Historical Cohort Of Children Research Articles

Clinical profile of children with parechovirus meningitis in Singapore

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127days, with the majority (96%) being ≤ 90days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. When compared to our historical cohort of EV meningitis ≤ 90days old, children with HPeV meningitis ≤ 90days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90days old (OR 6.3, 95% CI 2.7-14.2).

Long-term Outcome of Transjugular Intrahepatic Portosystemic Shunt in Children With Portal Hypertension.

A proportion of children with chronic liver disease have severe portal hypertension (PH) and a preserved synthetic and biliary function. In our institution these children have been managed with transjugular intrahepatic portosystemic shunts (TIPS). We aimed to evaluate the long-term patency of TIPS placed in pediatric patients with PH. Retrospective study of children who underwent TIPS in the last 15 years. We compared patients with cirrhotic PH to those with noncirrhotic PH, and all with an historical cohort of children who underwent a surgical portosystemic shunt. Kaplan-Meier analysis measured long-term shunt patency. Twenty-nine patients were recorded (cirrhotic PH = 11, noncirrhotic PH = 18, mean age 10.3 years[±4.3], mean weight 36.7 kg [±20.1], mean pediatric end-stage liver disease score 4.1 [±7.1]); in 5 TIPS was placed after split liver transplantation. Indication for TIPS was variceal bleeding in 18, refractory ascites in 11. Primary patency rates at 6 months and at 1, 2, and 4 years were 91%, 83%, 60%, and 46%, respectively. At last follow-up (mean of 2.8 years [±2.4, range 0.1-8.1 years]) secondary patency (after radiological revision) was 100%. The patency rate of the historical cohort of patients who underwent a surgical portosystemic shunt was 26 of 31 (82%) at a median follow-up of 12.5 years (1.6-25.8). TIPS appears to have a high mid-term patency rate, especially if monitored and revised. Its high clinical success rate, along with a minimally invasive approach, suggests that in this setting TIPS should not be regarded only as a bridge to liver transplantation.

A standardized technique of laparoscopic placement of peritoneal dialysis catheter with omentectomy and closure of patent processus vaginalis: a 3-in-1 minimally invasive surgical approach in children

Omental wrapping is a common cause for catheter failure in children on peritoneal dialysis (PD). Previous studies are conflicting in the benefits of omentectomy. We conducted a retrospective review on consecutive children aged < 18 years who underwent PD catheter placement by a standardized laparoscopic three-in-one (lap3-in-1) technique from 2013 to 2018. The laparoscopic approach combined catheter placement with well-defined indication and extent of omentectomy, and closure of any patent processus vaginalis (PPV). A historical cohort of children who had their first PD catheter placement by open surgery without omentectomy was identified as control for comparison. There were 33 and 32 children in the lap3-in-1 and control cohorts respectively without any difference in gender and median age at the time of surgery. 24/33 (73%) and 14/33 (42%) in the lap3-in-1 cohort required laparoscopic omentectomy and PPV closure. 4/33 (12.1%) had reoperations for catheter failures which equated 1 reoperation per 144 catheter months. None of the patients in lap3-in-1 cohort had reoperation due to omental wrapping or inguinal hernia, compared with 13/32 (41%; p<0.001) and 5/32(16%; p=0.02) in the control cohort. Kaplan Meier survival curves showed significantly longer catheter life in the lap3-in-1 cohort (p<0.001). In multivariate analysis by the COX proportional hazards model, the lap3-in-1 approach was found to have significantly reduced risk of reoperation for catheter failure (HR 0.11; 95%CI: 0.04 – 0.31; p<0.001). The lap3-in-1 technique promotes catheter longevity by accurately selecting those children who would benefit from omentectomy and ascertaining thoroughness of omentectomy. The technique also prevents subsequent development of inguinal hernia.

Radiologically isolated syndrome in children: Clinical and radiologic outcomes.

