Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. METHODS: Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). RESULTS: In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). CONCLUSIONS: Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.

Development and validation of machine learning models to identify high-risk surgical patients using automatically curated electronic health record data (Pythia): A retrospective, single-site study.

BACKGROUND: Pythia is an automated, clinically curated surgical data pipeline and repository housing all surgical patient electronic health record (EHR) data from a large, quaternary, multisite health institute for data science initiatives. In an effort to better identify high-risk surgical patients from complex data, a machine learning project trained on Pythia was built to predict postoperative complication risk. METHODS AND FINDINGS: A curated data repository of surgical outcomes was created using automated SQL and R code that extracted and processed patient clinical and surgical data across 37 million clinical encounters from the EHRs. A total of 194 clinical features including patient demographics (e.g., age, sex, race), smoking status, medications, comorbidities, procedure information, and proxies for surgical complexity were constructed and aggregated. A cohort of 66,370 patients that had undergone 99,755 invasive procedural encounters between January 1, 2014, and January 31, 2017, was studied further for the purpose of predicting postoperative complications. The average complication and 30-day postoperative mortality rates of this cohort were 16.0% and 0.51%, respectively. Least absolute shrinkage and selection operator (lasso) penalized logistic regression, random forest models, and extreme gradient boosted decision trees were trained on this surgical cohort with cross-validation on 14 specific postoperative outcome groupings. Resulting models had area under the receiver operator characteristic curve (AUC) values ranging between 0.747 and 0.924, calculated on an out-of-sample test set from the last 5 months of data. Lasso penalized regression was identified as a high-performing model, providing clinically interpretable actionable insights. Highest and lowest performing lasso models predicted postoperative shock and genitourinary outcomes with AUCs of 0.924 (95% CI: 0.901, 0.946) and 0.780 (95% CI: 0.752, 0.810), respectively. A calculator requiring input of 9 data fields was created to produce a risk assessment for the 14 groupings of postoperative outcomes. A high-risk threshold (15% risk of any complication) was determined to identify high-risk surgical patients. The model sensitivity was 76%, with a specificity of 76%. Compared to heuristics that identify high-risk patients developed by clinical experts and the ACS NSQIP calculator, this tool performed superiorly, providing an improved approach for clinicians to estimate postoperative risk for patients. Limitations of this study include the missingness of data that were removed for analysis. CONCLUSIONS: Extracting and curating a large, local institution's EHR data for machine learning purposes resulted in models with strong predictive performance. These models can be used in clinical settings as decision support tools for identification of high-risk patients as well as patient evaluation and care management. Further work is necessary to evaluate the impact of the Pythia risk calculator within the clinical workflow on postoperative outcomes and to optimize this data flow for future machine learning efforts.

Wide range of perioperative drugs and doses used in inguinal hernia repairs for premature infants.

OBJECTIVE: Characterize the types and doses of commonly administered perioperative drugs in inguinal hernia (IH) repair for premature infants. STUDY DESIGN: Single-center, retrospective cohort study. RESULTS: In total, 112 premature infants underwent IH repair between 2010 and 2015. Twenty-one drugs were used during IH repair, with each infant receiving a median seven drugs. Acetaminophen (88%), bupivacaine (84%), cisatracurium (74%), sevoflurane (72%), and propofol (71%) were the most commonly used agents. Thirty-two infants underwent additional procedures with IH repair. Additional procedures were not associated with a higher number of perioperative drugs, however infants with additional procedures were exposed to higher cumulative doses of cisatracurium (p < 0.001) and fentanyl (p = 0.002). CONCLUSION: There is wide variability in the drugs and doses used for a common surgical procedure in this population, even within a single center. Future research should focus on the safety and efficacy of the most commonly used perioperative drugs described in this study.

Pulmonary Valve Endocarditis: The Potential Utility of Multimodal Imaging Prior to Surgery.

BACKGROUND: The presence of echocardiographic (echo) evidence is a major criterion for the diagnosis of infective endocarditis (IE) by modified Duke criteria. Pulmonary valve (PV) IE, however, can be challenging to identify by echo. We sought to evaluate the added utility of multimodal imaging in PV IE. METHODS: This is a single-center case series. We retrospectively analyzed demographic, laboratory, imaging, clinical, and surgical data from patients diagnosed with PV IE from 2008 to 2018. RESULTS: A total of 23 patients were identified with definite PV IE by Duke criteria (83% male and ages 2 months to 70 years). Twenty-two patients had congenital heart disease, with 21 involving the right ventricular outflow tract (including three with transcatheter PV implant). Overall, 20 (87%) of 23 had positive blood cultures. A total of 17 (74%) of 23 patients demonstrated echo evidence of PV IE. In three cases, echo was negative (did not show vegetations) but showed new PV obstruction. In four cases with negative transthoracic echocardiogram and transesophageal echocardiogram, evidence of PV IE was subsequently seen by positron emission tomography/computed tomography (n = 2) or cardiac magnetic resonance imaging (n = 2). Pulmonary valve IE was confirmed at surgery by evaluation of pathologic samples in 20 cases. CONCLUSIONS: Multimodal imaging improves the ability to preoperatively identify endocardial involvement in PV IE in cases where echo is negative. Consideration should be given to revise Duke criteria to include new obstruction and endocardial involvement by multimodal imaging for PV IE.

Assessing Quality of Surgical Real-World Data from an Automated Electronic Health Record Pipeline.

