A regionally tailored epidemiological forecast and monitoring program to guide a healthcare system in the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods. METHODS: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance. RESULTS: A consolidated forecast and monitoring report was produced weekly and proved to be an effective, vital source of information and guidance as the healthcare system navigated the inherent uncertainty of the pandemic. Forecasts provided accurate and precise information that informed critical decisions on resource planning, bed capacity and staffing management, and infection prevention strategies. CONCLUSIONS: In this paper, we have presented the framework used in our epidemiological forecast and monitoring program at Atrium Health, as well as provided recommendations for implementation by other healthcare systems and institutions to facilitate use in future pandemics.

Blood Pressure Control in a Diverse Population of Hypertensive Patients With Heart Failure.

Hypertensive patients with heart failure (HF), with reduced or preserved ejection fraction, belong to a vulnerable subset with high mortality risks. In HF patients, the current clinical guideline recommends attaining a systolic blood pressure (BP) <130 mm Hg. However, levels of BP control and their correlates in this subgroup are not well understood. Our study aimed at establishing levels of BP control and its associated factors in a geographically, racially diverse population of hypertensive patients with HF. Our study involved 10,802 patients within a large health system in the Charlotte metropolitan area in 2019. We documented a high prevalence of systolic BP ≥130 mm Hg, 48.1% (95% confidence interval 47.4% to 48.8%), and of BP ≥130/80 mm Hg, 57.6% (57.0% to 58.3%). From a multivariate logistic regression model, systolic BP ≥130 mm Hg was associated with race-ethnicity (p <0.0001), gender (p = 0.0001), insurance (p <0.0001), attribution with a primary care physician (p = 0.0001). Non-Hispanic Blacks (vs non-Hispanic Whites odds ratio [OR] 1.38, 1.28 to 1.48), women (OR 1.12, 1.06 to 1.19), and uninsured patients (vs privately insured OR 1.43, 1.20 to 1.72) had a higher risk of systolic BP ≥130 mm Hg; patients with primary care physician attribution had a lower risk of systolic BP ≥130 mm Hg (OR 0.87, 0.81 to 0.94). Similar results were found with the outcome BP ≥130/80 mm Hg. Overall, further efforts are needed to optimize treatment in hypertensive patients with HF and improve health equity across patient communities.

Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Prevalence and Correlates of Uncontrolled Hypertension, Persistently Uncontrolled Hypertension, and Hypertensive Crisis at a Healthcare System.

BACKGROUND: Uncontrolled hypertension significantly increases risk of cardiovascular disease and death. This study examined the prevalence of uncontrolled hypertension, persistently uncontrolled hypertension, and hypertensive crisis and factors associated with these outcomes in a real-world patient cohort. METHODS: Electronic medical records from a large healthcare system in North Carolina were used to identify adults with uncontrolled hypertension (last ambulatory blood pressure [BP] measurement ≥140/90); persistently uncontrolled hypertension (≥2 ambulatory BP measurements with all readings ≥140/90); and hypertensive crisis (any BP reading ≥180/120) in 2019. Generalized linear mixed models tested the association between patient and provider characteristics and each outcome. RESULTS: The study cohort included 213,836 patients (mean age 63.1 (±14.0) years, 55.5% female, 70.8% white). Of these, 29.7% and 13.1% had uncontrolled hypertension and hypertensive crisis, respectively. Among those experiencing hypertensive crisis, >50% did not have uncontrolled hypertension. Of the 171,061 patients with ≥2 BP measurements, 5.9% had persistently uncontrolled hypertension. The likelihood of uncontrolled hypertension, persistently uncontrolled hypertension, and hypertensive crisis was higher in patients with black race (vs. white), self-pay (vs. private), prior emergency room visit, and no attributed primary care provider. Readings taken in the evening (vs. morning) and at specialty (vs. primary care) practices were more likely to meet thresholds for uncontrolled hypertension and hypertensive crisis. CONCLUSIONS: Hypertension control remains a significant challenge in healthcare. Health systems may benefit from segmenting their patient population based on factors such as race, prior healthcare use, and timing of BP measurement to prioritize outreach and intervention.

Concordance between clinical outcomes in the Systolic Blood Pressure Intervention Trial and in the electronic health record.

BACKGROUND: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied. METHODS: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data. RESULTS: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment. CONCLUSIONS: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives.

Age-related decreases in global metacognition are independent of local metacognition and task performance.

