Investigation of commonly used aortic aneurysm growth rate metrics: Comparing their suitability for clinical and research applications.

An aneurysm is a pathological widening of a blood vessel. Aneurysms of the aorta are often asymptomatic until they rupture, killing approximately 10,000 Americans per year. Fortunately, rupture can be prevented through early detection and surgical repair. However, surgical risk outweighs rupture risk for small aortic aneurysms, necessitating a policy of surveillance. Understanding the growth rate of aneurysms is essential for determining appropriate surveillance windows. Further, identifying risk factors for fast growth can help identify potential interventions. However, studies in the literature have applied many different methods for defining the growth rate of abdominal aortic aneurysms. It is unclear which of these methods is most accurate and clinically meaningful, and whether these heterogeneous methodologies may have contributed to the varied results reported in the literature. To help future researchers best plan their studies and to help clinicians interpret existing studies, we compared five different models of aneurysmal growth rate. We examined their noise tolerance, temporal bias, predictive accuracy, and statistical power to detect risk factors. We found that hierarchical mixed effects models were more noise tolerant than traditional, unpooled models. We also found that linear models were sensitive to temporal bias, assigning lower growth rates to aneurysms that were detected earlier in their course. Our exponential mixed model was noise-tolerant, resistant to temporal bias, and detected the greatest number of clinical risk factors. We conclude that exponential mixed models may be optimal for large studies. Because our results suggest that choice of method can materially impact a study's findings, we recommend that future studies clearly state the method used and demonstrate its appropriateness.

The N3C governance ecosystem: A model socio-technical partnership for the future of collaborative analytics at scale.

The National COVID Cohort Collaborative (N3C) is a public-private-government partnership established during the Coronavirus pandemic to create a centralized data resource called the "N3C data enclave." This resource contains individual-level health data from participating healthcare sites nationwide to support rapid collaborative analytics. N3C has enabled analytics within a cloud-based enclave of data from electronic health records from over 17 million people (with and without COVID-19) in the USA. To achieve this goal of a shared data resource, N3C implemented a shared governance strategy involving stakeholders in decision-making. The approach leveraged best practices in data stewardship and team science to rapidly enable COVID-19-related research at scale while respecting the privacy of data subjects and participating institutions. N3C balanced equitable access to data, team-based scientific productivity, and individual professional recognition - a key incentive for academic researchers. This governance approach makes N3C research sustainable and effective beyond the initial days of the pandemic. N3C demonstrated that shared governance can overcome traditional barriers to data sharing without compromising data security and trust. The governance innovations described herein are a helpful framework for other privacy-preserving data infrastructure programs and provide a working model for effective team science beyond COVID-19.

Effect of SARS-CoV-2 Infection and Infection Severity on Longer-Term Glycemic Control and Weight in People With Type 2 Diabetes.

OBJECTIVE: To evaluate the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severity of infection with longer-term glycemic control and weight in people with type 2 diabetes (T2D) in the U.S. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using longitudinal electronic health record data of patients with SARS-CoV-2 infection from the National COVID Cohort Collaborative (N3C). Patients were ≥18 years old with an ICD-10 diagnosis of T2D and at least one HbA1c and weight measurement prior to and after an index date of their first coronavirus disease 2019 (COVID-19) diagnosis or negative SARS-CoV-2 test. We used propensity scores to identify a matched cohort balanced on demographic characteristics, comorbidities, and medications used to treat diabetes. The primary outcome was the postindex average HbA1c and postindex average weight over a 1 year time period beginning 90 days after the index date among patients who did and did not have SARS-CoV-2 infection. Secondary outcomes were postindex average HbA1c and weight in patients who required hospitalization or mechanical ventilation. RESULTS: There was no significant difference in the postindex average HbA1c or weight in patients who had SARS-CoV-2 infection compared with control subjects. Mechanical ventilation was associated with a decrease in average HbA1c after COVID-19. CONCLUSIONS: In a multicenter cohort of patients in the U.S. with preexisting T2D, there was no significant change in longer-term average HbA1c or weight among patients who had COVID-19. Mechanical ventilation was associated with a decrease in HbA1c after COVID-19.

Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database.

