Inger Camilla Solberg

Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study)

Objective. Cohort studies of unselected and newly diagnosed patients are essential for a better understanding of the prognosis in ulcerative colitis (UC). The aim of this study was to evaluate the course of UC in a population-based inception cohort during the first 10 years, and to identify prognostic risk factors based on information gathered at diagnosis. Material and methods. From 1990 to 1994, a population-based cohort of 843 patients with inflammatory bowel disease was enrolled in South-Eastern Norway. The cohort was systematically followed-up at 1, 5 and 10 years after diagnosis. Results. Of 519 patients with UC, 423 completed the 10-year follow-up, 53 died and 43 were lost to follow-up. The mortality risk was not increased compared with that in the general population. The cumulative colectomy rate after 10 years was 9.8% (95% CI: 7.4–12.4%). Initial presentation with extensive colitis and erythrocyte sedimentation rate (ESR) ≥30 mm/h was associated with an increased hazard ratio (HR) (3.57, 95% CI: 1.60–7.96) and age ≥50 years at diagnosis, with reduced HR (0.28, 95% CI: 0.12–0.65) for subsequent colectomy. Relapsing disease was noted in 83%, but half (48%) of the patients were relapse free during the last 5 years. One-fifth (69/288) of patients with proctitis or left-sided colitis had progressed to extensive colitis. Conclusions. The prognosis for UC during the first 10 years was generally good. The colectomy rate was low, and a large proportion of patients were in remission as time progressed. Patients with initially extensive colitis and elevated ESR could benefit from an early potent medical treatment strategy.

Consecutive fecal calprotectin measurements to predict relapse in patients with ulcerative colitis receiving infliximab maintenance therapy

Background: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy. Methods: This prospective multicenter study enrolled adult patients with UC in clinical remission under infliximab maintenance therapy. Fecal calprotectin levels were measured every 4 weeks. Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined as a clinical need for change in treatment or an endoscopic Mayo subscore of ≥2 at week 52. Sustained deep remission was defined as a partial Mayo score <3 at all points and an endoscopic Mayo score 0 at week 52. Results: Full analysis was possible for 87 of 113 included patients with UC (77%). Of these patients, 30 (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have relapsed. Calprotectin levels in patients with sustained deep remission remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher calprotectin levels (median > 300 mg/kg) already 3 months before the flare. Further receiver operator curve analysis suggested that a calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and specificity (93.3%) to model flare. Two consecutive calprotectin measurements of >300 mg/kg with 1-month interval were identified as the best predictor of flare (61.5% sensitivity and 100% specificity). Conclusions: Fecal calprotectin can be used in daily practice to monitor patients with UC receiving infliximab maintenance therapy. Two consecutive measurements >300 mg/kg is more specific than a single measurement for predicting relapse.

Work disability in inflammatory bowel disease patients 10 years after disease onset: results from the IBSEN Study

Objective To compare the work disability (WD) rate in inflammatory bowel disease (IBD) patients 10 years after disease onset, with the WD rate in the background population,and to assess whether clinical or demographic factors in the early disease course could predict WD after 10 years disease. Design A large, population-based inception cohort (the Inflammatory Bowel in South Eastern Norway cohort) was prospectively followed up at 1, 5 and 10 years after diagnosis. At the 10-year follow-up data on WD were collected. Data on disability pension (DP) in the background population were retrieved from public databases. We calculated overall and age-standardised relative risks (RR) for DP. Logistic regression analysis was used to examine predictive factors. Results A total of 518 patients completed the 10-year follow-up (response rate 83.5%). The overall disability rate in the IBD population was 18.8%, and the RR was 1.8 (95% CI 1.4 to 2.3) for ulcerative colitis (UC) and 2.0 (95% CI 1.4 to 2.7) for Crohns disease (CD). The RR for DP was highest in patients aged below 40 years while patients aged over 60 years had no increased RR. Steroid treatment at the 1-year follow-up predicted WD after 10 years disease in both CD and UC. In UC, increased C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) at diagnosis, early colectomy, and more than two relapses during the first year of the disease also predicted WD. Conclusion Ten years after disease onset IBD patients had an increased RR for DP as compared with the background population. The youngest patients had the highest RR. Markers of severe disease course predicted WD.

Ulcerative colitis: no rise in mortality in a European-wide population based cohort 10 years after diagnosis

Background: Population based studies have revealed varying mortality for patients with ulcerative colitis but most have described patients from limited geographical areas who were diagnosed before 1990. Aims: To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis related mortality across Europe. Methods: Mortality 10 years after diagnosis was recorded in a prospective European-wide population based cohort of patients with ulcerative colitis diagnosed in 1991–1993 from nine centres in seven European countries. Expected mortality was calculated from the sex, age and country specific mortality in the WHO Mortality Database for 1995–1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. Results: At follow-up, 661 of 775 patients were alive with a median follow-up duration of 123 months (107–144). A total of 73 deaths (median follow-up time 61 months (1–133)) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to 1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a slightly higher risk in older age groups. For disease specific mortality, a higher SMR was found only for pulmonary disease. Mortality by European region was SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45–1.37) for the south. Conclusions: Higher mortality was not found in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease, and a trend towards an age related rise in SMR, was observed.

