C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease ...extent in patients with ulcerative colitis and to phenotype in patients with Crohn's disease, and to investigate the predictive value of CRP levels for disease outcome.
CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn's disease were alive and provided sufficient data for analysis.
Patients with Crohn's disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn's disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn's disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03).
CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn's disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn's disease.
Background and objectives
The 52‐week, randomized, double‐blind, noninferiority, government‐funded NOR‐SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar ...CT‐P13 was not inferior to continued treatment with infliximab originator. The NOR‐SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT‐P13 throughout the 78‐week study period (maintenance group) versus patients switched to CT‐P13 at week 52 (switch group). The primary outcome was disease worsening during follow‐up based on disease‐specific composite measures.
Methods
Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis.
Results
Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per‐protocol set). Adjusted risk difference was 5.9% (95% CI −1.1 to 12.9). Frequency of adverse events, anti‐drug antibodies, changes in generic disease variables and disease‐specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases.
Conclusion
The NOR‐SWITCH extension showed no difference in safety and efficacy between patients who maintained CT‐P13 and patients who switched from originator infliximab to CT‐P13, supporting that switching from originator infliximab to CT‐P13 is safe and efficacious.
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Aliment Pharmacol Ther 2011; 33: 106–114
Summary
Background Fatigue is reported to reduce health‐related quality of life (HRQOL) in chronic diseases. Studies on the importance of fatigue and its ...implications for the patient’s HRQOL in inflammatory bowel disease (IBD) remain scarce and need to be explored.
Aim To investigate the influence of chronic fatigue on both generic and disease‐specific HRQOL in IBD.
Methods Patients in remission, with mild and moderate IBD completed the Fatigue Questionnaire, the Short‐Form 36 (SF‐36) and the Norwegian version of the Inflammatory Bowel Disease Questionnaire (N‐IBDQ). In addition, demographic and clinical variables were obtained.
Results In total, 140 patients were included; the mean age of patients with chronic fatigue was 44.2 years (s.d. = 15.8), that of nonfatigued was 44.7 years (s.d. = 16.0). Ulcerative colitis (UC)/Crohn’s disease (CD) = 92/48. Chronic fatigue was associated, after controlling for covariates, with a reduction of HRQOL scores in 6/8 SF‐36 dimensions in UC and 5/8 dimensions in CD. In N‐IBDQ, chronic fatigue was associated with a reduction of HRQOL in four subdimensions and total score in CD and all dimensions in UC.
Conclusions Fatigue is associated with reduction of HRQOL scores in IBD. The physical HRQOL domains are particularly affected. The impact of fatigue on disability, sick leave, school and work attendance has to be studied further.
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by low immunoglobulin (Ig)G and IgA, and/or IgM. In addition to bacterial infections, a ...large subgroup has noninfectious inflammatory and autoimmune complications. We performed 16S ribosomal RNA-based profiling of stool samples in 44 CVID patients, 45 patients with inflammatory bowel disease (disease controls), and 263 healthy controls. We measured plasma lipopolysaccharide (LPS) and markers of immune cell activation (i.e., soluble (s) CD14 and sCD25) in an expanded cohort of 104 patients with CVID and in 30 healthy controls. We found a large shift in the microbiota of CVID patients characterized by a reduced within-individual bacterial diversity (alpha diversity, P<0.001) without obvious associations to antibiotics use. Plasma levels of both LPS (P=0.001) and sCD25 (P<0.0001) were elevated in CVID, correlating negatively with alpha diversity and positively with a dysbiosis index calculated from the taxonomic profile. Low alpha diversity and high dysbiosis index, LPS, and immune markers were most pronounced in the subgroup with inflammatory and autoimmune complications. Low level of IgA was associated with decreased alpha diversity, but not independently from sCD25 and LPS. Our findings suggest a link between immunodeficiency, systemic immune activation, LPS, and altered gut microbiota.
Summary
Background
The point prevalence estimates of anaemia in patients with inflammatory bowel disease (IBD) range between 6% and 74%. The variation is probably due to differences in the definition ...of anaemia and the study populations.
