Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness

Andrea L. Conroy, Michael Hawkes, Kyla Hayford, Sophie Namasopo, Robert O. Opoka, Chandy John, W. Conrad Liles, Kevin C. Kain

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: The development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally. Methods: We evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambaréné Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA). Model discrimination was evaluated by comparing areas under receiver operating characteristic curves (AUCs) and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Sub-analyses were performed in malaria versus non-malaria febrile illness (NMFI), and in early (≤48 hours) versus late (>48 hours) deaths. Results: In total, 2089 children with known outcomes were included in the study (99 deaths, 4.7% mortality). All three scoring systems yielded good discrimination (AUCs, 95% confidence interval (CI): LODS, 0.90, 0.88 to 0.91; SICK, 0.85, 0.83 to 0.86; PEDIA, 0.90, 0.88 to 0.91). Using the Youden index to identify the best cut-offs, LODS had the highest positive likelihood ratio (+LR, 95% CI: LODS, 6.5, 5.6 to 7.6; SICK, 4.4, 3.9 to 5.0; PEDIA, 4.4, 3.9 to 5.0), whereas PEDIA had the lowest negative likelihood ratio (-LR, 95% CI: LODS, 0.21, 0.1 to 0.3; SICK, 0.22, 0.1 to 0.3; PEDIA, 0.16, 0.1 to 0.3), LODS and PEDIA were well calibrated (P = 0.79 and P = 0.21 respectively), and had higher AUCs than SICK in discriminating between survivors and non-survivors in malaria (AUCs, 95% CI: LODS, 0.92, 0.90 to 0.93; SICK, 0.86, 0.84 to 0.87; PEDIA, 0.92, 0.90 to 0.93), but comparable AUCs in NMFI (AUCs, 95% CI: LODS, 0.86, 0.83 to 0.89; SICK, 0.82, 0.79 to 0.86; PEDIA, 0.87, 0.83 to 0.893). The majority of deaths in the study occurred early (n = 85, 85.9%) where LODS and PEDIA had good discrimination. Conclusions: All three scoring systems predicted outcome, but LODS holds the most promise as a clinical prognostic score based on its simplicity to compute, requirement for no equipment, and good discrimination.

Original languageEnglish (US)
Article number47
JournalCritical Care
Volume19
Issue number1
DOIs
StatePublished - Feb 23 2015
Externally publishedYes

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Organ Dysfunction Scores
Malaria
Fever
Pediatrics
Mortality
Area Under Curve
Inflammation
Confidence Intervals
Hospital Mortality
ROC Curve
Calibration
Observational Studies
Survivors
Prospective Studies

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness. / Conroy, Andrea L.; Hawkes, Michael; Hayford, Kyla; Namasopo, Sophie; Opoka, Robert O.; John, Chandy; Liles, W. Conrad; Kain, Kevin C.

In: Critical Care, Vol. 19, No. 1, 47, 23.02.2015.

Research output: Contribution to journalArticle

Conroy, Andrea L. ; Hawkes, Michael ; Hayford, Kyla ; Namasopo, Sophie ; Opoka, Robert O. ; John, Chandy ; Liles, W. Conrad ; Kain, Kevin C. / Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness. In: Critical Care. 2015 ; Vol. 19, No. 1.
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abstract = "Introduction: The development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally. Methods: We evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambar{\'e}n{\'e} Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA). Model discrimination was evaluated by comparing areas under receiver operating characteristic curves (AUCs) and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Sub-analyses were performed in malaria versus non-malaria febrile illness (NMFI), and in early (≤48 hours) versus late (>48 hours) deaths. Results: In total, 2089 children with known outcomes were included in the study (99 deaths, 4.7{\%} mortality). All three scoring systems yielded good discrimination (AUCs, 95{\%} confidence interval (CI): LODS, 0.90, 0.88 to 0.91; SICK, 0.85, 0.83 to 0.86; PEDIA, 0.90, 0.88 to 0.91). Using the Youden index to identify the best cut-offs, LODS had the highest positive likelihood ratio (+LR, 95{\%} CI: LODS, 6.5, 5.6 to 7.6; SICK, 4.4, 3.9 to 5.0; PEDIA, 4.4, 3.9 to 5.0), whereas PEDIA had the lowest negative likelihood ratio (-LR, 95{\%} CI: LODS, 0.21, 0.1 to 0.3; SICK, 0.22, 0.1 to 0.3; PEDIA, 0.16, 0.1 to 0.3), LODS and PEDIA were well calibrated (P = 0.79 and P = 0.21 respectively), and had higher AUCs than SICK in discriminating between survivors and non-survivors in malaria (AUCs, 95{\%} CI: LODS, 0.92, 0.90 to 0.93; SICK, 0.86, 0.84 to 0.87; PEDIA, 0.92, 0.90 to 0.93), but comparable AUCs in NMFI (AUCs, 95{\%} CI: LODS, 0.86, 0.83 to 0.89; SICK, 0.82, 0.79 to 0.86; PEDIA, 0.87, 0.83 to 0.893). The majority of deaths in the study occurred early (n = 85, 85.9{\%}) where LODS and PEDIA had good discrimination. Conclusions: All three scoring systems predicted outcome, but LODS holds the most promise as a clinical prognostic score based on its simplicity to compute, requirement for no equipment, and good discrimination.",
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T1 - Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness

AU - Conroy, Andrea L.