Predictive Value of Serologic Markers in a Population-based Norwegian Cohort with Inflammatory Bowel Disease

Background: Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti‐Saccharomyces cerevisiae antibodies (ASCA) are proposed to be specific markers for ulcerative colitis (UC) and Crohns disease (CD). Their prevalence and relationship to disease phenotype and outcome in unselected cohorts of patients with inflammatory bowel disease (IBD), however, is largely unclear. We studied the prevalence of these serologic markers in a population‐based IBD cohort 10 years after diagnosis, and examined whether their presence could be related to distinct subgroups and outcome of disease. Methods: Of 685 living IBD patients, 620 met for a 10‐year follow‐up, of whom 526 (UC, n = 357 and CD, n = 169) participated in this study. Results: Twenty‐seven percent (n = 46) of CD patients were ASCA‐positive and 31% (n = 109) of UC patients were pANCA‐positive. Positive ASCA was more frequent in CD patients with stricturing (P = 0.003) or penetrating (P = 0.012) complications than in those with inflammatory behavior at diagnosis. Moreover, the presence of ASCA was associated with an at least twice higher risk of evolving more severe disease behavior during follow‐up (P < 0.001). In UC, pANCA expression was related to female gender (P = 0.005) and the use of azathioprine (P < 0.001), and in CD, to colon‐limited disease and age ≥40 years at diagnosis (P = 0.009 and P = 0.001, respectively). Conclusions: The prevalence of ASCA in CD and pANCA in UC appears markedly lower than in referral‐based populations. Even with the low prevalence, our study gives further support to the role of ASCA and pANCA as markers for distinct phenotype and outcome of disease.

Health-related quality of life in patients with ulcerative colitis after a 10-year disease course: results from the IBSEN study.

Background: Ulcerative colitis (UC) negatively affects health‐related quality of life (HRQoL), but population‐based and long‐term data on this topic are scarce. Our aim was to determine the HRQoL in UC patients after a 10‐year disease duration. Methods: UC patients from a population‐based inception cohort met at a prescheduled 10‐year follow‐up visit. In addition to a clinical examination, interview, and blood samples, the patients completed the Short Form 36 (SF‐36) and the Norwegian Inflammatory Bowel Disease Questionnaire (N‐IBDQ). The SF‐36 scores were compared to scores from a general population sample using one‐sample t‐tests. Standardized scores were calculated and interpreted according to Cohens effect size index. The associations between relevant clinical and demographic factors and HRQoL were examined through linear regression analyses. Results: A total of 196 patients completed the HRQoL questionnaires (response rate: 80%), of whom 54% were women; the mean age of all patients was 48 years (range: 22–86). The SF‐36 scores were comparable to those of the general population except for lower scores in the General Health dimension. The SF‐36 scores were significantly lower in the presence of current symptoms, in patients who had used corticosteroids, and in patients who reported not working. Overall N‐IBDQ scores were equivalent to scores of patients in remission. Female gender, work status (not working), current symptoms, and smoking were associated with significantly lower N‐IBDQ scores. Conclusions: SF‐36 scores were not reduced compared to the general population sample. The presence of current symptoms, the use of corticosteroids, work status (not working), female gender, and smoking had a negative impact on HRQoL. (Inflamm Bowel Dis 2012)

A new protein superfamily includes two novel 3-methyladenine DNA glycosylases from Bacillus cereus, AlkC and AlkD

Soil bacteria are heavily exposed to environmental methylating agents such as methylchloride and may have special requirements for repair of alkylation damage on DNA. We have used functional complementation of an Escherichia coli tag alkA mutant to screen for 3‐methyladenine DNA glycosylase genes in genomic libraries of the soil bacterium Bacillus cereus. Three genes were recovered: alkC, alkD and alkE. The amino acid sequence of AlkE is homologous to the E. coli AlkA sequence. AlkC and AlkD represent novel proteins without sequence similarity to any protein of known function. However, iterative and indirect sequence similarity searches revealed that AlkC and AlkD are distant homologues of each other within a new protein superfamily that is ubiquitous in the prokaryotic kingdom. Homologues of AlkC and AlkD were also identified in the amoebas Entamoeba histolytica and Dictyostelium discoideum, but no other eukaryotic counterparts of the superfamily were found. The alkC and alkD genes were expressed in E. coli and the proteins were purified to homogeneity. Both proteins were found to be specific for removal of N‐alkylated bases, and showed no activity on oxidized or deaminated base lesions in DNA. B. cereus AlkC and AlkD thus define novel families of alkylbase DNA glycosylases within a new protein superfamily.

