Utilizing Consumer Health Posts for Pharmacovigilance: Identifying Underlying Factors Associated with Patients’ Attitudes Towards Antidepressants

Non-adherence to antidepressants is a major obstacle to antidepressants therapeutic benefits, resulting in increased risk of relapse, emergency visits, and significant burden on individuals and the healthcare system. Several studies showed that non-adherence is weakly associated with personal and clinical variables, but strongly associated with patients’ beliefs and attitudes towards medications. The traditional methods for identifying the key dimensions of patients’ attitudes towards antidepressants are associated with some methodological limitations, such as concern about confidentiality of personal information. In this study, attempts have been made to address the limitations by utilizing patients’ self report experiences in online healthcare forums to identify underlying factors affecting patients attitudes towards antidepressants. The data source of the study was a healthcare forum called “askapatients.com”. 892 patients’ reviews were randomly collected from the forum for the four most commonly prescribed antidepressants including Sertraline (Zoloft) and Escitalopram (Lexapro) from SSRI class, and Venlafaxine (Effexor) and duloxetine (Cymbalta) from SNRI class. Methodology of this study is composed of two main phases: I) generating structured data from unstructured patients’ drug reviews and testing hypotheses concerning attitude, II) identification and normalization of Adverse Drug Reactions (ADRs), Withdrawal Symptoms (WDs) and Drug Indications (DIs) from the posts, and mapping them to both The UMLS and SNOMED CT concepts. Phase II also includes testing the association between ADRs and attitude. The result of the first phase of this study showed that “experience of adverse drug reactions”, “perceived distress received from ADRs”, “lack of knowledge about medication’s mechanism”, “withdrawal experience”, “duration of usage”, and “drug effectiveness” are strongly associated with patients attitudes. However, demographic variables including “age” and “gender” are not associated with attitude. Analysis of the data in second phase of the study showed that from 6,534 identified entities, 73% are ADRs, 12% are WDs, and 15 % are drug indications. In addition, psychological and cognitive expressions have higher variability than physiological expressions. All three types of entities were mapped to 811 UMLS and SNOMED CT concepts. Testing the association between ADRs and attitude showed that from twenty-one physiological ADRs specified in the ASEC questionnaire, “dry mouth”, “increased appetite”, “disorientation”, “yawning”, “weight gain”, and “problem with sexual dysfunction” are associated with attitude. A set of psychological and cognitive ADRs, such as “emotional indifference” and “memory problem were also tested that showed significance association between these types of ADRs and attitude. The findings of this study have important implications for designing clinical interventions aiming to improve patients\u27 adherence towards antidepressants. In addition, the dataset generated in this study has significant implications for improving performance of text-mining algorithms aiming to identify health related information from consumer health posts. Moreover, the dataset can be used for generating and testing hypotheses related to ADRs associated with psychiatric mediations, and identifying factors associated with discontinuation of antidepressants. The dataset and guidelines of this study are available at https://sites.google.com/view/pharmacovigilanceinpsychiatry/hom

Natural language processing (NLP) for clinical information extraction and healthcare research

Introduction: Epilepsy is a common disease with multiple comorbidities. Routinely collected health care data have been successfully used in epilepsy research, but they lack the level of detail needed for in-depth study of complex interactions between the aetiology, comorbidities, and treatment that affect patient outcomes. The aim of this work is to use natural language processing (NLP) technology to create detailed disease-specific datasets derived from the free text of clinic letters in order to enrich the information that is already available. Method: An NLP pipeline for the extraction of epilepsy clinical text (ExECT) was redeveloped to extract a wider range of variables. A gold standard annotation set for epilepsy clinic letters was created for the validation of the ExECT v2 output. A set of clinic letters from the Epi25 study was processed and the datasets produced were validated against Swansea Neurology Biobank records. A data linkage study investigating genetic influences on epilepsy outcomes using GP and hospital records was supplemented with the seizure frequency dataset produced by ExECT v2. Results: The validation of ExECT v2 produced overall precision, recall, and F1 score of 0.90, 0.86, and 0.88, respectively. A method of uploading, annotating, and linking genetic variant datasets within the SAIL databank was established. No significant differences in the genetic burden of rare and potentially damaging variants were observed between the individuals with vs without unscheduled admissions, and between individuals on monotherapy vs polytherapy. No significant difference was observed in the genetic burden between people who were seizure free for over a year and those who experienced at least one seizure a year. Conclusion: This work presents successful extraction of epilepsy clinical information and explores how this information can be used in epilepsy research. The approach taken in the development of ExECT v2, and the research linking the NLP outputs, routinely collected health care data, and genetics set the way for wider research

Identifying predictors of suicide in severe mental illness : a feasibility study of a clinical prediction rule (Oxford Mental Illness and Suicide tool or OxMIS)

