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Anthracycline-induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane before anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages, 0 to 21 y) who received or did not receive dexrazoxane during the years 2008 to 2013. In total, 44 patients with AML (ages, 4.5 mo to 21.7 y) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, P=0.41) or 2-year overall survival (69% vs. 69%, P=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (P=0.0262) and shortening fraction (P=0.0381) trended significantly higher in patients that received dexrazoxane compared with those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane before anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or overall survival relative to institutional controls and seems to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.

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.

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 ( 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.

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.

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.

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.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).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 (p0.001), 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) (p0.001).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 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.

Background We sought to evaluate outcomes of congenital heart operations and resource use in patients with intrauterine growth restriction (IUGR). Methods This was a retrospective matched case-control study of 41 consecutive patients with IUGR matched 1:2 with a comparison cohort of 82 contemporaneous patients without IUGR who underwent congenital heart operations during the interval from January 1, 2000 to January 1, 2012. Matching was based on the Risk Adjustment for Congenital Heart Surgery (RACHS)-1 risk category, diagnostic category, age at operation, and gestational age. Results Operative mortality (6 of 41 cases [14.6%] for the study group versus 5 of 82 cases [6.1%] for controls) and any major adverse event (14 of 41 cases [34.2%] for the study group versus 23 of 82 cases [28%] for controls) occurred in a higher percentage of study patients, with insignificant p values. Important differences in secondary outcomes included the following: mean total length of stay (56.3 days versus 28.0 days for controls; p Conclusions IUGR is associated with a substantially increased length of hospital stay, postoperative morbidity, and resource use. These findings are relevant to risk stratification, prognosis, and potentially to contracting and reimbursement. IUGR merits further attention as an important risk factor in congenital heart operations.

Background— Children with congenital heart disease are at risk for developmental delay. This study sought to identify early risk factors for abnormal developmental trajectories in children with congenital heart disease. Methods and Results— Children with congenital heart disease at high risk for developmental delay, without known genetic abnormality, and with ≥3 assessments by the use of the Bayley Scales of Infant and Toddler Development, Third Edition, were studied. Logistic regression was used to assess the impact of patient and clinical factors on cognitive, language, and motor score trajectories; classified as: average or improved if all scores were ≥85 (P Conclusions— Longitudinal developmental surveillance identified early factors that can help quantify the risk of developmental delay over time. Strategies to improve modifiable factors and early therapeutic intervention can be targeted to children at highest risk.

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.

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.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.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.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.

Introduction Patients with early stage breast cancer receiving chemotherapy (CT) may experience persistent fatigue. The mechanisms for fatigue are not well understood. We hypothesized that CT-induced fatigue may involve perturbations in mitochondrial function. We therefore examined the development of fatigue in patients during adjuvant or neoadjuvant CT and measured mitochondrial function in their peripheral blood mononuclear cells (PBMCs). Methods Females with Stage I-III breast cancer patients, ages 35-75 years, were enrolled in an IRB-approved study. Patients with coexisting illnesses associated with chronic fatigue were excluded. Patients self-reported fatigue severity using the 14-question Fatigue Symptom Inventory (FSI) that rates fatigue intensity on a 10-point scale. Data [FSI and PBMCs] were collected prior to CT, mid-point in the course of CT, 2 - 3 weeks after completion of CT, and 3 and 6 months later. Mitochondrial function in PBMCs from patients was measured using a Seahorse Bioscience XF24 analyzer at corresponding times. Results Results on CT-induced fatigue are available for 67 patients. The overall fatigue score for each patient was measured as the sum of the scores for all 14 questions in the FSI. The average fatigue score for the 67 patients prior to chemotherapy was 20. Baseline fatigue scores for patients who had adjuvant CT were much greater than for patients receiving neoadjuvant CT (R2=1). Patient fatigue scores doubled after starting chemotherapy (average score 40, p < 0.001). Even though fatigue scores improved after treatment completion (average score 26 at 6 months), the scores did not return to baseline 6 months later (p=0.02). In our population, CT-induced fatigue did not correlate with patient age regardless of the CT regimen [r=0.3 and r= -.2, for doxorubicin plus cyclophosphamide (AC) vs docetaxel plus cyclophosphamide (TC) groups, respectively)] or a decrease in hemoglobin (r= -.3 and r=0.03, for AC and TC, respectively). None of these correlations could explain more than 9% of the change in treatment-induced fatigue (p=0.2). Preliminary analysis of mitochondrial function in 12 patients shows that 9 patients had a decrease in mitochondrial reserve capacity with an increase in CT-induced fatigue following completion of 4 cycles of CT. 3 patients had a decrease in mitochondrial reserve capacity but reported no significant change in their fatigue scores. Mitochondrial function data on all patients have been collected and are presently being analyzed. Conclusion Our study shows that early stage breast cancer patients treated with adjuvant or neoadjuvant CT may experience fatigue that can persist for months after completion of treatment and cannot be explained by the CT regimen, age, or anemia. Our initial results suggest a link between CT-induced fatigue and changes in mitochondrial function in some patients. Mitochondrial function analysis and its correlation with fatigue for all 67 patients will be completed and reported at SABCS. Mitochondrial function may prove to be a biomarker for CT-induced fatigue in certain patients and may help identify patients for whom interventions that stimulate mitochondria biogenesis, including pharmacologic agents and exercise, may be beneficial in ameliorating this side-effect. Citation Format: Kanchana Herath, Brian P Dranka, George M Lessmann, Donna McAllister, Raymond G Hoffmann, Balaraman Kalyanaraman, Christopher R Chitambar, Namrata I Peswani. Chemotherapy-induced fatigue and mitochondrial function in early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-08.

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.

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.

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 post-discharge 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 1-2 weeks after discharge. Descriptive statistics and odds ratios were calculated. Chi square test was used for comparisons between groups. Multivariable logistic regression models evaluated predictors of negative behavioral change after discharge. Results 97 patients were enrolled, 82 (85%) completed follow-up. Overall, 33 (40%) children were observed to be highly anxious pre-sedation and 18 (22%) had significant negative behavior changes after ED discharge. Independent predictors for negative behaviors were high anxiety (OR=9.0, 95% CI 2.3-35.7) and non-white 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 pre-procedure anxiety and almost one in four have significant negative behaviors 1-2 weeks after discharge. Highly anxious and non-white children have increased risk of negative behavioral changes which have not been previously recognized in the ED setting. This article is protected by copyright. All rights reserved.

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.

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.

Objective We sought to determine the association between low caregiver health literacy and child emergency department (ED) use, both the number and urgency of ED visits. Methods This year long cross-sectional study utilized the Newest Vital Sign questionnaire to measure the health literacy of caregivers accompanying children to a pediatric ED. Prior ED visits were extracted from a regional database. ED visit urgency was classified by resources utilized during the index ED visit. Regression analyses were used to model 2 outcomes—prior ED visits and ED visit urgency—stratified by chronic illness. Analyses were weighted by triage level. Results Overall, 503 caregivers completed the study; 55% demonstrated low health literacy. Children of caregivers with low health literacy had more prior ED visits (adjusted incidence rate ratio 1.5; 95% confidence interval 1.2, 1.8) and increased odds of a nonurgent index ED visit (adjusted odds ratio 2.4; 95% confidence interval 1.3, 4.4). Among children without chronic illness, low caregiver health literacy was associated with an increased proportion of nonurgent index ED visits (48% vs 22%; adjusted odds ratio 3.2; 1.8, 5.7). Conclusions Over half of caregivers presenting with their children to the ED have low health literacy. Low caregiver health literacy is an independent predictor of higher ED use and use of the ED for nonurgent conditions. In children without a chronic illness, low health literate caregivers had more than 3 times greater odds of presenting for a nonurgent condition than those with adequate health literacy.

The purpose of this study was to identify rates of adherence for three outpatient quality indicators noted by Wang et al. (Pediatrics 2011;128:484–493): (1) influenza vaccine, (2) pneumococcal immunizations, and (3)penicillin prophylaxis in patients with sickle cell disease (SCD) in a Medicaid sample. These variables were chosen based on Wang and colleagues' suggestion that these variables are important for the assessment of the quality of care of children with SCD. We hypothesized that the overall rate of adherence would be poor with adults having worse rates of adherence than children. We conducted a retrospective cohort study using the Wisconsin State Medicaid database over a 5-year period to assess the preventative medication adherence of individuals with SCD. Preventative medication variables in this study included influenza vaccination,pneumococcal immunizations (PCV7, PPV23), and penicillin prophylaxis. As predicted, the 2003–2007 Wisconsin State Medicaid database showed patients with SCD had low adherence in terms of recommended influenza vaccinations (21.58% adherent), PPV23 pneumococcal immunizations (43.47% adherent), and penicillin prophylaxis (18.18% adherent). Pneumococcal immunizations for PCV7 were higher than expected (77.27%adherent). Although children tended to adhere to recommended preventative medications more than adults,overall adherence was low. Although we cannot explain why adherence is low, it is likely due to multiple factors at the patient- and provider-level. We encourage patients and providers to create a partnership to meet adherence recommendations, and we describe our strategies for increasing adherence.

Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing the isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 uM). As compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 (SEM) μmol·gram−1 dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 (SEM) to 38.62 ± 3.14 μmol·15 min−1 perfusion·gm−1 dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone, coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H:quinone oxidoreductase 1 (NQO1) or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 (SEM) to 0.156 ± 0.037 (SEM) ml·min−1·cm H2O−1·gm−1 dry lung weight, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate/pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low molecular weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency.

Background Low health literacy in parents can potentially impact understanding of a child's diagnosis and treatment course. No reviews have addressed parent health literacy in the emergency department (ED), the relationship between parent health literacy and child ED utilization, or the impact of low literacy interventions on child ED utilization. Objective To systematically evaluate the peer-reviewed literature pertaining to parental health literacy and ED utilization. The following key questions were addressed: question (Q) 1) What is the prevalence of low health literacy, as estimated by validated health literacy measures, of parents in the ED? Q2) Is parent low health literacy related to ED use for children? Q3) Do low literacy interventions targeting parents likely to have low health literacy affect ED use for children? Data Sources The authors reviewed 483 unduplicated titles and abstracts published between 1980 and May 2012 using PubMed and CINAHL, with 117 retained for full review and 17 included in the final analytic review. Study Eligibility Criteria, Participants, and Interventions All included articles had a valid measure of parent health literacy and a Q1) descriptive measurement of the population, Q2) ED utilization, or Q3) utilized a low literacy educational intervention. Study Appraisal and Synthesis Methods One author extracted data verified by a second author. Studies were rated for quality by both authors. Results Q1) A median of 30% (interquartile range 22–36%) of parents in the ED possesses low health literacy. Q2) Studies investigating the relationship between health literacy and ED yielded mixed results. Q3) Seven of 8 low literacy interventions were associated with a reduction in ED use. Random effects pooled odds ratios from 6 studies showed intervention effectiveness (odds ratio 0.35; 95% CI 0.15–0.81). Limitations No intervention studies measured health literacy, limiting the ability to determine whether the low literacy intervention targeted health literacy. Conclusions and Implications of Key Findings Roughly 1 in 3 parents of children presenting to the ED have low health literacy. Importantly, interventions targeting parents likely to have low health literacy have an impact in reducing ED utilization.

Background Limited understanding of the interpretability of patient-reported pain scores may impact pain management. The current study assessed the minimal clinically significant improvement in pain and pain scores signifying patient-reported need for medication and treatment satisfaction in patients with sickle cell disease (SCD). Procedure Patients, 8–18-years-old, with SCD were recruited while receiving treatment for pain. Patients completed initial pain severity ratings using the Visual Analog Scale (VAS) and the Numeric Rating Scale (NRS). Serial assessments of pain severity, pain relief, perceived need for medication, and treatment satisfaction were completed in the emergency department and the hospitalization. Data were used to calculate the minimal clinically significant improvement in pain and pain scores associated with perceived need for pain medication and treatment satisfaction. Results Twenty-eight patients completed 305 assessments during 37 total visits. A decrease in pain severity score of 0.97 cm for the VAS and 0.9 for the NRS was found to be the minimum clinically significant improvement in pain. Pain scores >7.45 cm on the VAS or 7.5 on the NRS were suggestive of patient-reported need for pain medication. Pain scores

BACKGROUND von Willebrand factor (VWF) is a multimeric protein that binds platelets and collagen, facilitating hemostasis at sites of vessel injury. Measurement of VWF multimer distribution is critical for diagnosis of variant von Willebrand disease (VWD), particularly types 2A and 2B, but the typical measurement by gel electrophoresis is technically difficult and time-consuming. A comparison of VWF collagen binding (VWF:CB) and VWF multimer distribution was performed to evaluate the utility of VWF:CB as a diagnostic test. METHODS Participants were enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD. VWF:CB was analyzed with type III collagen and multimer distribution by agarose gel electrophoresis. The study population included 146 healthy controls, 351 individuals with type 1 VWD, and 77 with type 2 VWD. Differences between individuals with multimer group results within (controls) and outside the reference intervals were assessed with Mann–Whitney tests. RESULTS The mean VWF:CB/VWF antigen ratio was 1.10 for individuals with multimer distribution within the reference intervals and 0.51 for those with multimer distribution outside the reference intervals (P < 0.001). Sensitivity of VWF:CB for multimer abnormalities was 100% for healthy controls, 99% for patients with type 1, and 100% for patients with type 2A and type 2B VWD using a VWF:CB/VWF antigen cutoff ratio of 0.6, and decreased to 99% for all patients with a ratio of 0.7. With the exception of individuals with novel or unclassified mutations, the VWF:CB was able to correctly categorize participants with variant VWD. CONCLUSIONS These findings suggest that VWF:CB may substitute for multimer distribution in initial VWD testing, although further studies are needed to validate the clinical utility of VWF:CB.

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.

Introduction There is no study yet of the perception of risk in pediatric intensive care unit (PICU) physicians. The purpose of this study is to characterize these perceptions with respect to frequency and importance. Methods The study is a cross sectional survey of physician members of the Society of Critical Care Medicine who report caring for critically ill children. Perceived frequency and importance of risks to patient safety across 11 domains in the pediatric ICU was obtained through a validated survey. Mean problem score was tested for trend across frequency categories. Results 140 responses were obtained from 199 opened email invitations (73%) and 822 total emails (17%). The survey was internally valid with a Cronbach alpha value of 0.87. The most frequent risks to patient safety occurred in areas of ineffective communication, inadequate training and orientation, and poor hand hygiene. The most problematic risk domains were ineffective communication, healthcare acquired infections, inadequate training and orientation, and medication error. For most risk categories, as the perceived risk frequency increased, the mean perceived problem score of that risk decreased, excepting hand hygiene (p = 0.96) and central line infections (p = 0.27). Conclusions Risks related to communication, training and orientation, and hand hygiene are perceived as frequent. Risks related to communication, healthcare acquired infections, training and orientation, and medication errors are perceived as the most important. Variance in attitude toward these risks is significant for most domains. Understanding variance will be important in changing human behavior related to risk in the PICU.

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 HR2SD 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 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).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.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.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.

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.

Summary 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.

Sickle cell disease (SCD) pain is associated with colder temperatures and touch and described as "cold," "hot," and "shooting" suggesting hypersensitivity to tactile stimuli. Sickle mice exhibit hypersensitivity to thermal (cold, heat) and mechanical stimuli compared to controls. It is unknown whether humans experience this same hypersensitivity. Thus, we quantified thermal and mechanical sensitivity differences between patients with SCD and controls. Our primary hypothesis was that patients with SCD will exhibit hypersensitivity to thermal and mechanical stimuli compared to race-matched controls. Our secondary hypothesis was this hypersensitivity will be associated with older and female subjects, and with frequent pain and hemolysis in patients with SCD. A total of 55 patients and 57 controls ≥7 years completed quantitative sensory testing. Patients with SCD detected the sensation of cold and warm temperatures sooner as seen in their significantly lower median cold and heat detection thresholds [29.5°C vs. 28.6°C, P = 0.012 and 34.5°C vs. 35.3°C, P = 0.02] and experienced cold and heat pain sooner as seen in their significantly lower median cold and heat pain thresholds [21.1°C vs. 14.8°C, P = 0.01 and 42.7°C vs. 45.2°C, P = 0.04]. We found no mechanical threshold differences. Older age was associated with lower cold, heat, and mechanical pain thresholds in both groups. No association with pain, gender, or hemolysis was found. Patients with SCD exhibit hypersensitivity to thermal stimuli suggesting peripheral or central sensitization may exist and could contribute to SCD pain.

Summary. Background: von Willebrand factor (VWF) plays a key role in coagulation by tethering platelets to injured subendothelium through binding sites for collagen and platelet GPIb. Collagen binding assays (VWF:CB), however, are not part of the routine work-up for von Willebrand disease (VWD). Objectives: This study presents data on collagen binding for healthy controls and VWD subjects to compare three different collagens. Patients/Methods: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity and VWF:CB with types I, III and VI collagen were examined for samples obtained from the Zimmerman Program. Results: Mean VWF:CB in healthy controls was similar and highly correlated for types I, III and VI collagen. The mean VWF:CB/VWF:Ag ratios for types I, III and VI collagen were 1.31, 1.19 and 1.21, respectively. In type 1 VWD subjects, VWF:CB was similar to VWF:Ag with mean VWF:CB/VWF:Ag ratios for types I, III and VI collagen of 1.32, 1.08 and 1.1, respectively. For type 2A and 2B subjects, VWF:CB was uniformly low, with mean ratios of 0.62 and 0.7 for type I collagen, 0.38 and 0.4 for type III collagen, and 0.5 and 0.47 for type VI collagen. Conclusions: Normal ranges for type I, III and VI collagen are correlated, but higher values were obtained with type I collagen as compared with types III and VI. The low VWF:CB in type 2A and 2B subjects suggests that VWF:CB may also supplement analysis of multimer distribution. However, these results reflect only one set of assay conditions per collagen type and therefore may not be generalizable to all collagen assays.

OBJECTIVE: To determine if maternal knowledge of prematurity is improved when verbal gestational age-specific counseling is supplemented with written gestational age-specific information. METHODS: Prospective, randomized study of 60 pregnant participants assessed to be at risk for premature delivery between 23 and 34 weeks’ gestation. Counseling in the control group consisted of gestational age–specific verbal information, and counseling in the intervention group consisted of written gestational age–specific information 1 hour before the verbal gestational age–specific information. Both groups completed a Prematurity Knowledge Questionnaire after counseling and the State-Trait Anxiety Inventory before and after counseling. The Prematurity Knowledge Questionnaire consisted of questions regarding short-term problems (immature lungs, intraventricular hemorrhage, retinopathy, feeding problems, infection, apnea, and jaundice), long-term problems (chronic lung disease, postdischarge respiratory infections, visual impairment, hearing impairment, brain damage, and learning and behavior problems), and numerical outcome data (probabilities of survival, survival without significant morbidity, severe intraventricular hemorrhage, severe retinopathy, and chronic lung disease). RESULTS: Knowledge of short-term problems was not statistically different between the intervention (82%) and control groups (67%). Knowledge of long-term problems was better in the intervention (71%) than the control group (45%). Knowledge of numerical data was better in the intervention (48%) than the control group (29%). State-Trait Anxiety Inventory scores decreased after counseling in the intervention group. CONCLUSIONS: Supplementation of face-to-face verbal counseling with written information improved knowledge of long-term problems and knowledge of numerical outcome data, and it also decreased anxiety in women expecting a premature delivery.

We evaluated the population structure and temporal dynamics of the dominant community members within sewage influent from two wastewater treatment plants (WWTPs) in Milwaukee, WI. We generated > 1.1 M bacterial pyrotag sequences from the V6 hypervariable region of 16S rRNA genes from 38 influent samples and two samples taken upstream in the sanitary sewer system. Only a small fraction of pyrotags from influent samples (∼ 15%) matched sequences from human faecal samples. The faecal components of the sewage samples included enriched pyrotag populations from Lactococcus and Enterobacteriaceae relative to their fractional representation in human faecal samples. In contrast to the large number of distinct pyrotags that represent faecal bacteria such as Lachnospiraceae and Bacteroides, only one or two unique V6 sequences represented Acinetobacter, Aeromonas and Trichococcus, which collectively account for nearly 35% of the total sewage community. Two dominant Acinetobacter V6 pyrotags (designated Acineto tag 1 and Acineto tag 2) fluctuated inversely with a seasonal pattern over a 3-year period, suggesting two distinct Acinetobacter populations respond differently to ecological forcings in the system. A single nucleotide change in the V6 pyrotags accounted for the difference in these populations and corresponded to two phylogenetically distinct clades based on full-length sequences. Analysis of wavelet functions, derived from a mathematical model of temporal fluctuations, demonstrated that other abundant sewer associated populations including Trichococcus and Aeromonas had temporal patterns similar to either Acineto tag 1 or Acineto tag 2. Populations with related temporal fluctuations were found to significantly correlate with the same WWTP variables (5-day BOD, flow, ammonia, total phosphorous and suspended solids). These findings illustrate that small differences in V6 sequences can represent phylogenetically and ecologically distinct taxa. This work provides insight into microbial community composition and dynamics within the defined environment of urban sewer infrastructure.

Background Lack of a Food and Drug Administration (FDA)–approved skin testing reagent for latex allergy in the United States requires reliance on patient history and serologic assays for diagnosis. Objective To determine the diagnostic sensitivity, specificity, and predictive values of an FDA-cleared antilatex IgE serology test and an enzyme-linked immunosorbent assay (ELISA) with various sources of latex protein antigens in an at-risk but unselected population of health care workers. Methods Health care workers underwent duplicate latex and serologic testing for latex specific IgE with the CAP assay and ELISA from June 1, 1998, through December 31, 2002. Logistic regression with receiver operating characteristic curve analysis determined the values, resulting in 98% and 99% specificity for the CAP assay and ELISA, respectively. Results Results of paired skin and serologic tests were available for 792 participants. Forty duplicate skin test results (5%) were positive. For the CAP assay, sensitivity was 35%; specificity, 98%; positive predictive value, 48.3%; and negative predictive value, 96.6%. ELISA demonstrated similar results. Multivariable logistic regression yielding a 98% or 99% specificity for the various ELISAs demonstrated that the adjusted odds of a positive skin test result significantly increased with positive CAP assay and ELISA results using a powdered glove extract. Conclusions The performance of the FDA-cleared antilatex IgE serologic test for latex allergy has much lower sensitivity than previously reported. This finding confirms that this serologic test should be used only for patients with a history of latex allergy and not for screening the population with a low prevalence of latex sensitization.

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 > 1standard 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.

Aim: To quantify the relationship between 5-min Apgar scores and infant mortality for infants at the borderline of viability. Methods: Cohort study of 7008 infants 23–25 weeks’ gestation using 2002 US National Center for Health Statistics data. Using Cox proportional-hazards models, we quantified the relationship between Apgar score and infant mortality for all infants, and then infants surviving their first 24 h. Models were adjusted for gestational age, birth weight, gender, delivery method, plurality, maternal race, marital status and education. Results: Within one year, 46% of infants died. Of the non-survivors, deaths within 24 h were more common among infants with Apgar scores 0–3 (83%) than among infants with Apgar scores 7–10 (13%). When including all infants and adjusting for potential confounders, each 1-point increase in Apgar score decreased the hazard of mortality by 0.82. However, after excluding infants who died within 24 h, the hazard ratio increased to 0.95; although statistically significant, the practical impact was negated. Conclusions: For 23–25 week gestation infants surviving the first 24 h, the Apgar score loses clinical significance. Clinicians should be aware of the limitations of clinical assessments in the delivery room.

Objective: Temporomandibular joint and muscle disorders (TMJD) are ill-defined, painful debilitating disorders. This study was undertaken to identify the spectrum of clinical manifestations based on self-report from affected patients. Methods: A total of 1511 TMJD-affected individuals were recruited through the web-based registry of patients maintained by The TMJ Association, Ltd, a patient advocacy organization, and participated in the survey as well as 57 of their nonaffected friends. Results were also compared with US population for questions in common with the National Health and Nutrition Examination Survey. Results: The TMJD-affected individuals were on average 41 years of age and predominantly female (90%). Nearly 60% of both men and women reported recent pain of moderate-to-severe intensity with a quarter of them indicating interference or termination of work-related activities. In the case-control comparison, a higher frequency of headaches, allergies, depression, fatigue, degenerative arthritis, fibromyalgia, autoimmune disorders, sleep apnea, and gastrointestinal complaints were prevalent among those affected with TMJD. Many of the associated comorbid conditions were over 6 times more likely to occur after TMJD was diagnosed. Among a wide array of treatments used (46 listed), the most effective relief for most affected individuals (91%) was the use of thermal therapies—hot/cold packs to the jaw area or hot baths. Nearly 40% of individuals affected with TMJD patients reported one or more surgical procedures and nearly all were treated with one or many different medications. Results of these treatments were generally equivocal. Although potentially limited to the most severe TMJD affected individuals, the survey results provide a comprehensive dataset describing the clinical manifestations of TMJD. Discussion: The data provide evidence that TMJD represent a spectrum of disorders with varying pathophysiologies, clinical manifestations, and associated comorbid conditions. The findings underscore the complex nature of TMJD, the need for more extensive interdisciplinary basic and clinical research, and the development of outcome-based strategies to more effectively diagnose, prevent, and treat these chronic, debilitating conditions.

