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. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering. RESULTS: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63-3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19-1.74), p < 0.001); history of transfusion (1.48(1.13-1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21-1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47-0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47-0.76), p < 0.001); younger-age (1.07 (1.03-1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46-0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23-2.44) and 1.46(1.18-1.82) respectively compared to no splenomegaly. Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe malaria. CONCLUSIONS: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important. TRIAL REGISTRATION: ISRCTN ISRCTN84086586

Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial

Background The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4–6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint). Because data on the safety of blood components are scarce, we conducted a secondary analysis to examine the safety and efficacy of different pack types (whole blood vs red cell concentrates) on clinical outcomes. Methods This study is a secondary analysis of the TRACT trial data restricted to those who received an immediate transfusion (using whole blood or red cell concentrates). TRACT was an open-label, multicentre, factorial, randomised trial conducted in three hospitals in Uganda (Soroti, Mbale, and Mulago) and one hospital in Malawi (Blantyre). The trial enrolled children aged between 2 months and 12 years admitted to hospital with severe anaemia (haemoglobin <6 g/dL). The pack type used (supplied by blood banks) was based only on availability at the time. The outcomes were haemoglobin recovery at 8 h and 180 days, requirement for retransfusion, length of hospital stay, changes in heart and respiratory rates until day 180, and the main clinical endpoints (mortality until day 28 and day 180, and readmission until day 180), measured using multivariate regression models. Findings Between Sept 17, 2014, and May 15, 2017, 3199 children with severe anaemia were enrolled into the TRACT trial. 3188 children were considered in our secondary analysis. The median age was 37 months (IQR 18–64). Whole blood was the first pack provided for 1632 (41%) of 3992 transfusions. Haemoglobin recovery at 8 h was significantly lower in those who received packed cells or settled cells than those who received whole blood, with a mean of 1·4 g/dL (95% CI –1·6 to –1·1) in children who received 30 mL/kg and –1·3 g/dL (–1·5 to –1·0) in those who received 20 mL/kg packed cells versus whole blood, and –1·5 g/dL (–1·7 to –1·3) in those who received 30 mL/kg and –1·0 g/dL (–1·2 to –0·9) in those who received 20 mL/kg settled cells versus whole blood (overall p<0·0001). Compared to whole blood, children who received blood as packed or settled cells in their first transfusion had higher odds of receiving a second transfusion (odds ratio 2·32 [95% CI 1·30 to 4·12] for packed cells and 2·97 [2·18 to 4·05] for settled cells; p<0·001) and longer hospital stays (hazard ratio 0·94 [95% CI 0·81 to 1·10] for packed cells and 0·86 [0·79 to 0·94] for settled cells; p=0·0024). There was no association between the type of blood supplied for the first transfusion and mortality at 28 days or 180 days, or readmission to hospital for any cause. 823 (26%) of 3188 children presented with severe tachycardia and 2077 (65%) with tachypnoea, but these complications resolved over time. No child developed features of confirmed cardiopulmonary overload. Interpretation Our study suggests that the use of packed or settled cells rather than whole blood leads to additional transfusions, increasing the use of a scarce resource in most of sub-Saharan Africa. These findings have substantial cost implications for blood transfusion and health services. Nevertheless, a clinical trial comparing whole blood transfusion with red cell concentrates might be needed to inform policy makers

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pathogens causing urinary tract infections in infants: a European overview by the ESCAPE study group

Knowledge of the distribution spectrum of causative organisms and their resistance patterns has become a core requirement for the rational and effective management of urinary tract infections. In the context of a prospective trial on the use of antibiotic prophylaxis in infants with underling kidney malformations, we conducted an online survey among paediatric nephrologists on positive urine cultures (July 2010–June 2012) from both hospitalized and non-hospitalized infants under 24 months of age. We collected 4745 urine cultures (UCs) at 18 units in 10 European countries. Escherichia coli was the most frequent bacterium isolated from UCs; however, in 10/16 hospitals and in 6/15 community settings, E. coli was isolated in less than 50 % of the total positive UCs. Other bacterial strains were Klebsiella, Enterococcus, Proteus and Pseudomonas not only from hospital settings. E. coli showed a high resistance to amoxicillin and trimethoprim and variable to cephalosporin. Nitrofurantoin had a good rate of efficacy, with 11/16 hospitals and 11/14 community settings reporting a resistance lower than 5 %. Conclusion: E. coli is the most common organism causing UTIs in infants; however, other bacterial strains are frequently isolated. As a result, antibiotic prophylaxis should be more elastic and adaptable over time in order to guarantee maximum efficacy. © 2014, Springer-Verlag Berlin Heidelberg

Evaluation and management of recurrent urinary tract infections in children: state of the art

Urinary tract infections (UTIs) represent an important cause of febrile illness in young children and can lead to renal scarring and kidney failure. However, diagnosis and treatment of recurrent UTI in children is an area of some controversy. Guidelines from the American Academy of Pediatrics, National Institute for Health and Clinical Excellence and European Society of Paediatric Radiology differ from each other in terms of the diagnostic algorithm to be followed. Treatment of vesicoureteral reflux and antibiotic prophylaxis for prevention of recurrent UTI are also areas of considerable debate. In this review, we collate and appraise recently published literature in order to formulate evidence-based guidance for the diagnosis and treatment of recurrent UTI in children