Hydroxyurea therapy lowers TCD velocities in children with sickle cell disease

INTRODUCTION: Hydroxyurea (HU) improves hematologic parameters and decreases adverse events in patients with sickle cell disease (SCD). HU has been proposed as an alternative to chronic transfusions for secondary stroke prevention. Transcranial doppler (TCD) is an accepted method of stroke risk stratification in patients with SCD. We sought to determine if HU affects TCD velocities in children with SCD. METHODS: A cohort of 24 children with HbSS with a baseline TCDi prior to HU and a follow-up after at least 6 months of therapy was analyzed. Twenty-four age-matched children with HbSS formed the control group. Differences in hematologic parameters before and after HU therapy were evaluated. RESULTS: TCDi velocities decreased in the HU-treated patients. The adjusted mean change in TCDi velocities was -13.0 cm/sec (95% CI -20.19, -5.92) in the HU-treated group and +4.72 cm/sec (95% CI -3.24, 12.69) in the controls. Changes in TCDi between the two groups were statistically significant (P < 0.001). Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated patients. Four out of five patients with TCDi velocities >170 cm/sec had normalization of TCDi velocities on HU. Mean change was -34.75 cm/sec in this subgroup. No patients experienced cerebrovascular accidents (CVA) while on HU. CONCLUSIONS: HU-treated patients experienced statistically significant decreases in TCDi velocities compared to age-matched controls. Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated group. The decrease in TCDi velocities is not a consequence of changes in hematologic values in patients treated with HU.     

Health utility and quality of life in pediatric liver transplant recipients

To measure HU and HRQOL in pediatric liver transplant (LT) recipients, a cross‐sectional study of patient‐parent dyads was conducted. Direct HU were assessed in 48 adolescents ≥12 years using SG and TTO techniques. Indirect HU were measured by Health Utility Index 2 and HUI3 for subjects ≥12 years and CHU9D for ≥7 years. Patients reported HRQOL using PedsQL? GC and PedsQL? TM. A total of 108 dyads participated (55.6% female; 73.2% Caucasian; 42.6% biliary atresia; 35.2% living donor; 37.0% Medicaid). Mean age at survey was 13.6 ± 3.5 years, and time from LT was 8.9 ± 4.9 years. 61.2% were on monotherapy, 25 (23.2%) had acute rejection within 3 years, and 15 (13.9%) had a biliary obstruction within 5 years. Mean indirect HU and HRQOL scores by child report were lower than norms (P < .001). LRD recipients had higher PedsQL? GC, PedsQL? TM, and HUI3 scores (P < .01). HU in pediatric LT recipients are lower than norms. Availability of HU scores for post‐transplant health states will enable measurement of quality‐adjusted life years for future comparative effectiveness studies.     

Late allograft fibrosis in pediatric liver transplant recipients: Assessed by histology and transient elastography

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re‐transplantation. TE is a non‐invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05‐1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children.     

A prospective study to evaluate the depictability of the hepatic veins on abdominal contrast-enhanced CT in small children

Background  The optimal conditions for abdominal contrast-enhanced (CE) CT, especially with respect to depiction of the hepatic veins (HVs), have not been well studied in small children. Objective  We compared the depiction of the HVs in small children using scan delay times of 50 s and 60 s and a power injector. The degree of contrast enhancement of the HVs according to body weight was also evaluated. Materials and methods  A total of 50 CT studies in 31 children ages 2 days to 3 years 4 months (median 12 months) with a body weight less than 15 kg were prospectively evaluated. Nonionic contrast medium (300 mgI/ml) at a dose of 2 ml/kg and an injection rate calculated as (body weight in kilograms × 0.1) ml/s was injected through a 24-gauge intravenous catheter. Scan delay time was randomly chosen at 50 s or 60 s (25 times each). Subjective assessment of HV depiction was performed and the difference in CT number between the HV and hepatic parenchyma (HV−HP value) was calculated. Results  In all cases, subjective assessment of HV depiction was good and the HV−HP value was greater than 20 HU. The mean±SD HV−HP value was 47.7±13.2 HU. There were no differences in the mean HV−HP values between scan delay times of 50 s and 60 s (P=0.58). Conclusion  For small children, this protocol for pediatric abdominal CECT resulted in good depiction of the HVs with no difference between scan delay times of 50 s and 60 s.     

