Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Small bowel bacterial overgrowth in subjects living in residential care homes.

OBJECTIVES: in elderly people, bacterial overgrowth of the small bowel may be occult. The significance of positive breath tests are uncertain: many fit elderly subjects with positive tests show no evidence of malabsorption. We assessed the prevalence and significance of bacterial overgrowth in the small bowel in a relatively unselected elderly population. METHODS: residents of seven elderly people's homes had a glucose hydrogen breath test. A medical history and anthropomorphic measurements were recorded. Volunteers with positive breath tests were given doxycycline. After 4 months all volunteers were reassessed. RESULTS: of 140 residents, 62 were tested. Nine (14.5%) had a positive breath test. There was no difference in anthropomorphic and bowel habit data between those with positive and those with negative breath tests. After 4 months of antibiotic treatment, volunteers with a positive breath test had increased weight and body mass index, while those with a negative test had decreased weight and body mass index. CONCLUSIONS: the percentage of volunteers with a positive breath test was much lower than in previous studies. This may be due to the relatively unselected nature of the volunteers. Treatment of bacterial overgrowth resulted in a small but significant improvement in anthropometric indices. The lack of association of positive breath tests with baseline anthropomorphic measurements or bowel habit highlights the occult nature of the bacterial overgrowth and questions its clinical importance.

Biofilm formation by Helicobacter pylori.

Helicobacter pylori NCTC 11637 produces a water-insoluble biofilm when grown under defined conditions with a high carbon:nitrogen ratio in continuous culture and in 10% strength Brucella broth supplemented with 3 g l-1 glucose. Biofilm accumulated at the air/liquid interface of the culture. Light microscopy of frozen sections of the biofilm material showed few bacterial cells in the mass of the biofilm. The material stained with periodic acid Schiff's reagent. Fucose, glucose, galactose, and glycero-manno-heptose, N-acetylglucosamine and N-acetylmuramic acid were identified in partially purified and in crude material, using gas chromatography and mass spectrometry. The sugar composition strongly indicates the presence of a polysaccharide as a component of the biofilm material. Antibodies (IgG) to partially purified material were found in both sero-positive and sero-negative individuals. Treatment of the biofilm material with periodic acid reduced or abolished immunoreactivity. Treatment with 5 mol l-1 urea at 100 degrees C and with phenol did not remove antigenic recognition by patient sera. The production of a water-insoluble biofilm by H. pylori may be important in enhancing resistance to host defence factors and antibiotics, and in microenvironmental pH homeostasis facilitating the growth and survival of H. pylori in vivo.

The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients.

Diarrhoea is a common side effect of antibiotic therapy, especially in the elderly. Saccharomyces boulardii is a non-pathogenic yeast which has been demonstrated to reduce the frequency of diarrhoea in patients due to a variety of causes. We set out to assess its role in preventing antibiotic-related diarrhoea. Consecutive patients over the age of 65 admitted to medical wards, and who were being prescribed antibiotics, were randomized to receive either S. boulardii 113 g twice daily or placebo for as long as they received antibiotics. Bowel habit was monitored using a record of interdefaecatory intervals (IDI) and stool form graded 1-4 (hard to liquid). Stool samples were tested every fourth day for Clostridium difficile toxin. Of the 72 patients randomized, 69 completed the study. There was no difference in sex, age, duration of antibiotic use, length of hospital stay, IDI, stool form, the proportion of patients receiving laxatives, the number of patients experiencing watery stools (seven vs. five), or the presence of C. difficile toxin (five vs. three). No side effects were attributable to S. boulardii. There was no evidence that the concomitant use of S. boulardii with antibiotics alters patients' bowel habits or prevents the appearance of C. difficile toxin in the stool. Thus, S. boulardii cannot be recommended as a 'natural' way to prevent antibiotic-related diarrhoea. This highlights the need for proper evaluation of probiotics before their unrestricted use in medical practice.

Prevalence of Helicobacter pylori in respiratory physicians performing bronchoscopy: a comparison with gastroenterologists using the carbon 13 urea breath test.

BACKGROUND: The mode of transmission of Helicobacter pylori is unclear, but it has been shown that gastroenterologists are at a greater risk of acquiring the infection when performing endoscopy. The current study was designed to assess the risk H. pylori infection in respiratory physicians performing bronchoscopy compared to an at-risk group of gastroenterologists. We were interested in identifying whether the oral cavity is important in the transmission of H. pylori. MATERIALS AND METHODS: Respiratory physicians and gastroenterologists in southern England and Wales were invited to participate in the study. Medical, personal, and professional details were recorded, and H. pylori status was established using a carbon 13 urea breath test. RESULTS: The study included 30 gastroenterologists and 30 respiratory physicians. The groups were similar for age (mean age, 46.2 years [SD 8.7] and 43.9 years [SD 8.5], respectively), number of years in practice (mean, 16.1 [6.8] and 13.2 [5.5], respectively), amount of Third-World travel, and glove and drug use (antacids, H2 antagonists, proton pump inhibitors, promotility agents, and bismuth). The prevalence of upper gastrointestinal symptoms (indigestion, heartburn, abdominal pain) and history of previous peptic ulcer or hiatus hernia were similar for both groups. Fifteen of thirty gastroenterologists and three of thirty respiratory physicians had positive breath tests (chi square, p < .001, 1 df). There was no relation between age and H. pylori status. Within the group of gastroenterologists, performance of endoscopy without gloves for longer than 7 years was associated with an increased prevalence of infection (> 7 years, 11 of 15 breath-test-positive; < 7 years, 4 of 15 breath-test-positive [chi square, p = .01, 1 df]). CONCLUSIONS: Gastroenterologists in this study appeared to be at risk of infection, whereas respiratory physicians are not. Gastroenterologists who wear gloves during endoscopy appear to be at lower risk of H. pylori infection.

Use of in vitro methods to rank surfactants for irritation potential in support of new product development.

11 surfactant raw materials with potential applications in light-duty liquid cleaning products were evaluated in vitro using a human skin analogue (ATS SKIN(2) Model ZK1100) for predicting cytotoxicity (MTT reduction) and inflammation [prostaglandin E(2) (PGE(2)) release]. Two of the 11 raw materials, both in the same compound family, were selected to be individually combined with each of the other nine in a 90:10 (raw:selected raw) mixture. Selection criteria were based on desired performance characteristics and low irritation potential as suggested from the individual surfactant assay data. To determine whether irritation potential was mitigated, MTT and PGE(2) scores were again determined for each of the 18 combinations with the resulting data being compared with the untreated raw material data. A plot of the data indicated that one of two selected materials may have an 'anti-irritant' effect. For raw materials with intrinsic MTT scores of less than 50 mug/ml and with the original data corrected for possible dilution effects, a statistical comparison between individual raw materials and the two sets of combinations was done using a one-sample analysis. Both cytotoxicity (MTT) and inflammation (PGE(2)) were significantly decreased by the milder of the two selected raw materials. By factoring the data into future new product decisions, this methodology has become a useful and practical tool for Amway product development.