The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes

Detalhes bibliográficos
Autor(a) principal: Almeida, Alexandra Sofia Ribeiro de
Data de Publicação: 2020
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47654
Resumo: Trabalho de projeto de mestrado, Bioestatística, Universidade de Lisboa, Faculdade de Ciências, 2020
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spelling The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis OutcomesModelos de CoxModelos de CuraColite UlcerosaTrabalhos de projeto de mestrado - 2020Departamento de Estatística e Investigação OperacionalTrabalho de projeto de mestrado, Bioestatística, Universidade de Lisboa, Faculdade de Ciências, 2020Ulcerative colitis is an idiopathic chronic inflammatory bowel disease characterized by periods of remission and acute exacerbations, and unpredictable disease course. Despite the availability of new drugs, there are still a considerable proportion of patients that will be refractory to therapy, need colectomy or develop complications, highlighting the need for better predictive markers of disease course (Bryant et al. (2016)). Considering the endoscopic extent of the disease at the time of diagnosis, patients were divided into three major subgroups: inflammation limited to the rectum (E1), left-sided colitis with inflammation distally to the splenic flexure (E2) and extensive colitis with involvement proximal to the splenic flexure (E3). The combination of endoscopy and histology seems to provide a better indication of disease activity than endoscopy alone, especially in endoscopically non-inflamed mucosa. No study has assessed the prognostic value of histological features at diagnosis, and therefore it remains unknown whether the pre-treatment microscopic findings can predict the course of the disease. This research topic was proposed by two gastroenterology doctors (Catarina Frias Gomes under the guidance of Dr. Joana Torres), who developed the clinical part of the project, as well as the study protocol. This dissertation then made it possible to answer the questions posed, developing the statistical component (under the guidance of professor Dr. Marília Antunes). Herein, we designed a multicenter retrospective study to evaluate the prognostic value of histologic features in treatment-naïve proctitis and left-sided ulcerative colitis patients. The goals of this study were to evaluate the prevalence of microscopic inflammation in the macroscopically uninflamed mucosa, as well as the predictive value of the histological features of disease (in the endoscopically inflamed and non-inflamed mucosa) at the time of diagnosis. In Portugal there has been a considerable consumption of medical resources associated to UC. Between 2010 and 2017, around 3400 people were hospitalised due to this disease, with an average hospital stay of 10 days with a minimum of 0 days and a maximum of 109 days, making the study of hospitalisations due to this disease a very relevant issue in order to have a perspective of its occurrence, as well as to help in the monitoring of patients and in clinical and hospital administration decision making. In this work, we analyse the time to the need of hospitalisation of 93 patients diagnosed with UC in stages E1 and E2. Cox models were used since proportional hazards assumption was not rejected and Cox models are popular amongst medical researchers, especially concerning the parameter interpretation (Cox and Oakes (1984)). Moreover, according to (Nardi and Schemper (2003)), a good discrimination among parametric models require censoring not to exceed 40-50 per cent. Our data is of moderate size and about 85% of the cases correspond to censored times. Nevertheless, for comparison purposes, we consider fitting parametric models in future work since they can perform better than the Cox model if the required conditions are met. As said above, a large proportion of individuals had no hospitalisations despite their long disease history, suggesting that there are individuals who will never experience the event of interest, even if the time under observation could be prolonged indefinitely. Therefore, we considered the possible existence of “healed to hospitalisation” individuals. To explore this hypothesis, cure models were implemented considering the same set of covariates for comparison purposes (Cai et al. (2012)). It is assumed that the individuals come from a mixture of two populations – those who will experience a hospitalisation and those who will not. Besides producing an estimate of the probability of “cure”, it is expected to obtain a more realistic estimate of the survival function for the fraction of the population who will suffer the event. For the study of this outcome, all the 93 patients were considered, twelve of which had been hospitalized at some time and the remaining were considered censored. Variables age, extent of the disease to diagnosis, endoscopic severity to diagnosis, histological severity and involvement beyond the endoscopic margin were included as covariates. In the Cox model, only age was significant, with older individuals being expected to have later hospitalisations. After the study of the Cox models, and given the high percentage of censorships, the hypothesis that individuals who had not suffered the event until then would probably not suffer it even if the study was prolonged was raised. Thus, with interest in studying whether the censored individuals might be non susceptible to hospitalisations or whether they would suffer the event later, the idea of studying the cure models emerged. One of the main interests was to calculate what percentage of the population was non-susceptible, as well as to verify which variables could influence this choice. In the component defining the occurrence of cure, the only relevant variable was Nancy score, with higher level of Nancy score favouring susceptibility. None of the variables showed relevance to describe the failure time. Much can be improved as future work if one of the major limitations of this study, the sample size, is overcome. Due to the fact that the sample is small and the events of interest are infrequent, the results obtained throughout the study were not statistically significant and therefore could not be used to draw conclusions for clinical purposes nor to advise medical teams. However, since this is an exploratory study and as it is the first study in this area, the conclusions that are drawn (for example, which variables are good predictors for the occurrence of outcomes) can be used as a good indicator and starting point for future research.Antunes, Marília Cristina de Sousa, 1969-Torres, Joana Antunes, 1986-Repositório da Universidade de LisboaAlmeida, Alexandra Sofia Ribeiro de2021-05-04T17:10:36Z202020202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/47654TID:202697053enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:50:43Zoai:repositorio.ul.pt:10451/47654Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:39.665773Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
title The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
spellingShingle The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
Almeida, Alexandra Sofia Ribeiro de
Modelos de Cox
Modelos de Cura
Colite Ulcerosa
Trabalhos de projeto de mestrado - 2020
Departamento de Estatística e Investigação Operacional
title_short The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
title_full The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
title_fullStr The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
title_full_unstemmed The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
title_sort The Predictive value of Microscopic Inflammation beyond The Endoscopic Margin at Diagnosis in Ulcerative Colitis Outcomes
author Almeida, Alexandra Sofia Ribeiro de
author_facet Almeida, Alexandra Sofia Ribeiro de
author_role author
dc.contributor.none.fl_str_mv Antunes, Marília Cristina de Sousa, 1969-
Torres, Joana Antunes, 1986-
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Almeida, Alexandra Sofia Ribeiro de
dc.subject.por.fl_str_mv Modelos de Cox
Modelos de Cura
Colite Ulcerosa
Trabalhos de projeto de mestrado - 2020
Departamento de Estatística e Investigação Operacional
topic Modelos de Cox
Modelos de Cura
Colite Ulcerosa
Trabalhos de projeto de mestrado - 2020
Departamento de Estatística e Investigação Operacional
description Trabalho de projeto de mestrado, Bioestatística, Universidade de Lisboa, Faculdade de Ciências, 2020
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020-01-01T00:00:00Z
2021-05-04T17:10:36Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/47654
TID:202697053
url http://hdl.handle.net/10451/47654
identifier_str_mv TID:202697053
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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