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Bronicki R.A.,Childrens Hospital of Orange County | Bronicki R.A.,University of California at Los Angeles
Pediatric Critical Care Medicine | Year: 2011

Objective: To review the principles of venous oximetry; the physiology of oxygen transport balance; clinical studies on venous oximetry; and the assignment of a classification of recommendation and level of evidence. Data Source: A MEDLINE-based literature source. Conclusion: One of the tenets of critical care medicine is to provide a timely and accurate assessment of tissue oxygenation. In conjunction with other monitoring modalities, the routine deployment of central venous catheters readily enables the clinician to complete this task. Copyright © 2011 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.


Sender L.,University of California at Irvine | Zabokrtsky K.B.,Childrens Hospital of Orange County
Nature Reviews Clinical Oncology | Year: 2015

Adolescent and young adult (AYA) patients with cancer are a unique category of patients who, depending on age at time of diagnosis, might receive treatment from oncologists specializing either in the treatment of children or adults. In the USA, AYA oncology generally encompasses patients 15-39 years of age. AYA patients with cancer typically present with diseases that span the spectrum from 'paediatric' cancers (such as acute lymphoblastic leukaemia [ALL] and brain tumours) to 'adult' tumours (such as breast cancer and melanoma), as well as cancers that are largely unique to their age group (such as testicular cancer and bone tumours). Research indicates that outcomes of AYA patients with cancer are influenced not only by the treatment provided, but also by factors related to 'host' biology. In addition to the potential biological and cancer-specific differences between AYAs and other patients with cancer, AYA patients also often have disparate access to clinical trials and suffer from a lack of age-appropriate psychosocial support services and health services, which might influence survival as well as overall quality of life. In this Review, these issues are discussed, with a focus on two types of AYA cancer-ALL and melanoma-highlighting findings arising from the use of emerging technologies, such as whole-genome sequencing. © 2015 Macmillan Publishers Limited.


Factor XIII (FXIII) deficiency is an extremely rare congenital condition that is associated with a high risk of potentially life-threatening intracranial hemorrhage, poor wound healing, spontaneous abortion, and a life-long tendency towards spontaneous bleeding and severe bleeding after trauma or surgery. Routine prophylaxis with FXIII concentrate is recommended in all individuals with FXIII levels <1 IU/dL from the time of diagnosis, and in some severely affected patients with FXIII levels of 1-4 IU/dL. Fibrogammin® P is a highly purified, pasteurized, plasma-derived concentrate that has been available in Europe and other countries since 1993 and has recently been approved as Corifact™ in the USA. To support the US registration of Corifact™, a 52-week, prospective, multicenter, open-label study was conducted in 41 patients (mean age 19 years; range <1-42 years) with congenital FXIII deficiency. Corifact™/Fibrogammin® P was administered intravenously at an initial dose of 40 IU/kg every 4 weeks, with dosing adjusted to maintain a trough FXIII activity level of 5-20%. No spontaneous bleeding episodes requiring FXIII treatment were reported during the study (primary endpoint). Preoperative use of Corifact™/Fibrogammin® P successfully prevented postoperative bleeding in two surgeries. Corifact™/Fibrogammin® P was well tolerated during a total exposure of ∼455 subject-months. No patient withdrew from treatment, and there were no reports of virus transmission or thromboembolism-related events. This study adds to the wealth of data gained from clinical trials and almost 20 years of clinical use confirming that Corifact™/Fibrogammin® P is an effective and well-tolerated prophylactic treatment for congenital FXIII deficiency. © 2012 Elsevier Ltd.


Kunicki T.J.,Scripps Research Institute | Nugent D.J.,Childrens Hospital of Orange County
Blood | Year: 2010

Genetic and environmental factors contribute to a substantial variation in platelet function seen among normal persons. Candidate gene association studies represent a valiant effort to define the genetic component in an era where genetic tools were limited, but the single nucleotide polymorphisms identified in those studies need to be validated by more objective, comprehensive approaches, such as genome-wide association studies (GWASs) of quantitative functional traits in much larger cohorts of more carefully selected normal subjects. During the past year, platelet count and mean platelet volume, which indirectly affect platelet function, were the subjects of GWAS. The majority of the GWAS signals were located to noncoding regions, a consistent outcome of all GWAS to date, suggesting a major role for mechanisms that alter phenotype at the level of transcription or posttranscriptional modifications. Of 15 quantitative trait loci associated with mean platelet volume and platelet count, one located at 12q24 is also a risk locus for coronary artery disease. In most cases, the effect sizes of individual quantitative trait loci are admittedly small, but the results of these studies have led to new insight into regulators of hematopoiesis and megakaryopoiesis that would otherwise be unapparent and difficult to define. © 2010 by The American Society of Hematology.


