Dissertations / Theses on the topic 'Pediatric'

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O objetivo deste estudo é conhecer, analisar e refletir sobre como vem ocorrendo o Ensino da Pediatria na Graduação das Escolas Médicas do Rio de Janeiro, delineando algumas características dos docentes responsáveis por este ensino e correlacionando os dados obtidos com a literatura pertinente. A investigação destas questões se deu a partir de 15 Coordenadores, responsáveis pelo Ensino da Pediatria nos 16 Cursos de Graduação em Medicina em funcionamento no Estado. Optamos por desenvolver uma pesquisa de caráter exploratório, descritiva, realizada através de um estudo do tipo corte transversal e construída a partir de abordagem quantitativa e qualitativa. Os dados foram obtidos a partir de entrevistas semi-estruturadas e de documentos institucionais . Na organização do ensino entre os cursos investigados, observa-se que a inserção da pediatria, os cenários de aprendizagem utilizados, os critérios para seleção dos conteúdos divergem pouco entre si. As dificuldades mais referidas estão afeitas à infraestrutura e ao projeto pedagógico do curso, principalmente a questão da integração intra e inter disciplinas, a articulação docente assistencial e o sistema de avaliação que, para a maioria, encontra-se focado no processo avaliativo do aluno. Discutem-se alguns traços do perfil docente, além de se verificar que os atributos considerados mais significativos para o exercício da docência de pediatria estão baseados na perspectiva humanística, no gostar do que faz, no domínio do assunto, na capacidade de ensinar, na dedicação e na disponibilidade do docente. O percentual de titulação acadêmica encontrado revela a busca docente e institucional pela capacitação profissional. Acreditamos, com este estudo, estar contribuindo para a melhor compreensão do ensino da pediatria como parte fundamental para a formação geral do médico na graduação além de incentivar a busca de novos caminhos que apontem para a melhor qualidade e aperfeiçoamento deste ensino.
The aim of this study is understand, analyze and reflect about how the Pediatric’s Teaching in Undergraduated in Medical Schools of Rio de Janeiro, has been occuring, outlining some characteristics of the responsible professors for this teaching and correlating the obtained data with the pertinent literature. The research of this question was given to 15 coordinators, responsible for Pediatrics teaching at the 16 open undergraduated courses in the state. We opted to develop a research of investigative and descriptive character, carried through a crossover study and built from a quantitative and qualitative approach. The dada were obtained from semi-structured interviews and from institucional documents. Concerning the teaching organization among the investigated courses, it was observed that the insertion of pediatrics, the utilized scenes of learning, the criteria for the selection of the contents diverge a little bit between each other. The majority mentioned difficulties are related to the infrastructure and the pedagogical project of the course, mainly the intra and inter discipline integration questions, the assistencial teaching articulation and the evaluation system that, for the majority, has been focused in the scholar’s evaluation process. Some traces of the teaching profile have been debated, besides it has been verified that the attributes considered more significant for the exercise of Pediatrics teaching are based on the humanistic perspective, in being pleased to what one makes, in the domain of the subject, in the capacity for teaching, in the devotion and availability of the professor. The percentage of titled academic found, reveals the teaching and the institucional search for the professional qualification. We believe, with this study, to be contributing for a better understanding of the pediatrics teaching as a fundamental part for the doctor’s general formation in the undergraduated, besides stimulating the search of new ways that lead to a better quality and improvement of this teaching.
BV UNIFESP: Teses e dissertações

The purpose of this scholarly project was to examine the use of a high-fidelity simulation workshop to improve accuracy with pediatric dosage calculations among practicing pediatric nurses. The NLN Jeffries Simulation Theory provided a framework for this descriptive quantitative project. A convenience sample of 15 pediatric nurses completed a 10-question pediatric dosage calculation pre-test, a high-fidelity simulation workshop, a 10-question pediatric dosage calculation post-test, and a post-simulation evaluation survey. In addition, a one-month follow-up 10-question pediatric dosage calculation post-test and a one-month follow-up post- high-fidelity simulation workshop survey were administered via Survey Monkey^©, in which 12 pediatric nurse participants completed. Pre-tests and post-tests were analyzed for central tendency and a t-test analysis was performed for statistical significance. Results revealed statistical significance between pre-test and post-test as well as statistical significance between post-test and one-month follow-up post-test. The Likert scale post-simulation survey and one month post-simulation survey were analyzed for central tendency. The results from the post simulation survey and one-month follow-up survey revealed the participants agreed to strongly agreed the high-fidelity simulation workshop impacted their proficiency and accuracy in calculating pediatric dosages. The findings from this project provides insights into the use of high-fidelity simulation as a continuing education tool for the practicing pediatric nurse in relation to pediatric medication efficacy.

Now in its Second Edition, this text focuses exclusively on the management of hospitalized pediatric patients from admission to discharge. It is an excellent resource for residency programs, hospitalist fellowships, and continuing education for physicians whose practice includes the management of hospitalized newborns and children. Because pediatric hospital care is provided by a wide variety of healthcare professionals and in many different hospital settings, this text provides a framework for unified management and effective and efficient care. This edition includes new sections on emergency medicine and psychiatric hospitalization and expanded coverage of management of children with complex and chronic conditions.

The delivery process of the intravenous (IV) medication, one of the activities of greater responsibility of the nursing team, has a high incidence in child care in urgent and emergency situation. This process is considered highly complex and when not planned, controlled and monitored through indicators is exposed to unpredictable results affecting the quality of care. The objective was to evaluate the nursing practice in drug administration in child trough IV. Exploratory, descriptive, observational, quantitative study. It was developed in the urgency and emergency department in a pediatric referral hospital of the municipal sphere of Fortaleza. The study population consisted of 69 nurses whom participated in the drug administration via IV process that was in work schedules during the study period in the investigated unit. The sample of professionals was composed by 36 licensed practice nurses and 2 nurses. For the number of observations, it was considered the calculation for finite population with a total of 327 observations of intravenous medication delivery process. Interviews were carried out for data collection with the nursing staff and systematic observation of drug delivery process in children via IV. For data collection interviews were performed with the nursing staff and systematic observation by IV drug delivery process in children, considering seven stages, namely: medical prescription reading, hand hygiene, preparation of material and medication , guidance on the procedure, puncture technique and administration of the drug. Such steps have the total 47 shares. The data was stored in a database produced on the Windows Excel 2010 and analyzed according to the literature. The study was approved by the Ethics Committee under CAAE protocol 34651314.7.0000.5054. It was found that in 15% of the observations nursing professionals did not understand the prescription due to illegible handwriting professional. In 78.0% of the time there was no hand hygiene. It was found that all professionals used personal protective equipment (cap and mask), but none used gloves. Among the 327 observations included: peripheral intravenous device most commonly used was the scalp 21 (63.3%); selection of dorsal hand veins arc (83.9%); success on the first attempt of venipuncture (82.6%); explains the procedure for child and /or guardian (5.5%); calms the child (82.6%); performs antisepsis of the skin at the site to be punctured with a swab with 70% alcohol (100%); awaits antiseptic evaporation to then continue the procedure (45.6%); proper disposal of the materials used during the procedure (89.3%); checks the prescription immediately after drug administration (86.8%). It was found unsatisfactory performance in 23 actions by IV drug administration process. Therefore, we suggest the development of training for nursing professionals about medication delivery process.
O processo de administraÃÃo de medicamento por via intravenosa (IV), uma das atividades mais importante da equipe de Enfermagem, possui alta incidÃncia na assistÃncia à crianÃa em situaÃÃo de urgÃncia e emergÃncia. Tal processo à considerado de alta complexidade e, quando nÃo planejado, controlado e monitorado por meio de indicadores, fica exposto à imprevisibilidade de seus resultados, interferindo na qualidade da assistÃncia. Objetivou-se avaliar a prÃtica de enfermagem no processo de administraÃÃo de medicamento por via IV na crianÃa. Trata-se de um estudo exploratÃrio, descritivo, observacional, de natureza quantitativa, desenvolvido no setor de urgÃncia e emergÃncia de um hospital pediÃtrico de referÃncia da esfera municipal de Fortaleza-CE. A populaÃÃo do estudo foi constituÃda por 69 profissionais de enfermagem que participaram do processo de administraÃÃo de medicamento pela via IV e que estavam nas escalas de trabalho durante o perÃodo do estudo na unidade investigada. A amostra dos profissionais foi composta por 36 tÃcnicos de enfermagem e 2 enfermeiros. Para o nÃmero de observaÃÃes, considerou-se o cÃlculo para populaÃÃo finita, com um total de 327 observaÃÃes do processo de administraÃÃo de medicamento por via IV. Para a coleta de dados realizou-se entrevista com a equipe de enfermagem e observaÃÃo sistemÃtica do processo de administraÃÃo de medicamento por via IV na crianÃa, considerando sete etapas, quais sejam: leitura da prescriÃÃo mÃdica, higienizaÃÃo das mÃos, preparo do material e medicaÃÃo, orientaÃÃo acerca do procedimento, tÃcnica de punÃÃo e administraÃÃo do medicamento. Tais etapas possuem ao total 47 aÃÃes. Os dados foram armazenados em um banco de dados produzidos no Excel do Windows 2010, analisados estatisticamente e de acordo com a literatura pertinente. O estudo foi aprovado pelo Comità de Ãtica sob parecer N0 805.953. Constatou-se que em 15% das observaÃÃes o profissional de enfermagem nÃo compreendeu a prescriÃÃo mÃdica devido à letra ilegÃvel do profissional. Em 78,0% das observaÃÃes nÃo houve a higienizaÃÃo das mÃos. Identificou-se que todos os profissionais utilizaram equipamento de proteÃÃo individual (gorro e mÃscara), entretanto nenhum utilizou luvas. Dentre as 327 observaÃÃes destacaram-se como dispositivo intravenoso perifÃrico mais utilizado o scalp n 21 (63,3%); escolha das veias do arco dorsal da mÃo (83,9%); Ãxito na primeira tentativa da punÃÃo venosa (82,6%); orientaÃÃo sobre o procedimento para crianÃa e/ou responsÃvel (5,5%); acalma a crianÃa (82,6%); realizaÃÃo de antissepsia da pele no local a ser puncionado com algodÃo embebido com Ãlcool a 70% (100%); aguarda a evaporaÃÃo do antissÃptico para em seguida dar prosseguimento ao procedimento (45,6%); descarte adequado dos materiais utilizados durante o procedimento (89,3%); checou a prescriÃÃo imediatamente apÃs a administraÃÃo do medicamento (86,8%). Concluiu-se desempenho insatisfatÃrio em 23 aÃÃes do processo de administraÃÃo de medicamento por via IV. Portanto, sugere-se o desenvolvimento de capacitaÃÃo para os profissionais de enfermagem acerca do processo de administraÃÃo de medicamento.

