Critical carE Database for Advanced Research (CEDAR): An automated method to support intensive care units with electronic health record data.

Patients treated in an intensive care unit (ICU) are critically ill and require life-sustaining organ failure support. Existing critical care data resources are limited to a select number of institutions, contain only ICU data, and do not enable the study of local changes in care patterns. To address these limitations, we developed the Critical carE Database for Advanced Research (CEDAR), a method for automating extraction and transformation of data from an electronic health record (EHR) system. Compared to an existing gold standard of manually collected data at our institution, CEDAR was statistically similar in most measures, including patient demographics and sepsis-related organ failure assessment (SOFA) scores. Additionally, CEDAR automated data extraction obviated the need for manual collection of 550 variables. Critically, during the spring 2020 COVID-19 surge in New York City, a modified version of CEDAR supported pandemic response efforts, including clinical operations and research. Other academic medical centers may find value in using the CEDAR method to automate data extraction from EHR systems to support ICU activities.

A scalable method for supporting multiple patient cohort discovery projects using i2b2.

Although i2b2, a popular platform for patient cohort discovery using electronic health record (EHR) data, can support multiple projects specific to individual disease areas or research interests, the standard approach for doing so duplicates data across projects, requiring additional disk space and processing time, which limits scalability. To address this deficiency, we developed a novel approach that stored data in a single i2b2 fact table and used structured query language (SQL) views to access data for specific projects. Compared to the standard approach, the view-based approach reduced required disk space by 59% and extract-transfer-load (ETL) time by 46%, without substantially impacting query performance. The view-based approach has enabled scalability of multiple i2b2 projects and generalized to another data model at our institution. Other institutions may benefit from this approach, code of which is available on GitHub (https://github.com/wcmc-research-informatics/super-i2b2).

Linking Patient Encounters across Primary and Ancillary Electronic Health Record Systems: A Comparison of Two Approaches.

Background: To achieve scientific goals, researchers often require integration of data from a primary electronic health record (EHR) system and one or more ancillary EHR systems used during the same patient care encounter. Although studies have demonstrated approaches for linking patient identity records across different EHR systems, little is known about linking patient encounter records across primary and ancillary EHR systems. Objectives: We compared a patients-first approach versus an encounters-first approach for linking patient encounter records across multiple EHR systems. Methods: We conducted a retrospective observational study of 348,904 patients with 533,283 encounters from 2010 to 2020 across our institution's primary EHR system and an ancillary EHR system used in perioperative settings. For the patients-first approach and the encounters-first approach, we measured the number of patient and encounter links created as well as runtime. Results: While the patients-first approach linked 43% of patients and 49% of encounters, the encounters-first approach linked 98% of patients and 100% of encounters. The encounters-first approach was 20 times faster than the patients-first approach for linking patients and 33% slower for linking encounters. Conclusion: Findings suggest that common patient and encounter identifiers shared among EHR systems via automated interfaces may be clinically useful but not "research-ready" and thus require an encounters-first linkage approach to enable secondary use for scientific purposes. Based on our search, this study is among the first to demonstrate approaches for linking patient encounters across multiple EHR systems. Enterprise data warehouse for research efforts elsewhere may benefit from an encounters-first approach.

Implementation of a commercial federated network of electronic health record data to enable sponsor-initiated clinical trials at an academic medical center.

BACKGROUND: A commercial federated network called TriNetX has connected electronic health record (EHR) data from academic medical centers (AMCs) with biopharmaceutical sponsors in a privacy-preserving manner to promote sponsor-initiated clinical trials. Little is known about how AMCs have implemented TriNetX to support clinical trials. FINDINGS: At our AMC over a six-year period, TriNetX integrated into existing institutional workflows enabled 402 requests for sponsor-initiated clinical trials, 14 % (n = 56) of which local investigators expressed interest in conducting. Although clinical trials administrators indicated TriNetX yielded unique study opportunities, measurement of impact of institutional participation in the network was challenging due to lack of a common trial identifier shared across TriNetX, sponsor, and our institution. CONCLUSION: To the best of our knowledge, this study is among the first to describe integration of a federated network of EHR data into institutional workflows for sponsor-initiated clinical trials. This case report may inform efforts at other institutions.

A method to automate the discharge summary hospital course for neurology patients.

