Liu, Hongfang

Abstract Background: Next-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in precision oncology practice. Due to the heterogeneity of individual patient’s disease conditions and treatment journeys, not all targeted therapies were initiated despite actionable mutations. To better understand and support the clinical decision-making process in precision oncology, there is a need to examine real-world associations of patients’ genetic information and treatment choice.Methods: To fill the gap of insufficient use of real-world data (RWD) in electronic health records (EHRs), we generated a single Resource Description Framework (RDF) resource, called PO2RDF (precision oncology to RDF) by integrating information regarding gene, variant, disease, and drug from genetic reports and EHRs. Results: There are total 2,309,014 triples contained in the PO2RDF. Among them 32,815 triples are related to Gene, 34,695 triples are related to Variant, 8,787 triples are related to Disease, 26,154 triples are related to Drug. We performed one use case analysis to demonstrate the usability of the PO2RDF: we examined real-world associations between EGFR mutations and targeted therapies to confirm existing knowledge and detect off-label use. Conclusions: In conclusion, our work proposed to use RDF to organize and distribute clinical RWD that is otherwise inaccessible externally. Our work serves as a pilot study that will lead to new clinical applications and could ultimately stimulate progress in the field of precision oncology.

Objective: To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs). Methods: This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions. Results: 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4–6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89–2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17–1.54) after adjusting for all 16 comorbid chronic conditions. Conclusion: These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses.

Abstract Background: Next-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in oncology clinical practice. However, the utility of genetic information in clinical decision-making process has not been examined extensively from a real-world, data-driven perspective. Through mining real-world data (RWD) from clinical notes, we could extract patients’ genetic information and further associate treatment decisions with genetic information.Methods: We proposed a real-world evidence (RWE) study framework that incorporates context-based natural language processing (NLP) methods and data quality examination before final association analysis. The framework was demonstrated in a Foundation-tested women cancer cohort (N=196). Upon retrieval of patients’ genetic information using NLP system, we assessed the completeness of genetic data captured in unstructured clinical notes according to a genetic data-model. We examined the distribution of different topics regarding BRCA1/2 throughout patients’ treatment process, and then analyzed the association between BRCA1/2 mutation status and the discussion/prescription of targeted therapy. Results: We identified seven topics in clinical context of genetic mentions including: Information, Evaluation, Insurance, Order, Negative, Positive, and Variants of unknown significance (VUS). Our rule-based system achieved a precision of 0.87, recall of 0.93 and F-measure of 0.91. Our machine learning system achieved a precision of 0.901, recall of 0.899 and F-measure of 0.9 for four-topic classification and a precision of 0.833, recall of 0.823 and F-measure of 0.82 for seven-topic classification. We found in result-containing sentences, capture of BRCA1/2 mutation information was 75%, but detailed variant information (e.g. variant types) is largely missing. Using cleaned RWD, significant associations were found between BRCA1/2 positive mutation and targeted therapies.Conclusions: In conclusion, we demonstrated a framework to generate RWE using RWD from different clinical sources. Rule-based NLP system achieved the best performance for resolving contextual variability when extracting RWD from unstructured clinical notes. Data quality issues such as incompleteness and discrepancies exist thus manual data cleaning is needed before further analysis can be performed. Finally, we were able to use cleaned RWD to evaluate real-world utility of genetic information to initiate a prescription of targeted therapy.

Abstract The development and implementation of clinical decision support (CDS) that trains itself and adapts its algorithms based on new data—here referred to as Adaptive CDS—present unique challenges and considerations. Although Adaptive CDS represents an expected progression from earlier work, the activities needed to appropriately manage and support the establishment and evolution of Adaptive CDS require new, coordinated initiatives and oversight that do not currently exist. In this AMIA position paper, the authors describe current and emerging challenges to the safe use of Adaptive CDS and lay out recommendations for the effective management and monitoring of Adaptive CDS.

