Children's Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial.

To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the 'Treat' element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery.

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data.

Background: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions.

Methods: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia.

Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.

Purpose: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established.

Methods: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO 80-91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded.

The clinical spectrum of severe childhood malaria in Eastern Uganda.

Background: Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year.

Methods: A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda.

Mortality risk over time after early fluid resuscitation in African children.

Background: African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear.

Methods: In a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20-40 ml/kg 5% albumin or 0.

Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial.

Background: Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes.

Methods: Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole.

Transfusion Volume for Children with Severe Anemia in Africa.

Background: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level.

Methods: In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.

Immediate Transfusion in African Children with Uncomplicated Severe Anemia.

Background: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.

Methods: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter.

Evaluation of the diagnostic accuracy and cost of different methods for the assessment of severe anaemia in hospitalised children in Eastern Uganda.

Severe anaemia in children requiring hospital admission is a major public health problem in malaria-endemic Africa. Affordable methods for the assessment of haemoglobin have not been validated against gold standard measures for identifying those with severe anaemia requiring a blood transfusion, despite this resource being in short supply. We conducted a prospective descriptive study of hospitalized children aged 2 months - 12 years at Mbale and Soroti Regional Referral Hospitals, assessed to have pallor at triage by a nurse and two clinicians.

Haematological quality and age of donor blood issued for paediatric transfusion to four hospitals in sub-Saharan Africa.

Background And Objectives: Paediatric blood transfusion for severe anaemia in hospitals in sub-Saharan Africa remains common. Yet, reports describing the haematological quality of donor blood or storage duration in routine practice are very limited. Both factors are likely to affect transfusion outcomes.

Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa.

Background: Hyperlactataemia (HL) is a biomarker of disease severity that predicts mortality in patients with sepsis and malaria. Lactate clearance (LC) during resuscitation has been shown to be a prognostic factor of survival in critically ill adults, but little data exist for African children living in malaria-endemic areas.

Methods: In a secondary data analysis of severely ill febrile children included in the Fluid Expansion as Supportive Therapy (FEAST) resuscitation trial, we assessed the association between lactate levels at admission and LC at 8 h with all-cause mortality at 72 h (d72).

Children's Oxygen Administration Strategies Trial (COAST): A randomised controlled trial of high flow versus oxygen versus control in African children with severe pneumonia.

In Africa, the clinical syndrome of pneumonia remains the leading cause of morbidity and mortality in children in the post-neonatal period. This represents a significant burden on in-patient services. The targeted use of oxygen and simple, non-invasive methods of respiratory support may be a highly cost-effective means of improving outcome, but the optimal oxygen saturation threshold that results in benefit and the best strategy for delivery are yet to be tested in adequately powered randomised controlled trials.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

Background: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF).

Methods: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls.

Results: Of 3170 trial participants, 394 (12.

Validation of triple pass 24-hour dietary recall in Ugandan children by simultaneous weighed food assessment.

Background: Undernutrition remains highly prevalent in African children, highlighting the need for accurately assessing dietary intake. In order to do so, the assessment method must be validated in the target population. A triple pass 24 hour dietary recall with volumetric portion size estimation has been described but not previously validated in African children.

Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial.

Background: In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%).

Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score.

Background: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality.

Methods: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality.

Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness.

Background: Severe anaemia in children is a leading cause of hospital admission and a major cause of mortality in sub-Saharan Africa, yet there are limited published data on blood transfusion in this vulnerable group.

Methods: We present data from a large controlled trial of fluid resuscitation (Fluid Expansion As Supportive Therapy (FEAST) trial) on the prevalence, clinical features, and transfusion management of anaemia in children presenting to hospitals in three East African countries with serious febrile illness (predominantly malaria and/or sepsis) and impaired peripheral perfusion.

Results: Of 3,170 children in the FEAST trial, 3,082 (97%) had baseline haemoglobin (Hb) measurement, 2,346/3,082 (76%) were anaemic (Hb <10 g/dL), and 33% severely anaemic (Hb <5 g/dL).

Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.

Background: Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa, with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood (20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor outcome.

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial.

Background: Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events.

'The words will pass with the blowing wind': staff and parent views of the deferred consent process, with prior assent, used in an emergency fluids trial in two African hospitals.

Objective: To document and explore the views and experiences of key stakeholders regarding the consent procedures of an emergency research clinical trial examining immediate fluid resuscitation strategies, and to discuss the implications for similar trials in future.

Methods: A social science sub-study of the FEAST (Fluid Expansion As Supportive Therapy) trial. Interviews were held with trial team members (n = 30), health workers (n = 15) and parents (n = 51) from two purposively selected hospitals in Soroti, Uganda, and Kilifi, Kenya.

Mortality after fluid bolus in African children with severe infection.

Background: The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established.

Methods: We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B).