Tracking the impact of the National Institutes of Health Clinical and Translational Science Awards on child health research: developing and evaluating a measurement strategy.

Since 2006, the National Institutes of Health has provided institutional infrastructure grants, called Clinical and Translational Science Awards (CTSAs), to support adult and pediatric clinical and translational research in United States institutions. A CTSA Consortium Child Health Oversight Committee workgroup developed metrics to measure the impact of CTSAs on child health (CH) research. A cross-sectional survey to collect metric data was distributed to the 46 institutions that received CTSAs during 2006-09.

Chelation use and iron burden in North American and British thalassemia patients: a report from the Thalassemia Longitudinal Cohort.

Morbidity and mortality in thalassemia are associated with iron burden. Recent advances in organ-specific iron imaging and the availability of oral deferasirox are expected to improve clinical care, but the extent of use of these resources and current chelation practices have not been well described. In the present study, we studied chelation use and the change in iron measurements in 327 subjects with transfusion-dependent thalassemia (mean entry age, 22.

Predicting inpatient aggression using the InterRAI risk of harm to others clinical assessment protocol: a tool for risk assessment and care planning.

This study examined the ability of a risk assessment algorithm, the Risk of Harm to Others Clinical Assessment Protocol (RHO CAP) to predict inpatient aggression within a mental health and addictions treatment facility in Ontario, Canada. Anonymized patient records were retrospectively reviewed from April 1, 2004 to July 31, 2009 (N = 6,425). Survival analysis using Cox's regression was used to predict time to inpatient aggression using the RHO CAP.

A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload.

This was a 24-week, multicenter phase-2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form).

Patient-specific simulations and measurements of the magneto-hemodynamic effect in human primary vessels.

This paper investigates the main characteristics of the magneto-hemodynamic (MHD) response for application as a biomarker of vascular blood flow. The induced surface potential changes of a volunteer exposed to a 3 T static B0 field of a magnetic resonance imaging (MRI) magnet were measured over time at multiple locations by an electrocardiogram device and compared to simulation results. The flow simulations were based on boundary conditions derived from MRI flow measurements restricted to the aorta and vena cava.

Trends in anti-D immune globulin for childhood immune thrombocytopenia: usage, response rates, and adverse effects.

In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D.

Local tissue temperature increase of a generic implant compared to the basic restrictions defined in safety guidelines.

The objective of this study was to investigate if persons with implantable medical devices are intrinsically protected by the current electromagnetic safety guidelines. For inter-laboratory comparisons, the U.S.

Defects in the medial entorhinal cortex and dentate gyrus in the mouse model of Sanfilippo syndrome type B.

Sanfilippo syndrome type B (MPS IIIB) is characterized by profound mental retardation in childhood, dementia and death in late adolescence; it is caused by deficiency of α-N-acetylglucosaminidase and resulting lysosomal storage of heparan sulfate. A mouse model, generated by homologous recombination of the Naglu gene, was used to study pathological changes in the brain. We found earlier that neurons in the medial entorhinal cortex (MEC) and the dentate gyrus showed a number of secondary defects, including the presence of hyperphosphorylated tau (Ptau) detected with antibodies raised against Ptau in Alzheimer disease brain.

Local SAR enhancements in anatomically correct children and adult models as a function of position within 1.5 T MR body coil.

Usage of magnetic resonance imaging (MRI) is continuously increasing due to its excellent soft-tissue contrast and improving diagnostic values. MRI also has the advantage that it operates without ionizing radiation. The main safety concerns are torque, acceleration by the static field, nerve stimulation by the gradient fields, and tissue heating by the radio-frequency (RF) fields.

The use of a single von Willebrand factor-containing, plasma-derived FVIII product in hemophilia A immune tolerance induction: the US experience.

Background: Inhibitors are a serious complication for patients with severe hemophilia A. Immune tolerance induction (ITI) is the primary method for eradicating these inhibitors. The role of type of concentrate and in particular the use of von Willebrand factor-containing, plasma-derived factor VIII (VWF/pd-FVIII) concentrate in primary or rescue ITI remains unclear.

Homogenous protein programming in the mammalian left and right ventricle free walls.

Despite identical cardiac outputs, the right (RV) and left ventricle (LV) have very different embryological origins and resting workload. These differences suggest that the ventricles have different protein programming with regard to energy metabolism and contractile elements. The objective of this study was to determine the relative RV and LV protein expression levels, with an emphasis on energy metabolism.

Children and adults exposed to electromagnetic fields at the ICNIRP reference levels: theoretical assessment of the induced peak temperature increase.

To avoid potentially adverse health effects of electromagnetic fields (EMF), the International Commission on Non-Ionizing Radiation Protection (ICNIRP) has defined EMF reference levels. Restrictions on induced whole-body-averaged specific absorption rate (SAR(wb)) are provided to keep the whole-body temperature increase (T(body, incr)) under 1 °C during 30 min. Additional restrictions on the peak 10 g spatial-averaged SAR (SAR(10g)) are provided to prevent excessive localized tissue heating.

Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report.

An elevated tricuspid regurgitant jet velocity (TRV) is associated with hemolysis and early mortality in sickle cell disease, yet risk factors, clinical parameters, and mortality associated with this biomarker in thalassemia are poorly defined. This report summarizes the prevalence of an elevated TRV in 325 patients screened by Doppler echocardiography in the Thalassemia Clinical Research Network. A documented TRV was reported in 148 of 325 (46%) of patients.

