George, Elizabeth Clare;
(2018)
The "acutely sick" African child: applying new statistical methods to delineate mortality risks and identify ways to improve management.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The admission burden to paediatric wards in African hospitals is very high, and many children have life-threatening complications of common infectious diseases including malaria. In this setting the Fluid Expansion As Supportive Therapy (FEAST) trial unexpectedly showed that fluid resuscitation (giving a bolus of saline or albumin) to febrile children with impaired perfusion was harmful. This PhD used data from the FEAST trial to answer several important questions: 1) how can children at the highest risk of mortality be identified and prioritised in these low-income settings; 2) were there surrogate markers in bedside measures recorded over admission that could explain some of the detrimental impact of the bolus; and 3) did the bolus increase mortality risk immediately after administration or was there a different mechanism of action? Prognostic factors for mortality were identified in the FEAST data and a bedside risk score developed. The score was validated in data collected on children admitted to a rural district hospital in Kenya and compared to other risk scores. The heterogeneity of the effect of bolus over levels of different measures, including malaria parasitaemia, was explored. The proportion of treatment effect explained by measures recorded over time was calculated. No one measure was shown to be a suitable surrogate marker, but the impact of the bolus varied across levels of oxygen saturation, and across levels of base excess in those with malaria at baseline. Further insight into the mechanism by which the bolus had detrimental impact on the children in the FEAST trial was sought by modelling the mortality risk over time. The maximum mortality risk occurred in both arms within the first 2 hours but the risk in the bolus arm was slower to decrease, showing that children were recovering more slowly in the bolus arms compared to the no bolus arm.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The "acutely sick" African child: applying new statistical methods to delineate mortality risks and identify ways to improve management |
| Event: | UCL |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10051750 |
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