Ulcerative Colitis: Moum B

Henriksen M, Moum B. · Medisinsk avdeling, Sykehuset Østfold Fredrikstad, Cicignons gate 19, 1606 Fredrikstad. · Tidsskr Nor Laegeforen. · Pubmed #17952155 links to  free full text

Abstract: BACKGROUND: Colorectal cancer is a complication of longstanding inflammatory bowel disease. The association between cancer and inflammation is best documented in ulcerative colitis, but an increased risk of cancer is also found in patients with Crohn's disease. Surveillance with colonoscopy is commonly used to detect dysplasia and early cancer in patients with in ulcerative colitis. There has been an increased focus on chemoprevention during the last decade. MATERIAL AND METHOD: This paper is based on literature retrieved through non-systematic searches of the PubMed and Cochrane databases. RESULTS AND INTERPRETATION: Several recent studies indicate that the incidence of colorectal cancer in patients with ulcerative colitis is lower than previously shown; in some population-based studies it does not exceed that in the general population. Extensive use of 5-aminosalicylates (5-ASA) explains a substantial part of the declining risk. The effect of surveillance colonoscopy has not been documented through prospective and randomized studies. Several studies have shown an increased risk of colorectal cancer and cancer in the small bowel in patients with Crohn's disease. No evidence supports that treatment with 5-ASA reduces the risk of colorectal cancer in patients with Crohn's disease, or that regular use of surveillance colonoscopy reduces the risk of cancer or mortality in patients with longstanding chronic inflammatory disease.

Moum B, Ekbom A. · Medical Department SØ Fredrikstad, NO-1601 Fredrikstad, Norway. · Scand J Gastroenterol. · Pubmed #16170896 No free full text.

This publication has no abstract.

Moum B. · Medisinsk avdeling, Sykehuset Østfold Fredrikstad, 1601 Fredrikstad. · Tidsskr Nor Laegeforen. · Pubmed #14714043 links to  free full text

Abstract: BACKGROUND: Ulcerative colitis and Cohn's disease are characterised by exacerbations and remissions. Their aetiology is not known and treatment modalities are therefore focused on the inflammation. MATERIAL AND METHODS: A review is given of the literature on the clinical efficacy and safety of treatment with 5-aminosalicylates. RESULTS: Aminosalicylic acid has a well-documented efficacy in the acute treatment of mild and moderate ulcerative colitis as well as in maintaining remission in these patients. Its value for patients with Cohn's disease is at the best modest. There are several possible explanations: the variability of disease location, drug disposition and topical availability of the active drug. The usefulness of aminosalicylates has been demonstrated in the long-term treatment of ulcerative colitis for the prevention of colorectal cancer. 5-aminosalicylates have side effects that are comparable with placebo. INTERPRETATION: The benefit of 5-aminosalicylic acid is well documented in the treatment of active ulcerative colitis and for maintaining remission. The opposite is seen in relation to Cohn's disease.

Moum B. · Medisinsk avdeling Sykehuset Østfold Fredrikstad 1601 Fredrikstad. · Tidsskr Nor Laegeforen. · Pubmed #12523193 No free full text.

Abstract: BACKGROUND: Colonoscopy screening has been recommended as the method for preventing the development of cancer in ulcerative colitis. Factors that increase the risk of developing cancer are early onset of the disease, widespread disease, and a duration of over 10 years. MATERIAL AND METHODS: The results of screening have been disappointing. A critical review of relevant publications is given. RESULTS: Recent data have shown that the cancer risk in ulcerative colitis is lower than previously thought. One of the most important reasons seems to be the treatment with salazopyrine and 5-aminosalicylic acid. INTERPRETATION: Systematic follow-up of these patients by means of colonoscopy should include those who do not tolerate long-term medical treatment, patients with early onset of total colitis and protracted disease, and finally patients with higher risk of colorectal cancer because of their family history.

Moum B, Ekbom A. · Medical Department, County Hospital Ostfold Fredrikstad, Norway. · Dig Liver Dis. · Pubmed #12118955 No free full text.

