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Doctoral Thesis
DOI
https://doi.org/10.11606/T.22.2019.tde-31072019-125447
Document
Author
Full name
Luis Carlos Lopes Junior
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2017
Supervisor
Committee
Lima, Regina Aparecida Garcia de (President)
Nascimento, Lucila Castanheira
Santos, Manoel Antonio dos
Siqueira, Fernanda Paula Cerantola
Title in English
Neuroimmunoendocrine trajectories and the response to stress and fatigue in pediatric cancer patients under chemotherapy submitted to clown intervention
Keywords in English
Biomarcadores
Biomarkers
Cancer-related fatigue
Clown intervention
Estresse psicológico
Fadiga-relacionada ao câncer
Pacientes pediátricos hospitalizados
Pediatric cancer patients
Psiconeuroimunologia
Psychological stress Psychoneuroimmunology
Terapia do riso
Abstract in English
O câncer e o processo de hospitalização comumente cursam com forte impacto psicológico sobre as crianças e adolescentes, gerando estresse e fadiga. Isto aplica-se especialmente, para àqueles sob quimioterapia, pois esta, constitui-se em uma das experiências mais estressantes e ameaçadoras que pode exacerbar os sintomas relacionados ao câncer e levar a uma diminuição da qualidade de vida (QV). O estresse associado ao desenvolvimento do câncer pode causar disrupturas no eixo hipotálamo-hipófise-adrenal, e suprimir importantes vias neuroimunoendócrinas. Assim, intervenções destinadas a atenuar as alterações fisiológicas relacionadas ao estresse podem favorecer a recuperação do sistema imune e induzir alterações neuroimunoendócrinas para potencializar a vigilância imunológica durante o tratamento oncológico. Com o aumento da incidência de câncer, é crucial que os profissionais de saúde desenvolvam intervenções eficazes para o manejo dos sintomas oncológicos, de modo a aliviar a sobrecarga do tratamento nesses pacientes durante o processo de hospitalização, de modo a contribuir para um melhor prognóstico da doença. Ademais, pacientes pediátricos oncológicos podem se beneficiar de intervenções não-farmacológicas, por exemplo, a intervenção dos clowns, para aliviar os sintomas relacionados ao câncer. Contudo, poucos estudos têm investigado os mecanismos moleculares envolvendo a intervenção dos clowns. Nosso objetivo principal foi investigar os efeitos da intervenção dos clowns sobre o estresse psicológico e a fadiga-relacionada ao câncer (FRC) em pacientes pediátricos oncológicos sob quimioterapia. Além disso, nós investigamos se alterações nos níveis de cortisol, ?-amilase (sAA), citocinas e metaloproteinases de matriz (MMP-9) estão associadas com estresse psicológico e com FRC de pacientes pediátricos com osteossarcoma submetidos à intervenção dos clowns. Trata-se de um estudo quase-experimental pré-teste/pós-teste. Foram colhidas oito amostras de saliva em momentos idênticos, isto é, no baseline (pré-intervenção) e no pós-intervenção (+ 1h, + 4h, + 9h e + 13h após o despertar). As concentrações de cortisol salivar, sAA, citocinas e MMP-9 foram mensuradas por ELISA. Dados sociodemográficos e clínicos foram coletados via prontuários médicos, além disso, foram aplicadas a Escala de Estresse Infantil-ESI(TM) e a Escala Multidimensional de Fadiga-PedsQL(TM). Os escores das escalas foram comparados entre o baseline e o pós-intervenção, e também, foram correlacionados com os níveis dos biomarcadores. Para análise dos dados, utilizou-se da estatística descritiva e estatística não paramétrica. Em comparação com as medidas do baseline, observamos que os níveis de estresse psicológico total, bem como os de fadiga geral dos pacientes pediátricos oncológicos, melhoraram significativamente após a intervenção dos clowns ( p= 0.003; p= 0.049, respectivamente). Não houve correlações significativas entre as Áreas sob Curva (AUC) da sAA e do cortisol no baseline e nem no pós-intervenção. Além disso, a intervenção dos clowns reduziu os níveis de IL-1? e de cortisol nos pacientes pediátricos com osteossarcoma. A AUC da IL-1? correlacionou-se positivamente com AUC do cortisol e com a AUC da sAA no pósintervenção. Inversamente, os níveis de IL-6, TNF-?, IL-12p70, IL-10, TGF-? e MMP-9 não mostraram diferenças significativas no pós-intervenção. Em síntese, nossos resultados sugerem que a intervenção dos clowns é uma boa intervenção não-farmacológica para reduzir o estresse psicológico e a FRC em pacientes pediátricos oncológicos sob quimioterapia
