Summary Background Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially ...reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. Methods This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ0 thalassaemia, were aged 9–18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on99 Tc spleen scan) and renal function (glomerular filtration rate by99m Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2–4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00006400. Findings 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m2 , p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. Interpretation On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. Funding The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.
Acute chest syndrome (ACS) is a common, serious complication of sickle cell disease (SCD) and a leading cause of hospitalization and death in both children and adults with SCD. Little is known about ...the effectiveness of guideline-recommended antibiotic regimens for the care of children hospitalized with ACS.
To use a large, national database to describe patterns of antibiotic use for children with SCD hospitalized for ACS and to determine whether receipt of guideline-adherent antibiotics was associated with lower readmission rates.
Retrospective cohort study including 14 480 hospitalizations in 7178 children (age 0-22 years) with a discharge diagnosis of SCD and either ACS or pneumonia. Information was obtained from 41 children's hospitals submitting data to the Pediatric Health Information System from January 1, 2010, to December 31, 2016.
National Heart, Lung, and Blood Institute guideline-adherent (macrolide with parenteral cephalosporin) vs non-guideline-adherent antibiotic regimens.
Acute chest syndrome-related and all-cause 7- and 30-day readmissions.
Of the 14 480 hospitalizations, 6562 (45.3%) were in girls; median (interquartile range) age was 9 (4-14) years. Guideline-adherent antibiotics were provided in 10 654 of 14 480 hospitalizations for ACS (73.6%). Hospitalizations were most likely to include guideline-adherent antibiotics for children aged 5 to 9 years (3230 of 4047 79.8%) and declined to the lowest level for children 19 to 22 years (697 of 1088 64.1%). Between-hospital variation in antibiotic regimens was wide, with use of guideline-adherent antibiotics ranging from 24% to 90%. Children treated with guideline-adherent antibiotics had lower 30-day ACS-related (odds ratio OR, 0.71; 95% CI, 0.50-1.00) and all-cause (OR, 0.50; 95% CI, 0.39-0.64) readmission rates vs children who received other regimens (cephalosporin and macrolide vs neither drug class).
Current approaches to antibiotic treatment in children with ACS vary widely, but guideline-adherent therapy appears to result in fewer readmissions compared with non-guideline-adherent therapy. Efforts to increase the dissemination and implementation of SCD treatment guidelines are warranted as is comparative effectiveness research to strengthen the underlying evidence base.
Neurocognitive impairment occurs in children and adults with sickle cell anemia, but little is known about neurodevelopment in very young children. We examined the neurodevelopmental status of ...infants participating in the Pediatric Hydroxyurea Phase III Clinical Trial (Baby Hug) to determine relationships with age, cerebral blood flow velocity, and hemoglobin concentration.
Standardized measures of infant neurodevelopment were administered to 193 infants with hemoglobin SS or hemoglobin S-β(0) thalassemia between 7 and 18 months of age at the time of their baseline evaluation. Associations between neurodevelopmental scores and age, family income, parent education, hemoglobin concentration, and transcranial Doppler velocity were examined.
Mean functioning on the baseline neurodevelopment scales was in the average range. There were no mental development scores <70 (impaired); 22 children had scores in the clinically significant range, 11 with impaired psychomotor scores and 11 with problematic behavior rating scores. Significantly poorer performance was observed with older age at baseline. Behavior rating scores were an average of 2.82 percentile points lower per month of age, with similar patterns observed with parent report using adaptive behavior scales. Parent-reported functional abilities and hemoglobin were negatively associated with higher transcranial Doppler velocities.
Whereas overall functioning was in the normal range, behavioral and adaptive function was poorer with older age, even in this very young group of children. Explanatory mechanisms for this association between poorer developmental function and older age need to be identified.
Objective To assess the relationship between hospital volume and intensive care unit (ICU) transfer among hospitalized children with sickle cell disease (SCD). Study design We conducted a ...retrospective cohort study of 83 477 SCD-related hospitalizations at children's hospitals (2009-2012) using the Pediatric Health Information System database. Hospital-level all-cause and SCD-specific volumes were dichotomized (low vs high). Outcomes were within-hospital ICU transfer (primary) and length of stay (LOS) total (secondary). Multivariable logistic/linear regressions assessed the association of hospital volumes with ICU transfer and LOS. Results Of 83 477 eligible hospitalizations, 1741 (2.1%) involving 1432 unique children were complicated by ICU transfer. High SCD-specific volume (OR 0.77, 95% CI 0.64-0.91) was associated with lower odds of ICU transfer while high all-cause hospital volume was not (OR 0.87, 95% CI 0.73-1.04). A statistically significant interaction was found between all-cause and SCD-specific volumes. When results were stratified according to all-cause volume, high SCD-specific volume was associated with lower odds of ICU transfer at low all-cause volume (OR 0.46, 95% CI 0.38-0.55). High hospital volumes, both all-cause (OR 0.94, 95% CI 0.92-0.97) and SCD-specific (OR 0.86, 95% CI 0.84-0.88), were associated with shorter LOS. Conclusions Children's hospitals vary substantially in their transfer of children with SCD to the ICU according to hospital volumes. Understanding the practices used by different institutions may help explain the variability in ICU transfer among hospitals caring for children with SCD.