AU - Hawkes, Michael

AU - Hayford, Kyla

AU - Namasopo, Sophie

AU - Opoka, Robert O.

AU - John, Chandy

AU - Liles, W. Conrad

AU - Kain, Kevin C.

PY - 2015/2/23

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N2 - Introduction: The development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally. Methods: We evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambaréné Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA). Model discrimination was evaluated by comparing areas under receiver operating characteristic curves (AUCs) and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Sub-analyses were performed in malaria versus non-malaria febrile illness (NMFI), and in early (≤48 hours) versus late (>48 hours) deaths. Results: In total, 2089 children with known outcomes were included in the study (99 deaths, 4.7% mortality). All three scoring systems yielded good discrimination (AUCs, 95% confidence interval (CI): LODS, 0.90, 0.88 to 0.91; SICK, 0.85, 0.83 to 0.86; PEDIA, 0.90, 0.88 to 0.91). Using the Youden index to identify the best cut-offs, LODS had the highest positive likelihood ratio (+LR, 95% CI: LODS, 6.5, 5.6 to 7.6; SICK, 4.4, 3.9 to 5.0; PEDIA, 4.4, 3.9 to 5.0), whereas PEDIA had the lowest negative likelihood ratio (-LR, 95% CI: LODS, 0.21, 0.1 to 0.3; SICK, 0.22, 0.1 to 0.3; PEDIA, 0.16, 0.1 to 0.3), LODS and PEDIA were well calibrated (P = 0.79 and P = 0.21 respectively), and had higher AUCs than SICK in discriminating between survivors and non-survivors in malaria (AUCs, 95% CI: LODS, 0.92, 0.90 to 0.93; SICK, 0.86, 0.84 to 0.87; PEDIA, 0.92, 0.90 to 0.93), but comparable AUCs in NMFI (AUCs, 95% CI: LODS, 0.86, 0.83 to 0.89; SICK, 0.82, 0.79 to 0.86; PEDIA, 0.87, 0.83 to 0.893). The majority of deaths in the study occurred early (n = 85, 85.9%) where LODS and PEDIA had good discrimination. Conclusions: All three scoring systems predicted outcome, but LODS holds the most promise as a clinical prognostic score based on its simplicity to compute, requirement for no equipment, and good discrimination.

AB - Introduction: The development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally. Methods: We evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambaréné Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA). Model discrimination was evaluated by comparing areas under receiver operating characteristic curves (AUCs) and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Sub-analyses were performed in malaria versus non-malaria febrile illness (NMFI), and in early (≤48 hours) versus late (>48 hours) deaths. Results: In total, 2089 children with known outcomes were included in the study (99 deaths, 4.7% mortality). All three scoring systems yielded good discrimination (AUCs, 95% confidence interval (CI): LODS, 0.90, 0.88 to 0.91; SICK, 0.85, 0.83 to 0.86; PEDIA, 0.90, 0.88 to 0.91). Using the Youden index to identify the best cut-offs, LODS had the highest positive likelihood ratio (+LR, 95% CI: LODS, 6.5, 5.6 to 7.6; SICK, 4.4, 3.9 to 5.0; PEDIA, 4.4, 3.9 to 5.0), whereas PEDIA had the lowest negative likelihood ratio (-LR, 95% CI: LODS, 0.21, 0.1 to 0.3; SICK, 0.22, 0.1 to 0.3; PEDIA, 0.16, 0.1 to 0.3), LODS and PEDIA were well calibrated (P = 0.79 and P = 0.21 respectively), and had higher AUCs than SICK in discriminating between survivors and non-survivors in malaria (AUCs, 95% CI: LODS, 0.92, 0.90 to 0.93; SICK, 0.86, 0.84 to 0.87; PEDIA, 0.92, 0.90 to 0.93), but comparable AUCs in NMFI (AUCs, 95% CI: LODS, 0.86, 0.83 to 0.89; SICK, 0.82, 0.79 to 0.86; PEDIA, 0.87, 0.83 to 0.893). The majority of deaths in the study occurred early (n = 85, 85.9%) where LODS and PEDIA had good discrimination. Conclusions: All three scoring systems predicted outcome, but LODS holds the most promise as a clinical prognostic score based on its simplicity to compute, requirement for no equipment, and good discrimination.

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