Use of inhaled corticosteroids decreases hospital admissions for asthma in young children

Background  An active use of inhaled corticosteroids for asthma has been associated with less asthma exacerbations and hospital admissions in children aged more than 2 years. The present study aimed to investigate hospital admission rates in young children from two populations in relation to the age-specific use of maintenance medication for asthma. Methods  Annual data on children aged less than 24 months treated for asthma, including data on the use of maintenance medication based on the purchases of prescribed medications, and annual numbers of admissions to hospital and proportions of readmissions, were collected from 1995 to 1999 in two provinces of Finland. The inclusion criteria, three or more doctor-diagnosed wheezing episodes, were individually checked by the authors in each case. The mean number of children aged less than 24 months during the years of the study was 5490 in Kuopio and 9914 in Oulu area. Results  In the Kuopio area, during the years of the study, 16.5/1000 children aged less than 24 months were on maintenance medication for asthma, and 90% of them were receiving inhaled corticosteroids. In the Oulu area, the respective figures were 13.5/1000 (P<0.001) and 99%. The average admission rate was 7.9/1000 in the Kuopio area and 8.7/1000 in the Oulu area (P<0.05). The readmissions indicated the higher admission rates in the Oulu (40% of all admissions) than in the Kuopio (28%) area (P<0.01). Conclusion  Active use of maintenance therapy by inhaled corticosteroids was associated with a decreased need of hospital treatment in young children <24 months old with asthma, mainly because of less readmissions.     

Hepatic enhancement analysis in children using Smart Prep monitoring for 2 : 1 pitch helical scanning

Purpose. To analyze hepatic enhancement by using Smart Prep protocols appropriate for children of different weight groups and 2:1 pitch helical CT imaging as the investigative tools. Patients and methods. A group of 55 children ranging in weight between 20 and 180 lbs underwent 67 contrast-enhanced abdominal helical CT examinations using Smart Prep (GE Medical Systems, Milwaukee, Wisc.). Of these studies, 21 (31 %) were excluded because of failure to follow the prescribed Smart Prep protocols. Smart Prep protocols were established for nine different weight groups. Scan delay, aorta and liver time to peak, and liver enhancement over baseline were recorded. Results. Optimal abdominal CT studies with adequate contrast enhancement of hepatic and portal veins were obtained in 46 patients. There was no significant difference in the time between peak aortic and the liver enhancement among different weight groups (mean time 12.0 ± 7.1 s for all children). However, the mean hepatic enhancement over baseline in children weighing < 30 lbs was below 50 Hounsfield units (HU) compared to the rest of the children who had mean hepatic enhancement of > 50 HU. Conclusion. Two-thirds of the Smart Prep protocols were successfully implemented, and all of these resulted in good contrast enhancement of hepatic and portal veins. Optimal mean liver enhancement (> 50 HU) was seen in children ≥ 30 lbs. Children < 30 lbs had mean liver enhancement of 33 HU ± 7.2 above the baseline likely caused by contrast dose. Received: 20 October 1998 Accepted: 26 March 1999     

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea

Background

More evidence of the safety and effectiveness of hydroxyurea (HU) in community‐based cohorts of pediatric patients with sickle cell disease (SCD) are needed. The association of HU with organ‐specific clinical complications and adverse events is examined herein.

Methods

Medicaid medical and pharmacy claims for the calendar years January 1996 through December 2006 were used to identify a cohort of children and adolescent patients (ages 17 and under) with a diagnosis of SCD (homozygous) who were treated with HU and developed disparate complications or adverse side effects. Of the 2,194 pediatric SCD patients identified, 175 (8%) were treated with HU. Incidence density matching (1 case: 2 controls) was used to select the control group on age, gender, ethnicity, time in the Medicaid data set, and baseline severity resulting in a total study cohort of 523 cases.