Abstract Background Delirium is underdiagnosed in clinical practice and is not routinely coded for billing. Manual chart review can be used to identify the occurrence of delirium; however, it is labor-intensive and impractical for large-scale studies. Natural language processing (NLP) has the capability to process raw text in electronic health records (EHRs) and determine the meaning of the information. We developed and validated NLP algorithms to automatically identify the occurrence of delirium from EHRs. Methods This study used a randomly selected cohort from the population-based Mayo Clinic Biobank (N = 300, age ≥65). We adopted the standardized evidence-based framework confusion assessment method (CAM) to develop and evaluate NLP algorithms to identify the occurrence of delirium using clinical notes in EHRs. Two NLP algorithms were developed based on CAM criteria: one based on the original CAM (NLP-CAM; delirium vs no delirium) and another based on our modified CAM (NLP-mCAM; definite, possible, and no delirium). The sensitivity, specificity, and accuracy were used for concordance in delirium status between NLP algorithms and manual chart review as the gold standard. The prevalence of delirium cases was examined using International Classification of Diseases, 9th Revision (ICD-9), NLP-CAM, and NLP-mCAM. Results NLP-CAM demonstrated a sensitivity, specificity, and accuracy of 0.919, 1.000, and 0.967, respectively. NLP-mCAM demonstrated sensitivity, specificity, and accuracy of 0.827, 0.913, and 0.827, respectively. The prevalence analysis of delirium showed that the NLP-CAM algorithm identified 12 651 (9.4%) delirium patients, the NLP-mCAM algorithm identified 20 611 (15.3%) definite delirium cases, and 10 762 (8.0%) possible cases. Conclusions NLP algorithms based on the standardized evidence-based CAM framework demonstrated high performance in delineating delirium status in an expeditious and cost-effective manner.

Abstract Background : Next- generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in oncology clinical practice. However, the utility of genetic information in clinical decision-making process has not been examined extensively from a real-world, data-driven perspective. Through mining real-world data (RWD) from clinical notes, we could extract patients’ genetic information and further associate treatment decisions with genetic information. Methods : We proposed a real-world evidence (RWE) study framework that incorporates context-based natural language processing (NLP) methods and data quality examination before final association analysis. The framework was demonstrated in a Foundation-tested women cancer cohort (N=196). Upon retrieval of patients’ genetic information using NLP system, we assessed the completeness of genetic data captured in unstructured clinical notes according to a genetic data-model. We examined the distribution of different topics regarding BRCA1/2 throughout patients’ treatment process, and then analyzed the association between BRCA1/2 mutation status and the discussion/prescription of targeted therapy . Results: We identified seven topics in clinical context of genetic mentions including: Information, Evaluation, Insurance, Order, Negative, Positive, and Variants of unknown significance (VUS) . O ur rule-based system achieved a precision of 0.87, recall of 0.93 and F- measure of 0.91. Our machine learning system achieved a precision of 0.901, recall of 0.899 and F- measure of 0.9 for four-topic classification and a precision of 0.833, recall of 0.823 and F- measure of 0.82 for seven-topic classification. We found in result-containing sentences, capture of BRCA1/2 mutation information was 75%, but detailed variant information (e.g. variant types) is largely missing. Using cleaned RWD, significant associations were found between BRCA1/2 positive mutation and targeted therapies. Conclusions : In conclusion, we demonstrated a framework to generate RWE using RWD from different clinical sources. Rule-based NLP system achieved the best performance for resolving contextual variability when extracting RWD from unstructured clinical notes . Data quality issues such as incompleteness and discrepancies exist thus manual data cleaning is needed before further analysis can be performed. Finally, we were able to use cleaned RWD to evaluate real-world utility of genetic information to initiate a prescription of targeted therapy.