OBJECTIVE: Generation of automated clinical notes has been posited as a strategy to mitigate physician burnout. In particular, an automated narrative summary of a patient's hospital stay could supplement the hospital course section of the discharge summary that inpatient physicians document in electronic health record (EHR) systems. In the current study, we developed and evaluated an automated method for summarizing the hospital course section using encoder-decoder sequence-to-sequence transformer models. MATERIALS AND METHODS: We fine-tuned BERT and BART models and optimized for factuality through constraining beam search, which we trained and tested using EHR data from patients admitted to the neurology unit of an academic medical center. RESULTS: The approach demonstrated good ROUGE scores with an R-2 of 13.76. In a blind evaluation, 2 board-certified physicians rated 62% of the automated summaries as meeting the standard of care, which suggests the method may be useful clinically. DISCUSSION AND CONCLUSION: To our knowledge, this study is among the first to demonstrate an automated method for generating a discharge summary hospital course that approaches a quality level of what a physician would write.

Comparative Merits of Available Mortality Data Sources for Clinical Research.

Obtaining reliable data on patient mortality is a critical challenge facing observational researchers seeking to conduct studies using real-world data. As these analyses are conducted more broadly using newly-available sources of real-world evidence, missing data can serve as a rate-limiting factor. We conducted a comparison of mortality data sources from different stakeholder perspectives - academic medical center (AMC) informatics service providers, AMC research coordinators, industry analytics professionals, and academics - to understand the strengths and limitations of differing mortality data sources: locally generated data from sites conducting research, data provided by governmental sources, and commercially available data sets. Researchers seeking to conduct observational studies using extant data should consider these factors in sourcing outcomes data for their populations of interest.

Portability of natural language processing methods to detect suicidality from clinical text in US and UK electronic health records.

Background: In the global effort to prevent death by suicide, many academic medical institutions are implementing natural language processing (NLP) approaches to detect suicidality from unstructured clinical text in electronic health records (EHRs), with the hope of targeting timely, preventative interventions to individuals most at risk of suicide. Despite the international need, the development of these NLP approaches in EHRs has been largely local and not shared across healthcare systems. Methods: In this study, we developed a process to share NLP approaches that were individually developed at King's College London (KCL), UK and Weill Cornell Medicine (WCM), US - two academic medical centers based in different countries with vastly different healthcare systems. We tested and compared the algorithms' performance on manually annotated clinical notes (KCL: n = 4,911 and WCM = 837). Results: After a successful technical porting of the NLP approaches, our quantitative evaluation determined that independently developed NLP approaches can detect suicidality at another healthcare organization with a different EHR system, clinical documentation processes, and culture, yet do not achieve the same level of success as at the institution where the NLP algorithm was developed (KCL approach: F1-score 0.85 vs. 0.68, WCM approach: F1-score 0.87 vs. 0.72). Limitations: Independent NLP algorithm development and patient cohort selection at the two institutions comprised direct comparability. Conclusions: Shared use of these NLP approaches is a critical step forward towards improving data-driven algorithms for early suicide risk identification and timely prevention.

An architecture for research computing in health to support clinical and translational investigators with electronic patient data.

OBJECTIVE: Obtaining electronic patient data, especially from electronic health record (EHR) systems, for clinical and translational research is difficult. Multiple research informatics systems exist but navigating the numerous applications can be challenging for scientists. This article describes Architecture for Research Computing in Health (ARCH), our institution's approach for matching investigators with tools and services for obtaining electronic patient data. MATERIALS AND METHODS: Supporting the spectrum of studies from populations to individuals, ARCH delivers a breadth of scientific functions-including but not limited to cohort discovery, electronic data capture, and multi-institutional data sharing-that manifest in specific systems-such as i2b2, REDCap, and PCORnet. Through a consultative process, ARCH staff align investigators with tools with respect to study design, data sources, and cost. Although most ARCH services are available free of charge, advanced engagements require fee for service. RESULTS: Since 2016 at Weill Cornell Medicine, ARCH has supported over 1200 unique investigators through more than 4177 consultations. Notably, ARCH infrastructure enabled critical coronavirus disease 2019 response activities for research and patient care. DISCUSSION: ARCH has provided a technical, regulatory, financial, and educational framework to support the biomedical research enterprise with electronic patient data. Collaboration among informaticians, biostatisticians, and clinicians has been critical to rapid generation and analysis of EHR data. CONCLUSION: A suite of tools and services, ARCH helps match investigators with informatics systems to reduce time to science. ARCH has facilitated research at Weill Cornell Medicine and may provide a model for informatics and research leaders to support scientists elsewhere.

Design and validation of a FHIR-based EHR-driven phenotyping toolbox.

