Wasserman R.L.,Medical City Childrens Hospital |
Factor J.M.,Connecticut Childrens Medical Center |
Baker J.W.,Emanuel Hospital |
Katz Y.,Tel Aviv University |
And 10 more authors.
Journal of Allergy and Clinical Immunology: In Practice | Year: 2014
Background: Peanut allergy creates the risk of life-threatening anaphylaxis that can disrupt psychosocial development and family life. The avoidance management strategy often fails to prevent anaphylaxis and may contribute to social dysfunction. Peanut oral immunotherapy may address these problems, but there are safety concerns regarding implementation in clinical practice. Objective: The purpose of this report is to communicate observations about the frequency of epinephrine-treated reactions during peanut oral immunotherapy in 5 different allergy/immunology practices. Methods: Retrospective chart review of peanut oral immunotherapy performed in 5 clinical allergy practices. Results: A total of 352 treated patients received 240,351 doses of peanut, peanut butter, or peanut flour, and experienced 95 reactions that were treated with epinephrine. Only 3 patients received 2 doses of epinephrine, and no patient required more intensive treatment. A total of 298 patients achieved the target maintenance dose for a success rate of 85%. Conclusion: Peanut oral immunotherapy carries a risk of systemic reactions. In the context of oral immunotherapy, those reactions were recognized and treated promptly. Peanut oral immunotherapy may be a suitable therapy for patients managed by qualified allergists/immunologists. © 2014 American Academy of Allergy, Asthma & Immunology.
Carroll T.G.,Children's Medical Center Dallas |
Dimas V.V.,Children's Medical Center Dallas |
Raymond T.T.,University of Texas Southwestern Medical Center |
Raymond T.T.,Medical City Childrens Hospital
Pediatric Critical Care Medicine | Year: 2012
OBJECTIVES: To assess the feasibility of a large, randomized controlled trial of combination epinephrine-arginine vasopressin for in-pediatric intensive care unit cardiopulmonary arrest refractory to initial epinephrine dosing. DESIGN: Prospective, pilot, matched controlled clinical trial using exception from informed consent. SETTING: Pediatric intensive care unit in a university-affiliated tertiary care children's hospital. PATIENTS: All patients <18 yrs of age admitted to the pediatric intensive care unit with cardiopulmonary arrest requiring chest compressions and epinephrine (0.01 mg/kg) were eligible. INTERVENTIONS: Patients who remained in cardiopulmonary arrest despite an initial dose of epinephrine received arginine vasopressin (0.8 U/kg) rescue as the second vasopressor, followed by additional epinephrine if needed. MEASUREMENTS AND MAIN RESULTS: Outcome variables included return of spontaneous circulation (≥20 min), survival at 24 hrs, survival to hospital discharge, and neurologic status at discharge. Favorable neurologic status was defined as Pediatric Cerebral Performance Categories 1, 2, and 3, or no change from admission. Data were compared to a retrospective, matched cohort of patients who experienced cardiopulmonary arrest requiring ≥ two doses of vasopressor, and did not receive arginine vasopressin (n = 20). Of 2,654 patients admitted to the pediatric intensive care unit, 29 (1.1%) had refractory cardiopulmonary arrest: five patients were excluded, 14 missed for inclusion, and ten were enrolled. There was increased 24-hr survival (80% vs. 30%, odds ratio 9.33, 95% confidence interval 1.51-57.65) in arginine vasopressin patients. There was no significant difference in return of spontaneous circulation, survival to hospital discharge, or favorable neurologic status at discharge. CONCLUSIONS: These pilot data provide support for a larger randomized controlled trial of arginine vasopressin therapy during cardiopulmonary resuscitation for in-hospital pediatric cardiac arrest. Copyright © 2012 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Kolar J.C.,Medical City Childrens Hospital |
Salter E.M.,University of Texas at Dallas |
Weinberg S.M.,University of Pittsburgh
Journal of Craniofacial Surgery | Year: 2010
Although clinical descriptions of altered calvarial shape in isolated sagittal synostosis abound in the literature, systematic quantitative assessment of the total morphologic pattern of preoperative craniofacial dysmorphology remains limited in this population. To address this deficit, a retrospective study was undertaken of 256 preoperative patients younger than 6 years with isolated sagittal synostosis who were seen at the Dallas Craniofacial Center. Patients were examined using a battery of 23 anthropometric measurements of the head and face, from which 10 proportion indices were calculated. The measurements and proportions for each patient were compared with sex- and age-matched norms and converted to standard (Z) scores. The pooled data for each variable were analyzed using 1-sample t-tests. The patients were then separated into 2 age groups-younger than 6 months (n = 162) and 6 months or older (n = 94)-and compared via 2-sample t-tests to examine age-related differences. To further elucidate craniofacial growth patterns, standardized anthropometric measures were then correlated against age. Results indicated that the head was enlarged and elongated with compensatory transverse growth of the anterior cranial vault and reduction in the height of vertex. The face was enlarged, especially along the sagittal axis. The head and face were significantly larger relative to age in children younger than 6 months and show a general decrease in size relative to age in all dimensions except cranial length. The data indicate a complex pattern of dysmorphology, which involves the entire craniofacial complex, not just the cranial vault. Copyright © 2010 by Mutaz B. Habal, MD.
