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Weimers, P., Halfvarson, J., Sachs, M. C., Ludvigsson, J. F., Peter, I., Olén, O. & Burisch, J. (2019). Association between inflammatory bowel disease and Parkinson's disease: seek and you shall find? [Letter to the editor]. Gut, 68(1), 175-176
Open this publication in new window or tab >>Association between inflammatory bowel disease and Parkinson's disease: seek and you shall find?
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2019 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 1, p. 175-176Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
Epidemiology, inflammatory bowel disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-71215 (URN)10.1136/gutjnl-2018-316937 (DOI)30021791 (PubMedID)2-s2.0-85050249090 (Scopus ID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Weimers, P., Halfvarson, J., Sachs, M. C., Saunders-Pullman, R., Ludvigsson, J. F., Peter, I., . . . Olén, O. (2019). Inflammatory Bowel Disease and Parkinson's Disease: A Nationwide Swedish Cohort Study. Inflammatory Bowel Diseases, 25(1), 111-123
Open this publication in new window or tab >>Inflammatory Bowel Disease and Parkinson's Disease: A Nationwide Swedish Cohort Study
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2019 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 1, p. 111-123Article in journal (Refereed) Published
Abstract [en]

Background: Few studies have examined the association between inflammatory bowel disease (IBD) and Parkinson's disease (PD).

Methods: To estimate the incidence and relative risk of PD development in a cohort of adult IBD, we included all incident IBD patients (n = 39,652) in the Swedish National Patient Register (NPR) between 2002 and 2014 (ulcerative colitis [UC]: n = 24,422; Crohn's disease [CD]: n = 11,418; IBD-unclassified [IBD-U]: n = 3812). Each IBD patient was matched for sex, age, year, and place of residence with up to 10 reference individuals (n = 396,520). In a cohort design, all incident PD occurring after the index date was included from the NPR. In a case-control design, all incident PD occurring before the index date was included. The association between IBD and PD and vice versa was investigated by multivariable Cox and logistic regression.

Results: In IBD, there were 103 cases of incident PD, resulting in hazard ratios (HRs) for PD of 1.3 (95% confidence interval [CI], 1.0-1.7; P = 0.04) in UC, 1.1 (95% CI, 0.7-1.7) in CD, and 1.7 (95% CI, 0.8-3.0) in IBD-U. However, these effects disappeared when adjusting for number of medical visits during follow-up to minimize potential surveillance bias. In a case-control analysis, IBD patients were more likely to have prevalent PD at the time of IBD diagnosis than matched controls, with odds ratios of 1.4 (95% CI, 1.2-1.8) in all IBD patients, 1.4 (95% CI, 1.1-1.9) for UC, and 1.6 (95% CI, 1.1-2.3) for CD patients alone.

Conclusions: IBD is associated with an increased risk of PD, but some of this association might be explained by surveillance bias. 10.1093/ibd/izy190_video1izy190.video15785623138001.

Place, publisher, year, edition, pages
Lippincott-Raven Publishers, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-71220 (URN)10.1093/ibd/izy190 (DOI)29788069 (PubMedID)2-s2.0-85058603803 (Scopus ID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-08Bibliographically approved
Drobin, K., Assadi, G., Hong, M.-G., Andersson, E., Fredolini, C., Forsström, B., . . . Halfvarson, J. (2019). Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci. Inflammatory Bowel Diseases, 25(2), 306-316
Open this publication in new window or tab >>Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci
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2019 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed) Published
Abstract [en]

Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.

Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.

Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.

Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

Place, publisher, year, edition, pages
Lippincott-Raven Publishers, 2019
Keywords
inflammatory bowel disease, affinity proteomics, LACC1
National Category
Gastroenterology and Hepatology Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-69892 (URN)10.1093/ibd/izy326 (DOI)30358838 (PubMedID)
Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2019-01-14Bibliographically approved
Svensson, M., Bergman, D., Olén, O., Myrelid, P., Bohr, J., Wickbom, A., . . . Ludvigsson, J. F. (2019). Validating microscopic colitis (MC) in Swedish pathology registers. Scandinavian Journal of Gastroenterology
Open this publication in new window or tab >>Validating microscopic colitis (MC) in Swedish pathology registers
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is a diagnosis which relies on histopathologic criteria. This report examines the validity of having a diagnosis of MC in Swedish pathology registers.

METHODS: We reviewed patient charts from 215 randomly selected individuals from 15 pathology departments in five healthcare regions in Sweden with a relevant histopathology code for MC on colon biopsies. Information on clinical symptoms and laboratory data were obtained from medical chart review. We obtained sufficient data on 211 individuals for calculating positive predictive values (PPVs) for MC.