Patients with Crohn's disease experience reduced general health and vitality in the chronic stage: ten-year results from the IBSEN study.

BACKGROUND AND AIMS Data on the long-term effects of Crohns disease (CD) on health-related quality of life (HRQoL) is scarce. We aimed to determine the HRQoL in CD patients 10 years after disease onset, to compare the results to the general population and to identify variables that could affect HRQoL. METHODS CD patients from a population-based inception cohort (the IBSEN Study) met at a prescheduled ten-year follow-up. In addition to a structured interview, review of hospital records, clinical examination, laboratory tests and ileocolonoscopy, they completed a patient-reported questionnaire including the Short Form 36 (SF-36) and the Norwegian Inflammatory Bowel Disease Questionnaire (N-IBDQ). The SF-36 scores were compared to scores from the general population using one-sample t-tests. Standardized scores were calculated and interpreted according to Cohens effect size index. The associations between relevant clinical and demographic factors and HRQoL were examined through linear regression analyses. RESULTS Ninety-nine patients completed the HRQoL questionnaires (response rate 86%). Median age 39 years, 42% women. Compared to the general population the patients reported significantly lower SF-36 scores on the general health and vitality dimensions. IBDQ total scores were in line with scores of patients in remission. Except for current symptom severity no clinical parameters affected HRQoL scores. Work status and sick leave affected HRQoL negatively. CONCLUSIONS In this chronic stage of CD, reduced general health and vitality scores need attention while reductions in disease specific HRQoL seem to be less predominant.

Relationships between inflammatory bowel disease and perinatal factors: Both maternal and paternal disease are related to preterm birth of offspring

Background:The aims of this study were to explore the influences of familial, maternal, and paternal inflammatory disease (IBD) on perinatal outcomes in the offspring and the risk for development of IBD related to perinatal factors. Methods:Eighty‐five patients with Crohns disease (CD) and 86 with ulcerative colitis (UC) were included from a population‐based incidence study enrolled 1990–1994. Family and birth records of these patients, as well as of their 207 infants, were drawn from the Norwegian Medical Birth Registry, established in 1967, and compared with the national birth cohort from the same period. Results:Maternal (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.36, 3.39) and paternal IBD (OR = 3.02, 95% CI: 1.82, 5.01) influenced the risk of preterm birth (<37 weeks), which further increased if the affected parents had a first‐degree relative with IBD (OR = 4.29, 95% CI: 1.59, 11.63). Maternal CD was associated with lower birth weight in the offspring (crude difference: 271.79 g, 95% CI: 87.83, 455.77, versus controls). Maternal UC increased the risk of perinatal bacterial infection in the offspring (OR = 6.03, 95% CI: 2.03, 17.91). IBD patients (2.3%) were less likely to be delivered by cesarean section than controls (8.1%) (OR = 0.27, CI: 95%: 0.10, 0.73). Conclusions:Familial, maternal, and paternal IBD were linked to preterm birth, which might be explained by genetic mechanisms. The present protective effect of cesarean sections needs further clarification in future studies. Inflamm Bowel Dis 2009

Complementary and alternative medicine in patients with inflammatory bowel disease: The results of a population-based inception cohort study (IBSEN)

BACKGROUND AND AIMS The use of complementary and alternative medicine (CAM) has been increasing in recent decades. Our aim was to determine the proportion of CAM use among patients with inflammatory bowel disease (IBD) in a longitudinal, population-based cohort and to identify predictive factors for CAM use. METHODS The Inflammatory Bowel South-Eastern Norway (IBSEN) study is a population-based IBD cohort that has been followed prospectively for 10 years. The ten-year follow-up was conducted from 2000 to 2004 and included a questionnaire regarding CAM, a structured interview, a review of hospital records, a clinical examination, laboratory tests, and an ileocolonoscopy. RESULTS Of the 620 patients evaluated at the ten-year follow-up, 517 (84%) completed the CAM questionnaire, 353 had ulcerative colitis (UC), 164 had Crohns disease (CD), and 50% were male. Thirty percent reported the use of CAM at some point since their IBD diagnosis, and 7.5% reported current CAM use. More CD patients than UC patients reported CAM use (38% vs. 27%, respectively; p=0.01). Younger age, female gender, and higher education level predicted CAM use in UC, whereas younger age was the only predictor of CAM use in CD. Thirty-six percent of the CAM users were mostly satisfied or very satisfied with the treatment. CONCLUSION One third of the patients in this population-based cohort had used CAM at some point during a ten-year disease course, but only 7.5% reported current CAM use. CAM use was more common in the CD than in the UC patients. Only socio-demographic factors, such as age, gender and education, predicted CAM use.