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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
Keyword
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: 2018-01-19Bibliographically approved
Örtqvist, A. K., Lundholm, C., Halfvarson, J., Ludvigsson, J. F. & Almqvist, C. (2018). Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study. Gut, Article ID gutjnl-2017-314352.
Open this publication in new window or tab >>Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2017-314352Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Earlier studies on antibiotics exposure and development of IBD (Crohn's disease (CD) and ulcerative colitis (UC)) may have been biased by familial factors and gastroenteritis. We aimed to estimate the association between antibiotics during pregnancy or infantile age and very early onset (VEO) IBD.

DESIGN: In this cohort study of 827 239 children born in Sweden between 2006 and 2013, we examined the link between exposure to systemic antibiotics and VEO-IBD (diagnosis <6 years of age), using Cox proportional hazard regression models. Information on antibiotics and IBD was retrieved from the nationwide population-based Swedish Prescribed Drug Register and the National Patient Register. We specifically examined potential confounding from parental IBD and gastroenteritis.

RESULTS: Children exposed to antibiotics during pregnancy were at increased risk of IBD compared with general population controls (adjusted HR (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to 6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72 (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children with gastroenteritis 12 months prior to the first IBD diagnosis retained similar aHR for antibiotics during pregnancy and CD, while the association no longer remained significant for IBD.

CONCLUSION: We found that exposure to antibiotics during pregnancy, but not in infantile age, is associated with an increased risk of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in pregnancy may be due to changes in the microbiota.

Keyword
antibiotics, crohn’s colitis, epidemiology, inflammatory bowel disease, ulcerative colitis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-66361 (URN)10.1136/gutjnl-2017-314352 (DOI)29321166 (PubMedID)
Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-04-09Bibliographically approved
Eriksson, C., Rundquist, S., Cao, Y., Montgomery, S. & Halfvarson, J. (2018). Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study. Gut, Article ID gutjnl-2017-315521.
Open this publication in new window or tab >>Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2017-315521Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.

DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.

RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).

CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
Keyword
6-mercaptopurine, azathioprine, chronic ulcerative colitis, tnf-alpha
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66417 (URN)10.1136/gutjnl-2017-315521 (DOI)29618498 (PubMedID)
Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2018-04-19Bibliographically approved
Everhov, Å. H., Halfvarson, J., Myrelid, P., Sachs, M. C., Nordenvall, C., Söderling, J., . . . Olén, O. (2018). Incidence and Treatment of Patients Diagnosed With Inflammatory Bowel Diseases at 60 Years or Older in Sweden. Gastroenterology, 154(3), 518-528
Open this publication in new window or tab >>Incidence and Treatment of Patients Diagnosed With Inflammatory Bowel Diseases at 60 Years or Older in Sweden
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2018 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 154, no 3, p. 518-528Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS: Diagnosis of inflammatory bowel diseases (IBD) is increasing among elderly persons (60 years or older). We performed a nationwide population-based study to estimate incidence and treatment.

METHODS: We identified all incident IBD cases in Sweden, from 2006 through 2013, using national registers, and up to 10 matched population comparator subjects. We collected data on the patients' health care contacts and estimated incidence rates, health service burden, pharmacologic treatments, extra-intestinal manifestations, and surgeries in relation to age of IBD onset (pediatric, less than 18 years; adults, 18-59 years; elderly, 60 years or older).

RESULTS: Of 27,834 persons diagnosed with incident IBD, 6443 (23%) had a first diagnosis of IBD at 60 years or older, corresponding to an incidence rate of 35/100,000 person-years (10/100,000 person-years for Crohn's disease, 19 /100,000 person-years for ulcerative colitis, and 5/100,000 person-years for IBD unclassified). During a median follow-up period of 4.2 years (range 0-9 years), elderly patients had less IBD-specific outpatient health care but more IBD-related hospitalizations and overall health care use than adult patients with IBD. Compared to patients with pediatric or adult onset, elderly patients used fewer biologics and immunomodulators, but more systemic corticosteroids. Occurrence of extra-intestinal manifestations was similar in elderly and adult patients, but bowel surgery was more common in the elderly (13% after 5 years vs 10% in adults) (P<.001). The absolute risk of bowel surgery was higher in the elderly than in the general population, but in relative terms, the risk increase was larger in younger age groups.