Mulgrew K.W.,Childrens Hospital of Orange County
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2011

Childhood obesity is a serious health concern, especially in rural areas. Its management involves in-depth lifestyle and psychosocial assessment as well as patient-centered counseling. Telemedicine has increased the ability of patients in rural areas to obtain subspecialty consultations. Our objective was to determine whether a significant difference in quality of care, as measured by parent satisfaction, existed between consultations for childhood obesity delivered face to face and by telemedicine. We performed a pilot study in which questionnaires were distributed to parents of children under 12 years of age who had received consultations for childhood obesity at a university-affiliated pediatric weight management clinic, either face to face or by telemedicine. The questionnaires assessed various aspects of quality of care and patient-centered care including consulting providers' listening skills, ease of understanding instructions delivered to patients and their families, and the comfort level of parents in discussing health concerns. A total of 54 surveys were collected (22 telemedicine, 32 face-to-face). Of those, 25 (10 telemedicine, 15 face-to-face) met inclusion criteria. There was no difference in overall parent satisfaction with consultations between the two groups. However, parents rated telemedicine visits slightly lower than face-to-face visits when asked whether the provider explained things about the child's health in a way that was easy to understand (p=0.01). All parents of children who had received care via telemedicine said that they would participate in telemedicine consultations again. In our pilot, there was no significant difference in parent satisfaction between consultations for childhood obesity delivered face to face and by telemedicine. Therefore, preliminary evidence suggests that childhood obesity care delivered by telemedicine can improve access to quality patient-centered care in underserved rural areas. An important limitation is our sample size, which was not large enough to determine whether satisfaction in the telemedicine group was greater than in the face-to-face group.


Andolina J.R.,University of Rochester | Neudorf S.M.,Childrens Hospital of Orange County | Corey S.J.,Northwestern University
Blood | Year: 2012

Chronic myeloid leukemia (CML) is composed of 3% of pediatric leukemias, making evidence-based recommendations difficult. Imatinib has revolutionized the treatment for adult CML by eliminating allogeneic stem cell transplantation for almost all patients in chronic phase. Shown effective in pediatric CML, imatinib and successive tyrosine kinase inhibitors (TKI) have provided more therapeutic options. Because stem cell transplantation has been better tolerated in children and adolescents, the decision to treat by either TKI or transplantation is controversial. We present a recent case of a 12-month-old boy diagnosed with BCR-ABL + CML to highlight the controversies in treatment recommendations. We review the pediatric stem cell transplantation outcomes as well as the pediatric experience with imatinib and other TKIs. Finally, we compare the side effects as well as costs associated with allogeneic stem cell transplantation versus TKI therapy. We recommend that frontline therapy for pediatric CMLin chronic phase is TKI therapy without transplantation. Patients in accelerated or blast crisis or who fail to reach landmarks on TKIs either because of intolerance or resistance should pursue stem cell transplantation. Although we recommend adopting adult clinical experience to guide therapeutic decisionmaking, the issues of infant CML, drug formulation, pharmacokinetics, and adolescent compliance merit clinical investigation. © 2012 by The American Society of Hematology.


