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1.
  • Andersson, Per, et al. (författare)
  • Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease
  • 2022
  • Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 127
  • 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)
  • Systemic Inflammation in Preclinical Ulcerative Colitis
  • 2021
  • Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
  • 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)
  • The association between drugs and repeated treatment with budesonide in patients with microscopic colitis : a retrospective observational study
  • 2024
  • Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 17:January-December
  • 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)
  • Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer : a retrospective study
  • 2022
  • Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 22:1
  • 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)
  • Anti-Saccharomyces Cerevisiae antibodies are only modestly more common in subjects later developing Crohn's disease
  • 2023
  • Ingår i: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 68, s. 608-615
  • 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)
  • Increased incidence of late-onset inflammatory bowel disease and microscopic colitis after a Cryptosporidium hominis outbreak
  • 2022
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis Group. - 0036-5521 .- 1502-7708. ; 57:12, s. 1443-1449
  • 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)
  • Persisting symptoms after Cryptosporidium hominis outbreak : a 10-year follow-up from Östersund, Sweden
  • 2023
  • Ingår i: Parasitology Research. - : Springer Nature. - 0932-0113 .- 1432-1955. ; 122:7, s. 1631-1639
  • 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)
  • What is the significance of the Hill classification?
  • 2023
  • Ingår i: Diseases of the esophagus. - : Oxford University Press. - 1120-8694 .- 1442-2050. ; 36:9
  • 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)
  • Njurar
  • 2021. - 4:1
  • Ingår i: Kliniska Färdigheter : Mötet mellan patient och läkare - Mötet mellan patient och läkare. - 9789144135885 ; , s. 115-126
  • Bokkapitel (populärvet., debatt m.m.)
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10.
  • Eberhardson, Michael, et al. (författare)
  • Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates
  • 2022
  • Ingår i: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:4, s. 470-483
  • 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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11.
  • Gensmyr-Singer, Helena, et al. (författare)
  • The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease : a retrospective observational study
  • 2024
  • Ingår i: Therapeutic Advances in Gastroenterology. - : Sage Publications. - 1756-283X .- 1756-2848. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Thiopurines are commonly used to treat inflammatory bowel disease but withdrawal due to side effects are common. Thioguanine has been suggested to be better tolerated than conventional thiopurines. Objectives: We studied drug-survival of low dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines. Design: Retrospective observational study.Methods: All patients born 1956 and later, and who at least once started thiopurine treatment between 2006 and 2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. The Mantel–Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels were registered for the first 5 years of treatment.Results: In the study population, there was 379 initiated thiopurine treatments (210 for Crohn’s disease and 169 for ulcerative colitis) in 307 patients with inflammatory bowel disease (IBD). Low-dose thioguanine (median dose 11 mg; 25–75th percentile 7–19 mg) had been initiated in 31 patients. Overall, when including all thiopurine attempts, thioguanine had the longest drug-survival [Mantel–Cox rank test: thioguanine versus azathioprine p = 0.014; thioguanine versus 6-mercaptopurine (6-MP) p < 0.001]. For second-line thiopurine treatment thioguanine had longer drug-survival than 6-MP (Mantel–Cox rank test: p = 0.006). At 60 months, 86% of the patients who started low-dose thioguanine were still on treatment compared to 42% of the patients who started 6-MP (p = 0.022). The median 6-thioguanine nucleotide levels in patients treated with thioguanine was 364 pmol/8 × 108. Patients on thioguanine treatment showed significantly lower values of median mean corpuscular volume at follow-up than patients treated with azathioprine and 6-MP. Patients treated with 6-MP showed significantly lower levels of FC in the third year of treatment compared to patient treated with azathioprine (59 versus 109 µg/g; p = 0.023), but there was no significant difference in FC levels for thioguanine compared to azathioprine (50 versus 109 µg/g; p = 0.33).Conclusion: Treatment with a low dose of thioguanine is well-tolerated in patients with IBD and had a significantly higher drug-survival than conventional thiopurines.
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12.
  • Gensmyr-Singer, Helena, et al. (författare)
  • What happens to patients with inflammatory bowel disease who are intolerant to thiopurines?
