Retrospective identification of infection in the emergency department: A significant challenge in sepsis clinical trials

O’Neal, Catherine; Hamer, Diana; Musso, Mandi W.; Caffery, Terrell; Walker, Morgan; LaVie, Katherine W.; Berlinger, M.; Thomas, Christopher; Alwood, Shannon; Jagneaux, Tonya; Sánchez, Michael; O’Neal, Hollis R.

doi:10.1016/j.amjms.2022.02.008

Cited by 3 publications

(1 citation statement)

References 14 publications

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“…We developed a rigorous process to adjudicate for each component. First, coordinators extracted data from the EHR to complete an objective evaluation for infection using prespecified criteria ( 23 ) and organ dysfunction using SOFA ( 24 ). Subsequently, a site investigator with access to the entire EHR and blinded to the ISI result completed a clinical review and recorded pertinent clinical information.…”

Section: Methodsmentioning

confidence: 99%

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

O’Neal,

Sheybani,

Janz

et al. 2024

Critical Care Explorations

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OBJECTIVES: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. DESIGN: Prospective cohort study. SETTING: Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. PATIENTS: Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. INTERVENTIONS: All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. MEASUREMENTS AND MAIN RESULTS: Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5–15.7%) in band 1, 28.1% (95% CI, 21.3–35.8%) in band 2, and 49.4% (95% CI, 41.4–57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. CONCLUSIONS: Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.

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Section: Methodsmentioning

confidence: 99%

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

O’Neal,

Sheybani,

Janz

et al. 2024

Critical Care Explorations

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Advances in molecular agents targeting toll-like receptor 4 signaling pathways for potential treatment of sepsis

Zheng,

Gao,

Zhu

et al. 2024

European Journal of Medicinal Chemistry

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Cellular host response sepsis test for risk stratification of patients in the emergency department: A pooled analysis

O'Neal,

Sheybani,

Kraus

et al. 2024

Academic Emergency Medicine

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ObjectivesSepsis is one of the most common, costly, and misdiagnosed conditions in U.S. emergency departments (EDs). ED providers often treat on nonspecific signs, subjective suspicion, or presumption of infection, resulting in over‐ and undertreatment. An increased understanding of host response has opened a new direction for sepsis diagnostics. The IntelliSep test is a U.S. Food and Drug Administration–cleared cellular host response diagnostic that could help distinguish sepsis in ED settings. Our objective was to evaluate the potential of the cellular host response test to expedite appropriate care for patients who present with signs of infection.MethodsWe performed a pooled analysis of five adult (≥18 years) cohorts enrolled at seven geographically diverse U.S. sites in separate studies. Structured blinded adjudication was used to classify presence or absence of sepsis, and only patients with high confidence in the adjudicated label were included (n = 1002), defined as patients for whom there was consensus in the determination of sepsis per the Sepsis‐3 and severe sepsis per the Sepsis‐2 definitions between both the independent adjudication panel and the site‐level physician.ResultsAmong patients with signs or suspicion of infection, the test achieved similar or better performance compared to other indicators in identifying patients at high risk for sepsis (specificity > 83%) and significantly superior performance in identifying those at low risk (sensitivity > 92%; 0% sepsis‐associated mortality). The test also stratified severity of illness, as shown by 30‐day in‐hospital mortality (p < 0.001), hospital length of stay (p < 0.01), and use of hospital resources (p < 0.001).ConclusionsOur data suggest that the cellular host response test provides clinically actionable results for patients at both high and low risk for sepsis and provides a rapid, objective means for risk stratification of patients with signs of infection. If integrated into standard of care, the test may help improve outcomes and reduce unnecessary antibiotic use.

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Retrospective identification of infection in the emergency department: A significant challenge in sepsis clinical trials

Cited by 3 publications

References 14 publications

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use

Advances in molecular agents targeting toll-like receptor 4 signaling pathways for potential treatment of sepsis

Cellular host response sepsis test for risk stratification of patients in the emergency department: A pooled analysis

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