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  • 101.
    Sjöberg, Mats
    et al.
    Skaraborgs hospital, Lidköping.
    Walch, Andrea
    Medical University of Vienna.
    Meshkat, Mina
    Medical University of Vienna.
    Gustavsson, Anders
    Örebro University Hospital.
    Järnerot, Gunnar
    Örebro University Hospital.
    Vogelsang, Harald
    Medical University of Vienna.
    Hertervig, Erik
    Skåne University Hospital, Lund University.
    Novacek, Gottfried
    Medical University of Vienna.
    Friis-Liby, Ingalill
    Sahlgrenska University Hospital, Gothenburg.
    Blomquist, Lars
    Karolinska University Hospital, Solna.
    Angelberger, Sieglinde
    Medical University of Vienna.
    Karlen, Per
    Södersjukhuset, Stockholm.
    Grännö, Christer
    Ryhov Hospital, Jönköping.
    Vilien, Mogens
    Hilleroed Hospital, Denmark.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Verbaan, Hans
    Skåne University Hospital, Malmö.
    Hellström, Per M
    Karolinska University Hospital, Solna.
    Dejaco, Clemens
    Medical University of Vienna.
    Magnuson, Anders
    Örebro University Hospital.
    Halfvarson, Jonas
    Örebro University Hospital.
    Reinisch, Walter
    Medical University of Vienna.
    Tysk, Curt
    Örebro University Hospital.
    Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis: A retrospective observational study2012In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 18, no 2, p. 212-218Article in journal (Refereed)
    Abstract [en]

    Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. less thanbrgreater than less thanbrgreater thanMethods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. less thanbrgreater than less thanbrgreater thanResults: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. less thanbrgreater than less thanbrgreater thanConclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months follow-up. The superiority of CsA was seen principally during the first 15 days.

  • 102.
    Sjöwall, Christoffer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Bokarewa, Maria I
    University of Gothenburg.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Lindvall, Liselott
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation2012In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, no 4, p. 382-388Article in journal (Refereed)
    Abstract [en]

    The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.

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  • 103.
    Sjöwall, Christopher
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Autoantibodies to C-reactive protein is a common finding in SLE, but not in primary Sjögren’s syndrome, rheumatoid arthritis or inflammatory bowel disease2002In: Journal of Autoimmunity, ISSN 0896-8411, Vol. 19, no 3, p. 155-160Article in journal (Refereed)
    Abstract [en]

    The occurrence of antibodies to human C-reactive protein (CRP) was analysed by enzyme-linked immunosorbent assay (ELISA) in 56 patient sera known to contain antibodies to double-stranded DNA (dsDNA) and in 16 sera from patients with primary Sjögren's syndrome (SS), 15 rheumatoid arthritis, 31 Crohn's disease, and 37 ulcerative colitis. Eighty-seven per cent of the patients with anti-dsDNA antibodies had systemic lupus erythematosus (SLE) and the remaining had autoimmune hepatitis. The cut-off for positive anti-CRP test was set at the 95th percentile of 100 healthy blood donors. Twenty of 56 anti-dsDNA sera (36%) and two of 16 SS sera (13%) had antibodies reactive with human CRP, whereas all other samples were negative. Thirteen of 27 SLE patients (48%) were positive on at least one occasion. The sera containing anti-CRP antibodies only reacted with surface-bound antigen, but not with native CRP in solution. In conclusion, we found that autoantibodies to CRP are common in sera from patients with anti-dsDNA antibodies. It is not likely that this explains the relative failure of CRP response in patients with active SLE. However, it cannot be excluded that anti-CRP autoantibodies have other biological potentials of pathophysiological interest in SLE, for instance by binding to CRP deposited on cell and tissue surfaces.

  • 104.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almér, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Low expression of TPMT wild type alleles in a patient with absent TPMT activity2008Conference paper (Other academic)
  • 105.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almér, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Low Expression of TPMT wild type alleles in a patient with absent TPMT activity2008Conference paper (Other academic)
  • 106.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindqvist Appell, Malin
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Karlgren, Anna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Kidhall, Irene
    Div of Gastroenterology and Hepatology, Danderyd Hospital.
    Almér, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Explaining TPMT Genotype/Phenotype Discrepancy by Identification of a Novel Sequence Variant, TPMT*232007Conference paper (Other academic)
  • 107. Skovbjerg, H
    et al.
    Hansen, GH
    Niels-Christiansen, LL
    Anthonsen, D
    Ascher, H
    Midhagen, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology .
    Hallert, C
    Noren, O
    Sjostrom, H
    Intestinal tissue transglutaminase in coeliac disease of children and adults: Ultrastructural localization and variation in expression2004In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, no 12, p. 1219-1227Article in journal (Refereed)
    Abstract [en]

    Background: Tissue transglutaminase is the main antigen for the anti-endomysial antibodies used for diagnosis of coeliac disease and can with some specificity in vitro deamidate gliadins generating potent epitopes. The intestinal levels and the ultrastructural localization of tissue transglutaminase in normal and affected persons were investigated to provide further information on its role in this disease. Intestinal biopsies were taken from normal and coeliac children and adults. Methods: The level of transglutaminase was analysed by means of a quantitative enzymatic assay and its ultrastructural localization by immunogold electronmicroscopy using a monoclonal antibody against tissue transglutaminase. Results: In relation to normal individuals, the enzymatic activity of tissue transglutaminase in adult coeliac patients was increased. The enzyme was found in the enterocytes and in increased amount just beneath the enterocytes, where cytosolic and nuclear labelling of distinct elongated cells was seen in addition to extracellular labelling close to collagen fibrils. In children, the enzymatic activity and the immunogold labelling could not be shown to be related to disease. In all cases the enzyme activity was EDTA-sensitive. Conclusions: The increased amount of tissue transglutaminase activity in coeliac adults was shown to be due to the appearance of the enzyme in enterocytes and increased expression in the lamina propria. No evidence was found to support the idea of a changed localization or changed amounts as primary elements in coeliac disease pathogenesis, nor for the involvement of non-calcium dependent microbial transglutaminases.

  • 108. Order onlineBuy this publication >>
    Stjernman, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Crohn’s Disease in Sickness and in Health: Studies of Health Assessment Strategies and Impact on Health-Related Quality of Life2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims. Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) with potentially deleterious effects on well-being and daily-life functioning. A complete picture of health status in CD therefore comprises both disease activity (DA) and health-related quality of life (HRQL). Several measures of DA and HRQL in CD have been developed. Some have gained prominence as standard endpoints in clinical trials, but none has been validated in Swedish CD patients and their use in clinical practice has been limited. A conceptual health status model of five dimensions (Biological variables, Symptoms, Function, Worries, and Well-being) has been proposed for IBD health assessment, enabling the construction of the Short Health Scale (SHS), a four-item questionnaire intended to facilitate assessment and interpretation of HRQL in IBD.

    The aims of this thesis were: (1) to evaluate the Swedish versions of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Rating Form of IBD Patient Concerns (RFIPC); (2) to evaluate the Short Health Scale; (3) to study the relationship between DA and HRQL variables by identifying determinants of DA outcome and by validating the SHS health status model; (4) to describe the spectrum of disease-related worries and repercussions on general HRQL in a context of social variables, sickness, and disability.

