Clostridium difficile colitis (CDC) is associated with a higher risk of acute death among hospitalized ulcerative colitis (UC) patients. However, the risk of colectomy with CDC in these patients has varied across studies. No study has assessed the long-term health impact of CDC in UC patients. Therefore, the present study evaluated the impact of CDC on five-year health outcomes of hospitalized UC patients based on Ontario health administrative data. No overall association was observed between CDC and five-year risks of colectomy or death in overall cohort. However, patients who were discharged from hospital without undergoing colectomy demonstrated marginally higher five-year risks of colectomy and hospital re-admission. Mortality risk and length of stay during index hospitalization were also higher in patients with CDC. Analysis of a parallel cohort of UC patients derived using a published case definition corroborated most of these results, but demonstrated a higher five-year mortality risk with CDC.

Bakgrund: Crohns sjukdom och ulcerös kolit är två huvudtyper som utmärker inflammatorisk tarmsjukdom. Inflammatorisk tarmsjukdom påverkar mag- och tarmkanalen och har ett oförutsägbart sjukdomsförlopp. Inflammatorisk tarmsjukdom debuterar vanligtvis i åldern 15-30 och kan ge ogynnsamma konsekvenser i personens dagliga aktiviteter eftersom han eller hon är upptagen med att exempelvis studera, skapa karriär eller bilda familj. Sjukdomarna har flera gemensamma särdrag där de förekommer i så kallade skov med perioder med försämring då tarmslemhinnan blir inflammerad och sårig, vilket leder till symtom som exempelvis blodiga eller slemmiga diarréer, viktnedgång, buksmärtor och trötthet Syfte: Syftet med uppsatsen är att beskriva konsekvenser av att leva med Crohns sjukdom eller Ulcerös kolit hos vuxna personer. Metod: En litteraturöversikt. En litteratursökning gjordes som ledde till sex granskade artiklar. Resultatartiklarna analyserades sedan utifrån det valda syftet. Resultat: I analysen av resultatartiklarna framkom det fem olika återkommande teman. Dessa teman är fysiska konsekvenser av sjukdomen, psykiska konsekvenser av sjukdomen, sociala konsekvenser, förlust av kontroll samt påverkad föräldraroll. Flera teman innehöll subteman. Diskussion: Olika aspekter av patientens liv klarlades i resultatet vilket gör det möjligt för sjuksköterskan att i mötet med patienten kunna ge bra stöd och omsorg. Resultatet uppmärksammar de problem som patienten har i mötet med vårdpersonalen. Genom att upplysa och göra vården uppmärksam kring problemen så kan det underlättas för patienten i hans eller hennes behandling. Genom att lära patienten att hantera sin sjukdom och få behandling vid första tecken på återfall kan hans eller hennes lidande minska. / Background: Two main types that characterize inflammatory bowel disease are Crohn’s disease and ulcerative colitis. Inflammatory bowel disease affecting the digestive tract, and has an unpredictable disease course. Inflammatory bowel disease onset is usually between the ages of 15-30. It can cause adverse effects in a person’s daily activities because he or she is busy studying, building a career, raising a family and so on. Diseases have several common features. They occur in so-called relapses with periods of worsening when the gut lining becomes inflamed and ulcerated. It leads to symptoms such as bloody or slimy diarrhea, weight loss, abdominal pain and fatigue. Aim: The purpose of this paper is to describe the impact of living with Crohn's disease or ulcerative colitis in adults. Methods: A literature review. A literature search was performed which resulted in six peer-reviewed articles. Results Articles were then analyzed based on the selected object. Results: The analysis of the articles revealed five recurring themes. These themes are physical aspects of the disease, mental aspects of the disease, social aspects, and loss of control as well as being a parent whom are living with inflammatory bowel disease. Several themes also hold underlying themes. Discussions: Different aspects of the patients’ life were clarified in the results. It allowed the nurse to be prepared and provide god support and care when meeting with the patient.  The result highlights the problems that the patient has been in meetings with nursing staff. The attention on the problems in the patients’ treatment must be enlightened. By teaching patients to manage their condition and get treatment at the first sign of relapse, his or her suffering will decline.

