Children’s oxygen administration strategies trial (COAST): A randomised controlled trial of high flow versus oxygen versus control in African children with severe pneumonia

Background: 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. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia.Methods: In 4200 African children, aged 2 months to 12 years, presenting to 5 hospitals in East Africa with respiratory distress and hypoxia (oxygen saturation \u3c 92%), the COAST trial will simultaneously evaluate two related interventions (targeted use of oxygen with respect to the optimal oxygen saturation threshold for treatment and mode of delivery) to reduce shorter-term mortality at 48-hours (primary endpoint), and longer-term morbidity and mortality to 28 days in a fractional factorial design, that compares: Liberal oxygenation (recommended care) compared with a strategy that permits hypoxia to SpO2 \u3e or = 80% (permissive hypoxia); and High flow using AIrVO2TM compared with low flow delivery (routine care)

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

Background: 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. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia. Methods: In 4200 African children, aged 2 months to 12 years, presenting to 5 hospitals in East Africa with respiratory distress and hypoxia (oxygen saturation \u3c 92%), the COAST trial will simultaneously evaluate two related interventions (targeted use of oxygen with respect to the optimal oxygen saturation threshold for treatment and mode of delivery) to reduce shorter-term mortality at 48-hours (primary endpoint), and longer-term morbidity and mortality to 28 days in a fractional factorial design, that compares: Liberal oxygenation (recommended care) compared with a strategy that permits hypoxia to SpO2 \u3e or = 80% (permissive hypoxia); and High flow using AIrVO2TM compared with low flow delivery (routine care). Discussion: The overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of in-hospital mortality, 9-10% (for those with oxygen saturations of 80-92%) and 26-30% case fatality for those with oxygen saturations \u3c80%

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

Background: 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. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia. Methods: In 4200 African children, aged 2 months to 12 years, presenting to 5 hospitals in East Africa with respiratory distress and hypoxia (oxygen saturation or = 80% (permissive hypoxia); andHigh flow using AIrVO 2TM compared with low flow delivery (routine care). Discussion: The overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of in-hospital mortality, 9-10% (for those with oxygen saturations of 80-92%) and 26-30% case fatality for those with oxygen saturations <80%. Clinical trial registration: ISRCTN15622505 Trial status: Recruiting

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

Background: 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. There is, however, an accumulating literature about the harms of oxygen therapy across a range of acute and emergency situations that have stimulated a number of trials investigating permissive hypoxia. Methods: In 4200 African children, aged 2 months to 12 years, presenting to 5 hospitals in East Africa with respiratory distress and hypoxia (oxygen saturation &lt; 92%), the COAST trial will simultaneously evaluate two related interventions (targeted use of oxygen with respect to the optimal oxygen saturation threshold for treatment and mode of delivery) to reduce shorter-term mortality at 48-hours (primary endpoint), and longer-term morbidity and mortality to 28 days in a fractional factorial design, that compares: Liberal oxygenation (recommended care) compared with a strategy that permits hypoxia to SpO2 &gt; or = 80% (permissive hypoxia); andHigh flow using AIrVO2TM compared with low flow delivery (routine care). Discussion: The overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of in-hospital mortality, 9-10% (for those with oxygen saturations of 80-92%) and 26-30% case fatality for those with oxygen saturations &lt;80%. Clinical trial registration: ISRCTN15622505 Trial status: Recruiting</ns4:p

A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial

BackgroundChildren with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase.Methods and findingsIn a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2–5 days), which was similar between randomized groups (0.23 [95% CI −0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission,age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite. ConclusionsEmpirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM

Endoscopic injection sclerotherapy for bleeding varices in children with intrahepatic and extrahepatic portal venous obstruction: benefit of injection tract embolisation

BACKGROUND: The outcome of sclerotherapy for bleeding oesophageal varices may be influenced by injection technique. In a previous study at our institution, sclerotherapy was associated with a high re-bleeding rate and oesophageal ulceration. Embolisation of the injection tract was introduced in an attempt to reduce injection-related complications. METHODS: To determine the outcome and effectiveness of injection tract embolisation in reducing injection-related complications, we retrospectively reviewed a series of 59 children who underwent injection sclerotherapy for oesophageal varices (29 for extrahepatic portal vein obstruction (EHPVO) and 30 for intrahepatic disease) in our centre. RESULTS: Sclerotherapy resulted in variceal eradication in only 11.8% of the children (mean follow-up duration: 38.4 months). Variceal eradication with sclerotherapy alone was achieved in 20.7% and 3.3% of EHPVO and intrahepatic disease patients, respectively. Injection tract embolisation was successful in reducing the number of complications and re-bleeding rates. Complications that arose included: transient pyrexia (16.7%); deep oesophageal ulcers (6.7%); stricture formation (3.3%); and re-bleeding before variceal sclerosis (23%). CONCLUSION: Injection sclerotherapy did not eradicate oesophageal varices in most children. Injection tract embolisation by sclerosant was associated with fewer complications and reduced re-bleeding rates

