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Abstract 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=0.74xbody weight, total basal dose=0.28xTDD, CF=2,800/TDD, and ICR=13.5xbody 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: It is not known whether Latino children, the largest minority population in the United States, experience disparities in the timeliness of their access to health care. We compared timeliness of care among Latino, white, and African American children. METHODS: DESIGN: cross-sectional cohort from the 2000 Medical Expenditure Panel Survey. PATIENTS: children with a usual source of care. Outcome measure: timeliness of care was assessed using parent reports of their child's 1) routine care, 2) illness care, 3) phone help, and 4) experiencing of a brief wait time. Analysis: multiple logistic regression was used to determine the adjusted odds of not always receiving timely medical care. RESULTS: Four-thousand one-hundred twenty children were included. Latino children were less likely to always (P < .05) receive timely care compared with whites and African Americans, respectively, in 3 areas: routine care, phone help, and brief wait time. Multiple regression revealed decreased relative risks (RR, 95% CI) of always receiving timely medical care for Latinos in the same areas: routine care, compared with whites (0.88, 0.79-0.98) and African Americans (0.81, 0.70-0.93); phone help, compared with whites (0.84, 0.76-0.92) and African Americans (0.86, 0.76-0.960); and brief wait time, compared with whites (0.71, 0.65-0.80) and African Americans (0.81, 0.70-0.92). With parental survey language in the model, Latinos experienced decreased timeliness of care for routine care compared with African Americans (0.85, 0.72-0.98); phone help compared with whites (0.87, 0.77-0.96); and brief wait times compared with whites (0.79, 0.71-0.87). CONCLUSIONS: Latino children experience marked disparities in obtaining timely medical care, only some of which is associated with language differences. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis: Time to ambulation (walking) after hip fracture surgery impacts the frequency of postoperative complications and length of hospital stay.Methods: A retrospective observational study of a cohort of all patients admitted to a university teaching hospital with a principal International Classification of Diseases-9 diagnosis of a hip fracture during 3 calendar years.Results: A total of 131 participants were identified (68% were aged 65 years or older). Overall, the mean time to writing an order to ambulate a patient after a hip fracture surgery was 2 +/- 1.5 days. Time to ambulation after hip fracture surgery was significantly less in patients cared for on orthopedic surgery service compared to general surgery service (1.8 +/- 1 vs 2.5 +/- 2, p <.05) or general internal medicine service (2.5 +/- 1.5, p <.05). It did not relate, however, to patient's age, sex, or race, or to patient's functional status prior to admission, fracture site (femoral neck, intertrochanteric, or subtrochanteric), whether a femoral neck fracture is displaced or not, type of anesthesia (spinal/epidural vs general), type of surgery (open reduction and internal fixation vs hemiarthroplasty), degree of preoperative risk, number of medical conditions, or to obtaining physical therapy and/or medical consultation. Time to ambulation after surgery was an independent predictor for the development of pneumonia (1.5 OR [odds ratio]/day, p <.001), new onset delirium (1.7 OR/day, p <.001), and to prolonged length of hospital stay (B [slope coefficient] = 1.36, p <.0001) but not to the development of pressure ulcers, deep venous thrombosis, or urinary tract infection.Conclusions: Delayed ambulation after hip fracture surgery is related to the development of new onset delirium and pneumonia postoperatively as well as to increased length of hospital stay. Early ambulation after hip fracture surgery should be encouraged. [ABSTRACT FROM AUTHOR]

AIDS-related grief was examined and its association with coping among HIV-positive men and women explored. AIDS-related grief, psychological distress and coping were examined among a sample of 268 HIV-infected individuals, diverse with respect to gender, ethnicity, and sexual orientation. Participants exhibited elevated scores on measures of grief reaction and psychological distress including depressive symptoms, anxiety, and traumatic stress related to their losses. Hierarchical regression analyses revealed that severity of grief reaction was associated with escape-avoidance and self-controlling coping strategies, type of loss, depressive symptoms, and history of injection drug use. Interventions are needed to enhance coping and reduce psychological distress associated with the unique bereavement experienced by people living with HIV- and AIDS-related grief. [ABSTRACT FROM AUTHOR]

Understanding the antecedents of long-term patterns of sexual risk behavior is important for HIV/AIDS prevention research. This study assessed various psychosocial and demographic predictors of safer anal intercourse maintenance and of lapses to unsafe sex between 1984 and 1993 among 906 homosexually active men from the Chicago Coping & Change Study/MACS cohort. Semiannual self-reports of sexual activities were used to classify anal intercourse behavior patterns over a series of 2-year intervals. Two sorts of safer sex were evaluated: (1) definite safety, consistent condom use with all partners or abstinence and (2) modified safety, a broader standard that also included unprotected anal intercourse limited to a monogamous relationship. Results showed that the percentage of men who maintained definitely safe behavior increased from 16%0 of participants after the first 2 years of study to almost 63% during the 8th and 9th years (38% to 82% rates for modified safety). Lapses from definite safety peaked at 22% during the 3rd and 4th years, and 41% of the men lapsed from unfailing condom use at least once during the study (29% lapsed or relapsed by modifiedsafety criteria). Key predictors of long-term propensities (9-year rates)-both maintaining safer sex and lapse/relapse-included consistency of participation (a possible marker for behavior change intentions), predisposition toward risk taking, and age. Thus, personality traits that determine a person's level of commitment to behavior change, tendencies for risk taking, and age need to be considered when designing effective long-term HIV prevention interventions. [ABSTRACT FROM AUTHOR]

Protein hydrolysates might display diverse bioactivities with potential relevance to human and animal health and food technology. Enzymatic hydrolysis of agro-industrial by-products is increasingly focused. In this study, a crude protease from Bacillus sp. CL18 was applied to obtain antioxidant protein hydrolysates from porcine, bovine, poultry, and fish by-products. The crude enzyme hydrolyzed all the twelve investigated by-products, as detected by increased soluble protein contents after 4 h of proteolysis. Hydrolysates exhibited higher radical-scavenging, Fe 2+ -chelating and reducing power capacities than non-hydrolyzed by-products. Hydrolysis times (0-8 h) and enzyme-to-substrate (E/S) ratios (384, 860, and 1,400 U/g) were assessed to produce antioxidant bovine lung hydrolysates. The highest E/S ratio accelerated both hydrolysis and increases in antioxidant activities; however, it did not result in bioactivities higher than hydrolysates obtained with the intermediate E/S ratio. Optimal antioxidant activities could be reached after 6 h of hydrolysis using 860 U/g. Animal by-products are interesting sources of bioactive protein hydrolysates, which could be produced with a non-commercial bacterial protease. This might represent a promising strategy for the valorization of animal by-products generated in large amounts by the agri-food sector., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Bedside Pediatric Early Warning System score is a validated measure of severity of illness in acute care inpatient settings. Its potential as a remote assessment tool for interfacility transport has not been evaluated. We hypothesized that the Bedside Pediatric Early Warning System score was associated with need for intervention during the peritransport period and patient disposition., Methods: We retrospectively evaluated children transported by a regional pediatric team during a 6-month period. Bedside Pediatric Early Warning System scores were calculated at the triage phone call, the transport team arrival, and at transfer of care to the hospital team. The primary outcome was the receipt of significant intervention during the peritransport period, with additional outcomes of destination (ICU, ward, emergency department) in the regional hospital. Scores are presented as median values (interquartile range)., Results: There were 564 children who underwent transport; 139 (25%) received interventions; and 205 (36%) were transferred to the PICU, 231 (41%) to the ward, and 127 (23%) to the emergency department. Scores were 2 (1-5; median interquartile range) in children receiving no in-transport interventions, 8 (5-11) in children receiving any intervention (p < 0.001), and 10 (7-14) in children receiving more than one intervention. Children transferred to the PICU had higher scores 6 (3-10), than children transferred to a ward 3 (1-6) or the emergency department 2 (1-3) (p < 0.001)., Conclusions: The Bedside Pediatric Early Warning System score at the time of initial referral is a useful measure of severity of illness reflected by the subsequent provision of significant peritransport intervention and the transfer destination.

Objective: The purpose of this study was to determine the proportion of children undergoing procedural sedation for fracture reduction in the emergency department (ED) observed to experience negative postdischarge behaviors. Predictors of negative behaviors were evaluated, including anxiety., Methods: This was a prospective cohort study of children receiving intravenous ketamine sedation for ED fracture reduction. The child's anxiety prior to sedation was measured with the Modified Yale Preoperative Anxiety Scale. Negative behavioral changes were measured with the Post-Hospitalization Behavior Questionnaire 1 to 2 weeks after discharge. Descriptive statistics and odds ratios (ORs) were calculated. Chi-square test was used for comparisons between groups. Multivariable logistic regression models evaluated predictors of negative behavioral change after discharge., Results: Ninety-seven patients were enrolled; 82 (85%) completed follow-up. Overall, 33 (40%) children were observed to be highly anxious presedation and 18 (22%) had significant negative behavior changes after ED discharge. Independent predictors for negative behaviors were high anxiety (OR = 9.0, 95% confidence interval [CI] = 2.3-35.7) and nonwhite race (OR = 6.5, 95% CI = 1.7-25.0)., Conclusion: For children undergoing procedural sedation in the ED, two in five children have high preprocedure anxiety and almost one in four have significant negative behaviors 1 to 2 weeks after discharge. Highly anxious and nonwhite children have increased risk of negative behavioral changes that have not been previously recognized in the ED setting., (© 2017 by the Society for Academic Emergency Medicine.)

To investigate the association between low near infrared spectroscopy (NIRS) somatic oxygen saturation (<70%) at admission and the need for lifesaving interventions (LSI) in the initial 24 h of a PICU admission. Retrospective chart review of all unplanned admissions to the pediatric intensive care unit (PICU) with NIRS somatic oxygen saturation data available within 4 h of admission, excluding admissions with a cardiac diagnosis. LSI data were collected for the first 24 h after admission. Hemodynamic parameters, laboratory values, illness severity scores and diagnoses were collected. Included PICU admissions were stratified by lowest NIRS value in the first 4 h after admission: low NIRS (<70%) and normal NIRS (≥70%) groups. Rate of LSI from 4 h to 24 h was compared between the two groups. Association of LSI with NIRS saturation and other clinical and laboratory parameters was measured by univariate and multivariate methods. We reviewed 411 consecutive unplanned admissions to the PICU of which 184 (44%) patients underwent NIRS monitoring. A higher proportion of patients who underwent somatic NIRS monitoring required LSIs compared to those without NIRS monitoring (36.4 vs 5.7% respectively, p < 0.0001). The proportion of patients who required LSI was higher in the group with low NIRS (<70%) within the first 4 h compared to those with normal NIRS (≥70%) (77.1 vs 22.1%, p < 0.0001). Fluid resuscitation, blood products and vasoactive medications were the most common LSIs. Multivariable modeling showed NIRS < 70% and heart rate > 2SD for age to be associated with LSIs. ROC curve analysis of the combination of NIRS < 70% and HR >2SD for age had an area under the curve of 0.79 with 78% sensitivity and 76% specificity for association with LSI. Compared to the normal NIRS group, the low NIRS group had higher mortality (10.4 vs 0.7%, p = 0.005) and longer median hospital length of stay (2.9 vs 1.6 days, p < 0.0001). Low somatic NIRS oxygen saturation (<70%) in the first 4 h of an unplanned PICU admission is associated with need for higher number of subsequent lifesaving interventions up to 24 h after admission. Noninvasive, continuous, somatic NIRS monitoring may identify children at high risk of medical instability.

The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study. MRI-derived parameter maps included apparent diffusion coefficient (ADC), normalized cerebral blood flow (nCBF), normalized and standardized relative cerebral blood volume (nRCBV, sRCBV), peak signal-height (PSR) and percent signal-recovery (PSR). These were co-registered to the Stealth MRI and median values extracted from the spatially-matched biopsy regions. A ROC analysis accounting for multiple subject samples was performed, and the optimal threshold for distinguishing TE from GBM determined for each parameter. Histopathologic diagnosis of pure TE (n = 10) or pure GBM (n = 34) was confirmed in tissue samples from 15 consecutive subjects with analyzable data. Perfusion thresholds of sRCBV (3575; SN/SP% = 79.4/90.0), nRCBV (1.13; SN/SP% = 82.1/90.0), and nCBF (1.05; SN/SP% = 79.4/80.0) distinguished TE from GBM (P < 0.05), whereas ADC, PSR, and PH could not (P > 0.05). The thresholds for CBF and CBV can be applied to lesions with any admixture of tumor or treatment effect, enabling the identification of true tumor burden within enhancing lesions. This approach overcomes current limitations of averaging values from both tumor and TE for quantitative assessments.

Objectives: The Infant and Child Feeding Questionnaire (ICFQ) was created to facilitate early detection of feeding and swallowing problems. This is achieved by promoting effective communication between caregivers and health care providers resulting in referral for evaluation and treatment of feeding and swallowing problems by specialists. The purpose of this pilot study was to determine whether items from the ICFQ could be used to screen for differences between children with known feeding problems (FP) and without known feeding problems (NFP)., Methods: Caregivers of children ages 36 months or younger with FP and NFP were recruited to complete the ICFQ and demographic questions. T tests were completed to compare demographic characteristics of the research groups. Responses to ICFQ items were analyzed using receiver operating characteristic analysis and odds ratios to determine whether questionnaire items distinguished between study groups., Results: Sixty-four caregivers of children with FP and 57 caregivers of NFP children were recruited. Three participants in the NFP group did not meet inclusion criteria and were excluded from analysis. A combination of 4 ICFQ questions distinguished between groups (receiver operating characteristic = 0.974). Significant odds ratios were also found for 9 feeding behaviors that distinguished between groups., Conclusions: A subset of items from the ICFQ showed promise for distinguishing FP from NFP groups. Future work will expand the regional representation of the participant samples and obtain equal representation of participants across all age-adjusted questionnaires to determine whether the same combination of ICFQ items continues to distinguish between FP and NFP groups.

Objective: To describe preschool neurodevelopmental outcomes of children with complex congenital heart disease (CHD), who were evaluated as part of a longitudinal cardiac neurodevelopmental follow-up program, as recommended by the American Heart Association and the American Academy of Pediatrics, and identify predictors of neurodevelopmental outcomes in these children., Study Design: Children with CHD meeting the American Heart Association/American Academy of Pediatrics high-risk criteria for neurodevelopmental delay were evaluated at 4-5 years of age. Testing included standardized neuropsychological measures. Parents completed measures of child functioning. Scores were compared by group (single ventricle [1V]; 2 ventricles [2V]; CHD plus known genetic condition) to test norms and classified as: normal (within 1 SD of mean); at risk (1-2 SD from mean); and impaired (>2 SD from mean)., Results: Data on 102 patients were analyzed. Neurodevelopmental scores did not differ based on cardiac anatomy (1V vs 2V); both groups scored lower than norms on fine motor and adaptive behavior skills, but were within 1 SD of norms. Patients with genetic conditions scored significantly worse than 1V and 2V groups and test norms on most measures., Conclusions: Children with CHD and genetic conditions are at greatest neurodevelopmental risk. Deficits in children with CHD without genetic conditions were mild and may not be detected without formal longitudinal testing. Parents and providers need additional education regarding the importance of developmental follow-up for children with CHD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Local pediatric screening guidelines for venous thromboembolism (VTE) are developed from incomplete pediatric data and extrapolated from adult data in which immobility is a major risk factor. We hypothesized that screening guidelines centered on immobility are inadequate for identifying children at risk of central venous catheter (CVC)-associated VTE., Methods: This retrospective case-control (4:1) study at an academic, quaternary-level, free-standing children's hospital applied screening guidelines for VTE risk to all cases of VTE from July 2012 to April 2014. Cases and controls were classified as "at risk" or "not at risk" of VTE by guideline criteria. These guidelines assessed VTE risk factors, including CVC, as reported in the pediatric literature., Results: VTE prevalence was 0.5 per 100 admissions. Sixty-nine of 114 patients with radiographically confirmed VTE were classified as being "at risk" by the guidelines, with a sensitivity of 61%, specificity of 90.8%, a positive predictive value of 2.4%, and negative predictive value of 99.8%. There was no difference in screening guidelines sensitivity for identifying CVC-associated VTE versus non-CVC-associated VTE. Half of the 45 patients with VTE who were not captured as being "at risk" did not have decreased mobility, the entry point to the algorithm, and 80% of these patients had a CVC., Conclusions: Screening guidelines have low sensitivity for identifying hospitalized children at increased risk of both CVC-associated and other VTE events. Decreased mobility is not a requirement for CVC-associated VTE. Risk factors extrapolated from adult data are insufficient for identifying children at risk of VTE., (Copyright © 2017 by the American Academy of Pediatrics.)

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., (© 2016 John Wiley & Sons Ltd.)

Objective: Recent Pediatric Advanced Life Support (PALS) guidelines have deemphasized the use of advanced airways in short transport. It is unclear if guideline recommendations have altered practice. We sought to determine if a temporal change exists in the number of prehospital pediatric trauma intubations since the 2005 PALS guidelines update., Methods: This is an institutional review board-approved, retrospective, single-center study. Reviewed all pediatric trauma activations where patients younger than 19 years were intubated at the scene, en route or at the level 1 trauma center during 2006 to 2011. Specific complications collected were esophageal intubations, mainstem intubations and need for re-intubations., Results: There were 1012 trauma activations, 1009 pediatric patients, 300 (29.7%) intubated during transport to Children's Hospital of Wisconsin Pediatric Trauma Center (PTC) or upon arrival. Mean age of 9.5 ± 5.9 years. Fifty-seven percent (n = 172) were intubated before PTC, 31.7% (n = 95) field intubations, 25.7% (n = 77) outside facility intubations. 44% (n = 132) at PTC. Age was not a significant variable. There was no difference in the proportion of injured children requiring intubation who were intubated before arrival to the PTC. Those intubated in the field versus a facility had significantly increased mortality (P = 0.0002), longer hospital days (P = 0.0004) including intensive care unit days (P = 0.0003) and ventilator days (P = 0.0003) even when adjusted for illness severity., Conclusions: There was no significant change in the proportion of pretrauma room intubations following the 2005 PALS guidelines even when adjusted for illness or injury severity. Children injured farther from the PTC and more severely injured children were more likely to be intubated before arrival at the PTC.

Objectives: To identify patient, hospital, and central venous catheter factors that may influence the use of low-dose heparin infusion for central venous catheter patency in critically ill children., Design: Secondary analysis of an international multicenter observational study., Setting: Fifty-nine PICUs over four study dates in 2012, involving seven countries., Patients: Children less than 18 years old with a central venous catheter who were admitted to a participating unit and enrolled in the completed Prophylaxis against Thrombosis Practice study were included. All overflow patients were excluded., Interventions: None., Measurements and Main Results: Of the 2,484 patients in the Prophylaxis against Thrombosis Practice study, 1,312 patients had a central venous catheter. Five hundred seven of those patients used low-dose heparin infusion. The frequency of low-dose heparin infusion was compared across various patient, hospital, and central venous catheter factors using chi-square, Mann-Whitney U, and Fisher exact tests. In the multivariate analysis, age was not a significant factor for low-dose heparin infusion use. Patients with pulmonary hypertension had decreased low-dose heparin infusion use, whereas those with active surgical or trauma diagnoses had increased low-dose heparin infusion use. All centrally inserted central venous catheters were more likely to use low-dose heparin infusion when compared with peripherally inserted central venous catheters. The Asia-Pacific region showed increased low-dose heparin infusion use, along with community hospitals and smaller ICUs (< 10 beds)., Conclusions: Patient, central venous catheter, and hospital factors are associated with the use of low-dose heparin infusion in critically ill children. Further study is needed to evaluate the efficacy and persistence of low-dose heparin infusion use.

Nemaline myopathies (NMs) are a group of congenital muscle diseases caused by mutations in at least 10 genes and associated with a range of clinical symptoms. NM is defined on muscle biopsy by the presence of cytoplasmic rod-like structures (nemaline rods) composed of cytoskeletal material. Myofiber smallness is also found in many cases of NM and may represent a cause of weakness that can be counteracted by treatment. We have used i.p. injection of activin type IIB receptor (ActRIIB)-mFc (an inhibitor of myostatin signaling) to promote hypertrophy and increase strength in our prior murine work; we therefore tested whether ActRIIB-mFc could improve weakness in NM mice through myofiber hypertrophy. We report a study of ActRIIB-mFc treatment in the Acta1 H40Y mouse model of NM. Treatment of Acta1 H40Y mice produced significant increases in body mass, muscle mass, quadriceps myofiber size, and survival, but other measurements of strength (forelimb grip strength, ex vivo measurements of contractile function) did not improve. Our studies also identified that the complications of urethral obstruction are associated with mortality in male hemizygote Acta1 H40Y mice. The incidence of urethral obstruction and histologic evidence of chronic obstruction (inflammation) were significantly lower in Acta1 H40Y mice that had been treated with ActRIIB-mFc. ActRIIB-mFc treatment produces a mild benefit to the disease phenotype in Acta1 H40Y mice., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Approximately 20% to 25% of patients with von Willebrand disease (VWD) have a qualitative defect of the von Willebrand factor (VWF) protein activities. Variant VWD typically is classified as type 1C, 2A, 2B, 2M, or 2N depending on the VWF activity defect. Traditionally, diagnosis has relied on multiple clinical laboratory assays to assign VWD phenotype. We developed an enzyme-linked immunosorbent assay (ELISA) to measure the various activities of VWF on a single plate and evaluated 160 patient samples enrolled in the Zimmerman Program for the Molecular and Clinical Biology of von Willebrand Disease with type 2 VWD. Using linear discriminate analysis (LDA), this assay was able to identify type 1C, 2A, 2B, 2M, or 2N VWD with an overall accuracy of 92.5% in the patient study cohort. LDA jackknife analysis, a statistical resampling technique, identified variant VWD with an overall accuracy of 88.1%, which predicts the assay's performance in the general population. In addition, this assay demonstrated correlation with traditional clinical laboratory VWF assays. The VWF multiplex activity assay may be useful as a same-day screening assay when considering the diagnosis of variant VWD in an individual patient., (© 2016 by The American Society of Hematology.)

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., (© 2016 by The American Society of Hematology.)

Objective This study aims to determine the frequency that umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs) migrate into the cardiothymic silhouette after initial verification of correct placement. Study Design This is a single-center, retrospective study in neonates in whom a PICC or UVC was placed. The frequency of catheter tip migration into the cardiothymic silhouette requiring catheter manipulation was determined radiographically at 1 and 24 hours, respectively, after insertion. Results At 1 and 24 hours, 36 and 23% of UVCs (n = 41) migrated into the cardiothymic silhouette, respectively. At 1 and 24 hours, 23 and 11% of PICCs (n = 63) migrated into the cardiothymic silhouette, respectively. Migration was not associated with birth weight, weight at insertion, or postnatal age at insertion. Conclusion UVCs and PICCs frequently migrate into the cardiothymic silhouette increase the risk for development of a pericardial effusion. Serial radiographic assessment of catheter tip location is needed to assess catheter migration within the first 24 hours of line placement., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Context: There is no current standard among myopathologists for reporting muscle biopsy findings. The National Institute of Neurological Disorders and Stroke has recently launched a common data element (CDE) project to standardize neuromuscular data collected in clinical reports and to facilitate their use in research., Objective: To develop a more-uniform, prospective reporting tool for muscle biopsies, incorporating the elements identified by the CDE project, in an effort to improve reporting and educational resources., Design: The variation in current biopsy reporting practice was evaluated through a study of 51 muscle biopsy reports from self-reported diagnoses of genetically confirmed or undiagnosed muscle disease from the Congenital Muscle Disease International Registry. Two reviewers independently extracted data from deidentified reports and entered them into the revised CDE format to identify what was missing and whether or not information provided on the revised CDE report (complete/incomplete) could be successfully interpreted by a neuropathologist., Results: Analysis of the data highlighted showed (1) inconsistent reporting of key clinical features from referring physicians, and (2) considerable variability in the reporting of pertinent positive and negative histologic findings by pathologists., Conclusions: We propose a format for muscle-biopsy reporting that includes the elements in the CDE checklist and a brief narrative comment that interprets the data in support of a final interpretation. Such a format standardizes cataloging of pathologic findings across the spectrum of muscle diseases and serves emerging clinical care and research needs with the expansion of genetic-testing therapeutic trials.

Study Objective: The J-Tip (National Medical Products Inc, Irvine, CA) uses air instead of a needle to push lidocaine into the skin. To our knowledge, no studies have investigated its use for venipuncture in young children. We determine whether the J-Tip decreased venipuncture pain in young children compared with vapocoolant spray., Methods: Children aged 1 to 6 years were randomized into 3 groups: intervention (J-Tip), control (vapocoolant spray), and sham (vapocoolant spray and pop of an empty J-Tip). The procedure was videotaped and scored with the Face, Legs, Activity, Cry and Consolability (FLACC) tool at 3 points; baseline, before approach; device, at J-Tip deployment; and at venipuncture. The FLACC tool was scored 0 (none) to 10 (severe). Comparisons of pain scores over time were made with the generalized estimating equation. Venipuncture success and adverse effects were assessed and compared with χ(2)., Results: Two hundred five children enrolled: intervention 96, control 53, and sham 56. There were no between-group differences in baseline characteristics. There was no mean change in pain scores from device to venipuncture in the intervention group (0.26; 95% confidence interval [CI] -0.31 to 0.82), but there was an increase in pain in the control (2.82; 95% CI 1.91 to 3.74) and sham (1.68; 95% CI 0.83 to 2.52) groups. This change was greater for the control and sham compared to the intervention group. There was no difference in venipuncture success between groups. No severe adverse events occurred. Minor adverse events were the same between groups., Conclusion: Use of the J-Tip for children aged 1 to 6 years reduced venipuncture pain compared with vapocoolant spray or sham treatment., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: Studies showing the changes in workflow during transition from semi to full electronic medical records are lacking. This objective study is to identify the changes in workflow in the PICU during transition from semi to full electronic health record., Design: Prospective observational study. Children's Hospital of Wisconsin Institutional Review Board waived the need for approval so this study was institutional review board exempt. This study measured clinical workflow variables at a 72-bed PICU during different phases of transition to a full electronic health record, which occurred on November 4, 2012. Phases of electronic health record transition were defined as follows: pre-electronic health record (baseline data prior to transition to full electronic health record), transition phase (3 wk after electronic health record), and stabilization (6 mo after electronic health record). Data were analyzed for the three phases using Mann-Whitney U test with a two-sided p value of less than 0.05 considered significant., Setting: Seventy-two bed PICU., Patients: All patients in the PICU were included during the study periods., Measurements and Main Results: Five hundred and sixty-four patients with 2,355 patient days were evaluated in the three phases. Duration of rounds decreased from a median of 9 minutes per patient pre--electronic health record to 7 minutes per patient post electronic health record. Time to final note decreased from 2.06 days pre--electronic health record to 0.5 days post electronic health record. Time to first medication administration after admission also decreased from 33 minutes pre--electronic health record and 7 minutes post electronic health record. Time to Time to medication reconciliation was significantly higher pre-electronic health record than post electronic health record and percent of medication reconciliation completion was significantly lower pre--electronic health record than post electronic health record and percent of medication reconciliation completion was significantly higher pre--electronic health record than. There was no significant change in time between placement of discharge order and physical transfer from the unit [corrected].changes clinical workflow in a PICU with decreased duration of rounds, time to final note, time to medication administration, and time to medication reconciliation completion. There was no change in the duration from medical to physical transfer.

Purpose: Little is known about cancer-related distress during young adulthood. Results from the few studies that have directly assessed this age group have indicated that young adults (YAs) may be at greater risk of developing psychosocial difficulties due to their unique challenges of coping with cancer. This study's objective was to investigate cancer-related distress in YAs compared to older adults., Methods: This retrospective cross-sectional study compared the distress level of YAs (18-39 years old) with that of middle-aged (40-64 years old) and senior adults (65-90 years old) using the Distress Thermometer (DT) and associated Problem List (PL). Factors that may be associated with distress by age group were examined, including demographics, cancer type, and PL items endorsed., Results: YAs had higher cancer-related distress than senior adults but similar distress levels to middle-aged adults. Findings from distress comparisons across demographics, cancer types, and PL items endorsed suggest that YAs and middle-aged adults had similar distress patterns when compared to senior adults, who had the lowest DT scores. Multivariable analyses indicated age-related risk factors for high distress, including gynecologic cancers for YAs; divorced, single, or unemployed statuses for middle-aged adults; and being of Hispanic ethnicity for senior adults. Female gender and practical, emotional, and physical problems were associated with distress for all age groups., Conclusion: There is a differential impact of cancer by age. It is important to screen for cancer-related distress, paying attention to risk factors by age to determine age-appropriate supportive care needs.

Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed. We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain. We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis., (© 2015 by The American Society of Hematology.)

Given the availability of various pain severity scales, greater understanding of the agreement between pain scales is warranted. We compared Visual Analog Scale (VAS) and Numeric Rating Scale (NRS) pain severity ratings in children with sickle cell disease (SCD) to identify the relationship and agreement between pain scale ratings. Twenty-eight patients (mean ± SD age, 14.65 ± 3.12 y, 50% female) receiving pain interventions within the emergency department completed serial VAS and NRS pain severity ratings every 30 minutes. Data were used to calculate the relationship (Spearman correlation) and agreement (Bland-Altman approach) between the VAS and NRS. One hundred twenty-eight paired VAS-NRS measurements were obtained. VAS and NRS ratings were significantly correlated for the initial assessment (rs = 0.88, P < 0.001) and all assessments (rs = 0.87, P < 0.001). Differences between VAS and NRS means were -0.52 (P = 0.006) for the initial assessment and -0.86 (P < 0.001) across all assessments. The difference between VAS and NRS ratings decreased as pain severity increased across all assessments (P = 0.027), but not the initial assessment. Within pediatric patients with SCD, VAS and NRS ratings were found to trend together; however, VAS scores were found to be significantly lower than NRS scores across assessments. The agreement between the 2 measures improved at increasing levels of pain severity. These findings demonstrate that the VAS and NRS are similar, but cannot be used interchangeably when assessing self-reported pain in SCD.

Objectives: To determine if recommending strict rest improved concussion recovery and outcome after discharge from the pediatric emergency department (ED)., Methods: Patients aged 11 to 22 years presenting to a pediatric ED within 24 hours of concussion were recruited. Participants underwent neurocognitive, balance, and symptom assessment in the ED and were randomized to strict rest for 5 days versus usual care (1-2 days rest, followed by stepwise return to activity). Patients completed a diary used to record physical and mental activity level, calculate energy exertion, and record daily postconcussive symptoms. Neurocognitive and balance assessments were performed at 3 and 10 days postinjury. Sample size calculations were powered to detect clinically meaningful differences in postconcussive symptom, neurocognitive, and balance scores between treatment groups. Linear mixed modeling was used to detect contributions of group assignment to individual recovery trajectory., Results: Ninety-nine patients were enrolled; 88 completed all study procedures (45 intervention, 43 control). Postdischarge, both groups reported a 20% decrease in energy exertion and physical activity levels. As expected, the intervention group reported less school and after-school attendance for days 2 to 5 postconcussion (3.8 vs 6.7 hours total, P < .05). There was no clinically significant difference in neurocognitive or balance outcomes. However, the intervention group reported more daily postconcussive symptoms (total symptom score over 10 days, 187.9 vs 131.9, P < .03) and slower symptom resolution., Conclusions: Recommending strict rest for adolescents immediately after concussion offered no added benefit over the usual care. Adolescents' symptom reporting was influenced by recommending strict rest., (Copyright © 2015 by the American Academy of Pediatrics.)

Developmental bisphenol A (BPA) exposure is associated with adverse behavioral effects, although underlying modes of action remain unclear. Because BPA is a suspected xenoestrogen, the objective was to identify sex-based changes in adult zebrafish social behavior developmentally exposed to BPA (0.0, 0.1, or 1 μM) or one of two control compounds (0.1 μM 17β-estradiol [E2], and 0.1 μM GSK4716, a synthetic estrogen-related receptor γ ligand). A test chamber was divided lengthwise so each arena held one fish unable to detect the presence of the other fish. A mirror was inserted at one end of each arena; baseline activity levels were determined without mirror. Arenas were divided into three computer-generated zones to represent different distances from mirror image. Circadian rhythm patterns were evaluated at 1-3 (= AM) and 5-8 (= PM) h postprandial. Adult zebrafish were placed into arenas and monitored by digital camera for 5 min. Total distance traveled, percent of time spent at mirror image, and number of attacks on mirror image were quantified. E2, GSK4716, and all BPA treatments dampened male activity and altered male circadian activity patterns; there was no marked effect on female activity. BPA induced nonmonotonic effects (response curve changes direction within range of concentrations examined) on male percent of time at mirror only in AM. All treatments produced increased percent of time at the mirror during PM. Male attacks on the mirror were reduced by BPA exposure only during AM. There were sex-specific effects of developmental BPA on social interactions, and time of day of observation affected results.

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.

Background: Emergency department (ED) visits by children with sickle cell disease (SCD) are often classified as urgent based on resource utilization. This classification may not accurately reflect the potentially preventable nature of SCD visits. We sought to determine the proportion of SCD crisis-related pediatric ED visits that are possibly preventable., Procedure: We reviewed 2 years of ED visits with a diagnosis of SCD with crisis at a hospital with an established sickle cell program. Criteria for preventable visits were predefined by pediatric hematologists. Non-pain-related chief complaints requiring emergent evaluation or painful episodes preceded by 2 opioid doses were considered not preventable; others were potentially preventable., Results: The study included 603 visits by 187 patients; 33% were potentially preventable. Overall, 29% of visits were emergent based on non-pain-related emergent complaints. Of the remaining pain-related visits, 26% were preceded by 2 or more doses of opioids at home. Visits by children with asthma were 0.58 times as likely to be preventable, due to more non-pain-related emergent chief complaints (32%) and more children (36%) taking 2 or more opioid doses., Conclusions: Approximately two thirds of SCD crisis-related pediatric ED visits are not immediately preventable; that percentage is higher in children with asthma.

The aim of this study was to provide a descriptive analysis of a new clinical program integrating psychology services within a pediatric outpatient cardiology clinic. Patients with congenital heart disease (CHD) (n = 79) were referred for psychological services by their pediatric cardiologist. Parents completed the child behavior checklist, and the pediatric quality of life inventory generic core scales (PedsQL parent report). Teachers completed the teacher report form. Reasons for referral included: emotional problems (29%); attention problems (25%); learning problems (22%); behavior problems (16%); and developmental delay (8%). Parents and teachers reported higher rates of behavior problems and lower quality of life scores than the general population. Psychological evaluation suggested that incorporating a psychologist within a pediatric cardiology clinic may be beneficial for children with CHD in order to optimize their psychosocial functioning. Practice implications for implementing psychology services within a pediatric outpatient cardiology program are discussed.

Objective: We examined the performance of the Newest Vital Sign (NVS) and the Short Test of Functional Health Literacy in Adults (S-TOFHLA) in caregivers of children., Method: Caregivers of children ≤12 years old seeking care for their child in a pediatric emergency department (ED) were tested using the NVS and the S-TOFHLA to measure health literacy. The results were compared with ED use outcomes., Result: The S-TOFHLA was found to have a ceiling effect as compared to the NVS; few caregivers scored in low literacy categories (P < .0001). This finding was demonstrated in both lower (P = .01) and higher (P < .001) educational attainment groups. The NVS was predictive of ED use outcomes (P = .02 and P < .01) whereas the S-TOFHLA was not (P = .21 and P = .11)., Conclusions: The measures do not seem to function similarly nor predict health outcomes equally. The NVS demonstrates sensitivity in identifying limited health literacy in younger adult populations., (© The Author(s) 2014.)

Objectives: To demonstrate that low-molecular-weight heparin (enoxaparin) can be used in critically ill pediatric patients to achieve target anti-factor Xa concentrations and determine appropriate dosing corrected for age and illness severity., Design: Retrospective cohort study., Setting: Single tertiary level PICU., Patients: One hundred ninety-two children age 1 day through 18 years admitted to PICU undergoing every 12-hour enoxaparin therapy with at least one anti-factor Xa concentration obtained. Patients receiving renal replacement therapy or infants with corrected gestational age less than 37 weeks were excluded., Interventions: None., Measurements and Main Results: We collected patient characteristics including age, weight, height/length, gender, corrected gestational age, illness severity markers, diagnosis, creatinine, enoxaparin dose and times of administration, anti-factor Xa concentrations, and collection times. Only 42% of critically ill children (80 of 192) and only 29% of children (9 of 31) on inotropes achieved recommended target range of anti-factor Xa concentrations on initial recommended enoxaparin dosing (1.5 mg/kg/dose < 2 mo; 1 mg/kg/dose > 2 mo), but 81% were ultimately within target range with dose titration. Increased enoxaparin dose was required to reach target concentrations in younger patients and those with worse illness severity as evidenced by concurrent use of inotropes, previous ICU admission, mechanical ventilation, cardiac surgery, and increased risk of mortality defined by severity-of-illness scores., Conclusions: Enoxaparin can be used to reach recommended target range of anti-factor Xa concentrations in the PICU patient. However, younger patients and patients with higher illness severity are less likely to achieve target concentrations using currently recommended dosing and may require higher doses of enoxaparin to reach target anti-factor Xa concentrations. Starting enoxaparin dose at least 1.3 mg/kg dosed every 12 hours for treatment of thromboembolic disease in critically ill patients aged 61 days to 1 year or those requiring inotropic support should be confirmed in prospective study.

The genetic basis of type 2 diabetes remains incompletely defined despite the use of multiple genetic strategies. Multiparental populations such as heterogeneous stocks (HS) facilitate gene discovery by allowing fine mapping to only a few megabases, significantly decreasing the number of potential candidate genes compared to traditional mapping strategies. In the present work, we employed expression and sequence analysis in HS rats (Rattus norvegicus) to identify Tpcn2 as a likely causal gene underlying a 3.1-Mb locus for glucose and insulin levels. Global gene expression analysis on liver identified Tpcn2 as the only gene in the region that is differentially expressed between HS rats with glucose intolerance and those with normal glucose regulation. Tpcn2 also maps as a cis-regulating expression QTL and is negatively correlated with fasting glucose levels. We used founder sequence to identify variants within this region and assessed association between 18 variants and diabetic traits by conducting a mixed-model analysis, accounting for the complex family structure of the HS. We found that two variants were significantly associated with fasting glucose levels, including a nonsynonymous coding variant within Tpcn2. Studies in Tpcn2 knockout mice demonstrated a significant decrease in fasting glucose levels and insulin response to a glucose challenge relative to those in wild-type mice. Finally, we identified variants within Tpcn2 that are associated with fasting insulin in humans. These studies indicate that Tpcn2 is a likely causal gene that may play a role in human diabetes and demonstrate the utility of multiparental populations for positionally cloning genes within complex loci., (Copyright © 2014 by the Genetics Society of America.)

Objective: To examine the association between caregiver health literacy and the likelihood of a nonurgent emergency department (ED) visit in children presenting for fever., Methods: This cross-sectional study used the Newest Vital Sign to assess the health literacy of caregivers accompanying children with fever to the ED. Visit urgency was determined by resources utilized during the ED visit. Findings were stratified by race and child age. Chi-square and logistic regression analysis controlling for race were conducted to determine the association between low health literacy and ED visit urgency., Results: A total of 299 caregivers completed study materials. Thirty-nine percent of ED visits for fever were nonurgent, and 63% of caregivers had low health literacy. Low health literacy was associated with a higher proportion of nonurgent ED visits for fever (44% vs 31%, odds ratio 1.8, 95% confidence interval [CI] 1.1, 2.9). Low health literacy was associated with higher odds of a nonurgent visit in white and Hispanic caregivers but not in black caregivers. In regression analysis, children ≥ 2 years old had higher odds of a nonurgent visit if caregivers had low health literacy (adjusted odds ratio 2.0; 95% CI 1.1, 4.1); this relationship did not hold for children <2 years old (adjusted odds ratio 0.8; 95% CI 0.4, 1.8)., Conclusions: Nearly two-thirds of caregivers with their child in the ED for fever have low health literacy. Caregiver low health literacy is associated with nonurgent ED utilization for fever in children over 2 years of age. Future interventions could target health literacy skills regarding fever in caregivers of children ≥ 2 years., (Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Pediatric critical care and oncology providers care for patients who have life-threatening or serious illness, yet they receive little palliative care education., Objective: Compare oncology and critical care providers' attitudes regarding palliative care., Methods: An electronic survey assessed respondents' opinions of whether, when, and why palliative care should be utilized., Results: Response rate was 49%. Critical care physicians were more likely to incorporate palliative care for psychosocial support; oncologists for symptom control. Those with palliative care education were more likely to involve in palliative care, did so earlier and for reasons other than end-of-life planning., Conclusions: Oncology and critical care providers utilized palliative care for different reasons., (© The Author(s) 2013.)

Egg allergy is one of the most common food allergies in children. Most egg-allergic children are able to tolerate egg baked in product (EBP) and will likely outgrow his/her egg allergy. By introducing EBP in the diet of an egg-allergic child, diet can be expanded and family stress can be reduced. Recent evidence suggests that children who tolerate EBP and continue to consume it will have quicker resolution of egg allergy than those who strictly avoid EBP; therefore, we aimed to evaluate the egg-allergic children who underwent EBP oral food challenge (OFC) in our allergy clinic to help define any specific predictors to be used in predicting the outcome of such challenges. We performed a retrospective chart review and 43 egg-allergic patients underwent EBP OFC in our outpatient allergy office from January 2011 to December 2012 were excluded. Nine patients who did not have a prior history of symptomatic egg ingestion. Clinical characteristics and laboratory findings of the remaining 34 patients were all recorded and analyzed. Of the remaining 34 patients, 22 (64.7%) were boys. Average age of first reaction to egg was 12.90 months, with average age at EBP OFC of 71.32 months. The average of the most recent skin-prick test wheal size was 10.10 mm and serum-specific IgE to egg white was 3.21 kU/L. Twenty-eight of the 34 patients (82.4%) passed the EBP OFC. Of the six patients who failed, none required epinephrine. After analysis of all of the clinical characteristics and laboratory findings, no risk factors, such as skin-prick test wheal size, were identified to be associated with an increased risk of failing EBP OFC. EBP OFC is a valuable tool to assess tolerance. As seen in our group of patients, the majority of egg-allergic patients pass EBP OFC. Thus, OFC should be considered as a clinical tool to expand a patient's diet and to improve quality of life as early as possible. Because we were unable to determine any clinical or laboratory predictors helpful to select egg-allergic patients who are likely to pass EBP OFC, additional prospective studies are necessary to determine the ideal egg-allergic patient who is likely to pass EBP OFC.

Background and Objective: Reported rates of recurrence after enema reduction for intussusception are variable. Concerns for recurrence influence postreduction management. The objective of this study was to conduct a systematic review and meta-analysis to estimate overall, 24-hour, and 48-hour recurrence rates after enema reduction in children., Methods: PubMed, Cochrane Database, and OVID Medline were searched from 1946 through December 2011 using the search terms: intussusception, recurrence, and enema. Sixty-nine studies of patients age 0 to 18 years with radiographically proven intussusception reduced by enema that report the number of enema reductions and the number of recurrences were included. Extraction was done by the primary author (M.P.G.) with 10% of included studies independently audited to ensure concordance., Results: Overall recurrence rates were 12.7% (95% confidence interval [CI]: 11.1%-14.4%, I2 = 28.8%) for contrast enema (CE), 7.5% (95% CI: 5.7%-9.8%, I2 = 52.4%) for ultrasound-guided noncontrast enema (UGNCE), and 8.5% (95% CI: 6.9%-10.4%, I2 = 50.1%) for fluoroscopy-guided air enema (FGAE). Recurrence rates within 24 hours were 3.9% (95% CI: 2.2%-6.7%, I2 = 47.0%) for CE, 3.9% (95% CI: 1.5%-10.1%, I2 = 0.0%) for UGNCE, and 2.2% (95% CI: 0.7%-6.5%, I2 = 59.8%) for FGAE. Recurrence rates within 48 hours were 5.4% (95% CI 3.7%-7.8%, I2 = 32.3%) for CE, 6.6% (95% CI: 4.0%-10.7%, I2 = 0.0%) for UGNCE, and 2.7% (95% CI: 1.2%-6.5%, I2 = 73.8%) for FGAE. Most included studies are retrospective and vary in quality of reporting. Few studies reported detailed patient characteristics including timing of recurrences., Conclusions: The risk of early (within 48 hours) recurrence after enema reduction is low, suggesting outpatient management of well-appearing patients should be considered., (Copyright © 2014 by the American Academy of Pediatrics.)

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)