Abstract: The causes and mechanisms of action of inflammatory bowel disease have, so far, eluded discovery. Epidemiological studies have shown that ulcerative colitis tends to level off, whereas Crohn's disease tends to increase. Some of these changes may be due to diagnostic practices and increasing awareness of the disease and Crohn's colitis. The disease varies according to geographical location and a distribution along a north-south axis has been suggested. The differences may be due to study design, or may reflect differences in lifestyle, diet or be due to genetic predisposition triggered by environmental factors. Epidemiological studies designed to investigate such interactions may provide clues to its aetiology. Inflammatory bowel disease could, therefore, serve as a model for the importance of epidemiology when to test or reject the hypothesis of aetiology.

Moum B. · Medisinsk avdeling Sykehuset Østfold Fredrikstad 1603 Fredrikstad. · Tidsskr Nor Laegeforen. · Pubmed #11242875 No free full text.

Abstract: BACKGROUND: About one quarter of women with the diagnosis conceive after the diagnosis has been made, and patients and clinicians are concerned about the health of the foetus and the possible side effects of medical and surgical treatment. MATERIAL, METHODS AND RESULTS: A survey of the literature shows that the general outlook is positive. The lifetime risk of developing inflammatory bowel disease if one of the parents has ulcerative colitis or Crohn's disease is 5-10 per cent. The fertility seems to be more or less normal for ulcerative colitis and slightly lower for Crohn's. Women with active disease at the time of conception have a higher risk of early miscarriage, fetal death and still birth. It is therefore advisable that the disease is in a stable and inactive phase at the time of conception. The rule of thumb is that one in three gets worse and one in three improves during pregnancy. The indications for surgery are the same as for non-pregnant patients. Relapses during pregnancy should be treated in the same way as in non-pregnant patients. Apart from methotrexate, most drugs used regularly to treat ulcerative colitis and Crohn's disease can safely be used by pregnant women. The same guidelines as for non-pregnant patients apply in terms of indications and dosage. INTERPRETATION: In general there is no need to advise these patients against conceiving.

Moum B. · Medisinsk avdeling Sykehuset Østfold Fredrikstad 1603 Fredrikstad. · Tidsskr Nor Laegeforen. · Pubmed #11242874 No free full text.

Abstract: BACKGROUND, MATERIAL AND METHODS: Most studies of the prognosis of inflammatory bowel disease have not been population-based; they are retrospective reviews. Moreover, they lack uniform methods for assessment of outcome. The clinical course is difficult to predict and the prognosis has changed over the last decades as a result of progress in medical therapeutics and treatment principles and surgical methods. RESULTS: Patients suffering from Crohn's disease or ulcerative colitis will probably alternate between remission and relapse, with 10% having a relapse-free course after ten years, and only 1% having a continuously active course. There is a cumulative frequency of operation of 50-80% and of reoperation of 1/3 in Crohn's disease. In ulcerative colitis the overall probability of surgery is 1/3 for pancolitis and 10% for proctitis within five years of diagnosis, and the majority of patients are operated on within the first few years. Maintenance treatment with sulphasalazine (SASP) and 5-aminosalicylic acid (5-ASA) in ulcerative colitis has reduced relapse rates to about the half. INTERPRETATION: Changes in disease distribution in ulcerative colitis are part of the natural course of the disease. This should have implications for medical treatment strategies. Inflammatory bowel disease frequently requires potent medication with side-effects that limit patients' acceptance. Certain environmental factors as well as patient compliance are thought to determine the clinical outcome in ulcerative colitis and Crohn's disease.

Solberg IC, Lygren I, Jahnsen J, Aadland E, Høie O, Cvancarova M, Bernklev T, Henriksen M, Sauar J, Vatn MH, Moum B, Anonymous00083. · Department of Gastroenterology, Ullevål University Hospital, Oslo, Norway. · Scand J Gastroenterol. · Pubmed #19101844 No free full text.

Abstract: 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) > or =30 mm/h was associated with an increased hazard ratio (HR) (3.57, 95% CI: 1.60-7.96) and age > or =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.

Solberg IC, Lygren I, Cvancarova M, Jahnsen J, Stray N, Sauar J, Schreiber S, Moum B, Vatn MH, Anonymous00020. · Department of Gastroenterology, Ullevål University Hospital, Oslo, Norway. · Inflamm Bowel Dis. · Pubmed #19009607 No free full text.

