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Objective: Reoperation after aortic root replacement (ARR) is associated with increased operative risk and complexity. This study evaluated clinical outcomes and reoperation rates in patients undergoing ARR. Methods: From 2004 to 2021, 2700 adult patients underwent an ARR in a 2-institution database. Among 2542 surviving patients, 705 patients who had a history of previous cardiac surgery as well as 11 patients who underwent transcatheter aortic valve replacement after index ARR were excluded. Among the finalized cohort of 1826 patients, 88 (4.8%) underwent a reoperation (REDO) on the aortic valve or proximal aorta (root/ascending) a mean of 3.1 years after index ARR whereas 1738 (95%) did not undergo reoperation (no-REDO). A subgroup analysis was performed among those undergoing reoperation by indication including valve dysfunction (48%), endocarditis/graft infection (33%), and aortic aneurysm/dissection/rupture (12%). Reoperative indication was unknown in 6 patients (7%). Results: The REDO group was younger at time of index ARR (52 vs 58 years, P

Abstract Background Missing data in confounding variables present a frequent challenge in generating evidence using real-world data, including electronic health records (EHR). Our objective was to apply a recently published toolkit for characterizing missing data patterns and based on the toolkit results about likely missingness mechanisms, illustrate the decision-making process for analyses in an empirical case example. Methods We utilized the Structural Missing Data Investigations (SMDI) toolkit to characterize missing data patterns in the context of a pharmacoepidemiology study comparing cardiovascular outcomes of initiating sodium-glucose-cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase‐4 inhibitors (DPP‐4i) among older adults. The study used a linked EHR-Medicare claims dataset from Duke Health patients (2015–2017), focusing on partially observed confounders from EHR data (HbA1c lab and body mass index [BMI] values). Our analysis incorporated SMDI's descriptive functions and diagnostic tests to explore missingness patterns and determine missingness mitigation approaches. We used findings from these investigations to inform estimation of adjusted hazard ratios comparing the two classes of medications. Results High levels of missingness were noted for important confounding variables including HbA1c (63.6%) and BMI (16.5%). Diagnostic tests resulted in output that described: 1) the distributions of patient characteristics, exposure, and outcome between patients with or without an observed value of the partially observed covariate, 2) the ability to predict missingness based on observed covariates, and 3) estimate if the missingness of a partially observed covariate is differential with respect to the outcome. There was evidence that missingness could be sufficiently described using observed data, which allowed multiple imputation by chained equations using random forests to address missing confounder data in estimating treatment effects. Multiple imputation resulted in improved alignment of effect estimates with previous studies. Conclusions We were able to demonstrate the practical application of the SMDI toolkit in a real-world setting. Application of the SMDI toolkit and the resulting insights of potential missingness patterns can inform the choice of appropriate analytic methods and increase transparency of research methods in handling missing data. This type of approach can inform analytic decision making and may increase our ability to generate evidence from real-world data.

Hybrid repair of complex aortic arch disease typically requires aortic debranching to create a proximal landing zone for completion arch endografting. Despite advances in endograft technology, physician-modified endografting may be required to customize a prosthesis for challenging anatomy. We present a case of a complex distal arch aneurysm after a prior coarctation repair with a pediatric interposition graft several decades earlier, treated with hybrid repair by double transposition for arch debranching and physician-modified arch endografting for complete aneurysm exclusion.

Background: Despite clear associations between arrhythmia burden and cardiovascular risk, clinical risk scores that predict cardiovascular events do not incorporate individual-level arrhythmia characteristics from long-term continuous monitoring (LTCM). Objectives: This study evaluated the performance of risk models that use data from LTCM and patient claims for prediction of heart failure (HF) and ischemic stroke. Methods: We retrospectively analyzed features extracted from up to 14 days of LTCM electrocardiogram (ECG) data linked to patient-level claims data for 320,974 Medicare beneficiaries who underwent ZioXT ambulatory monitoring. We created predictive models for HF hospitalization, stroke hospitalization, and new-onset HF within 1 year using LASSO Cox regression for variable selection among ambulatory ECG variables and components of the CHA2DS2-VASc score. Results: A model that included components of the CHA2DS2-VASc and all ambulatory ECG variables had greater discrimination for HF hospitalization (C-statistic 0.85, 95% CI: 0.84-0.86) than the CHA2DS2-VASc (C-statistic 0.73, 95% CI: 0.72-0.74), but performed similarly to the CHA2DS2-VASc for prediction of stroke hospitalization (C-statistic 0.75 [95% CI: 0.74-0.77] vs 0.71 [95% CI: 0.70-0.72], respectively). Atrial fibrillation was associated with greater risk in the most predictive models (HF hospitalization, HR: 1.53 [95% CI: 1.35-1.72]; stroke hospitalization, HR: 1.58 [95% CI: 1.30-1.93]), and premature ventricular couplets were associated with greater risk of HF hospitalization (HR: 1.54, 95% CI: 1.43-1.65). Conclusions: The CHA2DS2-VASc performed modestly for prediction of stroke and HF events; predictive ability improved significantly with addition of LTCM ECG covariates. The presence of atrial fibrillation and ventricular ectopy on 14-day LTCM were strongly associated with HF events.

