Associations Between Volume of Early Intravenous Fluid and Hospital Outcomes in Septic Patients With and Without Heart Failure: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF). DESIGN: A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed. SETTING: An urban university-based hospital. PATIENTS: A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0-15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30-45 mL/kg (odds ratio = 0.61; 95% CI, 0.41-0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15-30 mL/kg for non-HF patients and 30-45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes. CONCLUSIONS: Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15-30 mL/kg across all patients without HF and 30-45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid-outcome associations and a focus on other conditions like HF.

Timing of antibiotic treatment identifies distinct clinical presentations among patients presenting with suspected septic shock.

Objective: Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high-risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock. Methods: Adults presenting to the emergency department (ED) June 2012-December 2018 diagnosed with sepsis (Sepsis-III electronic health record [EHR] criteria) and hypotension (non-resolving for ≥30 min, systolic blood pressure <90 mmHg) within 24 h. We categorized patients who received antibiotics before hypotension ("early"), 0-60 min after ("immediate"), and >60 min after ("late") treatment. Results: Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post-ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease (p < 0.05) and later onset of systemic inflammatory response syndrome (SIRS) criteria compared to early/immediate treatment subgroups (median 87 vs. 35 vs. 20 min, p < 0.0001). After adjustment, there was no difference in clinical outcomes among treatment subgroups. Conclusions: There was significant heterogeneity in presentation and timing of antibiotic initiation for suspected septic shock. Patients with later treatment commonly had hypotension on presentation, had more hypotension-associated comorbidities, and developed overt markers of infection (eg, SIRS) later. While these factors likely contribute to delays in clinician recognition of suspected septic shock, it may not impact sepsis outcomes.

Ventricular tachycardia and in-hospital mortality in the intensive care unit.

Background: Continuous electrocardiographic (ECG) monitoring is used to identify ventricular tachycardia (VT), but false alarms occur frequently. Objective: The purpose of this study was to assess the rate of 30-day in-hospital mortality associated with VT alerts generated from bedside ECG monitors to those from a new algorithm among intensive care unit (ICU) patients. Methods: We conducted a retrospective cohort study in consecutive adult ICU patients at an urban academic medical center and compared current bedside monitor VT alerts, VT alerts from a new-unannotated algorithm, and true-annotated VT. We used survival analysis to explore the association between VT alerts and mortality. Results: We included 5679 ICU admissions (mean age 58 ± 17 years; 48% women), 503 (8.9%) experienced 30-day in-hospital mortality. A total of 30.1% had at least 1 current bedside monitor VT alert, 14.3% had a new-unannotated algorithm VT alert, and 11.6% had true-annotated VT. Bedside monitor VT alert was not associated with increased rate of 30-day mortality (adjusted hazard ratio [aHR] 1.06; 95% confidence interval [CI] 0.88-1.27), but there was an association for VT alerts from our new-unannotated algorithm (aHR 1.38; 95% CI 1.12-1.69) and true-annotated VT(aHR 1.39; 95% CI 1.12-1.73). Conclusion: Unannotated and annotated-true VT were associated with increased rate of 30-day in-hospital mortality, whereas current bedside monitor VT was not. Our new algorithm may accurately identify high-risk VT; however, prospective validation is needed.

Racial, Ethnic, and Language-Based Inequities in Inpatient Opioid Prescribing by Diagnosis from Internal Medicine Services, a Retrospective Cohort Study.

Introduction: Opioid administration is extremely common in the inpatient setting, yet we do not know how the administration of opioids varies across different medical conditions and patient characteristics on internal medicine services. Our goal was to assess racial, ethnic, and language-based inequities in opioid prescribing practices for patients admitted to internal medicine services. Methods: We conducted a retrospective cohort study of all adult patients admitted to internal medicine services from 2013 to 2021 and identified subcohorts of patients treated for the six most frequent primary hospital conditions (pneumonia, sepsis, cellulitis, gastrointestinal bleed, pyelonephritis/urinary tract infection, and respiratory disease) and three select conditions typically associated with pain (abdominal pain, acute back pain, and pancreatitis). We conducted a negative binomial regression analysis to determine how average administered daily opioids, measured as morphine milligram equivalents (MMEs), were associated with race, ethnicity, and language, while adjusting for additional patient demographics, hospitalization characteristics, medical comorbidities, prior opioid therapy, and substance use disorders. Results: The study cohort included 61,831 patient hospitalizations. In adjusted models, we found that patients with limited English proficiency received significantly fewer opioids (66 MMEs, 95% CI: 52, 80) compared to English-speaking patients (101 MMEs, 95% CI: 91, 111). Asian (59 MMEs, 95% CI: 51, 66), Latinx (89 MMEs, 95% CI: 79, 100), and multi-race/ethnicity patients (81 MMEs, 95% CI: 65, 97) received significantly fewer opioids compared to white patients (103 MMEs, 95% CI: 94, 112). American Indian/Alaska Native (227 MMEs, 95% CI: 110, 344) patients received significantly more opioids. Significant inequities were also identified across race, ethnicity, and language groups when analyses were conducted within the subcohorts. Most notably, Asian and Latinx patients received significantly fewer MMEs and American Indian/Alaska Native patients received significantly more MMEs compared to white patients for the top six most frequent conditions. Most patients from minority groups also received fewer MMEs compared to white patients for three select pain conditions. Discussion. There are notable inequities in opioid prescribing based on patient race, ethnicity, and language status for those admitted to inpatient internal medicine services across all conditions and in the subcohorts of the six most frequent hospital conditions and three pain-associated conditions. This represents an institutional and societal opportunity for quality improvement initiatives to promote equitable pain management.

