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.

Les mutations du gène codant pour la protéine XIAP (X-Linked Inhibitor of Apoptosis Protein) sont à l’origine du syndrome lymphoprolifératif lié à l’X de type 2 (XLP-2). Il s’agit d’un déficit immunitaire rare caractérisé par une susceptibilité anormale à l’infection par le virus d’Epstein Barr (EBV). De plus, certains patients déficients en XIAP peuvent souffrir d’une pathologie intestinale parfois sévère. XIAP est molécule anti-apoptique qui a aussi été impliquée dans la signalisation et les fonctions de récepteurs de l’immunité innée, les récepteurs NOD1 et NOD2. Mon travail de thèse a eu pour objectif de caractériser cette pathologie intestinale et ses mécanismes physiopathologiques. Pour cela, nous avons étudié une cohorte de patients déficients en XIAP présentant une pathologie inflammatoire intestinale. Nous avons également recherché des mutations de XIAP dans une cohorte d’enfants ayant présenté comme unique signe clinique une pathologie intestinale précoce. Sur 83 patients testés, 3 patients porteurs de mutations de XIAP ont été identifiés. Nous avons ensuite montré que cette pathologie intestinale est très proche sur les plans clinique et histologique de la maladie de Crohn, qui est une des principales affections inflammatoires de l’intestin chez l’adulte. La maladie de Crohn est associée à des facteurs environnementaux et une susceptibilité génétique, dont les polymorphismes dans le gène NOD2 qui représentent le facteur plus important identifié à ce jour. Nous avons ensuite montré que les monocytes des patients déficients en XIAP ont un défaut de production d’IL-8, de MCP-1 et d’IL-10 en réponse à la stimulation de la voie NOD2. Par contre, nous n’avons pas mis en évidence d’excès d’apoptose des cellules épithéliales digestives chez les patients. En revanche, ils présentaient un nombre diminué de leur lymphocytes T innés circulants, Enfin, au cours de cette étude, nous avons identifié pour la première fois des femmes vectrices d’une mutation de XIAP à l’état hétérozygote, ayant développé des manifestations inflammatoires intestinales. Chez ces patientes, l’inactivation du chromosome X, qui normalement est biaisée en faveur de l’allèle sain chez les vectrices asymptomatiques, est de façon inhabituelle biaisée vers l’allèle muté contribuant à une diminution de l’expression de XIAP dans les monocytes et une altération de la voie NOD2. Ce travail a permis de montrer que le déficit en XIAP est responsable d’une forme monogénique de la maladie de Crohn. Nos résultats suggèrent que le défaut d’activation des monocytes par NOD2 est un mécanisme important de la pathogénèse de la maladie. Sur le plan thérapeutique, la greffe de moelle osseuse semble indiquée dans les formes sévères, puisque le principal défaut identifié est une anomalie du compartiment hématopoïétique, et chez deux de nos patients, elle a permis en effet une amélioration franche de la pathologie digestive qui était très sévère. / Mutations in the gene encoding for XIAP (X-Linked Inhibitor of Apoptosis Protein) are causing the X-linked lymphoproliferative syndrome type 2 (XLP-2). It is a rare immunodeficiency characterized by an abnormal susceptibility to infection with Epstein Barr virus (EBV). In addition, some XIAP-deficient patients may suffer from an intestinal disease that can be severe. XIAP is an anti-apoptotic molecule which has also been involved in the signaling and the functions of receptors of the innate immunity, NOD1 and NOD2. My thesis work aimed to characterize this intestinal pathology and its pathophysiology. For this, we studied a cohort of known XIAP-deficient patients with inflammatory bowel disease. We also looked for mutations of XIAP in a cohort of children who presented as the only clinical sign an early intestinal pathology. In 83 patients tested, three were identified as carrier of a XIAP mutation. We then showed that this intestinal pathology is clinically and histologically very close to Crohn’s disease, which is a major inflammatory bowel disease in adults. Crohn's disease is associated with environmental factors and genetic susceptibility, including polymorphisms in the NOD2 gene that represent the most important factor identified to date. We then showed that the monocytes from XIAP-deficient patients have a defect in production of IL-8, MCP-1 and IL-10 in response to stimulation of the NOD2 pathway. However, we did not reveal any excess of apoptosis in intestinal epithelial cells from XIAP-deficient patients. On the other hand, they showed a decreased number of their circulating innate T cells. Finally, during this study, we identified for the first time, female carriers of a mutation of XIAP in the heterozygous state, who developed intestinal inflammatory manifestations. In these patients, the inactivation of the X chromosome, which is normally biased toward the healthy allele in asymptomatic vectors, is biased to the unusually mutated allele contributing to a decrease of the expression of XIAP in monocytes and an alteration of the NOD2 pathway. This work showed that XIAP deficiency is responsible for a monogenic form of Crohn's disease. Our results suggest that the lack of monocyte activation by NOD2 is an important mechanism in the pathogenesis of the disease. Therapeutically, the bone marrow transplant seems indicated in severe cases, since the main identified defect is an abnormality of the hematopoietic compartment and in two of our patients, it allowed a clear improvement of the digestive pathology that was very severe.