OBJECTIVE: The purpose of the study is to evaluate the relationship between HbA1c and severity of coronavirus disease 2019 (COVID-19) outcomes in patients with type 2 diabetes (T2D) with acute COVID-19 infection. RESEARCH DESIGN AND METHODS: We conducted a retrospective study using observational data from the National COVID Cohort Collaborative (N3C), a longitudinal, multicenter U.S. cohort of patients with COVID-19 infection. Patients were ≥18 years old with T2D and confirmed COVID-19 infection by laboratory testing or diagnosis code. The primary outcome was 30-day mortality following the date of COVID-19 diagnosis. Secondary outcomes included need for invasive ventilation or extracorporeal membrane oxygenation (ECMO), hospitalization within 7 days before or 30 days after COVID-19 diagnosis, and length of stay (LOS) for patients who were hospitalized. RESULTS: The study included 39,616 patients (50.9% female, 55.4% White, 26.4% Black or African American, and 16.1% Hispanic or Latino, with mean ± SD age 62.1 ± 13.9 years and mean ± SD HbA1c 7.6% ± 2.0). There was an increasing risk of hospitalization with incrementally higher HbA1c levels, but risk of death plateaued at HbA1c >8%, and risk of invasive ventilation or ECMO plateaued >9%. There was no significant difference in LOS across HbA1c levels. CONCLUSIONS: In a large, multicenter cohort of patients in the U.S. with T2D and COVID-19 infection, risk of hospitalization increased with incrementally higher HbA1c levels. Risk of death and invasive ventilation also increased but plateaued at different levels of glycemic control.

A Large-Scale Observational Study on the Temporal Trends and Risk Factors of Opioid Overdose: Real-World Evidence for Better Opioids.

BACKGROUND: The USA is in the midst of an opioid overdose epidemic. To address the epidemic, we conducted a large-scale population study on opioid overdose. OBJECTIVES: The primary objective of this study was to evaluate the temporal trends and risk factors of inpatient opioid overdose. Based on its patterns, the secondary objective was to examine the innate properties of opioid analgesics underlying reduced overdose effects. METHODS: A retrospective cross-sectional study was conducted based on a large-scale inpatient electronic health records database, Cerner Health Facts®, with (1) inclusion criteria for participants as patients admitted between 1 January, 2009 and 31 December, 2017 and (2) measurements as opioid overdose prevalence by year, demographics, and prescription opioid exposures. RESULTS: A total of 4,720,041 patients with 7,339,480 inpatient encounters were retrieved from Cerner Health Facts®. Among them, 30.2% patients were aged 65+ years, 57.0% female, 70.1% Caucasian, 42.3% single, 32.0% from the South, and 80.8% in an urban area. From 2009 to 2017, annual opioid overdose prevalence per 1000 patients significantly increased from 3.7 to 11.9 with an adjusted odds ratio (aOR): 1.16, 95% confidence interval (CI) 1.15-1.16. Compared to the major demographic counterparts, being in (1) age group: 41-50 years (overall aOR 1.36, 95% CI 1.31-1.40) or 51-64 years (overall aOR 1.35, 95% CI 1.32-1.39), (2) marital status: divorced (overall aOR 1.19, 95% CI 1.15-1.23), and (3) census region: West (overall aOR 1.32, 95% CI 1.28-1.36) were significantly associated with a higher odds of opioid overdose. Prescription opioid exposures were also associated with an increased odds of opioid overdose, such as meperidine (overall aOR 1.09, 95% CI 1.06-1.13) and tramadol (overall aOR 2.20, 95% CI 2.14-2.27). Examination on the relationships between opioid analgesic properties and their association strengths, aORs, and opioid overdose showed that lower aOR values were significantly associated with (1) high molecular weight, (2) non-interaction with multi-drug resistance protein 1 or interaction with cytochrome P450 3A4, and (3) non-interaction with the delta opioid receptor or kappa opioid receptor. CONCLUSIONS: The significant increasing trends of opioid overdose at the inpatient care setting from 2009 to 2017 suggested an ongoing need for efforts to combat the opioid overdose epidemic in the USA. Risk factors associated with opioid overdose included patient demographics and prescription opioid exposures. Moreover, there are physicochemical, pharmacokinetic, and pharmacodynamic properties underlying reduced overdose effects, which can be utilized to develop better opioids.