Abstract: BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) are proposed to be specific markers for ulcerative colitis (UC) and Crohn's 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.

Aamodt G, Bukholm G, Jahnsen J, Moum B, Vatn MH, Anonymous00062. · Department of Epidemiology, Norwegian Institute of Public Health, Postbox 4404 Nydalen, 0403 Oslo, Norway. · Am J Epidemiol. · Pubmed #18801890 No free full text.

Abstract: Inflammatory bowel disease refers to a group of chronic diseases of unknown etiology related to both genetic and environmental factors. In this 1990-1993 study, the authors investigated associations between the content and quality of drinking water and the incidence of inflammatory bowel disease. They used data from a population-based cohort recruited in southeastern Norway and a registry of water quality derived from Norwegian waterworks that contained measurements of iron, aluminum, acidity (pH), color, turbidity, and coliform bacteria. The authors found that risk of developing inflammatory bowel disease, including ulcerative colitis and Crohn's disease, was associated with high iron content. The relative risk of developing inflammatory bowel disease increased by 21% (95% confidence interval: 9, 34) when the iron content in the drinking water increased by 0.1 mg/L. They found no association between the diseases and aluminum in the water, color of the water, and turbidity of the water. The authors suggest that the observations can be explained by 2 mechanisms. First, high iron concentration works as a catalyst for oxidative stress, which will cause inflammation and/or increase the rate of cell mutations. Second, iron content stimulates the growth of bacteria and increases the likelihood of inappropriate immune responses in genetically predisposed individuals.

Henriksen M, Jahnsen J, Lygren I, Stray N, Sauar J, Vatn MH, Moum B, Anonymous00036. · Department of Internal Medicine, Østfold Hospital Moss, 1535 Moss, Norway. · Gut. · Pubmed #18566104 No free full text.

Abstract: BACKGROUND AND AIMS: C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease extent in patients with ulcerative colitis and to phenotype in patients with Crohn's disease, and to investigate the predictive value of CRP levels for disease outcome. METHODS: CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn's disease were alive and provided sufficient data for analysis. RESULTS: Patients with Crohn's disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn's disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn's disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03). CONCLUSIONS: CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn's disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn's disease.

Aamodt G, Jahnsen J, Bengtson MB, Moum B, Vatn MH, Anonymous00312. · Faculty of Medicine, University of Oslo and EpiGen Institute, Akershus University Hospital, Norway. · Inflamm Bowel Dis. · Pubmed #18338775 links to  free full text

Abstract: BACKGROUND: The purpose was to study the spatial distribution of cases of inflammatory bowel disease (IBD) and characterize municipalities with high incidences in a search for environmental risk factors. METHODS: Spatial clustering of patients diagnosed with IBD during 1990-1993 were studied in 4 counties in southeastern Norway, and an ecological analysis was conducted to study the relationship between risk of IBD in the municipalities and their characteristics such as population, health care, urban/rural change, and socioeconomic change. RESULTS: One cluster consisting of 4 municipalities was identified for IBD in Østfold county (P = 0.011). The ecological analysis showed that the incidence rate of IBD was 33% (95% confidence interval [CI]: 2%-75%) higher in municipalities with the highest level of education compared to the lowest level of education and 35% (2%-78%) higher in urban than rural municipalities. The incidence rate was 11% (1%-20%) lower in municipalities with a high urban/rural change compared to municipalities with low urban/rural change. Individuals living in high-risk municipalities were 3 times (1.57-5.45) more likely to have a first-degree family member with IBD than individuals living in normal-risk municipalities. CONCLUSIONS: The geographic distribution of cases with IBD is not uniformly distributed and is related to urbanization, level of education, and moving pattern. Geographic distribution may be explained by either changes in environment-host relationships or neurobiological mechanisms due to stress and economic frustration. These factors and genetic predisposition might also explain increased familial clustering. Spatial clustering was significant neither for Crohn's disease CD nor ulcerative colitis (UC) but showed a stronger tendency within the CD group.

