Browsing by Author "Mahle, Rachael E"

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    ItemOpen Access
    Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study.
    (BMJ open, 2023-02) Blair, Paul W; Mehta, Rittal; Oppong, Chris Kwaku; Tin, Som; Ko, Emily; Tsalik, Ephraim L; Chenoweth, Josh; Rozo, Michelle; Adams, Nehkonti; Beckett, Charmagne; Woods, Christopher W; Striegel, Deborah A; Salvador, Mark G; Brandsma, Joost; McKean, Lauren; Mahle, Rachael E; Hulsey, William R; Krishnan, Subramaniam; Prouty, Michael; Letizia, Andrew; Fox, Anne; Faix, Dennis; Lawler, James V; Duplessis, Chris; Gregory, Michael G; Vantha, Te; Owusu-Ofori, Alex Kwame; Ansong, Daniel; Oduro, George; Schully, Kevin L; Clark, Danielle V

    Objectives

    We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana.

    Design

    Prospective cohort studies.

    Setting and participants

    From 2014 to 2021, participants with two or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in Cambodia and Ghana and hospitalised participants with suspected infection were enrolled in the USA. Cox proportional hazards regression was performed, and Harrell's C-statistic calculated to determine 28-day mortality prediction performance of the quick Sequential Organ Failure Assessment (qSOFA) score ≥2, SIRS score ≥3, National Early Warning Score (NEWS) ≥5, Modified Early Warning Score (MEWS) ≥5 or Universal Vital Assessment (UVA) score ≥2. Screening tools were compared with baseline risk (age and sex) with the Wald test.

    Results

    The cohorts included 567 participants (42.9% women) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia and 180 participants from Durham, North Carolina in the USA. The pooled mortality was 16.4% at 28 days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI 0.58 to 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% CI 0.64 to 0.73; p<0.001), qSOFA (C-statistic: 0.70, 95% CI 0.64 to 0.75; p<0.001), UVA score (C-statistic: 0.73, 95% CI 0.69 to 0.78; p<0.001), but not with SIRS (0.60; 95% CI 0.54 to 0.65; p=0.13). Within individual cohorts, only the UVA score in Ghana performed better than baseline risk (C-statistic: 0.77; 95% CI 0.71 to 0.83; p<0.001).

    Conclusions

    Among the cohorts, MEWS, NEWS, qSOFA and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.
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    ItemOpen Access
    Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-08) Mahle, Rachael E; Suchindran, Sunil; Henao, Ricardo; Steinbrink, Julie M; Burke, Thomas W; McClain, Micah T; Ginsburg, Geoffrey S; Woods, Christopher W; Tsalik, Ephraim L

    Background

    Host gene expression has emerged as a complementary strategy to pathogen detection tests for the discrimination of bacterial and viral infection. The impact of immunocompromise on host-response tests remains unknown. We evaluated a host-response test discriminating bacterial, viral, and noninfectious conditions in immunocompromised subjects.

    Methods

    An 81-gene signature was measured using real-time-polymerase chain reaction in subjects with immunocompromise (chemotherapy, solid-organ transplant, immunomodulatory agents, AIDS) with bacterial infection, viral infection, or noninfectious illness. A regularized logistic regression model trained in immunocompetent subjects was used to estimate the likelihood of each class in immunocompromised subjects.

    Results

    Accuracy in the 136-subject immunocompetent training cohort was 84.6% for bacterial versus nonbacterial discrimination and 80.8% for viral versus nonviral discrimination. Model validation in 134 immunocompromised subjects showed overall accuracy of 73.9% for bacterial infection (P = .04 relative to immunocompetent subjects) and 75.4% for viral infection (P = .30). A scheme reporting results by quartile improved test utility. The highest probability quartile ruled-in bacterial and viral infection with 91.4% and 84.0% specificity, respectively. The lowest probability quartile ruled-out infection with 90.1% and 96.4% sensitivity for bacterial and viral infection, respectively. Performance was independent of the type or number of immunocompromising conditions.

    Conclusions

    A host gene expression test discriminated bacterial, viral, and noninfectious etiologies at a lower overall accuracy in immunocompromised patients compared with immunocompetent patients, although this difference was only significant for bacterial infection classification. With modified interpretive criteria, a host-response strategy may offer clinically useful diagnostic information for patients with immunocompromise.