Metacognition refers to a capacity to reflect on and control other cognitive processes, commonly quantified as the extent to which confidence tracks objective performance. There is conflicting evidence about how "local" metacognition (monitoring of individual judgments) and "global" metacognition (estimates of self-performance) change across the lifespan. Additionally, the degree to which metacognition generalises across cognitive domains may itself change with age due to increased experience with one's own abilities. Using a gamified suite of performance-controlled memory and visual perception tasks, we measured local and global metacognition in an age-stratified sample of 304 healthy volunteers (18-83 years; N = 50 in each of 6 age groups). We calculated both local and global metrics of metacognition and quantified how and whether domain-generality changes with age. First-order task performance was stable across the age range. People's global self-performance estimates and local metacognitive bias decreased with age, indicating overall lower confidence in performance. In contrast, local metacognitive efficiency was spared in older age and remained correlated across the two cognitive domains. A stability of local metacognition indicates distinct mechanisms contributing to local and global metacognition. Our study reveals how local and global metacognition change across the lifespan and provide a benchmark against which disease-related changes in metacognition can be compared.

The spectrum of functional tic-like behaviours: Data from an international registry.

BACKGROUND AND PURPOSE: Between 2019 and 2022, there was a marked rise in adolescents/young adults seeking urgent help for functional tic-like behaviours (FTLBs). Given the global scale of this phenomenon, we aimed to pool cases from different institutions in an international registry to better characterize this spectrum and facilitate future longitudinal observation. METHODS: An international collaborative group from 10 tertiary referral centres for tic disorders collected retrospective data on FTLB patients who sought specialists' attention between the last quarter of 2019 and June 2022. An audit procedure was used for collection of data, which comprised demographics, course of presentation and duration, precipitating and predisposing factors, phenomenology, comorbidities, and pharmacological treatment outcome. RESULTS: During the study period, we collected data on 294 patients with FTLBs, 97% of whom were adolescents and young adults and 87% of whom were female. FTLBs were found to have a peak of severity within 1 month in 70% of patients, with spontaneous remissions in 20%, and a very high frequency of complex movements (85%) and vocalizations (81%). Less than one-fifth of patients had pre-existing primary tic disorder, 66% had comorbid anxiety disorders, 28% comorbid depressive disorders, 24% autism spectrum disorder and 23% attention deficit/hyperactivity disorder. Almost 60% explicitly reported exposure to tic-related social media content. The vast majority of pharmacologically treated patients did not report benefit with tic-suppressing medications. CONCLUSIONS: Our data from the largest multicentre registry of FTLBs to date confirm substantial clinical differences from primary tic disorders. Social modelling was the most relevant contributing factor during the pandemic. Future longitudinal analyses from this database may help understand treatment approaches and responsiveness.

Evaluating Racial/Ethnic Differences in Care Escalation Among COVID-19 Patients in a Home-Based Hospital.

The novel coronavirus disease 2019 (COVID-19) has infected over 414 million people worldwide with 5.8 million deaths, as of February 2022. Telemedicine-based interventions to expand healthcare systems' capacity and reduce infection risk have rapidly increased during the pandemic, despite concerns regarding equitable access. Atrium Health Hospital at Home (AH-HaH) is a home-based program that provides advanced, hospital-level medical care and monitoring for patients who would otherwise be hospitalized in a traditional setting. Our retrospective cohort study of positive COVID-19 patients who were admitted to AH-HaH aims to investigate whether the rate of care escalation from AH-HaH to traditional hospitalization differed based on patients' racial/ethnic backgrounds. Logistic regression was used to examine the association between care escalation within 14 days from index AH-HaH admission and race/ethnicity. We found approximately one in five patients receiving care for COVID-19 in AH-HaH required care escalation within 14 days. Odds of care escalation were not significantly different for Hispanic or non-Hispanic Blacks compared to non-Hispanic Whites. However, secondary analyses showed that both Hispanic and non-Hispanic Black patients were younger and with fewer comorbidities than non-Hispanic Whites. The study highlights the need for new care models to vigilantly monitor for disparities, so that timely and tailored adaptations can be implemented for vulnerable populations.

Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study.

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.

Metacognition in functional cognitive disorder.