Submitted by RODRIGO GALHARDI GASPARINI null (rggaspa@yahoo.com.br) on 2018-03-05T01:36:53Z No. of bitstreams: 1 Incidência e Prevalência de Doenças Inflamatórias Intestinais no Estado de Sâo Paulo - Brasil.pdf: 2020180 bytes, checksum: 64bba02d0cbc3e4d580ce7721fe858d7 (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-03-06T13:58:57Z (GMT) No. of bitstreams: 1 gasparini_rg_dr_bot.pdf: 2020180 bytes, checksum: 64bba02d0cbc3e4d580ce7721fe858d7 (MD5) / Made available in DSpace on 2018-03-06T13:58:57Z (GMT). No. of bitstreams: 1 gasparini_rg_dr_bot.pdf: 2020180 bytes, checksum: 64bba02d0cbc3e4d580ce7721fe858d7 (MD5) Previous issue date: 2018-02-23 / Introdução: As Doenças inflamatórias intestinais (DII), que tem como principais entidades a Retocolite Ulcerativa (RCU) e a Doença de Crohn (DC), tem altas taxas de incidência e prevalência em países desenvolvidos, especialmente da Europa e América do Norte, porém com aumento progressivo de sua frequência em todas os continentes. Este estudo visa estimar as taxas de incidência e prevalência das DII no Estado de São Paulo, Brasil, entre os anos de 2012 e 2015, e correlacionar os resultados com dados nacionais sobre estas doenças. Material e Método: Este é um estudo observacional analítico, do tipo descritivo e transversal. Foram incluídos dados epidemiológicos de 22.638 pacientes que iniciaram seu tratamento para Doença Inflamatória Intestinal através do programa de fornecimento gratuito de medicamentos do Estado de São Paulo, entre os anos de 2012 e 2015. As variáveis analisadas foram a data do início do tratamento, o diagnóstico clínico (DC ou RCU), a idade, gênero, cor/raça/etnia dos pacientes, assim como sua região de residência no Estado de São Paulo. As análises estatísticas incluíram média e desvio padrão para variáveis quantitativas. O nível de significância adotado foi de 1% Resultados: A taxa de incidência de DII no Estado de São Paulo foi, em média, de 13,31 casos novos / 100.000 habitantes / ano, enquanto a prevalência de DII no Estado de São Paulo foi de 52,5 casos / 100.000 habitantes. Os portadores de DC somavam 10.451 (46,16%), e os de RCU somavam 12.187 (53,83%), de 1 a 97 anos de idade, com média de 45,5 anos (DP = 16,7), sendo 9.124 (40,30%) do sexo masculino e 13.514 (59,70%) do sexo feminino. Conclusão: Este estudo demonstrou aumento das taxas de incidência e prevalência de Doenças Inflamatórias Intestinais no Estado de São Paulo. / Inflammatory bowel disease (IBD), which has as its main entities Ulcerative Colitis (UC) and Crohn's Disease (CD), have high rates of incidence and 11 prevalence in developed countries, especially in Europe and North America, but with increasing frequency in all continents. This study aims to verify the incidence and prevalence rates of IBD in São Paulo State, Brazil, between the years 2012 and 2015, and correlate with the national data on these diseases. Casuistic and Methods: This is an observational, descriptive and cross-sectional study. We included data from 22.638 patients who started their treatment for Inflammatory Bowel Disease through the Program of free medication supply of São Paulo State, between the years of 2012 and 2015. The variables analyzed were the date of beginning of treatment with drugs provided by the clinical diagnosis (CD or UC), the age, gender, color/race/ethnicity of the patients, as well as their region of residence in São Paulo State. Statistical analyses included mean and standard deviations for quantitative variables. The level of significance adopted was 1% Results: The incidence rate of IBD in the State of São Paulo was 13.31 new cases / 100.000 inhabitants per year, while the overall prevalence of IBD in the state of São Paulo was 52,5 cases/100.000 inhabitants. The patients with CD were 10,451 (46.16%), and those with UC were 12,187 (53.83%), from 1 to 97 years of age, with a mean of 45.5 years (SD = 16.7), of wich 9,124 (40.30%) were male and 13,514 (59.70%) were female. Conclusion: This study demonstrated an increase in the incidence and prevalence of Crohn's Disease and Ulcerative Colitis in the State of São Paulo.

Orientador: Alba Regina Monteiro Souza Brito / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-18T00:28:36Z (GMT). No. of bitstreams: 1 Socca_EduardoAugustoRabelo_M.pdf: 1268769 bytes, checksum: eee2c6686e3a3fb123101e6954836a0f (MD5) Previous issue date: 2010 / Resumo: Retocolite ulcerativa idiopática e doença de Crohn são doenças inflamatórias intestinais caracterizadas por inflamação crônica da mucosa, resultando em diarréia, fezes sanguinolentas, dores abdominais, anemia, febre, fadiga e perda de peso, tanto em homens quanto em mulheres. Acredita-se que essas manifestações sejam resultado de uma interação multifatorial envolvendo indivíduos geneticamente susceptíveis, condições ambientais específicas, desbalanço na microflora intestinal e desajuste da resposta imune. Drogas derivadas do acido 5-aminossalicilico (sulfassalazina, mesalamina), corticosteroides e agentes imunomoduladores são utilizadas, em conjunto no tratamento dessas patologias. No entanto tais drogas apresentam efeitos adversos importantes, o que acaba por motivar pesquisas envolvendo produtos naturais como alternativas de tratamento. Neste contexto, este trabalho avaliou os efeitos de antocianinas presentes nos frutos de Sambucus nigra L. (sabugueiro), espécie arbustiva