Katsanos KH, Vermeire S, Christodoulou DK, Riis L, Wolters F, Odes S, Freitas J, Hoie O, Beltrami M, Fornaciari G, Clofent J, Bodini P, Vatn M, Nunes PB, Moum B, Munkholm P, Limonard C, Stockbrugger R, Rutgeerts P, Tsianos EV, Anonymous00369. · Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece. · Digestion. · Pubmed #17598963 No free full text.

Abstract: OBJECTIVE: To determine dysplasia and cancer in the 1991-2004 European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS AND METHODS: A patient questionnaire and a physician per patient form were completed for each of the 1,141 inflammatory bowel disease patients (776 ulcerative colitis/365 Crohn's disease) from 9 centers (7 countries) derived from the EC-IBD cohort. Rates of detection of intestinal cancer and dysplasia as well as extra-intestinal neoplasms were computed. RESULTS: Patient follow-up time was 10.3 +/- 0.8 (range 9.4-11) years. The mean age of the whole group of IBD patients was 37.8 +/- 11.3 (range 16-76) years. Thirty-eight patients (3.3%; 26 with ulcerative colitis/12 with Crohn's disease, 21 males/17 females, aged 61.3 +/- 13.4, range 33-77 years), were diagnosed with 42 cancers. Cancers occurred 5.4 +/- 3.3 (range 0-11) years after inflammatory bowel disease diagnosis. Colorectal cancer was diagnosed in 8 (1 Crohn's disease and 7 ulcerative colitis patients--0.3 and 0.9% of the Crohn's disease and ulcerative colitis cohort, respectively) of 38 patients and 30 cancers were extra-intestinal. Four of 38 patients (10.5%) were diagnosed as having 2 cancers and they were younger compared to patients with one cancer (p = 0.0008). There was a trend for a higher prevalence of intestinal cancer in the northern centers (0.9%) compared to southern centers (0.3%, p = NS). Southern centers had more cases of extra-intestinal cancer compared to northern centers (2 vs. 3.8%, p = 0.08). Ten patients (0.9%; 8 with ulcerative colitis/2 with Crohn's disease, 8 males, aged 62.3 +/- 14.1 years) had colorectal dysplasia. CONCLUSIONS: In the first decade of the EC-IBD Study Group cohort follow-up study, the prevalence of cancer was as expected with most patients having a single neoplasm and an extra-intestinal neoplasm. In northern centers there was a trend for more intestinal cancers, while in southern centers there was a trend for more extra-intestinal cancers compared to northern centers.

Henriksen M, Jahnsen J, Lygren I, Vatn MH, Moum B, Anonymous00316. · Department of Internal Medicine, Østfold Hospital Moss, Moss, Norway. · Am J Gastroenterol. · Pubmed #17573793 No free full text.

Abstract: BACKGROUND: The influence of familial IBD on phenotype and course of disease in patients with CD and UC has not been studied in population-based cohorts. AIM: To compare phenotype and course of disease between IBD patients with a first-degree relative with IBD and sporadic cases in a population-based cohort followed prospectively for 5 yr. METHODS: Family history of IBD was registered at diagnosis and after 1 and 5 yr. Phenotype and course of disease were compared between sporadic and familial cases. RESULTS: Data for 200 patients with CD and 454 with UC were sufficient for analysis. A first-degree relative with IBD was registered in 14.5% of CD patients and 10.1% of UC patients. The concordance for type of disease was 82% and 70% for CD and UC, respectively. No differences between familial and sporadic cases as regards localization and behavior of disease in CD patients or disease extent in UC patients were observed. In CD patients with colonic involvement, those in the familial group were significantly younger at diagnosis than the sporadic cases. No difference in disease severity in CD patients was observed between the familial and sporadic groups. In UC patients relapse was more frequent in familial cases, but no difference was observed in the need for surgery or medical treatment. CONCLUSIONS: A family history of IBD does not seem to influence phenotype or to be an important prognostic factor for disease course in IBD patients.

Höie O, Wolters F, Riis L, Aamodt G, Solberg C, Bernklev T, Odes S, Mouzas IA, Beltrami M, Langholz E, Stockbrügger R, Vatn M, Moum B, Anonymous00240. · Sörlandet Hospital Arendal, Department of Medicine, Section for Gastroenterology, Arendal, Norway. · Am J Gastroenterol. · Pubmed #17555460 No free full text.

Abstract: OBJECTIVES: Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to almost 100% have been reported in regional studies. The aim of this study was to determine the relapse rate in UC in a European population-based cohort 10 yr after diagnosis and to identify factors that may influence the risk of relapse. METHODS: From 1991 to 1993, 771 patients with UC from seven European countries and Israel were prospectively included in a population-based inception cohort and followed for 10 yr. A relapse was defined as an increase in UC-related symptoms leading to changes in medical treatment or surgery. The cumulative relapse rate, time to first relapse, and number of relapses in the follow-up period were recorded and possible causative factors were investigated. RESULTS: The cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI 0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI 1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1-1.8). The number of relapses decreased with age, and current smokers had a lower relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2 (CI 1.1-1.3) times higher than in men. An inverse relation was found between the time to the first relapse and the total number of relapses. CONCLUSION: In 67% of patients, there was at least one relapse. Smoking status, level of education, and possibly female gender were found to influence the risk of relapse.

Hoie O, Wolters FL, Riis L, Bernklev T, Aamodt G, Clofent J, Tsianos E, Beltrami M, Odes S, Munkholm P, Vatn M, Stockbrügger RW, Moum B, Anonymous00328. · Sorlandet Hospital Arendal, Department of Medicine, Section for Gastroenterology, Arendal, Norway. · Gastroenterology. · Pubmed #17258717 No free full text.

Abstract: BACKGROUND & AIMS: The colectomy rate in ulcerative colitis (UC) is related to morbidity and to treatment decisions made during disease course. The aims of this study were to determine the colectomy risk in UC in the first decade after diagnosis and to identify factors that may influence the choice of surgical treatment. METHODS: In 1991-1993, 781 UC patients from 9 centers located in 7 countries in northern and southern Europe and in Israel were included in a prospective inception cohort study. After 10 years of follow-up, 617 patients had complete medical records, 73 had died, and 91 had been lost to follow-up. RESULTS: There were no significant differences in age, sex, or disease extent at diagnosis between patients followed for 10 years and those lost to follow-up. The 10-year cumulative risk of colectomy was 8.7%: 10.4% in the northern and 3.9% in the southern European centers (P < .001). Colectomy was more likely in extensive colitis than in proctitis, with an adjusted hazard ratio (HR) of 4.1 (95% CI: 2.0-8.4). Compared with the southern centers, the adjusted HR was 2.7 (95% CI: 1.3-5.6) for The Netherlands and Norway together and 8.2 (95% CI: 3.6-18.6) for Denmark. Age at diagnosis, sex, and smoking status at diagnosis had no statistically significant influence on colectomy rates. CONCLUSIONS: The colectomy rate was found to be lower than that in previous publications, but there was a difference between northern and southern Europe. Colectomy was associated with extensive colitis, but the geographic variations could not be explained.

Riis L, Vind I, Vermeire S, Wolters F, Katsanos K, Politi P, Freitas J, Mouzas IA, O'Morain C, Ruiz-Ochoa V, Odes S, Binder V, Munkholm P, Moum B, Stockbrügger R, Langholz E, Anonymous00158. · Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark. · Inflamm Bowel Dis. · Pubmed #17206636 links to  free full text

Abstract: BACKGROUND AND AIM: The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north-south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD cohort. METHODS: Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. RESULTS: Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. CONCLUSION: The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Höie O, Schouten LJ, Wolters FL, Solberg IC, Riis L, Mouzas IA, Politi P, Odes S, Langholz E, Vatn M, Stockbrügger RW, Moum B, Anonymous00102. · Sörlandet Hospital Arendal, Department of Medicine, Section for Gastroenterology, Arendal, Norway. · Gut. · Pubmed #17028127 No free full text.

Abstract: 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.

