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OBJECTIVES:Systemic corticosteroids are among the most common anti-inflammatory treatments in elderly-onset inflammatory bowel disease (IBD) patients. Steroid use and older age each independently predisposes to infections, and infections increase mortality in hospitalized older IBD patients. Therefore, our objective was to examine the risk of serious infections in elderly-onset IBD patients treated with oral corticosteroids, and explore how the timing of exposure affects the risk estimates.METHODS:Using the health-care databases of the province of Quebec, Canada, we conducted a population-based cohort study with a nested case-control analysis. Incident IBD patients aged ≥66 years were identified. Conditional logistic regression was performed to estimate crude and adjusted rate ratios (aRRs) with 95% confidence intervals (CIs).RESULTS:We identified 3,522 elderly-onset patients, of which 564 cases with serious infections were identified during a mean 4.4 years of follow-up (incidence rate 3.7 per 100 per year) and matched to 2,646 controls. The rate of serious infections was significantly higher in those exposed to oral corticosteroids any time during the previous 6-month period compared with those nonexposed (aRR 2.3; 95% CI 1.8-2.9). Those currently exposed (within 45 days) had a higher risk (aRR 2.8; 95% CI 2.1-3.7). The residual effect of oral corticosteroids remained marginally statistically significant up to the 90-day period before the index date (aRR 1.7; 95% CI 1.0-2.7).CONCLUSIONS:We found an excess relative risk for serious infections in elderly-onset IBD patients on oral corticosteroid therapy. Those with current exposure demonstrated a higher vulnerability to infections. [ABSTRACT FROM AUTHOR]

OBJECTIVES:In classifying Crohn's disease (CD) location, proximal (L4) disease includes esophagogastroduodenal (EGD) and jejunal disease. Our aim was to determine the influence of proximal disease on outcomes of behavior and need for surgery and to determine if there was significant clinical heterogeneity between EGD and jejunal disease.METHODS:We performed a cross-sectional query of the NIDDK (National Institute of Diabetes and Digestive and Kidney Disease) Inflammatory Bowel Disease Genetics Consortium (IBDGC) database of patients with a confirmed diagnosis of CD and phenotyped per the IBDGC manual. Presence of any L4, L4-EGD, L4-jejunal, and non-L4 disease (L1-ileal, L2-colonic, and L3-ileocolonic) was compared with demographic features including age, race, ethnicity, smoking and inflammatory bowel disease (IBD) family history, diagnosis age, disease duration, clinical outcomes of inflammatory, stricturing or penetrating behavior, and CD abdominal surgeries. Univariate and multivariable analyses were performed with R.RESULTS:Among 2,105 patients with complete disease location data, 346 had L4 disease (175 L4-EGD, 115 L4-jejunal, and 56 EGD and jejunal) with 321 having concurrent L1-L3 disease. In all, 1,759 had only L1-L3 disease. L4 vs. non-L4 patients were more likely (P<0.001) to be younger at diagnosis, non-smokers, have coexisting ileal involvement, and have stricturing disease. L4-jejunal vs. L4-EGD patients were at least twice as likely (P<0.001) to have had ileal disease, stricturing behavior, and any or multiple abdominal surgeries. Remarkably, L4-jejunal patients had more (P<0.001) stricturing behavior and multiple abdominal surgeries than non-L4 ileal disease patients. Logistic regression showed stricturing risks were ileal (without proximal) site (odds ratio (OR) 3.18; 95% confidence interval 2.23-4.64), longer disease duration (OR 1.33/decade; 1.19-1.49), jejunal site (OR 2.90; 1.89-4.45), and older age at diagnosis (OR 1.21/decade; 1.10-1.34). Multiple surgery risks were disease duration (OR 3.74/decade; 3.05-4.64), penetrating disease (OR 2.60; 1.64-4.21), and jejunal site (OR 2.39; 1.36-4.20), with short duration from diagnosis to first surgery protective (OR 0.87/decade to first surgery; 0.84-0.90).CONCLUSIONS:Jejunal disease is a significantly greater risk factor for stricturing disease and multiple abdominal surgeries than either EGD or ileal (without proximal) disease. The Montreal site classification should be revised to include separate designations for jejunal and EGD disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The objective of this study was to provide updated explicit and relevant consensus statements for clinicians to refer to when managing hospitalized adult patients with acute severe ulcerative colitis (UC).METHODS:The Canadian Association of Gastroenterology consensus group of 23 voting participants developed a series of recommendation statements that addressed pertinent clinical questions. An iterative voting and feedback process was used to do this in conjunction with systematic literature reviews. These statements were brought to a formal consensus meeting held in Toronto, Ontario (March 2010), when each statement was discussed, reformulated, voted upon, and subsequently revised until group consensus (at least 80% agreement) was obtained. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence.RESULTS:As a result of the iterative process, consensus was reached on 21 statements addressing four themes (General considerations and nutritional issues, Steroid use and predictors of steroid failure, Cyclosporine and infliximab, and Surgical issues).CONCLUSIONS:Key recommendations for the treatment of hospitalized patients with severe UC include early escalation to second-line medical therapy with either infliximab or cyclosporine in individuals in whom parenteral steroids have failed after 72 h. These agents should be used in experienced centers where appropriate support is available. Sequential therapy with cyclosporine and infliximab is not recommended. Surgery is an option when first-line steroid therapy fails, and is indicated when second-line medical therapy fails and/or when complications arise during the hospitalization. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4–5.5), colorectal disease (OR = 1.9; 95% CI: 1.1–3.4), perianal disease (OR = 1.7; 95% CI: 1.03–2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32–0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3–13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55–10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8–4.6) and erythema nodosum (3.3; 95% CI: 1.7–6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Crohn's disease (CD) is a chronic multifactorial disorder with diverse clinical features that are influenced by a heterogeneous set of genetic factors. TNF-α/TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response. Our purpose was to determine whether single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility to Crohn's disease and whether they are associated with clinical phenotype.METHODS: A cohort of 205 consecutively identified and unrelated patients with CD and 106 controls were recruited. Subjects were genotyped for polymorphisms in TNFRSF1A (position+36,−609), TNFRSF1B (+196,+1466), along with the three common CARD15 variants and phenotyped for disease behavior. Genotypic and allelic frequencies were compared between CD and controls and a logistic regression model was constructed to determine independent associations with specific clinical phenotypes.RESULTS: Only the TNFRSF1A+36 and TNFRSF1B+196 SNPs were associated with CD (p= 0.0019 and 0.034, respectively). The TNFRSF1A+36 mutation was negatively associated with stricturing disease phenotype (OR= 0.384; CI= 0.166–0.887). In contrast, the TNFRSF1B+196 was negatively associated with colitis (OR= 0.410; CI= 0.191–0.880). These associations were independent of CARD15 mutation status. Finally, TNFRSF1B+196 was negatively associated with surgery in CARD15 negative patients.CONCLUSIONS: These data constitute the first report of an association of TNFRSF1A and TNFRSF1B polymorphisms with CD in a Caucasian population and address the role of TNFR mutations in determining clinical heterogeneity in CD.(Am J Gastroenterol 2005;100:1126–1133) [ABSTRACT FROM AUTHOR]