Background Understanding the relationship between neighborhood environment and cardiovascular outcomes is important to achieve health equity and implement effective quality strategies. We conducted a population‐based cohort study to determine the association of neighborhood socioeconomic deprivation and 30‐day mortality and readmission rate for patients admitted with common cardiovascular conditions. Methods and Results We examined claims data from fee‐for‐service Medicare beneficiaries aged ≥65 years between 2017 and 2019 admitted for heart failure, valvular heart disease, ischemic heart disease, or cardiac arrhythmias. The primary exposure was the Area Deprivation Index; outcomes were 30‐day all‐cause death and unplanned readmission. More than 2 million admissions were included. After sequential adjustment for patient characteristics (demographics, dual eligibility, comorbidities), area health care resources (primary care clinicians, specialists, and hospital beds per capita), and admitting hospital characteristics (ownership, size, teaching status), there was a dose‐dependent association between neighborhood socioeconomic deprivation and 30‐day mortality rate for all conditions. In the fully adjusted model for death, estimated effect sizes of residence in the most disadvantaged versus least disadvantaged neighborhoods ranged from adjusted odds ratio 1.29 (95% CI, 1.22–1.36) for the heart failure group to adjusted odds ratio 1.63 (95% CI, 1.36–1.95) for the valvular heart disease group. Neighborhood deprivation was associated with increased adjusted 30‐day readmission rates, with estimated effect sizes from adjusted odds ratio 1.09 (95% CI, 1.05–1.14) for heart failure to adjusted odds ratio 1.19 (95% CI, 1.13–1.26) for arrhythmia. Conclusions Neighborhood socioeconomic disadvantage was associated with 30‐day mortality rate and readmission for patients admitted with common cardiovascular conditions independent of individual demographics, socioeconomic status, medical risk, care access, or admitting hospital characteristics.

Gastric malabsorptive conditions may prevent patients from deriving benefit from orally administered medications intended for enteric absorption. While malabsorption is an increasingly common issue, current data on alternative oral options for agitation in these patients are very sparse. Sublingual (SL) asenapine is absorbed transmucosally, bypassing gut absorption, making it a viable consideration. We report on three patients, one with short bowel syndrome, one with viral gastritis, and one with aortic dissection who were trialed on SL asenapine for agitation after failing alternative antipsychotics. Two of these patients had an extensive history of psychiatric admissions for bipolar disorder and substance-induced psychosis. All three patients had significant reductions in agitation within 1–5 days, with no reported adverse effects. However, benefit of SL asenapine was hindered in two of these patients as they began inappropriately swallowing the medication, reducing bioavailability to nil. Clinicians should consider the use of SL asenapine for medically complex agitated patients where gastric absorption is questionable. There is an urgent need for guidelines on this matter, as well as more, alternative dosage forms for various medications that may help with agitation in this population.

Objective: The impact of previous aortic root replacement (True-Redo) versus any previous operation (Any-Redo) on outcomes after reoperative aortic root replacement (redo-ROOT) is largely unknown. In this first multi-institutional study, the clinical impact True-Redo versus Any-Redo in the setting of redo-ROOT was reviewed. Methods: From 2004 to 2021, 822 patients underwent redo-ROOT at 2 major academic centers: 638 Any-Redo and 184 True-Redo. Matching based on preoperative demographics and concomitant operations resulted in 174 matched pairs. An independent risk factor analysis was performed to determine risk factors for early and late mortality. Results: Patients in the True-Redo group were younger, at 49.9 ± 15.1 versus 55.3 ± 14.7 years, P .05. Median cardiopulmonary bypass time (P

Objective: Redo aortic surgery has a higher risk of morbidity and mortality because it is technically complex due to mediastinal adhesions, infection, and previously implanted prostheses. In this study, we sought to benchmark our single-center experience comparing outcomes in patients undergoing aortic surgery after 1 versus multiple previous cardiac operations. Methods: Between 2004 and 2019, 429 patients underwent redo aortic surgery. They were classified as aortic surgery after 1 previous surgery (first redo surgery, n = 360) and aortic surgery after 2 or more (multiple) previous surgeries (multiple redo surgery, n = 69). Postoperative outcomes and long-term survival were compared, and risk factors for mortality were identified. Results: Thirty-day mortality was lower in first redo surgery compared with multiple redo surgery (12.3% vs 21.7%, P = .03). Age, cardiopulmonary bypass time, intra-aortic balloon pump use, postoperative cerebrovascular accident, absence of postoperative atrial fibrillation, intra-aortic balloon pump, and multiple redo surgery were independent predictors of 30-day mortality. Long-term survival was similar at 15 years. Patients who received first redo surgery were older (57.9 ± 14.0 years vs 50.3 ± 15.8 years, P = .0001) and had a higher incidence of hypertension (84.7% vs 73.9%, P = .02), whereas patients who received multiple redo surgery had a higher incidence of cerebrovascular disease (31.9% vs 20.3%, P = .03). Aortic valve replacement was the most common previous operation with higher incidence in multiple redo surgery. Incidence of previous aortic surgery was similar. Cardiopulmonary bypass (246 ± 67.3 minutes vs 219.9 ± 57.5 minutes, P = .009) and crossclamp times (208.2 ± 51.8 vs 181.9 ± 50.8 minutes, P = .004) were longer in multiple redo surgery. Incidence of reentry injury and balloon pump insertion were similar. Extracorporeal membrane oxygenation use was higher in multiple redo surgery. Postoperative complications occurred at similar rates, except for higher incidence of dialysis in multiple redo surgery (14.5% vs 7.2%, P = .04). Conclusions: Multiple redo aortic procedures have a higher morbidity and mortality compared with first redo aortic procedures, with linearly increasing short-term mortality risk but similar long-term survival with the number of redo procedures.