Global explosion of mobile technology has engendered a new instrument to address the challenges in public health and to revolutionize the paradigm of healthcare access and delivery system. Today mobile phone coverage has increased to a significant 90% of the world’s population. The rising ubiquity and infiltration of mobile phones has kindled the beginning of a new era in healthcare, mobile health (mHealth). mHealth is the amalgamation of mobile telecommunication and multimedia into an on the go mobile health care delivery system.

Pediatric Pal is a mHealth application targeted to care for children and help build a healthier tomorrow for them. Pediatric Pal is designed to be the “Drive Thru” for the pediatric healthcare system. The mhealth app focuses on giving patients access to a highly sophisticated medical diagnosis tool. By using latest searching technologies, the system can take a pattern of symptoms in everyday language and instantly compute from our vast database. The app design and development will be outsourced to a web design Hyperlink solutions agency. Database for the app will be maintained in house and test runs will be run within the house.

The main source of revenue for the app will be from user subscription and upfront cash payment. Premium downloads will bring in the extra revenue as well.

Pediatric Pal puts world’s medical knowledge at the patients fingertips and enables them to make sense of your symptoms. It will change the way patients speak to their doctor forever.

Thesis (Ph. D.)--Henry W. Bloch School of Business and Public Administration and Dept. of Economics. University of Missouri--Kansas City, 2007.
"A dissertation in public affairs and administration and education." Advisor: Robert D. Herman. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed July 30, 2008 Includes bibliographical references (leaves 86-90). Online version of the print edition.

Background: In recent years, the Accreditation Council for Graduate Medical Education (ACGME), and the Ambulatory Pediatric Association (APA) have developed detailed resident learning objectives and competencies. Maintaining adequate documentation that residents are fulfilling these objectives and competencies is a challenge. Objectives: To develop and evaluate use of an internet based curriculum, EPIC (East Tennessee Pediatric Internet Curriculum) to facilitate teaching and evaluation of the core competencies. Methods: Goals and content for the site were developed based on literature review and input from a pediatric internet committee. Resident internet-based learning is being evaluated using pre- and post- surveys over a six month period. Results: EPIC is a central location for residents to access information, including announcements, phone lists, and scheduling information. Educational content is organized around the six core competencies for resident education. For example, “Medical Knowledge”consists of a portfolio system developed for the ambulatory clinic. Portfolios include a checklist of pertinent information to be covered during a patient encounter and a related downloadable article to enhance resident knowledge. The section also includes links to other learning resources. An interactive discussion forum exists to facilitate discourse on medical and residency-related topics. Residents also complete online pre- and post- test questions during every clinical rotation and receive instant feedback on their responses. All 11 residents completed the pre-survey. Frequent or very frequent internet use was reported by 54% of residents to answer specific clinical questions and 45% of residents for general medical learning during the work day. Conclusion: Pediatric residents already utilize the internet to access medical information. EPIC accommodates residents’varying schedules and is a useful adjunct to other teaching and evaluation methods.

Background/Purpose: Healthcare transition is the “purposeful, planned movement of adolescents and young adults with chronic physical and medical conditions from child-centered to adult-oriented health care systems.” The American College of Physicians has partnered with national organizations, including the ACR, to develop guidelines and tools to promote a smooth transition to adult care. We aim to assess current transition practices and beliefs among North American pediatric rheumatology providers and to identify differences from a 2010 provider survey published by Chira et al. Methods: In April 2018, Childhood Arthritis and Rheumatology Research Alliance (CARRA) members received a 25-item online survey about healthcare transition. Got Transition’s Current Assessment of Health Care Transition Activities for Transitioning Youth to Adult Health Care Providers was used to measure clinical transition processes on a scale of 1 (basic) to 4 (comprehensive). Bivariate data analysis was used to compare 2010 and 2018 survey findings. Results: Over half of CARRA members completed the 2018 survey. Participants included pediatric rheumatologists (74%), adult- and pediatric-trained rheumatologists (4%), pediatric rheumatology fellows (18%), and other (4%), including emeritus faculty and mid-level providers. Most belonged to university-affiliated practices (87%) in the U.S. (91%). Providers aim to transfer patients at age 18 (23%) or 21 (33%), but the actual age of transfer is often 21 or older (56%). The most common target age to begin transition planning was 15-17 (49%). Few providers use the ACR transition tools (31%) or have a dedicated transition clinic (23%). Only 17% have a transition policy in place; 63% do not consistently address healthcare transition. Transition outcomes of interest included an adult rheumatology visit within 6 months of the last pediatric visit (80%), adherence to medications and plan of care (78%), continuous insurance coverage (78%), and patient-reported gaps in access to care (76%). When compared to the 2010 survey, improvement was noted in 3 of 12 transition barriers: availability of adult primary care providers, availability of adult rheumatologists, and transition knowledge and skills of pediatric staff (p<0.001). However, more providers cited the close bond among adolescents, parents and pediatric providers as a barrier (Figure 1). Conclusion: This survey of pediatric rheumatology providersdemonstrates some improvement in transition barriers since 2010, though most practices still maintain minimal support for patients and providers around healthcare transition. Further research is needed to understand how to effectively facilitate transition to adult care for young adults with childhood-onset rheumatic diseases.

Background: Dilated Cardiomyopathy (DCM) is the most common functional type of cardiomyopathy in children with significant morbidity and the leading indication for cardiac transplant over 5 years of age. Identification of baseline risk factors for failing medical management by etiologic grouping remain to be elucidated in a large populationbased study. The competing risk for heart death between all-cause mortality and heart transplantation is often overestimated in the literature and may obscure additional novel risk factors associated with poor clinical outcomes. Methods: The National Heart Lung and Blood Institute Pediatric Cardiomyopathy Registry collected longitudinal data from 1731 children with DCM in North America from 1990 to 2007. Composite endpoint (CEP) was the earlier occurrence of death or heart transplant. Univariate and multivariate predictors were identified from demographic and echocardiographic data (expressed as z-scores) collected within 30 days of diagnosis. A competing risk analysis was performed calculating cumulative incidence and identifying novel prognostic factors. All analyses were performed by etiologic group. Results: Multivariate Cox regression identified the highest mortality risk among children with idiopathic disease (N=1192, CEP: 41%) when diagnosed over age 6 years, and with congestive heart failure (CHF) and decreased left ventricular fractional shortening (FS). Risk factors for those with myocarditis (N=272, CEP: 26%) were older age, CHF, and increased left ventricular (LV) end-diastolic dimension (EDD); while for neuromuscular disease (N=139, CEP: 40%), it was a decreased FS and increased EDD. Only univariate predictors were identified for children with familial isolated cardiomyopathy (N=79, CEP: 44%) including: CHF, increased EDD, end-systolic dimension, or LV mass, and decreased FS or ejection fraction), while for children with inborn errors of metabolism (N=43, CEP: 33%) risk factors included: a positive family history of cardiomyopathy or genetic syndromes. The group of children with malformation syndromes (N=6, CEP: 50%) was not large enough to model. Comparison of cause-specific event rates between Kaplan-Meier and cumulative incidence demonstrated an overestimation with the former method. Competing risk multivariate regression showed similar models to those for CEP, with the following exceptions: for neuromuscular disease, an increased EDD had a larger hazard ratio for transplant than for death; for idiopathic disease, an increased EDD was associated with transplant, but not with death, and growth retardation (height-for-age zscore) was associated with death but not transplant. Conclusions: Within etiologic grouping, demographics and echocardiographic values at diagnosis have varying predictive value. Generally, the presence of symptomatic disease in the form of CHF, echocardiographic evidence of more severe DCM, and increased age were indicative of worse outcomes. These results help to validate those from conflicting studies; however, they suggest that etiology modifies the importance of particular factors. Analysis of competing risk provides an alternate interpretation of studies with composite endpoints and assists in the transfer of clinically relevant information. For children with idiopathic and neuromuscular disease, the degree of dilation had a differential effect that has gone unrecognized. The novel finding of reduced stature and its effect on mortality suggests a potential for treatment and mitigation of poor outcomes in idiopathic DCM. Both increased dilation and reduced stature could be used to improve the triage process and refer children to cardiac transplantation who otherwise might die prematurely and unnecessarily. Subsequent studies on the utility of these factors and their effect on improving survival are warranted.

