Building to learn: Information technology innovations to enable rapid pragmatic evaluation in a learning health system.

Background: Learning health systems (LHSs) iteratively generate evidence that can be implemented into practice to improve care and produce generalizable knowledge. Pragmatic clinical trials fit well within LHSs as they combine real-world data and experiences with a degree of methodological rigor which supports generalizability. Objectives: We established a pragmatic clinical trial unit ("RapidEval") to support the development of an LHS. To further advance the field of LHS, we sought to further characterize the role of health information technology (HIT), including innovative solutions and challenges that occur, to improve LHS project delivery. Methods: During the period from December 2021 to February 2023, eight projects were selected out of 51 applications to the RapidEval program, of which five were implemented, one is currently in pilot testing, and two are in planning. We evaluated pre-study planning, implementation, analysis, and study closure approaches across all RapidEval initiatives to summarize approaches across studies and identify key innovations and learnings by gathering data from study investigators, quality staff, and IT staff, as well as RapidEval staff and leadership. Implementation Results: Implementation approaches spanned a range of HIT capabilities including interruptive alerts, clinical decision support integrated into order systems, patient navigators, embedded micro-education, targeted outpatient hand-off documentation, and patient communication. Study approaches include pre-post with time-concordant controls (1), randomized stepped-wedge (1), cluster randomized across providers (1) and location (3), and simple patient level randomization (2). Conclusions: Study selection, design, deployment, data collection, and analysis required close collaboration between data analysts, informaticists, and the RapidEval team.

Evaluation of a Clinical Decision Support Tool to Guide Adoption of the American Heart Association Telemetry Monitoring Practice Standards.

BACKGROUND: The objectives of this study were to (1) evaluate telemetry use pre- and postimplementation of clinical decision support tools to support American Heart Association practice standards for telemetry monitoring and (2) understand the factors that may contribute to variation of telemetry monitoring in practice. METHODS AND RESULTS: First, we captured overall variability in telemetry use pre- and postimplementation of the clinical decision support intervention. We then conducted semistructured interviews with telemetry-ordering providers to identify key barriers and facilitators to adoption. During the study period, 399 physicians met criteria for inclusion and were divided into excessive and nonexcessive orderers. Distribution of telemetry use was bimodal. Among nonexcessive users, 24.4% of patient days were with telemetry compared with 51.6% among excessive users. On average, both excessive (6.1% reduction) and nonexcessive users (2.8% reduction) decreased telemetry use postimplementation, and these reductions were sustained over a 16-month period. Sixteen interviews were conducted. Physicians believed that the tool was successful because it caused them to more closely consider if telemetry was indicated for each patient. Physicians also voiced frustration with interruptions to their workflow, and some noted that they commonly use telemetry outside of practice standards to monitor patients who were acutely but not critically ill. CONCLUSIONS: Embedding telemetry practice standards into the electronic health record in the form of clinical decision support is effective at reducing excess telemetry use. Although the intervention was well received, there are persistent barriers, such as preexisting views on telemetry and existing workflow habits, that may inhibit higher adoption of standards.

Implementing Telestroke in the Inpatient Setting: Identifying Factors for Success.