Identifying risk of opioid use disorder for patients taking opioid medications with deep learning.

OBJECTIVE: The United States is experiencing an opioid epidemic. In recent years, there were more than 10 million opioid misusers aged 12 years or older annually. Identifying patients at high risk of opioid use disorder (OUD) can help to make early clinical interventions to reduce the risk of OUD. Our goal is to develop and evaluate models to predict OUD for patients on opioid medications using electronic health records and deep learning methods. The resulting models help us to better understand OUD, providing new insights on the opioid epidemic. Further, these models provide a foundation for clinical tools to predict OUD before it occurs, permitting early interventions. METHODS: Electronic health records of patients who have been prescribed with medications containing active opioid ingredients were extracted from Cerner's Health Facts database for encounters between January 1, 2008, and December 31, 2017. Long short-term memory models were applied to predict OUD risk based on five recent prior encounters before the target encounter and compared with logistic regression, random forest, decision tree, and dense neural network. Prediction performance was assessed using F1 score, precision, recall, and area under the receiver-operating characteristic curve. RESULTS: The long short-term memory (LSTM) model provided promising prediction results which outperformed other methods, with an F1 score of 0.8023 (about 0.016 higher than dense neural network (DNN)) and an area under the receiver-operating characteristic curve (AUROC) of 0.9369 (about 0.145 higher than DNN). CONCLUSIONS: LSTM-based sequential deep learning models can accurately predict OUD using a patient's history of electronic health records, with minimal prior domain knowledge. This tool has the potential to improve clinical decision support for early intervention and prevention to combat the opioid epidemic.

A large-scale retrospective study of opioid poisoning in New York State with implications for targeted interventions.

Opioid overdose related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP). To discover trends and patterns of opioid poisoning and the demographic and regional disparities, we analyzed large scale patient visits data in New York State (NYS). Demographic, spatial, temporal and correlation analyses were performed for all OP patients extracted from the claims data in the New York Statewide Planning and Research Cooperative System (SPARCS) from 2010 to 2016, along with Decennial US Census and American Community Survey zip code level data. 58,481 patients with at least one OP diagnosis and a valid NYS zip code address were included. Main outcome and measures include OP patient counts and rates per 100,000 population, patient level factors (gender, age, race and ethnicity, residential zip code), and zip code level social demographic factors. The results showed that the OP rate increased by 364.6%, and by 741.5% for the age group > 65 years. There were wide disparities among groups by race and ethnicity on rates and age distributions of OP. Heroin and non-heroin based OP rates demonstrated distinct temporal trends as well as major geospatial variation. The findings highlighted strong demographic disparity of OP patients, evolving patterns and substantial geospatial variation.

Predicting opioid overdose risk of patients with opioid prescriptions using electronic health records based on temporal deep learning.

The US is experiencing an opioid epidemic, and opioid overdose is causing more than 100 deaths per day. Early identification of patients at high risk of Opioid Overdose (OD) can help to make targeted preventative interventions. We aim to build a deep learning model that can predict the patients at high risk for opioid overdose and identify most relevant features. The study included the information of 5,231,614 patients from the Health Facts database with at least one opioid prescription between January 1, 2008 and December 31, 2017. Potential predictors (n = 1185) were extracted to build a feature matrix for prediction. Long Short-Term Memory (LSTM) based models were built to predict overdose risk in the next hospital visit. Prediction performance was compared with other machine learning methods assessed using machine learning metrics. Our sequential deep learning models built upon LSTM outperformed the other methods on opioid overdose prediction. LSTM with attention mechanism achieved the highest F-1 score (F-1 score: 0.7815, AUCROC: 0.8449). The model is also able to reveal top ranked predictive features by permutation important method, including medications and vital signs. This study demonstrates that a temporal deep learning based predictive model can achieve promising results on identifying risk of opioid overdose of patients using the history of electronic health records. It provides an alternative informatics-based approach to improving clinical decision support for possible early detection and intervention to reduce opioid overdose.

Detecting Miscoded Diabetes Diagnosis Codes in Electronic Health Records for Quality Improvement: Temporal Deep Learning Approach.

