Persistence of subcutaneous versus intravenous infliximab in a real-life cohort: A propensity-score matched comparative analysis.

BACKGROUND: There is limited comparative data on patients with inflammatory bowel disease (IBD) switched from intravenous to subcutaneous infliximab and those continuing intravenously. This study aimed to compare the persistence and tolerance of subcutaneous and intravenous infliximab and the outcomes of patients resuming intravenous infliximab. METHODS: We conducted a retrospective single-centre cohort study involving IBD patients treated with maintenance intravenous infliximab. The switch to subcutaneous infliximab was offered to patients in clinical remission receiving an intravenous dose ≤ 10 mg kg-1 every ≥ 6 weeks. The switch group was compared to controls remaining on intravenous infliximab due to refusal of the switch. RESULTS: With a median follow-up of 59 (46-67) weeks, subcutaneous infliximab was discontinued in 28/282 (10 %) patients and intravenous infliximab in 1/78 (1 %) patient (p = 0.01); after propensity score-matching of the two cohorts, persistence rates at 52 weeks were respectively 91 % (95 % CI 84-98) and 100 % (95 % CI 100-100, p = 0.01). Among the 28 who discontinued subcutaneous infliximab, 27 resumed intravenous infliximab, with 4 (1 % of the switch group) who permanently stopped infliximab. CONCLUSION: Switching from intravenous to subcutaneous infliximab led to a lower treatment persistance. In cases of poor tolerance or relapse under subcutaneous infliximab, resuming intravenous infliximab is effective.

Deep ulcers are associated with increased C-reactive protein in active ulcerative colitis.

BACKGROUND: Increased C-reactive protein (CRP) is used to diagnose and predict response to treatment in acute severe ulcerative colitis (UC). AIMS: To investigate the connection between CRP elevation and deep ulcers in UC. METHODS: Patients with active UC were enrolled in a multicenter prospective cohort and a retrospective cohort of consecutive patients undergoing colectomy from 2012 to 2019. RESULTS: Forty-one (9 (22%) with deep ulcers) patients were included in the prospective cohort: 4/5 (80%) patients with CRP > 100 mg/L, 2/10 (20%) patients with CRP between 30 and 100 mg/L and 3/26 (12%) patients with CRP < 30 mg/L had deep ulcers (p = 0.006). In the retrospective cohort [46 patients (31 (67%) with deep ulcers)], 14/14 (100%) patients with CRP > 100 mg/L, 11/17 (65%) patients with CRP between 30 and 100 mg/l and 6/15 (40%) patients with CRP < 30 mg/L had deep ulcers (p = 0.001). Positive predictive value of CRP > 100 mg/l for presence of deep ulcers was 80% and 100% in both cohorts, respectively. CONCLUSIONS: CRP elevation is a robust surrogate marker for presence of deep ulcers in UC. Elevated CRP or presence of deep ulcers could influence the choice of medical therapy in acute severe UC.

COVID-19 pandemic and lockdown stress consequences in people with and without Irritable Bowel Syndrome.

BACKGROUND: While all resources have been mobilized to fight COVID-19, this study aimed to analyze the consequences of lockdown and pandemic stress in participants with and without Irritable Bowel Syndrome (IBS). METHODOLOGY: An online survey was proposed to people with or without IBS during the exponential phase of the pandemic in France. The questionnaire included questions about socio-demographic data, conditions of confinement, activities carried out, IBS characteristics, measurement of stress level, consequences on sleep, fatigue, anxiety and depression, and quality of life (both perceived non-specific and specific for IBS). RESULTS/DISCUSSION: From March 31 to April 15, 2020, 304 participants, 232 with IBS and 72 without were included in the survey (mean age: 46.8 ± 16.8 years, female gender: 75.3%). Age, level of education, financial resources, living space per person and activities performed during confinement were identical in both groups. Stress linked to fear of COVID-19, lockdown and financial worries was at the same level in both groups, but the psychological consequences and deterioration of quality of life (QOL) were both higher in IBS participants. In a univariate analysis, teleworking, solitary confinement, and low household resources had a variable impact on the scores of depression, anxiety, fatigue and non-specific perceived QOL, but in a multivariate analysis, the only factor explaining a deterioration of non-specific QOL was the fact of suffering from IBS. CONCLUSION/PERSPECTIVES: Stress linked to the COVID-19 pandemic and confinement is high and equivalent in both IBS and non-IBS participants, with higher psychological and QOL consequences in IBS patients who have altered coping capacities.