Objective:To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed “radiologically isolated syndrome” or RIS).Methods:Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS.Results:We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%–60%) in a median of 2.0 years (interquartile range [IQR] 1.0–4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%–76%) in a median of 1.1 years (IQR 0.5–1.9 years). The presence of ≥2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4–86.2, p = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4–43.6, p = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex.Conclusions:We describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.

Renal tract abnormalities missed in a historical cohort of young children with UTI if the NICE and AAP imaging guidelines were applied

In a historical cohort of children with a urinary tract infection (UTI) who had already undergone all the imaging procedures, the aim was to determine renal tract abnormalities which would have been missed had we implemented the new guidelines from the National Institute for Health and Care Excellence in the United Kingdom (NICE) or the American Academy of Pediatrics (AAP). After a UTI episode, forty-three children (28 females, 65%) aged between 2 months and 2 years presenting at two general hospitals with a febrile UTI before 2008 underwent all the recommended imaging studies predating the new guidelines. Hydronephrosis was defined and graded according to the Society for Fetal Urology (SFU) classification. Hydronephrosis grade II (mild pelvicalyceal dilatation), grade III (moderate dilatation), and grade IV (gross dilatation with thinning of the renal cortex), duplication, vesicoureteral reflux (VUR) grade II and above, renal scarring and reduced renal uptake (<45%) on technetium-99m-labeled dimercaptosuccinic acid (DMSA) scintigraphy were considered significant abnormalities. We calculated the proportion of abnormalities which would have been missed had the new guidelines been used instead. The median of age was 7.6 months (mean 8.7, range 2-24 months), with the majority (n = 37, 86%) being under 1 year of age. Ultrasound (US) showed hydronephrosis in 14 (32%), all grade II. A voiding cystourethrogram (VCUG) was performed in all and showed VUR ≥ grade II in 16 (37%), including eight children (19%) where it was bilateral. DMSA scan showed scarring in 25 children (58%) of whom 11 (26%) had bilateral scars. Reduced differential renal uptake was present in 10 children (23%). Of the 29 children with normal US, 18 (62%) had renal scarring and nine (31%) had VUR ≥ grade II. The NICE guidelines would have missed 63% of the children with VUR ≥ grade II, including a high proportion of grades IV and V VUR, 44% of the children with renal scarring, and 20% of the children with decreased renal uptake, including some children with bilateral renal scarring and with decreased renal uptake. The AAP guidelines would have missed 56% of the children with VUR ≥ grade II, including a high proportion of grades IV and V VUR, and all children with renal scarring as well as those with decreased renal uptake. The prevalence of renal tract abnormalities missed by the new guidelines is high. They should be used with full awareness of their limitations.

Early patterns of wheezing in asthmatic and nonasthmatic children

The aim of this study was to describe the time patterns of wheezing in both asthmatic and nonasthmatic children during the first 36 months of life, and to determine whether there are asthma-related breakpoints in the incidence of wheezing. Data from a historical cohort of children followed from birth to 6 years (SLAM cohort) were used. Wheezing episodes until 36 months and asthma at 6 years were both recorded by a doctor. Monthly mean incidence rate of wheezing and rate ratio were calculated. Joinpoint regression models were built to identify breakpoints in the risk of wheeze. Complete information was available for 3739 children. Wheezing in the first 36 months was more frequent in asthmatic than in nonasthmatic children (rate ratio 2.62, 95% CI 1.81-3.78). Differences were appreciable within the first months and increased steadily thereafter because of a persistently high rate in asthmatic children. No breakpoint in the rate ratio could be identified. Asthmatic children exhibited a one-phase curve of incidence and nonasthmatic children exhibited a two-phase curve. However, children with allergic asthma also displayed a two-phase curve. There is no identifiable breakpoint during the first 36 months of life at which the incidence of wheezing in asthmatic children begins to stand out.

Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis

To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.

Evolución del estado nutricional en una cohorte de escolares chilenos: ¿Un cambio real o ficticio?