Aim
To retrospectively determine the prevalence of anaemia at diagnosis and at the 1‐, 5‐ and 10‐year follow‐ups in patients with IBD from a prospectively followed, population‐based inception cohort (the IBSEN Study). To compare the prevalence of anaemia after a 10‐year disease course with the prevalence of anaemia in the background population, and to assess clinical factors associated with anaemia at diagnosis and during follow‐up.
Methods
Newly diagnosed IBD patients were included in a population‐based, prospective cohort. Follow‐up was performed at 1, 5 and 10 years. All visits included clinical examinations and blood samples. Anaemia was defined according to the WHO.
Results
A total of 756 patients (UC, n = 519 and CD, n = 237) were included; 48.8% of CD and 20.2% of UC patients were anaemic at diagnosis (P < 0.001). The proportion of patients with anaemia decreased during the disease course in all patients, except in women with CD. After 10 years of disease, the relative risk for anaemia was increased in all groups, except for women with UC. The variables associated with anaemia were generally unchanged during the disease course, and elevated CRP was the strongest predictor of risk.
Conclusions
Anaemia was more common in CD than in UC. The prevalence of anaemia decreased during the disease course. Women with CD were at high risk for anaemia. Elevated CRP was independently associated with anaemia.
Loss of body armour, sometimes including a reduction in or loss of pelvic spines, is an adaptation observed in many isolated freshwater populations. Pelvic reduction in sticklebacks has previously ...been associated with recurrent, but variant, deletions within pelvic enhancer regions PelA and PelB, which regulate expression of the homeodomain transcription factor gene Pitx1. We investigated variation in nucleotide sequences of pelvic enhancers in sticklebacks collected from two small freshwater lakes in the same watercourse and a nearby marine site in subarctic Norway. Spineless, as well as asymmetrically spined and completely spined sticklebacks are present in the upper lake, while only specimens with complete spines are found at the other lake and the marine site. Observed variation at PelA between the three sites was mainly due to variable numbers of repeats at three fragile TG-repeat loci. The length of PelA, mainly at one of the TG-repeat loci, was consistently shorter among individuals in the upper lake compared with specimens from the two other sites. However, no obvious association was revealed between enhancer variants and pelvic status. No polymorphism was found at PelB. Thus, additional genetic factors and/or environmental cues need to be identified to fully explain the occurrence of pelvic reduction in sticklebacks in this lake.
Objectives: Patients are at risk of anemia post Roux-en-Y gastric bypass (RYGB). We sought to determine the prevalence of anemia and related nutritional deficiencies 5 years after RYGB and to ...evaluate adherence to nutritional supplements with iron, vitamin B12, and folate.
Material and methods: Patients operated with RYGB 2004-2006 were eligible for evaluation. Blood samples were collected and use of nutritional supplements was recorded preoperatively, and at outpatients' consultations 1, 2, and 5 years postoperatively. Of 203 patients operated, 184 (91%) completed the 5 year follow-up and were included in the study. Of these, 97% had valid measurements of hemoglobin both at baseline and after 5 years.
Results: During the 5 years after RYGB, the prevalence of anemia increased from 4% preoperatively to 24% in females, and from 0% to 7% in males. Ferritin levels decreased gradually in both genders. Iron deficiency increased from 6% preoperatively to 42% at 5 years in females, and from 0% to 9% in males. Vitamin B12 deficiency was not altered while folate deficiency decreased from 10% preoperatively to 1% at 5 years. Five years after surgery 25% reported the use of supplements with iron, while 83% used vitamin B12 and 65% used multivitamins with folate.
Conclusions: We observed a long-term increase in anemia and iron deficiency after RYGB in both genders, but most pronounced in women. Our postoperative protocol for prevention of vitamin B12 and folate deficiencies appear acceptable. Iron status and iron supplementation seems to need stronger emphasis during follow-up after RYGB.
Summary
Background
Primary sclerosing cholangitis is a progressive liver disease with a remarkably variable course. Biomarkers of disease activity or prognostic models predicting outcome at an ...individual level are currently not established.
Aim
To evaluate the prognostic utility of four biomarkers of basement membrane and interstitial extracellular matrix remodeling in patients with primary sclerosing cholangitis.