Results

Organ‐specific complications were more likely in the HU‐treated group compared to non‐HU‐treated group: cardiovascular complications (odds ratio [OR] = 3.15; confidence interval [CI] = 1.97–5.03); hepatic complications (OR 5.41; CI = 3.54–8.27); renal complications (OR 5.09; CI 3.37–7.67); and pulmonary complications (OR 4.07; CI 1.88–8.79). Many of these conditions began developing before HU was prescribed. Developing three or more complications was also more likely in the HU group (27.4% vs. 7.0%, P < 0.0001).

Conclusions

Extending previous findings to routine practice settings, HU is being administered to the most severely ill children with SCD, many of whom had already started to develop organ‐specific complications, but it is not associated with development of serious adverse events. Pediatr Blood Cancer. 2010;56:90–94. © 2010 Wiley‐Liss, Inc.     

Early outcome after craniospinal irradiation with pencil beam scanning proton therapy for children,adolescents and young adults with brain tumors

Central nervous system (CNS) tumors are the most common solid malignancies in children and adolescents and young adults (C-AYAs). Craniospinal irradiation (CSI) is an essential treatment component for some malignancies, but it can also lead to important toxicity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of dose delivered to organs at risk and, thus, potentially reduced acute and late toxicity. This study aims to report the clinical outcomes and toxicity rates after CSI for C-AYAs treated with PBSPT. Seventy-one C-AYAs (median age: 7.4 years) with CNS tumors were treated with CSI between 2004 and 2021. Medulloblastoma (n = 42: 59%) and ependymoma (n = 8; 11%) were the most common histologies. Median prescribed total PBSPT dose was 54 Gy_RBE (range: 18–60.4), and median prescribed craniospinal dose was 24 Gy_RBE (range: 18–36.8). Acute and late toxicities were coded according to Common Terminology Criteria for Adverse Events. After a median follow-up of 24.5 months, the estimated 2-year local control, distant control, and overall survival were 86.3%, 80.5%, and 84.7%, respectively. Late grade ≥3 toxicity-free rate was 92.6% at 2 years. Recurrent and metastatic tumors were associated with worse outcome. In conclusion, excellent tumor control with low toxicity rates was observed in C-AYAs with brain tumors treated with CSI using PBSPT.     

Outcomes of liver transplantation in pediatric recipients with cardiovascular disease

LT exerts considerable stress on the heart perioperatively. Limited data exist on impact of cardiovascular diseases on LT children. This study evaluated the outcomes of children with CVD who underwent LT and compared with pretransplant findings. From 518 LT recipients, 82 (15.8%) had CVD. Sixty patients were classified as low‐risk adjustment for congenital heart surgery 1 (RACHS 1 and 2). Five patients were classified as RACHS ≥3. The most common echocardiographic finding in the CVD patients (25/82) was ASD. CVD patients had more abnormal EKG (32.4% vs 14.5%, P < .001), abnormal chest X‐ray (11.8% vs 1.4%, P < .001), and altered echocardiography (89.7% vs 15.4%, P < .001) findings compared with the No‐CVD group pretransplant. Post‐transplant, significant differences between groups were observed related to abnormal EKG (14.7% vs 7.0%, P = .03) and echocardiography (48.5% vs 3.2%, P < .01) findings. Pretransplant ASD spontaneously closed in 22 patients. At 1 and 5 years post‐transplant, there was no difference in the survival rate between groups (P = .96). The prevalence of CVD in recipients of LT was high, and its presence was associated with significantly higher cardiac decompensation before and after LT. Minor and moderate cardiovascular disease did not impact the long‐term survival.     

