TY - JOUR
T1 - Predicting the risk of mortality during hospitalization in sick severely malnourished children using daily evaluation of key clinical warning signs
AU - Wen, Bijun
AU - Brals, Daniella
AU - Bourdon, Celine
AU - Erdman, Lauren
AU - Ngari, Moses
AU - Chimwezi, Emmanuel
AU - Potani, Isabel
AU - Thitiri, Johnstone
AU - Mwalekwa, Laura
AU - Berkley, James A.
AU - Bandsma, Robert H. J.
AU - Voskuijl, Wieger
N1 - Funding Information: We thank the many individuals and organizations who made this study possible, including all the children and their families who took part; the Department of Paediatrics and Child Health, Queen Elizabeth Central Hospital in Blantyre, Malawi; and the Kilifi District Hospital and Coast Provincial General Hospital in Mombasa, Kenya. This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation [Grant Number OPP1131320]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Funding Information: We thank the many individuals and organizations who made this study possible, including all the children and their families who took part; the Department of Paediatrics and Child Health, Queen Elizabeth Central Hospital in Blantyre, Malawi; and the Kilifi District Hospital and Coast Provincial General Hospital in Mombasa, Kenya. This work was supported, in whole or in part, by the Bill & Melinda Gates Foundation [Grant Number OPP1131320]. Under the grant conditions of the Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. Funding Information: The parent clinical trial was funded by the Thrasher Research Fund to R.H.J.B and J.A.B. number 9403. W.V., J.T., M.N., C.B., and J.A.B. are supported by the Bill & Melinda Gates Foundation (Grant Number OPP1131320). J.A.B. and L.M. are supported by the MRC/DfID/Wellcome Trust Global Health Trials Scheme (Grant Number MR/M007367/1). B.W. is supported by the Research Training Competition (RESTRACOMP) Graduate Scholarship at the Hospital for Sick Children and the Ontario Graduate Scholarship (OGS) at the University of Toronto. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: Despite adherence to WHO guidelines, inpatient mortality among sick children admitted to hospital with complicated severe acute malnutrition (SAM) remains unacceptably high. Several studies have examined risk factors present at admission for mortality. However, risks may evolve during admission with medical and nutritional treatment or deterioration. Currently, no specific guidance exists for assessing daily treatment response. This study aimed to determine the prognostic value of monitoring clinical signs on a daily basis for assessing mortality risk during hospitalization in children with SAM. Methods: This is a secondary analysis of data from a randomized trial (NCT02246296) among 843 hospitalized children with SAM. Daily clinical signs were prospectively collected during ward rounds. Multivariable extended Cox regression using backward feature selection was performed to identify daily clinical warning signs (CWS) associated with time to death within the first 21 days of hospitalization. Predictive models were subsequently developed, and their prognostic performance evaluated using Harrell’s concordance index (C-index) and time-dependent area under the curve (tAUC). Results: Inpatient case fatality ratio was 16.3% (n=127). The presence of the following CWS during daily assessment were found to be independent predictors of inpatient mortality: symptomatic hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever. Daily risk scores computed using these 7 CWS together with MUAC<10.5cm at admission as additional CWS predict survival outcome of children with SAM with a C-index of 0.81 (95% CI 0.77–0.86). Moreover, counting signs among the top 5 CWS (reduced consciousness, symptomatic hypoglycemia, chest indrawing, not able to complete foods, and MUAC<10.5cm) provided a simpler tool with similar prognostic performance (C-index of 0.79; 95% CI 0.74–0.84). Having 1 or 2 of these CWS on any day during hospitalization was associated with a 3 or 11-fold increased mortality risk compared with no signs, respectively. Conclusions: This study provides evidence for structured monitoring of daily CWS as recommended clinical practice as it improves prediction of inpatient mortality among sick children with complicated SAM. We propose a simple counting-tool to guide healthcare workers to assess treatment response for these children. Trial registration: NCT02246296
AB - Background: Despite adherence to WHO guidelines, inpatient mortality among sick children admitted to hospital with complicated severe acute malnutrition (SAM) remains unacceptably high. Several studies have examined risk factors present at admission for mortality. However, risks may evolve during admission with medical and nutritional treatment or deterioration. Currently, no specific guidance exists for assessing daily treatment response. This study aimed to determine the prognostic value of monitoring clinical signs on a daily basis for assessing mortality risk during hospitalization in children with SAM. Methods: This is a secondary analysis of data from a randomized trial (NCT02246296) among 843 hospitalized children with SAM. Daily clinical signs were prospectively collected during ward rounds. Multivariable extended Cox regression using backward feature selection was performed to identify daily clinical warning signs (CWS) associated with time to death within the first 21 days of hospitalization. Predictive models were subsequently developed, and their prognostic performance evaluated using Harrell’s concordance index (C-index) and time-dependent area under the curve (tAUC). Results: Inpatient case fatality ratio was 16.3% (n=127). The presence of the following CWS during daily assessment were found to be independent predictors of inpatient mortality: symptomatic hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever. Daily risk scores computed using these 7 CWS together with MUAC<10.5cm at admission as additional CWS predict survival outcome of children with SAM with a C-index of 0.81 (95% CI 0.77–0.86). Moreover, counting signs among the top 5 CWS (reduced consciousness, symptomatic hypoglycemia, chest indrawing, not able to complete foods, and MUAC<10.5cm) provided a simpler tool with similar prognostic performance (C-index of 0.79; 95% CI 0.74–0.84). Having 1 or 2 of these CWS on any day during hospitalization was associated with a 3 or 11-fold increased mortality risk compared with no signs, respectively. Conclusions: This study provides evidence for structured monitoring of daily CWS as recommended clinical practice as it improves prediction of inpatient mortality among sick children with complicated SAM. We propose a simple counting-tool to guide healthcare workers to assess treatment response for these children. Trial registration: NCT02246296
KW - Danger signs
KW - Mortality prediction
KW - SAM
KW - Severe malnutrition
KW - Sub-Saharan Africa
UR - http://www.scopus.com/inward/record.url?scp=85115157870&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12916-021-02074-6
DO - https://doi.org/10.1186/s12916-021-02074-6
M3 - Article
C2 - 34538239
SN - 1464-2662
VL - 19
JO - BMC medicine
JF - BMC medicine
IS - 1
M1 - 222
ER -