Real-Time Electronic Health Record Mortality Prediction During the COVID-19 Pandemic: A Prospective Cohort Study

Background: The SARS-CoV-2 virus has infected millions of people, overwhelming critical care resources in some regions. Many plans for rationing critical care resources during crises are based on the Sequential Organ Failure Assessment (SOFA) score. The COVID-19 pandemic created an emergent need to develop and validate a novel electronic health record (EHR)-computable tool to predict mortality. Research Questions: To rapidly develop, validate, and implement a novel real-time mortality score for the COVID-19 pandemic that improves upon SOFA. Study Design and Methods: We conducted a prospective cohort study of a regional health system with 12 hospitals in Colorado between March 2020 and July 2020. All patients >14 years old hospitalized during the study period without a do not resuscitate order were included. Patients were stratified by the diagnosis of COVID-19. From this cohort, we developed and validated a model using stacked generalization to predict mortality using data widely available in the EHR by combining five previously validated scores and additional novel variables reported to be associated with COVID-19-specific mortality. We compared the area under the receiver operator curve (AUROC) for the new model to the SOFA score and the Charlson Comorbidity Index. Results: We prospectively analyzed 27,296 encounters, of which 1,358 (5.0%) were positive for SARS-CoV-2, 4,494 (16.5%) included intensive care unit (ICU)-level care, 1,480 (5.4%) included invasive mechanical ventilation, and 717 (2.6%) ended in death. The Charlson Comorbidity Index and SOFA scores predicted overall mortality with an AUROC of 0.72 and 0.90, respectively. Our novel score predicted overall mortality with AUROC 0.94. In the subset of patients with COVID-19, we predicted mortality with AUROC 0.90, whereas SOFA had AUROC of 0.85. Interpretation: We developed and validated an accurate, in-hospital mortality prediction score in a live EHR for automatic and continuous calculation using a novel model, that improved upon SOFA. Study Question: Can we improve upon the SOFA score for real-time mortality prediction during the COVID-19 pandemic by leveraging electronic health record (EHR) data? Results: We rapidly developed and implemented a novel yet SOFA-anchored mortality model across 12 hospitals and conducted a prospective cohort study of 27,296 adult hospitalizations, 1,358 (5.0%) of which were positive for SARS-CoV-2. The Charlson Comorbidity Index and SOFA scores predicted all-cause mortality with AUROCs of 0.72 and 0.90, respectively. Our novel score predicted mortality with AUROC 0.94. Interpretation: A novel EHR-based mortality score can be rapidly implemented to better predict patient outcomes during an evolving pandemic

Assessment of Microbial Diversity in Biofilms Recovered from Endotracheal Tubes Using Culture Dependent and Independent Approaches

Ventilator-associated pneumonia (VAP) is a common nosocomial infection in mechanically ventilated patients. Biofilm formation is one of the mechanisms through which the endotracheal tube (ET) facilitates bacterial contamination of the lower airways. In the present study, we analyzed the composition of the ET biofilm flora by means of culture dependent and culture independent (16 S rRNA gene clone libraries and pyrosequencing) approaches. Overall, the microbial diversity was high and members of different phylogenetic lineages were detected (Actinobacteria, beta-Proteobacteria, Candida spp., Clostridia, epsilon-Proteobacteria, Firmicutes, Fusobacteria and gamma-Proteobacteria). Culture dependent analysis, based on the use of selective growth media and conventional microbiological tests, resulted in the identification of typical aerobic nosocomial pathogens which are known to play a role in the development of VAP, e.g. Staphylococcus aureus and Pseudomonas aeruginosa. Other opportunistic pathogens were also identified, including Staphylococcus epidermidis and Kocuria varians. In general, there was little correlation between the results obtained by sequencing 16 S rRNA gene clone libraries and by cultivation. Pyrosequencing of PCR amplified 16 S rRNA genes of four selected samples resulted in the identification of a much wider variety of bacteria. The results from the pyrosequencing analysis suggest that these four samples were dominated by members of the normal oral flora such as Prevotella spp., Peptostreptococcus spp. and lactic acid bacteria. A combination of methods is recommended to obtain a complete picture of the microbial diversity of the ET biofilm

Factors influencing physical activity and rehabilitation in survivors of critical illness: a systematic review of quantitative and qualitative studies

