Natural language processing to identify lupus nephritis phenotype in electronic health records.

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare autoimmune disorder characterized by an unpredictable course of flares and remission with diverse manifestations. Lupus nephritis, one of the major disease manifestations of SLE for organ damage and mortality, is a key component of lupus classification criteria. Accurately identifying lupus nephritis in electronic health records (EHRs) would therefore benefit large cohort observational studies and clinical trials where characterization of the patient population is critical for recruitment, study design, and analysis. Lupus nephritis can be recognized through procedure codes and structured data, such as laboratory tests. However, other critical information documenting lupus nephritis, such as histologic reports from kidney biopsies and prior medical history narratives, require sophisticated text processing to mine information from pathology reports and clinical notes. In this study, we developed algorithms to identify lupus nephritis with and without natural language processing (NLP) using EHR data from the Northwestern Medicine Enterprise Data Warehouse (NMEDW). METHODS: We developed five algorithms: a rule-based algorithm using only structured data (baseline algorithm) and four algorithms using different NLP models. The first NLP model applied simple regular expression for keywords search combined with structured data. The other three NLP models were based on regularized logistic regression and used different sets of features including positive mention of concept unique identifiers (CUIs), number of appearances of CUIs, and a mixture of three components (i.e. a curated list of CUIs, regular expression concepts, structured data) respectively. The baseline algorithm and the best performing NLP algorithm were externally validated on a dataset from Vanderbilt University Medical Center (VUMC). RESULTS: Our best performing NLP model incorporated features from both structured data, regular expression concepts, and mapped concept unique identifiers (CUIs) and showed improved F measure in both the NMEDW (0.41 vs 0.79) and VUMC (0.52 vs 0.93) datasets compared to the baseline lupus nephritis algorithm. CONCLUSION: Our NLP MetaMap mixed model improved the F-measure greatly compared to the structured data only algorithm in both internal and external validation datasets. The NLP algorithms can serve as powerful tools to accurately identify lupus nephritis phenotype in EHR for clinical research and better targeted therapies.

Data-driven automated classification algorithms for acute health conditions: applying PheNorm to COVID-19 disease.

OBJECTIVES: Automated phenotyping algorithms can reduce development time and operator dependence compared to manually developed algorithms. One such approach, PheNorm, has performed well for identifying chronic health conditions, but its performance for acute conditions is largely unknown. Herein, we implement and evaluate PheNorm applied to symptomatic COVID-19 disease to investigate its potential feasibility for rapid phenotyping of acute health conditions. MATERIALS AND METHODS: PheNorm is a general-purpose automated approach to creating computable phenotype algorithms based on natural language processing, machine learning, and (low cost) silver-standard training labels. We applied PheNorm to cohorts of potential COVID-19 patients from 2 institutions and used gold-standard manual chart review data to investigate the impact on performance of alternative feature engineering options and implementing externally trained models without local retraining. RESULTS: Models at each institution achieved AUC, sensitivity, and positive predictive value of 0.853, 0.879, 0.851 and 0.804, 0.976, and 0.885, respectively, at quantiles of model-predicted risk that maximize F1. We report performance metrics for all combinations of silver labels, feature engineering options, and models trained internally versus externally. DISCUSSION: Phenotyping algorithms developed using PheNorm performed well at both institutions. Performance varied with different silver-standard labels and feature engineering options. Models developed locally at one site also worked well when implemented externally at the other site. CONCLUSION: PheNorm models successfully identified an acute health condition, symptomatic COVID-19. The simplicity of the PheNorm approach allows it to be applied at multiple study sites with substantially reduced overhead compared to traditional approaches.

A Proposed Approach to Allegations of Sexual Boundary Violation in Health Care.