OBJECTIVES: To develop and validate a standards-based phenotyping tool to author electronic health record (EHR)-based phenotype definitions and demonstrate execution of the definitions against heterogeneous clinical research data platforms. MATERIALS AND METHODS: We developed an open-source, standards-compliant phenotyping tool known as the PhEMA Workbench that enables a phenotype representation using the Fast Healthcare Interoperability Resources (FHIR) and Clinical Quality Language (CQL) standards. We then demonstrated how this tool can be used to conduct EHR-based phenotyping, including phenotype authoring, execution, and validation. We validated the performance of the tool by executing a thrombotic event phenotype definition at 3 sites, Mayo Clinic (MC), Northwestern Medicine (NM), and Weill Cornell Medicine (WCM), and used manual review to determine precision and recall. RESULTS: An initial version of the PhEMA Workbench has been released, which supports phenotype authoring, execution, and publishing to a shared phenotype definition repository. The resulting thrombotic event phenotype definition consisted of 11 CQL statements, and 24 value sets containing a total of 834 codes. Technical validation showed satisfactory performance (both NM and MC had 100% precision and recall and WCM had a precision of 95% and a recall of 84%). CONCLUSIONS: We demonstrate that the PhEMA Workbench can facilitate EHR-driven phenotype definition, execution, and phenotype sharing in heterogeneous clinical research data environments. A phenotype definition that integrates with existing standards-compliant systems, and the use of a formal representation facilitates automation and can decrease potential for human error.

Comparing automated vs. manual data collection for COVID-specific medications from electronic health records.

INTRODUCTION: Data extraction from electronic health record (EHR) systems occurs through manual abstraction, automated extraction, or a combination of both. While each method has its strengths and weaknesses, both are necessary for retrospective observational research as well as sudden clinical events, like the COVID-19 pandemic. Assessing the strengths, weaknesses, and potentials of these methods is important to continue to understand optimal approaches to extracting clinical data. We set out to assess automated and manual techniques for collecting medication use data in patients with COVID-19 to inform future observational studies that extract data from the electronic health record (EHR). MATERIALS AND METHODS: For 4,123 COVID-positive patients hospitalized and/or seen in the emergency department at an academic medical center between 03/03/2020 and 05/15/2020, we compared medication use data of 25 medications or drug classes collected through manual abstraction and automated extraction from the EHR. Quantitatively, we assessed concordance using Cohen's kappa to measure interrater reliability, and qualitatively, we audited observed discrepancies to determine causes of inconsistencies. RESULTS: For the 16 inpatient medications, 11 (69%) demonstrated moderate or better agreement; 7 of those demonstrated strong or almost perfect agreement. For 9 outpatient medications, 3 (33%) demonstrated moderate agreement, but none achieved strong or almost perfect agreement. We audited 12% of all discrepancies (716/5,790) and, in those audited, observed three principal categories of error: human error in manual abstraction (26%), errors in the extract-transform-load (ETL) or mapping of the automated extraction (41%), and abstraction-query mismatch (33%). CONCLUSION: Our findings suggest many inpatient medications can be collected reliably through automated extraction, especially when abstraction instructions are designed with data architecture in mind. We discuss quality issues, concerns, and improvements for institutions to consider when crafting an approach. During crises, institutions must decide how to allocate limited resources. We show that automated extraction of medications is feasible and make recommendations on how to improve future iterations.

Using weak supervision and deep learning to classify clinical notes for identification of current suicidal ideation.

Mental health concerns, such as suicidal thoughts, are frequently documented by providers in clinical notes, as opposed to structured coded data. In this study, we evaluated weakly supervised methods for detecting "current" suicidal ideation from unstructured clinical notes in electronic health record (EHR) systems. Weakly supervised machine learning methods leverage imperfect labels for training, alleviating the burden of creating a large manually annotated dataset. After identifying a cohort of 600 patients at risk for suicidal ideation, we used a rule-based natural language processing approach (NLP) approach to label the training and validation notes (n = 17,978). Using this large corpus of clinical notes, we trained several statistical machine learning models-logistic classifier, support vector machines (SVM), Naive Bayes classifier-and one deep learning model, namely a text classification convolutional neural network (CNN), to be evaluated on a manually-reviewed test set (n = 837). The CNN model outperformed all other methods, achieving an overall accuracy of 94% and a F1-score of 0.82 on documents with "current" suicidal ideation. This algorithm correctly identified an additional 42 encounters and 9 patients indicative of suicidal ideation but missing a structured diagnosis code. When applied to a random subset of 5,000 clinical notes, the algorithm classified 0.46% (n = 23) for "current" suicidal ideation, of which 87% were truly indicative via manual review. Implementation of this approach for large-scale document screening may play an important role in point-of-care clinical information systems for targeted suicide prevention interventions and improve research on the pathways from ideation to attempt.