Abstract Objective Growing numbers of academic medical centers offer patient cohort discovery tools to their researchers, yet the performance of systems for this use case is not well understood. The objective of this research was to assess patient-level information retrieval methods using electronic health records for different types of cohort definition retrieval. Materials and Methods We developed a test collection consisting of about 100 000 patient records and 56 test topics that characterized patient cohort requests for various clinical studies. Automated information retrieval tasks using word-based approaches were performed, varying 4 different parameters for a total of 48 permutations, with performance measured using B-Pref. We subsequently created structured Boolean queries for the 56 topics for performance comparisons. In addition, we performed a more detailed analysis of 10 topics. Results The best-performing word-based automated query parameter settings achieved a mean B-Pref of 0.167 across all 56 topics. The way a topic was structured (topic representation) had the largest impact on performance. Performance not only varied widely across topics, but there was also a large variance in sensitivity to parameter settings across the topics. Structured queries generally performed better than automated queries on measures of recall and precision but were still not able to recall all relevant patients found by the automated queries. Conclusion While word-based automated methods of cohort retrieval offer an attractive solution to the labor-intensive nature of this task currently used at many medical centers, we generally found suboptimal performance in those approaches, with better performance obtained from structured Boolean queries. Future work will focus on using the test collection to develop and evaluate new approaches to query structure, weighting algorithms, and application of semantic methods.

Abstract Background: Next-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in oncology clinical practice. However, the utility of genetic information in clinical decision-making process has not been examined extensively from a real-world, data-driven perspective. Through mining real-world data (RWD) from clinical notes, we could extract patients’ genetic information and further associate treatment decisions with genetic information.Methods: We proposed a real-world evidence (RWE) study framework that incorporates context-based natural language processing (NLP) methods and data quality examination before final association analysis. The framework was demonstrated on a Foundation-tested women cancer cohort (N=196). Upon retrieval of patients’ genetic information using NLP system, we assessed completeness of genetic data captured in unstructured clinical notes according a genetic data-model. We examined the distribution of different topics regarding BRCA1/2 throughout patients’ treatment process, and then analyzed the association between BRCA1/2 mutation status and the discussion/prescription of targeted therapy. Results: We identified seven topics in clinical context of genetic mentions including: Information, Evaluation, Insurance, Order, Negative, Positive, and Variants of unknown significance (VUS). Our rule-based system achieved a precision of 0.87, recall of 0.93 and F-measure of 0.91. Our machine learning system achieved a precision of 0.901, recall of 0.899 and F-measure of 0.9 for four-topic classification and a precision of 0.833, recall of 0.823 and F-measure of 0.82 for seven-topic classification. We found in result-containing sentences, capture of BRCA1/2 mutation information was 75%, but detailed variant information (e.g. variant types) is largely missing. Using cleaned RWD, significant associations were found between BRCA1/2 positive mutation and targeted therapies.Conclusions: In conclusion, we demonstrated a framework to generate RWE using RWD from different clinical sources. Rule-based NLP system achieved the best performance for resolving contextual variability when extracting RWD from unstructured clinical notes. Data quality issue such as incompleteness and discrepancies exist thus manual data cleaning is needed before further analysis can be performed. Finally, we were able to use cleaned RWD to evaluate real-world utility of genetic information to initiate prescription of targeted therapy.

AbstractLarge observational data networks that leverage routine clinical practice data in electronic health records (EHRs) are critical resources for research on coronavirus disease 2019 (COVID-19). Data normalization is a key challenge for the secondary use of EHRs for COVID-19 research across institutions. In this study, we addressed the challenge of automating the normalization of COVID-19 diagnostic tests, which are critical data elements, but for which controlled terminology terms were published after clinical implementation. We developed a simple but effective rule-based tool called COVID-19 TestNorm to automatically normalize local COVID-19 testing names to standard LOINC (Logical Observation Identifiers Names and Codes) codes. COVID-19 TestNorm was developed and evaluated using 568 test names collected from 8 healthcare systems. Our results show that it could achieve an accuracy of 97.4% on an independent test set. COVID-19 TestNorm is available as an open-source package for developers and as an online Web application for end users (https://clamp.uth.edu/covid/loinc.php). We believe that it will be a useful tool to support secondary use of EHRs for research on COVID-19.