Disparities Associated With Electronic Behavioral Alerts for Safety and Violence Concerns in the Emergency Department.

STUDY OBJECTIVE: Although electronic behavioral alerts are placed as an alert flag in the electronic health record to notify staff of previous behavioral and/or violent incidents in emergency departments (EDs), they have the potential to reinforce negative perceptions of patients and contribute to bias. We provide characterization of ED electronic behavioral alerts using electronic health record data across a large, regional health care system. METHODS: We conducted a retrospective cross-sectional study of adult patients presenting to 10 adult EDs within a Northeastern United States health care system from 2013 to 2022. Electronic behavioral alerts were manually screened for safety concerns and then categorized by the type of concern. In our patient-level analyses, we included patient data at the time of the first ED visit where an electronic behavioral alert was triggered or, if a patient had no electronic behavioral alerts, the earliest visit in the study period. We performed a mixed-effects regression analysis to identify patient-level risk factors associated with safety-related electronic behavioral alert deployment. RESULTS: Of the 2,932,870 ED visits, 6,775 (0.2%) had associated electronic behavioral alerts across 789 unique patients and 1,364 unique electronic behavioral alerts. Of the encounters with electronic behavioral alerts, 5,945 (88%) were adjudicated as having a safety concern involving 653 patients. In our patient-level analysis, the median age for patients with safety-related electronic behavioral alerts was 44 years (interquartile range 33 to 55 years), 66% were men, and 37% were Black. Visits with safety-related electronic behavioral alerts had higher rates of discontinuance of care (7.8% vs 1.5% with no alert; P<.001) as defined by the patient-directed discharge, left-without-being-seen, or elopement-type dispositions. The most common topics in the electronic behavioral alerts were physical (41%) or verbal (36%) incidents with staff or other patients. In the mixed-effects logistic analysis, Black non-Hispanic patients (vs White non-Hispanic patients: adjusted odds ratio 2.60; 95% confidence interval [CI] 2.13 to 3.17), aged younger than 45 (vs aged 45-64 years: adjusted odds ratio 1.41; 95% CI 1.17 to 1.70), male (vs female: adjusted odds ratio 2.09; 95% CI 1.76 to 2.49), and publicly insured patients (Medicaid: adjusted odds ratio 6.18; 95% CI 4.58 to 8.36; Medicare: adjusted odds ratio 5.63; 95% CI 3.96 to 8.00 vs commercial) were associated with a higher risk of a patient having at least 1 safety-related electronic behavioral alert deployment during the study period. CONCLUSION: In our analysis, younger, Black non-Hispanic, publicly insured, and male patients were at a higher risk of having an ED electronic behavioral alert. Although our study is not designed to reflect causality, electronic behavioral alerts may disproportionately affect care delivery and medical decisions for historically marginalized populations presenting to the ED, contribute to structural racism, and perpetuate systemic inequities.

Development of a Novel Emergency Department Quality Measure to Reduce Very Low-Risk Syncope Hospitalizations.

STUDY OBJECTIVE: Emergency department (ED) evaluations for syncope are common, representing 1.3 million annual US visits and $2 billion in related hospitalizations. Despite evidence supporting risk stratification and outpatient management, variation in syncope hospitalization rates persist. We sought to develop a new quality measure for very low-risk adult ED patients with syncope that could be applied to administrative data. METHODS: We developed this quality measure in 2 phases. First, we used an existing prospective, observational ED patient data set to identify a very low-risk cohort with unexplained syncope using 2 variables: age less than 50 years and no history of heart disease. We then applied this to the 2019 Nationwide Emergency Department Sample (NEDS) to assess its potential effect, assessing for hospital-level factors associated with hospitalization variation. RESULTS: Of the 8,647 adult patients in the prospective cohort, 3,292 (38%) patients fulfilled these 2 criteria: age less than 50 years and no history of heart disease. Of these, 15 (0.46%) suffered serious adverse events within 30 days. In the NEDS, there were an estimated 566,031 patients meeting these 2 criteria, of whom 15,507 (2.7%; 95% confidence interval [CI] 2.48% to 3.00%) were hospitalized. We found substantial variation in the hospitalization rates for this very low-risk cohort, with a median rate of 1.7% (range 0% to 100%; interquartile range 0% to 3.9%). Factors associated with increased hospitalization rates included a yearly ED volume of more than 80,000 (odds ratio [OR] 3.14; 95% CI 2.02 to 4.89) and metropolitan teaching status (OR 1.5; 95% CI 1.24 to 1.81). CONCLUSION: In summary, our novel syncope quality measure can assess variation in low-value hospitalizations for unexplained syncope. The application of this measure could improve the value of syncope care.