Functional cognitive disorder is common but underlying mechanisms remain poorly understood. Metacognition, an individual's ability to reflect on and monitor cognitive processes, is likely to be relevant. Local metacognition refers to an ability to estimate confidence in cognitive performance on a moment-to-moment basis, whereas global metacognition refers to long-run self-evaluations of overall performance. Using a novel protocol comprising task-based measures and hierarchical Bayesian modelling, we compared local and global metacognitive performance in individuals with functional cognitive disorder. Eighteen participants with functional cognitive disorder (mean age = 49.2 years, 10 males) were recruited to this cross-sectional study. Participants completed computerized tasks that enabled local metacognitive efficiency for perception and memory to be measured using the hierarchical meta-d' model within a signal detection theory framework. Participants also completed the Multifactorial Memory Questionnaire measuring global metacognition, and questionnaires measuring anxiety and depression. Estimates of local metacognitive efficiency were compared with those estimated from two control groups who had undergone comparable metacognitive tasks. Global metacognition scores were compared with the existing normative data. A hierarchical regression model was used to evaluate associations between global metacognition, depression and anxiety and local metacognitive efficiency, whilst simple linear regressions were used to evaluate whether affective symptomatology and local metacognitive confidence were associated with global metacognition. Participants with functional cognitive disorder had intact local metacognition for perception and memory when compared with controls, with the 95% highest density intervals for metacognitive efficiency overlapping with the two control groups in both cognitive domains. Functional cognitive disorder participants had significantly lower global metacognition scores compared with normative data; Multifactorial Memory Questionnaire-Ability subscale (t = 6.54, P < 0.0001) and Multifactorial Memory Questionnaire-Satisfaction subscale (t = 5.04, P < 0.0001). Mood scores, global metacognitive measures and metacognitive bias were not significantly associated with local metacognitive efficiency. Local metacognitive bias [ß = -0.20 (SE = 0.09), q = 0.01] and higher depression scores as measured by the Patient Health Questionnaire-9 [ß = -1.40 (SE = 2.56), q = 0.01] were associated with the lower global metacognition scores. We show that local metacognition is intact, whilst global metacognition is impaired, in functional cognitive disorder, suggesting a decoupling between the two metacognitive processes. In a Bayesian model, an aberrant prior (impaired global metacognition), may override bottom-up sensory input (intact local metacognition), giving rise to the subjective experience of abnormal cognitive processing. Future work should further investigate the interplay between local and global metacognition in functional cognitive disorder.

Effect of a Multicomponent Sepsis Transition and Recovery Program on Mortality and Readmissions After Sepsis: The Improving Morbidity During Post-Acute Care Transitions for Sepsis Randomized Clinical Trial.

OBJECTIVES: To evaluate whether a nurse navigator-led, multicomponent Sepsis Transition And Recovery program improves 30-day mortality and readmission outcomes after sepsis hospitalization. DESIG: n: Multisite pragmatic randomized clinical trial. SETTING: Three hospitals in North Carolina from January 2019 to March 2020. PATIENTS: Eligible patients hospitalized for suspected sepsis and deemed high-risk for mortality or readmission by validated internal risk models. INTERVENTIONS: Patients were randomized to receive usual care alone (i.e., routine transition support, outpatient care; n = 342) or additional Sepsis Transition And Recovery support (n = 349). The 30-day intervention involved a multicomponent transition service led by a nurse navigator through telephone and electronic health record communication to facilitate best practice postsepsis care strategies during and after hospitalization including: postdischarge medication review, evaluation for new impairments or symptoms, monitoring comorbidities, and palliative care approach when appropriate. Clinical oversight was provided by a Hospital Medicine Transition Services team. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of mortality or hospital readmission at 30 days. Logistic regression models were constructed to evaluate marginal and conditional odds ratios (adjusted for prognostic covariates: age, comorbidity, and organ dysfunction at enrollment). Among 691 randomized patients (mean age = 63.7 ± 15.1 yr; 52% female), a lower percentage of patients in the Sepsis Transition And Recovery group experienced the primary outcome compared with the usual care group (28.7% vs 33.3%; risk difference, 4.7%; odds ratio, 0.80; 95% CI, 0.58-1.11; adjusted odds ratio, 0.80; 95% CI, 0.64-0.98). There were 74 deaths (Sepsis Transition And Recovery: 33 [9.5%] vs usual care: 41 [12.0%]) and 155 rehospitalizations (Sepsis Transition And Recovery: 71 [20.3%] vs usual care: 84 [24.6%]). CONCLUSIONS: In a multisite randomized clinical trial of patients hospitalized with sepsis, patients provided with a 30-day program using a nurse navigator to provide best practices for postsepsis care experienced a lower proportion of either mortality or rehospitalization within 30 days after discharge. Further research is needed to understand the contextual factors associated with successful implementation.