Jayaram N.,Saint Lukes Mid America Heart Institute |
Jayaram N.,Childrens Mercy Hospitals and Clinics |
Nadkarni V.,Children's Hospital of Philadelphia |
Berg R.A.,Children's Hospital of Philadelphia |
And 3 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2014
Background-Although survival after in-hospital cardiac arrest is likely to vary among hospitals caring for children, validated methods to risk-standardize pediatric survival rates across sites do not currently exist. Methods and Results-From 2006 to 2010, within the American Heart Association's Get With the Guidelines-Resuscitation registry for in-hospital cardiac arrest, we identified 1551 cardiac arrests in children (<18 years). Using multivariable hierarchical logistic regression, we developed and validated a model to predict survival to hospital discharge and calculated risk-standardized rates of cardiac arrest survival for hospitals with a minimum of 10 pediatric cardiac arrest cases. A total of 13 patient-level predictors were identified: age, sex, cardiac arrest rhythm, location of arrest, mechanical ventilation, acute nonstroke neurological event, major trauma, hypotension, metabolic or electrolyte abnormalities, renal insufficiency, sepsis, illness category, and need for intravenous vasoactive agents prior to the arrest. The model had good discrimination (C-statistic of 0.71), confirmed by bootstrap validation (validation C-statistic of 0.69). Among 30 hospitals with =10 cardiac arrests, unadjusted hospital survival rates varied considerably (median, 37%; interquartile range, 24- 42%; range, 0-61%). After risk-standardization, the range of hospital survival rates narrowed (median, 37%; interquartile range, 33-38%; range, 29-48%), but variation in survival persisted. Conclusions-Using a national registry, we developed and validated a model to predict survival after in-hospital cardiac arrest in children. After risk-standardization, significant variation in survival rates across hospitals remained. Leveraging these models, future studies can identify best practices at high-performing hospitals to improve survival outcomes for pediatric cardiac arrest. © 2014 American Heart Association, Inc.
Raymond T.T.,Medical City Childrens Hospital |
Sales G.,Children's Medical Center Dallas |
Morris M.C.,Childrens Hospital of New York Presbyterian
Pediatrics | Year: 2010
OBJECTIVE: When prospective informed consent is not feasible, clinical research that presents more than minimal risk can proceed only with an exception from informed consent. Our objectives were (1) to describe the inhospital community consultation and public disclosure process for a clinical trial and (2) to evaluate our inhospital public disclosure process. METHODS: Community consultation included parents, providers, and administrators in a PICU via focus groups, conferences, and other methods. Public disclosure consisted of a brochure and a poster in all PICU waiting rooms. These materials described risks and benefits of the trial, that no consent would be sought, howto "opt out," and howto provide feedback. A verbal questionnaire was administered to parents of potential patients during the trial to evaluate the public disclosure process. RESULTS: Eighty-one percent of 93 parents were aware of the ongoing trial. Seventy-six of 93 remembered seeing the brochure; of these, 26% did not read, 39% read quickly, and 35% read carefully. Thirty-seven of 93 parents remembered seeing the poster; of these, 51% did not read, 32% read quickly, and 17% read carefully. Sixty-seven percent reported that they would want to participate in the study, 9% would not, and 24% were undecided. Of the 7 parents who did not want to participate, 3 had opted out and 4 were unaware that they could opt out. CONCLUSIONS: Parents endorsed resuscitation research with an exception from informed consent. Public disclosure yielded >80% parental awareness. Efforts should be made to ensure awareness of the ability to opt out.
Gerrard M.,Sheffield Childrens Hospital |
Waxman I.M.,Columbia University |
Sposto R.,University of Southern California |
Auperin A.,CNRS Gustave Roussy Institute |
And 8 more authors.