RESULTS: In total, 200/211 patients with a histopathology diagnosis of MC were confirmed as also having a clinical diagnosis of MC after chart review, yielding a PPV of 95% (95%CI =91-97%). The PPV for CC was 95% (95%CI =87-98%) and 85% for LC (95%CI =78-90%). The median age at biopsy was 67 years (range 17-90 years), and 72% (n = 154) were women. The most common symptoms in patients with MC histopathology were diarrhea (96% of patients), weight loss (24%) and abdominal pain (13%). Four percent (4/111) of patients with available data on stool culture were positive for gastrointestinal pathogens (none had Clostridium difficile). In 81 patients with available celiac serology, five (6%) were positive. Twenty-six percent of all patients had at least one other autoimmune disease, the most frequent being hypothyroidism (8%) and celiac disease (6%).

CONCLUSIONS: This study found a high validity for MC as recorded in Swedish pathology registers.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Microscopic colitis, collagenous colitis, histopathology, lymphocytic colitis, validation
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-71183 (URN)10.1080/00365521.2018.1543446 (DOI)30600733 (PubMedID)
Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-01-09Bibliographically approved
Rundquist, S., Eriksson, C., Nilsson, L., Angelison, L., Jäghult, S., Björk, J., . . . Halfvarson, J. (2018). Clinical effectiveness of golimumab in Crohn's disease: an observational study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG).. Scandinavian Journal of Gastroenterology, 1-7
Open this publication in new window or tab >>Clinical effectiveness of golimumab in Crohn's disease: an observational study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG).
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, p. 1-7Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: The effectiveness of golimumab in Crohn's disease (CD) is largely unknown as it is not approved for the treatment of the disease. We aimed to identify the population of CD patients treated with golimumab in Sweden, to assess the effectiveness of golimumab (defined as the drug retention rate), and to identify predictors of drug discontinuation.

METHODS: Patients with CD who received at least one injection of golimumab were identified through the Swedish National Quality Registry for Inflammatory Bowel Disease, which includes prospectively collected clinical information. Cox regression models were used to identify predictors of golimumab discontinuation.

RESULTS: The study cohort involved 94 patients of whom the majority (96.8%) had previously discontinued at least one anti-tumour necrosis factor (anti-TNF) agent. The drug retention rate at 12 weeks was 85.1%. Predictors of golimumab discontinuation at 12 weeks were previous surgery (adjusted HR = 7.52, 95% CI: 1.12-50.36), concomitant corticosteroid use at baseline (adjusted HR = 5.70, 95% CI: 1.13-28.68) and female sex (adjusted HR = 6.59; 95% CI: 1.04-41.62). The median duration of follow-up was 89 (IQR: 32-158) weeks. The drug retention at the most recent follow-up was 35.1%. Predictors of golimumab discontinuation at the most recent follow-up were corticosteroid use at baseline (adjusted HR = 2.60, 95% CI: 1.17-5.79) and female sex (adjusted HR = 2.24; 95% CI: 1.19-4.23).

CONCLUSION: Patients with CD treated with golimumab were a treatment-refractory group. Despite this, more than one-third of the patients appeared to have had clinical benefit after a median follow-up of more than 1.5 years.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Crohn’s disease, Golimumab, IBD, SWIBREG, biological treatment
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-69893 (URN)10.1080/00365521.2018.1519597 (DOI)30353751 (PubMedID)
Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2018-11-07Bibliographically approved
Eriksson, C., Bergemalm, D., Vigren, L., Nilsson, L., Visuri, I., Hjortswang, H., . . . Halfvarson, J. (2018). Clinical effectiveness of golimumab: Interim analysis of the observational study of patients with ulcerative colitis on golimumab in the Swedish National Quality Registry for IBD-GO-SWIBREG. Paper presented at 13th Congress of ECCO – European Crohn’s and Colitis Organisation, Vienna, Austria, February 14-17, 2018. Journal of Crohn's & Colitis, 12(Suppl. 1), S409-S410
Open this publication in new window or tab >>Clinical effectiveness of golimumab: Interim analysis of the observational study of patients with ulcerative colitis on golimumab in the Swedish National Quality Registry for IBD-GO-SWIBREG
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S409-S410Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66750 (URN)000427318901372 ()
Conference
13th Congress of ECCO – European Crohn’s and Colitis Organisation, Vienna, Austria, February 14-17, 2018
Note

Funding Agency:

MSD

Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-08-31Bibliographically approved
Eriksson, C., Rundquist, S., Lykiardopoulos, V., Karlen, P., Grip, O., Söderman, C., . . . Halfvarson, J. (2018). Clinical effectiveness of vedolizumab: Interim analysis of the Swedish observational study on vedolizumab assessing effectiveness and healthcare resource utilisation in patients with Crohn's disease (SVEAH CD). Journal of Crohn's & Colitis, 12(Suppl. 1), S494-S495
Open this publication in new window or tab >>Clinical effectiveness of vedolizumab: Interim analysis of the Swedish observational study on vedolizumab assessing effectiveness and healthcare resource utilisation in patients with Crohn's disease (SVEAH CD)
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S494-S495Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66751 (URN)000427318902141 ()
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-08-30Bibliographically approved
Eriksson, C., Rundquist, S., Lykiardopoulos, V., Karlen, P., Grip, O., Söderman, C., . . . Halfvarson, J. (2018). Clinical effectiveness of vedolizumab: Interim analysis of the Swedish observational study on vedolizumab assessing effectiveness and healthcare resource utilisation in patients with ulcerative colitis (SVEAH UC). Journal of Crohn's & Colitis, 12(Suppl. 1), S382-S383
Open this publication in new window or tab >>Clinical effectiveness of vedolizumab: Interim analysis of the Swedish observational study on vedolizumab assessing effectiveness and healthcare resource utilisation in patients with ulcerative colitis (SVEAH UC)
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S382-S383Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66753 (URN)000427318901324 ()
Note

Funding Agency:

Takeda

Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-08-30Bibliographically approved
Siegel, C. A., Whitman, C. B., Spiegel, B. M. R., Feagan, B., Sands, B., Loftus, E. V., . . . Peyrin-Biroulet, L. (2018). Development of an index to define overall disease severity in IBD. Gut, 67(2), 244-254
Open this publication in new window or tab >>Development of an index to define overall disease severity in IBD
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 2, p. 244-254Article in journal (Refereed) Published
Abstract [en]

Background and aim: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.

Methods: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.

Results: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.

Conclusions: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

Place, publisher, year, edition, pages
London, United Kingdom: BMJ Publishing Group Ltd, 2018
Keywords
Crohn's Disease, IBD, Ulcerative Colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-53356 (URN)10.1136/gutjnl-2016-312648 (DOI)000419604800009 ()27780886 (PubMedID)
Note

Funding Agencies:

AbbVie  

Tillotts 

Available from: 2016-11-02 Created: 2016-11-02 Last updated: 2018-09-06Bibliographically approved
Carstens, A., Roos, A., Andreasson, A., Magnuson, A., Agréus, L., Halfvarson, J. & Engstrand, L. (2018). Differential clustering of faecal and mucosa-associated microbiota in healthy individuals. Journal of Digestive Diseases, 19(12), 745-752
Open this publication in new window or tab >>Differential clustering of faecal and mucosa-associated microbiota in healthy individuals
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2018 (English)In: Journal of Digestive Diseases, ISSN 1751-2972, E-ISSN 1751-2980, Vol. 19, no 12, p. 745-752Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Faecal samples are often used to characterise gut microbiota, since they are easily collected. However, whether or not the faecal microbiota differ from the mucosa-associated microbiota remains largely unknown. This may be specifically relevant in conditions that are characterised by complex mucosal microbe-host interactions, such as Crohn's disease. We aimed to determine the degree of agreement between faecal and mucosal microbiota profiles in healthy individuals, using two commonly used collection procedures.

MATERIAL AND METHODS: The gut microbiota composition of faecal samples (sent at ambient temperature before storage at -70°C) and of colonic biopsies (obtained at endoscopy and immediately stored at -70°C) was determined by sequencing the 16S rRNA gene. Thirty-one randomly selected healthy individuals from the population-based colonoscopy (Popcol) study were included.

RESULTS: Faecal samples were characterised by a reduced degree of richness (p<0.0001) and diversity (p=0.016), and also differences in several phyla, including a lower relative abundance of Proteobacteria (p<0.0001) and Verrucomicrobia (p=0.008) than in biopsies. Only 3 of 30 individuals had a similar faecal and mucosal microbiota profile, based on weighted UniFrac analysis. A difference in Crohn's disease dysbiosis-associated bacteria was observed, including a lower relative abundance of Faecalibacterium (p=0.004) and a higher relative abundance of Ruminococcus (p=0.001) in faeces than in biopsies.

CONCLUSIONS: Analysis of faecal samples that have been transported at ambient temperature does not adequately reflect the colonic mucosa-associated microbiota in healthy individuals. These findings have implications for the interpretation of the previous literature, and may be specifically relevant to studies on Crohn's disease.

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Asia, 2018
Keywords
Mucosa-associated microbiota, faecal microbiota
National Category
Microbiology in the medical area Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-70345 (URN)10.1111/1751-2980.12688 (DOI)30467977 (PubMedID)
Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2019-01-14Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0122-7234

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