    Methods. The thesis is based on clinical variables and HRQL data measured in a population-based cohort of 505 CD patients, consecutively included in conjunction with their regular outpatient visits at three hospitals (Jönköping, Örebro, Linköping). The HRQL questionnaires were evaluated regarding construct validity, reliability, and responsiveness. Multivariate analyses were used to investigate the relationship between Crohn’s Disease Activity Index (CDAI) and physician-assessed DA. The SHS health status model was validated with structural equation modelling (SEM). Disease-related worries and concerns, general HRQL, social variables, sickness, and work disability were compared with data from background population or patients with ulcerative colitis (UC).

    Results. The IBDQ had good validity, reliability, and responsiveness, but the original dimensional structure was not supported. The RFIPC was valid, and reliable, but less sensitive to change in disease activity. The SHS had the highest completion rate and proved adequate psychometric properties. The CDAI correlated weakly with the physician’s appraisal of disease activity, being more influenced by subjective health perception than objective disease activity. SEM showed that the SHS model had a good fit to measured data, explaining >98% of the covariance of the variables. Worries and general HRQL impairment were greater in CD than in UC, especially for women. Disease complications and impaired life achievements elicited most worries. CD patients had lower educational level. Female patients were more often living single. The rates of long-term sickness and disability were doubled compared with background population, with worse outcome for women.

    Conclusions. The IBDQ, the RFIPC, and the SHS all demonstrated adequate psychometric properties. The SHS was easier to administer and provided a more comprehensive picture of subjective health status. The weak correlation between CDAI and physician-assessed DA was explained by a strong influence of subjective variables on CDAI, stressing the importance of assessing DA and HRQL separately. The SHS health status model was further supported by SEM. CD has tangible effects on subjective health perception, worries and work capacity, especially for women.

    List of papers
    1. Evaluation of the Inflammatory Bowel Disease Questionnaire in Swedish patients with Crohn's disease
    Open this publication in new window or tab >>Evaluation of the Inflammatory Bowel Disease Questionnaire in Swedish patients with Crohn's disease
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    2006 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 8, p. 934-943Article in journal (Refereed) Published
    Abstract [en]

    Objective. Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). Material and methods. Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns, Short Form-36, and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. Results. The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. Conclusions. Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items. © 2006 Taylor & Francis.

    Keywords
    Health, Health-related quality of life, Inflammatory bowel disease, Quality of life
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-50177 (URN)10.1080/00365520500529488 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
    2. Worries and concerns in a large unselected cohort of patients with Crohns disease
    Open this publication in new window or tab >>Worries and concerns in a large unselected cohort of patients with Crohns disease
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    2010 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 6, p. 696-706Article in journal (Refereed) Published
    Abstract [en]

    Objective. Disease-related worries constitute an important dimension of patient-reported perception of health status in inflammatory bowel disease (IBD). The Rating Form of IBD Patient Concerns (RFIPC) questionnaire is purported to measure IBD-related worries. This study evaluated the psychometric properties of a Swedish translation of RFIPC in an unselected population of Crohns disease (CD) patients. The degree and nature of the worries were characterized and predictive factors for outcome of RFIPC and underlying dimensions were identified. Material and Methods. The RFIPC was completed by 447 CD patients in conjunction with regular visits. A physician global assessment of disease activity and four other health-related quality of life (HRQL) questionnaires were used for construct validity. Reliability and responsiveness were evaluated with follow-up visits. Underlying dimension and predictive factors were identified with factor analysis and multiple linear regression analysis. Results. Test-retest reliability was 0.90, correlation with corresponding HRQL measures 0.60-0.80 and responsiveness ratio 0.84. Median RFIPC sum score was lower than in previous studies. Top three concerns were ostomy, energy level and bowel control. Four dimensions were identified in descending order of concern: disease-related complications, daily-life achievements, intimacy, and stigmatization. Predictors of RFIPC score were disease activity, gender, and BMI (p andlt; 0.001-0.008). Conclusions. The Swedish version of RFIPC exhibited an adequate psychometric performance in CD patients, but was less sensitive to change in disease activity. The patients were more concerned about complications and achievement than intimacy and stigmatization. The strongest predictors of more worry were active disease, female gender and higher BMI.

    Place, publisher, year, edition, pages
    Taylor and Francis, 2010
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-56518 (URN)10.3109/00365521003734141 (DOI)000277365200008 ()
    Available from: 2010-05-21 Created: 2010-05-21 Last updated: 2017-12-12Bibliographically approved
    3. Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease
    Open this publication in new window or tab >>Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease
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    2008 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 1, p. 47-52Article in journal (Refereed) Published
    Abstract [en]

    Background: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). Methods: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. Results: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (rS = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (rS = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). Conclusions: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

    Keywords
    Bowel disease, Health, Health-related quality of life, Inflammatory, Quality of life
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-47877 (URN)10.1002/ibd.20255 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    4. Factors Predicting the Outcome of Disease Activity Assessment in Crohns Disease
    Open this publication in new window or tab >>Factors Predicting the Outcome of Disease Activity Assessment in Crohns Disease
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    2009 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1859-1866Article in journal (Refereed) Published
    Abstract [en]

    Background: The Crohns Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome. Methods: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified. Results: The correlation between CDAI and PGA was moderate. In patients with CDAI greater than 150, 72% of the total score were derived froth the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula. Conclusions: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.

    Keywords
    inflammatory bowel disease; Crohns disease; outcome assessment; disease activity
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-52906 (URN)10.1002/ibd.20975 (DOI)
    Available from: 2010-01-13 Created: 2010-01-12 Last updated: 2017-12-12Bibliographically approved
    5. Structural Equation Modeling of the Relationship between Disease Activity and Health-related Quality of Life Variables in Crohn’s Disease
    Open this publication in new window or tab >>Structural Equation Modeling of the Relationship between Disease Activity and Health-related Quality of Life Variables in Crohn’s Disease
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objective. Disease activity (DA) and health-related quality of life (HRQL) are two major endpoints in outcome assessment of Crohn’s disease (CD).  A health concept model of the relationship between DA and HRQL encompassing five dimensions (biological variables, symptoms, function, worries, and general well-being) in inflammatory bowel disease (IBD) has been postulated previously, forming the basis of the IBD HRQL instrument, the Short Health Scale (SHS). This study evaluates the model, using structural equation modeling technique (SEM) on DA and HRQL data from a cohort of CD patients.

    Methods. The relationships of the five dimensions represented by 14 health measures of 283 CD patients were analyzed by confirmatory factor analysis and SEM, using SPSS AMOS v18.0.

    Results. All parameter estimates proved significant, and the goodness-of-fit indices were good (χ2=104.2, df=69, p=0.004, CFI=0.986, RMSEA=0.043). A revision of the structural pathway, in which well-being precedes worries, was suggested from empirical data.

    Conclusion. The postulated health concept model proved to be a valid and plausible approximation of the relationship between disease activity and subjective health perception in CD. The results support the use of the SHS for subjective health assessment in CD.

    Keywords
    Crohn’s disease; inflammatory bowel disease; health-related quality of life; disease activity; structural equation modeling
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66242 (URN)
    Available from: 2011-03-09 Created: 2011-03-09 Last updated: 2011-03-09Bibliographically approved
    6. Unfavourable outcome for women in a study of health-related quality of life, social factors, and work disability in Crohn’s disease
    Open this publication in new window or tab >>Unfavourable outcome for women in a study of health-related quality of life, social factors, and work disability in Crohn’s disease
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    2011 (English)In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 23, no 8, p. 671-679Article in journal (Refereed) Published
    Abstract [en]

    Objective. The aim was to describe health-related quality of life (HRQL) and social factors, sickness and disability variables in a large population-based cohort of patients with Crohn’s disease (CD).