CONCLUSIONS: In a nationwide cohort study in Sweden, we associated diagnosis of IBD at age 60 years or older with a lower use of biologics and immunomodulators but higher absolute risk of bowel surgery, compared to diagnosis at a younger age. The large differences in pharmacological treatment of adults and elderly patients are not necessarily due to a milder course of disease and warrant further investigation.

Place, publisher, year, edition, pages
Saunders Elsevier, 2018
Keyword
CD, UC, age differences, bowel resection, colectomy
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-62953 (URN)10.1053/j.gastro.2017.10.034 (DOI)000424741500025 ()29102619 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Research CouncilSwedish Cancer Society
Note

Funding Agencies:

Swedish Medical Society (fund for research in gastroenterology)  

Swedish Medical Society (Ihre foundation)  

Mag-tarmfonden  

Jane and Dan Olsson foundation  

Mjölkdroppen foundation 

Bengt Ihre research fellowship in gastroenterology  

Karolinska Institutet foundations  

Stockholm County Council  

Karolinska Institutet (ALF)  

Janssen Pharmaceutica NV 

Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2018-03-12Bibliographically approved
Halfvarson, J., Cummings, F., Grip, O. & Savoye, G. (2018). Inflammatory bowel disease registries for collection of patient iron parameters in Europe. World Journal of Gastroenterology, 24(10), 1063-1071
Open this publication in new window or tab >>Inflammatory bowel disease registries for collection of patient iron parameters in Europe
2018 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 24, no 10, p. 1063-1071Article, review/survey (Refereed) Published
Abstract [en]

Iron deficiency without anemia and iron deficiency anemia are common and frequently overlooked complications of inflammatory bowel disease. Despite the frequency and impact of iron deficiency in inflammatory bowel disease, there are gaps in our understanding about its incidence, prevalence and natural history and, consequently, patients may be undertreated. Medical registries have a key role in collecting data on the disease's natural history, the safety and effectiveness of drugs in routine clinical practice, and the quality of care delivered by healthcare services. Even though iron deficiency impacts inflammatory bowel disease patients and healthcare systems substantially, none of the established European inflammatory bowel disease registries systematically collects information on iron parameters and related outcomes. Collection of robust iron parameter data from patient registries is one way to heighten awareness about the importance of iron deficiency in this disease and to generate data to improve the quality of patient care, patient outcomes, and thus quality of life. This objective could be achieved through collection of specific laboratory, clinical, and patient-reported measurements that could be incorporated into existing registries. This review describes the status of current European inflammatory bowel disease registries and the data they generate, in order to highlight their potential role in collecting iron data, to discuss how such information gathering could contribute to our understanding of iron deficiency anemia, and to provide practical information in regard to the incorporation of accumulated iron parameter data into registries.

Place, publisher, year, edition, pages
Baishideng Publishing Group, 2018
Keyword
Anemia, Iron deficiency, Registries, Inflammatory bowel disease, Patient care
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-66264 (URN)10.3748/wjg.v24.i10.1063 (DOI)000427449300001 ()29563751 (PubMedID)2-s2.0-85043681547 (Scopus ID)
Note

Funding Agency:

Vifor Pharma

Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Burisch, J., Kiudelis, G., Kupcinskas, L., Kievit, H. A., Andersen, K. W., Andersen, V., . . . Munkholm, P. (2018). Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study. Gut
Open this publication in new window or tab >>Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study
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2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD).

DESIGN: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

RESULTS: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).

CONCLUSION: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
Keyword
Crohn’s disease, epidemiology, surgery for Ibd
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-64714 (URN)10.1136/gutjnl-2017-315568 (DOI)29363534 (PubMedID)
Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-03-02Bibliographically approved
Melinder, C., Hiyoshi, A., Kasiga, T., Halfvarson, J., Fall, K. & Montgomery, S. (2018). Resilience to stress and risk of gastrointestinal infections. European Journal of Public Health (2), 364-369
Open this publication in new window or tab >>Resilience to stress and risk of gastrointestinal infections
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2018 (English)In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, no 2, p. 364-369Article in journal (Refereed) Published
Abstract [en]

Background: Exposure to psychological stress can elicit a physiological response that may influence characteristics of the gastrointestinal mucosa, including increased intestinal permeability, in turn possibly increasing susceptibility to gastrointestinal infections. We investigated whether low stress resilience in adolescence is associated with an 'increased' risk of gastrointestinal infections in subsequent adulthood.

