Pathak, Jyotishman

Abstract Objectives Social support (SS) and social isolation (SI) are social determinants of health (SDOH) associated with psychiatric outcomes. In electronic health records (EHRs), individual-level SS/SI is typically documented in narrative clinical notes rather than as structured coded data. Natural language processing (NLP) algorithms can automate the otherwise labor-intensive process of extraction of such information. Materials and Methods Psychiatric encounter notes from Mount Sinai Health System (MSHS, n = 300) and Weill Cornell Medicine (WCM, n = 225) were annotated to create a gold-standard corpus. A rule-based system (RBS) involving lexicons and a large language model (LLM) using FLAN-T5-XL were developed to identify mentions of SS and SI and their subcategories (eg, social network, instrumental support, and loneliness). Results For extracting SS/SI, the RBS obtained higher macroaveraged F1-scores than the LLM at both MSHS (0.89 versus 0.65) and WCM (0.85 versus 0.82). For extracting the subcategories, the RBS also outperformed the LLM at both MSHS (0.90 versus 0.62) and WCM (0.82 versus 0.81). Discussion and Conclusion Unexpectedly, the RBS outperformed the LLMs across all metrics. An intensive review demonstrates that this finding is due to the divergent approach taken by the RBS and LLM. The RBS was designed and refined to follow the same specific rules as the gold-standard annotations. Conversely, the LLM was more inclusive with categorization and conformed to common English-language understanding. Both approaches offer advantages, although additional replication studies are warranted.

Abstract Objective The purpose of this study was to conduct a scoping review of publications that explored blockchain technology in the context of interoperability and challenges of electronic health record (EHR) implementations. We synthesize the literature regarding standards and security, specifically regulation, regulatory operability, and conformance to standards. We review open practitioner questions that were not addressed in the studies as directions for further research. Materials and Methods We conducted a literature search in the OVID databases (Medline and Embase) on terms blockchain, implementation, interoperability, EHRs, security, and standards. The search resulted in 152 nonduplicate, peer-reviewed manuscripts, of which 15 were relevant to our objective and included for synthesis. Results Based on the search results, we analyzed the adoption of blockchain technology in the healthcare systems and challenges to EHR implementation of blockchain. From the synthesized research, we categorized and reported compelling factors of blockchain for EHR integration using current knowledge on blockchain research standardization and architectural challenges. Discussion Our research showed promise in implementing blockchain technology associated with EHRs, especially with Health Information Exchanges. The studies relevant for both EHR (n = 5) and blockchain (n = 10) reported compelling factors and limitations of the architecture. Security (n = 4) and interoperability (n = 4) features were reported as compelling requirements with lingering challenges. Standardization literature (n = 3) reported implementation challenges. Conclusion This study shows promise in implementing blockchain technology within EHR systems. The adoption is increasing; however, multiple implementation challenges remain from architectural perspectives (eg, scalability and performance), to security challenges (eg, legal requirements), and standard perspectives including patient-matching problems.

Abstract 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.

Abstract Objective Social determinants of health (SDoH) are nonclinical dispositions that impact patient health risks and clinical outcomes. Leveraging SDoH in clinical decision-making can potentially improve diagnosis, treatment planning, and patient outcomes. Despite increased interest in capturing SDoH in electronic health records (EHRs), such information is typically locked in unstructured clinical notes. Natural language processing (NLP) is the key technology to extract SDoH information from clinical text and expand its utility in patient care and research. This article presents a systematic review of the state-of-the-art NLP approaches and tools that focus on identifying and extracting SDoH data from unstructured clinical text in EHRs. Materials and Methods A broad literature search was conducted in February 2021 using 3 scholarly databases (ACL Anthology, PubMed, and Scopus) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 6402 publications were initially identified, and after applying the study inclusion criteria, 82 publications were selected for the final review. Results Smoking status (n = 27), substance use (n = 21), homelessness (n = 20), and alcohol use (n = 15) are the most frequently studied SDoH categories. Homelessness (n = 7) and other less-studied SDoH (eg, education, financial problems, social isolation and support, family problems) are mostly identified using rule-based approaches. In contrast, machine learning approaches are popular for identifying smoking status (n = 13), substance use (n = 9), and alcohol use (n = 9). Conclusion NLP offers significant potential to extract SDoH data from narrative clinical notes, which in turn can aid in the development of screening tools, risk prediction models, and clinical decision support systems.

