Pain Severity and Vitamin D Deficiency in IBD Patients

Pain and vitamin D deficiency are common in inflammatory bowel disease (IBD). Disease activity, fatigue, frequent relapses, prior surgery and psychological factors all seem to influence the experience of pain in IBD. Vitamin D deficiency has been associated with muscle and skeletal pain. This study aimed to determine whether there is an association between vitamin D deficiency and severity of pain in patients with IBD, and to investigate the influence of other socio-demographic and psychological variables on the experience of pain. Methods: Patients with IBD were recruited from nine hospitals in Norway in a multicenter cross-sectional study. The Brief Pain Inventory (BPI) questionnaire was used to measure pain. Disease activity was assessed using clinical disease activity indices, C-reactive protein (CRP) and fecal calprotectin. Regression models were fitted to explore a possible association between 25-hydroxyvitamin D and pain severity. Results: Of 407 patients included in the analyses, 229 (56%) had Crohn's disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency was present in half (203/407) of patients. Presence of pain was reported by 76% (309/407). More severe pain was associated with female gender and increased disease activity scores, but not with increased CRP or fecal calprotectin. In CD, patients without prior intra-abdominal surgery reported more severe pain. In multivariate analyses, there was no association between 25-hydroxyvitamin D and pain severity. Conclusions: In this study, no significant association between pain severity and vitamin D deficiency was revealed in patients with IBD.publishedVersio

Comparison of the Multiattribute Utility Instruments EQ-5D and SF-6D in a Europe-Wide Population-Based Cohort of Patients with Inflammatory Bowel Disease 10 Years after Diagnosis

Background. The treatment of chronic inflammatory bowel disease (IBD) is costly, and limited resources call for analyses of the cost effectiveness of therapeutic interventions. The present study evaluated the equivalency of the Short Form 6D (SF-6D) and the Euro QoL (EQ-5D), two preference-based HRQoL instruments that are broadly used in cost-effectiveness analyses, in an unselected IBD patient population. Methods. IBD patients from seven European countries were invited to a follow-up visit ten years after their initial diagnosis. Clinical and demographic data were assessed, and the Short Form 36 (SF-36) was employed. Utility scores were obtained by calculating the SF-6D index values from the SF-36 data for comparison with the scores obtained with the EQ-5D questionnaire. Results. The SF-6D and EQ-5D provided good sensitivities for detecting disease activity-dependent utility differences. However, the single-measure intraclass correlation coefficient was 0.58, and the Bland-Altman plot indicated numerous values beyond the limits of agreement. Conclusions. There was poor agreement between the measures retrieved from the EQ-5D and the SF-6D utility instruments. Although both instruments may provide good sensitivity for the detection of disease activity-dependent utility differences, the instruments cannot be used interchangeably. Cost-utility analyses performed with only one utility instrument must be interpreted with caution

Health-related quality of life in patients with newly diagnosed inflammatory bowel disease: an observational prospective cohort study (IBSEN III)

Purpose This unselected, population-based cohort study aimed to determine the level of health-related quality of life (HRQoL) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) at the time of diagnosis compared with a reference population and identify the demographic factors, psychosocial measures, and disease activity markers associated with HRQoL. Methods Adult patients newly diagnosed with CD or UC were prospectively enrolled. HRQoL was measured using the Short Form 36 (SF-36) and Norwegian Inflammatory Bowel Disease Questionnaires. Clinical significance was assessed using Cohen’s d effect size and further compared with a Norwegian reference population. Associations between HRQoL and symptom scores, demographic factors, psychosocial measures, and disease activity markers were analyzed. Results Compared with the Norwegian reference population, patients with CD and UC reported significantly lower scores in all SF-36 dimensions, except for physical functioning. Cohen’s d effect sizes for men and women in all SF-36 dimensions were at least moderate, except for bodily pain and emotional role for men with UC and physical functioning for both sexes and diagnoses. In the multivariate regression analysis, depression subscale scores ≥ 8 on the Hospital Anxiety and Depression Scale, substantial fatigue, and high symptom scores were associated with reduced HRQoL. Conclusion Patients newly diagnosed with CD and UC reported statistically and clinically significantly lower scores in seven of the eight SF-36 dimensions than the reference population. Symptoms of depression, fatigue, and elevated symptom scores were associated with poorer HRQoL.publishedVersio

