Mahua Dasgupta

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population.

Subjective Global Nutritional Assessment in Critically Ill Children

BACKGROUND Underweight children admitted to the pediatric intensive care unit (PICU) have a higher risk of mortality than normal-weight children. The authors hypothesized that subjective global nutrition assessment (SGNA) could identify malnutrition in the PICU and predict nutrition-associated morbidities. METHODS The authors prospectively evaluated the nutrition status of 150 children (aged 31 days to 5 years) admitted to the PICU with the use of SGNA and commonly used objective anthropometric and laboratory measurements. Each child was administered the SGNA by a dietitian while anthropometric measurements were performed by an independent assessor. To test interrater reproducibility, 76 children had SGNA performed by another dietitian. Occurrence of nutrition-associated complications was documented for 30 days after admission. RESULTS SGNA ratings of well nourished, moderately malnourished, or severely malnourished demonstrated moderate to strong correlation with several standard anthropometric measurements (P < .05). The laboratory markers did not demonstrate any correlation with SGNA. Interrater agreement showed moderate reliability (κ = 0.671). Length of stay, pediatric logistic organ dysfunction, and Pediatric Risk of Mortality III were not significantly different across the groups and did not correlate with SGNA.

Implementation of a Routine Developmental Follow-up Program for Children with Congenital Heart Disease: Early Results

OBJECTIVE To describe the implementation of a routine developmental follow-up program for children with congenital heart disease, summarize the developmental outcomes of the first clinic visits of the referred patients, and determine what factors predict variability in early developmental outcomes. DESIGN Infants with congenital heart disease who had cardiac surgery within the first 30 days of life, had a cyanotic lesion (with or without surgery) or were believed to be at risk for developmental delay due to comorbid conditions or perioperative complications such as seizures or stroke were referred to the program as part of standard clinical care. Patients were evaluated using the Bayley Scales of Infant and Toddler Development-III. This study reports results from 95 patients (January 2007-October 2009) who had their first developmental follow-up visit at less than 1 year of age. RESULTS   Patients were 7.2 ± 1.2 months at their first evaluation. Bayley scores (mean/standard deviation) for the entire group were: Cognitive 100.8 ± 11.9; Language 96.3 ± 12.7; and Motor 88.6 ± 18.6. Scores for language and motor achievement were significantly lower than population norms. 44% of children had at least one low score (defined as > 1 standard deviation below the mean). Of children meeting state criteria for early intervention services, 31% were not receiving any early intervention services. Risk factors for worse developmental outcomes (P < .05) included more open heart procedures, the presence of additional medical/genetic conditions, and the need for supplemental tube feedings. Developmental outcomes were not significantly related to gestational age, prenatal diagnosis, diagnostic category, or age at first surgery. CONCLUSIONS Implementation of a routine developmental follow-up program for congenital heart disease patients is possible and useful in identifying those patients who would benefit most from early intervention.

Mental health disorders influence admission rates for pain in children with sickle cell disease.

Patients with sickle cell disease (SCD) experience a broad range of mental health disorders placing them at risk for more complicated hospitalizations for pain. The current study examined the impact of mental health disorders on admission rates and hospital length of stay (LOS) for vaso‐occlusive pain events (VOE) in pediatric patients with SCD.

Effects of a Culturally Tailored Intervention on Changes in Body Mass Index and Health-Related Quality of Life of Latino Children and Their Parents

Purpose. To evaluate the effects of a multicomponent, family-based, culturally tailored intervention for overweight Latino children and their parents. Design. One group pretest/posttest with clinic comparison group. Setting. Community health center in Milwaukee, Wisconsin. Subjects. 54 Spanish-speaking, Latino families with children 8 to 11 years of age at enrollment and a body mass index (BMI) > 85th percentile. Thirty-one completed the 12-month follow-up. Main Outcome Measures. BMI, fitness measures, self-reported eating patterns, sedentary behaviors, and quality of life scales. Intervention. Index child and one (index) parent participated in interactive sessions and physical activity reinforced by family goal-setting, staff support, and supplemental activities. Results. Small but statistically significant changes in child BMI z score (Δ = –.13 SD, p < .001) and parent fitness (Δ = .74, p < .04) were documented by paired t-test. Quality of life increased significantly for children (combined Pediatric Quality of Life Inventory score Δ = 10.7, p < .001) and parents (Short Form Health Survey12 mental composite score Δ = 8, p < .022; Wilcoxon rank sum test). BMI z score for clinic comparison children (n = 31) increased significantly during the same time period (Δ = .23 SD, paired t = 4.32, p < .0002). Conclusions. A culturally tailored program for Latino families reduced BMI for enrolled children and significantly enhanced quality of life for children and parents. Intervention approaches that integrate cultural and social circumstances and emphasize goal setting and life style changes may be fruitful for this population of at-risk children. (Am J Health Promot 2011;25[4]:e1–e11.)

Increased recombinant activated factor VII use and need for surgical reexploration following a switch from aprotinin to epsilon-aminocaproic acid in infant cardiac surgery

STUDY OBJECTIVE To evaluate whether conversion from aprotinin to epsilon-aminocaproic acid (EACA) during infant cardiac surgery was associated with increased perioperative bleeding. DESIGN Structured retrospective chart review. SETTING University-affiliated large congenital cardiac surgery program. MEASUREMENTS Records from 145 infants (age < 1 yr) receiving aprotinin as antifibrinolytic therapy for cardiac surgery between 6/1/2006 and 12/31/2006 were compared with a cohort of infants receiving EACA for cardiac surgery between 6/1/2008 and 12/31/2008. Sixty-eight infants received aprotinin and 77 infants received EACA. Measured indicators of perioperative bleeding included transfusion volumes, recombinant activated clotting factor VIIa (rFVIIa) administration, need for reexploration, and perioperative chest tube output. MAIN RESULTS EACA treated patients received significantly more rFVIIa for uncontrolled bleeding (19/77 [25%] vs 3/68 [4%]; P < 0.001) and required surgical reexploration more frequently (21/77 [27%] vs 7/68 [10%]; P = 0.01]. Median (25th-75th percentiles) intraoperative platelet transfusion requirements were also increased after the switch to EACA (28 mL [0-58 mL] vs 0 mL [0 mL - 34.5 mL]), but this difference did not reach statistical significance (P = 0.06). CONCLUSIONS Bleeding in infant cardiac surgery increased following the change in antifibrinolytic therapy from aprotinin to EACA. Given the potential for major harm, especially thrombotic complications, from rFVIIa use, prospective studies examining the safety of postcardiopulmonary bypass rFVIIa administration in infants are necessary before the routine off-label use may be recommended.

Development of Optimal Kids Insulin Dosing System Formulas for Young Children with Type 1 Diabetes Mellitus

OBJECTIVE This study was designed to develop predictive formulas for precise insulin dosing in young children with type 1 diabetes (T1DM). RESEARCH DESIGN AND METHODS Consecutive 1-year data from a group of 14 young patients (eight girls, six boys) 3.9 ± 0.8 years old with diabetes duration of 2.0 ± 0.8 years, transitioned from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII), were analyzed to identify parameters governing optimal insulin dosing. Body mass index (BMI), total daily dose (TDD), total basal dose, insulin-to-carbohydrate ratio (ICR), correction factor (CF), and mean amplitude of glycemic excursion (MAGE) by continuous glucose monitoring and hemoglobin A(1c) (HbA(1c)) level were evaluated at baseline and every 3 months. The slopes of CF versus 1/TDD, bolus versus TDD, ICR versus 1/TDD, and CF versus ICR were determined. RESULTS Kids Insulin Dosing System (KIDS) slope constants at follow-up were associated with MAGE compared with baseline (P<0.0001) without significant changes in BMI (16.6 ± 1.5 vs. 16.7 ± 1.4 kg/m(2)) and HbA(1c) values (8.0 ± 0.50% vs. 7.8 ± 0.40%). The relationship between CF and TDD changed significantly during CSII compared with baseline MDI (P<0.0001), whereas the coefficients for ICR and TDD relationship remained relatively unchanged. The KIDS formulas estimated TDD=0.74×body weight, total basal dose=0.28×TDD, CF=2,800/TDD, and ICR=13.5×body weight/TDD. CONCLUSIONS The interrelationships among ICR, CF, TBD, and TDD remained stable on CSII and were accompanied by decreased glycemic excursions. The KIDS formulas may yield consistent and easy estimates of insulin dosing factors in very young patients with T1DM.