Abstract Background Despite great promise, trials that ascertain patient clinical data from electronic health records (EHR), referred to here as “EHR-sourced” trials, are limited by uncertainty about how existing trial sites and infrastructure can be best used to operationalize study goals. Evidence is needed to support the practical use of EHRs in contemporary clinical trial settings. Main text We describe a demonstration project that used EHR data to complement data collected for a contemporary multi-center pharmaceutical industry outcomes trial, and how a central coordinating center supported participating sites through the technical, governance, and operational aspects of this type of activity. We discuss operational considerations related to site selection, data extraction, site performance, and data transfer and quality review, and we outline challenges and lessons learned. We surveyed potential sites and used their responses to assess feasibility, determine the potential capabilities of sites and choose an appropriate data extraction strategy. We designed a flexible, multimodal approach for data extraction, enabling each site to either leverage an existing data source, create a new research datamart, or send all data to the central coordinating center to produce the requisite data elements. We evaluated site performance, as reflected by the speed of contracting and IRB approval, total patients enrolled, enrollment yield, data quality, and compared performance by data collection strategy. Conclusion While broadening the type of sites able to participate in EHR-sourced trials may lead to greater generalizability and improved enrollment, sites with fewer technical resources may require additional support to participate. Central coordinating center support is essential to facilitate the execution of operational processes. Future work should focus on sharing lessons learned and creating reusable tools to facilitate participation of heterogeneous trial sites.

Abstract Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 – 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

Abstract Background To determine if neighborhood socioeconomic deprivation independently predicts 30-day mortality and readmission for patients with sepsis or critical illness after adjusting for individual poverty, demographics, comorbidity burden, access to healthcare, and characteristics of treating healthcare facilities. Methods We performed a nationwide study of United States Medicare beneficiaries from 2017 to 2019. We identified hospitalized patients with severe sepsis and patients requiring prolonged mechanical ventilation, tracheostomy, or extracorporeal membrane oxygenation (ECMO) through Diagnosis Related Groups (DRGs). We estimated the association between neighborhood socioeconomic deprivation, measured by the Area Deprivation Index (ADI), and 30-day mortality and unplanned readmission using logistic regression models with restricted cubic splines. We sequentially adjusted for demographics, individual poverty, and medical comorbidities, access to healthcare services; and characteristics of treating healthcare facilities. Results A total of 1,526,405 admissions were included in the mortality analysis and 1,354,548 were included in the readmission analysis. After full adjustment, 30-day mortality for patients was higher for those from most-deprived neighborhoods (ADI 100) compared to least deprived neighborhoods (ADI 1) for patients with severe sepsis (OR 1.35 95% [CI 1.29–1.42]) or with prolonged mechanical ventilation with or without sepsis (OR 1.42 [95% CI 1.31, 1.54]). This association was linear and dose dependent. However, neighborhood socioeconomic deprivation was not associated with 30-day unplanned readmission for patients with severe sepsis and was inversely associated with readmission for patients requiring prolonged mechanical ventilation with or without sepsis. Conclusions A strong association between neighborhood socioeconomic deprivation and 30-day mortality for critically ill patients is not explained by differences in individual poverty, demographics, measured baseline medical risk, access to healthcare resources, or characteristics of treating hospitals.

Abstract Background Acute care inpatient admissions outside of psychiatric facilities have been increasingly identified as a critical touchpoint for opioid use disorder (OUD) treatment. We sought to describe non-opioid overdose hospitalizations with documented OUD and examine receipt of post-discharge outpatient buprenorphine. Methods We examined acute care hospitalizations with an OUD diagnosis in any position within US commercially-insured adults age 18–64 years (IBM MarketScan claims, 2013–2017), excluding opioid overdose diagnoses. We included individuals with ≥ 6 months of continuous enrollment prior to the index hospitalization and ≥ 10 days following discharge. We described demographic and hospitalization characteristics, including outpatient buprenorphine receipt within 10 days of discharge. Results Most (87%) hospitalizations with documented OUD did not include opioid overdose. Of 56,717 hospitalizations (49,959 individuals), 56.8% had a primary diagnosis other than OUD, 37.0% had documentation of an alcohol-related diagnosis code, and 5.8% end in a self-directed discharge. Where opioid use disorder was not the primary diagnosis, 36.5% were due to other substance use disorders, and 23.1% were due to psychiatric disorders. Of all non-overdose hospitalizations who had prescription medication insurance coverage and who were discharged to an outpatient setting (n = 49, 237), 8.8% filled an outpatient buprenorphine prescription within 10 days of discharge. Conclusions Non-overdose OUD hospitalizations often occur with substance use disorders and psychiatric disorders, and very few are followed by timely outpatient buprenorphine. Addressing the OUD treatment gap during hospitalization may include implementing medication for OUD for inpatients with a broad range of diagnoses.

Background In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. Methods and Results In the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow‐up: 26.2 months; interquartile range: 19.0–34.9 months). Median age was 67.6 years (interquartile range: 60.7–73.6 years). Among participants aged 0.05 for all). Conclusions Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Brain imaging with a high-spatiotemporal resolution is crucial for accurate brain-function mapping. Electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI) are two popular neuroimaging modalities with complementary features that record brain function with high temporal and spatial resolution, respectively. One popular non-invasive way to obtain data with both high spatial and temporal resolutions is to combine the fMRI activation map and EEG data to improve the spatial resolution of the EEG source localization. However, using the whole fMRI map may cause spurious results for the EEG source localization, especially for deep brain regions. Considering the head's conductivity, deep regions' sources with low activity are unlikely to be detected by the EEG electrodes at the scalp. In this study, we use fMRI's high spatial-frequency component to identify the local high-intensity activations that are most likely to be captured by the EEG. The 3D Empirical Mode Decomposition (3D-EMD), a data-driven method, is used to decompose the fMRI map into its spatial-frequency components. Different validation measurements for EEG source localization show improved performance for the EEG inverse-modeling informed by the fMRI's high-frequency spatial component compared to the fMRI-informed EEG source-localization methods. The level of improvement varies depending on the voxels' intensity and their distribution. Our experimental results also support this conclusion.