BACKGROUND: Diabetes affects more than 30 million patients across the United States. With such a large disease burden, even a small error in classification can be significant. Currently billing codes, assigned at the time of a medical encounter, are the "gold standard" reflecting the actual diseases present in an individual, and thus in aggregate reflect disease prevalence in the population. These codes are generated by highly trained coders and by health care providers but are not always accurate. OBJECTIVE: This work provides a scalable deep learning methodology to more accurately classify individuals with diabetes across multiple health care systems. METHODS: We leveraged a long short-term memory-dense neural network (LSTM-DNN) model to identify patients with or without diabetes using data from 5 acute care facilities with 187,187 patients and 275,407 encounters, incorporating data elements including laboratory test results, diagnostic/procedure codes, medications, demographic data, and admission information. Furthermore, a blinded physician panel reviewed discordant cases, providing an estimate of the total impact on the population. RESULTS: When predicting the documented diagnosis of diabetes, our model achieved an 84% F1 score, 96% area under the curve-receiver operating characteristic curve, and 91% average precision on a heterogeneous data set from 5 distinct health facilities. However, in 81% of cases where the model disagreed with the documented phenotype, a blinded physician panel agreed with the model. Taken together, this suggests that 4.3% of our studied population have either missing or improper diabetes diagnosis. CONCLUSIONS: This study demonstrates that deep learning methods can improve clinical phenotyping even when patient data are noisy, sparse, and heterogeneous.

Association of Proteinuria and Hematuria with Acute Kidney Injury and Mortality in Hospitalized Patients with COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is strongly associated with poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19), but data on the association of proteinuria and hematuria are limited to non-US populations. In addition, admission and in-hospital measures for kidney abnormalities have not been studied separately. METHODS: This retrospective cohort study aimed to analyze these associations in 321 patients sequentially admitted between March 7, 2020 and April 1, 2020 at Stony Brook University Medical Center, New York. We investigated the association of proteinuria, hematuria, and AKI with outcomes of inflammation, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. We used ANOVA, t test, χ2 test, and Fisher's exact test for bivariate analyses and logistic regression for multivariable analysis. RESULTS: Three hundred patients met the inclusion criteria for the study cohort. Multivariable analysis demonstrated that admission proteinuria was significantly associated with risk of in-hospital AKI (OR 4.71, 95% CI 1.28-17.38), while admission hematuria was associated with ICU admission (OR 4.56, 95% CI 1.12-18.64), IMV (OR 8.79, 95% CI 2.08-37.00), and death (OR 18.03, 95% CI 2.84-114.57). During hospitalization, de novo proteinuria was significantly associated with increased risk of death (OR 8.94, 95% CI 1.19-114.4, p = 0.04). In-hospital AKI increased (OR 27.14, 95% CI 4.44-240.17) while recovery from in-hospital AKI decreased the risk of death (OR 0.001, 95% CI 0.001-0.06). CONCLUSION: Proteinuria and hematuria both at the time of admission and during hospitalization are associated with adverse clinical outcomes in hospitalized patients with COVID-19.

Deep Learning on Electronic Health Records to Improve Disease Coding Accuracy.

Characterization of a patient's clinical phenotype is central to biomedical informatics. ICD codes, assigned to inpatient encounters by coders, is important for population health and cohort discovery when clinical information is limited. While ICD codes are assigned to patients by professionals trained and certified in coding there is substantial variability in coding. We present a methodology that uses deep learning methods to model coder decision making and that predicts ICD codes. Our approach predicts codes based on demographics, lab results, and medications, as well as codes from previous encounters. We are able to predict existing codes with high accuracy for all three of the test cases we investigated: diabetes, acute renal failure, and chronic kidney disease. We employed a panel of clinicians, in a blinded manner, to assess ground truth and compared the predictions of coders, model and clinicians. When disparities between the model prediction and coder assigned codes were reviewed, our model outperformed coder assigned ICD codes.

Geographic, Temporal, and Sociodemographic Differences in Opioid Poisoning.