BACKGROUND: Sexual boundary violations in the health care setting cause harm for victims, threaten an organization's culture, and create extraordinary organizational risk. The inherent complexities of health care organizations present unique challenges for the initial triage and response to reports of alleged violations. METHODS: A group of experts with experience in law, leadership, human resources, medicine, and health care operations identified processes for organizations to triage and implement an early response to allegations of sexual boundary violations. The group reviewed a series of 100 reports of alleged violations described by patients and coworkers from a 200-hospital professional accountability collaborative to identify the elements of an ideal initial triage and management approach. RESULTS: The group identified three domains to guide early triage and response to reports of boundary violations: (1) severity and acuity of the alleged violation; (2) roles and relationship(s) of the complainant, respondent, and other affected individuals; and (3) contextual information such as prior activity or other mitigating factors. The group identified leadership engagement; coordinated responses; clear articulation of values, policies, and procedures; aligned data reporting; thoughtful reviews; and securing appropriate resources as essential elements of an organization's response. CONCLUSION: A structured systematic approach to classify and respond to allegations of sexual boundary violation is described. The initial response should be guided by assessment of the severity and timing of the reported behavior, followed by assessment of roles and responsibilities with involvement of all relevant stakeholders. Contextual issues and special circumstances of relevance should be identified and incorporated into the response. Systems to identify, store, and retrieve behavior of concern should be improved and integrated.

Use of Electronic Health Record Data for Drug Safety Signal Identification: A Scoping Review.

INTRODUCTION: Pharmacovigilance programs protect patient health and safety by identifying adverse event signals through postmarketing surveillance of claims data and spontaneous reports. Electronic health records (EHRs) provide new opportunities to address limitations of traditional approaches and promote discovery-oriented pharmacovigilance. METHODS: To evaluate the current state of EHR-based medication safety signal identification, we conducted a scoping literature review of studies aimed at identifying safety signals from routinely collected patient-level EHR data. We extracted information on study design, EHR data elements utilized, analytic methods employed, drugs and outcomes evaluated, and key statistical and data analysis choices. RESULTS: We identified 81 eligible studies. Disproportionality methods were the predominant analytic approach, followed by data mining and regression. Variability in study design makes direct comparisons difficult. Studies varied widely in terms of data, confounding adjustment, and statistical considerations. CONCLUSION: Despite broad interest in utilizing EHRs for safety signal identification, current efforts fail to leverage the full breadth and depth of available data or to rigorously control for confounding. The development of best practices and application of common data models would promote the expansion of EHR-based pharmacovigilance.

Antibiotic clinical decision support for pneumonia in the ED: A randomized trial.

BACKGROUND: Electronic health record-based clinical decision support (CDS) is a promising antibiotic stewardship strategy. Few studies have evaluated the effectiveness of antibiotic CDS in the pediatric emergency department (ED). OBJECTIVE: To compare the effectiveness of antibiotic CDS vs. usual care for promoting guideline-concordant antibiotic prescribing for pneumonia in the pediatric ED. DESIGN: Pragmatic randomized clinical trial. SETTING AND PARTICIPANTS: Encounters for children (6 months-18 years) with pneumonia presenting to two tertiary care children s hospital EDs in the United States. INTERVENTION: CDS or usual care was randomly assigned during 4-week periods within each site. The CDS intervention provided antibiotic recommendations tailored to each encounter and in accordance with national guidelines. MAIN OUTCOME AND MEASURES: The primary outcome was exclusive guideline-concordant antibiotic prescribing within the first 24 h of care. Safety outcomes included time to first antibiotic order, encounter length of stay, delayed intensive care, and 3- and 7-day revisits. RESULTS: 1027 encounters were included, encompassing 478 randomized to usual care and 549 to CDS. Exclusive guideline-concordant prescribing did not differ at 24 h (CDS, 51.7% vs. usual care, 53.3%; odds ratio [OR] 0.94 [95% confidence interval [CI]: 0.73, 1.20]). In pre-specified stratified analyses, CDS was associated with guideline-concordant prescribing among encounters discharged from the ED (74.9% vs. 66.0%; OR 1.53 [95% CI: 1.01, 2.33]), but not among hospitalized encounters. Mean time to first antibiotic was shorter in the CDS group (3.0 vs 3.4 h; p = .024). There were no differences in safety outcomes. CONCLUSIONS: Effectiveness of ED-based antibiotic CDS was greatest among those discharged from the ED. Longitudinal interventions designed to target both ED and inpatient clinicians and to address common implementation challenges may enhance the effectiveness of CDS as a stewardship tool.