# Background Many medical devices in pediatric and newborn intensive care units can potentially expose healthcare workers (HCWs) and others to transmission of respiratory and other viruses and bacteria. Such fomites include ventilators, nebulizers, and monitoring equipment. # Approach We report the general, novel approach we have taken to identify and mitigate these risks and to protect HCWs, visitors and patients from exposure while maintaining the optimal performance of such respiratory equipment. # Findings The approach combined a high level of personal protective equipment (PPE), strict hand hygiene, air filtration and air conditioning and other relevant viral risk mitigation guidelines. This report describes the experiences from the SARS-CoV-2 pandemic to provide a reference framework that can be applied generally. The steps we took consisted of auditing our equipment and processes to identify risk through sources of potentially contaminated gas that may contain aerosolized virus, seeking advice and liaising with suppliers/manufacturers, devising mitigation strategies using indirect and direct approaches (largely filtering), performing tests on equipment to verify proper function and the absence of negative impacts and the development and implementation of relevant procedures and practices. We had a multidisciplinary team to guide the process. We monitored daily for hospital-acquired infections among staff caring for SARS-CoV-2 patients. # Conclusion Our approach was successful as we have continued to offer optimal intensive care to our patients, and we did not find any healthcare worker who was infected through the course of caring for patients at the bedside. The lessons learnt will be of benefit to future local outbreaks or pandemics.

Dilatation of the thoracic or abdominal aorta can progress to dissection or rupture with significant associated morbidity and mortality. Aortic disease remains a treatable contributor to mortality in the US and its burden is likely underestimated. Recent clinical studies have uncovered sex and gender distinctions in the epidemiology, pathophysiology, and outcomes of aortic disease. Despite this, there has been little progress in the application of these findings to clinical practice. Improved understanding of the sex-specific mechanisms of aortic disease may inform personalized indications for elective repair and thus reduce the morbidity of aortic catastrophe. The objective of this review is to summarize known clinical and biological sex differences in both thoracic and abdominal aortic disease and highlight promising areas for future investigation.

There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive-compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course. We describe a case of a 21-year-old male with a recent diagnosis of bipolar II disorder who developed a manic episode following the ingestion of psilocybin in the form of hallucinogenic mushrooms. Given the incidence of depression in those with bipolar disorder, impulsivity, and a tendency to abuse substances associated with the illness, further research is needed into the risks of psilocybin and other psychedelic use in those with bipolar disorder.

ObjectiveTo develop a Multi-Feature-Combined (MFC) model for proof-of-concept in predicting local failure (LR) in NSCLC patients after surgery or SBRT using pre-treatment CT images. This MFC model combines handcrafted radiomic features, deep radiomic features, and patient demographic information in an integrated machine learning workflow.MethodsThe MFC model comprised three key steps. (1) Extraction of 92 handcrafted radiomic features from the GTV segmented on pre-treatment CT images. (2) Extraction of 512 deep radiomic features from pre-trained U-Net encoder. (3) The extracted handcrafted radiomic features, deep radiomic features, along with 4 patient demographic information (i.e., gender, age, tumor volume, and Charlson comorbidity index), were concatenated as a multi-dimensional input to the classifiers for LR prediction. Two NSCLC patient cohorts from our institution were investigated: (1) the surgery cohort includes 83 patients with segmentectomy or wedge resection (7 LR), and (2) the SBRT cohort includes 84 patients with lung SBRT (9 LR). The MFC model was developed and evaluated independently for both cohorts, and was subsequently compared against the prediction models based on only handcrafted radiomic features (R models), patient demographic information (PI models), and deep learning modeling (DL models). ROC with AUC was adopted to evaluate model performance with leave-one-out cross-validation (LOOCV) and 100-fold Monte Carlo random validation (MCRV). The t-test was performed to identify the statistically significant differences.ResultsIn LOOCV, the AUC range (surgery/SBRT) of the MFC model was 0.858-0.895/0.868-0.913, which was higher than the three other models: 0.356-0.480/0.322-0.650 for PI models, 0.559-0.618/0.639-0.682 for R models, and 0.809/0.843 for DL models. In 100-fold MCRV, the MFC model again showed the highest AUC results (surgery/SBRT): 0.742-0.825/0.888-0.920, which were significantly higher than PI models: 0.464-0.564/0.538-0.628, R models: 0.557-0.652/0.551-0.732, and DL models: 0.702/0.791.ConclusionWe successfully developed an MFC model that combines feature information from multiple sources for proof-of-concept prediction of LR in patients with surgical and SBRT early-stage NSCLC. Initial results suggested that incorporating pre-treatment patient information from multiple sources improves the ability to predict the risk of local failure.