A Doença de Crohn (DC) pode levar à desnutrição protéico-calórica (DPC) devido ao comprometimento das funções digestivas e absortivas do intestino delgado, associadas à influência de tabus alimentares. O diagnóstico de DPC em estágios iniciais pode ter impacto favorável no controle da DC. Os objetivos deste estudo foram os de estudar os diferentes métodos de avaliação nutricional em pacientes portadores da DC e correlacioná-los às características da doença. Participaram do estudo 75 pacientes do Serviço de Gastroenterologia do Hospital de Clínicas de Porto Alegre, 37 do sexo masculino e 38 do sexo feminino, com média de idade de 38,2 anos (DP=13,3), em remissão (IADC <150) por mais de 3 meses, e que não estavam recebendo nutrição enteral ou parenteral. A avaliação nutricional foi realizada através de índice de massa corporal (IMC), prega cutânea do tríceps (PCT), circunferência do braço (CB), circunferência muscular do braço (CMB), avaliação subjetiva global (ASG), força do aperto da mão não dominante (FAM) e inquérito alimentar. Comparando os diferentes métodos de avaliação nutricional, 37,3% dos pacientes encontravam-se desnutridos pela PCT, 26,7% pela CB, 29,3% pela CMB, 18,7% pela ASG, 6,7% pelo IMC, enquanto que 73,3% deles em risco nutricional pela FAM. Os pacientes com sobrepeso e obesidade pelo IMC foram classificados como desnutridos pela PCT em 31,6% e 11,1%, e com risco nutricional em 73,7% e 77,8%, respectivamente. A prevalência de desnutrição é significativa em pacientes com DC, mesmo em remissão clínica. O IMC não deve ser utilizado como referência nesta população. A FAM detectou uma alta prevalência de risco nutricional em pacientes portadores de DC em remissão.Tornam-se necessários estudos que a correlacionem com métodos mais sensíveis, para avaliação do estado nutricional efetivo dos pacientes. / Crohn’s Disease (CD) may cause protein-calorie malnutrition (PCM) either due to small bowel malfunction than to other factors, as poor intake and food taboos. Recognizing PCM in its early stages may help to control the disease. This study aimed at studying different assessment methods of CD patients’ nutritional status, and to correlate these methods to the disease. Seventy five CD patients of the Gastroenterology Service of Hospital de Clinicas de Porto Alegre (HCPA), Rio Grande do Sul, being 37 males, with an average age of 38.2 (DP=13.3), in clinical remission (CDAI <150) for more than 3 months, and not receiving enteral or parenteral nutrition, were included. It was done a food recall and nutritional status was assessed by body mass index (BMI), triceps skin fold (TSF), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), subjective global assessment (SGA), and handgrip strength (HG). When the different nutritional status assessment methods were compared, we have found 26, 7% of the patients undernourished by MAC; 29, 3% by MAMC; 18, 7% by SGA; 6, 7% by BMI; 6, 67% by albumin; 14, 67% by transferrin; 37.3% by TSF and 73.3% were in nutritional risk by HGS. Out of the overweight and obese patients by BMI, 31.6% and 11.1% were respectively classified as undernourished by TSF, whereas 73.7% and 77.8% were considered in nutritional risk by HGS. Prevalence of malnutrition is significant in CD patients in clinical remission. BMI should not be used as reference in this population. HG detected the higher prevalence of nutritional risk in this population.