Genomes by design.

Next-generation DNA sequencing has revealed the complete genome sequences of numerous organisms, establishing a fundamental and growing understanding of genetic variation and phenotypic diversity. Engineering at the gene, network and whole-genome scale aims to introduce targeted genetic changes both to explore emergent phenotypes and to introduce new functionalities. Expansion of these approaches into massively parallel platforms establishes the ability to generate targeted genome modifications, elucidating causal links between genotype and phenotype, as well as the ability to design and reprogramme organisms. In this Review, we explore techniques and applications in genome engineering, outlining key advances and defining challenges.

Recoded organisms engineered to depend on synthetic amino acids.

Genetically modified organisms (GMOs) are increasingly used in research and industrial systems to produce high-value pharmaceuticals, fuels and chemicals. Genetic isolation and intrinsic biocontainment would provide essential biosafety measures to secure these closed systems and enable safe applications of GMOs in open systems, which include bioremediation and probiotics. Although safeguards have been designed to control cell growth by essential gene regulation, inducible toxin switches and engineered auxotrophies, these approaches are compromised by cross-feeding of essential metabolites, leaked expression of essential genes, or genetic mutations. Here we describe the construction of a series of genomically recoded organisms (GROs) whose growth is restricted by the expression of multiple essential genes that depend on exogenously supplied synthetic amino acids (sAAs). We introduced a Methanocaldococcus jannaschii tRNA:aminoacyl-tRNA synthetase pair into the chromosome of a GRO derived from Escherichia coli that lacks all TAG codons and release factor 1, endowing this organism with the orthogonal translational components to convert TAG into a dedicated sense codon for sAAs. Using multiplex automated genome engineering, we introduced in-frame TAG codons into 22 essential genes, linking their expression to the incorporation of synthetic phenylalanine-derived amino acids. Of the 60 sAA-dependent variants isolated, a notable strain harbouring three TAG codons in conserved functional residues of MurG, DnaA and SerS and containing targeted tRNA deletions maintained robust growth and exhibited undetectable escape frequencies upon culturing ∼10(11) cells on solid media for 7 days or in liquid media for 20 days. This is a significant improvement over existing biocontainment approaches. We constructed synthetic auxotrophs dependent on sAAs that were not rescued by cross-feeding in environmental growth assays. These auxotrophic GROs possess alternative genetic codes that impart genetic isolation by impeding horizontal gene transfer and now depend on the use of synthetic biochemical building blocks, advancing orthogonal barriers between engineered organisms and the environment.

Sepsis Fluid Metric Compliance and its Impact on Outcomes of Patients with Congestive Heart Failure, End-Stage Renal Disease or Obesity.

BACKGROUND: Emergency physicians express concern administering a 30-cc/kg fluid bolus to septic shock patients with pre-existing congestive heart failure (CHF), end-stage renal disease (ESRD), or obesity, due to the perceived risk of precipitating a fluid overload state. OBJECTIVE: Our aim was to determine whether there is a difference in fluid administration to septic shock patients with these pre-existing conditions in the emergency department (ED). Secondary objectives focused on whether compliance impacts mortality, need for intubation, and length of stay. METHODS: We conducted a retrospective chart review of 470,558 ED patient encounters at a single urban academic center during a 5-year period. RESULTS: Of 847 patients with septic shock, 308 (36.36%) had no pre-existing condition and 199 (23.49%), 17 (2.01%), and 154 (18.18%) had the single pre-existing condition of CHF, ESRD, and obesity, respectively, and 169 (19.95%) had multiple pre-existing conditions. Weight-based fluid compliance was achieved in 460 patients (54.31%). There was a lower likelihood of compliance among patients with CHF (adjusted odds ratio [aOR] 0.35; 95% confidence interval [CI] 0.24-0.52; p < 0.001), ESRD (aOR 0.11, 95% CI 0.04-0.32; p < 0.001), and obesity (aOR 0.29, 95% CI 0.19-0.44; p < 0.001) compared with patients with no pre-existing conditions. Compliance decreased further in patients with multiple pre-existing conditions (aOR 0.49, 95% CI 0.33-0.72; p < 0.001). Compliance was not associated with mortality in patients with CHF and ESRD, but was protective in patients with obesity and those with no pre-existing conditions. CONCLUSIONS: Septic shock patients with pre-existing CHF, ESRD, or obesity are less likely to achieve compliance with a 30-cc/kg weight-based fluid goal compared with those without these pre-existing conditions.