OBJECTIVE We evaluated the prevalence of endothelial dysfunction as measured by flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thickness (c-IMT) in relationship to vascular inflammatory biomarkers in preadolescent children with type 1 diabetes. RESEARCH DESIGN AND METHODS We studied 21 type 1 diabetic children (aged 8.3 ± 0.3 years with diabetes duration of 4.3 ± 0.4 years) and 15 group-matched healthy siblings (aged 7.6 ± 0.3 years). Fasting plasma glucose (FPG), lipid profile, HbA1c, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, homocysteine, and erythrocyte (red blood cell [RBC]) folate were evaluated in all subjects. Each subject underwent c-IMT and brachial artery FMD percentage (FMD%) measurements using high-resolution vascular ultrasound. RESULTS Type 1 diabetic children had higher FPG (173.4 ± 7.9 mg/dL vs. 81.40 ± 1.7 mg/dL; P < 0.0001), HbA1c (8.0 ± 0.2% vs. 5.0 ± 0.1%; P < 0.0001), and hs-CRP (1.8 ± 0.3 vs. 0.70 ± 0.2; P = 0.017) than control children without significant differences in BMI, homocysteine, and fibrinogen levels; RBC folate content; and c-IMT between the groups. Children with type 1 diabetes had lower FMD% than control children (7.1 ± 0.8% vs. 9.8 ± 1.1%; P = 0.04), whereas c-IMT did not differ between groups. CONCLUSIONS Preadolescent children with type 1 diabetes and mean diabetes duration of 4 years displayed evidence of low-intensity vascular inflammation and attenuated FMD measurements. These data suggest that endothelial dysfunction and systemic inflammation, known harbingers of future cardiovascular risk, are present even in preadolescent children.

OBJECTIVES: To assess the relationship between body mass index (BMI) and waist–hip ratio (WHR) and the clinical end points of cognitive impairment and probable dementia in a cohort of older women enrolled in the Women's Health Initiative Memory Study (WHIMS). DESIGN: Prospective, randomized clinical trial of hormone therapies with annual cognitive assessments and anthropometrics. SETTING: Fourteen U.S. clinical sites of the WHIMS. PARTICIPANTS: Seven thousand one hundred sixty-three postmenopausal women aged 65 to 80 without dementia. MEASUREMENTS: Annual cognitive assessments, average follow-up of 4.4 years, including classification of incident cognitive impairment and probable dementia. Height, weight, waist, and hip measurements were assessed at baseline, and a waist–hip ratio (WHR) of 0.8 or greater was used as a marker of central adiposity. RESULTS: There were statistically significant interactions between BMI and WHR and incident cognitive impairment and probable dementia with and without adjustment for a panel of cognitive risk factors. Women with a WHR of 0.80 or greater with a BMI of 20.0 to 24.9 kg/m2 had a greater risk of cognitive impairment and probable dementia than more-obese women or women with a WHR less than 0.80, although women with a WHR less than 0.80 and a BMI of 20.0 to 24.9 kg/m2 had poorer scores on cognitive assessments. CONCLUSION: WHR affects the relationship between BMI and risk of cognitive impairment and probable dementia in older women. Underweight women (BMI

Colorectal cancer (CRC) is the third most common cancer in the United States and a leading cause of cancer related mortality. Routine screening decreases incidence and mortality; however rates of screening remain low. Physician recommendation is a key determinant of screening rates; thus, physician availability may also influence CRC incidence and mortality.Data on CRC incidence and stage at diagnosis was obtained for each county in Pennsylvania from the Pennsylvania cancer registry. Physician density (per 100,000 population) was calculated for each county using physician counts from the American Medical Association. Pearson correlation coefficients and linear regression models were used to examine the association between physician density and CRC incidence and outcomes.Primary care physician density (Pearson's correlation coefficient: -0.25, p=0.05) and gastroenterologist density (correlation coefficient -0.25, p=0.04) inversely correlated with county-level incidence of late-stage CRC. However, this association was seen only in non-metropolitan counties or those with low population density. On linear regression, non-metropolitan counties which had a high density of gastroenterologists had an incidence of late-stage CRC that was lower by 4/100,000 (reduction of 14%). Low population density counties had lower incidence of late-stage CRC by 5/100,000 (reduction of 17%) when they had at least 3.3 gastroenterologists/100,000 population compared to counties with a lower gastroenterologist-per-population ratio. Gastroenterologist density did not correlate with reduced late-stage CRC incidence prior to institution of Medicare coverage for colonoscopy for routine CRC screening.Higher gastroenterologist or PCP density is associated with 14-17% lower incidence of late-stage CRC in non-metropolitan counties or those with low population density. Efforts at increasing physician supply should target these underserved areas.