A Doença de Crohn (DC) pode levar à desnutrição protéico-calórica (DPC) devido ao comprometimento das funções digestivas e absortivas do intestino delgado, associadas à influência de tabus alimentares. O diagnóstico de DPC em estágios iniciais pode ter impacto favorável no controle da DC. Os objetivos deste estudo foram os de estudar os diferentes métodos de avaliação nutricional em pacientes portadores da DC e correlacioná-los às características da doença. Participaram do estudo 75 pacientes do Serviço de Gastroenterologia do Hospital de Clínicas de Porto Alegre, 37 do sexo masculino e 38 do sexo feminino, com média de idade de 38,2 anos (DP=13,3), em remissão (IADC <150) por mais de 3 meses, e que não estavam recebendo nutrição enteral ou parenteral. A avaliação nutricional foi realizada através de índice de massa corporal (IMC), prega cutânea do tríceps (PCT), circunferência do braço (CB), circunferência muscular do braço (CMB), avaliação subjetiva global (ASG), força do aperto da mão não dominante (FAM) e inquérito alimentar. Comparando os diferentes métodos de avaliação nutricional, 37,3% dos pacientes encontravam-se desnutridos pela PCT, 26,7% pela CB, 29,3% pela CMB, 18,7% pela ASG, 6,7% pelo IMC, enquanto que 73,3% deles em risco nutricional pela FAM. Os pacientes com sobrepeso e obesidade pelo IMC foram classificados como desnutridos pela PCT em 31,6% e 11,1%, e com risco nutricional em 73,7% e 77,8%, respectivamente. A prevalência de desnutrição é significativa em pacientes com DC, mesmo em remissão clínica. O IMC não deve ser utilizado como referência nesta população. A FAM detectou uma alta prevalência de risco nutricional em pacientes portadores de DC em remissão.Tornam-se necessários estudos que a correlacionem com métodos mais sensíveis, para avaliação do estado nutricional efetivo dos pacientes. / Crohn’s Disease (CD) may cause protein-calorie malnutrition (PCM) either due to small bowel malfunction than to other factors, as poor intake and food taboos. Recognizing PCM in its early stages may help to control the disease. This study aimed at studying different assessment methods of CD patients’ nutritional status, and to correlate these methods to the disease. Seventy five CD patients of the Gastroenterology Service of Hospital de Clinicas de Porto Alegre (HCPA), Rio Grande do Sul, being 37 males, with an average age of 38.2 (DP=13.3), in clinical remission (CDAI <150) for more than 3 months, and not receiving enteral or parenteral nutrition, were included. It was done a food recall and nutritional status was assessed by body mass index (BMI), triceps skin fold (TSF), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), subjective global assessment (SGA), and handgrip strength (HG). When the different nutritional status assessment methods were compared, we have found 26, 7% of the patients undernourished by MAC; 29, 3% by MAMC; 18, 7% by SGA; 6, 7% by BMI; 6, 67% by albumin; 14, 67% by transferrin; 37.3% by TSF and 73.3% were in nutritional risk by HGS. Out of the overweight and obese patients by BMI, 31.6% and 11.1% were respectively classified as undernourished by TSF, whereas 73.7% and 77.8% were considered in nutritional risk by HGS. Prevalence of malnutrition is significant in CD patients in clinical remission. BMI should not be used as reference in this population. HG detected the higher prevalence of nutritional risk in this population.