Automated Extraction of Tumor Staging and Diagnosis Information From Surgical Pathology Reports.

PURPOSE: Typically stored as unstructured notes, surgical pathology reports contain data elements valuable to cancer research that require labor-intensive manual extraction. Although studies have described natural language processing (NLP) of surgical pathology reports to automate information extraction, efforts have focused on specific cancer subtypes rather than across multiple oncologic domains. To address this gap, we developed and evaluated an NLP method to extract tumor staging and diagnosis information across multiple cancer subtypes. METHODS: The NLP pipeline was implemented on an open-source framework called Leo. We used a total of 555,681 surgical pathology reports of 329,076 patients to develop the pipeline and evaluated our approach on subsets of reports from patients with breast, prostate, colorectal, and randomly selected cancer subtypes. RESULTS: Averaged across all four cancer subtypes, the NLP pipeline achieved an accuracy of 1.00 for International Classification of Diseases, Tenth Revision codes, 0.89 for T staging, 0.90 for N staging, and 0.97 for M staging. It achieved an F1 score of 1.00 for International Classification of Diseases, Tenth Revision codes, 0.88 for T staging, 0.90 for N staging, and 0.24 for M staging. CONCLUSION: The NLP pipeline was developed to extract tumor staging and diagnosis information across multiple cancer subtypes to support the research enterprise in our institution. Although it was not possible to demonstrate generalizability of our NLP pipeline to other institutions, other institutions may find value in adopting a similar NLP approach-and reusing code available at GitHub-to support the oncology research enterprise with elements extracted from surgical pathology reports.

Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance.

COVID-19 has proven to be a metabolic disease resulting in adverse outcomes in individuals with diabetes or obesity. Patients infected with SARS-CoV-2 and hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality compared to those who do not develop hyperglycemia. Nevertheless, the pathophysiological mechanism(s) of hyperglycemia in COVID-19 remains poorly characterized. Here we show that insulin resistance rather than pancreatic beta cell failure is the prevalent cause of hyperglycemia in COVID-19 patients with ARDS, independent of glucocorticoid treatment. A screen of protein hormones that regulate glucose homeostasis reveals that the insulin sensitizing adipokine adiponectin is reduced in hyperglycemic COVID-19 patients. Hamsters infected with SARS-CoV-2 also have diminished expression of adiponectin. Together these data suggest that adipose tissue dysfunction may be a driver of insulin resistance and adverse outcomes in acute COVID-19.

Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2.

Individuals infected with SARS-CoV-2 who also display hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality. Nevertheless, the pathophysiological mechanism of hyperglycemia in COVID-19 remains poorly characterized. Here, we show that hyperglycemia is similarly prevalent among patients with ARDS independent of COVID-19 status. Yet among patients with ARDS and COVID-19, insulin resistance is the prevalent cause of hyperglycemia, independent of glucocorticoid treatment, which is unlike patients with ARDS but without COVID-19, where pancreatic beta cell failure predominates. A screen of glucoregulatory hormones revealed lower levels of adiponectin in patients with COVID-19. Hamsters infected with SARS-CoV-2 demonstrated a strong antiviral gene expression program in the adipose tissue and diminished expression of adiponectin. Moreover, we show that SARS-CoV-2 can infect adipocytes. Together these data suggest that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin-angiotensin-aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.

A Method to Improve Availability and Quality of Patient Race Data in an Electronic Health Record System.

BACKGROUND: Although federal regulations mandate documentation of structured race data according to Office of Management and Budget (OMB) categories in electronic health record (EHR) systems, many institutions have reported gaps in EHR race data that hinder secondary use for population-level research focused on underserved populations. When evaluating race data available for research purposes, we found our institution's enterprise EHR contained structured race data for only 51% (1.6 million) of patients. OBJECTIVES: We seek to improve the availability and quality of structured race data available to researchers by integrating values from multiple local sources. METHODS: To address the deficiency in race data availability, we implemented a method to supplement OMB race values from four local sources-inpatient EHR, inpatient billing, natural language processing, and coded clinical observations. We evaluated this method by measuring race data availability and data quality with respect to completeness, concordance, and plausibility. RESULTS: The supplementation method improved race data availability in the enterprise EHR up to 10% for some minority groups and 4% overall. We identified structured OMB race values for more than 142,000 patients, nearly a third of whom were from racial minority groups. Our data quality evaluation indicated that the supplemented race values improved completeness in the enterprise EHR, originated from sources in agreement with the enterprise EHR, and were unbiased to the enterprise EHR. CONCLUSION: Implementation of this method can successfully increase OMB race data availability, potentially enhancing accrual of patients from underserved populations to research studies.

