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

      research-article
      , MSc, MD, PhD 1 , 2 , , , MD, MSc 3 , 4 , , PhD 5 , , PhD 5 , , DPhil 5
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          Could a prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors be developed using index sepsis illness characteristics as predictors?

          Findings

          In this cohort study of 94 748 patients in adult general critical care units in England, unplanned rehospitalization or death in the first year after hospital discharge occurred for 51% of patients in the derivation cohort and 53% of patients in the validation cohort. The prognostic score is calculated using 8 predictors: previous hospitalizations in the preceding year, age, socioeconomic status, preadmission dependence, number of comorbidities, admission type, site of infection, and admission blood hemoglobin level.

          Meaning

          This score provides clinically useful information for prognosis discussions and planning follow-up care for 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.

          Abstract

          This cohort study uses data from the Intensive Care National Audit & Research Centre Case Mix Programme database to derive and validate a parsimonious prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors.

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          Most cited references23

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          Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.

          The performance of a predictive model is overestimated when simply determined on the sample of subjects that was used to construct the model. Several internal validation methods are available that aim to provide a more accurate estimate of model performance in new subjects. We evaluated several variants of split-sample, cross-validation and bootstrapping methods with a logistic regression model that included eight predictors for 30-day mortality after an acute myocardial infarction. Random samples with a size between n = 572 and n = 9165 were drawn from a large data set (GUSTO-I; n = 40,830; 2851 deaths) to reflect modeling in data sets with between 5 and 80 events per variable. Independent performance was determined on the remaining subjects. Performance measures included discriminative ability, calibration and overall accuracy. We found that split-sample analyses gave overly pessimistic estimates of performance, with large variability. Cross-validation on 10% of the sample had low bias and low variability, but was not suitable for all performance measures. Internal validity could best be estimated with bootstrapping, which provided stable estimates with low bias. We conclude that split-sample validation is inefficient, and recommend bootstrapping for estimation of internal validity of a predictive logistic regression model.
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            Decision curve analysis.

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              Increased 1-year healthcare use in survivors of severe sepsis.

              Hospitalizations for severe sepsis are common, and a growing number of patients survive to hospital discharge. Nonetheless, little is known about survivors' post-discharge healthcare use. To measure inpatient healthcare use of severe sepsis survivors compared with patients' own presepsis resource use and the resource use of survivors of otherwise similar nonsepsis hospitalizations. This is an observational cohort study of survivors of severe sepsis and nonsepsis hospitalizations identified from participants in the Health and Retirement Study with linked Medicare claims, 1998-2005. We matched severe sepsis and nonsepsis hospitalizations by demographics, comorbidity burden, premorbid disability, hospitalization length, and intensive care use. Using Medicare claims, we measured patients' use of inpatient facilities (hospitals, long-term acute care hospitals, and skilled nursing facilities) in the 2 years surrounding hospitalization. Severe sepsis survivors spent more days (median, 16 [interquartile range, 3-45] vs. 7 [0-29]; P < 0.001) and a higher proportion of days alive (median, 9.6% [interquartile range, 1.4-33.8%] vs. 1.9% [0.0-7.9%]; P < 0.001) admitted to facilities in the year after hospitalization, compared with the year prior. The increase in facility-days was similar for nonsepsis hospitalizations. However, the severe sepsis cohort experienced greater post-discharge mortality (44.2% [95% confidence interval, 41.3-47.2%] vs. 31.4% [95% confidence interval, 28.6-34.2%] at 1 year), a steeper decline in days spent at home (difference-in-differences, -38.6 d [95% confidence interval, -50.9 to 26.3]; P < 0.001), and a greater increase in the proportion of days alive spent in a facility (difference-in-differences, 5.4% [95% confidence interval, 2.8-8.1%]; P < 0.001). Healthcare use is markedly elevated after severe sepsis, and post-discharge management may be an opportunity to reduce resource use.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                14 September 2020
                September 2020
                14 September 2020
                : 3
                : 9
                : e2013580
                Affiliations
                [1 ]Guy’s and St Thomas’ NHS Foundation Trust, ICU Support Offices, St Thomas’ Hospital, London, United Kingdom
                [2 ]School of Immunology & Microbial Sciences, King’s College London, London, United Kingdom
                [3 ]Interdepartmental Division of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
                [4 ]Associate Editor, JAMA Network Open
                [5 ]Intensive Care National Audit & Research Centre, Napier House, London, United Kingdom
                Author notes
                Article Information
                Accepted for Publication: June 2, 2020.
                Published: September 14, 2020. doi:10.1001/jamanetworkopen.2020.13580
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Shankar-Hari M et al. JAMA Network Open.
                Corresponding Author: Manu Shankar-Hari, MSc, MD, PhD, First Floor, East Wing, St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust London, London SE17EH, UK ( manu.shankar-hari@ 123456kcl.ac.uk ).
                Author Contributions: Drs Shankar-Hari and Harrison had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Harrison and Rowan contributed equally to this work.
                Concept and design: Shankar-Hari, Rubenfeld, Harrison, Rowan.
                Acquisition, analysis, or interpretation of data: Shankar-Hari, Ferrando-Vivas, Harrison, Rowan.
                Drafting of the manuscript: Shankar-Hari, Rowan.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Shankar-Hari, Rubenfeld, Harrison.
                Obtained funding: Shankar-Hari.
                Administrative, technical, or material support: Rowan.
                Supervision: Harrison, Rowan.
                Conflict of Interest Disclosures: Dr Rubenfeld reported serving as a consultant for Endpoint Health. Dr Harrison reported receiving grants from the National Institute for Health Research during the conduct of the study. No other disclosures were reported.
                Funding/Support: Dr Shankar-Hari is funded by a National Institute for Health Research Clinician Scientist Award (CS-2016-16-011) for this research project. This publication presents independent research funded by the National Institute for Health Research.
                Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Disclaimer: The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, or the Department of Health and Social Care. Dr Rubenfeld is an associate editor of JAMA Network Open, but he was not involved in any of the decisions regarding review of the manuscript or its acceptance.
                Additional Contributions: As part of the preparation for this research, in the write up of theNational Institute for Health Research Clinician Scientist Award application, Dr Manu Shankar-Hari (CS-2016-16-011) consulted survivors of sepsis to explore the longer-term health care requirements, which informed the analysis plan for this study.
                Additional Information: The data used in this study are accessible from the UK National Intensive Care Admissions dataset managed by the Intensive Care National Audit & Research Centre data set. A free-to-use online tool is available at https://sepsis-ssip-score.org.uk/ssip_score.
                Article
                zoi200514
                10.1001/jamanetworkopen.2020.13580
                7490647
                32926114
                20d675c7-728f-49a9-bb7f-5672289b8098
                Copyright 2020 Shankar-Hari M et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 22 February 2020
                : 2 June 2020
                Categories
                Research
                Original Investigation
                Online Only
                Critical Care Medicine

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