  • 2024
  • Ingår i: Inflammatory Intestinal Diseases. - : S. Karger. - 2296-9403 .- 2296-9365. ; 9:1, s. 135-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The clinical consequences for patients with inflammatory bowel disease (IBD) who stop treatment owing to side effects have not been fully investigated.Methods: This retrospective observational study aimed to compare patients who discontinued thiopurine treatment due to side effects with those who tolerated thiopurine treatment in the use of other IBD drugs, surgery, and fecal calprotectin values in the first 5 years after the start of thiopurine treatment.Results: The proportion of patients with IBD who initiated thiopurine treatment at our clinic was 44% (32% ulcerative colitis and 64% Crohn’s disease) and 31% (n = 94) of those patients had to stop thiopurine treatment within 5 years due to side effects. Patients who discontinued thiopurine treatment due to intolerance were significantly older (median age 33 vs. 27 years, p = 0.003), significantly more often used prednisolone (89 vs. 76%, p = 0.009), and used to a lesser extent TNF inhibitors at the start of thiopurine treatment (3% vs. 9%, p = 0.062). Budesonide treatment and non-TNF inhibitor second-line therapy were significantly more commonly used in patients who discontinued thiopurine treatment owing to side effects, but there were no statistically significant differences in the use of other treatments. The proportion of patients with a median FC >200 μg/g was significantly higher during follow-up in patients with UC who discontinued thiopurine treatment owing to side effects.Conclusions: Patients who discontinued thiopurines owing to side effects were prescribed more budesonide and non-TNF inhibitor second-line therapy, but there were no differences in the use of TNF inhibitors, prednisolone, or surgery.
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13.
  • Holmgren, Johanna, et al. (författare)
  • The Risk of Serious Infections Before and After Anti-TNF Therapy in Inflammatory Bowel Disease : A Retrospective Cohort Study
  • 2023
  • Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press. - 1078-0998 .- 1536-4844. ; 19:3, s. 339-348
  • Tidskriftsartikel (refereegranskat)abstract
    • Lay Summary: The incidence rate of serious infection among inflammatory bowel disease patients did not increase with anti-TNF therapy compared with 1 year before treatment start. A decrease in incidence rate could be seen more than 1 year after initiation of anti-TNF.Background: Serious infections have been observed in patients with inflammatory bowel disease (IBD) on anti-TNF use-but to what extent these infections are due to anti-TNF or the disease activity per se is hard to disentangle. We aimed to describe how the rates of serious infections change over time both before and after starting anti-TNF in IBD.Methods: Inflammatory bowel disease patients naive to anti-TNF treatment were identified at 5 centers participating in the Swedish IBD Quality Register, and their medical records examined in detail. Serious infections, defined as infections requiring in-patient care, the year before and after the start of anti-TNF treatment were evaluated.Results: Among 980 patients who started their first anti-TNF therapy between 1999 and 2016, the incidence rate of serious infections was 2.19 (95% CI,1.43-3.36) per 100 person years the year before and 2.11 (95% CI, 1.33-3.34) per 100 person years 1 year after treatment start. This corresponded to an incidence rate ratio 1 year after anti-TNF treatment of 0.97 (95% CI, 0.51-1.84). Compared with before anti-TNF therapy, the incidence of serious infection was significantly decreased more than 1 year after treatment (incidence rate ratio 0.56; 95% CI, 0.33-0.95; P = .03).Conclusions: In routine clinical practice in Sweden, the incidence rate of serious infection among IBD patients did not increase with anti-TNF therapy. Instead, serious infections seemed to decrease more than 1 year after initiation of anti-TNF treatment.
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14.