Evaluation of the portability of computable phenotypes with natural language processing in the eMERGE network.

The electronic Medical Records and Genomics (eMERGE) Network assessed the feasibility of deploying portable phenotype rule-based algorithms with natural language processing (NLP) components added to improve performance of existing algorithms using electronic health records (EHRs). Based on scientific merit and predicted difficulty, eMERGE selected six existing phenotypes to enhance with NLP. We assessed performance, portability, and ease of use. We summarized lessons learned by: (1) challenges; (2) best practices to address challenges based on existing evidence and/or eMERGE experience; and (3) opportunities for future research. Adding NLP resulted in improved, or the same, precision and/or recall for all but one algorithm. Portability, phenotyping workflow/process, and technology were major themes. With NLP, development and validation took longer. Besides portability of NLP technology and algorithm replicability, factors to ensure success include privacy protection, technical infrastructure setup, intellectual property agreement, and efficient communication. Workflow improvements can improve communication and reduce implementation time. NLP performance varied mainly due to clinical document heterogeneity; therefore, we suggest using semi-structured notes, comprehensive documentation, and customization options. NLP portability is possible with improved phenotype algorithm performance, but careful planning and architecture of the algorithms is essential to support local customizations.

Do electronic health record systems "dumb down" clinicians?

A panel sponsored by the American College of Medical Informatics (ACMI) at the 2021 AMIA Symposium addressed the provocative question: "Are Electronic Health Records dumbing down clinicians?" After reviewing electronic health record (EHR) development and evolution, the panel discussed how EHR use can impair care delivery. Both suboptimal functionality during EHR use and longer-term effects outside of EHR use can reduce clinicians' efficiencies, reasoning abilities, and knowledge. Panel members explored potential solutions to problems discussed. Progress will require significant engagement from clinician-users, educators, health systems, commercial vendors, regulators, and policy makers. Future EHR systems must become more user-focused and scalable and enable providers to work smarter to deliver improved care.

Development and Validation of Inpatient Hypoglycemia Models Centered Around the Insulin Ordering Process.

BACKGROUND: The insulin ordering process is an opportunity to provide clinicians with hypoglycemia risk predictions, but few hypoglycemia models centered around the insulin ordering process exist. METHODS: We used data on adult patients, admitted in 2019 to non-ICU floors of a large teaching hospital, who had orders for subcutaneous insulin. Our outcome was hypoglycemia, defined as a blood glucose (BG) <70 mg/dL within 24 hours after ordering insulin. We trained and evaluated models to predict hypoglycemia at the time of placing an insulin order, using logistic regression, random forest, and extreme gradient boosting (XGBoost). We compared performance using area under the receiver operating characteristic curve (AUCs) and precision-recall curves. We determined recall at our goal precision of 0.30. RESULTS: Of 21 052 included insulin orders, 1839 (9%) were followed by a hypoglycemic event within 24 hours. Logistic regression, random forest, and XGBoost models had AUCs of 0.81, 0.80, and 0.79, and recall of 0.44, 0.49, and 0.32, respectively. The most significant predictor was the lowest BG value in the 24 hours preceding the order. Predictors related to the insulin order being placed at the time of the prediction were useful to the model but less important than the patient's history of BG values over time. CONCLUSIONS: Hypoglycemia within the next 24 hours can be predicted at the time an insulin order is placed, providing an opportunity to integrate decision support into the medication ordering process to make insulin therapy safer.

An updated, computable MEDication-Indication resource for biomedical research.