Les colites microscopiques.

Microscopic colitis is frequently found as a cause of chronic watery diarrhea in women after menopause. The disease can be associated with a medication side effect in half of the patients (non-steroidal anti-inflammatory drugs or proton pump inhibitors for instance). Colonic biopsies are mandatory for the diagnosis of microscopic colitis and should be performed in several locations of the colon. Management of microscopic colitis is first based on avoiding iatrogenic factors and smoking together with symptomatic treatment of diarrhea (loperamide, cholestyramine). In case of failure or severe symptoms, budesonide is the key treatment. The aim of the treatment is to achieve clinical remission, defined as less than 3 liquid stools per day, to improve quality of life. After a first course of budesonide, recurrence of diarrhea is frequent and a maintenance therapy can be prescribed for several months. In case of intolerance or refractoriness, second-line therapy (immunosuppressants, biological therapy, surgery) should be discussed in multidisciplinary team meeting.

Expectations of IBS patients concerning disease and healthcare providers: Results of a prospective survey among members of a French patients' association.

BACKGROUND AND AIMS: IBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients' organization. PATIENTS AND METHODS: From January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP. RESULTS: 222/330 (67%) responded (women: 68.5%, 46.5±17.7 years, disease duration: 8.8±0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS>300 in 53% and HAD score>19 in 45%). QoL impairment was correlated with disease severity and HAD score (r=-0.707 and r=-0.484, P<0.001 respectively), but not with IBS subtype. Expectations for IBS were "improved health", "better information on causes and treatments" (94%) and "better disease recognition" (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients' organization. CONCLUSIONS: French IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients' organization.

The 2018 ISDE achalasia guidelines

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Frequency of and Factors Associated With Sexual Dysfunction in Patients With Inflammatory Bowel Disease.

BACKGROUND: Improvement of quality of life is a main objective in inflammatory bowel disease [IBD] management. Data on sexual dysfunction [SD] in IBD are scarce. This study compared rates of SD between IBD patients and healthy controls [HC], and searched for predictors of SD. METHODS: All consecutive IBD patients seen in two tertiary centres during 2 months were invited to fill an anonymous validated questionnaire on their sexual function [Female Sexual Index Function and International Index of Erectile Function]. The same questionnaires were filled by HC and by patients with irritable bowel syndrome [IBS] enrolled as a second comparative group. RESULTS: In all, 358 IBD patients filled the questionnaire [192 women]-including 238 with Crohn's disease and 120 with ulcerative colitis-and 110 HC [54 women] and 107 IBS patients [54 women]. In women, SD rates were 53.6% in IBD vs 28% in HC [p < 0.01] and 77.5% in IBS [p = 0.10] patients; in men, figures were 16.9% in IBD, 7.4% in HC [p = 0.64], and 26.4% in IBS [p = 0.60]. An erectile dysfunction [ED] was reported by 43% of IBD patients, 13% of HC [p < 0.01] and 55% of IBS patients [p = 0.60 vs IBD]. Predictors of SD and ED were social and emotional functioning, anxiety in women and depression in men. IBD activity was not associated with SD. CONCLUSIONS: In IBD, 54% of women have an SD and 43% of men an ED. These rates are significantly higher than in HC, mostly driven by psychological factors, and independent from disease severity.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

BACKGROUND: An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD). METHODS: Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings. KEY RESULTS: Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux. CONCLUSIONS AND INFERENCES: The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.

Randomized clinical trial of sacral nerve stimulation for refractory constipation.