  • Hovstadius, Henrik, et al. (författare)
  • Elevated Faecal Calprotectin in Patients with a Normal Colonoscopy : Does It Matter in Clinical Practice? A Retrospective Observational Study
  • 2021
  • Ingår i: Inflammatory Intestinal Diseases. - : S. Karger. - 2296-9403 .- 2296-9365. ; 6, s. 101-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Faecal calprotectin (FC) is commonly used as a diagnostic tool for patients with gastrointestinal (GI) symptoms. However, there is uncertainty in daily clinical practice how to interpret an elevated FC in patients with a normal colonoscopy. We investigated if patients with a normal colonoscopy but with an elevated FC more often were diagnosed with a GI disease in a 3-year follow-up period.Methods: Patients referred for colonoscopy (n = 1,263) to the Umeå University Hospital endoscopy unit between 2007 and 2013 performed a FC test (CALPRO®) on the day before bowel preparation. A medical chart review was performed on all patients who had normal findings on their colonoscopy (n = 585, median age 64 years).Results: Thirty-four percent of the patients (n = 202) with normal colonoscopy had elevated FC (>50 μg/g), and these patients were more frequently diagnosed with upper GI disease during the follow-up period than patients with normal FC levels (9.9 vs. 4.7%; p = 0.015). The upper GI diseases were mainly benign (i.e., gastritis). In a binary logistic regression analysis controlling for age, gender, nonsteroid anti-inflammatory drug use, and proton-pump inhibitor use, there was no difference for a new diagnosis of upper GI disease in the follow-up period (multivariate OR 1.70; 95% CI: 0.77–3.74). There was no difference in a new diagnosis of lower GI disease (6.4 vs. 5.2%; p = 0.545) or cardiovascular disease/death (multivariate OR 1.68; 95% CI: 0.83–3.42) in the follow-up period between patients with elevated versus normal FC levels.Conclusions: In patients with a normal colonoscopy, a simultaneously measured increased FC level was not associated with an increased risk for significant GI disease during a follow-up period of 3 years.
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15.
  • Högberg, Cecilia, et al. (författare)
  • Patient-reported and doctor-reported symptoms when faecal immunochemical tests are requested in primary care in the diagnosis of colorectal cancer and inflammatory bowel disease : a prospective study
  • 2020
  • Ingår i: BMC Family Practice. - : BioMed Central. - 1471-2296. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rectal bleeding and a change in bowel habits are considered to be alarm symptoms for colorectal cancer and they are also common symptoms for inflammatory bowel disease. However, most patients with these symptoms do not have any of these diseases. Faecal immunochemical tests (FITs) for haemoglobin are used as triage tests in Sweden and other countries but little is known about the symptoms patients have when FITs are requested.Objective: Firstly, to determine patients’ symptoms when FITs are used as triage tests in primary care and whether doctors record the symptoms that patients report, and secondly to evaluate the association between symptoms, FIT results and possible prediction of colorectal cancer or inflammatory bowel disease.Methods and materials: This prospective study included 364 consecutive patients for whom primary care doctors requested a FIT. Questionnaires including gastrointestinal symptoms were completed by patients and doctors.Results: Concordance between symptoms reported from patients and doctors was low. Rectal bleeding was recorded by 43.5% of patients versus 25.6% of doctors, FITs were negative in 58.3 and 52.7% of these cases respectively. The positive predictive value (PPV) of rectal bleeding recorded by patients for colorectal cancer or inflammatory bowel disease was 9.9% (95% confidence interval [CI] 5.2–14.7); for rectal bleeding combined with a FIT the PPV was 22.6% (95% CI 12.2–33.0) and the negative predictive value (NPV) was 98.9% (95% CI 96.7–100). For patient-recorded change in bowel habits the PPV was 6.1% (95% CI 2.4–9.8); for change in bowel habits combined with a FIT the PPV was 18.2% (95% CI 9.1–30.9) and the NPV 100% (95% CI 90.3–100).Conclusions: Doctors should be aware that, during consultations, they do not record all symptoms experienced by patients. FITs requested in primary care, when found positive, may potentially be of help in prioritising referrals, also when patients present with rectal bleeding or change in bowel habits.
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16.
  • Karling, Pontus, et al. (författare)
  • Det svårare samtalet
  • 2021. - 4
  • Ingår i: Kliniska färdigheter. - Lund : Studentlitteratur AB. - 9789144135885 ; , s. 39-44
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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17.
  • Karling, Pontus, et al. (författare)
  • Samtalet mellan patient och läkare
  • 2021. - 4
  • Ingår i: Kliniska färdigheter. - Lund : Studentlitteratur AB. - 9789144135885 ; , s. 29-33
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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18.
  • Larsson, Viktoria, et al. (författare)
  • Long-term postoperative opioid prescription after cholecystectomy or gastric by-pass surgery : a retrospective observational study
  • 2021
  • Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 21:3, s. 569-576
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Opioids are commonly prescribed post-surgery. We investigated the proportion of patients who were prescribed any opioids 6–12 months after two common surgeries – laparoscopic cholecystectomy and gastric by-pass (GBP) surgery. A secondary aim was to examine risk factors prior to surgery associated with the prescription of any opioids after surgery. Methods: We performed a retrospective observational study on data from medical records from patients who underwent cholecystectomy (n=297) or GBP (n=93) in 2018 in the Region of Västerbotten, Sweden. Data on prescriptions for opioids and other drugs were collected from the patients` medical records. Results: There were 109 patients (28%) who were prescribed opioids after discharge from surgery but only 20 patients (5%) who still received opioid prescriptions 6–12 months after surgery. All 20 of these patients had also been prescribed opioids within three months before surgery, most commonly for back and joint pain. Only 1 out of 56 patients who were prescribed opioids preoperatively due to gallbladder pain still received prescriptions for opioids 6–12 months after surgery. Although opioid use in the early postoperative period was more common among patients who underwent cholecystectomy, the patients who underwent GBP were more prone to be “long-term” users of opioids. In the patients who were prescribed opioids within three months prior to surgery, 8 out of 13 patients who underwent GBP and 12 of the 96 patients who underwent cholecystectomy were still prescribed opioids 6–12 months after surgery (OR 11.2; 95% CI 3.1–39.9, p=0,0002). Affective disorders were common among “long-term” users of opioids and prior benzodiazepine and amitriptyline use were significantly associated with “long-term” opioid use. Conclusions: The proportion of patients that used opioids 6–12 months after cholecystectomy or GBP was low. Patients with preoperative opioid-use experienced a significantly higher risk of “long-term” opioid use when undergoing GBP compared to cholecystectomy. The indication for being prescribed opioids in the “long-term” were mostly unrelated to surgery. No patient who was naïve to opioids prior surgery was prescribed opioids 6–12 months after surgery. Although opioids are commonly prescribed in the preoperative and in the early postoperative period to patients with gallbladder disease, there is a low risk that these prescriptions will lead to long-term opioid use. The reasons for being prescribed opioids in the long-term are often due to causes not related to surgery.
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19.
  • Lindhagen, Sara, et al. (författare)
  • A more frequent disease monitorering but no increased disease activity in patients with inflammatory bowel disease during the first year of the SARS-CoV-2 pandemic : A retrospective study
  • 2022
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis Group. - 0036-5521 .- 1502-7708. ; 57:2, s. 169-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The SARS-CoV-2 pandemic abruptly switched the healthcare service for patients with inflammatory bowel disease (IBD) towards a telemedicine dominated approach. The aim of this study was to investigate the impact of this switch on monitoring of patients and on disease activity.Material: The pre-pandemic year included 868 patients and the first year of the pandemic included 891 patients. Medical records were retrospectively checked for contacts, changes in medical treatment, performed fecal calprotectin (FC) tests and colonoscopies.Results: The scheduled follow-up visits to a doctor for patients with IBD shifted from mostly face-to-face pre-pandemic (from 389 to 118 appointments) to mostly telephone-based during the pandemic (from 13 to 423 appointments). There was a 21.3% increase in mean overall scheduled health contacts (p <.001) and a 20.0% increase for the mean number of FC tests (p <.001) in the year of the pandemic compared to the pre-pandemic year. The proportion of patients who had a surveillance colonoscopy was significant lower in the year of the pandemic compared to the pre-pandemic year (12.7% vs 20.1%; p =.002). There were no difference in the proportion of patients with a median FC > 200 mg/kg (18.2% vs 17.1%; p =.767) and in the proportion of patients who changed their medical treatment (24.7% vs 23.9%; p =.713) in the first year of the pandemic compared to the prepandemic year.Conclusions: The shift towards a telemedicine oriented IBD healthcare service in the first year of the pandemic significantly increased the scheduled contacts, as well as the frequency of FC testing. However, there was a significant decrease in performed surveillance colonoscopies. Between the two periods observed, the patients showed no difference in medical treatment or in disease activity.
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20.
  • Lundgren, David, 1966-, et al. (författare)
  • Preclinical Markers in Inflammatory Bowel Disease. A Nested Case-Control Study
  • 2021
  • Ingår i: Crohn's and Colitis 360. - : Oxford University Press. - 2631-827X. ; 3:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Our objective was to determine if patients who later develop inflammatory bowel disease (IBD) show signs of increased inflammatory activity in plasma measured with high sensitivity C-reactive protein (CRP), calprotectin, and albumin before the clinical onset of IBD.Methods: We identified 96 subjects who later developed IBD (70 ulcerative colitis [UC] and 26 Crohn's disease [CD]). High sensitivity CRP, calprotectin, and albumin were analyzed in frozen plasma, donated from cases and sex-age matched controls 1-15 years before diagnosis.Results: We found that subjects who later developed UC had lower albumin levels, and subjects who later developed CD had higher CRP levels than controls. Multivariable conditional logistic regression with albumin, calprotectin, and CRP showed a lower risk for developing IBD and UC with higher albumin levels (odds ratio [OR] 0.79, confidence interval [CI] 0.69-0.90; respective OR 0.77, CI 0.66-0.91). Higher CRP levels were associated with an increased risk of developing CD (OR 1.314, CI 1.060-1.630). When adjusting for body mass index or smoking in the logistic regression model, similar results were found. Plasma calprotectin levels in the preclinical period among patients with IBD did not differ from controls.Conclusions: In this nested case-control study, subjects who later developed IBD had signs of low-grade systemic inflammation, indicated by significantly higher CRP plasma levels in CD and lower albumin plasma levels in UC, before the onset of clinical disease.
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21.
  • Lundgren, David, 1966- (författare)
  • The significance of low-grade inflammation in the gastrointestinal tract
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundGastrointestinal (GI) symptoms are commonly reported in a normal population. Mostly, the symptoms are of benign cause but occasionally the symptoms can be signs of a more harmful disease. In general, it is difficult to distinguish whether the reported symptoms are caused by a benign (functional) or organic (i.e., inflammatory) disease. To make this distinction, the tools available in clinical practice are medical history, blood and faecal tests, radiology, endoscopy and histological evaluation. Mucosal inflammation usually separates organic from functional disease and, in patients with inflammatory bowel disease (IBD), mucosal inflammation correlates with disease activity. Faecal calprotectin (FC) corresponds well with mucosal inflammation and is in clinical practice often used as the first line non-invasive test for gut inflammation. Although the sensitivity of the FC test to detect gut inflammation is good, there are uncertainties in how to interpret a modestly elevated FC level (i.e., in the span of 50-200µg/g) and in patients with IBD, there is a disagreement into which degree of inflammatory remission it is sufficient to reach.AimThe overall aim of this thesis was to study factors associated with low-grade inflammation based on biochemical markers, and to study the clinical significance of low-grade inflammation in patients with IBD and other patients with elevated FC levels. Is low-grade inflammation associated with reported gastrointestinal symptoms in patients with IBD and could low-grade inflammation be detected in the pre-clinical phase of IBD? How should an elevated FC level in patients with a normal colonoscopy be interpreted and could it be a risk factor for gastrointestinal disease or associated with other factors? Could low-grade inflammation cause IBS-like symptoms in patients with IBD?Methods and resultsThree of the manuscripts on which this thesis is based are from the Faecal and Endoscopic Colorectal Study in Umeå Sweden (FECSU) which consists of 1263 patients that underwent colonoscopy during the period of May 2007 to February 2013. The patients that accepted to participate in the FECSU study performed a FC test the day before the bowel preparation for the colonoscopy and simultaneously filled in questionnaires of gastrointestinal symptoms (GSRS), symptoms of anxiety and depression (HADS) and current medications. A thorough medical chart review that focused on endoscopic evaluations, histological judgements and medical history was performed. The included patients with IBD (n=157) in the FECSU study were analysed separately. Patients with ulcerative colitis (UC) in endoscopic remission reported lower total scores on GSRS-irritable bowel syndrome (GSRS-IBS) than controls (6 vs 10.5; p=0.062). However there was a moderate, yet