A Doença de Crohn (DC) pode levar à desnutrição protéico-calórica (DPC) devido ao comprometimento das funções digestivas e absortivas do intestino delgado, associadas à influência de tabus alimentares. O diagnóstico de DPC em estágios iniciais pode ter impacto favorável no controle da DC. Os objetivos deste estudo foram os de estudar os diferentes métodos de avaliação nutricional em pacientes portadores da DC e correlacioná-los às características da doença. Participaram do estudo 75 pacientes do Serviço de Gastroenterologia do Hospital de Clínicas de Porto Alegre, 37 do sexo masculino e 38 do sexo feminino, com média de idade de 38,2 anos (DP=13,3), em remissão (IADC <150) por mais de 3 meses, e que não estavam recebendo nutrição enteral ou parenteral. A avaliação nutricional foi realizada através de índice de massa corporal (IMC), prega cutânea do tríceps (PCT), circunferência do braço (CB), circunferência muscular do braço (CMB), avaliação subjetiva global (ASG), força do aperto da mão não dominante (FAM) e inquérito alimentar. Comparando os diferentes métodos de avaliação nutricional, 37,3% dos pacientes encontravam-se desnutridos pela PCT, 26,7% pela CB, 29,3% pela CMB, 18,7% pela ASG, 6,7% pelo IMC, enquanto que 73,3% deles em risco nutricional pela FAM. Os pacientes com sobrepeso e obesidade pelo IMC foram classificados como desnutridos pela PCT em 31,6% e 11,1%, e com risco nutricional em 73,7% e 77,8%, respectivamente. A prevalência de desnutrição é significativa em pacientes com DC, mesmo em remissão clínica. O IMC não deve ser utilizado como referência nesta população. A FAM detectou uma alta prevalência de risco nutricional em pacientes portadores de DC em remissão.Tornam-se necessários estudos que a correlacionem com métodos mais sensíveis, para avaliação do estado nutricional efetivo dos pacientes. / Crohn’s Disease (CD) may cause protein-calorie malnutrition (PCM) either due to small bowel malfunction than to other factors, as poor intake and food taboos. Recognizing PCM in its early stages may help to control the disease. This study aimed at studying different assessment methods of CD patients’ nutritional status, and to correlate these methods to the disease. Seventy five CD patients of the Gastroenterology Service of Hospital de Clinicas de Porto Alegre (HCPA), Rio Grande do Sul, being 37 males, with an average age of 38.2 (DP=13.3), in clinical remission (CDAI <150) for more than 3 months, and not receiving enteral or parenteral nutrition, were included. It was done a food recall and nutritional status was assessed by body mass index (BMI), triceps skin fold (TSF), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), subjective global assessment (SGA), and handgrip strength (HG). When the different nutritional status assessment methods were compared, we have found 26, 7% of the patients undernourished by MAC; 29, 3% by MAMC; 18, 7% by SGA; 6, 7% by BMI; 6, 67% by albumin; 14, 67% by transferrin; 37.3% by TSF and 73.3% were in nutritional risk by HGS. Out of the overweight and obese patients by BMI, 31.6% and 11.1% were respectively classified as undernourished by TSF, whereas 73.7% and 77.8% were considered in nutritional risk by HGS. Prevalence of malnutrition is significant in CD patients in clinical remission. BMI should not be used as reference in this population. HG detected the higher prevalence of nutritional risk in this population.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-06-29T12:26:21Z No. of bitstreams: 1 flaviadagostovidaldelima.pdf: 355141 bytes, checksum: 78434d53eec0d7cb95f79e23003b8079 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-07-05T14:45:52Z (GMT) No. of bitstreams: 1 flaviadagostovidaldelima.pdf: 355141 bytes, checksum: 78434d53eec0d7cb95f79e23003b8079 (MD5) / Made available in DSpace on 2016-07-05T14:45:52Z (GMT). No. of bitstreams: 1 flaviadagostovidaldelima.pdf: 355141 bytes, checksum: 78434d53eec0d7cb95f79e23003b8079 (MD5) Previous issue date: 2012-02-29 / A doença de Crohn (DC) é uma doença Inflamatória intestinal crônica até o presente momento incurável. Embora fatores psicológicos tenham sido inicialmente considerados participantes da etiologia da DC, esta hipótese foi descartada. Apesar de existirem evidências crescentes de que sintomas depressivos e ansiosos são muito frequentes em pacientes com DC, poucos dados a cerca da oscilação destes sintomas psicológicos durante o curso clínico da doença, particularmente em suas fases de remissão e recidiva estão disponíveis. Os objetivos deste estudo foram avaliar em pacientes portadores de DC a possível ocorrência de oscilação do humor (sintomas