    Methods. HRQL was measured with SF-36 in 497 adult CD patients at three outpatient clinics. Comparisons were made with age-gender-matched background population and with ulcerative colitis (UC). Social factors, employment, sickness compensation, and disability pension for CD, were compared with national population registers.

    Results. CD had a greater negative effect on HRQL than did UC. This difference was more pronounced for women. Compared with background population, CD patients had lower educational level, and had a two-fold rise in long-term sickness and disability pension rate. CD women had higher rates of sickness and disability than CD men and were more often living single, though procreation was not affected.

    Conclusion. This study characterized the burden of CD in a large population-based cohort. CD had higher impact on HRQL, compared with UC. CD women had worse outcome in subjective health status, but not in objective assessment of disease activity. Women also had higher rates of sickness, disability pension, and single living. The mechanism underlying the gender-related inequalities in outcome for CD warrants further elucidation.

    Place, publisher, year, edition, pages
    Lippincott Wilkins and Williams, 2011
    Keywords
    Crohn’s disease; inflammatory bowel disease; health-related quality of life; disability; sickness; social factors
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-66248 (URN)10.1097/MEG.0b013e328346f622 (DOI)000292503100006 ()
    Available from: 2011-03-09 Created: 2011-03-09 Last updated: 2017-12-11Bibliographically approved
    Download full text (pdf)
    Crohn’s Disease in Sickness and in Health : Studies of Health Assessment Strategies and Impact on Health-Related Quality of Life
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  • 109.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Järnerot, Ggunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Evaluation of the Inflammatory Bowel Disease Questionnaire in Swedish patients with Crohn's disease2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 8, p. 934-943Article in journal (Refereed)
    Abstract [en]

    Objective. Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). Material and methods. Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns, Short Form-36, and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. Results. The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. Conclusions. Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items. © 2006 Taylor & Francis.

  • 110.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden, Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 1, p. 47-52Article in journal (Refereed)
    Abstract [en]

    Background: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). Methods: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. Results: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (rS = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (rS = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). Conclusions: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

  • 111.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Svensson, Erland
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Structural Equation Modeling of the Relationship between Disease Activity and Health-related Quality of Life Variables in Crohn’s DiseaseManuscript (preprint) (Other academic)
    Abstract [en]

    Objective. Disease activity (DA) and health-related quality of life (HRQL) are two major endpoints in outcome assessment of Crohn’s disease (CD).  A health concept model of the relationship between DA and HRQL encompassing five dimensions (biological variables, symptoms, function, worries, and general well-being) in inflammatory bowel disease (IBD) has been postulated previously, forming the basis of the IBD HRQL instrument, the Short Health Scale (SHS). This study evaluates the model, using structural equation modeling technique (SEM) on DA and HRQL data from a cohort of CD patients.

    Methods. The relationships of the five dimensions represented by 14 health measures of 283 CD patients were analyzed by confirmatory factor analysis and SEM, using SPSS AMOS v18.0.

    Results. All parameter estimates proved significant, and the goodness-of-fit indices were good (χ2=104.2, df=69, p=0.004, CFI=0.986, RMSEA=0.043). A revision of the structural pathway, in which well-being precedes worries, was suggested from empirical data.

    Conclusion. The postulated health concept model proved to be a valid and plausible approximation of the relationship between disease activity and subjective health perception in CD. The results support the use of the SHS for subjective health assessment in CD.

  • 112.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Factors Predicting the Outcome of Disease Activity Assessment in Crohns Disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1859-1866Article in journal (Refereed)
    Abstract [en]

    Background: The Crohns Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome. Methods: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified. Results: The correlation between CDAI and PGA was moderate. In patients with CDAI greater than 150, 72% of the total score were derived froth the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula. Conclusions: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.

  • 113.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, S-701 85 Örebro/School of Health and Medical Sciences, Örebro University, Örebro; Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Unfavourable outcome for women in a study of health-related quality of life, social factors, and work disability in Crohn’s disease2011In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 23, no 8, p. 671-679Article in journal (Refereed)
    Abstract [en]

    Objective. The aim was to describe health-related quality of life (HRQL) and social factors, sickness and disability variables in a large population-based cohort of patients with Crohn’s disease (CD).

    Methods. HRQL was measured with SF-36 in 497 adult CD patients at three outpatient clinics. Comparisons were made with age-gender-matched background population and with ulcerative colitis (UC). Social factors, employment, sickness compensation, and disability pension for CD, were compared with national population registers.

    Results. CD had a greater negative effect on HRQL than did UC. This difference was more pronounced for women. Compared with background population, CD patients had lower educational level, and had a two-fold rise in long-term sickness and disability pension rate. CD women had higher rates of sickness and disability than CD men and were more often living single, though procreation was not affected.

    Conclusion. This study characterized the burden of CD in a large population-based cohort. CD had higher impact on HRQL, compared with UC. CD women had worse outcome in subjective health status, but not in objective assessment of disease activity. Women also had higher rates of sickness, disability pension, and single living. The mechanism underlying the gender-related inequalities in outcome for CD warrants further elucidation.

  • 114.
    Stjernman, Henrik
    et al.
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Örebro University Hospital, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Worries and concerns in a large unselected cohort of patients with Crohns disease2010In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 45, no 6, p. 696-706Article in journal (Refereed)
    Abstract [en]

    Objective. Disease-related worries constitute an important dimension of patient-reported perception of health status in inflammatory bowel disease (IBD). The Rating Form of IBD Patient Concerns (RFIPC) questionnaire is purported to measure IBD-related worries. This study evaluated the psychometric properties of a Swedish translation of RFIPC in an unselected population of Crohns disease (CD) patients. The degree and nature of the worries were characterized and predictive factors for outcome of RFIPC and underlying dimensions were identified. Material and Methods. The RFIPC was completed by 447 CD patients in conjunction with regular visits. A physician global assessment of disease activity and four other health-related quality of life (HRQL) questionnaires were used for construct validity. Reliability and responsiveness were evaluated with follow-up visits. Underlying dimension and predictive factors were identified with factor analysis and multiple linear regression analysis. Results. Test-retest reliability was 0.90, correlation with corresponding HRQL measures 0.60-0.80 and responsiveness ratio 0.84. Median RFIPC sum score was lower than in previous studies. Top three concerns were ostomy, energy level and bowel control. Four dimensions were identified in descending order of concern: disease-related complications, daily-life achievements, intimacy, and stigmatization. Predictors of RFIPC score were disease activity, gender, and BMI (p andlt; 0.001-0.008). Conclusions. The Swedish version of RFIPC exhibited an adequate psychometric performance in CD patients, but was less sensitive to change in disease activity. The patients were more concerned about complications and achievement than intimacy and stigmatization. The strongest predictors of more worry were active disease, female gender and higher BMI.

  • 115.
    Theibaut, R
    et al.
    AP HP, INSERM.
    Douchin, V
    AP HP, INSERM.
    Jung, C
    AP HP, INSERM.
    Merlin, F
    AP HP, INSERM.
    Colombel, J F
    Hop Calmette.
    Lemann, M
    Hop St Louis.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, C
    Orebro University Hospital.
    OMorain, C
    Trinity College Dublin.
    Gassull, M
    Hospital Badalona Germans Trias and Pujol.
    Finkel, Y
    Karolinska Institute.
    Zouali, H
    Fdn Jean Dausset.
    Pascoe, L
    Fdn Jean Dausset.
    Hugot, J P
    AP HP, INSERM.
    Letter: RIP2 Polymorphisms in Inflammatory Bowel Diseases2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 4, p. 1055-1055Article in journal (Other academic)
    Abstract [en]

    n/a

  • 116.
    Thiebaut, R
    et al.
    University of Paris.
    Kotti, S
    University of Paris.
    Jung, C
    University of Paris.
    Merlin, F
    University of Paris.
    Colombel, J F
    Hop Calmette.
    Lemann, M
    Hop St Louis.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, C
    University of Örebro.
    Morain, M O
    Adelaide & Meath Hospital.
    Gassull, M
    Hospital University Germans Trias & Pujol.
    Binder, V
    Herlev Hospital.
    Finkel, Y
    Karolinska Children's Hospital.
    Pascoe, L
    CEPH, Paris.
    Hugot, J-P
    Hop Robert Debre.
    TNFSF15 Polymorphisms Are Associated With Susceptibility to Inflammatory Bowel Disease in a New European Cohort2009In: AMERICAN JOURNAL OF GASTROENTEROLOGY, ISSN 0002-9270, Vol. 104, no 2, p. 384-391Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Inflammatory bowel disease (IBD), e. g., Crohns disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD.

    METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied.

    RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P = 0.001) (OR = 1.25 (1.05-1.50)) and CD (P = 0.02) (OR = 1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A.

    CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.

  • 117. Tysk, C
    et al.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Andersson, M
    Befrits, R
    Hertervig, E
    Kilander, A
    Lindgren, S
    Suhr, O
    Nationella riktlinjer för handläggning av akut svårt skov av ulcerös kolit2008Report (Other academic)
    Abstract [sv]

      

  • 118.
    van Asseldonk, Dirk P
    et al.
    Vrije University Amsterdam Medical Centre, Amsterdam, The Netherlands.
    Sanderson, Jeremy
    Guys and St Thomas Hospital, London, UK.
    de Boer, Nanne K H
    Vrije University Amsterdam Medical Centre, Amsterdam, The Netherlands.
    Sparrow, Miles P
    Alfred Hospital, Melbourne, Australia.
    Lemann, Marc
    Hôpital Saint Louis, Paris, France.
    Ansari, Azhar
    East Surrey Hospital, Red Hill, UK.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Florin, Timothy H J
    University of Queensland, Brisbane, Australia.
    Gearry, Richard B
    University of Otago, Christchurch, New Zealand.
    Mulder, Chris J
    Vrije University Amsterdam Medical Centre, Amsterdam, The Netherlands.
    Mantzaris, Gerassimos
    Evangelisms Hospital, Athens, Greece.
    van Bodegraven, Ad A
    Vrije University Amsterdam Medical Centre, Amsterdam, The Netherlands.
    Difficulties and possibilities with thiopurine therapy in inflammatory bowel disease-Proceedings of the first Thiopurine Task Force meeting2011In: DIGESTIVE AND LIVER DISEASE, ISSN 1590-8658, Vol. 43, no 4, p. 270-276Article in journal (Refereed)
    Abstract [en]

    Background: Thiopurines, such as azathioprine and mercaptopurine, are of pivotal importance in the treatment of inflammatory bowel disease. Although these drugs have been used for several decades, still many questions remain unanswered. Aim: To provide an overview of clinically and scientifically challenging topics concerning thiopurine therapy in inflammatory bowel disease treatment. Methods: The first meeting of the Thiopurine Task Force Interest Group was held during the 2009 United European Gastroenterology Week in London (GASTRO2009). The topics of this meeting were of particular clinical and scientific interest. Additional literature was identified by performing a Pubmed search using the search terms inflammatory bowel disease, azathioprine, 6-mercaptopurine and thioguanine. Results: The following topics were discussed: therapeutic drug monitoring; the synergy of thiopurines with aminosalicylates and allopurinol; serious adverse events such as opportunistic infections, hepatotoxicity, carcinogenicity and pancreatitis; prolongation of thiopurines during clinical remission; indications for thiopurines in the postoperative setting; and the potential use of thioguanine. Specific interesting and clinically relevant topics for potential future research are provided. Conclusions: Thiopurines remain central to inflammatory bowel disease treatment, although future studies are required to substantiate a more personalised medicine approach to their use.

  • 119.
    Vigren, Lina
    et al.
    Lund University.
    Sjöberg, Klas
    Lund University.
    Benoni, Cecilia
    Lund University.
    Tysk, Curt
    Örebro University of Hospital.
    Bohr, Johan
    Örebro University of Hospital.
    Kilander, Anders
    Sahlgrenska University Hospital.
    Larsson, Lasse
    Sahlgrenska University Hospital.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Is smoking a risk factor for collagenous colitis?2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 11, p. 1334-1339Article in journal (Refereed)
    Abstract [en]

    Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohns disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking inmicroscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. Materials and methods. 116 patients (92 women) with median age of 62 years (interquartile range 55-73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. Results. Of the 116 CC patients, 37% were smokers compared with 17% of controls (p andlt; 0.001, odds ratio (OR) 2.95). In the age group 16-44 years, 75% of CC patients were smokers compared with 15% of controls (p andlt; 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers - at 42 years of age (median) compared with 56 years in non-smokers (p andlt; 0.003). Although the proportion with active disease did not differ between smokers and nonsmokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). Conclusions. Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers.

  • 120.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Monitoring of thiopurine metabolites - A high-performance liquid chromatography method for clinical use2013In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 75, p. 145-152Article in journal (Refereed)
    Abstract [en]

    A high-performance liquid chromatography method capable of measuring thiopurine mono-, di-, and triphosphates separately in red blood cells (RBCs) was developed. RBCs were isolated from whole blood using centrifugation. Proteins were precipitated using dichloromethane and methanol. The thioguanine nucleotides (TGNs) were derivatised using potassium permanganate before analysis. Analytes were separated by ion-pairing liquid chromatography using tetrabutylammonium ions and detected using UV absorption and fluorescence. The method was designed for use in clinical trials. Ten patient samples were analysed to demonstrate clinical application and to establish pilot ranges for all analytes. less thanbrgreater than less thanbrgreater thanThe method measured thioguanosine mono-(TGMP), di-(TGDP), and triphosphate (TGTP), as well as methylthioinosine mono- (meTIMP), di- (meTIDP) and triphosphate (meTITP) in RBCs collected from patients treated with thiopurine drugs (azathioprine, 6-mercaptopurine, and 6-thioguanine). less thanbrgreater than less thanbrgreater thanLOQ was 0.3, 3, 2, 30, 30 and 40 pmol/8 x 10(8) RBC, for TGMP, TGDP, TGTP, meTIMP, meTIDP and meTITP, respectively. Between-day precision were below 14% for all analytes at all concentrations and samples were stable at 4 degrees C for 8 h after sampling.

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  • 121.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Monitoring of thiopurine metabolites: A high-performance liquid chromatography method for clinical useManuscript (preprint) (Other academic)
    Abstract [en]

    high-performance liquid chromatography method capable of measuring thiopurine mono-, di-, and triphosphates separately in red blood cells (RBCs) was developed. RBC:s were isolated from whole blood using centrifugation. Proteins were precipitated using dichloromethane and methanol. The thioguanine nucleotides (TGNs) were derivatised using potassium permanganate before analysis. Analytes were separated by ion-pairing liquid chromatography using tetrabutylammonium ions and detected using UV absorption and fluorescence. The method was designed for use in clinical trials in thiopurine therapy and proven valid by analysis of authentic patient samples.