Development and Validation of the Quick COVID-19 Severity Index: A Prognostic Tool for Early Clinical Decompensation.

STUDY OBJECTIVE: The goal of this study is to create a predictive, interpretable model of early hospital respiratory failure among emergency department (ED) patients admitted with coronavirus disease 2019 (COVID-19). METHODS: This was an observational, retrospective, cohort study from a 9-ED health system of admitted adult patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) and an oxygen requirement less than or equal to 6 L/min. We sought to predict respiratory failure within 24 hours of admission as defined by oxygen requirement of greater than 10 L/min by low-flow device, high-flow device, noninvasive or invasive ventilation, or death. Predictive models were compared with the Elixhauser Comorbidity Index, quick Sequential [Sepsis-related] Organ Failure Assessment, and the CURB-65 pneumonia severity score. RESULTS: During the study period, from March 1 to April 27, 2020, 1,792 patients were admitted with COVID-19, 620 (35%) of whom had respiratory failure in the ED. Of the remaining 1,172 admitted patients, 144 (12.3%) met the composite endpoint within the first 24 hours of hospitalization. On the independent test cohort, both a novel bedside scoring system, the quick COVID-19 Severity Index (area under receiver operating characteristic curve mean 0.81 [95% confidence interval {CI} 0.73 to 0.89]), and a machine-learning model, the COVID-19 Severity Index (mean 0.76 [95% CI 0.65 to 0.86]), outperformed the Elixhauser mortality index (mean 0.61 [95% CI 0.51 to 0.70]), CURB-65 (0.50 [95% CI 0.40 to 0.60]), and quick Sequential [Sepsis-related] Organ Failure Assessment (0.59 [95% CI 0.50 to 0.68]). A low quick COVID-19 Severity Index score was associated with a less than 5% risk of respiratory decompensation in the validation cohort. CONCLUSION: A significant proportion of admitted COVID-19 patients progress to respiratory failure within 24 hours of admission. These events are accurately predicted with bedside respiratory examination findings within a simple scoring system.

US-Pro: An Application Enabling Efficient, High-Throughput Ultrasound Video Processing.

We describe a new graphical user interface-based application, US-Pro, designed to enable customized, high-throughput ultrasound video anonymization and dynamic cropping before output to video or high-efficiency disk storage. This application is distributed in a Docker container environment, which supports facile software installation on the most commonly used operating systems, as well as local processing of data sets, precluding the external transfer of electronic protected health information. The US-Pro application will facilitate the reproducible production of large-scale ultrasound video data sets for varied applications, including machine-learning analysis, educational distribution, and quality assurance review.

Automating risk stratification for geriatric syndromes in the emergency department.

BACKGROUND: Geriatric emergency department (GED) guidelines endorse screening older patients for geriatric syndromes in the ED, but there have been significant barriers to widespread implementation. The majority of screening programs require engagement of a clinician, nurse, or social worker, adding to already significant workloads at a time of record-breaking ED patient volumes, staff shortages, and hospital boarding crises. Automated, electronic health record (EHR)-embedded risk stratification approaches may be an alternate solution for extending the reach of the GED mission by directing human actions to a smaller subset of higher risk patients. METHODS: We define the concept of automated risk stratification and screening using existing EHR data. We discuss progress made in three potential use cases in the ED: falls, cognitive impairment, and end-of-life and palliative care, emphasizing the importance of linking automated screening with systems of healthcare delivery. RESULTS: Research progress and operational deployment vary by use case, ranging from deployed solutions in falls screening to algorithmic validation in cognitive impairment and end-of-life care. CONCLUSIONS: Automated risk stratification offers a potential solution to one of the most pressing problems in geriatric emergency care: identifying high-risk populations of older adults most appropriate for specific GED care. Future work is needed to realize the promise of improved care with less provider burden by creating tools suitable for widespread deployment as well as best practices for their implementation and governance.