Title in English
Neuroimmunoendocrine trajectories and the response to stress and fatigue in pediatric cancer patients under chemotherapy submitted to clown intervention
Keywords in English
Biomarcadores
Biomarkers
Cancer-related fatigue
Clown intervention
Estresse psicológico
Fadiga-relacionada ao câncer
Pacientes pediátricos hospitalizados
Pediatric cancer patients
Psiconeuroimunologia
Psychological stress Psychoneuroimmunology
Terapia do riso
Abstract in English
Cancer and the hospitalization process often have a psychological impact on the children and adolescents, usually leading to intense stress as well as fatigue. This especially applies to children and adolescents who have been submitted to chemotherapy, since it still constitutes a stressful and threatening experience for them and may exacerbate cancer symptom burden clusters, leading to a decrease in their health related quality of life (QoL). In addition, stress associated with cancer development leads to disturbances/disruption in the hypothalamicpituitary-adrenal (HPA) axis and suppresses important neuroimmunoendocrine pathways. Hence, interventions aimed at attenuating the physiological changes related to stress favor the recovery of the immune system and, consequently, induce alterations in neuroimmunoendocrine factors that increase immunological surveillance during cancer treatment. With the increase in cancer rates, it is crucial that healthcare professionals develop effective interventions to support pediatric cancer patients during the hospitalization process in order to relieve the burden of cancer treatment, which may contribute to a better prognosis of the disease. In an attempt to alleviate some of the cancer-related symptoms, pediatric oncology patients can take advantage of non-pharmacological interventions, including clown intervention, which can be a very advantageous approach to reduce unpleasant symptoms in pediatric cancer patients. However, few studies have investigated the molecular mechanisms that mediate health outcomes of clown intervention. The main purpose of this study was to investigate the effects of the clown intervention on psychological stress and cancer-related fatigue (CRF) in pediatric cancer inpatients undergoing chemotherapy. Also, we aimed to investigate whether changes in the levels of biomarkers, including cortisol, ?-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) are associated with psychological stress and CRF levels in pediatric osteosarcoma inpatients following clown intervention. A pretestposttest quasi-experimental study was undertaken with pediatric cancer inpatients. Eight nonfasting saliva samples were collected at identical times upon clown intervention, i.e., at baseline (pre-intervention) and post-intervention (+ 1h, + 4h, + 9h, and + 13h post awakening). Salivary cortisol, sAA, cytokines and MMP-9 concentrations were measured using high sensitivity Enzyme-Linked Immuno Sorbent Assay. Sociodemographic and clinical data, and Child Stress Scale-ESI(TM) and PedsQL(TM) Multidimensional Fatigue Scale were applied and the results were compared at baseline and after the clown intervention, and also correlated with biomarker trajectories. Data analysis was performed using nonparametric statistical tests. In comparison with baseline measurements, the overall psychological stress for pediatric cancer inpatients as well as their perception of fatigue improved upon clown intervention (p= 0.003; p= 0.049, respectively). There were no significant correlations between sAA and cortisol for both Areas Under Curve (AUC) at baseline or at post-intervention. Also, clown intervention reduced IL1? and salivary cortisol levels in pediatric osteosarcoma inpatients. Additionally, AUC for IL1? positively correlated with AUC for cortisol as well as with AUC for sAA at postintervention. In contrast, levels of IL-6, TNF-?, IL-12p70, IL-10, TGF-? and MMP-9 did not show significant differences upon clown intervention. Overall, our results suggest that clown intervention is a good non-pharmacological intervention to reduce psychological stress and CRF in pediatric cancer inpatients undergoing chemotherapy
 
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Publishing Date
2019-10-08
 
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