: ObjectivesTo determine the association between psychosocial characteristics and time to relapse in patients with inactive ulcerative colitis.: MethodsSixty patients with clinically and endoscopically inactive ulcerative colitis were followed for 1 yr, or less if they relapsed. Demographic, psychosocial, and clinical data were obtained. Stressful life events (Psychiatric Epidemiology Research Interview Life Events Scale), psychological distress (Symptom Checklist-90R), and perceived stress (Perceived Stress Scale) were recorded monthly by self-report. Multivariate time-dependent Cox regression was used to identify the independent determinants of earlier time to clinical relapse.: ResultsThe patients'' mean age was 39 yr (SD = 9.4), 37 (62%) were female, and 22 (37%) relapsed during the 1-yr follow-up. Univariate Cox regression indicated a weak association between number of stressful events in the preceding month and time to relapse (p = 0.09). This association strengthened in multivariate analysis (p = 0.02, hazard ratio = 1.26 per event, 95% CI = 1.04–1.53) after adjustment for significant covariates.: ConclusionsAfter controlling for demographic and clinical variables, more recent stressful events were associated with earlier time to relapse. These findings, which support a biopsychosocial model of disease, might help clinicians identify patients who might benefit from more intensive maintenance medical therapy and behavioral medicine interventions to reduce stress and improve coping. [Copyright &y& Elsevier]