BackgroundThe advent of transcatheter aortic valve replacement (TAVR) has directly impacted the lifelong management of patients with aortic valve disease. The U.S. Food and Drug Administration has approved TAVR for all surgical risk: prohibitive (2011), high (2012), intermediate (2016), and low (2019). Since then, TAVR volumes are increasing and surgical aortic valve replacements (SAVR) are decreasing. This study sought to evaluate trends in isolated SAVR in the pre- and post-TAVR eras.MethodsFrom January 2000 to June 2020, 3,861 isolated SAVRs were performed at a single academic quaternary care institution which participated in the early trials of TAVR beginning in 2007. A formal structural heart center was established in 2012 when TAVR became commercially available. Patients were divided into the pre-TAVR era (2000–2011, n = 2,426) and post-TAVR era (2012–2020, n = 1,435). Data from the institutional Society of Thoracic Surgeons National Database was analyzed.ResultsThe median age was 66 years, similar between groups. The post-TAVR group had a statistically higher rate of diabetes, hypertension, dyslipidemia, heart failure, more reoperative SAVR, and lower STS Predicted Risk of Mortality (PROM) (2.0% vs. 2.5%, p

Background Declines of the Eastern oyster, Crassostrea virginica, and its numerous ecological benefits have spurred oyster restoration initiatives. Successful restoration of a self-sustaining oyster population requires evaluating the temporal and spatial patterns of recruitment (settlement and survival) of oyster larvae in the target waterbody. Restoration of the Eastern oyster population in the Maryland Coastal Bays (MCBs), USA, a shallow lagoonal estuary, is of interest to federal, state, and non-governmental, but the location and timing of natural recruitment is not known. Methods We assessed the spatial and temporal variation in oyster larval recruitment throughout the MCBs using horizontal ceramic tiles and PVC plates. Newly settled oyster larvae (recruits) were monitored biweekly from June to September 2019 and 2020 at 12 sites in the MCBs and a comparison site in Wachapreague, Virginia. Water quality measurements collected included temperature, salinity, dissolved oxygen, pH, and turbidity. The objectives of this study were to determine (1) the most effective substrate and design for monitoring oyster recruitment, (2) the spatial and temporal distribution of oyster larval recruitment in the MCBs, and (3) patterns in oyster larval recruitment that would be applicable to other lagoonal estuaries. Results (1) Ceramic tiles were more effective than PVC plates for recruiting oyster larvae. (2) Peak settlement began during the period from late June through July, and oyster recruitment was greatest at sites closest to the Ocean City and Chincoteague inlets. (3) Areas near broodstock that have slow flushing rates to retain larvae may provide the best environments for recruitment of oysters to lagoonal estuaries. Discussion As the first study on oyster larval recruitment in the MCBs, our results provide insight into their spatial and temporal distribution, methods that can serve as a foundation for future recruitment studies in other lagoonal estuaries, and baseline data that can be used to inform stakeholders and evaluate the success of oyster restoration projects in MCBs.

BackgroundCannabis (Δ9-THC) is the most commonly consumed illicit drug. The Agricultural Improvement Act of 2018 removed hemp, a strain of Cannabis sativa, as a controlled substance. This law allowed the plant to be processed into its components, which contain

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N = 20), recent SRC youth (N = 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p = 0.032), decreased functional connectivity between the caudate and each of the pallidum (p = 0.035) and thalamus (p = 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p < 0.038); no changes were observed in recovered asymptomatic youth (N = 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N = 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p = 0.011) and reduced activity in the cerebellum (p = 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p < 0.014), reduced activity of the pallidum (p = 0.002), increased CBF in the caudate (p = 0.005), and reduced diffusivity in the central corpus callosum (p < 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome.

Abstract Background The electronic health record (EHR) contains a wealth of clinical data that may be used to streamline the identification of potential clinical trial participants. However, there is little empirical information on site-level facilitators of and barriers to optimal use of EHR systems with respect to trial recruitment. Methods We conducted qualitative focus groups and quantitative surveys as part of the EHR Ancillary Study, which is being conducted alongside the multicenter, global, Harmony Outcomes Trial comparing albiglutide to standard care for the prevention of cardiovascular events in type 2 diabetes. Subject matter experts used findings from focus groups to draft a 20-question survey examining the use of the EHR for participant identification, common site recruitment strategies, and variation in perceived barriers to optimal use of the EHR. The final survey was fielded with 446 site investigators actively enrolling participants in the main trial. Results Nearly two-thirds of respondents were study coordinators (63.2%), 23.1% were principal investigators, and 13.7% held other research roles. Approximately half of the respondents reported using the EHR to find potential trial participants. Of these, 79.4% reported using EHR searches in conjunction with other recruitment methods, including reviewing of upcoming clinic schedules (75.3%) and contacting past trial participants (71.2%). Important barriers to optimal use of the EHR included the lack of availability of certain research-focused EHR modules and limitations on the ability to contact patients cared for by other providers. Of survey respondents who did not use the EHR to find potential participants, one-quarter reported that the EHR was not accessible in their country; this finding varied from 2.6% of respondents in North America to 50% of respondents in the Asia Pacific. Conclusions While EHR screening was commonly used for recruitment in a cardiovascular outcomes trial, important technical, governance, and regulatory barriers persist. Multifaceted, scalable, and customizable strategies are needed to support the optimal use of the EHR for trial participant identification. Trial registration ClinicalTrials.gov NCT02465515. Registered on 8 June 2015