Introduction: Phenome-wide association studies (PheWAS) using electronic medical record (EMR)-linked biobanks have been used not only to identify and replicate known associations of genetic variants with disease phenotypes but have also resulted in the discovery of potentially novel genotype-phenotype relationships. The natriuretic peptide (NP) system plays an important role in a broad range of disease processes including cardiovascular and inflammatory diseases. We hypothesized that performing a PheWAS using previously known functional genetic variants of the NP system may result in novel disease associations that could provide mechanistic insights in an unbiased manner. Methods: We scanned for associations between 9 single-nucleotide polymorphisms (SNPs) in the NP system and 27 EMR-derived chronic disease phenotypes in 3,025 individuals participating in a case-control study of peripheral arterial disease. The EMR phenotypes were identified using two or more ICD-9-CM diagnosis codes based on the AHRQ Clinical Classifications Software (CCS). The relationship of SNPs and phenotypes were modeled using logistic regression adjusting for gender. Results: We identified rs5065, a SNP located in the stop codon of exon 3 of the NPPA gene, to be the strongest associated SNP with rheumatoid arthritis (RA) (OR=0.78, p=0.0008, q-value=0.11). The SNP leads to the extension of atrial natriuretic peptide (ANP) by 2 additional arginines at the C terminus. Cardiovascular disease is known to be the leading cause of death in patients with RA and ANP plays an important immunomodulatory role by inhibiting inducible nitric oxide synthase, reducing TNF-α production and attenuating prostaglandin E2 production in macrophages. Circulating NPs have been used to screen for occult cardiac disease and are associated with mortality in RA. This study demonstrates for the first time the importance of the relationship between genetic variation in the NP system and RA. Conclusions: PheWAS was successfully used as a tool to identify a novel association of functional genetic variation in the NPPA gene with RA. The observation is hypothesis generating and further replication studies are required to determine the role of rs5065 in cardiovascular outcomes of RA.

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.

AbstractIntroductionWe sought to assess longitudinal electronic health records (EHRs) using machine learning (ML) methods to computationally derive probable Alzheimer's Disease (AD) and related dementia subphenotypes.MethodsA retrospective analysis of EHR data from a cohort of 7587 patients seen at a large, multi‐specialty urban academic medical center in New York was conducted. Subphenotypes were derived using hierarchical clustering from 792 probable AD patients (cases) who had received at least one diagnosis of AD using their clinical data. The other 6795 patients, labeled as controls, were matched on age and gender with the cases and randomly selected in the ratio of 9:1. Prediction models with multiple ML algorithms were trained on this cohort using 5‐fold cross‐validation. XGBoost was used to rank the variable importance.ResultsFour subphenotypes were computationally derived. Subphenotype A (n = 273; 28.2%) had more patients with cardiovascular diseases; subphenotype B (n = 221; 27.9%) had more patients with mental health illnesses, such as depression and anxiety; patients in subphenotype C (n = 183; 23.1%) were overall older (mean (SD) age, 79.5 (5.4) years) and had the most comorbidities including diabetes, cardiovascular diseases, and mental health disorders; and subphenotype D (n = 115; 14.5%) included patients who took anti‐dementia drugs and had sensory problems, such as deafness and hearing impairment.The 0‐year prediction model for AD risk achieved an area under the receiver operating curve (AUC) of 0.764 (SD: 0.02); the 6‐month model, 0.751 (SD: 0.02); the 1‐year model, 0.752 (SD: 0.02); the 2‐year model, 0.749 (SD: 0.03); and the 3‐year model, 0.735 (SD: 0.03), respectively. Based on variable importance, the top‐ranked comorbidities included depression, stroke/transient ischemic attack, hypertension, anxiety, mobility impairments, and atrial fibrillation. The top‐ranked medications included anti‐dementia drugs, antipsychotics, antiepileptics, and antidepressants.ConclusionsFour subphenotypes were computationally derived that correlated with cardiovascular diseases and mental health illnesses. ML algorithms based on patient demographics, diagnosis, and treatment demonstrated promising results in predicting the risk of developing AD at different time points across an individual's lifespan.

AbstractObjectiveTo identify depression subphenotypes from Electronic Health Records (EHRs) using machine learning methods, and analyze their characteristics with respect to patient demographics, comorbidities, and medications.Materials and MethodsUsing EHRs from the INSIGHT Clinical Research Network (CRN) database, multiple machine learning (ML) algorithms were applied to analyze 11 275 patients with depression to discern depression subphenotypes with distinct characteristics.ResultsUsing the computational approaches, we derived three depression subphenotypes: Phenotype_A (n = 2791; 31.35%) included patients who were the oldest (mean (SD) age, 72.55 (14.93) years), had the most comorbidities, and took the most medications. The most common comorbidities in this cluster of patients were hyperlipidemia, hypertension, and diabetes. Phenotype_B (mean (SD) age, 68.44 (19.09) years) was the largest cluster (n = 4687; 52.65%), and included patients suffering from moderate loss of body function. Asthma, fibromyalgia, and Chronic Pain and Fatigue (CPF) were common comorbidities in this subphenotype. Phenotype_C (n = 1452; 16.31%) included patients who were younger (mean (SD) age, 63.47 (18.81) years), had the fewest comorbidities, and took fewer medications. Anxiety and tobacco use were common comorbidities in this subphenotype.ConclusionComputationally deriving depression subtypes can provide meaningful insights and improve understanding of depression as a heterogeneous disorder. Further investigation is needed to assess the utility of these derived phenotypes to inform clinical trial design and interpretation in routine patient care.

AbstractIntroductionElectronic 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.MethodsWe 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.ResultsCQL 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.ConclusionsCQL 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.