Factors associated with quality of care in inflammatory bowel diseases: a view from patient's side using the IQCARO quality of care decalogue.

BACKGROUND: Quality of care (QoC) is a highly important topic in inflammatory bowel disease (IBD). We recently elaborated a decalogue of QoC indicators (IQCARO-QoC) developed by IBD patients. The aim of the present study was to assess the factors associated with patients' evaluation of QoC in Spain using the IQCARO-QoC Decalogue recently developed by IBD patients. METHODS: A survey including patients' socio-demographic and clinical characteristics, and the IQCARO-QoC Decalogue, was completed by IBD patients. We described patients' assessment of QoC across Spanish patients. A univariable and multivariable analysis was performed to explore the associations between patients' characteristics and QoC. RESULTS: Questionnaires from 788 participant patients were analysed. Participants' mean age was 43.4 years, 63% were females and 58% had Crohn's disease. The mean QoC score was 8.1 (± 2.4 SD) points out of a maximum of 10. Items with the lowest score were related to the provision of information and the implication of the medical team throughout the entire patient care. Factors associated with better QoC scores included: being employed better disease control, fewer numbers of unscheduled visits, and being followed by a gastroenterologist specialized in IBD. CONCLUSIONS: Spanish patients' reported QoC seems to be globally good although there is room for improvement, especially in providing adequate information to patients. Care provided by specialized IBD gastroenterologists seems to be related with higher QoC scores.

Fungal and Bacterial Loads: Noninvasive Inflammatory Bowel Disease Biomarkers for the Clinical Setting.

Microbiome sequence data have been used to characterize Crohn's disease (CD) and ulcerative colitis (UC). Based on these data, we have previously identified microbiomarkers at the genus level to predict CD and CD relapse. However, microbial load was underexplored as a potential biomarker in inflammatory bowel disease (IBD). Here, we sought to study the use of fungal and bacterial loads as biomarkers to detect both CD and UC and CD and UC relapse. We analyzed the fecal fungal and bacterial loads of 294 stool samples obtained from 206 participants using real-time PCR amplification of the ITS2 region and the 16S rRNA gene, respectively. We combined the microbial data with demographic and standard laboratory data to diagnose ileal or ileocolonic CD and UC and predict disease relapse using the random forest algorithm. Fungal and bacterial loads were significantly different between healthy relatives of IBD patients and nonrelated healthy controls, between CD and UC patients in endoscopic remission, and between UC patients in relapse and non-UC individuals. Microbial load data combined with demographic and standard laboratory data improved the performance of the random forest models by 18%, reaching an average area under the receiver operating characteristic curve (AUC) of 0.842 (95% confidence interval [CI], 0.65 to 0.98), for IBD diagnosis and enhanced CD and UC discrimination and CD and UC relapse prediction. Our findings show that fecal fungal and bacterial loads could provide physicians with a noninvasive tool to discriminate disease subtypes or to predict disease flare in the clinical setting.IMPORTANCE Next-generation sequence data analysis has allowed a better understanding of the pathophysiology of IBD, relating microbiome composition and functions to the disease. Microbiome composition profiling may provide efficient diagnosis and prognosis tools in IBD. However, the bacterial and fungal loads of the fecal microbiota are underexplored as potential biomarkers of IBD. Ulcerative colitis (UC) patients have higher fecal fungal and bacterial loads than patients with ileal or ileocolonic CD. CD patients who relapsed harbor more-unstable fungal and bacterial loads than those of relapsed UC patients. Fecal fungal and bacterial load data improved prediction performance by 18% for IBD diagnosis based solely on clinical data and enhanced CD and UC discrimination and prediction of CD and UC relapse. Combined with existing laboratory biomarkers such as fecal calprotectin and C-reactive protein (CRP), microbial loads may improve the diagnostic accuracy of IBD and of ileal CD and UC disease activity and prediction of UC and ileal CD clinical relapse.

Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study.

BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.

Factors that impact health-related quality of life in adults with celiac disease: a multicenter study.