Clinical Outcomes of Direct Oral Anticoagulants vs Warfarin for Extended Treatment of Venous Thromboembolism.

Importance: Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin. Objective: To compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE. Design, Setting, and Participants: This cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023. Exposure: Dispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE. Main Outcomes and Measures: The primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression. Results: A total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment. Conclusions and Relevance: In this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.

Performance of point-of-care severity scores to predict prognosis in patients admitted through the emergency department with COVID-19.

BACKGROUND: Identifying COVID-19 patients at the highest risk of poor outcomes is critical in emergency department (ED) presentation. Sepsis risk stratification scores can be calculated quickly for COVID-19 patients but have not been evaluated in a large cohort. OBJECTIVE: To determine whether well-known risk scores can predict poor outcomes among hospitalized COVID-19 patients. DESIGNS, SETTINGS, AND PARTICIPANTS: A retrospective cohort study of adults presenting with COVID-19 to 156 Hospital Corporation of America (HCA) Healthcare EDs, March 2, 2020, to February 11, 2021. INTERVENTION: Quick Sequential Organ Failure Assessment (qSOFA), Shock Index, National Early Warning System-2 (NEWS2), and quick COVID-19 Severity Index (qCSI) at presentation. MAIN OUTCOME AND MEASURES: The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and vasopressors receipt. Patients scored positive with qSOFA ≥ 2, Shock Index > 0.7, NEWS2 ≥ 5, and qCSI ≥ 4. Test characteristics and area under the receiver operating characteristics curves (AUROCs) were calculated. RESULTS: We identified 90,376 patients with community-acquired COVID-19 (mean age 64.3 years, 46.8% female). 17.2% of patients died in-hospital, 28.6% went to the ICU, 13.7% received mechanical ventilation, and 13.6% received vasopressors. There were 3.8% qSOFA-positive, 45.1% Shock Index-positive, 49.8% NEWS2-positive, and 37.6% qCSI-positive at ED-triage. NEWS2 exhibited the highest AUROC for in-hospital mortality (0.593, confidence interval [CI]: 0.588-0.597), ICU admission (0.602, CI: 0.599-0.606), mechanical ventilation (0.614, CI: 0.610-0.619), and vasopressor receipt (0.600, CI: 0.595-0.604). CONCLUSIONS: Sepsis severity scores at presentation have low discriminative power to predict outcomes in COVID-19 patients and are not reliable for clinical use. Severity scores should be developed using features that accurately predict poor outcomes among COVID-19 patients to develop more effective risk-based triage.

Assessment of the Risk of Venous Thromboembolism in Nonhospitalized Patients With COVID-19.

Importance: Patients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood. Objectives: To assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE. Design, Setting, and Participants: A retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021. Exposures: Patient demographic and clinical characteristics identified from integrated electronic health records. Main Outcomes and Measures: The primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data. Results: A total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]). Conclusions and Relevance: In this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