Analysis of the local worst-case SAR exposure caused by an MRI multi-transmit body coil in anatomical models of the human body.

Multi-transmit coils are increasingly being employed in high-field magnetic resonance imaging, along with a growing interest in multi-transmit body coils. However, they can lead to an increase in whole-body and local specific absorption rate (SAR) compared to conventional body coils excited in circular polarization for the same total incident input power. In this study, the maximum increase of SAR for three significantly different human anatomies is investigated for a large 3 T (128 MHz) multi-transmit body coil using numerical simulations and a (generalized) eigenvalue-based approach.

From serendipity to therapy.

My postdoctoral training in the biosynthesis of plant polysaccharides at the University of California, Berkeley, led me, rather improbably, to study mucopolysaccharide storage disorders in the intramural program of the National Institutes of Health (NIH). I have traced the path from studies of mucopolysaccharide turnover in cultured cells to the development of therapy for patients. The key experiment started as an accident, i.

Thirty-day readmission rates following hospitalization for pediatric sickle cell crisis at freestanding children's hospitals: risk factors and hospital variation.

Background: Readmission within 30 days after hospitalization for sickle cell crisis was developed by The National Association of Children's Hospitals (NACHRI) to improve hospital quality, however, there have been few studies validating this.

Procedure: We performed a retrospective examination of 12,104 hospitalizations for sickle crisis from July 1, 2006 and December 31, 2008 at 33 freestanding children's hospitals in the Pediatric Health Information System (PHIS) database. Hospitalizations met NACHRI criteria; inpatient admission, APR DRG code 662, age < 18, discharge home, and length of stay within 2 SD of the mean.

Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia.

Background: Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies.

Methods: The objective of this study was to evaluate univariate and multivariable predictors of platelet count response to rituximab.

Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population.

Background: Since pediatric immune thrombocytopenia (ITP) is relatively infrequent, comparisons among clinical studies are critical but have previously been limited by differences in terminology. In 2009, an international working group (IWG) developed consensus criteria to enhance comparability in future studies in adults and children.

Methods: We performed a retrospective medical record review of all pediatric ITP patients seen at a single children's hospital with a first visit between 2003 and 2010 and applied both historical (criteria(Hist) ) and IWG (criteria(IWG) ) ITP criteria to available clinical data.

Transition from pediatric to adult care for sickle cell disease: results of a survey of pediatric providers.

As recently as the 1970s, children born with sickle cell disease (SCD) were unlikely to survive into adulthood. With advances in medical care, most patients now survive childhood and live into their forties or beyond [1,2]. A better transition from pediatric- to adult-focused care is therefore increasingly important [3].

Iron chelation adherence to deferoxamine and deferasirox in thalassemia.

The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review.

Renal dysfunction in patients with thalassaemia.

Little is known about the effects of thalassaemia on the kidney. Characterization of underlying renal function abnormalities in thalassaemia is timely because the newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine the prevalence and correlates of renal abnormalities in thalassaemia patients, treated before deferasirox was widely available, using 24-h collections of urine.

Red cell alloimmunization in a diverse population of transfused patients with thalassaemia.

Red blood cell (RBC) transfusion is the primary treatment for severe forms of thalassaemia. Pre-storage screening has resulted in decreased transfusion-transmitted infections, but anti-RBC antibodies remain a major problem. We report on 697 participants who had ever received transfusions.

Exposure and safety of higher doses of recombinant factor VIIa ≥250 μg kg(-1) in individuals with congenital haemophilia complicated by alloantibody inhibitors: the Haemophilia and Thrombosis Research Society Registry experience (2004-2008).

Recombinant factor VIIa (rFVIIa) is a well-established treatment for managing bleeding episodes in individuals with congenital haemophilia complicated by alloantibody inhibitors (CHwI). The safety and efficacy of standard dosing (90-120 μg kg(-1) every 2-3 h) are well-established; however, the desire to optimize therapy with one or more higher doses instead of multiple lower doses has created a need for evidence of the safety and efficacy of such regimens. Analysis of data from the Haemophilia and Thrombosis Research Society (HTRS) Registry was performed on episodes where doses of ≥250 μg kg(-1) were reported.

Update on iron chelators in thalassemia.

Over the past four decades, there have been dramatic improvements in survival for patients with thalassemia major due in large measure to improved iron chelators. Two chelators are approved for use in the United States and Canada, parenteral deferoxamine and oral deferasirox. Three are available in much of the rest of the world, where oral deferiprone is also approved (in the United States, deferiprone is only available in studies, for emergency use, or on a "compassionate-use" basis).

The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols.

The optimal management of asparaginase-associated thrombotic complications is not well-defined. We report the features, management and outcome of paediatric (ages 0-18years) and adult (18-50years) patients with acute lymphoblastic leukaemia (ALL) with asparaginase-related venous thromboembolic events (VTE) treated at Dana-Farber Cancer Institute on clinical trials for newly diagnosed ALL between 1991-2008. Of 548 patients, 43 (8%) had VTE, including 27/501 (5%) paediatric and 16/47 (34%) adult patients.