Paediatric tic-like presentations during the COVID-19 pandemic.

BACKGROUND AND AIM: Clinical centres have seen an increase in tic-like movements during the COVID-19 pandemic. A series of children and adolescents are described. METHODS: A retrospective chart review of 34 consecutive paediatric patients presenting with sudden onset tic-like movements, seen over 6 months. RESULTS: 94% of patients were female, with an average age of sudden onset or increase of tic-like movements of 13.7 years. 44% had a previous diagnosis of tics, and 47% initially presented to an emergency department. Comorbid psychiatric and neurodevelopmental disorders were reported in 91% with 68% reporting anxiety. CONCLUSION: We highlight a dramatic presentation of sudden onset functional tic-like movements in predominantly female adolescents to help inform identification and management. There is need to research the neurobiological underpinnings and environmental exacerbating factors leading to these presentations and to explore effective therapeutic strategies.

Forecasting COVID-19 Hospital Census: A Multivariate Time-Series Model Based on Local Infection Incidence.

BACKGROUND: COVID-19 has been one of the most serious global health crises in world history. During the pandemic, health care systems require accurate forecasts for key resources to guide preparation for patient surges. Forecasting the COVID-19 hospital census is among the most important planning decisions to ensure adequate staffing, number of beds, intensive care units, and vital equipment. OBJECTIVE: The goal of this study was to explore the potential utility of local COVID-19 infection incidence data in developing a forecasting model for the COVID-19 hospital census. METHODS: The study data comprised aggregated daily COVID-19 hospital census data across 11 Atrium Health hospitals plus a virtual hospital in the greater Charlotte metropolitan area of North Carolina, as well as the total daily infection incidence across the same region during the May 15 to December 5, 2020, period. Cross-correlations between hospital census and local infection incidence lagging up to 21 days were computed. A multivariate time-series framework, called the vector error correction model (VECM), was used to simultaneously incorporate both time series and account for their possible long-run relationship. Hypothesis tests and model diagnostics were performed to test for the long-run relationship and examine model goodness of fit. The 7-days-ahead forecast performance was measured by mean absolute percentage error (MAPE), with time-series cross-validation. The forecast performance was also compared with an autoregressive integrated moving average (ARIMA) model in the same cross-validation time frame. Based on different scenarios of the pandemic, the fitted model was leveraged to produce 60-days-ahead forecasts. RESULTS: The cross-correlations were uniformly high, falling between 0.7 and 0.8. There was sufficient evidence that the two time series have a stable long-run relationship at the .01 significance level. The model had very good fit to the data. The out-of-sample MAPE had a median of 5.9% and a 95th percentile of 13.4%. In comparison, the MAPE of the ARIMA had a median of 6.6% and a 95th percentile of 14.3%. Scenario-based 60-days-ahead forecasts exhibited concave trajectories with peaks lagging 2 to 3 weeks later than the peak infection incidence. In the worst-case scenario, the COVID-19 hospital census can reach a peak over 3 times greater than the peak observed during the second wave. CONCLUSIONS: When used in the VECM framework, the local COVID-19 infection incidence can be an effective leading indicator to predict the COVID-19 hospital census. The VECM model had a very good 7-days-ahead forecast performance and outperformed the traditional ARIMA model. Leveraging the relationship between the two time series, the model can produce realistic 60-days-ahead scenario-based projections, which can inform health care systems about the peak timing and volume of the hospital census for long-term planning purposes.

Experiences of assessing mental capacity in England and Wales: A large-scale survey of professionals.