Although the survival rate of childhood cancer is high, nearly two thirds of these survivors experience negative long-term secondary side effects from cancer treatments. Infertility is one such side effect that can have a prominent impact on quality of life as the patient ages. It is important for nurses working with pediatric oncology patients to provide the patient and family with education about risk for infertility and fertility preservation (FP) in order to allow families to make decisions about FP before cancer treatment starts. However, pediatric oncology nurses report being uneducated about FP guidelines and are hesitant to broach this subject with families. The purpose of this HIM thesis is to review nurse perceived barriers related to educating patients and their families about the risk for infertility following cancer treatments and FP and to make recommendations for improving communication between nurses and families about FP. A search was performed using CINAHL, PreCINAHL, PsychINFO, PsychARTICLES, and Medline databases and examined peer-reviewed quantitative and qualitative research studies. Key terms used in the database searches were ped' OR child', onco' OR cancer', fert', and nurs'. Findings indicated that there were many barriers for pediatric oncology nurses, which inhibited the discussion of FP with patients and families such as lack of knowledge and resources, provider attitudes toward FP, and patient factors. Based on the findings, the researcher identified several interventions to aid pediatric oncology nurses in overcoming these barriers to FP discussion.
B.S.N.
Bachelors
Nursing
Nursing

Most pediatric orthopaedic interventions are intended to improve or preserve physical function, yet their outcomes have been assessed using primarily surrogate measures (e.g., radiographic indices) that may not accurately represent patients'function. Physical function may be more appropriately measured with activity-based scales, but these have been infrequently applied in surgical studies. The purpose of this study was to identify existing activity-based physical-function scales appropriate for pediatric orthopaedics, to present criteria useful for scale selection, and to discuss the special problems of measuring physical function in children. Twenty-one scales relevant to pediatric orthopaedics are described according to their target population, purpose, method of administration, content, and quality of standardization. These scales have been further classified according to a new taxonomy. The unique aspects of measuring physical function in children are discussed and include the effect of age and development, method of reporting, and question formats. Standardized measures of physical function based on physical-activity ability exist and should be used more frequently to assess pediatric orthopaedic interventions