The use of neuropathic pain drugs in children with sickle cell disease is associated with older age, female sex, and longer length of hospital stay.

Although neuropathic pain is increasingly recognized in sickle cell disease (SCD), it is unknown how neuropathic pain drugs are used in children with SCD. Thus, we investigated use of these drugs and hypothesized older age and female sex are associated with increased neuropathic drug use and the use of these drugs is associated with longer length of stay. We analyzed the Pediatric Health Information System (2004 to 2009) including all inpatient visits aged 0 to 18 years with any SCD-related (all genotypes) discharge diagnosis. To limit confounding we excluded psychiatric and seizure visits. Antiepileptics, tricyclic antidepressants, and selective serotonin reuptake inhibitors were drugs of interest. Generalized Estimating Equations determined the impact of age and sex on neuropathic drug use and the impact of neuropathic drug use on length of stay. We analyzed 53,557 visits; 2.9% received≥1 neuropathic drugs. The odds of receiving a neuropathic drug increased significantly with age (reference group, 0 to 4 y: 5 to 10, odds ratio [OR], 5.7; 11 to 14: OR, 12.5; 15 to 18: OR, 22.8; all P<0.0001] and female sex (OR, 1.5; P=0.001). Neuropathic drug use was associated with longer length of stay (risk ratio, 8.3; P<0.0001). Neuropathic drug use in children with SCD was associated with older age, female sex, and longer length of stay.

Predictors of Pouchitis After Ileal Pouch-Anal Anastomosis in Children.

Objectives: Predictive factors for the development of pouchitis after ileal pouch-anal anastomosis (IPAA) in children have not been well studied. In this retrospective study, the incidence and risk factors that predict pouchitis in children with IPAA will be identified. Methods: The records of patients who underwent IPAA surgery at Childrens Hospital of Wisconsin between January 2000 and December 2013 were reviewed retrospectively. Patients with clinical, endoscopic, and histological findings consistent with pouchitis were identified. The groups of patients with and without pouchitis or chronic pouchitis were compared to determine which demographic, pathological, or disease characteristics may serve as predictive factors for the development of pouchitis or chronic pouchitis. Results: Out of a total of 60 patients who underwent IPAA, preoperative diagnosis was ulcerative colitis (UC) in 43 and familial adenomatous polyposis (FAP) in 17. Pouchitis was identified in 24 (56%) patients with UC and 2 (12%) patients with FAP. Subgroup analysis of patients with UC revealed that chronic pouchitis occurred in 15 (35%) patients. The median follow-up period from construction of the IPAA was 35 months (range 4.59–104.26 months). The study analysis revealed that a higher Pediatric Ulcerative Colitis Activity Index score at the time of diagnosis was a significant predictive factor for both pouchitis (P = 0.001) and chronic pouchitis (P = 0.02). Conclusions: Patients with UC and a higher PUCAI score at the time of diagnosis have a higher risk for developing pouchitis.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use.

Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme‐linked immunosorbent assay. Independent samples t‐test compared SP levels between: (i) SCD baseline and controls, and (ii) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7‐19 years old. Mean ± standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32·4 ± 11·6 vs. 22·9 ± 7·6, P = 0·0009). SP in SCD pain was higher than baseline (78·1 ± 43·4 vs. 32·4 ± 11·6, P = 0·004). Haemolysis correlated with increased SP: Hb (r = −0·7, P = 0·0002), reticulocyte count (r = 0·61, P = 0·0016), bilirubin (r = 0·68, P = 0·0216), lactate dehydrogenase (r = 0·62, P = 0·0332), aspartate aminotransferase (r = 0·68, P = 0·003). Patients taking hydroxycarbamide had increased SP (β = 29·2, P = 0·007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment.