Abstract: 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 Crohn's 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.
Abstract: In this systematic review we focus on the current use of and knowledge on health related quality of life in unselected, population-based IBD cohorts. We made a systematic literature search and included for comprehensive review papers that described a population-based cohort and that used validated HRQoL instruments. We show that even studies defined by the authors as population-based do not always meet the criteria set for being population-based. The heterogeneity of the study populations we have reviewed emphasizes that "population-based" must be defined very meticulously and that study populations need to be scrutinized with regard to all characteristics of the cohort before one can compare their results. Different definitions of study populations as population-based affect outcomes. We also show that use of the same HRQoL questionnaires does not guarantee comparable results as there are several different versions of the questionnaires, the different translations are not always comparable and at last there are several methods of computing and presenting the data. Detailed accumulation of knowledge and thorough meta analyses is therefore difficult hence we find it necessary to raise a discussion on the need of standardization in this field of research and we make some simple recommendations on factors we find important.
Abstract: BACKGROUND: Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. AIMS: To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. METHODS: Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. RESULTS: Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort. CONCLUSIONS: Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.
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.
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.
Abstract: BACKGROUND:: The aim was to compare clustering of time at diagnosis and phenotype of inflammatory bowel disease (IBD) between affected parents and children and to explore generational differences in age at diagnosis (AAD) as well as the concordance of clinical characteristics. METHODS:: Eighty-four affected pairs from 45 families were included from 5 counties in southeastern Norway between August 2003 and December 2006; 43 were sib-sib pairs and 39 parent-child pairs. Clinical data were obtained by phone interviews and by hospital records. RESULTS:: The difference in median AAD was 17.0 years (P < 0.001) and 2.0 years (P = 0.29) in parent-child and sib-sib pairs, respectively. When the time interval between diagnosis in parent and child was split into 2 groups, below and above 5 years, 64% of pairs with ulcerative colitis (UC) offspring were diagnosed within 5 years, compared to 24% of pairs with Crohn's disease (CD) offspring (odds ratio [OR] = 5.7, 95% confidence interval [CI]: 1.4, 23.8). Concordance for smoking habits was low in 26 pairs with mixed disease (kappa = 0.15), whereas patients with CD tended to be current smokers. CONCLUSIONS:: Most of the children acquire their disease at an earlier time in life compared to their parents, suggesting genetic anticipation. The time interval between diagnosis of the parents and offspring was lower when the offspring developed UC compared to CD, which might reflect the influence of shared environment on the generational difference in AAD in UC families. This study confirmed the effect of smoking habits on IBD phenotype. Inflamm Bowel Dis 2009.
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.
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.
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.
Abstract: BACKGROUND AND AIMS: Mucosal healing (MH) in inflammatory bowel disease may be an important sign of efficacy of treatment and a prognostic marker of long-term disease. The aim of the study was to examine both the possible predictors of mucosal healing and the impact of healing on subsequent course of disease. METHODS: In 740 incident patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 1990 and 1994 (before biologic therapy was available), demographics and symptoms were recorded. Clinical and endoscopic evaluations were done at baseline before treatment and repeated after 1 and 5 years in 495 patients. RESULTS: In UC patients, education longer than 12 years and extensive disease at diagnosis were significant predictors of MH after 1 year (adjusted P = .004 and P = .02, respectively). MH was significantly associated with a low risk of future colectomy (P = .02). In patients with CD, fever at diagnosis and medical treatment without steroids were significant predictors for MH (adjusted P = .03 and P = .01, respectively). MH was significantly associated with less inflammation after 5 years (P = .02), decreased future steroid treatment (P = .02). CONCLUSIONS: Several factors predicted subsequent MH. Education as predictor may implicate the importance of coping, compliance, or lifestyle. MH after 1 year of treatment is predictive of reduced subsequent disease activity and decreased need for active treatment. The present results give further strength to the use of mucosal healing as a clinical indicator and treatment goal in inflammatory bowel disease.
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.
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.
Abstract: BACKGROUND & AIMS: Most studies concerning the clinical course in CD are retrospective or based on selected patient groups. Our aim was to assess the course of CD in a prospective population-based follow-up study and to identify possible prognostic risk factors for complications on the basis of information obtained at initial diagnosis. METHODS: From 1990-1994, a population-based cohort of 843 new cases of inflammatory bowel disease was recruited in South-Eastern Norway. The cohort was systematically followed up at 1, 5, and 10 years after diagnosis. RESULTS: Of 237 patients classified as CD, 197 completed the 10 years of follow-up, 18 died, and 22 were lost to follow-up. The cumulative relapse rate during the first 10 years was 90% (95% confidence interval, 86%-94%), and the cumulative probability of surgery was 37.9% (95% confidence interval, 31.4%-44.4%). Terminal ileal location (P < .001), stricturing (P = .004), penetrating behavior (P < .001), and age younger than 40 years (P = .03) at diagnosis were independent risk factors for subsequent surgery. A total of 53% (n = 105) of the patients had developed stricturing or penetrating disease at 10 years. A large proportion of patients (44%) were in clinical remission during the last 5 years of follow-up. CONCLUSIONS: The prognosis for CD seems better than previously reported. The probability of surgery was low, and fewer than expected developed complicated disease behavior. Nevertheless, the cumulative relapse rate of 90% and the finding of prognostic risk factors for subsequent surgery might call for attention to early effective medical treatment strategies.
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.
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.
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.
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.
Abstract: BACKGROUND: NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. METHODS: CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. RESULTS: The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. CONCLUSIONS: Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.
Abstract: BACKGROUND: There are few population-based, prospective studies on the clinical course in patients with Crohn's disease (CD). AIM: To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification. METHODS: All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990-1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy. RESULTS: Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period. CONCLUSIONS: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.
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.
Abstract: OBJECTIVE: Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. MATERIAL AND METHODS: A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. RESULTS: Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. CONCLUSIONS: In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.
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.
Abstract: BACKGROUND: The insertion of self-expanding metal stents (SEMS) for palliation of dysphagia in patients with malignant stenosis of the esophagus and cardia, is a well-established procedure. The aim of this retrospective study was to evaluate the results of esophageal stenting in terms of functioning, need of retreatment and survival after stenting. PATIENTS AND METHODS: 37 patients with unresectable esophageal and cardial carcinoma treated with SEMS between January 1997 and May 2004 were retrospectively analysed. RESULTS: One patient died the day the stent was introduced. Otherwise, no major procedural complications were observed. The median time to repeated hospital contact was 25 days, most often due to recurrence of dysphagia. Tumor ingrowth or overgrowth was primarily treated with argon plasma coagulation (APC). Ten patients underwent repeat stent insertion. The median survival time after the first stent insertion was 88 days. CONCLUSION: Insertion of SEMS in patients with inoperable carcinoma in esophagus and cardia should be regarded as a safe procedure. In our study, many patients could stay at home for months without recurrence of dysphagia that needed treatment.
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.
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.
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.
Abstract: BACKGROUND: No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. METHODS: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. RESULTS: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30-2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10-3.14)) and males (SMR 1.79 (95% CI 1.11-2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32-3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80-2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. CONCLUSIONS: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.
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.
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.
Abstract: BACKGROUND: In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. AIMS: To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. METHODS: A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. RESULTS: A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13-2.10)) whereas age >/=40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70-0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21-0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32-7.89)). CONCLUSIONS: A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.
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.
Abstract: This article reports quality of life (QoL) aspects of a study that investigated the efficacy of three treatment regimens in gastro-oesophageal reflux disease patients. Following a 4-week symptom-control phase (esomeprazole 40 mg once daily), patients were randomised to 6 months' esomeprazole 20 mg once daily continuously (n = 658), on-demand (n = 634) or ranitidine 150 mg twice daily continuously (n = 610). Esomeprazole 40 mg once daily improved QoL during the symptom-control phase. At 6 months, both esomeprazole regimens were more effective than ranitidine in all dimensions of the Quality of Life in Reflux and Dyspepsia questionnaire (p < 0.0001). Esomeprazole continuous and on-demand led to a significant improvement in symptoms (Overall Treatment Evaluation questionnaire) compared with ranitidine (continuous: 80.2%, on-demand: 77.8%, vs. ranitidine 47.0%; p < 0.001). Esomeprazole once daily continuously maintained QoL better than esomeprazole on-demand and was associated with greater patient satisfaction. In conclusion, esomeprazole 20 mg once daily continuously and on-demand were more effective than ranitidine continuously for maintaining QoL.
Abstract: OBJECTIVE: To describe the prevalence and characteristics of non-inflammatory joint pain (NIJP) in patients with chronic inflammatory bowel disease (IBD) and its impact on patients' health related quality of life (HRQOL). METHODS: In a population based cohort, 521 patients (80%) were clinically investigated 6 years after onset of IBD. NIJP was defined as a history of joint pain during the last 3 months prior to examination and the absence of concomitant signs or symptoms of inflammatory or degenerative joint disease or chronic pain syndromes. HRQOL was registered by the generic Medical Outcome Study Short Form 36 (SF-36) and by the disease specific IBDQ. RESULTS: NIJP was reported by 85 (16%) patients and significantly more often in conjunction with Crohn's disease (CD, 22%) compared to ulcerative colitis (UC, 14%). The prevalence of NIJP was similar in men and women. No correlation with extension of intestinal disease, use of systemic medication, or frequency of surgery was found. NIJP exerted significant impact on HRQOL measured by SF-36 and IBDQ. CONCLUSIONS: NIJP occurs frequently in IBD and more often in CD than in UC. NIJP significantly alters HRQOL and should be taken into account in trials estimating outcome in IBD and in clinical practice by attending clinicians.
Abstract: OBJECTIVES: We assessed health-related quality of life (HRQOL) on the basis of a cross-sectional design in a population-based cohort of inflammatory bowel disease patients followed prospectively for 5 years after diagnosis. The aim was to investigate the influence of the course of disease, drug therapy, and relapse pattern on the patients' HRQOL. METHODS: All patients completed the validated Norwegian version of the Inflammatory Bowel Disease Questionnaire (N-IBDQ). We present data from 497 patients, 328 with ulcerative colitis and 169 with Crohn's disease. The mean age was 43.3 years, and 48% were female. RESULTS: Crohn's disease patients treated with systemic steroids or azathioprine had a statistically significant reduction in the N-IBDQ total score compared with non-users. Patients with a more severe disease pattern had a lower N-IBDQ total score. Patients reporting a relapse during the observation period had a significantly lower total score and dimension scores than patients without relapse in both diagnostic groups, and likewise there was a statistically significant decrease in N-IBDQ total score for those with extra-intestinal manifestations compared with those without. A multiple linear regression model showed that the number of relapses during the preceding year in ulcerative colitis, and sex (female gender) in Crohn's disease were the strongest predictor of a reduction in N-IBDQ total score. CONCLUSION: Treatment with systemic steroids or immunosuppressive drugs, a relapsing disease and the presence of extra-intestinal manifestations were associated with a clinically significant reduction in the patients' HRQOL.
Abstract: This study assesses the difference in direct medical costs between on-demand treatment with esomeprazole 20 mg, continuous treatment with esomeprazole 20 mg once-daily and continuous treatment with ranitidine 150 mg twice-daily to prevent symptomatic relapse in patients with gastroesophageal reflux disease over 26 weeks. Two hundred eighty-one GP clinics in Norway enrolled 2156 patients to an open, randomized, parallel group, Norwegian society perspective study during 2000-2001. The total direct medical costs of each strategy were 171.9 Euros for on-demand esomeprazole (n = 634), 221.6 Euros for ranitidine (n = 610) and 248.8 Euros for continuous esomeprazole (n = 658). The total costs for on-demand and continuous esomeprazole treatment and ranitidine treatment were 221.5, 286.5 and 295.8 Euros, respectively. The highest proportion of costs was because of the study medication cost in each strategy. The on-demand and continuous treatment strategies with esomeprazole were found to be cost-effective, compared with ranitidine.
Abstract: One option for patients with symptoms of gastroesophageal reflux disease (GERD) is treatment with proton pump inhibitors without prior endoscopy. Continuous or on-demand maintenance therapy are options for symptom-free patients. This study assessed the efficacy of three different treatment options in GERD patients in Norway. About 395 General Practitioners enrolled 2156 patients with symptoms of GERD in an open, randomised, parallel group trial. Following a 4-week symptom control phase [esomeprazole 40 mg once daily (od)], patients received either esomeprazole 20 mg od continuously or on-demand or ranitidine 150 mg twice-daily continuously for 6 months. The percentage of patients with no heartburn at the end of the study was maintained most effectively in the esomeprazole 20 mg continuous group (72.2%) and least effectively in the ranitidine group (32.5%). Significantly, more patients were completely/very satisfied with esomeprazole continuous (82.2%) and esomeprazole on-demand (75.4%) than with ranitidine continuous (33.5%) treatment (p < 0.0001). More patients were kept in remission, symptom free and were overall more satisfied with esomeprazole treatment than ranitidine.
Abstract: BACKGROUND: We compared health-related quality of life (HRQOL) in a population-based cohort of Norwegian patients with inflammatory bowel disease (IBD) with a normal reference population by means of the short form-36 (SF-36) questionnaire, including the effect of age, sex, educational status, and symptom severity and the psychometric properties of the questionnaire. METHODS: The SF-36 was self-administered and was answered by the patients at the hospital at 2 occasions that were 6 months apart. RESULTS: Five hundred fourteen patients with IBD were eligible for analysis: 348 with ulcerative colitis (UC) and 166 with Crohn's disease (CD). The comparison group consisted of 2323 Norwegian people. The dimension scores for SF-36 were significantly lower in 6 of 8 dimensions for patients with UC and in 7 of 8 dimensions for patients with CD than for the reference population. In both patients with UC and patients with CD, we found lower scores in elderly patients, which also was found in the background population. Women scored lower than men in all dimension scores. In both patients with UC and patients with CD, there was a statistically significant reduction in HRQOL score with increasing symptoms. The SF-36 has satisfactory reliability and discriminant ability for scores for all dimensions in both patients with UC and patients with CD. However, when measuring responsiveness, the figures were generally low. This finding, together with the high ceiling effects, may indicate that the SF-36 has limitations regarding detecting deterioration or improvement over time. CONCLUSION: We have shown that HRQOL in a Norwegian population-based cohort of patients with IBD, measured with the SF-36, is lower than that of a Norwegian reference population. In general, the SF-36 was found to have satisfactory psychometric properties in this IBD population.
Abstract: BACKGROUND: Health-related quality of life (HRQOL) has become an important tool in evaluating patient satisfaction in inflammatory bowel disease (IBD). So far, few prospective follow-up studies have been done to identify variables that influence HRQOL. We aimed to identify demographic and clinical variables that influence HRQOL 5 years after diagnosis in patients with ulcerative colitis (UC) or Crohn disease (CD) included in a prospective follow-up study from 1990 to 1994 (the IBSEN study). METHODS: All patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire translated into Norwegian and validated. We present data from 497 patients (328 UC patients and 169 CD patients, mean age 43.3 years, 48% female). The impact of age, gender, smoking, symptom severity, disease distribution, rheumatic symptoms and surgery on IBD patients' HRQOL was analysed. RESULTS: Women had a reduction in IBDQ total score of 10 points compared to men, CD patients had a reduction of 7.5 compared to UC patients. The patients with moderate/severe symptoms had a 50 points lower score than the patients without symptoms. The patients with rheumatic symptoms had a 10 points lower total score than the patients without these symptoms. All differences were statistically significant. The multiple regression analysis showed that symptom severity, rheumatic symptoms and female gender were the strongest predictors of reduction in HRQOL for both diagnosis groups. CONCLUSION: IBD symptoms, rheumatic symptoms and female gender have a significant influence on patients' HRQOL as measured by IBDQ. This was confirmed by the regression analysis.
Abstract: OBJECTIVES: Few prospective population-based studies have been carried out on the incidence of inflammatory bowel disease (IBD). In a population-based study of pediatric IBD in southeastern Norway, patients <16 years at the time of diagnosis were followed up prospectively. The study reports on changes in diagnosis and clinical outcome 5 years after diagnosis. METHODS: From 1990 to 1993 new cases of IBD were registered in a population of 174,482 children aged less than 16 years. The patients' diagnoses were systematically evaluated 1 year after diagnosis and the patients were followed up clinically for up to 5 years after diagnosis. Results: Sixteen cases of Crohn's disease (CD), 14 cases of ulcerative colitis (UC) and 3 cases of indeterminate colitis (IND) were initially registered. After 1 year IND were reclassified as UC (n=2) or CD (n=1). Altogether, 18% (6/33) had their diagnosis changed during the 5 years of follow-up, which yielded a mean annual incidence of 2.7/100,000 for CD and 2.0/100,000 for UC. Of the children with CD, more than 80% had relapses during the 5-year period, and 6 of 18 had surgery. Two-thirds of the children with UC had relapses during the 5-year period, and 3 patients underwent colectomy. CONCLUSIONS: An incidence of 4.7/100,000 is comparable to that found in most other studies made in Europe. The relationship between UC and CD in children was found to differ from that in the adult population. One of 5 patients had their diagnosis changed during the follow-up period. Pediatric UC seems to have a more serious course of disease than in the adult IBD population, which may be explained by the higher risk of pancolitis at diagnosis.
Abstract: BACKGROUND: Patients with endoscopy-negative reflux disease have reflux symptoms, mainly heartburn, but not mucosal breaks characteristic of erosive oesophagitis. Standard-dose proton pump inhibitors can provide symptom relief in endoscopy-negative reflux disease but the effect of greater acid suppression has not been studied. AIM: To test the hypothesis that esomeprazole produces heartburn resolution in a greater proportion of patients with ENRD than omeprazole. METHODS: Three multi-centre randomized, controlled, double-blind, 4-week acute treatment studies were conducted in endoscopy-negative reflux disease patients. In study A (n = 1282), patients received either esomeprazole 40 mg, esomeprazole 20 mg or omeprazole 20 mg daily; in studies B (n = 693) and C (n = 670) patients received either esomeprazole 40 mg or omeprazole 20 mg (B), and esomeprazole 20 mg or omeprazole 20 mg (C), respectively. RESULTS: Resolution of heartburn at 4 weeks (no heartburn symptoms during the last 7 days) was achieved in similar proportions of patients in each treatment arm in study A (esomeprazole 40 mg, 56.7%; esomeprazole 20 mg, 60.5%; omeprazole 20 mg, 58.1%), study B (esomeprazole 40 mg, 70.3%; omeprazole 20 mg, 67.9%) and study C (esomeprazole 20 mg, 61.9%; omeprazole 20 mg, 59.6%). There were no significant differences between treatment groups within each study. CONCLUSIONS: More than 60% of endoscopy-negative reflux disease patients reported heartburn resolution but, after 4 weeks of therapy, these proportions did not differ significantly between treatments.
Abstract: BACKGROUND AND STUDY AIMS: The text report is the primary tool for documenting endoscopic findings but there is no consensus on the content and structure of these reports. Therefore, at four Norwegian hospitals, the content of endoscopy reports concerning ulcerative colitis was assessed. Quality indices for the medical history of active ulcerative colitis and endoscopic signs of inflammation were determined, as well as technical items in the report. The effect of structured compared with free-text reporting was evaluated. MATERIALS AND METHODS: Endoscopy reports in 445 cases of ulcerative colitis were retrieved. Two of the hospitals used a semi-structured computerized documentation system, and two hospitals used transcription-based free-text reports. RESULTS: A substantial amount of information was missing in the majority of the reports. Individual endoscopic signs of inflammation were defined in 27 % - 77 % of the reports. Various clinical symptoms of active ulcerative colitis were defined in 1 % - 44 % of the reports. We observed a reminder effect of structured systems in that they prompted more informative reports. There was a tendency towards better free-text documentation in the transcription-based systems than in the free text of the semi-structured ones. CONCLUSIONS: There is a potential for improving the content, completeness and standardization of endoscopy reports. Standardization efforts may be a part of the solution.
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.
Abstract: BACKGROUND: Most incidence studies of ulcerative colitis (UC) and Crohn disease (CD) have dealt with adults and there are have been few population-based prospective studies of the incidence of inflammatory bowel disease (IBD) in children. The aim of this study was to determine the incidence after re-evaluation of the diagnosis of UC and CD in childhood and adolescence in a prospective population-based survey. METHODS: From 1 January 1990 to 31 December 1993, all newly diagnosed patients with UC and CD under the age of 16 years were registered. On 1 January 1992 there were 174,482 children in the study population. The diagnosis was based on internationally accepted criteria and all clinical data were reviewed by two gastroenterologists independently of each other. All patients were subjected to a second evaluation 1 year after inclusion in the study. Patients initially diagnosed as indeterminate colitis (IND) were also reassessed. RESULTS: A total of 14 cases of UC, 13 cases of CD and 2 cases of IND were registered during the study period. At re-evaluation of the two patients diagnosed as IND, one was reclassified as having UC and one as having CD. This yielded a mean annual incidence of 2.14 (95% CI 1.20-3.54) per 100,000 for UC and 2.00 (95% CI 1.10-3.36) per 100,000 for CD. The male:female ratio in UC was 4.0 and 1.8 in CD. Median time interval from onset of symptoms to diagnosis was 4 months for UC and 5 months for CD. A high proportion of the children with UC (80%; 12/15) had extensive colitis. Four patients with CD had a first-degree relative with IBD. CONCLUSION: This study does not support an increased incidence of paediatric CD over the past decade. The incidence of paediatric UC seems to have remained stable over the past 30 years. In the CD group, we find a high incidence of IBD in first-degree relatives.
Abstract: BACKGROUND: Crohn's disease is a heterogeneous disorder for which NOD2 (CARD 15) has been identified as a susceptibility gene. We investigate the relation between NOD2 genotype and phenotypic characteristics of patients with Crohn's disease. METHODS: Hypotheses about the relation between NOD2 genotype and Crohn's disease phenotype were generated retrospectively from a group of 446 German patients with this disorder. Positive findings (p<0.10) were verified in prospectively established cohorts of 106 German and 55 Norwegian patients with Crohn's disease. All patients were genotyped for the main coding mutations in NOD2, denoted SNP8, SNP12, and SNP13, with Taqman technology. FINDINGS: In the retrospective cohort, six clinical characteristics showed noteworthy haplotype association: fistulising, ileal, left colonic and right colonic disease, stenosis, and resection. In the German prospective cohort, these haplotype associations could be replicated for ileal (p=0.006) and right colonic disease (p < or =0.001). A similar trend was noted in the Norwegian patients. INTERPRETATION: We recorded a distinct relation between NOD2 genotype and phenotype of Crohn's disease. Test strategies with NOD2 variations to predict the clinical course of Crohn's disease could lead to the development of new therapeutic paradigms.
Abstract: OBJECTIVE: To study the occurrence of spondyloarthropathies (SpA) in patients with inflammatory bowel disease (IBD) seen 6 years after IBD diagnosis. METHODS: In a population based cohort of 654 patients with IBD, 521 patients (80%) were investigated, which included a complete rheumatological examination. Radiographs of the sacroiliac joints and lumbar spine were performed in 406 of these patients (78%). The development of SpA was analyzed with regard to the presence of HLA-B27, duration of IBD symptoms, and the extent of intestinal inflammation. RESULTS: The occurrence of ankylosing spondylitis (AS) was 2.6% in ulcerative colitis and 6% in Crohn's disease (p = 0.08), yielding an overall prevalence of 3.7% in IBD. No correlation between localization or extent of the intestinal inflammation and presence of AS was found. HLA-B27 was present in 73% of cases with AS. The overall prevalence of SpA was 22%. Inflammatory back pain without AS (IBP) was found in 18% of the patients. Typical features of SpA were rare, while fibromyalgia was common in IBP, indicating that IBP is not a precursor or manifestation of SpA in patients with IBD. The prevalence of radiological sacroiliitis without clinical features of SpA was 2.0%. CONCLUSION: AS occurred frequently in patients with newly diagnosed IBD. IBP did not seem to predispose to AS or other forms of SpA. The overall prevalence of SpA was 22%, whereas the prevalence of asymptomatic radiological sacroiliitis was low.
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.
Abstract: BACKGROUND: The use of quality of life (QoL) questionnaires in clinical medicine must be based on instruments that are reliable and valid. The aim of this study was to describe the translation of the Inflammatory Bowel Disease Questionnaire (IBDQ) into Norwegian, its scaling assumptions and the psychometric properties of the translated questionnaire. METHOD: All patients included were recruited from an ongoing epidemiological study started in 1990 (the IBSEN trial), based on the registration of undiagnosed cases of Crohn disease (CD) or ulcerative colitis (UC) in subjects permanently residing in the study area the year before registration. At the 5-year follow-up visit in the hospital, all patients between 18 and 75 years of age were invited to participate in this QoL study, and those willing were interviewed and asked to complete the two QoL questionnaires, IBDQ and SF-36, on two different occasions separated by 6 months. The IBDQ was tested for validity, reliability and responsiveness. RESULTS: In total, 497 patients (93%) completed the IBDQ questionnaire at visit 1, and 493 (92%) completed SF-36. The mean age was 43.3 years, 48% were female. We found that the Norwegian version of the IBDQ (N-IBDQ) consists of five underlying dimensions in contrast to the four dimensions previously reported. Psychometric testing of the N-IBDQ indicates that the questionnaire is valid, reliable, has a high degree of responsiveness and that the results are comparable to those reported from other groups, even though our findings are based on a different factorial structure than the original McMaster version. CONCLUSION: The N-IBDQ consists of five different dimensions in contrast to the four dimensions previously reported. Good item internal consistency, validity, reliability and responsiveness were demonstrated.
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.
Abstract: BACKGROUND: There are few data on how patients on maintenance treatment of reflux oesophagitis take their medication. This study was designed to investigate the dosing patterns of patients on on-demand treatment and to compare lansoprazole with omeprazole in this regard. METHODS: Patients with reflux oesophagitis, initially treated until absence of symptoms, took capsules of either lansoprazole (30 mg) or omeprazole (20 mg) for 6 months; they were instructed to take the medication only when reflux symptoms occurred. In order to document dosing patterns, the medication was dispensed in bottles supplied with a Medication Event Monitoring System recording date and time the bottles were opened. There were regular follow-up visits with assessment of symptoms. RESULTS: Three-hundred patients were eligible for analysis according to 'all patients treated'. A dosing pattern was found of an increased intake mornings and evenings and constant intervals between intakes. Although there was no correlation between oesophagitis grade or initial symptoms and the amount of medication consumed, the patients had significantly fewer reflux symptoms the more medication they consumed. There was no difference in the number of capsules consumed between the lansoprazole (0.73 capsules/day) and omeprazole groups (0.71 capsules/day). Nor was there any difference between the groups in reflux symptoms during the course of the study. CONCLUSION: Despite rigorous instructions to take medication on demand, the results suggest that it is patient habits more so than symptoms that determine the frequency and interval of medication intake. Symptoms are not therefore decisive for the amount of medication consumed.
Abstract: OBJECTIVE: To study the prevalence of Sjögren's syndrome (SS), tear and saliva production and sicca symptoms in patients with inflammatory bowel disease (IBD) seen six years after IBD diagnosis. METHODS: In a population based cohort of 654 patients with IBD, 521 patients (80%) and a control group consisting of 68 healthy subjects were investigated. SS was diagnosed according to the European Criteria proposed by the American-European Consensus Group (US-EU criteria) and the European criteria. Maximum (supposing positive biopsies) and minimum prevalences (supposing negative biopsies) were estimated. RESULTS: Dryness of eyes and mouth were similarly distributed between patients with ulcerative colitis (UC) and Crohn's disease (CD) and between patients and controls. The prevalence of SS was 0-4.2% and 0-5.7% (minimum-maximum) according to the US-EU criteria and the European criteria, respectively. The controls fulfilled neither of the criteria. CONCLUSION: Sjögren's syndrome, sicca symptoms, tear and saliva production were not increased in patients with IBD compared to controls, indicating a lack of association between SS and IBD.
Abstract: BACKGROUND: Endoscopy is the cornerstone of the diagnosis and treatment of acute conditions in the upper part of the gastrointestinal tract. The need for 24-hour availability of gastroscopy for these conditions has not previously been assessed. MATERIAL AND METHODS: We assessed the need for emergency gastroscopy in cases of acute upper gastrointestinal bleeding and obstruction by foreign bodies. The assessment was made by a gastroenterologist before gastroscopy was performed, and was based on the available clinical data for the period lasting from admission to hospital to the time of examination. RESULTS: A total of 162 patients were referred and examined. About half of them arrived at the hospital outside working hours. Of these, 47% were assessed as being in need of emergency gastroscopy. We therefore found that emergency gastroscopy outside working hours was needed twice a month per 100,000 people. INTERPRETATION: Round-the-clock endoscopy should be available at acute-care hospitals in the same way as other emergency help.
Abstract: OBJECTIVES: As inflammatory bowel disease is a chronic disorder, usually with an early onset in life, quality of care plays an important role for patients. The aim of this study was to develop a questionnaire to measure quality of care through the eyes of patients with inflammatory bowel disease. METHODS: Ten generic questions were already available because the questionnaire is based on an existing instrument. Patients with inflammatory bowel disease in seven countries were involved in the development of additional disease-specific items. Validation and first field testing of the total questionnaire (QUOTE-IBD) was performed in The Netherlands. RESULTS: A total of 380 patients cooperated in the development of 13 disease-specific items, with high internal reliability (Cronbach's alpha = 0.83). Another 162 patients were involved in validating and testing of the QUOTE-IBD, which consists of 23 items in total. Pearson's correlation coefficient between QUOTE-IBD and visual analog scale scores of health care items was 0.55. Intraclass correlation coefficient of two assessments was 0.64. First testing showed that patients gave relatively poor marks to some part of health care services, such as providing information about extraintestinal complaints and the psychological as well as physical approach to complaints. CONCLUSIONS: A short, valid, reliable questionnaire was developed to measure the opinions of patients with inflammatory bowel disease on quality of health care. The QUOTE-IBD can be used for identification of areas for improvement, with the aim of optimizing health care in inflammatory bowel disease.
Abstract: BACKGROUND: Most patients with gastro-oesophageal reflux disease (GERD), regardless of endoscopic status, suffer symptomatic relapse within 6 months of stopping acid suppressant therapy. AIM: To assess the efficacy of 'on-demand' treatment of GERD with esomeprazole, the first proton pump inhibitor developed as an optical isomer. METHODS: In this multicentre, double-blind study, 342 endoscopy-negative GERD patients demonstrating complete resolution of heartburn during the final week of a 4-week treatment period with esomeprazole 20 mg or omeprazole 20 mg once daily were randomized to receive esomeprazole 20 mg or placebo on demand (maximum of one dose per day) for a further 6 months. Use of rescue antacids was permitted. RESULTS: All 342 patients (191 males), aged 19-79 (mean 49) years, were evaluable in the intention-to-treat analysis. The proportion of patients who discontinued treatment due to insufficient control of heartburn was significantly higher among placebo compared to esomeprazole recipients (51% vs. 14%; P < 0.0001). Patients randomized to esomeprazole on-demand therapy remained in the study longer than those in the placebo group (mean 165 vs. 119 days). Over 50% took the study medication for periods of 1--3 consecutive days (esomeprazole) or 4--13 consecutive days (placebo). Use of antacids was > 2-fold higher among placebo recipients. The frequency of adverse events was similar in the two groups, when adjusted for time spent in the study, as were the clinical laboratory profiles. CONCLUSIONS: On-demand therapy with esomeprazole 20 mg is effective and well tolerated in maintaining symptom control in endoscopy-negative GERD.
Abstract: OBJECTIVES: To estimate the occurrence of peripheral arthritis (PA) 6 yr after diagnosis of inflammatory bowel disease (IBD). METHODS: In a population-based cohort of 654 patients with a definite diagnosis of IBD, 521 patients (80%) were clinically examined by a rheumatologist 6 yr after IBD diagnosis. RESULTS: PA related to IBD (PAIBD) was detected at examination in four patients (point prevalence 0.8%). If the patients' own reports of PA were accepted, 12% of the cases had developed such manifestations. The striking difference may be explained by the nature of PAIBD exhibiting a short-lasting, self-limiting, non-destructive course and by possible differences in the validity of both methods of ascertainment. CONCLUSION: Our results indicate that PAIBD occurs in a considerable number of IBD patients during the first years after diagnosis, but the point prevalence of PAIBD is low.
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.
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.
Abstract: OBJECTIVE: To assess the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in a population based cohort of patients with inflammatory bowel disease (IBD). METHODS: Patients in a prospective survey on newly diagnosed IBD were, 5 years after study entry, invited to a clinical examination including the investigation of musculoskeletal manifestations. A total of 521 patients were examined, corresponding to 80% of surviving cases with definite diagnoses of ulcerative colitis (UC) and Crohn's disease (CD). The diagnoses of FM and CWP strictly followed the American College of Rheumatology classification criteria of 1990. RESULTS: At clinical examination, FM was diagnosed in 18 patients (3.5%), 3.7% with UC and 3.0% with CD. The prevalence was 6.4% in females and 0.4% in males. Thirty-eight patients (7.3%) had CWP (8.5% with UC; 4.8% with CD). The female:male ratio was 27:3 in the UC group and 8:0 in CD. In 19 patients (50%), CWP occurred after onset of IBD. No correlation with the extent of intestinal inflammation and the occurrence of FM and CWP was found. CONCLUSION: The prevalences of FM and CWP in patients with IBD were similar to those of the general population. There were no differences in prevalence of FM and CWP between UC and CD. Chronic idiopathic inflammation of the intestine does not appear to predispose to chronic widespread pain.
Abstract: BACKGROUND: By argon plasma coagulation (APC), a current is applied to tissues as ionised gas. Special probes have recently been developed for applying the gas through flexible endoscopes. In the field of therapeutic endoscopy, this method is promising for several diseases in the gastrointestinal tract. MATERIAL AND METHODS: At Ostfold Hospital in Fredrikstad, Norway, 122 treatments in 80 patients were performed during the years 1997-99. RESULTS: The new method was useful for endoscopic treatment of haemorrhages, tumour debulking and tumour ingrowth and overgrowth in oesophageal stents. Abdominal pain was related to insufflation of air and gas. Complications related to the method were not observed. INTERPRETATION: Our experience with this new method was very positive. The method was effective, had a very low complication rate, and the equipment was easy to use. The application of APC in premalignant conditions is discussed.
Abstract: Gastrooesophageal reflux disease has a variety of symptoms in children. 24-hour pH monitoring in the lower oesophagus is the gold standard for documenting gastrooesophageal reflux. We present our experience with 24-hour pH monitoring in children. 150 pH recordings in 120 children were performed. Clinical background and results from pH monitoring were recorded, in addition to supplementary examinations and treatment. No complications were recorded, but ten recordings (8.3%) were unsuccessful. Mean age was 3.5 years (median 13 months; range one month to 15 years). 44% had a pathological reflux index. Indications for pH monitoring were dominated by regurgitation/vomiting (63%), failure to thrive (45%) and respiratory symptoms (32%). Of the supplementary examinations performed, upper gastrointestinal contrast series provided no additional information (34 children), while endoscopy (20 children) showed oesophagitis in 11. Medical treatment was prescribed in 66% of the cases based on the pH monitoring results and clinical evaluation. Five patients were given anti-reflux surgery, and ten received gastrostomy. Our experience with this recording technique is good. pH monitoring should be available in paediatric departments, as a large number of the recordings had clinical consequences for the patient.
Abstract: It is difficult to predict the clinical course of inflammatory bowel disease (IBD). Moderately sick Crohn's disease (CD) patients and patients with distal ulcerative colitis (UC) may get better even without medical or surgical treatment. Once better, they may continue in remission even without treatment. If they are not treated, there are several factors that predict whether they will maintain remission. Most patients will probably alternate between remission and relapse, with 10% having a relapse-free course after 10 years, and only 1% having a continuously active course. Frequent relapses initially are associated with active disease later on, but the disease activity course is independent of the response to the initial medical treatment. There is a cumulative frequency of operation of 50-80% and of reoperation of 33% in CD, which suggests that CD has a more serious course than UC. In UC, the overall probability of surgery is 33% for pancolitis and 10% for proctitis within 5 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 UC has reduced relapse rates to about half over a 1-year follow-up period. The use of 5-ASA for maintenance of CD has been shown to result in only a modest therapeutic gain, while azathioprine and 6-mercaptopurine (6-MP) improve the relapse frequency for at least 3 years whilst on treatment. Changes in disease distribution in UC are part of the natural course of the disease, which should have implications for medical treatment strategies, and affects the risk of colectomy and colonic cancer. Certain enviromental factors are thought to determine disease activity and disease outcome in UC and CD. Patient compliance with prescribed medication and clinical check-ups must be considered another non-specific variable affecting the clinical outcome. IBD frequently requires potent medication with side effects that limit patients' acceptance. Such patients often resort to medicinal herbs, acupuncture, and homeopathy, which may alter the expected course.
Abstract: OBJECTIVE: Colonoscopy has replaced barium enema as the method for determining the extent of disease in patients with ulcerative colitis (UC). Normally, the extent of disease is determined by direct visualization of the mucosa, but biopsies are also used with increasing frequency. Very little is known about the extent to which these two ways of assessing the extent of disease are correlated and whether the correlation differs over time. The aim of this study was to determine the changes in extent of disease assessed by direct visualization and by histological examination of the mucosa at the time of diagnosis and after 1 yr of follow-up in a cohort of incident cases of UC patients. METHODS: All new cases of UC in a defined population were identified during a 4-yr period (496 patients). Of these, 384 patients (78%) were available for follow-up and were subjected to a second colonoscopy with representative biopsies taken from both normal and affected mucosa. RESULTS: After 1 yr there were macroscopical signs of progression in 14%; 22% showed regression, and 30% had a normal colonoscopy. The histological changes from diagnosis until follow-up showed progression in 20%, 24% showed regression, and 24% had normal histological findings. Histological examination showed more extensive disease than did direct visualization in 4% of patients at diagnosis and in 28% at follow-up, whereas direct visualization showed more extensive disease than did histological examination in 18% of patients at diagnosis and 12% at follow-up. The best correlation at both diagnosis and follow-up was seen in pancolitis (99% and 88%, respectively). CONCLUSIONS: With regard to the extent of colonic involvement in the UC patients, we found less agreement between endoscopic and histological evaluation at the follow-up examination than at the start of the study. This could indicate that biopsies represent a better indicator than endoscopical examination for long term prognosis. Further studies are needed to confirm this finding.
Abstract: OBJECTIVE: To evaluate the cure rate of Helicobacter pylori infection, including the impact of in vitro metronidazole resistance (M-R), and the side effects of a simplified 10-day bismuth triple therapy in routine clinical practice. METHODS: From September 1995 to March 1996, 248 consecutive H. pylori-positive patients received 10 days of bismuth subnitrate 150 mg, oxytetracycline 500 mg, and metronidazole 400 mg, all t.id. Before treatment, upper endoscopy, including biopsy specimens for microbiological analysis and IgG serology were performed. M-R was found in 45% of females and 36% of males. At least 2 months after treatment, H. pylori status was assessed by the 14C urea breath test (n = 131), endoscopy (n = 37), urea breath test and endoscopy (n = 63), or solely by IgG serology (n = 7). Ten patients withdrew. IgG serology was performed again after 1 yr. RESULTS: H. pylori infection was cured in 205 patients: 86% by all-patients-treated analysis and 83% by intention-to-treat analysis. When patients were classified according to pretreatment metronidazole susceptibility, cure of infection was achieved in 76% of females harboring M-R strains versus 96% of those with sensitive strains (p = 0.002) and in 81% versus 88% (p = 0.34) of males with M-R versus sensitive strains, respectively. Twelve patients (5 %) had to stop treatment prematurely because of severe side effects, but eight of them were treated successfully. One case of H. pylori infection (0.6 %) was detected at 1-yr follow-up. CONCLUSIONS: Ten-day bismuth triple therapy t.i.d. was effective in curing H. pylori infection in the context of routine clinical practice. The efficacy was reduced in females harboring M-R strains.
Abstract: BACKGROUND: In this study we assessed the accuracy of IgG serology and other tests in confirming Helicobacter pylori eradication. METHODS: The outcome of anti-H. pylori therapy was established by at least two of the following tests: rapid urease test (RUT), culture, 14C urea breath test (non-capsule or capsule UBT), and IgG serology (Orion Diagnostica Pyloriset New EIA-G). RESULTS: Successful H. pylori eradication was confirmed in 698 of 794 patients (88%). The percentage decrease in IgG antibody titre was related to the patients' pre-treatment IgG titre and time interval after treatment. A decrease in IgG titres of 40% or more confirmed H. pylori eradication with 100% specificity, whereas the sensitivity was 82%, 90%, 98%, and 98% 3, 4, 5, and 6 months after therapy, respectively. The 40% cut-off confirmed eradication 3 to 6 months after therapy in 328 of 339 patients (97%) with pre-treatment IgG titres of >700, in 36 of 45 patients (80%) with pre-treatment titres of 300-700, and in 5 of 12 patients (42%) with pretreatment titres of <300. The sensitivity and specificity of the other tests 2 months after treatment were as follows: RUT, 84% and 100%; culture, 88% and 100%; non-capsule UBT, 100% and 89%; and capsule UBT, 100% and 97%. CONCLUSION: A decrease in IgG antibody titre of 40% or more 3 to 6 months after therapy and the capsule 14C UBT at the 2-month follow-up were both highly accurate in confirming H. pylori eradication.
Abstract: BACKGROUND: In this study we compared the accuracy of seven diagnostic tests in diagnosing Helicobacter pylori infection. METHODS: Over 1 year 351 consecutive dyspeptic patients were tested for H. pylori infection by means of antral biopsy specimens for the rapid urease test (RUT), culture, microscopy (acridine stain), and the laboratory urease test (LUT) and, in addition, with 14C urea breath test (UBT), IgG serology, and IgA serology (Orion Diagnostica Pyloriset New EIA-G and New EIA-A). The criterion for H. pylori infection was a minimum of three positive tests. Before being tested, 38% of the patients had used an H2-receptor antagonist (H2RA). RESULTS: Two-hundred and twenty-four patients (64%) were H. pylori-positive. The sensitivity and specificity of the tests were as follows (percentages): RUT, 85, 99; culture, 93, 100; microscopy, 81, 98; LUT, 80, 100; UBT, 95, 95; IgG serology, 99, 91; and IgA serology, 88, 91. The accuracy of the RUT and LUT was reduced in patients receiving H2RA therapy (P=0.04 and 0.01, respectively). CONCLUSIONS: Culture, UBT, and IgG serology were all superior to the other four tests in diagnosing H. pylori infection. Invasive urease-based tests were less accurate in patients receiving H2RAs.
Abstract: OBJECTIVES: To compare cure rates of Helicobacter pylori (H. pylori) infection, ulcer healing, and side effects of three simplified regimens of triple therapy in patients with peptic ulcer disease. METHODS: Two hundred thirty-one patients were prospectively randomized to receive either regimen OAM (omeprazole 20 mg b.i.d., amoxicillin 750 mg b.i.d., and metronidazole 400 g b.i.d.), OCM (omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), or BCM (bismuth subcitrate 240 mg b.i.d., clarithromycin 250 mg b.i.d., and metronidazole 400 mg b.i.d.), all for 10 days. Side effects were reported immediately afterward in a self-administered questionnaire. Upper endoscopy was carried out before treatment and 2 months after treatment. Three antral and three corpus biopsy specimens were analyzed microbiologically and with rapid urease test to determine the presence of H. pylori. Altogether 143 patients (62%) had an active ulcer at start of treatment. Metronidazole resistant (M-R) H. pylori strains were found in 30% of patients, while none had clarithromycin resistant (C-R) strains. RESULTS: According to intention-to-treat analysis, H. pylori cure rates were 91, 95, and 95% with OAM, OCM, and BCM, respectively (p = 0.63). In patients with metronidazole-sensitive (M-S) strains versus M-R strains, the cure rates were 96 versus 77% with OAM (p = 0.025), 94 versus 94% with OCM, and 94 versus 96% with BCM. Ulcer healing rates were 95, 94, and 92%, respectively (p = 0.91). There were no significant differences in side effects between the regimens, and only five patients (2%) had to stop the treatment prematurely. CONCLUSIONS: All treatment regimens were highly effective for cure of H. pylori infection and for ulcer healing. Metronidazole resistance reduced the efficacy of OAM, but was of no importance for the efficacy of OCM or BCM. Side effects were of minor importance.
Abstract: A 77 year-old man developed intermittent diarrhoea and malabsorption. Endoscopic findings and preliminary histological examination indicated ulcerative colitis. Special staining of biopsies from the duodenum and colon revealed amyloid deposits. Classification of the amyloid fibril protein verified AL-amyloidosis, and the diagnosis primary idiopathic amyloidosis was made. Amyloid deposit in the gastrointestinal tract are a common feature of primary and secondary amyloidosis. The symptoms and findings are nonspecific and resemble those of chronic inflammatory bowel disease and ischemic colitis. Secondary amyloidosis can be seen as a rare complication of Crohn's disease and ulcerative colitis. Special staining is necessary to show amyloid deposit, and the distinction between primary and secondary amyloidosis requires immunohistochemistry.
Abstract: BACKGROUND: In this study we compared the cure rates of two clarithromycin-based regimens in patients in whom anti-Helicobacter pylori therapy had previously failed. METHODS: Thirty-three patients were randomized to receive either regimen OAC (20 mg omeprazole, 750 mg amoxicillin, and 250 mg clarithromycin) or BTC (240 mg bismuth subcitrate, 750 mg oxytetracycline, and 250 mg clarithromycin), all twice daily for 10 days. A further 28 patients were all treated with OAC. Previously failed therapy included combinations of bismuth (B), omeprazole (O), tetracycline (T), metronidazole (M), amoxicillin (A), or clarithromycin (C) in BTM (n = 48), OAM (n = 13), OA (n = 7), OCM (n = 2), or BCM (n = 1). H. pylori infection was confirmed by culture of biopsy specimens, and antimicrobial susceptibility testing was performed with the E test. RESULTS: H. pylori infection was cured in all patients (n = 18) with OAC and in 8 patients (53%) with BTC (P = 0.001) in the randomized group and in 27 patients (96%) receiving OAC in the open-label group. CONCLUSIONS: Ten-day OAC is highly effective and superior to BTC in patients in whom metronidazole-based treatment has previously failed.
Abstract: BACKGROUND: The clinical course and prognosis in ulcerative colitis (UC) and Crohn's disease (CD) have been described in many studies, mostly retrospective. Such studies are hampered by problems such as inclusion over a long time period, proper definitions, incomplete case records, and outdated methods of diagnosis. In a prospective study we identified 846 patients with inflammatory bowel disease (IBD) over a 4-year period from 1990 to 1993. Uniform diagnostic and therapeutic strategies were used as a basis for later assessment of the short-term clinical course in different subgroups of UC and CD and analysis of potential risk factors for relapse or surgery. METHODS: At the time of follow-up, a mean of 16.2 months after diagnosis, 496 UC patients and 232 CD patients, altogether 98%, were available for evaluation. A colonoscopy was performed in 88% (410 of 465) of the UC patients attending a clinical examination and in 76% (164 of 216) of the CD patients. RESULTS: Eleven patients with UC and five patients with CD died during follow-up, four of complications related to IBD. The cumulative 1-year relapse rate in the remaining patients was 50% for UC and 47% for CD. Of the patients with relapses 11 % of the UC patients and 10% of the CD patients had a chronic relapsing course without any difference with regard to the various disease categories in UC or CD. An increased risk of relapse was found in patients less than 50 years old only in UC. In UC a higher risk for surgery was found in patients with extensive colitis compared with left-sided colitis (P = 0.011), and CD patients with small-bowel involvement had a higher risk of surgery than patients with disease confined to the colon (P = 0.021). There was no excess risk of relapse or surgery in smokers as compared with non-smokers or former smokers, nor did the risk of relapse vary with the level of cigarette consumption in either UC or CD patients. CONCLUSION: The high relapse rate of around 50% for both UC and CD calls for a review of the existing treatment. Further follow-up will be necessary to improve our ability to make clinical decisions relating to medical and surgical treatment options.
Abstract: OBJECTIVES: To compare the efficacy and side effects of standard bismuth triple therapy with those of omeprazole-based triple therapy in patients with Helicobacter pylori infection and duodenal ulcer disease. METHODS: One hundred patients were prospectively recruited and randomized to receive either bismuth subnitrate 75 mg q.i.d., oxytetracycline 500 mg q.i.d., and metronidazole 400 mg b.i.d. (regimen BTM), or omeprazole 20 mg b.i.d., amoxicillin 750 mg b.i.d., and metronidazole 400 mg b.i.d. (regimen OAM), both for 14 days. Upper endoscopy (with antral biopsy specimens for microbiology and antral and corpus biopsy specimens for histology) was performed before treatment, after 2 months, and again 1 yr after treatment. Serum samples for serology (IgG) were taken. Patients with in vitro metronidazole-resistant (M-R) H. pylori strains were excluded. In a nonrandomized study, 41 patients with M-R strains were given either BTM or OAM. RESULTS: According to intention-to-treat analysis, H. pylori cure rates were 91% and 96% with BTM and OAM, respectively (p = 0.45). In the BTM group, the mean total side effect score was higher (p < 0.001), and more severe side effects were reported (32% vs. 4%, p < 0.001). In the nonrandomized group of patients with M-R strains, H. pylori cure rates were 88% and 67% with BTM and OAM, respectively. All of the successfully treated patients were still H. pylori-negative after 1 yr. CONCLUSIONS: Both treatment regimens were highly effective in curing H. pylori infection in patients with metronidazole-sensitive strains. Omeprazole-based triple therapy was tolerated better than standard bismuth-based triple therapy.
Abstract: BACKGROUND: The incidence figures for ulcerative colitis (UC) and Crohn's disease (CD) have been difficult to interpret, and geographical variations may be due to differences in classification criteria and study design. Few studies have based the incidence on prospective systematic follow up to confirm the initial diagnosis. METHODS: Between 1990 and 1993, in a prospective incidence study of inflammatory bowel disease (IBD) in south eastern Norway, 527 cases of UC, 228 cases of CD, 36 cases of indeterminate colitis (IND), and 55 cases of possible IBD were identified, yielding an annual incidence of 13.6, 5.9, 0.9, and 1.4 per 10(5) respectively. The diagnosis and all clinical data were reviewed by two gastroenterologists independently of each other. One to two years after diagnosis, all patients were offered a clinical follow up in which the initial diagnosis was assessed. RESULTS: Between the time of diagnosis and the follow up, 16 patients had died, four of complications related to IBD. Of the remaining 830 patients, 98% (814/830) were available for follow up, 93% (772/830) attended a clinical examination which included a colonoscopy in 77% (637/830), and the remainder had had a telephone interview, or reassessment based on hospital records, or both. Twenty seven patients were reclassified as not having IBD (3%), and 65 patients were characterised as possible IBD (8%). Of the patients initially classified as UC, 88% had their diagnosis confirmed, compared with 91% with an initial diagnosis of CD. In patients with indeterminate colitis, 33% were classified as definite UC and 17% as CD. This reclassification of patients yielded a corrected annual incidence of 12.8 for UC and 6.0 for CD. CONCLUSION: At follow up one to two years after the diagnosis of IBD, the initial incidence was only marginally altered. This is probably due to uniform inclusion criteria and careful diagnostic methods. The study also illustrates the importance of the re-evaluation of the initial diagnosis as close to 10%, both among patients with UC and CD, were reclassified at follow up.
Abstract: BACKGROUND: Standardized criteria for Crohn's disease (CD) have only recently been developed, and prospective community-based incidence studies have been performed only during the past 3 decades. Geographic variations in incidence may therefore be due to differences in study design. METHODS: From 1 January 1990 to 31 December 1993 all new cases of CD in four counties in southeastern Norway were prospectively registered. RESULTS: A total of 225 new cases yielded an annual incidence of 5.8/10(5), with the highest incidence in mixed rural-urban areas. A peak of 11.2/10(5) in the annual incidence was found for the age group 15 to 24 years, with no significant differences in the overall annual incidence by gender. An average duration of 6 months of disease before diagnosis was unchanged during the 4 years. About half of the patients had isolated colonic disease, and one-quarter had isolated small-bowel disease. CONCLUSIONS: This study confirms the high incidence figures for Scandinavia, with a particularly high incidence in mixed rural-urban areas. Ileocolonoscopy improves the accuracy of the diagnosis and of the determination of disease extent, which may have therapeutic implications for the treatment and follow-up of patients.
Abstract: BACKGROUND: The incidence of ulcerative colitis (UC) has been difficult to interpret because prospective studies have only been performed during the past 3 decades. Geographic variations may therefore be due to differences in study design. METHOD: From 1 January 1990 to 31 December 1993 all new cases of UC in four counties in southeastern Norway were prospectively registered. Cases diagnosed as indeterminate colitis (IND) when endoscopy and histopathology were inconclusive or diverged with regard to diagnosis of UC or Crohn's disease (CD) were also included in the study. RESULTS: A total of 525 cases of UC and 93 cases of IND yielded an mean annual incidence of 13.6/10(5) and 2.4/10(5), respectively. There were differences in incidence between counties, and a peak of 21.5/10(5) in the annual incidence was found for the age group 25 to 34 years in UC. The distribution was about equal for each of the groups proctitis and left-sided and extensive colitis. The time interval from onset of symptoms to diagnosis was 4 months. CONCLUSION: In this study one of the highest incidences of UC in the world has been found. The classification 'indeterminate colitis' seems reasonable to use in some of the cases to prevent misclassification at the initial stage of diagnosis.
Abstract: Several retrospective studies have reported seasonal variations in the relapse of ulcerative colitis, and two studies have found seasonality in the onset of ulcerative colitis, with a peak from August to January. This study was designed to investigate possible seasonal variations of onset of ulcerative colitis (UC) and Crohn's disease (CD). Patients with symptoms of one year or less were recruited from a prospective study of the incidence of inflammatory bowel disease, and the onset of symptoms was recorded month by month for four consecutive years. A total of 420 patients with UC and 142 patients with CD were included. There was monthly seasonality (p = 0.028) in symptomatic onset in December and January for UC but not for CD. It was found that environmental agents with known seasonality can be of importance for the seasonal variations of disease onset in UC.
Abstract: To assess the feasibility of a prospective incidence study of inflammatory bowel disease (IBD), the registration methods and incidence figures during 1990 were evaluated. The study was a collaboration between 14 hospitals in an area of close to one million inhabitants. Common diagnostic criteria for ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IND) were established prior to the start of the study. There was an overall incidence rate for IBD of 19.3 per 10(5) inhabitants, with 10.6 for UC, 5.1 for CD and 3.6 for IND. The age-specific incidence rates showed a peak between 25 and 34 years for UC and between 15 and 25 for CD. There was a male predominance for UC and a female preponderance for CD. These results are comparable with the previous registrations in western and northern areas of Norway.
Abstract: Side effects of herbal and health food products have been infrequently reported such as hepatic damage after use of such products. Four such patients were treated in our department in the course of two years. In all four patients, the use of herbal remedies was the probable cause of serious hepatic damage, but both etiology and pathogenesis were difficult to establish. Two major areas of concern are inaccurate formulation and contaminated preparations. As long as no therapeutic effect can be demonstrated from this type of medicine, serious side effects are unacceptable. A critical attitude should be adopted towards these medicines and the use of them.
Abstract: Cytomegalovirus disease is seen mainly in immunocompromised patients. While gastrointestinal symptoms are difficult to interpret, the typical finding at endoscopy of the upper alimentary tract is ulcers. Diagnosis of cytomegalovirus disease is based on typical histological findings in biopsy specimens. Antiviral treatment should be started when cytomegalovirus disease is detected in transplant patients. If it is decided to treat patients suffering from AIDS, lifelong maintenance treatment is required. Early diagnosis by means of endoscopy and biopsies is very important, and will decide the outcome of instituted treatment.
Abstract: Cytomegalovirus infections in immunocompromised patients may cause serious illness, particularly in patients with HIV-disease and in transplant recipients. There is an increasing number of reports of cytomegalovirus infections involving the alimentary tract, especially colitis. Diagnosis of cytomegalovirus disease is at present based on specific histological findings. Antibody findings can be difficult to interpret. The slow growth of cytomegalovirus in cultures makes this method less useful in the acute setting of diagnosis. It is important to recognize cytomegalovirus colitis as a differential diagnosis to idiopathic inflammatory bowel disease. In fulminant disease, colectomy should be considered in addition to antiviral treatment.
Abstract: Cytomegalovirus (CMV) colitis is uncommon in patients who are not gravely immunodepressed. We report a case of fatal CMV colitis in a 54-year-old woman on low dose steroid therapy. She was admitted to hospital after sudden onset of abdominal pain and hemorrhagic watery diarrhea. After 25 days in the hospital, treatment with high dosage of methylprednisolone was started for presumed ulcerative colitis. Her condition worsened and she died 52 days after admission. It is important to recognize CMV colitis as differential diagnosis to inflammatory bowel disease, particularly when the colitis is refractory to immunosuppressive treatment.
Abstract: During a seven-year period, symptomatic cytomegalovirus (CMV)-infection was diagnosed in 21.5% (n = 10) of all AIDS patients at the National Hospital of Norway (retinitis n = 8, colitis n = 3, pneumonitis n = 2, gastritis n = 1). Symptomatic cytomegalovirus-infection was associated with a poor long-term prognosis (median survival 174 days, range 10-415). Median CD4+ lymphocyte counts at onset of symptomatic cytomegalovirus-infection was 24 x 10(6)/l (range 6-68). Regular ophthalmological examination of HIV-infected patients with severe immunodeficiency, and endoscopy with multiple mucosal biopsies in patients with suspected cytomegalovirus-infection of the gastrointestinal tract, were of major importance in diagnosing symptomatic cytomegalovirus-infection. Six patients received an induction course of ganciclovir, and foscarnet was administered in two patients due to leukopenia. Problems of toxicity to the available anti-CMV agents make the development of additional therapeutic approaches desirable.