The MEDication-Indication (MEDI) knowledgebase has been utilized in research with electronic health records (EHRs) since its publication in 2013. To account for new drugs and terminology updates, we rebuilt MEDI to overhaul the knowledgebase for modern EHRs. Indications for prescribable medications were extracted using natural language processing and ontology relationships from six publicly available resources: RxNorm, Side Effect Resource 4.1, Mayo Clinic, WebMD, MedlinePlus, and Wikipedia. We compared the estimated precision and recall between the previous MEDI (MEDI-1) and the updated version (MEDI-2) with manual review. MEDI-2 contains 3031 medications and 186,064 indications. The MEDI-2 high precision subset (HPS) includes indications found within RxNorm or at least three other resources. MEDI-2 and MEDI-2 HPS contain 13% more medications and over triple the indications compared to MEDI-1 and MEDI-1 HPS, respectively. Manual review showed MEDI-2 achieves the same precision (0.60) with better recall (0.89 vs. 0.79) compared to MEDI-1. Likewise, MEDI-2 HPS had the same precision (0.92) and improved recall (0.65 vs. 0.55) than MEDI-1 HPS. The combination of MEDI-1 and MEDI-2 achieved a recall of 0.95. In updating MEDI, we present a more comprehensive medication-indication knowledgebase that can continue to facilitate applications and research with EHRs.

ConceptWAS: A high-throughput method for early identification of COVID-19 presenting symptoms and characteristics from clinical notes.

OBJECTIVE: Identifying symptoms and characteristics highly specific to coronavirus disease 2019 (COVID-19) would improve the clinical and public health response to this pandemic challenge. Here, we describe a high-throughput approach - Concept-Wide Association Study (ConceptWAS) - that systematically scans a disease's clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic. METHODS: We created a natural language processing pipeline to extract concepts from clinical notes in a local ER corresponding to the PCR testing date for patients who had a COVID-19 test and evaluated these concepts as predictors for developing COVID-19. We identified predictors from Firth's logistic regression adjusted by age, gender, and race. We also performed ConceptWAS using cumulative data every two weeks to identify the timeline for recognition of early COVID-19-specific symptoms. RESULTS: We processed 87,753 notes from 19,692 patients subjected to COVID-19 PCR testing between March 8, 2020, and May 27, 2020 (1,483 COVID-19-positive). We found 68 concepts significantly associated with a positive COVID-19 test. We identified symptoms associated with increasing risk of COVID-19, including "anosmia" (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 3.21-7.50), "fever" (OR = 1.43, 95% CI = 1.28-1.59), "cough with fever" (OR = 2.29, 95% CI = 1.75-2.96), and "ageusia" (OR = 5.18, 95% CI = 3.02-8.58). Using ConceptWAS, we were able to detect loss of smell and loss of taste three weeks prior to their inclusion as symptoms of the disease by the Centers for Disease Control and Prevention (CDC). CONCLUSION: ConceptWAS, a high-throughput approach for exploring specific symptoms and characteristics of a disease like COVID-19, offers a promise for enabling EHR-powered early disease manifestations identification.

Real-time clinical note monitoring to detect conditions for rapid follow-up: A case study of clinical trial enrollment in drug-induced torsades de pointes and Stevens-Johnson syndrome.

Identifying acute events as they occur is challenging in large hospital systems. Here, we describe an automated method to detect 2 rare adverse drug events (ADEs), drug-induced torsades de pointes and Stevens-Johnson syndrome and toxic epidermal necrolysis, in near real time for participant recruitment into prospective clinical studies. A text processing system searched clinical notes from the electronic health record (EHR) for relevant keywords and alerted study personnel via email of potential patients for chart review or in-person evaluation. Between 2016 and 2018, the automated recruitment system resulted in capture of 138 true cases of drug-induced rare events, improving recall from 43% to 93%. Our focused electronic alert system maintained 2-year enrollment, including across an EHR migration from a bespoke system to Epic. Real-time monitoring of EHR notes may accelerate research for certain conditions less amenable to conventional study recruitment paradigms.