    The method measured thioguanosine mono- (TGMP), di- (TGDP), and triphosphate (TGTP), as well as methylthioinosine mono- (meTIMP), di- (meTIDP) and triphosphate (meTITP) in RBCs collected from patients treated with thiopurine drugs (azathioprine, 6-mercaptopurine, and 6-thioguanine).

    LOQ was 0.3, 3, 2, 30, 30 and 40 pmol/8x10^8 RBC, for TGMP, TGDP, TGTP, meTIMP, meTIDP and meTITP, respectively. Between-day precision were below 14% for all analytes at all concentrations and samples were stable at 5 °C for 8 hours after sampling.

  • 122.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Andersson, David
    Department of Gastroenterology, Skåne University Hospital, Lund, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Hindorf, Ulf
    Department of Gastroenterology, Skåne University Hospital, Lund, Sweden.
    Therapeutic drug monitoring of thiopurines in inflammatory bowel disease: Evaluating the benefit of measuring mono-, di-, and triphosphates separatelyManuscript (preprint) (Other academic)
    Abstract [en]

    The thiopurines are widely used in the treatment of inflammatory bowel diseases but are limited by poor dose-effect relationship and large interindividual variability in clinical effects. Many attempts have been made to predict response by therapeutic drug monitoring of phosphorylated and methylated metabolites grouped together as thioguanine nucleotides and methylthioinosine monophosphate. We have developed a method to determine the individual metabolites, thioguanosine mono-, di-, and triphosphates, as well as methylthioinosine mono-, di-, and triphosphates, separately in red blood cells.

    This aim of this study was to assess the ability of our novel method to predict clinical outcome compared to the routine method in 82 patients with inflammatory bowel diseases.

    TPMT wild-type patients with TGN levels below the cut-off level were more likely to have an active disease when TGN was measured by both the routine method (p < 0.05), the novel method (p<0.05), and when TGTP was measured separately (p < 0.01). TGN levels and TGTP were, however, not correlated to disease activity in TPMT defective patients. Patients with meTIN levels above 1500 pmol were more likely to have an active disease (39%, 18/46 vs. 17%, 5/30; p = 0.02). We observed good correlations between the mono-, di-, and triphosphates and their respective sums (R2 > 0.88) and the TGTP ratio (TGTP/(TGDP+TGTP)) was not different in patients with active disease or in clinical remission.

    Thiopurine metabolites should still be measured by the routine method, since the novel and technically more challenging method, including determination of TGTP and TGTP ratio, does not offer a clinical advantage compared to the routine method.

  • 123.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Almer, Sven H C
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Monitoring of thiopurine metabolites in patients with inflammatory bowel disease-what is actually measured?2009In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 31, no 3, p. 345-50Article in journal (Refereed)
    Abstract [en]

    Azathioprine and 6-mercaptopurine are often used in the treatment of patients with inflammatory bowel disease (IBD). They are prodrugs and undergo a complex metabolism to active and inactive metabolites. Thiopurine treatment is monitored in many laboratories by measuring metabolite concentrations in erythrocytes (red blood cells). The metabolites of interest are not measured directly but as hydrolysis products, which can be produced from several metabolites. The aim of this study was to examine which metabolites are actually measured during routine monitoring. Samples from 18 patients treated with a thiopurine were analyzed by a typical routine high-performance liquid chromatography method for therapeutic drug monitoring and by a newly developed specific method measuring thioguanosine monophosphate (TGMP), thioguanosine diphosphate (TGDP), and thioguanosine triphosphate (TGTP), as well as methylthioinosine monophosphate (meTIMP), and the results were compared. 6-Thioguanine nucleotide (TGN) values detected by the routine method were 69% (range 40%-90%) of the sum of TGMP, TGDP, and TGTP measured by the specific method. TGTP and TGDP contributed 85% (range 78%-90%) and 14% (range 10%-21%) of the TGN total, respectively. Thioguanosine was not found in any patient sample. The concentration of meTIMP obtained by the routine method was 548% of the value obtained by the specific method (range 340%-718%). The difference in TGN measurements between the routine and specific methods can be explained by low hydrolysis efficiency in the routine method, although the most likely explanation for the difference in meTIMP values is that not yet identified metabolites are codetermined in the routine high-performance liquid chromatography method. Concentrations reported as TGN during therapeutic drug monitoring of thiopurine metabolites consist of TGDP and TGTP with a minor contribution of the TGMP. Concentrations reported as meTIMP or methyl mercaptopurine consist in part of meTIMP, but other not yet identified metabolites are codetermined.

  • 124.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    How Should Thiopurine Treatment be Monitored? Methodological Aspects2010In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 29, no 04-Jun, p. 278-283Article in journal (Refereed)
    Abstract [en]

    Monitoring of thiopurine metabolites is important due to a complex metabolism with large interindividual variation, but the suitability of currently used methods has been questioned. The drawbacks include poor reproducibility, the inability to differentiate between the different analytes, as well as the use of a nontarget matrix. Further research should be directed toward measuring thiopurine metabolites in mononuclear cells, measuring the different nucleotides specifically, as well as measuring the incorporation of thioguanine into DNA. The studies should not be limited to thioguanosine nucleotides but include methylthioinosine nucleotides as well.

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  • 125.
    Vikingsson, Svante
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Coulthard, S
    Newcastle University, Northern Institute for Cancer Research.
    Josefsson, Martin
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linkoping.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rapid Method to Measure Thioguanine Incorporation Into DNA2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no Supplement 1, p. S650-S650Article in journal (Other academic)
    Abstract [en]

    Background: The thiopurine drugs, 6-mercaptopurine, azathioprine, and thioguanine, are used in the treatment of acute lymphoblastic leukaemia (ALL). During treatment the thioguanine nucleotides formed are incorporated into the DNA, causing apoptosis due to the cells inability to repair the resulting damage. This mechanism is believed to be important for the effects of thiopurine drugs. We have developed a novel method for the determination of thioguanine incorporation into DNA which is both faster and cheaper than earlier methods.

    Monitoring the effects of thiopurine treatment by measuring thiopurine metabolites in erythrocytes has proven to be elusive due to the lack of good correlation between measured concentrations and thiopurine effects. If the incorporation is the main mechanism of thiopurine action, a reliable method capable of measuring the incorporation in an ordinary blood sample, such as the method we have developed, should provide a significantly better correlation with treatment effect.

    Material and Methods: Briefly, DNA extracted from buffy coat is degraded using nuclease P1 and alkaline phosphatase to produce free nucleosides which are purified by filtration. Thioguanosine and thymidine are separated and detected using an LC-MS/MS system and the ratio between the bases provides a measurement of the extent of thioguanine incorporation in DNA. The method has been successfully applied to cell culture samples as well as samples from patients treated orally with thiopurines.

    Results: In 8 inflammatory bowel disease patients treated with azathioprine the measured incorporation ranged from 2.2 to 8.4 thioguanine bases for every 10 000 thymidine bases (median 5.2). This is in agreement with earlier reports on incorporation in childhood leukemia patients.

    Conclusions: With the presented method it is possible to determine the incorporation of thioguanine into DNA during thiopurine treatment in a cost effective manner, but further research is needed to determine if there is a place for this type of methods in the monitoring of thiopurine treatment.

    An ongoing study aims to compare the incorporation to treatment effects as well as conventional measurements of erythrocyte metabolite levels. By this study we hope to determine if incorporation is a more reliable measurement to predict treatment effect and if the erythrocyte metabolite levels correlate with the incorporation.

  • 126.
    Wallerstedt, Sven
    et al.
    Sahlgrenska University Hospital, Göteborg, Sweden .
    Simren, Magnus
    Sahlgrenska University Hospital, Göteborg, Sweden .
    Wahlin, Staffan
    Karolinska University Hospital Huddinge, Sweden .
    Loof, Lars
    Center for Clinical Research, Västerås, Sweden.
    Hultcrantz, Rolf
    Karolinska University Hospital, Solna, Sweden .
    Sjöberg, Klas
    Skåne University Hospital, Malmö, Sweden .
    Sandberg Gertzen, Hanna
    University Hospital, Örebro, Sweden.
    Prytz, Hanne
    Skåne University Hospital, Lund, Sweden .
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Oden, Anders
    Chalmers University, Gothenburg, Sweden.
    Moderate hyperkalemia in hospitalized patients with cirrhotic ascites indicates a poor prognosis2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 3, p. 358-365Article in journal (Refereed)
    Abstract [en]

    Objective. Development of ascites in patients with liver cirrhosis is an ominous sign with a poor outcome. A liver transplantation must be considered, and it then becomes important to know if there are any factors indicating a worsened prognosis. Material and methods. We used official registers for a follow-up study of at least 5 years considering the prognosis of 155 prospectively recruited in-patients with cirrhotic ascites from medical units at nine Swedish university hospitals. All patients had undergone at least one diagnostic ascites tap, and had initially been questioned about background factors and physically examined according to a standardized case record form, followed by sampling of blood, urine, and ascites. Results. Death occurred within 1 year after inclusion in 53% of the cases, and was primarily liver-related in 70%. In a multivariable analysis, the two ordinary variables that showed the strongest correlation with risk of death were serum potassium and abdominal tenderness. All 22 patients with a serum potassium concentration of at least 4.8 mmol/L (maximum 5.8 mmol/L) died within 1 year after inclusion. Potassium concentration was related to renal function and potassium-saving drugs. Conclusion. This follow-up study of a prospectively recruited cohort of in-patients with cirrhotic ascites confirms their poor prognosis. Awareness of an elevated serum potassium value, which would reflect a threatened renal function, seems essential, because it may offer a simple way to identify cases with the worst prognosis. An area for further research should be to explore the significance of including serum potassium in prognostic models.

  • 127.
    Walter, Susanna A.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Linköping University, Faculty of Health Sciences.
    Bodemar, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Pre-experimental stress in patients with irritable bowel syndrome: high cortisol values already before symptom provocation with rectal distensions2006In: Neurogastroenterology and Motility, ISSN 1350-1925, Vol. 18, no 12, p. 1069-1077Article in journal (Refereed)
    Abstract [en]

    Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se. In twenty-four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment (P = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls (P = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation (P = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.

  • 128.
    Walter, Susanna A.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Bodemar, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences.
    Sympathetic (electrodermal) activity during repeated maximal rectal distensions in patients with irritable bowel syndrome and constipation2008In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 20, no 1, p. 43-52Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is associated with visceral hypersensitivity, stress and autonomic dysfunction. Sympathetic activity during repeated events indicates excitatory or inhibitory mechanisms such as sensitization or habituation. We investigated skin conductance (SC) during repetitive rectal distensions at maximal tolerable pressure in patients with IBS and chronic constipation. Twenty-seven IBS patients, 13 constipation patients and 18 controls underwent two sets of isobaric rectal distensions. First, maximal tolerable distension was determined and then it was repeated five times. Skin conductance was measured continuously. Subjective symptom assessment remained steady in all groups. The baseline values of SC were higher in IBS patients than in patients with constipation and significantly lower in constipation patients than in controls. The maximal SC response to repetitive maximal distensions was higher in IBS patients compared with constipation patients. The amplitude of the initial SC response decreased successively with increased number of distensions in patients with IBS and constipation but not in controls. Irritable bowel syndrome and constipation patients habituated to maximal repetitive rectal distensions with decreasing sympathetic activity. Irritable bowel syndrome patients had higher sympathetic reactivity and baseline activity than constipation patients. A lower basal SC in constipation patients compared with controls suggests an inhibition of the sympathetic drive in constipation patients.

  • 129.
    Walter, Susanna A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Kjellström, Lars
    Department of Gastroenterology, Sabbatsbergs Hospital, Karolinska Institutet, Stockholm, Sweden.
    Talley, Nicholas J
    Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
    Andreasson, Anna Nixon
    Center for Family and Community Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nyhlin, Henry
    Department of Gastroenterology, Karolinska Institutet, Stockholm, Sweden.
    Agréus, Lars
    Center for Family and Community Medicine, Karolinska Institutet, Stockholm, Sweden.
    Prospective Diary Evaluation of Unexplained Abdominal Pain and Bowel Dysfunction: A Population-Based Colonoscopy Study2011In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 56, no 5, p. 1444-1451Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Diagnostic criteria for irritable bowel syndrome (IBS) have not been validated by prospective symptom diary. We investigated the bowel patterns in community subjects with and without non-organic abdominal pain, and compared the symptoms with subjects fulfilling the Rome II criteria (IBS).

    METHODS: From the Swedish population register, a random sample completed an abdominal symptom questionnaire. Responders were subsequently invited for a clinical evaluation and offered a colonoscopy regardless of whether they had abdominal symptoms or not. A total of 268 subjects underwent colonoscopy, clinical evaluation by gastroenterologist, laboratory investigations, and completed the Rome questionnaire and prospective gastrointestinal (GI) symptom diaries for 1 week. Twenty-three subjects of 268 were excluded due to organic GI disease.

    RESULTS: Subjects recorded 2,194 bowel movements and 370 abdominal pain episodes on 1,504 days. Subjects with pain in the diary (n = 81) had higher stool frequency (P = 0.01), more urgency (P = 0.0002), feelings of incomplete evacuation (P = 0.0002), nausea (P = 0.0009), and abdominal bloating (P = 0.0005) than subjects without pain (n = 151). Twenty-eight subjects (12%) fulfilled the Rome II criteria for IBS. Together, they had 96 pain episodes but only 4% were improved by defecation; 29% of the pain episodes started or worsened after a meal. Subjects with IBS and other subjects with non-organic abdominal pain (n = 64) exhibited no differences in terms of the proportions of pain episodes improved by defecation, bloating, stool frequency, consistency, or defecatory symptoms.

    CONCLUSIONS: Current criteria for IBS that rely on recall of the relationship between abdominal pain and bowel disturbance may overcall this association when measured prospectively.

  • 130.
    Walter, Susanna A.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Ragnarsson, Gudmundur
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Bodemar, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    New criteria for irritable bowel syndrome based on prospective symptom evaluation2005Other (Other academic)
  • 131.
    Walter, Susanna
    et al.
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Gotthard, Ricci
    Bergmark, M.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    A population-based study on bowel habits in a Swedish community: prevalence of faecal incontinence and constipation2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 37, no 8, p. 911-916Article in journal (Refereed)
    Abstract [en]

    Background: The self-reported bowel habits and the prevalence of faecal incontinence and constipation in men and women between the ages of 31 and 76 are assessed.

    Methods: A postal questionnaire was sent to a random sample ( n = 2000) of the total population of persons between the ages of 31 and 76 living in the County of Östergötland, Sweden.

    Results: The response rate was 80.5%. Overall, 67.8% reported one bowel movement per day and 4.4% had more than 21 or less than 3 bowel movements per week. This means that 95.6% had between 3 bowel movements a day to 3 bowel movements a week. Among women, 4.3%, and among men, 1.7%, reported less than 3 bowel movements per week. Women and men used the same terms to describe the definition of constipation. Women had a significantly higher self-reported prevalence of constipation than men ( P < 0.0001). About 20% of all women considered themselves constipated. The use of laxatives increased with age and 22% and 10% of elderly women and men, respectively, used laxatives including bulking agents for at least every fourth toilet procedure. About 10% reported leakage of faeces more often than once a month in the case of loose stools. With solid faeces, the rate of leakage was 1.4% and 0.4% for women and men, respectively. Soiling of underclothes more than once a month occurred in 21% of men and in 14.5% of women ( P = 0.006) and involuntary daily leakage of gas in 5.9% of men and 4.9% of women (n.s.).

    Conclusions: Constipation and faecal incontinence are common problems in a general Swedish population.

  • 132.
    Walter, Susanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Holmgren, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Association between bowel symptoms, symptom severity, and quality of life in Swedish patients with fecal incontinence2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Objectives. The association between abdominal symptoms, disease severity of fecal incontinence (FI), and quality of life (QoL) is not yet clear. We hypothesized that it would become clearer by prospective diary data. We also aimed to compare QoL of FI patients with ulcerative colitis (UC) patients in relapse and remission.

    Material and methods. Sixty-five consecutive female patients with FI recorded bowel symptoms prospectively on diary cards. QoL was evaluated with the disease specific short health scale questionnaire (SHS). Patients with UC in remission and relapse were used as a reference group regarding SHS.

    Results. FI patients had median 3.5 leakage episodes/week. In all, 48% of bowel movements were associated with urgency. Urgency was correlated to decreased QoL according to SHS domains: symptoms (Rho = 0.54, p = 0.0002), function (Rho = 0.48, p = 0.0008), and disease related worry (Rho = 0.32, p = 0.027). Abdominal pain and bloating, reported by nearly half of patients, correlated to deceased QoL but not to number of leakages. QoL of patients with FI compared to UC in active phase (n = 35) was similar. FI patients had decreased QoL compared to UC in remission (n = 94) in all dimensions of SHS: symptoms (p < 0.0001), function (p < 0.0001), disease related worry (p < 0.0001), and general well being (p = 0.03).

    Conclusion. Urgency and irritable bowel syndrome (IBS)-like symptoms were associated with decreased QoL in FI. Therefore, IBS should be considered as an important confounding factor in FI QoL studies. QoL in patients with FI was considerably decreased, in a similar extent as in patients with UC in relapse.

  • 133.
    Walter, Susanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Kjellstrom, Lars
    Karolinska Institute.
    Nyhlin, Henry
    Karolinska Institute.
    Talley, Nicholas J
    Mayo Clinic Florida.
    Agreus, Lars
    Karolinska Institute.
    Assessment of normal bowel habits in the general adult population: the Popcol study2010In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 45, no 5, p. 556-566Article in journal (Refereed)
    Abstract [en]

    Objective. Defining normal stool habit is important when evaluating diarrhoea or constipation, but common confounders such as irritable bowel syndrome (IBS) or the intake of medications with gastrointestinal side effects have not been considered in earlier population based studies defining what is normal. We hypothesized that the exclusion of subjects with common confounders would help to better understand what are "normal bowel habits". We aimed to prospectively study bowel habits in a carefully studied random sample of the general population. Material and methods. Two hundred and sixty-eight randomly selected subjects between 18 and 70 years completed symptom diaries for one week and were clinically evaluated by a gastroenterologist. They also had a colonoscopy and laboratory investigations to exclude organic disease. Results. One hundred and twenty-four subjects had no organic gastrointestinal abnormality, IBS, or relevant medication; 98% of them had between three stools per day and three per week. Seventy-seven percent of all stools were normal, 12% hard, and 10% loose in consistency. Urgency was reported by 36%; straining by 47% and incomplete defecation by 46%. After the exclusion of subjects with organic abnormalities, women had significantly more symptoms than men in terms of abdominal pain, bloating, constipation, urgency, and feeling of incomplete evacuation but these gender differences disappeared after excluding subjects with IBS. Conclusions. This study confirms that normal stool frequency is between three per week and three per day. We could not demonstrate any gender or age differences in terms of stool frequency, defecatory symptoms or abdominal bloating. Some degree of urgency, straining, and incomplete evacuation should be considered normal.

  • 134.
    Walter, Susanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Münch, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ost, A
    Karolinska Institute.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls2010In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 22, no 5, p. 534-+Article in journal (Refereed)
    Abstract [en]

    Background Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. Methods Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re-assessed. Key Results All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. Conclusions andamp; Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.

  • 135.
    Walter, Susanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Skagerström, Eva
    Bodemar, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Subgroups of irritable bowel syndrome: a new approach2004In: European Journal of Gastroenterology and Hepatology, ISSN 0954-691X (print) 1473-5687 (online), Vol. 16, no 10, p. 991-994Article in journal (Refereed)
    Abstract [en]

    Objectives: The newly revised Rome criteria for the definition of irritable bowel syndrome (IBS), derived from the consensus of experts in the field, were developed in order to identify subgroups of IBS patients for research. The criteria have, to our knowledge, never been validated. Both when trying to include IBS patients in studies and in clinical practice we found it difficult to apply the Rome 2 supportive criteria.

    Aim: To study the variation of stool consistency and defecatory symptoms in IBS patients prospectively with diary cards and to validate the Rome 2 supportive criteria.

    Methods: Sixty IBS patients, included by interview according to the Rome 1 criteria, recorded their bowel symptoms on diary cards over 40 days. Four subgroups were found, characterised by loose-stool-predominant, hard-stool-predominant, alternating stool consistency, and loose stools only. Urgency, straining and feeling of incomplete evacuation occurred in all but seven individuals, irrespective of subgroup.

    Results: The Rome 2 criteria could subclassify seven patients into diarrhoea-predominant IBS based on stool consistency and absence of straining and could subclassify no patients into constipation-predominant IBS, as urge was present in nearly all patients. Fifty-three patients could not be classified according to the Rome 2 criteria, as they had defecatory symptoms of all kinds.

    Conclusion: As the Rome 2 supportive criteria use the presence or absence of specific defecatory symptoms as an instrument for categorising IBS patients into diarrhoea- and constipation-predominant subgroups, these criteria could not be used for the majority of IBS patients in this study and should be reconsidered.