Background: Oxford Mental Illness and Suicide tool (OxMIS) is a brief, scalable, freely available, structured risk assessment tool to assess suicide risk in patients with severe mental illness (schizophrenia-spectrum disorders or bipolar disorder). OxMIS requires further external validation, but a lack of large-scale cohorts with relevant variables makes this challenging. Electronic health records provide possible data sources for external validation of risk prediction tools. However, they contain large amounts of information within free-text that is not readily extractable. In this study, we examined the feasibility of identifying suicide predictors needed to validate OxMIS in routinely collected electronic health records. Methods: In study 1, we manually reviewed electronic health records of 57 patients with severe mental illness to calculate OxMIS risk scores. In study 2, we examined the feasibility of using natural language processing to scale up this process. We used anonymized free-text documents from the Clinical Record Interactive Search database to train a named entity recognition model, a machine learning technique which recognizes concepts in free-text. The model identified eight concepts relevant for suicide risk assessment: medication (antidepressant/antipsychotic treatment), violence, education, self-harm, benefits receipt, drug/alcohol use disorder, suicide, and psychiatric admission. We assessed model performance in terms of precision (similar to positive predictive value), recall (similar to sensitivity) and F1 statistic (an overall performance measure). Results: In study 1, we estimated suicide risk for all patients using the OxMIS calculator, giving a range of 12 month risk estimates from 0.1-3.4%. For 13 out of 17 predictors, there was no missing information in electronic health records. For the remaining 4 predictors missingness ranged from 7-26%; to account for these missing variables, it was possible for OxMIS to estimate suicide risk using a range of scores. In study 2, the named entity recognition model had an overall precision of 0.77, recall of 0.90 and F1 score of 0.83. The concept with the best precision and recall was medication (precision 0.84, recall 0.96) and the weakest were suicide (precision 0.37), and drug/alcohol use disorder (recall 0.61). Conclusions: It is feasible to estimate suicide risk with the OxMIS tool using predictors identified in routine clinical records. Predictors could be extracted using natural language processing. However, electronic health records differ from other data sources, particularly for family history variables, which creates methodological challenges

CREATE: Clinical Record Analysis Technology Ensemble

In this thesis, we describe an approach that won a psychiatric symptom severity prediction challenge. The challenge was to correctly predict the severity of psychiatric symptoms on a 4-point scale. Our winning submission uses a novel stacked machine learning architecture in which (i) a base data ingestion/cleaning step was followed by the (ii) derivation of a base set of features defined using text analytics, after which (iii) association rule learning was used in a novel way to generate new features, followed by a (iv) feature selection step to eliminate irrelevant features, followed by a (v) classifier training algorithm in which a total of 22 classifiers including new classifier variants of AdaBoost and RandomForest were trained on seven different data views, and (vi) finally an ensemble learning step, in which ensembles of best learners were used to improve on the accuracy of individual learners. All of this was tested via standard 10-fold cross-validation on training data provided by the N-GRID challenge organizers, of which the three best ensembles were selected for submission to N-GRID\u27s blind testing. The best of our submitted solutions garnered an overall final score of 0.863 according to the organizer\u27s measure. All 3 of our submissions placed within the top 10 out of the 65 total submissions. The challenge constituted Track 2 of the 2016 Centers of Excellence in Genomic Science (CEGS) Neuropsychiatric Genome-Scale and RDOC Individualized Domains (N-GRID) Shared Task in Clinical Natural Language Processing

PhenoDEF: a corpus for annotating sentences with information of phenotype definitions in biomedical literature

Background Adverse events induced by drug-drug interactions are a major concern in the United States. Current research is moving toward using electronic health record (EHR) data, including for adverse drug events discovery. One of the first steps in EHR-based studies is to define a phenotype for establishing a cohort of patients. However, phenotype definitions are not readily available for all phenotypes. One of the first steps of developing automated text mining tools is building a corpus. Therefore, this study aimed to develop annotation guidelines and a gold standard corpus to facilitate building future automated approaches for mining phenotype definitions contained in the literature. Furthermore, our aim is to improve the understanding of how these published phenotype definitions are presented in the literature and how we annotate them for future text mining tasks. Results Two annotators manually annotated the corpus on a sentence-level for the presence of evidence for phenotype definitions. Three major categories (inclusion, intermediate, and exclusion) with a total of ten dimensions were proposed characterizing major contextual patterns and cues for presenting phenotype definitions in published literature. The developed annotation guidelines were used to annotate the corpus that contained 3971 sentences: 1923 out of 3971 (48.4%) for the inclusion category, 1851 out of 3971 (46.6%) for the intermediate category, and 2273 out of 3971 (57.2%) for exclusion category. The highest number of annotated sentences was 1449 out of 3971 (36.5%) for the “Biomedical & Procedure” dimension. The lowest number of annotated sentences was 49 out of 3971 (1.2%) for “The use of NLP”. The overall percent inter-annotator agreement was 97.8%. Percent and Kappa statistics also showed high inter-annotator agreement across all dimensions. Conclusions The corpus and annotation guidelines can serve as a foundational informatics approach for annotating and mining phenotype definitions in literature, and can be used later for text mining applications