BACKGROUND: Significant analysis errors can be caused by nonvalidated data quality of electronic health records data. To determine surgical data fitness, a framework of foundational and study-specific data analyses was adapted and assessed using conformance, completeness, and plausibility analyses. STUDY DESIGN: Electronic health records-derived data from a cohort of 241,695 patients undergoing 412,182 procedures from October 1, 2014 to August 31, 2018 at 3 hospital sites was evaluated. Data quality analyses tested CPT codes, medication administrations, vital signs, provider notes, labs, orders, diagnosis codes, medication lists, and encounters. RESULTS: Foundational checks showed that all encounters had procedures within the inclusion period, all admission dates occurred before discharge dates, and race was missing for 1% of patients. All procedures had associated CPT codes, 69% had recorded blood pressure, pulse, temperature, respiration rate, and oxygen saturation. After curation, all medication matched RxNorm medication naming standards, 84% of procedures had current outpatient medication lists, and 15% of procedures had missing procedure notes. Study-specific checks temporally validated CPT codes, intraoperative medication doses were in conventional units, and of the 13,500 patients who received blood pressure medication intraoperatively, 93% had a systolic blood pressure >140 mmHg. All procedure notes were completed within less than 30 days of the procedure and 93% of patients after total knee arthroplasty had postoperative physical therapy notes. All patients with postoperative troponin-T lab values ≥0.10 ng/mL had more than 1 ECG with relevant diagnoses. Postoperative opioid prescription decreased by 8.8% and nonopioid use increased by 8.8%. CONCLUSIONS: High levels of conformance, completeness, and clinical plausability demonstrate higher quality of real-world data fitness and low levels demonstrate less-fit-for-use data.

The relationship between impaired control, impulsivity, and alcohol self-administration in nondependent drinkers.

Impaired control over drinking is a significant marker of alcohol use disorder (AUD), and a potential target of intervention (Heather, Tebbutt, Mattick, & Zamir, 1993; Leeman, Toll, Taylor, & Volpicelli, 2009). Impaired control may be related to, but conceptually distinct from, impulsivity (Leeman, Patock-Peckham, & Potenza, 2012; Leeman, Ralevski, et al., 2014). However, the relationship between impaired control, impulsivity, and alcohol consumption, particularly in nondependent drinkers is less clear. This study aimed to characterize these relationships using a free-access intravenous alcohol self-administration (IV-ASA) paradigm in nondependent drinkers (N = 48). Results showed individuals with higher self-reported impaired control achieved higher blood alcohol concentrations (BAC) during the IV-ASA session and reported greater hedonic subjective responses to alcohol. Higher impaired control was also associated with greater positive urgency and reward sensitivity. Moderated-mediation analysis showed that the relationship between positive urgency and peak BAC was mediated by impaired control, and partially moderated by subjective alcohol response. These findings highlight the critical role of impaired control over drinking on alcohol consumption and subjective responses in nondependent drinkers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele.

BACKGROUND: Gastroschisis and omphalocele are the most common anterior abdominal wall defects affecting infants. There are few large cohort studies describing the frequency of associated anomalies in infants with these 2 conditions. We describe associated anomalies and outcomes in infants with these defects using a large, multi-center clinical database. METHODS: We identified all infants with gastroschisis or omphalocele from a prospectively collected database of infants discharged from 348 neonatal intensive care units in North America from 1997 to 2012. Maternal and patient demographic data, associated anomalies, and outcome data were compared between infants with gastroschisis and omphalocele. RESULTS: A total of 4687 infants with gastroschisis and 1448 infants with omphalocele were identified. Infants with omphalocele were more likely to be diagnosed with at least 1 other anomaly compared with infants with gastroschisis (35% vs. 8%, p<0.001). Infants with omphalocele were more likely to develop pulmonary hypertension compared with those with gastroschisis (odds ratio [OR] 7.78; 95% confidence interval 5.81, 10.41) and had higher overall mortality (OR 6.81 [5.33, 8.71]). CONCLUSION: Infants with omphalocele were more likely to have other anomalies, be diagnosed with pulmonary hypertension, and have higher mortality than infants with gastroschisis.

Clinical outcomes in very low birth weight infants with major congenital heart defects.

BACKGROUND: The combination of major congenital heart disease (CHD) and prematurity is associated with poor prognosis, but previous studies have not fully characterized morbidity and mortality in this population. We conducted a retrospective cohort study of very low birth weight (VLBW) infants with major CHD to describe outcomes, including mortality, over time. METHODS: We included all infants <1500 g birth weight with major CHD discharged from Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We report incidences of major CHD in VLBW infants and compare mortality and morbidity by infant birth weight, type of major CHD, and time period. RESULTS: Of 105,539 VLBW infants, 299 (0.3%) were diagnosed with 15 different major CHDs. Coarctation of the aorta (n=67, 22%), atrioventricular septal defect (n=58, 19%), and tetralogy of Fallot (n=53, 18%) were the most common major CHDs identified. Overall mortality was 163/299 (55%). Mortality was ≥70% for 10 lesions and <30% for isolated aortic valve stenosis (6/30, 20%). Mortality in infants with major CHD did not significantly change over time: 76/133 (57%) in 1997-2005, 49/95 (52%) in 2006-2009, and 38/71 (54%) in 2010-2012 (p=0.70). The majority of infants suffered ≥1 comorbidity or died (218/299, 73%). CONCLUSION: Major CHD is associated with high morbidity and mortality. While mortality varies by lesion, overall survival and incidence of major morbidity have not improved over time.