Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors

Abstract

Importance: The longer-term risk of rehospitalizations and death of adult sepsis survivors is associated with index sepsis illness characteristics.

Objective: To derive and validate a parsimonious prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors.

Design, setting, and participants: This cohort study used data from the Intensive Care National Audit & Research Centre Case Mix Programme database on adult sepsis survivors identified from consecutive critical care admissions to 192 adult general critical care units in England, United Kingdom, between April 1, 2009, and March 31, 2014 (94 748 patients in the derivation cohort), and between April 1, 2014, and March 31, 2015 (24 669 patients in the validation cohort). Statistical analysis was performed from July 5 to October 31, 2019. Generic characteristics (age, sex, race/ethnicity, 2015 Index of Multiple Deprivation [IMD2015] in England quintiles, preadmission dependence, previous hospitalizations in the year preceding index sepsis admission, comorbidity, admission type, Acute Physiology and Chronic Health Evaluation II physiology score, hospital length of stay, worst blood lactate and blood hemoglobin concentrations, and type of hospital) and sepsis-specific characteristics (site of infection, numbers of organ dysfunctions, and organ support) at the index sepsis admission were used as predictors.

Main outcomes and measures: Prognostic score derived and validated using multivariable logistic regression for the outcome of unplanned rehospitalization or death in the first year after hospital discharge of adult sepsis survivors, as well as clinical usefulness assessed using decision curve analysis. Prognostic score validation was performed for internal validation with bootstrapping and temporal cohort external validation.

Results: This cohort study included 94 748 patients (51 164 men [54.0%]; mean [SD] age, 61.3 [17.0] years) in the derivation cohort and 24 669 patients (13 255 men [53.7%]; mean [SD] age, 62.1 [16.8%]) in the validation cohort. Unplanned rehospitalization or death in the first year after hospital discharge occurred for 48 594 patients (51.3%) in the derivation cohort and 13 129 patients (53.2%) in the validation cohort. Eight independent predictors were identified and weighted to generate a prognostic score for every patient: previous hospitalizations, age in 10-year increments, IMD2015 in England quintiles, preadmission dependence, comorbidities, admission type, blood hemoglobin level, and site of infection. The total prognostic score ranged from 0 to 22 points, with lower scores indicating a lower risk of the outcome. The derivation and validation cohorts had similar rates of prognostic scores of 0 to 4 points (5088 of 16 684 patients [30.5%] and 471 of 1725 patients [27.3%]) and prognostic scores of 11 points or more (15 732 of 21 641 patients [72.7%] and 5753 of 7952 patients [72.3%]). The area under the receiver operating characteristic curve for the prognostic score was 0.675 (95% CI, 0.672-0.679). The decision curve analysis highlighted an optimal score cutoff of 7 points or more.

Conclusions and relevance: The prognostic score reported in this study uses 8 internationally feasible predictors measured during the index sepsis admission and provides clinically useful information on sepsis survivors' risk of unplanned rehospitalization or death in the first year after hospital discharge.

Figure 1.. Cumulative Incidence Plots for Unplanned Rehospitalization, Infection-Related Rehospitalization, and Mortality by Rehospitalization Status

A, The cumulative all-cause unplanned rehospitalization rates (blue line) at 30, 90, 180, and 365 days were 16.9%, 28.4%, 36.9%, and 46.9%, respectively. The cumulative infection-related rehospitalization rates (orange line) at 30, 90, 180, and 365 days were 7.7%, 14.1%, 19.4%, and 26.7%, respectively (see eTable 3 in the Supplement for further information). B, The cumulative all-cause mortality rates among patients with 1 or more rehospitalizations (blue line) at 30, 90, 180, and 365 days were 17.4%, 26.2%, 32.8%, and 40.5%, respectively. These are reported using Cox proportional hazards regression models.

Figure 2.. Description and Assessment of Clinical Prediction Model in Derivation Cohort

A, Distribution of prognostic score by strata. B, Cumulative incidence of unplanned rehospitalization or death at 1 year after hospital discharge by prognostic score strata. C, Sensitivity and specificity of the score at different cutoff points. D, Calibration plot compares the observed (dotted line) vs predicted (solid line) risk of outcome events of unplanned rehospitalizations or death in the first year after hospital discharge. The distribution of outcome over the deciles is indicated by the bar graphs at the bottom, with patients with outcomes represented above the line and those without outcomes represented below the line. AUROC indicates area under the receiver operating characteristic curve.

Figure 3.. Clinical Usefulness With Decision Curve Analysis (DCA) of Prognostic Score

A, The x-axis of DCA graphs refers to the threshold probability, which is the risk of 1-year unplanned rehospitalization or death between 0 and 1, above which the clinician or patient would choose treatment. The y-axis shows the net benefit in units of the benefit associated with correctly identifying 1 unplanned rehospitalization or death. Decision curves are shown for scores of 5 or more, 7 or more, and 11 or more. B, Proportions by score strata for rehospitalization, for deaths in those who experience 1 or more rehospitalization episodes within that strata, and deaths without rehospitalization during the 365-day follow-up period.