OBJECTIVES: To determine whether body mass index (BMI) is independently associated with cognitive function in postmenopausal women and the relationship between body fat distribution as estimated by waist-hip ratio (WHR). DESIGN: Cross-sectional data analysis. SETTING: Baseline data from the Women’s Health Initiative (WHI) hormone trials. PARTICIPANTS: Eight thousand seven hundred forty-five postmenopausal women aged 65 to 79 free of clinical evidence of dementia who completed the baseline evaluation in the WHI hormone trials. MEASUREMENTS: Participants completed a Modified Mini-Mental State Examination (3MSE), health and lifestyle questionnaires, and standardized measurements of height, weight, body circumference, and blood pressure. Statistical analysis was performed of associations between 3MSE score, BMI, and WHR after controlling for known confounders. RESULTS: With the exception of smoking and exercise, vascular disease risk factors, including hypertension, waist measurement, heart disease, and diabetes mellitus, were significantly associated with 3MSE score and were included as covariables in subsequent analyses. BMI was inversely related to 3MSE score; for every 1-unit increase in BMI, 3MSE score decreased 0.988 points (Po.001) after adjusting for age, education, and vascular disease risk factors. BMI had the most pronounced association with poorer cognitive functioning scores in women with smaller waist measurements. In women with the highest WHR, cognitive scores increased with BMI. CONCLUSION: Higher BMI was associated with poorer cognitive function in women with smaller WHR. Higher WHR, estimating central fat mass, was associated with higher cognitive function in this cross-sectional study. Further research is needed to clarify the mechanism for this association. J Am Geriatr Soc 58:1427–1432, 2010.

Background The objectives of this study were to evaluate factors that influence agreement between parent-proxy and child self-report of health-related quality of life (HRQL) in sickle cell disease. We hypothesized that the mental health of the parent, parental HRQL and child characteristics would affect agreement. Procedure In a cross-sectional study of children with sickle cell disease, HRQL of the child and the parent's HRQL and mental health were assessed. The effect of parent and child characteristics on agreement between parent-proxy and child self-report of HRQL were determined. Results Rates of agreement between parent-proxy and child self-report of HRQL ranged between 42% and 49%. Parents with increased symptoms of distress had an increased odds of reporting a worse physical (Odds Ratio (OR) 1.12) and psychosocial HRQL (OR 1.10) compared to the child's self-report. Severe sickle cell disease was associated with an increased odds of the parent reporting the child's physical HRQL was worse, (OR 4.68) compared to the child's self-report. Conclusions Greater symptoms of distress in the parent are associated with worse parent-proxy report of the child's HRQL. Severe sickle cell disease is associated with greater disagreement between parent-proxy and child self-report of HRQL. These findings broaden our understanding of factors that influence proxy-reporting of a child's HRQL. Pediatr Blood Cancer. 2010;55:714–721. © 2010 Wiley-Liss, Inc.

Clostridium difficile-associated disease (CDAD) is associated with antibiotic use, acid suppression, and hospitalization, all of which occur frequently in cirrhosis. The aim was to define the effect of CDAD on outcomes and identify risk factors for its development in cirrhosis.Case-control studies using the de-identified national (Nationwide Inpatient Sample, NIS) and an identified liver transplant center database of hospitalized cirrhotics with and without CDAD were performed. The NIS 2005 was queried for mortality, charges, and length of stay (LOS) in cirrhotics with/without CDAD. Outcomes of cirrhosis and infections were also analyzed. In the transplant center database, risk factors for CDAD were defined in hospitalized cirrhotics with/without CDAD who were age matched in a 1:2 ratio.The NIS 2005 included 1,165 cirrhotics with and 82,065 without CDAD. Cirrhotics with CDAD had a significantly higher mortality (13.8% vs. 8.2%, P0.001), LOS (14.4 days vs. 6.7 days, P0.001), and charges ($79,351 vs. $35,686, P0.001) compared with those without CDAD. On multivariate analysis, CDAD was associated with higher mortality (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.29-1.85), charges, and LOS despite controlling for cirrhosis complications and infections. In the transplant center database, 54 cirrhotics with and 108 cirrhotics without CDAD were included. Outpatient spontaneous bacterial peritonitis prophylaxis (35% vs. 13%, P=0.01), inpatient antibiotic (63% vs. 35%, P=0.0001), and proton pump inhibitor (PPI) use (74% vs. 31%, P=0.0001) were significantly higher in those with CDAD.Cirrhotics with CDAD have a higher mortality, LOS, and charges on the NIS 2005 compared with those without CDAD. Antibiotic and PPI use are risk factors for CDAD development in hospitalized cirrhotics.