ConceptWAS: a high-throughput method for early identification of COVID-19 presenting symptoms.

Objective: Identifying symptoms highly specific to COVID-19 would improve the clinical and public health response to infectious outbreaks. Here, we describe a high-throughput approach - Concept-Wide Association Study (ConceptWAS) that systematically scans a disease's clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic. Methods: Using the Vanderbilt University Medical Center (VUMC) EHR, we parsed clinical notes through a natural language processing pipeline to extract clinical concepts. We examined the difference in concepts derived from the notes of COVID-19-positive and COVID-19-negative patients on the PCR testing date. We performed ConceptWAS using the cumulative data every two weeks for early identifying specific COVID-19 symptoms. Results: We processed 87,753 notes 19,692 patients (1,483 COVID-19-positive) subjected to COVID-19 PCR testing between March 8, 2020, and May 27, 2020. We found 68 clinical concepts significantly associated with COVID-19. We identified symptoms associated with increasing risk of COVID-19, including "absent sense of smell" (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 3.21-7.50), "fever" (OR = 1.43, 95% CI = 1.28-1.59), "with cough fever" (OR = 2.29, 95% CI = 1.75-2.96), and "ageusia" (OR = 5.18, 95% CI = 3.02-8.58). Using ConceptWAS, we were able to detect loss sense of smell or taste three weeks prior to their inclusion as symptoms of the disease by the Centers for Disease Control and Prevention (CDC). Conclusion: ConceptWAS is a high-throughput approach for exploring specific symptoms of a disease like COVID-19, with a promise for enabling EHR-powered early disease manifestations identification.

Natural Language Processing and Machine Learning to Enable Clinical Decision Support for Treatment of Pediatric Pneumonia.

Pneumonia is the most frequent cause of infectious disease-related deaths in children worldwide. Clinical decision support (CDS) applications can guide appropriate treatment, but the system must first recognize the appropriate diagnosis. To enable CDS for pediatric pneumonia, we developed an algorithm integrating natural language processing (NLP) and random forest classifiers to identify potential pediatric pneumonia from radiology reports. We deployed the algorithm in the EHR of a large children's hospital using real-time NLP. We describe the development and deployment of the algorithm, and evaluate our approach using 9-months of data gathered while the system was in use. Our model, trained on individual radiology reports, had an AUC of 0.954. The intervention, evaluated on patient encounters that could include multiple radiology reports, achieved a sensitivity, specificity, and positive predictive value of0.899, 0.949, and 0.781, respectively.

Evaluation of a Novel System to Enhance Clinicians' Recognition of Preadmission Adverse Drug Reactions.

BACKGROUND: Often unrecognized by providers, adverse drug reactions (ADRs) diminish patients' quality of life, cause preventable admissions and emergency department visits, and increase health care costs. OBJECTIVE: This article evaluates whether an automated system, the Adverse Drug Effect Recognizer (ADER), could assist clinicians in detecting and addressing inpatients' ongoing preadmission ADRs. METHODS: ADER uses natural language processing to extract patients' medications, findings, and past diagnoses from admission notes. It compares excerpted information to a database of known medication adverse effects and promptly warns clinicians about potential ongoing ADRs and potential confounders via alerts placed in patients' electronic health records (EHRs). A 3-month intervention trial evaluated ADER's impact on antihypertensive medication ordering behaviors. At the time of patient admission, ADER warned providers on the Internal Medicine wards of Vanderbilt University Hospital about potential ongoing preadmission antihypertensive medication ADRs. A retrospective control group, comprised similar physicians from a period prior to the intervention, received no alerts. The evaluation compared ordering behaviors for each group to determine if preadmission medications changed during hospitalization or at discharge. The study also analyzed intervention group participants' survey responses and user comments. RESULTS: ADER identified potential preadmission ADRs for 30% of both groups. Compared with controls, intervention providers more often withheld or discontinued suspected ADR-causing medications during the inpatient stay (p < 0.001). Intervention providers who responded to alert-related surveys held or discontinued suspected ADR-causing medications more often at discharge (p < 0.001). CONCLUSION: Results indicate that ADER helped physicians recognize ADRs and reduced ordering of suspected ADR-causing medications. In hospitals using EHRs, ADER-like systems could improve clinicians' recognition and elimination of ongoing ADRs.