pertencente a família Adoxaceae, em modelo de colite ulcerativa induzida pelo acido 2,4,6-trinitrobenzeno sulfônico (TNBS). Os frutos do sabugueiro apresentam grandes concentrações de metabolitos secundários como antocianinas, alem de outros compostos fenólicos, que acabam por conferir aos frutos propriedades antioxidantes, anti-inflamatorias, imunomoduladoras e laxativas. Neste trabalho, foram avaliadas as propriedades antioxidantes e anti-inflamatorias da fração de antocianinas monoméricas presentes nos frutos de S. nigra. Os resultados comprovaram o efeito antioxidante in vitro das antocianinas, sendo elas eficazes em reduzir tanto o radical 2,2-difenil-1-picrilhidrazil (DPPH), teste que avalia a redução do radical via transferência de elétrons, quanto a taxa de oxidação do radical 2,2 azobis amidinopropano (AAPH), teste que verifica a oxidação do radical via transferência de átomos de hidrogênio. Nos ensaios in vivo concluiu-se que a dose de 5mg.Kg-1 de antocianinas apresentou a melhor resposta em reduzir a lesão causada pelo TNBS, sendo efetiva em manter os níveis de GSH (5,709 ± 0,931) comparado ao grupo TNBS (0,8525 ± 0,298) e ao grupo salina (6,610 ± 3,926). Essas antocianinas foram efetivas ainda em aumentar a atividade da SOD (8,487 ± 2,505), quando comparada com o grupo TNBS (3,884 ± 0,925) e ao grupo salina (12,240 ± 4,199), e reduzir a atividade da MPO (4,519 ± 2,016), quando comparada ao grupo TNBS (7,572 ± 2,572) e ao grupo salina (1,314 ± 0,319). Os resultados obtidos na avaliação da atividade das enzimas GPx (17,03 ± 3,951 no grupo tratado e 22,13 ± 11,510 no grupo TNBS) e GR (0,6524 ± 0,1180 no grupo tratado e 0,7249 ± 0,3968 no grupo TNBS), comparados ao grupo salina (84,22 ± 41,88) e (2,131 ± 0,9858) respectivamente, indicam que houve queda na ativação destas enzimas apos 24h de indução da colite, sendo que esta situação não foi revertida apos administração das antocianinas. Do mesmo modo não foram encontradas alterações nos níveis de LPO (5,756 ± 1,884 no grupo tratado e 5,113 ± 0,8254 no grupo TNBS) comparados ao grupo salina (4,688 ± 1,126) . Já os ensaios anti-inflamatórios revelaram atividade antiinflamatória promissora, visto que as antocianinas foram capazes de manter os níveis de IL-10 (466,7 ± 56,32) próximos aqueles obtidos no grupo não-colitico (492,4 ± 154,5), quando comparados ao grupo TNBS (264,8 ± 66,35), e de reduzir a produção de IL-12 (202,3 ± 53,33) quando comparados com os animais não tratados (319,3 ± 111,5) e ao grupo salina (149,8 ± 51,76). Neste estudo concluiu-se que as antocianinas presentes nos frutos de sabugueiro apresentam atividade antioxidante, alem de aumentar os níveis de IL-10, citocina essa que, provavelmente, participa na redução dos níveis de citocinas pro - inflamatórias como IL-12 e, consequentemente, a expressão de mediadores inflamatórios / Abstract: Ulcerative colitis and Crohn's disease are inflammatory bowel disease characterized by chronic inflammation of the mucosa, resulting in diarrhea, bloody stools, abdominal pain, anemia, fever, fatigue and weight loss in both men and women. It is believed that these manifestations are the result of a multifactorial interaction involving genetically susceptible individuals, environmental conditions, imbalance in intestinal microflora and immune response imbalance. Drugs derived from 5-aminosalicylic acid (sulfasalazine, mesalamine), corticosteroids and immunomodulatory agents are used together to treat these diseases. However, such drugs have significant adverse effects, which ultimately motivate research involving natural products as alternative treatments. In this context, this study evaluated the effects of anthocyanins in the fruits of Sambucus nigra L. (Elderberry), shrub species belonging to the family Adoxaceae, in a model of ulcerative colitis induced by 2,4,6-trinitrobenzenes sulfonic acid (TNBS). The fruits of elderberry have large concentrations of secondary metabolites such as anthocyanins and other phenolic compounds, which ultimately give the fruit antioxidant, anti-inflammatory, immunomodulatory and laxative properties. In this study we investigated the antioxidant and anti-inflammatory properties of the monomeric anthocyanins fraction in the fruits of S. nigra. The results confirmed the in vitro antioxidant effect of anthocyanins, which were effective in reducing both the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test to evaluate the reduction of the radical via electron transfer and the rate of oxidation 2,2 azobis amidinopropane (AAPH), a test that checks radical oxidation via the transfer of hydrogen atoms. In vivo tests concluded that the dose of anthocyanins 5mg.Kg-1 had the best response to reduce the damage caused by TNBS, being effective in maintaining the levels of GSH (5.709 ± 0.931) compared to TNBS group (0, 8525 ± 0.298) and the saline group (6.610 ± 3.926). These anthocyanins were also effective in increasing the activity of SOD (8.487 ± 2.505) compared with the TNBS group (3.884 ± 0.925) and the saline group (12.240 ± 4.199), and reduce the activity of MPO (4.519 ± 2.016) when compared to TNBS group (7.572 ± 2.572) and the saline group (1.314 ± 0.319). The results obtained in the enzymatic activities of GPx (17.03 ± 3.951 in the treated group and 22.13 ± 11.510 in group TNBS) and GR (0.6524 ± 0.1180 in the treated group and 0.7249 ± 0.3968 TNBS