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation

Background and aims We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5’-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). Methods We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n = 158) sampled prior to and serially after LT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n = 51) or with primary biliary cholangitis (PBC) (n = 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. Results In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. Conclusions Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. Impact and implications We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.publishedVersio

Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway

Background and aim: Modern treatment strategies for inflammatory bowel disease (IBD) are postulated to change the natural disease course. Inception cohort studies are the gold standard for investigating such changes. We have initiated a new population-based inception cohort study; Inflammatory bowel disease in South Eastern Norway III (IBSEN III). In this article, we describe the study protocol and baseline characteristics of the cohort. Methods: IBSEN III is an ongoing, population-based observational inception cohort study with prospective follow-up. Adult and pediatric patients with suspected IBD in the South-Eastern Health Region of Norway (catchment area of 2.95 million inhabitants in 2017), during the 3-year period from 2017 to 2019, were eligible for inclusion. Comprehensive clinical, biochemical, endoscopic, demographic, and patient-reported data were collected at the time of diagnosis and throughout standardized follow-up. For a portion of the patients, extensive biological material was biobanked. Results: The study included 2168 patients, of whom 1779 were diagnosed with IBD (Crohn's disease: 626, ulcerative colitis: 1082, IBD unclassified: 71). In 124 patients, there were subtle findings indicative of, but not diagnostic for, IBD. The remaining 265 patients were classified as symptomatic non-IBD controls. Conclusion: We have included patients in a comprehensive population-based IBD cohort from a catchment population of 2.95 million, and a unique biobank with materials from newly diagnosed and treatment-naïve IBD patients and symptomatic non-IBD controls. We believe this cohort will add important knowledge about IBD in the years to come.publishedVersio

Childbearing is Associated with a Short-term Reduced Risk of Crohn’s Disease in Mothers

Our aim in this study was to analyze the importance of childbearing for risk of inflammatory bowel disease. Using data from the Norwegian Population Register and the Norwegian Patient Register, we fitted discrete-time hazard models for diagnosis of Crohn disease (CD) or ulcerative colitis (UC) among men and women aged 18–81 years in 2011–2016. Year and various sociodemographic factors were controlled for. The data included 4,304 CD cases and 8,866 UC cases. Women whose youngest child was ≤4 years of age had lower CD risk the following year than childless women (odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.62, 0.86). There was no such reduction in CD risk among fathers. Men whose youngest child was aged ≥20 years had higher risks of CD (OR = 1.22, 95% CI: 1.01, 1.49) and UC (OR = 1.15, 95% CI: 1.02, 1.30) than childless men. UC risk was also increased among men whose youngest child was aged ≤4 years (OR = 1.14, 95% CI: 1.02, 1.27). The short-term reduction in women’s CD risk after a birth may reflect biological effects of pregnancy. Alternatively, it may reflect residual confounding or lifestyle effects of parenthood that are of special relevance for CD in women. In particular, differences in use of oral contraceptives (which it was not possible to control for) may have contributed to the observed pattern

Regional differences in anti-TNF-a therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study

Background and aims: During the last decades, substantial progress has been made in both medical and surgical treatment of inflammatory bowel disease (IBD). The aim of this study was to determine the use of anti-TNFs and surgery during the first 3 years after diagnosis in IBD patients across the four health regions in Norway using nationwide patient registry data. Methods: This study used nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti-TNF exposure and major surgery was calculated for patients diagnosed in 2010–2012. The analyses were stratified by diagnosis and health region. All patients were followed for an equal period of 3 years from diagnosis. Results: The study population included 8,257 IBD patients first registered between 2010 and 2012, of whom 2,829 were diagnosed with Crohn’s disease (CD) and 5,428 with ulcerative colitis (UC). Across Norway’s health regions, the cumulative incidence of major surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the highest surgery rates for both UC and CD. Conclusions: Cumulative incidence of anti-TNF exposure and surgery varied significantly across Norway’s health regions during the three first years after IBD diagnosis