Continuous subcutaneous insulin infusion (CSII) is a safe and effective alternative to insulin injections in pediatric type 1 diabetes mellitus. CSII can be associated with an increased risk of hypoglycemia and diabetic ketoacidosis (DKA) in some patients. In our Center, patients/guardians are screened for proficiency in diabetes management skills as a prerequisite to initiation of CSII. We reviewed the clinical data from our patients to assess the predictors associated with nonadherence to CSII therapy.We retrospectively collected clinical data on all our CSII initiations between July 1999 to June 2003, including: body mass index, hemoglobin A1c (HbA1c), total daily dose, bolus to basal insulin ratio, hypoglycemic episodes (blood glucose60 mg/dL/week), mean fasting self-monitored blood glucose (SMBG), severity of lipohypertrophy, DKA, and pubertal status.Forty-six patients 9.90 +/- 3.4 years old (28 girls and 18 boys) started CSII in the 4-year period. While 39 patients (85%) 9.8 +/- 3.5 years old currently remain on CSII, seven patients (15%) 11.2 +/- 0.9 years old discontinued CSII. Fifteen patients (32.6%) were prepubertal at CSII initiation, and none discontinued CSII in this cohort, whereas seven of 31 (22.6%) pubertal patients discontinued CSII. The patients who continued CSII were similar to the CSII-discontinued cohort at baseline. At 12 months, rising HbA1c was the only predictor of future nonadherence to CSII. At 24 months, the discontinuation group had higher mean fasting SMBG levels and severe lipohypertrophy (P0.05). None of the prepubertal patients discontinued CSII, while all seven patients (100%) in the CSII-discontinued group were pubertal (P0.001).Extensive screening by a multidisciplinary diabetes team prior to initiation of CSII regimen results in relatively lower discontinuation rates and a higher chance of maintaining optimal glycemic control (HbA1C8%) compared to previous studies.

Objective Children enrolled in Medicaid have disproportionately high emergency department (ED) visit rates. Despite the growing importance of patient reported quality-of-care assessments, little is known about the association between parent-reported quality of primary care and ED utilization for these high-risk children. Our goal was to determine the association between parent-reported primary care quality and subsequent ED utilization for children in Medicaid. Methods We studied a retrospective cohort of children enrolled in Wisconsin Medicaid. Parents of children sampled during fall 2002 and fall 2004 completed Consumer Assessment of Healthcare Providers and Systems surveys assessing their child's primary care quality in 3 domains: family centeredness, timeliness, and realized access. Primary outcomes were the rates of subsequent nonurgent and urgent ED visits, extracted from claims data for the year after survey completion. Negative binomial regression was used to determine the association between the domains of care and ED utilization. Results A total of 5468 children were included. High-quality family centeredness was associated with a 27% (95% confidence interval [95% CI] 11%–40%) lower nonurgent ED visit rate, but no lowering of the urgent visit rate. High-quality timeliness was associated with 18% (95% CI, 3%–31%) lower nonurgent and 18% (95% CI, 1%–33%) lower urgent visit rates. High-quality realized access was associated with a 27% (95% CI, 8%–43%) lower nonurgent visit rate and a 33% (95% CI, 14%–48%) lower urgent visit rate. Conclusions Parent-reported high-quality timeliness, family centeredness, and realized access for a publicly insured child are associated with lower nonurgent ED, with high-quality timeliness and realized access associated with lower urgent ED utilization.

Background & Aims Minimal hepatic encephalopathy (MHE) is associated with impaired driving skills. It is not clear whether patients have insight into this. The Driving Behavior Survey (DBS) is a validated self- or observer-administered questionnaire. DBS consists of a total score (maximum, 104) and an attention-related driving skills section (maximum, 40). DBS was used to compare self-assessment with observer-assessment of driving skills in cirrhotic patients tested for MHE. Methods Forty-seven nonalcoholic cirrhotic patients and 40 controls underwent psychometric tests, DBS, and driving simulation with navigation/driving tasks. An adult familiar with the subject's driving completed the DBS independently. Simulator performances, total DBS scores, and driving skill scores were compared between/within groups (MHE+, MHE−, and controls) with respect to self-assessment and observer assessment. Results Thirty-six patients were MHE+ and 11 were MHE−. MHE+ had a significantly higher simulator crash (MHE+, 3; MHE−, 1.2; controls, 1.7; P = .001) and illegal turn rate (MHE+, 1.2; MHE−, 0.3; controls, 0.1; P = .0001). Despite this worse performance, MHE+ patients rated themselves similar to MHE− patients and control groups on total ( P = .28) and driving skills scores ( P = .19). Observer assessment in MHE+ was significantly lower for total ( P = .0001) and driving skills ( P = .0001) compared with observer assessment for MHE− patients and control groups. MHE+ patients were rated significantly lower on driving skills (34 vs 37; P = .02) and trended lower in the total score ( P = .08) by observers compared with self-ratings. In contrast, MHE− and control groups rated themselves similar to their observers on driving skills and total DBS scores. Conclusions MHE patients have poor insight into their driving skills. A part of the MHE patient's clinical interview should be to increase awareness of this driving impairment.