depressivos e/ou ansiosos), bem como os possíveis fatores associados à mesma. Neste estudo prospectivo longitudinal 50 pacientes (30 mulheres e 20 homens, com média de idade de 40,6 anos e variação de 18 a 65 anos) com diagnóstico estabelecido de DC foram avaliados durante o período de agosto de 2009 a dezembro de 2010. As principais características sócio demográficas e clínicas relacionados à DC foram registradas. Adotou-se a classificação de Viena para determinação do fenótipo da DC e, para a atividade clinica, o índice de atividade da DC. Os sintomas depressivos e ansiosos foram avaliados por instrumentos de auto avaliação do estado psicológico, o Inventário de Depressão de Beck (IBD) e a Sub-escala de Ansiedade da Escala Hospitalar de Ansiedade e Depressão (HADS-A). Os instrumentos foram aplicados na inclusão no estudo e, a seguir, em intervalos de quatro meses, durante 12 meses subsequentes. A maioria dos pacientes apresentava o fenótipo inflamatório da doença (86%), 18(36%) já haviam se submetido a algum procedimento cirúrgico para tratamento de complicações da DC, sendo que 41(82%) pacientes estavam em remissão clínica na inclusão. Quatorze (28%) pacientes apresentaram humor depressivo de base e 28 (56%) sintomas de ansiedade. Oscilação do humor ocorreu em 29 pacientes (58%); destes 14 (28%) evoluíram com sintomas depressivos e/ou ansiosos a partir do humor normal de base, enquanto 15 (30%) apresentaram normalização do humor depressivo e/ ou ansioso de base. Dos 29 (58%) pacientes com oscilação do humor, 19 (38%) não apresentaram mudança na atividade clínica da doença (p=0,015), enquanto 10 (20%) tiveram alteração na atividade da DC, sendo que 5 (10%) apresentaram reativação da doença previamente em remissão e 5 (10%) remissão da doença que inicialmente encontrava-se em atividade. Os pacientes do sexo feminino e aqueles que não se apresentavam história de cirurgia prévia devido a complicações da DC exibiram significantemente maior oscilação do humor (p=0,04 para ambos). Observou-se uma tendência dos participantes que consumiam álcool a apresentarem maior oscilação do humor (p=0,06), embora o número de pacientes com ingestão alcoólica (n=3) foi pequeno para a análise estatística robusta. Neste estudo verificou-se elevada incidência (58%) de oscilação do humor em pacientes com DC. Não houve correlação entre a oscilação do humor com a mudança de atividade clínica da doença (p=0,15). Conclui-se que os pacientes do sexo feminino e aqueles que não se submeteram a cirurgia prévia devido a complicações da DC apresentaram significantemente maior oscilação do humor. Avaliação psicológica periódica pode ser útil para detecção e possível abordagem da oscilação do humor em pacientes com DC. / Introduction: Crohn Disease (CD) is a chronic inflammatory bowel disease not curable until now. Although psychological issues have been initially considered participants in the etiology of CD this hypothesis was is currently discharged. There are rising evidence that depressive symptoms and anxiety are very frequently in these patients, but little data about humor oscillation and it influence in clinical course of the disease is available. Objective: Estimate the incidence of mood disorders in patients with CD and the possible issues associated with them. Methodology: This prospective longitudinal study evaluate 50 patients (60% female gender; mean age 40.6 yrs) with CD assisted by our institution in a 16 months period time. The clinic activity of the disease was measured by the Crohn’s Activity Index and the mood disorders by Beck Depression Inventory and Hospital Anxiety Scale. The instruments used to assess psychological status were applied in the inclusion and then each four months. Results: The major phenotype of CD found was the inflammatory (86%), 36% had a past history of surgery due to CD complications, 82% had no active disease in the admission period. Humor oscillation (HO) was observed in 58% of patients; 28% had depressive and or anxiety symptoms and 30% had normalization of their baseline depressive or anxiety humor. In 38% of the patients with HO there was no change in disease activity 9p:0.015), while 20% had some degree of variation in clinical activity. Female gender and the absence of previous surgery related to CD were associated with HO (p:0.04). Conclusion: Female gender and the absence of previous surgery due to CD’s complications were associated with HO. Periodically Female gender and previous surgery related to CD’s complication are associated with HO. Periodically psychological evaluation can be worthy for detection and management of HO patients with CD.