Malcolm Begg,1 J Nicole Hamblin,1 Emily Jarvis,2 Glyn Bradley,3 Stephen Mark,4 David Michalovich,5 Mark Lennon,6 Hannah E Wajdner,5 Augustin Amour,5 Robert Wilson,1 Ken Saunders,5 Rikako Tanaka,7 Saki Arai,7 Teresa Tang,8 Cedric Van Holsbeke,9 Jan De Backer,9 Wim Vos,9 Ingrid L Titlestad,10 J Mark FitzGerald,11 Kieran Killian,12 Jean Bourbeau,13 Claude Poirier,14 François Maltais,15 Anthony Cahn,1 Edith M Hessel1 1Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK; 2Biostatistics, GlaxoSmithKline R&D, Stevenage, UK; 3Computational Biology, Medicinal Science and Technology, GlaxoSmithKline, Stevenage, UK; 4Study Management, Clinical Development, GlaxoSmithKline, Mississauga, ON, Canada; 5Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK; 6Nonclinical and Translational Statistics, GlaxoSmithKline, Stevenage, UK; 7Data Management & Strategy, Clinical Development, GlaxoSmithKline, Tokyo, Japan; 8Pharma Safety, Clinical Development, GlaxoSmithKline, Brentford, Middlesex, UK; 9FLUIDDA nv, Kontich, 2550, Belgium; 10Department of Respiratory Medicine, Odense University Hospital and University of Southern Denmark, Odense, Denmark; 11Centre for Heart and Lung Health, University of British Columbia, Vancouver, BC, Canada; 12Cardiorespiratory Research Laboratory, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada; 13Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada; 14Department of Medicine, Respiratory Medicine Division, University of Montreal, Montreal, QC, Canada; 15Institut Universitaire de Cardiologie et de Pneumologie de Québe, Université Laval, Quebec City, QC, CanadaCorrespondence: Malcolm BeggRefractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, Herts, UKEmail malcolm.5.begg@gsk.comBackground: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg). Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.Results: In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD. Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients. In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals − 46, 315mL) with a probability that the true treatment ratio was > 0% (Pr(θ> 0)) of 93% was observed in AECOPD. However, FRI endpoints remained unchanged.Conclusion: We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group. We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD.Keywords: nemiralisib, sputum, transcriptomics, COPD exacerbations, PI3Kdelta

For over a decade, the team from the Aortic Institute at Yale University has worked closely with the bioengineering team of Dr. Wei Sun at Georgia Tech University. This paper presents the products of that collaboration.We provide clinical context by describing thoracic aortic dissection and its genesis as a prelude to the bioengineering findings. We discuss the genesis of aortic dissection, from the fundamental underlying genetic abnormality, through the degenerative aortic process, to the acute inciting factors and the dissection event itself. The inciting factor is usually an extreme hypertensive episode, occasioned by exertion or emotion.The bioengineering findings include the following: The aortic wall is stronger in the circumferential direction than in the longitudinal. Bicuspid aortic valve and bovine aortic arch morphology do not compromise aortic strength. Biaxial testing reveals a non-liner stress-strain response of aortic tissues. Dissected tissues become stronger over time, reflecting fibrotic connective tissue ingrowth in response to the dramatic tissue injury from the dissection event. Human aortic tissues stiffen at advanced age, in contradistinction to those of aged animals (porcine).Combining clinical and bioengineering perspectives yields a more complete and correlative understanding of the genesis of thoracic aortic dissection.

The analysis of large, multisite neuroimaging datasets provides a promising means for robust characterization of brain networks that can reduce false positives and improve reproducibility. However, the use of different MRI scanners introduces variability to the data. Managing those sources of variability is increasingly important for the generation of accurate group-level inferences. ComBat is one of the most promising tools for multisite (multiscanner) harmonization of structural neuroimaging data, but no study has examined its application to graph theory metrics derived from the structural brain connectome. The present work evaluates the use of ComBat for multisite harmonization in the context of structural network analysis of diffusion-weighted scans from the Advancing Concussion Assessment in Pediatrics (A-CAP) study. Scans were acquired on six different scanners from 484 children aged 8.00–16.99 years [Mean = 12.37 ± 2.34 years; 289 (59.7%) Male] ~10 days following mild traumatic brain injury (n = 313) or orthopedic injury (n = 171). Whole brain deterministic diffusion tensor tractography was conducted and used to construct a 90 x 90 weighted (average fractional anisotropy) adjacency matrix for each scan. ComBat harmonization was applied separately at one of two different stages during data processing, either on the (i) weighted adjacency matrices (matrix harmonization) or (ii) global network metrics derived using unharmonized weighted adjacency matrices (parameter harmonization). Global network metrics based on unharmonized adjacency matrices and each harmonization approach were derived. Robust scanner effects were found for unharmonized metrics. Some scanner effects remained significant for matrix harmonized metrics, but effect sizes were less robust. Parameter harmonized metrics did not differ by scanner. Intraclass correlations (ICC) indicated good to excellent within-scanner consistency between metrics calculated before and after both harmonization approaches. Age correlated with unharmonized network metrics, but was more strongly correlated with network metrics based on both harmonization approaches. Parameter harmonization successfully controlled for scanner variability while preserving network topology and connectivity weights, indicating that harmonization of global network parameters based on unharmonized adjacency matrices may provide optimal results. The current work supports the use of ComBat for removing multiscanner effects on global network topology.