  • 136.
    Wei, G.
    et al.
    Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Bergquist, A.
    Department of Gastroenterology and Hepatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Broome, U.
    Broomé, U., Department of Gastroenterology and Hepatology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Lindgren, S.
    Gastroenterology and Hepatology Division, Department of Medicine, University Hospital MAS, Malmö, Sweden.
    Wallerstedt, S.
    Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Sangfelt, P.
    Gastroenterology and Hepatology Division, Department of Medicine, University Hospital, Uppsala, Sweden.
    Danielsson, A.
    Danielsson, Å., Gastroenterology and Hepatology Division, Department of Medicine, University Hospital, Umeå, Sweden.
    Sandberg-Gertzen, H.
    Sandberg-Gertzén, H., Gastroenterology and Hepatology Division, Department of Medicine, University Hospital, Örebro, Sweden.
    Loof, L.
    Lööf, L., Center for Clinical Research, Central Hospital, Västerås, Sweden.
    Prytz, H.
    Gastroenterology and Hepatology Division, Department of Medicine, University Hospital, Lund, Sweden.
    Bjornsson, E.
    Björnsson, E., Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden, Department of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
    Acute liver failure in Sweden: Etiology and outcome2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 3, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Objective. To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994-2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score with transplant-free deaths as a positive outcome. Research design and methods. Adult patients in Sweden with international normalized ratio (INR) of =1.5 due to severe liver injury with and without encephalopathy at admission between 1994-2003 were included. Results. A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive-predictive value (PPV) of 67%, negative-predictive value (NPV) of 84% in the acetaminophen group. Positive-predictive value and negative-predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score >30 had a positive-predictive value of 21%, negative-predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively. Conclusions. Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score <30 predicts a good prognosis in acetaminophen patients without transplantation. © 2007 Blackwell Publishing Ltd.

  • 137. Werner, M
    et al.
    Prytz, H
    Ohlsson, B
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bjornsson, E
    Bergquist, A
    Wallerstedt, S
    Sandberg-Gertzen, H
    Hultcrantz, R
    Sangfelt, P
    Weiland, O
    Danielsson, A
    Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: A nationwide study2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 10, p. 1232-1240Article in journal (Refereed)
    Abstract [en]

    Objective. Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH. Material and methods. Analyses were performed in 473 patients identified as having probable or definite AIH. Results. The incidence of AIH was 0.85/100,000 (95% CI 0.69-1.01) inhabitants, which is somewhat lower than reported previously. The point prevalence amounted to 10.7/100,000 (95% CI 8.8-13.1), and 76% of the cases were females. The age-related incidence curve was bimodal but men were found to have only one incidence peak in the late teens, whereas women had a peak after menopause. AIH was presented as a spectrum of clinical settings from detected "en passant" to acute liver failure. Almost 30% of patients already had liver cirrhosis at diagnosis. Autoantibodies indicative of AIH type 1 were found in 79% of cases. Other concomitant autoimmune diseases were frequently found (49%). Conclusions. The incidence and prevalence figures confirm that AIH is a fairly uncommon disease in the Swedish population. Symptoms at presentation were unspecific, but almost half of the patients were jaundiced, with around 30% having liver cirrhosis. The majority of Swedish AIH patients had AIH type 1. © 2008 Informa UK Ltd.

  • 138.
    Werner, Marten
    et al.
    Umeå University Hospital.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Prytz, Hanne
    Lund University Hospital.
    Lindgren, Stefan
    Malmö University Hospital.
    Wallerstedt, Sven
    Karolinska University Hospital.
    Sandberg-Gertzen, Hanna
    Örebro University Hospital.
    Hultcrantz, Rolf
    Karolinska University Hospital.
    Sangfelt, Per
    Uppsala University Hospital.
    Weiland, Ola
    Karolinska University Hospital.
    Danielsson, Ake
    Umeå University Hospital.
    Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients2009In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 50, no 2, p. 388-393Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk. The aim was to investigate the risks of malignancies in a large cohort of AIH patients.

    Methods: Four hundred and seventy-three patients with AIH were matched to the Swedish national cancer register as well as to the death cause register.

    Results: We found an overall higher risk of malignancies in the cohort of A I H patients from the date of diagnosis with a SIR of 1.51 (95% CI 1.10-2.03). SIR in the subpopulation of well defined catchment areas and complete case finding was 23.28 (95% CI 7.5-54.34) for HCC. Lymphomas were found a SIR of 13.09 (95% CI 4.22-30.56).

    Conclusions: There was an overall increased risk of malignancies in a cohort of AIH patients, which manly was caused by hepatobiliary cancers. However, the true risk of HCC in an AIH cirrhotic cohort has yet to be investigated. A significantly higher risk of lymphomas was also found, but no clear cut association to the use of immune modulators.

  • 139.
    Werner, Marten
    et al.
    Umeå University Hospital.
    Wallerstedt, Sven
    Sahlgrens University Hospital.
    Lindgren, Stefan
    Malmö University Hospital.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bjornsson, Einar
    Sahlgrens University Hospital.
    Bergquist, Annika
    Karolinska University Hospital.
    Prytz, Hanne
    Lund University Hospital.
    Sandberg-Gertzen, Hanna
    Örebro University Hospital.
    Hultcrantz, Rolf
    Karolinska University Hospital.
    Sangfelt, Per
    Uppsala University Hospital.
    Weiland, Ola
    Karolinska University Hospital.
    Ohlsson, Bodil
    Malmö University Hospital.
    Danielsson, Ake
    Umeå University Hospital.
    Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response2010In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 45, no 4, p. 457-467Article in journal (Refereed)
    Abstract [en]

    Objectives. Autoimmune hepatitis (AIH) is a liver disease which, if untreated, may lead to liver cirrhosis and hepatic failure. Limited data exist regarding factors predicting the long-term outcome. The aims of this study were to investigate symptoms at presentation, prognostic features, management and treatment in relation to long-term outcome of AIH. Material and methods. A cohort of 473 Swedish patients with AIH was characterized regarding initial symptoms and signs, factors predicting death and future need for liver transplantation. Survival and causes of death were retrieved from Swedish national registers. Results. At diagnosis, fatigue was a predominant symptom (69%), 47% of the patients were jaundiced and 30% had liver cirrhosis. Another 10% developed cirrhosis during follow-up. Markedly elevated alanine aminotransferase levels at presentation were correlated with a better outcome. A high international normalized ratio (INR) at diagnosis was the only risk factor predicting a need for later liver transplantation. Histological cirrhosis, decompensation and non-response to initial treatment were all factors that correlated with a worse outcome. Overall life expectancy was generally favourable. However, most deaths were liver-related, e.g. liver failure, shock and gastrointestinal bleeding. Conclusions. Cirrhosis at diagnosis, a non-response to initial immune-suppressive treatment or elevated INR values were associated with worse outcome and a need for later liver transplantation. In contrast, an acute hepatitis-like onset with intact synthetic capacity indicated a good response to treatment and favourable long-term prognosis. Lifetime maintenance therapy is most often required.

  • 140.
    Zouali, H
    et al.
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Lesage, S
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Merlin, F
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Cezard, J
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Colombel, J
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Belaiche, J
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, C
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    O'Morain, C
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Gassull, M
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Modigliani, R
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Gower-Rousseau, C
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Chamaillard, M
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Thomas, G
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    Hugot, JP
    Hop St Louis, Dept Gastroenterol, Paris, France Hosp Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain Adelaide & Meath Hosp, Dept Gastroenterol, Dublin, Ireland Orebro Med Ctr Hosp, Dept Gastroenterol, S-70185 Orebro, Sweden Linkoping Univ, Inst Mol & Klin Med, Linkoping, Sweden CHU Liege, Dept Gastroenterol, Liege, Belgium Hop Calmette, Lille, France Hop Robert Debre, F-75019 Paris, France Fdn Jean Dausset, Paris, France.
    CARD4/NOD1 in inflammatory bowel disease.2002In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 71, no 4, p. 1877-Conference paper (Other academic)
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