significant association between GSRS-diarrhoea score and FC levels in the span £ 200 µg/g (rho 0.38;p=0.004) in patients with UC. To investigate pre-clinical biomarkers of IBD we identified 96 patients with IBD in the “Västerbotten Intervention Program (VIP)” and the “Mammography screening project” (MA). In the pre-clinical study in patients with IBD we found that patients who later developed UC had lower plasma albumin levels and patients who later developed Crohn’s disease (CD) had higher levels of CRP in plasma, reflecting signs of a low-grade systemic inflammation years before diagnosis. Plasma calprotectin levels were not elevated before IBD-diagnosis. In the FECSU study, all non-IBD patients with a normal colonoscopy were studied for factors associated with an elevated FC level. Patients with a FC > 50 µg/g more often used Proton-pump inhibitors (PPI) (multivariate OR: 3.843; CI: 2.338-6.316), Non-steroidal anti-ivinflammatory drugs (NSAID) (multivariate OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (ASA) (multivariate OR: 2.934; CI: 1.085-3.448). One third of the patients with a normal colonoscopy had elevated FC levels (> 50 µg/g) and these patients were observed three years after the colonoscopy. There was no increased risk for developing gastrointestinal disease in the patients with an increased baseline FC level and a normal colonoscopy during the observation period.ConclusionPatients with longstanding UC in remission did not experience more IBS-like symptoms than controls. In patients with UC in remission, the FC levels in the lower span were moderately associated with symptoms of diarrhoea. Patients with IBD had elevated inflammatory biochemical markers in blood in the pre-clinical phase. P- CRP and P-albumin were more sensitive to detect a low grade systemic inflammation than P-calprotectin in the pre-clinical phase of IBD. More than one-third of the patients with a normal colonoscopy had a slightly elevated FC. In patients with a normal colonoscopy, the use of PPI, NSAID and ASA was associated with an increased FC level. No significant gastrointestinal disease developed in the patients with an increased FC level together with a normal colonoscopy during the three-year period following colonoscopy. 
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22.
  • Meyer, Antoine, et al. (författare)
  • Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis
  • 2024
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 59:4, s. 558-568
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nutri-score is now widely available in food packages in Europe.Aim: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.Results: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p-trend: 0.76).Conclusions: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.
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23.
  • Mårild, Karl, 1982, et al. (författare)
  • Histologic activity in inflammatory bowel disease and risk of serious infections : A nationwide study
  • 2024
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 22:4, s. 831-846
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Individuals with inflammatory bowel disease (IBD) are at increased risk of serious infections, but whether this risk varies by histological disease activity is unclear.METHODS: A national population-based study of 55,626 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies followed through 2016. Serious infections were defined as having an inpatient infectious disease diagnosis in the Swedish National Patient Register. We used Cox regression to estimate hazard ratios (HRs) for serious infections in the 12 months following documentation of histologic inflammation (vs. histological remission), adjusting for social and demographic factors, chronic comorbidities, prior IBD-related surgery and hospitalization. We also adjusted for IBD-related medications in sensitivity analyses.RESULTS: With histological inflammation vs. remission, there was 4.62 (95%CI=4.46-4.78) and 2.53 (95%CI=2.36-2.70) serious infections per 100 person-years of follow-up, respectively (adjusted [a]HR=1.59; 95%CI=1.48-1.72). Histological inflammation (vs. remission) were associated with an increased risk of serious infections in ulcerative colitis (UC, aHR=1.68; 95%CI=1.51-1.87) and Crohn's disease (CD, aHR=1.59; 95%CI=1.40-1.80). The aHRs of sepsis and opportunistic infections were 1.66 (95%CI=1.28-2.15) and 1.71 (95%CI=1.22-2.41), respectively. Overall, results were consistent across age groups, sex and education level and remained largely unchanged after adjustment for IBD-related medications (aHR=1.47; 95%CI=1.34-1.61).CONCLUSION: Histological inflammation of IBD was an independent risk factor of serious infections, including sepsis, suggesting that achieving histological remission may reduce infections in IBD.