Blood | Year: 2013
Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/ Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 x the upper limit of normal, 23:19. Six MLBL patients (14%) had < a 20% response to initial COP (cyclophosphamide, vincristine, and prednisone) therapy. Central pathology revealed approximately 50% with classical features of primary MLBL. Five-year event-free survival for the stage III MLBL and non-MLBL DLBCL groups was 66% (95% confidence interval [CI], 49%-78%) and 85% (95% CI, 71%-92%), respectively (P < .001; 14%). The 5-year overall survival in the 42 MLBL patients was 73% (95% CI, 56%-84%).We conclude that MLBL in adolescent patients is associated with significantly inferior event-free survival compared with stage III non-MLBL DLBCL and can be of multiple histologies. Alternate treatment strategies should be investigated in the future taking into account both adult MLBL approaches and more recent biologic findings in adult MLBL. © 2013 by The American Society of Hematology.
Galardy P.J.,Mayo Medical School |
Hochberg J.,New York Medical College |
Perkins S.L.,University of Utah |
Harrison L.,New York Medical College |
And 2 more authors.
British Journal of Haematology | Year: 2013
Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent complications in newly diagnosed children with advanced mature B cell non-Hodgkin lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid reduction of uric acid in paediatric patients at risk for TLS. However, the safety and efficacy of rasburicase for the treatment or or prevention of TLS has not been prospectively evaluated. Children with newly diagnosed stage III-IV, bone marrow+ and/or central nervous system+ mature B-NHL received hydration and rasburicase prior to cytoreductive therapy. Rasburicase was safe and well-tolerated and there were no grade III-IV toxicities probably or directly related to rasburicase. Patients with an initial lactate dehydrogenase ≥2× upper limit of normal had a significantly elevated uric acid level (P = 0·005), increased incidence of TLS (P-0·005) and lower glomerular filtration rate (GFR; P < 0·001). Following rasburicase, there was only a 9% and 5% incidence of LTLS and CTLS, respectively. Furthermore, there was a significant improvement in estimated GFR from Day 0 to Day 7 following rasburicase (P = 0·0007) and only 1·3% of patients required new onset renal assisted support after rasburicase administration. A TLS strategy incorporating rasburicase prior to cytoreductive chemotherapy proved safe and effective in preventing new onset renal failure and was associated with a significant improvement in GFR. © 2013 John Wiley & Sons Ltd.
Niimi K.S.,Medical City Childrens Hospital |
Fanning J.J.,Pediatric Acute Care Associates
Journal of Extra-Corporeal Technology | Year: 2014
Acquired antithrombin (AT) deficiency has been associated with patients on extracorporeal membrane oxygenation (ECMO) as a result of hemodilution, blood coagulation activation, and the use of heparin. Replacement of AT has been typically utilized through the use of fresh-frozen plasma or AT concentrate. Antithrombin alfa (ATryn®) is a recombinant form of AT (rAT) with an identical amino acid sequence as that of plasma-derived antithrombin. The primary objective of this study is to examine the relationship of rAT dose to measured plasma antithrombin activity in a small series of patients who received rAT while on ECMO. A retrospective chart review was performed of all patients at Medical City Children's Hospital who received ATryn while supported on ECMO between December 2011 and April 2012. Five patients were identified and the patients' weight, bolus dose of ATryn, drip rate of ATryn, and AT blood levels were collected for analysis. The median age of these patients was 1 month (range, 1 day to 3.75 years). Because no dosing guidelines exist for pediatric ECMO, a starting dose of ATryn was chosen based on the manufacturer's labeled indication (prevention of thromboembolic events in patients with AT hereditary deficiency). The median dose of rAT was 368 IU/kg/day (range, 104-520 IU/kg/day) to obtain AT activity level of 80-120%. The average time to reach the targeted AT activity level (80-120%) was 12.7 hours (range, 11-17 hours). Our findings suggest that the published ATryn dose may be inadequate to reach desired AT activity concentrations for pediatric patients on ECMO. Difference in patient population, use of extracorporeal circuits, and the use of heparin are likely explanations for this finding. We would also recommend frequent checking of AT levels while delivering this drug because making timely adjustments is necessary for achieving and maintaining the target AT activity level.
Wasserman R.L.,Medical City Childrens Hospital |
Melamed I.,e International Research Centers |
Nelson R.P.,Indiana University |
Knutsen A.P.,University Institute of Health Sciences |
And 4 more authors.
