Helicobacter pylori infection is not associated with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoinflammatory disease caused by genetic susceptibility and environmental triggers, which include infectious agents. Helicobacter pylori, a bacterium that frequently colonizes the stomach, is associated with the development of certain autoinflammatory disorders. This study examined a possible association between H. pylori infection and RA. METHOD: This cohort study was performed in the Central Denmark Region. Patients were enrolled from primary healthcare centres after a urea breath test (UBT) for H. pylori and followed for a median of 8 years. Nationwide administrative registries provided information about the patients' diagnoses, country of birth, and gender. Comorbidity was determined using the Charlson Comorbidity Index. We compared the prevalence of RA via odds ratios (ORs) and incidences using Cox regression to calculate the hazard ratios (HRs) by comparing H. pylori-positive and H. pylori-negative individuals and adjusting for confounding variables. RESULTS: A total of 56 000 people diagnosed as H. pylori positive or negative had similar rates of comorbidity. No link was found between H. pylori and RA. There was no difference in RA prevalence until time of UBT [OR = 0.91, 95% confidence interval (CI) 0.70-1.19)] or incidence of new RA cases after UBT (HR = 0.80, 95% CI 0.56-1.13) between H. pylori-positive and -negative subjects. Validation via four other RA definitions provided similar results. CONCLUSION: This study found no association between H. pylori infection and RA. This result does not support the involvement of H. pylori in a gut-joint axis of importance for RA development.

Mucosal and systemic immune modulation by Trichuris trichiura in a self-infected individual.

Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T-helper (h)1-, Th2-, Th17- and Treg-associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2-dominated T cell response at the expense of the Th1-response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity.

Faecal egg counts and expulsion dynamics of the whipworm, Trichuris trichiura following self-infection.

More than 400 million humans are estimated to be infected with the intestinal helminth parasite, Trichuris trichiura. The infection is chronic in nature and high-intensity infection can lead to colitis, anaemia, Trichuris Dysentery Syndrome and reduced cognitive performance. Single doses of 400 mg albendazole or 500 mg mebendazole (MBZ) are used in mass drug administration programmes, but this has been shown to be insufficient. In this study, worm expulsion dynamics are described after MBZ treatment, given as a multi-dose and single-dose treatment in two separate T. trichiura self-infection studies. Worm expulsion dynamics post-treatment showed a similar pattern regardless of the dose regime, with the first worms observed on day 2 and the last worms expelled on days 9 and 13 post-treatment. Establishment of a chronic infection was observed following the inefficient single-dose treatment. The prepatent period was 13-16 weeks in both studies and worms were found to have a lifespan of at least 1 year and 10 months. These self-infection studies provide key information on the chronicity of T. trichiura infections, expulsion dynamics after anthelmintic treatment and the prepatent period, as well as the fecundity of female worms, which was around 18,000 eggs/female per day.

Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease associated with a dysregulated T cell response towards intestinal microflora. Vitamin D has immune modulatory effects on T cells through the nuclear vitamin D receptor (VDR) in vitro. It is unclear how oral vitamin D treatment affects VDR expression. The aim of this study was to establish a flow cytometry protocol, including nuclear and cytoplasmic VDR expression, and to investigate the effects of vitamin D treatment on T cell VDR expression in CD patients. The flow cytometry protocol for VDR staining was developed using the human acute monocytic leukaemia cell line (THP-1). The protocol was evaluated in anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) from vitamin D3- (n = 9) and placebo-treated (n = 9) CD patients. Anti-VDR-stained PBMCs were examined by flow cytometry, and their cytokine production was determined by cytokine bead array. VDR, CYP27B1 and RXRα mRNA expression levels in CD4(+) T cells were measured by quantitative reverse transcriptase polymerase chain reaction. The flow cytometry protocol enabled detection of cytoplasmic and nuclear VDR expression. The results were confirmed by confocal microscopy and supported by correlation with VDR mRNA expression. VDR expression in CD4(+) T cells increased following stimulation. This VDR up-regulation was inhibited with 30% by vitamin D treatment compared to placebo in CD patients (P = 0027). VDR expression was correlated with in-vitro interferon-γ production in stimulated PBMCs (P = 0.01). Flow cytometry is a useful method with which to measure intracellular VDR expression. Vitamin D treatment in CD patients reduces T cell receptor-mediated VDR up-regulation.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Soluble CD163, a specific macrophage activation marker, is decreased by anti-TNF-α antibody treatment in active inflammatory bowel disease.