: ObjectiveThe aim of this study was to identify determinants of nonadherence to medication in outpatients with established inflammatory bowel disease (IBD).: MethodsTen gastroenterologists and 153 of their IBD patients participated in this prospective study. Demographic, clinical, and psychosocial characteristics, as well as patient-physician discordance, were assessed at an office visit. Nonadherence to medication was assessed 2 wk later. Separate generalized estimating equations were used to identify determinants of nonadherence.: ResultsPhysicians averaged 47.9 yr in age (range 30.1–57.5 yr), and 90% were male. Patients averaged 37.0 yr (SD = 15.1), and 87 (56.9%) were female. In all, 63 patients (41.2%) were nonadherent to medication; of these, 51 (81.0%) indicated unintentional nonadherence, 23 (36.5%) intentional nonadherence, and 11 (17.5%) both. Overall nonadherence was predicted by disease activity (OR = 0.55, p = 0.0022), new patient status (OR = 2.14, p = 0.0394), disease duration (OR = 0.50, p = 0.0001), and scheduling a follow-up appointment (OR = 0.30, p = 0.0059), whereas higher discordance on well-being was predictive only in psychologically nondistressed patients (p = 0.0026 for interaction). Unintentional nonadherence was predicted by age (OR = 0.97, p = 0.0072), new patient status (OR = 2.80, p = 0239), and higher discordance on well-being in psychologically nondistressed patients (p = 0.0504). Intentional nonadherence was predicted by disease duration (OR = 0.55, p = 0032), scheduling a follow-up appointment (OR = 0.12, p = 0.0001), certainty that medication would be helpful (OR = 0.99, p = 0.0409), and total patient-physician discordance (OR = 1.59, p = .0120).: ConclusionsThese findings suggest that the therapeutic relationship, as well as individual clinical and psychosocial characteristics, influence adherence to medication. [Copyright &y& Elsevier]

OBJECTIVE:The aim of this study was to identify the independent psychosocial correlates of patient-physician discordance in adult outpatients with inflammatory bowel disease.METHODS:This cross-sectional study was conducted in three university-affiliated tertiary care settings. Psychological distress, social support, perceived stress, and negative life events were assessed, as were demographic, lifestyle, and clinical characteristics. Patient-physician discordance was assessed with 10-item questionnaires.RESULTS:Ten gastroenterologists and 200 of their patients participated. Patients and their physicians disagreed most on discussion of personal issues. Patients with Crohn’s disease had statistically significantly higher discordance on disease activity and physical limitation, as well as higher average overall discordance scores than patients with ulcerative colitis. Mean discordance levels were similar across different physicians. Higher psychological distress and more perceived stress were independently associated with higher discordance after controlling for Crohn’s disease, active disease, being with the treating physician for less than 1 yr, and recommendation for further medical investigation. Psychological distress was the most important correlate of overall discordance.CONCLUSIONS:Increased physician awareness that psychologically distressed patients have difficulty processing of clinically relevant information may lead to improved doctor-patient communication during an office visit. [Copyright &y& Elsevier]

OBJECTIVES: The objectives of this study were to compare the psychological status of patients in active and inactive disease states, to assess social support, and to identify correlates of psychological distress in patients with inflammatory bowel disease (IBD). METHODS: This cross-sectional study was conducted in 200 patients (mean age 36.7 yr [SD = 14.8], 119 [59.5%] female) with long-standing IBD who were seen in tertiary care. Psychosocial assessments included psychological distress (Symptom Checklist-90R). social support (Social Support Questionnaire-6), perceived stress (Perceived Stress Scale-10), and recent minor stressful events (Weekly Stress Inventory). Disease activity was assessed with the Harvey Bradshaw Index. RESULTS: Patients reported higher levels of satisfaction with social support and smaller network sizes compared with normative values. Using multiple linear regression, the independent correlates of psychological distress (p = 0.0001: adjusted R² = 0.62) were as follows: active disease (p = 0.0234), less time since diagnosis (p = 0.0012), and greater number (p = 0.0001) and impact of stressful events (p = 0.0003). A statistically significant interaction term (p = 0.0171) revealed that the relationship between psychological distress and perceived stress changes depending on the level of satisfaction with social support. For patients with low levels of perceived stress, satisfaction with social support did not affect levels of psychological distress. However, for patients who experienced moderate to high levels of perceived stress, high satisfaction with social support decreased the level of psychological distress. CONCLUSIONS: These findings suggest that strategies aimed at improving social support can have a favorable impact on psychological distress and, ultimately, can improve health outcomes in patients with IBD. [ABSTRACT FROM AUTHOR]

Lung toxicity associated with 5-aminosalicylate (5-ASA) agents is a rare entity. We report the case of a 32-yr-old woman with ulcerative colitis who developed progressive shortness of breath while taking one of the 5-ASA drugs, oral mesalamine. Bilateral pulmonary infiltrates, peripheral eosinophilia, and histological findings consistent with acute pneumonitis characterized the lung injury. Although the differential diagnosis is broad, mesalamine-induced lung damage must be considered in patients who develop unexplained respiratory symptoms while taking this agent. [ABSTRACT FROM AUTHOR]