group) compared to saline group (84.22 ± 41.88) and (2.131 ± 0.9858) respectively, indicate that there was a decrease in the activation of these enzymes after 24h of colitis induction. Likewise there were no changes in the levels of LPO (5.756 ± 1.884 in the treated group and 5.113 ± 0.8254 in group TNBS) compared to saline group (4.688 ± 1.126). The anti-inflammatory assays have shown promising antiinflammatory activity, whereas anthocyanins were able to maintain levels of IL-10 (466.7 ± 56.32) than those obtained in non-colitis group (492.4 ± 154 , 5), when compared to TNBS group (264.8 ± 66.35), and reduce the production of IL-12 (202.3 ± 53.33) compared with untreated animals (319.3 ± 111 , 5) and the saline group (149.8 ± 51.76). In this study it was concluded that anthocyanins present in elderberry fruits have antioxidant activity, and increased levels of IL-10, this cytokine, which probably participates in reducing levels of proinflammatory cytokines such as IL-12 and consequently the expression of inflammatory mediators / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

No trato digestório a colite ulcerativa apresenta necrose no intestino como processos patofisiológicos. Este projeto visou estudar neurônios com códigos químicos do sistema nervoso entérico (SNE) e a morfologia estrutural do intestino grosso de animais com colite ulcerativa. Grupos: a) Colite: injetados com TNBS, b) PBS: injetados com PBS e c) controle. Os tecidos foram preparados por métodos imunohistoquímicos de duplas marcações do receptor P2X7 com NOS, ChAT, Calb, Calr, anti-HuC/D (pan-neuronal) e S100 (células glias). No grupo Colite, no plexo mioentérico, o receptor P2X7 estava diminuído. No tecido lesado apresentou aumento de neutrófilos e da lâmina própria, alteração de colágeno e destruição do epitélio e células caliciformes. Reduziram colocalizações de neurônios com receptor no plexo mioentérico e aumento no plexo submucoso. Houve reduções nas densidades e áreas dos neurônios no SNE. Conclui-se que a colite afetou os neurônios entéricos e células gliais, causou alterações morfológicas, sendo assim, pode afetar motilidade intestinal. / In the digestive tract ulcerative colitis have a bowel necrosis as pathophysiological processes. This project aimed to study neurons with their respective chemicals codes the enteric nervous system (ENS) as well as structural morphology of the distal colon of animals with ulcerative colitis. Groups: a) colitis: TNBS injected, b) PBS: PBS injected and c) control. The tissues were prepared by immunohistochemical methods for double marking with P2X7 receptor, ChAT, Calb, Calr, anti-HUC / D (pan-neuronal) and S100 (glial cells). In the colitis group, the myenteric plexus, the P2X7 receptor decreased. In the injured tissue showed increased neutrophils, alteration and destruction of collagen and epithelial goblet cells. There were reduced colocalizations of neurons with receptor in myenteric plexus and increase in submucosal plexus. There were reductions in the densities and areas neurons of ENS. Concluded that colitis affected enteric neurons and glial cells, causing morphological changes and could be affect intestinal motility.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-07-14T11:38:20Z No. of bitstreams: 1 lilianaandradechebli.pdf: 509558 bytes, checksum: 46eb6aa1950b8cf02f40073b054ed6c3 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-07-19T14:23:32Z (GMT) No. of bitstreams: 1 lilianaandradechebli.pdf: 509558 bytes, checksum: 46eb6aa1950b8cf02f40073b054ed6c3 (MD5) / Made available in DSpace on 2016-07-19T14:23:32Z (GMT). No. of bitstreams: 1 lilianaandradechebli.pdf: 509558 bytes, checksum: 46eb6aa1950b8cf02f40073b054ed6c3 (MD5) Previous issue date: 2011-10-17 / Colite ulcerativa é uma doença inflamatória intestinal idiopática da mucosa colônica caracterizada clinicamente por episódios intermitentes de exacerbações alternados com períodos de remissão. Os corticosteroides permanecem como uma das drogas mais efetivas no tratamento das exacerbações moderadas a graves da colite ulcerativa. Entretanto, eles não são adequados para terapia de manutenção devido à falta de eficácia na prevenção de recorrências. Além disso, seu uso associa-se frequentemente com vários efeitos adversos e, aproximadamente, 25% dos pacientes que respondem aos corticosteroides serão incapazes de tolerar sua retirada sem que apresentem recorrências sintomáticas. Consequentemente, ―dependência de esteróides‖ em pacientes com colite ulcerativa é um problema de grande relevância na prática e manutenção da remissão sem esteróides é meta importante a ser alcançada. Diversas modalidades terapêuticas podem ser empregadas em pacientes com colite ulcerativa córtico-dependente (CUCD). Tradicionalmente, a escolha é entre a cirurgia ou o escalonamento do tratamento clínico, que geralmente envolve o uso de imunossupressores. O tratamento com azatioprina (AZA) tem tido amplo uso neste cenário. Entretanto, estudos no longo prazo avaliando a eficácia da AZA na CUCD são inexistentes. Os objetivos deste estudo foram avaliar em pacientes com CUCD, a eficácia da AZA no longo prazo para manutenção da remissão clínica sem esteróides, bem como a segurança desta droga neste contexto. Neste estudo de coorte prospectivo observacional, pacientes adultos com CUCD foram recrutados para tratamento com AZA durante o período