Activated macrophages shed the haemoglobin-haptoglobin scavenger receptor CD163 into the circulation as soluble(s)-CD163. We measured sCD163 as an in vivo macrophage activation marker in patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving antitumour necrosis factor (TNF)-α antibody or prednisolone treatment. We also investigated the CD163 expression on circulating monocytes. 58 patients with CD, 40 patients with UC and 90 healthy controls (HC) were included. All patients had active disease at inclusion and were followed for 6 weeks of anti-TNF-α antibody or prednisolone treatment. We measured plasma sCD163 levels at baseline, 1 day, 1 week and 6 weeks after initiating treatment. CD163 expression on circulating CD14(+) monocytes was measured in 21 patients with CD receiving anti-TNF-α antibody treatment. Baseline sCD163 levels were elevated in patients with CD [1.99 (1.80-2.18) mg/l] and in patients with UC [2.07 (1.82-2.32) mg/l] compared with HC [1.51 (1.38-1.63) mg/l] (P < 0.001). Anti-TNF-α antibody treatment induced a rapid decrease in sCD163 levels in patients with CD and in patients with UC 1 day after treatment initiation (P < 0.05). One week of prednisolone treatment did not induce a reduction in sCD163 levels. Anti-TNF-α treatment normalized sCD163 levels in patients with UC, whereas patients with CD exhibited sustained increased sCD163 levels. In patients with CD, CD163 expression on CD14(+) monocytes was increased compared with HC. This study highlights that active CD and UC are associated with increased macrophage activation, as indicated by elevated sCD163 levels and monocytic CD163 expression. Anti-TNF-α antibody treatment induced a rapid decrease in sCD163 levels, suggesting a specific effect on macrophage activation in inflammatory bowel diseases.

Toll-like receptor-induced granulocyte-macrophage colony-stimulating factor secretion is impaired in Crohn's disease by nucleotide oligomerization domain 2-dependent and -independent pathways.

Pattern recognition receptors (PRRs) are an integral part of the innate immune system and govern the early control of foreign microorganisms. Single nucleotide polymorphisms (SNPs) in the intracellular pattern recognition receptor nucleotide-binding oligomerization domain-containing protein (NOD2, nucleotide oligomerization domain 2) are associated with Crohn's disease (CD). We investigated the impact of NOD2 polymorphisms on cytokine secretion and proliferation of peripheral blood mononuclear cells (PBMCs) in response to Toll-like receptor (TLR) and NOD2 ligands. Based on NOD2 SNP analyses, 41 CD patients and 12 healthy controls were studied. PBMCs were stimulated with NOD2 and TLR ligands. After 18 h culture supernatants were measured using multiplex assays for the presence of human cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha. In CD patients, TLR-induced GM-CSF secretion was impaired by both NOD2-dependent and -independent mechanisms. Moreover, TNF-alpha production was induced by a TLR-2 ligand, but a down-regulatory function by the NOD2 ligand, muramyl dipeptide, was impaired significantly in CD patients. Intracellular TLR ligands had minimal effect on GM-CSF, TNF-alpha and IL-1beta secretion. CD patients with NOD2 mutations were able to secrete TNF-alpha, but not GM-CSF, upon stimulation with NOD2 and TLR-7 ligands. CD patients have impaired GM-CSF secretion via NOD2-dependent and -independent pathways and display an impaired NOD2-dependent down-regulation of TNF-alpha secretion. The defect in GM-CSF secretion suggests a hitherto unknown role of NOD2 in the pathogenesis of CD and is consistent with the hypothesis that impaired GM-CSF secretion in part constitutes a NOD2-dependent disease risk factor.

Long-term effect of medical treatment of diarrhoea in 377 patients with SeHCAT scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study.