SOFA score performs worse than age for predicting mortality in patients with COVID-19.

The use of the Sequential Organ Failure Assessment (SOFA) score, originally developed to describe disease morbidity, is commonly used to predict in-hospital mortality. During the COVID-19 pandemic, many protocols for crisis standards of care used the SOFA score to select patients to be deprioritized due to a low likelihood of survival. A prior study found that age outperformed the SOFA score for mortality prediction in patients with COVID-19, but was limited to a small cohort of intensive care unit (ICU) patients and did not address whether their findings were unique to patients with COVID-19. Moreover, it is not known how well these measures perform across races. In this retrospective study, we compare the performance of age and SOFA score in predicting in-hospital mortality across two cohorts: a cohort of 2,648 consecutive adult patients diagnosed with COVID-19 who were admitted to a large academic health system in the northeastern United States over a 4-month period in 2020 and a cohort of 75,601 patients admitted to one of 335 ICUs in the eICU database between 2014 and 2015. We used age and the maximum SOFA score as predictor variables in separate univariate logistic regression models for in-hospital mortality and calculated area under the receiver operator characteristic curves (AU-ROCs) and area under precision-recall curves (AU-PRCs) for each predictor in both cohorts. Among the COVID-19 cohort, age (AU-ROC 0.795, 95% CI 0.762, 0.828) had a significantly better discrimination than SOFA score (AU-ROC 0.679, 95% CI 0.638, 0.721) for mortality prediction. Conversely, age (AU-ROC 0.628 95% CI 0.608, 0.628) underperformed compared to SOFA score (AU-ROC 0.735, 95% CI 0.726, 0.745) in non-COVID-19 ICU patients in the eICU database. There was no difference between Black and White COVID-19 patients in performance of either age or SOFA Score. Our findings bring into question the utility of SOFA score-based resource allocation in COVID-19 crisis standards of care.

Geriatric End-of-Life Screening Tool Prediction of 6-Month Mortality in Older Patients.

Importance: Emergency department (ED) visits by older adults with life-limiting illnesses are a critical opportunity to establish patient care end-of-life preferences, but little is known about the optimal screening criteria for resource-constrained EDs. Objectives: To externally validate the Geriatric End-of-Life Screening Tool (GEST) in an independent population and compare it with commonly used serious illness diagnostic criteria. Design, Setting, and Participants: This prognostic study assessed a cohort of patients aged 65 years and older who were treated in a tertiary care ED in Boston, Massachusetts, from 2017 to 2021. Patients arriving in cardiac arrest or who died within 1 day of ED arrival were excluded. Data analysis was performed from August 1, 2023, to March 27, 2024. Exposure: GEST, a logistic regression algorithm that uses commonly available electronic health record (EHR) datapoints and was developed and validated across 9 EDs, was compared with serious illness diagnoses as documented in the EHR. Serious illnesses included stroke/transient ischemic attack, liver disease, cancer, lung disease, and age greater than 80 years, among others. Main Outcomes and Measures: The primary outcome was 6-month mortality following an ED encounter. Statistical analyses included area under the receiver operating characteristic curve, calibration analyses, Kaplan-Meier survival curves, and decision curves. Results: This external validation included 82 371 ED encounters by 40 505 unique individuals (mean [SD] age, 76.8 [8.4] years; 54.3% women, 13.8% 6-month mortality rate). GEST had an external validation area under the receiver operating characteristic curve of 0.79 (95% CI, 0.78-0.79) that was stable across years and demographic subgroups. Of included encounters, 53.4% had a serious illness, with a sensitivity of 77.4% (95% CI, 76.6%-78.2%) and specificity of 50.5% (95% CI, 50.1%-50.8%). Varying GEST cutoffs from 5% to 30% increased specificity (5%: 49.1% [95% CI, 48.7%-49.5%]; 30%: 92.2% [95% CI, 92.0%-92.4%]) at the cost of sensitivity (5%: 89.3% [95% CI, 88.8-89.9]; 30%: 36.2% [95% CI, 35.3-37.1]). In a decision curve analysis, GEST outperformed serious illness criteria across all tested thresholds. When comparing patients referred to intervention by GEST with serious illness criteria, GEST reclassified 45.1% of patients with serious illness as having low risk of mortality with an observed mortality rate 8.1% and 2.6% of patients without serious illness as having high mortality risk with an observed mortality rate of 34.3% for a total reclassification rate of 25.3%. Conclusions and Relevance: The findings of this study suggest that both serious illness criteria and GEST identified older ED patients at risk for 6-month mortality, but GEST offered more useful screening characteristics. Future trials of serious illness interventions for high mortality risk in older adults may consider transitioning from diagnosis code criteria to GEST, an automatable EHR-based algorithm.