Odes S, Vardi H, Friger M, Wolters F, Russel MG, Riis L, Munkholm P, Politi P, Tsianos E, Clofent J, Vermeire S, Monteiro E, Mouzas I, Fornaciari G, Sijbrandij J, Limonard C, Van Zeijl G, O'morain C, Moum B, Vatn M, Stockbrugger R, Anonymous00376. · Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel. · Gastroenterology. · Pubmed #16952541 No free full text.

Abstract: BACKGROUND & AIMS: Economic analysis in chronic diseases is a prerequisite for planning a proper distribution of health care resources. We aimed to determine the cost of inflammatory bowel disease, a lifetime illness with considerable morbidity. METHODS: We studied 1321 patients from an inception cohort in 8 European countries and Israel over 10 years. Data on consumption of resources were obtained retrospectively. The cost of health care was calculated from the use of resources and their median prices. Data were analyzed using regression models based on the generalized estimating equations approach. RESULTS: The mean annual total expenditure on health care was 1871 Euro/patient-year for inflammatory bowel disease, 1524 Euro/patient-year for ulcerative colitis, and 2548 Euro/patient-year for Crohn's disease (P < .001). The most expensive resources were medical and surgical hospitalizations, together accounting for 63% of the cost in Crohn's disease and 45% in ulcerative colitis. Total and hospitalization costs were much higher in the first year after diagnosis than in subsequent years. Differences in medical and surgical hospitalizations were the primary cause of substantial intercountry variations of cost; the mean cost of health care was 3705 Euro/patient-year in Denmark and 888 Euro/patient-year in Norway. The outlay for mesalamine, a costly medication with extensive use, was greater than for all other drugs combined. Patient age at diagnosis and sex did not affect costs. CONCLUSIONS: In this multinational, population-based, time-dependent characterization of the health care cost of inflammatory bowel disease, increased expenditure was driven largely by country, diagnosis, hospitalization, and follow-up year.

Henriksen M, Jahnsen J, Lygren I, Sauar J, Schulz T, Stray N, Vatn MH, Moum B, Ibsen Study Group. · Department of Internal Medicine, Østfold Hospital, Moss, Norway. · Scand J Gastroenterol. · Pubmed #16938716 No free full text.

Abstract: OBJECTIVE: An exact diagnosis of inflammatory bowel disease (IBD) and further subclassification may be difficult even after clinical, radiological and histological examinations. A correct subclassification is important for the success of both medical and surgical therapeutic strategies, but there is a dearth of information available on the frequency of changes in diagnosis in population-based studies. The objective of this work was prospectively to re-evaluate the diagnosis in an unselected cohort of IBD patients during the first five years after the initial diagnosis. MATERIAL AND METHODS: Patients classified as IBD or possible IBD in the period 1990-94 (the IBSEN cohort) had their diagnosis re-evaluated after 1 and 5 years. Initially, the patients were classified as ulcerative colitis (UC), Crohn's disease (CD), indeterminate colitis (IC) or possible IBD. At the 5-year visit, patients were classified as UC, CD or non-IBD. RESULTS: A total of 843 patients (518 UC, 221 CD, 40 IC and 64 possible IBD) were identified. Clinical information was available for 94% of the patients who survived after 5 years. A change in diagnosis was found in 9% of the patients initially classified as UC or CD. A change to non-IBD was more frequent than a change between UC and CD. A large proportion of patients initially classified as IC or possible IBD were diagnosed as non-IBD after 5 years (22.5% versus 50%). When IBD was confirmed in these groups, UC was more frequent than CD. Two changes in diagnosis during follow-up were observed in 2.8% of the patients; this was more frequent in patients initially classified as IC or possible IBD. CONCLUSIONS: There are obvious diagnostic problems in a minority of patients with IBD; a systematic follow-up is therefore important in these patients.

Riis L, Vind I, Politi P, Wolters F, Vermeire S, Tsianos E, Freitas J, Mouzas I, Ruiz Ochoa V, O'Morain C, Odes S, Binder V, Moum B, Stockbrügger R, Langholz E, Munkholm P, Anonymous00091. · Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. · Am J Gastroenterol. · Pubmed #16863558 No free full text.