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.

Objective: Treatment compliance in children with Crohn’s disease is associated with higher levels of symptom remission. We hypothesized that the management, comorbidities, and complications for children with Crohn’s disease would differ based on a diagnosis of noncompliance. Methods: Using the Kids’ Inpatient Database for 2006-2012, we identified young patients (<21 >years) with a diagnosis of Crohn’s disease. Diagnoses and procedures were analyzed according to a recorded diagnosis of noncompliance. Multivariable logistic regression analysis was performed to examine the association between noncompliance and the outcomes of interest. Results: There were 28,337 pediatric Crohn’s disease hospitalizations identified with 1,028 (3.6%) hospitalizations having a diagnosis of both Crohn’s disease and noncompliance. The mean age of the study population was 15.9 years and 48.9% were girls. Black patients ( multivariable adjusted odds ratio, aOR,2.27; 95% CI:1.84-2.79) and those in the lowest income quartile (aOR 1.57; 95% CI:1.20-2.05) had an increased likelihood of a noncompliance diagnosis than respective comparison groups. Noncompliant patients had an increased likelihood of concurrent depression, nutritional deficiency, and anemia. Patients with a diagnosis of noncompliance had lower rates of intestinal obstruction (4.0% vs 6.3%), intraabdominal abscesses (2.0% vs 4.2%,), and underwent fewer major surgical procedures (aOR 0.40; 95% CI:0.31-0.53) and large bowel resections (aOR 0.44; 95% CI:0.31-0.64) than patients without this diagnosis. Conclusions: We found significant differences in socioeconomic status and race among hospitalized children with Crohn’s disease with, as compared to those without, a diagnosis of noncompliance. Children with noncompliance have different comorbidities, disease-related complications, and are managed differently. Possible explanations for observed treatment differences include a reluctance to offer surgery to those with a diagnosis of noncompliance, a refusal of intervention by noncompliant patients, or implicit bias. Further investigation is warranted to better define noncompliance in this population and to determine the implications of this diagnosis.