de 36 meses. AZA foi ajustada para a dose alvo de 2-3 mg/Kg/dia. A redução da dose de esteróides durante o estudo seguiu um esquema previamente padronizado. A avaliação primária de eficácia foi a taxa anual de pacientes que alcançaram resposta sustentada a AZA sem esteróides. Resposta sustentada foi definida como a retirada completa dos corticosteroides e manutenção da remissão clínica sem a necessidade de se reintroduzir esteróides durante pelo menos seis meses adicionais. As principais avaliações de eficácia secundária foram: dose cumulativa anual de esteróides, número anual de recorrências da colite após introdução da AZA e efeitos adversos. Em base intenção de tratar, a proporção de pacientes permanecendo em remissão sem esteróides em 12, 24, e 36 meses foi 0.55, 0.52, e 0.45, respectivamente. Significante diminuição na taxa de recidivas clínicas assim como no requerimento para esteróides foram observados durante três anos de tratamento com AZA comparado com o ano prévio (P=0.000 para ambos). Pacientes com e sem resposta sustentada foram similares de acordo com demografia, extensão da doença, dose de AZA, uso de esteróides e 5-ASA. Apenas a duração menor da doença (<36 meses) associou-se à remissão sem esteróides (P=0.02, OR 3.12 95% IC 1.89-7.64). AZA foi bem tolerada e o perfil risco-benefício favorável. Neste estudo, AZA mostrou eficácia sustentada para manutenção da remissão clínica sem esteróides e para poupar esteróides durante três anos de terapia em pacientes com CUCD. Pacientes com colite ulcerativa de início mais recente são aqueles que mais provavelmente alcançarão remissão sustentada sem esteróides no final de 12 meses enquanto em uso de AZA. Isto parece se manter por até 36 meses. / Ulcerative colitis (UC) is a lifelong, immune-mediated inflammatory condition of the colonic mucosa, which is characterized by a relapsing and remitting course. Corticosteroids remain one of the most effective therapies for inducing remission in patients with moderate-to-severe UC. Nonetheless, corticosteroids are not used in maintenance therapy, mainly because undesirable side effects outweigh the possible benefits. Furthermore, approximately 25% of the patients is unable to support its withdrawal without relapsing, suggesting that the need to start steroid therapy in UC is associated with a dismal long-term prognosis. Thus, corticosteroid dependence in patients with UC is a pivotal clinical problem and maintenance of steroid-free remission is an important current evolving treatment goal. Patients with steroid dependent UC are usually given a choice between colectomy or stepped-up medical treatment, which traditionally involves prescription of an immunosuppressive drug. Azathioprine (AZA) therapy has found widespread use for this setting in clinical practice. However, studies assessing the efficacy of azathioprine in steroid-dependent ulcerative colitis (SD-UC) are scarce. The purpose of this trial was to explore the efficacy and safety of AZA in maintaining long-term steroid-free remission in SD-UC patients and the factors associated to sustained response. In this observational cohort study 42 subjects with SD-UC were recruited for AZA therapy during a 3-year period. AZA was adjusted for a target dose of 2-3 mg/Kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the annual rate of steroid-free response to AZA. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. On an intention-to-treat basis, the proportion of patients remaining in steroid-free remission at 12, 24, and 36 months was 0.55, 0.52, and 0.45, respectively. A significant decrease in the flare-ups rate and in requirement for steroids were observed during 3 years on AZA compared with the previous year (P=0.000 for both). Patients with and without sustained response were comparable according to demographics, extent of disease, dose of AZA, steroids and 5-ASA use. Only disease duration <36 months was associated to off-steroids remission (P=0.02, OR 3.12 95% CI 1.89-7.64). The AZA benefit-risk profile was favorable. In this open-label observational trial AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 3 years of therapy in SD-UC. Patients with earlier UC are those who most probably will have sustained steroid-free remission at the end of 12 months while on AZA. This appears to sustain until 36 months.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-14T14:16:56Z No. of bitstreams: 1 lilianaandradechebli.pdf: 4797149 bytes, checksum: 48711245cd6bc4dca1d8093d1e776787 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-29T12:12:52Z (GMT) No. of bitstreams: 1 lilianaandradechebli.pdf: 4797149 bytes, checksum: 48711245cd6bc4dca1d8093d1e776787 (MD5) / Made available in DSpace on 2017-06-29T12:12:52Z (GMT). No. of bitstreams: 1 lilianaandradechebli.pdf: 4797149 bytes, checksum: 48711245cd6bc4dca1d8093d1e776787 (MD5) Previous issue date: 2009-08-06 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / Colite ulcerativa é uma condição inflamatória imuno-mediada da mucosa colônica, caracterizada por curso intermitente e recorrente. Corticosteróides permanecem como uma das terapias mais efetivas para induzir remissão em pacientes com colite ulcerativa moderada a severa. Todavia, corticosteróides não são usados como terapia de manutenção, principalmente porque os efeitos colaterais indesejáveis superam seus possíveis benefícios. Além