PURPOSE: To identify, evaluate and synthesise studies examining the barriers and enablers for survivors of critical illness to participate in physical activity in the ICU and post-ICU settings from the perspective of patients, caregivers and healthcare providers. METHODS: Systematic review of articles using five electronic databases: MEDLINE, CINAHL, EMBASE, Cochrane Library, Scopus. Quantitative and qualitative studies that were published in English in a peer-reviewed journal and assessed barriers or enablers for survivors of critical illness to perform physical activity were included. Prospero ID: CRD42016035454. RESULTS: Eighty-nine papers were included. Five major themes and 28 sub-themes were identified, encompassing: (1) patient physical and psychological capability to perform physical activity, including delirium, sedation, illness severity, comorbidities, weakness, anxiety, confidence and motivation; (2) safety influences, including physiological stability and concern for lines, e.g. risk of dislodgement; (3) culture and team influences, including leadership, interprofessional communication, administrative buy-in, clinician expertise and knowledge; (4) motivation and beliefs regarding the benefits/risks; and (5) environmental influences, including funding, access to rehabilitation programs, staffing and equipment. CONCLUSIONS: The main barriers identified were patient physical and psychological capability to perform physical activity, safety concerns, lack of leadership and ICU culture of mobility, lack of interprofessional communication, expertise and knowledge, and lack of staffing/equipment and funding to provide rehabilitation programs. Barriers and enablers are multidimensional and span diverse factors. The majority of these barriers are modifiable and can be targeted in future clinical practice

Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome

Abstract Background Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia. Methods We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study. Our primary predictor variable was the number of days receiving NMB between study enrollment and day 3. Our primary outcome variables were the change in concentration of biomarkers of epithelial injury (serum surfactant protein-D (SP-D)), endothelial injury (von Willebrand factor (VWF)), and systemic inflammation (interleukin (IL)-8). Multivariable regression analysis was used to compare the change in biomarker concentration controlling for multiple covariates. Patients were stratified by treatment arm (12 versus 6 cm3/kg) and by an initial arterial oxygen tension (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio of 120. Results A total of 446 (49%) patients had complete SP-D, VWF, and IL-8 measurements on study enrollment and day 3. After adjusting for baseline differences, each day of NMB was associated with a decrease in SP-D (−23.7 ng/ml/day, p = 0.029), VWF (−33.5% of control/day, p = 0.015), and IL-8 (−362.6 pg/ml/day, p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving low tidal volume ventilation. However, patients with a P/F ratio of greater than 120 or receiving high tidal volume ventilation had either no change or an increase in SP-D, WVF, or IL-8 concentrations. Conclusion NBM is associated with decreased biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients receiving low tidal volume ventilation and those with a P/F ratio less than or equal to 120

Outcomes in systemic sclerosis-related lung disease after lung transplantation.

BackgroundLung disease is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related lung disease (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extrapulmonary involvement will yield worse outcomes. We sought to evaluate posttransplantation outcomes in persons with SSc-LD with esophageal involvement compared with persons with nonconnective tissue disease-related interstitial lung disease (nCTD-ILD).MethodsFrom 1998 to 2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than "mild nonspecific disorder". The primary outcome was posttransplantation survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Student's t test.ResultsSurvival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (P = 0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared with 91% and 64% in the nCTD-ILD group, respectively. There were no differences in fBOS (P = 0.83). Rates of acute rejection were less in SSc-ILD (P = 0.05). Esophageal dysfunction was not associated with worse outcomes (P>0.55).ConclusionsPersons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplantation may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes

Outcomes in systemic sclerosis-related lung disease after lung transplantation.

BackgroundLung disease is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related lung disease (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extrapulmonary involvement will yield worse outcomes. We sought to evaluate posttransplantation outcomes in persons with SSc-LD with esophageal involvement compared with persons with nonconnective tissue disease-related interstitial lung disease (nCTD-ILD).MethodsFrom 1998 to 2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than "mild nonspecific disorder". The primary outcome was posttransplantation survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Student's t test.ResultsSurvival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (P = 0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared with 91% and 64% in the nCTD-ILD group, respectively. There were no differences in fBOS (P = 0.83). Rates of acute rejection were less in SSc-ILD (P = 0.05). Esophageal dysfunction was not associated with worse outcomes (P>0.55).ConclusionsPersons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplantation may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes