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Wood J.R.,Childrens Hospital Los Angeles | Miller K.M.,Jaeb Center for Health Research | Maahs D.M.,Barbara Davis Center for Childhood Diabetes | Beck R.W.,Childrens Hospital Los Angeles | And 5 more authors.
Diabetes Care | Year: 2013

Objective-To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids. Research design and methods-Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year. ResultsAmerican Diabetes Association HbA1c targets of ,8.5% for those younger than 6 years, ,8.0% for those 6 to younger than 13 years old, and ,7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of ,85th percentile. Conclusions-Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry. © 2013 by the American Diabetes Association.

Wood J.C.,Childrens Hospital | Zhang P.,Shire Pharmaceuticals | Rienhoff H.,Ferrokin Biosciences, Inc. | Abi-Saab W.,Shire Pharmaceuticals | Neufeld E.,Childrens Hospital of Boston
American Journal of Hematology | Year: 2014

MRI relaxometry (R2, R2*) has generally replaced liver biopsy for estimation of liver iron stores in response to iron chelation, but there have been no longitudinal studies comparing R2 and R2* techniques. We use R2 and R2* liver iron concentration (LIC) estimates, transfusional iron burdens, and drug compliance data to calculate iron chelation efficiency (ICE) in patients undergoing a Phase II trial of SPD602. Fifty-one patients underwent a baseline examination, 39 patients completed 1 year, and 26 patients completed 2 years. Baseline LICR2 and LICR2* estimates were unbiased, but had limits of agreement exceeding 50%, suggesting that these techniques cannot be interchanged with one another in the same patient. However, ICE estimates across the two techniques compared more favorably, with r2 values reaching 0.89 at 2 years. 95 confidence intervals for efficiency estimates were 0.0±4.1%. These data indicate that clinical trial and clinical effectiveness data calculated using LICR2 and LICR2* estimates can be compared to one another, even though LIC estimates may be disparate on cross-sectional analysis. While the choice of MRI assessment technique for clinical trials and for clinical management depends on many logistical considerations, one can have confidence comparing conclusions on clinical effectiveness. © 2014 Wiley Periodicals, Inc.

Priromprintr B.,University of Southern California | Silka M.J.,University of Southern California | Rhodes J.,Childrens Hospital of Boston | Batra A.S.,University of California at Los Angeles
Heart Rhythm | Year: 2016

Background Although percutaneous Melody valve implant has become an accepted alternative to surgical pulmonary valve replacement in patients with congenital heart disease, the benefit regarding frequency and severity of arrhythmias remains undefined. Objective The purpose of this study was to evaluate the impact of Melody valve implant on the type and frequency of arrhythmias during cardiopulmonary exercise testing (CPET) and subsequent clinical outcome. Methods As part of the phase I Melody valve clinical trial, 136 patients with congenital heart disease underwent prospective serial evaluation including CPET before implant, 6 months after implant, and annually thereafter for 5 years. Arrhythmias were defined as premature ventricular complexes (PVCs) and supraventricular or ventricular tachycardia (VT). Results Before Melody implant, PVCs occurred in 55 patients (40%) and nonsustained ventricular tachycardia (NSVT) in 1 patient during CPET. Median age at valve implantation was 19.0 years (range 7–53 years). During median follow-up of 4.9 years (range 0.8–7.3 years), there was no significant change in the proportion of patients with PVCs during CPET at any follow-up interval (40%–45%). However, postimplant, NSVT occurred in 18 patients, including 8 during CPET. Diagnoses in the patients with NSVT were tetralogy of Fallot (11), transposition (2), and post-Ross procedure (5). Improved hemodynamic status was not associated with resolution or prevention of arrhythmias. Conclusion Despite improvement in hemodynamics, Melody valve implant was not associated with resolution or prevention of arrhythmias during CPET. PVCs or VT may be related to pathologic hypertrophy, fibrosis, dilation, or possible mechanical effects of the Melody device. © 2016 Heart Rhythm Society

Boretsky K.,Childrens Hospital of Boston | Visoiu M.,University of Pittsburgh | Bigeleisen P.,University of Maryland, Baltimore
Paediatric Anaesthesia | Year: 2013

Background Paravertebral perineural blocks are used to prevent pain in the thoracoabdominal dermatomes. Traditionally, a landmark-based technique is used in children, while ultrasound-guided (UG) techniques are being employed in adult patients. Objective To describe an UG technique for placement of thoracic paravertebral nerve block (TPVNB) catheters in pediatric patients. Methods Retrospective chart review of a series of 22 pediatric patients' ages 6 months to 17 years with weights from 6.25 kg to 135 kg using a transverse in-plane technique. Catheters were placed both bilateral and unilateral for a variety of thoracic and abdominal procedures. A linear ultrasound transducer was used in all cases with frequency of oscillation and transducer length chosen based on individual patient characteristics of age, weight, and BMI. Results The median pain scores at 12, 24, 36, and 48 h were 1.2 (interquartile range, 4.5), 0.84 (interquartile range 3.0), 1.6 (interquartile range 2.9), and 0.83 (interquartile range 1.74), respectively. The median dose of opioid expressed as morphine equivalents consumed during the first 24 h after surgery was 0.14 mg·kg-1 (interquartile range, 0.78 mg·kg-1) and from 24 to 48 h the median dose was 0.11 mg·kg-1 (interquartile range 0.44 mg·kg-1). No complications were noted, and catheters were left an average of 3 days with a range of 1-5 days with good pain relief. Conclusion This technical description demonstrates the feasibility of placing PVNB catheters using a transverse in-line ultrasound-guided technique in a wide range of pediatric patients. © 2013 John Wiley & Sons Ltd.

McCormick M.C.,Boston University | McCormick M.C.,Beth Israel Deaconess Medical Center | Litt J.S.,Beth Israel Deaconess Medical Center | Litt J.S.,Childrens Hospital of Boston | And 2 more authors.
Annual Review of Public Health | Year: 2011

The high rate of premature births in the United States remains a public health concern. These infants experience substantial morbidity and mortality in the newborn period, which translate into significant medical costs. In early childhood, survivors are characterized by a variety of health problems, including motor delay and/or cerebral palsy, lower IQs, behavior problems, and respiratory illness, especially asthma. Many experience difficulty with school work, lower health-related quality of life, and family stress. Emerging information in adolescence and young adulthood paints a more optimistic picture, with persistence of many problems but with better adaptation and more positive expectations by the young adults. Few opportunities for prevention have been identified; therefore, public health approaches to prematurity include assurance of delivery in a facility capable of managing neonatal complications, quality improvement to minimize interinstitutional variations, early developmental support for such infants, and attention to related family health issues. © 2011 by Annual Reviews. rights reserved.

Harrison S.,Childrens Hospital of Boston | Vavken P.,Childrens Hospital of Boston | Kevy S.,Childrens Hospital Boston Affiliate | Jacobson M.,Childrens Hospital of Boston | And 2 more authors.
American Journal of Sports Medicine | Year: 2011

Background: Platelet-rich plasma (PRP) has been increasingly used in sports medicine applications. Platelets are thought to release growth factors important in wound healing, including transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF-AB), and vascular endothelial growth factor (VEGF). However, little is known about the effect of platelet activator choice on growth factor release kinetics. Hypothesis: The choice of platelet activator would affect the timing and level of growth factor release from PRP. Study Design: Controlled laboratory study. Methods: Platelet-rich plasma aliquots were activated with either thrombin or collagen. A control group of whole blood aliquots was clotted with thrombin. Supernatant containing the released growth factors was collected daily for 1 week. Levels of TGF-β1, PDGF-AB, and VEGF were measured using enzyme-linked immunosorbent assay (ELISA). Results: The use of thrombin as an activator resulted in immediate release of TGF-β1 and PDGF-AB, while the collagen-activated PRP clots released similar amounts each day for 5 days. The use of collagen as an activator resulted in an 80% greater cumulative release of TGF-β1 from the PRP aliquots over 7 days (P <.001). Concentrating platelets to 3 times the systemic blood level resulted in a 3-fold higher release of TGF-β1, 2.5-fold greater release of PDGF, and 5-fold greater release of VEGF (all P <.0001) when compared with whole blood control clots, but no significant differences in the timing of release were noted. Conclusion: These experiments demonstrated that the choice of platelet activator can significantly influence the release kinetics of cytokines from PRP, with thrombin resulting in an immediate release and collagen having a more sustained release pattern. Clinical Relevance: The level and rate of growth factor release depends on the selected platelet activator, a factor that should be considered when selecting a PRP system for a given application. © 2011 The Author(s).

Reichman D.E.,Brigham and Women's Hospital | Laufer M.R.,Childrens Hospital of Boston | Laufer M.R.,Brigham and Women's Hospital
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2010

The following review seeks to summarise the current data regarding reproductive outcomes associated with congenital uterine anomalies. Such malformations originate from adverse embryologic events ranging from agenesis to lateral and vertical fusion defects. Associated renal anomalies are common both for the symmetric and asymmetric malformations. While fertility is minimally impacted upon by müllerian anomalies in most cases, such malformations have historically been associated with poor obstetric outcomes such as recurrent miscarriage, second trimester loss, preterm delivery, malpresentation and intrauterine foetal demise (IUFD). The following review delineates the existing literature regarding such outcomes and indicates therapies, where applicable, to optimise the care of such patients. © 2009 Elsevier Ltd. All rights reserved.

Tikkanen A.U.,Childrens Hospital of Boston
Cardiology in the young | Year: 2012

Advances in medical and surgical care have contributed to an important increase in the survival rates of children with congenital heart disease. However, survivors often have decreased exercise capacity and health-related issues that affect their quality of life. Cardiac Rehabilitation Programmes have been extensively studied in adults with acquired heart disease. In contrast, studies of children with congenital heart disease have been few and of limited scope. We therefore undertook a systematic review of the literature on cardiac rehabilitation in children with congenital heart disease to systematically assess the current evidence regarding the use, efficacy, benefits, and risks associated with this therapy and to identify the components of a successful programme. We included studies that incorporated a cardiac rehabilitation programme with an exercise training component published between January, 1981 and November, 2010 in patients under 18 years of age. A total of 16 clinical studies were found and were the focus of this review. Heterogeneous methodology and variable quality was observed. Aerobic and resistance training was the core component of most studies. Diverse variables were used to quantify outcomes. No adverse events were reported. Cardiac Rehabilitation Programmes in the paediatric population are greatly underutilised, and clinical research on this promising form of therapy has been limited. Questions remain regarding the optimal structure and efficacy of the programmes. The complex needs of this unique population also mandate that additional outcome measures, beyond serial cardiopulmonary exercise testing, be identified and studied.

Becerra L.,Childrens Hospital of Boston | Becerra L.,Harvard University | Navratilova E.,University of Arizona | Porreca F.,University of Arizona | And 2 more authors.
Journal of Neurophysiology | Year: 2013

In humans, functional magnetic resonance imaging (fMRI) activity in the anterior cingulate cortex (ACC) and the nucleus accumbens (NAc) appears to reflect affective and motivational aspects of pain. The responses of this reward-aversion circuit to relief of pain, however, have not been investigated in detail. Moreover, it is not clear whether brain processing of the affective qualities of pain in animals parallels the mechanisms observed in humans. In the present study, we analyzed fMRI blood oxygen level-dependent (BOLD) activity separately in response to an onset (aversion) and offset (reward) of a noxious heat stimulus to a dorsal part of a limb in both humans and rats. We show that pain onset results in negative activity change in the NAc and pain offset produces positive activity change in the ACC and NAc. These changes were analogous in humans and rats, suggesting that translational studies of brain circuits modulated by pain are plausible and may offer an opportunity for mechanistic investigation of pain and pain relief. © 2013 the American Physiological Society.

Harrison S.L.,Childrens Hospital of Boston | Vavken P.,Childrens Hospital of Boston | Murray M.M.,Childrens Hospital of Boston
Journal of Orthopaedic Research | Year: 2011

In this work, we hypothesized that the concentration of erythrocytes in a provisional scaffold would have a significant effect on three of the major biological processes occurring in early wound healing. ACL fibroblast proliferation, collagen production, and scaffold contraction were measured in collagen gels containing fibroblasts and erythrocytes in subphysiologic (1 × 108 erythrocytes/ml), physiologic (1 × 109 erythrocytes/ml), and supraphysiologic (1 × 1010 erythrocytes/ml) concentrations. Fibroblast-seeded gels containing only platelet-poor plasma were used as a control group. All gels were cultured for 1, 14, and 21 days. DNA, ELISA for procollagen and scaffold size measurements were used to quantify the three above parameters of wound healing. Samples with concentrations of erythryocytes lower than that in whole blood stimulated greater fibroblast proliferation and scaffold contraction than those with erythrocyte concentrations similar to that in whole blood (p < 0.027; p < 0.03). Increasing the erythrocyte concentration over that in the whole blood stimulated fibroblast collagen production (p < 0.009) and limited scaffold contraction (p < 0.031). Further work examining the role of the erythrocyte in the early provisional scaffold is warranted. © 2011 Orthopaedic Research Society.

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