Sickle cell disease (SCD) is associated with a large spectrum of renal abnormalities, one of which, microalbuminuria/proteinuria (MA/P), is a known predictor of end-stage renal disease. We studied 90 ...children with SCD (57% male; mean age 11.4 ± 5.2 years) to determine the prevalence and examine clinical correlates of MA/P. The average of two spot urine microalbumin-to-creatinine samples obtained 6 months apart was recorded. Medical records were reviewed for demographic and biochemical data. Medication use, resting office blood pressures (BP), vaso-occlusive pain crises (VOC), and monthly transfusions were recorded. Fourteen children (15.5%) had MA/P. Hemoglobin (Hb) levels were significantly lower in the children with MA than in those without MA/P (8.8 ± 1.1 vs. 9.8 ± 1.4 g/dL, respectively) and were significantly correlated with MA (rho = 0.24,
p
= 0.03). Children with MA were more likely to have abnormal BP (
p
= 0.058), with 5/14 being hypertensive or pre-hypertensive. In a multivariate logistic regression model of MA, both Hb and BP classification remained in the final model. MA is a simple screening biomarker of early kidney injury in children with SCD. Larger studies to evaluate predictive factors of MA and the relationship to BP are needed.
Pulmonary diseases form major sources of morbidity and mortality in children with sickle cell disease (SCD). The objective of the study was to determine the prevalence of lung function abnormalities ...and asthma and their association with acute chest syndrome (ACS) in children with SCD. This was a cross-sectional retrospective study of 127 children with SCD; we collected information regarding ACS and asthma and pulmonary function test (PFT) data. Based on PFT results, the patients were assigned to one pattern of lung function normal, obstructive lung disease (OLD), restrictive lung disease (RLD). Statistical analyses included Pearson correlation, prevalence odds ratio (POR), cross-tabulation, and multiple binary logistic regression. OLD was noted in 35% and RLD in 23% of the patients, with the remainder exhibiting a normal PFT pattern. Forty-six percent of patients had asthma, 64% of whom had a history of ACS. OLD (r = .244, P = .008, POR = 2.8) and asthma (r = .395, P < .001, POR = 5.4) were significantly associated with a history of ACS. There was a negative correlation between having normal PFT data and a history of ACS (r = −.289, P = .002, POR = .3). Asthma and pulmonary function abnormalities are prevalent in children with SCD, with OLD being more common than RLD. There is an association between asthma, OLD, and ACS, however causality cannot be proven due to the study design. We stress the importance of actively investigating for a clinical diagnosis of asthma in all patients with SCD and suggest that PFT data may help detect patients at lower risk for ACS.
Summary
This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high‐dose, anti‐D immune globulin (anti‐D) (75 μg/kg) as initial treatment for childhood immune ...thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high‐dose anti‐D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti‐D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti‐D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high‐dose anti‐D are effective first‐line therapies for childhood ITP. However, we observed increased ADRs in the high‐dose anti‐D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high‐dose anti‐D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.
Introduction:
Transfusion of blood products can be associated with a wide variety of complications ranging in level of severity. The most lethal of these are Transfusion-Associated Circulatory ...Overload (TACO) and Transfusion-Related Acute Lung injury (TRALI). Over the five year period from 2012-2016, TRALI was the leading cause of transfusion-associated fatalities, closely followed by TACO. However, the incidence of these potentially lethal transfusion reactions in the pediatric population is not well known. Our objective is to describe the incidence of these transfusion reactions in pediatric patients and describe their associated morbidity and mortality.
Materials/Methods:
We used the Pediatric Health Information System (PHIS), an electronic database of children's hospitals in the USA. Data was obtained from 45 children's hospitals in 2005-2015 for patients ≤ 21 years of age who received transfusion of packed red blood cells, platelets, whole blood, coagulation factors, other serum and exchange transfusion. From this group of patients, we then identified patients who developed TRALI and TACO. Patients were identified by ICD9 codes for transfusion of various blood products and related adverse events. We abstracted data on demographics, medication use, length of stay (LOS), hospital charges and mortality.
Results:
During the study period, 383,154 inpatient encounters in which patients received a blood product transfusion were identified. Overall the number of blood product transfusions has remained stable (Figure 1). There were 982 transfusion reactions per 100,000 hospital encounters over this period and the incidence rates of each type of transfusion reaction are described in Table 1. In our patient cohort, 108 cases of TRALI and 102 cases of TACO were identified. Cohorts were similar with regards to gender distribution. Distributions of age and race differed between the TRALI and TACO cohorts compared to the all transfusions cohort (Table 2). The morbidity, mortality and hospital charges of encounters complicated by TRALI and TACO are described in Table 3. In the TRALI cohort, a significantly greater number of patients required mechanical ventilation, ECMO or transfer to the ICU and had a greater increase in mortality in comparison to the all transfusion cohort. The TACO cohort had a significantly increased number of patients who required ECMO or ICU transfer compared to the all transfusions cohort. Length of stay was significantly greater for patients in the TRALI cohort compared to the all transfusions cohort. Patients diagnosed with either TRALI or TACO had significantly increased costs associated with hospitalization.
Conclusion:
Our study demonstrated that both TRALI and TACO are associated with an excess morbidity and mortality. However, the number of cases of TRALI and TACO in our study were fewer than what was expected based on previous studies. This indicates that TRALI and TACO are likely under-diagnosed and under-reported. Efforts should be made to increase awareness of recognizing and reporting of these transfusion reactions to improve the outcome of these potentially lethal complications.
Display omitted
No relevant conflicts of interest to declare.
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