Abstract Background Here we describe a unique case of clozapine-associated hypothermia during initial titration of this medication in an acute inpatient psychiatry setting. Only a handful of cases on this topic have been published. We discuss possible pharmacologic mechanisms supporting or refuting the propensity of clozapine to induce hypothermia, as well as risk factors for clozapine-induced hypothermia, and a comparison to clozapine-induced hyperthermia. Case presentation A 70 year-old African American female with treatment-refractory schizoaffective disorder developed hypothermia with a nadir temperature of 89 °F (31.7 °C) after 7 days on clozapine, on a total dose of 50 mg twice daily. Accompanying symptoms included bradycardia, hypotension, QTc prolongation, tachypnea, hypoxemia, and an absence of shivering. The patient was transferred to the ICU, and rewarmed within 10 h with the discontinuation of her clozapine, ziprasidone, and carvedilol. Broad spectrum antibiotics were initiated, but discontinued shortly after, as the patient had no leukocytosis, and blood cultures were negative. Discussion While hypoglycemia, hypothyroidism, sepsis, and stroke were effectively ruled out, alternative drug-disease (including chronic kidney disease), and drug-drug interactions were considered possible contributing features. Benzodiazepines, valproic acid, ziprasidone, and the numerous antihypertensive agents the patient was taking were considered as either primary or compounding factors for hypothermia. After exclusion or inclusion of these alternative causes, we calculated a score of 4 (possible) for clozapine-induced hypothermia on the Naranjo Scale. Conclusions Clozapine-induced hypothermia may occur more commonly than clinicians believe. Practitioners should be cognizant of this potentially fatal phenomenon, and monitor for temperature dysregulations while on clozapine, especially during initial titration, in those with multiple comorbid factors, and on additional medications that may contribute to hypothermia.

How COVID-19 vaccine is distributed within low- and middle-income countries has received little attention outside of equity or logistical concerns but may ultimately affect campaign impact in terms of infections, severe cases, or deaths averted. In this study we examined whether subnational (urban-rural) prioritization may affect the cumulative two-year impact on disease transmission and burden of a vaccination campaign using an agent-based model of COVID-19 in a representative COVID-19 Vaccines Global Access (COVAX) Advanced Market Commitment (AMC) setting. We simulated a range of vaccination strategies that differed by urban-rural prioritization, age group prioritization, timing of introduction, and final coverage level. Urban prioritization averted more infections in only a narrow set of scenarios, when internal migration rates were low and vaccination was started by day 30 of an outbreak. Rural prioritization was the optimal strategy for all other scenarios, e.g., with higher internal migration rates or later start dates, due to the presence of a large immunological naive rural population. Among other factors, timing of the vaccination campaign was important to determining maximum impact, and delays as short as 30 days prevented larger campaigns from having the same impact as smaller campaigns that began earlier. The optimal age group for prioritization depended on choice of metric, as prioritizing older adults consistently averted more deaths across all of the scenarios. While guidelines exist for these latter factors, urban-rural allocation is an orthogonal factor that we predict to affect impact and warrants consideration as countries plan the scale-up of their vaccination campaigns.

Abstract Impairments of cognitive function during alterations in arterial blood gases (e.g., high‐altitude hypoxia) may result from the disruption of neurovascular coupling; however, the link between changes in arterial blood gases, cognition, and cerebral blood flow (CBF) is poorly understood. To interrogate this link, we developed a multimodal empirical strategy capable of monitoring neural correlates of cognition and CBF simultaneously. Human participants performed a sustained attention task during hypoxia, hypercapnia, hypocapnia, and normoxia while electroencephalographic (EEG) activity and CBF (middle and posterior cerebral arteries; transcranial Doppler ultrasound) were simultaneously measured. The protocol alternated between rest and engaging in a visual target detection task that required participants to monitor a sequence of brief‐duration colored circles and detect infrequent, longer duration circles (targets). The target detection task was overlaid on a large, circular checkerboard that provided robust visual stimulation. Spectral decomposition and event‐related potential (ERP) analyses were applied to the EEG data to investigate spontaneous and task‐specific fluctuations in neural activity. There were three main sets of findings: (1) spontaneous alpha oscillatory activity was modulated as a function of arterial CO2 (hypocapnia and hypercapnia), (2) task‐related neurovascular coupling was disrupted by all arterial blood gas manipulations, and (3) changes in task‐related alpha and theta band activity and attenuation of the P3 ERP component amplitude were observed during hypocapnia. Since alpha and theta are linked with suppression of visual processing and executive control and P3 amplitude with task difficulty, these data suggest that transient arterial blood gas changes can modulate multiple stages of cognitive information processing.

Abstract Precisely controlled synaptic glutamate concentration is essential for the normal function of the N‐methyl D‐aspartate (NMDA) receptors. Atypical fluctuations in synaptic glutamate homeostasis lead to aberrant NMDA receptor activity that results in the pathogenesis of neurological and psychiatric disorders. Therefore, glutamate concentration‐dependent NMDA receptor modulators would be clinically useful agents with fewer on‐target adverse effects. In the present study, we have characterized a novel compound (CNS4) that potentiates NMDA receptor currents based on glutamate concentration. This compound alters glutamate potency and exhibits no voltage‐dependent effect. Patch‐clamp electrophysiology recordings confirmed agonist concentration‐dependent changes in maximum inducible currents. Dynamic Ca2+ and Na+ imaging assays using rat brain cortical, striatal and cerebellar neurons revealed CNS4 potentiated ion influx through native NMDA receptor activity. Overall, CNS4 is novel in chemical structure, mechanism of action and agonist concentration‐biased allosteric modulatory effect. This compound or its future analogs will serve as useful candidates to develop drug‐like compounds for the treatment of treatment‐resistant schizophrenia and major depression disorders associated with hypoglutamatergic neurotransmission.