AIM: To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS: A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires: the gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS: Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a gluten-free diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72 P < 0.001 and 80 vs 70 P < 0.001, respectively). Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION: In untreated celiac disease, the most important factors that influence patient perception of health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.

Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin.

BACKGROUND: Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. OBJECTIVE: To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. DESIGN: Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g/day) and randomly allocated to receive either oligofructose-enriched inulin (12 g/day, p.o., n = 10) or placebo (12 g/day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. RESULTS: Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 +/- 659 microg/g; day 7: 1033 +/- 393 microg/g, P < 0.05) but not in the placebo group (day 0: 5834 +/- 1563 microg/g; day 7: 4084 +/- 1395 microg/g, n.s.). Changes in faecal concentration of human DNA were not significant. CONCLUSION: In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin.

[Spanish translation, adaptation, and validation of the 32-item questionnaire on quality of life for inflammatory bowel disease(IBDQ-32)]. / Traducción, adaptación y validación al español del cuestionario de calidad de vida de 32 ítems (IBDQ-32) de la enfermedad inflamatoria intestinal.

INTRODUCTION: The measurement of health-related quality of life (HRQoL) has an established relevance in the assessment, management, and follow-up of inflammatory bowel disease. The most commonly used measuring instrument is the 32-item version of Inflammatory Bowel Disease Questionnaire (IBDQ-32), which has never been adapted to Spanish. OBJECTIVE: To translate IBDQ-32 into Spanish, and to establish its validity, reliability, and sensitivity both in ulcerative colitis and Crohn s disease. METHOD: A prospective study in two phases -translation into Spanish and subsequent validation of IBDQ-32. Translation was based on the validated Spanish version of IBDQ-36, and IBDQ-32 items not included in IBDQ-36 were translated from scratch. Once the IBDQ32 translation was completed a comprehension-specific questionnaire was administered. To establish IBDQ-32 psychometric properties a group of patients completed both the validated Spanish version of IBDQ-36 and IBDQ-32. RESULTS: Eighty-four patients (53 with Crohn s disease and 31 with ulcerative colitis) were included. Median overall scores in both questionnaires for all 84 patients did not differ (6.1 vs. 6.2, p = ns), and Spearman s correlation was highly significant (r = 0.97, p < 0.001). The ability to discriminate between patients in flare-up or remission was also equivalent for both questionnaires (6.4 vs. 6.4 with r = 0.96 in remission and 3.8 vs. 3.9 with r = 0.95 active, p < 0.001 for remission vs. activity). These results were obtained in both the analyses for CD and UC independently (6.4 vs. 6.4 and 6.7 vs. 6.6, respectively; p = ns). CONCLUSION: The Spanish version of IBDQ-32 is valid and discriminating for patients with Crohn s disease or ulcerative colitis.

[Inflammatory bowel disease in celiac patients]. / Enfermedad inflamatoria intestinal en pacientes celíacos.

INTRODUCTION: A potential association between celic disease and inflammatory bowel disease hs been suggested, which may explain the fact that both disorders occasionally present in one patient or in his/her first-degree relatives more frequently than expected. OBJECTIVE: To establish the prevalence of Crohn s disease and ulcerative colitis in celiac patients and their relatives. METHOD: A cross-sectional, prospective epidemiological study in a group of celiac patients, their first-degree relatives, and a control group with similar epidemiological characteristics including the relatives of patients presenting at the ER for acute conditions. A semistructured interview was used to identify the presence of Crohn s disease and ulcerative colitis in celiac patients and their relatives. RESULTS: In all, 86 celiac patients and 432 relatives were included, who were compared to 809 control subjects (129 patients with acute conditions and 680 first-degree relatives). Three cases of Crohn s disease were identified among celiac patients, and 4 cases among their relatives. Only 1 case of Crohn s disease was detected in the control group (p < 0.01). No cases of ulcerative colitis were detected in any of the study groups. CONCLUSION: Patients with celiac disease and their relatives have a greater predisposition to Crohn s disease versus the control population.

Current epidemiology and accessibility to diet compliance in adult celiac disease.