disso, em um ano, menos da metade dos pacientes com colite ulcerativa que requerem corticosteróides terão resposta sustentada, aproximadamente um terço dos pacientes necessitarão de colectomia e um quarto não tolerarão a retirada do mesmo sem que apresentem recidiva da doença. Assim, dependência de corticóides em paciente com colite ulcerativa é problema clínico fundamental e manutenção da remissão sem esteróides é uma importante meta terapêutica no presente. Em pacientes com colite ulcerativa córtico-dependente, usualmente é colocado a escolha entre colectomia ou escalonamento do tratamento clínico, o qual tradicionalmente envolve a prescrição de droga imunossupressora. A terapia com tiopurinas tem tido amplo uso neste cenário na prática clínica. Entretanto, estudos avaliando a eficácia da azatioprina (AZA) na colite ulcertiva córtico-dependente são escassos. Os objetivos deste estudo foram avaliar em pacientes com colite ulcerativa dependente de esteróides, a eficácia da AZA na manutenção da remissão clínica sem esteróides, bem como os possíveis fatores associados à resposta sustentada a esta droga. Neste estudo de coorte observacional, pacientes adultos com colite ulcerativa dependente de esteróides foram recrutados para tratamento com AZA durante o período de 12 meses. AZA foi ajustada para a dose alvo de 2-3 mg/Kg/dia. A redução da dose de esteróides durante o estudo seguiu um esquema previamente padronizado. A avaliação primária de eficácia foi a taxa anual de pacientes que alcançaram resposta sustentada a AZA sem esteróides. Avaliações secundárias incluíram o número anual de recorrências clínicas, dose mediana de esteróides utilizadas durante o ano e segurança do tratamento. O total de 42 pacientes foi incluído. Na análise intenção de tratar, a proporção de pacientes permanecendo em remissão sustentada sem esteróides no final de 12 meses foi de 0,55. Observou-se significante redução na taxa de recorrências clínicas, assim como no requerimento de esteróides durante 12 meses de tratamento com AZA quando comparado com o ano anterior ao uso desta droga. (P=0,000 para ambas as comparações). Apenas a duração da doença < 36 meses antes do início da AZA foi associada à remissão clínica sem esteróides (P=0,02, OR 3,12 95% IC 1,89-7,64). AZA foi bem tolerada e o seu perfil risco-beneficio favorável. AZA mostrou eficácia sustentada para a manutenção da remissão clínica sem esteróides, bem como efeito poupador de esteróides durante 12 meses de terapia em pacientes com colite ulcerativa dependente de esteróides. Os pacientes com colite ulcerativa de início mais precoce são aqueles que mais provavelmente alcançarão remissão sustentada sem esteróides durante o uso de AZA. / Ulcerative colitis (UC) is a lifelong, immune-mediated inflammatory condition of the colonic mucosa, which is characterized by a relapsing and remitting course. Corticosteroids remain one of the most effective therapies for inducing remission in patients with moderate-to-severe UC. Nonetheless, corticosteroids are not used in maintenance therapy, mainly because undesirable side effects outweigh the possible benefits. Furthermore, at one year, less than half of UC patients who require steroids have a sustained response, nearly one-third of patients require colectomy, and approximately a quarter is unable to support its withdrawal without relapsing. Thus, corticosteroid dependence in patients with UC is a pivotal clinical problem and maintenance of steroid-free remission is an important current evolving treatment goal. Patients with steroid dependent UC are usually given a choice between colectomy or stepped-up medical treatment, which traditionally involves prescription of an immunosuppressive drug. Thiopurine therapy has found widespread use for this setting in clinical practice. However, studies assessing the efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (UC) are scarce. The purpose of this trial was to explore the efficacy of AZA in maintaining steroid-free remission in steroid-dependent UC patients as well as the factors associated to sustained response. In this observational cohort study adult subjects with steroid-dependent UC were recruited for AZA therapy during a 12 months period. AZA was adjusted for a target dose of 2-3 mg/Kg/day. Steroid therapy was tapered off following a standardized regimen. The primary endpoint was the rate of patients with sustained steroid-free response to AZA at the end of 12 months. Secondary endpoints included clinical recurrence, yearly steroid dose, and safety of treatment. A total of 42 patients were included. On an intention-to-treat basis, the proportion of patients remaining in sustained steroid-free remission at 12 months was 0.55. A significant decrease in the flare-ups rate as well as in requirement for steroids were observed during 12 months while on AZA compared with the previous year (P=0.000). Only disease duration of <36 months before the initiation of AZA was associated to off-steroids remission (P=0.02, OR 3.12 (95% CI 1.89-7.64)). AZA was well tolerated and its benefit-risk profile favorable. AZA showed sustained efficacy for maintenance of clinical remission off steroids and steroid sparing through 12 months of therapy in patients with steroid dependent UC. Patients with earlier UC are those who most probably will have sustained steroid-free remission while on AZA.