BACKGROUND: Inpatient telestroke programs have emerged as a solution to provide timely stroke care in underserved areas, but their successful implementation and factors influencing their effectiveness remain underexplored. This study aimed to qualitatively evaluate the perspectives of inpatient clinicians located at spoke hospitals participating in a newly established inpatient telestroke program to identify implementation barriers and facilitators. METHODS: This was a formative evaluation relying on semistructured qualitative interviews with 16 inpatient providers (physicians and nurse practitioners) at 5 spoke sites of a hub-and-spoke inpatient telestroke program. The Integrated-Promoting Action on Research Implementation in Health Services framework guided data analysis, focusing on the innovation, recipients, context, and facilitation aspects of implementation. Interviews were transcribed and coded using thematic analysis. RESULTS: Fifteen themes were identified in the data and mapped to the Integrated-Promoting Action on Research Implementation in Health Services framework. Themes related to the innovation (the telestroke program) included easy access to stroke specialists, the benefits of limiting patient transfers, concerns about duplicating tests, and challenges of timing inpatient telestroke visits and notes to align with discharge workflow. Themes pertaining to recipients (care team members and patients) were communication gaps between teams, concern about the supervision of inpatient telestroke advanced practice providers and challenges with nurse empowerment. With regard to the context (hospital and system factors), providers highlighted familiarity with telehealth technologies as a facilitator to implementing inpatient telestroke, yet highlighted resource limitations in smaller facilities. Facilitation (program implementation) was recognized as crucial for education, standardization, and buy-in. CONCLUSIONS: Understanding barriers and facilitators to implementation is crucial to determining where programmatic changes may need to be made to ensure the success and sustainment of inpatient telestroke services.

Decreasing Opioid Addiction and Diversion Using Behavioral Economics Applied Through a Digital Engagement Solution: Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. OBJECTIVE: Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). METHODS: A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. RESULTS: This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. CONCLUSIONS: Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. TRIAL REGISTRATION: ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52882.

A Symptom-Based Natural Language Processing Surveillance Pipeline for Post-COVID-19 Patients.

Post-acute sequelae of SARS CoV-2 (PASC) are a group of conditions in which patients previously infected with COVID-19 experience symptoms weeks/months post-infection. PASC has substantial societal burden, including increased healthcare costs and disabilities. This study presents a natural language processing (NLP) based pipeline for identification of PASC symptoms and demonstrates its ability to estimate the proportion of suspected PASC cases. A manual case review to obtain this estimate indicated our sample incidence of PASC (13%) was representative of the estimated population proportion (95% CI: 19±6.22%). However, the high number of cases classified as indeterminate demonstrates the challenges in classifying PASC even among experienced clinicians. Lastly, this study developed a dashboard to display views of aggregated PASC symptoms and measured its utility using the System Usability Scale. Overall comments related to the dashboard's potential were positive. This pipeline is crucial for monitoring post-COVID-19 patients with potential for use in clinical settings.

Validation of a Proprietary Deterioration Index Model and Performance in Hospitalized Adults.

Importance: The Deterioration Index (DTI), used by hospitals for predicting patient deterioration, has not been extensively validated externally, raising concerns about performance and equitable predictions. Objective: To locally validate DTI performance and assess its potential for bias in predicting patient clinical deterioration. Design, Setting, and Participants: This retrospective prognostic study included 13 737 patients admitted to 8 heterogenous Midwestern US hospitals varying in size and type, including academic, community, urban, and rural hospitals. Patients were 18 years or older and admitted between January 1 and May 31, 2021. Exposure: DTI predictions made every 15 minutes. Main Outcomes and Measures: Deterioration, defined as the occurrence of any of the following while hospitalized: mechanical ventilation, intensive care unit transfer, or death. Performance of the DTI was evaluated using area under the receiver operating characteristic curve (AUROC) and area under the precision recall curve (AUPRC). Bias measures were calculated across demographic subgroups. Results: A total of 5 143 513 DTI predictions were made for 13 737 patients across 14 834 hospitalizations. Among 13 918 encounters, the mean (SD) age of patients was 60.3 (19.2) years; 7636 (54.9%) were female, 11 345 (81.5%) were White, and 12 392 (89.0%) were of other ethnicity than Hispanic or Latino. The prevalence of deterioration was 10.3% (n = 1436). The DTI produced AUROCs of 0.759 (95% CI, 0.756-0.762) at the observation level and 0.685 (95% CI, 0.671-0.700) at the encounter level. Corresponding AUPRCs were 0.039 (95% CI, 0.037-0.040) at the observation level and 0.248 (95% CI, 0.227-0.273) at the encounter level. Bias measures varied across demographic subgroups and were 14.0% worse for patients identifying as American Indian or Alaska Native and 19.0% worse for those who chose not to disclose their ethnicity. Conclusions and Relevance: In this prognostic study, the DTI had modest ability to predict patient deterioration, with varying degrees of performance at the observation and encounter levels and across different demographic groups. Disparate performance across subgroups suggests the need for more transparency in model training data and reinforces the need to locally validate externally developed prediction models.