BACKGROUND: The widespread of serologic diagnosis for celiac disease has brought about an epidemiologic shift. Little up-to-date information is available on relevant epidemiologic issues regarding diagnosis, information, and therapy. OBJECTIVE: To examine forms of presentation, diagnostic difficulties, follow-up, information sources, and treatment-related issues regarding celiac disease. METHOD: A cross-sectional observational study using a self-completed questionnaire. RESULTS: Seventy-three adult patients were included; 15.0% of cases were diagnosed over 60 years of age. Most were non-smokers (91.8%). The rate of first-degree relatives with celiac sprue was 10.9%. The disease had a classic presentation in only 54.7% of cases. A functional gastrointestinal disorder was initially suspected in 42.4% of patients. Diet adherence is adequate, with unintentional lack of compliance in 15.5% of patients. Diet results in absent or improved symptoms in virtually all patients, but most of them consider compliance a challenge. Forty percent had difficulty finding gluten-free food, and 50.8% had problems in labelling recognition. CONCLUSIONS: Celiac disease presents at any age, has a great variety of manifestations, and responds very well to gluten-free diet. It is crucial that patients be highly motivated and informed, and that they know for certain which foods and manufactured products are to be to used. Therefore, adequate control will result from coordination and cooperation regarding all resources involved, including medical care, and information provided by associations and other sources such as the Web.

Perception of lactose intolerance impairs health-related quality of life.

BACKGROUND/OBJECTIVES: Chronic conditions impair perception of well-being. Malabsorption of lactose is the most frequent form of malabsorption and manifests as lactose intolerance. There is a lack of information regarding their impact on self-perception of health. The objective of this study is to determine the subjective impact of self-reported lactose intolerance or objective lactose malabsorption on patient health by using a patient-reported outcome to measure health-related quality of life (HRQOL) and modification of lactose-containing food diet. SUBJECTS/METHODS: A 3-year prospective, cross-sectional study was performed in patients referred for a lactose hydrogen breath test. Patients were asked about their subjective opinion relative to their lactose tolerance and completed a validated, specific questionnaire to determine symptoms of intolerance during habitual consumption of dairy. A 50-g lactose breath test was then performed. Patients were grouped as absorbers vs malabsorbers and tolerant vs intolerants. RESULTS: A total of 580 patients were included (median age 30 years, 419 female). Overall, 324 patients (56%) considered themselves lactose intolerant and that perception was associated with avoidance of dairy consumption (55% vs only 9% of self-defined tolerants). Self-perception of intolerance was associated with lower HRQOL scores (median, 60 vs 70, P<0.01). In contrast, lactose objective malabsorption was not clearly associated with dairy avoidance (41% of malabsorbers avoided dairy vs 31% of absorbers). However, HRQOL scores were also significantly lower in malabsorbers than in absorbers (60 vs 70 respectively, P<0.001). CONCLUSIONS: Subjective perception of lactose intolerance affects the decision to avoid dairy even more than objective malabsorption. However, both self-perception of lactose intolerance and objective lactose malabsorption are associated with poorer perceived quality of life.

Impairment of health-related quality of life in patients with inflammatory bowel disease: a Spanish multicenter study.

BACKGROUND: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health-related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. METHODS: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. RESULTS: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. CONCLUSIONS: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.

Perceived health status in celiac disease.

INTRODUCTION: Chronic conditions modify perceived health in affected individuals. For this reason celiac disease, being a chronic condition, may impair health-related quality of life (HRQOL). OBJECTIVE: To analyze the impact of celiac disease in affected individuals. METHOD: Observational, cross-sectional, prospective study in patients with celiac disease by administering two HRQOL questionnaires: EuroQol-5D and GastroIntestinal Quality of Life (GIQLI). RESULTS: 54 stable patients on a gluten-free diet for a median 60 months, and 9 newly diagnosed individuals still on their usual diet were included. Overall GIQLI score was significantly higher, meaning a better HRQOL, in treated celiac patients versus pre-treated celiac patients (3.1 [2.7-3.5] vs. 2.4 [2.1-2.6], p < 0.01). Similarly, EuroQol s health status preference value was also significantly better in treated patients (0.87[0.8-1.0] vs. 0.7 [0.5-0.8], p < 0.01). EuroQol s visual analogic scale had also better scores, representing a better perceived health, among treated patients (80.0 [70.0-90.0] vs. 65.0 [40.0-71.0], p < 0.05). In comparison to EuroQol-5D scores among the healthy Spanish population, values obtained for celiac patients under treatment are similar to those seen in the general population. CONCLUSIONS: celiac disease impairs perceived health in affected individuals, which improves and reaches results similar to those in the general population when on a gluten-free diet.

