RESUMO
OBJECTIVES: Environmental factors play an important role in the pathogenesis of Crohn's Disease (CD). In particular, by virtue of the instability of the microbiome and development of immunologic tolerance, early life factors may exert the strongest influence on disease risk and phenotype. METHODS: We used data from 1119 CD subjects recruited from RISK inception cohort to examine the impact of early life environment on disease progression. Our primary exposures of interest were breastfeeding in infancy and exposure to maternal, active, or passive smoke. Our primary outcomes were development of complicated (stricturing or penetrating) disease, and need for CD-related hospitalization, and surgery. Multivariable logistic regression models were used to define independent associations, adjusting for relevant covariates. RESULTS: Our study cohort included 1119 patients with CD among whom 15% had stricturing (B2) or penetrating disease (B3) by 3 years. 331 patients (35%) and 95 patients (10.6%) required CD-related hospitalizations and surgery respectively. 74.5% were breastfed in infancy and 31% were exposed to smoking among whom 7% were exposed to maternal smoke. On multivariable analysis, a history of breastfeeding was inversely associated with complicated (B2/B3 disease) 0.65, CI 95% 0.44-96; P = 0.03) in pediatric CD. Maternal smoking during pregnancy was associated with increased risk of hospitalization during the 3-year follow-up period (OR 1.75, CI 95% 1.05-2.89; P = 0.03). CONCLUSIONS: Early life environmental factors influence the eventual phenotypes and disease course in CD.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Doença de Crohn/diagnóstico , Exposição Ambiental/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adolescente , Criança , Colo/patologia , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Doença de Crohn/complicações , Doença de Crohn/etiologia , Doença de Crohn/terapia , Progressão da Doença , Exposição Ambiental/estatística & dados numéricos , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , América do Norte/epidemiologia , Fenótipo , Gravidez , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fumar/epidemiologia , Fatores de Tempo , Poluição por Fumaça de Tabaco/estatística & dados numéricosRESUMO
BACKGROUND: Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown. METHODS: We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. FINDINGS: Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%. INTERPRETATION: Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy. FUNDING: Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
Assuntos
Doença de Crohn/complicações , Adalimumab/uso terapêutico , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Criança , Estudos de Coortes , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/microbiologia , Progressão da Doença , Feminino , Microbioma Gastrointestinal , Humanos , Infliximab/uso terapêutico , Obstrução Intestinal/etiologia , Masculino , Prognóstico , Pontuação de Propensão , Estudos Prospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
INTRODUCTION: Psychological morbidity in those diagnosed with cancer has been shown to result in poorer quality of life and increase the risk of mortality. As a result, researchers have designed and tested psychosocial interventions to improve quality of life and survival of patients diagnosed with cancer. METHODS: A systematic review of the literature was performed to describe the psychosocial interventions that have been tested in patients with gastrointestinal cancers. Databases such as MEDLINE, PsychINFO, PubMed, MedLine, and Cochrane Reviews were searched. The searches were inclusive of studies published in English between 1966 and October 2013. Raters conducted full-text review of the resulting articles for the following eligibility criteria: (1) participants were 18 years or older, (2) the majority of patients in the sample were diagnosed with a gastrointestinal cancer, (3) the trial was testing a psychosocial intervention, and (4) random assignment to one or more interventions versus a usual care, placebo, attention control, or waiting-list control condition. RESULTS: The interventions that were eligible for this review included psychosocial or behavioral intervention (e.g., cognitive behavioral therapy, problem solving, educational, and collaborative care), physical activity, and/or psychopharmacologic treatment (e.g., selective serotonin reuptake inhibitor). Interventions that included dietary changes were not included in the present review. Study quality was also assessed using the Physiotherapy Evidence Database (PEDro) system. The results of the review resulted in a finding of eight studies to have been conducted, testing psychosocial interventions, in patients with gastrointestinal cancers. Findings of these studies suggested that the interventions were effective in reducing psychological and physical symptoms associated with the cancer, improved quality of life, and reduced immune system dysregulation, and one study demonstrated an improvement in survival. Two studies reported no benefit from psychosocial intervention when compared with a control group. The quality of the studies varied greatly, but reporting of the details of the trials, and the methodological rigor, improved over time. CONCLUSION: Further research is warranted to design and test interventions that may be effective in patients diagnosed with gastrointestinal cancers.
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Neoplasias Gastrointestinais/psicologia , Psicoterapia/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , PrognósticoRESUMO
BACKGROUND & AIMS: We examined the incidence of Crohn's disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis. METHODS: Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed. RESULTS: Overall, 76 (9%) underwent a first CD-related surgery, 57 (7%) underwent a first bowel surgery (bowel resection, ostomy, strictureplasty, or appendectomy), and 19 (2%) underwent a first non-bowel surgery (abscess drainage or fistulotomy). The cumulative risks for bowel surgery, non-bowel surgery, and all CD-related surgeries were 3.4%, 1.4%, and 4.8%, respectively, at 1 year after diagnosis and 13.8%, 4.5%, and 17.7%, respectively, at 5 years after diagnosis. Older age at diagnosis, greater disease severity, and stricturing or penetrating disease increased the risk of bowel surgery. Disease between the transverse colon and rectum decreased the risk. Initiation of immunomodulator therapy within 30 days of diagnosis, sex, race, and family history of inflammatory bowel disease did not influence the risk of bowel surgery. CONCLUSIONS: In an analysis of pediatric patients with CD, the 5-year cumulative risk of bowel surgery was lower than that reported in recent studies of adult and pediatric patients but similar to that of a recent retrospective pediatric study. Initiation of immunomodulator therapy at diagnosis did not alter the risk of surgery within 5 years of diagnosis.
Assuntos
Doença de Crohn/patologia , Doença de Crohn/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Medição de Risco , Adolescente , Criança , Pré-Escolar , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Incidência , Lactente , Recém-Nascido , MasculinoRESUMO
OBJECTIVES: Although it is known that extraintestinal manifestations (EIMs) commonly occur in pediatric inflammatory bowel disease (IBD), little research has examined rates of EIMs and their relation to other disease-related factors in this population. The purpose of this study was to determine the rates of EIMs in pediatric IBD and examine correlations with age, sex, diagnosis, disease severity, and distribution. PATIENTS AND METHODS: Data were prospectively collected as part of the Pediatric IBD Collaborative Research Group Registry, an observational database enrolling newly diagnosed IBD patients <16 years old since 2002. Rates of EIM (occurring anytime during the period of enrollment) and the aforementioned variables (at baseline) were examined. Patients with indeterminate colitis were excluded from the analysis given the relatively small number of patients. RESULTS: One thousand nine patients were enrolled (mean age 11.6 +/- 3.1 years, 57.5% boys, mean follow-up 26.2 +/- 18.2 months). Two hundred eighty-five (28.2%) patients experienced 1 or more EIMs. Eighty-seven percent of EIM occurred within the first year. Increased disease severity at baseline (mild vs moderate/severe) was associated with the occurrence of any EIM (P < 0.001), arthralgia (P = 0.024), aphthous stomatitis (P = 0.001), and erythema nodosum (P = 0.009) for both Crohn disease (CD) and ulcerative colitis (UC) during the period of follow-up. Statistically significant differences in the rates of EIMs between CD and UC were seen for aphthous stomatitis, erythema nodosum, and sclerosing cholangitis. CONCLUSIONS: EIMs as defined in this study occur in approximately one quarter of pediatric patients with IBD. Disease type and disease severity were commonly associated with the occurrence of EIMs.