Health Literacy and Treatment Satisfaction Among Patients with Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) treatment requires complex management, and patients with limited health literacy (HL) may perceive higher burden and lower benefits associated with their treatment. OBJECTIVE: To examine the association of HL with treatment satisfaction among patients with VTE. DESIGN: Retrospective cohort study PARTICIPANTS: Kaiser Permanente Southern and Northern California members who were taking oral anticoagulants (OAC) for incident VTE between 2015 and 2018 were surveyed. Main Measures HL was assessed using a 3-item HL assessment and dichotomized as having adequate or limited HL. High treatment burden and low treatment benefit were defined as Anti-Clot Treatment Scale (ACTS) scores below the 25th percentile of the distributions for ACTS Burdens and Benefits survey components, respectively. Using Poisson regression, multivariable adjusted risk ratios (RR) and 95% confidence intervals (CI) were calculated for the association of HL with high treatment burden and low treatment benefits. RESULTS: Among 2154 respondents, 397 (18.4%) had limited HL. Patients with limited vs adequate HL were older (47.9% vs 27.5% aged ≥ 75 years, p<0.001), more likely to use a non-English language when discussing their health (10.8% vs 1.7%, p<0.001), to have less than high school education (10.1% vs 1.7%, p<0.001), and to self-rate their health as fair or poor (47.6% vs 25.5%, p<0.001). After multivariable adjustment, patients with limited HL were more likely to have higher perceived treatment burden (RR 1.24, 95% CI 1.07, 1.45) and lower perceived treatment benefits (RR 1.21, 95% CI 1.08, 1.37). CONCLUSIONS: Limited HL was associated with lower OAC treatment satisfaction, though absolute differences in satisfaction scores were small. Further examination of the intersection of HL with VTE treatment satisfaction and compliance among older and non-English speaking patients is warranted.

Health-related quality of life associated with warfarin and direct oral anticoagulants in venous thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users. MATERIALS AND METHODS: We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics. RESULTS: Overall, 2230 patients (43.1 % women and 31.8 % >75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users. CONCLUSIONS: Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE.

Increased rates of secondary bacterial infections, including Enterococcus bacteremia, in patients hospitalized with coronavirus disease 2019 (COVID-19).

OBJECTIVE: We compared the rates of hospital-onset secondary bacterial infections in patients with coronavirus disease 2019 (COVID-19) with rates in patients with influenza and controls, and we investigated reports of increased incidence of Enterococcus infections in patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: An academic quaternary-care hospital in San Francisco, California. PATIENTS: Patients admitted between October 1, 2019, and October 1, 2020, with a positive SARS-CoV-2 PCR (N = 314) or influenza PCR (N = 82) within 2 weeks of admission were compared with inpatients without positive SARS-CoV-2 or influenza tests during the study period (N = 14,332). METHODS: National Healthcare Safety Network definitions were used to identify infection-related ventilator-associated complications (IVACs), probable ventilator-associated pneumonia (PVAP), bloodstream infections (BSIs), and catheter-associated urinary tract infections (CAUTIs). A multiple logistic regression model was used to control for likely confounders. RESULTS: COVID-19 patients had significantly higher rates of IVAC and PVAP compared to controls, with adjusted odds ratios of 4.7 (95% confidence interval [CI], 1.7-13.9) and 10.4 (95 % CI, 2.1-52.1), respectively. COVID-19 patients had higher incidence of BSI due to Enterococcus but not BSI generally, and whole-genome sequencing of Enterococcus isolates demonstrated that nosocomial transmission did not explain the increased rate. Subanalyses of patients admitted to the intensive care unit and patients who required mechanical ventilation revealed similar findings. CONCLUSIONS: COVID-19 is associated with an increased risk of IVAC, PVAP, and Enterococcus BSI compared with hospitalized controls, which is not fully explained by factors such as immunosuppressive treatments and duration of mechanical ventilation. The mechanism underlying increased rates of Enterococcus BSI in COVID-19 patients requires further investigation.

Identifying the Sickest During Triage: Using Point-of-Care Severity Scores to Predict Prognosis in Emergency Department Patients With Suspected Sepsis.

BACKGROUND: Sepsis progresses rapidly and is associated with considerable morbidity and mortality. Bedside risk stratification scores can quickly identify patients at greatest risk of poor outcomes; however, there is lack of consensus on the best scale to use. OBJECTIVE: To compare the ability of quick Sequential Organ Failure Assessment (qSOFA), the National Early Warning System (NEWS2), and the Shock Index-which does not require mental status assessment-to predict poor outcomes among patients with suspected sepsis during triage. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of adults presenting to an academic emergency department (ED) from June 2012 to December 2018 who had blood cultures and intravenous antibiotics within 24 hours. MAIN OUTCOMES AND MEASURES: Clinical data were collected from the electronic health record. Patients were considered positive at qSOFA ≥2, Shock Index >0.7, or NEWS2 ≥5 scores. We calculated test characteristics and area under the receiver operating characteristics curves (AUROCs) to predict in-hospital mortality and ED-to-intensive care unit (ICU) admission. RESULTS: We included 23,837 ED patients; 1,921(8.1%) were qSOFA-positive, 4,273 (17.9%) Shock Index-positive, and 11,832 (49.6%) NEWS2-positive. There were 1,427 (6.0%) deaths and 3,149 (13.2%) ED-to-ICU admissions in the sample. NEWS2 had the highest sensitivity for in-hospital mortality (76.0%) and ED-to-ICU admission (78.9%). qSOFA had the highest specificity for in-hospital mortality (93.4%) and ED-to-ICU admission (95.2%). Shock Index exhibited the highest AUROC for in-hospital mortality (0.648; 95 CI, 0.635-0.662) and ED-to-ICU admission (0.680; 95% CI, 0.617-0.689). Test characteristics were similar among those with sepsis. CONCLUSIONS: Institution priorities should drive score selection, balancing sensitivity and specificity. In our study, qSOFA was highly specific and NEWS2 was the most sensitive for ruling out patients at high risk. Performance of the Shock Index fell between qSOFA and NEWS2 and could be considered because it is easy to implement.