Shortened questionnaire on quality of life for inflammatory bowel disease.

Questionnaires for measuring quality of life in patients with inflammatory bowel disease usually include a large number of items and are time-consuming for both administration and interpretation. Our aim was to elaborate and validate a short quality-of-life questionnaire with the most representative items from the Spanish version of the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) using the Rasch analysis. The responses to 311 IBDQ-36 questionnaires from 167 patients with ulcerative colitis (UC) and 144 with Crohn's disease (CD) were analyzed. IBDQ-36 was shortened with successive Rasch analyses until all the remaining items showed acceptable separation and goodness-of-fit properties. Validation of the short questionnaire was studied in a new group of 125 patients by determining its validity and reliability. A 9-item short questionnaire was obtained (IBDQ-9). Its correlation with IBDQ-36 was excellent (r = 0.91). Correlation between IBDQ-9 and clinical indices of activity was statistically significant in UC (r = 0.70) and CD (r= 0.70). IBDQ-9 score discriminates adequately between patients in clinical remission or relapse (P < 0.01). Sensitivity to change was determined in 14 patients who improved clinically, showing significant IBDQ-9 changes between both determinations (P < 0.01), with an effect size of -2.67 in UC and -5.29 in CD. IBDQ-9 was also homogeneous, with a Cronbach's alpha of 0.95 in UC and 0.91 in CD. In 35-clinically stable patients, test-retest reliability was good, with a statistically-significant correlation between both questionnaires (r = 0.76 in UC and 0.86 in CD, P < 0.01) and an intraclass correlation coefficient of 0.82 in UC and 0.84 in CD. In conclusion, a short and valid questionnaire to measure quality of life in patients with inflammatory bowel disease was obtained using a new measurement model. Its use should facilitate comprehension of the impact of inflammatory bowel disease.

Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in active ulcerative colitis.

The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.

Hydrogen breath test with glucose in exocrine pancreatic insufficiency.

The present study was designed to investigate the prevalence of bacterial overgrowth in patients with exocrine pancreatic insufficiency by using the hydrogen breath test with glucose. Thus, in 30 patients with exocrine pancreatic insufficiency (in 15 due to chronic pancreatitis and in 15 associated to primary immunodeficiency), established by quantifying trypsin output before and after stimulation with cerulein using a duodenal perfusion technique, a glucose test was performed by administering 50 g of glucose and quantifying H2 in the breath by gas chromatography. The glucose test was positive in six of 15 patients with chronic pancreatitis but in only one of 15 immunodeficient patients (p < 0.05). Age, sex, etiology, time of evolution, associated diabetes, pancreatic calcifications, duodenal pH, or duodenal trypsin output did not differ between patients with and those without bacterial overgrowth. Previous gastroduodenal surgery was more common in chronic pancreatitis patients with overgrowth (six of six vs. four of nine; p < 0.05). Five patients with a positive glucose test were treated with antibiotics for 2 weeks and became negative in two of them. These results suggest that a positive glucose test indicating overgrowth is relatively common in exocrine pancreatic insufficiency due to chronic pancreatic, especially in patients with previous gastroduodenal surgery.

Influence of inflammatory bowel disease on different dimensions of quality of life.