Orientador: José Murilo Robilotta Zeitune / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T02:57:17Z (GMT). No. of bitstreams: 1 Parente_JoseMiguelLuz_D.pdf: 3595737 bytes, checksum: a5229b134d3c146b3029f45e146e580e (MD5) Previous issue date: 2014 / Resumo: Introdução: Doença de Crohn (DC) e Retocolite Ulcerativa Idiopática (RCUI) são as duas principais doenças inflamatórias intestinais (DII), cuja prevalência é mais expressiva no norte da Europa, Estados Unidos da América e Canadá. Mais recentemente, elas passaram a ser detectadas em frequência crescente em todos os continentes. O objetivo desta pesquisa foi analisar as características demográficas e fenótipos clínicos dos pacientes com DII no Nordeste brasileiro, referentes à época da confirmação do diagnóstico. Casuística e Método: Este é um estudo descritivo e transversal, o qual foi aprovado pelo Comitê de Ética e Pesquisa da UFPI. Foram incluídos censitariamente os pacientes com DII que faziam seguimento clínico em serviços especializados de hospitais universitários em todas as capitais do Nordeste do Brasil. As variáveis analisadas foram: as características demográficas e socioeconômicas, e os dados clínicos de DC e RCUI de acordo com a classificação de Montreal. As análises estatísticas incluíram: média, mediana e desvio padrão para variáveis quantitativas; teste do qui-quadrado (c2) de Pearson para análise das variáveis qualitativas. O nível de significância adotado foi de 5%. Resultados: Foram incluídos 913 indivíduos com DII, sendo 486 (52,1%) com RCUI, 412 (44,2%) com DC e 35 (3,7%) com colite não classificada (CNC). A idade dos pacientes variou de 8 anos a 83 anos, média de 37,9 (DP = 14,4) anos, sendo 469 (50,3%) mulheres. Em todo o período estudado (1975 ¿ 2013), o atraso na confirmação diagnóstica foi de 31,0 meses. As características preponderantes dos pacientes com DC, segundo a classificação de Montreal foram: idade entre 17 e 40 anos (A2), localização com envolvimento de cólons (L2) e comportamento inflamatório (B1). Para os pacientes com RCUI, houve predomínio de pacientes com idade entre 17 e 40 anos e extensão da doença até ângulo esplênico (E2). Conclusão: Este estudo demonstrou que houve expressivo aumento na frequência de DC e RCUI na região Nordeste do Brasil nos últimos trinta anos / Abstract: Introduction: Usually, inflammatory bowel diseases (IBD), as Crohn's disease (CD) and ulcerative colitis (UC), have been described in northern Europe, United States of America and Canada. In the last decades, IBD frequency has been also increased in all continents. The aim of the study was to analyze the demographic characteristics and clinical phenotypes of IBD in the northeastern of Brazil, according to the time of the diagnosis. Casuistic and methods: This is a cross-sectional study, which was approved by the Institutional Ethics and Research Committee. We included patients who were undergoing medical treatment for IBD in specialized centers in the Federal University Hospitals from all Northeasthern areas in Brazil. Demographic and socioeconomic characteristics were analyzed, as well as clinical data of CD and UC according to the Montreal classification. Statistical analyses included mean, median and standard deviations for quantitative variables, and the Pearson chi-square (c2) test for qualitative variables. The level of significance adopted was 5%. Results: A total of 913 patients with IBD were included, 486 (52,1%) with UC, 412 (44,2%) with CD and 35 (3,7%) with unclassified colitis (UnC). The ages ranged from 8 years to 83 years, mean 37.9 (SD = 14.4) years. Of the total, 469 (50.3%) were women. Throughout the study period (1975 ¿ 2013), the delay in diagnosis confirmation was 31.0 months. The predominant characteristics of CD patients, according to the Montreal classification were: age between 17 and 40 years (A1); colon location (L2); and inflammatory behavior (B1). For patients with UC, there was a predominant age between 17 and 40 years, and left colitis (E2). Conclusion: This study showed that there was significant increase in the frequency of IBD (CD and UC) in northeastern of Brazil over the past thirty years / Doutorado / Medicina Interna / Doutor em Ciências Médicas

Living with inflammatory bowel disease (IBD) affects physical, psychological and social dimensions, limiting the ability to engage in daily activities. Persons with IBD may need frequent and lifelong contacts with the healthcare (HC), highlighting the importance of quality care. High quality HC for persons with IBD involves a partnership between the HC professionals and the person living with the disease. Information is essential, the more a person knows about their disease, the more concordant and satisfied with their treatment they are likely to be. The overall aim of this thesis was to describe the knowledge need, life situation and perception of HC among persons living with IBD, in order to develop a questionnaire to evaluate the quality of HC. This thesis is based on three studies that are presented in four papers. Qualitative methods were used to describe aspects of life situation in relation to the disease, whereas quantitative method was used to develop