Automatable end-of-life screening for older adults in the emergency department using electronic health records.

BACKGROUND: Emergency department (ED) visits are common at the end-of-life, but the identification of patients with life-limiting illness remains a key challenge in providing timely and resource-sensitive advance care planning (ACP) and palliative care services. To date, there are no validated, automatable instruments for ED end-of-life screening. Here, we developed a novel electronic health record (EHR) prognostic model to screen older ED patients at high risk for 6-month mortality and compare its performance to validated comorbidity indices. METHODS: This was a retrospective, observational cohort study of ED visits from adults aged ≥65 years who visited any of 9 EDs across a large regional health system between 2014 and 2019. Multivariable logistic regression that included clinical and demographic variables, vital signs, and laboratory data was used to develop a 6-month mortality predictive model-the Geriatric End-of-life Screening Tool (GEST) using five-fold cross-validation on data from 8 EDs. Performance was compared to the Charlson and Elixhauser comorbidity indices using area under the receiver-operating characteristic curve (AUROC), calibration, and decision curve analyses. Reproducibility was tested against data from the remaining independent ED within the health system. We then used GEST to investigate rates of ACP documentation availability and code status orders in the EHR across risk strata. RESULTS: A total of 431,179 encounters by 123,128 adults were included in this study with a 6-month mortality rate of 12.2%. Charlson (AUROC (95% CI): 0.65 (0.64-0.69)) and Elixhauser indices (0.69 (0.68-0.70)) were outperformed by GEST (0.82 (0.82-0.83)). GEST displayed robust performance across demographic subgroups and in our independent validation site. Among patients with a greater than 30% mortality risk using GEST, only 5.0% had ACP documentation; 79.0% had a code status previously ordered, of which 70.7% were full code. In decision curve analysis, GEST provided greater net benefit than the Charlson and Elixhauser scores. CONCLUSIONS: Prognostic models using EHR data robustly identify high mortality risk older adults in the ED for whom code status, ACP, or palliative care interventions may be of benefit. Although all tested methods identified patients approaching the end-of-life, GEST was most performant. These tools may enable resource-sensitive end-of-life screening in the ED.

Dementia risk analysis using temporal event modeling on a large real-world dataset.

The objective of the study is to identify healthcare events leading to a diagnosis of dementia from a large real-world dataset. This study uses a data-driven approach to identify temporally ordered pairs and trajectories of healthcare codes in the electronic health record (EHR). This allows for discovery of novel temporal risk factors leading to an outcome of interest that may otherwise be unobvious. We identified several known (Down syndrome RR = 116.1, thiamine deficiency RR = 76.1, and Parkinson's disease RR = 41.1) and unknown (Brief psychotic disorder RR = 68.6, Toxic effect of metals RR = 40.4, and Schizoaffective disorders RR = 40.0) factors for a specific dementia diagnosis. The associations with the greatest risk for any dementia diagnosis were found to be primarily related to mental health (Brief psychotic disorder RR = 266.5, Dissociative and conversion disorders RR = 169.8), or neurologic conditions or procedures (Dystonia RR = 121.9, Lumbar Puncture RR = 119.0). Trajectory and clustering analysis identified factors related to cerebrovascular disorders, as well as diagnoses which increase the risk of toxic imbalances. The results of this study have the ability to provide valuable insights into potential patient progression towards dementia and improve recognition of patients at risk for developing dementia.

Cluster Analysis of Primary Care Physician Phenotypes for Electronic Health Record Use: Retrospective Cohort Study.