Predictors of discharge disposition and mortality following hospitalization with SARS-CoV-2 infection.

IMPORTANCE: The SARS-CoV-2 pandemic has overwhelmed hospital capacity, prioritizing the need to understand factors associated with type of discharge disposition. OBJECTIVE: Characterization of disposition associated factors following SARS-CoV-2. DESIGN: Retrospective study of SARS-CoV-2 positive patients from March 7th, 2020, to May 4th, 2022, requiring hospitalization. SETTING: Midwest academic health-system. PARTICIPANTS: Patients above the age 18 years admitted with PCR + SARS-CoV-2. INTERVENTION: None. MAIN OUTCOMES: Discharge to home versus PAC (inpatient rehabilitation facility (IRF), skilled-nursing facility (SNF), long-term acute care (LTACH)), or died/hospice while hospitalized (DH). RESULTS: We identified 62,279 SARS-CoV-2 PCR+ patients; 6,248 required hospitalizations, of whom 4611(73.8%) were discharged home, 985 (15.8%) to PAC and 652 (10.4%) died in hospital (DH). Patients discharged to PAC had a higher median age (75.7 years, IQR: 65.6-85.1) compared to those discharged home (57.0 years, IQR: 38.2-69.9), and had longer mean length of stay (LOS) 14.7 days, SD: 14.0) compared to discharge home (5.8 days, SD: 5.9). Older age (RRR:1.04, 95% CI:1.041-1.055), and higher Elixhauser comorbidity index [EI] (RRR:1.19, 95% CI:1.168-1.218) were associated with higher rate of discharge to PAC versus home. Older age (RRR:1.069, 95% CI:1.060-1.077) and higher EI (RRR:1.09, 95% CI:1.071-1.126) were associated with more frequent DH versus home. Blacks, Asians, and Hispanics were less likely to be discharged to PAC (RRR, 0.64 CI 0.47-0.88), (RRR 0.48 CI 0.34-0.67) and (RRR 0.586 CI 0.352-0.975). Having alpha variant was associated with less frequent PAC discharge versus home (RRR 0.589 CI 0.444-780). The relative risks for DH were lower with a higher platelet count 0.998 (CI 0.99-0.99) and albumin levels 0.342 (CI 0.26-0.45), and higher with increased CRP (RRR 1.006 CI 1.004-1.007) and D-Dimer (RRR 1.070 CI 1.039-1.101). Increased albumin had lower risk to PAC discharge (RRR 0.630 CI 0.497-0.798. An increase in D-Dimer (RRR1.033 CI 1.002-1.064) and CRP (RRR1.002 CI1.001-1.004) was associated with higher risk of PAC discharge. A breakthrough (BT) infection was associated with lower likelihood of DH and PAC. CONCLUSION: Older age, higher EI, CRP and D-Dimer are associated with PAC and DH discharges following hospitalization with COVID-19 infection. BT infection reduces the likelihood of being discharged to PAC and DH.

Robust Methods for Quantifying the Effect of a Continuous Exposure From Observational Data.