The preparticipation screening for athlete participation in sports typically entails a comprehensive medical and family history and a complete physical examination. A 12-lead electrocardiogram (ECG) can increase the likelihood of detecting cardiac diagnoses such as hypertrophic cardiomyopathy, but this diagnostic test as part of the screening process has engendered considerable controversy. The pro position is supported by argument that international screening protocols support its use, positive diagnosis has multiple benefits, history and physical examination are inadequate, primary prevention is essential, and the cost effectiveness is justified. Although the aforementioned myriad of justifications for routine ECG screening of young athletes can be persuasive, several valid contentions oppose supporting such a policy, namely, that the sudden death incidence is very (too) low, the ECG screening will be too costly, the false-positive rate is too high, resources will be allocated away from other diseases, and manpower is insufficient for its execution. Clinicians, including pediatric cardiologists, have an understandable proclivity for avoiding this prodigious national endeavor. The controversy, however, should not be focused on whether an inexpensive, noninvasive test such as an ECG should be mandated but should instead be directed at just how these tests for young athletes can be performed in the clinical imbroglio of these disease states (with variable genetic penetrance and phenotypic expression) with concomitant fiscal accountability and logistical expediency in this era of economic restraint. This monumental endeavor in any city or region requires two crucial elements well known to business scholars: implementation and execution. The eventual solution for the screening ECG dilemma requires a truly innovative and systematic approach that will liberate us from inadequate conventional solutions. Artificial intelligence, specifically the process termed "machine learning" and "neural networking," involves complex algorithms that allow computers to improve the decision-making process based on repeated input of empirical data (e.g., databases and ECGs). These elements all can be improved with a national database, evidence-based medicine, and in the near future, innovation that entails a Kurzweilian artificial intelligence infrastructure with machine learning and neural networking that will construct the ultimate clinical decision-making algorithm. © Springer Science+Business Media, LLC 2012.


Shi Y.,University of California at Irvine | Aledia A.S.,University of California at Irvine | Galant S.P.,University of California at Irvine | Galant S.P.,Childrens Hospital of Orange County | George S.C.,University of California at Irvine
Journal of Allergy and Clinical Immunology | Year: 2013

Background: We previously showed that impulse oscillometry (IOS) indices of peripheral airway function are associated with asthma control in children. However, little data exist on whether dysfunction in the peripheral airways can predict loss of asthma control. Objective: We sought to determine the utility of peripheral airway impairment, as measured by IOS, in predicting loss of asthma control in children. Methods: Fifty-four children (age, 7-17 years) with controlled asthma were enrolled in the study. Spirometric and IOS indices of airway function were obtained at baseline and at a follow-up visit 8 to 12 weeks later. Physicians who were blinded to the IOS measurements assessed asthma control (National Asthma Education and Prevention Program guidelines) on both visits and prescribed no medication change between visits. Results: Thirty-eight (70%) patients maintained asthma control between 2 visits (group C-C), and 16 patients had asthma that became uncontrolled on the follow-up visit (group C-UC). There was no difference in baseline spirometric results between the C-C and C-UC groups, except for FEV1/forced vital capacity ratio (86% vs 82%, respectively; P < .01). Baseline IOS results, including resistance of the respiratory system at 5 Hz (R5; 6.4 vs 4.3 cm H2O · L -1 · s), frequency dependence of resistance (difference of R5 and resistance of the respiratory system at 20 Hz [R5-20]; 2.0 vs 0.7 cm H 2O · L-1 · s), and reactance area (13.1 vs 4.1 cm H2O · L-1), of group C-UC were significantly higher than those of group C-C (P < .01). Receiver operating characteristic analysis showed baseline R5-20 and reactance area effectively predicted asthma control status at the follow-up visit (area under the curve, 0.91 and 0.90). Conclusion: Children with controlled asthma who have increased peripheral airway IOS indices are at risk of losing asthma control. © 2012 American Academy of Allergy, Asthma & Immunology.


Patent
Childrens Hospital Of Orange County | Date: 2013-08-22

The present invention includes a method and device for the isolation of lymphocytes, particularly splenic lymphocytes, for administration to patients. In particular for patients undergoing a splenectomy, administration of splenic lymphocytes may increase a patients immunity and reduce the likelihood of post-splenectomy infections and other complications.


Patent
Childrens Hospital Of Orange County | Date: 2016-09-26

A method of potentiating an immune response against a cancer, non-cancerous tumor or both in a patient is provided. The method includes administering splenocytes harvested from all or a part of a patients spleen. The splenocytes can be administered in combination with a biological response modifier to potentiate an immune response against a cancer, non-cancerous tumor or both in a patient.

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