INTRODUCTION: Not enough is known about the epidemiology of opioid poisoning to tailor interventions to help address the growing opioid crisis in the U.S. The objective of this study is to expand the current understanding of opioid poisoning through the use of data analytics to evaluate geographic, temporal, and sociodemographic differences of opioid poisoning- related hospital visits in a region of New York State with high opioid poisoning rates. METHODS: This retrospective cohort study utilized patient-level New York State all-payer hospital data (2010-2016) combined with Census data to evaluate geographic, patient, and community factors for 9,714 Long Island residents with an opioid poisoning-related inpatient or outpatient hospital facility discharge. Temporal, 7-year opioid poisoning rates and trends were evaluated, and geographic maps were generated. Overall, significance tests and tests for linear trend were based upon logistic regression. Analyses were completed between 2017 and 2018. RESULTS: Since 2010, Long Island and New York State opioid poisoning hospital visit rates have increased 2.5- to 2.7-fold (p<0.001). Opioid poisoning hospital visit rates decreased for men, white patients, and self-payers (p<0.001) and increased for Medicare payers (p<0.001). Communities with high opioid poisoning rates had lower median home values, higher percentages of high school graduates, were younger, and more often white patients (p<0.01). Maps displayed geographic patterns of communities with high opioid poisoning rates overall and by age group. CONCLUSIONS: Findings highlight the changing demographics of the opioid poisoning epidemic and utility of data analytics tools to identify regions and patient populations to focus interventions. These population identification techniques can be applied in other communities and interventions.

Serverless OpenHealth at data commons scale-traversing the 20 million patient records of New York's SPARCS dataset in real-time.

In a previous report, we explored the serverless OpenHealth approach to the Web as a Global Compute space. That approach relies on the modern browser full stack, and, in particular, its configuration for application assembly by code injection. The opportunity, and need, to expand this approach has since increased markedly, reflecting a wider adoption of Open Data policies by Public Health Agencies. Here, we describe how the serverless scaling challenge can be achieved by the isomorphic mapping between the remote data layer API and a local (client-side, in-browser) operator. This solution is validated with an accompanying interactive web application (bit.ly/loadsparcs) capable of real-time traversal of New York's 20 million patient records of the Statewide Planning and Research Cooperative System (SPARCS), and is compared with alternative approaches. The results obtained strengthen the argument that the FAIR reproducibility needed for Population Science applications in the age of P4 Medicine is particularly well served by the Web platform.

Machine Learning Based Opioid Overdose Prediction Using Electronic Health Records.

Opioid addiction in the United States has come to national attention as opioid overdose (OD) related deaths have risen at alarming rates. Combating opioid epidemic becomes a high priority for not only governments but also healthcare providers. This depends on critical knowledge to understand the risk of opioid overdose of patients. In this paper, we present our work on building machine learning based prediction models to predict opioid overdose of patients based on the history of patients' electronic health records (EHR). We performed two studies using New York State claims data (SPARCS) with 440,000 patients and Cerner's Health Facts database with 110,000 patients. Our experiments demonstrated that EHR based prediction can achieve best recall with random forest method (precision: 95.3%, recall: 85.7%, F1 score: 90.3%), best precision with deep learning (precision: 99.2%, recall: 77.8%, F1 score: 87.2%). We also discovered that clinical events are among critical features for the predictions.

Social Media Based Analysis of Opioid Epidemic Using Reddit.

Opioid-abuse epidemic in the United States has escalated to national attention due to the dramatic increase of opioid overdose deaths. Analyzing opioid-related social media has the potential to reveal patterns of opioid abuse at a national scale, understand opinions of the public, and provide insights to support prevention and treatment. Reddit is a community based social media with more reliable content curated by the community through voting. In this study, we collected and analyzed all opioid related discussions from January 2014 to October 2017, which contains 51,537 posts by 16,162 unique users. We analyzed the data to understand the psychological categories of the posts, and performed topic modeling to reveal the major topics of interest. We also characterized the extent of social support received from comments and scores by each post. Last, we analyzed statistically significant difference in the posts between anonymous and non-anonymous users.

A Containerized Software System for Generation, Management, and Exploration of Features from Whole Slide Tissue Images.

