Enhancing Pain Assessment in Pediatric Sickle Cell Disease by Applying Quality Improvement Science.

Objective: Standardized pain assessment and interventions are recommended for youth hospitalized for pain. This quality improvement (QI) project integrated into a pediatric psychology service aimed to increase the standardized assessment of pain-related functional ability for youth with sickle cell disease (SCD) hospitalized for pain.

Methods: Children and adolescents (n=102) with SCD referred for psychology consultation for poor coping in response to pain during hospitalization completed a validated self-report of functional ability in addition to pain intensity during inpatient psychology visits.

A Phase 3 Trial of l-Glutamine in Sickle Cell Disease.

Background: Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Oral therapy with pharmaceutical-grade l-glutamine (USAN, glutamine) has been shown to increase the proportion of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, which probably reduces oxidative stress and could result in fewer episodes of sickle cell-related pain.

Methods: In a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial, we tested the efficacy of pharmaceutical-grade l-glutamine (0.

Widespread Pain Among Youth With Sickle Cell Disease Hospitalized With Vasoocclusive Pain: A Different Clinical Phenotype?

Objectives: The purpose of this study was to describe the clinical phenotype of widespread pain (WSP) among youth with sickle cell disease (SCD) hospitalized with vasoocclusive pain.

Materials And Methods: One hundred fifty-six youth with SCD, between 7 and 21 years of age hospitalized at 4 children's hospitals for a vasoocclusive episode were evaluated. Data were collected during 1 day of the hospitalization.

Impact of red blood cell alloimmunization on sickle cell disease mortality: a case series.

Background: Although red blood cell (RBC) transfusion represents an integral component of sickle cell disease (SCD) care, transfusion support for some patients can result in alloimmunization to RBC antigens. Alloimmunized patients with SCD appear to experience worse survival compared to nonalloimmunized patients. While this difference in mortality may in part be due to underlying immunologic differences related to disease severity, it may also reflect direct clinical consequences of RBC alloimmunization.

Development and validation of the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ).

Unlabelled: Physical function and functional recovery are important aspects of the acute pain experience in children and adolescents in hospitalized settings. Measures of function related to pediatric acute pain do not exist currently, limiting understanding of recovery in youth undergoing acute and procedural pain. To address this gap, we developed and assessed the clinical utility and preliminary validity of the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ).

Elevated tricuspid regurgitant velocity as a marker for pulmonary hypertension in children with sickle cell disease: less prevalent and predictive than previously thought?

Although elevated tricuspid regurgitant velocity (TRV), an echocardiographic marker for pulmonary hypertension, has previously been tied to mortality in adult patients with sickle cell disease, recent data demonstrated that it correlates poorly with catheterization findings. We describe the largest echocardiographic evaluation of pediatric patients with sickle cell disease to date, specifically the results of a protocol whereby a TRV≥250 cm/s prompted further evaluation. We investigated if elevated TRV would independently identify patients at risk for increased morbidity.

Management of refractory pain in hospitalized adolescents with sickle cell disease: changing from intravenous opioids to continuous infusion epidural analgesia.

Background: Prolonged hospitalizations for sickle cell disease painful episodes are not uncommon, as analgesic options are often suboptimal.

Observations: Seven patients (15.4 ± 3.

Validation of the sickle cell disease pain burden interview-youth.

Unlabelled: The purpose of this study was to develop and validate a brief, clinically relevant, multidimensional interview to assess pain burden among children and adolescents with sickle cell disease (SCD). The Sickle Cell Disease Pain Burden Interview-Youth (SCPBI-Y) was developed using a panel of experts, patients, and caregivers. Validation was undertaken with children and youth with SCD, ages 7 to 21 years (N = 129), recruited from 4 urban children's hospitals.

SickleREMOTE: A Two-Way Text Messaging System for Pediatric Sickle Cell Disease Patients.

Sickle cell disease, the most common hemoglobinopathy in the world, affects patient lives from early childhood. Effective care of sickle cell disease requires frequent medical monitoring, such as tracking the frequency, severity, and duration of painful events. Conventional monitoring includes paper- or web-based reporting diaries.

TNP-470 promotes initial vascular sprouting in xenograft tumors.

TNP-470 (AGM-1470), an analogue of fumagillin, was one of the first molecules proposed to have antiangiogenic properties. This concept was based on its ability to inhibit both endothelial proliferation in vitro and tumor growth in vivo in a number of xenograft models. Yet, subsequent investigations indicated that the biochemical activities associated with TNP-470 are not selective for endothelial cells.

Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis.

The potential for avoiding acquired resistance to therapy has been proposed as one compelling theoretical advantage of antiangiogenic therapy based on the normal genetic status of the target vasculature. However, previous work has demonstrated that tumors may resume growth after initial inhibition if antiangiogenic blockade is continued for an extended period. The mechanisms of this recurrent growth are unclear.

Human epidermal growth factor receptor signaling contributes to tumor growth via angiogenesis in her2/neu-expressing experimental Wilms' tumor.

Background: The human epidermal growth factor family (HER) members play a significant role in the mesenchymal-to-epithelial transition during renal tubulogenesis. HER misexpression has been linked also to loss of growth control, invasiveness, and promotion of angiogenesis in breast cancers and other human malignant tumors

Methods: The authors screened Wilms' tumor samples and derived cell lines for expression of her2/neu, which was detected in both unfavorable and favorable histology tissues. Xenografts were implanted in mice using her2/neu(+) and her2/neu(-) cell lines and the effect of specific blockade tested using monoclonal anti-her2/neu antibody.

Thalidomide is anti-angiogenic in a xenograft model of neuroblastoma.

Thalidomide has previously been shown to have anti-angiogenic properties. More recently, clinical efficacy of this agent has been demonstrated in multiple myeloma and prostate cancer. Neuroblastoma is the most frequent solid tumor of the abdomen of childhood, yet children with this disease frequently have metastases at presentation.

Blockade of her2/neu decreases VEGF expression but does not alter HIF-1 distribution in experimental Wilms tumor.

Her2/neu regulates angiogenesis in human breast cancer, in part by stabilizing hypoxia-inducible factor 1alpha (HIF-1alpha), causing accumulation of the HIF-1 heterodimer and thus increasing expression of the proangiogenic cytokine VEGF. Her2/neu has recently been shown to be overexpressed in a subset of Wilms tumors. Using her2/neu (+) and her2/neu (-) Wilms tumor cell lines, we tested the effect of blocking anti-her2/neu antibody in vitro and in vivo.

Regression of established tumors and metastases by potent vascular endothelial growth factor blockade.

Vascular endothelial growth factor (VEGF) is a critical promoter of blood vessel growth during embryonic development and tumorigenesis. To date, studies of VEGF antagonists have primarily focused on halting progression in models of minimal residual cancer. Consistent with this focus, recent clinical trials suggest that blockade of VEGF may impede cancer progression, presumably by preventing neoangiogenesis.

Anti-VEGF antibody in experimental hepatoblastoma: suppression of tumor growth and altered angiogenesis.

Background: Hepatoblastoma is the most common primary hepatic malignancy of childhood, frequently presenting as advanced disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen and survival factor critical to growth and angiogenesis in many human cancers. Inhibition of VEGF effectively suppresses tumorigenesis in multiple experimental models.

Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma.

Vascular endothelial growth factor (VEGF) plays a key role in human tumor angiogenesis. We compared the effects of inhibitors of VEGF with different specificities in a xenograft model of neuroblastoma. Cultured human neuroblastoma NGP-GFP cells were implanted intrarenally in nude mice.