Recent advances in technology have facilitated the prospect of automatic cardiac auscultation by using digital stethoscopes. This in turn creates the need for development of algorithms capable of automatic segmentation of the heart sound. Pediatric heart sound segmentation is a challenging task due to various factors including the significant influence of respiration on the heart sound. This project studies the application of homomorphic filtering and Hidden Markov Model for the purpose of pediatric heart sound segmentation. The efficacy of the proposed method is evaluated on a publicly available dataset and its performance is compared with those of three other existing methods. The results show that our proposed method achieves accuracy of 92.4% ±1.1% and 93.5% ±1.1% in identification of first and second heart sound components, and is superior to four other existing methods in term of accuracy or time complexity.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by recurrent genetic aberrations. The prognosis of childhood AML has significantly improved over the last two decades, nevertheless the 30% of cases still relapse1–3. Intensive efforts have been devoted to identify new genetic abnormalities and altered signalling pathways to better stratify patients in different risk classes in order to improve children survival treating them with a more specific therapy. However still half of the AML cases do not present a recurrent genetic aberration. Thus, during this PhD I focused on the identification of new molecular markers at diagnosis and the evaluation of known markers during the disease follow up. The prognostic value of these markers has been evaluated to improve patients stratification and whenever possible to suggest novel tailored treatments. The overall goal of this study was also to functionally dissect the leukemogenic mechanism of action of these new molecular markers, in order to find suitable candidate gene/pathway to be targeted in novel personalized therapies. Initially, a screening of new markers at diagnosis was performed in a large Italian cohort of pediatric AML defining the incidence of genetic abnormalities previously described as single case reports or as novel rearrangements identified by next-generation sequencing. The del(4)(q12)FIP1L1-PDGFRA, t(16;21)(p11;q22)FUS-ERG, t(8;16)(p11;p13)MOZ-CB, t(11;17)(q23;q12-21)MLL-AF17, t(4;11)(q35;q23)MLL-ARGB2, t(3;5)(q25;q34)NPM1-MLF1, MLLPTD, and t(11;17)(p15.5;p13)NUP98-PHF23 were finally classified to be rare events at diagnosis. An exception was the translocation t(5;11)(q35;p15.5)NUP98-NSD1 which reached an incidence of 4% and was found to occur together with FLT3-ITD mutation in more than 50% of cases. Then, the mutations of the oncogene c-KIT were taken into evaluation in a selected subset of CBF-rearranged patients since these abnormalities were previously reported to be frequent in adults with CFB-AML at diagnosis4. I defined a high frequency of c-KIT mutations for RUNX1-RUNX1T1 (25%) and for CBFB-MYH11 (18.5%) rearranged pediatric patients. Prognostic value of c-KIT mutations was determined only for the RUNX1-RUNX1T1 rearranged patients, suggesting that they could be further evaluated for a targeted therapy with tyrosine kinase inhibitors. Then, I take into consideration the evaluation of a molecular marker detected at diagnosis during therapy course, by evaluating the role of monitoring the minimal residual disease (MRD) by Real time RQ-PCR . In pediatric AML, post-treatment MRD monitoring of biomarkers has been rarely used in the clinical management of patients:. molecular markers suitable for MRD detection still remains debated. I improved knowledge for patients with AML1-ETO rearrangement and in FLT3-ITD mutation, revealing that MRD levels after induction chemotherapy were prognostically significant in identifying those with higher risk to relapse and die These new group of patients , within the same genetic subgroup, may benefit of novel risk stratification or pre-emptive therapy strategies supporting the t(8;21) and FLT3-ITD as reliable molecular markers for disease monitoring also during follow up. A large part of this PhD program was committed to dissect the biology of some recurrent aberrancies being their functional role investigation mandatory to develop new targeted therapies to improve children cure. I hypothesized that biology might explain the difference in therapy response highlighted in the MRD study performed on FLT3-ITDpatientswhere half of them was found to reduce MRD levels less than 2 logs from diagnosis with a consequent high risk of relapse and death. By gene expression analyses , I showed that these patients had a different gene expression profile related to epigenetic control, most concerning methylation and acetylation of histones. These findings may suggest that the use of epigenetic drugs, combined with conventional strategies, could be a new therapeutic opportunity for a the FLT3-ITD patients showing high MRD levels after the end of first induction course. A second functional study was carried on the t(6;11)(q27;q23)MLL-AF6 rearrangement. In the Italian AML cohort, 10% of AML patients are MLL-rearranged5 and among them the t(6;11) cases present the worst prognosis5,6. By in vitro studies, I found that wild type AF6 protein co-localized with RAS in the bone marrow of healthy donors, while AF6 was sequestered into the nucleus provoking RAS overactivation in t(6;11)(q27;q23) rearranged AML. The role of AF6 in RAS inhibition was confirmed by AF6 silencing or treatment with RAS antagonists, revealing the implication of RAS pathway in the aggressiveness of MLL-AF6 leukemia. This discovery confirmed the usefulness of Tipifarnib, a drug currently used in RASopathies7, in this AML subgroup, and opens for new targeted therapies to overcome their poor outcome. The third functional study was performed on a gene recently found implicated in several translocations being not rare (4.6%) in pediatric AML at diagnosis and with outcome severe prognosis, NUP988–10. I deep inside the biology of all the NUP98 detected rearrangements, and identified a specific gene expression pattern as well as a typical outcome. Gene ontology revealed an enrichment in biological processes linked to the nuclear organization and chromosome instability, confirmed also by in vitro studies on NUP98-NSD1 rearranged primary cells. Moreover, I reported CREB control in the transcription of NUP98 and consequently of its chimeras. Altogether, these findings open for further studies into the leukemogenic mechanism of NUP98-rearranged AML, and highlight CREB as a possible therapeutic target to decrease the oncogenic properties of NUP98-chimeras. Finally, during this PhD a variety of molecular lesions were identified permitting a more detailed diagnosis for pediatric AML. The prognostic significance of each marker was evaluated and included in the risk classes stratification of the new AIEOP LAM 2013 protocol, conferring to genetics a strong role in guiding therapeutic strategies. Functional studies were able to characterize new candidate genes that can be specific for a subgroups of AML patients with detrimental prognosis, to be further studied for their therapeutic role and when possible for a even more personalized therapy. All together, this work achieved results that are currently translated into clinical management, and will contribute to the improvement of the outcome of AML children.
La leucemia acuta mieloide (LAM) è una malattia geneticamente eterogenea,caratterizzata da ricorrenti anomalie molecolari. Nonostante la prognosi dei pazienti pediatrici affetti da LAM sia notevolmente migliorata negli ultimi anni, il tasso di ripresa di malattia è di circa il 30% 1–3. Numerosi studi sono emersi per identificare nuove anomalie genetiche o vie di segnale deregolate nella LAM pediatrica al fine di migliorare la stratificazione dei pazienti nelle diverse classi di rischio, e di conseguenza poter adottare dei percorsi terapeutici specifici e più mirati. Ad oggi tuttavia, per circa il 50% dei casi non si trova alla diagnosi un marcatore molecolare noto in grado di garantire una corretta stratificazione del paziente. Per tale ragione il mio dottorato di ricerca ha avuto come primo scopo la ricerca e l’identificazione di nuovi marcatori molecolari alla diagnosi , e di studiarne il ruolo prognostico affinché si possa garantire una più corretta diagnosi a un più alto numero di pazienti, e si possa valutarne in caso un ruolo anche come marker di monitoraggi durante la terapia del paziente. Infine, allo scopo puramente diagnostico, è stato abbinato uno scopo di ricerca di base, cioè caratterizzare il processo neoplastico mediato da alcuni di questi marcatori molecolari, cercando di identificare dei geni malattia che possano servire essere dei candidati target terapeutici, utili a porre le basi per una gestione sempre più personalizzata e quindi efficace della terapia. Inizialmente ho effettuato una serie di screening molecolari con l’intento di valutare l'incidenza di alcune anomalie genetiche precedentemente conosciute solo tramite case report o identificate tramite sequenziamento massivo dell’RNA. In particolare, ho definito la del(4)(q12)FIP1L1-PDGFRA, la t(16;21)(p11;q22)FUS-ERG, la t(8;16)(p11;p13)MOZ-CBP, la t(11;17)(q23;q12-21)MLL-AF17, t(4;11)(q35;q23)MLL-ARGB2, la t(3;5)(q25;q34)NPM1-MLF1, il MLLPTD, e la t(11;17)(p15.5;p13)NUP98-PHF23 come eventi mutazionali rari nella coorte pediatrica italiana arruolata nel protocollo LAM 2001-02 (totale pazienti N=482). Al contrario, la t(5;11)(q35;p15.5)NUP98-NSD1 è stata riscontrata avvenire con una frequenza del 4%, e spesso in concomitanza alla mutazione FLT3-ITD (nel 50% dei casi). Tale traslocazione è stata inoltre valutata per il suo peso prognostico, rivelandosi un fattore prognostico negativo perché associato ad un elevato rischio di recidiva e morte. Poi, un altro screening ha riguardato la valutazione delle presenza di mutazioni a carico del gene c-KIT, in un gruppo di pazienti già con riarrangiamento del CBF. Le mutazioni di questo recettore delle tirosin chinasi sono già state ampiamente descritte in numerosi studi soprattutto riguardanti pazienti adulti affetti da LAM4. I risultati confermano un’alta frequenza di mutazione di c-KIT anche nei pazienti pediatrici con t(8;21)RUNX1-RUNX1T1 (25%) e con inv(16)CBFB-MYH11 ( 18.5%). Il valore prognostico negativo è risultato significativo solo nel gruppo con RUNX1-RUNX1T1, per i quali, l’identificazione di queste mutazioni potrebbero supportare l’uso di eventuali terapie con inibitori delle tirosin chinasi per migliorare la loro cura. Oltre alla diagnosi, il marcatore molecolare può avere un ruolo fondamentale anche durante il corso della malattia. Mi sono occupata di mettere a punto lo studio della malattia residua minima (MRM) mediante PCR quantitativa per tre importanti marker ricorrenti nelle LAM pediatriche. Ad oggi, il monitoraggio della MRM nella LAM pediatrica è scarsamente utilizzato. Qui, si propone il monitoraggio della MRM tramite la RQ-PCR dopo chemioterapia di induzione nei pazienti con t(8;21) e FLT3-ITD in grado di individuare i pazienti a più alto rischio di recidivare. Aver identificato la t(8;21) e FLT3-ITD come buoni marcatori molecolari per il monitoraggi della MRM, consentirà ai clinici di poter valutare delle strategie alternative in quei pazienti che potrebbero beneficiare di terapie farmacologiche supplementari al fine di evitare la ripresa della malattia. Infine, molto tempo del mio dottorato è stato impegnato alla caratterizzazione biologica e funzionale di alcuni marcatori molecolari ricorrenti con il fine ultimo di identificare nuovi possibili target terapeutici per migliorare la cure e la sopravvivenza dei pazienti. In primis, ipotizzando che la diversa risposta terapeutica dei casi FLT3-ITD abbia origine da una diversità biologia, abbiamo effettuato delle analisi di espressione genica su questo gruppo di pazienti. Questo studio ha permesso di identificare un profilo di espressione genica caratteristico per i pazienti che riducendo meno la malattia dopo l’induzione vanno incontro a un più alto rischio di ricadere. I processi biologici arricchiti in questi pazienti sono risultati riguardare la metilazione e l’acetilazione degli istoni, suggerendo che eventuali agenti deacentilanti o demetilanti, in combinazione con la terapia convenzionale, possano migliorare la sopravvivenza libera da avventi avversi di questi pazienti. Un altro studio funzionale ha preso in esame la t(6;11)(q27;q23)MLL-AF6. Circa il 10% della popolazione pediatrica italiana presenta uno dei riarrangiamenti a carico del gene MLL , tra questi la t(6;11) presenta la prognosi peggiore5,6. Attraverso studi in vitro, ho rivelato che la proteina AF6 endogena si localizza nel citoplasma insieme all’oncogene RAS in cellule di midollo osseo sano. Viceversa, nei pazienti con traslocazione t(6;11), AF6 è stato riscontrato essere nel nucleo impedendo il fisiologico controllo di RAS nel citoplasma, comportandone un’iper-attivazione della via. Sia il silenziamento di AF6 sia il trattamento con inibitori di RAS hanno confermato il ruolo chiave del pathway di RAS nel sostenere l’aggressività di questa leucemia. Infine, lo studio ha comprovato il Tipifarnib, farmaco già in uso nelle RASopatie7, come nuovo farmaco utilizzabile nei pazienti pediatrici con t(6;11). Il terzo studio funzionale ha riguardato un gene molto nuovo nella LAM pediatrica, il gene NUP98. Le traslocazioni somatiche associate a questo gene8–10 si sono riscontrate non rare nella corte pediatrica LAM italiana (4.6%). Lo studio più funzionale ha poi chiarito che ciascuna di queste traslocazioni identificate una diversa biologia così come un diverso ruolo prognostico . Grazie all’analisi di espressione genica ho identificato l’instabilità genetica come il processo biologico maggiormente deregolato in questo gruppo di pazienti con NUP98-LAM. Tale processo è stato verificato in vitro grazie a colture cellulari primarie di pazienti NUP98-NSD1 riarrangiati. Inoltre, ho dimostrato che il fattore di trascrizione CREB controlla la trascrizione del gene NUP98, cosi come di tutte le oncoproteine che si riscontrano nelle LAM mantenere l’N terminale dello stesso. Questi risultati identificano il ruolo funzionale della chimera NUP98-NSD1, e candidano CREB a possibile bersaglio terapeutico per combattere l’espressione della chimera e quindi la progressione della malattia . In conclusione, durante i tre anni di dottorato di ricerca ho caratterizzato una serie di marcatori molecolari che hanno permesso una migliore e più dettagliata stratificazione dei pazienti alla diagnosi. Dato il valore prognostico dei vari marcatori, essi sono stati inclusi nel nuovo protocollo terapeutico LAM 2013, che conferisce alla genetica molecolare un ruolo determinante nel guidare la terapia. Infine gli studi funzionali hanno finora portato all‘identificazione di nuovi target specifici in vari sottogruppi di LAM a prognosi infausta. Studi futuri sono in corso per valutare questi biomarcatori come target terapeutici da utilizzare per incrementare le possibilità di curare i bambini affetti da LAM .