A cornerstone of clinical medicine is intervening on a continuous exposure, such as titrating the dosage of a pharmaceutical or controlling a laboratory result. In clinical trials, continuous exposures are dichotomized into narrow ranges, excluding large portions of the realistic treatment scenarios. The existing computational methods for estimating the effect of continuous exposure rely on a set of strict assumptions. We introduce new methods that are more robust towards violations of these assumptions. Our methods are based on the key observation that changes of exposure in the clinical setting are often achieved gradually, so effect estimates must be "locally" robust in narrower exposure ranges. We compared our methods with several existing methods on three simulated studies with increasing complexity. We also applied the methods to data from 14 k sepsis patients at M Health Fairview to estimate the effect of antibiotic administration latency on prolonged hospital stay. The proposed methods achieve good performance in all simulation studies. When the assumptions were violated, the proposed methods had estimation errors of one half to one fifth of the state-of-the-art methods. Applying our methods to the sepsis cohort resulted in effect estimates consistent with clinical knowledge.

Prevalence of Medical Contraindications to Nirmatrelvir/Ritonavir in a Cohort of Hospitalized and Nonhospitalized Patients With COVID-19.

This analysis describes the prevalence of contraindications to nirmatrelvir/ritonavir among 66 007 patients with coronavirus disease 2019 in a large health care system. A possible contradiction was present in 9830 patients (14.8%), with the prevalence of contraindications increasing with higher acuity of illness.

Predictors of Postacute Sequelae of COVID-19 Development and Rehabilitation: A Retrospective Study.

OBJECTIVE: To examine the frequency of postacute sequelae of SARS-CoV-2 (PASC) and the factors associated with rehabilitation utilization in a large adult population with PASC. DESIGN: Retrospective study. SETTING: Midwest hospital health system. PARTICIPANTS: 19,792 patients with COVID-19 from March 10, 2020, to January 17, 2021. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Descriptive analyses were conducted across the entire cohort along with an adult subgroup analysis. A logistic regression was performed to assess factors associated with PASC development and rehabilitation utilization. RESULTS: In an analysis of 19,792 patients, the frequency of PASC was 42.8% in the adult population. Patients with PASC compared with those without had a higher utilization of rehabilitation services (8.6% vs 3.8%, P<.001). Risk factors for rehabilitation utilization in patients with PASC included younger age (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-1.00; P=.01). In addition to several comorbidities and demographics factors, risk factors for rehabilitation utilization solely in the inpatient population included male sex (OR, 1.24; 95% CI, 1.02-1.50; P=.03) with patients on angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers 3 months prior to COVID-19 infections having a decreased risk of needing rehabilitation (OR, 0.80; 95% CI, 0.64-0.99; P=.04). CONCLUSIONS: Patients with PASC had higher rehabilitation utilization. We identified several clinical and demographic factors associated with the development of PASC and rehabilitation utilization.

Comparison of Outcomes and Process of Care for Patients Treated at Hospitals Dedicated for COVID-19 Care vs Other Hospitals.