Lipodystrophy in pediatric HIV

Objective  To assess fat accumulation in children with HIV/AIDS on long term HAART using CDC defined Body mass Index (BMI) criteria and measured Bioelectric Impedance (BI). Methods  Prospective study of 48 HIV infected children (ages 6–15 years) on HAART to determine the incidence of lipodystrophy and evaluate methods of determining body fat accumulation. Lipodystrophy was diagnosed using clinical features-truncal obesity with facial/limb wasting. BMI (weight in kg/height in meters2) was plotted on CDC curves to predict the risk of obesity. BI was performed using Omron’s HBF301 body fat analyzer and reported as TBF %/height. Serum cholesterol and triglycerides were measured. Results were compared using ANOVA Results  Average duration of HAART was 2.4 years. Forty five of 48 patients were on protease inhibitors. Fifteen (31%) developed Lipodystrophy, but CDC BMI curves identify only 7/15 as overweight or at risk for obesity. However, TBF/Ht of 30% (using BI) was 85% sensitive and 88% specific in identifying Lipodystrophy. Hyperlipidemia occurred in 28/48 (58%) overall, in 14/15 (93%) diagnosed with lipodystrophy. Conclusion  Lipodystrophy is a significant problem in children with HIV/AIDS on HAART. BI is more useful than BMI in identifying patients with abnormal fat accumulation and should be incorporated in their routine assessment in the ambulatory setting.     

Correlation of clinical and chest radiograph findings in pediatric submersion cases

Background

Submersion injuries are a leading cause of injury death in children in the United States. The clinical course of a submersion patient varies depending on the presence of anoxic brain injury and acute respiratory failure.

Objective

We studied changes in clinical findings and chest radiograph findings and determined the sensitivity/specificity of the presenting chest radiograph in predicting clinical improvement within the first 24 h in pediatric submersion cases.

Materials and methods

We conducted a cross-sectional study of pediatric submersion patients through age 18 years treated at a children’s hospital from 2010 to 2013. We reviewed demographics, comorbidities, prehospital/hospital course and chest radiographic findings. Clinical improvement occurred when a child demonstrated normal vital signs and mentation. We compared radiographic findings among children based on clinical improvement up to 24 h post submersion. Using odds ratios, we calculated associations between radiographic findings and clinical improvement. We studied the sensitivity/specificity of the presenting chest radiograph in predicting clinical improvement within 24 h.

Results

One hundred forty-two of 262 (54%) patients had initial chest radiographs; 41% had follow-up radiographs. The odds of an abnormal initial chest radiograph were 4 times higher in children with respiratory distress or abnormal mentation at emergency department (ED) presentation compared to children without these findings (odds ratio [OR]=4.83; 95% confidence interval [CI]=2.1–10.85; P<0.001). Improvement in radiographic findings occurred in 85% of children within 24 h. Children with an abnormal initial chest radiograph were 87% less likely to improve clinically by 24 h (P<0.001). A presenting chest radiograph that was normal or with mild pulmonary edema/atelectasis predicted clinical improvement within 24 h (sensitivity 95%, specificity 57%).

Conclusion

Most chest radiographic findings improve in pediatric submersion patients who recover within the first 24 h. An initial chest radiograph that is normal or with mild pulmonary edema/atelectasis satisfactorily predicts clinical improvement by 24 h post submersion.

     

Long-term follow-up of pediatric sickle cell disease patients with abnormal high velocities on transcranial Doppler

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.     

Magnetic resonance imaging of the small bowel in children with idiopathic inflammatory bowel disease: evaluation of disease activity

Background  Examinations using ionizing radiation are frequently used in the evaluation of disease activity in children affected by idiopathic inflammatory bowel disease (IBD). Objective  To develop an MR imaging protocol without the need for fluoroscopic insertion of an enteral tube and to assess the disease activity in children with IBD. Materials and methods  Included in the study were 37 children (22 girls and 15 boys; age range 7–15 years, mean 11.67 years) with IBD who underwent MR imaging of the small bowel. Of these 37 children, 32 had Crohn disease and 5 had indeterminate colitis. A water solution containing herbal fibres was administered orally or through a nasogastric tube. Patients were imaged on a 1.5-T MR scanner with T1-weighted and Τ2-weighted sequences followed by a dynamic study using 3-D T1-W images after intravenous administration of gadolinium. Results  The percentage enhancement of the bowel wall was significantly increased in patients with abnormal C-reactive protein (CRP) values compared to patients with CRP values in the normal range (P<0.001). A relatively weak but significant correlation between percentage enhancement of the bowel wall and CRP values was noted during all phases of enhancement. Conclusion  This MR imaging protocol is a safe and well-tolerated method for evaluating disease activity and extraintestinal manifestations of IBD in children.     