Objective: Clinical scoring systems attempt to improve the diagnostic accuracy of pediatric appendicitis. The Pediatric Appendicitis Score (PAS) was the first score created specifically for children and showed excellent performance in the derivation study when administered by pediatric surgeons. Our objective was to validate the score in a non-referred population by medical physicians. Methods: A convenience sample of children, 4 -18 years old with suspected appendicitis, presenting to the Montreal Children's Hospital emergency department was prospectively evaluated. Score components were collected on standardized forms by emergency physicians who were blind to final diagnosis. Outcomes were ascertained by review of pathologic specimens for children undergoing surgery and by telephone follow-up for children who were discharged home. Patients with histology confirmed appendicitis and those without appendicitis (includes patients who underwent appendectomy but who had negative histology) were compared. We present information about the diagnostic accuracy of the Pediatric Appendicitis Score. Results: Of the enrolled children who met inclusion criteria (n=246), 83 (34%) had pathology proven appendicitis. Using the single cut-point suggested in the derivation study (PAS 5), yielded an unacceptably high number of false positives (37.6%) and negatives (7.2%). The score's performance improved when two cut-points were used. When children with PAS < or = 4 were discharged home without further investigations, the sensitivity was 97.6% with NPV 97.7%. When a PAS of 8 or more determined the need for appendectomy, the score s specificity was 95.1% with PPV 85.2%. Using this strategy, the negative appendectomy rate was 8.8%, missed appendicitis rate was 2.4% and 41% of imaging investigations would have been avoided. Conclusion: The PAS is a useful tool in the evaluation of children with possible appendicitis. Scores < or = 4 help rule out appendicitis while scor
Objectif: Les systèmes de scores cliniques tentent d'améliorer l'exactitude du diagnostique de l'appendicite aiguë chez l'enfant. Le Score d'Appendicite Pédiatrique (PAS) était le premier score créé spécifiquement pour les enfants et avait démontré une excellente performance dans l'étude de dérivation lorsque administrée par des chirurgiens pédiatriques. Notre objectif était de valider le score dans une population non-référée par les médecins médicaux. Méthodes: Un groupe de convenance d'enfants, ages de 4 à 18 ans, se présentant à l'urgence de l'Hôpital de Montréal pour Enfants avec une suspicion d'appendicite a été évalué prospectivement. Les composantes du score étaient collectées sur des formulaires standardisés par les médecins d'urgence, à aveugle. Les résultats ont été établis par l'examen des spécimens pathologiques pour les enfants subissant la chirurgie et par suivi de téléphonique pour les enfants qui ont eu leur congé de l'hôpital. Les patients présentant l'histologie ont confirmé l'appendicite et ceux sans appendicite (inclut des patients qui a subi l'appendectomy mais qui a eu l'histologie négative) ont été comparés. Nous présentons des informations sur l'exactitude diagnostique du Score d'Appendicite Pédiatrique. Résultats: Des enfants inscrits qui ont répondu aux critères d'inclusion (n=246), 83 (34%) ont eu la pathologie appendicite prouvée. En utilisant le seuil suggéré dans l'étude de dérivation (PAS 5), rapporté un nombre exagérément élevé de faux positifs (37.6%) et de faux négatifs (7.2%) a été obtenu. La performance du score était améliorée lorsque deux seuils étaient employés. Quand des enfants avec un score PAS de < ou = 4 ont eu leur congeé sans investigations suppleméntaires, la sensibilité était 97.6% avec une valeur négatif prédictive de 97.7%. Quand un PAS 8 ou plus a déterminé la nécessité d'une appendicectomie, la spécificité du score était 9

Emergency department (ED) use for behavioral-health-associated diagnoses has steadily increased in adult and pediatric populations, accounting for 1 out of every 8 ED visits. The increase in pediatric behavioral health ED visits, combined with limited resources for treatment, has created a challenge for EDs faced with extended boarding and constant observation of this population. The generalized behavioral health guidelines used at the practice site have not been adapted for the pediatric population. This project focused on providing age- and developmentally appropriate best practice guidelines for children under constant observation in the children's emergency department (CED) using Havelock's theory of planned change as the framework. Practice in the CED was compared to best practice recommendations identified in the literature and community standards including workflow, defined roles and responsibilities, addressing the needs of the parent/guardians, and defined outcomes. These best practices were incorporated in a guideline developed to provide age- and developmentally appropriate recommendations. An expert panel comprising the behavioral health nurse manager and children's emergency department nurse manager reviewed the guideline using the AGREE II tool, and the guideline was revised based on the composite results from the 6 domains in the AGREE II tool. Based on these composite results and panel feedback, domain 5 was revised to include an auditing and monitoring plan. In addition to improving the safety and care for the CED patient population, this project also serves to increase awareness of the topic while emphasizing on the need for additional research and evidence-based practice focused on pediatric behavioral health patients.

Antimicrobial resistance has become a global problem. Italian pediatric antimicrobial prescription rates are among the highest in Europe (EU). As a first step for antimicrobial stewardship (AS) implementation, clinical pathways (CP) outlining standard of care for acute otitis media (AOM), and group A streptococcus (GAS) pharyngitis and community-acquired pneumonia (CAP) were developed and implemented in our pediatric emergency department (PED) in collaboration with Children’s Hospital of Philadelphia. Aims. The primary aim of this study was to assess changes in antibiotic prescription one year after the CP implementation for AOM, GAS pharyngitis and CAP; secondary aim was to compare treatment failure before and after CPs implementation. Methods. CPs were implemented at the Department for Woman and Child Health of Padua on October 1st 2015. The first before/after quasi-experimental study has been conducted between the Pre-intervention period (from 15/10/2014 to 15/04/2015), Post-intervention period (from 15/10/2015 to 15/04/2016) and 1-Year post intervention period (from 15/10/2016 to 15/04/2017). ITS was used to determine the effect of the intervention, chi squared test to define the treatment failure and Kruskal Wallis test to compare antibiotic dosages and durations. Results. AOM: after CP implementation there was an increase in “wait and see” (21.7% vs. 33.1% vs. 28.9%, p=0.08) and in the use of amoxicillin as first line therapy (25.1% vs. 34.5%, p<0.001), with a decrease from 53.2% to 32.4% (p<0.001) in overall prescription of broad-spectrum antibiotics. Amoxicillin prescriptions increased (32% Pre vs. 51.6% Post and 52.8% 1-Year Post, p<0,001) with a decrease in overall prescription of broad-spectrum antibiotics. Among fully immunized with no complicated OMA, broad-spectrum antibiotics were prescribed in only 4.7% of cases (29.8%, Pre vs. 7.2% Post, p<0.001). Pharyngitis: During 1-year Post intervention period 63.2% of patients received a diagnosis Goup A Steptococcus pharyngitis (50.7% Pre vs 45.4% Post), reflecting the increasing age of the population examined (more patients aged 3-15 years). Amoxicillin was the choice for 93.2% of patients (53.6% Pre and 93.4% Post). CAP: prescriptions/patients rate has decreased to 1.02 (1.3 Pre, 1.12 Post) reflecting an increase use of monotherapy. 82.5% of patients received amoxicillin (52.1% Pre vs. 69.9% Post, p<0.001) and macrolide prescriptions decreased to 2.1% (19.7 Pre vs. 6.5% Post). No statistically significant difference in treatment failure was seen for all the pathologies examined. Conclusions. A reduction in broad-spectrum antibiotic prescriptions for AOM. Gas pharyngitis and CAP without compromising clinical outcomes indicates effectiveness of CPs in this setting. Furthermore their effects after more than one year suggests CPs are useful and suitable tool.
La resistenza antimicrobica è un problema globale che sta diventando sempre più importante a causa dell'abuso di antibiotici. Il tasso di prescrizionein Italia è tra i più alti in Europa.Pertanto risulta opportuno implementare dei programmi di stewardship al fine fi migliorare le prescrizioni antibiotiche.Come primo passo per lo sviluppo di una stewardship antibiotica, in Pronto Soccorso pediatrico di Padova sono stati implementatideiclinicalpathways (CPs) delineanti uno standard di cure per otite media acuta,faringotonsillite e polmonite acquisita in comunità. Scopo.L’obiettivo primario di questo studio è quello di valutarela differenza nella gestione della terapia antibioticaad un anno dall’implementazione deiCPs.. Scopo secondario è confrontare i fallimenti terapeutici prima e dopo l’implementazione dei CPs. Metodi. L’implementazione è avvenuta dal 1 ottobre 2015 nel Pronto Soccorso Pediatrico di Padova, dopo una collaborazione con il Children’s Hospital di Philadelphia, e, in tale occasione, si sono tenuti tre seminari per presentare il progetto ai medici del Pronto Soccorso e sono stati consegnati a ciascuno i CPssottoforma di pocket card. Si è valutata la differenza delle prescrizioni tra il periodo 15/10/2014-15/04/2015 (periodo Pre intervento) e il periodo 15/10/2015-15/04/2016 (periodo Post) e i risultati sono stati presentati in settembre 2016. L’osservazione del presente studio è avvenuta nel periodo 15/10/2016-15/04/2017 (periodo 1-year post). Tutti i risultati del periodo 1-year postsono stati confrontati con quelli del periodo Pre e del periodo Post. Abbiamo valutato le differenze tra i tre gruppi per quanto riguarda la variazione delle prescrizioni con l’ITS, il confronto tra dosaggi e durata con il test di Kruskal Wallis e i tassi di fallimento terapeutico con il test del chi quadro . Risultati. In caso di otite media acuta (OMA) nel periodo 1-year postl'aumento delle scelta della vigile attesa come first-line therapy si è mantenuto stabilmente al di soprade; periodo Pre (21.7% vs 28.9%)(p=0,008). In caso di terapia antibiotica, è aumentata la scelta di amoxicillina (52,8%, nel Pre 32% e nel Post 51,6%, p<0,001) e diminuita la scelta di antibiotico ad ampio spettro. Tra i pazienti vaccinati e senza OMA complicata la scelta ad ampio spettro è ricaduta sul 4,7% dei pazienti(nel Pre 29,8%, nel Post 7,2%, p<0,001). Per quanto riguarda i pazienti con diagnosi di faringotonsillite: la diagnosi di faringotonsillite streptococcica è stata posta nel 63,2% dei casi nel 1-Year post (nel Pre 50,7%, nel Post 45,4%) contestualmente all'incremento, statisticamente significativo,della popolazione nella fascia di età 3-15 anni. .La scelta è ricaduta per il 93,2% sull’amoxicillina (nel Pre 53,6%, nel Post 93,4%). Per la polmonite acquisita in comunità, il rapporto prescrizione/pazienti è diminuito a 1,02 (nel Pre 1,3, nel Post 1,12,) aumentando perciò l’opzione della monoterapia. La scelta dell’amoxicillinaè avvenuta nell’82,5% dei casi (nel Pre 52,1%, nel Post 69,6%, p<0,001) con diminuzione soprattuttodelle prescrizioni di macrolidi 2,1% (nel Pre 19,7%, nel Post 6,5%).Nessuna differenza statisticamente significativa e' stata riscontrata nel fallimento terapeuticodi tutte e tre le patologie analizzate otite media acuta (p=0,31), faringotonsillite (p=0,98) e polmonite acquisita in comunità (p=0,11). Conclusioni. I risultati ottenuti confermano l’efficacia dei CPs e la validità del metodo usato per implementarli in un ambiente come il Pronto Soccorso Pediatrico.