BACKGROUND: Excessive amounts of bile acids entering the colon due to bile acid malabsorption cause chronic bile acid diarrhoea. Diagnosis is possible by measuring the retention fraction of orally ingested 75 Selenium homotaurocholic acid (SeHCAT). The knowledge of long-term effects of medical treatment is sparse. AIM: To describe diarrhoea, adherence to treatment, treatment effects and quality of life in a large, well-defined cohort of patients with bile acid diarrhoea. METHODS: A retrospective survey was performed among 594 patients with bile acid malabsorption verified by SeHCAT scans at our unit between 2003 and 2016. Questionnaires about medical history, diarrhoea, use of medication, and quality of life scores were mailed to all patients. RESULTS: Among 594 patients 377 (69%) responded. Among respondents, 121 (32%) had bile acid diarrhoea due to ileal disease or resection (type 1), 198 (52%) idiopathic bile acid diarrhoea (type 2) and 58 (16%) bile acid diarrhoea due to other non-ileal disease, mainly cholecystectomy (type 3). At follow-up, half of the patients, 184 (50%), reported improvement of diarrhoea. However, 273 patients (74%) still reported diarrhoea and 234 (62%) regularly used anti-diarrhoeal medication. In spite of treatment, 235 (64%) considered reduced quality of life by diarrhoea and 184 (50%) reported that diarrhoea was unaltered or worse than before established diagnosis. CONCLUSION: Many patients with bile acid diarrhoea continue to have bothersome diarrhoea in spite of correct diagnosis and treatment.

Regional gastrointestinal transit times in severe ulcerative colitis.

BACKGROUND: Gastrointestinal (GI) dysmotility may present secondary to inflammatory bowel disease. The main aim of this study was to investigate GI motility in ulcerative colitis (UC) patients during severe disease activity. METHODS: Twenty patients with severe UC were studied with a novel telemetric capsule system (3D-Transit) designed for minimally invasive, ambulatory assessment of total and regional GI transit times. Ten patients were available for follow-up during remission. Data were compared to those of 20 healthy subjects (HS). KEY RESULTS: Total GI transit time was significantly longer in patients with severe UC (median 44.5 h [range 9.9-102.7 h]) than in HS (median 27.6 h [range 9.6-56.4 h]) (p = 0.032). Additionally, during severe UC, transit time was prolonged through the proximal colon (p = 0.003) and there were strong trends toward longer than normal small intestinal transit time (HS: median 4.9 h [range 3.4-8.3 h] vs severe UC patients: median 5.9 h [range 3.9-11.9 h]; p = 0.053) and colorectal transit times (HS: median 18.2 h [range 1.5-43.7] vs severe UC patients: median 34.9 h [range 0.4-90.9 h]; p = 0.056). Our data further indicate that total GI and colorectal transit times may be prolonged in UC during early remission. CONCLUSIONS & INFERENCES: Total GI transit times are significantly prolonged during severe UC.

Response, relapse and mucosal immune regulation after infliximab treatment in fistulating Crohn's disease.

BACKGROUND: Infliximab reduces mucosal inflammation in some, but not all, patients with Crohn's disease. AIM: To monitor clinical data and changes in mucosal cytokine levels after infliximab treatment to identify differences between responders and non-responders. METHODS: Twenty-six patients with fistulating Crohn's disease received three infliximab infusions at weeks 0, 2 and 6. Follow-up was for 1 year and included clinical examination, colonoscopy, ano-rectal ultrasound and magnetic resonance imaging. Biopsies were taken at weeks 0, 8, 26 and 52. Cell cultures were established and analysed for tumour necrosis factor-alpha, interferon-gamma and interleukin-10 levels, and related to clinical status and fistula healing. RESULTS: Eleven of 15 patients (73%) with active disease (Crohn's disease activity index > 150) obtained remission (Crohn's disease activity index < 150) at 8 weeks. In in vitro cell cultures, there was reduced tumour necrosis factor-alpha and interleukin-10 production at week 26, with the latter persistent throughout the study period. When the disease deteriorated or relapsed, there was increased interferon-gamma production in in vitro cell cultures. Fistula healing was associated with reduced production of interferon-gamma, tumour necrosis factor-alpha and interleukin-10. CONCLUSIONS: Infliximab down-regulates mucosal immune activation in Crohn's disease. Monitoring of mucosal cytokine levels after infliximab treatment by whole biopsy cultures may be useful as interleukin-10, tumour necrosis factor-alpha and interferon-gamma production are different in responders and at relapse.