Introduction: In the 2016 U.S. Presidential election, voters in communities with recent stagnation or decline in life expectancy were more likely to vote for the Republican candidate than in prior Presidential elections. We aimed to assess the association between change in life expectancy and voting patterns in the 2020 Presidential election. Methods: With data on county-level life expectancy from the Institute for Health Metrics and Evaluation and voting data from a GitHub repository of results scraped from news outlets, we used weighted multivariable linear regression to estimate the association between the change in life expectancy from 1980 to 2014 and the proportion of votes for the Republican candidate and change in the proportion of votes cast for the Republican candidate in the 2020 Presidential election. Results: Among 3110 U.S counties and Washington, D.C., change in life expectancy at the county level was negatively associated with Republican share of the vote in the 2020 Presidential election (parameter estimate −7.2, 95% confidence interval, −7.8 to −6.6). With the inclusion of state, sociodemographic, and economic variables in the model, the association was attenuated (parameter estimate −0.8; 95% CI, −1.5 to −0.2). County-level change in life expectancy was positively associated with change in Republican vote share 0.29 percentage points (95% CI, 0.23 to 0.36). The association was attenuated when state, sociodemographic, and economic variables were added (parameter estimate 0.24; 95% CI, 0.15 to 0.33). Conclusion: Counties with a less positive trajectory in life expectancy were more likely to vote for the Republican candidate in the 2020 U.S. Presidential election, but the Republican candidate's share improved in some counties that experienced marked gains in life expectancy. Associations were moderated by demographic, social and economic factors.

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real‐world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines–Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker. Over 12‐month follow‐up, compared with a discharge prescription of angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all‐cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72–0.94; P=0.004) but not all‐cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89–1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91–1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all‐cause mortality (adjusted HR, 0.69; 95% CI, 0.60–0.79; P

Abstract Soil moisture data from the Oklahoma Mesonet have been used in numerous fields within the Earth sciences, including agriculture, hydrology, and meteorology. Soil matric potentials measured by heat dissipation sensors at Oklahoma Mesonet stations have been converted to soil volumetric water content estimates using soil water retention curve parameters estimated by the Rosetta pedotransfer function. Recently, an improved version of Rosetta, Rosetta3, was released. Informed by this new pedotransfer function and soil sampling at additional locations, an improved version of the Oklahoma Mesonet soil physical property database, MesoSoil v2.0, has been created. This article presents this new soil database, compares soil water retention parameters estimated using Rosetta3 with those derived from the original Rosetta model, and describes the effects of changes in those parameters on estimated volumetric water content. Using the Rosetta3 model led to changes in the estimated water retention parameters, most notably decreases in the parameter α, which is related to the inverse of the air‐entry potential. These changes resulted in volumetric water content estimates that differed from those based on Rosetta1, with mean absolute differences averaging 0.02 cm3 cm–3 across all site‐years and the greatest differences occurring during wet periods. The mean volumetric water content estimated using the Rosetta3 parameters across more than 100 sites was not significantly different from that determined by soil sampling. The updated database is publicly available and may be found here: http://soilphysics.okstate.edu/data.

Purpose: Our purpose was to describe preliminary dosimetric and clinical results of a recumbent total skin electron beam therapy (TSEBT) technique and compare this to a conventional standing TSEBT technique. Methods and Materials: A customized treatment platform with recessed side wheels was constructed and commissioned for patients to be treated in a recumbent position. Dosimetric and clinical information was collected for patients treated with this new recumbent technique in addition to that of a cohort of patients treated contemporaneously using the conventional standing method. Dose delivery and clinical outcomes were compared for patients treated with the recumbent and standing techniques. Results: Between 2017 and 2019, 27 patients were treated with TSEBT with the recumbent (n = 13) or conventional standing technique (n = 14) at our institution. Measured dose at 15 body sites could be directly compared. Of these, 10 showed no significant difference between the two techniques while five sites showed significant differences in median measured dose, including the top of left shoulder, right biceps, bend of left elbow, upper back, and medial right thigh (P < .003). Measured dose was significantly higher with the standing technique at these sites with the exception of the upper back. Rates of complete response (25% vs 23%), partial response (50% vs 69%), and stable disease (17% vs 8%) were similar between the standing and recumbent cohorts, respectively (P = .78). Conclusions: We have developed, commissioned, and implemented a floor-based, recumbent technique that allows for treatment of patients who would otherwise not be eligible for TSEBT. Dosimetric and clinical measurements suggest that this technique is a viable alternative to the standing method.

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.

Patient experience is an important dimension of health care quality and is assessed using the standard Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey for inpatients. The HCAHPS scores may vary based on survey response rate and hospital size. The objective of this study was to describe the association between survey response rate and HCAHPS scores and examine whether the relationship varies based on hospital size. Medicare’s Hospital Compare publicly reported HCAHPS data were used. Pearson correlation, controlling for number of staffed beds, and linear regression models were used for the analysis. Hospitals were grouped into quartiles based on number of staffed beds to delineate the effect of increasing hospital size on the relationship between survey response rate and HCAHPS scores. A significant association between HCAHPS survey response rate and all examined HCAHPS domain scores was observed. The effect size across HCAHPS domains varied based on hospital size. The relationship between HCAHPS score and survey response rate differed significantly between hospitals in the smallest and largest size quartiles for discharge information, nurse communication, and hospital quietness. While a causal relationship cannot be inferred from this study, the response rate could be a direct and/or indirect driver of HCAHPS scores. Future research should be aimed to further explore the basis of this relationship and to determine how it may inform the interpretation of HCAHPS results.