El paciente infectado por VIH presenta, en nuestro entorno, una mayor esperanza de vida con prácticamente ausencia de episodios definitorios de SIDA. La cuestión es si esta mayor esperanza de vida está libre de enfermedades concomitantes o si van a aparecer otras nuevas. La enfermedad hepática es un buen ejemplo de este cambio epidemiológico. El paciente infectado por VIH presenta un riesgo de afectación hepática a través, tanto de la acción directa del virus como del efecto de los fármacos antirretrovirales. Por otra parte, las tasas de infección de VHB y VHC son considerablemente más altas en estos pacientes, al compartir la mayor parte de las vías de transmisión. Los pacientes infectados por el VIH pueden presentar coinfecciones por virus hepatotropos serológicamente silentes: la infección VHB oculta y la infección por VHC seronegativa, que no se diagnostican con los métodos habituales. Estas entidades suponen un aumento del riesgo de reactivación de la enfermedad, progresión y evolución a daño hepático crónico y grave, sobre todo en los niños que adquieren el virus precozmente. La inclusión rutinaria del cribado de hepatitis ocultas sería una herramienta útil para identificar a los pacientes con riesgo de descompensación hepática, de especial interés en los niños que viven con el VIH, ya que se enfrentan a una perspectiva de coinfección, y riesgo de daño hepático, de por vida. A través de este estudio transversal en la cohorte nacional de pacientes VIH pediátricos (CoRISPe) se abordó la prevalencia de coinfección por VHB y VHC, así como la coinfección por hepatitis ocultas. De forma secundaria, se realizó una valoración no invasiva de la fibrosis hepática a través de marcadores bioquímicos (ALT/AST ratio, APRI index, FIB-4 score). Se incluyó un total de 254 pacientes. Tres (1.2%) presentaron una VHB crónica y 13 (5%) una infección crónica por VHC. Seis niños se consideraron probables casos de infección VHB oculta, 2 con anti-HBc aislado y 4 con un patrón serológico anti-HBc+/anti-HBs+, a pesar de la negatividad de la PCR a VHB en plasma. Dos pacientes (0.8%) presentaron infección VHC seronegativa. No se realizaron biopsias hepáticas en este estudio por razones éticas. La evaluación no invasiva de la fibrosis hepática fue patológica en los 3 y en 7 de los 13 con infecciones por VHB y VHC, respectivamente, advirtiendo de una posible fibrosis subyacente. Una paciente infectado por VHC mostró alteración simultánea de los tres marcadores incluidos en el estudio. Cinco de los 6 casos de probable VHB oculta mostraron ALT/AST ratios alteradas pero con normalidad en el APRI y FIB-4 score. Los dos casos de infección VHC seronegativa presentaron valores anormales. En los niños infectados por VIH sin coinfección por virus hepatotropos, el 77% mostró ALT/AST ratios elevadas mientras que el 5.7% presentó valores anormales de APRI. Sólo un paciente mostró un FIB-4 score elevado. En ausencia de datos más amplios sobre coinfección en población pediátrica infectada por el VIH, la prevalencia de VHB y VHC en CoRISPe es similar a lo descrito previamente. Aunque la tasa de coinfección por hepatitis ocultas en esta cohorte fue baja (3.1%) parece razonable la inclusión de técnicas de diagnóstico molecular que aumenten la sensibilidad en el diagnóstico de las hepatitis ocultas. Se necesitan más datos para evaluar la idoneidad del uso de los scores bioquímicos para valoración de fibrosis hepática en esta población pediátrica, con el objetivo de aumentar la sensibilidad y especificidad, y correlacionar los resultados con la biopsia hepática, que sigue siendo la técnica de referencia.
HIV-infected patients can now enjoy a longer life expectancy with almost no AIDS defining episodes if diagnosed promptly, as is the case for most vertically infected children in our setting. The question is whether this longer life expectancy is free of comorbidities or whether other medical conditions will appear. Liver disease is a good example of this epidemiological change. A worse outcome of liver disease is expected through both the direct action of the virus and the effect of the antiretroviral drugs. Moreover, HIV itself is considered a risk factor that contributes to increased MTCT of the hepatitis virus. Furthermore, the infection rates of HBV and HCV are considerably higher in patients living with HIV, as they share most of the transmission routes. HIV-infected patients prone to uncommon variations of hepatotropic coinfections which are serologically silent, namely, occult hepatitis B infection and seronegative HCV infection. These entities bring an increased risk of disease reactivation, progression and evolution to chronic and severe liver damage, especially in children who acquire the virus early in life. Current regular screening methods may miss the diagnosis of these coinfections in immunocompromised patients. The inclusion of screening for OBI and seronegative hepatitis C in routine HIV patient monitoring would be a useful tool to identify those patients at risk of hepatic decompensation. In HIV-infected children who face the prospect of a lifetime coinfection, this possibility would be of particular interest, and highly beneficial, as it would become possible to anticipate secondary clinical conditions and future complications. This is a cross-sectional study among the Spanish cohort of HIV-infected children (CoRISPe) in order to assess the prevalence of HBV and HCV infection and occult hepatitis as well. Secondarily noninvasive liver fibrosis assessment through biochemical serum markers was made. A total of 254 patients were included in this study. Three (1.2%) and 13 (5%) patients respectively had serological markers compatible with overt cHBV and cHCV infection. Two patients showed spontaneous clearance of HCV infection. Six children were considered probable OBI cases, 2 presenting with anti-HBc alone and 4 with an anti-HBc+/anti-HBs+ serological pattern, although blood HBV DNA testing was negative in all cases. Two patients (0.8%) had seronegative HCV infection. Noninvasive assessment of liver fibrosis was pathological in all 3 with overt cHBV and in 7 out of 13 with overt cHCV, warning of a possible underlying fibrosis. One HCV-infected patient showed simultaneous alteration of the three scores included in the study. Five out of 6 probable OBI cases appeared to have altered ALT/AST ratio but APRI index and FIB-4 scores were normal in all patients with occult hepatitis. Both cases of seronegative HCV infection showed abnormal scores values. Among HIV-monoinfected children, 77% showed raised ALT/AST ratios, while 5.7% presented APRI abnormal values. Just one patient showed FIB-4 score abnormality. The HBV and HCV prevalence coinfection rates in this cohort appear to be in keeping with previously published data, in the absence of wider prevalence coinfection data for the HIV-infected pediatric population. The global rate of occult hepatitis coinfection cases detected in this cohort was low (3.1%). However, molecular diagnosis assays are indicated to increase the sensitivity of detection and minimize the risk of under-diagnosis and its clinical implications in adulthood. Further research is needed to assess the suitability of using biochemical scores in these populations in order to approach good levels of sensitivity and specificity, and to correlate this method to liver fibrosis assessed by imaging and/or biopsy.

Class of 2017 Abstract
Objectives: To assess the perceived confidence level of community pharmacists in utilizing weight-based dosing, dispensing prescriptions, counseling, and recommending over-the-counter medications for the pediatric population in rural and non-rural settings. Methods: A 33-item questionnaire generated through REDCap was distributed to 11,280 pharmacists registered with the Arizona State Board of Pharmacy via email from March 14 to April 4 of 2017. The survey collected information on the participants’ experiences in managing pediatric prescriptions and demographics. Results: Of the 11,280 surveys distributed, a total of 857 responses were submitted by the end of the survey period (7.6%) and 482 responses were included in the analysis; 49 (10.2%) were practicing in rural areas and 433 (89.8%) were practicing in non-rural areas (including urban and suburban) in Arizona. There was no significant difference in the rural group compared to the non-rural group regarding experiences with dispensing pediatric medications. In regards to the confidence level, there was a significant difference between the two groups in calculating and recommending weight-based dosing for prescription and OTC pediatric medications (p = 0.022 and 0.031, respectively) and identifying a dosing error in pediatric prescriptions (p = 0.016). Conclusions: Community pharmacists practicing in rural and non-rural settings in Arizona had similar experiences with dispensing pediatric medications and confidence levels in managing medications for pediatric patients.

