Rapid discrimination of the phenotypic variants of von Willebrand disease.

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.

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

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

Spatial discrimination of glioblastoma and treatment effect with histologically-validated perfusion and diffusion magnetic resonance imaging metrics.

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.

Correlation of Bedside Pediatric Early Warning System Score to Interventions During Peritransport Period.

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.

Low near infrared spectroscopic somatic oxygen saturation at admission is associated with need for lifesaving interventions among unplanned admissions to the pediatric intensive care unit.

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.

Treatment with ActRIIB-mFc Produces Myofiber Growth and Improves Lifespan in the Acta1 H40Y Murine Model of Nemaline Myopathy.

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.

Preschool Neurodevelopmental Outcomes in Children with Congenital Heart Disease.

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.

Crucial role for the VWF A1 domain in binding to type IV collagen.

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.

Preliminary Study of a Caregiver-based Infant and Child Feeding and Swallowing Screening Tool.

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.

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

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

Factors Associated With Continuous Low-Dose Heparin Infusion for Central Venous Catheter Patency in Critically Ill Children Worldwide.

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.

Migration of Central Venous Catheters in Neonates: A Radiographic Assessment.

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.

The Effects of Pediatric Advanced Life Support Guidelines on Pediatric Trauma Airway Management.

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.

Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice.

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.

Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model.

Low molecular weight heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven, and the issue of antithrombotic prophylaxis is intensely debated. Using a murine model of factor V Leiden-associated placental failure, we show that treatment of the mother with LMWH allows placental development to proceed and affords significant protection from fetal loss. Nonetheless, the therapeutic effect of LMWH is not replicated by anticoagulation; fondaparinux and a direct Xa inhibitor, C921-78, achieve anticoagulation similar to LMWH but produce little or no improvement in pregnancy outcome. Genetic attenuation of maternal platelet aggregation is similarly ineffective. In contrast, even a partial loss of thrombin sensitivity of maternal platelets protects pregnancies. Neonates born from these pregnancies are growth retarded, suggesting that placental function is only partially restored. The placentae are smaller but do not reveal any evidence of thrombosis. Our data demonstrate an anticoagulation-independent role of LMWH in protecting pregnancies and provide evidence against the involvement of thrombotic processes in thrombophilia-associated placental failure. Importantly, thrombin-mediated maternal platelet activation remains central in the mechanism of placental failure.

No increase in bleeding identified in type 1 VWD subjects with D1472H sequence variation.

The diagnosis of von Willebrand disease (VWD) is complicated by issues with current laboratory testing, particularly the ristocetin cofactor activity assay (VWF:RCo). We have recently reported a sequence variation in the von Willebrand factor (VWF) A1 domain, p.D1472H (D1472H), associated with a decrease in the VWF:RCo/VWF antigen (VWF:Ag) ratio but not associated with bleeding in healthy control subjects. This report expands the previous study to include subjects with symptoms leading to the diagnosis of type 1 VWD. Type 1 VWD subjects with D1472H had a significant decrease in the VWF:RCo/VWF:Ag ratio compared with those without D1472H, similar to the findings in the healthy control population. No increase in bleeding score was observed, however, for VWD subjects with D1472H compared with those without D1472H. These results suggest that the presence of the D1472H sequence variation is not associated with a significant increase in bleeding symptoms, even in type 1 VWD subjects.

A Randomized Clinical Trial of Jet-Injected Lidocaine to Reduce Venipuncture Pain for Young Children.

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.

The proportion of potentially preventable emergency department visits by patients with sickle cell disease.

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

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

A Comparison of Pain Assessment Measures in Pediatric Sickle Cell Disease: Visual Analog Scale Versus Numeric Rating Scale.

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.