Importance: Early in the SARS-CoV-2 pandemic, the M Health Fairview Hospital System established dedicated hospitals for establishing cohorts and caring for patients with COVID-19, yet the association between treatment at COVID-19-dedicated hospitals and mortality and complications is not known. Objective: To analyze the mortality rate and complications associated with treatment at the COVID-19-dedicated hospitals. Design, Setting, and Participants: This retrospective cohort study evaluated data prospectively collected from March 1, 2020, through June 30, 2021, from 11 hospitals in Minnesota, including 2 hospitals created solely to care for patients with COVID-19. Data obtained included demographic characteristics, treatments, and outcomes of interest for all patients with a confirmed COVID-19 infection admitted to this hospital system during the study period. Exposures: Patients were grouped based on whether they received treatment from 1 of the 2 COVID-19-dedicated hospitals compared with the remainder of the hospitals within the hospital system. Main Outcomes and Measures: Multivariate analyses, including risk-adjusted logistic regression and propensity score matching, were performed to evaluate the primary outcome of in-hospital mortality and secondary outcomes, including complications and use of COVID-specific therapeutics. Results: There were 5504 patients with COVID-19 admitted during the study period (median age, 62.5 [IQR, 45.0-75.6] years; 2854 women [51.9%]). Of these, 2077 patients (37.7%) (median age, 63.4 [IQR, 50.7-76.1] years; 1080 men [52.0%]) were treated at 1 of the 2 COVID-19-dedicated hospitals compared with 3427 (62.3%; median age, 62.0 [40.0-75.1] years; 1857 women (54.2%) treated at other hospitals. The mortality rate was 11.6% (n = 241) at the dedicated hospitals compared with 8.0% (n = 274) at the other hospitals (P < .001). However, risk-adjusted in-hospital mortality was significantly lower for patients in the COVID-19-dedicated hospitals in both the unmatched group (n = 2077; odds ratio [OR], 0.75; 95% CI, 0.59-0.95) and the propensity score-matched group (n = 1317; OR, 0.78; 95% CI, 0.58-0.99). The rate of overall complications in the propensity score-matched group was significantly lower (OR, 0.81; 95% CI, 0.66-0.99) and the use of COVID-19-specific therapeutics including deep vein thrombosis prophylaxis (83.9% vs 56.9%; P < .001), high-dose corticosteroids (56.1% vs 22.2%; P < .001), remdesivir (61.5% vs 44.5%; P < .001), and tocilizumab (7.9% vs 2.0; P < .001) was significantly higher. Conclusions and Relevance: In this cohort study, COVID-19-dedicated hospitals had multiple benefits, including providing high-volume repetitive treatment and isolating patients with the infection. This experience suggests improved in-hospital mortality for patients treated at dedicated hospitals owing to improved processes of care and supports the use of establishing cohorts for future pandemics.

Patient Heterogeneity and the J-Curve Relationship Between Time-to-Antibiotics and the Outcomes of Patients Admitted With Bacterial Infection.

OBJECTIVES: Sepsis remains a leading and preventable cause of hospital utilization and mortality in the United States. Despite updated guidelines, the optimal definition of sepsis as well as optimal timing of bundled treatment remain uncertain. Identifying patients with infection who benefit from early treatment is a necessary step for tailored interventions. In this study, we aimed to illustrate clinical predictors of time-to-antibiotics among patients with severe bacterial infection and model the effect of delay on risk-adjusted outcomes across different sepsis definitions. DESIGN: A multicenter retrospective observational study. SETTING: A seven-hospital network including academic tertiary care center. PATIENTS: Eighteen thousand three hundred fifteen patients admitted with severe bacterial illness with or without sepsis by either acute organ dysfunction (AOD) or systemic inflammatory response syndrome positivity. MEASUREMENTS AND MAIN RESULTS: The primary exposure was time to antibiotics. We identified patient predictors of time-to-antibiotics including demographics, chronic diagnoses, vitals, and laboratory results and determined the impact of delay on a composite of inhospital death or length of stay over 10 days. Distribution of time-to-antibiotics was similar across patients with and without sepsis. For all patients, a J-curve relationship between time-to-antibiotics and outcomes was observed, primarily driven by length of stay among patients without AOD. Patient characteristics provided good to excellent prediction of time-to-antibiotics irrespective of the presence of sepsis. Reduced time-to-antibiotics was associated with improved outcomes for all time points beyond 2.5 hours from presentation across sepsis definitions. CONCLUSIONS: Antibiotic timing is a function of patient factors regardless of sepsis criteria. Similarly, we show that early administration of antibiotics is associated with improved outcomes in all patients with severe bacterial illness. Our findings suggest identifying infection is a rate-limiting and actionable step that can improve outcomes in septic and nonseptic patients.

A 12-hospital prospective evaluation of a clinical decision support prognostic algorithm based on logistic regression as a form of machine learning to facilitate decision making for patients with suspected COVID-19.