a questionnaire measuring quality of care. Study I and II have an inductive qualitative design. In study I, qualitative interviews with 30 people were performed to describe the knowledge need and experience of critical incidents in daily life while living with IBD. The interviews in study I were analyzed using content analysis (results presented in Paper I) and critical incident technique (results presented in Paper II). In study II, the perceptions of HC among persons living with IBD was explored in five focus group interviews and two individual interviews, in total n=26. Study III aimed to develop and evaluate a questionnaire, measuring quality of care among persons with IBD, including 318 persons with IBD and 8 professionals. The knowledge need among persons with IBD focused on managing symptoms and course of the disease and learning to assimilate the information in order to manage everyday life. Losing bowel control was of great concern for most of the informants in the study. Many of the informants said that “the bowel ruled their life” and that it influenced them to a great extent in their daily lives. The perception of HC among persons with IBD meant being met with respect and mutual trust, receiving information at the right time, shared decision-making, competence and communication, access to care, accommodation, continuity of care and the pros and cons of specialized care. The quality of care questionnaire QoC-IBD was constructed in five dimensions, building on the results from Study I and II. The dimensions were trust and respect, decision-making, information, continuity of care and access to care consisting of 21 questions in total. QoC-IBD is a short, self-administrated questionnaire that measures experiences of healthcare among persons with IBD with promising validity and reliability. To improve quality of care, HC is recommended to consider individual care needs and take the person’s daily life and social context into account. The QoC-IBD questionnaire measures the subjective experience of quality of care. Further testing in clinical practice is necessary to evaluate if QoC-IBD can be used to evaluate the care given and areas of improvement in HC for persons living with IBD.

La rectocolite hémorragique (RCH) est une maladie inflammatoire chronique de l'intestin responsable d'un handicap et d'une altération de la qualité de vie pouvant exposer les patients à des complications sévères en dépit des thérapeutiques actuelles. L'objectif de cette thèse était d'analyser les voies possibles d'amélioration de la prise en charge thérapeutique des patients à partir de données expérimentales et cliniques. Au niveau expérimentale nous nous sommes intéressés au mécanisme impliqué dans la régulation de l'expression de PPARγ, récepteur nucléaires aux propriétés anti-inflammatoires, primitivement diminuée au cours de la RCH et cible des 5-aminosalicylés. Il a été montré que son expression était d'une part sous le contrôle de la stéroidogenèse intraépithéliale, elle-même sous contrôlée par LRH-1 et d'autre part que l'hypoxie épithéliale diminuait son expression via une sur-expression de miR-27a. Par ailleurs, les effets de l'hypoxie sur l'expression de PPARγ étaient inversés en présence de sildénafil. Sur le versant clinique, l'analyse d'une nouvelle stratégie thérapeutique ciblant la cicatrisation muqueuse, c'est à dire l'abrogation de l'inflammation colique macroscopique était efficace et possible dans la pratique clinique. Cet objectif semble aujourd’hui fondamental pour diminué la morbi-mortalité induite par cette maladie. Enfin nous avons observé l'efficacité des anti-TNF dans le cas spécifique de la rectite réfractaire et l'importance de son utilisation prolongée pour éviter les rechutes de la maladie et l’obtention d’une rémission prolongée. / Ulcerative colitis (UC) is a chronic disabling and relapsing inflammatory disease of the colonic mucosa that for more than half of patients results in chronic intermittent or continuous symptoms of increased stool frequency, fecal urgency and rectal bleeding The aim of the present work was to assess experimental ways and new therapeutic strategies with current treatments to improve long-term outcomes of UC. We focused experimental work on the peroxisome proliferator-activated receptor γ (PPARγ), a key factor of gut homeostasis and a target of mesalamine. The mechanism of primary impaired expression of PPARγ in colonic epithelial cells (CEC) during UC remains unknown. We demonstrated the control of PPARγ expression by intracellular CEC production of cortisol and the lack of cortisol production during UC that may participate towards the decreased expression of PPARγ. Furthermore hypoxia, a driver of mucosal inflammation during UC, markedly decreased PPARγ expression through the over-expression of miR-27a that was reversible by the use of sildenafil. From a clinic point of view, we assessed the efficacy and feasibility of a treat to target strategy which implies treatment optimization to achieve mucosal healing a key factor of long-term outcomes. Finally we addressed the long-term outcomes of patients treated with infliximab including the case of refractory proctitis.