would like to thank my thesis supervisor, Dr Devendra Amre, for his guidance. I would also like to extend my gratitude to the CHU Ste-Justine Research Center and the Ste-Justine Foundation, as well as the Department of Biomedical Sciences of the University of Montreal, for their generous support. / L'importance des déterminants génétiques de la maladie de Crohn (MC) chez l'enfant est bien connue, mais nos connaissances sur la contribution des facteurs de risque environnementaux demeurent limitées. Parmi les facteurs de risque du déclenchement de la MC chez l'adulte, figure le tabac. Le lien entre le tabagisme actif et le déclenchement de la MC a été maintes fois démontré. Cependant, les études menées jusqu'à présent sur l'influence de la fumée secondaire sur le déclenchement de la MC chez l'enfant ne sont pas consistantes, et ont souvent montré des résultats contradictoires. Le principal objectif de notre étude était donc de déterminer l'influence de l'exposition à la fumée secondaire pendant la grossesse et durant l'enfance sur le déclenchement de la MC chez l'enfant. Méthodes: Nous avons mené une étude cas-témoins auprès d'enfants caucasiens. Les cas avaient reçu un diagnostic de MC avant l'âge de 20 ans à la clinique de gastroentérologie pédiatrique du CHU-Sainte-Justine de Montréal (n=132), et les témoins (n=131) ont été sélectionnés parmi les patients du service de gastroentérologie ou d'orthopédie du même hôpital, sans histoire de maladie chronique intestinale. Nous avons apparié les cas et les témoins selon le moment du diagnostic (± 3 mois) et leur lieu de résidence (à l'aide du code postal). L'information sur l'exposition à la fumée secondaire au cours de la grossesse et durant l'enfance, ainsi que les autres facteurs de risque ont été colligés à l'aide d'un questionnaire. L'analyse des déterminants du déclenchement de la MC a été faite par régression logistique pour estimer le ratio de cote (RC) ainsi que les intervalles de confiance correspondant (IC95%). Résultats: L'âge moyen (± ET) des cas était légèrement plus élevé que celui des témoins (12,7 ± 4,0 vs. 11,4 ± 4,7; p=0,01). Le sexe était réparti de manière égale entre les groupes. L’histoire familiale s'est avérée significativement associée à la MC (p=0,01). La régression logistique multivariée n'a montré aucun lien statistiquement significatif entre le tabagisme de la mère pendant la grossesse et la MC, en comparant les mères qui ont fumé pendant la grossesse avec celles qui n’ont fumé ni pendant la / positively associated with the disease. In children, there is interest in understanding whether passive exposure to environmental tobacco smoke (ETS) could confer similar risks. However, current studies have provided inconsistent results. The major objective of our study was thus to comprehensively ascertain whether ETS exposure during pregnancy and childhood was associated with the risk of developing CD in children. Methods: We carried out a case-control study based on Caucasian children diagnosed with CD (n=132) prior to age 20 at a pediatric gastroenterology clinic in Montreal (CHU-Sainte-Justine). Controls (n=131) were children having visited the orthopedic or gastroenterology clinics, who did not have a past/current history of IBD, were diagnosed within ± 3 months of case diagnosis and resided in the same geographic area (based on the first 3 digits of the postal code) as the cases. Information on ETS during and post-pregnancy and other potential risk factors for CD was acquired using a structured questionnaire. Associations between ETS and CD were analyzed using unconditional logistic regression. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated. Results: The mean age (±SD) of the cases 12.7 (±4.0) was slightly higher than the controls (11.4±4.7) (p-value=0.01). Gender was equally distributed between the groups. Family history was positively associated with CD (p-value=0.01). Multivariate logistic regression did not reveal any association with CD when mothers who smoked during pregnancy were compared to those who neither smoked during pregnancy nor post-pregnancy (OR=1.55, 95% CI=0.84-2.86). Paternal smoking during pregnancy was also not associated with risk of CD (OR=0.95, 95% CI=0.33-2.75). Exposure of ETS to the child during childhood via maternal smoking appeared to increase risk (OR=3.54, 95% CI=0.71-17.57) but the risks were not iv significant. Paternal smoking during childhood also appeared to enhance risk of CD, in particular when the parents also smoked during pregnancy (OR=2.52, 95% CI=1.11-5.72). Conclusions: ETS exposure per se during pregnancy does not seem to confer risks of CD in children. However, ETS exposure during childhood either from maternal or paternal smoking appears to contribute to risk of CD in the child. Further studies are required to validate these associations.