Methods: Data were provided by Swedish registers for a cohort of 237 577 men who underwent military conscription assessment in late adolescence (1969-76). As part of the assessment procedure, certified psychologists evaluated stress resilience through semi-structured interviews. The cohort was followed from conscription assessment until 31 December 2009 (up to age 57 years). Cox regression assessed the association of stress resilience with gastrointestinal infections (n = 5532), with adjustment for family background measures in childhood and characteristics in adolescence. Peptic ulcer disease (PUD) in adulthood was modelled as a time-dependent covariate.

Results: Compared with high stress resilience, lower stress resilience was associated with a 'reduced' risk of gastrointestinal infections after adjustment for family background in childhood, characteristics in adolescence and PUD in adulthood, with hazard ratios (and 95% confidence intervals) of 0.88 (0.81-0.97) and 0.83 (0.77-0.88) for low and moderate stress resilience, respectively.

Conclusion: Lower stress resilience in adolescence is associated with reduced risk of gastrointestinal infections in adulthood, rather than the hypothesized increased risk.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2018
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-62194 (URN)10.1093/eurpub/ckx179 (DOI)29048469 (PubMedID)
Available from: 2017-11-09 Created: 2017-11-09 Last updated: 2018-04-10Bibliographically approved
Eriksson, C., Rundquist, S., Lykiardopoulos, B., Karlén, P., Grip, O., Söderman, C., . . . Halfvarson, J. (2017). A Swedish observational study (SVEAH) on vedolizumab assessing effectiveness and healthcare resource utilization in patients with inflammatory bowel disease. Journal of Crohn's & Colitis, 11(Suppl. 1), S262-S263
Open this publication in new window or tab >>A Swedish observational study (SVEAH) on vedolizumab assessing effectiveness and healthcare resource utilization in patients with inflammatory bowel disease
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S262-S263Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57782 (URN)10.1093/ecco-jcc/jjx002.489 (DOI)000398606900471 ()28172603 (PubMedID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2018-04-19Bibliographically approved
Kuja-Halkola, R., Lebwohl, B., Halfvarson, J., Emilsson, L., Magnusson, P. K. & Ludvigsson, J. F. (2017). Birth weight, sex, and celiac disease: a nationwide twin study. Clinical Epidemiology, 9, 567-577
Open this publication in new window or tab >>Birth weight, sex, and celiac disease: a nationwide twin study
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2017 (English)In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, p. 567-577Article in journal (Refereed) Published
Abstract [en]

Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.

Materials and methods: Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.

Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD-non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97-1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11-2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.

Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.

Place, publisher, year, edition, pages
DOVE Medical Press Ltd., 2017
Keyword
autoimmune, gestational age, gluten, registries, risk factors, twins
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-62848 (URN)10.2147/CLEP.S149181 (DOI)000414865700001 ()
Funder
Swedish Society of MedicineSwedish Research Council
Available from: 2017-11-27 Created: 2017-11-27 Last updated: 2017-11-29Bibliographically approved
Burisch, J., Halfvarson, J., Kupcinskas, L., Hernandez, V., Kaimakliotis, I., Valpiani, D., . . . Munkholm, P. (2017). Change in Crohn's disease behavior in a prospective European population-based inception cohort - the ECCO-EpiCom cohort. Journal of Crohn's & Colitis, 11(Suppl. 1), S452-S453
Open this publication in new window or tab >>Change in Crohn's disease behavior in a prospective European population-based inception cohort - the ECCO-EpiCom cohort
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S452-S453Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57779 (URN)10.1093/ecco-jcc/jjx002.851 (DOI)000398606901261 ()28175198 (PubMedID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2017-10-18Bibliographically approved
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