OBJECTIVE: To prospectively evaluate a logistic regression-based machine learning (ML) prognostic algorithm implemented in real-time as a clinical decision support (CDS) system for symptomatic persons under investigation (PUI) for Coronavirus disease 2019 (COVID-19) in the emergency department (ED). METHODS: We developed in a 12-hospital system a model using training and validation followed by a real-time assessment. The LASSO guided feature selection included demographics, comorbidities, home medications, vital signs. We constructed a logistic regression-based ML algorithm to predict "severe" COVID-19, defined as patients requiring intensive care unit (ICU) admission, invasive mechanical ventilation, or died in or out-of-hospital. Training data included 1,469 adult patients who tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within 14 days of acute care. We performed: 1) temporal validation in 414 SARS-CoV-2 positive patients, 2) validation in a PUI set of 13,271 patients with symptomatic SARS-CoV-2 test during an acute care visit, and 3) real-time validation in 2,174 ED patients with PUI test or positive SARS-CoV-2 result. Subgroup analysis was conducted across race and gender to ensure equity in performance. RESULTS: The algorithm performed well on pre-implementation validations for predicting COVID-19 severity: 1) the temporal validation had an area under the receiver operating characteristic (AUROC) of 0.87 (95%-CI: 0.83, 0.91); 2) validation in the PUI population had an AUROC of 0.82 (95%-CI: 0.81, 0.83). The ED CDS system performed well in real-time with an AUROC of 0.85 (95%-CI, 0.83, 0.87). Zero patients in the lowest quintile developed "severe" COVID-19. Patients in the highest quintile developed "severe" COVID-19 in 33.2% of cases. The models performed without significant differences between genders and among race/ethnicities (all p-values > 0.05). CONCLUSION: A logistic regression model-based ML-enabled CDS can be developed, validated, and implemented with high performance across multiple hospitals while being equitable and maintaining performance in real-time validation.

Responding to COVID-19 Through Interhospital Resource Coordination: A Mixed-Methods Evaluation.

OBJECTIVES: The COVID-19 pandemic stressed hospital operations, requiring rapid innovations to address rise in demand and specialized COVID-19 services while maintaining access to hospital-based care and facilitating expertise. We aimed to describe a novel hospital system approach to managing the COVID-19 pandemic, including multihospital coordination capability and transfer of COVID-19 patients to a single, dedicated hospital. METHODS: We included patients who tested positive for SARS-CoV-2 by polymerase chain reaction admitted to a 12-hospital network including a dedicated COVID-19 hospital. Our primary outcome was adherence to local guidelines, including admission risk stratification, anticoagulation, and dexamethasone treatment assessed by differences-in-differences analysis after guideline dissemination. We evaluated outcomes and health care worker satisfaction. Finally, we assessed barriers to safe transfer including transfer across different electronic health record systems. RESULTS: During the study, the system admitted a total of 1209 patients. Of these, 56.3% underwent transfer, supported by a physician-led System Operations Center. Patients who were transferred were older (P = 0.001) and had similar risk-adjusted mortality rates. Guideline adherence after dissemination was higher among patients who underwent transfer: admission risk stratification (P < 0.001), anticoagulation (P < 0.001), and dexamethasone administration (P = 0.003). Transfer across electronic health record systems was a perceived barrier to safety and reduced quality. Providers positively viewed our transfer approach. CONCLUSIONS: With standardized communication, interhospital transfers can be a safe and effective method of cohorting COVID-19 patients, are well received by health care providers, and have the potential to improve care quality.

Implementation of an Anticoagulation Practice Guideline for COVID-19 via a Clinical Decision Support System in a Large Academic Health System and Its Evaluation: Observational Study.