Incidence and prevalence of inflammatory bowel disease in norway and the impact of different case definitions: A nationwide registry study

Background: Countries have different diagnostic procedures and treatment regimens for inflammatory bowel disease (IBD) patients. In addition to differences in population characteristics, completeness of data and health registries, different follow-up time and case definitions can have a large impact on estimates of the incidence and prevalence of IBD. Aim: The aim of this study was to use hospital and prescription data to estimate incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC), using different case definitions. Methods: This study used nationwide data from the Norwegian Patient Registry (2008 to 2017) and the Norwegian Prescription Database (2004 to April 2018). Incidence and prevalence were estimated using different case definitions of an IBD patient, varying the number of IBD-related hospital visits and IBD prescriptions required. The base case definition included patients with at least one IBD hospital visit and two IBD prescriptions or two IBD hospital visits. Results: From 2010 to 2017, 16,758 incident IBD patients fulfilled our base case definition, with 6045 diagnosed with CD (36.1%) and 10,713 (63.9%) with UC. For CD, 47.2% of the patients were male while 53.8% of UC patients were male. The base case incidence varied between 14.1 and 16.0 per 100,000 person-years for CD and 24.7 and 28.4/100,000 person-years for UC patients in the years 2010– 2017. When we required at least two IBD hospital visits, not utilizing the prescription data, the CD incidence was 22.3 per 100,000 person-years in 2010 and 13.9 per 100,000 person-years in 2017. For UC, the incidence was 47.4 and 20.6 per 100,000 person-years in 2010 and 2017. In 2017, the prevalence of CD was 0.27% (95% CI: 0.26– 0.27) and 0.50% (95% CI: 0.490– 0.502) for UC. Conclusion: According to our base case definition, the incidence of IBD in Norway was stable from 2010 to 2017. Both the incidence and prevalence of IBD in Norway is among the highest in the world. Moreover, the study also highlights the consequences of different case definitions

Serological antibodies and surgery in a population-based inception cohort of Crohn's disease patients - the IBSEN study

Introduction: Serological antibodies have been associated with complicated disease course in Crohn’s disease (CD), including the need for surgery. Aim: The aim of this study was to investigate if a panel of relevant antibodies could predict surgery in a prospective population-based cohort of patients with CD. Methods: The population-based IBSEN cohort has been followed prospectively for 20years. At the 10and 20-year follow-up, the following panel of serological antibodies was analysed: pANCA, ASCA IgA, ASCA IgG, anti-OmpC, anti-I2, and anti-CBir1. At the 20-year follow-up or until lost to follow-up, all CDrelated surgeries were registered. Results: Serum was available from 159 patients at 10-year follow-up and 135 patients at 20-year follow-up. In 113 patients, serum was available at both time points. No significant change of antibody status (positive vs. negative) was found from 10-year to 20-year follow-up. Negative pANCA, positive ASCA IgA and positive ASCA IgG at 10-year follow-up were all individually associated with increased risk for CD-related surgery. There was no association between anti-OmpC, anti-I2 or anti-CBir1 and CDrelated surgery. In a multiple regression model including disease location and behaviour, only stricturing or penetrating disease behaviour and negative pANCA remained significantly associated with higher odds for surgery. Conclusion: Positive ASCA IgA and IgG, and negative pANCA were associated with higher odds for CD-related surgery in univariate analysis. Since disease phenotype changes during the disease course, while serological antibodies are stable, our results support the use of pANCA, ASCA IgA and ASCA IgG as prognostic markers in CD