Clinical Pharmacokinetics | Year: 2011
Background and Objectives: Immunoglobulin replacement is a standard therapy for patients with primary immunodeficiencies. Subcutaneous administration of immunoglobulin offers more constant IgG levels than intravenous administration and simplifies administration for some patients. Use of L-proline as an excipient contributes to the stability of highly concentrated IgG preparations. The aims of the present study were to evaluate the pharmacokinetics of IgPro20 (Hizentra®), a new 20%subcutaneous IgG solution, and compare the area under the serum concentration-time curve (AUC) with that of a similar intravenous 10% IgG solution (IgPro10; Privigen®). At the request of the US FDA, an algorithm for determining IgG trough level ratios (TLRs) was developed in order to provide physicians with a practical tool for monitoring doses during steady-state IgPro20 therapy. Methods: This was a prospective, open-label, multicentre, single-arm, phase III clinical trial conducted in the US. The study was performed in a primary-care setting. Eligible patients were males or females aged 6-75 years with a primary immunodeficiency (common variable immunodeficiency or X-linked agammaglobulinaemia) who had received regular treatment with IgPro10 for at least 3 months prior to entering this study and had achieved serum trough concentration (Ctrough) values ‡5g/L. IgPro20 was administered subcutaneously once weekly at initial doses equivalent to 130% of patients' previous doses, based on the results obtained in a Vivaglobin® study and due to an FDA request. After runin, each patient's dose was adjusted to achieve an AUC comparable to that achieved with IgPro10 administered intravenously. Results: Eighteen patients completed the study. Mean IgPro20 : IgPro10 dose ratio (dose adjustment coefficient) was 1.53 (range 1.26-1.87). The resulting mean AUCs were 105.6 g®day/L for IgPro20 versus 103.2 ®day/L for IgPro10 (geometric mean ratio 1.002; lower one-sided 95% confidence limit [CL] 0.951). Thus, the primary endpoint of the study was met, as this result exceeded the pre-specified criterion of the lower one-sided 95% CL of ≥0.8 for non-inferiority. At these AUCs, which were considered equivalent, the mean IgPro20 : IgPro10 TLR, determined by the developed algorithm, was 1.29 (range 1.18-1.73). Titres of specific antibodies tested were well above respective product specifications, suggesting that protection against infection would be effective. Conclusion: Steady-state AUCs with subcutaneous IgPro20 and intravenous IgPro10 were equivalent. Mean dose adjustment coefficient and mean TLR can be used for initial dose conversion without risk of underprotection but vary too widely to be considered measures of equivalence. © 2011 Adis Data Information BV. All rights reserved.
Kolar J.C.,Medical City Childrens Hospital
Journal of Craniofacial Surgery | Year: 2011
Objective: To compare our data with recent studies that have suggested a change in the distribution of the forms of nonsyndromal synostosis in the clinical population, we conducted a retrospective analysis of the diagnoses of children with isolated synostosis examined at a large craniofacial center between 1987 and 2009. This also included the range of nonsyndromal multisuture synostoses. Design: A retrospective chart review of all preoperative patients with nonsyndromal synostosis seen between 1987 and 2009 was performed. Only patients with a radiologically confirmed craniosynostosis were included. Data on patients' sex and laterality in unilateral synostoses were collected. Two temporally distinct subgroups (1996-2000 and 2005-2009) were defined to evaluate changes in the distribution of the most common forms of isolated craniosynostosis using the Fisher exact test. Results: A total of 690 patients met the inclusion criteria. The largest group of patients had sagittal synostosis, with metopic synostosis as the second most common diagnosis, representing one-fourth of the patients, followed closely by unilateral coronal synostosis. All other synostoses encompassed one-eighth of the group. Patients with sagittal or metopic synostosis were overwhelmingly male, whereas those with unilateral coronal synostosis were predominantly female. Patients with unilateral synostoses were affected primarily at the right suture. Conclusions: Data from our patients indicate a much higher incidence of metopic synostosis than has been reported in the traditional clinical literature but is consistent with recent published data. The causes of this are unclear at this point, but the Fisher exact test excludes an increase in the frequency of metopic synostosis. Improved clinical diagnosis or ascertainment bias remains a possibility. Further research is needed to elucidate the answer to this question. Our data also indicate the occurrence of a small number of rare multisuture synostoses of unknown origin. Copyright © 2011 by Mutaz B. Habal, MD.