditional random fields (CRF)

GNTeam at 2018 n2c2:Feature-augmented BiLSTM-CRF for drug-related entity recognition in hospital discharge summaries

Monitoring the administration of drugs and adverse drug reactions are key parts of pharmacovigilance. In this paper, we explore the extraction of drug mentions and drug-related information (reason for taking a drug, route, frequency, dosage, strength, form, duration, and adverse events) from hospital discharge summaries through deep learning that relies on various representations for clinical named entity recognition. This work was officially part of the 2018 n2c2 shared task, and we use the data supplied as part of the task. We developed two deep learning architecture based on recurrent neural networks and pre-trained language models. We also explore the effect of augmenting word representations with semantic features for clinical named entity recognition. Our feature-augmented BiLSTM-CRF model performed with F1-score of 92.67% and ranked 4th for entity extraction sub-task among submitted systems to n2c2 challenge. The recurrent neural networks that use the pre-trained domain-specific word embeddings and a CRF layer for label optimization perform drug, adverse event and related entities extraction with micro-averaged F1-score of over 91%. The augmentation of word vectors with semantic features extracted using available clinical NLP toolkits can further improve the performance. Word embeddings that are pre-trained on a large unannotated corpus of relevant documents and further fine-tuned to the task perform rather well. However, the augmentation of word embeddings with semantic features can help improve the performance (primarily by boosting precision) of drug-related named entity recognition from electronic health records