Methods
Serum samples were available from 138 large‐duct primary sclerosing cholangitis patients (of which 102 74% with IBD) recruited 2008‐2012 and 52 ulcerative colitis patients (controls). The median follow‐up time was 2.2 (range 0‐4.3) years. Specific biomarkers of type III and V collagen formation (PRO‐C3 and PRO‐C5, respectively) and type III and IV collagen degradation (C3M and C4M, respectively) were assessed. The Enhanced Liver Fibrosis test, including procollagen type III N‐terminal peptide, tissue inhibitor of metalloproteinase‐1 and hyaluronic acid was assessed for comparison.
Results
All markers were elevated in primary sclerosing cholangitis compared to ulcerative colitis patients (P < 0.001). PRO‐C3 showed the largest difference between the two groups with a threefold increase in primary sclerosing cholangitis compared to ulcerative colitis patients. Patients with high baseline serum levels of all markers, except C3M, had shorter survival compared to patients with low baseline serum levels (P < 0.001). Combining PRO‐C3 and PRO‐C5 the odds ratio for predicting transplant‐free survival was 47 compared to the Enhanced Liver Fibrosis test's odds ratio of 11.
Conclusions
Extracellular matrix remodeling is elevated in primary sclerosing cholangitis patients compared to ulcerative colitis patients. Furthermore, the interstitial matrix marker PRO‐C3 was identified as a potent prognostic marker and an independent predictor of transplant‐free survival in primary sclerosing cholangitis.
Aliment Pharmacol Ther 2012; 35: 133–141
Summary
Background Patients with inflammatory bowel disease (IBD) often complain of fatigue.
Aim To investigate the prevalence and characteristics of ...fatigue among IBD out‐patients in Scandinavia and to provide normative values for fatigue in IBD patients.
Methods A cross‐sectional study was conducted on 425 IBD patients from six out‐patient centres in Denmark, Norway and Sweden. Fatigue was measured using the Multidimensional Fatigue Inventory. The patients were also screened for anaemia and iron deficiency. Each centre included approximately 5% of their IBD cohort. The patients were enrolled consecutively from the out‐patient clinics, regardless of disease activity and whether the visit was scheduled. The fatigue analysis was stratified for age and gender.
Results Using the 95th percentile of the score of the general population as a cut‐off, approximately 44% of the patients were fatigued. When comparing the IBD patients with disease activity to the IBD patients in remission, all dimensions of fatigue were statistically significant (P < 0.05). Being anaemic or iron deficient was not associated with increased fatigue. Being a male patient with ulcerative colitis treated with corticosteroids was a strong determinant for increased fatigue. The normative ranges for IBD fatigue were calculated.
Conclusions Fatigue in IBD is common regardless of anaemia or iron deficiency. Fatigue in IBD is most marked for patients <60 years of age. Stratifying for gender and age is necessary when analysing fatigue, as fatigue is expressed differently between groups.
Summary
Background
The diagnosis of gastro‐oesophageal reflux disease (GERD) remains challenging. An algorithm, facilitated by a questionnaire, may provide a more structured and cost‐effective care ...of patients.
Aim
To compare symptom control achieved with empirical therapy for GERD, in an algorithm based on the GerdQ (new structured pathway, NSP), with that of current care after endoscopy (ordinary clinical pathway, OCP).
Methods
Patients with symptoms of GERD, but without alarm features, were randomised in an open, parallel‐group study and followed for 4–8 weeks. In the NSP, GerdQ score was used as a basis for both diagnosis and a treatment algorithm. Patients with high likelihood of GERD were treated empirically with a PPI whereas patients with low likelihood of GERD received therapy chosen by the clinician. In the OCP, diagnosis and treatment were based on endoscopy or pH‐metry findings. The statistical hypothesis was non‐inferiority of NSP to OCP.
Results
A total of 147 patients (86.5%) in the NSP and 133 patients (80.1%) in the OCP arm were responders. Overall, NSP was non‐inferior to OCP, but not superior (P = 0.14). Patients with high likelihood of GERD had significantly better symptom relief in the NSP (P = 0.03), whereas those with low likelihood of GERD showed a numerical difference in favour of an endoscopy‐based approach (OCP). NSP saved 146 € per patient.
Conclusions
A symptom‐based approach using GerdQ reduced health care costs without loss in efficacy. Patients with high likelihood GERD benefited from empirical treatment. An algorithm based on GerdQ may provide physicians with a tool for a more structured care of patients (ClinicalTrials.gov NCT00842387).
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