BACKGROUND: Open studies have reported favourable results for sacral nerve stimulation in the treatment of refractory constipation. Here, its efficacy was assessed in a double-blind crossover RCT. METHODS: Patients with at least two of the following criteria were included: fewer than three bowel movements per week; straining to evacuate on more than 25 per cent of attempts; or sensation of incomplete evacuation on more than 25 per cent of occasions. Response to therapy was defined as at least three bowel movements per week and/or more than 50 per cent improvement in symptoms. Responders to an initial 3-week peripheral nerve evaluation were offered permanent implantation of a pulse generator and were assigned randomly in a crossover design to two 8-week intervals of active or sham stimulation. At the end of the two trial periods, the patients received active stimulation until the final evaluation at 1 year. RESULTS: Thirty-six patients (34 women; mean(s.d.) age 45(14) years) underwent peripheral nerve evaluation. Twenty responded and received a permanent stimulator. A positive response was observed in 12 of 20 and 11 of 20 patients after active and sham stimulation periods respectively (P = 0·746). Pain related to the device occurred in five patients and wound infection or haematoma in three, leading to definitive removal of the pulse generator in two patients. At 1 year, 11 of the 20 patients with an implanted device continued to respond. Stimulation had no significant effect on colonic transit time. CONCLUSION: These results do not support the recommendation of permanent implantation of a pulse generator in patients with refractory constipation who initially responded to temporary nerve stimulation. Registration number: NCT01629303 (http://www.clinicaltrials.gov).

Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high-resolution manometry.

BACKGROUND: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. METHODS: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. KEY RESULTS: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. CONCLUSION & INFERENCES: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.

A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors.

BACKGROUND: The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. The aim of this study was to characterize pharyngeal and esophageal pH-impedance reflux patterns in a group of patients with suspected laryngopharyngeal reflux and to determine predictive factors of response to proton pump inhibitors. METHODS: Patients with chronic pharyngolaryngeal symptoms were evaluated with a symptom score questionnaire, laryngoscopy, and 24-hour pharyngeal and esophageal pH-impedance monitoring at baseline and after 8-week treatment with esomeprazole 40 mg b.i.d. Response to treatment was defined by a diminution of more than 50% of the score for the primary symptom. Reflux patterns and baseline impedance values were compared to those obtained in 46 healthy subjects. KEY RESULTS: Twenty-four patients were included (17 women, median age 54 years), all previously refractory to antisecretory therapy. Symptom scores were 46 (32-62) and 40 (27-76) off and on therapy, respectively (P=.1). There was no significant difference between patients and controls for pH-impedance reflux parameters and baseline values off and on therapy in distal and proximal esophagus and in the pharynx. Median numbers of pharyngeal reflux were 0 and 0 off and on therapy, respectively. Only two patients were responders to treatment, both with excessive distal reflux but no pharyngeal reflux. Only one patient had abnormal pharyngeal reflux but did not respond to proton pump inhibitors. CONCLUSIONS: Patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH-impedance reflux. In these patients, laryngopharyngeal reflux is unlikely.

24-hour pH-impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study.

BACKGROUND: Treatment of gastro-esophageal reflux refractory symptoms is challenging. This monocenter retrospective study assessed the value of preoperative pH-impedance monitoring 'on' therapy to predict functional outcome after laparoscopic fundoplication in patients with refractory reflux symptoms. METHODS: Patients with a preoperative pH-impedance monitoring 'on' proton pump inhibitors (PPIs) twice daily were assessed at least 6 months after a laparoscopic fundoplication for refractory reflux symptoms. Failure of fundoplication was defined by a Visick score > 2. Postoperative symptoms were assessed by the reflux disease questionnaire (RDQ). The pH-impedance parameters analyzed were the number of reflux events (total, acid, non-acid), esophageal acid exposure time, esophageal bolus exposure time, and symptom-reflux association defined by symptom index (SI) >50% and symptom association probability (SAP) >95%. KEY RESULTS: Thirty-three patients (18 female patients, median age 46 years) were assessed after a mean follow-up of 41.3 (range 7-102.2) months. Seven (21.2%) patients were considered as failures. Compared to patients with favorable outcome, these patients were more often 'on' PPI therapy (86% vs 23%, p < 0.05) and had higher RDQ scores in each domain: heartburn (p < 0.05), regurgitation (p < 0.05) and dyspepsia (p < 0.05). A positive SAP was the only pH-impedance parameter statistically associated with successful postoperative outcome (p = 0.004). CONCLUSIONS & INFERENCES: On therapy, a preoperative positive symptom association probability is the only pH-impedance parameter associated with favorable outcome after laparoscopic fundoplication for refractory reflux symptoms. These results should be confirmed by prospective studies.

Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.

BACKGROUND: A substantial proportion of patients with gastro-oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying. AIM: To evaluate the effect of revexepride, a novel prokinetic 5-hydroxytryptamine type 4 (5-HT4 ) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs. METHODS: A phase 2b, double-blind, parallel-group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e-diary data captured patients' symptoms over an 8-week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation-free days in the second half of the study (weeks 5-8). RESULTS: In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation-free days increased from baseline (range, 15.0-18.8%) to week 8 (62.3-70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose-dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment-emergent adverse events (TEAEs) was revexepride dose-dependent. Only one serious TEAE occurred and none resulted in death. CONCLUSIONS: Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.

Inter-observer agreement for diagnostic classification of esophageal motility disorders defined in high-resolution manometry.

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment.

BACKGROUND: Approximately, 20-30% of patients with gastro-esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5-HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI. METHODS: This was a phase II, exploratory, multicenter, randomized, placebo-controlled, double-blind, parallel-group study in patients with GERD who experienced persistent symptoms while taking a stable dose of PPIs (ClinicalTrials.gov identifier: NCT01370863). Patients were randomized to either revexepride (0.5 mg, three times daily) or matching placebo for 4 weeks. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires. KEY RESULTS: In total, 67 patients were enrolled in the study. There were no significant differences between study arms in the number, the mean proximal extent or the bolus clearance times of liquid-containing reflux events. Changes from baseline in the number of heartburn, regurgitation, and other symptom events were minimal for each treatment group and no clear trends were observed. CONCLUSIONS & INFERENCES: No clear differences were seen in reflux parameters between the placebo and revexepride groups.

Olmesartan-associated enteropathy: results of a national survey.

BACKGROUND: Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan. AIM: To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans. METHODS: French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included. RESULTS: Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration). CONCLUSIONS: Olmesartan causes a severe and immune-mediated enteropathy, with or without villous atrophy. Enteropathy associated with other sartans seems to be very rare.

Transcutaneous electrical tibial nerve stimulation in the treatment of fecal incontinence: a randomized trial (CONSORT 1a).

OBJECTIVES: The objective of this study was to show that although transcutaneous electrical tibial nerve stimulation (TENS) is being increasingly used to treat fecal incontinence (FI), its efficacy has never been proved using controlled trials. METHODS: In this randomized, double-blind, sham-controlled trial, 144 patients aged 30-82 years from nine centers were randomly assigned to receive either active or sham stimulations for 3 months. The primary end point was the response to treatment based on the number of incontinence and urgency episodes. Secondary end points were severity scores, quality of life scores, delay to postpone defecation, patient self-assessment of treatment efficacy, physician assessment of TENS efficacy, anorectal manometry, and adverse events. RESULTS: No statistically significant difference was seen between active and sham TENS in terms of an improvement in the median number of FI/urgency episodes per week. Thirty-four patients (47%) who received the active TENS treatment exhibited a >30% decrease in the FI severity score compared with 19 patients (27%) who received the sham treatment (odds ratio 2.4, 95% confidence interval 1.1-5.1, P=0.02). No differences in delay to postpone defecation, patient self-assessment of treatment efficacy, or anorectal manometry were seen between the two groups. The evaluating physicians rated the active stimulations as more effective than the sham stimulations (P=0.01). One minor therapy-related adverse event was observed (1.5%) (see Supplementary Consort 1b). CONCLUSIONS: We failed to demonstrate any benefit of TENS on our primary end-point.