BACKGROUND: Studies evaluating strategies for the rapid development, implementation, and evaluation of clinical decision support (CDS) systems supporting guidelines for diseases with a poor knowledge base, such as COVID-19, are limited. OBJECTIVE: We developed an anticoagulation clinical practice guideline (CPG) for COVID-19, which was delivered and scaled via CDS across a 12-hospital Midwest health care system. This study represents a preplanned 6-month postimplementation evaluation guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. METHODS: The implementation outcomes evaluated were reach, adoption, implementation, and maintenance. To evaluate effectiveness, the association of CPG adherence on hospital admission with clinical outcomes was assessed via multivariable logistic regression and nearest neighbor propensity score matching. A time-to-event analysis was conducted. Sensitivity analyses were also conducted to evaluate the competing risk of death prior to intensive care unit (ICU) admission. The models were risk adjusted to account for age, gender, race/ethnicity, non-English speaking status, area deprivation index, month of admission, remdesivir treatment, tocilizumab treatment, steroid treatment, BMI, Elixhauser comorbidity index, oxygen saturation/fraction of inspired oxygen ratio, systolic blood pressure, respiratory rate, treating hospital, and source of admission. A preplanned subgroup analysis was also conducted in patients who had laboratory values (D-dimer, C-reactive protein, creatinine, and absolute neutrophil to absolute lymphocyte ratio) present. The primary effectiveness endpoint was the need for ICU admission within 48 hours of hospital admission. RESULTS: A total of 2503 patients were included in this study. CDS reach approached 95% during implementation. Adherence achieved a peak of 72% during implementation. Variation was noted in adoption across sites and nursing units. Adoption was the highest at hospitals that were specifically transformed to only provide care to patients with COVID-19 (COVID-19 cohorted hospitals; 74%-82%) and the lowest in academic settings (47%-55%). CPG delivery via the CDS system was associated with improved adherence (odds ratio [OR] 1.43, 95% CI 1.2-1.7; P<.001). Adherence with the anticoagulation CPG was associated with a significant reduction in the need for ICU admission within 48 hours (OR 0.39, 95% CI 0.30-0.51; P<.001) on multivariable logistic regression analysis. Similar findings were noted following 1:1 propensity score matching for patients who received adherent versus nonadherent care (21.5% vs 34.3% incidence of ICU admission within 48 hours; log-rank test P<.001). CONCLUSIONS: Our institutional experience demonstrated that adherence with the institutional CPG delivered via the CDS system resulted in improved clinical outcomes for patients with COVID-19. CDS systems are an effective means to rapidly scale a CPG across a heterogeneous health care system. Further research is needed to investigate factors associated with adherence at low and high adopting sites and nursing units.

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

Heterogeneity in COVID-19 Patients at Multiple Levels of Granularity: From Biclusters to Clinical Interventions.

Several studies have shown that COVID-19 patients with prior comorbidities have a higher risk for adverse outcomes, resulting in a disproportionate impact on older adults and minorities that fit that profile. However, although there is considerable heterogeneity in the comorbidity profiles of these populations, not much is known about how prior comorbidities co-occur to form COVID-19 patient subgroups, and their implications for targeted care. Here we used bipartite networks to quantitatively and visually analyze heterogeneity in the comorbidity profiles of COVID-19 inpatients, based on electronic health records from 12 hospitals and 60 clinics in the greater Minneapolis region. This approach enabled the analysis and interpretation of heterogeneity at three levels of granularity (cohort, subgroup, and patient), each of which enabled clinicians to rapidly translate the results into the design of clinical interventions. We discuss future extensions of the multigranular heterogeneity framework, and conclude by exploring how the framework could be used to analyze other biomedical phenomena including symptom clusters and molecular phenotypes, with the goal of accelerating translation to targeted clinical care.

Metformin and Covid-19: Focused Review of Mechanisms and Current Literature Suggesting Benefit.

Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C, and in-vitro assays of zika. In the current Covid-19 pandemic, which has rapidly spread throughout the world, 4 observational studies have been published showing reduced mortality among individuals with home metformin use. There are several potential overlapping mechanisms by which metformin may reduce mortality from Covid-19. Metformin's past anti-infectious benefits have been both against the infectious agent directly, as well as by improving the underlying health of the human host. It is unknown if the lower mortality suggested by observational studies in patients infected with Covid-19 who are on home metformin is due to direct activity against the virus itself, improved host substrate, or both.