OBJECTIVE: To establish the impairment of different dimensions of quality of life in inflammatory bowel disease (IBD). DESIGN: Prospective observational study. PARTICIPANTS: 289 patients [160 with ulcerative colitis (UC) and 129 with Crohn's disease (CD)]. MEASURES: Health-related quality of life was assessed by means of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Psychological General Well Being Index (PGWBI). RESULTS: In active IBD, all dimensions of the quality of life scored significantly lower than in inactive IBD, indicating a poor quality of life. Social impairment was the least impaired dimension of the IBDQ in active UC and CD, compared with digestive and systemic symptoms. In inactive IBD, the systemic symptoms domain received the lowest score (P < 0.01). In a subgroup of 22 patients studied before and after remission, emotional function was the most impaired dimension after achieving remission. The Psychological General Well Being Index was significantly impaired in active UC [78.5 (range 64-89)] and CD [76.5 (range 69-97)] relative inactive IBD [104 (range 93-111)] vs 106 (95-113), respectively; P < 0.05]. CONCLUSIONS: Quality of life is impaired in IBD. During relapse, clinicians should pay attention to digestive symptoms and psychological distress. In remission, they should be sensitive to systemic symptoms.

Effects of smoking on the presentation and clinical course of inflammatory bowel disease.

OBJECTIVE: To evaluate the influence of regular smoking on the presentation and clinical course of inflammatory bowel disease. METHODS: We performed a case-control study interviewing 160 inflammatory bowel disease patients (63 with Crohn's disease (CD) and 97 with ulcerative colitis (UC)) and 140 first-degree relatives as controls. The risk of developing the disease relative to a smoking habit was calculated as the odds ratio. Furthermore, to evaluate the influence of smoking on the subsequent course of inflammatory bowel disease, we performed a multivariate analysis that included pertinent variables such as the need for surgery, number of hospitalizations and relapses. RESULTS: The pattern of smoking in UC patients was different from that in CD patients. In UC there was a significant predominance of non-smokers and ex-smokers (P = 0.02), whereas smoking habits in CD were not different from those in controls. Giving up smoking was a risk factor to develop UC (odds ratio: 3.2, P = 0.02). In UC, non-smokers and specially ex-smokers need surgery more frequently than smokers (P < 0.01). Otherwise the relapse/year index was not influenced by smoking. In CD there was a non-significant association between smoking habits and the various clinical parameters analysed. UC patients who begin smoking after diagnosis of the disease present a significant reduction in the number of recurrences. CONCLUSION: Smoking habit significantly affects the presentation and clinical course of UC, whereas in CD, a smoking habit does not have any apparent influence on the disease.

Helicobacter pylori eradication prevents recurrence from peptic ulcer haemorrhage.

BACKGROUND: Successful eradication of Helicobacter pylori infection clearly modifies the natural history of peptic ulcer disease and prevents further recurrences of duodenal and gastric ulcers. However, there are few prospective studies about actual rates of rebleeding after H. pylori eradication, a highly relevant aspect of management as re-infection, relapse of ulcer disease for other reasons (i.e. anti-inflammatory agents) or idiopathic ulcers unrelated to H. pylori may develop and cause further bleeding episodes. OBJECTIVE: To determine the incidence of bleeding episodes after eradication of H. pylori infection in patients who had bled from an H. pylori-positive peptic ulcer. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients who bled from a gastric or duodenal ulcer were treated with appropriate triple and/or quadruple therapy. H. pylori eradication was confirmed by urea breath test 4 weeks after treatment. Patients received no further treatment but were followed clinically and additional urea breath tests were performed every 6 months. Endoscopy with antral and corpus biopsies and urea breath test were repeated as soon as patients manifested any dyspeptic symptoms that might signal recurrence. RESULTS: A total of 103 patients with bleeding duodenal ulcer were included in the study; H. pylori was successfully eradicated in 93 of these patients, who were followed for a median interval of 27 months. The yearly re-infection rate was calculated to be 0.6%. There were no instances of rebleeding in any patients during the follow-up period. CONCLUSIONS: Even after prolonged follow-up, successful H. pylori eradication prevents rebleeding.

Effects of thromboxane synthase inhibition on in vivo release of inflammatory mediators in chronic ulcerative colitis.

