BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given offlabel. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n ¼ 59) or placebo (n ¼ 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity 2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label Gastroenterology 2019;157:74-86 CLINICAL AT treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.
The mechanisms by which the lifestyle risk factors obesity, physical inactivity, and low fiber intake predispose to colorectal cancer (CRC) are unclear. Chronic bowel inflammation predisposes to malignancy in cases of inflammatory bowel disease. Many lifestyle risk factors for CRC are associated with evidence of systemic inflammation as indicated by circulating levels of Creactive protein (CRP), but it is unknown how this relates to inflammation at tissue level. Little is known about the degree of bowel inflammation in general population and the factors that affect it. Therefore, we aimed to assess the relation of levels of bowel inflammation in the general population and lifestyle risk factors for CRC, and to additionally assess whether these associations, if present, were attenuated by controlling for evidence of systemic inflammation.Average CRC risk subjects (320) of either sex aged 50 -70 were recruited in South London. A stool sample was provided for calprotectin measurement (a marker of bowel inflammation), serum for CRP, and a detailed dietary and lifestyle questionnaire completed.There was a significant positive relationship between fecal calprotectin and increasing age (P ؍ 0.002), obesity (P ؍ 0.04), physical inactivity (P ؍ 0.01), and an inverse relationship with fiber intake (P ؍ 0.02) and vegetable consumption (P ؍ 0.04). The relationship with obesity was attenuated by controlling for serum CRP.Fecal calprotectin levels are associated with lifestyle risk factors for colorectal cancer. Low-level asymptomatic bowel inflammation may be the link between lifestyle and the pathogenesis of CRC, and circulating proinflammatory cytokines may be part of the mechanism for this link.
Calprotectin is a calcium and zinc binding protein of the S100 family derived predominantly from neutrophils and monocytes. It is detectable in body fluids and tissue samples and is emerging as a valuable marker in the diagnosis, and the monitoring and determining of the prognosis of commonly encountered gastroenterological conditions. Fecal calprotectin, in particular, has for a long time been regarded as a promising marker of gastrointestinal pathology and has now been established as a routine test in Norway and at several centers in the UK.
The fundamental pathological process behind ulcerative colitis and Crohn's disease is intestinal inflammation. As the precise cause of this is not yet completely understood, current treatment strategies are aimed at reducing or eliminating the inflammation. Endoscopic examination and histological analysis of biopsy specimens remain the `gold standard' methods for detecting and quantifying bowel inflammation; however, these techniques are costly, invasive, and repeated examinations are unpopular with patients. Disease activity questionnaires and laboratory `inflammatory markers', although widely used, show an unreliable correlation with endoscopy and histology. New markers need to be developed to detect and quantify bowel inflammation. These would be of use diagnostically and also an aid to pharmacological treatment.
There is strong evidence indicating that inflammatory bowel disease (IBD) is increasing among black and minority ethnic (BME) communities. Despite this rise in prevalence, there is a paucity of research relating to ethnicity and IBD outside the USA. Furthermore, the symptoms of IBD are reported to start during childhood or adolescence in 20-25% of people with the condition. It is therefore important that young people's experiences of diagnosis, treatment and living with IBD are fully understood to ensure effective services and information provision. The study reported on in this paper was commissioned by a UK charity (Crohn's and Colitis UK) with the aim of increasing understanding of the specific issues and service needs of young people with IBD from BME communities. Empirical research entailed in-depth semi-structured interviews with 20 young people from BME groups accessed through gastroenterology departments at three collaborating NHS hospitals in England serving ethnically diverse populations. Interviews were carried out from June to December 2010 and sought to capture young people's views with IBD. A thematic analysis of their experiences identified many commonalities with other young people with IBD, such as the problematic route to formal diagnosis and the impact of IBD on education. The young people also experienced tensions between effective self-management strategies and cultural norms and practices relating to food. Moreover, the ability of parents to provide support was hampered for some young people by the absence of culturally competent services that were responsive to the families' communication needs. The findings highlight the need for more culturally appropriate information concerning IBD, and improved responsiveness to young people with IBD within primary care and the education system, as well as culturally competent messaging relating to the specific nature of the condition among the wider South Asian and black communities.
A new, highly sensitive assay for CRP may help to distinguish FBD from IBD.
BackgroundOver 250 000 people in the UK are affected with inflammatory bowel disease (IBD) and approximately 10 000 new cases are diagnosed every year. These chronic bowel conditions have been shown to affect both work and recreational activity. In the general population, regular exercise has numerous benefits to health and well-being and there are additional benefits for those with IBD. However, people with IBD face significant challenges in trying to take regular exercise.ObjectiveWith the renewed focus on sport brought about by the recent London Olympics, Crohn's and Colitis UK surveyed its members to explore their sport and fitness habits.Methods918 members participated in the survey, which is the largest survey of its kind, investigating the exercise habits of people with IBD.ResultsThe survey showed widespread uptake of exercise in those with IBD, with a large number feeling better for it. However, it also identified a considerable number of respondents who reported a significant negative impact of IBD on their ability to take up, enjoy and derive benefit from sporting activities.ConclusionAsking questions about sporting leisure activity in clinical consultations may identify those in need of help and support and possibly identify factors to be dealt with, in order to enable them to take part in these beneficial activities.
Pancreatic exocrine insufficiency (PEI) occurs when the insufficient secretion or function of pancreatic enzymes leads to maldigestion, most commonly as a result of chronic pancreatitis and pancreatic cancer. The condition is associated with significant morbidity and reductions in quality of life, even in milder forms. The challenges in approaching this condition include the non-specific presentation of mild to moderate PEI, and the lack of a convenient, accurate diagnostic test in this cohort. Classical symptoms appear late in the disease, and the diagnosis should be considered before steatorrhoea develops. Direct pancreatic function tests are the reference standard for diagnosis, but are invasive and not widely available. The faecal elastase-1 (FE-1) stool test is widely available and has been shown to be as effective as the 13C-mixed triglyceride breath test in more advanced disease. We recommend a pragmatic diagnostic approach that combines clinical history, assessment of nutritional status and measurement of FE-1. The critical first step is to consider the diagnosis. Once the diagnosis is confirmed, pancreatic enzyme replacement therapy should be initiated. The variety of enzyme preparations and recommended dosing regimens can present a challenge when selecting an adequate initial dose. Non-response should be actively sought and addressed in a systematic manner. This article discusses these challenges, and presents a practical approach to the diagnosis and management of PEI.
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