Overcoming gaps: regional collaborative to optimize capacity management and predict length of stay of patients admitted with COVID-19.

OBJECTIVE: Ensuring an efficient response to COVID-19 requires a degree of inter-system coordination and capacity management coupled with an accurate assessment of hospital utilization including length of stay (LOS). We aimed to establish optimal practices in inter-system data sharing and LOS modeling to support patient care and regional hospital operations. MATERIALS AND METHODS: We completed a retrospective observational study of patients admitted with COVID-19 followed by 12-week prospective validation, involving 36 hospitals covering the upper Midwest. We developed a method for sharing de-identified patient data across systems for analysis. From this, we compared 3 approaches, generalized linear model (GLM) and random forest (RF), and aggregated system level averages to identify features associated with LOS. We compared model performance by area under the ROC curve (AUROC). RESULTS: A total of 2068 patients were included and used for model derivation and 597 patients for validation. LOS overall had a median of 5.0 days and mean of 8.2 days. Consistent predictors of LOS included age, critical illness, oxygen requirement, weight loss, and nursing home admission. In the validation cohort, the RF model (AUROC 0.890) and GLM model (AUROC 0.864) achieved good to excellent prediction of LOS, but only marginally better than system averages in practice. CONCLUSION: Regional sharing of patient data allowed for effective prediction of LOS across systems; however, this only provided marginal improvement over hospital averages at the aggregate level. A federated approach of sharing aggregated system capacity and average LOS will likely allow for effective capacity management at the regional level.

Metabolic surgery may protect against admission for COVID-19 in persons with nonalcoholic fatty liver disease.

BACKGROUND: SARS-CoV-2 (COVID-19) disease causes significant morbidity and mortality through increased inflammation and thrombosis. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are states of chronic inflammation and indicate advanced metabolic disease. OBJECTIVE: The purpose of this observational study was to characterize the risk of hospitalization for COVID-19 in patients with NAFLD/NASH and evaluate the mitigating effect of various metabolic treatments. SETTING: Retrospective analysis of electronic medical record data of 26,896 adults from a 12-hospital Midwest healthcare system with a positive COVID-19 polymerase chain reaction (PCR) test from March 1, 2020, to January 26, 2021. METHODS: Variable selection was guided by the least absolute shrinkage and selection operator (LASSO) method, and multiple imputation was used to account for missing data. Multivariable logistic regression and competing risk models were used to assess the odds of being hospitalized within 45 days of a COVID-19 diagnosis. Analysis assessed the risk of hospitalization among patients with a prescription for metformin and statin use within the 3 months prior to the COVID-19 PCR result, history of home glucagon-like peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by sex and race. RESULTS: A history of NAFLD/NASH was associated with increased odds of admission for COVID-19 (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.57-2.26; P < .001) and mortality (OR, 1.96; 95% CI, 1.45-2.67; P < .001). Each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for COVID-19 (OR, 1.24; 95% CI, 1.14-1.35; P < .001). NAFLD/NASH increased the risk of hospitalization in men, but not women, and increased the risk of hospitalization in all multiracial/multiethnic subgroups. Medication treatments for metabolic syndrome were associated with significantly reduced risk of admission (OR, .81; 95% CI, .67-.99; P < .001 for home metformin use; OR, .71; 95% CI, .65-.83; P < .001 for home statin use). MBS was associated with a significant decreased risk of admission (OR, .48; 95% CI, .33-.69; P < .001). CONCLUSIONS: NAFLD/NASH is a significant risk factor for hospitalization for COVID-19 and appears to account for risk attributed to obesity. Other significant risks include factors associated with socioeconomic status and other co-morbidities, such as history of venous thromboembolism. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm the risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.