| 1. |
- Andersson, Per, et al.
(författare)
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Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 127
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Tidskriftsartikel (refereegranskat)abstract
- Background: Corticosteroids, immunomodulators (IM) and tumour necrosis factor antagonists (anti-TNF) are commonly used in the treatment of inflammatory bowel disease (IBD) but they also supress the defence against infectious disease. The aim of this study was to analyse the incidence of infectious events in patients with IBD and the association to concomitant medical therapy.Methods: We performed a retrospective medical chart review of patients with IBD aged 18–65 years included in the Swedish Registry of Inflammatory Bowel Disease in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period 01 January 2006, to 31 January 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection.Results: During a period of 5,120 observation-years, we observed 1,394 events in 593 patients. The mean number of infectious events per 100 person-years was 27.2 (standard deviation [SD]: 0.46). There were no differences in mean incidence rates between patients treated with no immunosuppression (23.0 events per 100 person-years, SD: 50.4), patients treated with IM monotherapy (27.6 events per 100 person-years, SD: 49.9), patients treated with anti-TNF monotherapy (34.3 events per 100 person-years, SD: 50.1) and patients on combination therapy (22.5 events per 100-person-years, SD: 44.2). In a multivariate logistic regression, female gender (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI]: 1.49–3.37) and combination therapy (AOR: 3.46; 95% CI: 1.52–7.85) were associated with higher risks of infection (>32 events per 100 person years). Also, patients treated with any immunosuppression treatment for 25–75% (AOR: 2.29; 95% CI: 1.21–4.34) and for >75% (AOR: 1.93; 95% CI: 1.19–3.12) of the observation period were at higher risks compared to patients treated with immunosuppression <25% of the observation period.Conclusion: We observed no significant difference in risk for infections between patients on monotherapy with IM or anti-TNF and patients with low use of immunosuppression, but there was a significant risk for combination therapy.
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| 2. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 3. |
- Bjurström, Oliver, et al.
(författare)
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The association between drugs and repeated treatment with budesonide in patients with microscopic colitis : a retrospective observational study
- 2024
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Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 17:January-December
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC).Objectives: We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC.Design: Retrospective observational study.Methods: All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied.Results: Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th–75th percentile 4–10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06–12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39–2.90), PPIs (OR: 1.09, 95% CI: 0.45–2.63), SSRI (OR: 1.41, 95% CI: 0.82–2.44), or statins (OR: 0.83, 95% CI: 0.35–1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis.Conclusion: The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins.
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| 4. |
- Blad, Nathalie, et al.
(författare)
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Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer : a retrospective study
- 2022
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Faecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice.Methods: In two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women).Results: Ninety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27–9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01–14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04–5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03–12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24–1.52).Conclusions: Elevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.
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| 5. |
- Bodecker-Zingmark, L., et al.
(författare)
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Anti-Saccharomyces Cerevisiae antibodies are only modestly more common in subjects later developing Crohn's disease
- 2023
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Ingår i: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 68, s. 608-615
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.Aims: To study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.Methods: Antibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.Results: The mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.Conclusions: We found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.
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| 6. |
- Boks, Marije, et al.
(författare)
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Increased incidence of late-onset inflammatory bowel disease and microscopic colitis after a Cryptosporidium hominis outbreak
- 2022
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis Group. - 0036-5521 .- 1502-7708. ; 57:12, s. 1443-1449
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In 2010, 27,000 inhabitants (45% of the population) of Östersund, Sweden, contracted clinical cryptosporidiosis after drinking water contaminated with Cryptosporidium hominis. After the outbreak, local physicians perceived that the incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC), Crohn's disease (CD), and IBD-unclassified, and microscopic colitis (MC) increased. This study assessed whether this perception was correct.MATERIALS AND METHODS: This observational study included adult patients (≥18 years old) from the local health care region who were diagnosed with pathology-confirmed IBD or MC during 2006-2019. We collected and validated the diagnosis, date of diagnosis, age at diagnosis, and sex from the Swedish quality register SWIBREG and electronic patient records. Population data were collected from Statistics Sweden. The incidences for 2006-2010 (pre-outbreak) and 2011-2019 (post-outbreak) were evaluated by negative binomial regression analysis and presented as incidence rate ratios (IRRs). Data were analyzed for IBD, for UC and CD separately, and MC.RESULTS: During the study period, we identified 410 patients with new onset IBD and 155 new cases of MC. Overall, we found a trend toward an increased incidence of IBD post-outbreak (IRR 1.39, confidence interval (CI) 0.99-1.94). In individuals ≥40 years old, the post-outbreak incidence significantly increased for IBD (IRR 1.69, CI 1.13-2.51) and CD (IRR 2.23, CI 1.08-4.62). Post-outbreak incidence of MC increased 6-fold in all age groups (IRR 6.43, CI 2.78-14.87).CONCLUSIONS: The incidence of late-onset IBD and MC increased after the Cryptosporidium outbreak. Cryptosporidiosis may be an environmental risk factor for IBD and MC.
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| 7. |
- Boks, Marije, et al.
(författare)
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Persisting symptoms after Cryptosporidium hominis outbreak : a 10-year follow-up from Östersund, Sweden
- 2023
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Ingår i: Parasitology Research. - : Springer Nature. - 0932-0113 .- 1432-1955. ; 122:7, s. 1631-1639
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Tidskriftsartikel (refereegranskat)abstract
- In late 2010, an outbreak of Cryptosporidium hominis affected 27,000 inhabitants (45%) of Östersund, Sweden. Previous research shows that abdomen and joint symptoms commonly persist up to 5 years post-infection. It is unknown whether Cryptosporidium is associated with sequelae for a longer duration, how persisting symptoms present over time, and whether sequelae are associated with prolonged infection. In this prospective cohort study, a randomly selected cohort in Östersund was surveyed about cryptosporidiosis symptoms in 2011 (response rate 69.2%). A case was defined as a respondent reporting new diarrhoea episodes during the outbreak. Follow-up questionnaires were sent after 5 and 10 years. Logistic regressions were used to examine associations between case status and symptoms reported after 10 years, with results presented as adjusted odds ratios (aOR) with 95% confidence intervals. Consistency of symptoms and associations with case status and number of days with symptoms during outbreak were analysed using X 2 and Mann–Whitney U tests. The response rate after 10 years was 74% (n = 538). Case status was associated with reporting symptoms, with aOR of ~3 for abdominal symptoms and ~2 for joint symptoms. Cases were more likely to report consistent symptoms. Cases with consistent abdominal symptoms at follow-up reported 9.2 days with symptoms during the outbreak (SD 8.1), compared to 6.6 days (SD 6.1) for cases reporting varying or no symptoms (p = 0.003). We conclude that cryptosporidiosis was associated with an up to threefold risk for reporting symptoms 10 years post-infection. Consistent symptoms were associated with prolonged infection.
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| 8. |
- Brännström, Lisa, et al.
(författare)
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What is the significance of the Hill classification?
- 2023
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Ingår i: Diseases of the esophagus. - : Oxford University Press. - 1120-8694 .- 1442-2050. ; 36:9
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not.
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| 9. |
- Clyne, Naomi, et al.
(författare)
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Njurar
- 2021. - 4:1
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Ingår i: Kliniska Färdigheter : Mötet mellan patient och läkare - Mötet mellan patient och läkare. - 9789144135885 ; , s. 115-126
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Bokkapitel (populärvet., debatt m.m.)
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| 10. |
- Eberhardson, Michael, et al.
(författare)
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Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
- 2022
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Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. Method: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09–1.46; p = 0.002). Conclusion: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.
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