OBJECTIVE: To evaluate the effects of a thromboxane inhibitor on the production of eicosanoids by the colonic mucosa of patients with chronic ulcerative colitis. PATIENTS AND METHODS: Fourteen patients with active left-sided ulcerative colitis were divided into in two treatment groups. Seven patients received oral ridogrel (300 mg twice daily) and seven 5-aminosalicylic acid (5-ASA; 1 g twice daily) for 4 weeks. Intracolonic eicosanoid and elastase release were measured using a colonic double-lumen perfusion technique. An isotonic solution was infused 50 cm from the anal verge at the rate of 5 ml/min, and recovered by siphonage 30 cm distally. Effluents were assayed for thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) by radioimmunoassay (RIA), and for polymorphonuclear elastase by immunoactivation. Clinical and colonoscopic criteria were used to determine activity before and after treatment. RESULTS: Four of the seven patients in the ridogrel group and five of the seven in the 5-ASA group showed clinical and colonoscopic improvement. Intraluminal elastase release decreased in every responding patient in the 5-ASA group (P < 0.05) and in three out of seven responders in the ridogrel group. Basal eicosanoid release was similar in both groups. In the responders, 5-ASA significantly reduced the release of the three eicosanoids (P < 0.05). Ridogrel reduced the release of TXB2 to 31% of basal levels (P < 0.01) but the release of PGE2 and LTB4 was not affected. CONCLUSIONS: These results suggest that ridogrel is an oral active selective inhibitor of thromboxane synthetase, which modifies the pattern of colonic eicosanoid generation in patients with chronic ulcerative colitis. Oral ridogrel may be a useful treatment for patients with non-severe ulcerative colitis, although specific indications require further studies.

Genetic heterogeneity within ulcerative colitis determined by an interleukin-1 receptor antagonist gene polymorphism and antineutrophil cytoplasmic antibodies.

BACKGROUND: Although there is strong evidence implicating genetic predisposition in the pathogenesis of the chronic inflammatory bowel diseases, the number and identity of susceptibility genes remain uncertain. Cytokine genes are tentative candidate loci, but data regarding association studies in different populations are conflicting. AIMS: To determine potential associations of interleukin-1 receptor antagonist (IL-1ra), tumour necrosis factor alpha (TNF alpha), and tumour necrosis factor beta (TNF beta) gene polymorphisms with ulcerative colitis or subsets of ulcerative colitis in a Spanish population. METHODS: Genotyping for IL-1ra, TNF alpha and TNF beta gene polymorphisms was performed by the polymerase chain reaction in 95 patients with ulcerative colitis and 74 healthy controls. A variable number of tandem repeats (VNTR) in the IL-1ra gene, and a single base pair polymorphism in the TNF alpha gene promoter region (-308) and in the first intron of the TNF beta gene were analysed. Anti-neutrophil cytoplasmic antibodies (ANCA) were detected using an indirect immunofluorescence assay. RESULTS: There were no significant differences between ulcerative colitis patients and controls in either polymorphism analysed, nor between ulcerative colitis subgroups as a function of the clinical disease pattern. However, when stratified by their ANCA status, perinuclear ANCA (p-ANCA) ulcerative colitis showed an increased frequency of the genotype 1,2 of the IL-1ra gene compared with ANCA-negative ulcerative colitis (52% versus 28%; P = 0.02, Pcorr = 0.1). Furthermore, p-ANCA ulcerative colitis had a statistically significant increase of this genotype compared with cytoplasmic ANCA (c-ANCA)/ANCA-negative ulcerative colitis (52% versus 26.5%; P = 0.01, Pcorr = 0.05). CONCLUSIONS: In the Spanish population studied, the polymorphisms analysed in the IL-1ra, TNF alpha and TNF beta genes are unlikely to be important in the overall susceptibility to ulcerative colitis. However, the combination of a subclinical (p-ANCA) and a genetic (IL-1ra gene) marker identified a distinct ulcerative colitis subgroup (p-ANCA; IL-1ra genotype 1,2). These findings provide further evidence of genetic heterogeneity within ulcerative colitis, and support the concept that ANCA may represent a subclinical marker of genetic heterogeneity.