| 1. |
- Alaish, Ram, et al.
(författare)
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Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment
- 2017
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Ingår i: International journal of clinical pharmacology and therapeutics. - : DUSTRI-VERLAG DR KARL FEISTLE. - 0946-1965. ; 55:7, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naive to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naive to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with.MCV = 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naive to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.
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| 2. |
- Andersen, Vibeke, et al.
(författare)
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Fibre intake and the development of inflammatory bowel disease : A European prospective multi-centre cohort study (EPIC-IBD)
- 2018
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 12:2, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.
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| 3. |
- Angelison, Leif, et al.
(författare)
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Long-term outcome of infliximab treatment in chronic active ulcerative colitis : a Swedish multicentre study of 250 patients
- 2017
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell Publishing Inc.. - 0269-2813 .- 1365-2036. ; 45:4, s. 519-532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.
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| 4. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Markers of systemic inflammation in preclinical ulcerative colitis
- 2019
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Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 7:8_suppl, s. 111-111
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Data on the preclinical stage of ulcerative colitis (UC) are sparse. At diagnosis, UC often shows a modest increase in systemic inflammatory markers like C-reactive protein (CRP). However, a subclinical inflammation with elevated levels of CRP and interleukin-6 (IL6) in serum have been observed several years before diagnosis [1]. First-degree relatives, including healthy twin siblings, also display elevated levels of some inflammatory markers as a consequence of shared genetic and environmental risk factors [2]. It is reasonable to believe that the preclinical inflammation, reflecting early pathogenic mechanisms, ultimately leads to a diagnosis of UC.Aim and Method: We aimed to deeper examine the systemic preclinical inflammation in UC using a comprehensive set of protein markers. Cases with UC were identified at clinical follow-up of a prospectively collected population-based cohort of healthy individuals from northern Sweden. Plasma samples from cases and controls were subjected to proximity extension assay for relative quantification of 92 protein markers of inflammation. Results were validated in an inception cohort of treatment naïve, newly diagnosed patients with UC (n=101) vs. healthy controls (n=50). In addition, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of twins with UC (n=41) and matched healthy controls (n=37) were explored.Results: Pre-diagnostic plasma samples from 72 cases who later in life developed UC and 140 controls, matched for gender, age, year of health survey and area of residence, were identified (table 1). Six proteins were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. A receiver-operating curve based prediction model using the six protein markers combined with sex, age, smoking status and time to diagnose was set up for validation. The model discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings vs. healthy controls and four out of six proteins were upregulated similarly as in the pre-diagnostic samples. The relative levels of the six proteins showed an intermediate upregulation in pre-diagnostic samples and samples from healthy twin siblings compared to samples at diagnosis of UC. Only one protein showed a significant correlation with time to diagnosis in the pre-diagnostic samples. Using pathway analysis, the six protein upregulations pointed towards subclinical inflammation in UC being caused by dysregulation of four immune pathways.Conclusions: This is the first comprehensive characterisation of preclinical systemic inflammation in UC. Inflammatory proteins were upregulated several years prior to diagnosis of UC and to some extent these alterations were also seen in healthy twin siblings of UC patients. Characterisation of the preclinical stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.
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| 5. |
- Bonfiglio, F., et al.
(författare)
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Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome
- 2018
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 155:1, s. 168-179
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.
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| 6. |
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| 7. |
- Eklöf, Vincy, 1984-, et al.
(författare)
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Cancer-associated fecal microbial markers in colorectal cancer detection
- 2017
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 141:12, s. 2528-2536
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.
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| 8. |
- Eklöf, Vincy, 1984-, et al.
(författare)
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The Combined Value of Faecal Haemoglobin andCalprotectin in Diagnosis of Colorectal Cancer inSymptomatic Patients Referred to Colonoscopy
- 2019
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Ingår i: Academic Journal of Gastroenterology & Hepatology (AJGH). - San Fransisco : Iris Publishers. ; 1:3, s. 1-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To investigate the diagnostic value of a combined analyses of faecal immunological haemoglobin (FIT) and faecal calprotectin (FC) in detection of colorectal cancer (CRC).Methods: Out-patients (n=1440) referred to the endoscopy unit were analysed for FIT and FC in stool samples collected before the colonoscopy bowel preparation. The samples were collected from one defecation by the patients at home. Patients with IBD were excluded leaving stool samples from 1133 patients for further analyses. FIT was analysed using the immunological Analyse F.O.B Test and FC was analysed using the CALPRO® Calprotectin Elisa Test. Sensitivity and specificity to detect CRC was calculated for the individual tests, as well as for combined FIT/FC tests.Results: Out of the included patients, 38 were diagnosed with CRC, 9 with high grade dysplasia (HGD), and 133 with low grade dysplasia (LGD). FIT was analysed in 673 (59.4%), FC in 1021 (90.1%) and both FIT and FC in 561 (49.5%) patients. A ROC curve analysis showed that the most accurate cut-off level for FC in detecting CRC in our study was 105.5 µg/g. The sensitivity for CRC when using FIT, FC (cut-off > 100 µg/g) and the combination of FIT and FC (at least one positive test) was 65.5%, 74.1% and 94.4%, respectively. The corresponding specificity was 84.8%, 74.9% and 68.3%, respectively.Conclusion: Combined analyses of FIT and FC improved sensitivity for detection of CRC. Further studies in larger cohorts are required to find the optimal cut-off levels for different combinations of tests.
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| 9. |
- Englund, Hanna, et al.
(författare)
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Radiation exposure in patients with inflammatory bowel disease and irritable bowel syndrome in the years 2001-2011
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:3, s. 300-305
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare cumulative ionizing radiation in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) for the years 2001-2011. To study how radiation exposure change over time in patients with newly diagnosed IBD and factors associated with radiation exposure.MATERIAL AND METHODS: All radiological investigations performed between 1 January 2001 and 31 December 2011 were retrospectively recorded in patients with Crohn's disease (CD) (n = 103), ulcerative colitis (UC) (n = 304) and IBS (n = 149). Analyses were done with Mann-Whitney and Chi-Square test.RESULTS: The median total cumulative radiation exposure in mSv for CD (20.0, inter quartile range (IQR) 34.8), UC (7.01, IQR 23.8), IBS (2.71, IQR 9.15) and the proportion of patients who had been exposed for more than 50 mSv during the study period (CD 19%, UC 11%, IBS 3%) were significantly higher in the patients with CD compared to patients with UC (p < .001) and IBS (p < .001), respectively. In turn, patients with UC had significantly higher doses than patients with IBS (p = .005). Risk factors for radiation exposure were female gender (CD), early onset (UC), ileocolonic location (CD), previous surgery (CD and UC), depression (IBS) and widespread pain (IBS). In newly diagnosed CD, there was a significant decline in median cumulative radiation dose in mSv (17.2 vs. 12.0; p = .048) during the study period.CONCLUSIONS: Patients with CD are at greatest risk for high cumulative radiation exposure, but there is a decline in exposure during the late 2000s. Non-colectomized patients with UC and patients with IBS have a relatively low risk of cumulative radiation exposure.
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| 10. |
- Eriksson, Carl, 1981-, et al.
(författare)
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Long-term effectiveness of vedolizumab in inflammatory bowel disease : a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 52:6-7, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index<5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index<3 in ulcerative colitis (UC).Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p<.0001 in both groups). Faecal-calprotectin decreased in CD (p<.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.
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