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Derivation of Novel Risk Prediction Scores for Community-Acquired Sepsis and Severe Sepsis*

Wang, Henry E. MD, MS; Donnelly, John P. MSPH; Griffin, Russell PhD; Levitan, Emily B. ScD; Shapiro, Nathan I. MD, MPH; Howard, George DrPH; Safford, Monika M. MD

doi: 10.1097/CCM.0000000000001666
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Objective: We sought to derive and internally validate a Sepsis Risk Score and a Severe Sepsis Risk Score predicting future sepsis and severe sepsis events among community-dwelling adults.

Design: National population-based cohort.

Setting: United States.

Subjects: A total of 30,239 community-dwelling adults 45 years old or older in the national REasons for Geographic And Racial Differences in Stroke cohort.

Interventions: None.

Measurements and Main Results: Over a median of 6.6 years (interquartile range, 5.1–8.1 yr) of follow-up, there were 1,532 first sepsis (prevalence 8.3 per 1,000 person-years) and 1,151 first severe sepsis (6.2 per 1,000 person-years) events. Risk factors in the best derived Sepsis Risk Score and Severe Sepsis Risk Score included chronic lung disease, age 75 years or older, peripheral artery disease, diabetes, tobacco use, white race, stroke, atrial fibrillation, coronary artery disease, obesity, hypertension, deep vein thrombosis, male sex, high-sensitivity C-reactive protein greater than 3.0 mg/dL, cystatin C ≥1.11 mg/dL, estimated glomerular filtration rate less than 60 mL/min/1.73 m2, and albumin-to-creatinine ratio protein greater than 30 μg/mg. Sepsis Risk Score risk categories were very low (0–3 points; 2.3 events per 1,000 person-years), low (4–6; 4.1), medium (7–9; 6.5), high (10–12; 9.7), and very high (13–38; 21.1). Severe Sepsis Risk Score risk categories were very low (0–5 points; 1.5 events per 1,000 person-years), low (6–9; 3.4), medium (10–13; 6.7), high (14–17; 9.9), and very high (18–45; 22.1). The Sepsis Risk Score and Severe Sepsis Risk Score exhibited good discrimination (bootstrapped C index, 0.703 and 0.742) and calibration (p = 0.65 and 0.06).

Conclusions: The Sepsis Risk Score and Severe Sepsis Risk Score predict 10-year sepsis and severe sepsis risk among community-dwelling adults and may aid in sepsis prevention or mitigation efforts.

Supplemental Digital Content is available in the text.

1Department of Emergency Medicine, University of Alabama School of Medicine, Birmingham, AL.

2Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.

3Division of Preventive Medicine, Department of Medicine, University of Alabama School of Medicine, Birmingham, AL.

4Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA.

5Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL.

*See also p. 1425.

Dr. Wang, Dr. Shapiro, Mr. Howard, Ms. Levitan, Dr. Griffin, and Dr. Safford conceived the study. Dr. Wang, Dr. Safford, Dr. Shapiro, and Mr. Howard obtained funding. Dr. Wang, Mr. Howard, Dr. Griffin, and Dr. Safford oversaw data collection. Dr. Wang, Mr. Donnelly, Dr. Griffin, and Ms. Levitan conducted the analysis. Dr. Wang drafted the article and all authors contributed to its critical review. Dr. Wang assumes overall responsibility for the article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported by award R01-NR012726 from the National Institute for Nursing Research, UL1-RR025777 from the National Center for Research Resources, as well as by grants from the Center for Clinical and Translational Science and the Lister Hill Center for Health Policy of the University of Alabama at Birmingham. The parent REasons for Geographic And Racial Differences in Stroke (REGARDS) study was supported by cooperative agreement U01-NS041588 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. Representatives of the funding agencies have been involved in the review of the article but not directly involved in the collection, management, analysis, or interpretation of the data.

Dr. Wang received grant funding from the National Institutes of Health (NIH) and received support for article research from the NIH. Mr. Donnelly received support for article research from the NIH. His institution received funding from the AHRQ Predoctoral Fellowship in Health Services Research. He is currently supported by grant T32-HS013852 from the Agency for Healthcare Research and Quality, Rockville, MD. Dr. Levitan received funding from Robinson Calcagnie Robinson Shapiro Davis. His institution received funding from Amgen. Dr. Shapiro received support from Rapid Pathogen Screening, Cumberland pharma, Thermo-fischer, and Siemens. He received support for article research from the NIH. His institution received support from the NIH. Dr. Howard received support for article research from the NIH. Dr. Safford reports the following potential conflicts of interest: Amgen—salary support to study patterns of statin use in Medicare and other large databases; diaDexus—salary support for a research grant on lipids and coronary heart disease outcomes; diaDexus—consulting to help with U.S. Food and Drug Administration application; NIH, Agency for Healthcare Research and Quality—salary support for research grants. Dr. Griffen disclosed that he does not have any potential conflicts of interest.

For information regarding this article, E-mail: hwang@uabmc.edu

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