COVID-19 and Risk of VTE in Ethnically Diverse Populations.

BACKGROUND: Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking. RESEARCH QUESTION: Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19? STUDY DESIGN AND METHODS: We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19. RESULTS: We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/µL. INTERPRETATION: Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19.

Anticoagulant treatment satisfaction with warfarin and direct oral anticoagulants for venous thromboembolism.

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen's d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p < 0.0001) and ACTS Benefits scores (10.21 v. 9.84, p = 0.046) for DOACs vs. warfarin, respectively. The magnitude of the difference was small (Cohen's d of 0.29 for ACTS Burdens and 0.12 for ACTS Benefits). Patients taking DOACs for venous thromboembolism were on average more satisfied with anticoagulant treatment than were warfarin users, although the magnitude of the difference was small.

Are Antimotility Agents Safe for Use in Clostridioides difficile Infections? Results From an Observational Study in Malignant Hematology Patients.

OBJECTIVES: To evaluate the safety of antimotility agents (AAs) in a population of patients with hematologic malignancies and concurrent Clostridioides difficile infection (CDI) and to describe the outcomes of AA use in a hospital setting. PATIENTS AND METHODS: We used the electronic health record to identify patients who were hospitalized in the adult malignant hematology service who had 1 or more toxin-positive C difficile stool assay between April 1, 2012, and September 21, 2017. We reviewed medical charts to obtain information on the use of AAs and any subsequent gastrointestinal complications. RESULTS: There were 339 patients who were stool toxin positive for CDI during the study period. Of those, 94 patients (27%) were prescribed AAs within 14 days of CDI diagnosis. All patients received CDI antimicrobial therapy within the first 24 hours. There were 2 adverse gastrointestinal events in the group that received AAs and 6 in the group that did not receive AAs. The risk of adverse events did not differ between patients who received AAs and those who did not (adjusted odds ratio, 0.36; 95% CI, 0.06 to 2.10). The mean age of the full cohort was 52.7±15.5 years, and the mean length of stay was 26.7±22.6 days. Early AA use (<48 hours of diagnosis) was not associated with increased adverse effects. CONCLUSION: There was no increase in the incidence of gastrointestinal events in the arm that used AAs compared with the control arm. The evidence suggests that for patients with hematologic malignancies and CDI, the addition of AAs to appropriate antimicrobial therapy poses no additional risk.

Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses.

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: A retrospective cohort study of patients with and without COVID-19.

BACKGROUND: Most data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses. METHODS: We examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes. FINDINGS: Among 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p < 0.001). Patients with COVID-19 were more often hospitalized (79% vs. 56%, p = 0.014). When hospitalized, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p < 0.001) and more often developed ARDS (23% vs. 3%, p < 0.001). Most comorbidities, medications, symptoms, vital signs, laboratories, treatments, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. FUNDING: National Center for Advancing Translational Sciences, National Heart Lung Blood Institute, National Institute of Allergy and Infectious Diseases, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative.

Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2.

We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune response, with reduced expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation and interactions with lymphoid cells. Patients with COVID-19 also exhibited significantly reduced proportions of neutrophils and macrophages, and increased proportions of goblet, dendritic and B-cells, compared to other viral ARIs. Using machine learning, we built 26-, 10- and 3-gene classifiers that differentiated COVID-19 from other acute respiratory illnesses with AUCs of 0.980, 0.950 and 0.871, respectively. Classifier performance was stable at low viral loads, suggesting utility in settings where direct detection of viral nucleic acid may be unsuccessful. Taken together, our results illuminate unique aspects of the host transcriptional response to SARS-CoV-2 in comparison to other respiratory viruses and demonstrate the feasibility of COVID-19 diagnostics based on patient gene expression.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19.

BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses. .

Time to Recognition of Sepsis in the Emergency Department Using Electronic Health Record Data: A Comparative Analysis of Systemic Inflammatory Response Syndrome, Sequential Organ Failure Assessment, and Quick Sequential Organ Failure Assessment.

OBJECTIVES: Early identification of sepsis is critical to improving patient outcomes. Impact of the new sepsis definition (Sepsis-3) on timing of recognition in the emergency department has not been evaluated. Our study objective was to compare time to meeting systemic inflammatory response syndrome (Sepsis-2) criteria, Sequential Organ Failure Assessment (Sepsis-3) criteria, and quick Sequential Organ Failure Assessment criteria using electronic health record data. DESIGN: Retrospective, observational study. SETTING: The emergency department at the University of California, San Francisco. PATIENTS: Emergency department encounters between June 2012 and December 2016 for patients greater than or equal to 18 years old with blood cultures ordered, IV antibiotic receipt, and identification with sepsis via systemic inflammatory response syndrome or Sequential Organ Failure Assessment within 72 hours of emergency department presentation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed timestamped electronic health record data from 16,612 encounters identified as sepsis by greater than or equal to 2 systemic inflammatory response syndrome criteria or a Sequential Organ Failure Assessment score greater than or equal to 2. The primary outcome was time from emergency department presentation to meeting greater than or equal to 2 systemic inflammatory response syndrome criteria, Sequential Organ Failure Assessment greater than or equal to 2, and/or greater than or equal to 2 quick Sequential Organ Failure Assessment criteria. There were 9,087 patients (54.7%) that met systemic inflammatory response syndrome-first a median of 26 minutes post-emergency department presentation (interquartile range, 0-109 min), with 83.1% meeting Sequential Organ Failure Assessment criteria a median of 118 minutes later (interquartile range, 44-401 min). There were 7,037 patients (42.3%) that met Sequential Organ Failure Assessment-first, a median of 113 minutes post-emergency department presentation (interquartile range, 60-251 min). Quick Sequential Organ Failure Assessment was met in 46.4% of patients a median of 351 minutes post-emergency department presentation (interquartile range, 67-1,165 min). Adjusted odds of in-hospital mortality were 39% greater in patients who met systemic inflammatory response syndrome-first compared with those who met Sequential Organ Failure Assessment-first (odds ratio, 1.39; 95% CI, 1.20-1.61). CONCLUSIONS: Systemic inflammatory response syndrome and Sequential Organ Failure Assessment initially identified distinct populations. Using systemic inflammatory response syndrome resulted in earlier electronic health record sepsis identification in greater than 50% of patients. Using Sequential Organ Failure Assessment alone may delay identification. Using systemic inflammatory response syndrome alone may lead to missed sepsis presenting as acute organ dysfunction. Thus, a combination of inflammatory (systemic inflammatory response syndrome) and organ dysfunction (Sequential Organ Failure Assessment) criteria may enhance timely electronic health record-based sepsis identification.

The Association between Limited English Proficiency and Sepsis Mortality.

BACKGROUND: Limited English proficiency (LEP) has been implicated in poor health outcomes. Sepsis is a frequently fatal syndrome that is commonly encountered in hospital medicine. The impact of LEP on sepsis mortality is not currently known. OBJECTIVE: To determine the association between LEP and sepsis mortality. DESIGN: Retrospective cohort study. SETTING: 800-bed, tertiary care, academic medical center. PATIENTS: Electronic health record data were obtained for adults admitted to the hospital with sepsis between June 1, 2012 and December 31, 2016. MEASUREMENTS: The primary predictor was LEP. Patients were defined as having LEP if their self-reported primary language was anything other than English and interpreter services were required during hospitalization. The primary outcome was inpatient mortality. Mortality was compared across races stratified by LEP using chi-squared tests of significance. Bivariable and multivariable logistic regressions were performed to investigate the association between mortality, race, and LEP, adjusting for baseline characteristics, comorbidities, and illness severity. RESULTS: Among 8,974 patients with sepsis, we found that 1 in 5 had LEP, 62% of whom were Asian. LEP was highly associated with death across all races except those identifying as Black and Latino. LEP was associated with a 31% increased odds of mortality after adjusting for illness severity, comorbidities, and other baseline characteristics, including race (OR 1.31, 95% CI 1.06-1.63, P = .02). CONCLUSIONS: In a single-center study of patients hospitalized with sepsis, LEP was associated with mortality across nearly all races. This is a novel finding that will require further exploration into the causal nature of this association.