Well-curated sets of pathology image features will be critical to clinical studies that aim to evaluate and predict treatment responses. Researchers require information synthesized across multiple biological scales, from the patient to the molecular scale, to more effectively study cancer. This article describes a suite of services and web applications that allow users to select regions of interest in whole slide tissue images, run a segmentation pipeline on the selected regions to extract nuclei and compute shape, size, intensity, and texture features, store and index images and analysis results, and visualize and explore images and computed features. All the services are deployed as containers and the user-facing interfaces as web-based applications. The set of containers and web applications presented in this article is used in cancer research studies of morphologic characteristics of tumor tissues. The software is free and open source. Cancer Res; 77(21); e79-82. ©2017 AACR.

Towards Generation, Management, and Exploration of Combined Radiomics and Pathomics Datasets for Cancer Research.

Cancer is a complex multifactorial disease state and the ability to anticipate and steer treatment results will require information synthesis across multiple scales from the host to the molecular level. Radiomics and Pathomics, where image features are extracted from routine diagnostic Radiology and Pathology studies, are also evolving as valuable diagnostic and prognostic indicators in cancer. This information explosion provides new opportunities for integrated, multi-scale investigation of cancer, but also mandates a need to build systematic and integrated approaches to manage, query and mine combined Radiomics and Pathomics data. In this paper, we describe a suite of tools and web-based applications towards building a comprehensive framework to support the generation, management and interrogation of large volumes of Radiomics and Pathomics feature sets and the investigation of correlations between image features, molecular data, and clinical outcome.

Spatio-temporal Analysis for New York State SPARCS Data.

Increased accessibility of health data provides unique opportunities to discover spatio-temporal patterns of diseases. For example, New York State SPARCS (Statewide Planning and Research Cooperative System) data collects patient level detail on patient demographics, diagnoses, services, and charges for each hospital inpatient stay and outpatient visit. Such data also provides home addresses for each patient. This paper presents our preliminary work on spatial, temporal, and spatial-temporal analysis of disease patterns for New York State using SPARCS data. We analyzed spatial distribution patterns of typical diseases at ZIP code level. We performed temporal analysis of common diseases based on 12 years' historical data. We then compared the spatial variations for diseases with different levels of clustering tendency, and studied the evolution history of such spatial patterns. Case studies based on asthma demonstrated that the discovered spatial clusters are consistent with prior studies. We visualized our spatial-temporal patterns as animations through videos.

Large-scale Analysis of Opioid Poisoning Related Hospital Visits in New York State.

Opioid related deaths are increasing dramatically in recent years, and opioid epidemic is worsening in the United States. Combating opioid epidemic becomes a high priority for both the U.S. government and local governments such as New York State. Analyzing patient level opioid related hospital visits provides a data driven approach to discover both spatial and temporal patterns and identity potential causes of opioid related deaths, which provides essential knowledge for governments on decision making. In this paper, we analyzed opioid poisoning related hospital visits using New York State SPARCS data, which provides diagnoses of patients in hospital visits. We identified all patients with primary diagnosis as opioid poisoning from 2010-2014 for our main studies, and from 2003-2014 for temporal trend studies. We performed demographical based studies, and summarized the historical trends of opioid poisoning. We used frequent item mining to find co-occurrences of diagnoses for possible causes of poisoning or effects from poisoning. We provided zip code level spatial analysis to detect local spatial clusters, and studied potential correlations between opioid poisoning and demographic and social-economic factors.

OpenHealth Platform for Interactive Contextualization of Population Health Open Data.

The financial incentives for data science applications leading to improved health outcomes, such as DSRIP (bit.ly/dsrip), are well-aligned with the broad adoption of Open Data by State and Federal agencies. This creates entirely novel opportunities for analytical applications that make exclusive use of the pervasive Web Computing platform. The framework described here explores this new avenue to contextualize Health data in a manner that relies exclusively on the native JavaScript interpreter and data processing resources of the ubiquitous Web Browser. The OpenHealth platform is made publicly available, and is publicly hosted with version control and open source, at https://github.com/mathbiol/openHealth. The different data/analytics workflow architectures explored are accompanied with live applications ranging from DSRIP, such as Hospital Inpatient Prevention Quality Indicators at http://bit.ly/pqiSuffolk, to The Cancer Genome Atlas (TCGA) as illustrated by http://bit.ly/tcgascopeGBM.