Thiopurine methyltransferase genotype distribution in patients with Crohn's disease.

BACKGROUND: Inter-individual response to azathioprine is partly due to inter-individual variation in the thiopurine methyltransferase (TPMT) activity. The TPMT genotype, which reflects the TPMT activity, has previously been studied in healthy Caucasians, with the most common variant allele being TPMT*3A. TPMT genotyping in adult patients with Crohn's disease has never been performed systematically. AIM: To determine the TPMT genotype distribution in adult patients with Crohn's disease. METHODS: One hundred and twenty randomly selected Danish patients (64 females and 56 males) with azathioprine-dependent Crohn's disease were included, and a polymerase chain reaction assay was used for TPMT genotyping. The patients were genotyped for the low-level genotype G460-->A and A719-->G transitions. RESULTS: One hundred and nine patients (90.3%; 95% confidence interval, 84.1-95.3) had a wild-type/ wild-type genotype, whereas 10 patients (8.3%; 95% confidence interval, 4.1-14.8) had one non-functional mutant allele and one patient (0.8%; 95% confidence interval, 0.02-4.6) had two non-functional mutant alleles. Only the TPMT*3A variant allele was found. CONCLUSIONS: The study showed a TPMT genotype distribution amongst adult Danish patients with Crohn's disease which was similar to the distribution of TPMT variant alleles normally found in healthy Caucasians.

Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year.

INTRODUCTION: Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated. AIMS: To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose-response relationship. PATIENTS AND METHODS: In an open 12-month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise >/= 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention. RESULTS: Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017). CONCLUSIONS: Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.

Outcome of pre-hospital antibiotic treatment of meningococcal disease.

OBJECTIVE: To assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. DESIGN: A 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark. SUBJECTS: 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. MAIN OUTCOME MEASURES: Death. RESULTS: 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae, and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio (OR) for death in patients treated with antibiotics was high (OR = 3.2; 95% CI, 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. If skin bleeding was replaced in the models by the presence of disseminated intravascular coagulation on admission, the OR for death in patients with pre-hospital antibiotic treatment was 35.9 (95% CI, 2.9-441.8) in the presence of disseminated intravascular coagulation and 1.9 (95% CI, 0.2-19.5) in its absence. CONCLUSIONS: Pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings but provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

Antibiotic resistance patterns among blood culture isolates in a Danish county 1981-1995.

All episodes of bacteraemia during a 15-year period (1981-1995) in the County of Northern Jutland, Denmark, were analysed with regard to antibiotic resistance. A total of 8840 isolates from 7938 episodes of bacteraemia was identified. Over time, no changes in bacterial aetiology were noted. Three isolates of Staphylococcus aureus were methicillin resistant (0.2%) and six were gentamicin resistant (0.4%). Among coagulase-negative staphylococci a 14% increase in resistance to penicillin was observed (95% confidence intervals, CI: 2-26%). Likewise, the frequency of resistance to methicillin, gentamicin and erythromycin increased, the corresponding figures being 38% (CI: 26-50%), 26% (CI: 14-38%) and 32% (CI: 16-50%), respectively, whereas a 14% decrease in resistance to streptomycin was recorded (CI: 4-24%). A 20% (CI: 2-37%) increase of coagulase-negative staphylococci resistant to three or more antibiotics was observed. The frequency of ampicillin resistance increased by 9% among Escherichia coli (CI: 4-13%) and by 10% (CI: 6-14%) in all Enterobacteriaceae. Among Enterobacteriaceae the level of resistance to third-generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones remained low (<1%). The frequency of resistance to three or more antibiotics remained fairly stable among Enterobacteriaceae, although a slight increase was noted among E. coli (5%; CI: 0-10%) The recommended regimen for empirical antibiotic treatment in this region (a combination of penicillin G or ampicillin and an aminoglycoside) provided an overall coverage of 94% (CI: 94-95%), although a slight decrease was noted at the end of the period. In conclusion, acquired antibiotic resistance was maintained at a low level compared with most other European countries and regions during the 15-year period studied.

[Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography]. / Detektion af kolangiokarcinom ved primaer skleroserende cholangitis ved hjaelp af positron-emissionstomografi.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC). PET scanning can assess metabolism in vivo. The glucose analogue [18 F]fluoro-2-deoxy-D-glucose (FDG) accumulates in malignant tumours because of high glucose metabolism. PET scanning of the liver was performed after intravenous FDG in nine patients with PSC, six with PSC + CC, and five controls. "Hot spots" with radioactivity accumulation were seen in each PSC + CC patient, but not in the two other groups. Values of net metabolic clearance of FDG, K (ml min-1 100 ml-1 tissue), was in CC hot spots 1.59 to 4.17 (median, 2.34; n = 6); in reference liver tissues of these patients 0.40 to 0.69 (0.49); in PSC 0.23 to 0.53 (0.36); in controls 0.20 to 0.34 (0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < 0.001). FDG-PET may detect small CC tumours and be useful in therapeutic management of PSC.

[Antibiotic pre-hospital treatment and the course of meningococcal disease]. / Antibiotisk behandling før indlaeggelse og forløbet af meningokoksygdom.

The aim of the study was to assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. It was carried out as a 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark, and included 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. The main outcome measure was death. We found that 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio for death in patients treated with antibiotics was high (3.2; 95% CI 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. It is concluded that pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings and provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage--a placebo-controlled study.

BACKGROUND: Nonvariceal acute upper gastrointestinal bleeding (AUGIB) is often accompanied by post-discharge anaemia. AIM: To investigate whether iron treatment can effectively treat anaemia and to compare a 3-month regimen of oral iron treatment with a single administration of intravenous iron prior to discharge. METHODS: Ninety-seven patients with nonvariceal AUGIB and anaemia were enrolled in a double-blind, placebo-controlled, randomised study. The patients were allocated to one of three groups, receiving a single intravenous administration of 1000 mg of iron; oral iron treatment, 200 mg daily for 3 months; or placebo, respectively. The patients were followed up for 3 months. RESULTS: From week 4 onwards, patients receiving treatment had significantly higher haemoglobin levels compared with patients who received placebo only. At the end of treatment, the proportion of patients with anaemia was significantly higher in the placebo group (P < 0.01) than in the treatment groups. Intravenous iron appeared to be more effective than oral iron in ensuring sufficient iron stores. CONCLUSIONS: Iron treatment is effective and essential for treating anaemia after nonvariceal acute upper gastrointestinal bleeding. The route of iron supplementation is less important in terms of the increase in haemoglobin levels. Iron stores are filled most effectively if intravenous iron supplementation is administered (ClinicalTrials.gov identifier: NCT00978575).

Pilot study trialling a new ambulatory method for the clinical assessment of regional gastrointestinal transit using multiple electromagnetic capsules.

BACKGROUND: Gastrointestinal (GI) motor disorders often involve several regions of the GI tract. Therefore, easy and safe assessment of whole gut and regional motility is valuable for more precise diagnosis. 3D-Transit is a novel method for ambulatory evaluation of total and regional gastrointestinal transit times (GITT) based on the anatomical localization of ingestible electromagnetic capsules. The main purpose of this study was to test the performance of the 3D-Transit system. METHODS: Twenty healthy volunteers each ingested three electromagnetic capsules over a period of two consecutive days. Standard radio-opaque markers (ROM) were also ingested to assess the agreement between total GITT obtained with both methods. KEY RESULTS: Investigations were well-tolerated and three capsules could be tracked simultaneously with minimal data loss (Capsule 1: median: 0.2% of time (range 0-25.3%). Region specific contraction patterns were identified and used for computation of total and regional GITT in all subjects. Inter-observer agreement was 100% for total GITT (median variation 0%) but less for regional GITT. Day-to-day and diurnal variations were significant for total and regional GITT. Total GITT assessed by 3D-Transit capsules were moderately well-correlated to those assessed with standard ROM (Spearman's rho = 0.7). CONCLUSIONS & INFERENCES: 3D-transit is a well-tolerated and minimal invasive ambulatory method for assessment of GI motility. By providing both total and regional transit times, the 3D-Transit system holds great promise for future clinical studies of GI function in health and disease.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.