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24.
  • Pagoldh, Jenny, et al. (författare)
  • Irritable bowel syndrome-like symptoms in treated microscopic colitis patients compared with controls : a cross-sectional study
  • 2020
  • Ingår i: Gastroenterology Report. - : Oxford University Press. - 2052-0034. ; 8:5, s. 374-380
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence of irritable bowel syndrome (IBS)-like symptoms is high in untreated patients with microscopic colitis MC), but there is uncertainty of the prevalence of IBS-like symptoms in treated patients. We assessed the degree of IBS-like symptoms in patients with MC in comparison to control subjects, and investigated the association between IBS-like symptoms and faecal calprotectin (FC) in MC patients. Methods: Patients with an established MC diagnosis (n = 57) were compared to sex- and age-matched controls (n = 138) for scores in the GSRS-IBS (Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome) and HADS (Hospital Anxiety Depression Scale). In MC patients, an FC level was simultaneously analysed. Results: The median interval from MC diagnoses to the time the subjects participated in the study was 5.5 years (25th-75th percentiles; 4.5-9.5 years). The total GSRS-IBS score, subscores for abdominal pain, bloating, and diarrhoea were significantly higher in MC patients compared to controls (all P< 0.001). There was a significant correlation between FC levels and reported bowel frequency (P = 0.023), but there was no correlation between FC levels and GSRS-IBS scores. Patients with MC had significantly higher scores on anxiety (HADS-A) (P< 0.001) and used more selective serotonin-reuptake-inhibitor drugs (P = 0.016) than the control subjects. However, only the control subjects (not the patients with MC) showed significant correlations between GSRS-IBS scores and HADS scores. Conclusions: Patients with MC reported more IBS-like symptoms and anxiety than control subjects but neither FC levels nor symptoms of affectivity were significantly correlated with IBS-like symptoms.
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25.
  • Pettersson, Nina, et al. (författare)
  • Increased chronic pain in patients with ulcerative colitis is mostly associated to increased disease activity. A cross-sectional case-control study
  • 2020
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:10, s. 1193-1199
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Backgrounds/aims: Musculoskeletal symptoms are common in patients with ulcerative colitis (UC), but no study has compared the prevalence of chronic pain to controls from a general population. Methods: Patients with UC (n = 1164) and controls (n = 3867) were sent questionnaires comprising demography, history of pain, pain localization and UC patients’ Patient-Simple Clinical Colitis Activity Index. Chronic regional pain (ChRP) and chronic widespread pain (ChWP) were defined as having pain for at least 3 months. Results: The response rate for the patients with UC was 49.0% and for the control persons 61.7% (p '.001). The reported prevalence of ChRP and ChWP was higher in patients with UC versus controls (33.1% vs. 24.2%; p '.001 and 19.8% vs. 12.5%; p '.001). The patients with UC reported significantly more pain in the regions ‘lower back’, ‘hip/upper leg’ and ‘lower leg/foot’ compared to controls. The patients with P-SCCAI (Formula presented.) 5 (n = 121) reported more ChWP than patients with P-SCCAI '5 (n = 426) (46.3% vs. 12.7%; p '.001) and controls (n = 2425) (46.3 vs. 12.5%; p '.001) in all body regions. No significant difference in ChWP was found between patients with P-SCCAI '5 and controls (12.7% vs. 12.5%; p =.917). Conclusions: Patients with UC reported more chronic pain than controls from the general population, especially from the lower back and hip region. Higher UC disease activity was associated with more pain in all body regions.
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