Mapping Local Biospecimen Records to the OMOP Common Data Model.

Research to support precision medicine for leukemia patients requires integration of biospecimen and clinical data. The Observational Medical Outcomes Partnership common data model (OMOP CDM) and its Specimen table presents a potential solution. Although researchers have described progress and challenges in mapping electronic health record (EHR) data to populate the OMOP CDM, to our knowledge no studies have described populating the OMOP CDM with biospecimen data. Using biobank data from our institution, we mapped 26% of biospecimen records to the OMOP Specimen table. Records failed mapping due to local codes for time point that were incompatible with the OMOP reference terminology. We recommend expanding allowable codes to encompass research data, adding foreign keys to leverage additional OMOP tables with data from other sources or to store additional specimen details, and considering a new table to represent processed samples and inventory.

Characterizing Basic and Complex Usage of i2b2 at an Academic Medical Center.

Developed to enable basic queries for cohort discovery, i2b2 has evolved to support complex queries. Little is known whether query sophistication - and the informatics resources required to support it - addresses researcher needs. In three years at our institution, 609 researchers ran 6,662 queries and requested re-identification of 80 patient cohorts to support specific studies. After characterizing all queries as "basic" or "complex" with respect to use of sophisticated query features, we found that the majority of all queries, and the majority of queries resulting in a request for cohort re-identification, did not use complex i2b2 features. Data domains that required extensive effort to implement saw relatively little use compared to common domains (e.g., diagnoses). These findings suggest that efforts to ensure the performance of basic queries using common data domains may better serve the needs of the research community than efforts to integrate novel domains or introduce complex new features.

Toward cross-platform electronic health record-driven phenotyping using Clinical Quality Language.

INTRODUCTION: Electronic health record (EHR)-driven phenotyping is a critical first step in generating biomedical knowledge from EHR data. Despite recent progress, current phenotyping approaches are manual, time-consuming, error-prone, and platform-specific. This results in duplication of effort and highly variable results across systems and institutions, and is not scalable or portable. In this work, we investigate how the nascent Clinical Quality Language (CQL) can address these issues and enable high-throughput, cross-platform phenotyping. METHODS: We selected a clinically validated heart failure (HF) phenotype definition and translated it into CQL, then developed a CQL execution engine to integrate with the Observational Health Data Sciences and Informatics (OHDSI) platform. We executed the phenotype definition at two large academic medical centers, Northwestern Medicine and Weill Cornell Medicine, and conducted results verification (n = 100) to determine precision and recall. We additionally executed the same phenotype definition against two different data platforms, OHDSI and Fast Healthcare Interoperability Resources (FHIR), using the same underlying dataset and compared the results. RESULTS: CQL is expressive enough to represent the HF phenotype definition, including Boolean and aggregate operators, and temporal relationships between data elements. The language design also enabled the implementation of a custom execution engine with relative ease, and results verification at both sites revealed that precision and recall were both 100%. Cross-platform execution resulted in identical patient cohorts generated by both data platforms. CONCLUSIONS: CQL supports the representation of arbitrarily complex phenotype definitions, and our execution engine implementation demonstrated cross-platform execution against two widely used clinical data platforms. The language thus has the potential to help address current limitations with portability in EHR-driven phenotyping and scale in learning health systems.

A Method for Integrating Healthcare Provider Organization and Research Sponsor Systems and Workflows to Support Large-Scale Studies.

Healthcare provider organizations (HPOs) increasingly participate in large-scale research efforts sponsored by external organizations that require use of consent management systems that may not integrate seamlessly with local workflows. The resulting inefficiency can hinder the ability of HPOs to participate in studies. To overcome this challenge, we developed a method using REDCap, a widely adopted electronic data capture system, and novel middleware that can potentially generalize to other settings. In this paper, we describe the method, illustrate its use to support the NIHAll of Us Research Program and PCORI ADAPTABLE studies at our HPO, and encourage other HPOs to test replicability of the method to facilitate similar research efforts. Code is available on GitHub at https://github.com/wcmc-research-informatics/.