BACKGROUND: Electronic health records (EHRs) have become ubiquitous in US office-based physician practices. However, the different ways in which users engage with EHRs remain poorly characterized. OBJECTIVE: The aim of this study is to explore EHR use phenotypes among ambulatory care physicians. METHODS: In this retrospective cohort analysis, we applied affinity propagation, an unsupervised clustering machine learning technique, to identify EHR user types among primary care physicians. RESULTS: We identified 4 distinct phenotype clusters generalized across internal medicine, family medicine, and pediatrics specialties. Total EHR use varied for physicians in 2 clusters with above-average ratios of work outside of scheduled hours. This finding suggested that one cluster of physicians may have worked outside of scheduled hours out of necessity, whereas the other preferred ad hoc work hours. The two remaining clusters represented physicians with below-average EHR time and physicians who spend the largest proportion of their EHR time on documentation. CONCLUSIONS: These findings demonstrate the utility of cluster analysis for exploring EHR use phenotypes and may offer opportunities for interventions to improve interface design to better support users' needs.

Patterns of Care Partner Communication for Persons Living with Dementia in the Emergency Department.

Introduction: Nearly half of all persons living with dementia (PLwD) will visit the emergency department (ED) in any given year and ED visits by PLwD are associated with short-term adverse outcomes. Care partner engagement is critical in the care of PLwD, but little is known about their patterns of communication with ED clinicians. Methods: We performed a retrospective electronic health record (EHR) review of a random sampling of patients ≥ 65 years with a historical diagnosis code of dementia who visited an ED within a large regional health network between 1/2014 and 1/2022. ED notes within the EHRs were coded for documentation of care partner communication and presence of a care partner in the ED. Logistic regression was used to identify patient characteristics associated with the composite outcome of either care partner communication or care partner presence in the ED. Results: A total of 460 patients were included. The median age was 83.0 years, 59.3% were female, 11.3% were Black, and 7.6% Hispanic. A care partner was documented in the ED for 22.4% of the visits and care partner communication documented for 43.9% of visits. 54.8% of patients had no documentation of care partner communication nor evidence of a care partner at the bedside. In multivariate logistic regression, increasing age (OR, (95% CI): 1.06 (1.04-1.09)), altered mental status (OR: 2.26 (1.01-5.05)), and weakness (OR: 3.38 (1.49-7.65)) significantly increased the probability of having care partner communication documented or a care partner at the bedside. Conclusion: More than half of PLwD in our sample did not have clinician documentation of communication with a care partner or a care partner in the ED. Further studies are needed to use these insights to improve communication with care partners of PLwD in the ED.

Automated multilabel diagnosis on electrocardiographic images and signals.

The application of artificial intelligence (AI) for automated diagnosis of electrocardiograms (ECGs) can improve care in remote settings but is limited by the reliance on infrequently available signal-based data. We report the development of a multilabel automated diagnosis model for electrocardiographic images, more suitable for broader use. A total of 2,228,236 12-lead ECGs signals from 811 municipalities in Brazil are transformed to ECG images in varying lead conformations to train a convolutional neural network (CNN) identifying 6 physician-defined clinical labels spanning rhythm and conduction disorders, and a hidden label for gender. The image-based model performs well on a distinct test set validated by at least two cardiologists (average AUROC 0.99, AUPRC 0.86), an external validation set of 21,785 ECGs from Germany (average AUROC 0.97, AUPRC 0.73), and printed ECGs, with performance superior to signal-based models, and learning clinically relevant cues based on Grad-CAM. The model allows the application of AI to ECGs across broad settings.

Methods, challenges, and promise of next-generation sequencing in cancer biology.

It is generally accepted that cancers result from the aggregation of somatic mutations. The emergence of next-generation sequencing (NGS) technologies during the past half-decade has enabled studies of cancer genomes with high sensitivity and resolution through whole-genome and whole-exome sequencing approaches, among others. This saltatory advance introduces the possibility of assembling multiple cancer genomes for analysis in a cost-effective manner. Analytical approaches are now applied to the detection of a number of somatic genome alterations, including nucleotide substitutions, insertions/deletions, copy number variations, and chromosomal rearrangements. This review provides a thorough introduction to the cancer genomics pipeline as well as a case study of these methods put into practice.