Advances in monolingual and crosslingual automatic disability annotation in Spanish

Background Unlike diseases, automatic recognition of disabilities has not received the same attention in the area of medical NLP. Progress in this direction is hampered by obstacles like the lack of annotated corpus. Neural architectures learn to translate sequences from spontaneous representations into their corresponding standard representations given a set of samples. The aim of this paper is to present the last advances in monolingual (Spanish) and crosslingual (from English to Spanish and vice versa) automatic disability annotation. The task consists of identifying disability mentions in medical texts written in Spanish within a collection of abstracts from journal papers related to the biomedical domain. Results In order to carry out the task, we have combined deep learning models that use different embedding granularities for sequence to sequence tagging with a simple acronym and abbreviation detection module to boost the coverage. Conclusions Our monolingual experiments demonstrate that a good combination of different word embedding representations provide better results than single representations, significantly outperforming the state of the art in disability annotation in Spanish. Additionally, we have experimented crosslingual transfer (zero-shot) for disability annotation between English and Spanish with interesting results that might help overcoming the data scarcity bottleneck, specially significant for the disabilities.This work was partially funded by the Spanish Ministry of Science and Innovation (MCI/AEI/FEDER, UE, DOTT-HEALTH/PAT-MED PID2019-106942RB-C31), the Basque Government (IXA IT1570-22), MCIN/AEI/ 10.13039/501100011033 and European Union NextGeneration EU/PRTR (DeepR3, TED2021-130295B-C31) and the EU ERA-Net CHIST-ERA and the Spanish Research Agency (ANTIDOTE PCI2020-120717-2)

Adverse Drug Event Detection, Causality Inference, Patient Communication and Translational Research

Adverse drug events (ADEs) are injuries resulting from a medical intervention related to a drug. ADEs are responsible for nearly 20% of all the adverse events that occur in hospitalized patients. ADEs have been shown to increase the cost of health care and the length of stays in hospital. Therefore, detecting and preventing ADEs for pharmacovigilance is an important task that can improve the quality of health care and reduce the cost in a hospital setting. In this dissertation, we focus on the development of ADEtector, a system that identifies ADEs and medication information from electronic medical records and the FDA Adverse Event Reporting System reports. The ADEtector system employs novel natural language processing approaches for ADE detection and provides a user interface to display ADE information. The ADEtector employs machine learning techniques to automatically processes the narrative text and identify the adverse event (AE) and medication entities that appear in that narrative text. The system will analyze the entities recognized to infer the causal relation that exists between AEs and medications by automating the elements of Naranjo score using knowledge and rule based approaches. The Naranjo Adverse Drug Reaction Probability Scale is a validated tool for finding the causality of a drug induced adverse event or ADE. The scale calculates the likelihood of an adverse event related to drugs based on a list of weighted questions. The ADEtector also presents the user with evidence for ADEs by extracting figures that contain ADE related information from biomedical literature. A brief summary is generated for each of the figures that are extracted to help users better comprehend the figure. This will further enhance the user experience in understanding the ADE information better. The ADEtector also helps patients better understand the narrative text by recognizing complex medical jargon and abbreviations that appear in the text and providing definitions and explanations for them from external knowledge resources. This system could help clinicians and researchers in discovering novel ADEs and drug relations and also hypothesize new research questions within the ADE domain

Named Entity Recognition in Electronic Health Records: A Methodological Review

Objectives A substantial portion of the data contained in Electronic Health Records (EHR) is unstructured, often appearing as free text. This format restricts its potential utility in clinical decision-making. Named entity recognition (NER) methods address the challenge of extracting pertinent information from unstructured text. The aim of this study was to outline the current NER methods and trace their evolution from 2011 to 2022. Methods We conducted a methodological literature review of NER methods, with a focus on distinguishing the classification models, the types of tagging systems, and the languages employed in various corpora. Results Several methods have been documented for automatically extracting relevant information from EHRs using natural language processing techniques such as NER and relation extraction (RE). These methods can automatically extract concepts, events, attributes, and other data, as well as the relationships between them. Most NER studies conducted thus far have utilized corpora in English or Chinese. Additionally, the bidirectional encoder representation from transformers using the BIO tagging system architecture is the most frequently reported classification scheme. We discovered a limited number of papers on the implementation of NER or RE tasks in EHRs within a specific clinical domain. Conclusions EHRs play a pivotal role in gathering clinical information and could serve as the primary source for automated clinical decision support systems. However, the creation of new corpora from EHRs in specific clinical domains is essential to facilitate the swift development of NER and RE models applied to EHRs for use in clinical practice