La maladie de Crohn (MC) est une affection inflammatoire chronique du tube digestif dont l’étiologie est multifactorielle. Les lésions intestinales des patients atteints de MC sont anormalement colonisées par des souches pathogènes d’Escherichia coli appartenant au pathovar AIEC pour «Adherent-Invasive Escherichia coli ». Ces souches sont capables d’adhérer et d’envahir les cellules épithéliales intestinales, et ont la capacité de survivre et de se multiplier en macrophages en induisant une synthèse intense de cytokines pro-inflammatoires. Les AIEC pourraient ainsi être impliquées dans l’induction et/ou l’entretien de l’état inflammatoire de la muqueuse intestinale.L’objectif de ce travail est d’identifier les déterminants bactériens des AIEC qui vont intervenir dans les étapes précoces de l’implantation des AIEC au niveau intestinal et de définir quel est le rôle des facteurs micro-environnementaux de l’hôte dans cette implantation.Nous montrons que l’AIEC LF82 possède une activité mucinolytique qui est portée par le gène vat-AIEC et qui favorise la traversée du mucus et la colonisation intestinale. Nous avons retrouvé ce gène chez 42% des souches AIEC isolées de patients atteints de MC, et chez 97% des souches AIEC appartenant au phylogroupe B2. Par ailleurs, nous avons montré que les sels biliaires augmentent l’expression de cette mucinase.Nous avons ensuite étudié l’influence des sels biliaires sur l’expression globale des gènes de la souche LF82. Les sels biliaires modifient profondément le métabolisme de la souche, induisant une diminution globale des voies de biosynthèse (protéines, lipides) et une augmentation des voies de dégradation (alcools, acides carboxyliques, polyamines, …). L’étude du catabolisme de l’éthanolamine et du propanediol indique que les AIEC pourraient se servir de ces substrats pour s’implanter au sein de la flore iléale. De plus, les analyses transcriptomiques révèlent que les sels biliaires augmentent l’expression de gènes codant des facteurs de virulence comme l’invasine IbeA, les systèmes de sécrétion de type VI et la yersiniabactine. Nous montrons également qu’ils favorisent la formation de biofilm chez les souches AIEC.Ces données indiquent que les sels biliaires constituent un signal permettant à la souche AIEC LF82 de mettre en place différentes voies métaboliques et déterminants bactériens nécessaires à son implantation au niveau intestinal.Mots-clé : Escherichia coli, maladie de Crohn, mucines, serine protéase, mucinase, AIEC, / The etiology of Crohn's disease (CD) involves disorders in host genetic factors and intestinal microbiota. Ileal mucosa of CD patients is often abnormally colonized by adherent-invasive Escherichia coli (AIEC). These strains isolated from the intestinal mucosa of CD patients are able to adhere to intestinal epithelial cells (IECs). This adhesion to IECs promotes the invasion of cells by the bacteria. Furthermore, the invasive ability of AIEC strains allows bacteria to translocate across the human intestinal epithelium, move into the deep tissues and activate immune cells continuously upon arrival. Thus AIEC could be involved in the inflammatory state of the intestinal mucous membrane. The aim of this study was to identify components of AIEC virulence, which might favor their implantation in the gut of CD patients and to define the role of several chemical factors from the ileal environment. Here, we reported a protease called Vat-AIEC from AIEC which favors the penetration of AIEC through the mucus layer and enhances gut colonization. The screening of E. coli strains isolated from CD patients revealed a preferential vat-AIEC association with AIEC strains belonging to the B2 phylogroup. Besides, Vat-AIEC transcription was increased with bile salts from the ileum environment. Then a global RNA sequencing (RNA-seq) of E. coli LF82 has been used to observe the impact of bile salts on the expression of bacterial genes. The results demonstrate the explosive effect of bile salts with a dysregulation of about 40% of the genome, with a global upregulation of genes involved in degradation and downregulation of those implicated in several biosynthesis. Our results show that LF82 use ethanolamine as a nitrogen source and propane diol as a carbon source, which can favor their colonization in the gut compared to the other bacteria. We also studied virulence genes expression in the presence of bile salts. They increase the expression of several virulence factors like the IbeA invasion, the type 6 secretion systems and the yersiniabactin. Furthermore, we noticed an increased expression of genes implicated in biofilm formation. These results improve the understanding of the global regulatory network in the presence of bile salts and thus of AIEC implantation in the human gut of CD patients.