Mechanistic interrogation of the asymmetric lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine.

A fundamental mechanistic study of the s-BuLi/chiral diamine-mediated lithiation-trapping of N-thiopivaloyl azetidine and pyrrolidine is reported. We show that lithiated thiopivalamides are configurationally unstable at -78 °C. Reaction then proceeds via a dynamic resolution of diastereomeric lithiated intermediates and this accounts for the variable sense and degree of asymmetric induction observed compared to N-Boc heterocycles.

Reducing patient re-identification risk for laboratory results within research datasets.

OBJECTIVE: To try to lower patient re-identification risks for biomedical research databases containing laboratory test results while also minimizing changes in clinical data interpretation. MATERIALS AND METHODS: In our threat model, an attacker obtains 5-7 laboratory results from one patient and uses them as a search key to discover the corresponding record in a de-identified biomedical research database. To test our models, the existing Vanderbilt TIME database of 8.5 million Safe Harbor de-identified laboratory results from 61 280 patients was used. The uniqueness of unaltered laboratory results in the dataset was examined, and then two data perturbation models were applied-simple random offsets and an expert-derived clinical meaning-preserving model. A rank-based re-identification algorithm to mimic an attack was used. The re-identification risk and the retention of clinical meaning for each model's perturbed laboratory results were assessed. RESULTS: Differences in re-identification rates between the algorithms were small despite substantial divergence in altered clinical meaning. The expert algorithm maintained the clinical meaning of laboratory results better (affecting up to 4% of test results) than simple perturbation (affecting up to 26%). DISCUSSION AND CONCLUSION: With growing impetus for sharing clinical data for research, and in view of healthcare-related federal privacy regulation, methods to mitigate risks of re-identification are important. A practical, expert-derived perturbation algorithm that demonstrated potential utility was developed. Similar approaches might enable administrators to select data protection scheme parameters that meet their preferences in the trade-off between the protection of privacy and the retention of clinical meaning of shared data.

A new weakly coordinating aluminate anion incorporating a chelating perfluoro-bis-anilido ligand.

The synthesis of the fully fluorinated bis-anilido ligand N,N'-bis-pentafluorophenyl-3,4,5,6-tetrafluorophenylene-1,2-diamine, 1 is described. Reaction of one or two equivalents of 1 with AlMe(3) gives aluminium compounds incorporating one or two ligands, the latter being the protonated form of a new weakly coordinating anion (WCA), 3-H. Alternatively, reaction of 1 with LiAlH(4) yields the lithium salt of this anion, 3-Li, which may be employed as a reagent for preparing the trityl and N,N-dimethylanilinium salts of the aluminate anion. All ion pairs are fully characterized and the use of 3-Ph(3)C to generate titanium-based alkyl cations is also described.

Feasibility of mobile phone-based management of chronic illness.

According to the CDC, chronic conditions such as heart disease, cancer, and diabetes cause 75% of healthcare spending in the United States and contribute to nearly seven in ten American deaths. However, despite the prevalence and high-cost of chronic disease, they are also among the most preventable of health problems1. How can we use technology to improve self-care, reduce costs, and lessen the burden on medical professionals? Devices to help manage chronic illness have been marketed for years, but are these specialized devices really necessary? In this paper, the authors identify the aspects of the major chronic illnesses that most need to be controlled and monitored in the US today and explore the feasibility of using current mobile phone technology to improve the management of chronic illness. Here we show that even the average mobile phone is capable of improving the management of all relevant health features in some way.