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. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes. METHODS: We evaluated the safety and efficacy of a higher volume of whole blood (30 ml/kg; Tx30: n = 78) against the standard volume (20 ml/kg; Tx20: n = 82) in Ugandan children (median age 36 months (interquartile range (IQR) 13 to 53)) for 24-hour anemia correction (hemoglobin >6 g/dl: primary outcome) and 28-day survival. RESULTS: Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01). From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001). Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none secondary to volume overload. CONCLUSION: A higher initial transfusion volume prescribed at hospital admission was safe and resulted in an accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical trial to establish the effect on short and longer-term survival is warranted. TRIAL REGISTRATION: ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011.

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. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. METHODS: Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. RESULTS: Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. CONCLUSIONS: Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. TRIAL REGISTRATION: ISRCTN69856593.

Antibiotic prescription among children with common cold at a district hospital in Uganda.

BACKGROUND: Most childhood infections are of viral origin making antibiotics unnecessary. They are, however, the most frequently prescribed drugs dispensed to children, resulting in inappropriate antibiotic prescriptions, which are one of the main drivers of antibiotic resistance. AIM: The study aimed to determine the prevalence of antibiotic prescriptions and identify its associated factors among children below 5 years with common cold who attend the outpatient department in Tororo General Hospital. SETTING: The study was carried out in Tororo General Hospital, Eastern Uganda. METHODS: A cross-sectional survey using consecutive sampling was performed among children below 5 years with common cold attending the outpatient department. Data were collected using an interviewer-administered, structured questionnaire and analysed using STATA version 14.0. Prevalence of antibiotic prescriptions was calculated. Bivariate analysis using chi-square test and multivariate analysis using logistic regression was performed to establish factors associated with antibiotic prescription. RESULTS: The prevalence of antibiotic prescriptions for common cold among children below 5 years was 23.3%. Factors associated with antibiotic prescription for common cold were duration of symptoms of more than 5 days (OR, 95% CI: 4.49; 1.16-17.23, p = 0.029) and being attended to by a clinical officer (OR, 95% CI: 0.19; 0.04-0.91, p = 0.038). CONCLUSION: There is inappropriate antibiotic prescription among children with common cold in Tororo General Hospital. There is need for antibiotic stewardship programmes to promote optimal antibiotic use in primary care facilities.Contribution: The study's findings can be used to develop context-specific antibiotic stewardship programmes tailored to promote judicious use of antibiotics in primary care.

Availability, functionality and access of blood pressure machines at the points of care in public primary care facilities in Tororo district, Uganda.

BACKGROUND: Early diagnosis of hypertension prevents a significant number of complications and premature deaths. In resource-variable settings, diagnosis may be limited by inadequate access to blood pressure (BP) machines. We sought to understand the availability, functionality and access of BP machines at the points of care within primary care facilities in Tororo district, Uganda. METHODS: This was an explanatory sequential mixed-methods study combining a structured facility checklist and key informant interviews with primary care providers. The checklist was used to collect data on availability and functionality of BP machines within their organisational arrangements. Key informant interviews explored health providers' access to BP machines. RESULTS: The majority of health facilities reported at least one working BP machine. However, Health providers described limited access to machines because they are not located at each point of care. Health providers reported borrowing amongst themselves within their respective units or from other units within the facility. Some health providers purchase and bring their own BP machines to the health facilities or attempted to restore the functionality of broken ones. They are motivated to search the clinic for BP machines for some patients but not others based on their perception of the patient's risk for hypertension. CONCLUSION: Access to BP machines at the point of care was limited. This makes hypertension screening selective based on health providers' perception of the patients' risk for hypertension. Training in proper BP machine use and regular maintenance will minimise frequent breakdowns.