ORCID Profile
0000-0003-2750-7533
Current Organisation
University of Oxford
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Publisher: F1000 Research Ltd
Date: 03-11-2022
DOI: 10.12688/GATESOPENRES.13635.2
Abstract: Introduction : Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org ) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination . The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725.
Publisher: Cold Spring Harbor Laboratory
Date: 26-11-2021
DOI: 10.1101/2021.11.24.21266806
Abstract: Mortality during acute illness among children in low- and middle-income settings remain unacceptably high and there is increasing recognition of the importance of post-discharge mortality. A comprehensive understanding of pathways underlying mortality among acutely ill children is needed to develop interventions and improve guidelines. We aimed to determine the incidence, timing and contributions of proximal and underlying exposures for mortality among acutely ill young children from admission to hospital until 6 months after discharge in sub-Saharan Africa and South Asia in the context of guideline-based care. A prospective stratified cohort study recruiting acutely ill children at admission to hospital with follow up until 180 days after discharge from hospital (November 2016-July 2019). Nine urban and rural hospitals in sub-Saharan Africa and South Asia across a range of facility levels, and local prevalences of HIV and malaria. Inclusion criteria were age 2-23 months, admission to hospital with acute, non-traumatic medical illness and stratified into three groups by anthropometry. Children were excluded if currently receiving pulmonary resuscitation, had a known condition requiring surgery within 6 months or known terminal illness with death expected within 6 months. Acute mortality occurring within 30-days from admission post-discharge mortality within 180-days from discharge characteristics with direct and indirect associations with mortality within a multi-level a priori framework including demographic, clinical, anthropometric characteristics at admission and discharge from hospital, and pre-existing child-, caregiver- and household-level characteristics. Of 3101 participants (median age 11 months), 1218 were severely wasted/kwashiorkor, 763 moderately wasted and 1120 were not wasted. Of 350 deaths, 182 (52%) occurred during index admission, 234 (67%) within 30-days of admission and 168 (48%) within 180-days post-discharge. Ninety (54%) post-discharge deaths occurred at home. The ratio of inpatient to post-discharge mortality was consistent across anthropometric strata and sites. Large high and low risk groups could be disaggregated for both early and post-discharge mortality. Structural equation models identified direct pathways to mortality and multiple socioeconomic, clinical and nutritional domains acting indirectly through anthropometric status. Among erse sites in Africa and South Asia, almost half of mortality occurs post-discharge. Despite being highly predictable, these deaths are not addressed in current guidelines. A fundamental shift to a risk-based approach to inpatient and post-discharge management is needed to further reduce childhood mortality and clinical trials of these approaches with outcomes of mortality, readmission and cost are warranted. ClinicalTrials.gov: NCT03208725
Publisher: Springer Science and Business Media LLC
Date: 31-05-2016
Publisher: Elsevier BV
Date: 03-2023
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Caroline Tigoi.