Considering the high prevalence of obesity among children attending elementary schools, it is important to know the evolution of body weight when these children reach adolescent.To analyze the changes in nutritional status of children between the first year of elementary school and the first year of high school.A historical cohort of children that were assessed when they started elementary school in 1997 was evaluated again eight years later Weight and height were measured and body mass index (BMI) was calculated. Obesity was considered as a BMI over percentile 95 of Center for Disease Control (CDC) references. The concordance between nutritional assessment in both periods and the risk of obesity during adolescence, based on previous weight were also calculated.Data from 117,815 children were analyzed. The prevalence of obesity in the first year of elementary school and the first year of high school was 14.6% and 7%, respectively. The mean weight increase during the eight years period was 32.6+/-8.4 kg corresponding to 108%+/-28.1% of the expected increase. There was a low diagnostic concordance between both assessment periods. There was a reduction of under and overweight and a higher proportion of subjects with normal weight in the second assessment period. The risk for being obese in the first year of high school was 6.4 times greater for children that were obese in the first year of elementary school (confidence intervals 6.1-6.9.There was an important reduction in the proportion of obesity between the age of 6 and 14 years. The risk of obesity at 14 years of age was strongly influenced by the presence of obesity at 6 years of age. The broader BMIranges for normality for high school children could give a false image of the nutritional status of teenagers .

Evolution of nutritional status in a cohort of school age children

Considering the high prevalence of obesity among children attending elementary schools, it is important to know the evolution of body weight when these children reach adolescent. To analyze the changes in nutritional status of children between the first year of elementary school and the first year of high school. A historical cohort of children that were assessed when they started elementary school in 1997 was evaluated again eight years later Weight and height were measured and body mass index (BMI) was calculated. Obesity was considered as a BMI over percentile 95 of Center for Disease Control (CDC) references. The concordance between nutritional assessment in both periods and the risk of obesity during adolescence, based on previous weight were also calculated. Data from 117,815 children were analyzed. The prevalence of obesity in the first year of elementary school and the first year of high school was 14.6% and 7%, respectively. The mean weight increase during the eight years period was 32.6+/-8.4 kg corresponding to 108%+/-28.1% of the expected increase. There was a low diagnostic concordance between both assessment periods. There was a reduction of under and overweight and a higher proportion of subjects with normal weight in the second assessment period. The risk for being obese in the first year of high school was 6.4 times greater for children that were obese in the first year of elementary school (confidence intervals 6.1-6.9. There was an important reduction in the proportion of obesity between the age of 6 and 14 years. The risk of obesity at 14 years of age was strongly influenced by the presence of obesity at 6 years of age. The broader BMIranges for normality for high school children could give a false image of the nutritional status of teenagers .

203: IORT for Neuroblastoma: Outcome and Morbidity

Local control for patients with neuroblastoma remains a formidable challenge. Intraoperative radiation therapy (IORT) has been explored as a vehicle to potentially improve local control while minimizing side effects of external beam radiation. In this study we aim to assess the clinical outcome and morbidities of IORT as part of a multimodality treatment in a historical cohort of children with neuroblastoma. Between 1986 and 2004, 41 patients with neuroblastoma received IORT at a single institution. Two patients were lost to follow-up soon after surgery and were therefore excluded from this analysis. Mean age at diagnosis was 4 years (range 9 months-20.3 years), and mean age at time of IORT was 4.4 years (range 11 months-20.6 yrs). 32 had stage 4 disease, six stage 3, and one stage 2. IORT was delivered at the time of surgical resection using a linear accelerator with beam energies ranging from 4 MeV to 16 MeV. The median dose per field was 10 Gy (range 7-15 Gy). One to four separate fields were used in each case (1 field = 25, 2 fields=7, 3 fields =2, 4 fields =5). All sites of IORT were intraabdominal. Thirty five patients received IORT as part of initial therapy and 4 patients received IORT both at initial diagnosis and recurrence. Sixteen patients had external beam radiation to the primary tumor site and five patients had total body irradiation (TBI) as part of an autologous bone marrow transplant (ABMT). Median follow up time was 46 months (range 6 months-16.6 years), and, 67% of patients were alive at last follow up. Sixty-four percent of patients were without evidence of disease and of the 13 patients who died, five died without evidence of disease. Six patients had locally recurrent disease after initial surgery with IORT. Two of these patients had successful salvage after local recurrence with a second surgery and IORT in addition to chemotherapy. The overall local control rate with this multimodality treatment is 90%. Of the 39 patients, 10 (26%) were known to have hypertension, vascular stenosis or middle aortic syndrome. Two of the patients who are alive without evidence of disease have had vascular bypasses for stenotic vessels. Two patients died without evidence of disease from mesenteric ischemia due to stenotic vessels. Of the 10 patients with these clinical findings, 50% had multiple fields treated using IORT, and had aggressive surgeries with a goal of gross total resection. The mean ages at the time of IORT and surgery were 48 months and 58 months respectively for those who did and did not experience vascular consequences. Patients treated with IORT as part of multimodality therapy for neuroblastoma have excellent local disease control. In this group of patients, serious complications such as hypertension, vessel stenosis and death are reported for the first time. It remains unclear whether these vascular complications are due to the disease process, treatment factors, or both. The influence of patient age, number of IORT fields, and addition of EBRT are being assessed.