Diagnostic performance of visible severe wasting for identifying severe acute malnutrition in children admitted to hospital in Kenya

OBJECTIVE: To determine the diagnostic value of visible severe wasting in identifying severe acute malnutrition at two public hospitals in Kenya. METHODS: This was a cross-sectional study of children aged 6 to 59.9 months admitted to one rural and one urban hospital. On admission, mid-upper arm circumference (MUAC), weight and height were measured and the presence of visible severe wasting was assessed. The diagnostic performance of visible severe wasting was evaluated against anthropometric criteria. FINDINGS: Of 11,166 children admitted, 563 (5%) had kwashiorkor and 1406 (12.5%) were severely wasted (MUAC &lt; 11.5 cm). The combined sensitivity and specificity of visible severe wasting at the two hospitals, as assessed against a MUAC &lt; 11.5 cm, were 54% (95% confidence interval, CI: 51-56) and 96% (95% CI: 96-97), respectively; at one hospital, its sensitivity and specificity against a weight-for-height z-score below -3 were 44.7% (95% CI: 42-48) and 96.5% (95% CI: 96-97), respectively. Severely wasted children who were correctly identified by visible severe wasting were consistently older, more severely wasted, more often having kwashiorkor, more often positive to the human immunodeficiency virus, ill for a longer period and at greater risk of death. Visible severe wasting had lower sensitivity for determining the risk of death than the anthropometric measures. There was no evidence to support measuring both MUAC and weight-for-height z-score. CONCLUSION: Visible severe wasting failed to detect approximately half of the children admitted to hospital with severe acute malnutrition diagnosed anthropometrically. Routine screening by MUAC is quick, simple and inexpensive and should be part of the standard assessment of all paediatric hospital admissions in the study setting

The children\u27s oxygen administration strategies trial

Background: The life-saving role of oxygen therapy in children with clinically-defined severe pneumonia is not yet established. We hypothesised liberal oxygenation strategies and/or respiratory support may improve the high in-hospital mortality. Methods: The open-label fractional-factorial COAST trial in Ugandan and Kenyan children aged \u3e28 days with feature of severe pneumonia. In stratum A (severe hypoxaemia: SpO2 \u3c80%) children were randomised to high flow nasal therapy (HFNT: OptiFlow™) or low flow oxygen (LFO: standard care). In stratum B (hypoxaemia: SpO2 80-91%) children were randomised to HFNT or LFO (liberal strategies) or control (no immediate oxygen) (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or \u3e3hours receipt of oxygen were excluded. The primary endpoint was 48-hour mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. Findings: The Trial Steering Committee recommended halting recruitment for feasibility after 1842/4200 (44%) children enrolled. Of 1852 recruited, 388 in stratum A (median 7 months; median age SpO2 75%) were randomised to HFNT (n=194) or LFO (n=194) and 1454 in stratum B (median 9 months; median SpO2 88%) were randomised to HFNT (n=363) vs LFO (n=364) vs control (n=727). Per-protocol 109/726(15%) of controls received oxygen (when SpO2 \u3c80%). In stratum A, 48-hour mortality was 9.3% (18/388) for HFNT vs. 13.4% (26/194) for LFO groups. In stratum B 48-mortality was 1.1% (4/363) for HFNT vs. 2.5% (9/364) LFO and 1.4% (10/727) for controls. In stratum B, adjusted (a)odds ratio (aOR) for 48-hour mortality in liberal vs permissive comparison was 1.16 (0.49-2.74;p=0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06;p=0.08). Respective strata-specific 28-day mortality rates were: 18.6%(HFNT) versus 23.4%(LFO) and 3.3%(HFNT) versus 4.1%(LFO) versus 3.9%(control). Neurocognitive sequelae, assessed using Kilifi Neurodevelopmental Index, were rare in all groups. Interpretation: Conservative oxygen strategies appear safe and respiratory support with HFNT showing potential benefit should prompt further trials

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\u3e28 days with severe pneumonia and severe hypoxaemia stratum (SpO2\u3c80%) to high-flow nasal therapy (HFNT) or low-fow oxygen (LFO: standard care) and hypoxaemia stratum (SpO2 80–91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or\u3e3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. Results: The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO2 75%) randomised to HFNT (n=194) or LFO (n=194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO2 88%) randomised to HFNT (n=363) vs LFO (n=364) vs per‑ missive hypoxaemia (n=727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO2\u3c80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49–2.74; p=0.73); HFNT vs LFO comparison was 0.60 (0.33–1.06; p=0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. Conclusions: Respiratory support with HFNT showing potential beneft should prompt further trial