The purpose of the present study was to establish the prevalence of sensory, neurological and systemic impairments in the Inuit pediatric population (0-18 years) in 13 communities of the Baffin region of the Northwest Territories, Canada.
A data collection instrument (DCI) was developed to obtain clinical data from medical files in each of the Community Health Centres. Impairments rather than disabilities were described and possible causal factors were identified. Data collection took place during the month of June, 1989.
Nearly 13% of Inuit children living in the Baffin area have impairments. Of this group, 15.9% have multiple impairments. The prevalence of children with sensory impairments is 49.4/1000, with neurological impairments is 28.7/1000, with systemic impairments is 30.2/1000 and with multiple impairments is 20.5/1000 children. Over 50% of the impairments reported were due to infectious diseases such as meningitis and chronic otitis media.
The results of this study provide a basis for the development of community based programs which emphasize prevention of impairments in children.
Recommendations for the development of appropriate rehabilitation programs are discussed in the context of the policies of the Canadian government pertaining to the needs of Aboriginal persons with disabilities.

This business plan proposes a neurofeedback therapy clinic to treat children diagnosed with Attention-deficit/hyperactivity disorder (ADHD) and are in search of a non-pharmaceutical intervention. ADHD is the most commonly diagnosed disorder among children between the ages 4-18. By stimulating arousal in the frontal portion of the brain through neurofeedback therapy, the symptoms of ADHD can be regulated. This proposal includes a market analysis, a feasibility and SWOT analysis, a review of legal and regulatory issues, and finally, a financial analysis.

Résumé : Les biopsies liquides ouvrent de nouveaux champs d'applications dans la prise en charge des patients au diagnostic, au cours de leur suivi et également en recherche translationnelle. Ces dernières années, de nombreux efforts ont été consacrés au développement de l'ADN tumoral circulant (ADNct) et des cellules tumorales circulantes (CTC). Il y a malgré tout de nombreux terrains encore en friches dans les cancers de l'enfant, et parmi eux dans les sarcomes pédiatriques.Nous avons souhaité explorer dans ce travail différents aspects des applications cliniques éventuelles et d'utilisation de ces technologies pour la compréhension de la biologie des tumeurs. La première partie de ce projet est une revue de la littérature qui se rapporte à l'application de l'ADNct dans les cancers solides pédiatriques. Nous présentons ensuite un travail de recherche qui vise à utiliser les CTC à visée diagnostique dans les sarcomes à translocation. Cette étude présente une approche permettant d'identifier des fusions pathognomoniques de sarcome à partir de très faibles quantités de tissu fixé, de CTC sur des modèles murins ou chez des patients. La deuxième étude présentée s'intéresse à la détection de l'ADNct au diagnostic de rhabdomyosarcome en utilisant les altérations de nombre de copie de chromosome, les réarrangements chromosomiques et les variants de nucléotide. Nous avons démontré que la détection au diagnostic est faisable et a un impact pronostique fort sur le devenir des patients. La dernière partie de ce manuscrit présente le développement d'un processus de traitement d'échantillons de patient pour détecter et isoler des cellules tumorales circulantes dans le but d'analyser les particularités génomiques de cette population à une résolution cellulaire.Ce travail explore certains aspects de l'utilisation de la biopsie liquide dans les sarcomes pédiatriques, parmi de nombreux autres. Il est crucial dans le développement de ce champ de recherche, de maîtriser les particularités intrinsèques de chaque type tumoral et des technologies disponibles. Nous avons démontré l'utilité d'une telle approche au diagnostic dans deux applications. Cette aire de recherche ouvre de nombreuses possibilités qui appellent à poursuivre les efforts afin d'élargir les applications en recherche et en clinique
Abstract: Liquid biopsy is an opportunity for improved diagnosis, treatment monitoring and genomic studies in oncology. Substantial effort in recent years has focused on circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). However, pediatric cancer, including sarcomas, are still largely unexplored disease areas in this field.In this work, we sought to explore several aspects of liquid biopsy applied to pediatric sarcomas including their clinical use at diagnosis and as a tool to understand tumor biology. We first present a review of the literature demonstrating the feasibility of applying liquid biopsy to pediatric solid malignancies. Then, we report a methodological study using CTC for diagnostic purposes in translocation driven sarcomas. This approach identified fusions from as little as two unstained slides of FFPE tumor biopsy tissue, from CTC collected from tumor-bearing mice, and from liquid biopsy samples from patients with known fusion-positive cancers. The second study focuses on ctDNA for prognostication at the time of diagnosis in rhabdomyosarcoma by detecting copy number alterations, rearrangements, and single-nucleotide variants. Our study demonstrates that baseline ctDNA detection is feasible and has prognostic value. The last part of this work presents the development of a workflow to isolate single sarcoma cancer cells for sequencing, with an ultimate goal to analyze CTC genomic features at a single-cell resolution.This work explores several clinically and scientifically relevant aspects of liquid biopsy in pediatric sarcoma. We showed that liquid biopsy has utility at diagnosis in two different applications. Further development in this field will require a strong knowledge of tumor-specific biology, the clinical care of patients with these diseases, and the adaption of new technologies. My findings demonstrate the transformative possibilities this research may bring to the care of patients with pediatric sarcomas

This study aimed to establish a better candidacy protocol for pediatric heart transplant patients at the University of Arizona Medical Center through a retrospective chart review of pediatric heart transplants held there between the years of 2004 -2009. Sequential patterns related to noncompliance investigated included patient and guardian demographics and past medical, familial, social and psychiatric history. Trends between gender and noncompliance were found as 5/5 noncompliant rejectors were male. Four out of the 5 were between the ages of 16.5 and 21 years old. Seventy percent of medication changes due to medication intolerance were associated with noncompliance. Patients with family members currently or previously suffering from life-threatening illnesses (7/16) had a greater likelihood of having subtherapeutic immunosuppressive trough levels. Of noncompliant rejectors, 4/5 (80%) had a duration of illness prior to transplant > than 6 months. Also, 4/4 patients with pre-transplant depression experienced rejection and 2/4 were noncompliant rejectors.

Background and aims Malnutrition is a state in which a deficiency or imbalance of energy, proteins and other nutrients causes measurable adverse effects on functional and clinical outcomes. In particular, the nutritional status of ill children often declines after admission to the hospital and deteriorates during the course of diseases. The reported prevalence of malnutrition in pediatric hospitals ranges from 6 to 30%, however there are currently no recommendations on nutritional evaluation and risk of hospital malnutrition screening. Ill children are expected to differ in their energy expenditure when compared to healthy counterparts , to the point that growth may cease during the metabolic response to disease or injury, especially if they are in critical conditions. The most accurate method for determining resting energy expenditure is indirect calorimetry which is based on the measurement of basal metabolism from gas exchanges. However the application of this technique remains still sporadic. Alternatively, in the daily clinical practice, energy expenditure is commonly calculated by the use of predictive equations whose algorithms are based on healthy populations and are not disease-specific. The aim of this research project wasat first to assess the nutritional status of ill children admitted to a tertiary health care of northern Italy by measuring the prevalence of malnutrition and the risk of developing it during hospitalization. In the second step, we investigated energy expenditure in the course of disease in a heterogeneous population of acutely and chronically ill children to evaluate the accuracy of the WHO, Harris-Benedict and Schofield formulae in this population. Methods A prospective observational study was at first performed in five pediatric units at the IRCCS Foundation Ca’ Granda-Ospedale Maggiore Policlinico in Milan, Italy. In 245 subjects, anthropometric measurements (weight and length) were evaluated within 24 h of admission and repeated the day of discharge in order to assess wasting, stunting, and obesity according to WHO definitions. A fasting blood sample was collected to analyze nutrition-related haematochemical indexes and to test their role in predicting the length of stay. The nutritional risk was assess using the STRONGkids questionnaire. Then, a cross-sectional study including 236 infants, children and adolescents, consecutively admitted to the same five Units of this Italian Pediatric Hospital, was performed. Resting energy expenditure was measured by indirect calorimetry and estimated using the WHO, Harris-Benedict and Schofield formulae. Results The study population of the first study showed a malnutrition prevalence at admission of 10.2% wasting,and 6.5% stunting, moreover a prevalence of 7% obesity was found. Length of stay was mildly related to the STRONGkids score and was inversely associated with serum albumin. An inverse associations for serum albumin was found also with the questionnaire score. The second analysis showed a mean (standard deviation) bias between the estimated and measured resting energy expenditure of -1 (234), 82 (286), -3 (233) and -2 (214) kcal/die for the WHO, Harris-Benedict, Schofield-weight and Schofield-weight and height formulae, respectively. Conclusions To assess nutritional status, nutritional risk and appropriate biochemical indices at admission may help to predict the length of hospital stay and to optimize clinical interventions and follow-up. Furthermore, in ill children standard equations may be inaccurate and feeding strategies based on these equations might result in unintended underfeeding or overfeeding. Cumulative effects of energy imbalance can negatively impact patient outcomes and must be prevented. Accurate assessment of energy expenditure with the use of indirect calorimetry might optimize when possible energy intake during disease providing adequate feeding strategies.