Abstract: BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) often affects patients in their fertile age. The aim of this study was to describe pregnancy outcome in a European cohort of IBD patients. As data are limited regarding the effect of pregnancy on disease course, our second objective was to investigate whether pregnancy influences disease course and phenotype in IBD patients. METHODS: In a European cohort of IBD patients, a 10-yr follow-up was performed by scrutinizing patient files and approaching the patients with a questionnaire. The cohort comprised 1,125 patients, of whom 543 were women. Data from 173 female ulcerative colitis (UC) and 93 Crohn's disease (CD) patients form the basis for the present study. RESULTS: In all, 580 pregnancies, 403 occurring before and 177 after IBD was diagnosed, were reported. The rate of spontaneous abortion increased after IBD was diagnosed (6.5% vs. 13%, p = 0.005), whereas elective abortion was not significantly different. 48.6% of the patients took medication at the time of conception and 46.9% during pregnancy. The use of cesarean section increased after IBD diagnosis (8.1% vs 28.7% of pregnancies). CD patients pregnant during the disease course, did not differ from patients who were not pregnant during the disease course regarding the development of stenosis (37% vs 52% p = 0.13) and resection rates (mean number of resections 0.52 vs 0.66, p = 0.37). The rate of relapse decreased in the years following pregnancy in both UC (0.34 vs 0.18 flares/yr, p = 0.008) and CD patients (0.76 vs 0.12 flares/yr, p = 0.004). CONCLUSIONS: Pregnancy did not influence disease phenotype or surgery rates, but was associated with a reduced number of flares in the following years.

Henriksen M, Jahnsen J, Lygren I, Sauar J, Kjellevold Ø, Schulz T, Vatn MH, Moum B, Anonymous00320. · Department of Internal Medicine, Østfold Hospital, Moss, Norway. · Inflamm Bowel Dis. · Pubmed #16804390 links to  free full text

Abstract: BACKGROUND: The majority of studies concerning the clinical course and prognosis in ulcerative colitis (UC) are old, retrospective in design, or hospital based. We aimed to identify clinical course and prognosis in a prospective, population-based follow-up study MATERIALS AND METHODS: Patients diagnosed with inflammatory bowel disease (IBD) or possible IBD in southeastern Norway during the period 1990-1994 were followed prospectively for 5 years. The evaluation at 5 years included an interview, clinical examination, laboratory tests, and colonoscopy. RESULTS: Of 843 patients diagnosed with IBD, 454 patients who had definite UC and for whom there were sufficient data for analysis were alive 5 years after inclusion in the study. The frequency of colectomy in this population was 7.5%. Forty-one percent of the patients were not taking any kind of medication for IBD at 5 years. Of the patients initially diagnosed with proctitis, 28% had progressed during the observation period, 10% to extensive colitis. The majority of the patients (57%) had no intestinal symptoms at 5 years, and only a minority (7%) had symptoms that interfered with everyday activities. Among the patients who underwent colonoscopy at the 5-year visit, symptoms were frequently reported in patients without macroscopic inflammation (44%). A relapse-free course was observed in 22% of the patients. A decrease in symptoms during the follow-up period was the most frequent course taken by the disease and was observed in 59% of the cases. The extent of disease was unrelated to symptoms at 5 years and also to relapse rate and course of disease during the 5-year period. CONCLUSIONS: The disease course and prognosis of UC appears better than previously described in the literature. The frequency of surgery was low, and only a minority of the patients had symptoms that interfered with their everyday activities 5 years after diagnosis.

Wolters FL, Russel MG, Sijbrandij J, Schouten LJ, Odes S, Riis L, Munkholm P, Langholz E, Bodini P, O'Morain C, Katsanos K, Tsianos E, Vermeire S, Van Zeijl G, Limonard C, Hoie O, Vatn M, Moum B, Stockbrügger RW, The European Collaborative Study Group On Inflammatory Bowel Disease. · Department of Gastroenterology and Hepatology, University Hospital Maastricht, Maastricht, The Netherlands. · Scand J Gastroenterol Suppl. · Pubmed #16782622 No free full text.