Post-marketing evaluation of the short term safety of COMVAX ®

We report an evaluation of the short-term safety of a pediatric bivalent combination vaccine containing RECOMBIVAXHB ® and Liquid PedvaxHIB ®, COMVAX ®. Safety was assessed through identification of medical utilization; potential adverse events were identified through computerized clinical databases for deaths, hospitalizations, emergency room visits, and outpatient clinic visits. We calculated relative risks whenever there was at least one diagnosis-specific event in the risk period following vaccination and compared the rates in specific time windows following vaccination with rates at 31–60 days following vaccination and also with rates in a historical cohort of children. A total of 27,802 doses of COMVAX ® were administered, with 127 separate adverse event codes with statistically significant elevated risks, and 66 codes with significantly decreased risks. Most potentially serious diagnoses appeared in four major categories: “Respiratory Events”; “Gastroenteritis”; “Adverse Effect of Medicinal and Biological Substance, NOS”; and “Fever”. There was no consistent pattern to indicate increased risks for serious respiratory or gastrointestinal illness. For fever, most of the findings appeared to be explained by changes in data collection or by concomitant vaccination with M-M-R -II ®. There was an increased risk for fever hospitalizations following shot 1. The total number of children hospitalized with fever was seven out of 12,468 children; all recovered fully. In this study population of 27,802 vaccine recipients, COMVAX appeared to have a favorable safety profile.

Tissue transglutaminase and endomysial autoantibodies measured in an historical cohort of children and young adults in whom coeliac disease was suspected.

To evaluate whether anti-endomysial and anti-transglutaminase antibodies are relevant important markers of coeliac disease in an historical group of patient sera. Sera from 196 children suspected to suffer from coeliac disease were analysed for these antibodies. A total of 233 serum samples were obtained simultaneously with a biopsy. Coeliac disease was confirmed in 37 (19%) patients. Antibodies against guinea pig transglutaminase were determined by enzyme-linked immunosorbent assay (ELISA); endomysial antibodies were determined by immunofluorescence. In 17 samples, immunoglobulin A (IgA) anti-transglutaminase levels were increased; 16 of these came from coeliac patients. High levels correlated with high prediagnostic or challenge-related gluten intake. The additional anti-transglutaminase-positive patient was assumed to suffer from sequelae to gastroenteritis. Raised IgA anti-transglutaminase levels were correlated with presence of coeliac disease. Negative tests were seen in some coeliac patients when on a gluten-containing diet. The IgA anti-transglutaminase test using guinea pig antigen was less sensitive than anti-endomysial antibodies but rather specific for active coeliac disease. In our study, anti-endomysial antibodies were more specific than anti-transglutaminase antibodies for active coeliac disease.