Background: The Mental Capacity Act (2005) of England and Wales described in statute a test to determine whether a person lacked the "mental capacity" to make a particular decision. No large-scale survey has explored experiences of capacity assessment across professional groups. Methods: We administered an opportunistic self-report questionnaire survey of professionals who undertake capacity assessments in England and Wales (n= 611). Topics of interest included; how often and where capacity assessment took place, self-ratings of competency and challenges experienced in assessment, use of psychological testing and concerns about undue influence. We analysed the quantitative responses using a mixed-methods approach using regression methods for the quantitative ratings and a thematic analysis for qualitative data. Results: Our sample included 307/611 (50.2%), social workers, 89/611 (14.6%) psychiatrists, 62/611 (10.1%) nurses, 46/611 (7.5%) clinical psychologists, 30/611 (4.9%) doctors from other medical specialties, 12/611 (2.0%) speech and language therapists and 8/611 (1.3%) solicitors. 53% of these professionals undertook more than 25 capacity assessments per year, with psychiatrists, social workers and nurses undertaking them the most frequently. Most professionals reported high self-ratings of confidence in their assessment skills, although non-psychiatrist doctors rated themselves significantly lower than other groups (p< .005). Most professionals (77.1%) were at least moderately concerned about undue influence, with people with dementia and learning disabilities and older adults considered to be the most at risk. Qualitative themes for challenges in capacity assessment included inter-disciplinary working, complicated presentations and relational issues such as interpersonal influence. Requests for support mainly focused on practical issues. Conclusions: Most professionals feel confident in their ability to assess capacity but note substantial challenges around practical and relational issues. Undue influence is a particularly common concern amongst professionals when working with service users with dementia and learning disabilities which public services and policy makers need to be mindful of.

Protocol for a two-arm pragmatic stepped-wedge hybrid effectiveness-implementation trial evaluating Engagement and Collaborative Management to Proactively Advance Sepsis Survivorship (ENCOMPASS).

BACKGROUND: Sepsis survivors experience high morbidity and mortality, and healthcare systems lack effective strategies to address patient needs after hospital discharge. The Sepsis Transition and Recovery (STAR) program is a navigator-led, telehealth-based multicomponent strategy to provide proactive care coordination and monitoring of high-risk patients using evidence-driven, post-sepsis care tasks. The purpose of this study is to evaluate the effectiveness of STAR to improve outcomes for sepsis patients and to examine contextual factors that influence STAR implementation. METHODS: This study uses a hybrid type I effectiveness-implementation design to concurrently test clinical effectiveness and gather implementation data. The effectiveness evaluation is a two-arm, pragmatic, stepped-wedge cluster randomized controlled trial at eight hospitals in North Carolina comparing clinical outcomes between sepsis survivors who receive Usual Care versus care delivered through STAR. Each hospital begins in a Usual Care control phase and transitions to STAR in a randomly assigned sequence (one every 4 months). During months that a hospital is allocated to Usual Care, all eligible patients will receive usual care. Once a hospital transitions to STAR, all eligible patients will receive STAR during their hospitalization and extending through 90 days from discharge. STAR includes centrally located nurse navigators using telephonic counseling and electronic health record-based support to facilitate best-practice post-sepsis care strategies including post-discharge review of medications, evaluation for new impairments or symptoms, monitoring existing comorbidities, and palliative care referral when appropriate. Adults admitted with suspected sepsis, defined by clinical criteria for infection and organ failure, are included. Planned enrollment is 4032 patients during a 36-month period. The primary effectiveness outcome is the composite of all-cause hospital readmission or mortality within 90 days of discharge. A mixed-methods implementation evaluation will be conducted before, during, and after STAR implementation. DISCUSSION: This pragmatic evaluation will test the effectiveness of STAR to reduce combined hospital readmissions and mortality, while identifying key implementation factors. Results will provide practical information to advance understanding of how to integrate post-sepsis management across care settings and facilitate implementation, dissemination, and sustained utilization of best-practice post-sepsis management strategies in other heterogeneous healthcare delivery systems. TRIAL REGISTRATION: NCT04495946 . Submitted July 7, 2020; Posted August 3, 2020.

Realizing a learning health system through process, rigor and culture change.

While many healthcare organizations strive to achieve the patient care benefits of being a learning health system (LHS), myriad challenges stand in the way of successful implementation. The reality of creating a true LHS requires top-to-bottom commitment to culture change with the necessary vision, leadership, and investment. The Center for Outcomes Research and Evaluation (CORE) is a multidisciplinary research unit embedded within a large, vertically integrated healthcare system in the southeastern United States. We used a two-pronged approach to: a) methodically recruit a team of experts, while generating early wins that demonstrated real success; and b) build relationships and buy-in across organizational leadership. Building out a team with diverse expertise created the ability to deploy pragmatic, data-driven research designs that fit seamlessly into real-world care delivery, resulting in agile study execution that aligns with health system timelines. Case study examples from hospital readmissions and antibiotic stewardship illustrate how our LHS operationalizes practice-informed research and research-informed practice. Lessons from this experience can serve as a blueprint for other healthcare systems or networks seeking to expand the promise of the LHS framework to improve health for patients and communities.