Class of 2013 Abstract
Specific Aims: To evaluate the level of didactic and experiential pediatric education currently provided in ACPE-accredited Doctorate of Pharmacy (PharmD) programs throughout the United States by comparing geographic location and type of institution. Methods: Questionnaires were administered electronically to pediatric clinicians through the American College of Clinical Pharmacy (ACCP) Pediatric Practice and Research Network (PRN) listserve and consisted of demographic questions as well as questions regarding the number of hours of didactic pediatric education within courses, the number of hours of experiential education, and the specific pediatric experiences available to students. Main Results: Questionnaires were completed by 36 Colleges of Pharmacy (29%) and included 26 dedicated pediatric faculty, 9 adjunct pediatric faculty, and 1 non-pediatric faculty who were the primary instructors for pediatric education. The average reported number of pediatric didactic hours was 16.3±19.2 hours. Pediatric didactic education was similar between private and state funded institutions (p=0.24) as well as geographic location (p=0.74). The percentages of students taking the different types of experiential rotations were similar between state funded and private institutions (p=0.64). There was a significant difference between regions for the percentage of students participating in pediatric APPE rotations (p<0.001). Specifically, the Northeast and Midwest regions showed a higher percentage than the South Atlantic, South Central, and West regions (p<0.001). Programs commonly reported the following pediatric rotations: general pediatrics (78%), pediatric critical care (69%), neonatal critical care (67%), and pediatric ambulatory care (28%). Conclusion: Pediatric didactic and experiential education appears to be consistent between state and privately-funded institutions as well as between geographic regions with the exception of a higher percentage of students in the Northeast and Midwest participating in pediatric APPE.

Disordered sleep affects 20-40% of children and adolescents. Such disorders can result in academic difficulties, emotional regulation difficulties, and decreased immune system functioning. Behavioral treatments are the empirically supported treatment for pediatric sleep problems. With most children getting yearly well-child visits, pediatric medical professionals are in an optimal position to identify sleep difficulties and refer children for treatment. However, research suggests that medical professionals receive limited formal education in disordered sleep, and they more frequently recommend medication over behavioral interventions. Therefore, referrals to psychologists for behavioral treatments may often be warranted. The factors that influence medical professionals’ referral decisions have not been investigated. The current study investigated factors implicated in referral behaviors including pediatric medical professionals’ knowledge, screening patterns, treatment preferences, and referral patterns in the area of pediatric behavioral disordered sleep. A total of 65 medical professionals were recruited to complete an online survey to investigate these factors. Results indicated that participants in the current study demonstrated significantly higher sleep knowledge and rates of screening than what was found in a previous study. Regarding predictors of sleep knowledge, taken together, specialty, years in practice, and screening behaviors significantly predicted sleep knowledge scores. Additionally, sleep knowledge of participants who indicated that a referral was necessary when presented with a hypothetical case example of a child presenting with disordered sleep was significantly lower than the sleep knowledge of those who did not refer. Further, rates of referral were significantly lower than reported in previous research. Confidence in managing sleep problems and rates of providing behavioral recommendations were also explored. Overall, results of the current study indicate that pediatric medical professionals may benefit from additional training in the area of pediatric behavioral sleep and increased awareness of appropriate referral sources. Further exploration into the influence of screening behaviors and treatment preferences on referral behavior is necessary.

Purpose: To assess dental students and pediatric dental residents’ knowledge and attitudes towards motivational interviewing and evaluate the efficacy of a pediatric-focused brief motivational interviewing training program. Methods: A total of 66 participants were enrolled; 35% were third year dental students, 46% were fourth year dental students and 18% were pediatric dental residents. Participants completed three questionnaires: the first before the training, the second immediately after the training and the third approximately 3.5 months after the training. Results: A significant increase in correct responses was found for 4 of the 5 questions assessing participants’ knowledge. Participants were satisfied with the training (94%) and were interested in further training (89%). Participants believed patients and their parents would benefit from the intervention (97%). Conclusions: The pediatric-focused BMI training program is a valuable addition to pre-doctoral and residency curricula by preparing students and residents to employ this beneficial technique.

Integrated care is rapidly becoming the new paradigm of healthcare and with the transition into integrated practice, many providers from various disciplines must determine how best to work as a team to improve patient outcomes. One particular setting where the logistics of integrated practice must be scrutinized is pediatric primary care, specifically in rural areas, as many psychological problems are presented in pediatric primary care, and rural children are at greater risk for engaging in unhealthy behaviors, such as sedentary lifestyle, poorer nutrition, and greater substance use. All of these concerns can be ameliorated with successful referral to behavioral health consultants (BHC) who can assist in treating these various psychosocial issues. In order for the BHC to assist with patients with psychosocial concerns, other medical providers must be able to recognize and refer these patients to the BHC. The purpose of this study was to determine the prevalence of psychosocial concerns in pediatric primary care and how often the attending medical provider noticed these concerns and referred the patient for behavioral health services. The study also examined what types of psychosocial concerns were raised, and if the referral was not addressed during the same visit, the latency between the initial referral and the behavioral health service. Retrospective electronic health record data (N=300) was collected from the well visits of all 4 and 5 year old patients in 2014 from a rural Appalachian pediatric primary care clinic. Results indicated that when a psychosocial issue was raised, the majority of medical providers appropriately referred the patient to the BHC. Psychosocial concerns were raised in 21.3% (n=64) of visits. When psychosocial concerns were raised, 62.5% (n=40) were referred for behavioral health services with 87.5% (n=35) to the in house BHC. When patients were referred to the in-house BHC, 83.3% (n =30) received services immediately, while patients who were not seen immediately, 16.7% (n=5), waited for an average 21 days to be seen by the BHC. The most common psychosocial concerns raised were related to toilet training, temper tantrums, sleep hygiene, and hyperactivity. These findings highlight the high prevalence of psychosocial issues presented in rural pediatric primary care and the continued education of providers about recognizing these concerns so the appropriate referral can be made. These findings also highlight the need for more integrated practice as primary care is the often the primary source of healthcare in rural areas and by addressing all concerns about patient well-being in this setting via integrated care, patient physical and mental health outcomes can be greatly improved.

Background and aims. Medulloblastoma (MB) is the most frequent embryonal tumor of the CNS and the most common malignat pediatric brain tumor, arising mainly in the fourth ventricle. MB is characterized by four molecularly defined subgroups with distinct clinicopathological features and prognosis: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4). Standard therapy is ineffective in subsets of MB, thus there is a great need to identify novel prognostic markers and treatment targets. Junctional adhesion molecules (JAM)-A, -B, -C may be relevant candidate for this role, based on clinical and preclinical data. The aim of this study was to examine gene and protein expression of JAMs and assess their prognostic value by relying on both open access large datasets and a sample of pediatric MB. Methods. In the gene expression study, founded on two public datasets (n=763 and n=223), combined risk stratification models based on transcript levels of JAM genes (namely F11R, JAM-2 and JAM-3) and clinically relevant features were identified by multivariate Cox proportional hazards analysis. In the experimental study, we sought to examine the immunohistochemical expression of JAM-A,B,C in a sample of pediatric MB (n=65). Nanostring profiling and immunohistochemistry were adopted to obtain molecular classification. Association and survival analyses were conducted to validate trascriptomic findings. Results. Gene expression analyses showed that JAMs were differentially expressed across consensus molecular subgroups of MB (p<0.0001). In particular, JAM-3 was differentially expressed between MBGrp3 and MBGrp4 and its overexpression was significantly associated with large cell/anaplastic (LC/A) pathology (p=0,007) and shorter survival (p=0,002). These findings were only partially supported by immunohistochemical data, since high expression (3+) of JAM-C was strongly associated with a subset of MBGrp3 with LC/A pathology but did not differentiate between MBGrp3 and MBGrp4. Further, survival analyses displayed a trend for a shorter survival in patients with high expression of JAM-C. Thus, JAM-C may be useful to identify a subset of MBGrp3 with LC/A pathology carrying poor clinical outcomes. Conclusions. JAM-C may have a role as subtyping marker and prognostic factor in pediatric MB. Our findings are consistent with recent evidence suggesting that MBGrp3 and MBGrp4 display significant molecular overlap. In particular, JAM-C is useful to identify a subset of MBGrp3 showing LC/A pathology and dismal prognosis which could at least partially correspond to a recently identified high-risk subtype of MBGrp3 showing LC/A pathology and harbouring MYC amplification. Given the lack of reliable immunohistochemical markers for such emerging subgroup, further studies are needed to investigate the role of JAM-C in relation to clinicopathological features, molecular characteristics and overall prognosis.