Abstract: OBJECTIVE: To give a general outline of a 10-year clinical follow-up study of a population-based European cohort of inflammatory bowel disease (IBD) patients and to present the first results in terms of clinical outcome parameters and risk factors. MATERIALS AND METHODS: A population-based cohort of newly, prospectively, diagnosed cases was initiated between 1991 and 1993. The 2201 patients with IBD (706 had Crohn's disease (CD), 1379 had ulcerative colitis (UC) and 116 had indeterminate colitis) originated from 20 different areas in 11 different European countries and Israel. For the 10-year follow-up of this cohort, electronic data-collecting instruments were made available through an Internet-based website. Data concerning vital status, disease activity, medication use, surgical events, cancer, pregnancy, fertility, quality of life and health-care costs were gathered. A blood sample was obtained from patients and controls to perform genotypic characterization. RESULTS: Thirteen centres from eight European countries and Israel participated. In 958 (316 CD and 642 UC) out of a total of 1505 IBD patients (64%) from these 13 centres, a complete dataset was obtained at follow-up. Even though an increased mortality risk was observed in CD patients 10 years after diagnosis, a benign disease course was observed in this patient group in terms of disease recurrence. A correlation between ASCA and CARD15 variants in CD patients and complicated disease course was observed. A north-south gradient was observed regarding colectomy rates in UC patients. Direct costs were found to be highest in the first year after diagnosis and greater in CD patients than in UC patients, with marked differences between participating countries. CONCLUSIONS: This 10-year clinical follow-up study of a population-based European cohort of IBD patients provides updated information on disease outcome of these patient groups.

Bernklev T, Jahnsen J, Henriksen M, Lygren I, Aadland E, Sauar J, Schulz T, Stray N, Vatn M, Moum B. · Medical Department, Rikshospitalet, University of Oslo, Oslo, Norway. · Inflamm Bowel Dis. · Pubmed #16670530 links to  free full text

Abstract: BACKGROUND: The goal of this study was to determine the rate of work disability, unemployment, and sick leave in an unselected inflammatory bowel disease (IBD) cohort and to measure the effect of working status and disability on the patient's health-related quality of life (HRQOL). MATERIALS AND METHODS: All eligible patients were clinically examined and interviewed at the 5-year follow-up visit. In addition, they completed the 2 HRQOL questionnaires, the Short Form-36 Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire validated for use in Norway (N-IBDQ). Data regarding sick leave, unemployment, and disability pension (DP) also were collected. RESULTS: All together, 495 patients were or had been in the workforce during the 5-year follow-up period since diagnosis. Forty-two patients (8.5%) were on DP compared with 8.8% in the background population. Women with Crohn's disease (CD) had the highest probability of receiving DP (24.6%). A total of 58 patients (11.7%) reported they were unemployed at 5 years. This was equally distributed between men and women but was more frequent in patients with ulcerative colitis. Sick leave for all causes was reported in 47% with ulcerative colitis and 53% with CD, whereas IBD-related sick leave was reported in 18% and 23%, respectively. A majority (75%) had been sick <4 weeks, and a relatively small number of patients (25%) contributed to a large number of the total sick leave days. Both unemployment and DP reduced HRQOL scores, but the most pronounced effect on HRQOL was found in patients reporting IBD-related sick leave, measured with SF-36 and N-IBDQ. The observed differences also were highly clinically significant. Multiple regression analysis confirmed that IBD-related sick leave was the independent variable with the strongest association to the observed reduction in HRQOL scores. CONCLUSIONS: Unemployment or sick leave is more common in IBD patients than in the Norwegian background population. The number of patients receiving DP is significantly increased in women with CD but not in the other patient groups. Unemployment, sick leave, and DP are related to the patient's HRQOL in a negative way, but this effect is most pronounced in patients reporting IBD-related sick leave.

Medici V, Mascheretti S, Croucher PJ, Stoll M, Hampe J, Grebe J, Sturniolo GC, Solberg C, Jahnsen J, Moum B, Schreiber S, Vatn MH. · Department of General and Internal Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-University, Schittenhelmstrasse 12, Kiel 24105, Germany. · Eur J Hum Genet. · Pubmed #16493449 links to  free full text

Abstract: The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of F(ST), indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P=0.048). The population attributable risk percentage (PAR%) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88%), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P=0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.