Barriers to medication adherence in children,adolescents, and young adults prescribed anticoagulation

Pediatric and adolescent and young adult (AYA) thromboembolism is treated with anticoagulation, but little is known about adherence. The aims of this study were to describe barriers to adherence among children and AYAs (ages 0–25 years) prescribed anticoagulants and to explore the relationship between barriers and self-reported adherence. Nearly 75% of patients and caregivers reported barriers, and a larger number of barriers was associated with missing at least one dose in the past month per both patient (r_pb = 0.48, p = .01) and caregiver (r_pb = 0.52, p = .01) report. Limitations, clinical implications, and future directions are discussed.     

Evaluation of bowel function in healthy children: untreated constipation is common

Aim

We evaluated bowel function in healthy children with regard to gender and age.

Methods

The study was carried out in 2016 at a tertiary children's hospital. Healthy children aged 3.5 years to 15 years who were admitted to the hospital, siblings to patients or offspring of staff members were included. Validated self‐report questionnaires and internally developed questions regarding obstructive outlet‐ and gas‐related symptoms were used.

Results

A total of 310 participants (50% girls) were included, which corresponded to a 94% answer frequency. Respondents were divided into a younger age group (3.5 years to seven years), consisting of 135 children, and an older age group (eight years to 15 years), consisting of 175 children. Younger children reported more foul odours than older children (50% vs. 29%, p = 0.001) and more obstructive symptoms (21% vs. 10%, p = 0.01). There was no difference between the age groups regarding constipation (19% vs 16%, NS). Overall, 55% of those with constipation had no treatment for the condition, although they reported abdominal pain (51%) and problems with foul odours (57%).

Conclusion

Healthy children frequently reported constipation, abdominal pain and gas‐related problems, but treatment was rare. Overall, bowel function seemed to improve during childhood, although constipation remained largely untreated.     

Fundal Changes in Children Receiving Vigabatrin

Visual field defects and other abnormalities are reported in patients receiving the newer antiepileptic Vigabatrin (VGB). Field testing in children younger than 6 years and those with mental retardation is difficult. The authors, therefore, studied ophthalmoscopic abnormalities in seven pediatric patients receiving VGB for median duration of 9 month (range, 3–32 months). Abnormal findings were seen in two (33.3%) in the form of surface wrinkling retinopathy and abnormal macular reflexes. The proportion of abnormal findings was in agreement with previous reports. Thus it is concluded that simple ophthalmoscopy by an ophthalmologist picks up the abnormalities due to ocular toxicity of VGB, and helps in rationalizing further AED therapy in the clinic.     

Evaluation of children with urinary tract infection – Impact of the 2011 AAP guidelines on the diagnosis of vesicoureteral reflux using a historical series

ObjectiveTo clarify the impact of the updated American Academy of Pediatrics guidelines for the evaluation of children presenting with initial febrile urinary tract infection (UTI) on the diagnosis of vesicoureteral reflux (VUR) in children with normal renal sonograms.Materials and methodsChildren with VUR followed between 2002 and 2004 were evaluated using criteria specified in the AAP guidelines. A total of 49 children (42 girls) who were 2–24 months of age at diagnosis of VUR made following initial febrile UTI were included.Results40.8% of ultrasounds were abnormal. While children with abnormal ultrasounds were more likely to have scintigraphic evidence of renal damage than children with normal ultrasounds (50% vs 17%, p = 0.026), one third of the children with abnormal renal scans had normal RBUS. There was no statistically significant difference in diagnosis of grade 3 or higher VUR between groups (p = 0.136).ConclusionsMost children in this series would not have been diagnosed with VUR after initial febrile UTI. More worrisome, 17.2% of children with normal ultrasound had renal injury identified on renal scanning, and 62.1% had grade 3 or higher VUR. These findings reinforce concerns that the new guidelines may miss or delay diagnosis of clinically significant VUR.